Pneumocystis Jirovecii Pneumonia Prophylaxis Research Articles

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 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.

Dismal prognosis of Pneumocystis jirovecii pneumonia in patients with multiple myeloma

Patients with multiple myeloma (MM) are at high risk for infections, including opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP). We conducted a retrospective analysis of patients with MM developing PJP over a 6-year period between January 2016 and December 2021 at the University Hospital of Würzburg by screening cases of microbiologically documented PJP. A total of 201 positive results for P. jirovecii in respiratory specimens were retrospectively retrieved through our microbiology database. Of these cases, 13 patients with MM fulfilled the definition of probable PJP according to EORTC fungal disease definitions. We observed two peaks in PJP incidence, one after stem cell transplantation during first-line treatment (n = 5) and the other in heavily pretreated patients with six or more prior lines of therapy (n = 6). There was high morbidity with nine (69%) patients admitted to the ICU, seven of whom (78%) required mechanical ventilation, and high mortality (62%, n = 8). Notably, only two of the 13 patients (15%) had received PJP prophylaxis. The main reason for discontinuation of prophylaxis with trimethoprim-sulfamethoxazole was grade IV neutropenia. The observed morbidity and mortality of PJP in MM patients are significant and even higher than reported for patients with other hematologic malignancies. According to most current guidelines, the use of prophylaxis would have been clearly recommended in no more than three (23%) of the 13 patients. This illustrates the need to critically reconsider the indications for PJP prophylaxis, which remain incompletely defined.

Selective PI3Kδ Inhibitor Parsaclisib Combined with HDAC Inhibitor Chidamide in Patients with Relapsed/Refractory Peripheral T-Cell Lymphoma: Preliminary Results of a Phase Ib/Ⅱ Study

Background: Peripheral T-cell lymphoma (PTCL) is a highly heterogenous non-Hodgkin lymphoma with poor survival. Pts with relapsed/refractory PTCL (r/r PTCL) have extremely poor prognosis and limited treatment options. Conventional salvage treatments have a median progression-free survival (PFS) of only 3-4 months. Parsaclisib, a potent, highly-selective, next-generation PI3Kδ inhibitor has shown encouraging efficacy and favorable safety profile in B-cell malignancies. We developed a phase Ib/II study to evaluate the safety and efficacy of parsaclisib with HDAC inhibitor (HDACi) chidamide in r/r PTCL (NCT05083208). Here, we report the preliminary results of this study. Method: Eligible pts were ≤ 75 years old adults with histologically confirmed PTCL who received ≥ prior line of systemic therapy. Phase Ib dose-escalation study determined the maximum tolerated dose (MTD) of parsaclisib with chidamide using a 3 + 3 design. Parsaclisib was administered once daily at 3 dose levels (dose-level (DL) 1: 10 mg; DL2: 15 mg; DL3: 20mg) in the first 8 weeks followed by 2.5 mg QD in the subsequent treatment. Chidamide was administered at a fixed dose of 20 mg twice a week throughout the study. Once the MTD was established, pts were enrolled into phase 2 study to further characterize safety and efficacy. MTD of parsaclisib and objective response rate (ORR) were the primary endpoints; complete response rate (CRR), PFS, overall survival (OS) and tolerability were secondary endpoints. Prophylaxis for Pneumocystis jirovecii pneumonia (PJP) and cytomegalovirus (CMV) infection in the first 8 weeks were required. Results: From March 2022 to July 27, 2023 (date cut-off), 11 pts were recruited with a median age of 52 (39-74) years old. The median number of prior systemic therapies was 2 (1-5). Of 6 pts treated at DL1, 1 had dose-limiting toxicity (DLT) (grade 3 elevation of ALT/AST). No DLT was observed in 3 pts at DL2 and 2 at DL3. The DLT was resolved subsequently but the patient died from lymphoma progression. Treatment-emergent adverse events (TEAEs) were observed in all pts. The TEAEs were mainly hematologic toxicities and gastrointestinal reactions, most of which were grade 1/2. Grade 3/4 TEAEs were neutropenia (n=4), leukopenia (n=1), elevation of ALT/AST (n=1), and diarrhea (n=1) (Table 1). TEAE led to dose interruption in one patient. In 9 pts evaluable for responses (1 withdrew from this study and 1 was unevaluable), 5 (55.6%) pts achieved complete response (CR) and one (11.1%) partial response at the first efficacy assessment. In 7 pts previously exposed to chidamide, 4 pts achieved CR and 2 of them had a PFS &amp;gt; 16 months (Table 2 and Figure 1). Conclusion: Preliminary data demonstrated that selective PI3Kδ Inhibitor parsaclisib with HDACi chidamide was tolerable and produced promising responses in r/r PTCL, including patients previously exposed to chidamide. This trial is currently ongoing.

Incidence of Pneumonia Among Bruton Tyrosine Kinase Inhibitors in Chronic Lymphocytic Leukemia: A Systematic Review and Meta-Analysis of Clinical Trials

Introduction: Bruton tyrosine kinase (BTK) signaling is critical for the proliferation and survival of malignant B lymphocytes in chronic lymphocytic leukemia (CLL). BTK inhibitors (BTKi) are used in the front-line setting as well as for relapsed/refractory (R/R) CLL. Three BTKi are currently approved by the United States Food and Drug Administration (US FDA) for CLL - ibrutinib, acalabrutinib, and zanubrutinib. However, there are some uncertainties on the risk of infections, especially pneumonia, from BTKi due to its potential off-target effects and its immunomodulatory effects on innate and adaptive immune response. The newer second-generation BTKi, acalabrutinib and zanubrutinib, have attenuated off-target effects compared to ibrutinib. We hereby evaluate the incidence of pneumonia, including Pneumocystis jirovecii pneumonia (PJP) and other fungal pneumonia, from BTKi monotherapy in patients with treatment naïve as well as relapsed CLL and compare the incidence among different BTKi. Methods: This systematic review identified clinical trials from MEDLINE, Embase, and CENTRAL databases from the inception to 30 June 2023. The number of cases with any grade and at least grade 3 lung infection/pneumonia, PJP and other fungal pneumonia, along with the total number of patients in the arms with BTKi monotherapy were extracted from each trial per the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The incidence meta-analysis was performed using “meta” package version 6.5-0 of R version 4.2.2, via random-effects model. Pooled incidence and its associated 95% confidence interval (CI) were reported for each outcome .I² statistic was used to determine the heterogeneity of the studies. Subgroup analyses by type of BTKi (ibrutinib, acalabrutinib, and zanubrutinib) and treatment history (treatment-naïve and R/R) were performed. Results: After two rounds of review, eighteen clinical trials containing twenty arms of BTKi monotherapy were eligible for the meta-analysis. Among these, four trials reported the incidences of PJP and three reported on fungal pneumonia. The pooled incidence of any grade pneumonia in patients with CLL on BTKi therapy was 0.13 (95% CI, 0.10-0.16, I2 = 80%) [Figure (Fig) 1a]. The pooled incidence of grade 3 or higher pneumonia was 0.08 (95% CI, 0.06-0.10, I2 = 68%) [Fig 1b]. There were no differences in the incidences of any grade (p = 0.61) or grade 3 and higher pneumonia (p = 0.30) among patients treated with ibrutinib, acalabrutinib, or zanubrutinib in the subgroup analyses [Fig 1c and 1d respectively]. However, the pooled incidences of any grade and grade 3 or higher pneumonia were greater in R/R CLL patients compared to those who were treatment-naïve (0.15 vs 0.07, p&amp;lt;0.01 and 0.10 vs 0.05, p = 0.04, respectively) [Fig 1e and 1f respectively]. The pooled incidences of PJP and other fungal pneumonia were 0.01 (95% CI, 0.00-0.02, I2 = 10%) and 0.01 (95% CI, 0.00-0.02, I2 = 0%), respectively. Conclusion: Our study showed no significant differences in the incidence of pneumonia of any grade or at least grade 3 among patients treated with newer second-generation BTKi vs first-generation BTKi. Risk of pneumonia should not be a factor to choose among BTKi. Of note, the incidence of pneumonia was higher in R/R CLL patients on BTKi therapy when compared to treatment naïve CLL. R/R CLL are likely to have increased infections due to complement dysfunction and progressive immunodeficiency (decreased IgG and IgA levels). Fungal pneumonia, including PJP, are uncommon in CLL, and the subgroup analyses were not able to distinguish any differences among different BTKi. PJP prophylaxis is still considered during BTKi therapy in treatment naïve and R/R CLL, but true risk vs benefit is unknown.

Establishment of a Clinical Pharmacist-Led Multiple Myeloma Clinic with Collaborative Prescribing Model at the National Center for Cancer Care and Research in Qatar

Introduction Multiple Myeloma (MM) is a chronic and incurable hematologic malignancy affecting the plasma cells, and is more prevalent among the elderly. Interprofessional patient care showed superiority over physician-only care in multiple settings, including MM. (Sweiss K et al.2019)In Qatar, real-world data analysis of MM patients treated in the ambulatory setting at the National Center for Cancer Care and Research (NCCCR) showed that clinical pharmacists (CPs) had an evident role in therapy optimization and ensuring adherence to treatment protocol schedule and supportive medications.(Elazzazy S et al.,2023) We aimed to provide a more structured and accessible link to MM patients considering the complexity of their treatment protocols and supportive care through the establishment of a clinical pharmacist-led clinic (CPLC). The most common challenges to optimum care of MM patients in the NCCCR before CPLC were identified and categorized (Figure 1) and then used to design the collaborative model for the MM CPLC (Figure 2). Methods The collaborative MM CPLC was initiated at NCCCR in February 2022. A collaborative practice agreement was established for this clinic, to allow clinical pharmacists -managing MM patients- to issue refills for supportive medications, and order any necessary laboratory tests. To investigate the quality of care provided by the clinic, data was retrospectively collected and analyzed for all MM patients managed in the clinic between February 2022 and February 2023. All patients who were newly diagnosed with MM were eligible for referral by the attending physician. Dedicated advanced hematology CPs provided consultation twice weekly for referred patients without additional fees. The provided services (in-person or virtual) included thorough medication profile review (prescribed antineoplastic and refills of supportive medications), and ordering follow-up laboratory tests. Services also included assessment and optimization of medication adherence, including immunomodulators and supportive medications (i.e., Venous Thromboembolism (VTE) prophylaxis, antimicrobial prophylaxis, bone modifying agents and vaccinations), providing comprehensive patient education, and communicating the recommended adjustments with physicians. Results During the 12-month period, there was a total of 22 patients referred to the clinic. The average age for patients was 51 years (range 36-72). Patient characteristics are summarized in Table 1. The total number of documented encounters with the pharmacists was 73 visits, corresponding to a median of 4 visits per patient (range 1-11). The total amount of time spent with each patient over the course of their referral was 15 minutes. A total of 343 CPs interventions (average of 5 interventions per visit) were performed with an acceptance rate of 100%. The most common intervention was medication reconciliation (n=124), followed by monitoring for medication outcomes (n=72, safety and efficacy), addition of required medication (n=40), patient education (n=27), issuing refills (n=24), drug interactions review and management (n=19), suggesting referrals to relevant subspecialities (n=16), identification of adverse drug reactions (n=7), and required dose adjustments (n=12). Twenty-two medication refills for supportive medications and eight pre-chemotherapy laboratory investigations were issued and ordered by CPs, respectively. All newly diagnosed patients were started on the appropriate bisphosphonate therapy without the previously observed delay, with the median from diagnosis to initiation being 14 days [range from 1 to 117 days]. All clinic patients were maintained on the appropriate VTE prophylaxis (aspirin [n=14], rivaroxaban [n=7], warfarin [n=1]). All patients were adherent to antiviral and Pneumocystis jirovecii Pneumonia prophylaxis. Conclusion CPLC for MM patients treated in the ambulatory setting provided a robust and timely link to patients in alignment with the published literature. The newly implemented collaborative prescribing model in MM clinic encouraged the expansion of pharmacy services in other ambulatory clinics. Our collaborative model could be potentially applied to different cancer settings to optimize a safe and effective patient care. Further analysis is planned to compare the adherence to international MM care guidelines pre- and post-launch of our CPLC.

830. Risk factors for late Pneumocystis jirovecii pneumonia in kidney transplant recipients: A Case-Control Study of United States Renal Data System Data

Abstract Background Organ transplant recipients are at increased risk of potentially life-threatening opportunistic infections, including Pneumocystis jirovecii pneumonia (PJP). Given the use of effective prophylaxis, PJP has become less common, especially during the first-year post-transplant. Recent data has shown that the risk of infection has shifted within the first 2 years after discontinuing prophylaxis. We aimed to determine risk factors for late posttransplant PJP using a national database. Methods Using the United States Renal Data System database, we performed a retrospective case-control study of patients who underwent kidney transplant from 1998 through 2019. To evaluate risk factors for late PJP, we performed logistic regression analysis by comparing characteristics between infected patients and their matched uninfected controls. Results We identified 407 cases with PJP and matched to 1628 controls (1:4). 60 (14.7%) of the cases occurred within one year post transplant and 347 (85.3%) patients were diagnosed after one year of transplant. In the late period, the median time between transplant and PJP diagnosis was 68.7 (IQR 28 -134.2) months. Seventy cases (20.1%) occurred between 12 and 24 months. In multivariate analysis (table 1), risk factors for late infection included a higher Elixhauser Comorbidity Index (ECI), history of cytomegalovirus disease, older donor age, use of antilymphocyte agents, history of re-transplant and a longer time of hemodialysis prior to transplant. Of note, in the early period, we found that having a living donor was protective. Multivariate analysis of risk factors for late Pneumocystis jirovecii pneumonia Conclusion Our findings highlight the importance of a timely transplant to mitigate the risk of post-transplant PJP in the late post-transplant period where prophylaxis is not routinely used. These results also raise the consideration of PJP prophylaxis in the late period in patients diagnosed with CMV disease, history of re transplant and recent use of antilymphocyte agents. Disclosures Paschalis Vergidis, MD, MSc, AbbVie: Advisor/Consultant|Ansun: Grant/Research Support|Cidara: Grant/Research Support|Scynexis: Grant/Research Support

Incidence, timing, and management of infections in patients receiving teclistamab for the treatment of relapsed/refractory multiple myeloma in the MajesTEC-1 study.

Patients with relapsed/refractory multiple myeloma are at increased risk of infection. Infections during treatment with teclistamab, the first B-cell maturation antigen-directed bispecific antibody approved for triple-class-exposed relapsed/refractory multiple myeloma, was examined in the phase 1/2 MajesTEC-1 study. Patients (N=165) received subcutaneous teclistamab 1.5mg/kg weekly after a step-up dosing schedule (0.06mg/kg and 0.3mg/kg, each separated by 2-4days). Patients were monitored frequently for infections; prophylaxis and management were per institutional guidelines. At a median follow-up of 22.8months (range, 0.3-33.6), infections were reported in 132 patients (80.0%). Grade 3/4 infections occurred in 91 patients (55.2%), including COVID-19 (21.2%), respiratory infections (19.4%), Pneumocystis jirovecii pneumonia (4.2%), viral infections (4.2%), and gastrointestinal infections (1.2%). Twenty-one patients died from infections (18 from COVID-19). Median time to first onset of any-grade and grade 3 to 5 infections was 1.7 and 4.2months, respectively. Overall, 70.9% of patients had ≥1 postbaseline immunoglobulin G (IgG) level <400mg/dL; median time to IgG <400mg/dL was 1.2months (range, 0.2-19.8) and 46.1% received ≥1 dose of IgG replacement. Grade 3/4 neutropenia occurred in 65.5% of patients (median time to grade ≥3 neutropenia/febrile neutropenia was 2.3months [range, 0-18.1]). Based on the infection profile of B-cell maturation antigen-targeted bispecific antibodies such as teclistamab, it is recommended that clinicians and patients remain vigilant for a range of infection types throughout treatment to facilitate prompt intervention. Appropriate screening, prophylaxis, and management of infections, hypogammaglobulinemia, and neutropenia are important. NCT03145181/NCT04557098 (ClinicalTrials.gov) PLAIN LANGUAGE SUMMARY: Before starting teclistamab, patients should be up to date with vaccinations (including COVID-19) and screened for hepatitis B and C and HIV. Teclistamab should not be given to patients with any active infections. Prophylactic antimicrobials should be administered per institutional guidelines. Prophylaxis for Pneumocystis jirovecii pneumonia and herpes simplex/varicella zoster virus is recommended during teclistamab treatment. Close monitoring of infections and immunoglobulin G (IgG) levels should continue throughout teclistamab treatment. IgG replacement (administered every 3-6weeks) should be used to maintain IgG ≥400mg/dL. Growth factors should be considered for grade ≥3 neutropenia with infection/fever and grade 4 neutropenia.

Utilizing a best practice advisory (BPA) to increase pneumocystis jirovecii pneumonia (PJP) prophylaxis prescribing for patients with cancer on high dose corticosteroids.

391 Background: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic fungal infection that can cause severe respiratory infection in immunocompromised patients. Corticosteroid use is a common risk factor for developing PJP in non-human immunodeficiency virus (HIV) patients. Corticosteroids are commonly prescribed medications for cancer patients to help with symptom control from cancer treatment (e.g. nausea, vomiting, and pain) as well as for immunotherapy related adverse events. The risk of developing PJP is significantly increased for patients on prednisone equal to or greater than 20 mg per day x 1 month or equivalent. Steroid related PJP (srPJP) is associated with a 30-50% mortality in non-HIV patients. Methods: We conducted an IRB-approved retrospective chart review of individuals diagnosed with PJP at an academic medical center and 6 partner hospitals between 2016-2022. Patients were excluded if they had a diagnosis of HIV or prior hematopoietic stem cell transplant (HSCT). We then created a best practice advisory (BPA) built into the electronic health record to notify clinicians if a patient is at risk of developing srPJP based on their outpatient corticosteroid prescription. The BPA is triggered system-wide if a clinician signs an outpatient prescription for a prednisone or equivalent steroid dose of 20 mg or more for a duration of at least 3 weeks. The BPA will suggest PJP prophylaxis and link to an order for the clinician to select. Results: There were 96 identified cases of srPJP in non HIV/HSCT patients. None of these patients received antibiotic prophylaxis. Among these cases, 32 patients died from ARDS due to PJP, a mortality of 33.3%. 45% of identified cases were related to steroids prescribed for cancer management, and 68% of these received dexamethasone as the primary steroid. The BPA launched in April 2023 system wide across UC Health. Since launching the BPA in April 2023, it has been triggered 911 times with action taken by selecting an order for PJP prophylaxis 24.5% of the time. Conclusions: Despite the efficacy of prophylaxis, many patients at risk of developing srPJP do not receive prophylaxis. Since launching the BPA, preliminary data shows that the BPA has increased the orders placed for concurrent PJP prophylaxis. Further work must be done to determine if these orders for concurrent PJP prophylaxis were signed and if the BPA can increase PJP prophylaxis prescribing for patients on high dose corticosteroids and ultimately decrease srPJP cases and deaths.

Incidence of Pneumocystis Jiroveci Pneumonia in Patients With ANCA-Associated Vasculitis Initiating Therapy With Rituximab or Cyclophosphamide.

This manuscript assesses the incidence of Pneumocystis jiroveci pneumonia (PJP) among patients receiving contemporary treatment regimens for antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and adverse events associated with PJP prophylaxis. Incident users of rituximab or cyclophosphamide for AAV were identified in the TriNetX electronic health records database from 2011 to 2022. The incidence rates (IRs) of PJP in the first 6 months of induction therapy with rituximab and/or cyclophosphamide and during postinduction maintenance therapy with rituximab were calculated. Cox proportional hazard models were used to estimate hazard ratios (HRs) and confidence intervals (CIs) for the risk of adverse events commonly associated with PJP prophylaxis. We identified 1,461 AAV cases who received induction therapy with rituximab (69.7%), cyclophosphamide (18.9%), or both (11.4%). Prophylaxis prescribed within 30 days of induction included trimethoprim-sulfamethoxazole (30.7%), atovaquone (5.4%), dapsone (3.8%), and pentamidine (0.8%). During induction therapy, 10 cases of PJP were identified (IR 15.0 cases per 1,000 patient-years); no deaths occurred. In adjusted analyses, those who received prophylaxis had a higher risk of leukopenia (HR 3.1; 95% CI 1.1-8.6), rash (HR 1.9; 95% CI 1.0-3.6), and nephropathy (HR 2.6; 95% CI 1.3-5.1) than those who did not.During rituximab maintenance therapy (n=709), five cases of PJP were identified (IR 2.1 cases per 1,000 person-years), one of whom died during the hospitalization associated with a PJP diagnosis. Rates of PJP in patients with AAV were lower than previously observed, and few cases occurred during rituximab maintenance therapy. PJP prophylaxis was associated with adverse events.

Antimicrobial Prophylaxis in Lymphoma by Chemotherapy Regimen

Treatment of lymphomas involves a wide variety of chemotherapy, immunotherapy, and targeted-agents tailored to disease biology and patient characteristics. Each of these regimens carry their own risk of opportunistic infections in an immunocompromised population. In addition to the treatment associated immunosuppression, lymphoma itself is immunosuppressive. Lymphoma associated immunosuppression is secondary to increased production of abnormal lymphocytes resulting in decreased production of normally functioning lymphocytes. Additionally, lymphoma cells induce both humoral and cellular immunosuppression through effects on numerous cytokines, T-cells, myeloid-derived suppressor cells, and macrophages. Clinical trials, patient co-morbidities, and institutional preferences all play a role in determining the preferred antimicrobial prophylaxis. While there is a paucity of data on systematic reviews and guidelines for standardized chemotherapy regimens in lymphoma patients, the efficacy and recommendations for antimicrobial prophylaxis in specific chemotherapy regimens for lymphoma has not been fully reviewed. According to the National Comprehensive Cancer Network, lymphoma is generally regarded as an ‘intermediate risk’ cancer with regards to overall infection risk. This results in discordance between research data and clinical practice. This is reiterated in the SIGNIFICANT trial which reported that while guidelines previously advised against fluoroquinolone prophylaxis in lymphoma and solid cancers, a survey of 3,600 physicians revealed that 45% routinely used fluoroquinolone prophylaxis despite these recommendations. This review article analyzes numerous research studies with summarization of findings and antimicrobial prophylaxis recommendations based on specific lymphoma chemotherapy regimens. With regards to each specific chemotherapy regimen assessed, indications for antibacterial, anti-viral, anti-fungal, and Pneumocystis jiroveci pneumonia (PJP) prophylaxis were determined for each regimen. The degree of immunosuppression and the necessary prophylaxis varies across different regimens and lymphoma subgroups; and thus, an individualized approach is necessary to optimize the supportive care during lymphoma treatment.

Impact of thrice-weekly cotrimoxazole prophylaxis on creatinine and potassium plasma levels in kidney transplant recipients.

Cotrimoxazole (CTX) 800/160mg daily or thrice-weekly is recommended as prophylaxis of Pneumocystis jirovecii pneumonia in kidney transplant recipients. Cotrimoxazole 800/160 daily elevates plasma creatinine and potassium levels but whether the thrice-weekly regimen does so is unknown. Medical records of 225 kidney transplant recipients at Cliniques Universitaires Saint-Luc were analyzed retrospectively. All received thrice-weekly CTX 800/160 for 6months after transplantation. Monthly laboratory results, co-medications, and tacrolimus trough levels were compared. Standard statistical tests were used. One month after CTX stop, creatinine level decreased by 0.11mg/dl (8%, p = 0.029). This contrasts with its stability in previous and subsequent months. No co-medication change accounted for this decrease. The decrease averaged 0.17mg/dl (p < 0.01) in the highest initial creatinine tertile. The higher the initial creatinine level, the greater the decrease after CTX stop (p < 0.001), and urea levels remained stable after CTX stop. Potassium levels decreased by 0.09mmol/L (p = 0.021) one month after CTX stop, and decreased by 0.23mmol/L (p < 0.01) in the highest initial potassium level tertile. Our study pinpoints the impact of CTX 800/160 thrice-weekly on creatinine and potassium levels in kidney transplant recipients. This should be considered when interpreting the evolution of plasma creatinine over time, especially in patients with graft dysfunction. Thus, creatinine levels of cohorts with 6months versus lifelong CTX require different interpretations.

Prevalence of Trimethoprim-Sulfamethoxazole Adverse Reaction Mislabelling in Australia

Introduction: Trimethoprim-sulfamethoxazole (TMP-SMX) is an important antibiotic, with the most compelling indications for Pneumocystis jirovecii pneumonia prophylaxis and methicillin-resistant Staphylococcus aureus treatment. Previous adverse reactions (AR) to TMP-SMX may limit the usability of TMP-SMX. Electronic medical record (EMR) of AR for other antibiotics has previously been shown to be inaccurate; however, the extent to which this occurs for TMP-SMX is unknown. Methods: A multi-centre retrospective observational study was conducted for consecutive inpatient admissions over a 2.5-year period commencing 2020. Adverse reactions to TMP-SMX recorded in the EMR were collected and reviewed by two independent medical officers using pre-defined expert criteria for the classification of allergies and intolerances. Results: TMP-SMX AR were present in the EMR of 759 individuals (prevalence 0.6%). The majority were labelled as allergy (725, 95.5%) rather than intolerance (34, 4.5%). Most common AR were rash, vomiting, and swelling. When classified against the gold-standard expert criteria, there were 437 allergies (57.6%) and 159 intolerances (21.0%). Overall, the number of incorrect EMR AR labels was 133/759 (17.5%). Both medical and surgical specialties had significant numbers of patients with TMP-SMX AR labels and incorrectly classified EMR AR labels. Conclusion: TMP-SMX AR labels affect inpatients admitted under multiple specialty units. The user-entered categorization as allergy or intolerance labels in EMRs are frequently used incorrectly. These incorrect labels may inappropriately contraindicate the use of TMP-SMX, and formal evaluation of TMP-SMX ARs with immunological assessment and relabelling where appropriate may increase the use of this agent.

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.