Meningococcemia

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Practice Essentials

Meningococcemia is defined as dissemination of meningococci (Neisseria meningitidis) into the bloodstream (see the image below). Patients with acute meningococcemia may present with (1) meningitis (2) meningitis with meningococcemia, or (3) meningococcemia without clinically apparent meningitis.



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A 9-month-old baby in septic shock with purpuric Neisseria meningitis skin lesions. Photo by D. Scott Smith, MD, taken at Stanford University Hospital....

See Pediatric Vaccinations: Do You Know the Recommended Schedules?, a Critical Images slideshow, to help stay current with the latest routine and catch-up immunization schedules for 16 vaccine-preventable diseases.

Signs and symptoms

Patients with acute meningococcemia may present with meningitis alone, meningitis and meningococcemia, meningococcemia without clinically apparent meningitis.

The clinical presentation of meningococcemia may include any of the following:

Serogroup W disease may be associated with atypical presentations, including septic arthritis, pneumonia, endocarditis, and epiglottitis.

The meningitis of meningococcemia is associated with the following[1, 2]

Meningococcemia is characterized by the following[3] :

Physical findings may include the following:

See Clinical Presentation for more detail.

Diagnosis

Laboratory findings in the early stages of meningococcal disease are often nonspecific. Definitive diagnosis requires retrieval of meningococci from blood, cerebrospinal fluid, joint fluid, or skin lesions. Studies may include the following:

See Workup for more detail.

Management

Clinical guideline summaries related to meningococcal disease include the following:

Patients with a rash consistent with meningococcemia should be started immediately on parenteral antibiotics, especially in the setting of factors that are associated with poor clinical outcomes, as follows:

Antibiotics recommended for the treatment of meningococcemia include the following:

See Treatment and Medication for more detail.

Background

N meningitidis is an encapsulated gram-negative diplococcus (seen in the image below). There are at least 12 serogroups of the bacterium based on capsular polysaccharide antigenic differences. Serogroups A, B, C, Y, and W-135 cause 90% of human disease (See Pathophysiology, Etiology, and Workup.)



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Gram-negative intracellular diplococci. Courtesy Professor Chien Liu.

Patients with acute meningococcemia may present with 1 of 3 syndromes: meningitis, meningitis with meningococcemia, or meningococcemia without obvious meningitis.[7] Of cases of invasive meningococcal disease, 30%-50% present with meningitis alone, 40% have meningitis with bacteremia, and 7%-10% have invasion of the bloodstream alone. (See Presentation and Workup.) N meningitides remains a major infectious cause of childhood death in developed countries. The mortality rate remains around 10%, although, in some specialist centers, it has decreased to less than 5%overall. There has been little improvement in morbidity and mortality since the beginning of the antibiotic era because of the inability of antimicrobials to prevent the cardiovascular collapse brought about by the organism’s endotoxin.[8]



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Dorsum of the hand showing petechiae. Courtesy of Professor Chien Liu.

Carriers

Approximately 2% of children younger than 2 years, 5% of children up to 17 years, and 20-40% of young adults are carriers of N meningitidis. Overcrowded conditions (eg, schools, military camps) can significantly increase the carrier rate. (See Pathophysiology, Etiology, and Epidemiology.)

Screening of military recruits performed during recent epidemics demonstrated that, although as many as 95% of recruits were oropharyngeal carriers, only 1% developed systemic disease. Because very few of those infected had ever been in contact with another patient with a similar history, asymptomatic carriage is thought to be the major source of transmission of pathogenic strains. (See Pathophysiology and Etiology.)

Immunity to N meningitidis appears to be acquired through intermittent nasal carriage of meningococci and by antigenic cross-reaction with enteric flora during the first 2 decades of life.

Chronic meningococcemia

Chronic meningococcemia is a rare (< 200 documented cases) clinical presentation of N meningitidis that is most often observed in adults. In this condition, painful skin lesions similar to those seen in in gonococcemia are present on the extremities, with migratory polyarthritis and tenosynovitis. Antibiotic treatment results in a prompt response.

Pathophysiology

The fundamental pathologic change in meningococcemia is widespread vascular injury characterized by endothelial necrosis, intraluminal thrombosis, and perivascular hemorrhage. Endotoxin, cytokines, and free radicals damage the vascular endothelium, producing platelet deposition and vasculitis. The deleterious effects of cytokines play a major role in the pathogenesis of meningococcemia by causing severe hypotension, reduced cardiac output, and increased endothelial permeability.[9]

The clinical picture of meningococcemia is the product of compartmental intravascular infection and intracranial bacterial growth and inflammation. The pathogen binds tightly to the endothelial cells by type IV pili. From this arises microcolonies on the apical portion of the endothelial cell.[10] These bacteria invade the subarachnoid space with resultant meningitis in 50%-70% of cases. In a study of 862 patients, 37%-49% developed meningitis without shock, 10%-18% developed shock without meningitis, 7%-12% developed both, and 10%-18% with mild meningococcemia developed neither meningitis nor shock.[11]

Multiple organ failure, shock, and death may ensue as a result of anoxia in vital organs and massive disseminated intravascular coagulation (DIC).

Patients with fulminant meningococcemia develop thrombosis and hemorrhage in the skin, the mucous membranes, the serosal surfaces, the adrenal sinusoids, and the renal glomeruli. Adrenal hemorrhage is rarely extensive. Thrombosis of the glomerular capillaries may cause renal cortical necrosis, the chief characteristic of the generalized Shwartzman reaction, which is a model of DIC.[12] Thrombi containing numerous leukocytes are occasionally found in the lungs, and extensive intra-alveolar hemorrhage can occur. Myocarditis, when it occurs, carries a poor prognosis with a high mortality risk.

Virulence factors

Meningococci have 3 important virulence factors,[13] as follows:

A polysaccharide capsule (which also determines the serogroup) enables the organism to resist phagocytosis.[9]

An LOS can be shed in large amounts by a process called blebbing, causing fever, shock, and other pathophysiology. This is considered the principal factor that produces the high endotoxin levels in meningococcal sepsis. Meningococcal LOS interacts with human cells, producing proinflammatory cytokines and chemokines, including interleukin 1 (IL-1), IL-6, and tumor necrosis factor (TNF). LOS is one of the important structures that mediate meningococcal attachment to and invasion into epithelial cells.[14]

LOS triggers the innate immune system by activating the Toll-like receptor 4MD2 cell surface receptor complex and myeloid in non-myeloid human sounds. The degree of activation of complement then coagulation system is directly related to the bacterial load.[15]

IgA1 protease cleaves lysosomal membrane glycoprotein-1 (LAMP1), helping the organism to survive intracellularly.

Septicemia

The clinical syndrome results from the activation and continued stimulation of the immune system by proinflammatory cytokines. This process is directly caused by bacterial components, such as endotoxins released from the bacterial cell wall, and is indirectly caused by the activation of inflammatory cells. The clinical spectrum of meningococcal septicemia is produced by 4 basic processes (ie, capillary leak, coagulopathy, metabolic derangement, myocardial failure). Combined, the processes produce multiorgan failure that usually causes cardiorespiratory depression and, possibly, renal, neurologic, and gastrointestinal (GI) failure.[16]

Capillary leak

From presentation until 2-4 days after illness onset, vascular permeability massively increases. Albumin and other plasma proteins leak into the intravascular space and urine, causing severe hypovolemia. This is initially compensated for by homeostatic mechanisms, including vasoconstriction. However, progression of the leak results in decreased venous return to the heart and a significantly reduced cardiac output.

Hypovolemia that is resistant to volume replacement is associated with increased mortality due to meningococcal sepsis. Children with severe disease often require fluid resuscitation involving volumes several times their blood volume in the first 24 hours of the illness, mostly in the first few hours. Pulmonary edema is common and occurs after 40-60 mL/kg of fluid has been given; it is treated with artificial ventilation.

Although capillary leak is the most important clinical event, the underlying pathophysiology is unclear. Some evidence suggests that meningococci and neutrophils cause the loss of negatively charged glycosaminoglycans, which are normally present on the endothelium. Also, the repulsive effect of albumin may be reduced in meningococcal infection; this change allows the protein leak. Albumin is normally confined to the vasculature because of its large size and negative charge, which repels the endothelial negative charge.

Coagulopathy

In meningococcemia, a severe bleeding tendency is often simultaneously present with severe thrombosis in the microvasculature of the skin, often in a glove-and-stocking distribution that can necessitate amputation of digits or limbs. Clinicians face a dilemma because supplying platelets, coagulation factors, and fibrinogen may worsen the process. Meningococcal infection affects the main pathways of coagulation.

Endothelial injury results in platelet-release reactions. Along with stagnant circulation due to local vasoconstriction, platelet plugs form to start the process of intravascular thrombosis. In the plasma, soluble coagulation factors are consumed, and the natural inhibitors of coagulation (eg, the tissue factor pathway inhibitor antithrombin III) are down-regulated; this process further encourages thrombosis.

The protein C pathway probably plays a key role in the pathogenesis of purpura fulminans. A very similar rash occurs in neonates with congenital protein C deficiency and in older children who develop antibodies to protein S following varicella infection. Many patients with meningococcal infection are unable to activate protein C in the microvasculature due to endothelial downregulation of thrombomodulin.[17] Protein C and S levels are low in children with meningococcal disease. However, low levels may occur in patients with septic shock without purpura fulminans. Plasma anticoagulants (tissue factor pathway inhibitor and antithrombin) are also down-regulated in meningococcal sepsis.

The fibrinolytic system in meningococcal disease is down-regulated as well, reducing plasmin generation and removing an aspect of endogenous negative feedback to clot formation. In addition, plasminogen activator inhibitor levels are dramatically increased, further reducing the efficacy of the endogenous tissue plasminogen activator.

Metabolic derangement

Severe electrolyte abnormalities, including hypokalemia, hypocalcemia, hypomagnesemia, and hypophosphatemia, may occur in the setting of severe acidosis.

Myocardial failure

Myocardial function remains impaired even after circulating blood volume is restored and metabolic abnormalities are corrected. Reduced ejection fractions and elevated plasma troponin I levels indicate myocardial damage. A gallop rhythm is often audible, with elevated central venous pressure and hepatomegaly. Hemodynamic studies in patients with meningococcal sepsis have shown that the severity of disease is related to the degree of myocardial dysfunction.

Myocardial failure in meningococcal sepsis is undoubtedly multifactorial, but various proinflammatory mediators (eg, nitric oxide, TNF-alpha, IL-1B) released in sepsis appear to have a direct negative inotropic effect on the heart, depressing myocardial function. A study using new microarray technology showed that IL-6 is the key factor that causes myocardial depression in meningococcemia.[18, 19]

It has recently been demonstrated that meningococcal infection leads to human coronary microvascular thrombosis, vasculitis, and vascular leakage.[20]

Other factors that reduce myocardial function, such as acidosis, hypoxia, hypoglycemia and electrolyte disturbances, are all common in severe meningococcal disease.

Meningitis

Meningococcal meningitis generally has a better prognosis than septicemia. After bacteria enter the meninges, they multiply in the CSF and pia arachnoid. In the early stages of infection, the tight junctions between the endothelial cells that form the blood-brain barrier isolate the CSF from the immune system; this isolation allows bacterial multiplication. Eventually, inflammatory cells enter the CSF and release cytokines that play a central role in the pathophysiology of meningeal inflammation.[16, 1]

Neurologic damage is a consequence of the following 3 main processes:

Cerebral edema may be caused by increased secretion of CSF, diminished reabsorption of CSF, and/or breakdown of the blood-brain barrier. Obstructive hydrocephalus may cause increased accumulation of CSF between cells.

Increased ICP secondary to cerebral edema, loss of cerebrovascular autoregulation, and reduced arterial perfusion pressure secondary to shock reduce cerebral blood flow in bacterial meningitis. Reduced cerebral blood flow with vasculitis and thrombosis of cerebral vessels may cause ischemia and neuronal injury.

Etiology

N meningitidis is a gram-negative diplococcus (see the image below) that grows well on solid media supplemented with blood and incubated in a moist atmosphere enriched with carbon dioxide.



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Gram-negative intracellular diplococci. Courtesy Professor Chien Liu.

Oxidase and catalase are biochemical markers for preliminary identification of N meningitidis. Sugar fermentations are required for final identification of the species. N meningitidis ferments glucose and maltose but not sucrose or lactose.

Agglutination reactions with immune serum are used to segregate meningococci into 13 serogroups: A, B, C, D, X, Y, Z, E, W-135, H, I, K, and L, depending on the group-specific capsular polysaccharide antigen. Ninety-eight percent of infections are caused by encapsulated serogroups A, B, C, Y, and W-135, although of these groups, A, B, and C occur most frequently in meningococcal disease. The cell wall of pathogenic meningococci contains a toxic lipopolysaccharide or endotoxin that is chemically identical to enteric bacilli endotoxin.

Transmission

The human nasopharynx is the only known reservoir for N meningitidis. The organism is transmitted via aerosols and nasopharyngeal secretions. Meningococcal infection is preceded by nasopharyngeal colonization. Attachment to the nasopharyngeal epithelial cells is aided by meningococci-expressed pili, such as the type IV pilus encoded by pilC, which binds to human cell surface protein CD46.

Meningococci then enter the bloodstream and spread to specific sites, such as the meninges or joints, or disseminate throughout the body. Five percent of individuals become long-term carriers, most of whom are asymptomatic. In outbreaks, the carriage rate of an epidemic strain can reach 90%. The likelihood of acquiring infection is increased 100-1000 times in intimate contacts of individuals with meningococcemia.

A study of 14,000 teenagers in the United Kingdom found that attendance at pubs or clubs, intimate kissing, and cigarette smoking were each independently and strongly associated with an increased risk of meningococcal carriage.[21]

Immunity

Passively transferred maternal antibody provides temporary protection to infants for the first 3-6 months of life. As the child grows older, asymptomatic exposure to a variety of encapsulated and nonencapsulated N meningitidis strains increases protective bacterial immunity. Most individuals acquire immunity to meningococcal disease by age 20 years; protective IgM and IgG are found in up to 95% of young adults.

An episode of meningococcal disease confers group-specific immunity, but a second episode may be caused by another meningococcal serogroup.

Susceptibility

Complement deficiency

A genetic component to host susceptibility to meningococcemia is becoming more established. IgG antibodies that have specificity for meningococcal polysaccharides mediate bactericidal activity. Complement is needed for expression of this activity. Terminal complement deficiency is well known to predispose individuals to meningococcemia.

Genetic variants of mannose-binding lectin, a plasma opsonin that initiates another pathway of complement activation, may account for nearly one third of the cases of invasive meningococcal disease.

Meningococcemia is particularly common among individuals with deficiencies of terminal complement components C5-C9 or properdin. These late complement components are required for bacteriolysis of meningococci.

An estimated 50-60% of individuals with late complement component deficiencies develop at least 1 episode of meningococcal disease. Many of these patients experience multiple episodes of infection.

Acquired complement deficiencies that occur in association with systemic lupus erythematosus, multiple myeloma, severe liver disease, enteropathies, and nephrotic syndrome also predispose to meningococcal infection.

Interleukin abnormalities

Specific genetic polymorphisms are likely to predispose individuals to mortality in severe sepsis. An association has been described between increased risk of mortality in children with meningococcal disease and polymorphisms in the IL-1 cluster.

An innate anti-inflammatory cytokine profile (low level of TNF and high level of IL-10) is also associated with fatal meningococcal disease.

Coagulation pathway abnormalities

Polymorphisms in the genes that control the coagulation pathways are being evaluated. Patients with the prothrombotic factor V Leiden mutation are at higher risk for thrombotic complications, such as amputations and skin grafting, but do not have increased mortality in meningococcemia.

Other

An increased type-1 plasminogen activator inhibitor response to TNF meningococcal septicemia has been demonstrated to result from a polymorphism in the PAI-1 gene.

Another study reported that a toll-like receptor 4 variant genotype was associated with increased mortality in children with invasive meningococcal disease.[22]

Risk factors

Most patients with meningococcal disease were previously healthy; however, patients with certain medical conditions are at increased risk for developing meningococcal infection. Risk factors include the following:

Patients with anatomic or functional asplenia are also at increased risk for invasive meningococcal disease.

Epidemiology

Occurrence in the United States

From 2006-2015, 7,924 cases of meningococcal disease were reported (average annual incidence of 0.26 cases per 100,000 population), 2,290 (35.8%) of which were serogroup B, 1,827 (28.5%) were serogroup Y, 1,457 (22.8%) were serogroup C, 436 (6.8%) were serogroup W, and 392 (6.1%) were other serogroups.[25] Although endemic in North America, meningococcal infections follow a pattern of multiyear cycles. The most recent peak occurred in 1996 (1.1 cases/100,000 population). In contrast, the incidence in 2005 was 0.4 cases/100,000 population. This decline began before the use of conjugate vaccine among adolescents in 2005.[26] By 2011, the incidence had decreased to 0.3 cases/100,000 population.[27] In 2006, 1194 cases of meningococcal disease were reported in the United States; 974 cases were reported in 2007.[28, 29] From January 2014 through December 2016, 1,174 confirmed or probable meningococcal cases were reported.[30]

Serogroup B infections have occurred in college outbreaks, especially among freshmen.[31] Data have also shown that college-attending students are at a higher risk of invasive meningococcal disease than nonattenders, and all outbreaks in the 2011-2019 period involved serogroup B disease.[32] High overall vaccination coverage rather than use during outbreaks would be an effective strategy, as the serogroup B meningococcal (MenB) vaccine may not be associated with reduced carriage or acquisition rates.[33]

A systematic review of carriage rates in the Americas from 2001-2018 found the second highest rate (24%) in the United States.[34]

Outbreaks account for less than 5% of meningococcal infections in the United States. They may be restricted to a closed population or may involve a larger community. In a Los Angeles County outbreak of meningococcal disease, nearly one half of community residents with the disease had had contact with persons who had been incarcerated.[35]

The increased risk of invasive meningococcal disease among young adults who live in close quarters under stressful situations has been long recognized. The prototype of this type of outbreak is that among military recruits living in crowded barracks. Resultant disruption and basic training prompted the Department of Defense to initiate development of the original meningococcal vaccines.[36]

Between 2010 and March 2013, 22 cases of meningococcal infection, serogroup C, were documented in New York City among men who have sex with men (MSM). Sixteen of these occurred in 2013. Fifty percent involved blacks. Fifty-five percent of infected persons were also HIV-positive. Seven cases were fatal.

In 2012, the incidence of meningococcal disease among MSM aged 18-64 years in New York City was 12.6 per 1000 population, compared with 0.16 per 500,000 non-MSM population. In 2014, there were 4 additional cases. Several outbreaks were reported in Los Angeles during the same time.[37] Serogroup C disease has been associated with a significantly higher number of cases.[38]

In the HAART era, the relative risk of meningococcal disease among persons with HIV infection was 10, with the greatest likelihood among those with CD4 counts less than 200/µL.[39]

The incidence of meningococcal infection among healthcare workers and first responders is quite low. However, it is estimated that the rate of acquisition of meningococcal by microbiological laboratory workers infection in the United States is significant. The vast majority of cases were associated with absence of any respiratory protection during the time that the specimens were handled.[40]

Thirty-five percent of meningococcal disease cases are caused by serogroup C, 32% by serogroup B, and 26% by serogroup Y.[41] Since 2005, the year that the quadrivalent (serogroup A, C, W-135, and Y) conjugated meningococcal vaccine was made available, there has been a rise in outbreaks of serogroup B infection on college campuses.[42]

Patients with complement deficiencies have a higher proportion of meningococcal disease caused by serotypes Y and W-135.

International occurrence

Serogroups A, B, and C account for most cases of meningococcal disease worldwide. Serogroups A and C predominate in Asia and Africa, while serogroups B and C predominate in Europe, North America, and South America.

An international outbreak of meningococcal disease associated with serogroup W-135 occurred following the return of travelers who participated in the annual hajj (pilgrimage) to Mecca, in Saudi Arabia, in 2000 and 2001.[43, 44, 45]

Outbreaks have also occurred in Africa, parts of Asia, South America, and the former Soviet republics. Serogroup A is usually implicated in these epidemics. Indeed, for more than a century, serogroup A meningococcal disease has been endemic in the African Meningitis Belt (see the map below), which extends from Ethiopia in eastern Africa to Senegal in West Africa. Large-scale outbreaks occur at cyclic intervals of 7-10 years through these central African countries, with attack rates as high as 400-500 cases per 100,000 population.[46]



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Areas with frequent epidemics of meningococcal disease. This is known as the Meningitis Belt of Africa; visitors to these locales may benefit from men....

Meningococcal disease may also be a significant, but underreported, problem in developing Asian countries.[47]

Europe and the United Kingdom

In Europe, invasive meningococcal disease is caused predominantly by serogroup B.

In September 2015, the United Kingdom became the first country to introduce the meningococcal multicomponent vaccine (4CMenB) vaccine to be administered at age 2, 4, and 12 months. This vaccine may also provide cross-protection against the endemic hypervirulent serogroup W strain.[48] This has significantly reduced the predicted cases of serogroup B infection. The overall incidence of invasive meningococcal disease over the past decade has also decreased, from 2 per 100,000 in 2006/2007 to 1 per 100,000 since 2011/2012.

Based on data from 2017-2018, serogroup B remains the most important cause of invasive meningococcal disease in England (54%, 404/755), serogroup W disease (26%), serogroup Y disease (12%), and serogroup C disease (8%).[49]

Climate-related demographics

Meningococcal infections in the United States and Northern Europe are most common in the winter, while cases of meningococcal disease in the African Meningitis Belt increase at the end of the dry season.

Race- and sex-related demographics

Mortality rates may be significantly higher in blacks than in whites and Asians.[50]

Meningococcal disease is somewhat more prevalent in males (1.2 cases per 100,000) than in females (1 case per 100,000).

Age-related demographics

In epidemics of meningococcal disease, people of any age may be affected, with the case distribution shifted toward older individuals.[51]

Endemic meningococcal disease is most common in children aged 6-36 months. Children younger than 6 months are protected by maternal antibodies, (although occult meningococcemia, an uncommon form of infection, affects children aged 3-24 months). (See the image below.)



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Lesions caused by Neisseria meningitis bacteremia on the palm of the hand of a 9-month-old infant. Photo by D. Scott Smith, MD, taken at Stanford Univ....

A second, less dramatic peak in incidence occurs among teenagers and college students; this may be due to changes in social behavior and increases in close interpersonal contact in these populations. About one third of meningococcal disease cases occur in adults.

In New York City, from 1989-2000, the overall incidence rates of meningococcal disease decreased. The median age of patients with meningococcal disease increased from 15 years in 1989-1991 to 30 years in 1998-2000.[52]

Prognosis

Meningococcal disease can progress very quickly and can result in loss of life, neurologic impairment, or peripheral gangrene. Patients with terminal complement component deficiency have a more favorable prognosis. A fatal outcome is highly associated with properdin deficiencies. Coagulopathy with a partial thromboplastin time of greater than 50 seconds or a fibrinogen concentration of less than 150 µg/dL are also markers of poor prognosis.

A multicenter study evaluating the serogroups in children with N meningitis infection found that meningococcal disease continues to result in substantial morbidity and mortality in children. The study found that, overall, 55 (44%) of isolates were serogroup B, 32 (26%) were serogroup C, and 27 (22%) were serogroup Y. All but 1 isolate (intermediate) were susceptible to penicillin. The overall mortality rate in this pediatric population was 8%.[53]

Cases of meningococcal meningitis without coma or focal neurological deficits have markedly better outcomes. Most of these patients recover completely when appropriate antimicrobial therapy is administered promptly upon presentation.

Isolated meningococcal meningitis (5% mortality rate) has a better prognosis than meningococcal septicemia (10%-40% mortality rate).

Patients with higher bacterial loads on polymerase chain reaction (PCR) testing are more likely to die or have permanent disease sequelae and experience longer hospital stays.[54]

Morbidity

Complications of meningococcal infection include the following:

Complications of meningococcemia may occur at the time of acute disease or during the recovery phase. Patients with fulminant meningococcemia may develop respiratory insufficiency and require mechanical ventilation. Those with severe DIC may bleed into their lungs, urinary tract, and gastrointestinal tract. Ischemic complications of DIC have been reported in up to 50% of survivors of fulminant meningococcemia.

Complications of meningococcal infection include immune complex disease leading to arthritis, pericarditis, myocarditis, and pneumonitis 10-14 days after the primary infection. Up to 5% of patients with meningococcemia develop a nonpurulent pericarditis with substernal chest pain and dyspnea approximately 1 week after the onset of illness. Involvement of the pericardium in meningococcal disease is a well-recognized, but rare, complication. It has been described with N meningitidis serotypes C, B, W-135, and Y.[57]

Meningococcal meningitis may progress to mental obtundation, stupor, or coma, which may be related to increased ICP, and such patients are prone to herniation. Other rare complications of meningitis include acute and delayed venous thrombosis, which usually manifests as a focal neurologic deficit.

Meningococcal infection may spread through the bloodstream and localize in other parts of the body, where it can cause suppurative complications. Septic arthritis, purulent pericarditis,[58] and endophthalmitis[59] can occur but are uncommon.

Meningococcal pneumonia has been described and probably results from aspiration of N meningitidis. The W-135 serogroup of meningococci was found to be more likely to cause this form of meningococcal disease, as well as pericarditis and septic arthritis.

Approximately 10% of patients with meningococcal disease develop nonsuppurative arthritis, usually of the knee joints. The nonsuppurative arthritis of meningococcal disease may result from tenosynovitis due to meningococcemia or a postinfectious immunologic process.

Recurrent meningococcal disease has been associated with hereditary deficiencies of various terminal components of the complement system.

Myocarditis is a complication with a high mortality risk. The frequency may be more common than is clinically recognized.[60]

Sequelae

A case-control study examined outcomes in patients who had survived meningococcal disease in adolescence and found that they had poorer mental health, social support, quality of life, and educational outcomes, as well as greater fatigue, than did well-matched controls.[61]

A European study found that approximately 4% of survivors of meningococcal infection had sequelae. In the United Kingdom, approximately 5% of survivors have neurologic sequelae, mainly sensorineural deafness. Amputation or skin grafting due to digital or limb ischemia and severe skin necrosis is required in 2-5% of survivors in the United Kingdom.

In the United States in 2005, 11-19% of survivors of meningococcal infection had serious health sequelae, including sensorineural hearing loss, amputations, and cognitive impairment.

A study from the Netherlands involving patients who had survived meningococcal septic shock in childhood found that 35% of these patients had some degree of neurologic impairment; chronic headache accounted for the largest proportion of impairment symptoms.[62]

Another study from the Netherlands examined skin scarring and orthopedic sequelae following meningococcal septic shock. Forty-eight percent of children had skin scarring, ranging from extremely disfiguring scars to those that were barely visible; 14% of patients had orthopedic sequelae; 8% had undergone amputation; and 6% had lower limb length discrepancy (more common in patients who were particularly young when admitted to the pediatric intensive care unit [PICU] for meningococcal septic shock). Patients with scars or orthopedic sequelae had significantly higher illness severity scores. (See the images below.)[63]



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A 9-month-old baby in septic shock with purpuric Neisseria meningitis skin lesions. Photo by D. Scott Smith, MD, taken at Stanford University Hospital....



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The leg of a 9-month-old infant in septic shock with a rapidly evolving purpuric rash. Photo by D. Scott Smith, MD, taken at Stanford University Hospi....



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Neisseria meningitis purpuric lesions on the ear and cheek of a 9-month-old infant who is in septic shock. Photo by D. Scott Smith, MD, taken at Stanf....

Mortality

The case-fatality rate of meningococcal infections varies depending on the prevalence of disease, the clinical form of disease, and the socioeconomic conditions of the society in which the infections occur. In the United States, the case-fatality rate is approximately 10%.

Specialty units in geographic areas with a high incidence of meningococcal infections have reduced their mortality rates to less than 5%.

The prognosis of fulminant meningococcemia is guarded. Approximately one half of patients who present with this form of meningococcal disease do not survive, even with prompt administration of appropriate antimicrobial therapy. Most deaths occur within 48 hours. The mortality rate can be as high as 70% in developing countries. Survivors of fulminant meningococcemia may have ischemic complications.

Cases of fulminant meningococcemia can also be associated with the complication of massive adrenal hemorrhage (Waterhouse-Friderichsen syndrome). In these cases, the mortality rate is close to 100%.

A mortality rate of 40-80% in patients with meningococcemia is associated with the acute onset of petechiae less than 12 hours before admission, shock, coma, high fever, low peripheral leukocyte count, thrombocytopenia, high serum antigen titer, absence of meningitis, metabolic acidosis, and DIC. Half of all patients with shock who die do so within the first 12 hours of hospitalization.[64] Meningococcemia associated with DIC has a mortality rate of higher than 90%.

Isolated meningococcal meningitis (5% mortality rate) has a better prognosis than meningococcal septicemia (10-40% mortality rate). In 2005, the mortality rate in the United States was 10-14%. Meningococcal meningitis without antibiotic therapy is uniformly fatal.

Patient Education

Health education improves public recognition of nonblanching rashes associated with meningococcal disease and was instrumental in reducing mortality in the United Kingdom.

Parents readily recognize the tumbler test; if a rash does not fade when a glass tumbler is pressed against the skin, the rash is nonblanching, and medical advice should be sought immediately.

Further information is available from the charities and patient-support organizations such as the Meningitis Research Foundation (MRF) and The National Meningitis Trust.

For patient education information, see the Children's Health Center, the Brain and Nervous System Center, and the Infections Center, as well as Meningitis in Adults, Meningitis in Children, and Brain Infection.

History

The clinical pattern of meningococcemia varies. Persons with meningococcal disease may present with a nonspecific prodrome of cough, headache, and sore throat. After a few days of upper respiratory symptoms, the temperature rises abruptly, often after a chill. Malaise, weakness, myalgias, headache, nausea, vomiting, and arthralgias are common presenting symptoms.

A skin rash, which is essential for recognizing meningococcemia, is the characteristic manifestation. The skin rash may advance from a few ill-defined lesions to a widespread petechial eruption within a few hours. Meningococcemia’s potential rapidity of progression cannot be stressed enough.

In fulminant meningococcemia, a hemorrhagic eruption, hypotension, and cardiac depression, as well as rapid enlargement of petechiae and purpuric lesions, may be apparent within hours of the initial presentation. (See the image below.)



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Purpura in a young adult with fulminant meningococcemia.

Meningitis

Meningitis is associated with the following[1] :

In adults, bacterial meningitis has a characteristic clinical pattern, although the progression of symptoms varies somewhat. Symptoms of meningitis may accompany the petechiae of meningococcemia and may produce the predominant features on presentation.

Bacterial meningitis is a febrile illness of short duration; the major symptoms include headache and a stiff neck. Lethargy or drowsiness is common. Confusion, agitated delirium, and stupor are rarer; however, coma is an ominous prognostic sign.

The clinical pattern of bacterial meningitis is often atypical in young children because headache and nuchal rigidity are frequently absent. Irritability, especially upon movement, is a common presenting manifestation of meningitis in a young child. Convulsions may signal the onset of meningitis at this age. Progression of the illness results in the development of lassitude and a more constant fever, often accompanied by abdominal discomfort. Projectile vomiting may occur.

Septicemia

Septicemia may be confused with influenza, particularly when myalgia is prominent. Meningococcal septicemia is characterized by the following[3] :

Symptoms of meningitis and septicemia may occur together and may complicate the distinction between an acute depression in level of consciousness due to hypotension and that due to elevated ICP.

Chronic meningococcemia

Chronic meningococcemia is an intermittent bacteremic illness that lasts from at least 1 week to as long as several months. The fever tends to be intermittent, with afebrile periods ranging from 2-10 days, during which the patient seems completely healthy. As the disease progresses, the febrile periods become more common, and the fever may become continuous.[66]

Eventually, a skin eruption or some other manifestation of meningococcal disease appears during a febrile episode. Cutaneous manifestations are variable and can consist of rose-colored macules and papules, indurated nodules, petechiae, purpura, or large hemorrhagic areas.

Case reports associate chronic meningococcemia with the absence of a terminal component of complement. Clinically, it can be confused with the dermatitis-arthritis syndrome associated with subacute gonococcemia.

The course of chronic meningococcemia is as variable as the cutaneous findings. Patients may recover spontaneously or progress to systemic complications such as meningitis. The prognosis for treated patients is excellent, with a cure rate of nearly 100% with appropriate antibiotic therapy. Penicillin G at 6-12 million U/day in divided doses for a minimum of 7 days is effective therapy.

Physical Examination

Patients with meningococcal disease appear severely ill. Tachycardia and mild hypotension are present. Patients with acute meningococcemia usually present with moderate fever (average, 39.5°C) and no signs of shock. High fever (average, 40.6°C) is present in fulminant meningococcemia.

Congestive heart failure, gallops, and pulmonary edema may be present in meningococcal disease. Other evidence of end-organ damage may also rapidly appear.

Patients with fulminant meningococcemia rapidly deteriorate clinically, with hypotension and respiratory failure.

Pericarditis can occur during the acute disease or in the recovery period and is associated with serogroup C disease.

Dermatologic manifestations

Petechiae develop in 50%-80% of patients with meningococcal disease and involve the axillae, flanks, wrists, and ankles, although they can progress to any part of the body. Lesions commonly begin on the trunk and legs in areas where pressure is applied. (See the images below.)



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Dorsum of the hand showing petechiae. Courtesy of Professor Chien Liu.



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Petechiae on lower extremities. Courtesy of Professor Chien Liu.



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Scattered petechiae in a patient with acute meningococcemia.



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The legs of a 22-year-old woman in septic shock with a rapidly evolving purpuric rash. Photo by D. Scott Smith, MD, taken at Stanford University Hospi....

Petechiae are often located in the center of lighter-colored macules. They are discrete lesions 1-2mm in diameter. Confluence of lesions results in hemorrhagic patches, often with central necrosis. In some cases, a transient maculopapular rash develops, usually lasting for less than 48 hours. Rash may be missed early in an individual with dark skin.[67]

Critically ill patients with sepsis may develop rapidly progressing petechiae, ecchymoses, and extensive, palpable purpura or retiform purpura, accompanied by DIC and vascular collapse.

Skin lesions tend to occur in crops on any part of the body, occasionally presenting on the conjunctivae and the mucous membranes (see the first image below). The face is usually spared, and involvement of the palms and the soles is less common (see the second image below).



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Conjunctival petechiae. Courtesy of Professor Chien Liu.



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Petechiae on the palm. Courtesy of Professor Chien Liu.

Fulminant meningococcemia

Fulminant meningococcemia is associated with a purpuric eruption, as shown in the image below. Lesions are generally characterized by maplike purpuric or necrotic areas.

Hemorrhages may appear on the buccal mucosa and the conjunctivae. Less frequently, fulminant meningococcemia presents as purpura fulminans (see the image below). In rare cases, no skin lesions develop. Symmetrical, peripheral gangrene has been described in this form. Amputation may be required in severe cases of necrosis.



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Child with severe meningococcal disease and purpura fulminans.

Additional signs of fulminant meningococcemia

Signs of meningitis are typically absent. However, cyanosis, hypotension, and profound shock eventually appear.

Patients with fulminant meningococcemia usually present with a high fever (average temperature, 40.6°C). The blood pressure is lowered, and pulmonary insufficiency develops within a few hours.

Many patients with fulminant meningococcemia die despite appropriate antibiotic therapy and intensive care. Patients with fatal forms of fulminant meningococcemia are likely to die within 24-48 hours of presentation.

Signs of meningococcal septicemia

Fever, rash, tachycardia, hypotension, cool extremities, and an initially normal level of consciousness indicate meningococcal septicemia.

Confusion, cold extremities, poor capillary refill, and increasing tachycardia may herald a precipitous decrease in blood pressure.

An increasing respiratory rate suggests pulmonary edema or shock. Generalized edema develops as a result of capillary leak syndrome, and myocardial depression further impairs tissue perfusion.

Signs of meningitis

The characteristic physical examination findings of meningitis include pain and resistance to neck flexion. Other signs of meningeal irritation can also be elicited. Children with meningitis may have none of these findings.

The Kernig sign is positive when the leg cannot be extended more than 135° on the thigh when flexed 90° at the hip. The Brudzinski sign is positive when neck flexion causes involuntary flexion of the thighs and the legs.

Focal neurologic signs are uncommon presenting findings of bacterial meningitis. However, nuchal rigidity may not be elicited in patients who are comatose and who may have signs of focal or diffuse neurologic deficits.

Papilledema is not a presenting feature of bacterial meningitis and suggests the presence of an accompanying process.

A common presenting sign of meningococcal meningitis is petechiae. Most patients with meningitis are febrile, although the height of fever varies.

Approach Considerations

Definitive diagnosis of meningococcal infection requires culture of meningococci from blood, spinal fluid, joint fluid, or, occasionally, from skin lesions.

The early stages of meningococcal disease may be misdiagnosed as a benign viral infection, and the patient may be discharged from an emergency department for care at home. Petechiae may be difficult to appreciate at the early stage and are more difficult to recognize in individuals who have dark skin.

The laboratory findings in the early stages of meningococcal disease are nonspecific and often unremarkable. For example, patients with fulminant meningococcemia may present with a normal white blood cell (WBC) count or leukopenia.

A study of adults with fulminant meningococcemia found that the following 4 variables at the time of admission portend a fatal outcome:

Blood culture

Cultures in meningococcal infection produce transparent, nonpigmented colonies that are oxidase positive and nonhemolytic. Overall, the sensitivity of blood culture is 50%-60% in untreated patients.[68]

In meningococcemia, organisms have been isolated by blood culture in almost 100% of patients. The results are not available for 12-24 hours.

Perform the blood cultures before the administration of antibiotics. These can be drawn in rapid succession so as not to delay the institution of appropriate antibiotics.

Throat culture

A throat culture should be obtained; however, the diagnosis of meningococcemia cannot be made solely from a positive result from throat culture, because asymptomatic colonization is not uncommon.

Complement deficiencies should be sought for complicated infections and recurrent or familial disease.

Diagnosis of chronic meningococcemia

The diagnosis of chronic meningococcemia is confirmed with the identification of N meningitidis from blood cultures. Multiple cultures are often necessary to confirm bacteremia because of the high rate of false-negative test results. Alternatively, a novel N meningitidis–specific polymerase chain reaction assay performed on skin biopsy specimens may prove to be helpful for this diagnostic challenge.[69]

Chronic meningococcemia differs histopathologically from acute meningococcemia in that no bacteria are present, thrombi do not occlude capillaries and venules, and endothelial swelling does not occur. The most common finding in a person with chronic meningococcemia is a leukocytoclastic angiitis.

Imaging studies

Chest radiography is useful to evaluate for pneumonia and acute respiratory distress syndrome. Echocardiography can be used to evaluate for myocardial dysfunction and pericarditis. Deep muscle and bone involvement can be evaluated with magnetic resonance imaging (MRI).

Hematologic Studies

Collect blood cultures (2 sets, with at least 10 mL per bottle) in any febrile patient with petechiae. A complete blood count (CBC), platelet count, blood urea nitrogen (BUN) study, and creatinine clearance evaluation, as well as a series of coagulation studies, can be used to evaluate a consumptive coagulopathy. Coagulation is often disturbed in septicemia because of the consumption and loss of clotting factors.

Gram stain of the peripheral blood buffy coat may reveal gram-negative diplococci in fulminant meningococcemia.

Rapid latex antigen tests may assist with diagnosis. The latex agglutination test has 50-100% sensitivity and high specificity, but it has a high rate of false-negative results.

Coagulation tests

DIC is a laboratory diagnosis, but no single laboratory test is diagnostic. Instead, DIC is recognized clinically by a pattern of changes in numerous coagulation tests. Typically, these changes include lowered platelet count, prolonged prothrombin time, prolonged partial thromboplastin time, lowered fibrinogen levels, and the presence of fibrin-split products in the circulation. Not all of these changes are found in all patients. Fibrinogen, an acute-phase reactant, may be elevated in patients with DIC.

White blood cell count

In patients with meningococcal infections, the WBC count and C-reactive protein level may be elevated at presentation or may increase during the subsequent 24 hours. However, these values are not reliable markers of infection.

In a study of 128 consecutive children with meningococcal sepsis who were admitted to a pediatric intensive care unit, only 14% had a WBC count of more than 20 X 109/L, and 71% had a WBC count of less than 15 X 109/L.

A low WBC count is a poor prognostic finding and should raise concerns about disease rapid progression.

Metabolic abnormalities

Biochemical disturbance is common in children who have shock with or without impaired renal function. The following abnormalities frequently occur:

Other

Evaluate for evidence of end-organ damage (eg, kidney or hepatic failure) with appropriate blood tests.

Needle Aspirates and Skin Biopsy

Gram-negative diplococci may be observed in punch biopsy and needle aspiration specimens of skin lesions or buffy coat preparations. Gram-negative diplococci may also be recovered from joint fluid. Findings on Gram stains of skin lesions remain positive for up to 2 days after the start of antibiotics and form a rapid means of diagnosis, including when meningitis is not present and when spinal fluid culture findings are negative owing to the administration of antibiotics. (See the image below.)



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Gram-negative intracellular diplococci. Courtesy Professor Chien Liu.

In one study, needle aspirates or skin biopsy specimens from patients with meningococcal sepsis tested using Gram stain yielded a 72% sensitivity; in another study, sensitivity was reportedly 80% using scraped material from petechiae.[70] However, a third investigation, a prospective, controlled study combining Gram stain and culture of skin biopsy specimens, reported a sensitivity of 56%.[71]

Histology

Leukocytoclastic vasculitis, thrombosis, and organisms are often demonstrated in biopsy specimens collected from patients with acute meningococcemia.

Cutaneous petechiae and purpura correspond to thrombi in the dermal vessels composed of neutrophils, platelets, and fibrin. Acute vasculitis with neutrophils and nuclear dust present within and around vessels leads to hemorrhage into the surrounding tissue. Meningococci can often be seen in the luminal thrombi and vessel walls. Intraepidermal and subepidermal neutrophilic pustules also may be present.

Perivascular lymphocytic infiltrate with few neutrophils characterize chronic meningococcemia, although leukocytoclastic vasculitis may be seen in biopsies of petechiae.

Serogrouping-Serotyping

Meningococcal polymerase chain reaction assay

Meningococcal PCR is a rapid method for diagnosing CSF infection.[72] It may not be available commercially in the United States but has been used extensively in the United Kingdom. PCR of spinal fluid yields a sensitivity and specificity of more than 90% in the diagnosis of meningococcal meningitis. It is useful when antibiotics have been administered and can be used to rapidly type strains in developing epidemics.[73, 74, 69, 75, 76, 77, 78, 54]

Diagnosis and serogrouping of N meningitidis infection can also be performed on formalin-fixed tissue samples using immunohistochemical analysis and PCR.[73, 74]

Slide agglutination test

With serogrouping, polysaccharide antigens on the capsule are identified by a slide agglutination test using polyclonal antibodies.

Enzyme-linked immunosorbent assay

With serotyping and serosubtyping, outer membrane proteins (PorB and PorA) can be identified by an enzyme-linked immunosorbent assay (ELISA) using monoclonal antibodies.

Lumbar Puncture

Brain imaging studies before a lumbar puncture (LP) are unnecessary unless the patient is obtunded, has focal neurologic signs, has experienced a seizure within the previous week, or presents with papilledema.

Perform LP for CSF evaluation. Immediately stain and culture the spinal fluid. (CSF culture yields a sensitivity of up to 70% in untreated patients.)

Gram stain of the CSF should be performed immediately and examined microscopically. Organisms can be observed in the CSF in approximately half of patients who present with meningococcal meningitis. (Gram stain can have a higher yield than blood cultures.)

Send the CSF for a WBC count, a WBC differential, total protein content, and glucose studies. Send additional tests as indicated for ruling out other diagnoses.

Bacterial meningitis produces various inflammatory changes in the CSF. The CSF becomes turbid with more than 1000 WBC/µL, and the cells are predominantly polymorphonuclear. The intracranial pressure (ICP) may be elevated. The total protein content is increased, and the glucose level, which is normally 60% of the simultaneous blood glucose level, becomes lowered (hypoglycorrhachia).

Detection of N meningitidis capsular polysaccharide antigen in CSF and urine with rapid serologic tests based on latex particle agglutination is commercially available.

Contraindications for lumbar puncture

In the presence of purpura or petechiae, LP may be hazardous and may add few data to aid in the diagnosis. In a patient with a depressed level of consciousness, shock, or any of the features listed below, lumbar puncture can be delayed, and treatment can immediately begin.

The following are contraindications to lumber puncture (unless increased intracranial pressure [ICP] is ruled out):

Approach Considerations

Because mortality may be reduced with early antibiotic therapy, patients with a meningococcal rash should receive parenteral antibiotics by means of an intravenous (IV) or intramuscular (IM) route as soon as the diagnosis is suspected. In the United Kingdom, prehospital treatment with benzylpenicillin is recommended.[79]

Intramuscular antibiotic injections may be less effective in a patient with shock and poor tissue perfusion.

Other than antimicrobial treatment, supportive measures in meningococcal disease may be needed to correct circulatory collapse. Any adrenal insufficiency requires corticosteroid replacement.

Medical care for meningococcal infections should also address community management and the emergency management of meningococcal septicemia and meningitis.[8] This may include treating shock and increased ICP, as well as the use of new and experimental therapies.[3]

Chemoprophylaxis for meningococcal infection should be administered to intimate household, daycare center, and nursery school contacts of sporadic cases. Vaccinate household and other intimate contacts.

Although increasingly well recognized and managed in children, meningococcal disease often is poorly managed in adults in medical settings. Fluid resuscitation may not be sufficiently aggressive, early intubation often is not considered, and the rapidity of disease progression in an adult often is not understood.

For information regarding the recognition and management of meningococcal disease in family practice, see the chart below. Additional resources are available at Meningitis.org.



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Chart for family practice recognition and management of meningococcal disease (courtesy of Meningitis.org).

Treatment of complications

Any complications of meningococcal disease must also be treated. One of the most common complications that occurs during the course of treatment is arthritis, which has been found in about 10% of patients with meningococcal disease. This complication usually occurs within the first few days of treatment and manifests as effusion of a large joint, often the knee. Joint effusions usually resolve without a change in therapy; occasionally, repeated arthrocentesis is needed to control symptoms.

Other possible complications include ischemic conditions caused by the coagulation abnormality and neurologic complications of meningitis. The patient must be observed for any neurologic sequelae; the frequency of neurologic abnormalities seems to be related to the severity of the acute disease. Some neurologic sequelae can develop in the absence of meningitis.

Inpatient care

Hospitalization is required for severely ill patients with fever, headache, and petechiae. Promptly begin antibiotic treatment. Respiratory precautions generally include placement of the patient in a private room with proper air handling and the use of a respiratory mask by any person entering the patient's room. Discontinue respiratory isolation precautions after 24 hours of antibiotics.

Monitor blood pressure, urine output, and cardiac function, as well as platelets, fibrin, and fibrin degradation products.

Supportive care may be needed, including maintenance of fluid and electrolyte balance and vasoactive drugs in shock (eg, dopamine).

Suspect fulminant meningococcemia in patient with hypotension and severe coagulation abnormalities. In such cases, monitoring in an intensive care setting is required.

Diet and activity

Patients with meningitis or fulminant meningococcemia are at risk of vomiting and should be prevented from taking anything by mouth prior to substantial clinical improvement with antimicrobial therapy.

The level of patient activity is determined by the severity of the presentation. Bed rest is recommended for patients suspected of having meningococcal disease. In most severe cases, patients are bed bound.

Transfer

Once the patient is stabilized, attempt to transfer him or her to a tertiary care center because meningococcal sepsis frequently produces multisystem organ dysfunction. Transfer to a PICU is necessary in approximately 20% of pediatric cases of meningococcal infection.

Guidelines

Several clinical guideline summaries related to meningococcal disease are available, as follows:

Emergency Management of Meningococcal Infection

Although many meningococcal infections rapidly improve when treated with antibiotics, meningococcal disease may quickly progress in some cases; the time lag from the appearance of the first symptoms to death may be only a few hours.

Because the mortality rate in meningococcal disease is 10%, all patients with fever and petechiae warrant urgent initial assessment and treatment and subsequent careful and repeated assessment. The initial assessment should be conducted to identify major clinical problems.

The following findings may help in the identification of severely ill patients whose condition may deteriorate and who are likely to need intensive care:

Shock and increased ICP, which are underlying processes in meningococcal disease that lead to death, may coexist. However, increased ICP is more common in patients with only meningitis.

For information about the emergency management of meningococcal disease in children and adults, see the flow charts below.



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Flow chart shows guidelines for the emergency management of meningococcal disease in children. These guidelines may be reprinted for use in clinical a....



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Flow chart shows guidelines for the emergency management of meningococcal disease in adult patients. These guidelines may be reprinted for use in clin....

Managing shock

After basic life support and antibiotics are administered, the next priority is treating shock. Basic life support should include the administration of oxygen at a rate of 10-15L/min by means of a facial mask.

Any patient with cool extremities, prolonged capillary refill time, and tachycardia should be considered to have shock.

The initial therapy for shock is volume replacement at a rate of 20mL/kg. In the United Kingdom, the use of 4.5% human albumin solution is generally recommended, although some US and UK centers use normal saline. A satisfactory response to volume replacement is a reduction in heart rate and improved peripheral perfusion. The first bolus of fluid may be repeated to achieve this response.

The patient's condition may stabilize with only volume replacement, but the patient requires close monitoring and reassessment to detect further signs of shock or pulmonary edema (due to capillary leak syndrome). The goal of circulatory support is to maintain tissue perfusion and oxygenation.[29]

Patients who do not respond to initial volume replacement require further volume replacement and may need inotropic support, such as the use of dopamine or dobutamine (10-20 mcg/kg/min), which may be administered via a peripheral vein until central venous access is established. Patients with persistent hypotension may need an infusion of adrenaline (0.1-5 mcg/kg/min), which must be administered via central venous access.

Endotracheal intubation and ventilation are recommended in patients who still have signs of shock after they have received volume replacement of more than 40mL/kg. Even patients who are apparently awake and alert have a high risk of pulmonary edema.

Some patients require fluid replacement with as much as twice their circulating blood volume in the first hours after presentation, but additional volume should be administered only after positive pressure ventilation is established.

Biochemical correction of acidosis, hypoglycemia, hypokalemia, hypocalcemia, and hypomagnesemia is usually required. Correct coagulopathy and anemia with the use of fresh frozen plasma and blood, as appropriate.

Managing raised intracranial pressure

Suspect increased ICP if the patient has a decreased level of consciousness; focal neurological signs; unequal, dilated or poorly reacting pupils; abnormal posturing or seizures; or relative hypertension or bradycardia or if the patient is agitated or combative. Because papilledema is a late sign, its absence should not reassure the treating team, because raised ICP can still be present.

After initiating basic life support measures and administering antibiotics, the therapeutic goal is to maintain oxygen and nutrient delivery to the brain. For this reason, shock must be corrected in individuals with both shock and increased ICP to maintain cerebral perfusion pressure. After correcting shock with volume replacement and inotropic support as necessary, cautiously manage the fluid balance to avoid further increasing the ICP.

Consider the use of mannitol (0.25 g/kg IV over 10 min), followed by furosemide (1 mg/kg IV), when increased ICP is suspected. These drugs can help to control the ICP during elective intubation.

Immediately institute measures to stabilize the ICP. These may include intubation and ventilation in order to control PaCO2 between 4-4.5 kPa, sedation and muscle relaxation, and elevation of the patient's head by 30°.

In addition, find and correct biochemical abnormalities and treat seizures, if present, using standard resuscitation guidelines; do not attempt lumbar puncture.

Treatment of patients with limited shock and no increased ICP

Reassess patients with limited shock and no increased ICP, as well as patients who respond rapidly to minimal volume replacement, for signs of deterioration during the first 48 hours following admission.

The use of corticosteroids in meningitis may be considered. Several studies revealed that adjunctive dexamethasone reduces sensorineural hearing loss (but not mortality or other neurologic sequelae) in children and infants with H influenzae type B meningitis. Few adverse effects occur with dexamethasone administration. No reports of delayed CSF sterilization or treatment failure are known. A meta-analysis of findings from randomized, controlled trials suggested that such treatment has a benefit in preventing sequelae in meningococcal meningitis and pneumococcal meningitis in childhood.

Although data are poor for meningococcal meningitis, the pathophysiologic events are likely to be similar to those of other forms of bacterial meningitis. In some animal models, anti-inflammatory therapy was beneficial. No evidence of the benefits of steroid use in patients with septic shock is known, and steroid use is necessary only with meningitis.

If hypoadrenalism is suspected because of resistance to large doses of inotropic drugs, administer adrenal replacement doses of hydrocortisone.

Steroids have not yet been proven helpful in septicemia. A phase 2, multicenter pilot study is underway in the United Kingdom to examine the safety and endocrine/inflammation/coagulation profiles seen in low-dose replacement corticosteroid therapy for sepsis in children and to inform a large, multicenter trial. Replacement corticosteroids should not currently be used routinely in pediatric sepsis (and are now controversial in adult sepsis).[81, 82]

Pharmacologic Therapy

The most important measure in treating meningococcemia is early detection and rapid administration of antibiotics. Penicillin G has been the antibiotic of choice for susceptible isolates. A third-generation cephalosporin (eg, cefotaxime, ceftriaxone) can be used initially in septic patients while the diagnosis is being confirmed or in countries such as the United Kingdom or Spain, where penicillin-resistant strains of N meningitidis have been isolated.[83, 84] . Because of failure effectiveness and easier administration schedule, the third-generation cephalosporins have become the preferred class of antibiotics.

These cephalosporins penetrate sufficiently into CSF from blood and are useful in the treatment of bacterial meningitis. They are known to have a potent action against meningococci, as do chloramphenicol, and rifampin. Meningococci have also been found to be susceptible to ciprofloxacin at low concentrations.

Meningococci are not inherently susceptible to vancomycin, polymyxin, or achievable serum levels of aminoglycoside antibiotics.

Intensive supportive care is required for patients with fulminant meningococcemia. Components of treatment include antibiotic therapy, ventilatory support, inotropic support, and IV fluids. Central venous access facilitates the administration of massive amounts of volume expanders and inotropic medications needed for adequate tissue perfusion. If disseminated intravascular coagulation (DIC) is present, fresh frozen plasma may be indicated. Treatment is individualized depending on the severity of hemodynamic compromise of the patient.

Empiric therapy

Empiric antibiotic therapy ensures coverage of likely meningeal pathogens when no rash is present, when the etiology of meningitis is uncertain, and when an immediate microbiologic diagnosis is unavailable. This therapy can be modified in favor of appropriate specific therapy when the organism is grown or when its antibiotic sensitivities are known.

A third-generation cephalosporin is the appropriate antibiotic until culture results are available. Although meningococcal infection is the most common bacterial cause of a petechial or purpuric rash and meningitis, other organisms (including H influenzae type B and Streptococcus pneumoniae) can cause shock and a nonblanching rash.

Although H influenzae type B is now an uncommon cause of meningitis in developed countries with modern vaccination programs, antibiotic therapy should cover this organism. Most cases of bacterial meningitis are due to N meningitides, and most other cases are due to S pneumoniae. In the United States, most cases are due to S pneumoniae.

Empiric antibiotic therapy for meningitis based on age is as follows:

In 2007 the US Food and Drugs Administration (FDA) issued an alert that led to changes in the prescribing information for ceftriaxone. Dilution, mixing, or y-site infusion with calcium-containing IV solutions may increase the risk for precipitant to formin vivo. Initially, the FDA recommended that ceftriaxone no longer be administered within 48 hours of the completion of calcium-containing solutions, including parenteral nutrition, regardless of whether the drugs were administered by different infusion catheters.[85, 86]

In the United Kingdom, the Medicines and Healthcare Products Regulatory Agency (MRHA) issued a drug safety bulletin stating that ceftriaxone should not be given simultaneously with calcium-containing infusions.[87]

However, in April 2009, the FDA changed its advice; the agency no longer cautions against the use of ceftriaxone and calcium-containing solutions, except in neonates younger than 28 days.[88]

Chloramphenicol 100 mg/kg/day in 4 divided doses (up to 4 g/day maximum dose) can be given as an alternative, although this is associated with increased mortality compared with other regimens and cannot be recommended as a first-line treatment.[89]

Dexamethasone is indicated in the treatment of known or suspected pneumococcal meningitis in adults and children with H influenzae type B meningitis. It is of no benefit in meningococcal meningitis. If started empirically, it should be discontinued as soon as N meningitides is retrieved.[90]

Surgical Treatment of Ischemic Complications

Patients who survive the initial acute phase of fulminant meningococcemia are at increased risk for serious complications as a result of poor tissue perfusion.[91]

Early in the course of tissue injury, conservative therapy is recommended until a distinct line of demarcation is apparent between viable and nonviable tissue.

Once the patient is stable, débridement of all necrotic tissue is essential and may necessitate extensive removal of skin, subcutaneous tissue, and muscle. Large defects may be covered using microvascular free flaps or skin grafts. The use of artificial skin can spare the patient immediate use of autograft sites, which frequently are limited.[92] Avoid early limb amputation, because significant tissue recovery may occur as the disease progresses.

Poor tissue perfusion may also lead to dental complications that require extensive extraction of severely affected teeth.[93]

Anecdotally, fasciotomy may preserve limb and digit function in severe meningococcal septicemia when impending peripheral gangrene and increased compartment pressures are present. Measure compartment pressures and assess peripheral pulses with Doppler ultrasonography when patients have impaired limb perfusion or severe edema.

Monitoring and Follow-Up

Pericarditis can occur while patients are recuperating from meningococcemia. Consider pericarditis in patients with fever and shortness of breath upon minimal exertion during the recovery period.

Late skeletal deformities are rare, but epiphyseal avascular necrosis and epiphyseal-metaphyseal defects have been described. These usually occur in the lower extremities and result in angular deformity and inequality of leg length.

Observe patients for any late neurologic sequelae. Abnormal findings on electroencephalography or cerebral computed tomography (CT) scanning, as well as epileptogenic activity, sensorineural hearing loss, impaired vestibular function, and neuropsychological impairment, have been found in up to 30% of survivors 1 year after an episode of meningococcal disease. The frequency of serious neurologic sequelae in individuals who survive an episode is 3%.

Follow-up care at least 6 weeks after meningococcal infection should include the following:

Vaccination

Meningococci are gram-negative diplococci. Pathogenic strains are enveloped in a polysaccharide capsule, which facilitates invasion and which is an obvious target for candidate vaccines. The serogroup of the organism is assigned from the reaction of sera to the polysaccharide capsule.[94, 95, 96]

Purified polysaccharide vaccines against encapsulated bacteria (which, in addition to meningococci, include Haemophilus and pneumococci) are poorly immunogenic in young children. In contrast, the conjugate vaccine for group C meningococci in which the serogroup C meningococcal polysaccharide is conjugated to the protein CRM197 appears to provide immunogenic protection to young children. It was administered to all children during 1999-2000 in the United Kingdom.

In January 2001, the short-term effectiveness of this vaccine in England was reported to be 97% for teenagers and 92% for toddlers. These early results confirmed the superiority of this vaccine to plain C polysaccharide vaccines.

The UK immunization schedule has since changed to include a meningococcal booster at 12 months (combined with H influenzae type b [Hib] booster) because studies showed that the efficacy of the vaccine declined at 1 year to around 80%.

The guidelines on meningococcal B vaccination by the Advisory Committee on Immunization Practices (ACIP) are as follows:[97, 98]

Types of vaccines

Four meningococcal vaccines are available in the United States: 1 quadrivalent polysaccharide vaccine (MPSV4), 2 quadrivalent conjugate vaccines (MenACWY), and 1 bivalent conjugate vaccine (meningococcal groups C and Y and Hib tetanus toxoid conjugate vaccine [Hib-MenCY-TT]). Age range and dosing information for these are as follows[6] :

The Hib-MenCY-TT vaccine, licensed in June 2012, was the first meningococcal vaccine approved for use in young infants. It is indicated only for infants at high risk for meningococcal disease.[101, 102] The CDC decided not to recommend its routine use in all infants, because the current frequency of meningococcal disease is low and because the vaccine does not contain serotype B, which is responsible for more than half of meningococcal disease cases in children aged 0-59 months.

In October 2013, the ACIP voted to expand the recommendations for the MenACWY-CRM vaccine to include use in infants and young toddlers who are at increased risk for meningococcal disease.[103] The expanded recommendations include the following:

The recommended administration schedule for MenACWY-CRM vaccine is at ages 2, 4, 6, and 12 months, with booster doses 3 years after the primary vaccination series and every 5 years thereafter for children who remain at increased risk.

Administration of quadrivalent meningococcal conjugate vaccine (serogroup A, C, W, and Y [MCV 4]) was recommended to protect the high-risk adolescent population. A recent study demonstrated that the meningococcal carriage problems were reduced from 7% prior to vaccine availability in 2005 to 3.2%-4% afterward. Nongroupable (nonpathogenic) strains comprised 88% of the meningococci isolated from the nasopharynx of tested adolescents. Such a reduction may explain, at least partially, the dramatic reduction of severe meningococcal disease.[104]

Serogroup B vaccines

Vaccines against group B serotypes are difficult to make. Because the polysaccharide capsule of the group B meningococcus is chemically and antigenically identical to human brain and fetal antigens, it is poorly immunogenic in humans, and its use may induce autoimmunity.

Other bacterial components, such as bacterial outer membrane proteins, are being investigated for use in vaccines. Vaccines have been prepared by using simple complexes of these proteins. These include vaccines involving outer membrane vesicles, containing outer membrane proteins in spheres of the bacterial lipid membrane.

Although some serogroup B vaccine trials demonstrate an overall efficacy of more than 50%, protection for the most vulnerable age group has not been demonstrated. In those individuals with a detectable immune response, serum bactericidal activity after vaccination seems to be limited to the strain in the vaccine.

In December 2013, Bexsero was administered during an N meningitidis outbreak at Princeton University. The outbreak strain processed antigens that were closely related to those of the vaccine. Although 33.9% of those vaccinated showed no evidence of antibody response to the outbreak strain, no cases of meningococcal disease were reported in this group.[105]

Safety considerations

The safety of meningococcal polysaccharide vaccine in pregnant women has not been evaluated, and it should be avoided unless the risk of infection is high. The vaccine is also not routinely indicated for health care workers in the United States.

The risk of Guillain-Barré Syndrome (GBS) seems to be slightly increased among recipients of the MCV4 vaccine.[106] The CDC estimated the rate to be 0.2 per 100,000 person-months in individuals aged 11-19 years who received the vaccine. The background rate was estimated at 0.11 per 100,000 person-months in this population group.

The CDC recommends that persons with a history of GBS not receive MCV4, although persons with a history of GBS at especially high risk for meningococcal disease (eg, microbiologists routinely exposed to isolates of N meningitidis) might consider vaccination.

Prevention of Secondary Cases

Antimicrobial chemoprophylaxis of close contacts is the primary means of preventing secondary cases of sporadic meningococcal disease. Person-to-person transmission can be interrupted by administration of an antimicrobial that eradicates the asymptomatic nasopharyngeal carrier state. Sulfonamides, rifampin, minocycline, ciprofloxacin, and ceftriaxone are the drugs that have been shown to eradicate meningococci from the nasopharynx.

Because the rate of disease in secondary contacts is highest immediately after the onset of the disease in the patient, chemoprophylaxis should be administered as soon as possible, preferably within 24 hours. If chemoprophylaxis is delayed by more than 14 days, it is probably of limited value, although it is still recommended until 4 weeks after the patient's presentation.

Infection risks

Meningococcal infection is probably introduced into families by asymptomatic adults and then spread through 1 or more household contacts to infect younger family members. Household contacts are defined as individuals who live in the same house with a person who has a meningococcal disease. An operational definition commonly used by public health authorities includes persons eating and sleeping under the same roof as the index case.

The attack rate of meningococcal disease among household contacts has been estimated to be several hundred times greater than that in the general population. The secondary attack rate is inversely proportional to age and is estimated to be approximately 10% in household contacts aged 1-4 years.

The risk of acquiring meningococcal disease may also be increased in other closed populations, such as those of daycare facilities and nursery schools.

Health care workers who are exposed to aerosol secretions from patients with meningococcal disease are 25 times more likely to contract the disease than is the general population.

The likelihood of acquiring infection is increased 100-1000 times in intimate contacts of individuals with meningococcemia.

Chemoprophylaxis

The American Academy of Pediatrics recommends antimicrobial chemoprophylaxis for contacts of persons with invasive meningococcal disease, including household members, individuals at daycare centers and nursery schools, and persons directly exposed to the patient's oral secretions (eg, kissing, sharing of food or beverages) within the 7 days preceding the onset of the illness in the index case.

The decision to administer chemoprophylaxis to other populations should be reached only after consultation with public health authorities, who have a better understanding of the patterns of disease that currently exist in the community.

Consider antimicrobial chemoprophylaxis in hospital personnel who have had direct exposure to the oral secretions of a patient with meningococcal disease from such activities as mouth-to-mouth resuscitation, endotracheal intubation, or endotracheal tube management.

To further decrease the risk of infection in the clinical setting, staff caring for patients with known or suspected meningococcal infections should wear masks, in addition to taking standard precautions.

Patients with meningococcal disease who are hospitalized should be placed on respiratory precautions for the first 24 hours of effective antimicrobial therapy. When this is done, the risk for hospital personnel with casual or indirect contact is believed to be negligible. Antimicrobial chemoprophylaxis is not recommended in hospital personnel who have only casual or indirect contact with a patient with meningococcal disease.

For travelers, antimicrobial chemoprophylaxis should be considered for any passenger who had direct contact with respiratory secretions from an index patient or for anyone seated directly next to an index patient on a prolonged flight (ie, one that lasts ≥8h).

Prophylactic drugs

Rifampin is commonly used for meningococcal prophylaxis of household contacts in the United States, where one third of the prevalent strains are sulfadiazine resistant. A 2-day course of rifampin is recommended. The rapid emergence of rifampin-resistant meningococci precludes the use of this drug in large populations. Chemoprophylaxis of sulfadiazine-resistant meningococci with rifampin should be accompanied by close observation of household contacts for signs of disease.

A single dose of ciprofloxacin has been found to provide an effective alternative to rifampin for the eradication of meningococcal carriage in adults. Ciprofloxacin is not recommended in persons younger than 18 years because it has caused cartilage damage in immature experimental animals.

A single IM injection of ceftriaxone has been found to eradicate meningococcal carriage. The chemoprophylactic dose of ceftriaxone is 250 mg IM in adults and 125 mg IM in children. Ceftriaxone is preferred in children who refuse oral medication and may be used in pregnancy.

Meningococcal isolates that are susceptible to sulfadiazine can be eradicated with a 2-day course of sulfadiazine. The high incidence of adverse effects has limited acceptance of minocycline as a means of eradicating the carrier state.

Meningococcal disease can be prevented by vaccination with group-specific meningococcal capsular polysaccharides.[107] Purified polysaccharides of groups A, C, Y, and W-135 meningococci have been used to stimulate group-specific humoral bactericidal antibodies.

Consultations

Consultations in meningococcal disease include the following:

Make sure that the local department of health is notified of suspected and/or proven cases of meningococcal infection to assist in the evaluation of close contacts and in prophylaxis.

Advisory Committee on Immunization Practices Guidelines on Meningococcal B Vaccination

The guidelines on meningococcal B vaccination by the Advisory Committee on Immunization Practices (ACIP) are as follows:[97, 98]

Medication Summary

Antimicrobial therapy is directed toward treatment of active infection or is used prophylactically to protect persons exposed to N meningitidis through close contact. Most patients with uncomplicated meningococcemia defervesce within the first 24 hours of antibiotic therapy.

Drugs effective in treating active meningococcal infection include penicillin G, chloramphenicol in patients who are allergic to penicillin, and some cephalosporins (ie, cefotaxime, ceftriaxone) used to treat pediatric patients. Meningococcal resistance to penicillins has occurred; the mechanism of resistance involves altered penicillin-binding proteins.

The duration of antimicrobial treatment is dictated by clinical response and the manifestation of the disease, although 10-14 days should be sufficient with a sensitive organism.

Individuals with at least 4 hours of close contact with an index patient during the week before onset of illness are at an increased risk for infection. Individuals at risk include housemates, daycare contacts, cellmates, or individuals exposed to infected nasopharyngeal secretions (eg, through kissing, mouth-to-mouth resuscitation, intubation, suctioning).

Rifampin and ciprofloxacin are commonly used for chemoprophylaxis. Rifampin may eradicate carriage in up to 80-90% of individuals, but resistant strains have occurred.[108] Other agents that can be used include ceftriaxone and azithromycin. A single dose of intramuscular ceftriaxone may be used in children or adults. Vaccination should be adjunctive to antibiotic chemoprophylaxis in susceptible contacts in epidemics.

The eradication of carriage is also indicated in the index case unless third-generation cephalosporins have been used.

A single intramuscular dose of an oily suspension of chloramphenicol has been shown to be as effective as 5 days of penicillin in persons with meningococcal meningitis, and this may be useful in resource-poor settings.

Meropenem (Merrem IV)

Clinical Context:  Meropenem is a bactericidal broad-spectrum carbapenem antibiotic that inhibits cell-wall synthesis. It is effective against most gram-positive and gram-negative bacteria. Meropenem has slightly increased activity against gram-negatives and slightly decreased activity against staphylococcal and streptococcal organisms compared with imipenem.

Penicillin G (Pfizerpen-G)

Clinical Context:  Penicillin G interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms.

Treat suspected meningococcal disease with a high dose in the initial 48 hours of therapy because meningitis is a likely complication. This is the preferred agent for the initial community management of suspected meningococcal disease.

Infections caused by organisms classified as relatively resistant to penicillin, based on a minimum inhibitory concentration (MIC) of 0.1-1 µg/mL of penicillin, seem to respond to this drug as well as fully susceptible organisms do.

Chloramphenicol

Clinical Context:  Chloramphenicol can be used in patients with penicillin and cephalosporin allergies. It binds to 50S bacterial-ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. It is effective against gram-negative and gram-positive bacteria. Chloramphenicol-resistant strains are found in Southeast Asia but are rare in the United States.

Ceftriaxone

Clinical Context:  Ceftriaxone is a third-generation cephalosporin with broad-spectrum, gram-negative activity. It has lower efficacy against gram-positive organisms. Ceftriaxone arrests bacterial growth by binding to 1 or more penicillin-binding proteins. It has successfully been used to treat pediatric meningococcal meningitis. It is useful in special circumstances (ie, relatively penicillin-resistant organisms, hypersensitivity reactions to penicillin or chloramphenicol).

Ceftriaxone is a first-line antibiotic for empiric therapy of meningitis or sepsis while culture and susceptibility data are pending. Cefotaxime or ceftriaxone are the preferred agents for the treatment of confirmed meningococcal disease.

Cefotaxime (Claforan)

Clinical Context:  Cefotaxime is a third-generation cephalosporin with a gram-negative spectrum. It has lower efficacy against gram-positive organisms. Cefotaxime has been used successfully in pediatric meningococcal meningitis

The drug is more expensive than penicillin, but most authorities believe that it is as efficacious as penicillin in the treatment of meningococcal disease.

Cefotaxime arrests bacterial cell wall synthesis, which, in turn, inhibits bacterial growth. It is used for penicillin-resistant strains.

Cefotaxime is used as a first-line antibiotic for the empiric therapy of meningitis or sepsis while culture and susceptibility data are pending. Cefotaxime or ceftriaxone are the preferred agents for the treatment of confirmed meningococcal disease.

Ampicillin

Clinical Context:  A broad-spectrum penicillin that interferes with bacterial cell-wall synthesis during active replication, causing bactericidal activity against susceptible organisms.

Rifampin (Rifadin)

Clinical Context:  Rifampin is a semisynthetic derivative of rifamycin B that inhibits bacterial and mycobacterial RNA synthesis by binding to the beta subunit of deoxyribonucleic acid (DNA)–dependent RNA polymerase, thus inhibiting binding to DNA and blocking RNA transcription.

Rifampin is commonly used for meningococcal prophylaxis of household contacts in United States, where one third of prevalent strains are sulfadiazine resistant.

Ciprofloxacin (Cipro, Cipro XR)

Clinical Context:  Ciprofloxacin is a fluoroquinolone. It inhibits bacterial DNA synthesis and, consequently, growth. A single dose of 500mg has been found to provide an effective alternative to rifampin for the eradication of meningococcal carriage in adults. Ciprofloxacin is commonly used for meningococcal prophylaxis. It is not recommended for persons younger than 18 years because it has caused cartilage damage in immature experimental animals. Resistance has been reported, and it should only be used if the strain is known to be susceptible.

Azithromycin (Zithromax, Zmax)

Clinical Context:  Azithromycin is a semisynthetic antibiotic that is structurally similar to erythromycin. It inhibits protein synthesis in bacterial cells by binding to the 50S subunit of bacterial ribosomes.

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. People who come into household contact with patients who have meningococcal disease are at risk of acquiring this illness. Person-to-person transmission can be interrupted by chemoprophylaxis, which eradicates the asymptomatic nasopharyngeal carrier state. Rifampin, quinolones, and sulfonamides are the antimicrobials used to eradicate meningococci from the nasopharynx.

Mortality in meningococcal infections may be reduced with early antibiotic therapy. Regarding community management, because mortality may be reduced with early antibiotic therapy, patients with a meningococcal rash should receive parenteral benzyl penicillin by means of an IV or IM route as soon as the diagnosis is suspected. IM antibiotic injections may be less effective in a patient with shock and poor tissue perfusion. Give cefotaxime, ceftriaxone, or chloramphenicol to patients who are allergic to penicillin. Empiric antibiotic therapy for meningitis based on age is as follows:

- Neonates - Ampicillin and cefotaxime

- Infants aged 1-3 months - Ampicillin and cefotaxime

- Older infants, children, and adults - Cefotaxime or ceftriaxone

Dopamine

Clinical Context:  Stimulates adrenergic and dopaminergic receptors. Its hemodynamic effect is dependent on the dose. Lower doses predominantly stimulate dopaminergic receptors that, in turn, produce renal and mesenteric vasodilation. Cardiac stimulation and renal vasodilation are produced by higher doses. After initiating therapy, increase the dose by 1-4 mcg/kg/min every 10-30 minutes until the optimal response is obtained. More than 50% of patients are satisfactorily maintained on doses less than 20 mcg/kg/min.

Dobutamine

Clinical Context:  Dobutamine is a first-line drug in meningococcal sepsis without central venous access. It produces vasodilation and increases the inotropic state; higher doses may increase heart rate and exacerbate myocardial ischemia. Dobutamine may be given via peripheral cannula prior to central venous access.

Epinephrine (Adrenalin)

Clinical Context:  Epinephrine is used for persistent hypotension. It has alpha-agonist effects (eg, increased peripheral vascular resistance, reversed peripheral vasodilatation, systemic hypotension, and vascular permeability) and beta-agonist effects (eg, bronchodilatation, chronotropic cardiac activity, positive inotropic effects).

Class Summary

These agents are used to support circulation in patients with shock.

Mannitol (Osmitrol)

Clinical Context:  Mannitol may reduce subarachnoid-space pressure by creating an osmotic gradient between CSF in the arachnoid space and plasma. It is not for long-term use.

Class Summary

These agents are used to control ICP during elective intubation. Osmotic diuretics raise the osmolality of plasma and renal tubular fluid, which creates an osmotic inhibition of water transport in the proximal tubule. This subsequently decreases the gradient for passive sodium absorption in the ascending limb of the loop of Henle. The increased urinary flow is achieved by nonelectrolyte solute diuresis. Increases in the glomerular filtration rate may also be observed.

Furosemide (Lasix)

Clinical Context:  Furosemide lowers ICP by (1) lowering cerebral sodium uptake, (2) affecting water transport into astroglial cells by inhibiting the cellular membrane cation-chloride pump, and (3) decreasing CSF production by inhibiting carbonic anhydrase. It is administered after mannitol.

Class Summary

Mannitol may reduce subarachnoid-space pressure by creating an osmotic gradient between CSF in the arachnoid space and plasma. It is not for long-term use.

Dexamethasone (Decadron)

Clinical Context:  Dexamethasone may reduce sensorineural hearing loss in children and infants with H influenzae type B meningitis. Administer this agent to all children with suspected bacterial meningitis (the pathophysiology is likely to be similar). Dexamethasone does not reduce CNS clearance of bacteria or cause treatment failure.

Class Summary

These agents elicit anti-inflammatory and immunosuppressive properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli.

Meningitis group A C Y and W-135 vaccine diphtheria conjugate vaccine (Menactra, Menveo)

Clinical Context:  Diphtheria toxoid conjugate vaccine induces the production of bactericidal antibodies specific to capsular polysaccharides of serogroups A, C, Y, and W-135.

Meningococcal Polysaccharide Vaccine A/C/Y/W-135

Clinical Context:  This is a quadrivalent vaccine for meningitis prophylaxis. It is considered an adjunct to antibiotic chemoprophylaxis.

Meningococcal C and Y/haemophilus influenza type B vaccine (MenHibrix)

Clinical Context:  Contains antigenic capsular polysaccharides (ie, meningococcal serogroups A and C, Haemophilus influenzae type b) that convey active immunity by stimulating endogenous antibody production; antibodies have been associated with protection from invasive meningococcal disease.

Meningococcal group B vaccine (Bexsero, Trumenba)

Clinical Context:  Protection against invasive meningococcal disease is conferred mainly by complement-mediated antibody-dependent killing of N meningitidis.

Class Summary

These agents may be used to prevent and control outbreaks of serogroup C meningococcal disease.

What is meningococcemia?What are the signs and symptoms of acute meningococcemia?What are the signs and symptoms of meningitis in meningococcemia?What are the signs and symptoms of meningococcemia?What are the physical findings characteristic of meningococcemia?What is the role of lab testing in the diagnosis of meningococcemia?Which organizations have released treatment guidelines for meningococcemia?When should patients with a meningococcemia rash be treated?Which antibiotics are recommended in the treatment of meningococcemia?What is N meningitidis?What are the possible presentations of acute meningococcemia?What are the carrier rates for N meningitidis?What is chronic meningococcemia?What is the pathophysiology of meningococcemia?What is the clinical progression of meningococcemia?What are the manifestations of fulminant meningococcemia?What are the virulence factors associated with meningococcemia?What is the pathophysiology of septicemia in meningococcemia?What is the role of vascular permeability in the pathophysiology of meningococcemia?What is the role of coagulopathy in the pathophysiology of meningococcemia?Which metabolic derangements may occur in meningococcemia?What causes myocardial failure in patients with meningococcemia?What is the pathophysiology of meningitis in meningococcemia?What causes meningococcemia?How is meningococcemia transmitted?How is immunity against meningococcemia acquired?What is the role of terminal complement deficiency in the etiology of meningococcemia?Which genetic factors increase the risk for mortality from meningococcemia?Which risks are increased in patients with meningococcemia and the prothrombotic factor V Leiden mutation?What is the role of the PAI-1 gene in the etiology of meningococcemia?What are the risk factors for meningococcemia?What is the incidence of meningococcemia in the US?What is the global incidence of meningococcemia?What is the incidence of meningococcemia in Europe and the United Kingdom?How does climate-affect the incidence of meningococcemia?What are the racial predilections for meningococcemia?How does the prevalence of meningococcemia vary by sex?How does the incidence of meningococcemia vary by age?What is the prognosis of meningococcemia?What are possible complications of meningococcemia?What is the prevalence of immune complex disease due to meningococcal infection?What are the complications of meningococcal meningitis?What are the suppurative complications of meningococcemia?What is the prevalence of nonsuppurative arthritis in meningococcemia?What are possible complications of recurrent meningococcal disease?What are the sequelae associated with meningococcemia?What is the mortality rate for meningococcemia?What information about meningococcemia should patients receive?Which history associated with is characteristic of meningococcemia?What are the signs and symptoms of meningitis in meningococcemia?What are the signs and symptoms of septicemia in meningococcemia?Which history findings suggest chronic meningococcemia?Which physical findings are characteristic of meningococcemia?What are the dermatologic manifestations of meningococcemia?Which physical findings are characteristic of fulminant meningococcemia?Which physical findings are characteristic of meningococcal septicemia?Which physical findings are characteristic of meningitis in meningococcemia?Which conditions should be included in the cutaneous differential diagnoses of meningococcemia?Which conditions should be included in the differential diagnoses of chromic meningococcemia?How are rheumatic diseases differentiated from meningococcemia?Which conditions should be included in the differential diagnoses of meningococcemia when petechiae and fever are present?Which conditions should be included in the differential diagnoses of meningococcal infection?What are the differential diagnoses for Meningococcemia?What is the role of lab testing in the diagnosis of meningococcemia?Which factors increase the risk for mortality in fulminant meningococcemia?What is the role of blood cultures in the workup of meningococcemia?What is the role of throat cultures in the workup of meningococcemia?How is chronic meningococcemia diagnosed?What is the role of imaging studies in the workup of meningococcemia?When is blood culture indicated in the workup of meningococcemia?What does a gram stain reveal in the workup of fulminant meningococcemia?How is a rapid latex antigen test used in the workup of meningococcemia?What is the role of coagulation tests in the workup of meningococcemia?What is the role of white blood cell count in the workup of meningococcemia?Which metabolic abnormalities may be present in meningococcemia?How is end-organ damage assessed in the workup of meningococcemia?What is the role of needle aspirations and skin biopsies in the workup of meningococcemia?Which findings of biopsy specimens are characteristic of acute meningococcemia?What are the indications of cutaneous petechiae and purpura in the histology of meningococcemia?Which histologic findings are characteristic of chronic meningococcemia?What is the role of polymerase chain reaction (PCR) assay in the workup of meningococcemia?What is the role of a slide agglutination test use in the workup of meningococcemia?What is the role of enzyme-linked immunosorbent assay (ELISA) in the workup of meningococcemia?When are brain imaging studies indicated in the workup of meningococcemia?What is the role of lumbar puncture in the workup of meningococcemia?When is a lumbar puncture contraindicated in the workup of meningococcemia?What is the initial treatment of suspected meningococcemia?What is included in the medical management septicemia and meningitis in meningococcemia?Who should receive chemoprophylaxis and vaccination against meningococcal infection?How is meningococcemia managed in adults?What are the complications of meningococcemia and how are they managed?What is included in the inpatient care for meningococcemia?Which dietary modifications are used in the treatment of meningococcemia?Which activity modifications are used in the treatment of meningococcemia?When is transfer indicated for the treatment of meningococcemia?Which organizations have published treatment guidelines for meningococcemia?What is included in the initial treatment of meningococcemia symptoms?What are the indications for intensive care in meningococcemia?What is the treatment algorithm for emergency management of meningococcemia?What is included in basic life support for meningococcemia?What are the indications of shock in meningococcemia?What is the initial therapy for shock in meningococcemia?What is the treatment of meningococcemia in patients who do not respond to initial volume replacement?When are endotracheal intubation and ventilation indicated in the treatment of meningococcemia?When should additional fluid replacement be administered in the treatment of meningococcemia?What corrections are required in the management of shock in meningococcemia?What are the indications of increased intracranial pressure (ICP) in meningococcemia?How is intracranial pressure (ICP) managed in patients with meningococcemia?What is included in the treatment of meningococcemia in patients with limited shock and no increased intracranial pressure (ICP)?What is the role of antibiotics in the treatment of meningococcemia?What is the role of cephalosporins in the treatment of meningococcemia?Which medications are ineffective in the treatment of meningococcemia?What is included in intensive supportive care for fulminant meningococcemia?What is the role of empiric therapy in the treatment of meningococcemia?Which antibiotic should be administered prior to culture results for meningococcemia?When should agents against H influenzae type B be included in empiric therapy for meningococcemia?What is the empiric antibiotic therapy for meningitis in meningococcemia?What is the role of ceftriaxone in the empiric therapy for meningococcemia?What is the role of dexamethasone in the empiric therapy for meningococcemia?What is the role of surgery in the treatment of meningococcemia?What are the signs of pericarditis in meningococcemia?Which skeletal deformities may occur in meningococcemia?What is included in monitoring for late neurologic sequelae of meningococcemia?What is included in the follow-up care of meningococcemia?What is the increased risk of Guillain-Barré Syndrome (GBS) from the MCV4 meningococcal vaccine?What type of vaccines are used to prevent meningococcemia?What is the effectiveness of purified polysaccharide vaccines against meningococcemia?What are the guidelines on meningococcal B vaccination by the Advisory Committee on Immunization Practices (ACIP)?What are the types of vaccines are available against meningococcemia?What are the ACIP expanded recommendations for the MenACWY-CRM vaccine to prevent meningococcemia?What is the role of serogroup B vaccines in the prevention of meningococcemia?What is the efficacy of serogroup B vaccines against meningococcemia?What is the safety of the meningococcal polysaccharide vaccine in pregnant women?How are secondary cases of sporadic meningococcal disease prevented?How is chemoprophylaxis used in the prevention of meningococcemia?What are the infection risks for secondary cases of meningococcemia?What are the American Academy of Pediatrics (AAP) recommendations for antimicrobial chemoprophylaxis to prevent secondary cases of meningococcemia?What is the role of public health authorities in the prevention of secondary meningococcemia?When is antimicrobial chemoprophylaxis against meningococcemia indicated for hospital personnel?When is antimicrobial chemoprophylaxis against meningococcemia indicated for travelers?What is the role of rifampin in the management of meningococcemia?What is the role of ciprofloxacin in the management of meningococcemia?What is the role of ceftriaxone in the management of meningococcemia?What is the role of sulfadiazine in the management of meningococcemia?How is meningococcemia prevented?Which specialist consultations are needed in the management of meningococcemia?What are the ACIP guidelines on meningococcal B vaccination?What is the focus of antimicrobial therapy for meningococcemia?Which drugs are effective in treating active meningococcal infection?What is the duration of antimicrobial treatment for meningococcemia?Which individuals are at increased risk for meningococcemia?How are rifampin and ciprofloxacin used in the management of meningococcemia?What is the role of chloramphenicol in the treatment of meningococcemia?Which medications in the drug class Vaccines, Inactivated, Bacterial are used in the treatment of Meningococcemia?Which medications in the drug class Corticosteroids are used in the treatment of Meningococcemia?Which medications in the drug class Diuretics, Loop are used in the treatment of Meningococcemia?Which medications in the drug class Diuretics, Osmotic Agents are used in the treatment of Meningococcemia?Which medications in the drug class Inotropic Agents are used in the treatment of Meningococcemia?Which medications in the drug class Antimicrobial agents are used in the treatment of Meningococcemia?

Author

Mahmud H Javid, MBBS, Consultant in Infectious Diseases, Shifa International Hospital, Pakistan

Disclosure: Nothing to disclose.

Coauthor(s)

Shadab Hussain Ahmed, MD, AAHIVS, FACP, FIDSA, Professor of Clinical Medicine, The School of Medicine at Stony Brook University Medical Center; Adjunct Clinical Associate Professor, Department of Medicine, New York College of Osteopathic Medicine of New York Institute of Technology; Attending Physician, Department of Medicine, Division of Infectious Diseases, Director of HIV Prevention Services, Administrative HIV Designee, Nassau University Medical Center

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

John L Brusch, MD, FACP, Assistant Professor of Medicine, Harvard Medical School; Consulting Staff, Department of Medicine and Infectious Disease Service, Cambridge Health Alliance

Disclosure: Nothing to disclose.

Acknowledgements

Katrina Cathie, BM (Hons), MRCPCH, Fellow in Paediatric Clinical Research, Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, UKKatrina Cathie, BM(Hons), MRCPCH is a member of the following medical societies: Royal College of Paediatrics and Child Health

Disclosure: Nothing to disclose.

Joanna L Chan, MD Mohs Fellow, California Skin Institute

Joanna L Chan, MD is a member of the following medical societies: American Academy of Dermatology and American Society for Dermatologic Surgery

Disclosure: Nothing to disclose.

Joseph Domachowske, MD Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York Upstate Medical University

Joseph Domachowske, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Dirk M Elston, MD Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Saul N Faust, MA, MBBS, PhD, MRCPCH Senior Lecturer in Pediatric Immunology and Infectious Diseases, University of Southampton; Director, Wellcome Trust Clinical Research Facility, Southampton University Hospitals NHS Trust, UK

Saul N Faust, MA, MBBS, PhD, MRCPCH is a member of the following medical societies: British Paediatric Allergy, Immunology and Infectious Group, European Society for Paediatric Infectious Diseases, International Society for Infectious Diseases, and Royal College of Paediatrics and Child Health

Disclosure: Xoma Consulting fee Consulting; GSK Honoraria Consulting; Wyeth travel and registration fee to conference investigator in study being presented at meeting; Sanofi Pasteur Consulting fee Consulting; Pfizer Consulting fee Consulting

Aaron Glatt, MD Professor of Clinical Medicine, New York Medical College; President and CEO, Former Chief Medical Officer, Departments of Medicine and Infectious Diseases, St Joseph Hospital (formerly New Island Hospital)

Aaron Glatt, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Infectious Diseases Society of America, International AIDS Society, and SocietyforHealthcareEpidemiology of America

Disclosure: Nothing to disclose.

Thomas A Hoffman, MD Professor, Department of Internal Medicine, Division of Infectious Diseases, Jackson Memorial Hospital, University of Miami

Thomas A Hoffman, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

David Jaimovich, MD Chief Medical Officer, Joint Commission International and Joint Commission Resources

David Jaimovich, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Michael Levin, PhD, FRCP, FRCPCH Head, Professor, Imperial College School of Medicine at St Mary's Hospital, Department of Pediatrics, London, England

Disclosure: Nothing to disclose.

Lester F Libow, MD Dermatopathologist, South Texas Dermatopathology Laboratory

Lester F Libow, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Texas Medical Association

Disclosure: Nothing to disclose.

Joseph Richard Masci, MD Professor of Medicine, Professor of Preventive Medicine, Mount Sinai School of Medicine; Director of Medicine, Elmhurst Hospital Center

Joseph Richard Masci, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, Association of Professors of Medicine, and Royal Society of Medicine

Disclosure: Nothing to disclose.

Mary D Nettleman, MD, MS, MACP Professor and Chair, Department of Medicine, Michigan State University College of Human Medicine

Mary D Nettleman, MD, MS, MACP is a member of the following medical societies: American College of Physicians, Association of Professors of Medicine, Central Society for Clinical Research, Infectious Diseases Society of America, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Gregory J Raugi, MD, PhD Professor, Department of Internal Medicine, Division of Dermatology, University of Washington at Seattle School of Medicine; Chief, Dermatology Section, Primary and Specialty Care Service, Veterans Administration Medical Center of Seattle

Gregory J Raugi, MD, PhD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Nanette Silverberg,MD Assistant Clinical Professor, Department of Dermatology, Columbia University College of Physicians and Surgeons; Director of Pediatric Dermatology, Department of Dermatology, St Luke's Roosevelt Hospital Center, Maimonides Medical Center and Beth Israel Medical Center

Nanette Silverberg is a member of the following medical societies: American Academy of Dermatology, American Academy of Pediatrics, American Association of University Women, American Medical Association, American Medical Women's Association, Dermatology Foundation, International Society of Pediatric Dermatology, Phi Beta Kappa, Sigma Xi, Society for Pediatric Dermatology, and Women's Dermatologic Society

Disclosure: Nothing to disclose.

Darvin Scott Smith, MD, MSc, DTM&H Adjunct Assistant Professor, Department of Microbiology and Immunology, Stanford University School of Medicine; Chief of Infectious Diseases and Geographic Medicine, Department of Internal Medicine, Kaiser Redwood City Hospital

Darvin Scott Smith, MD, MSc, DTM&H is a member of the following medical societies: American Medical Association, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, and International Society of Travel Medicine

Disclosure: Nothing to disclose.

Russell W Steele, MD Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Elizabeth L Tanzi, MD Co-Director, Laser Surgery, Washington Institute of Dermatologic Laser Surgery; Assistant Professor, Department of Dermatology, Johns Hopkins University School of Medicine

Elizabeth L Tanzi, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, and American Society for Laser Medicine and Surgery

Disclosure: Nothing to disclose.

Michael J Wells, MD Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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A 9-month-old baby in septic shock with purpuric Neisseria meningitis skin lesions. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.

Scattered petechiae in a patient with acute meningococcemia.

Child with severe meningococcal disease and purpura fulminans.

Gram-negative intracellular diplococci. Courtesy Professor Chien Liu.

Dorsum of the hand showing petechiae. Courtesy of Professor Chien Liu.

Gram-negative intracellular diplococci. Courtesy Professor Chien Liu.

Areas with frequent epidemics of meningococcal disease. This is known as the Meningitis Belt of Africa; visitors to these locales may benefit from meningitis vaccine. Image courtesy of CDC.

Lesions caused by Neisseria meningitis bacteremia on the palm of the hand of a 9-month-old infant. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.

A 9-month-old baby in septic shock with purpuric Neisseria meningitis skin lesions. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.

The leg of a 9-month-old infant in septic shock with a rapidly evolving purpuric rash. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.

Neisseria meningitis purpuric lesions on the ear and cheek of a 9-month-old infant who is in septic shock. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.

Purpura in a young adult with fulminant meningococcemia.

Dorsum of the hand showing petechiae. Courtesy of Professor Chien Liu.

Petechiae on lower extremities. Courtesy of Professor Chien Liu.

Scattered petechiae in a patient with acute meningococcemia.

The legs of a 22-year-old woman in septic shock with a rapidly evolving purpuric rash. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.

Conjunctival petechiae. Courtesy of Professor Chien Liu.

Petechiae on the palm. Courtesy of Professor Chien Liu.

Child with severe meningococcal disease and purpura fulminans.

Gram-negative intracellular diplococci. Courtesy Professor Chien Liu.

Chart for family practice recognition and management of meningococcal disease (courtesy of Meningitis.org).

Flow chart shows guidelines for the emergency management of meningococcal disease in children. These guidelines may be reprinted for use in clinical areas and are available at Meningitis.org.

Flow chart shows guidelines for the emergency management of meningococcal disease in adult patients. These guidelines may be reprinted for use in clinical areas and are available from Meningitis.org.

Dorsum of the hand showing petechiae. Courtesy of Professor Chien Liu.

Petechiae on the palm. Courtesy of Professor Chien Liu.

Petechiae on lower extremities. Courtesy of Professor Chien Liu.

Conjunctival petechiae. Courtesy of Professor Chien Liu.

Gram-negative intracellular diplococci. Courtesy Professor Chien Liu.

Scattered petechiae in a patient with acute meningococcemia.

Purpura in a young adult with fulminant meningococcemia.

The legs of a 22-year-old woman in septic shock with a rapidly evolving purpuric rash. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.

A 9-month-old baby in septic shock with purpuric Neisseria meningitis skin lesions. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.

The leg of a 9-month-old infant in septic shock with a rapidly evolving purpuric rash. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.

Neisseria meningitis purpuric lesions on the ear and cheek of a 9-month-old infant who is in septic shock. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.

Lesions caused by Neisseria meningitis bacteremia on the palm of the hand of a 9-month-old infant. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.

Areas with frequent epidemics of meningococcal disease. This is known as the Meningitis Belt of Africa; visitors to these locales may benefit from meningitis vaccine. Image courtesy of CDC.

Child with severe meningococcal disease and purpura fulminans.

Flow chart shows guidelines for the emergency management of meningococcal disease in children. These guidelines may be reprinted for use in clinical areas and are available at Meningitis.org.

Flow chart shows guidelines for the emergency management of meningococcal disease in adult patients. These guidelines may be reprinted for use in clinical areas and are available from Meningitis.org.

Chart for family practice recognition and management of meningococcal disease (courtesy of Meningitis.org).