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Pharmacogenomics Oct 2023Intravenous pentamidine is used for prophylaxis against pneumonia, an infection seen in hematopoietic stem cell transplant recipients. Pentamidine is partially...
Intravenous pentamidine is used for prophylaxis against pneumonia, an infection seen in hematopoietic stem cell transplant recipients. Pentamidine is partially metabolized by , which is vulnerable to pharmacogenetic variation. This retrospective study evaluated allogeneic hematopoietic stem cell transplant patients who received intravenous pentamidine as pneumonia prophylaxis. The primary objective was the association between phenotype and discontinuation of pentamidine due to drug-related side effects based on univariate logistic regression (N = 81). Ten patients (12.3%) discontinued pentamidine because of side effects. There was no difference in discontinuation between phenotype groups (p = 0.18) or discontinuation due to side effects (p = 0.76). Overall, no association was seen between phenotypes and pentamidine-related side effects (p = 0.475). Drug discontinuation rates and pneumonia infection rates were low.
Topics: Humans; Pentamidine; Pneumonia, Pneumocystis; Antifungal Agents; Retrospective Studies; Cytochrome P-450 CYP2C19; Pneumocystis carinii; Drug-Related Side Effects and Adverse Reactions; Phenotype
PubMed: 37846549
DOI: 10.2217/pgs-2023-0093 -
BMC Pulmonary Medicine Jul 2023Interstitial lung disease (ILD) is a frequently observed comorbidity in autoimmune diseases such as dermatomyositis/polymyositis (DM/PM), and it is significantly...
Rapidly progressive interstitial lung disease combined with pneumocystis jiroveci pneumonia in a patient with single anti-TIF-1γ antibody positive dermatomyositis in the context of an underlying tumor.
BACKGROUND
Interstitial lung disease (ILD) is a frequently observed comorbidity in autoimmune diseases such as dermatomyositis/polymyositis (DM/PM), and it is significantly associated with specific autoantibody types. One unique antibody type is the anti-transcription intermediate factor-1γ antibody (anti-TIF-1γ Ab), which has a positive rate of only 7%. It is often found in combination with malignancy and rarely with ILD, particularly rapidly progressive ILD (RPILD). In some cases, the presence of ILD in individuals with DM may indicate a paraneoplastic syndrome. Pneumocystis jiroveci pneumonia (PJP) typically occurs due to intensive immunosuppressive therapy, human immunodeficiency virus (HIV) infection, or malignancy, and rarely as an isolated condition.
CASE PRESENTATION
A 52-year-old man with a history of rapid weight loss but non-HIV infected and not immunosuppressed who presented with fever, cough, dyspnea, weakness of the extremities, characteristic rash and mechanic's hand. Pathogenic tests suggested PJP, laboratory tests suggested a single anti-TIF-1γ Ab positive DM, imaging suggested ILD, and pathology revealed no malignancy. RPILD and acute respiratory distress syndrome (ARDS) developed after anti-infection and steroid hormone therapy. After mechanical support therapy such as Extracorporeal Membrane Oxygenation (ECMO), the patient developed late-onset cytomegalovirus pneumonia (CMVP), complicated bacterial infection, and ultimately death. Additionally, we discuss the potential causes of rapid weight loss, the mechanisms by which anti-TIF-1γ Ab may lead to ILD, and the possible connection between anti-TIF-1γ Ab positivity, rapid weight loss, immune abnormalities, and opportunistic infections.
CONCLUSIONS
This case emphasizes the importance of early recognition of malignant tumors and pulmonary lesions, assessment of the body's immune status, prompt initiation of immunosuppressive treatment, and prevention of opportunistic infections in individuals with single anti-TIF-1γ Ab positive DM presenting with rapid weight loss.
Topics: Male; Humans; Middle Aged; Pneumocystis carinii; Dermatomyositis; Neoplasms; Autoantibodies; Lung Diseases, Interstitial; Transcription Factors; Pneumonia, Pneumocystis; Opportunistic Infections; Weight Loss; Retrospective Studies
PubMed: 37415133
DOI: 10.1186/s12890-023-02542-0 -
International Journal of Infectious... Sep 2023This study aimed to explore the role of fungal burden in risk stratification of patients without HIV-negative patients with Pneumocystis pneumonia (PCP).
OBJECTIVES
This study aimed to explore the role of fungal burden in risk stratification of patients without HIV-negative patients with Pneumocystis pneumonia (PCP).
METHODS
This was a retrospective analysis of the characteristics associated with 30-day mortality in patients who were positive for P. jirovecii using polymerase chain reaction in bronchoalveolar lavage fluid between 2006 and 2017 in a multicenter cohort from Central Norway. The fungal burden was indicated by the cycle threshold (C) values from semiquantitative real-time polymerase chain reaction targeting the β-tubulin gene.
RESULTS
We included 170 patients with proven or probable PCP. The all-cause 30-day mortality was 18.2%. After adjusting for host characteristics and premorbid corticosteroid use, a higher fungal burden was associated with a higher risk of dying: adjusted odds ratio 1.42 (95% confidence interval 0.48-4.25) for a C value 31-36, increasing to odds ratio 5.43 (95% confidence interval 1.48-19.9) for a C value ≤30 compared with patients with a C value ≥37. The Charlson comorbidity index (CCI) improved the risk stratification: patients with a C value ≥37 and CCI ≤2 had a 9% mortality risk compared with 70% among those with a C value ≤30 and CCI ≥6. Comorbid cardiovascular disease, solid tumors, immunological disorders, premorbid corticosteroids, hypoxemia, abnormal leukocyte counts, low serum albumin, and C-reactive protein ≥100 were also independently associated with 30-day mortality. The sensitivity analyses did not suggest selection bias.
CONCLUSION
Fungal burden may improve the risk stratification of patients without HIV-negative patients with PCP.
Topics: Humans; Pneumonia, Pneumocystis; Pneumocystis carinii; Retrospective Studies; Real-Time Polymerase Chain Reaction; Bronchoalveolar Lavage Fluid; HIV Infections; Risk Assessment; Immunocompromised Host
PubMed: 37339716
DOI: 10.1016/j.ijid.2023.06.013 -
PloS One 2024Pneumocystis jirovecii pneumonia (PJP) is a well-known and frequent opportunistic infection in HIV patients. However, there has been an increase in the number of reports...
INTRODUCTION
Pneumocystis jirovecii pneumonia (PJP) is a well-known and frequent opportunistic infection in HIV patients. However, there has been an increase in the number of reports of PJP in other immunosuppressed patients with autoimmune inflammatory disorders or because of chemotherapy and high doses of steroids, especially when used in combination as part of immunosuppressive therapy.
OBJECTIVE
Despite the increasing importance of PJP in non-HIV patients, there is a lack of comprehensive and updated information on the epidemiology, pathogenesis, diagnosis, microbiology, treatments, and prophylaxis of this infection in this population. Therefore, the objective of this systematic review is to synthesize information on these aspects, from a perspective of evidence-based medicine.
METHODS
The protocol is prepared following the preferred reporting items for systematic reviews and meta-analyses (PRISMA-P) guidelines. We will perform a systematic review of literature published between January 2010 and July 2023, using the databases PubMed, Google Scholar, ScienceDirect, and Web of Science. In addition, manual searches will be carried out through related articles, and references to included articles. The main findings and clinical outcomes were extracted from all the eligible studies with a standardized instrument. Two authors will independently screen titles and abstracts, review full texts, and collect data. Disagreements will be resolved by discussion, and a third reviewer will decide if there is no consensus. We will synthesize the results using a narrative or a meta-analytic approach, depending on the heterogeneity of the studies.
EXPECTED RESULTS
It is expected that this systematic review will provide a comprehensive and up-to-date overview of the state-of-the-art of PJP in non-HIV patients. Furthermore, the study will highlight possible gaps in knowledge that should be addressed through new research.
CONCLUSIONS
Here, we present the protocol for a systematic review which will consider all existing evidence from peer-reviewed publication sources relevant to the primary and secondary outcomes related to diagnosing and managing PJP in non-HIV patients.
Topics: Humans; Immunocompromised Host; Pneumonia, Pneumocystis; Systematic Reviews as Topic; Pneumocystis carinii
PubMed: 38722952
DOI: 10.1371/journal.pone.0302055 -
Arthritis Care & Research Feb 2024This manuscript assesses the incidence of Pneumocystis jiroveci pneumonia (PJP) among patients receiving contemporary treatment regimens for antineutrophil cytoplasmic...
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.
Topics: Humans; Rituximab; Pneumocystis carinii; Incidence; Pneumonia, Pneumocystis; Cyclophosphamide; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
PubMed: 37643919
DOI: 10.1002/acr.25222 -
Modern Rheumatology Nov 2023This study investigated the current practice of prophylactic treatment against Pneumocystis jirovecii pneumonia (PCP) and its effectiveness in patients with... (Observational Study)
Observational Study
OBJECTIVES
This study investigated the current practice of prophylactic treatment against Pneumocystis jirovecii pneumonia (PCP) and its effectiveness in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV).
METHODS
This study included 319 patients registered from 53 institutions in Japan and newly diagnosed with AAV. During the 2-year observation period, we examined the frequency of usage, effectiveness and safety of prophylactic drugs against PCP.
RESULTS
Most patients received prophylactic drugs against PCP with the initiation of immunosuppressive agents, and >50% of them remained on chemoprophylaxis against PCP at 2 years after. The initial daily dose of oral prednisolone and the proportion of cyclophosphamide administration were higher in patients who received chemoprophylaxis against PCP than in those who did not. PCP occurred in nine patients (3%) and resulted in the death of four. The incidence rate of PCP in patients who received chemoprophylaxis was 1.13/100 patient-years (95% confidence interval, 0.38-2.68) and that in those who did not was 2.74 (1.04-6.02). The incidence rate ratio was 0.41 (0.11-1.53).
CONCLUSIONS
The markedly low incidence of PCP may be attributed to the continuous chemoprophylaxis against PCP received by >50% of Japanese patients with AAV, although the effectiveness of chemoprophylaxis against PCP was not statistically confirmed.
Topics: Humans; Pneumonia, Pneumocystis; East Asian People; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Immunosuppressive Agents; Chemoprevention; Pneumocystis carinii
PubMed: 36197746
DOI: 10.1093/mr/roac124 -
Epidemiology and Infection Oct 2023Secondary pneumonia occurs in 8-24% of patients with Coronavirus 2019 (COVID-19) infection and is associated with increased morbidity and mortality. Diagnosis of...
Secondary pneumonia occurs in 8-24% of patients with Coronavirus 2019 (COVID-19) infection and is associated with increased morbidity and mortality. Diagnosis of secondary pneumonia can be challenging. The purpose of this study was to evaluate the use of plasma microbial cell free DNA sequencing (mcfNGS) in the evaluation of secondary pneumonia after COVID-19. We performed a single-center case series of patients with COVID-19 who underwent mcfNGS to evaluate secondary pneumonia and reported the organisms identified, concordance with available tests, clinical utility, and outcomes. In 8/13 (61%) cases, mcfNGS detected 1-6 organisms, with clinically significant organisms identified in 4 cases, including , and spp. Management was changed in 85% (11/13) of patients based on results, including initiation of targeted therapy, de-escalation of empiric antimicrobials, and avoiding contingent escalation of antifungals. mcfNGS may be helpful to identify pathogens causing secondary pneumonia, including opportunistic pathogens in immunocompromised patients with COVID-19. However, providers need to carefully interpret this test within the clinical context.
Topics: Humans; Pneumonia, Pneumocystis; COVID-19; Pneumocystis carinii; Anti-Infective Agents; High-Throughput Nucleotide Sequencing
PubMed: 37886888
DOI: 10.1017/S0950268823001711 -
Clinical Infectious Diseases : An... Apr 2024
Review
Topics: Adult; Humans; Glucocorticoids; Opportunistic Infections; Pneumocystis; Pneumonia, Pneumocystis
PubMed: 38598566
DOI: 10.1093/cid/ciae129 -
International Journal of Clinical... Nov 2023At our institution, patients with hematological disease who require pneumonia (PJP) prophylaxis were administered atovaquone at a low dose (750 mg/day). However, there...
OBJECTIVE
At our institution, patients with hematological disease who require 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.
MATERIALS AND METHODS
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.
RESULTS
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.
CONCLUSION
In hematological disease patients with relatively low risk of PJP, low-dose atovaquone may prevent the onset of PJP.
Topics: Humans; Adult; Middle Aged; Aged; Aged, 80 and over; Pneumonia, Pneumocystis; Atovaquone; Pneumocystis carinii; Trimethoprim, Sulfamethoxazole Drug Combination; Hematologic Diseases; Retrospective Studies
PubMed: 37622674
DOI: 10.5414/CP204368 -
Internal Medicine (Tokyo, Japan) Mar 2024
Topics: Humans; Pneumonia, Pneumocystis; Immunosuppressive Agents; Cytomegalovirus; Cytomegalovirus Infections; Immunocompromised Host; Pneumocystis carinii
PubMed: 37438137
DOI: 10.2169/internalmedicine.2026-23