Pelvic Inflammatory Disease

Background

Pelvic inflammatory disease (PID) is an infectious and inflammatory disorder of the upper female genital tract, including the uterus, fallopian tubes, and adjacent pelvic structures. Infection and inflammation may spread to the abdomen, including perihepatic structures (Fitz-Hugh−Curtis syndrome). The classic high-risk patient is a menstruating woman younger than 25 years who has multiple sex partners, does not use contraception, and lives in an area with a high prevalence of sexually transmitted disease (STD).

PID is initiated by infection that ascends from the vagina and cervix into the upper genital tract. Chlamydia trachomatis is the predominant sexually transmitted organism associated with PID. Of all acute PID cases, less than 50% test positive for the sexually transmitted organisms such as Chlamydia trachomatis and Neisseria gonorrhea.^[90]

) Other organisms implicated in the pathogenesis of PID include, Gardnerella vaginalis (which causes bacterial vaginosis (BV), Haemophilus influenzae, and anaerobes such as Peptococcus and Bacteroides species. Laparoscopic studies have shown that in 30-40% of cases, PID is polymicrobial. (See Etiology.)

The diagnosis of acute PID is primarily based on historical and clinical findings. Clinical manifestations of PID vary widely.  Many patients exhibit few or no symptoms, whereas others have acute, serious illness. The most common presenting complaint is lower abdominal pain. Many women report an abnormal vaginal discharge. (See Presentation.)

The differential diagnosis includes appendicitis, cervicitis, urinary tract infection, endometriosis, ovarian torsion and adnexal tumors. Ectopic pregnancy can be mistaken for PID; indeed, PID is the most common incorrect diagnosis in cases of ectopic pregnancy. Consequently, a pregnancy test is mandatory in the workup of women of childbearing age who have lower abdominal pain. (See DDx.)

PID may produce tubo-ovarian abscess (TOA) and may progress to peritonitis and Fitz-Hugh−Curtis syndrome (perihepatitis; see the image below).^[1] Note that a rare but life-threatening complication of acute rupture of a TOA may result in diffuse peritonitis and necessitate urgent abdominal surgery.^{[2, 3, 4, 5]} See Imaging in Pelvic Inflammatory Disease and Tubo-Ovarian Abscess for more information.

View Image

"Violin-string" adhesions of chronic Fitz-Hugh-Curtis syndrome.

Laparoscopy is the current criterion standard for the diagnosis of PID. No single laboratory test is highly specific or sensitive for the disease, but studies that can be used to support the diagnosis include the erythrocyte sedimentation rate (ESR), the C-reactive protein (CRP) level, and chlamydial and gonococcal DNA probes and cultures, endometrial biopsy, imaging studies (eg, ultrasonography, computed tomography [CT], and magnetic resonance imaging [MRI]) may be helpful in unclear cases. (See Workup.)

Most patients with PID are treated in an outpatient setting. In selected cases, however, physicians should consider hospitalization. (See Treatment.)

Empirical antibiotic treatment is recommended for patients with otherwise unexplained uterine or adnexal tenderness and cervical motion tenderness, according to guidelines from the Centers for Disease Control and Prevention (CDC).^[6] Antibiotic regimens for PID must be effective against C trachomatis and N gonorrhoeae, as well as against gram-negative facultative organisms, anaerobes, and streptococci. (See Treatment and Medication.)

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Pathophysiology

Most cases of PID are presumed to occur in 2 stages. The first stage is acquisition of a vaginal or cervical infection. This infection is often sexually transmitted and may be asymptomatic. The second stage is direct ascent of microorganisms from the vagina or cervix to the upper genital tract, with infection and inflammation of these structures.

The mechanism (or mechanisms) by which microorganisms ascend from the lower genital tract is unclear. Studies suggest that multiple factors may be involved. Although cervical mucus provides a functional barrier against upward spread, the efficacy of this barrier may be decreased by vaginal inflammation and by hormonal changes that occur during ovulation and menstruation.

In addition, antibiotic treatment of sexually transmitted infections can disrupt the balance of endogenous flora in the lower genital tract, causing normally nonpathogenic organisms to overgrow and ascend. Opening of the cervix during menstruation, along with retrograde menstrual flow, may also facilitate ascent of microorganisms.

Intercourse may contribute to the ascent of infection through rhythmic uterine contractions occurring during orgasm. Bacteria may also be carried along with sperm into the uterus and fallopian tubes.^[7]

In the upper genital tract, a number of microbial and host factors appear to influence the degree of inflammation that occurs and, thus, the amount of subsequent scarring that develops. Infection of the fallopian tubes initially affects the mucosa, but inflammation may rapidly become transmural. This inflammation, which appears to be mediated by complement, may increase in intensity with subsequent infections.

Inflammation may extend to uninfected parametrial structures, including the bowel. Infection may extend via spillage of purulent materials from the fallopian tubes or via lymphatic spread beyond the pelvis to produce acute peritonitis and acute perihepatitis (Fitz-Hugh−Curtis syndrome).

Pregnancy-related factors

PID rarely occurs in pregnancy; however, chorioamnionitis can occur in the first 12 weeks of gestation, before the mucous plug solidifies and seals off the uterus from ascending bacteria. Fetal loss may result. Concurrent pregnancy influences the choice of antibiotic therapy for PID and demands that an alternative diagnosis of ectopic pregnancy be excluded. Uterine infection is usually limited to the endometrium but may be more invasive in a gravid or postpartum uterus.

Genetic factors

Genetically mediated variation in immune response plays an important role in susceptibility to PID.^[8] Variants in the genes that regulate toll-like receptors (TLRs), an important component in the innate immune system, have been associated with an increased progression of C trachomatis infection to PID.^[9]

Den Hartog et al found a possible contributing role of 5 single-nucleoside polymorphisms (SNPs) in 4 genes encoding pattern recognition receptors in local tubal cells and circulating immune cells (eg, macrophages). The presence of 2 or more SNPs appeared to correlate with increased laparoscopically identifiable tubal pathology.^[10]

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Etiology

The organisms most commonly isolated in cases of acute PID are N gonorrhoeae and C trachomatis.^[11] C trachomatis is an intracellular bacterial pathogen and the predominant sexually transmitted organism that causes PID.

In the United States, N gonorrhoeae is no longer the primary organism associated with PID, but gonorrhea remains the second most frequently reported sexually transmitted disease, after chlamydial infection. Clinically, gonorrheal infection may be asymptomatic or may manifest similarly to chlamydial infection; however, it more often produces more acute symptomatic disease. An estimated 10-20% of untreated chlamydial or gonorrheal infections progress to PID.^{[12, 13, 14]}

Cultures of specimens collected during laparoscopy have demonstrated that PID is a polymicrobial infection in as many as 30-40% of cases. Polymicrobial PID may begin as an isolated infection with N gonorrhoeae or C trachomatis, which causes inflammation of the upper genital tract that facilitates the involvement of other pathogens (anaerobes, facultative anaerobes, and other bacteria). These other organisms are increasingly isolated as inflammation increases and abscesses form.

In addition to N gonorrhoeae and C trachomatis,^[15] organisms involved in PID include the following:

• Gardnerella vaginalis
• Mycoplasma hominis
• Mycoplasma genitalium ^{[16, 17]}
• Ureaplasma urealyticum
• Herpes simplex virus 2 (HSV-2)
• Trichomonas vaginalis
• Cytomegalovirus (CMV)
• Haemophilus influenzae
• Streptococcus agalactiae
• Enteric gram-negative rods (eg, Escherichia coli)
• Enterococcus, described in 2 individuals post IUD insertion^[18]
• Peptococcus species
• Anaerobes

The microbiology of PID reflects the predominant sexually transmitted pathogens within a specific population, as well as some organisms less commonly seen in that population. Bacterial vaginosis (BV) may lead to vaginal inflammation, which could facilitate ascending infection with BV-associated organisms (eg, G vaginalis).  However evidence is unclear if detecting and treating BV reduces PID related infection.^[91] In some regions, PID may be from a granulomatous salpingitis caused by Mycobacterium tuberculosis or Schistosoma species.^[19]

In a cross-sectional study of 736 women with PID, patients with Trichomonas infections demonstrated a 4-fold increase in the histologic evidence of acute endometritis. Coinfection with HSV-2, N gonorrhoeae, C trachomatis, and BV were associated with histologic evidence of acute endometritis. HSV-2 was associated with fallopian tube inflammation and lower tract ulcerations that may contribute to disruption of the endocervical canal mucous barrier.^[20]

HIV infection is associated with an increased incidence of infection with C trachomatis, Candida, and human papillomavirus (HPV). N gonorrhoeae can facilitate HIV transmission via modulation of HIV-specific immune responses.^[21] Women with HIV infection also have an increased risk of progression to PID and TOA.^[22]

Microbial virulence appears to play a significant role in PID. Bjartling et al studied different chlamydial strains recovered from patients with PID and found less symptomatic disease in infection produced by a less virulent variant strain.^[23] Features that may increase the likelihood that a lower tract infection will progress to frank PID include expression of chlamydial heat shock protein 60 (CHSP60) in C trachomatis^[24] and expression of P9Opa(b) protein in N gonorrhoeae.^[25]

A study by Haggerty et al found an association between PID and bacterial vaginosis-associated bacteria. The four new species detected were Sneathia (Leptotrichia) sanguinegens, S. amnionii, Atopobium vaginae, and BV-associated bacteria 1.^{[26, 27]}

Risk factors

Risk factors for PID include multiple sexual partners, a history of prior STIs, and a history of sexual abuse.^[28] Frequent vaginal douching has been considered a risk factor for PID,^[29] but studies reveal no clear association.^[30] Gynecologic surgical procedures which affect the cervix such as endometrial biopsy, curettage (after termination of pregnancy), and hysteroscopy break the cervical barrier, predisposing women to ascending infections.^{[31, 32]}

Younger age has been found to be associated with an increased risk of PID. Likely reasons include increased cervical mucosal permeability, a larger zone of cervical ectopy, a lower prevalence of protective antichlamydial antibodies, and increased risk-taking behaviors. Older women with PID are more likely to be affected with non STI organisms.

Contraception

Different forms of contraception may affect the incidence and severity of PID. Appropriately used barrier contraception has clearly been shown to decrease the acquisition of most STIs.^[33]

Studies of oral contraceptive pills (OCPs) have found differing effects on PID risks. On one hand, some authors suggest that OCPs increase the risk of endocervical infection, probably by increasing the zone of cervical ectopy. On the other hand, some evidence indicates that OCPs can decrease the risk of symptomatic PID, possibly by increasing cervical mucus viscosity, decreasing menstrual anterograde and retrograde flow, and modifying local immune responses. Still other studies have suggested that OCPs may not have any effect on PID incidence.^[33]

Use of an intrauterine device (IUD) has been linked to a 2- to 9-fold increased risk of PID, but current IUDs may pose a substantially lower risk.^[34] In a large retrospective cohort study from 2012, the overall risk of PID in women receiving IUDs was 0.54%.^[35]

Kelly et al reported 9.6 cases of PID per 1,000 IUD insertions, with the most significant risk in the first 20 days.^[36] Meirik et al validated the risk of PID within the first month after insertion and also found that the risk appears to be modified by the patient’s number of sexual partners and age and by the community prevalence of STIs.^[37] The CDC notes that the risk of PID is greatly reduced by testing for—and, if necessary, treating—STI before IUD insertion.^{[38, 39]} This testing can be completed in the same day as insertion and patients confirmed to have STI’s should be treated. Additionally, IUDs need not be removed if PID is detected. Patients should be treated and re-evaluated clinically. If pain persists or symptoms are not improving, that is an indication to remove the IUD.^[38]

PID may have a different microbial profile in IUD users. Viberga et al found that in women with PID, Fusobacterium and Peptostreptococcus species were significantly more common in IUD users than in non-IUD users. Actinomyces species were found almost exclusively in patients with IUDs.^[40]

Bilateral tubal ligation (BTL) has not been found to provide protection against PID. However, patients with BTL may have delayed or milder forms of PID.^[41]

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Epidemiology

United States statistics

Among 1,171 sexually experienced reproductive-aged women in the 2013-2014 National Health and Nutrition Education Survey (NHANES) the prevalence of self-reported lifetime PID was 4.4%. Therefore approximately 2.5 million women aged 18–44 nationwide have received a diagnosis of PID in their lifetime (95% CI = 1.8–3.2 million).^[91]  The CDC has estimated that more than 1 million women experience an episode of PID every year. The disease leads to approximately 2.5 million office visits and 125,000-150,000 hospitalizations yearly.^{[43, 44]}

International statistics

No specific international data are available for PID incidence worldwide. In 2005, however, the World Health Organization (WHO) estimated that approximately 448 million new cases of curable STIs occur annually in individuals aged 15-49 years.^[45] Factors contributing to the difficulty of determining the actual worldwide incidence and prevalence of PID include the following^[46] :

• Nonrecognition of disease on the part of patients
• Difficulties in obtaining access to care
• The often subjective method of disease diagnosis
• The lack of diagnostics and laboratory facilities in many developing countries
• Underfunded and overstretched public health systems

Worldwide, WHO has determined that STIs rank in the top 5 disease categories for which adults seek care. Women in resource-poor countries, especially those in sub-Saharan Africa and Southeast Asia, experience an increased rate of complications and sequelae.

The annual rate of PID in high-income countries has been reported to be as high as 10-20 per 1000 women of reproductive age. Public health efforts implemented in Scandinavia to decrease the prevalence of STIs have been quite effective in reducing the incidence of PID.^{[47, 48]}

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Prognosis

PID has 3 principal complications, as follows:

• Chronic pelvic pain
• Infertility
• Ectopic pregnancy

Chronic pelvic pain occurs in approximately 25% of patients with a history of PID. This pain is thought to be related to cyclic menstrual changes, but it also may be the result of adhesions or hydrosalpinx.

Impaired fertility is a major concern in women with a history of PID. Infection and inflammation can lead to scarring and adhesions within tubal lumens. Of women with tubal factor infertility, 50% have no history of PID but have scarring of the fallopian tubes and exhibit antibodies to C trachomatis. The rate of infertility increases with the number of episodes of infection. These sequela help guide the CDC recommendation and United States Preventative Services Task Force (USPSTF) to annually screen sexually active females under age 25 or those older than age 25 who are high risk for C. trachomatis.^[93]  The risk of ectopic pregnancy is increased 15-50% in women with a history of PID. Ectopic pregnancy is a direct result of damage to the fallopian tube.

PID may produce TOA and extend to produce pelvic peritonitis and Fitz-Hugh−Curtis syndrome (perihepatitis).^{[49, 50]} TOA is reported in as many as one third of women hospitalized for PID. Acute rupture of a TOA with resultant diffuse peritonitis is a rare but life-threatening event that calls for urgent abdominal surgery.^{[2, 3, 4, 5]}

Approximately 125,000-150,000 hospitalizations occur yearly in the United States because of PID.^[43] Women in resource-poor countries, especially those in sub-Saharan Africa and Southeast Asia, experience an increased rate of complications and sequelae; reasons for these higher rates include lack of access to care and inability to afford optimal care.

Studies of Taiwanese databases that included more than 60,000 women diagnosed with PID found that PID was an independent risk factor for myocardial infarction in patients older than 55 years^[51] and that risk of stroke was increased in the 3 years following PID.^[52] Another large-scale study from Taiwan found that the risk of ovarian cancer is also increased, particularly in women who have had at least 5 episodes of PID.^[53]  A study by Trabert et al that included two independent populations reported that antibodies against prior or current C. trachomatis (Pgp3) doubled the risk for ovarian cancer.^[89]

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Patient Education

Patient education should focus on methods of preventing PID and STIs, including reducing the number of sexual partners, avoiding unsafe sexual practices, and routinely using appropriate barrier protection. Adolescents are at increased risk for PID and should therefore be advised to delay the onset of sexual activity until age 16 years or older.^[54]

After treatment, women should be counseled to abstain from sexual activity or educated to use barrier protection strictly and appropriately until their symptoms have fully abated and they have completed their antibiotic regimen. The woman’s sexual partner should also be treated for STI if necessary.

For patient education information, see the Pelvic Inflammatory Disease (PID) Directory, Women’s Health Center, Sexual Health Center, and Pregnancy Center, as well as Pelvic Inflammatory Disease, Ectopic Pregnancy, Birth Control Overview, Birth Control Methods, and Female Sexual Problems.

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History

The classic patient at high risk for pelvic inflammatory disease (PID) is a menstruating woman younger than 25 years who has multiple sex partners, does not use contraception, and lives in an area with a high prevalence of sexually transmitted infections (STIs). Young age at first intercourse is also a risk factor for PID. Use of an intrauterine device (IUD) for contraception confers a relative risk of 2.0-3.0 for the first 4 months following insertion, but risk subsequently decreases to baseline. Follow-up is recommended within the first month after IUD insertion.

Women who are not sexually active have a very low incidence of upper genital tract infection, as do women who have undergone total abdominal hysterectomy. Bilateral tubal ligation (BTL) does not provide protection against PID; however, patients who have had BTL may have delayed and milder forms of the disease.

Depending on the severity of the infection, patients with PID may be minimally symptomatic or may present with toxic symptoms of fever (temperature 38° C [100.4° F] or higher), nausea, vomiting, and severe pelvic and abdominal pain. Gonococcal PID is thought to have an abrupt onset with more toxic symptoms than nongonococcal disease. Gonorrhea- and chlamydia-associated infections are more likely to cause symptoms toward the end of menses and in the first 10 days following menstruation.

Lower abdominal pain is usually present. The pain is typically described as dull, aching or crampy, bilateral, and constant; it begins a few days after the onset of the last menstrual period and tends to be accentuated by motion, exercise, or coitus. Pain from PID usually lasts less than 7 days; if the pain lasts longer than 3 weeks, the likelihood that PID is the correct diagnosis declines substantially.

Abnormal vaginal discharge is present in approximately 75% of cases. Unanticipated vaginal bleeding, often postcoital, is reported in about 40% of cases.^[55] Temperature higher than 38°C (found in 30% of cases), nausea, and vomiting manifest late in the clinical course of the disease. Abnormal uterine bleeding is present in more than one-third of patients.^[94]

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Physical Examination

Because of the potential serious complications of untreated PID and the endemic prevalence of the infection, the Centers for Disease Control and Prevention (CDC) has adopted an approach designed to maximize diagnosis by using minimal criteria. The CDC also urges clinicians to maintain a low threshold for diagnosis and empiric treatment.

The CDC recommends instituting empiric treatment of PID when a sexually active young woman who is at risk for STI has:

• Pelvic or lower abdominal pain (no identifiable cause for her illness)

AND, on pelvic examination, 1 or more of the following minimal criteria^[6] :

• Cervical motion tenderness
• Uterine tenderness
• Adnexal tenderness

A temperature higher than 38.3° C (101° F) and the presence of an abnormal cervical or vaginal mucopurulent discharge enhance the specificity of the minimum criteria, as do selected laboratory tests.

Rebound lower abdominal tenderness and involuntary guarding may be noted and suggest associated peritonitis. The positive predictive value of these findings will vary, depending on the prevalence of PID in a given population.

A large multicenter trial found adnexal tenderness to be the most sensitive physical examination finding (sensitivity, 95%).^[56] Mucopurulent cervicitis is common and, if absent, has substantial negative predictive value. Adnexal fullness or disproportionate unilateral adnexal tenderness may indicate the development of a tubo-ovarian abscess (TOA).

Molander et al found the following 3 variables to be significant predictors of the diagnosis, correctly classifying 65% of patients with laparoscopically documented PID^[57] :

• Adnexal tenderness
• Fever
• Elevated erythrocyte sedimentation rate (ESR)

Right upper quadrant tenderness, especially if associated with jaundice, may indicate associated Fitz-Hugh−Curtis syndrome. A prospective cohort study in 117 incarcerated adolescents documented a 4% incidence of Fitz-Hugh−Curtis syndrome in those with mild-to-moderate PID.^[58]

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Approach Considerations

A number of procedures can be performed to improve the diagnosis of pelvic inflammatory disease (PID) and its complications. These procedures are not necessary, nor are they indicated, in the management of every case of PID. However, because of the difficulty of definitive clinical diagnosis and the number of surgical and gynecologic emergencies that may have similar presentations, the clinician should be aware of these modalities.

Procedures that may be appropriate for some patients, along with the corresponding findings specific for PID, are as follows:

• Laparoscopic confirmation
• Transvaginal ultrasonographic scanning or magnetic resonance imaging (MRI) showing thickened, fluid-filled tubes with or without free pelvic fluid or tubo-ovarian abscess (TOA)
• Endometrial biopsy showing endometritis

Laparoscopy is the criterion standard for the diagnosis of PID, but the diagnosis of PID in emergency departments and clinics is often based on clinical criteria, with or without additional laboratory and imaging evidence.^[60] No single test is highly specific and sensitive for PID, but laboratory tests, imaging studies, and procedures may be used to increase the specificity of the diagnosis.

Additional criteria that improve diagnostic specificity include the following:

• Oral temperature higher than 38.3° C (101° F)
• Abnormal cervical or vaginal mucopurulent discharge
• Abundant white blood cells (WBCs) on saline microscopy of vaginal secretions
• Elevated erythrocyte sedimentation rate (ESR) (≥40 mm/h)
• Elevated C-reactive protein (CRP) level (≥ 60 mg/L)
• Laboratory evidence of cervical infection with N gonorrhoeae or C trachomatis (via culture or DNA probe)

In addition, obtaining a sample from the urethra in women with suspected PID can increase the diagnostic yield for gonorrhea and chlamydial infection. This step is recommended only if the more sensitive nucleic acid amplification test (NAAT) is unavailable.^[11]

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Laboratory Studies

Perform a pregnancy test. If the results are positive, the possibility of ectopic pregnancy must be addressed. Pregnancy also directly influences selection of an antibiotic regimen and consideration of the patient for admission.

On a complete blood count (CBC), fewer than 50% of women with acute PID have a WBC count higher than 10,000/µL. Because of its poor sensitivity and specificity, an elevated WBC count is not among the diagnostic criteria for PID formulated by the Centers for Disease Control and Prevention (CDC). Blood cultures are not helpful in the diagnosis of PID.

In fact, no single test is highly specific and sensitive for PID; however, a number of tests may be used to increase the specificity of the clinical diagnosis. Vaginal secretions that have been treated with saline and potassium hydroxide can be examined for leukorrhea (>10 WBC/high-power field; >1 WBC/epithelial cell), trichomoniasis, and clue cells.^{[16, 61]} The presence of leukorrhea was found to be the most sensitive, laboratory indicator of upper tract infection, though not a specific one; the absence of leukorrhea is a negative predictor of PID.

Gonorrhea DNA probes and cultures are generally used to support the diagnosis and to provide epidemiologic data for public health departments. However, they are frequently negative in later stages of PID.^[62]

Chlamydial vulvovaginal or endocervical DNA probes and cultures are generally used to support the diagnosis and to provide epidemiologic data for public health departments, though recovery rates from the cervix vary widely (5-56%).^[63] Quantitative culture for Chlamydia identifies rapidly replicating bacteria that appear to be associated with active disease. However, DNA probe and culture results are often not available to the emergency physician at the time of initial evaluation.

One study suggested that women with high titers of immunoglobulin G (IgG) chlamydial antibodies, acute pelvic pain, and a clinical picture suggestive of PID were more likely to have salpingitis than adhesions alone.^[64] Those patients with high titers and chronic pelvic pain but with a clinical picture that did not suggest PID were more likely to have adhesions alone. In the investigators’ view, their limited data suggested that serologic testing might help establish the diagnosis.

Although the 2015 CDC guidelines mention Mycoplasma genitalium contributing to milder forms of PID, there is no clear consensus on the value of testing for this organism.^[95]

Other tests that may be considered include the following:

• Rapid protein reagin (RPR) test for syphilis (the incidence of which is again increasing in the United States)
• Hepatitis virus and HIV
• Urinalysis to help exclude urinary tract infections – Note, however, that a positive urinalysis does not exclude PID, because any inflammatory process in the contiguous pelvis can produce WBCs in the urine

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Transvaginal Ultrasonography

Ultrasonographic scanning may be performed for cases of suspected PID in which clinical findings are nondiagnostic. Transvaginal ultrasonography is superior to transabdominal ultrasonography for diagnosing PID, as well as endometrial abnormalities and pelvic masses (see the images below).^[61] This modality is readily available and noninvasive and can be performed at the patient’s bedside.

View Image

Transabdominal ultrasonogram shows anechoic tubular structures in adnexa; finding is compatible with hydrosalpinx.

View Image

Endovaginal ultrasonogram reveals tubular structure with debris in left adnexa; finding is compatible with pyosalpinx.

View Image

Ultrasonogram shows markedly heterogeneous and thickened endometrium; finding is compatible with endometritis.

View Image

Ultrasonogram reveals bilateral complex masses in patient who had pyometrium; finding is compatible with tubo-ovarian abscess.

View Image

Transabdominal ultrasonogram demonstrates echogenic region within endometrium with dirty shadowing; finding is compatible with air in endometrium and ....

There are no large randomized trials addressing the specificity and sensitivity of bedside ultrasonography for the diagnosis of PID. The literature demonstrates that the accuracy of this technique depends on the criteria used to indicate PID, the quality of the equipment, and the experience of the individual operator performing the test.

Transvaginal ultrasonography has poor sensitivity (81%) and specificity (78%) in mild or atypical PID.^[61] Helpful findings include thickened (>5 mm), fluid-filled fallopian tubes; thickened cilia; indistinct endometrial borders; ovaries with multiple small cysts; and moderate-to-large amounts of free pelvic fluid in acute, severe PID.^[65] Small amounts of free pelvic fluid have not been shown to be a discriminatory finding. These findings alone are not sufficiently specific to permit a definitive diagnosis of PID.

In the patient who appears toxic or has asymmetric pelvic findings, ultrasonographic scanning is an important diagnostic tool for the identification of a TOA. Pelvic abscesses may be seen as complex adnexal masses with multiple internal echoes. The modality has been shown to demonstrate as many as 70% of adnexal masses missed on physical examination.

Pelvic ultrasonographic scanning is also useful in evaluating the possibility of ectopic pregnancy in patients whose differential diagnosis includes both that condition and PID. The modality can also be helpful in evaluating other disorders in the differential diagnosis, including hemorrhagic ovarian cyst, ovarian torsion, endometrioma, and appendicitis. (At some adult academic medical centers, however, ultrasonography is considered adequate as a solo imaging modality to rule out appendicitis.)

Ultrasonographic results in patients with PID may be normal or nonspecific because salpingitis alone is not usually associated with imaging findings.^[66] Positive ultrasonographic findings in PID may include the following:

• The uterus may be ill defined because of inflammation; however, inflammation of the uterus is an unusual finding
• Endometritis may result in central-endometrial-cavity echo thickening and heterogeneity
• Hydrosalpinx is depicted as a fluid-filled fallopian tube – If the fallopian tube walls are thickened and if debris is present within the tube, pyosalpinx should be considered in the differential diagnosis, but a pyosalpinx may be imaged as an echoless tube, whereas an imaged echo-filled tube may be from proteinaceous but noninfected fluid in a hydrosalpinx
• Oophoritis results in enlarged ovaries with ill-defined margins that often appear adherent to the uterus; adjacent free fluid may be present in the adnexa or cul-de-sac
• TOAs are depicted as complex adnexal masses with thickened walls and central fluid
• Pelvic infection, with findings of tubal inflammation and hydrosalpinx detected by Doppler studies, is one of the most specific criteria in diagnosing PID^[6]

Thickening of the endometrium is nonspecific for PID because this finding may also be seen with endometrial hyperplasia, polyps, or cancer. Knowledge of the patient’s clinical findings and other signs of infection can help in the differential diagnosis.

Hydrosalpinx and pyosalpinx can usually be readily distinguished from pelvic veins and bowel by visualizing the color flow within the patent blood vessels and peristalsis within the bowel.

Imaging findings in TOAs are usually nonspecific and must be distinguished from the following:

• Endometriomas
• Ectopic pregnancies
• Hemorrhagic cysts
• Ovarian tumors
• Abscesses from adjacent organs

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Laparoscopy

Laparoscopy is the criterion standard for the diagnosis of PID. It is significantly more specific and sensitive than are clinical criteria alone. The minimum criteria for diagnosing PID laparoscopically include tubal wall edema, visible hyperemia of the tubal surface, and the presence of exudate on the tubal surfaces and fimbriae.

Pelvic masses consistent with TOA or ectopic pregnancy can be directly visualized. Hepatic abscess exudate or adhesions may be visible. Material can be obtained for definitive culture and histologic studies.

The main drawbacks of laparoscopy are that the procedure is expensive and invasive, exhibits interobserver variability, and requires an operating room and anesthesia.^[57] In addition, findings on laparoscopy do not necessarily correlate with the severity of illness, in that only the surfaces of structures are visible through the scope. In as many as 20% of cases, laparoscopy may not define PID fully.

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Computed Tomography

Computed tomography (CT) may also be used as the initial diagnostic study for the investigation of nonspecific pelvic pain in a female, and PID may be found incidentally. Because of concerns about radiation exposure, ultrasonography is preferred to CT as the triaging tool in a female child or adolescent with right lower quadrant or pelvic pain.

In cases of PID in which no evidence of an abscess is found, CT scan findings are nonspecific. Inflammation obliterates the pelvic fat planes, with thickening of the fascial planes. Endometritis manifests as enlargement of the uterine cavity. If hydrosalpinx is present, a fluid-filled tubular structure may be seen in the adnexa.

Typically, a TOA is visualized as a mass; the mass may have regular margins and contain debris similar to that seen in endometriomas or hemorrhagic cysts. The margins may be thick and irregular. There may also be an associated low-attenuation area that may represent an adjacent or contained fluid-filled fallopian tube.^[67] Many adult centers prefer CT to ultrasonography when a diagnosis of appendicitis is in question.

Tubular, fluid-filled, nonvascular structures in the pelvis that are associated with an adnexal mass are suggestive of dilated fallopian tubes that correlate with cases of PID. A finding of an adjacent or surrounding complex mass confirms the diagnosis of TOA.

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Magnetic Resonance Imaging

Although MRI has relatively high specificity (95%) and sensitivity (95%) in this setting,^[61] it is costly and is rarely indicated in cases of acute PID.

Hydrosalpinx is visualized on MRI as a tubular structure with low signal intensity on T1-weighted scans and high signal intensity on T2-weighted images. If the walls are thickened, pyosalpinx should be considered in the differential diagnosis.^[68] Oophoritis may be evidenced by enlarged, polycystic-appearing ovaries with ill-defined margins and adjacent fluid.

TOAs often appear as thick-walled masses with low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. Occasionally, TOAs may be isointense or hyperintense on T1-weighted images and may have heterogeneous signal intensity on T2-weighted images.

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Culdocentesis

Culdocentesis can be performed rapidly in the emergency department. With the advent of transvaginal ultrasonographic scanning, culdocentesis is rarely performed today, but it remains valuable in settings where current technology is unavailable.

For the procedure, an 18-gauge spinal needle attached to a 20-mL syringe is inserted transvaginally into the cul-de-sac. Normally, this yields only 2-4 mL of clear to straw-colored free pelvic fluid; purulent fluid indicates an infectious or inflammatory process.

The potential positive findings of leukocytes and bacteria are nonspecific: They may indicate PID, or they may be a product of another infectious or inflammatory process in the pelvis (eg, appendicitis or diverticulitis), or they may result from contamination with vaginal contents. A yield of more than 2 mL of nonclotting blood is consistent with ectopic pregnancy.

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Endometrial Biopsy

Endometrial biopsy can be used to determine the histopathologic diagnosis of endometritis, a condition that is uniformly associated with salpingitis. Endometrial biopsy is approximately 90% specific and 90% sensitive. The procedure is performed with an endometrial suction pipette or curette and is well tolerated. Specimens for culture may also be obtained during the procedure, but these are frequently contaminated with vaginal flora.

Current CDC guidelines recommend endometrial biopsy in women undergoing laparoscopy who have no visible signs of salpingitis, on the grounds that endometritis may be the only sign of PID.^[6] Diagnostic use of endometrial biopsy in the emergency department is limited; significant operator training is required, and the results of the procedure are not immediately available to the clinician.

Endometrial biopsy findings usually confirm the presence of infection but rarely identify the causative organism. Chronic endometritis is more commonly seen than acute endometritis.

• References

Approach Considerations

Treatment of pelvic inflammatory disease (PID) addresses the relief of acute symptoms, eradication of current infection, and minimization of the risk of long-term sequelae. These sequelae, including chronic pelvic pain, ectopic pregnancy, tubal factor infertility (TFI), and implantation failure with in vitro fertilization attempts, may occur in as many as 25% of patients.^[69]

From a public health perspective, treatment is aimed at the expeditious eradication of infection in order to reduce the risk of transmission of infection to new sexual partners. In addition, identification and treatment of current and recent partners are indicated for further reduction of sexually transmitted infections (STIs). Each state has specific guidelines on expedited partner treatment which can be found here. (https://www.cdc.gov/std/ept/legal/default.htm)

Early diagnosis and treatment appear to be critical in the preservation of fertility. Current guidelines suggest that empirical treatment should be initiated in at-risk women who have lower abdominal pain, adnexal tenderness, and cervical motion tenderness. In view of the diagnostic difficulties and the potential for serious sequelae, the Centers for Disease Control and Prevention (CDC) advises that physicians maintain a low threshold for aggressive patient treatment, with overtreatment preferred to no or delayed treatment.^[6]

Therapy with antibiotics alone is successful in 33-75% of cases. If surgical treatment is warranted, the current trend is toward conservation of reproductive potential with simple drainage, adhesiolysis, and copious irrigation or unilateral adnexectomy, if possible. Further surgical therapy is needed in 15-20% of cases so managed.

Based on studies done with the copper IUD, the CDC advises that there is insufficient evidence to recommend removal of intrauterine devices (IUDs) in women diagnosed with acute PID. However, antibiotics and close clinical follow-up is mandatory if the IUD is left in place.^[66]

Current evidence suggests that adherence to clinical guidelines for PID diagnosis and management is less than optimal.^{[70, 71, 72]} A systematic review of the literature revealed limited research on strategies to improve patient and practitioner adherence to guidelines. Interventions that make it easier to manage patients and provision of the entire treatment course to the patient at the time of evaluation improved compliance.^[70]

• References

Consultations

Patients who do not improve in 72 hours should be reevaluated for possible laparoscopic or surgical intervention and for reconsideration of other possible diagnoses. Laparoscopy should be used if the diagnosis is in doubt. Laparoscopic pelvic lavage, abscess drainage, and adhesion lysis may be necessary.

Most TOAs (60-80%) resolve with antibiotic administration. If patients do not respond appropriately, laparoscopy may be useful for identifying loculations of pus requiring drainage. An enlarging pelvic mass may indicate bleeding secondary to vessel erosion or a ruptured abscess. Unresolved abscesses may be drained percutaneously via posterior colpotomy, under computed tomographic (CT) or ultrasonographic guidance, laparoscopically, or through laparotomy. For more information on treatment of TOA, see Fallopian Tube Disorders.

The advantages of laparoscopy include direct visualization of the pelvis and more accurate bacteriologic diagnosis if cultures are obtained. However, laparoscopy is not always available in acute PID; moreover, it is costly and requires general anesthesia.

Laparotomy is usually reserved for patients experiencing surgical emergencies (eg, abscesses that have ruptured or that have not responded to medical management and laparoscopic drainage) and for patients who are not candidates for laparoscopic management. Treatment is guided by intraoperative findings and the patient’s desire for fertility maintenance.

Surgical treatment may involve unilateral salpingo-oophorectomy or hysterectomy and bilateral salpingo-oophorectomy. Ideally, the operation is performed after the acute infection and inflammation have resolved. In patients with recurrent PID, dense pelvic adhesions may render surgery difficult.

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Prevention

Randomized, controlled trials suggest that preventing chlamydial infection reduces the incidence of PID.^[73] In addition, anyone who has had sexual contact with a woman with PID in the 60 days preceding the onset of her symptoms should be treated empirically for C trachomatis and N gonorrhoeae. CDC guidelines recommend that even if a patient last had sexual intercourse more than 60 days before symptom onset or diagnosis, the most recent sex partner should be treated.^[6]

Urethral gonococcal or chlamydial infection in the partner of an infected woman is highly likely and is frequently asymptomatic in men. Even in clinical settings where men do not receive treatment, arrangements for care or referral of male sex partners should be made.

Regardless of whether a woman’s sex partners were treated, women diagnosed with chlamydial or gonococcal infection should follow up with repeat testing within 3-6 months. These women have a high rate of reinfection within 6 months of treatment.^[6] Adolescents are more likely to have recurrent PID than adults are and so may require a different approach to follow-up.^[74]

Improved education, routine screening,^[75] diagnosis, and empirical treatment of these infections should reduce the incidence and prevalence of these processes and the development of long-term sequelae. Education should concentrate on strategies to prevent PID and STIs, including reducing the number of sexual partners, avoiding unsafe sexual practices, and routinely using appropriate barrier protection. Adolescents, being at an increased risk for PID, should be advised to delay the onset of sexual intercourse until age 16 years or older.^[54]

Women with PID should be counseled to abstain from sexual activity or use barrier protection strictly and appropriately until their symptoms and those of their partner^[6] have fully abated and they have completed their entire treatment regimen.

The US Preventive Services Task Force (USPSTF) recommends screening for chlamydial infection in all sexually active nonpregnant women up to age 25 years and in nonpregnant women aged 25 years or older who are at increased risk (grade A recommendation), as well as in all pregnant women up to age 25 years and in pregnant women aged 25 years or older who are at increased risk (grade B recommendation). The USPSTF recommends against routine screening for women aged 25 years and older if they are not at increased risk (grade C recommendation).^[76]

The USPSTF does not provide recommendations for Chlamydia screening in men; the available evidence is insufficient to allow accurate weighing of benefits and risks.^[76] However, a 2008 demonstration project suggested that the combination of (a) partner notification and (b) screening of men with a relatively high prevalence of chlamydial infection and a larger number of partners would be more cost-effective than expanding screening to low-risk women would be.^[77]

Some patients treated for STIs and PID fail to comply with medication regimens because of low medical literacy and a poor understanding of their diagnosis. These individuals frequently do not follow up or notify partners. Patients should be fully educated about these issues, as well as about the advisability of testing and treatment for other STIs, including HIV infection, hepatitis, and syphilis. In particular, the 2015 CDC guidelines state that HIV testing should be offered to all women diagnosed with acute PID.^{[6, 96]}

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Outpatient Versus Inpatient Treatment

Most patients with PID are managed as outpatients, and the available data do not clearly indicate that patients benefit from hospitalization. However, hospitalization should be considered for patients with the following conditions:

• Uncertain diagnosis
• Pelvic abscess on ultrasonographic scanning
• Pregnancy
• Inability to tolerate outpatient oral antibiotic regimen
• Severe illness
• Immunodeficiency (eg, patients with HIV infection who have a low CD4 count or patients who are using immunosuppressive medications)
• Failure to improve clinically after 72 hours of outpatient therapy

Worldwide, more than 90% of HIV-positive individuals with PID are treated as outpatients.^[78] A 2006 study in Nairobi, with investigators blinded to patient HIV status, demonstrated that HIV-infected women were more likely to have severe PID and that clinical improvement in PID took longer in HIV-infected women, irrespective of their CD4 count; however, no change in antibiotic regimen was necessary.^[79]

Most patients show a clinical response within 48-72 hours after initiation of medical therapy. If a patient continues to have fever, chills, uterine tenderness, adnexal tenderness, and cervical motion tenderness, consider other possible causes and consider performing a diagnostic laparoscopy.

Hospital admission of HIV-infected patients and of adolescents should be reviewed on an individual basis. Admission decisions are based on the following factors:

• Diagnostic certainty
• Illness severity
• Likelihood of compliance with an outpatient regimen
• Whether or not the patient is pregnant
• Coexisting immunosuppression or illness
• Risk factors for significant anaerobic infection (eg, IUD use, a recent pelvic procedure, or the presence of a tubo-ovarian abscess [TOA])
• The following consultations may be helpful:
• Obstetrician/gynecologist
• Surgeon (especially if appendicitis or another intra-abdominal process cannot be excluded)
• Infectious disease consultant (especially in patients who are HIV-positive and may be on highly active antiretroviral treatment [HAART])

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Antibiotic Therapy

In the emergency department, clinic, or office setting, treatment should be expeditiously initiated and should include empirical broad-spectrum antibiotics to cover the full complement of common organisms. All regimens must be effective against C trachomatis and N gonorrhoeae, as well as against gram-negative facultative organisms, anaerobes, and streptococci.

To avoid inappropriate treatment, physicians should be aware of current guidelines and current national and local patterns of drug resistance in their patient populations.^[80] The Royal College of Obstetricians and Gynaecologists (RCOG) recommends treating women with PID who are infected with HIV with the same antibiotic regimens used to treat women who are HIV-negative.^[11]

A number of studies carried out between 1992 and 2006 demonstrated the effectiveness of various parenteral and oral regimens in eliminating acute symptoms and achieving microbiologic cure.^[60] No differences in outcome were identified between inpatient and outpatient management in a large, randomized, multicenter clinical study that compared inpatient and outpatient oral and parenteral antibiotic regimens in the documented elimination of endometrial and tubal infection.^[81]

Patients on an intravenous (IV) PID regimen can be transitioned to oral antibiotics 24 hours after clinical improvement. These should be continued for a total of 14 days. Oral therapy usually involves doxycycline; however, azithromycin can also be used.^[82] In patients who have developed a TOA, oral therapy should include clindamycin or metronidazole.

All patients should be reevaluated in 72 hours for evidence of clinical improvement and compliance with their antibiotic regimen. Multiple studies have shown poor compliance with doxycycline therapy, and approximately 20-25% of patients have never filled their prescriptions.

Outpatient and inpatient regimens

The Centers for Disease Control and Prevention (CDC) has outlined antibiotic regimens for outpatient and inpatient treatment of PID.^[83]

For outpatient treatment, the CDC lists 2 currently accepted treatment regimens, labeled as A and B.^[6] Regimen A consists of the following:

• Ceftriaxone 250 mg intramuscularly (IM) once as a single dose plus
• Doxycycline 100 mg orally twice daily for 14 days
• Metronidazole 500 mg orally twice daily for 14 days can be added if there is evidence or suspicion of vaginitis or if the patient underwent gynecologic instrumentation in the preceding 2-3 weeks

Regimen B consists of the following:

• Cefoxitin 2 g IM once as a single dose concurrently with probenecid 1 g orally in a single dose, or another single-dose parenteral third-generation cephalosporin (eg, ceftizoxime or cefotaxime) plus
• Doxycycline 100 mg orally twice daily for 14 days
• Metronidazole 500 mg orally twice daily for 14 days can be added if there is evidence or suspicion of vaginitis or if the patient underwent gynecologic instrumentation in the preceding 2-3 weeks

Inpatient treatment

For inpatient treatment of PID, the CDC also lists 2 currently accepted treatment regimens, again labeled as A and B.^[6] Regimen A consists of the following:

• Cefoxitin 2 g IV every 6 hours or cefotetan 2 g IV every 12 hours plus
• Doxycycline 100 mg orally or IV every 12 hours

This regimen is continued for 24 hours after the patient remains clinically improved, after which doxycycline 100 mg is given orally twice daily for a total of 14 days. If a TOA is present, clindamycin or metronidazole is used with doxycycline for more effective anaerobic coverage.

Regimen B consists of the following:

• Clindamycin 900 mg IV every 8 hours plus
• Gentamicin IV in a loading dose of 2 mg/kg, followed by a maintenance dosage of 1.5 mg/kg q8h

IV therapy may be discontinued 24 hours after the patient improves clinically, and oral therapy with 100 mg doxycycline twice daily should be continued for a total of 14 days. If TOA is present, clindamycin or metronidazole may be used with doxycycline for more effective anaerobic coverage.

An alternative parenteral regimen is ampicillin-sulbactam 3 g IV every 6 hours in conjunction with doxycycline 100 mg orally or IV every 12 hours.

Additional information on antibiotic therapy

Oral doxycycline has the same bioavailability as the IV form and avoids the painful infusion and vein sclerosis associated with the latter. Gentamicin dosing may be every 24 hours. Other third-generation cephalosporins may be substituted for cefoxitin and ceftriaxone.

For individuals who are allergic to cephalosporins, spectinomycin is recommended in Europe and Canada; however, this agent is currently unavailable in the United States. A 2-g azithromycin dose may also be used in these patients, but it is not routinely recommended, because of concerns about rapid development of resistance to this antibiotic^{[84, 85]} and about potential intolerance of this dose. For more information, see the CDC’s Antibiotic-Resistant Gonorrhea Web site and Gonococcal Infections.

In April 2007, the CDC ceased to recommend fluoroquinolone antibiotics for treatment of gonorrhea in the United States.^[86] This change was based on analysis of data from the CDC’s Gonococcal Isolate Surveillance Project (GISP), which showed that the prevalence of fluoroquinolone-resistant gonorrhea cases in heterosexual men had reached 6.7%, an 11-fold increase from 0.6% in 2001. Fluoroquinolones may be a treatment option for disseminated gonococcal infection if antimicrobial susceptibility can be documented.

With fluoroquinolones no longer advocated, the drugs recommended for treatment of gonorrhea are limited to cephalosporins. However, gonococcal resistance to cephalosporins has also been increasing in the United States. GISP data showed that from 2000 to 2010, the percentage of isolates with elevated minimum inhibitory concentrations rose from 0.2% to 1.4% for cefixime and from 0.1% to 0.3% for ceftriaxone.

Consequently, the CDC no longer recommends the use of oral cephalosporins for gonococcal infections. For treatment of uncomplicated urogenital, anorectal, and pharyngeal gonorrhea, the CDC recommends a single IM dose of ceftriaxone 250 mg together with either a single oral dose of azithromycin 1 g or twice-daily oral administration of doxycycline 100 mg for 7 days.^[87]

If ceftriaxone is not readily available, cefixime 400 mg can be given orally in combination with either azithromycin or doxycycline; if ceftriaxone cannot be given because of severe allergy, azithromycin 2 g can be given orally in a single dose. However, patients treated with one of these alternative regimens should return 1 week after treatment for a test of cure.^[87]

• References

SPILF/CNGOF Pelvic Inflammatory Disease Guidelines

Diagnosis of Pelvic Inflammatory Disease

Positive diagnosis of pelvic inflammatory disease (PID) is based on adnexal pain or tenderness upon cervical motion, reinforced by associated signs, including fever, leukorrhea, and metrorrhagia.^[97]

Pelvic clinical examination is recommended in women with PID-compatible symptoms.

Laboratory Studies

Hyperleukocytosis accompanied by a high C-reactive protein (CRP) level suggests complicated PID or an alternative diagnosis (eg, acute appendicitis). Suspected PID should prompt serum analysis, including complete blood count (CBC) and CRP testing.

Imaging Studies

Pelvic ultrasonography is too insensitive and unspecific for diagnosis of uncomplicated PID, although ultrasonography is recommended to evaluate for signs of complicated PID (eg, polymorphic collection) or an alternate diagnosis. Initiation of antibiotic therapy should not be delayed awaiting ultrasonography.

Abdominal-pelvic CT scanning with contrast is useful to exclude urinary, digestive, or gynecological differential diagnoses.

Laparoscopy is not recommended for PID diagnosis.

Microbiologic Diagnosis

Chlamydia trachomatis is the most common bacterial cause of PID, particularly in women younger than 30 years.^[98]

In uncomplicated cases of PID, endocervical sampling during gynecological examination under speculum is recommended to obtain a microbiological diagnosis, as follows:

• First swab: Direct examination via smear (Gram stain, May-Grünwald Giemsa [MGG] stain)
• Second swab: Sent via adapted transport for culture (Neisseria gonorrhoeae and facultative vaginal flora bacteria), with antibiotic susceptibility testing
• Third swab: Sent by appropriate transport for analysis via nucleic acid amplification techniques (NAATs) (for N gonorrhoeae, C trachomatis,Mycoplasma genitalium).

PID diagnosis is supported by NAAT positive for N gonorrhoeae, C trachomatis, and/or M genitalium from a genital sample. Conversely, negative NAAT results do not exclude a sexually transmitted infection (STI) agent for PID diagnosis.

If speculum use is not possible, vaginal sampling is performed. C trachomatis serology is not useful as a first-line diagnostic test for PID or as a tool for monitoring PID.

Follow-up for Pelvic Inflammatory Disease

The PID recurrence rate is 15%-21%, of which 20%-34% cases are due to recurrent STI.^[99]

Follow-up is recommended. Personalized text message reminders improve the likelihood of follow-up compliance.

NAAT of vaginal samples to evaluate for N gonorrhoeae, C trachomatis, and M genitalium should be performed 3-6 months after treatment of STI-associated PID to rule out reinfection. Condom use after STI-associated PID reduces the recurrence risk. Systematic oral contraceptives are not recommended after PID.

Prior to insertion of an intrauterine device, vaginal sampling for microbiological diagnosis is recommended.

Women with PID are at high risk of ectopic pregnancy.

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Medication Summary

Treatment of pelvic inflammatory disease (PID) should include empirical broad-spectrum antibiotics to cover the full complement of common causes. Antibiotics chosen should be effective against Chlamydia trachomatis and Neisseria gonorrhoeae, as well as against gram-negative facultative organisms, anaerobes, and streptococci. The Centers for Disease Control and Prevention (CDC) has outlined antibiotic regimens for outpatient and inpatient treatment of PID.

• References

Azithromycin (Zithromax, Zmax)

• Dosing, Interactions, etc.

Clinical Context:  Azithromycin acts by binding to the 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Nucleic acid synthesis is not affected. This drug concentrates in phagocytes and fibroblasts, as demonstrated by in vitro incubation techniques. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues.

Azithromycin is used to treat mild-to-moderate microbial infections. Plasma concentrations are very low, but tissue concentrations are much higher, giving the drug value in treating intracellular organisms. Azithromycin has a long tissue half-life. Azithromycin is related to erythromycin. It is considered by many to be treatment of choice for C trachomatis genitourinary infection because it may be administered as a single dose, which improves adherence to treatment.

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Class Summary

Macrolides are a class of antibiotics discovered in the bacterium Streptomyces. These agents are characterized by molecules made up of large-ring lactones. Many macrolides inhibit protein biosynthesis.

• References

Ceftriaxone (Rocephin)

• Dosing, Interactions, etc.

Clinical Context:  Cephalosporins are a group of broad-spectrum, semisynthetic beta-lactam antibiotics that are derived from the mold Cephalosporium (now termed Acremonium). They interfere with bacterial cell wall synthesis. Cephalosporin N and C are chemically related to penicillins, and cephalosporin P resembles fusidic acid.

Cephalosporins are grouped into generations according to their spectrum of antimicrobial activity. Third-generation cephalosporins are less active against gram-positive organisms then first-generation cephalosporins are. They are highly active against Enterobacteriaceae, Neisseria, and Haemophilus influenzae.

• References

Cefotaxime (Claforan)

Clinical Context:  Cefotaxime is a third-generation cephalosporin with a broad gram-negative spectrum, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms. It arrests bacterial cell wall synthesis by binding to 1 or more of the penicillin-binding proteins, thereby in turn inhibiting bacterial growth. Cefotaxime is used to treat bloodstream infection and gynecologic infections caused by susceptible organisms.

• References

Ceftizoxime (Cefizox)

• Dosing, Interactions, etc.

Clinical Context:  Ceftizoxime is a third-generation cephalosporin with broad-spectrum gram-negative activity. It has lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. It arrests bacterial growth by binding to 1 or more penicillin-binding proteins. Its gram-negative spectrum includes Moraxella catarrhalis. Dose selection depends on the severity of the infection and the susceptibility of the organism.

• References

Class Summary

Cephalosporins are a group of broad-spectrum, semisynthetic beta-lactam antibiotics that are derived from the mold Cephalosporium (now termed Acremonium). They interfere with bacterial cell wall synthesis. Cephalosporin N and C are chemically related to penicillins, and cephalosporin P resembles fusidic acid.

Cephalosporins are grouped into generations according to their spectrum of antimicrobial activity. Third-generation cephalosporins are less active against gram-positive organisms then first-generation cephalosporins are. They are highly active against Enterobacteriaceae, Neisseria, and Haemophilus influenzae.

• References

Cefoxitin (Mefoxin)

• Dosing, Interactions, etc.

Clinical Context:  Cefoxitin is a second-generation cephalosporin indicated for infections with gram-positive cocci and gram-negative rods. Infections caused by cephalosporin- or penicillin-resistant gram-negative bacteria may respond to cefoxitin.

• References

Cefotetan (Cefotan)

• Dosing, Interactions, etc.

Clinical Context:  Cefotetan is a second-generation cephalosporin indicated for infections caused by susceptible gram-positive cocci and gram-negative rods. The dose and route of administration depend on the condition of the patient, the severity of infection, and the susceptibility of the causative organism.

• References

Class Summary

Cephalosporins are a group of broad-spectrum, semisynthetic beta-lactam antibiotics that are derived from the mold Cephalosporium (now termed Acremonium). They interfere with bacterial cell wall synthesis. Cephalosporin N and C are chemically related to penicillins, and cephalosporin P resembles fusidic acid.

Cephalosporins are grouped into generations according to their spectrum of antimicrobial activity. Compared with first-generation cephalosporins, second-generation agents have increased activity against gram-negative bacteria and decreased activity against gram-positive bacteria.

• References

Doxycycline (Vibramycin)

• Dosing, Interactions, etc.

Clinical Context:  Doxycycline inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.

• References

Class Summary

Tetracyclines are bacteriostatic broad-spectrum antibiotics derived from cultures of Streptomyces bacteria; they inhibit protein synthesis in susceptible organisms. These agents work by reversibly binding to the 30S ribosome of the microbial RNA and preventing the attachment of aminoacyl-tRNA with the acceptor site on the 70S ribosome.

• References

Clindamycin (Cleocin)

Clinical Context:  Clindamycin is a lincosamide used for treatment of serious skin and soft tissue staphylococcal infections. It is also effective against aerobic and anaerobic streptococci (except enterococci). It inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

• References

Metronidazole (Flagyl)

• Dosing, Interactions, etc.

Clinical Context:  An imidazole ring–based antibiotic active against various anaerobic bacteria and protozoa, metronidazole is used in combination with other antimicrobial agents (except for treatment of Clostridium difficile enterocolitis).

• References

Class Summary

Lincosamide antibiotics (eg, clindamycin) inhibit protein synthesis. Imidazole antibiotics (eg, metronidazole) arrest RNA-dependent protein synthesis.

• References

Gentamicin (Garamycin)

• Dosing, Interactions, etc.

Clinical Context:  Gentamicin is an aminoglycoside antibiotic that provides gram-negative coverage. It is used in combination with an agent that is effective against gram-positive organisms and one that covers anaerobes. Dosing regimens are numerous. Adjust dose on the basis of creatinine clearance and changes in volume of distribution. Measure at least a trough level, drawn on the third or fourth dose (0.5 hours before dosing); a peak level may be drawn 0.5 hours after a 30-minute infusion.

• References

Class Summary

Aminoglycosides are a group of injectable bactericidal antibiotics that act by inhibiting bacterial protein synthesis. All aminoglycosides share the potential for ototoxicity and nephrotoxicity.

• References

Ampicillin-sulbactam (Unasyn)

• Dosing, Interactions, etc.

Clinical Context:  This formulation combines ampicillin with a beta-lactamase inhibitor. It interferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms.

• References

Class Summary

An acid-stable semisynthetic penicillin, ampicillin has a broader spectrum of antimicrobial action than penicillin G does. It inhibits the growth of gram-positive and gram-negative bacteria. It is not resistant to penicillinase, but when it is combined with the beta-lactamase inhibitor sulbactam, the spectrum of activity is increased.

• References

Probenecid

• Dosing, Interactions, etc.

Clinical Context:  Probenecid inhibits tubular secretion of penicillin and usually increases penicillin plasma levels, regardless of the route of penicillin administration. It is used as an adjuvant to therapy with penicillin, ampicillin, methicillin, oxacillin, cloxacillin, or nafcillin. A 2- to 4-fold elevation of penicillin plasma levels is demonstrated.

• References

Class Summary

Uricosuric agents are used to increase serum concentrations of certain antibiotics and other drugs.

• References