Pneumonia in Immunocompromised Patients

Back

Overview

Pneumonia in the immunocompromised host is a complex infection and inflammation of the lower respiratory tract, complicated by widespread multi-drug antibiotic resistance, and aided by medical advances such as improvements in diagnostic measures and immunosuppressive agents. Though overall patient survival has increased, pneumonia is both the most common invasive infection in immunocompromised patients and continues to carry a high mortality and morbidity rate.[1, 2, 3, 4, 5]

The major immunocompromised host groups are those with:



View Image

Chest radiograph of HIV-infected patient with PJP shows diffuse patchy infiltrates with predominantly perihilar and interstitial prominence, as well a....



View Image

Chest CT of HIV-infected patient with PJP shows early findings of diffuse ground glass opacities, and chronic findings of linear opacities and thicken....

Complications

Pneumonia in immunocompromised is often complicated by superinfection, drug toxicity, empyema, sepsis, pneumothorax, and acute respiratory distress syndrome (ARDS).

Causes of Pneumonia

The number of potential pulmonary pathogens is increasing as a result of new immunosuppressive therapies, the emergence of multi-drug­-resistant organisms, and improved diagnostic modalities.

There are four major groups of pathogens responsible for pneumonia in immunocompromised patients. Depending on the underlying immune defect, the likelihood of each of these etiologies for infection is varied.

  1. Bacterial: Tuberculosis (TB) and non-­TB mycobacteria, mainly Mycobacterium avium complex (MAC)
  2. Fungal: Pneumocystis jirovecii, Aspergillus fumigatus, Candida, Cryptococcus neoformans, Mucormycosis species, and other fungi including Coccidioides immitis and Histoplasma capsulatum.
  3. Viruses: ­Cytomegalovirus (CMV), community-acquired respiratory infections including influenza, and herpes simplex virus (HSV) and varicella zoster virus (VZV)
  4. Parasites: ­Strongyloides, Toxoplasmosis

HIV/AIDS

Patients with human immunodeficiency virus (HIV) are at risk for a number of pulmonary infections. Pneumocystis jirovecii (formerly Pneumocystis carinii) remains the most common opportunistic infection in this group, while the incidence of mycobacterial infections has decreased significantly.[6]

HIV causes dysfunction of cell-mediated and humoral immunity. CD4 T cells principally help other cells achieve their effector function. Low CD4 counts, which correlate with the degree of immunosuppression, cause a disruption of B-cell differentiation. Impaired B-cell functions, particularly memory cells, are correlated with increased risk of infection.[7]

Despite the advances in the development of highly active antiretroviral therapy (HAART), pulmonary disease remains an important cause of mortality and morbidity in persons with HIV/AIDS.[8, 9, 10]

Tuberculosis

HIV is considered to be the greatest risk factor for TB.[11] Patients with HIV are more likely not only to contract TB, but progress from latent to active TB.[12] In addition, they have a higher mortality risk from TB. 



View Image

Chest radiograph in a patient with HIV infection and focal infiltrates due to tuberculosis.

The clinical manifestations of TB in persons with HIV depend on the degree of immunosuppression. In severely immunocompromised individuals, the typical presentation of TB becomes less frequent. Instead of upper lobe cavitary disease, some of these patients present with lower lobe primary pneumonias, nonspecific patterns, or even no chest radiograph findings.[13]

Tuberculin skin test (TST) is more likely to be negative in persons with HIV. Typically, interferon-gamma release assays (IGRAs) are the gold standard for identification of TB-infected individuals; however, in HIV patients, the sensitivity of IGRAs is diminished. In studies, IGRAs perform similarly to the TST. Since both methods have a modest predictive value and suboptimal sensitivity, the choice of test should be based on country guidelines and resource considerations.[14]

Recent studies have shown that the timing of HAART and tuberculosis therapy is important in those concurrently infected. Withholding HAART until the third week of anti-tuberculosis therapy likely reduced TB mortality.[15]

Bacterial pneumonia

The most common bacterial causes of community-acquired pneumonia (CAP) in patients with HIV are the same as those in the general population[16] , the top three being Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus.[17, 18, 19]

However, the risks of contracting Streptococcus pneumonia are increased 10,000-fold in a patient with HIV.[20]  Protease inhibitor (PI)­ containing ART regimens show great effect in lowering this risk.[21]

In a nosocomial setting, Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae, and Enterobacter species are common.

Fungal pneumonia

Fungal pneumonias are divided into opportunistic (i.e. PCP, Candida, Aspergillus, Mucor species) and endemic (Histoplasma capsulatum, Coccidioides immitis, Cryptococcus neoformans).

 

Opportunistic: Pneumocystis jirovecii pneumonia (PJP)

Pneumocystis jirovecii infection remains the most common opportunistic infection among patients with HIV.

It becomes a concern in individuals when CD4 count drops below 200, which is when prophylaxis with Trimethoprim-sulfamethoxazole (TMP-SMX) is recommended. When the A-a gradient is >35 or a room air arterial blood gas pO2< 70, adjuvant corticosteroids are recommended.

Transmission and infectivity of P. jirovecii is incompletely understood, in most cases attributed to reactivation of latently colonized patients.[22]

Opportunistic: Aspergillus

Invasive aspergillus pneumonia is one of the four aspergillosis syndromes that primarily affects immunosuppressed individuals.

In solid organ and hematopoietic transplant patients, there is a bimodal distribution of incidence with peaks during 1. prolonged neutropenia before engraftment and 2. in later stages with corticosteroid therapy in treatment of graft-versus-host disease.

Patients with leukemia and lymphoma have a higher incidence of invasive aspergillosis which is associated with a higher mortality rate.[23]

Invasive aspergillosis is also being increasingly observed in patients with severe COPD who remain on long-term corticosteroid therapy.[24]

There are no reliable biomarkers for detection of fungal cell wall constituents or other specific measures, thus, the recommendation continues to be close monitoring of clinical signs and symptoms for prevention and prophylaxis of opportunistic fungal pneumonias.[25]

Endemic: Cryptococcus neoformans

Cryptococcal pneumonia is more severe in patients with HIV. Patients with pulmonary disease frequently progress to disseminated disease.​[26]

Most cases are the result of the reactivation of a latent infection.

Endemic: Histoplasma capsulatum

For the immunocompetent host, histoplasmosis is frequently asymptomatic or self-­limited. In the setting of HIV/AIDS, this infection is much more common and frequently progresses to disseminated disease.

This infection is endemic to certain areas of the United States, particularly in states bordering the Ohio River valley and the lower Mississippi River.

Spores of the mold phase are inhaled and cause a localized or patchy bronchopneumonia. CD4 lymphocytes normally activate macrophages to control the infection.[27]

Endemic: Coccidioides immitis

Coccidioides immitis is an organism endemic to large parts of the southwestern United States.

Spores are inhaled and then ingested by pulmonary macrophages. Impaired cell­-mediated immunity in persons with HIV accounts for an increased risk of infection in these patients.[28]  

Viruses

Varicella ­zoster virus

Visceral dissemination of primary varicella, especially pneumonitis, has been reported in persons with HIV.[29]

Parasites

Strongyloides stercoralis

Strongyloides is an human intestinal nematode which can reproduce and persist in the body indefinitely, and affects millions of people worldwide. In immunocompromised individuals, this autoinfective cycle can be amplified into a hyperinfection syndrome. Increased parasite burden migrates rom the gastrointestinal tract, where it causes GI bleeding, into a systemic process. Filariform larvae have been found in the respiratory system, where they cause respiratory distress and sepsis secondary to pneumonia, and the neurological system causing meningitis.

Though the two conditions most often shown to trigger hyperinfection are glucocorticoid treatment and human T-lymphotropic virus type 1 infection, it is also associated with HIV/AIDS and hematologic malignancy. Anthelmintic agents such as ivermectin have been used successfully in both treatment as well as primary and secondary prevention in patients with risk factors.[30]



View Image

Chest radiograph demonstrating diffuse bilateral infiltrates in a patient with Pneumocystis carinii pneumonia.



View Image

High-resolution computed tomography scan obtained through the upper lobes in the prone position in a patient with a history of Pneumocystis carinii pn....



View Image

Chest radiograph in a patient with HIV infection, bilateral perihilar infiltrates, and Pneumocystis carinii pericarditis.

 

Other Causes of Immunodeficiency

Malignancy/neutropenia

Malignancy, especially hematologic malignancy, is a large risk factor for developing pneumonia. The pathogenicity and severity of disease is related to the degree and duration of neutropenia. Most infectious etiologies are polymicrobial including gram-positive and gram-negative organisms from the upper respiratory tract. However, in about 10-25% of patients, an infectious focus is not identified in sputum, with the only evidence of infection being a positive blood culture.[31]

Patients with profound, prolonged neutropenia are more susceptible to invasive fungal pathogens such as aspergillus species, and the agents of mucormycosis. 

Viruses are also involved, primarily VZV. Respiratory viruses such as influenza, respiratory syncytial virus (RSV), Adenovirus, and Metapneumovirus are increasingly documented in neutropenic patients.

Mortality in patients with febrile neutropenia is 30-50%.[32, 33]

The American Society of Clinical Oncology (ASCO) recommend prophylaxis (eg, with trimethoprim-sulfamethoxazole) for patients receiving chemotherapy regimens associated with >3.5% risk for Pneumocystis jirovecii pneumonia.[34, 35]

 



View Image

CT of AML patient with a fungal pneumonia in the right upper lobe characterized by a cavitary lesion without air fluid levels. Courtesy of Radiopaedia....

Transplant immunosuppression

Solid-organ and bone-marrow transplant patients have a heightened risk of pulmonary infection as well. The specific organ, timeframe since transplant, and use of immunosuppressive medications are all important in predicting these complications.

CMV pneumonitis is common in solid organ transplant, particularly lung, recipients. The risk is higher if the donor is seropositive and the recipient seronegative. Interestingly, the opposite is seen in hematological stem cell transplant (HCT) patients, where there is a higher risk for CMV pneumonitis among seropositive recipients transplanted with seronegative stem cells.

Nocardia species are another notable cause of pulmonary infection in organ transplant patients requiring long-term immunosuppression.

Reactivation of viruses causing pneumonia is a large concern in HCT patients, even in autologous transplants. Human herpesvirus 6 (HHV-6) reactivation is most common (seen in up to 60% of patients), followed by EBV (up to 30%).[36, 37, 38]

HHV-6 infection is especially important in that it has been shown to be a predictor of subsequent CMV infection.[39]

Solid organ and HCT recipient are at risk also of hyperinfection with Strongyloides stercoralis, which may be accompanied by gram-negative bacterial sepsis and pneumonia.

Autoimmune diseases

Infections in persons with autoimmune conditions can result from the effects of immunosuppressive therapies as well as their underlying condition.

In systemic lupus erythematosus (SLE), distinguishing infection from an autoimmune flare is important. Treatment with steroids in the setting of infection could be deleterious. 

Complement deficiencies and elevated Fc gamma III and granulocyte-macrophage colony-stimulating factor (GM-CSF) levels may contribute to increased susceptibility to infection in patients with SLE.[40]  

Low complement, the use of more than 20 mg prednisone daily, and the use of cyclophosphamide in patients with SLE were important risk factors in multivariate analyses.[41]

Consideration of initiating prophylaxis for Pneumocystic jiroveci in SLE patients exceeding 20 mg of prednisone a day or with usage of cyclophosphamide has been proposed.[42]

The large majority of infectious complications are due to bacterial pathogens. Viral infections (CMV, VZV) are also common.

In connective tissue diseases, the primary condition and the use of immunosuppressive medications place patients at increased risk. One meta-analysis showed that 29% of patients developed a serious infection, and 24% died from this infection—most reported as bacteremia or pneumonia.[43]

Primary immunodeficiencies

Persons with primary immunodeficiencies are susceptible to pulmonary infections, the spectrum of which is largely determined by their underlying immune dysfunction: humoral, cellular, or combined deficiencies.

Humoral immunity deficiencies impact the ability to create functional antibodies. Characteristic infections are bacterial-based, recurrent, upper and lower respiratory tract infections. Common pathogens include the encapsulated bacteria Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis, as well as Giardia, Cryptosporidia, and Campylobacter.

Cellular deficiencies affect T-cell development and function. Dysfunction of T cells invariably has an impact on B-cell activity; therefore, most of these conditions manifest as combined deficiencies. Infections are common from viruses (RSV, HSV, VZV, CMV, EBV, influenza), mycobacteria, and fungi (Candida, Cryptococcus, and Pneumocystis).

Steroids

Patients taking steroids long-term are at higher risk for pulmonary infections.[44]

Steroids alter phagocytic function of alveolar macrophages, delay the mobilization of immune cells, and affect antigen presentation. 

The dose and duration of use are predictive of increased risk of pneumonia. Low-dose and short-term use carry minimal additional risk of pneumonia, while dosages more than 10 mg/d or cumulatively 700 mg of prednisone increase patients' risk of pulmonary infection.[45]

Asplenic patients

Asplenic patients are at particularly high risk for acquiring infections from encapsulated organisms.[20] They also have a higher rate of infection from pneumonias overall.[46]

In asplenic patients, the overall incidence of invasive pneumococcal disease is 500 cases per 100,000 per year.[20]

Clinical Presentation

Patient history

The underlying cause of immunosuppression is a crucial aspect of the history.

Nonspecific findings may include the following:

Physical examination

Pulmonary findings may be nonspecific in immunocompromised patients.

Findings at physical examination may include the following:

Differential Diagnosis

The differential diagnosis for pneumonia in immunocompromised patients includes the noninfectious causes of pulmonary disease:

Laboratory Studies

Laboratory studies that should be obtained include a complete blood count (CBC) with differential, basic metabolic panel, arterial blood gas (ABG), lactate dehydrogenase (LDH) level, erythrocyte sedimentation rate (ESR), and C reactive protein (CRP).

If tuberculosis is suspected, sputum culture, sputum Gram stain, acid-fast bacillus (AFB) smear, and AFB culture should be collected while patients are in isolation. 

Two sets of blood cultures, despite their low yield and infrequent impact on care, are considered standard of care.[47, 48]  They are especially important in immunosuppressed individuals as they may at times be the only objective finding of infection.

Recently, procalcitonin (PCT) level has been shown to be a reliable biomarker with good sensitivity and specificity for bacterial causes of pneumonia or other infection. As it is triggered by bacterial endotoxin, procalcitonin levels can be a useful adjuvant to distinguish bacterial etiologies of infection from viral, fungal, or autoimmune causes. Trending of PCT level is also established to be useful for initiating and guiding antibiotic therapy.[49, 50, 51]

Other routine laboratory studies may be clinically indicated, such as viral nasal swabs, urine antigen testing (Legionella pneumophila, Histoplasma capsulatum, Streptococcus pneumoniae), PCR studies (CMV, HHV6), serum antigen testing (cryptococcus, galactomannan), and other assays such as serum 1,3 beta-D-Glucan.[52]

Chest Radiography

Chest radiography is usually the initial imaging modality.

The timing, progression, and distribution of findings are helpful in identifying correlations.

The most typical findings on chest radiography include infiltrates with consolidation, peribronchovascular lesions, and nodular space-occupying lesions. 

Other findings include atelectasis, cavitation, pleural effusions, lymphadenopathy, and cardiomegaly.

Some findings are correlated with certain etiologies of pulmonary infection; however, the pattern of radiographic findings is often unreliable in immunocompromised patients given the decreased inflammatory response.

For instance, as many as 14% of chest radiographic findings are normal in AIDS patients with pulmonary TB.[53]



View Image

Chest radiograph demonstrating diffuse bilateral infiltrates in a patient with Pneumocystis carinii pneumonia.



View Image

Chest radiograph in a patient with HIV infection and focal infiltrates due to tuberculosis.

Chest CT Scanning

Chest computed tomography (CT) can often detect abnormalities that may or may not be well visualized on chest radiography, and thus are useful in identifying small or early consolidations, characterizing extent and heterogenicity of disease, facilitating earlier diagnoses, and directing therapeutic management.[54]



View Image

High-resolution computed tomography scan obtained through the upper lobes in the prone position in a patient with a history of Pneumocystis carinii pn....

CT is especially effective at defining extent of disease, including when multiple patterns of injury are occurring simultaneously.

The other major benefit of CT imaging is its utility in therapeutic procedures, including lung biopsy and tissue excision.

Lung Sampling

Lung sampling may be performed by bronchoscopy, transbronchial biopsy (TBB), or video-assisted thoracic surgery (VATS).

Bronchoscopy, the least invasive of these three sampling modalities, allows collection of diagnostic samples by bronchoalveolar lavage (BAL), fibrobronchial aspirate (FBAS), and protected specimen brush (PSB). This technique is high-yield for diagnosis of pneumonias, especially in conjunction with clinical and non-invasive methods. BAL has been specifically shown to be a highly sensitive and moderately specific test to diagnose of Pneumocystic jirovecii in HIV patients.[55]

The role of BAL in diagnosing pulmonary infections also established in non-HIV immunocompromised patients.[56, 57] Some sources suggest transbronchial biopsy in conjunction with BAL in non-HIV immunocompromised patients to detect other processes such as drug-induced lung injury or bronchiolitis obliterans.

TBB is established in diagnosis of diffuse parenchymal lung disease including interstitial fibrosis, but has shown promise in identifying fungal or viral pneumonia and inflammatory reactions.[58, 59]

Initial Treatment

Prehospital Care

Prehospital care should be initiated as soon as possible, and includes:

Emergency Department Care

Emergency department care encompasses the same measures as prehospital care above, but also includes:

Consultations

Consultation with the following consultants may be considered:

If outpatient management is possible, arrange for follow-up with a primary care practitioner within 24 hours.

Pharmacologic Treatment

Pharmacologic therapy consists mainly of empiric antibiotics awaiting results of diagnostic studies.

Taking into consideration each patient's characteristics and risk factors, a narrow differential diagnosis can be established and help tailor therapy to the most likely organism and prevent overuse of anti-microbe therapy.

A meta-analysis by Wang et al indicated that in HIV-infected patients with P jiroveci pneumonia, early adjunctive corticosteroid treatment may lead to a 0.55 times reduced risk of mortality compared with patients who do not receive the adjunctive therapy.[62]

Prevention

Optimization of treatment of the underlying immunocompromise is a first approach to prevention of pneumonia in immunocompromised individuals. This includes HAART, chemo and radiation therapy, and other measures depending on the type of immunocompromise.

However, despite optimal therapy, prevention of opportunistic and endemic pulmonary infections can be difficult.

Vaccination against pneumococcal and influenza, as well as prophylaxis against bacteria, viruses, and fungi, are other methods of prevention.

In rheumatologic disorders in which corticosteroids and/or immunomodulators such as TNF-inhibitors play a role in symptom control, the optimization of the level of immunosuppression is as important as prophylaxis against microbial infection.

 

How is pneumonia characterized in immunocompromised patients?Which immunocompromised host groups are at highest risk for pneumonia?What are the possible complications of pneumonia in immunocompromised patients?What causes pneumonia in immunocompromised patients?What causes pneumonia in patients with HIV infection?What is the clinical presentation of TB in patients with HIV infection?How is TB diagnosed and treated in patients with HIV infection?What causes bacterial pneumonia in patients with HIV infection?What are the types of fungal pneumonia in patients with HIV infection?How does Pneumocystis jirovecii pneumonia (PJP) develop in patients with HIV infection?Which immunocompromised patients have the highest incidence of aspergillus pneumonia?What causes cryptococcal pneumonia in immunocompromised patients?What causes histoplasmosis pneumonia in immunocompromised patients?What causes coccidioides immitis pneumonia in immunocompromised patients?Which viruses cause pneumonia in immunocompromised patients?How do strongyloides cause pneumonia in immunocompromised patients?What are the risk factors for pneumonia in immunocompromised cancer patients?What are the risk factors for pneumonia in immunocompromised transplant patients?What are the risk factors for pneumonia in immunocompromised patients with autoimmune conditions?What are the risk factors for pneumonia in patients with primary immunodeficiencies?What is the increased risk for pneumonia in immunocompromised patients on long-term steroid therapy?What is the incidence of pneumonia in immunocompromised asplenic patients?Which clinical history findings are characteristic of pneumonia in immunocompromised patients?Which physical findings are characteristic of pneumonia in immunocompromised patients?Which conditions are included in the differential diagnoses of pneumonia in immunocompromised patients?What is the role of lab tests in the workup of pneumonia in immunocompromised patients?What is the role of chest radiography in the workup of pneumonia in immunocompromised patients?What is the role of chest CT scanning in the workup of pneumonia in immunocompromised patients?What is the role of lung sampling in the workup of pneumonia in immunocompromised patients?What is included in prehospital care for immunocompromised patients with pneumonia?What is the initial ED treatment of suspected pneumonia in immunocompromised patients?Which diagnostic tests are performed in the ED when pneumonia is suspected in immunocompromised patients?How is pneumonia in immunocompromised patients treated?Which specialist consultations are beneficial to immunocompromised patients with pneumonia?What is the role of medications in the treatment of pneumonia in immunocompromised patients?How is pneumonia prevented in immunocompromised patients?

Author

Julie B Zhao, MD, Physician, Department of Emergency Medicine, NewYork-Presbyterian-Weill Cornell Medical Center

Disclosure: Nothing to disclose.

Coauthor(s)

Richard D Shin, MD, Director of Simulation, Department of Emergency Medicine, New York-Presbyterian Queens; Clinical Assistant Professor of Emergency Medicine in Medicine, Weill Cornell Medical College; Emergency Physician, Envision Physician Services

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.

Paul Blackburn, DO, FACOEP, FACEP, Attending Physician, Department of Emergency Medicine, Maricopa Medical Center

Disclosure: Nothing to disclose.

Chief Editor

Barry E Brenner, MD, PhD, FACEP, Professor of Emergency Medicine, Professor of Internal Medicine, Program Director for Emergency Medicine, Sanz Laniado Medical Center, Netanya, Israel

Disclosure: Nothing to disclose.

Additional Contributors

Christopher I Doty, MD, FAAEM, FACEP, Professor of Emergency Medicine, Vice Chair, Department of Emergency Medicine, University of Kentucky-Chandler Medical Center

Disclosure: Nothing to disclose.

Dana A Stearns, MD, Assistant Director of Undergraduate Education, Department of Emergency Medicine, Massachusetts General Hospital; Associate Director, Undergraduate Clerkship in Surgery, Massachusetts General Hospital/Harvard Medical School; Assistant Professor of Surgery, Harvard Medical School

Disclosure: Nothing to disclose.

Marie Abdallah, MD, Primary Care and Infectious Diseases Physician, Kings County Hospital

Disclosure: Nothing to disclose.

Michael H Augenbraun, MD, FACP, Professor of Medicine and Preventive Medicine and Community Health, Director of 3rd Year Medical Clerkship, State University of New York Downstate College of Medicine; Hospital Epidemiologist and Director, Department of Epidemiology, University Hospital of Brooklyn; Medical Director of Sexually Transmitted Diseases Clinic, Director of Lumbar Puncture Clinic, Kings County Hospital Center

Disclosure: Nothing to disclose.

Acknowledgements

David J Wallace, MD, MPH Critical Care Medicine Fellow, University of Pittsburgh Medical Center

David J Wallace, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American College of Emergency Physicians, and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

References

  1. Ettinger NA, Trulock EP. Pulmonary considerations of organ transplantation. Part I. Am Rev Respir Dis. 1991 Jun. 143(6):1386-405. [View Abstract]
  2. Fishman JA, Rubin RH. Infection in organ-transplant recipients. N Engl J Med. 1998 Jun 11. 338(24):1741-51. [View Abstract]
  3. Ramsey PG, Rubin RH, Tolkoff-Rubin NE. The renal transplant patient with fever and pulmonary infiltrates: etiology, clinical manifestations, and management. 3. Baltimore: Medicine; 1980 May. 59: 206-22.
  4. Rosenow EC 3rd. Diffuse pulmonary infiltrates in the immunocompromised host. Clin Chest Med. 1990 Mar. 11(1):55-64. [View Abstract]
  5. Winston DJ, Emmanouilides C, Busuttil RW. Infections in liver transplant recipients. Clin Infect Dis. 1995 Nov. 21(5):1077-89; quiz 1090-1. [View Abstract]
  6. Joos L, Chhajed PN, Wallner J, Battegay M, Steiger J, Gratwohl A. Pulmonary infections diagnosed by BAL: a 12-year experience in 1066 immunocompromised patients. Respir Med. 2007 Jan. 101(1):93-7. [View Abstract]
  7. Hart M, Steel A, Clark SA, Moyle G, Nelson M, Henderson DC, et al. Loss of discrete memory B cell subsets is associated with impaired immunization responses in HIV-1 infection and may be a risk factor for invasive pneumococcal disease. J Immunol. 2007 Jun 15. 178(12):8212-20. [View Abstract]
  8. Beck JM, Rosen MJ, Peavy HH. Pulmonary complications of HIV infection. Report of the Fourth NHLBI Workshop. Am J Respir Crit Care Med. 2001 Dec 1. 164(11):2120-6. [View Abstract]
  9. Boyton RJ. Infectious lung complications in patients with HIV/AIDS. Curr Opin Pulm Med. 2005 May. 11(3):203-7. [View Abstract]
  10. Kanmogne GD. Noninfectious pulmonary complications of HIV/AIDS. Curr Opin Pulm Med. 2005 May. 11(3):208-12. [View Abstract]
  11. Schneider E, Moore M, Castro KG. Epidemiology of tuberculosis in the United States. Clin Chest Med. 2005 Jun. 26(2):183-95, v. [View Abstract]
  12. Trends in tuberculosis incidence--United States, 2006. MMWR Morb Mortal Wkly Rep. 2007 Mar 23. 56(11):245-50. [View Abstract]
  13. Hsieh SM, Hung CC, Chen MY, Chang SC, Hsueh PR, Luh KT, et al. Clinical features of tuberculosis associated with HIV infection in Taiwan. J Formos Med Assoc. 1996 Dec. 95 (12):923-8. [View Abstract]
  14. Cattamanchi A, Smith R, Steingart KR, Metcalfe JZ, Date A, Coleman C. Interferon-gamma release assays for the diagnosis of latent tuberculosis infection in HIV-infected individuals: a systematic review and meta-analysis. J Acquir Immune Defic Syndr. 2011 Mar 1. 56(3):230-8. [View Abstract]
  15. Nagu TJ, Aboud S, Mwiru R, Matee MI, Rao M, Fawzi WW, et al. Tuberculosis associated mortality in a prospective cohort in Sub Saharan Africa: Association with HIV and antiretroviral therapy. Int J Infect Dis. 2017 Mar. 56:39-44. [View Abstract]
  16. Hirschtick RE, Glassroth J, Jordan MC, Wilcosky TC, Wallace JM, Kvale PA. Bacterial pneumonia in persons infected with the human immunodeficiency virus. Pulmonary Complications of HIV Infection Study Group. N Engl J Med. 1995 Sep 28. 333(13):845-51. [View Abstract]
  17. Polsky B, Gold JW, Whimbey E, Dryjanski J, Brown AE, Schiffman G, et al. Bacterial pneumonia in patients with the acquired immunodeficiency syndrome. Ann Intern Med. 1986 Jan. 104(1):38-41. [View Abstract]
  18. Witt DJ, Craven DE, McCabe WR. Bacterial infections in adult patients with the acquired immune deficiency syndrome (AIDS) and AIDS-related complex. Am J Med. 1987 May. 82(5):900-6. [View Abstract]
  19. Park DR, Sherbin VL, Goodman MS, Pacifico AD, Rubenfeld GD, Polissar NL. The etiology of community-acquired pneumonia at an urban public hospital: influence of human immunodeficiency virus infection and initial severity of illness. J Infect Dis. 2001 Aug 1. 184(3):268-77. [View Abstract]
  20. Ortqvist A, Hedlund J, Kalin M. Streptococcus pneumoniae: epidemiology, risk factors, and clinical features. Semin Respir Crit Care Med. 2005 Dec. 26(6):563-74. [View Abstract]
  21. Sullivan JH, Moore RD, Keruly JC, Chaisson RE. Effect of antiretroviral therapy on the incidence of bacterial pneumonia in patients with advanced HIV infection. Am J Respir Crit Care Med. 2000 Jul. 162(1):64-7. [View Abstract]
  22. Helweg-Larsen J, Tsolaki AG, Miller RF, Lundgren B, Wakefield AE. Clusters of Pneumocystis carinii pneumonia: analysis of person-to-person transmission by genotyping. QJM. 1998 Dec. 91(12):813-20. [View Abstract]
  23. Martínez-Hernández L, Vilar-Compte D, Cornejo-Juárez P, Volkow-Fernández P. [Nosocomial pneumonia in patients with haematological malignancies]. Gac Med Mex. 2016 Jul-Aug. 152 (4):465-72. [View Abstract]
  24. Tutar N, Metan G, Koç AN, Yilmaz I, Bozkurt I, Simsek ZO, et al. Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease. Multidiscip Respir Med. 2013 Sep 4. 8 (1):59. [View Abstract]
  25. Samanta P, Singh N. Complications of invasive mycoses in organ transplant recipients. Expert Rev Anti Infect Ther. 2016 Dec. 14 (12):1195-1202. [View Abstract]
  26. Wasser L, Talavera W. Pulmonary cryptococcosis in AIDS. Chest. 1987 Oct. 92(4):692-5. [View Abstract]
  27. Wheat LJ, Kauffman CA. Histoplasmosis. Infect Dis Clin North Am. 2003 Mar. 17(1):1-19, vii. [View Abstract]
  28. Anstead GM, Graybill JR. Coccidioidomycosis. Infect Dis Clin North Am. 2006 Sep. 20(3):621-43. [View Abstract]
  29. Wallace MR, Hooper DG, Pyne JM, Graves SJ, Malone JL. Varicella immunity and clinical disease in HIV-infected adults. South Med J. 1994 Jan. 87(1):74-6. [View Abstract]
  30. Keiser PB, Nutman TB. Strongyloides stercoralis in the Immunocompromised Population. Clin Microbiol Rev. 2004 Jan. 17 (1):208-17. [View Abstract]
  31. Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011 Feb 15. 52(4):e56-93. [View Abstract]
  32. Rosenow EC 3rd, Wilson WR, Cockerill FR 3rd. Pulmonary disease in the immunocompromised host. 1. Mayo Clin Proc. 1985 Jul. 60(7):473-87. [View Abstract]
  33. Rosenow EC 3rd. Diffuse pulmonary infiltrates in the immunocompromised host. Clin Chest Med. 1990 Mar. 11(1):55-64. [View Abstract]
  34. Taplitz RA, Kennedy EB, Bow EJ, Crews J, Gleason C, Hawley DK, et al. Antimicrobial Prophylaxis for Adult Patients With Cancer-Related Immunosuppression: ASCO and IDSA Clinical Practice Guideline Update. J Clin Oncol. 2018 Sep 4. JCO1800374. [View Abstract]
  35. Nelson R. New Guidelines: Antimicrobial Prophylaxis for Cancer Patients. Medscape Medical News. Available at https://www.medscape.com/viewarticle/902129. September 18, 2018; Accessed: January 7, 2019.
  36. Inazawa N, Hori T, Nojima M, Saito M, Igarashi K, Yamamoto M, et al. Virus reactivations after autologous hematopoietic stem cell transplantation detected by multiplex PCR assay. J Med Virol. 2017 Feb. 89 (2):358-362. [View Abstract]
  37. Kadakia MP, Rybka WB, Stewart JA, Patton JL, Stamey FR, Elsawy M. Human herpesvirus 6: infection and disease following autologous and allogeneic bone marrow transplantation. Blood. 1996 Jun 15. 87(12):5341-54. [View Abstract]
  38. Wilborn F, Schmidt CA, Zimmermann R, Brinkmann V, Neipel F, Siegert W. Detection of herpesvirus type 6 by polymerase chain reaction in blood donors: random tests and prospective longitudinal studies. Br J Haematol. 1994 Sep. 88(1):187-92. [View Abstract]
  39. Crocchiolo R, Giordano L, Rimondo A, Bologna M, Sarina B, Morabito L, et al. Human Herpesvirus 6 replication predicts Cytomegalovirus reactivation after allogeneic stem cell transplantation from haploidentical donor. J Clin Virol. 2016 Nov. 84:24-26. [View Abstract]
  40. Zandman-Goddard G, Shoenfeld Y. Infections and SLE. Autoimmunity. 2005 Nov. 38(7):473-85. [View Abstract]
  41. Bosch X, Guilabert A, Pallares L, Cerveral R, Ramos-Casals M, Bove A. Infections in systemic lupus erythematosus: a prospective and controlled study of 110 patients. Lupus. 2006. 15(9):584-9. [View Abstract]
  42. Mecoli CA, Saylor D, Gelber AC, Christopher-Stine L. Pneumocystis jiroveci pneumonia in rheumatic disease: a 20-year single-centre experience. Clin Exp Rheumatol. 2017 Jan 27. [View Abstract]
  43. Falagas ME, Manta KG, Betsi GI, Pappas G. Infection-related morbidity and mortality in patients with connective tissue diseases: a systematic review. Clin Rheumatol. 2007 May. 26(5):663-70. [View Abstract]
  44. White DA. Drug-induced pulmonary infection. Clin Chest Med. 2004 Mar. 25(1):179-87. [View Abstract]
  45. Singh JM, Palda VA, Stanbrook MB, Chapman KR. Corticosteroid therapy for patients with acute exacerbations of chronic obstructive pulmonary disease: a systematic review. Arch Intern Med. 2002 Dec 9-23. 162(22):2527-36. [View Abstract]
  46. Robinette CD, Fraumeni JF Jr. Splenectomy and subsequent mortality in veterans of the 1939-45 war. Lancet. 1977 Jul 16. 2(8029):127-9. [View Abstract]
  47. Ramanujam P, Rathlev NK. Blood cultures do not change management in hospitalized patients with community-acquired pneumonia. Acad Emerg Med. 2006 Jul. 13(7):740-5. [View Abstract]
  48. Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007 Mar 1. 44 Suppl 2:S27-72. [View Abstract]
  49. Savaş Bozbaş Ş, Er Dedekargınoğlu B, Ulubay G, Haberal M. Role of Serum Procalcitonin Levels in Solid-Organ Transplant Patients. Exp Clin Transplant. 2016 Nov. 14 (Suppl 3):116-120. [View Abstract]
  50. Kaziani K, Sotiriou A, Dimopoulos G. Duration of pneumonia therapy and the role of biomarkers. Curr Opin Infect Dis. 2017 Apr. 30 (2):221-225. [View Abstract]
  51. Yan ST, Sun LC, Jia HB, Gao W, Yang JP, Zhang GQ. Procalcitonin levels in bloodstream infections caused by different sources and species of bacteria. Am J Emerg Med. 2016 Dec 10. [View Abstract]
  52. Onishi A, Sugiyama D, Kogata Y, Saegusa J, Sugimoto T, Kawano S, et al. Diagnostic accuracy of serum 1,3-β-D-glucan for pneumocystis jiroveci pneumonia, invasive candidiasis, and invasive aspergillosis: systematic review and meta-analysis. J Clin Microbiol. 2012 Jan. 50 (1):7-15. [View Abstract]
  53. Greenberg SD, Frager D, Suster B, Walker S, Stavropoulos C, Rothpearl A. Active pulmonary tuberculosis in patients with AIDS: spectrum of radiographic findings (including a normal appearance). Radiology. 1994 Oct. 193(1):115-9. [View Abstract]
  54. Rano A, Agusti C, Sibila O, Torres A. Pulmonary infections in non-HIV-immunocompromised patients. Curr Opin Pulm Med. 2005 May. 11(3):213-7. [View Abstract]
  55. Fan LC, Lu HW, Cheng KB, Li HP, Xu JF. Evaluation of PCR in bronchoalveolar lavage fluid for diagnosis of Pneumocystis jirovecii pneumonia: a bivariate meta-analysis and systematic review. PLoS One. 2013 Sep 4. 8 (9):e73099. [View Abstract]
  56. Hohenadel IA, Kiworr M, Genitsariotis R, Zeidler D, Lorenz J. Role of bronchoalveolar lavage in immunocompromised patients with pneumonia treated with a broad spectrum antibiotic and antifungal regimen. Thorax. 2001 Feb. 56 (2):115-20. [View Abstract]
  57. Rañó A, Agustí C, Jimenez P, Angrill J, Benito N, Danés C, et al. Pulmonary infiltrates in non-HIV immunocompromised patients: a diagnostic approach using non-invasive and bronchoscopic procedures. Thorax. 2001 May. 56 (5):379-87. [View Abstract]
  58. Kropski JA, Pritchett JM, Mason WR, Sivarajan L, Gleaves LA, Johnson JE, et al. Bronchoscopic cryobiopsy for the diagnosis of diffuse parenchymal lung disease. PLoS One. 2013 Nov 12. 8 (11):e78674. [View Abstract]
  59. Tomassetti S, Cavazza A, Colby TV, Ryu JH, Nanni O, Scarpi E, et al. Transbronchial biopsy is useful in predicting UIP pattern. Respir Res. 2012 Oct 29. 13:96. [View Abstract]
  60. Newberry L, O'Hare B, Kennedy N, Selman A, Omar S, Dawson P, et al. Early use of corticosteroids in infants with a clinical diagnosis of Pneumocystis jiroveci pneumonia in Malawi: a double-blind, randomised clinical trial. Paediatr Int Child Health. 2017 Feb 1. 1-8. [View Abstract]
  61. Vaglum P, Friis S, Vaglum S, Larsen F. Comparison between personality disorder diagnoses in DSM-III and DSM-III-R: reliability, diagnostic overlap, predictive validity. Psychopathology. 1989. 22 (6):309-14. [View Abstract]
  62. Wang LI, Liang H, Ye LI, Jiang J, Liang B, Huang J. Adjunctive corticosteroids for the treatment of Pneumocystis jiroveci pneumonia in patients with HIV: A meta-analysis. Exp Ther Med. 2016 Feb. 11 (2):683-687. [View Abstract]
  63. Dohn MN, White ML, Vigdorth EM, Ralph Buncher C, Hertzberg VS, Baughman RP. Geographic clustering of Pneumocystis carinii pneumonia in patients with HIV infection. Am J Respir Crit Care Med. 2000 Nov. 162(5):1617-21. [View Abstract]
  64. Bultink IE, Hamann D, Seelen MA, Hart MH, Dijkmans BA, Daha MR. Deficiency of functional mannose-binding lectin is not associated with infections in patients with systemic lupus erythematosus. Arthritis Res Ther. 2006. 8(6):R183. [View Abstract]
  65. Yoshikawa T. Human herpesvirus 6 infection in hematopoietic stem cell transplant patients. Br J Haematol. 2004 Feb. 124(4):421-32. [View Abstract]

Chest radiograph of HIV-infected patient with PJP shows diffuse patchy infiltrates with predominantly perihilar and interstitial prominence, as well as a few pneumatocoeles up to 1cm in size. Courtesy of Radiopaedia (https://radiopaedia.org/), case of Dr Andrew Dixon, rID 9613.

Chest CT of HIV-infected patient with PJP shows early findings of diffuse ground glass opacities, and chronic findings of linear opacities and thickening of interlobular septa. Courtesy of Radiopaedia (https://radiopaedia.org/), case of Dr Yune Kwong, rID 26697.

Chest radiograph in a patient with HIV infection and focal infiltrates due to tuberculosis.

Chest radiograph demonstrating diffuse bilateral infiltrates in a patient with Pneumocystis carinii pneumonia.

High-resolution computed tomography scan obtained through the upper lobes in the prone position in a patient with a history of Pneumocystis carinii pneumonia. This image shows parenchymal and subpleural cysts and patchy fibrosis that resulted from the Pneumocystis carinii infection.

Chest radiograph in a patient with HIV infection, bilateral perihilar infiltrates, and Pneumocystis carinii pericarditis.

CT of AML patient with a fungal pneumonia in the right upper lobe characterized by a cavitary lesion without air fluid levels. Courtesy of Radiopaedia (https://radiopaedia.org/), case of Dr Roberto Schubert, rID 17628.

Chest radiograph demonstrating diffuse bilateral infiltrates in a patient with Pneumocystis carinii pneumonia.

Chest radiograph in a patient with HIV infection and focal infiltrates due to tuberculosis.

High-resolution computed tomography scan obtained through the upper lobes in the prone position in a patient with a history of Pneumocystis carinii pneumonia. This image shows parenchymal and subpleural cysts and patchy fibrosis that resulted from the Pneumocystis carinii infection.

Chest radiograph demonstrating diffuse bilateral infiltrates in a patient with Pneumocystis carinii pneumonia.

High-resolution computed tomography scan obtained through the upper lobes in the prone position in a patient with a history of Pneumocystis carinii pneumonia. This image shows parenchymal and subpleural cysts and patchy fibrosis that resulted from the Pneumocystis carinii infection.

Chest radiograph in a patient with HIV infection, bilateral perihilar infiltrates, and Pneumocystis carinii pericarditis.

Chest radiograph in a patient with HIV infection and focal infiltrates due to tuberculosis.

Chest radiograph of HIV-infected patient with PJP shows diffuse patchy infiltrates with predominantly perihilar and interstitial prominence, as well as a few pneumatocoeles up to 1cm in size. Courtesy of Radiopaedia (https://radiopaedia.org/), case of Dr Andrew Dixon, rID 9613.

Chest CT of HIV-infected patient with PJP shows early findings of diffuse ground glass opacities, and chronic findings of linear opacities and thickening of interlobular septa. Courtesy of Radiopaedia (https://radiopaedia.org/), case of Dr Yune Kwong, rID 26697.

CT of AML patient with a fungal pneumonia in the right upper lobe characterized by a cavitary lesion without air fluid levels. Courtesy of Radiopaedia (https://radiopaedia.org/), case of Dr Roberto Schubert, rID 17628.