Risk Of Pneumocystis Jirovecii Pneumonia Research Articles

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.

Clinical characteristics and risk factors for late-onset pneumocystis jirovecii pneumonia in kidney transplantation recipients.

Pneumocystis jirovecii pneumonia (PJP) is a common and troublesome complication of kidney transplantation. In the era of prophylaxis, the peak incidence of PJP after kidney transplantation and specific characteristics of late-onset PJP have always been debated. We performed a retrospective study by analysing the data of post-transplantation pneumonia in adult kidney transplantation recipients between March 2014 and December 2021 in The Affiliated First Hospital of University of Science and Technology of China (USTC). A total of 361 patients were included and divided into early-onset PJP, late-onset PJP and non-PJP groups. The characteristics of each group and related risk factors for the late-onset patients were investigated. Some patients developed PJP 9 months later with a second higher occurrence between month 10 and 15 after transplantation. Compared with non-PJP, ABO-incompatible and cytomegalovirus (CMV) viremia were significantly associated with late onset of PJP in multivariate analysis. The use of tacrolimus, CMV viremia, elevated CD8(+) T cell percent and hypoalbuminemia were risk factors for late PJP. Receiver operating characteristic curve analysis demonstrated that a combination of those factors could increase the sensitivity of prediction remarkably, with an area under the curve of 0.82, a sensitivity of 80% and a specificity of 83%. PJP could occur months after kidney transplantation. ABO-incompatible transplant recipients are at high risk of PJP. In the later stages of transplantation, CMV viremia, T lymphocyte subsets percentage and serum albumin levels should be monitored in patients using tacrolimus.

Prevalence of Pneumocystis jirovecii Colonization in Non-Critical Immunocompetent COVID-19 Patients: A Single-Center Prospective Study (JiroCOVID Study).

Pneumocystis jirovecii pneumonia (PJP) is an invasive fungal infection (IFI) that occurs mainly in immunocompromised hosts. After observing a high prevalence of PJP as a complication of COVID-19 in immunocompetent patients, we conducted a study to evaluate the prevalence of P. jirovecii colonization with PCR on oral washing samples (OWS) among non-immunocompromised and non-critical patients admitted with COVID-19 pneumonia at our university hospital. All patients over 18 years of age admitted to the Infectious Diseases Unit for SARS-CoV-2 pneumonia between July 2021 and December 2022 were included. Patients undergoing invasive mechanical ventilation or ECMO, those with risk factors for developing PJP, and those receiving prophylaxis for P. jirovecii were excluded. Samples were collected by gargling with 10 mL of 0.9% NaCl on day 14 of the hospital stay or at discharge. Of 290 screened patients, 59 (20%) met the inclusion criteria and were enrolled. Only 1 of 59 patients (1.7%) tested positive for P. jirovecii detection with PCR, and the same patient was the only one to develop PJP in the follow-up period. Our results are in line with the previous findings of other studies that confirmed a very low prevalence of P. jirovecii colonization on OWS in the immunocompetent population. Despite the limitations of the study, the fact that the only patient who tested positive for P. jirovecii was the only one in our cohort to develop PJP leads us to reflect on the role of this non-invasive sample in predicting the risk of PJP in patients with COVID-19.

Risk Factors of Pneumocystis jirovecii Pneumonia in Patients with Inflammatory Bowel Disease: A Nationwide Population-Based Study.

: Pneumocystis jirovecii pneumonia (PJP) is a rare but potentially fatal infection. This study was conducted to investigate the risk factors for PJP in inflammatory bowel disease (IBD) patients. : This nationwide, population-based study was conducted in Korea using claims data. Cases of PJP were identified in patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) between 2010 and 2017, and the clinical data of each patient was analyzed. Dual and triple therapy was defined as the simultaneous prescription of two or three of the following drugs: steroids, calcineurin inhibitors, immunomodulators, and biologics. : During the mean follow-up period (4.6±2.3 years), 84 cases of PJP were identified in 39,462 IBD patients (31 CD and 53 UC). For CD patients, only age at diagnosis >40 years (hazard ratio [HR], 6.12; 95% confidence interval [CI], 1.58 to 23.80) was significantly associated with the risk of PJP, whereas in UC patients, diagnoses of diabetes (HR, 2.51; 95% CI, 1.19 to 5.31) and chronic obstructive pulmonary disease (HR, 3.41; 95% CI, 1.78 to 6.52) showed significant associations with PJP risk. Triple therapy increased PJP risk in both UC (HR, 3.90; 95% CI, 1.54 to 9.88) and CD patients (HR, 5.69; 95% CI, 2.32 to 14.48). However, dual therapy increased PJP risk only in UC patients (HR, 2.53; 95% CI, 1.36 to 4.70). Additionally, 23 patients (27%) received intensive care treatment, and 10 (12%) died within 30 days. : PJP risk factors differ in CD and UC patients. Considering the potential fatality of PJP, prophylaxis should be considered for at-risk IBD patients.

Prevention of pneumocystis pneumonia in patients with hematological diseases: Efficacy oflow-dose atovaquone.

At our institution, patients with hematological disease who require Pneumocystis jirovecii pneumonia (PJP) prophylaxis were administered atovaquone at a low dose (750 mg/day). However, there have been few reports on the efficacy of low-dose atovaquone administration, and the purpose of this study is, therefore, to investigate its effectiveness. We investigated the expression of PJP in patients with hematological disease who received atovaquone administration. Atovaquone was administered at a low dose of 750 mg once daily, and the follow-up time was the period of PJP prophylaxis that included atovaquone administration. 85 patients were included in the study. The median age of the study population was 72 years (range: 33-97). The duration of atovaquone treatment and follow-up time were 150 days (22-1,018) and 258 days (22-1,457), respectively. In hematologic diseases, multiple myeloma was high in 31 patients and malignant lymphoma in 28 patients. No patients exhibited PJP during the observation period. In hematological disease patients with relatively low risk of PJP, low-dose atovaquone may prevent the onset of PJP.

Invasive fungal diseases in patients with autoimmune diseases: a case series from the French RESSIF network

ObjectivesWe aimed to describe patients with autoimmune diseases (AID) developing invasive fungal disease (IFD) and identify factors associated with short-term mortality.MethodsWe analysed cases of IFD associated with AID from the...

Cotrimoxazole as a Preventative Intervention for Pneumocystis Pneumonia in Pemphigus Patients Treated with Rituximab: A Retrospective Study.

Pneumocystis jirovecii pneumonia (PJP) is a severe, life-threatening complication in patients treated with rituximab. However, there is no consensus on the primary prophylaxis for it in rituximab-treated pemphigus patients. Therefore, we sought to investigate the prophylactic efficacy and safety profile of cotrimoxazole for reducing the risk of developing PJP in pemphigus patients receiving rituximab. This single-center retrospective study investigated 148 pemphigus patients undergoing a first cycle of rituximab between 2008 and 2021 at a tertiary referral center in northern Taiwan. Patients were divided into the prophylaxis group (N = 113) and the control group (N = 35) according to whether or not cotrimoxazole was administered. The primary outcome was the 1-year incidence of PJP in the two groups, while the secondary outcome was the incidence of cotrimoxazole-related adverse events. Of the 148 patients enrolled in this study, three patients, all in the control group, developed PJP during the 1-year follow-up. The incidence of PJP (8.6%) in the control group was significantly higher than that in the prophylaxis group (0%) (p = 0.012). The incidence of cotrimoxazole-related adverse events was 2.7%, and none of the cases were associated with life-threatening conditions. In addition, the cumulative prednisolone dose was associated with a trend of a higher risk of PJP (p = 0.0483). Prophylactic cotrimoxazole significantly reduces the risk of PJP in a certain high-risk population and has a tolerable safety profile.

Risk factors and outcomes of Pneumocystis pneumonia in solid organ transplant recipients: Impact of posttransplant lymphoproliferative disorder.

Pneumocystis jirovecii pneumonia (PJP) is a potentially fatal infection afflicting the immunocompromised population, including solid organ transplant (SOT) recipients. Several risk factors have been described; however, little is known regarding the risk of PJP in SOT recipients with posttransplant lymphoproliferative disorder (PTLD). We performed a nested case-control study of SOT recipients diagnosed with PJP from 2000 to 2020. PJP was defined as positive microscopy or polymerase chain reaction testing with compatible symptoms and radiographic findings. Control patients were matched 2:1 by year of first transplant, first transplanted organ, transplant center, and sex. Multivariable conditional logistic regression was performed to test associations with PJP and Cox regression analyzed post-PJP outcomes. Sixty-seven PJP cases were matched to 134 controls. The most common transplant was kidney (55.2%). Fourteen patients had a history of PTLD, 12 of whom developed PJP. After adjusting for age, acute rejection, cytomegalovirus infection, PJP prophylaxis, and lymphopenia (lymphocyte count<.5×109 /L), PTLD was independently associated with PJP (OR 14.0, 95% CI 1.7-114.5; p=.014). Lymphopenia was also a significant association (OR 8.2, 95% CI 3.2-20.7; p<.001). PJP was associated with mortality within 90days of diagnosis (p<.001), but not after 90days (p=.317). PJP was also associated with 90-day death-censored renal allograft loss (p=.026). PTLD is independently associated with PJP after adjustment for recognized risk factors. This is likely influenced by PTLD-directed chemotherapy, particularly rituximab-containing regimens. PJP is associated with early mortality, but this effect is not persistent after 90days. PJP prophylaxis should be considered in SOT recipients with PTLD.

Risk of Pneumocystis jirovecii Pneumonia among Solid Organ Transplant Recipients: A Population-Based Study.

Few studies have comprehensively investigated the occurrence of Pneumocystis jirovecii pneumonia (PJP) among solid organ transplant (SOT) recipients. This study investigated the risk of PJP after organ transplantation. Each patient who underwent SOT was propensity-score-matched with four non-SOT individuals in terms of sex, age, insured salary, urbanization of residence, comorbidities, and year of enrollment. When considering the 3-year follow-up, the patients who had undergone SOT were at higher risk of PJP, with the adjusted odds ratio (aOR) being 17.18 (95% confidence interval (CI): 8.80-33.53). Furthermore, SOT recipients were also at higher PJP risk than the patients without SOT at 6 months, 1 year, and 2 years, with the aOR being 22.64 (95% CI: 7.53-68.11), 26.19 (95% CI: 9.89-69.37), and 23.06 (95% CI: 10.23-51.97), respectively. Patients comorbid with HIV infection, hematological malignancies, or vasculitis were at higher risk (aOR = 59.08, 95% CI = 20.30-171.92), (aOR = 11.94, 95% CI = 5.36-26.61), and (aOR = 21.72, 95% CI = 2.41-195.81), respectively. The recipients of SOT were at higher risk of PJP, and PJP can develop at any stage after transplantation. SOT recipients comorbid with HIV, hematologic malignancies, or vasculitis were at higher PJP risk.

356. Risk Assessment of Pneumocystis jirovecii Pneumonia among Hospitalized Patients with Hypoxic Respiratory Failure - A Proposed Multivariable Calculator Based on Previous Prednisone Equivalent Dose

Abstract Background Corticosteroids increase the risk of Pneumocystis jirovecii pneumonia (PJP). It is unknown how much corticosteroid dose exposure would modify the risk of PJP in different populations. We aim to develop a PJP risk calculator based on the previous dose of corticosteroids and modulated by additional clinical factors. Methods A multicenter retrospective case-control study was performed on patients tested for PJP within the UCHealth system from 2000 to 2021. We developed a model for estimating PJP risk based on previous prednisone equivalent daily dose (PEDD) and adjustable for additional clinical variables. PJP was fit to a generalized additive model (GAM), with a spline for prednisone dose and additive covariates for demographics and risk factors. We used a multicenter federated network to calibrate the model to estimate the PJP prevalence among hospitalized patients with hypoxic respiratory failure. Results We had a complete sample of 199 patients, 104 cases with PJP, and 95 controls. Patients with HIV (OR: 19 CI: 6.3-60.8, p&amp;lt; 0.0001), diabetes (OR: 4.1 CI: 1.2-14.8, p&amp;lt; 0.0288), and autoimmune disease (OR: 5.2 CI: 1.4-19.2, p&amp;lt; 0.0139) were more likely to have PJP. Patients with preexisting lung disease (OR: 0.3 CI: 0.1-0.6, p&amp;lt; 0.0041) and on PJP prophylaxis (OR: 0.06 CI: 0.02-0.2, p&amp;lt; 0.0001) were less likely to have PJP. 36.8% of controls and 49% of cases were on steroids with a mean PEDD of 15 mg/day and 20.4 mg/day, respectively. We found a prevalence of PJP of 0.126% among hospitalized patients with hypoxic respiratory failure. The developed model can estimate the PJP risk based on a previous PEDD in 32 different clinical combinations: e.g., a PEDD of 20 mg/day would give a calculated annual PJP risk of approximately 1.74% (95% CI: [0.39, 7.42]) if a patient has autoimmune disease only but 6.29% (95% CI: [1.34, 24.91]) if a patient has HIV only (Figure 1). Figure 1.Predicted probability of PJP based on previous prednisone dose among hospitalized patients with hypoxic respiratory failure for three different clinical scenarios Conclusion Previous corticosteroid dose alone is inadequate to inform of an increased risk of PJP. A multivariable calculator incorporating the absence or presence of additional traditional risk factors could optimally stratify the PJP risk. Future directions include validating the findings in external cohorts and modeling PJP risk in the ambulatory setting to inform the need for PJP prophylaxis. Disclosures All Authors: No reported disclosures.

Combine use of glucocorticoid with other immunosuppressants is a risk factor for Pneumocystis jirovecii pneumonia in autoimmune inflammatory disease patients: a meta-analysis.

To determine whether the combined use of glucocorticoid with other immunosuppressants increased the risk of Pneumocystis jirovecii pneumonia (PCP) in autoimmune inflammatory disease (AIID) patients. The data were collected from the PubMed, Cochrane Library, and Web of Science databases. We excluded HIV-infected patients and those < 16years of age, and included patients who combined use of glucocorticoid with other immunosuppressants or used glucocorticoid alone. The number of patients who were affected by PCP after therapy as the primary outcome and the number of patients with fatal outcomes, which included death, endotracheal tube intubation, PO2 < 60mmHg, and other serious clinical symptoms due to PCP, as the secondary outcome. Odds ratios with 95% confidence intervals and variance tests were used to analyze the data. The outcomes showed that the combined use of glucocorticoid with other immunosuppressants increased the risk of PCP in AIID patients (odds ratio = 2.85, 95% confidence intervals 1.75 to 4.64, I2 = 0%, P < 0.0001), which may be a consequence of the drug regimen reducing the lymphocyte count. Furthermore, the prognosis of patients receiving this drug regimen was poorer than with glucocorticoid alone (odds ratio = 2.31, 95% confidence intervals 1.02 to 5.23, I2 = 0%, P = 0.04). The combined use of glucocorticoid with other immunosuppressants increased the risk of PCP in AIID patients and resulted in poorer prognoses. It is therefore clear that appropriate prophylaxis was vital in AIID patients to minimize the risk of PCP. Key Points • We demonstrated that the combined use of glucocorticoid with other immunosuppressants increased the risk of PCP in AIID patients and resulted in poorer prognoses. • As there are no standard prophylactic guidelines, we wish this work will be evidence to guide clinical prophylaxis.

Pneumocystis Jirovecii Pneumonia in Systemic Lupus Erythematosus: A Nationwide Cohort Study in Taiwan.

To evaluate Pneumocystis jirovecii pneumonia (PJP) infection risk in patients with systemic lupus erythematosus (SLE) in Taiwan. We identified 24,367 patients with SLE from the National Health Insurance research database between 1997 and 2012 and compared the PJP incidence rates (IRs) with those in 243,670 age- and sex-matched non-SLE controls. PJP risk in the patients was evaluated using a Cox multivariate proportional hazards model. The SLE patients exhibited a significantly higher PJP risk than the controls, with an IR of 2.63 per 10,000 person-years and IR ratio of 27.65 (95% confidence interval 17.2-45.3; P < 0.001). Male sex (hazard ratio [HR] 2.42, P < 0.01), end-stage renal disease (ESRD; HR 1.74, P=0.01), recent use of mycofenolate mofetil (MMF; HR 4.43, P < 0.001), intravenous steroid pulse therapy (HR 108.73, P < 0.001), and average oral dosage of >7.5 mg/day prednisolone or equivalent treatment (HR 4.83, P < 0.001) were associated with PJP in SLE, whereas hydroxychloroquine use reduced its risk (HR 0.51, P=0.01). Of note, cyclophosphamide was not associated with PJP infection in the multivariate Cox proportional hazard model. Patients with SLE have a considerably high PJP risk. Cyclophosphamide does not increase PJP risk. Male sex, ESRD, MMF use, intravenous steroid pulse therapy, and oral prednisolone or equivalent treatment (>7.5 mg/day) are risk factors for PJP, whereas hydroxychloroquine use reduces PJP risk.

Pneumocystis jirovecii Pneumonia in Patients with Rheumatic Diseases: Risk Assessment and Prophylaxis

Pneumocystis jirovecii pneumonia (PJP) is an uncommon opportunistic infection in patients with rheumatic diseases with high mortality. Unlike other non-HIV conditions, international guideline for PJP prophylaxis in rheumatic diseases is currently lacking. Recent evidence regarding the risk of PJP and effectiveness of prophylaxis has been accumulating. This Review provides an update on the information about risk factors associated with PJP in patients with rheumatic diseases based on rheumatic diagnoses, use of immunosuppressive agents and other disease-related factors. The second part of the article summarizes evidence regarding the effectiveness of PJP prophylaxis by considering both disease-related and therapy-related factors. Finally, the Review outlined the currently available disease-specific recommendations and local guidelines, and appreciate the factors that influence physicians’ decision.

36. Evaluation of a Best Practice Alert (BPA) to Improve Pneumocystis jirovecii Prophylaxis Prescribing in Cancer Patients Receiving High-dose Corticosteroids in an Outpatient Setting

Abstract Background In patients (pts) with cancer, the risk of Pneumocystis jirovecii pneumonia (PJP) is a function of dose and duration of corticosteroids (CS), underlying immunodeficiency, and immunosuppressive drugs. Trimethoprim/sulfamethoxazole (TMP/SMX) and atovaquone (ATO) are effective prophylaxis (ppx) agents against PJP. Guidelines recommend PJP ppx for pts on &amp;gt; 20 mg /day of prednisone or its equivalent for ≥ 1 month. A best practice alert (BPA) to identify pts receiving CS may assist with improving PJP ppx prescribing in cancer pts. Methods PJP BPA was created to identify pts on CS (excluding hydrocortisone) with no active prescription for TMP/SMX or ATO ppx in EMR. Dapsone and pentamidine excluded since not preferred agents at our institution. PJP case: positive PJP polymerase chain reaction (PCR) from bronchoalveolar lavage (BAL) &amp;gt; 84 copies or positive PJP direct fluorescent antibody (DFA) or cytology with clinical and radiographic suspicion. PJP PCR from BAL &amp;lt; 84 copies/ml with negative DFA and cytology excluded. Preventable PJP (P-PJP): pts after CS &amp;gt; = 30 days without PJP ppx. Non-preventable PJP (NP-PJP) : pts after CS &amp;lt; 30 consecutive days, or on PJP ppx (non-compliance, failure), or day +1 to +30 post hematopoietic cell transplant (HCT). Pre-intervention (pre-i) PJP pts 3/1/2018 to 7/31/19 (17 months), post-intervention (post-i) PJP pts 8/1/19 to 2/1/20 (18 months) evaluated to assess BPA impact on PJP inpatient (inpt) admissions. Results In the post-i, the BPA fired 3,588 times in 1,302 pts. Pre-i: 20 P-PJP, 13 NP-PJP out of 33 pts. Post-i: 6 P-PJP, 25 NP-PJP out of 31 pts. The BPA fired in 4/31 PJP pts in the post-i period: 2/6 of P-PJP, 2/25 NP-PJP. The number of P-PJP decreased from 20 to 6 in the post-i period (p=0.0097). Conclusion Implementation of a decision support tool significantly decreased the number of P-PJP. The BPA was limited by identifying pts after CS were prescribed after the initial visit leading to periods of CS use without ppx and inability to calculate CS dosing and length of prescription. BPA provided passive education in the outpatient setting and future opportunities include refining the EMR to better identify pts at risk for developing PJP. Disclosures All Authors: No reported disclosures

Primary Prophylaxis for Pneumocystis jirovecii Pneumonia in Patients Receiving Rituximab

Although previous studies suggested that rituximab increases the risk of Pneumocystis jirovecii pneumonia (PJP), it is uncertain whether its primary prophylaxis for PJP is justified. Does the benefit of primary prophylaxis for PJP in patients receiving rituximab treatment outweigh the potential risk of the prophylaxis? This retrospective study included 3,524 patients (hematologic diseases, 2,500; rheumatic diseases, 559; pre/post-solid organ transplantation, 465) first exposed to rituximab between 2002 and 2018 in a tertiary referral center in South Korea. Patients were classified into a control group (n= 2,523) and a prophylaxis group (n= 1,001) according to the administration of prophylactic trimethoprim-sulfamethoxazole (TMP-SMX) during the first 28days after the start of rituximab (intention-to-treat analysis). In addition, exposure to TMP-SMX was examined as a time-varying variable (time-varying analysis). The primary outcome was the prophylactic effect of TMP-SMX on the 1-year incidence of PJP. Inverse probability of treatment weights was applied to minimize the baseline imbalance. The secondary outcome included the incidence of adverse drug reactions (ADRs) related to TMP-SMX. Over 2,759.9 person-years, 92 PJP infections occurred, with a mortality rate of 27.2%. The prophylaxis group showed a significantly lower incidence of PJP (adjusted subdistribution hazard ratio, 0.20 [95%CI, 0.10-0.42]) than the control group. This result was consistent with the results of time-varying analysis, in which only one PJP infection occurred during TMP-SMX administration (adjusted subdistribution hazard ratio, 0.01 [0.003-0.16]). The incidence of ADRs related to TMP-SMX was 18.1 (14.6-22.2)/100 person-years, and most were of mild to moderate severity. On the basis of 10 severe ADRs, the number needed to harm was 101 (61.9-261.1), whereas the number needed to prevent one PJP infection was 32 (24.8-39.4). TMP-SMX prophylaxis significantly reduces PJP incidence with a tolerable safety profile in patients receiving rituximab treatment.

Reducing the Risk of Death From Pneumocystis jirovecii Pneumonia After Radical Radiation Therapy to the Lung

AimsLung cancer is the leading cause of cancer death. Radiotherapy given in the curative setting is associated with a 3% risk of death from Pneumocystis jirovecii pneumonia (PJP). Prolonged courses of high-dose steroids also increase the risk of PJP. International guidelines recommend the use of chemoprophylaxis with trimethoprim-sulfamethoxazole for patients at high risk. We assessed the effect of an intervention designed to reduce the impact of PJP. Materials and methodsProphylaxis guidelines were introduced in 2016. Case records of patients treated with radical radiotherapy were examined for the periods 2014 to 2015 (pre-intervention) and 2017 to 2018 (post-intervention). In total, 247 patients were treated pre-intervention and 334 post-intervention. ResultsFreedom from PJP death at 1 year was 96% before intervention and 99% after (hazard ratio 0.3, 95% confidence interval 0.1–0.9, P = 0.029). Although the rate of use of chemoprophylaxis according to the guideline rose from 1% to 13% (P = 0.003), the use of high-dose steroids also fell from 35% to 16% (P < 0.00001). ConclusionsReducing radiotherapy-associated infections is an important component of radical treatment in lung cancer. Highlighting chemoprophylaxis guidelines reduced the death rate from PJP, with an associated more judicious use of steroids. Advocating prophylaxis in patients with lymphocyte count <0.6 × 109/l is the next intervention to be studied.

Routine Prophylaxis of Pneumocystis Pneumonia from the Fourth Cycle of R-CHOP Regimen in DLBCL Patients

▪Introduction: In our previous report, approximately 10% of diffuse large B cell (DLBCL) patients experienced non-neutropenic fever (NNF) during R-CHOP chemotherapy, and interstitial pneumonitis comprised approximately 55% of NNF cases. Pneumocystis jirovecii is one of the most common pathogens causing interstitial pneumonia, and increasing evidences suggest that R-CHOP may increase the risk of PJP with reported incidence of 5%.Method: A total of 404 patients with newly diagnosed DLBCL between Jan 2012 and Aug 2016 who were registered in the prospective study and were treated with R-CHOP were analyzed in this study. Before Mar 2014, primary prophylaxis for Pneumocystis jirovecii pneumonia (PJP) was not performed, whereas, bactrim (1 table daily) was dosed from the initiation of 4th cycle of R-CHOP chemotherapy thereafter. With this change of institutional strategy, we hypothesized that the incidence of PJP may differ by prophylaxis strategy.Results: The median age was 56 years (range, 20-85) and 297 patients (73.5%) completed 6 cycles of R-CHOP chemotherapy. The rest completed 1 (n=18, 4.5%), 2 (n=4, 1.0%), 3 (n=23, 5.7%), 4 (n=37, 9.2%), 5 (n=14, 3.5%), 7 (n=3, 0.7%) and 8 (n=8, 2.0%) cycles of treatment. Overall, 3 (0.7%) and 9 patients (2.2%) were diagnosed with definite and probable PJP during the period, and the incidence of definite plus probable PJP was 5.4%. Of 404 patients in the cohort, 220 (54.5%) patients were the candidates for routine prophylaxis with Bactrim. The incidence of definite and probable PJP before prophylaxis was 4.9% (9 out of 184 patients), which was decreased to 1.4% (3 out of 220 patients) after routine prophylaxis with bactrim (p=0.038). In the era of prophylaxis, 3 cases of PJP were all occurred before the 4th cycle and there was no PJP cases after the 4th cycle, while 6 PJP cases before Mar 2014 were noticed after 4-6 cycles of R-CHOP (0% vs 3.3%, p=0.007).Conclusion: Routine prophylaxis with bactrim during later cycles of R-CHOP regimen significantly reduces the incidence rate of PJP in DLBCL patients. DisclosuresKim:Novartis: Research Funding; Donga: Research Funding; Takeda: Research Funding; J&J: Research Funding; Kyowa-Kirin: Research Funding; Celltrion, Inc: Consultancy, Honoraria; Mundipharma: Research Funding; Roche: Research Funding.

Pneumocystis jirovecii pneumonia in autoimmune rheumatic diseases: a nationwide population-based study.

ObjectiveTo compare Pneumocystis jirovecii pneumonia (PJP) risk between patients with autoimmune rheumatic diseases (ARD) and the general populationMethodsWe identified patients with ARD recorded in the National Health Insurance Research Database of Taiwan from 2002 to 2015 and randomly selected a comparison cohort from the general population matched for age and sex. We analyzed PJP risk stratified by sex, age, comorbidities, and medications using Cox proportional hazard model.ResultsWe enrolled 103,117 patients with ARD. PJP risk significantly increased in patients with any ARD and with each individual ARD like rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren’s syndrome (SjS), polymyositis and dermatomyositis (PM/DM), systemic sclerosis (SSc), and systemic vasculitis. Patients with PM/DM showed prominent risk with incidence rate of 12.47/100,000 patient year (95% confidence interval (CI), 32.16–86.70). In a time-dependent Cox proportional hazard model with comorbidities and medications as covariates, PM/DM, SSc, SLE, and SjS significantly increased adjusted hazard ratios (aHR) of 5.40, 5.12, 4.09, and 3.64, respectively (95% CI of 2.82–10.35, 2.16–12.13, 2.41–6.95, and 2.06–6.42, respectively). AHR after adjusting for male sex, cancer, human immunodeficiency virus infection (HIV), and interstitial lung disease also significantly increased. Use of daily oral steroid dose of >10 mg conferred the highest risk followed by mycophenolate. Use of injected steroids, cyclophosphamide, biological agents, methotrexate, and cyclosporine conferred a significantly higher risk.ConclusionUnderlying ARD significantly predisposes patients to PJP, with PM/DM posing the highest threat. In addition to underlying disease, comorbidities and concomitant immunosuppressants are major risks. The strongest risk is recent daily steroid dose of >10 mg. Mycophenolate seems to be a more prominent risk factor than cyclophosphamide.Key Points• Autoimmune rheumatic diseases (ARD) significantly increased the overall risk of PJP, and so did each individual ARD.• Use of steroids, mycophenolate, cyclophosphamide, biological agents, methotrexate, and cyclosporine all significantly increased risk of PJP.• Male, elderly, malignancy, HIV, and interstitial lung disease are also related to increased risk of PJP.• Underlying ARD, comorbidities, and use of immunosuppressant should all be considered in determining the overall risk of PJP.

The risk factor analysis and treatment experience in pneumocystis jirovecii pneumonia after kidney transplantation.

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection among solid organ transplantation. The occurrence of PJP is dangerous and fatal if there is no early identification and sufficient treatment. The aim of this study was to evaluate the risk factors and provide appropriate strategies of prophylaxis and treatment for PJP after kidney transplantation in our centre. From January 2009 to December 2018, a total of 167 kidney transplantation recipients with pneumonia were enrolled, including 47 PJP patients as PJP group and 120 non-PJP patients as control group. The clinical characteristics of the two groups were analysed retrospectively. Multivariate analysis showed that high total dosage of ATG [OR, 2.03; 95% CI, 1.12-3.68] and cytomegalovirus (CMV) infection were independent risk factors for PJP. Trimethoprim-sulfamethoxazole (TMP-SMX) (1.44g q6h)-based treatment was used for 2weeks, and its dosage and course were adjusted according to the therapeutic effect and side effects. Forty-five cases were recovered after 3months of follow-up, and two patients died of respiratory failure. TMP-SMX (0.48g/day) prophylaxis was used for 3-6months and prolonged to 7-8months after treatment for acute rejection, which reduced the incidence of PJP compared with those without prophylaxis. Our study suggests that the high total dosage of ATG and CMV infection indicate the increased risk of PJP. The strategies of prophylaxis and treatment for PJP after kidney transplantation in our centre were effective.