Pneumonia por Pneumocystis jirovecii

A pneumonia por Pneumocystis (PPC) pode ser prevenida em pacientes positivos para o vírus do HIV pela implementação da terapia antirretroviral (TAR) combinada com o objetivo de restaurar e preservar a função imunológica.[22]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and American Academy of Pediatrics. Panel on Opportunistic Infections in Children with and Exposed to HIV. Guidelines for the prevention and treatment of opportunistic infections in children with and exposed to HIV: Pneumocystis jirovecii pneumonia. Nov 2013 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/pediatric-opportunistic-infection/pneumocystis-jirovecii-pneumonia?view=full [32]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Pneumocystis pneumonia. Sep 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-opportunistic-infection/pneumocystis-pneumonia [46]Green H, Paul M, Vidal J, et al. Prophylaxis of Pneumocystis pneumonia in immunocompromised non-HIV-infected patients: systematic review and meta-analysis of randomized controlled trials. Mayo Clinic Proc. 2007 Sep;82(9):1052-9. http://www.ncbi.nlm.nih.gov/pubmed/17803871?tool=bestpractice.com

É necessário um tratamento profilático primário específico em todos os pacientes com risco elevado de infecção com PPC.

Adulto ou adolescente, HIV-positivo[32]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Pneumocystis pneumonia. Sep 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-opportunistic-infection/pneumocystis-pneumonia

• Os pacientes HIV-positivos que não apresentam sintomas ou sinais clínicos de PPC necessitam de quimioprofilaxia primária nas seguintes circunstâncias:

  • Contagem de células CD4 <100 células/microlitro, independentemente dos níveis plasmáticos de HIV

  • Contagem de células CD4 entre 100 e 200 células/microlitro se os níveis de RNA do HIV no plasma estiverem acima dos limites de detecção.

• Os pacientes que recebem pirimetamina/sulfadiazina para o tratamento ou a supressão da toxoplasmose não requerem profilaxia adicional para PPC.

Crianças com HIV ou com risco de HIV[22]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and American Academy of Pediatrics. Panel on Opportunistic Infections in Children with and Exposed to HIV. Guidelines for the prevention and treatment of opportunistic infections in children with and exposed to HIV: Pneumocystis jirovecii pneumonia. Nov 2013 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/pediatric-opportunistic-infection/pneumocystis-jirovecii-pneumonia?view=full

• A profilaxia da PPC é recomendada para os seguintes grupos de crianças:

  • Idade entre 1 e 12 meses, HIV-positivos, independentemente da porcentagem ou contagem de células CD4

  • Com idade entre 1 e <6 anos e que são HIV-positivas, com contagem de células CD4 <500 células/microlitro ou porcentagem de CD4 <15%

  • Com idade ≥6 a 12 anos que são HIV-positivas e com contagens de células CD4 de <200 células/microlitro ou porcentagem de CD4 <15%

  • Lactentes com diagnóstico de HIV indeterminado de mães HIV-positivas.

Pacientes HIV-negativos imunocomprometidos[31]Stern A, Green H, Paul M, et al. Prophylaxis for Pneumocystis pneumonia (PCP) in non-HIV immunocompromised patients. Cochrane Database Syst Rev. 2014 Oct 1;(10):CD005590. http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005590.pub3/full http://www.ncbi.nlm.nih.gov/pubmed/25269391?tool=bestpractice.com [47]Taplitz RA, Kennedy EB, Bow EJ, et al. Antimicrobial prophylaxis for adult patients with cancer-related immunosuppression: ASCO and IDSA clinical practice guideline update. J Clin Oncol. 2018 Oct 20;36(30):3043-54. https://ascopubs.org/doi/10.1200/JCO.18.00374?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed http://www.ncbi.nlm.nih.gov/pubmed/30179565?tool=bestpractice.com [48]Tomblyn M, Chiller T, Einsele H, et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009 Oct;15(10):1143-238. https://www.bbmt.org/article/S1083-8791(09)00300-0/fulltext http://www.ncbi.nlm.nih.gov/pubmed/19747629?tool=bestpractice.com [49]Fishman JA, Gans H, AST Infectious Diseases Community of Practice. Pneumocystis jiroveci in solid organ transplantation: guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13587. http://www.ncbi.nlm.nih.gov/pubmed/31077616?tool=bestpractice.com

• As indicações para profilaxia de PPC após a avaliação do risco para PPC incluem os pacientes com:

  • Neoplasias hematológicas

  • Transplante de células hematopoéticas

  • Outras neoplasias malignas em que o esquema de quimioterapia esteja associado a um risco >3.5% de PPC

  • Transplante de órgão sólido

  • Uso crônico de corticosteroides com ou sem outros medicamentos imunossupressores

  • Certas imunodeficiências primárias (por exemplo, imunodeficiência combinada grave).

O agente profilático de escolha em crianças, adolescentes e adultos é o sulfametoxazol/trimetoprima (SMX/TMP), na ausência de contraindicações.[22]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and American Academy of Pediatrics. Panel on Opportunistic Infections in Children with and Exposed to HIV. Guidelines for the prevention and treatment of opportunistic infections in children with and exposed to HIV: Pneumocystis jirovecii pneumonia. Nov 2013 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/pediatric-opportunistic-infection/pneumocystis-jirovecii-pneumonia?view=full [32]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Pneumocystis pneumonia. Sep 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-opportunistic-infection/pneumocystis-pneumonia ​​ As alternativas para adolescentes e adultos, independentemente do status sorológico para Toxoplasma gondii, incluem a dapsona associada a pirimetamina e ácido folínico; ou a atovaquona. As alternativas para adolescentes e adultos soronegativos para Toxoplasma gondii incluem: dapsona, pentamidina aerossolizada ou pentamidina intravenosa.[32]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Pneumocystis pneumonia. Sep 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-opportunistic-infection/pneumocystis-pneumonia A dapsona, a atovaquona e a pentamidina aerossolizada são alternativas adequadas nas crianças. A pentamidina intravenosa também pode ser considerada nas crianças >2 anos de idade, quando outras opções não estiverem disponíveis.[22]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and American Academy of Pediatrics. Panel on Opportunistic Infections in Children with and Exposed to HIV. Guidelines for the prevention and treatment of opportunistic infections in children with and exposed to HIV: Pneumocystis jirovecii pneumonia. Nov 2013 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/pediatric-opportunistic-infection/pneumocystis-jirovecii-pneumonia?view=full A deficiência de glicose-6-fosfato desidrogenase (G6PD) deve ser investigada em todos os pacientes antes do início da dapsona, se possível. Para obter informações completas sobre a profilaxia da PPC, consulte as seções de Manejo.

Embora haja dados que sugerem que a transmissão do organismo ocorre de pessoa a pessoa, o isolamento respiratório de pacientes com PPC não é recomendado atualmente.[32]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Pneumocystis pneumonia. Sep 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-opportunistic-infection/pneumocystis-pneumonia [50]Helweg-Larsen J, Tsolaki AJ, Miller RF, et al. Clusters of Pneumocystis carinii pneumonia: analysis of person-to-person transmission by genotyping. QJM. 1998 Dec;91(12):813-20. http://www.ncbi.nlm.nih.gov/pubmed/10024946?tool=bestpractice.com [51]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 Jun;36(6):1737-40. http://www.ncbi.nlm.nih.gov/pubmed/9620410?tool=bestpractice.com [52]Schmoldt S, Schuhegger R, Wendler T, et al. Molecular evidence of nosocomial Pneumocystis jiroveci transmission among 16 patients after kidney transplantation. J Clin Microbiol. 2008 Mar;46(3):966-71. http://www.ncbi.nlm.nih.gov/pubmed/18216217?tool=bestpractice.com [53]Morris A, Beard CB, Huang L. Update on the epidemiology and transmission of Pneumocystis carinii. Microbes Infect. 2002 Jan;4(1):95-103. http://www.ncbi.nlm.nih.gov/pubmed/11825780?tool=bestpractice.com

Vacinas estão atualmente em fase de desenvolvimento.[54]Zheng M, Shellito JE, Marrero L, et al. CD4+ T cell-independent vaccination against Pneumocystis carinii in mice. J Clin Invest. 2001 Nov;108(10):1469-74. http://www.ncbi.nlm.nih.gov/pubmed/11714738?tool=bestpractice.com [55]Wells J, Haidaris CG, Wright TW, et al. Active immunization against Pneumocystis carinii with a recombinant P. carinii antigen. Infect Immunol. 2006 Apr;74(4):2446-8. http://www.ncbi.nlm.nih.gov/pubmed/16552076?tool=bestpractice.com [56]Theus SA, Smulian AG, Steele P, et al. Immunization with the major surface glycoprotein of Pneumocystis carinii elicits a protective response. Vaccine. 1998 Jul;16(11-12):1149-57. http://www.ncbi.nlm.nih.gov/pubmed/9682373?tool=bestpractice.com [57]Cobos Jiménez V, Rabacal W, Rayens E, et al. Immunization with <i>Pneumocystis</i> recombinant KEX1 induces robust and durable humoral responses in immunocompromised non-human primates. Hum Vaccin Immunother. 2019;15(9):2075-2080. https://www.doi.org/10.1080/21645515.2019.1631135 http://www.ncbi.nlm.nih.gov/pubmed/31348719?tool=bestpractice.com [58]Tesini BL, Wright TW, Malone JE, et al. Immunization with Pneumocystis Cross-Reactive Antigen 1 (Pca1) Protects Mice against Pneumocystis Pneumonia and Generates Antibody to Pneumocystis jirovecii. Infect Immun. 2017 Apr;85(4):. https://www.doi.org/10.1128/IAI.00850-16 http://www.ncbi.nlm.nih.gov/pubmed/28031260?tool=bestpractice.com [59]Kling HM, Norris KA. Vaccine-Induced Immunogenicity and Protection Against Pneumocystis Pneumonia in a Nonhuman Primate Model of HIV and Pneumocystis Coinfection. J Infect Dis. 2016 May 15;213(10):1586-95. https://www.doi.org/10.1093/infdis/jiw032 http://www.ncbi.nlm.nih.gov/pubmed/26823337?tool=bestpractice.com

Pacientes que tiveram infecção por PPC, foram tratados e estão assintomáticos recebem profilaxia secundária, de acordo com o mesmo esquema de profilaxia primária para cada grupo de pacientes.

Recomenda-se profilaxia secundária para pacientes HIV-positivos que tiveram PPC; esta deve ser iniciada após a conclusão do tratamento da PPC e continuar até que ocorra uma reconstituição imune com terapia antirretroviral.[22]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and American Academy of Pediatrics. Panel on Opportunistic Infections in Children with and Exposed to HIV. Guidelines for the prevention and treatment of opportunistic infections in children with and exposed to HIV: Pneumocystis jirovecii pneumonia. Nov 2013 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/pediatric-opportunistic-infection/pneumocystis-jirovecii-pneumonia?view=full [32]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Pneumocystis pneumonia. Sep 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-opportunistic-infection/pneumocystis-pneumonia

A profilaxia secundária pode ser descontinuada para a maioria dos pacientes com base nos mesmos critérios para descontinuar a profilaxia primária. A profilaxia da PPC não deve ser descontinuada nos lactentes infectados com HIV e <1 ano de idade. A profilaxia deve continuar por toda a vida nos pacientes que desenvolverem PPC apesar de uma contagem de CD4 >200 células/microlitro.