Management of Pneumocystis Jirovecii pneumonia in HIV infected patients: current options, challenges and future directions

Castro, José G.; Morrison-Bryant, Maya

doi:10.2147/hiv.s7720

Cited by 31 publications

(33 citation statements)

References 69 publications

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“…The 5-mg/kg/day dose we have used in this study in mice is equivalent to 0.3 mg/kg/day (or 18 mg for 60 kg of body weight) in humans, because the effective dose for mice is approximately 10-fold higher than that for humans (36). PMQ has been used at 15 to 30 mg per day in combination with clindamycin (1,800 mg/day) as the second-line drug for treatment of PCP (37). Another side effect of PMQ is acute hemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency (33).…”

Section: Discussionmentioning

confidence: 99%

Vitamin D as Supplemental Therapy for Pneumocystis Pneumonia

Lei

Zhang

Zimmerman

et al. 2016

Antimicrob Agents Chemother

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The combination of all-trans retinoic acid (ATRA) and primaquine (PMQ) has been shown to be effective for therapy of Pneumocystis pneumonia (PCP). Since a high concentration of ATRA has significant adverse effects, the possibility that vitamin D can be used to replace ATRA for PCP therapy was investigated. C57BL/6 mice were immunosuppressed by depleting CD4؉ cells and infected with Pneumocystis murina 1 week after initiation of immunosuppression. Three weeks after infection, the mice were treated orally for 3 weeks with vitamin D 3 (VitD3) alone, PMQ alone, a combination of VitD3 and PMQ (VitD3-PMQ), or a combination of trimethoprim and sulfamethoxazole (TMP-SMX). Results showed that VitD3 (300 IU/kg/day) had a synergistic effect with PMQ (5 mg/kg/day) for therapy of PCP. Flow cytometric studies showed that this VitD3-PMQ combination recovered the CD11b low CD11c high alveolar macrophage population in mice with PCP as effectively as TMP-SMX. The VitD3-PMQ combination also reduced the massive infiltration of inflammatory cells into the lungs and the severity of lung damage. VitD3 was also shown to reduce the dose of TMP-SMX required for effective treatment of PCP. Taken together, results of this study suggest that a VitD3-PMQ combination can be used as an alternative therapy for PCP. Pneumocystis jirovecii is the causative organism of Pneumocystis pneumonia (PCP), which is a common opportunistic disease in patients with AIDS. According to the 2014 CDC statistics, the incidence of PCP in the United States is 9% among hospitalized AIDS patients and 1% among solid organ transplant recipients (1). The mortality rate of PCP ranges from 5% to 40% in patients with treatment and approaches 100% in those without treatment (1). Pneumocystis organisms are also found in other mammalian species, and those found in mice are called P. murina. P. carinii refers to the major form of Pneumocystis found in rats. Although Pneumocystis organisms are classified as fungi, they are not susceptible to most antifungal drugs. Currently, the most effective regimen for PCP therapy is the combination of trimethoprim and sulfamethoxazole (TMP-SMX). However, approximately 10% of people are allergic to sulfa drugs (2), and many AIDS patients fail therapy with TMP-SMX (3). In addition, TMP-SMX may cause adverse effects, such as rash, fever, neutropenia, thrombocytopenia, or transaminase elevation (3).In PCP, alveolar macrophages (AMs) are defective in phagocytosis and reduced in number (4). We have found that the expression of the PU.1 gene in AMs is decreased during PCP (5). This PU.1 downregulation may be a cause of AM dysfunction because PU.1 regulates the expression of many macrophage receptors (5-9). Since PU.1 also regulates the differentiation of monocytes into AMs (10), its decrease in expression would adversely affect this process, resulting in a decreased number of AMs during PCP. We have also found that myeloid-derived suppressor cells (MDSCs) accumulate in the lungs of mice and rats with PCP (11). The number of these cells increases a...

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Section: Discussionmentioning

confidence: 99%

Vitamin D as Supplemental Therapy for Pneumocystis Pneumonia

Lei

Zhang

Zimmerman

et al. 2016

Antimicrob Agents Chemother

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“…Os efeitos adversos mais comuns são a toxidermia, a febre, a toxicidade hepática e medular e, ainda, a hipercaliemia, os quais surgem em 20% a 85% dos casos. 12,27,37,47 Estes efeitos adversos foram replicados no presente estudo, verificando-se 23,5% de toxicidade associada ao TMP-SMX, correspondentes a 88,6% do total dos efeitos adversos reportados no processo clínico, sendo os mais comuns a toxidermia, a hipercaliemia e a toxicidade medular. A utilização continuada do fármaco em profilaxia e a colonização por Pneumocystis levantam preocupações relativamente à possibilidade de se selecionarem mutações de resistência que possam contribuir para o insucesso terapêutico.…”

Section: Discussionunclassified

“…14,20,[24][25][26] A utilização de corticóides melhora o prognóstico na subpopulação de doentes com hipoxemia (pressão parcial de oxigénio inferior a 70 mmHg ou com gradiente alvéolo-arterial superior a 35 mmHg, em ar ambiente), diminuindo a resposta inflamatória na PPc, a qual está na génese da perda de integridade do tecido pulmonar. 1,27,28 Os objectivos deste estudo foram analisar as características de uma população co-infectada por VIH e PPc, comparando-a com as referências disponíveis, e avaliar comparativamente subpopulações de doentes, consoante o conhecimento prévio da infecção por VIH, o método de diagnóstico de PPc e o resultado na alta, por forma a tentar determinar que condições individuais, clínicas, parâmetros analíticos e imagiológicos, e atitudes terapêuticas estariam associados a uma maior frequência de doença, gravidade, e a uma diferente evolução clínica. …”

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Pneumonia por Pneumocystis em 107 Doentes com Infecção por VIH Internados no Serviço de Doenças Infecciosas, Hospital de Santa Maria, Lisboa (2002 - 2013)

Grilo

Pereira

2016

Acta Med Port

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(75,7%). A mortalidade foi de 13,1%. Discussão: Na análise comparativa entre grupos, constantou-se que os doentes utilizadores de drogas injectáveis conhecem com maior frequência o estado de seropositividade para o vírus da imunodeficiência humana, previamente ao internamento, o que poderá ser explicado pela maior implementação de programas de proximidade e de rastreio oportunista junto das populações de utilizadores de drogas injectáveis. No entanto, o seguimento e tratamento não são mantidos devido à má adesão aos mesmos, pelo que os doentes apresentam um risco aumentado para o desenvolvimento de pneumonia por Pneumocystis jirovecii e de outras doenças relacionadas com a sida. Apesar de a apresentação clínica da pneumonia por Pneumocystis jirovecii, no grupo de doentes avaliado, ser coincidente com o quadro mais comum desta patologia, o recurso aos cuidados de saúde foi tardio, sobretudo nos doentes com apresentação inaugural da infecção por vírus da imunodeficiência humana, e o diagnóstico difícil, quer pelas características inerentes às técnicas de diagnóstico de pneumonia por Pneumocystis, à presença de infecção respiratória concomitante e ao grau de suspeição clínica. Conclusão: Neste grupo de doentes, as características estudadas são semelhantes às descritas na literatura, particularmente considerando o padrão epidemiológico da infecção por vírus da imunodeficiência humana e Pneumocystis jirovecii em Portugal, sendo as principais diferenças encontradas a maior frequência de diagnóstico de pneumonia por Pneumocystis jirovecii em utilizadores de drogas injectáveis, comparativamente ao grupo de homens que têm relações sexuais com homens, a importância de episódios prévios/ recorrentes de pneumonia por Pneumocystis jirovecii como factor de risco, e a frequência em que está presente patologia pulmonar concomitante. Os doentes falecidos apresentaram menos achados imagiológicos sugestivos de Pneumocystis jirovecii, e a idade avançada constituiu um factor pior prognóstico nesta população. Palavras-chave: Infecções por VIH; Pneumocystis jirovecii; Pneumonia por Pneumocystis; Portugal. ABSTRACTIntroduction: Pneumocystis jirovecii pneumonia remains one of the most common opportunistic illnesses in patients infected with the human immunodeficiency virus. It is currently the most reported AIDS-defining infection in Portugal. The aims of this study were to analyze the features of a human immunodeficiency virus /Pneumocystis jirovecii pneumonia coinfected population, to compare it with the current literature, and to evaluate comparatively subpopulations of patients based on the previous knowledge of the human immunodeficiency virus infection, Pneumocystis jirovecii pneumonia diagnostic method and discharge results. Material and Methods: A retrospective, observational, non-controlled study was conducted. The 107 patients admitted to the Department of Infectious Diseases at Santa Maria Hospital, in Lisbon, between the 1st of January 2002 and the 31st of December 2013, that presented the simultaneous diagnosis of human im...

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“…8 PCR has a sensitivity and specificity of about 90% but should be used cautiously because it cannot differentiate between colonisation and active disease, so false positive rates are high. 8 Given the risk of biopsy (haemorrhage, pneumothorax) most centres use bronchial alveolar lavage as the first line investigation when samples cannot be obtained non-invasively.…”

Section: Discussionmentioning

confidence: 99%

An atypical cause of respiratory failure

Sylvester

2015

BMJ

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Management of Pneumocystis Jirovecii pneumonia in HIV infected patients: current options, challenges and future directions

Cited by 31 publications

References 69 publications

Vitamin D as Supplemental Therapy for Pneumocystis Pneumonia

Vitamin D as Supplemental Therapy for Pneumocystis Pneumonia

Pneumonia por Pneumocystis em 107 Doentes com Infecção por VIH Internados no Serviço de Doenças Infecciosas, Hospital de Santa Maria, Lisboa (2002 - 2013)

An atypical cause of respiratory failure

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