Pneumocystis Jirovecii Enfeksiyonu: Epidemiyoloji, Klinik Özellikler, Tanı ve Tedavi
Özet
Pneumocystis jiroveci bağışıklık sistemi baskılanmış hastalarda özellikle akciğer tutulumu ile seyreden fırsatçı bir patojendir. Risk grupları arasında insan immun yetmezlik virusu (HIV) ile yaşayan bireyler, solid organ veya hematolojik malignitesi olanlar, transplantasyon yapılanlar, uzun süre kortikosteroid (KS) kullananlar, immunsupresif tedavi alanlar yer almaktadır. İmmunkompetan kolonize bireyler bulaş açısından rezervuar görevi yapmaktadır. Literatürde insandan insana bulaş ve olası çevresel rezervuarların varlığı ele alınmıştır. Çevresel rezervuarlar hava ve su olup, kamp ve yürüyüş aktiviteleri ile ilişkilendirilmiştir. Trofik formların alveol epiteline bağlanmasıyla, alveolar epitel hücreleri ve alveolar makrofajlar ile etkileşim sonucu hem organizmada hem de akciğer hücrelerinde bir hücresel yanıt kaskadı tetiklenir. Trofozoitlerin pnömositlere bağlanması sonucu tetiklenen bu kaskad sonucunda alveolar septalarda ödem, kalınlaşma ve fibrozis oluşur. Bu değişimlerin klinik yansıması akciğer kompliyansı ve gaz değişiminde bozulma, hipoksi, alveolar- arteryel oksijen gradiyentinde artma, respiratuar alkaloz, difüzyon kapasitesinde azalma ile sonuçlanan interstisyel plazma hücreli pnömoni tablosudur. Tanıda BAL’ da organizmanın immünofloresan veya özel boyalarla mikroskobik olarak gösterilmesi altın standarttır. Tedavide trimetoprim sulfametoksazol (TMP-SXT) birinci seçenek ilaçtır. TMP-SXT 21 gün süre ile kullanılmalıdır. Orta ve ağır şiddetteki, PaO2 <70 mmHg veya alveoler/arteryel oksijen gradiyenti >35 mmHg olan olgularda tedaviye KS eklenmesi önerilmektedir.
Pneumocystis jiroveci is especially harmful to the lungs in immunocompromised patients.
It is an opportunistic pathogen that progresses with infection. Human immunity among risk groups people living with HIV, solid organ or hematological those with malignancy, those who have undergone transplantation, those who use corticosteroids (CS) for a long time users and those receiving immunosuppressive treatment. Immunocompetent colonized Individuals act as reservoirs for transmission from humans in literatüre. Transmission to humans and the existence of possible environmental reservoirs are discussed. The environmental reservoirs are air and water and are associated with camping and hiking activities. By binding of trophic forms to the alveolar epithelium, a cellular response cascade is triggered in both the organism and lung cells as a result of interaction with alveolar epithelial cells and alveolar macrophages. As a result of this cascade triggered by the binding of trophozoites to pneumocytes, Edema, thickening and fibrosis occur in the alveolar septa. These changes are clinically. Its reflection is impaired lung compliance and gas exchange, hypoxia, alveolar-
increased arterial oxygen gradient, respiratory alkalosis, decreased diffusion capacity
It is a picture of interstitial plasma cell pneumonia resulting in a decrease in In diagnosis, microscopic demonstration of the organism in BAL with immunofluorescence or special dyes is the gold standard. Trimethoprim sulfamethoxazole (TMP-SXT) is the first choice drug in treatment. TMP-SXT should be used for 21 days. It is recommended to add CS to the treatment in moderate and severe cases with PaO2 <70 mmHg or alveolar/arterial oxygen gradient >35 mmHg.
Referanslar
Thomas CF Jr, Limper AH. Pneumocystis pneumonia. N Engl J Med. 2004; 350:2487-2498. DOI: 10.1056/NEJMra032588
Thomas CF Jr, Limper AH. Current insights into the biology and pathogenesis of Pneumocystispneumonia. Nat Rev Microbiol. 2007; 5: 298-308. DOI: 10.1038/nrmicro1621
Ng VL, Yajko DM, Hadley WK. Extrapulmonary pneumo- cystosis. Clin Microbiol Rev. 1997; 10: 401-418. DOI: 10.1128/CMR.10.3.401
Rodriguez M, Fishman JA. Prevention of infection due to pneumocystis spp. in human immunodeficiency virüs-negative immunocompromised patients. Clin Microbiol Rev. 2004;17:770-782. DOI: 10.1128/CMR.17.4.770-782.2004
Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America: Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Available from: https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/pneumocystis (2023) (Accessed 15th July 2024).
Vera C, Rueda ZV. Transmission and colonization of Pneumocystis jirovecii. J Fungi 2021;7(11):979. DOI: 10.3390/jof7110979
Edman JC, Kovacs JA, Masur H, et al. Ribosomal RNA sequence shows Pneumocystis carinii to be a member of the Fungi. Nature. 1988; 334:519-522. DOI: 10.1038/334519a0
Catherinot E, Lanternier F, Bougnoux ME, et al. Pneumocystis jirovecii pneumonia. Infect Dis Clin North Am. 2010;24:107–138. DOI: 10.1016/j.idc.2009.10.010
Hughes WT. Prologue to AIDS: the recognition of infectious opportunists. Medicine (Baltimore.) 1998;77:227–232. DOI: 10.1097/00005792-199807000-00001
McDonald EG, Afshar A, Assiri B, et al. Pneumocystis jirovecii pneumonia in people living with HIV: a review. Clin Microbiol Rev. 2024; 37:e0010122. DOI: 10.1128/cmr.00101-22
Olsson M, Lidman C, Latouche S, et al. Identification of Pneumocystis carinii f. sp. hominis gene sequences in filtered air in hospital environments. J Clin Microbiol. 1998; 36:1737–1740. DOI: 10.1128/JCM.36.6.1737-1740.1998
Hughes, WT, Bartley DL, Smith BM. A natural source of infection due to Pneumocystis carinii. J. Infect. Dis. 1983; 147, 595. DOI: 10.1093/infdis/147.3.595
Choukri F, Menotti J, Sarfati C, et al. Quantification and spread of Pneumocystis jirovecii in the surrounding air of patients with Pneumocystis pneumonia. Clin. Infect. Dis. 2010; 51: 259–265. DOI: 10.1086/653933
Navin TR, Rimland D, Lennox JL, et al. Risk factors for community-acquired pneumonia among persons infected with human immunodeficiency virus. J Infect Dis. 2020;181:158–164. DOI: 10.1086/315196
Keely SP, Stringer JR, Baughman RP, et al. Genetic variation among Pneumocystis carinii hominis isolates in recurrent pneumocystosis. J Infect Dis. 1995;595–598. DOI: 10.1093/infdis/172.2.595
Elbüken G. Pneumocystis jiroveci enfeksiyonu ve akciğer tutulumu. Uludağ Üniversitesi Tıp Fakültesi Dergisi. 2007;33:97-103.
Kennedy CA,Goetz MB. Atypical roentgenographic manifestations of Pneumocystis carinii pneumonia. Arch. Intern. Med. 1992;152: 1390–1398.
Hsu JM, Hass A, Gingras MA, et al. Radiographic features in investigated for Pneumocystis jirovecii pneumonia: a nested case-control study. BMC Infect Dis. 2020: 20:492. DOI: 10.1186/s12879-020-05217-x
Quist J, Hill AR. Serum lactate dehydrogenase (LDH) in Pneumocystis carinii pneumonia, tuberculosis, and bacterial pneumo¬nia. Chest. 1995; 108:415–418. DOI: 10.1378/chest.108.2.415
Esteves F, Calé SS, Badura R, et al. Diagnosis of Pneumocystis pneumonia: evaluation of four serologic biomarkers. Clin Microbiol Infect. 2015;21:379. DOI: 10.1016/j.cmi.2014.11.025
Vogel MN, Weissgerber P, Goeppert B, et al. Accuracy of serum LDH elevation for the diagnosis of Pneumocystis jiroveci pneumonia. Swiss Med Wkly. 2011;141:w13184. DOI: 10.4414/smw.2011.13184
Del Corpo O, Butler-Laporte G, Sheppard DC, et al. Diagnostic accuracy of serum (1-3)-β-D-glucan for Pneumocystis jirovecii pneumonia: a systematic review and meta- analysis. Clinical Microbiology and Infection. 2020; 26:1137–1143. DOI: 10.1016/j.cmi.2020.05.024
Juniper T, Eades CP, Gil E, et al. Use of Β-D-Glucan in diagnosis of suspected Pneumocystis Jirovecii pneumonia in adults with HIV infection. Int J STD AIDS. 2021; 32:1074–1077. DOI: 10.1177/09564624211022247
McTaggart LR, Wengenack NL, Richardson SE. Validation of the Mycassay Pneumocystis kit for detection of Pneumocystis Jirovecii in Bronchoalveolar Lavage specimens by comparison to a laboratory standard of direct Immunofluorescence microscopy, real-time PCR, or conventional PCR. J Clin Microbiol. 2012; 50:1856–1859. DOI: 10.1128/JCM.05880-11
Senécal J, Smyth E, Del Corpo O, et al. Non-invasive diagnosis of Pneumocystis jirovecii pneumonia: a systematic review and meta-analysis. Clin Microbiol Infect. 2022; 28:23–30. DOI: 10.1016/j.cmi.2021.08.017
Bateman M, Oladele R, Kolls JK. Diagnosing Pneumocystis jirovecii pneumonia: a review of current methods and novel approaches. Med Mycol. 2020;58:1015–1028. DOI: 10.1093/mmy/myaa024
Bedrossian C.W., Mason M.R., Gupta P.K. Rapid cytologic diagnosis of Pneumocystis: a comparison of effective techniques. Semin Diagn Pathol. 1989; 6(3): 245–61.
Kovacs JA, Ng VL, Masur H, et al. Diagnosis of Pneumocystis carinii pneumonia: improved detection in sputum with use of monoclonal antibodies. N Engl J Med. 1988;318:589–593. DOI: 10.1056/NEJM198803103181001
Alanio A, Desoubeaux G, Sarfati C, et al. Real-time PCR assay-based strategy for differentiation between active Pneumocystis jirovecii pneumonia and colonization in immunocompromised patients. Clin Microbiol Infect. 2011;17:1531–1537. DOI: 10.1111/j.1469-0691.2010.03400.x
Matsumura Y, Ito Y, Iinuma Y, et al. Quantitative real-time PCR and the (1 → 3)-β-d-glucan assay for differentiation between Pneumocystis jirovecii pneumonia and colonization. Clin Microbiol Infect. 2012;18:591–597. DOI: 10.1111/j.1469-0691.2011.03605.x
Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. 2023. Available from: https://www. idsociety.org/practice-guideline/prevention-and-treatment-of- opportunistic-infections-among-adults-and-adolescents.
Kaplan JE, Benson C, Holmes KK, et al. Centers for Disease Control and Prevention (CDC), National Institutes of Health, HIV Medicine Association of the Infectious Diseases Society of America. 2009. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from CDC,the National Institutes of health, and the HIV medicine Association of the infectious diseases society of America. MMWR Recomm Rep. 58:1–207.
Ryom L, De Miguel R, Cotter AG, et al. Major revision version 11.0 of the European AIDS clinical society 1083 guidelines 2021. HIV Med. 2022;23:849–858. DOI: 10.1111/hiv.13268
Kirby AJ, Munoz A, Detels R, et al. Thrush and fever as measures of immunocompetence in HIV-1-infected men. J Acquir Immune Defic Syndr. 1994; 7:1242-1249.
Ioannidis JP, Cappelleri JC, Skolnik PR, et al. A meta- analysis of the relative efficacy and toxicity of Pneumocystis carinii prophylactic regimens. Arch Intern Med. 1996;156:177–188
DiRienzo AG, van Der Horst C, Finkelstein DM et al. Efficacy of trimethoprim-sulfamethoxazole for the prevention of bacterial infections in a randomized prophylaxis trial of patients with advanced HIV infection. AIDS Res Hum Retroviruses. 2002; 18: 89–94. DOI: 10.1089/08892220252779629
Schneider MM, Nielsen TL, Nelsing S,et al. Efficacy and toxicity of two doses of trimethoprim-sulfamethoxazole as primary prophylaxis against Pneumocystis carinii pneumonia in patients with human immunodeficiency virus. J Infect Dis. 1995;171:1632–1636. DOI: 10.1093/infdis/171.6.1632
Ena J, Amador C, Pasquau F, et al. Once-a-month administration of intravenous pentamidine to patients infected with human immunodeficiency virus as prophylaxis for Pneumocystis carinii pneumonia. Clin Infect Dis. 1994;18:901–904. DOI: 10.1093/clinids/18.6.901
Cushion MT, Ashbaugh A. The long-acting echinocandin, rezafungin, prevents Pneumocystis pneumonia and eliminates Pneumocystis from the lungs in prophylaxis and murine treatment models. J Fungi. 2021;7:747. DOI: 10.3390/jof7090747
Butler-Laporte G, Smyth E, Amar-Zifkin A, et al. Low-dose TMP-SMX in the treatment of Pneumocystis jirovecii pneumonia: a systematic review and meta-analysis. Open Forum Infect Dis. 2020;7:ofaa112. DOI: 10.1093/ofid/ofaa112
Creemers-Schild D, Kroon FP, Kuijper EJ, et al. Treatment of Pneumocystis pneumonia with intermediate-dose and step-down to low-dose trimethoprim-sulfamethoxazole: lessons from an observational cohort study. Infection. 2016;44:291–299. DOI: 10.1007/s15010-015-0851-1
Block F, Schmitt T, Schwarz M. Pentamidine, an inhibitor of spinal flexor reflexes in rats, is a potent N-methyl-D-aspartate (NMDA) antagonist in vivo. Neurosci Lett. 1993;155:208–211. DOI: 10.1016/0304-3940(93)90709-t
Chan C, Montaner J, Lefebvre EA, et al. Atovaquone suspension compared with aerosolized pentamidine for prevention of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected subjects intolerant of trimethoprim or sulfonamides. J Infect Dis. 1999;180:369–376. DOI: 10.1086/314893
Hughes W, Leoung G, Kramer F, et al. Comparison of atovaquone (566C80) with trimethoprim-sulfamethoxazole to treat Pneumocystis carinii pneumonia in patients with AIDS. N Engl J Med. 1993;328:1521–1527. DOI: 10.1056/NEJM199305273282103
Huang Y-S, Yang J-J, Lee N-Y, et al. Treatment of Pneumocystis jirovecii pneumonia in HIV-infected patients: a review. Expert Rev Anti Infect Ther. 2017;15:873–892. DOI: 10.1080/14787210.2017.1364991
Kato H, Hagihara M, Asai N,et al. Efficacy of trimethoprim-sulfamethoxa¬ zole in combination with an echinocandin as a first-line treatment option for Pneumocystis pneumonia: a systematic review and meta- analysis. Antibiotics. 2022;11:719. DOI: 10.3390/antibiotics11060719
Tian Q, Si J, Jiang F, et al. Caspofungin combined with TMP/SMZ as a first-line therapy for moderate-to-severe PCP in patients with human immunodeficiency virus infection. HIV Med. 2021;22(4):307–313. DOI: 10.1111/hiv.13013
Sucher AJ, Chahine EB, Balcer HE. Echinocandins: the newest class of antifungals. Ann Pharmacother. 2009;43:1647–1657. DOI: 10.1345/aph.1M237
Bozzette SA, Sattler FR, Chiu J, et al. The use of corticosteroids in Pneumocystis carinii pneumonia. J Infect Dis. 1990;162:1365–1369. DOI: 10.1093/infdis/162.6.1365
Referanslar
Thomas CF Jr, Limper AH. Pneumocystis pneumonia. N Engl J Med. 2004; 350:2487-2498. DOI: 10.1056/NEJMra032588
Thomas CF Jr, Limper AH. Current insights into the biology and pathogenesis of Pneumocystispneumonia. Nat Rev Microbiol. 2007; 5: 298-308. DOI: 10.1038/nrmicro1621
Ng VL, Yajko DM, Hadley WK. Extrapulmonary pneumo- cystosis. Clin Microbiol Rev. 1997; 10: 401-418. DOI: 10.1128/CMR.10.3.401
Rodriguez M, Fishman JA. Prevention of infection due to pneumocystis spp. in human immunodeficiency virüs-negative immunocompromised patients. Clin Microbiol Rev. 2004;17:770-782. DOI: 10.1128/CMR.17.4.770-782.2004
Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America: Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Available from: https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/pneumocystis (2023) (Accessed 15th July 2024).
Vera C, Rueda ZV. Transmission and colonization of Pneumocystis jirovecii. J Fungi 2021;7(11):979. DOI: 10.3390/jof7110979
Edman JC, Kovacs JA, Masur H, et al. Ribosomal RNA sequence shows Pneumocystis carinii to be a member of the Fungi. Nature. 1988; 334:519-522. DOI: 10.1038/334519a0
Catherinot E, Lanternier F, Bougnoux ME, et al. Pneumocystis jirovecii pneumonia. Infect Dis Clin North Am. 2010;24:107–138. DOI: 10.1016/j.idc.2009.10.010
Hughes WT. Prologue to AIDS: the recognition of infectious opportunists. Medicine (Baltimore.) 1998;77:227–232. DOI: 10.1097/00005792-199807000-00001
McDonald EG, Afshar A, Assiri B, et al. Pneumocystis jirovecii pneumonia in people living with HIV: a review. Clin Microbiol Rev. 2024; 37:e0010122. DOI: 10.1128/cmr.00101-22
Olsson M, Lidman C, Latouche S, et al. Identification of Pneumocystis carinii f. sp. hominis gene sequences in filtered air in hospital environments. J Clin Microbiol. 1998; 36:1737–1740. DOI: 10.1128/JCM.36.6.1737-1740.1998
Hughes, WT, Bartley DL, Smith BM. A natural source of infection due to Pneumocystis carinii. J. Infect. Dis. 1983; 147, 595. DOI: 10.1093/infdis/147.3.595
Choukri F, Menotti J, Sarfati C, et al. Quantification and spread of Pneumocystis jirovecii in the surrounding air of patients with Pneumocystis pneumonia. Clin. Infect. Dis. 2010; 51: 259–265. DOI: 10.1086/653933
Navin TR, Rimland D, Lennox JL, et al. Risk factors for community-acquired pneumonia among persons infected with human immunodeficiency virus. J Infect Dis. 2020;181:158–164. DOI: 10.1086/315196
Keely SP, Stringer JR, Baughman RP, et al. Genetic variation among Pneumocystis carinii hominis isolates in recurrent pneumocystosis. J Infect Dis. 1995;595–598. DOI: 10.1093/infdis/172.2.595
Elbüken G. Pneumocystis jiroveci enfeksiyonu ve akciğer tutulumu. Uludağ Üniversitesi Tıp Fakültesi Dergisi. 2007;33:97-103.
Kennedy CA,Goetz MB. Atypical roentgenographic manifestations of Pneumocystis carinii pneumonia. Arch. Intern. Med. 1992;152: 1390–1398.
Hsu JM, Hass A, Gingras MA, et al. Radiographic features in investigated for Pneumocystis jirovecii pneumonia: a nested case-control study. BMC Infect Dis. 2020: 20:492. DOI: 10.1186/s12879-020-05217-x
Quist J, Hill AR. Serum lactate dehydrogenase (LDH) in Pneumocystis carinii pneumonia, tuberculosis, and bacterial pneumo¬nia. Chest. 1995; 108:415–418. DOI: 10.1378/chest.108.2.415
Esteves F, Calé SS, Badura R, et al. Diagnosis of Pneumocystis pneumonia: evaluation of four serologic biomarkers. Clin Microbiol Infect. 2015;21:379. DOI: 10.1016/j.cmi.2014.11.025
Vogel MN, Weissgerber P, Goeppert B, et al. Accuracy of serum LDH elevation for the diagnosis of Pneumocystis jiroveci pneumonia. Swiss Med Wkly. 2011;141:w13184. DOI: 10.4414/smw.2011.13184
Del Corpo O, Butler-Laporte G, Sheppard DC, et al. Diagnostic accuracy of serum (1-3)-β-D-glucan for Pneumocystis jirovecii pneumonia: a systematic review and meta- analysis. Clinical Microbiology and Infection. 2020; 26:1137–1143. DOI: 10.1016/j.cmi.2020.05.024
Juniper T, Eades CP, Gil E, et al. Use of Β-D-Glucan in diagnosis of suspected Pneumocystis Jirovecii pneumonia in adults with HIV infection. Int J STD AIDS. 2021; 32:1074–1077. DOI: 10.1177/09564624211022247
McTaggart LR, Wengenack NL, Richardson SE. Validation of the Mycassay Pneumocystis kit for detection of Pneumocystis Jirovecii in Bronchoalveolar Lavage specimens by comparison to a laboratory standard of direct Immunofluorescence microscopy, real-time PCR, or conventional PCR. J Clin Microbiol. 2012; 50:1856–1859. DOI: 10.1128/JCM.05880-11
Senécal J, Smyth E, Del Corpo O, et al. Non-invasive diagnosis of Pneumocystis jirovecii pneumonia: a systematic review and meta-analysis. Clin Microbiol Infect. 2022; 28:23–30. DOI: 10.1016/j.cmi.2021.08.017
Bateman M, Oladele R, Kolls JK. Diagnosing Pneumocystis jirovecii pneumonia: a review of current methods and novel approaches. Med Mycol. 2020;58:1015–1028. DOI: 10.1093/mmy/myaa024
Bedrossian C.W., Mason M.R., Gupta P.K. Rapid cytologic diagnosis of Pneumocystis: a comparison of effective techniques. Semin Diagn Pathol. 1989; 6(3): 245–61.
Kovacs JA, Ng VL, Masur H, et al. Diagnosis of Pneumocystis carinii pneumonia: improved detection in sputum with use of monoclonal antibodies. N Engl J Med. 1988;318:589–593. DOI: 10.1056/NEJM198803103181001
Alanio A, Desoubeaux G, Sarfati C, et al. Real-time PCR assay-based strategy for differentiation between active Pneumocystis jirovecii pneumonia and colonization in immunocompromised patients. Clin Microbiol Infect. 2011;17:1531–1537. DOI: 10.1111/j.1469-0691.2010.03400.x
Matsumura Y, Ito Y, Iinuma Y, et al. Quantitative real-time PCR and the (1 → 3)-β-d-glucan assay for differentiation between Pneumocystis jirovecii pneumonia and colonization. Clin Microbiol Infect. 2012;18:591–597. DOI: 10.1111/j.1469-0691.2011.03605.x
Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. 2023. Available from: https://www. idsociety.org/practice-guideline/prevention-and-treatment-of- opportunistic-infections-among-adults-and-adolescents.
Kaplan JE, Benson C, Holmes KK, et al. Centers for Disease Control and Prevention (CDC), National Institutes of Health, HIV Medicine Association of the Infectious Diseases Society of America. 2009. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from CDC,the National Institutes of health, and the HIV medicine Association of the infectious diseases society of America. MMWR Recomm Rep. 58:1–207.
Ryom L, De Miguel R, Cotter AG, et al. Major revision version 11.0 of the European AIDS clinical society 1083 guidelines 2021. HIV Med. 2022;23:849–858. DOI: 10.1111/hiv.13268
Kirby AJ, Munoz A, Detels R, et al. Thrush and fever as measures of immunocompetence in HIV-1-infected men. J Acquir Immune Defic Syndr. 1994; 7:1242-1249.
Ioannidis JP, Cappelleri JC, Skolnik PR, et al. A meta- analysis of the relative efficacy and toxicity of Pneumocystis carinii prophylactic regimens. Arch Intern Med. 1996;156:177–188
DiRienzo AG, van Der Horst C, Finkelstein DM et al. Efficacy of trimethoprim-sulfamethoxazole for the prevention of bacterial infections in a randomized prophylaxis trial of patients with advanced HIV infection. AIDS Res Hum Retroviruses. 2002; 18: 89–94. DOI: 10.1089/08892220252779629
Schneider MM, Nielsen TL, Nelsing S,et al. Efficacy and toxicity of two doses of trimethoprim-sulfamethoxazole as primary prophylaxis against Pneumocystis carinii pneumonia in patients with human immunodeficiency virus. J Infect Dis. 1995;171:1632–1636. DOI: 10.1093/infdis/171.6.1632
Ena J, Amador C, Pasquau F, et al. Once-a-month administration of intravenous pentamidine to patients infected with human immunodeficiency virus as prophylaxis for Pneumocystis carinii pneumonia. Clin Infect Dis. 1994;18:901–904. DOI: 10.1093/clinids/18.6.901
Cushion MT, Ashbaugh A. The long-acting echinocandin, rezafungin, prevents Pneumocystis pneumonia and eliminates Pneumocystis from the lungs in prophylaxis and murine treatment models. J Fungi. 2021;7:747. DOI: 10.3390/jof7090747
Butler-Laporte G, Smyth E, Amar-Zifkin A, et al. Low-dose TMP-SMX in the treatment of Pneumocystis jirovecii pneumonia: a systematic review and meta-analysis. Open Forum Infect Dis. 2020;7:ofaa112. DOI: 10.1093/ofid/ofaa112
Creemers-Schild D, Kroon FP, Kuijper EJ, et al. Treatment of Pneumocystis pneumonia with intermediate-dose and step-down to low-dose trimethoprim-sulfamethoxazole: lessons from an observational cohort study. Infection. 2016;44:291–299. DOI: 10.1007/s15010-015-0851-1
Block F, Schmitt T, Schwarz M. Pentamidine, an inhibitor of spinal flexor reflexes in rats, is a potent N-methyl-D-aspartate (NMDA) antagonist in vivo. Neurosci Lett. 1993;155:208–211. DOI: 10.1016/0304-3940(93)90709-t
Chan C, Montaner J, Lefebvre EA, et al. Atovaquone suspension compared with aerosolized pentamidine for prevention of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected subjects intolerant of trimethoprim or sulfonamides. J Infect Dis. 1999;180:369–376. DOI: 10.1086/314893
Hughes W, Leoung G, Kramer F, et al. Comparison of atovaquone (566C80) with trimethoprim-sulfamethoxazole to treat Pneumocystis carinii pneumonia in patients with AIDS. N Engl J Med. 1993;328:1521–1527. DOI: 10.1056/NEJM199305273282103
Huang Y-S, Yang J-J, Lee N-Y, et al. Treatment of Pneumocystis jirovecii pneumonia in HIV-infected patients: a review. Expert Rev Anti Infect Ther. 2017;15:873–892. DOI: 10.1080/14787210.2017.1364991
Kato H, Hagihara M, Asai N,et al. Efficacy of trimethoprim-sulfamethoxa¬ zole in combination with an echinocandin as a first-line treatment option for Pneumocystis pneumonia: a systematic review and meta- analysis. Antibiotics. 2022;11:719. DOI: 10.3390/antibiotics11060719
Tian Q, Si J, Jiang F, et al. Caspofungin combined with TMP/SMZ as a first-line therapy for moderate-to-severe PCP in patients with human immunodeficiency virus infection. HIV Med. 2021;22(4):307–313. DOI: 10.1111/hiv.13013
Sucher AJ, Chahine EB, Balcer HE. Echinocandins: the newest class of antifungals. Ann Pharmacother. 2009;43:1647–1657. DOI: 10.1345/aph.1M237
Bozzette SA, Sattler FR, Chiu J, et al. The use of corticosteroids in Pneumocystis carinii pneumonia. J Infect Dis. 1990;162:1365–1369. DOI: 10.1093/infdis/162.6.1365
