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Nonadherence to Primary Prophylaxis against Pneumocystis jirovecii Pneumonia  [PDF]
James D. Heffelfinger, Andrew C. Voetsch, Glenn V. Nakamura, Patrick S. Sullivan, A. D. McNaghten, Laurence Huang
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0005002
Abstract: Background Despite the effectiveness of prophylaxis, Pneumocystis jirovecii pneumonia (PCP) continues to be the most common serious opportunistic infection among HIV-infected persons. We describe factors associated with nonadherence to primary PCP prophylaxis. Methodology/Principal Findings We used 2000–2004 data from the Supplement to HIV/AIDS Surveillance (SHAS) project, a cross-sectional interview project of HIV-infected persons ≥18 years conducted in 18 states. We limited the analysis to persons who denied having prior PCP, reported having a current prescription to prevent PCP, and answered the question “In the past 30 days, how often were you able to take the PCP medication(s) exactly the way your doctor told you to take them?” We used multivariable logistic regression to describe factors associated with nonadherence. Of 1,666 subjects prescribed PCP prophylaxis, 305 (18.3%) were nonadherent. Persons were more likely to be nonadherent if they reported using marijuana (adjusted odds ratio [aOR] = 1.6, 95% confidence interval [CI] = 1.1–2.4), non-injection drugs other than marijuana (aOR = 1.5, 95% CI = 1.0–2.1), or injection drugs (aOR = 2.3, 95% CI = 1.3–4.1) in the past year; their mental health was “not good” for ≥1 day during the past month (aOR = 1.6, 95% CI = 1.2–2.2); their most recent CD4 count was <200 cells/μL (aOR = 1.6, 95% CI = 1.1–2.2); or taking ART usually (aOR = 9.6, 95% CI = 6.7–13.7) or sometimes/rarely/never (aOR = 18.4, 95% CI = 11.1–30.4), compared with always, as prescribed. Conclusion/Significance Providers should inquire about and promote strategies to improve adherence to PCP prophylaxis, particularly among persons who use illicit drugs, have mental health issues, and who are not compliant with ART to reduce the occurrence of PCP.
Prophylaxis and Treatment of Pneumocystis jirovecii Pneumonia after Renal Transplantation
O. Rettkowski,A. Hamza,M. Tajjour,P. Fornara
Transplantationsmedizin , 2008,
Abstract: Urologic complications after kidney transplantation such as urine fistula or With the introduction of new immunosuppressants Pneumocystis pneumonia (PCP) remains to be a threat to kidney transplant recipients. Based on the results from our kidney transplantation center an overview concerning incidence, prophylaxis, therapy and outcome is provided. The incidence of PCP at our center was 0.75 cases per 100 patients and year (period May 2002 to December 2007), the frequency with reference to the 316 kidney transplantations performed was 4.1%. 13 cases of PCP occurred during the observation period and 3 of these patients (23%) died from the pneumonia. In only 4 patients (31%) a complete restitution of the transplant function was achieved. The letality of PCP among kidney graft recipients is up to 50% - thus a prophylactic treatment in the early post-transplantation period is recommended for at least 4 months and should be lengthened depending on the course of immunosuppression. Administration of 80/400 mg TMP/SMZ is highly effective in preventing PCP and adverse effects from TMP/SMZ seem to be rare using this regimen.
Pneumocystis jiroveci pneumonia prophylaxis is a challenge in granulomatosis with polyangiitis patients treated with rituximab.  [PDF]
Emilio Besada
PeerJ , 2015, DOI: 10.7287/peerj.preprints.149v1
Abstract: All strategies to prevent Pneumocystis jiroveci pneumonia (PCP) during rituximab treatment have their rationale in patients with granulomatosis with polyangiitis (GPA) and to some extent in patients with other autoimmune diseases (AID). Risk factors of PCP and severe infections are very similar in GPA patients. The decision of PCP prophylaxis should not be limited at RTX initiation and during RTX treatment, but should be reassessed continuously in all GPA patients. Since PCP increases the mortality risk in GPA (and AID) patients, the treating physician should always consider PCP as a possible diagnosis in patients treated with RTX - receiving or not PCP prophylaxis.
Discontinuation of Pneumocystis jirovecii Pneumonia Prophylaxis with CD4 Count <200 Cells/μL and Virologic Suppression: A Systematic Review  [PDF]
Cecilia T. Costiniuk, Dean A. Fergusson, Steve Doucette, Jonathan B. Angel
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0028570
Abstract: Background HIV viral load (VL) is currently not part of the criteria for Pneumocystis jirovecii pneumonia (PCP) prophylaxis discontinuation, but suppression of plasma viremia with antiretroviral therapy may allow for discontinuation of PCP prophylaxis even with CD4 count <200 cells/μL. Methods A systematic review was performed to determine the incidence of PCP in HIV-infected individuals with CD4 count <200 cells/μL and fully suppressed VL on antiretroviral therapy but not receiving PCP prophylaxis. Results Four articles examined individuals who discontinued PCP prophylaxis with CD4 count <200 cells/μL in the context of fully suppressed VL on antiretroviral therapy. The overall incidence of PCP was 0.48 cases per 100 person-years (PY) (95% confidence interval (CI) (0.06–0.89). This was lower than the incidence of PCP in untreated HIV infection (5.30 cases/100 PY, 95% CI 4.1–6.8) and lower than the incidence in persons with CD4 count <200 cells/μL, before the availability of highly active antiretroviral therapy (HAART), who continued prophylaxis (4.85/100 PY, 95% CI 0.92–8.78). In one study in which individuals were stratified according to CD4 count <200 cells/μL, there was a greater risk of PCP with CD4 count ≤100 cells/μL compared to 101–200 cells/μL. Conclusion Primary PCP prophylaxis may be safely discontinued in HIV-infected individuals with CD4 count between 101–200 cells/μL provided the VL is fully suppressed on antiretroviral therapy. However, there are inadequate data available to make this recommendation when the CD4 count is ≤100 cells/μL. A revision of guidelines on primary PCP prophylaxis to include consideration of the VL is merited.
Profilaxis de neumonía por Pneumocystis jiroveci en ni os y adultos sometidos a trasplante de órganos sólidos y de precursores hematopoyéticos Prophylaxis against Pneumocystis pneumonia in pediatric and adult patients undergoing solid organ or hematopoietic stem cells transplantation
M. Pilar Gambra,Teresa Bidart
Revista chilena de infectología , 2012,
Abstract: Pneumocystis jiroveci es un patógeno importante en pacientes sometidos a TOS y TPH. Se recomienda proilaxis universal a todos los pacientes adultos y ni os sometidos a TOS o TPH porque su uso reduce signiicati-vamente la ocurrencia y mortalidad asociada a neumonía por este agente. El medicamento de elección es cotrimoxa-zol (A1) tres veces por semana, en dosis bajas, esquema que ha demostrado igual eicacia y mejor tolerancia que el esquema diario y/o con dosis altas. La proilaxis se inicia 7 a 14 días post trasplante en TOS y posterior al implante en TPH, con una duración promedio de 6 meses salvo en trasplante de hígado y pulmón en que se prolonga por 1 a o, al igual que en TPH con grado importante de inmunosupresión. Son alternativas de profilaxis dapsona (B2), pentamidina aerosolizada (B2) y atavacuona (C2). Pneumocystis jiroveci is an important pathogen in patients undergoing SOT and HSCT. Universal prophylaxis is recommended for all adults and children with SOT and HSCT, considering that its use significantly reduces the occurrence and mortality associated with pneumonia by this agent. The drug of choice is cotrimoxazole (A1) three times a week, low-dose scheme, that has proved equally effective and better tolerated than the daily regimen and/or at high doses. Prophylaxis starts 7 to 14 days post transplant in SOT recipients and post-implant in HSCT, with an average duration of 6 months except in liver and lung transplant as in HSCT with significant degree of immunosuppression, that lasts for 1 year. Alternatives for prophylaxis are dapsone (B2), aerosolized pentamidine (B2) and atovaquone (C2).
Critical Importance of Long-Term Adherence to Care in HIV Infected Patients in the cART Era: New Insights from Pneumocystis jirovecii Pneumonia Cases over 2004–2011 in the FHDH-ANRS CO4 Cohort  [PDF]
Blandine Denis, Marguerite Guiguet, Nathalie de Castro, Frédéric Mecha?, Matthieu Revest, Aba Mahamat, Giovanna Melica Gregoire, Olivier Lortholary, Dominique Costagliola
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0094183
Abstract: Objective To describe characteristics and outcomes of HIV-infected patients with Pneumocystis jirovecii pneumonia (PCP) over 2004–2011 in France, in particular in those previously enrolled (PE) in the French Hospital Database on HIV (FHDH). Methods PE patients with an incident PCP were compared with patients with an inaugural PCP revealing HIV infection (reference). Adequate adherence to care was defined as a CD4 measurement at least every 6 months. Immune reconstitution (CD4≥200/mm3) and risk of death were studied using Kaplan-Meier estimates and multivariable Cox proportional hazards models. Results In a context of a decreasing incidence of PCP, 1259 HIV-infected patients had a PCP diagnosis, and 593 (47%) were PE patients of whom 161 (27%) have had a prior history of AIDS-defining clinical illness (prior ADI). Median time since enrolment was 8 years for PE patients; 74% had received cART. Median proportion of time with adequate adherence to care was 85% (IQR, 66–96) for all FHDH enrollees, but only 45% (IQR, 1–81) for PE patients during the 2 years before PCP. Median CD4 cell count (38/mm3) and HIV viral load (5.2 log10 copies/ml) at PCP diagnosis did not differ between PE patients and the reference group. Three year mortality rate of 25% was observed for PE prior ADI group, higher than in PE non-prior ADI group (8%) and the reference group (9%) (p<0.0001). In the PE prior ADI group, poor prognosis remained even after adjustment for virological control and immune reconstitution (HR, 2.4 [95%CI, 1.5–3.7]). Conclusion Almost 50% of PCP diagnoses in HIV-infected patients occurred presently in patients already in care, mainly with a previous cART prescription but with waning adherence to care. Having repeated ADI is contributing to the risk of death beyond its impact on immune reconstitution and viral suppression: special efforts must be undertaken to maintain those patients in care.
Use of a population-based survey to determine incidence of AIDS-defining opportunistic illnesses among HIV-positive persons receiving medical care in the United States
Patrick S Sullivan, Maxine Denniston, AD McNaghten, Susan E Buskin, Stephanie T Broyles, Eve D Mokotoff
AIDS Research and Therapy , 2007, DOI: 10.1186/1742-6405-4-17
Abstract: We used data from a 1998 population-based survey of persons in care for HIV infection to demonstrate the utility of population-based survey data for the calculation of OI rates, with inference to populations in care for HIV infection in three geographic areas: King County Washington, selected health districts in Louisiana, and the state of Michigan.The overall OI rate was 13.8 per 100 persons with HIV infection in care during 1998 (95% CI, 10.2–17.3). In 1998, an estimated 11.3% of all persons with HIV in care in these areas had at least one OI diagnosis (CI, 8.8–13.9). The most commonly diagnosed OIs were Pneumocystis jiroveci pneumonia (PCP) (annual incidence 2.4 per 100 persons, CI 1.0–3.8) and cytomegalovirus retinitis (annual incidence 2.4 per 100 persons, CI 1.0–3.7). OI diagnosis rates were higher in Michigan than in the other two geographic areas, and were different among patients who were white, black and of other races, but were not different by sex or history of injection drug use.Data from population-based surveys – and, in the coming years, clinical outcomes surveillance systems in the United States – can be used to calculate OI rates with improved generalizability, and such rates should be used in the future as a meaningful indicator of clinical outcomes in persons with HIV infection in care.Since the advent of combination antiretroviral therapy (cART), each occurrence of an incident opportunistic illness (OI) in a person with HIV infection is a failure of secondary HIV prevention: new OI diagnoses may represent a failure of early diagnosis of HIV infection, failure to link a diagnosed person to effective medical care, failure to prescribe cART and/or OI prophylaxis when indicated, problems with adherence to cART and/or OI prophylaxis, or drug-resistant HIV infection that is not adequately controlled by prescribed cART. Reliable population-based estimates of OI incidence are thus a high-level measure of multiple goals of prevention and care programs, r
Falla de la profilaxis con cotrimoxazol para la neumonía por Pneumocystis jiroveci con el uso concomitante de leucovorina: Reporte de un caso Failure of cotrimoxazole prophylaxis for Pneumocystis jiroveci pneumonia with concomitant use of leucovorin: Case report  [cached]
Macarena Bonacic,Alfredo Silva,Marcelo Wolff
Revista chilena de infectología , 2012,
Abstract: The concomitant use of leucovorin and cotrimoxazole in PCP can lead to therapeutic failure and increased risk of death due to antagonism. It is important to keep this possible antagonistic interaction in mind even during prophylaxis. This paper presents a case with this failure outcome.
The Pneumocystis life cycle
Aliouat-Denis, Cécile-Marie;Martinez, Anna;Aliouat, El Moukhtar;Pottier, Muriel;Gantois, Nausicaa;Dei-Cas, Eduardo;
Memórias do Instituto Oswaldo Cruz , 2009, DOI: 10.1590/S0074-02762009000300004
Abstract: first recognised as "schizonts" of trypanosoma cruzi, pneumocystis organisms are now considered as part of an early-diverging lineage of ascomycetes. as no robust long-term culture model is available, most data on the pneumocystis cell cycle have stemmed from ultrastructural images of infected mammalian lungs. although most fungi developing in animals do not complete a sexual cycle in vivo, pneumocystis species constitute one of a few exceptions. recently, the molecular identification of several key players in the fungal mating pathway has provided further evidence for the existence of conjugation and meiosis in pneumocystisorganisms. dynamic follow-up of stage-to-stage transition as well as studies of stage-specific proteins and/or genes would provide a better understanding of the still hypothetical pneumocystislife cycle. although difficult to achieve, stage purification seems a reasonable way forward in the absence of efficient culture systems. this mini-review provides a comprehensive overview of the historical milestones leading to the current knowledge available on the pneumocystis life cycle.
Autoimmune inflammatory disorders, systemic corticosteroids and pneumocystis pneumonia: A strategy for prevention
Evin Sowden, Andrew J Carmichael
BMC Infectious Diseases , 2004, DOI: 10.1186/1471-2334-4-42
Abstract: In adults with AID, the risk of PCP is related to treatment with systemic steroid, ill-defined individual variation in steroid sensitivity and CD4+ lymphocyte count. Rather than opting for PCP prophylaxis on the basis of disease or treatment with cyclophosphamide, we argue the case for carrying out CD4+ lymphocyte counts on selected patients as a means of identifying individuals who are most likely to benefit from PCP prophylaxis.Corticosteroids, lymphopenia and a low CD4+ count in particular, have been identified as risk factors for the development of PCP in adults with AID. Trimethoprim-sulfamethoxazole (co-trimoxazole) is an effective prophylactic agent, but indications for its use remain ill-defined. Further prospective trials are required to validate our proposed prevention strategy.Pneumocystis carinii was identified a hundred years ago by Chagas [1] and recognised as a pathogen in marasmic children at the end of World War II [2]. The organism came to the fore again in the early 1980s when apparently healthy homosexual men developed PCP and heralded the acquired immunodeficiency syndrome (AIDS) epidemic [3]. With highly active antiretroviral therapy (HAART) and prophylactic antibiotics, attention has turned to PCP in human immunodeficiency virus (HIV) negative individuals. We recently treated a young woman with steroid-based immunosuppression for dermatomyositis. Four months after diagnosis, she was admitted acutely breathless to the intensive care unit with a presumptive diagnosis of PCP. Although the final diagnosis was rapidly progressive alveolitis related to dematomyositis, it prompted us to consider whether we should use PCP prophylaxis for selected patients receiving systemic steroids for AID. In this article we explore the background of PCP in HIV negative patients, consider the incidence of PCP in AID, discuss predisposing factors and propose a strategy for prevention.Pneumocystis pneumonia is caused in humans by the recently renamed Pneumocystis jiro
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