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Research Square Apr 2024Immune checkpoint inhibitor-related pneumonitis (ICI-P) is a condition associated with high mortality, necessitating prompt recognition and treatment initiation. This...
PURPOSE
Immune checkpoint inhibitor-related pneumonitis (ICI-P) is a condition associated with high mortality, necessitating prompt recognition and treatment initiation. This study aimed to assess the impact of implementing a clinical care pathway algorithm on reducing the time to treatment for ICI-P.
METHODS
Patients with lung cancer and suspected ICI-P were enrolled, and a multi-modal intervention promoting algorithm use was implemented in two phases. Pre- and post-intervention analyses were conducted to evaluate the primary outcome of time from ICI-P diagnosis to treatment initiation.
RESULTS
Of the 82 patients admitted with suspected ICI-P, 73.17% were confirmed to have ICI-P, predominantly associated with non-small cell lung cancer (91.67%) and stage IV disease (95%). Pembrolizumab was the most commonly used immune checkpoint inhibitor (55%). The mean times to treatment were 2.37 days in the pre-intervention phase and, 3.07 days (=0.46), and 1.27 days (=0.40) in the post-intervention phases 1 and 2, respectively. Utilization of the immunotoxicity order set significantly increased from 0% to 27.27% (p = 0.04) after phase 2. While there were no significant changes in ICU admissions or inpatient mortality, outpatient pulmonology follow-ups increased statistically significantly, demonstrating enhanced continuity of care. The overall mortality for patients with ICI-P was 22%, underscoring the urgency of optimizing management strategies. Notably, all patients discharged on high-dose corticosteroids received appropriate gastrointestinal prophylaxis and prophylaxis against Pneumocystis jirovecii pneumonia infections at the end of phase 2.
CONCLUSION
Implementing a clinical care pathway algorithm for ICI-P management standardizes care practices and enhances patient outcomes, underscoring the importance of structured approaches.
PubMed: 38659939
DOI: 10.21203/rs.3.rs-4209489/v1 -
Cureus Mar 2024Pneumocystis pneumonia (PCP) primarily affects immunosuppressed patients, with trimethoprim-sulfamethoxazole (TMP-SMX) commonly used for prophylaxis. However, there is...
Pneumocystis Pneumonia in Locally Advanced Breast Cancer Despite Prophylactic Use of Trimethoprim-Sulfamethoxazole During Prednisolone Treatment for a Pembrolizumab-Induced Immune-Related Adverse Event: A Case Report.
Pneumocystis pneumonia (PCP) primarily affects immunosuppressed patients, with trimethoprim-sulfamethoxazole (TMP-SMX) commonly used for prophylaxis. However, there is insufficient information on PCP occurrence despite TMP-SMX prophylaxis. We encountered a 57-year-old woman with locally advanced breast cancer developing PCP despite prophylactic intake of TMP-SMX, during treatment with prednisolone for Stevens-Johnson syndrome (SJS) induced by pembrolizumab. This case underscores the need to pay attention to the possibility of PCP development even during TMP-SMX prophylaxis. Dosage and duration adjustments according to the patient's condition and weight may be required.
PubMed: 38659518
DOI: 10.7759/cureus.56868 -
BMC Pulmonary Medicine Apr 2024The prevalence of non-HIV related Pneumocystis jirovecii pneumonia (PJP) is increasing with use of immunosuppressive therapies. There are case reports of solid organ...
BACKGROUND
The 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 PRESENTATION
A 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.
CONCLUSIONS
Herein, 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.
Topics: Humans; Male; Hypercalcemia; Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Immunocompromised Host; Rituximab; Trimethoprim, Sulfamethoxazole Drug Combination; Immunosuppressive Agents; Prednisone; Bronchoscopy
PubMed: 38658913
DOI: 10.1186/s12890-024-03007-8 -
Saudi Medical Journal Apr 2024To assess the prevalence, risk factors, and associated complications of pneumothorax that are present in patients with human immunodeficiency virus (HIV) at our...
OBJECTIVES
To assess the prevalence, risk factors, and associated complications of pneumothorax that are present in patients with human immunodeficiency virus (HIV) at our institution and to provide an updated local study addressing the association between pneumothorax and HIV.
METHODS
This retrospective cohort study examined 161 patients who were admitted with a diagnosis of HIV from June 2017 to May 2022. They were divided into 2 groups depending on the presence of pneumothorax during their stay. Multiple variables were studied, including age, gender, tuberculosis infection, pneumocystis jiroveci pneumonia (PJP)infection, bacterial pneumonia, and pneumothorax type and treatment course.
RESULTS
There were 11 patients diagnosed with pneumothorax (prevalence rate: 6.8%). Bacterial lung infection was found in 9 (81.8%) of these patients, while fungal infection was found in 6 (54.5%) (<0.001, 0.010). The MTB was found in 3 (27.3%) patients (=0.728), while none were infected with PJP. Intercostal tube insertion was attempted in 9 (81.8%) patients, the mean duration of tube stay was 39.3±30.7 days, and the mortality rate was 72.7% (=0.007).
CONCLUSION
Pneumothorax in patients with HIV is a manifestation of the progression of the disease and its poor outcome. It has a complicated treatment course and a high mortality rate.
Topics: Humans; Pneumothorax; Male; Female; Retrospective Studies; Adult; Prevalence; HIV Infections; Middle Aged; Risk Factors; Pneumonia, Pneumocystis; Chest Tubes; Cohort Studies; Pneumonia, Bacterial
PubMed: 38657977
DOI: 10.15537/smj.2024.45.4.20230807 -
Open Forum Infectious Diseases Apr 2024The performance of chest x-ray (CXR) features for pneumonia (PCP) diagnosis has been evaluated in small studies. We conducted a systematic review and meta-analysis to...
BACKGROUND
The performance of chest x-ray (CXR) features for pneumonia (PCP) diagnosis has been evaluated in small studies. We conducted a systematic review and meta-analysis to describe CXR changes in adults with HIV-associated laboratory-confirmed PCP, comparing these with non-PCP respiratory disease.
METHODS
We searched databases for studies reporting CXR changes in people >15 years old with HIV and laboratory-confirmed PCP and those with non-PCP respiratory disease. CXR features were grouped using consensus terms. Proportions were pooled and odds ratios (ORs) generated using random-effects meta-analysis, with subgroup analyses by CD4 count, study period, radiology review method, and study region.
RESULTS
Fifty-one studies (with 1821 PCP and 1052 non-PCP cases) were included. Interstitial infiltrate (59%; 95% CI, 52%-66%; 36 studies, n = 1380; = 85%) and ground-glass opacification (48%; 95% CI, 15%-83%; 4 studies, n = 57; = 86%) were common in PCP. Cystic lesions, central lymphadenopathy, and pneumothorax were infrequent. Pleural effusion was rare in PCP (0%; 95% CI, 0%-2%). Interstitial infiltrate (OR, 2.3; 95% CI, 1.4-3.9; = 60%), interstitial-alveolar infiltrate (OR, 10.2; 95% CI, 3.2-32.4; = 0%), and diffuse CXR changes (OR, 7.3; 95% CI, 2.7-20.2; = 87%) were associated with PCP diagnosis. There was loss of association with alveolar infiltrate in African studies.
CONCLUSIONS
Diffuse CXR changes and interstitial-alveolar infiltrates indicate a higher likelihood of PCP. Pleural effusion, lymphadenopathy, and focal alveolar infiltrates suggest alternative causes. These findings could be incorporated into clinical algorithms to improve diagnosis of HIV-associated PCP.
PubMed: 38628951
DOI: 10.1093/ofid/ofae146 -
Infection and Drug Resistance 2024To investigate the value of metagenomic Next-Generation Sequencing (mNGS) in diagnosing pneumonia (PJP) in non-human immunodeficiency virus (HIV)-infected patients.
OBJECTIVE
To investigate the value of metagenomic Next-Generation Sequencing (mNGS) in diagnosing pneumonia (PJP) in non-human immunodeficiency virus (HIV)-infected patients.
METHODS
In this retrospective study, non-HIV-infected patients with PJP and those diagnosed with non-PJP from August 2022 to December 2024 were selected as subjects. The presence of (PJ) and other co-pathogens in bronchoalveolar lavage fluid (BALF) was analyzed, and the diagnostic efficacy of NGS, polymerase chain reaction (PCR) and serum 1,3-β-D-glucan (BDG) in PJP was compared with the reference standard of clinical compound diagnosis.
RESULTS
Eighty-nine non-HIV-infected patients were recruited, with dyspnea as the primary symptom (69.66%) and solid malignant tumor as the most common underlying disease (20.22%). Taking clinical compound diagnosis as the reference standard, the sensitivity, specificity, negative predictive value and positive predictive value of mNGS were higher than those detected by PCR and serum BDG. Among 42 non-HIV-infected patients with PJP who underwent mNGS and conventional pathogen detection of BALF, 6 had simple PJ infection and 36 had combined PJ infection. The detection rate of mNGS in mixed infections was significantly higher than that of conventional pathogen detection (85.71 vs 61.70%, = 0.012). A total of 127 pathogens were detected in BALF using mNGS, among which fungi had the highest detection rate (46.46%). The fungi, viruses and bacteria detected were mainly , human gammaherpesvirus 4 and .
CONCLUSION
mNGS is highly effective in diagnosing non-HIV-infected patients with PJP and exhibits ideal performance in the detection of co-pathogens. In addition, it has certain value for clinical diagnosis and guidance of targeted anti-infective drug treatment.
PubMed: 38628239
DOI: 10.2147/IDR.S450878 -
International Journal of Infectious... Jun 2024In hematology, prophylaxis for Pneumocystis jirovecii pneumonia (PCP) is recommended for patients undergoing hematopoietic stem cell transplantation and in selected...
A retrospective study of intravenous pentamidine for Pneumocystis jirovecii pneumonia prophylaxis in adult patients with hematologic malignancies-its utility during respiratory virus pandemics.
OBJECTIVES
In 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.
RESULTS
A 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.
CONCLUSIONS
Pentamidine administered IV monthly is safe and effective.
Topics: Humans; Pentamidine; Pneumonia, Pneumocystis; Hematologic Neoplasms; Male; Retrospective Studies; Middle Aged; Female; Adult; Hematopoietic Stem Cell Transplantation; Aged; COVID-19; Pneumocystis carinii; Administration, Intravenous; Young Adult; SARS-CoV-2; Antifungal Agents; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 38615824
DOI: 10.1016/j.ijid.2024.107059 -
ELife Apr 2024Anticancer treatments can result in various adverse effects, including infections due to immune suppression/dysregulation and drug-induced toxicity in the lung. One of...
Anticancer treatments can result in various adverse effects, including infections due to immune suppression/dysregulation and drug-induced toxicity in the lung. One of the major opportunistic infections is pneumonia (PCP), which can cause severe respiratory complications and high mortality rates. Cytotoxic drugs and immune-checkpoint inhibitors (ICIs) can induce interstitial lung diseases (ILDs). Nonetheless, the differentiation of these diseases can be difficult, and the pathogenic mechanisms of such diseases are not yet fully understood. To better comprehend the immunophenotypes, we conducted an exploratory mass cytometry analysis of immune cell subsets in bronchoalveolar lavage fluid from patients with PCP, cytotoxic drug-induced ILD (DI-ILD), and ICI-associated ILD (ICI-ILD) using two panels containing 64 markers. In PCP, we observed an expansion of the CD16 T cell population, with the highest CD16 T proportion in a fatal case. In ICI-ILD, we found an increase in CD57 CD8 T cells expressing immune checkpoints (TIGIT LAG3 TIM-3 PD-1), FCRL5 B cells, and CCR2 CCR5 CD14 monocytes. These findings uncover the diverse immunophenotypes and possible pathomechanisms of cancer treatment-related pneumonitis.
Topics: Humans; CD8-Positive T-Lymphocytes; Neoplasms; Pneumonia; B-Lymphocytes; Drug-Related Side Effects and Adverse Reactions; Lung Diseases, Interstitial
PubMed: 38607373
DOI: 10.7554/eLife.87288 -
International Journal of STD & AIDS Apr 2024Receipt of nebulised pentamidine in people with HIV was audited to identify if individuals were appropriately receiving nebulised pentamidine, and whether national...
Receipt of nebulised pentamidine in people with HIV was audited to identify if individuals were appropriately receiving nebulised pentamidine, and whether national guidelines were being followed when prophylaxis was commenced and discontinued. Of 76 people with who received nebulised pentamidine, the main indication for starting nebulised pentamidine was a co-trimoxazole adverse drug reaction. Co-trimoxazole desensitization was not attempted before starting nebulised pentamidine. The main indication for stopping nebulised pentamidine prophylaxis was when immune reconstitution occurred. This single centre audit revealed that national guidelines were being followed in most cases. The lack of information regarding the reason for starting or stopping nebulised pentamidine prophylaxis, or detail of the clinician's concerns about potential poor adherence with oral regimens of prophylaxis as a reason for choosing nebulised pentamidine prophylaxis, identifies a need for improved documentation of clinicians' decision-making. Introduction of pharmacist-led interventions/alerts using patients' electronic records, similar to those used in primary care, would enable the specialist pharmacy team to identify when and if co-trimoxazole desensitization has been offered and discussed/declined before a clinician prescribes nebulised pentamidine as well as enabling identification of those in who pentamidine prophylaxis has been continued, despite "immune reconstitution".
PubMed: 38606484
DOI: 10.1177/09564624241245155 -
Clinical Microbiology and Infection :... Jul 2024Pneumocystis jirovecii pneumonia (PCP) is a common opportunistic infection among people living with HIV (PWH), particularly among new and untreated cases. Several... (Meta-Analysis)
Meta-Analysis Comparative Study Review
Comparative efficacy and safety of Pneumocystis jirovecii pneumonia prophylaxis regimens for people living with HIV: a systematic review and network meta-analysis of randomized controlled trials.
BACKGROUND
Pneumocystis jirovecii pneumonia (PCP) is a common opportunistic infection among people living with HIV (PWH), particularly among new and untreated cases. Several regimens are available for the prophylaxis of PCP, including trimethoprim-sulfamethoxazole (TMP-SMX), dapsone-based regimens (DBRs), aerosolized pentamidine (AP), and atovaquone.
OBJECTIVES
To compare the efficacy and safety of PCP prophylaxis regimens in PWH by network meta-analysis.
METHODS
DATA SOURCES: Embase, MEDLINE, and CENTRAL from inception to June 21, 2023.
STUDY ELIGIBILITY CRITERIA
Comparative randomized controlled trials (RCTs).
PARTICIPANTS
PWH.
INTERVENTIONS
Regimens for PCP prophylaxis either compared head-to-head or versus no treatment/placebo.
ASSESSMENT OF RISK OF BIAS
Cochrane risk-of-bias tool for RCTs 2.
METHODS OF DATA SYNTHESIS
Title or abstract and full-text screening and data extraction were performed in duplicate by two independent reviewers. Data on PCP incidence, all-cause mortality, and discontinuation due to toxicity were pooled and ranked by network meta-analysis. Subgroup analyses of primary versus secondary prophylaxis, by year, and by dosage were performed.
RESULTS
A total of 26 RCTs, comprising 55 treatment arms involving 7516 PWH were included. For the prevention of PCP, TMP-SMX was ranked the most favourable agent and was superior to DBRs (risk ratio [RR] = 0.54; 95% CI, 0.36-0.83) and AP (RR = 0.53; 95% CI, 0.36-0.77). TMP-SMX was also the only agent with a mortality benefit compared with no treatment/placebo (RR = 0.79; 95% CI, 0.64-0.98). However, TMP-SMX was also ranked as the most toxic agent with a greater risk of discontinuation than DBRs (RR = 1.25; 95% CI, 1.01-1.54) and AP (7.20; 95% CI, 5.37-9.66). No significant differences in PCP prevention or mortality were detected among the other regimens. The findings remained consistent within subgroups.
CONCLUSIONS
TMP-SMX is the most effective agent for PCP prophylaxis in PWH and the only agent to confer a mortality benefit; consequently, it should continue to be recommended as the first-line agent. Further studies are necessary to determine the optimal dosing of TMP-SMX to maximize efficacy and minimize toxicity.
Topics: Humans; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Network Meta-Analysis; Trimethoprim, Sulfamethoxazole Drug Combination; Pneumocystis carinii; HIV Infections; AIDS-Related Opportunistic Infections; Dapsone; Pentamidine; Atovaquone; Antifungal Agents; Treatment Outcome
PubMed: 38583518
DOI: 10.1016/j.cmi.2024.03.037