Opportunistic infection explained

An opportunistic infection is an infection caused by pathogens (bacteria, fungi, parasites or viruses) that take advantage of an opportunity not normally available. These opportunities can stem from a variety of sources, such as a weakened immune system (as can occur in acquired immunodeficiency syndrome or when being treated with immunosuppressive drugs, as in cancer treatment),^[1] an altered microbiome (such as a disruption in gut microbiota), or breached integumentary barriers (as in penetrating trauma). Many of these pathogens do not necessarily cause disease in a healthy host that has a non-compromised immune system, and can, in some cases, act as commensals until the balance of the immune system is disrupted.^{[2] [3]} Opportunistic infections can also be attributed to pathogens which cause mild illness in healthy individuals but lead to more serious illness when given the opportunity to take advantage of an immunocompromised host.^[4]

Types of opportunistic infections

A wide variety of pathogens are involved in opportunistic infection and can cause a similarly wide range in pathologies. A partial list of opportunistic pathogens and their associated presentations includes:

Bacteria

• Clostridioides difficile (formerly known as Clostridium difficile) is a species of bacteria that is known to cause gastrointestinal infection and is typically associated with the hospital setting.^{[5] [6]}
• Legionella pneumophila is a bacterium that causes Legionnaire's disease, a respiratory infection.^{[7] [8]}
• Mycobacterium avium complex (MAC) is a group of two bacteria, M. avium and M. intracellulare, that typically co-infect, leading to a lung infection called mycobacterium avium-intracellulare infection.^{[9] [10]}
• Mycobacterium tuberculosis is a species of bacteria that causes tuberculosis, a respiratory infection.^[11]
• Pseudomonas aeruginosa is a bacterium that can cause respiratory infections. It is frequently associated with cystic fibrosis and hospital-acquired infections.^[12]
• Salmonella is a genus of bacteria, known to cause gastrointestinal infections.^[13]
• Staphylococcus aureus is a bacterium known to cause skin infections and sepsis, among other pathologies. Notably, S. aureus has evolved several drug-resistant strains, including MRSA.^{[14] [15]}
• Streptococcus pneumoniae is a bacterium that causes respiratory infections.
• Streptococcus pyogenes (also known as group A Streptococcus) is a bacterium that can cause a variety of pathologies, including impetigo and strep throat, as well as other, more serious, illnesses.^{[16] [17]}

Fungi

• Aspergillus is a fungus, commonly associated with respiratory infection.^{[18] [19]}
• Candida albicans is a species of fungus that is associated with oral thrush and gastrointestinal infection.^{[20] [21]}
• Coccidioides immitis is a fungus known for causing coccidioidomycosis, more commonly known as Valley Fever.^[22]
• Cryptococcus neoformans is a fungus that causes cryptococcosis, which can lead to pulmonary infection as well as nervous system infections, like meningitis.^{[23] [24]}
• Histoplasma capsulatum is a species of fungus known to cause histoplasmosis, which can present with an array of symptoms, but often involves respiratory infection.^{[25] [26]}
• Pseudogymnoascus destructans (formerly known as Geomyces destructans) is a fungus that causes white-nose syndrome in bats.^[27]
• Microsporidia is a group of fungi that infect species across the animal kingdom, one species of which can cause microsporidiosis in immunocompromised human hosts.^[28]
• Pneumocystis jirovecii (formerly known as Pneumocystis carinii) is a fungus that causes pneumocystis pneumonia, a respiratory infection.^[29]

Parasites

• Cryptosporidium is a protozoan that infects the gastrointestinal tract.^[30]
• Toxoplasma gondii is a protozoan, known for causing toxoplasmosis.^{[31] [32]}

Viruses

• Cytomegalovirus is a family of opportunistic viruses, most frequently associated with respiratory infection.^[33]
• Human polyomavirus 2 (also known as JC virus) is known to cause progressive multifocal leukoencephalopathy (PML).^{[34] [35]}
• Human herpesvirus 8 (also known as Kaposi sarcoma-associated herpesvirus) is a virus associated with Kaposi sarcoma, a type of cancer.^{[36] [37]}

Causes

Immunodeficiency or immunosuppression are characterized by the absence of or disruption in components of the immune system, leading to lower-than-normal levels of immune function and immunity against pathogens. They can be caused by a variety of factors, including:

• Malnutrition
• Fatigue
• Recurrent infections
• Immunosuppressing agents for organ transplant recipients
• Advanced HIV infection
• Chemotherapy for cancer
• Genetic predisposition
• Skin damage
• Antibiotic treatment leading to disruption of the physiological microbiome, thus allowing some microorganisms to outcompete others and become pathogenic (e.g. disruption of intestinal microbiota may lead to Clostridium difficile infection)
• Medical procedures
• Pregnancy
• Aging
• Leukopenia (i.e. neutropenia and lymphocytopenia)
• Burns

The lack of or the disruption of normal vaginal microbiota allows the proliferation of opportunistic microorganisms and will cause the opportunistic infection bacterial vaginosis.^{[38] [39] [40] [41]}

Opportunistic Infection and HIV/AIDS

HIV is a virus that targets T cells of the immune system and, as a result, HIV infection can lead to progressively worsening immunodeficiency, a condition ideal for the development of opportunistic infection.^{[42] [43]} Because of this, respiratory and central nervous system opportunistic infections, including tuberculosis and meningitis, respectively, are associated with later-stage HIV infection, as are numerous other infectious pathologies.^{[44] [45]} Kaposi's sarcoma, a virally-associated cancer, has higher incidence rates in HIV-positive patients than in the general population.^[46] As immune function declines and HIV-infection progresses to AIDS, individuals are at an increased risk of opportunistic infections that their immune systems are no longer capable of responding properly to. Because of this, opportunistic infections are a leading cause of HIV/AIDS-related deaths.^[47]

Prevention

Since opportunistic infections can cause severe disease, much emphasis is placed on measures to prevent infection. Such a strategy usually includes restoration of the immune system as soon as possible, avoiding exposures to infectious agents, and using antimicrobial medications ("prophylactic medications") directed against specific infections.^[48]

Restoration of immune system

• In patients with HIV, starting antiretroviral therapy is especially important for restoration of the immune system and reducing the incidence rate of opportunistic infections^{[49] [50]}
• In patients undergoing chemotherapy, completion of and recovery from treatment is the primary method for immune system restoration. In a select subset of high risk patients, granulocyte colony stimulating factors (G-CSF) can be used to aid immune system recovery.^{[51] [52]}

Avoidance of infectious exposure

The following may be avoided as a preventative measure to reduce risk of infection:

• Eating undercooked meat or eggs, unpasteurized dairy products or juices.
• Potential sources of tuberculosis (high risk healthcare facilities, regions with high rates of tuberculosis, patients with known tuberculosis).
• Any oral exposure to feces.^[53]
• Contact with farm animals, especially those with diarrhea: source of Toxoplasma gondii, Cryptosporidium parvum.
• Cat feces (e.g. cat litter): source of Toxoplasma gondii, Bartonella spp.
• Soil/dust in areas where there is known histoplasmosis, coccidiomycosis.
• Reptiles, chicks, and ducklings that are a common source of Salmonella.
• Unprotected sexual intercourse with individuals with known sexually transmitted infections.

Prophylactic medications

Individuals at higher risk are often prescribed prophylactic medication to prevent an infection from occurring. A person's risk level for developing an opportunistic infection is approximated using the person's CD4 T-cell count and other indications. The table below provides information regarding the treatment management of common opportunistic infections.^{[54] [55] [56]}

Opportunistic infections	Indication(s) for prophylactic medications	Preferred agent(s)	When to discontinue agent(s)	Secondary prophylactic/maintenance agent(s)
Mycobacterium tuberculosis	Upon diagnosis of HIV, any positive screening test, or prior medical history of Mycobacterium tuberculosis.	Rifampicin Isoniazid Pyridoxine Pyrazinamide Ethambutol	These current agents' doses/frequency will discontinue after two months. Depending on clinical presentation, maintenance agents will continue for at least four more months.	Rifampicin, isoniazid, and pyridoxine
Pneumocystis jiroveci	CD4 count is less than 200 cells/mm^3 or less than 14%. The person has documented medical history of recurrent oropharyngeal candidiasis.	Trimethoprim-sulfamethoxazole	This current agent doses/frequency will discontinue after 21 days. Secondary prophylactic agent dose/frequency will continue until the CD4 count is above 200 cells/mm^3 and the HIV viral load is undetectable for at least three months while taking antiretroviral therapy.	Trimethoprim-sulfamethoxazole
Toxoplasma gondii	CD4 count is less than 100 cells/mm^3 or less than 14%, and the person has a positive serology for Toxoplasma gondii.	Trimethoprim-sulfamethoxazole	This agent will discontinue after six weeks. Secondary prophylactic medications will continue until the CD4 count is above 200 cells/mm^3 and HIV viral load is undetectable for at least six months while taking antiretroviral therapy.	Sulfadiazine, pyrimethamine, and folinic acid
Mycobacterium avium complex disease	CD4 count is less than 50 cells/mm^3 and has a detectable viral load while taking antiretroviral therapy.	Clarithromycin and ethambutol Rifabutin may be added depending on clinical presentation.	These agent(s) will discontinue after 12 months only if the person does not have any symptoms that will be concerning for persistent Mycobacterium avium complex disease and their CD4 count is above 100 cells/mm^3, and while their HIV viral load is undetectable for at least six months while taking antiretroviral therapy.	N/A

Alternative agents can be used instead of the preferred agents. These alternative agents may be used due to allergies, availability, or clinical presentation. The alternative agents are listed in the table below.

Opportunistic infections	Alternative agent(s)
Mycobacterium tuberculosis	Rifabutin
Pneumocystis jiroveci	Dapsone Atovaquone Pentamidine
Toxoplasma gondii	Dapsone, pyrimethamine, and folinic acid Atovaquone, pyrimethamine, and folinic acid
Mycobacterium avium complex disease	Azithromycin and ethambutol

Treatment

Treatment depends on the type of opportunistic infection, but usually involves different antibiotics.

Veterinary treatment

Opportunistic infections caused by feline leukemia virus and feline immunodeficiency virus retroviral infections can be treated with lymphocyte T-cell immunomodulator.

Notes and References

1. Book: Justiz Vaillant AA, Qurie A . Immunodeficiency . 2021 . http://www.ncbi.nlm.nih.gov/books/NBK500027/ . StatPearls . Treasure Island (FL) . StatPearls Publishing . 29763203 . 2021-03-09 .
2. Schroeder MR, Stephens DS . Macrolide Resistance in Streptococcus pneumoniae . Frontiers in Cellular and Infection Microbiology . 6 . 98 . 2016-09-21 . 27709102 . 5030221 . 10.3389/fcimb.2016.00098 . free .
3. Achermann Y, Goldstein EJ, Coenye T, Shirtliff ME . Propionibacterium acnes: from commensal to opportunistic biofilm-associated implant pathogen . Clinical Microbiology Reviews . 27 . 3 . 419–40 . July 2014 . 24982315 . 4135900 . 10.1128/CMR.00092-13 .
4. Caballero MT, Polack FP . Respiratory syncytial virus is an "opportunistic" killer . Pediatric Pulmonology . 53 . 5 . 664–667 . May 2018 . 29461021 . 5947624 . 10.1002/ppul.23963 .
5. Czepiel J, Dróżdż M, Pituch H, Kuijper EJ, Perucki W, Mielimonka A, Goldman S, Wultańska D, Garlicki A, Biesiada G . 6 . Clostridium difficile infection: review . European Journal of Clinical Microbiology & Infectious Diseases . 38 . 7 . 1211–1221 . July 2019 . 30945014 . 6570665 . 10.1007/s10096-019-03539-6 .
6. Guh AY, Kutty PK . Clostridioides difficile Infection . Annals of Internal Medicine . 169 . 7 . ITC49–ITC64 . October 2018 . 30285209 . 6524133 . 10.7326/AITC201810020 .
7. Chahin A, Opal SM . Severe Pneumonia Caused by Legionella pneumophila: Differential Diagnosis and Therapeutic Considerations . Infectious Disease Clinics of North America . 31 . 1 . 111–121 . March 2017 . 28159171 . 7135102 . 10.1016/j.idc.2016.10.009 .
8. Berjeaud JM, Chevalier S, Schlusselhuber M, Portier E, Loiseau C, Aucher W, Lesouhaitier O, Verdon J . 6 . Legionella pneumophila: The Paradox of a Highly Sensitive Opportunistic Waterborne Pathogen Able to Persist in the Environment . Frontiers in Microbiology . 7 . 486 . 2016-04-08 . 27092135 . 4824771 . 10.3389/fmicb.2016.00486 . free .
9. Falkinham JO . Mycobacterium avium complex: Adherence as a way of life . AIMS Microbiology . 4 . 3 . 428–438 . 2018 . 31294225 . 6604937 . 10.3934/microbiol.2018.3.428 .
10. Pan SW, Shu CC, Feng JY, Su WJ . Treatment for Mycobacterium avium complex lung disease . Journal of the Formosan Medical Association = Taiwan Yi Zhi . 119 . S67–S75 . June 2020 . Suppl 1 . 32446754 . 10.1016/j.jfma.2020.05.006 . free .
11. Gordon SV, Parish T . Microbe Profile: Mycobacterium tuberculosis: Humanity's deadly microbial foe . Microbiology . 164 . 4 . 437–439 . April 2018 . 29465344 . 10.1099/mic.0.000601 . free .
12. Pang Z, Raudonis R, Glick BR, Lin TJ, Cheng Z . Antibiotic resistance in Pseudomonas aeruginosa: mechanisms and alternative therapeutic strategies . Biotechnology Advances . 37 . 1 . 177–192 . January–February 2019 . 30500353 . 10.1016/j.biotechadv.2018.11.013 . free .
13. Lamas A, Miranda JM, Regal P, Vázquez B, Franco CM, Cepeda A . A comprehensive review of non-enterica subspecies of Salmonella enterica . Microbiological Research . 206 . 60–73 . January 2018 . 29146261 . 10.1016/j.micres.2017.09.010 .
14. Jenul C, Horswill AR . Regulation of Staphylococcus aureus Virulence . Microbiology Spectrum . 7 . 2 . April 2019 . 30953424 . 6452892 . 10.1128/microbiolspec.GPP3-0031-2018 .
15. Kong C, Neoh HM, Nathan S . Targeting Staphylococcus aureus Toxins: A Potential form of Anti-Virulence Therapy . Toxins . 8 . 3 . 72 . March 2016 . 26999200 . 4810217 . 10.3390/toxins8030072 . free .
16. Jespersen MG, Lacey JA, Tong SY, Davies MR . Global genomic epidemiology of Streptococcus pyogenes . Infection, Genetics and Evolution . 86 . 104609 . December 2020 . 33147506 . 10.1016/j.meegid.2020.104609 . free .
17. Brouwer S, Barnett TC, Rivera-Hernandez T, Rohde M, Walker MJ . Streptococcus pyogenes adhesion and colonization . FEBS Letters . 590 . 21 . 3739–3757 . November 2016 . 27312939 . 10.1002/1873-3468.12254 . 10033/619157 . 205213711 . free .
18. Latgé JP, Chamilos G . Aspergillus fumigatus and Aspergillosis in 2019 . Clinical Microbiology Reviews . 33 . 1 . e00140–18, /cmr/33/1/CMR.00140–18.atom . December 2019 . 31722890 . 6860006 . 10.1128/CMR.00140-18 .
19. José RJ, Periselneris JN, Brown JS . Opportunistic bacterial, viral and fungal infections of the lung . Medicine . 48 . 6 . 366–372 . June 2020 . 32390758 . 7206443 . 10.1016/j.mpmed.2020.03.006 .
20. Akpan A, Morgan R . Oral candidiasis . Postgraduate Medical Journal . 78 . 922 . 455–9 . August 2002 . 12185216 . 1742467 . 10.1136/pmj.78.922.455 .
21. Erdogan A, Rao SS . Small intestinal fungal overgrowth . Current Gastroenterology Reports . 17 . 4 . 16 . April 2015 . 25786900 . 10.1007/s11894-015-0436-2 . 3098136 .
22. Mu A, Shein TT, Jayachandran P, Paul S . Immune Reconstitution Inflammatory Syndrome in Patients with AIDS and Disseminated Coccidioidomycosis: A Case Series and Review of the Literature . Journal of the International Association of Providers of AIDS Care . 16 . 6 . 540–545 . 2017-09-14 . 28911256 . 10.1177/2325957417729751 . free .
23. Kwon-Chung KJ, Fraser JA, Doering TL, Wang Z, Janbon G, Idnurm A, Bahn YS . Cryptococcus neoformans and Cryptococcus gattii, the etiologic agents of cryptococcosis . Cold Spring Harbor Perspectives in Medicine . 4 . 7 . a019760 . July 2014 . 24985132 . 4066639 . 10.1101/cshperspect.a019760 .
24. Maziarz EK, Perfect JR . Cryptococcosis . Infectious Disease Clinics of North America . 30 . 1 . 179–206 . March 2016 . 26897067 . 5808417 . 10.1016/j.idc.2015.10.006 .
25. Horwath MC, Fecher RA, Deepe GS . Histoplasma capsulatum, lung infection and immunity . Future Microbiology . 10 . 6 . 967–75 . 2015-06-10 . 26059620 . 4478585 . 10.2217/fmb.15.25 .
26. Mittal J, Ponce MG, Gendlina I, Nosanchuk JD . Histoplasma Capsulatum: Mechanisms for Pathogenesis . Current Topics in Microbiology and Immunology . 422 . 157–191 . 2018 . 30043340 . 7212190 . 10.1007/82_2018_114 . Springer International Publishing . 978-3-030-30236-8 . Cham . Rodrigues ML .
27. Seyedmousavi S, Bosco SM, de Hoog S, Ebel F, Elad D, Gomes RR, Jacobsen ID, Jensen HE, Martel A, Mignon B, Pasmans F, Piecková E, Rodrigues AM, Singh K, Vicente VA, Wibbelt G, Wiederhold NP, Guillot J . 6 . Fungal infections in animals: a patchwork of different situations . Medical Mycology . 56 . suppl_1 . 165–187 . April 2018 . 29538732 . 6251577 . 10.1093/mmy/myx104 .
28. Stentiford GD, Becnel JJ, Weiss LM, Keeling PJ, Didier ES, Bjornson S, Freeman MA, Brown MJ, Roesel K, Sokolova Y, Snowden KF, Solter L . 6 . Microsporidia - Emergent Pathogens in the Global Food Chain . Trends in Parasitology . 32 . 4 . 336–348 . April 2016 . 26796229 . 4818719 . 10.1016/j.pt.2015.12.004 .
29. Sokulska M, Kicia M, Wesołowska M, Hendrich AB . Pneumocystis jirovecii--from a commensal to pathogen: clinical and diagnostic review . Parasitology Research . 114 . 10 . 3577–85 . October 2015 . 26281787 . 4562001 . 10.1007/s00436-015-4678-6 .
30. Gerace E, Lo Presti VD, Biondo C . Cryptosporidium Infection: Epidemiology, Pathogenesis, and Differential Diagnosis . European Journal of Microbiology & Immunology . 9 . 4 . 119–123 . December 2019 . 31934363 . 6945992 . 10.1556/1886.2019.00019 .
31. Mendez OA, Koshy AA . Toxoplasma gondii: Entry, association, and physiological influence on the central nervous system . PLOS Pathogens . 13 . 7 . e1006351 . July 2017 . 28727854 . 5519211 . 10.1371/journal.ppat.1006351 . Gubbels MJ . free .
32. Hunter CA, Sibley LD . Modulation of innate immunity by Toxoplasma gondii virulence effectors . Nature Reviews. Microbiology . 10 . 11 . 766–78 . November 2012 . 23070557 . 3689224 . 10.1038/nrmicro2858 .
33. Fonseca Brito L, Brune W, Stahl FR . Cytomegalovirus (CMV) Pneumonitis: Cell Tropism, Inflammation, and Immunity . International Journal of Molecular Sciences . 20 . 16 . 3865 . August 2019 . 31398860 . 6719013 . 10.3390/ijms20163865 . free .
34. Bohra C, Sokol L, Dalia S . Progressive Multifocal Leukoencephalopathy and Monoclonal Antibodies: A Review . Cancer Control . 24 . 4 . 1073274817729901 . 2017-11-01 . 28975841 . 5937251 . 10.1177/1073274817729901 .
35. Kartau M, Sipilä JO, Auvinen E, Palomäki M, Verkkoniemi-Ahola A . Progressive Multifocal Leukoencephalopathy: Current Insights . Degenerative Neurological and Neuromuscular Disease . 9 . 109–121 . 2019-12-02 . 31819703 . 6896915 . 10.2147/DNND.S203405 . free .
36. Radu O, Pantanowitz L . Kaposi sarcoma . Archives of Pathology & Laboratory Medicine . 137 . 2 . 289–94 . February 2013 . 23368874 . 10.5858/arpa.2012-0101-RS .
37. Cesarman E, Damania B, Krown SE, Martin J, Bower M, Whitby D . Kaposi sarcoma . Nature Reviews. Disease Primers . 5 . 1 . 9 . January 2019 . 30705286 . 6685213 . 10.1038/s41572-019-0060-9 .
38. Africa CW, Nel J, Stemmet M . Anaerobes and bacterial vaginosis in pregnancy: virulence factors contributing to vaginal colonisation . International Journal of Environmental Research and Public Health . 11 . 7 . 6979–7000 . July 2014 . 25014248 . 4113856 . 10.3390/ijerph110706979 . free .
39. Mastromarino P, Vitali B, Mosca L . Bacterial vaginosis: a review on clinical trials with probiotics . The New Microbiologica . 36 . 3 . 229–38 . July 2013 . 23912864 .
40. Mastromarino P, Vitali B, Mosca L . Bacterial vaginosis: a review on clinical trials with probiotics . The New Microbiologica . 36 . 3 . 229–38 . July 2013 . 23912864 .
41. Knoester M, Lashley LE, Wessels E, Oepkes D, Kuijper EJ . First report of Atopobium vaginae bacteremia with fetal loss after chorionic villus sampling . Journal of Clinical Microbiology . 49 . 4 . 1684–6 . April 2011 . 21289141 . 3122803 . 10.1128/JCM.01655-10 .
42. Doitsh G, Greene WC . Dissecting How CD4 T Cells Are Lost During HIV Infection . Cell Host & Microbe . 19 . 3 . 280–91 . March 2016 . 26962940 . 4835240 . 10.1016/j.chom.2016.02.012 .
43. Fenwick C, Joo V, Jacquier P, Noto A, Banga R, Perreau M, Pantaleo G . T-cell exhaustion in HIV infection . Immunological Reviews . 292 . 1 . 149–163 . November 2019 . 31883174 . 7003858 . 10.1111/imr.12823 .
44. Bruchfeld J, Correia-Neves M, Källenius G . Tuberculosis and HIV Coinfection . Cold Spring Harbor Perspectives in Medicine . 5 . 7 . a017871 . February 2015 . 25722472 . 4484961 . 10.1101/cshperspect.a017871 .
45. Tenforde MW, Shapiro AE, Rouse B, Jarvis JN, Li T, Eshun-Wilson I, Ford N . Treatment for HIV-associated cryptococcal meningitis . The Cochrane Database of Systematic Reviews . 2018 . CD005647 . July 2018 . 7 . 30045416 . 6513250 . 10.1002/14651858.CD005647.pub3 . Cochrane Infectious Diseases Group .
46. Rees CA, Keating EM, Lukolyo H, Danysh HE, Scheurer ME, Mehta PS, Lubega J, Slone JS . 6 . Mapping the Epidemiology of Kaposi Sarcoma and Non-Hodgkin Lymphoma Among Children in Sub-Saharan Africa: A Review . Pediatric Blood & Cancer . 63 . 8 . 1325–31 . August 2016 . 27082516 . 7340190 . 10.1002/pbc.26021 .
47. Book: Sadiq U, Shrestha U, Guzman M . Prevention Of Opportunistic Infections In HIV . 2021 . http://www.ncbi.nlm.nih.gov/books/NBK513345/. StatPearls . Treasure Island (FL) . StatPearls Publishing . 30020717 . 2021-03-09 .
48. Book: Schlossberg D . Clinical Infectious Disease. 2015-04-23. Cambridge University Press. 978-1-107-03891-2. 688–.
49. Ledergerber B, Egger M, Erard V, Weber R, Hirschel B, Furrer H, Battegay M, Vernazza P, Bernasconi E, Opravil M, Kaufmann D, Sudre P, Francioli P, Telenti A . 6 . AIDS-related opportunistic illnesses occurring after initiation of potent antiretroviral therapy: the Swiss HIV Cohort Study . JAMA . 282 . 23 . 2220–6 . December 1999 . 10605973 . 10.1001/jama.282.23.2220 .
50. Brooks JT, Kaplan JE, Holmes KK, Benson C, Pau A, Masur H . HIV-associated opportunistic infections--going, going, but not gone: the continued need for prevention and treatment guidelines . Clinical Infectious Diseases . 48 . 5 . 609–11 . March 2009 . 19191648 . 10.1086/596756 . 39742988 .
51. Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR . 6 . Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america . Clinical Infectious Diseases . 52 . 4 . e56-93 . February 2011 . 21258094 . 10.1093/cid/cir073 .
52. Smith TJ, Khatcheressian J, Lyman GH, Ozer H, Armitage JO, Balducci L, Bennett CL, Cantor SB, Crawford J, Cross SJ, Demetri G, Desch CE, Pizzo PA, Schiffer CA, Schwartzberg L, Somerfield MR, Somlo G, Wade JC, Wade JL, Winn RJ, Wozniak AJ, Wolff AC . 6 . 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline . Journal of Clinical Oncology . 24 . 19 . 3187–205 . July 2006 . 16682719 . 10.1200/JCO.2006.06.4451 . free .
53. Web site: 26 May 2020. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. 28 November 2020.
54. Book: Dyer . Mary . Comprehensive Primary Care for Adults With HIV . Kerr . Christine . McGowan . Joseph P. . Fine . Steven M. . Merrick . Samuel T. . Stevens . Lyn C. . Hoffmann . Christopher J. . Gonzalez . Charles J. . 2021 . Johns Hopkins University . New York State Department of Health AIDS Institute Clinical Guidelines . Baltimore (MD) . 33625815.
55. Web site: European AIDS Clinical Society Guidelines .
56. Web site: Table 2. Treatment of HIV-Associated Opportunistic Infections (Includes Recommendations for Acute Treatment and Secondary Prophylaxis/Chronic Suppressive/Maintenance Therapy) NIH . 2023-02-20 . clinicalinfo.hiv.gov . en.