Pneumocystis Jirovecii Pneumonia Prophylaxis Research Articles

Clinical practice pattern of Pneumocystis pneumonia prophylaxis in systemic lupus erythematosus: a cross-sectional study from lupus registry of nationwide institutions (LUNA).

Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in patients undergoing immunosuppressive therapy, such as glucocorticoid (GC) medication, for systemic autoimmune diseases like systemic lupus erythematosus (SLE). Despite the confirmed effectiveness of PCP prophylaxis, its clinical administration, especially in conjunction with GC dosage, remains unclear. We aimed to describe the clinical practice of PCP prophylaxis in association with SLE in Japan, evaluate the relationship between GC dosage and PCP prophylaxis, and explore the practice patterns associated with PCP prophylaxis. This cross-sectional study used data from the Lupus Registry of Nationwide Institutions in Japan from 2016 to 2021 and included patients diagnosed with SLE. Using descriptive statistics, multivariate analysis, and decision tree analysis, we examined the prevalence of PCP prophylaxis and its association with the GC dosage. Out of 1,460 patients, 21% underwent PCP prophylaxis. The frequency of prophylaxis decreased with a decrease in GC dosage. After adjusting for confounders, logistic regression revealed the odds ratio of PCP prophylaxis increased with higher prednisolone (PSL) doses: 3.7 for 5 ≤ PSL < 7.5mg, 5.2 for 7.5 ≤ PSL < 10mg, 9.0 for 10 ≤ PSL < 20mg, and 43.1 for PSL ≥ 20mg, using PSL < 5mg as the reference. Decision tree analysis indicated that a PSL dosage of < 11mg/day and immunosuppressant use were key determinants of PCP prophylaxis. This study provides valuable insights into PCP prophylaxis practices in patients with SLE in Japan, underscoring the importance of GC dosage and concomitant immunosuppressant use.

Incidence of Pneumocystis jirovecii Pneumonia and Prophylaxis-Associated Adverse Events Among Patients with Systemic Lupus Erythematosus.

Pneumocystis jirovecii Pneumonia (PJP) is an opportunistic infection that may affect patients with systemic lupus erythematosus (SLE). The objective of this project was to describe the incidence of PJP among patients with SLE. A retrospective cohort analysis of the TriNetX database. Included patients had ≥2 ICD9- CM/ICD10-CM codes for SLE separated by at least 30 days and were new users of mycophenolate mofetil or cyclophosphamide. The incidence of PJP over the first six months of therapy was calculated; adverse events were assessed using incident rate ratios (IRR) and Cox proportional hazards regressions. A total of 6,017 patients with SLE were identified. Most were female (5,176, 86%) and Black or African American (2,138, 35.5%). Induction medications included mycophenolate mofetil (5,208, 86.6%), cyclophosphamide (505, 8.4%), or both (304, 5.1%); the most common PJP prophylaxis was trimethoprim/sulfamethoxazole (1,126, 18.7%). Five PJP cases were identified over 2,752 person years, one of whom received PJP prophylaxis, for an incidence rate of 1.8 cases per 1000 person years. In adjusted analysis, patients who received prophylaxis had a higher risk of neutropenia (hazard ratio (HR) 2.5, CI 1.4-4.4), leukopenia (HR 1.9, CI 1.3-2.8), nephropathy (HR 1.7, CI 1.4-2.1), and hyperkalemia (HR 1.4, CI 0.9-2.0). PJP rarely affects patients with SLE undergoing therapy with mycophenolate mofetil or cyclophosphamide; prophylaxis against PJP is associated with adverse events. The majority of patients with SLE and PJP had structural lung disease. These data do not support universal prescribing of PJP prophylaxis for patients with SLE without lung disease.

Effectiveness and safety of lower dose sulfamethoxazole/trimethoprim for Pneumocystis jirovecii pneumonia prophylaxis in patients with systemic rheumatic diseases receiving moderate-to high-dose glucocorticoids

ObjectivesTo compare the effectiveness and safety of low-dose sulfamethoxazole/trimethoprim (SMX/TMP) for Pneumocystis jirovecii pneumonia (PCP) prophylaxis in patients with systemic rheumatic disease (SRD) who were receiving glucocorticoids. MethodsWe retrospectively analyzed data obtained from Japanese patients with SRD who received glucocorticoids between January 2006 and April 2024. Patients were divided into two groups based on the initial dose of SMX/TMP: low-dose (one tablet twice weekly on non-consecutive days); conventional-dose (one tablet per day). The primary endpoint was the incidence of PCP after 1 year since the initiation of SMX/TMP. Secondary endpoints were discontinuation rates of SMX/TMP therapy and severe adverse drug reactions (ADRs) after 1 year since the initiation of SMX/TMP in both groups, before and after adjusting for patient characteristics. ResultsA total of 186 patients were included in this study: 60 in the low-dose group and 126 in the conventional-dose group. No patients developed PCP within one year after starting SMX/TMP; however, two patients in the low-dose group required escalation of the SMX/TMP dose to the conventional dose due to subclinical PCP. In the adjusted analysis, the low-dose group had a significantly lower discontinuation rate and a lower incidence rate of severe ADRs than the conventional-dose group. ConclusionsLower-dose SMX/TMP therapy was as effective as conventional therapy for PCP prophylaxis and was associated with lower discontinuation rates in patients with SRD receiving glucocorticoids.

Efficacy of Pneumocystis jirovecii Pneumonia Prophylaxis in Preventing Infections among Patients with Kidney Disease Receiving Rituximab Therapy

Efficacy of Pneumocystis jirovecii Pneumonia Prophylaxis in Preventing Infections among Patients with Kidney Disease Receiving Rituximab Therapy

Development of a clinical risk score for the prediction of Pneumocystis jirovecii pneumonia in hospitalised patients

BackgroundThe performance and availability of invasive and non-invasive investigations for the diagnosis of Pneumocystis jirovecii pneumonia (PCP) vary across clinical settings. Estimating the pre-test probability of PCP is essential to the optimal selection and interpretation of diagnostic tests, such as the 1,3-β-D-glucan assay (BDG), for the prioritization of bronchoscopy, and to guide empiric treatment decisions. We aimed to develop a multivariable risk score to estimate the pre-test probability of PCP.MethodsThe score was developed from a cohort of 626 individuals who underwent bronchoscopy for the purposes of identifying PCP in a Canadian tertiary-care centre, between 2015 and 2018. We conducted a nested case-control study of 57 cases and 228 unmatched controls. Demographic, clinical, laboratory, and radiological data were included in a multivariable logistic regression model to estimate adjusted odds ratios for PCP diagnosis. A clinical risk score was derived from the multivariable model and discrimination was assessed by estimating the score’s receiver operating characteristic curve.ResultsParticipants had a median age of 60 years (interquartile range [IQR] 49–68) and 115 (40%) were female; 40 (14%) had HIV and 49 (17%) had a solid organ transplant (SOT). The risk score included prior SOT or HIV with CD4 ≤ 200/µL (+ 2), serum lactate dehydrogenase ≥ 265.5 IU/mL (+ 2), radiological pattern typical of PCP on chest x-ray (+ 2) or CT scan (+ 2.5), and PCP prophylaxis with trimethoprim-sulfamethoxazole (-3) or other antimicrobials (-2). The median score was 4 points (IQR, 2-4.5) corresponding to a 28% probability of PCP. The risk prediction model had good discrimination with a c-statistic of 0.79 (0.71–0.84). Given the operating characteristics of the BDG assay, scores ≤ 3 in patients without HIV, and ≤ 5.5 in those with HIV, paired with a negative BDG, would be expected to rule out PCP with 95% certainty.ConclusionWe propose the PCP Score to estimate pre-test probability of PCP. Once validated, it should help clinicians determine which patients to refer for invasive investigations, when to rely on serological testing, and in whom to consider pre-emptive treatment.

Infection prophylaxis among patients with antineutrophil cytoplasmic antibody (ANCA) vasculitis: a scoping review.

Severe infections associated with the use of strong immunosuppressive medication are a leading cause of morbidity and mortality in patients with ANCA vasculitis (AV). While guidelines conditionally recommend trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis for Pneumocystis jirovecii pneumonia in AV patients, robust evidence on prophylaxis strategies is lacking. This scoping review aimed to assess the existing evidence on infection prophylaxis in AV patients, identify knowledge gaps, and guide future study design. A comprehensive search of six databases and relevant references identified original studies in English from January 1, 2000, to July 31, 2020. Inclusion criteria encompassed studies evaluating the impact of any antimicrobial prophylaxis strategy on infection-related outcomes in AV patients receiving immunosuppressive treatment. Studies were screened by four researchers using a blinded approach. Data was extracted by two reviewers, with differences resolved via consensus in consultation with a third reviewer. Nineteen studies met inclusion criteria, including two randomized trials and 17 cohort studies, with TMP-SMX being the most commonly assessed prophylactic strategy. The studies varied in sample sizes, outcomes measured, prophylactic strategies employed, and proportion of patients who received the regimen. Most cohort studies included no or limited control of potential confounding factors. This scoping review suggests significant variation in AV patients' receipt of TMP-SMX and alternative infection prophylaxis approaches. Observational studies using large secondary healthcare databases with rigorous designs are needed to provide high-quality evidence of the real-world effectiveness of antimicrobial prophylactic regimens, to improve clinical decision-making and quality of care for AV patients receiving immunosuppressive treatment.

Sulfamethoxazole-Trimethoprim Prophylaxis in Pediatric Oncology Patients With Glucose-6-Phosphate Dehydrogenase Deficiency.

We sought to determine whether Pneumocystis jirovecii pneumonia prophylaxis with sulfamethoxazole-trimethoprim (SMX-TMP) is associated with an increased frequency of acute hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency versus non-G6PD-deficient controls in a pediatric oncology population. There was no statistically significant difference in change in hemoglobin or transfusion requirements after starting SMX-TMP between groups. These findings suggest no increased risk of acute hemolytic anemia with SMX-TMP administered at prophylaxis doses in patients with G6PD deficiency.

Perception of pneumocystis jirovecii pneumonia (PJP) prophylaxis in glioma patients receiving concurrent temozolomide and radiation- a patient and physician survey.

Pneumocystis jirovecii pneumonia (PJP) prophylaxis is required by provincial and national drug monographs during glioma treatment using temozolomide (TMZ) concurrently with radiation (TMZ-RT). However, real-world data suggest the potential benefits of PJP prophylaxis may not outweigh its potential harms in this population. We conducted a single-center patient survey and a national physician survey to explore the role of PJP prophylaxis amongst glioma patients undergoing TMZ-RT. 23% (31/133) of physicians and 60% (44/73) of patients completed a survey. The median patient age was 42 (range 20-77); 85% (34/40) had completed adjuvant TMZ. Although only 2.4% (1/41) of patients received PJP prophylaxis, only one person (without PJP prophylaxis) was hospitalized for pneumonia. When presented with hypothetical PJP risks, 13.2% (5/38) of patients were concerned about PJP infection, while 26% (10/38) were concerned about potential side effects from prophylactic antibiotics. Most physicians (77%, 17/22) perceived the evidence for PJP prophylaxis as weak; 58% (11/19) did not routinely prescribe prophylaxis, and 73% (16/22) felt that PJP prophylaxis should be limited to patients with additional risk factors. Over 95% of physicians estimated that the incidence of PJP was < 1% in their last 5 years of practice regardless of PJP prophylaxis. For 73% (16/22) of physicians, to prescribe PJP prophylaxis, the risk of PJP infection needed to be 3-8%. The current recommendation to routinely prescribe PJP prophylaxis in patients receiving TMZ-RT in the absence of other risk factors warrants reconsideration.

Variance in Pneumocystis jirovecii prophylaxis practice for pediatric patients undergoing hematopoietic cell transplantation.

Pneumocystis jirovecii pneumonia (PJP) in hematopoietic cell transplant (HCT) recipients can be prevented by efficient prophylaxis. We surveyed HCT centers in North America to assess their PJP prophylaxis practices. Most institutions used intravenous (IV) pentamidine (29.6%) or inhaled pentamidine (14.8%); 37% institutions changed from trimethoprim/sulfamethoxazole (TMP-SMX) to another medication after conditioning; and 44% administered no PJP prophylaxis during the pre-engraftment period. Most institutions avoided using TMP-SMX during the pre-engraftment period, mainly because of concerns about myelotoxicity, despite this being the preferred PJP prophylaxis agent. There is a need to evaluate the effects of TMP-SMX on engraftment.

Opportunistic Infections, Mortality Risk, and Prevention Strategies in Patients With Vacuoles, E1 Enzyme, X-Linked, Autoinflammatory, Somatic (VEXAS) Syndrome

Abstract Background VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a genetic disorder characterized by bone marrow failure and systemic inflammation, putting patients at risk for infections. This study comprehensively examines the prevalence of opportunistic infections in patients with VEXAS, evaluating their impact on clinical outcomes and potential preventive measures. Methods Patients with confirmed VEXAS were included. Survival analysis and logistic regression were used to identify associations between opportunistic infections and mortality. Infection rates (IRs) for Pneumocystis jirovecii pneumonia (PJP) and alphaherpesviruses were calculated over a prospective 8-month observation period in relationship to prophylaxis. Results Of 94 patients with VEXAS, 6% developed PJP; 15% had alphaherpesvirus reactivation, with varicella zoster virus (VZV) being the most common herpesvirus; and 10% contracted a nontuberculous mycobacterial (NTM) infection. Risk of death was significantly increased per month following a diagnosis of PJP (hazard ratio [HR], 72.41 [95% confidence interval {CI}, 13.67–533.70]) or NTM (HR, 29.09 [95% CI, 9.51–88.79]). Increased odds for death were also observed in patients with a history of herpes simplex virus (HSV) reactivation (odds ratio [OR], 12.10 [95% CI, 1.29–114.80]) but not in patients with VZV (OR, 0.89 [95% CI, .30–2.59]). Prophylaxis for PJP (IR, 0.001 vs 0 per person-day, P &amp;lt; .01) and VZV (IR, 0.006 vs 0 per person-day, P = .04) markedly decreased infection rates with a number needed to treat of 4 and 7, respectively. Conclusions Opportunistic infections are common in patients with VEXAS. Patients who develop PJP, HSV, or NTM are at increased risk for death. Prophylaxis against PJP and VZV is highly effective.

Pneumocystis pneumonia in intensive care: clinical spectrum, prophylaxis patterns, antibiotic treatment delay impact, and role of corticosteroids. A French multicentre prospective cohort study.

Severe Pneumocystis jirovecii pneumonia (PJP) requiring intensive care has been the subject of few prospective studies. It is unclear whether delayed curative antibiotic therapy may impact survival in these severe forms of PJP. The impact of corticosteroid therapy combined with antibiotics is also unclear. This multicentre, prospective observational study involving 49 adult intensive care units (ICUs) in France was designed to evaluate the severity, the clinical spectrum, and outcomes of patients with severe PJP, and to assess the association between delayed curative antibiotic treatment and adjunctive corticosteroid therapy with mortality. We included 158 patients with PJP from September 2020 to August 2022. Their main reason for admission was acute respiratory failure (n = 150, 94.9%). 12% of them received antibiotic prophylaxis for PJP before ICU admission. The ICU, hospital, and 6-month mortality were 31.6%, 35.4%, and 40.5%, respectively. Using time-to-event analysis with a propensity score-based inverse probability of treatment weighting, the initiation of curative antibiotic treatment after 96h of ICU admission was associated with faster occurrence of death [time ratio: 6.75; 95% confidence interval (95% CI): 1.48-30.82; P = 0.014]. The use of corticosteroids for PJP was associated with faster occurrence of death (time ratio: 2.48; 95% CI 1.01-6.08; P = 0.048). This study showed that few patients with PJP admitted to intensive care received prophylactic antibiotic therapy, that delay in curative antibiotic treatment was common and that both delay in curative antibiotic treatment and adjunctive corticosteroids for PJP were associated with accelerated mortality.

Pneumocystis jirovecii Pneumonia in a Liver Transplant Recipient With an Adverse Reaction to Trimethoprim/Sulfamethoxazole Treated With a Sulfonamide Desensitization Protocol: Case Report

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic fungal infection that, in immunocompromised patients, can progress to respiratory failure and death. Since trimethoprim/sulfamethoxazole (TMP/SMX) chemoprophylaxis has become a standard management, the prognosis has improved. However, there are patients with a history of TMP/SMX intolerance who cannot receive chemoprophylaxis. We report on a 53-year-old male liver recipient treated with a standard triple immunosuppressive regimen in whom TMP/SMX was waived because of a history of allergy manifested as a generalized rash with edema more than 30 years ago. At transplantation, the immunologic risk was assessed as low, and liver graft function was normal. In the third month after engraftment, he developed dyspnea at rest required constant passive oxygen therapy. Ceftriaxone, azithromycin, and clindamycin were implemented. Mycophenolate acid was stopped, and tacrolimus was reduced. High-resolution computed tomography revealed interstitial pneumonia. Pneumocystis jirovecii pneumoniae was diagnosed from bronchoalveolar lavage. Instead of TMP/SMX, pentamidine and caspofungin were also used for PJP, with no improvement. After 3 weeks, the patient deteriorated. Because of his life-threatening condition, TMP/SMX was introduced in the sulfonamide desensitization protocol, including hydrocortisone and clemastinum. Within 4 days, the patient stabilized with no signs of TMP/SMX intolerance. Pneumonia subsided within a month, and TMP/SMX was prescribed lifelong. Prophylaxis for PJP with TMP/SMX still remains an important issue in transplant recipients. Adverse reaction to TMP/SMX in the past is not always a contraindication to reintroducing prophylaxis. The decision of prophylaxis avoidance should be analyzed carefully; in uncertain cases, a sulfonamide desensitization protocol should be considered.

A case of hypercalcemia from Pneumocystis jirovecii in an immunosuppressed non-HIV patient

BackgroundThe prevalence of non-HIV related Pneumocystis jirovecii pneumonia (PJP) is increasing with use of immunosuppressive therapies. There are case reports of solid organ transplant recipients on immunosuppressive therapy presenting with mild hypercalcemia, leading to a diagnosis of PJP. Recent studies have shown efficacy of PJP prophylaxis for patients treated with rituximab with a favourable adverse effect profile.Case PresentationA 78-year-old male with a history of PR3-ANCA vasculitis, chronic kidney disease and heart failure with reduced ejection fraction presented to our tertiary care hospital with a two-week history of confusion and non-productive cough. Background immunosuppression with rituximab was completed every six months. The patient was found to have hypercalcemia and new infiltrates and ground glass opacities on cross-sectional imaging. Bronchoscopy was performed that was positive for Pneumocystis jirovecii. He was treated with 21 days of trimethoprim-sulfamethoxazole and prednisone with resolution of symptoms and hypercalcemia.ConclusionsHerein, we present a novel case of PJP in a non-transplant recipient preceded by hypercalcemia. Our case demonstrates the importance for a high suspicion for PJP in chronically immunosuppressed patients on rituximab presenting with PTH-independent hypercalcemia.

A retrospective study of intravenous pentamidine for Pneumocystis jirovecii pneumonia prophylaxis in adult patients with hematologic malignancies—its utility during respiratory virus pandemics

ObjectivesIn hematology, prophylaxis for Pneumocystis jirovecii pneumonia (PCP) is recommended for patients undergoing hematopoietic stem cell transplantation and in selected categories of intensive chemotherapy for hematologic malignancies. Trimethoprim-sulfamethoxazole (TMP-SMX) is the recommended first-line agent; however, its use is not straightforward. Inhaled pentamidine is the recommended second-line agent; however, aerosolized medications were discouraged during respiratory virus outbreaks, especially during the COVID-19 pandemic, in view of potential contamination risks. Intravenous (IV) pentamidine is a potential alternative agent. We evaluated the effectiveness and tolerability of IV pentamidine use for PCP prophylaxis in adult allogeneic hematopoietic stem cell transplantation recipients and patients with hematologic malignancies during COVID-19. ResultsA total of 202 unique patients who received 239 courses of IV pentamidine, with a median of three doses received (1-29). The largest group of the patients (49.5%) who received IV pentamidine were undergoing or had received a hematopoietic stem cell transplant. The most common reason for not using TMP-SMX prophylaxis was cytopenia (34.7%). We have no patients who had breakthrough PCP infection while on IV pentamidine. None of the patients developed an infusion reaction or experienced adverse effects from IV pentamidine. ConclusionsPentamidine administered IV monthly is safe and effective.

Infection risk and antimicrobial prophylaxis in bendamustine-treated patients with indolent non-Hodgkin lymphoma: An Australasian Lymphoma Alliance study.

Infection and lymphopenia are established bendamustine-related complications. The relationship between lymphopenia severity and infection risk, and the role of antimicrobial prophylaxis, is not well described. This multicentre retrospective study analysed infection characteristics and antimicrobial prophylaxis in 302 bendamustine-treated indolent non-Hodgkin lymphoma patients. Lymphopenia (<1 × 109/L) was near universal and time to lymphocyte recovery correlated with cumulative bendamustine dose. No association between lymphopenia severity and duration with infection was observed. Infections occurred in 44% of patients (50% bacterial) with 27% hospitalised; 32% of infections occurred ≥3 months post bendamustine completion. Infection was associated with obinutuzumab and/or maintenance anti-CD20 therapy, prior therapy and advanced stage. Twenty-four opportunistic infections occurred in 21 patients: ten varicella zoster virus (VZV), seven herpes simplex virus (HSV), one cytomegalovirus, one progressive multifocal leucoencephalopathy, one nocardiosis, one Pneumocystis jiroveci pneumonia (PJP) and three other fungal infections. VZV/HSV and PJP prophylaxis were prescribed to 42% and 54% respectively. Fewer VZV/HSV infections occurred in patients receiving prophylaxis (HR 0.14, p = 0.061) while PJP prophylaxis was associated with reduced risk of bacterial infection (HR 0.48, p = 0.004). Our study demonstrates a significant infection risk regardless of lymphopenia severity and supports prophylaxis to mitigate the risk of early and delayed infections.

Chronic glucocorticoid management in neuromuscular disease: A survey of neuromuscular neurologists.

Glucocorticoids (GC) are first-line therapy for many neuromuscular diseases. There is a lack of guidelines regarding the prevention and management of GC complications in the context of neuromuscular disease, introducing the potential for practice variation, that may compromise quality of care. Our aim was to evaluate the practice patterns among Canadian adult neuromuscular neurologists on the screening, management, and treatment of GC-related complications and to identify variances in practice. A web-based anonymous questionnaire was disseminated to 99 Canadian adult neuromuscular neurologists. Questions addressed patterns of screening, prevention, monitoring, and treatment of GC-induced adverse events, including infection prophylaxis, vaccination, bone health, hyperglycemia, and other complications. Seventy-one percent completed the survey. Of those, 52% perform screening blood work prior to initiating GC, 56% screen for infections, and 18% for osteoporosis. The majority monitor glycemic control and blood pressure (>85%). Thirty-two (46%) reported that they do not primarily monitor GC complications, but rather provide recommendations to the primary care physician. Pneumocystis jiroveci pneumonia prophylaxis was never used by 29%, and 29% recommend vaccinations prior to GC initiation. Calcium supplementation was recommended by 80% to prevent osteoporosis. Only 36% were aware of any existing guidelines for preventing GC complications, and 91% endorsed a need for neurology-specific guidelines. There is substantial variability in the management of GC adverse effects among neuromuscular neurologists, often not corresponding to limited published literature. Our results support the need for improved education and neurology-specific guidelines to help standardize practice and improve and prevent complications.

Effect of Pneumocystis jirovecii pneumonia prophylaxis on hematologic toxicity in patients receiving chemoradiation for primary brain tumors.

Diffuse gliomas are managed with radiation and temozolomide; however, this therapy often results in hematologic toxicities. Patients undergoing chemoradiation also risk contracting Pneumocystis jirovecii pneumonia (PJP), and frequently receive prophylaxis against PJP during treatment. Independent of chemoradiation, some PJP prophylaxis drugs have the potential to cause myelosuppression, which could require cessation of chemotherapy. Here, we evaluate differences in the frequency of hematologic toxicities during chemoradiation when patients receive PJP prophylaxis. This retrospective chart review evaluated patients with primary brain tumors treated with radiation and concurrent temozolomide. Analyses were performed to assess the effect of the type of PJP prophylaxis on risk for neutropenia, lymphopenia, or thrombocytopenia and the severity of these adverse effects as defined using the Common Terminology Criteria for Adverse Events. Of the 217 patients included in this analysis, 144 received trimethoprim-sulfamethoxazole (TMP/SMX) and 69 received pentamidine. Of the patients who received TMP/SMX, 15.3% developed an absolute neutrophil count < 1500 cells/µL compared with 7.2% of patients receiving pentamidine (p = 0.10). Platelet count < 100,000/µL occurred in 18.1% of patients who received TMP/SMX and 20.3% of patients who received pentamidine (p = 0.70). No significant differences in lymphocyte counts between therapies were seen. Severity of hematologic toxicities were similar between PJP prophylaxis groups. These findings suggest that the type of PJP prophylaxis does not significantly affect the risk for hematologic toxicity in brain tumor patients receiving radiation and temozolomide. Additional studies are merited to evaluate the higher rate of neutropenia in patients on TMP/SMX observed in this study.

Pneumocystis jirovecii Pneumonia Prophylaxis in Patients with ANCA Vasculitis on Rituximab Maintenance Therapy.

Although an increased risk of Pneumocystis jirovecii pneumonia (PJP) has been reported in adults receiving rituximab for induction therapy, current evidence is lacking on the utility of PJP prophylaxis in ANCA-associated vasculitis (AAV) patients on maintenance rituximab therapy. The purpose of this study was to compare the incidence of PJP pneumonia and the outcomes of AAV patients with and without PJP prophylaxis. We performed an observational, single-center, retrospective study examining patients with AAV in clinical remission and on rituximab maintenance therapy. We divided the patients into two groups: those with and without PJP prophylaxis. We explored factors associated with PJP prophylaxis use. We additionally looked at several outcomes, including PJP infections, infections requiring hospitalizations, end-stage kidney disease (ESKD), and death. Data were analyzed using T test, Fisher's exact test, univariate, and multivariate logistic regression as appropriate. A total of 129 patients with mean follow-up time of 7.2 (5.4) years were included: 44% received PJP prophylaxis and 56% of patients did not. There were no PJP infections in the entire cohort. Lung involvement was associated with increased odds of prescribing PJP prophylaxis (OR: 4.09 [95% CI: 1.8-9.82]). PJP prophylaxis did not decrease infection rates requiring hospitalizations, ESKD, or death. Glucocorticoid use, however, was associated with increased rates of infections requiring hospitalizations (OR: 5.54 [95% CI: 2.01-15.4]) and death (OR: 4.67 [95% CI: 1.36-15.71]) even after adjustment for age, gender, and use of PJP prophylaxis. Regardless of the use of PJP prophylaxis during the maintenance phase of AAV management, PJP pneumonia was not observed. AAV patients with lung involvement were more likely to be on PJP prophylaxis.

Pneumocystis jirovecii pneumonia in people living with HIV: a review.

SUMMARYPneumocystis jirovecii is a ubiquitous opportunistic fungus that can cause life-threatening pneumonia. People with HIV (PWH) who have low CD4 counts are one of the populations at the greatest risk of Pneumocystis jirovecii pneumonia (PCP). While guidelines have approached the diagnosis, prophylaxis, and management of PCP, the numerous studies of PCP in PWH are dominated by the 1980s and 1990s. As such, most studies have included younger male populations, despite PCP affecting both sexes and a broad age range. Many studies have been small and observational in nature, with an overall lack of randomized controlled trials. In many jurisdictions, and especially in low- and middle-income countries, the diagnosis can be challenging due to lack of access to advanced and/or invasive diagnostics. Worldwide, most patients will be treated with 21 days of high-dose trimethoprim sulfamethoxazole, although both the dose and the duration are primarily based on historical practice. Whether treatment with a lower dose is as effective and less toxic is gaining interest based on observational studies. Similarly, a 21-day tapering regimen of prednisone is used for patients with more severe disease, yet other doses, other steroids, or shorter durations of treatment with corticosteroids have not been evaluated. Now with the widespread availability of antiretroviral therapy, improved and less invasive PCP diagnostic techniques, and interest in novel treatment strategies, this review consolidates the scientific body of literature on the diagnosis and management of PCP in PWH, as well as identifies areas in need of more study and thoughtfully designed clinical trials.

Characteristics and Prognosis Factors of Pneumocystis jirovecii Pneumonia According to Underlying Disease: A Retrospective Multicenter Study

Pneumocystis jirovecii pneumonia (PcP) remains associated with high rates of mortality, and the impact of immunocompromising underlying disease on the clinical presentation, severity, and mortality of PcP has not been adequately evaluated. Does the underlying disease and immunosuppression causing PcP impact the outcome and clinical presentation of the disease? In this multicenter retrospective observational study, conducted from January 2011 to December 2021, all consecutive patients admitted with a proven or probable diagnosis of PcP according to the European Organisation for Research and Treatment of Cancer consensus definitions were included to assess the epidemiology and impact of underlying immunosuppressive diseases on overall and 90-day mortality. Overall, 481 patients were included in the study; 180 (37.4%) were defined as proven PcP and 301 (62.6%) were defined as probable PcP. Patients with immune-mediated inflammatory diseases (IMIDs) or solid tumors had a statistically poorer prognosis than other patients with PcP at day 90. In multivariate analysis, among the HIV-negative population, solid tumor underlying disease (OR, 5.47; 95%CI, 2.16-14.1; P< .001), IMIDs (OR, 2.19; 95%CI, 1.05-4.60; P= .037), long-term corticosteroid exposure (OR, 2.07; 95%CI, 1.03-4.31; P= .045), cysts in sputum/BAL smears (OR, 1.92; 95%CI, 1.02-3.62; P= .043), and SOFA score at admission (OR, 1.58; 95%CI, 1.39-1.82; P< .001) were independently associated with 90-day mortality. Prior corticotherapy was the only immunosuppressant associated with 90-day mortality (OR, 1.67; 95%CI, 1.03-2.71; P= .035), especially for a prednisone daily dose≥ 10mg (OR, 1.80; 95%CI, 1.14-2.85; P= .010). Among patients who were HIV-negative, long-term corticosteroid prior to PcP diagnosis was independently associated with increased 90-day mortality, specifically in patients with IMIDs. These results highlight both the needs for PcP prophylaxis in patients with IMIDs and to early consider PcP curative treatment in severe pneumonia among patients with IMIDs.