Cases Of Pneumocystis Jirovecii Pneumonia Research Articles

Clinical Course, Radiological Manifestations, and Outcome of Pneumocystis jirovecii Pneumonia in HIV Patients and Renal Transplant Recipients.

BackgroundPneumocystis jirovecii pneumonia (PCP) is a frequent opportunistic infection in immunocompromised patients. In literature, presentation and outcome of PCP differs between patients with human immunodeficiency virus (HIV) infection and renal transplant recipients (RTRs).MethodsWe conducted a cross-sectional study of patients with PCP based on the HIV and renal transplant registries at our institution. Radiological and clinical data from all confirmed PCP cases between 2005 and 2012 were compared.ResultsForty patients were included: 16 with HIV and 24 RTRs. Radiologically, HIV patients had significantly more areas of diffuse lung affection (81% HIV vs. 25% RTR; p = 0.02), more ground glass nodules 5–10 mm (69% vs. 4%; p = <0.001) and enlarged hilar lymph nodes were found only in HIV patients (44%). Cough and dyspnea were the most common clinical signs (>80%) in both groups. Duration from illness onset to hospital presentation was longer in the HIV patients (median of 18 vs. 10 days (p = 0.02)), implying a less fulminant clinical course. Sixty percent of PCP cases in RTRs occurred >12 months after transplantation. Lengths of hospitalization, admission rates to the intensive care unit, and requirements for mechanical ventilation were similar. Outcome in both groups was favourable.ConclusionsWhile important differences in radiological presentation of PCP between HIV patients and RTRs were found, clinical presentation was similar. PCP only rarely presented with fulminant respiratory symptoms requiring ICU admission, with similar results and outcomes for HIV patients and RTRs. Early diagnosis and treatment is mandatory for clinical success.

Atypical Pneumocystis jirovecii pneumonia in previously untreated patients with CLL on single-agent ibrutinib

AbstractIbrutinib is not known to confer risk for Pneumocystis jirovecii pneumonia (PCP). We observed 5 cases of PCP in 96 patients receiving single-agent ibrutinib, including 4 previously untreated. Clinical presentations included asymptomatic pulmonary infiltrates, chronic cough, and shortness of breath. The diagnosis was often delayed. Median time from starting ibrutinib to occurrence of PCP was 6 months (range, 2-24). The estimated incidence of PCP was 2.05 cases per 100 patient-years (95% confidence interval, 0.67-4.79). At the time of PCP, all patients had CD4 T-cell count >500/μL (median, 966/μL) and immunoglobulin G (IgG) >500 mg/dL (median, 727 mg/dL). All patients underwent bronchoalveolar lavage. P jirovecii was identified by polymerase chain reaction in all 5 cases; direct fluorescence antibody staining was positive in 1. All events were grade ≤2 and resolved with oral therapy. Secondary prophylaxis was not given to 3 patients; after 61 patient-months of follow up, no recurrence occurred. Lack of correlation with CD4 count and IgG level suggests that susceptibility to PCP may be linked to Bruton tyrosine kinase (BTK) inhibition. If confirmed, this association could result in significant changes in surveillance and/or prophylaxis, possibly extending to other BTK inhibitors. This trial was registered at www.clinicaltrials.gov as #NCT01500733 and #NCT02514083.

Laboratory-based surveillance of Pneumocystis jirovecii pneumonia in South Africa, 2006–2010i

Background: We aimed to establish the characteristics of patients with confirmed Pneumocystis jirovecii pneumonia recruited by passive, sentinel laboratory-based surveillance.Method: The study design was prospective, observational, cross-sectional, laboratory-based sentinel surveillance. Laboratorybased surveillance of Pneumocystis jirovecii pneumonia (PJP), formerly known as Pneumocystis carinii pneumonia (PCP), was conducted in six South African provinces at 61 hospitals, of which 17 were sentinel sites, where surveillance officers collected clinical and demographic data from cases. A case was defined as a patient with a respiratory tract specimen that was confirmed positive for P. jirovecii by immunofluorescent microscopy or PCR test, either as a first diagnosis or ≥ 30 days after the last confirmed laboratory diagnosis of PJP. The chi-square test or Fisher’s exact test were used to compare the categorical variables.Results: From 2006–2010, 1 537 cases of PJP were recorded. Eighty-nine per cent (460/518) were found to be human immunodeficiency virus (HIV)-infected. This was a first diagnosis of HIV infection in 57% of the cases. The case fatality ratio was 34% (177/525). Recurrent infection was significantly more common in the 26- to 45-year age group, compared to children aged ≤ 5 years (odds ratio 1.7, 95% confidence interval: 1.1–2.8) (p 0.040). Treatment for tuberculosis was common in cases aged ≥ 5 years (37%, 85/229).Conclusion: PJP was the acquired immune deficiency syndrome-defining illness in more than half of the patients detected through laboratory-based surveillance. The high mortality rate and number of recurrent cases is noteworthy. This study may not have reflected the full spectrum of clinical presentation of the disease as case report forms were only completed for hospitalised patients at sentinel surveillance sites.

Efficacy of once-weekly dapsone dosing for Pneumocystis jirovecii pneumonia prophylaxis post transplantation.

Pneumocystis jirovecii pneumonia (PCP) remains a concern after organ transplantation. In 2005, the University of Kentucky (UK) Transplant Center implemented a novel dosing regimen of weekly dapsone as an alternative for patients with contraindications or intolerability to trimethoprim-sulfamethoxazole (TMP-SMZ), which remains the drug of choice. The purpose of this study was to compare the efficacy of weekly dapsone with TMP-SMZ in preventing PCP post transplantation. A single-center, cohort, retrospective review of kidney and liver transplant patients from January 2005 to December 2012 was conducted. Patients who were identified as dapsone cases were matched in a 1:1 ratio with TMP-SMZ controls based on type of transplant, age, primary diagnosis, and gender. The primary endpoint assessed was the diagnosis of PCP at 6 and 12 months post transplant. A total of 158 patients were included in the study. No documented cases of PCP occurred in either study group at 6 or 12 months (P = 1.0). In dapsone patients 35 (44%) cases of breakthrough infection occurred, compared to 24 (30%) in the TMP-SMZ group (P = 0.07) within 12 months post transplant. In the dapsone group, 52 (65%) patients were hospitalized within 6 months post transplant compared to 36 (46%) patients in the TMP-SMZ group (P = 0.01). Similar results were seen in patients hospitalized within 12 months post transplant; 49% of patients were switched from TMP-SMZ to dapsone owing to renal dysfunction. No documented cases of PCP occurred in either study group. Future studies are warranted to show the efficacy of weekly dapsone dosing compared to other PCP prophylaxis regimens.

Pneumocystis Jirovecii Pneumonia (PCP) in Children with Cancer: A Retrospective Cohort Analysis from the Pediatric Health Information System (PHIS) Database, 2004-2009

Background: Pneumocystis jirovecii pneumonia (PCP) is an opportunistic fungal infection that can develop in the setting of deficient cell-mediated immunity. Children with hematologic malignancies and children undergoing immunosuppressive treatment for other types of cancer are at risk of developing PCP. However, the epidemiology of PCP in children with cancer is not well described. We sought to determine the prevalence of PCP in hospitalized children with cancer in the U.S. and to identify risk factors for PCP in this population.Methods: This retrospective cohort study included pediatric patients with newly diagnosed cancer at 45 children’s hospitals in the U.S. between January 1, 2004, and December 31, 2009. Data was obtained from the Pediatric Health Information System (PHIS). Patients were included if they were 0 to 20 years of age and had an index hospitalization with an ICD-9 diagnosis code for a malignant condition (140 to 239.39). Patients who had a benign tumor, >1 cancer type, or non-specific cancer codes, and those who received a hematopoietic stem cell transplant were excluded. Groups were defined for cancer types by ICD-9 codes: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Non-Hodgkin lymphoma (NHL), Hodgkin disease (HD), central nervous system (CNS), and solid non-CNS tumors. Patients within the cohort who had a diagnosis of PCP (ICD-9 code 136.3) within 3 years of their cancer diagnosis were considered PCP cases. The relative risk for PCP was calculated according to demographics and cancer types. The data were analyzed for trends in the incidence of PCP cases by year, the time to PCP diagnosis following cancer diagnosis, and the regional distribution of PCP in the U.S.Results: A total of 33,067 pediatric cancer patients met the criteria for inclusion in the study. Of these patients, 169 (0.5%) were classified as PCP cases (Table 1). Patients with ALL and AML had the highest relative risks of PCP, when compared with other cancer types. Patients of Asian race had the highest relative risk of PCP, when compared with patients of other races. [Display omitted] Figure 1 depicts that the time to the development of PCP was relatively short in patients with NHL (median 33 days, IQR: 0-253 days) and AML (median 70 days, IQR: 0-149 days). In contrast, PCP was diagnosed later in patients with ALL, (median 347 days, IQR; 168-675 days). The number of new PCP cases did not significantly vary by year of diagnosis. Regional differences in the diagnosis of PCP by the locations of PHIS institutions were not identified. [Display omitted] Conclusions: This study represents the largest cohort analysis of PCP in children with cancer. Among children with cancer who were hospitalized at major U.S. children’s hospitals during the study period, the prevalence of PCP was 0.5%. The relative risk of PCP was increased in patients with leukemia when compared with other cancer types. However, PCP was identified in all cancer types. The variation in time to diagnosis of PCP is hypothesized to be due to differences in the intensity and duration of immunosuppressive therapy by cancer type. DisclosuresNo relevant conflicts of interest to declare.

Once weekly trimethoprim-sulfamethoxazole for Pneumocystis jirovecii pneumonia prophylaxis in children with cancer

Journal of Paediatrics and Child HealthVolume 50, Issue 6 p. 491-491 Heads UpFree Access Once weekly trimethoprim-sulfamethoxazole for Pneumocystis jirovecii pneumonia prophylaxis in children with cancer First published: 01 June 2014 https://doi.org/10.1111/jpc.12556_3AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Before the use of trimethoprim-sulfamethoxazole prophylaxis, up to 43% of children with cancer developed Pneumocystis jirovecii pneumonia (PCP). Current recommendations for prophylaxis vary considerably, from daily dosing to thrice weekly dosing. A multi-centre Italian prospective survey compared treatment regimens in 2466 children with newly diagnosed cancer from 2009 to 2011, including 1093 with solid tumours and 1373 with leukaemia/lymphoma.1 Of these patients, 1371 received the 3-day/week prophylaxis regimen, 406 received the 2-day/week regimen and 689 received the 1-day/week regimen (5–10 mg/kg/day in two doses). Only two cases of PCP (0.08%) were reported, both in the 2-day/week group, and both had ceased prophylaxis. The authors concluded that a 1 day per week regimen of trimethoprim/sulfamethoxazole may be sufficient to prevent PCP in immunosuppressed children with cancer. Take home message: 1 day per week trimethoprim/sulfamethoxazole dosing for PCP prophylaxis appears sufficient to prevent PCP in immunosuppressed children with cancer, is simpler than twice or thrice weekly dosing and may improve adherence. This regimen merits consideration in children with cancer and potentially in children at risk of PCP from primary immunodeficiency, transplantation or other medical immunosuppression. Reference 1 Caselli D et al. J. Pediatr. 2014; 164: 389– 392. Reviewer: Brendan McMullan, Sydney Children's Hospital, Randwick, brendan.mcmullan@sesiahs.health.nsw.gov.au Volume50, Issue6June 2014Pages 491-491 ReferencesRelatedInformation

‘Once weekly trimethoprim-sulfamethoxazole for Pneumocystis jirovecii pneumonia prophylaxis in children with cancer’

Journal of Paediatrics and Child HealthVolume 50, Issue 5 p. 415-415 Heads UpFree Access ‘Once weekly trimethoprim-sulfamethoxazole for Pneumocystis jirovecii pneumonia prophylaxis in children with cancer’ First published: 15 April 2014 https://doi.org/10.1111/jpc.12549_2AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Before the use of trimethoprim-sulfamethoxazole prophylaxis, up to 43% of children with cancer developed Pneumocystis jirovecii pneumonia (PCP). Current recommendations for prophylaxis vary considerably, from daily dosing to thrice weekly dosing. A multi-centre Italian prospective survey compared treatment regimens in 2466 children with newly diagnosed cancer from 2009 to 2011, including 1093 with solid tumours and 1373 with leukaemia/lymphoma.1 Of these patients, 1371 received the 3-day/week prophylaxis regimen, 406 received the 2-day/week regimen, and 689 received the 1-day/week regimen (5–10 mg/kg/day in two doses). Only two cases of PCP (0.08%) were reported, both in the 2-day/week group, and both had ceased prophylaxis. The authors concluded that a one-day-per-week regimen of trimethoprim/sulfamethoxazole may be sufficient to prevent PCP in immunosuppressed children with cancer. Take home message: One-day-per-week trimethoprim-sulfamethoxazole dosing for PCP prophylaxis appears sufficient to prevent PCP in immunosuppressed children with cancer, is simpler than twice or thrice weekly dosing, and may improve adherence. This regimen merits consideration in children with cancer and potentially in children at risk of PCP from primary immunodeficiency, transplantation or other medical immunosuppression. Reference 1 Caselli D et al. J. Pediatr. 2014; 164: 389– 392. Reviewer: Brendan McMullan, Sydney Children's Hospital, Randwick ([email protected]) Volume50, Issue5May 2014Pages 415-415 ReferencesRelatedInformation

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.

ObjectiveTo 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).MethodsPE 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.ResultsIn 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]).ConclusionAlmost 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.

Pneumocystis jirovecii pneumonia associated with gemcitabine chemotherapy: experience at an Australian center and recommendations for targeted prophylaxis

Pneumocystis jirovecii pneumonia (PJP) is seen increasingly in non-human immunodeficiency virus (HIV) infected immunocompromised populations, but few cases have previously been reported in association with gemcitabine therapy. We identified all patients administered gemcitabine between March 2009 and December 2012 at the Peter MacCallum Cancer Centre. Cases of PJP were identified using accepted definitions. Overall, 288 gemcitabine-treated patients were identified. Nine cases of PJP were detected, corresponding to an overall rate of 3.1% (95% confidence interval [CI] 1.5–5.7%). PJP was diagnosed during gemcitabine therapy in seven patients, a median of 67 (range 31–109) days from commencement. Among patients with lymphoma, 4/22 developed PJP, corresponding to a rate of 18.2% (95% CI 6.1–38.2%). Fewer infections were associated with breast, lung and gastrointestinal malignancies (1/24 [4.2%], 3/118 [2.5%] and 1/61 [1.6%], respectively). A risk-based tool incorporating concomitant steroid therapy can be applied to target high-risk populations who would benefit from PJP prophylaxis during gemcitabine therapy.

Late‐onset Pneumocystis jirovecii pneumonia in solid organ transplant recipients

Anti-Pneumocystis prophylaxis is recommended for at least 6-12 months after solid organ transplantation, as most cases of Pneumocystis jirovecii pneumonia (PCP) occur during the first year post transplantation. Herein, we report 4 cases of late-onset PCP (>1 year post transplant). PCP appeared in a range of 50-68 months post transplant. Two cases had history of humoral rejection episodes treated with rituximab, and the other 2 had low CD4+ T-cell count (<200 cells/mm(3) ) at the time of diagnosis. All 4 patients survived. In conclusion, although the number of cases is low, we must be aware of the possibility of late-onset PCP in solid organ transplant patients. The role of previous use of rituximab or persistent CD4+ T-cell lymphopenia should be addressed in future studies.

Pneumocystis jirovecii pneumonia in two patients with systemic lupus erythematosus after rituximab therapy

New cases of Pneumocystis jirovecii pneumonia (PJP) have recently been reported in patients with systemic lupus erythematosus (SLE) after rituximab therapy. Several factors may contribute to susceptibility to P. jirovecii infection in this type of patients, including the immunological characteristics of the disease, the mechanisms of rituximab action, environmental factors, and the biological characteristics of the fungus. We report two patients with SLE who developed PJP after rituximab therapy.

Outbreak of Pneumocystis Pneumonia in Renal and Liver Transplant Patients Caused by Genotypically Distinct Strains of Pneumocystis jirovecii

An outbreak of 29 cases of Pneumocystis jirovecii pneumonia (PCP) occurred among renal and liver transplant recipients (RTR and LTR) in the largest Danish transplantation centre between 2007 and 2010, when routine PCP prophylaxis was not used. P. jirovecii isolates from 22 transplant cases, 2 colonized RTRs, and 19 Pneumocystis control samples were genotyped by restriction fragment length polymorphism and multilocus sequence typing analysis. Contact tracing was used to investigate transmission. Potential risk factors were compared between PCP cases and matched non-PCP transplant patients. Three unique Pneumocystis genotypes were shared among 19 of the RTRs, LTRs, and a colonized RTR in three distinct clusters, two of which overlapped temporally. In contrast, Pneumocystis control samples harbored a wide range of genotypes. Evidence of possible nosocomial transmission was observed. Among several potential risk factors, only cytomegalovirus viremia was consistently associated with PCP (P=0.03; P=0.009). Mycophenolate mofetil was associated with PCP risk only in the RTR population (P=0.04). We identified three large groups infected with unique strains of Pneumocystis and provide evidence of an outbreak profile and nosocomial transmission. LTRs may be infected in PCP outbreaks simultaneously with RTRs and by the same strains, most likely by interhuman transmission. Patients are at risk several years after transplantation, but the risk is highest during the first 6 months after transplantation. Because patients at risk cannot be identified clinically and outbreaks cannot be predicted, 6 months of PCP chemoprophylaxis should be considered for all RTRs and LTRs.

Combination of caspofungin and low‐dose trimethoprim/sulfamethoxazole for the treatment of severe Pneumocystis jirovecii pneumonia in renal transplant recipients

Pneumocystis jirovecii pneumonia (PJP) is a severe and life-threatening complication in immunocompromised patients. Trimethoprim/sulfamethoxazole (TMP-SMZ) is well known for its effectiveness as prophylaxis of PJP. However, the use of TMP-SMZ is associated with various adverse effects that may not be tolerated by critically ill patients. Caspofungin is recommended for invasive fungal infections, but the treatment of PJP after solid organ transplantation (SOT) is an off-label use of this drug. In this study, three cases of severe PJP in renal transplant recipients treated with a combination of caspofungin and low-dose TMP-SMZ were presented. Initial findings indicated that the combined treatment may be beneficial for the treatment of PJP and decrease the incidence of TMP-SMZ-related adverse effects.

Low incidence of Pneumocystis jirovecii pneumonia in an unprophylaxed liver transplant cohort

Liver transplant recipients are managed with a range of immunosuppressive regimens that place them at heightened risk of life-threatening opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP). No routine PJP prophylaxis is used at out institution. We reviewed the incidence of PJP in this cohort of unprophylaxed liver transplant recipients. We examined all liver transplants performed between January 2000 and January 2012 in Ireland's National Liver Transplant Centre, St. Vincent's University Hospital, Dublin. Cases were identified through a computerized database and through the histopathology and microbiology registration system. The diagnosis of PJP was confirmed by identification of Pneumocystis cysts in bronchoalveolar lavage (BAL) fluid or on autopsy specimens using Grocott-Gomori methenamine-silver nitrate or modified Wright-Giemsa staining methods. During the study period, 687 liver transplants were performed. We found 7 cases of PJP with an incidence rate of 0.84 per 1000 person transplant years. Five cases occurred within 12months of transplant with 2 cases occurring at 56 and 60months, respectively. Two cases were diagnosed at postmortem; 1 previously had negative cytology from BAL, while the other could not be bronchoscoped because of rapid deterioration in the clinical condition. Three of the 5 treated patients died. The incidence of PJP in this cohort was very low, but the case fatality rate was high. Two cases occurred well after the usual recommended period of prophylaxis. In institutions with a very low risk of infection, targeted rather than universal prophylaxis may be reasonable.

Pneumocystis jirovecii Pneumonia in Tropical and Low and Middle Income Countries: A Systematic Review and Meta-Regression

Objective Pneumocystis jirovecii pneumonia (PCP), the commonest opportunistic infection in HIV-infected patients in the developed world, is less commonly described in tropical and low and middle income countries (LMIC). We sought to investigate predictors of PCP in these settings.DesignSystematic review and meta-regression.MethodsMeta-regression of predictors of PCP diagnosis (33 studies). Qualitative and quantitative assessment of recorded CD4 counts, receipt of prophylaxis and antiretrovirals, sensitivity and specificity of clinical signs and symptoms for PCP, co-infection with other pathogens, and case fatality (117 studies).ResultsThe most significant predictor of PCP was per capita Gross Domestic Product, which showed strong linear association with odds of PCP diagnosis (p<0.0001). This was not explained by study design or diagnostic quality. Geographical area, population age, study setting and year of study also contributed to risk of PCP. Co-infection was common (444 episodes/1425 PCP cases), frequently with virulent organisms. The predictive value of symptoms, signs or simple tests in LMIC settings for diagnosis of PCP was poor. Case fatality was >30%; treatment was largely appropriate. Prophylaxis appeared to reduce the risk for development of PCP, however 24% of children with PCP were receiving prophylaxis. CD4 counts at presentation with PCP were usually <200×103/ml.ConclusionsThere is a positive relationship between GDP and risk of PCP diagnosis. Although failure to diagnose infection in poorer countries may contribute to this, we also hypothesise that poverty exposes at-risk patients to a wide range of infections and that the relatively non-pathogenic P. jirovecii is therefore under-represented. As LMIC develop economically they eliminate the conditions underlying transmission of virulent infection: P. jirovecii, ubiquitous in all settings, then becomes a greater relative threat.

Late‐onset Pneumocystis jirovecii pneumonia post–fludarabine, cyclophosphamide and rituximab: implications for prophylaxis

ObjectiveFludarabine, cyclophosphamide and rituximab (FCR) therapy for lymphoid malignancies has historically been associated with a low reported incidence of Pneumocystis jirovecii pneumonia (PJP). However, prophylaxis was routinely used in early studies, and molecular diagnostic tools were not employed. The objective of this study was to review the incidence of PJP during and post‐FCR in the era of highly sensitive molecular diagnostics and 18F‐fluorodeoxyglucose (FDG) positron emission tomography (PET)–computerised tomography (CT).MethodsAll patients treated with standard FCR at the Peter MacCallum Cancer Centre (March 2009 to June 2012) were identified from a medications management database. Laboratory‐confirmed PJP cases during this time were identified from an electronic database.ResultsOverall, 66 patients were treated with a median of 5.5 FCR cycles. Eight PJP cases were identified, 6 of whom had received chemotherapy prior to FCR. In 5 cases, 18F‐FDG PET demonstrated bilateral ground‐glass infiltrates. Median CD4+ lymphocyte counts at time of PJP diagnosis and 9–12 months following FCR were 123 and 400 cells/μL, respectively. In patients receiving no prophylaxis, 9.1% developed PJP during FCR. The rate following FCR was 18.4%, with median onset at 6 months (2.4–24 months).ConclusionGiven the high rate of late‐onset PJP, consideration should be given for extended PJP prophylaxis for up to 12 months post‐FCR, particularly in pretreated patients. Further evaluation of the role of CD4+ monitoring is warranted to quantify risk of disease development and to guide duration of prophylaxis.

Increasing Pneumocystis pneumonia, England, UK, 2000-2010.

After an increase in the number of reported cases of Pneumocystis jirovecii pneumonia in England, we investigated data from 2000–2010 to verify the increase. We analyzed national databases for microbiological and clinical diagnoses of P. jirovecii pneumonia and associated deaths. We found that laboratory-confirmed cases in England had increased an average of 7% per year and that death certifications and hospital admissions also increased. Hospital admissions indicated increased P. jirovecii pneumonia diagnoses among patients not infected with HIV, particularly among those who had received a transplant or had a hematologic malignancy. A new risk was identified: preexisting lung disease. Infection rates among HIV-positive adults decreased. The results confirm that diagnoses of potentially preventable P. jirovecii pneumonia among persons outside the known risk group of persons with HIV infection have increased. This finding warrants further characterization of risk groups and a review of P. jirovecii pneumonia prevention strategies.

Accuracy ofβ-D-glucan for the diagnosis of Pneumocystis jirovecii pneumonia: a meta-analysis

Pneumocystis jirovecii pneumonia (PCP) can affect various types of immunocompromised patients. We sought to evaluate the diagnostic accuracy of (1 → 3)-β-D-glucan (BDG) for the diagnosis of PCP. We carried out a meta-analysis of relevant studies, identified through PubMed and Scopus. Eligible studies were those that reported BDG diagnostic data in cases with documented PCP and controls with other conditions. Cases of invasive fungal infections and healthy controls were excluded. We performed a bivariate meta-analysis of sensitivity and specificity and constructed a hierarchical summary receiver operating characteristics (HSROC) curve. Fourteen studies were included in the meta-analysis. BDG data were analysed for 357 PCP cases and 1723 controls. The average (95% confidence interval) sensitivity and specificity of BDG were 94.8% (90.8–97.1%) and 86.3% (81.7–89.9%), respectively. The positive and negative likelihood ratios were 6.9 (5.1–9.3) and 0.06 (0.03–0.11), respectively. The area under the HSROC curve was 0.965 (0.945–0.978). Serum BDG shows excellent sensitivity and very good specificity in the diagnosis of PCP. Still, in clinical practice the test results should be interpreted in the context of the underlying clinical characteristics of the individual patient.

Pneumocystis pneumonia in hospitalized patients: a detailed examination of symptoms, management, and outcomes in human immunodeficiency virus (HIV)‐infected and HIV‐uninfected persons

Pneumocystis jirovecii pneumonia (PCP) is a life-threatening infection for immunocompromised individuals. Robust data and clear guidelines are available for prophylaxis and treatment of human immunodeficiency virus (HIV)-related PCP (HIV-PCP), yet few data and no guidelines are available for non-HIV-related PCP (NH-PCP). We postulated that prevention and inpatient management of HIV-PCP differed from NH-PCP. We performed a retrospective case review of all pathologically confirmed cases of PCP seen at the University of Alabama Medical Center from 1996 to 2008. Data on clinical presentation, hospital course, and outcome were collected using a standardized data collection instrument. Bivariate analysis compared prophylaxis, adjunctive corticosteroids, and clinical outcomes between patients with HIV-PCP and NH-PCP. Our analysis of the cohort included 97 cases of PCP; 65 HIV and 32 non-HIV cases. Non-HIV cases rarely received primary prophylaxis (4% vs. 38%, P=0.01) and received appropriate antibiotics later in the course of hospitalization (5.2days vs. 1.1days, P<0.005). Among transplant patients, NH-PCP was diagnosed a mean of 1066days after transplantation and most patients were on low-dose corticosteroids (87%) at the time of disease onset. No significant differences in adjunctive corticosteroid use (69% vs. 77%, P=0.39) and 90-day mortality (41% vs. 28%, P=0.20) were detected. Patients who have undergone organ or stem cell transplant remain at risk for PCP for many years after transplantation. In our cohort, patients who developed NH-PCP were rarely given prophylaxis, and initiation of appropriate antibiotics was significantly delayed compared to cases of HIV-PCP. Medical providers should be aware of the ongoing risk for NH-PCP, even late after transplantation, and consider more aggressive approaches to both prophylaxis and earlier empirical therapy for PCP.

A Pneumocystis jirovecii pneumonia outbreak in a single kidney-transplant center: role of cytomegalovirus co-infection

Pneumocystis jirovecii pneumonia (PCP) and cytomegalovirus (CMV) infection represent possible complications of medical immunosuppression. Between 2005 and 2010, non-human immunodeficiency virus (HIV) PCP patients admitted to a nephrology unit were analyzed for outcome, CMV comorbidity, and patient-to-patient contacts prior to PCP. In contrast to 2002-2004 (no cases) and 2008-2010 (10 cases), a PCP outbreak of 29 kidney-transplant recipients and one patient with anti-glomerular basement membrane disease occurred between 2005 and 2007. None of the patients were on PCP chemoprophylaxis. In four PCP patients, the genotyping data of bronchoalveolar lavage specimen showed an identical Pneumocystis strain. PCP cases had a higher incidence of CMV infection (12 of 30 PCP patients) and CMV disease (four patients) when compared to matched PCP-free controls (p < 0.05). Cotrimoxazole and, if applicable, ganciclovir were started 2.0 ± 4.0days following admission, and immunosuppressive medication was reduced. In-hospital mortality was 10% and the three-year mortality was 20%. CMV co-infection did not affect mortality. CMV co-infection more frequently occurred during a cluster outbreak of non-HIV PCP in comparison to PCP-free controls. Here, CMV awareness and specific therapy of both CMV infection and PCP led to a comparatively favorable patient outcome. The role of patient isolation should be further investigated in incident non-HIV PCP.