Myelotoxicity and kidney dysfunction related to the use of trimethoprim-sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia: a case report of severe adverse events with a common drug.

Trimethoprim-sulfamethoxazole (TMP-SMX) is the primary therapeutic option for Pneumocystis jirovecii pneumonia (PCP). Gastrointestinal symptoms and cutaneous rash are common side effects, with hyperkalemia being uncommon in patients without kidney dysfunction, and myelotoxicity being even rarer. We present the case of a male patient with hypertension and a recent diagnosis of non-Hodgkin lymphoma, undergoing rituximab treatment for two months. He was admitted to the intensive care unit due to dyspnea, tachypnea, and pleuritic pain, requiring mechanical ventilation. Chest computed tomography showed bilateral and multilobed ground-glass opacities, compromising more than 80% of the lung parenchyma. Pulmonary tuberculosis and COVID-19 were ruled out. An angiotomography and Doppler ultrasound revealed an extensive pulmonary thrombus and deep venous thrombosis. Empiric treatment with TMP-SMX for PCP was initiated, but within four days, the patient experienced metabolic acidosis and severe hyperkalemia, necessitating hemodialysis. He also presented with progressive pancytopenia and critical levels of leukopenia and thrombocytopenia. The hypothesis of TMP-SMX-induced myelotoxicity was suspected. Considering the unavailability of an alternative treatment, it was opted to continue TMP-SMX and initiate a granulocyte-colony-stimulating factor. However, the patient maintained medullary deterioration, becoming refractory to the transfusion of blood derivates. On the 17th day of treatment, a clinical decision was made to suspend TMP-SMX, leading to improvements within 48 hours in marrow and kidney functions, metabolic acidosis, and hyperkalemia. Despite all efforts, the patient died after 35 days of hospitalization due to hospital-acquired infections. This case highlights the importance of clinicians recognizing potential myelotoxicity with TMP-SMX and promptly discontinuing the drug if necessary.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Short-term effectiveness and safety of rituximab versus cyclophosphamide for life-threatening ANCA-associated vasculitis: a propensity score analysis of the real-world nationwide database.

OBJECTIVES: Life-threatening antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with rapidly progressive glomerulonephritis (RPGN) and/or alveolar haemorrhage (AH) has a poor prognosis. Rituximab (RTX) is as effective as cyclophosphamide (CY) in remission induction therapy; however, the effectiveness and safety of RTX have not been established in life-threatening AAV. This study aimed to investigate the short-term effectiveness and safety of RTX in life-threatening AAV with RPGN and/or AH. METHODS: Between April 2018 and March 2020, cases treated with systemic glucocorticoids and RTX or intravenous CY (IVCY) was extracted from a Japanese nationwide inpatient database. Effectiveness was evaluated by in-hospital mortality and severe renal dysfunction requiring haemodialysis (HD) at discharge. Safety was evaluated by the in-hospital incidence of infections. The propensity score (PS) for RTX was estimated. Multivariable Cox and logistic regression with adjustment for PS were conducted to estimate the association of RTX with outcomes. RESULTS: From 16 001 612 hospitalised records, 687 life-threatening AAV cases were extracted. No significant difference in in-hospital mortality (adjusted HR 1.06; 95% CI 0.62 to 1.80) was found between the groups. Although the RTX group had a lower risk of fungal infections (adjusted OR (aOR) 0.45; 95% CI 0.23 to 0.84) and pneumocystis pneumonia (aOR 0.58; 95% CI 0.32 to 1.00), they might have an increased risk of severe renal dysfunction requiring HD at discharge (aOR 2.58; 95% CI 1.02 to 6.91). CONCLUSIONS: In life-threatening AAV, RTX has similar short-term effectiveness on mortality to IVCY. Although RTX might have a lower risk of fungal infections and pneumocystis pneumonia, the short-term renal prognosis might be inferior to IVCY.

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.

Pneumocystis Pneumonia Infection Following the Initiation of Pembrolizumab Therapy for Lung Adenocarcinoma.

Pneumocystis pneumonia (PCP) is an opportunistic infection that presents a ground-glass appearance in the lungs on chest radiography. Interstitial lung disease is a commonly reported adverse effect of immune checkpoint inhibitor (ICI) treatment; however, there are few reports of ICI treatment-associated PCP infection. A 77-year-old man with lung adenocarcinoma was administered pembrolizumab and hospitalized for dyspnea 2 weeks after treatment. Chest computed tomography showed bilateral ground-glass opacities in all lung lobes. PCP was therefore diagnosed, and steroids and sulfamethoxazole-trimethoprim were initiated. Following treatment, the patient's condition improved promptly. This report suggests that ICI treatment can cause PCP infection.

Pneumocystis jirovecii pneumonia in a patient treated with trastuzumab-deruxtecan.

Trastuzumab-deruxtecan (T-DXd) is a novel antibody drug conjugate that has improved treatment outcomes in patients with ERBB2-positive cancer, including locally advanced or metastatic gastric and gastro-oesophageal junction adenocarcinoma. One of the reported side effects of this medication is drug-induced pneumonitis. We present in this case report, a diagnostic dilemma of a patient presenting with clinical and radiographical features of drug-induced pneumonitis but was found to have pneumocystis jirovecii pneumonia (PJP). Our case is the first of PJP in a patient treated with T-DXd, highlighting the increasing incidence of this opportunistic infection in patients with solid malignancy. It also highlights the clinical and radiographical similarities between the PJP and drug-induced pneumonitis.

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

OBJECTIVE: 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. METHODS: The data were collected from the PubMed, Cochrane Library, and Web of Science databases. We excluded HIV-infected patients and those < 16 years 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 < 60 mmHg, 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. RESULTS: 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). CONCLUSION: 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.

Low-dose trimethoprim-sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia (LOW-TMP): protocol for a phase III randomised, placebo-controlled, dose-comparison trial.

INTRODUCTION: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection of immunocompromised hosts with significant morbidity and mortality. The current standard of care, trimethoprim-sulfamethoxazole (TMP-SMX) at a dose of 15-20 mg/kg/day, is associated with serious adverse drug events (ADE) in 20%-60% of patients. ADEs include hypersensitivity reactions, drug-induced liver injury, cytopenias and renal failure, all of which can be treatment limiting. In a recent meta-analysis of observational studies, reduced dose TMP-SMX for the treatment of PJP was associated with fewer ADEs, without increased mortality. METHODS AND ANALYSIS: A phase III randomised, placebo-controlled, trial to directly compare the efficacy and safety of low-dose TMP-SMX (10 mg/kg/day of TMP) with the standard of care (15 mg/kg/day of TMP) among patients with PJP, for a composite primary outcome of change of treatment, new mechanical ventilation, or death. The trial will be undertaken at 16 Canadian hospitals. Data will be analysed as intention to treat. Primary and secondary outcomes will be compared using logistic regression adjusting for stratification and presented with 95% CI. ETHICS AND DISSEMINATION: This study has been conditionally approved by the McGill University Health Centre; Ethics approval will be obtained from all participating centres. Results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04851015.

Pneumocystis Pneumonia in a Patient with Ovarian Cancer Receiving Olaparib Therapy.

We herein report a case of pneumocystis pneumonia (PCP) in a 77-year-old woman with ovarian cancer who was receiving olaparib therapy. After the patient's second relapse of ovarian cancer, she was administered olaparib as maintenance therapy following successful completion of docetaxel and carboplatin therapy. On receiving olaparib, she showed symptoms of a fever and malaise. Based on laboratory and imaging findings, she was diagnosed with PCP. After treatment with corticosteroids and trimethoprim/sulfamethoxazole followed by atovaquone, the patient's general condition improved. The lymphocytopenia observed after olaparib administration may have been associated with the development of PCP.

Factors Associated with Pneumocystis jirovecii Pneumonia in Patients with Rheumatoid Arthritis Receiving Methotrexate: A Single-center Retrospective Study.

Objective To investigate the risk factors for the development of Pneumocystis jirovecii pneumonia (PCP) in patients with rheumatoid arthritis (RA) undergoing methotrexate (MTX) therapy. Methods This single-center retrospective cohort study included consecutive patients with RA who received MTX for at least one year. The study population was divided into PCP and non-PCP groups, depending on the development of PCP, and their characteristics were compared. We excluded patients who received biologic disease-modifying anti-rheumatic drugs (DMARDs), Janus kinase inhibitors, and anti-PCP drugs for prophylaxis. Results Thirteen patients developed PCP, and 333 did not develop PCP. At the initiation of MTX therapy, the PCP group had lower serum albumin levels, a higher frequency of pulmonary disease and administration of DMARDs, and received a higher dosage of prednisolone (PSL) than the non-PCP group. A multivariate Cox regression analysis revealed that the concomitant use of PSL [hazard ratio (HR) 5.50, p=0.003], other DMARDs (HR 5.98, p=0.002), and serum albumin <3.5 mg/dL (HR 4.30, p=0.01) were risk factors for the development of PCP during MTX therapy. Patients with these risk factors had a significantly higher cumulative probability of developing PCP than patients who lacked these risk factors. Conclusion Clinicians should pay close attention to patients with RA who possess risk factors for the development of PCP during MTX therapy.

Pneumocystis jirovecii pneumonia as a complication of etoposide therapy.

Two patients receiving oral etoposide therapy developed Pneumocystis jirovecii pneumonia during chemotherapy with significant lymphopenia without corticosteroid use. In this commentary we discuss cellular mechanisms by which etoposide induced CD4+ T lymphocyte dysfunction and reduced survival may lead to predisposition to P. jirovecii infection.

The Changing Landscape of Pneumocystis Jiroveci Infection in Kidney Transplant Recipients: Single-Center Experience of Late-Onset Pneumocystis Pneumonia.

BACKGROUND: Pneumocystis jiroveci pneumonia (PCP) is a life-threatening pulmonary infection after kidney transplantation (KTx). Its onset in the current era of modern immunosuppression and of routine use of universal PCP prophylaxis seems to differ from its onset in previous decades in terms of late onset with subtle clinical presentation, indicating a need for increased vigilance. METHODS: We retrospectively studied all KTx recipients from our center who underwent bronchoscopy and bronchoalveolar lavage (BAL) between 2009 and 2018. Of these, all cases with confirmed PCP any time after the first post-KTx year were included in the analysis. RESULTS: Among 60 patients with KTx who had undergone bronchoscopy and BAL, 12 cases with late-onset PCP were identified. PCP appeared late at a median of 10.8 (interquartile range, 2.4-15.8) years after transplantation. Patients' mean age was 59 years, and all were receiving stable low-dose immunosuppression. Most of the patients (67%) had received PCP prophylaxis after KTx. Five out of 12 patients (42%) had concomitant cytomegalovirus (CMV) reactivation at the time of PCP. In almost all cases, clinical presentation was mild. Treatment consisted of trimethoprim-sulfamethoxazole (TMP-SMX) and intravenous corticosteroid administration, and concomitant immunosuppression was temporarily reduced or withdrawn. Outcome was generally good. None of the patients developed respiratory insufficiency or required mechanical ventilation. One patient died as a result of sepsis, and 3 more with preexisting advanced chronic kidney disease subsequently lost their grafts. CONCLUSION: Renal transplant recipients are at risk of late-onset PCP, even at a steady state of low-dose maintenance immunosuppression. Because of its subtle clinical presentation, high suspicion of the disease is warranted. Its early recognition and proper management are essential for a successful outcome.

[Early recurrence of pneumocystis pneumonia post trimethoprim-sulfamethoxazole therapy that developed after chemotherapy for follicular lymphoma].

A 75-year-old man was treated with bendamustine-containing chemotherapy for follicular lymphoma. Trimethoprim-sulfamethoxazole (TMP-SMX) for pneumocystis pneumonia (PCP) prophylaxis was discontinued at the last course of the chemotherapy. However, the patient developed PCP 6 months after the last course, and treatment with TMP-SMX (480 mg/day) was initiated. The TMP-SMX dose was reduced after 3 weeks of treatment. However, PCP recurred 6 days after dose reduction. Increasing the TMP-SMX dose to the therapeutic dose improved PCP. The dose was reduced to a maintenance dose after 7 weeks of the therapeutic dose of TMP-SMX treatment, and PCP did not recur thereafter. This case demonstrated that the early recurrence of PCP after appropriate treatment duration in immunocompromised conditions after chemotherapy, including bendamustine, may require prolonged treatment.

An Usual Presentation of Pneumocystis jirovecii Pneumonia in a Woman Treated With Immune Checkpoint Inhibitor.

We describe a case of Pneumocystis jirovecii pneumonia in an 18-year-old female individual with refractory primary mediastinal B-cell lymphoma treated with the immune checkpoint inhibitor pembrolizumab. She received 11 doses of pembrolizumab without immune-related adverse events (irAEs) before the diagnosis of P. jirovecii pneumonia. However, prophylactic trimethoprim/sulfamethoxazole was discontinued 6 months of postautologous stem cell transplant per standard guidelines. This case report highlights the importance of judicious infectious disease evaluation while on immune checkpoint inhibitor therapy as symptoms can often mimic irAEs. Furthermore, the benefits of immunosuppressive therapy for the treatment of presumptive irAEs must be weighed against the possible increased risk for opportunistic infections.

Caspofungin combined with TMP/SMZ as a first-line therapy for moderate-to-severe PCP in patients with human immunodeficiency virus infection.

OBJECTIVES: The effectiveness of trimethoprim/sulfamethoxazole (TMP/SMZ) for pneumocystis pneumonia (PCP) is limited with adverse events. Caspofungin, by inhibiting the cyst form of Pneumocystis jirovecii, may be an alternative therapy for PCP. However, the availability of clinical data about caspofungin combined with TMP/SMZ in the treatment of PCP in HIV-infected patients is limited. Thus, we aimed to examine the clinical effectiveness and safety of caspofungin combined with TMP/SMZ as a first-line therapy for moderate-to-severe PCP in HIV-infected patients. METHODS: From January 2017 to December 2019, data of HIV-infected patients with moderate-to-severe PCP who received either TMP/SMZ alone or caspofungin combined with TMP/SMZ as first-line therapy were retrospectively reviewed to assess the effectiveness and safety of each regimen. The Kaplan-Meier curve and log-rank test were used for survival analysis. RESULTS: A total of 278 patients met the criteria. The overall positive response rate of PCP treatment was 48.92%, and the overall all-cause in-hospital mortality rate was 33.09%. Patients who received combination therapy consisting of caspofungin and TMP/SMZ had a better positive response rate (59.44% vs. 37.78%, P < 0.001) and lower all-cause in-hospital mortality rate (24.48% vs. 42.22%, P = 0.003). Also, patients who received combination therapy had higher survival rate during a hospital stay (75.52% vs. 57.78%, P = 0.004), and those who received longer combination therapy were more likely to have higher survival rate (P = 0.042). We found that age (P = 0.019), CD4 cell count (P = 0.001) and therapeutic regimen (P = 0.002) were significant risk factors for all-cause in-hospital mortality rate in univariate analysis. In multivariate analysis, only CD4 cell count and therapeutic regimen were statistically significant factors associated with all-cause in-hospital mortality rate. Patients with a CD4 count of > 30 cells/µL and patients who received combination therapy consisting of caspofungin and TMP/SMZ were more likely to survive from PCP (P = 0.011 and P = 0.002, respectively). There were no additional severe adverse events caused by adding caspofungin. CONCLUSIONS: For HIV-infected patients with moderate-to-severe PCP, combination therapy with caspofungin and TMP/SMZ is an effective and promising first-line therapy with no greater number of adverse events compared with TMP/SMZ monotherapy. Patients who received caspofungin had better positive response rates and lower all-cause in-hospital mortality rates. Also, we recommend early initiation of caspofungin.

Practical approach to monitoring and prevention of infectious complications associated with systemic corticosteroids, antimetabolites, cyclosporine, and cyclophosphamide in nonmalignant hematologic diseases.

Corticosteroids constitute a first-line therapy for adults and children suffering from nonmalignant immune-mediated hematologic diseases. However, high disease relapse rates during the tapering period or upon drug discontinuation result in long-term corticosteroid use that increases the risk of infection. This same concept applies to other immunosuppressive agents, such as antimetabolites, calcineurin inhibitors, and cyclophosphamide. Corticosteroids are associated with a length-of-treatment and dose-dependent risk for infection. Screening and antimicrobial prophylaxis against tuberculosis, hepatitis B, Strongyloides stercoralis, and Pneumocystis jirovecii pneumonia (PJP) might be indicated in patients who are scheduled to be on high-dose corticosteroids for >4 weeks (>30 mg of prednisone-equivalent dose [PEQ]) or in patients chronically treated (≥8 weeks of continuous or intermittent corticosteroid use) with moderate doses (≥15 to <30 mg PEQ). Antimetabolites (azathioprine, mycophenolate) increase the risk of progressive multifocal leukoencephalopathy (PML); however, other opportunistic infections and viral reactivation have also been reported. In case of new onset of neurological symptoms, PML needs to be considered, and an urgent neurology consultation should be obtained. Cyclophosphamide-induced myelosuppression can lead to serious infections related to neutropenia. PJP prophylaxis should be considered with combination therapy of cyclophosphamide and corticosteroids until a PEQ dose ≤ 5 mg/d is reached. Data on infectious risk when cyclosporine is used in patients with nonmalignant hematologic diseases are lacking. Discontinuation of any immunosuppressive agent during an episode of infection is recommended. In all patients, adherence to an age-based immunization schedule is appropriate.

Pneumocystis jirovecii Pneumonia in Patients With Metastatic Prostate Cancer on Corticosteroids for Malignant Spinal Cord Compression: Two Case Reports and a Guideline Review.

Pneumocystis jirovecii, formerly known as Pneumocystis carinii, is an atypical fungal pathogen best known for causing Pneumocystis jirovecii pneumonia (PCP). The epidemiology of PCP is changing such that patients without HIV infection now comprise the largest subset of individuals diagnosed with PCP. While those with hematologic malignancies and organ transplants are at greatest risk for non-HIV-related PCP, this review will focus on PCP in patients with solid tumors. They are at risk for PCP due to their chemotherapy regimens and use of steroids in the management of various complications of treatment, and possibly because of the immunosuppressive effect of the cancer itself. In particular, patients with solid tumors being treated for metastatic spinal cord compression are at great risk for PCP. Patients with solid tumors and PCP face greater mortality than those with HIV infection. Multiple reviews have attempted to describe the ideal regimen of corticosteroids for metastatic spinal cord compression, but there is little consensus. We present 2 cases of patients with metastatic spinal cord compression due to prostate cancer undergoing radiation therapy and treatment with corticosteroids. These cases highlight the difficulties in predicting the length of corticosteroid therapy and the dangers that patients face without appropriate prophylaxis. This article will also provide a review of the current guidelines for PCP prophylaxis in patients undergoing treatment for metastatic spinal cord compression. We recommend empiric treatment with trimethoprim-sulfamethoxazole or dapsone in those patients with a sulfa allergy in all patients with solid tumors when any high-dose steroids are started for the treatment of metastatic spinal cord compression. Further research is needed to assess the epidemiology of PCP in patients with solid tumors and additional trials are necessary to refine PCP prophylaxis.

Pneumocystis jirovecii Pneumonia and Other Infections in Idiopathic Inflammatory Myositis.

PURPOSE OF REVIEW: The management of patients with idiopathic inflammatory myositis (IIM) can be complex and challenging due to the myriad of complications they can experience. The continued use of corticosteroids, in addition to the rise of combination immunosuppressive therapy, has contributed to the ongoing concern for infection. Perhaps the most feared infection in IIM patients is Pneumocystis jirovecii pneumonia (PJP) given its infrequent occurrence yet high mortality. The field has been, and continues to be, without evidence-based guidelines to help clinicians determine which patients with IIM to prescribe prophylaxis. Herein, we review this literature to provide the clinician with an up-to-date view of infections in IIM. RECENT FINDINGS: In the past 5 years, a number of studies have been reported highlighting various infectious complications, which help us better understand their frequency and associated risk factors. In addition, data has been published on the potential harms of PJP prophylaxis, to better inform the risk/benefit of our decision-making. Infection remains a major contributor to morbidity and mortality in IIM. A better understanding of which patient subgroups are at risk for particular infections will inform optimal management strategies.

Preadmission Corticosteroid Therapy and the Risk of Respiratory Failure in Adults Without HIV Presenting With Pneumocystis Pneumonia.

BACKGROUND: Corticosteroid therapy is a well-recognized risk factor for Pneumocystis pneumonia (PCP); however, it has also been proposed as an adjunct to decrease inflammation and respiratory failure. OBJECTIVE: To determine the association between preadmission corticosteroid use and risk of moderate-to-severe respiratory failure at the time of PCP presentation. METHODS: This retrospective cohort study evaluated HIV-negative immunosuppressed adults diagnosed with PCP at Mayo Clinic from 2006 to 2016. Multivariable regression models were used to evaluate the association between preadmission corticosteroid exposure and moderate-to-severe respiratory failure at presentation. RESULTS: Of the 323 patients included, 174 (54%) used preadmission corticosteroids with a median daily dosage of 20 (interquartile range: 10-40) mg of prednisone or equivalent. After adjustment for baseline demographics, preadmission corticosteroid therapy did not decrease respiratory failure at the time of PCP presentation (odds ratio: 1.23, 95% confidence interval: 0.73-2.09, P = .38). Additionally, after adjusting for inpatient corticosteroid administration, preadmission corticosteroid use did not impact the need for intensive care unit admission (P = .98), mechanical ventilation (P = .92), or 30-day mortality (P = .11). CONCLUSIONS: Corticosteroid exposure before PCP presentation in immunosuppressed HIV-negative adults was not associated with a reduced risk of moderate-to-severe respiratory failure.