Pneumocystis Carinii Pneumonia Research Articles

Use of echinocandins combined with clindamycin in Pneumocystis pneumonia: a case series of 14 patients.

Pneumocystis jirovecii pneumonia (PcP) is an opportunistic infection for which the standard of care is co-trimoxazole. However, safety concerns and intolerance may compromise its utility. To evaluate the safety and efficacy of the combination of echinocandins and clindamycin to treat PcP. We investigated 14 patients treated with a co-trimoxazole-free combined regimen that included echinocandins and clindamycin. Clinical cure was achieved in 8 out of 14 patients, while 5 had a fatal outcome due to their primary disease; however, only one patient died due to PcP. Echinocandin and clindamycin may be a safe and effective alternative treatment for patients who cannot be given co-trimoxazole for PcP.

Low-dose trimethoprim-sulfamethoxazole treatment for Pneumocystis pneumonia: a systematic review and meta-analysis

BackgroundThe recommended standard treatment for Pneumocystis jirovecii pneumonia (PJP) is high-dose trimethoprim-sulfamethoxazole (TMP-SMX) (15–20 mg/kg/d TMP). However, the standard regimen may cause a high incidence of dose-related adverse events (AEs). Therefore, we aimed to conduct a systematic review and meta-analysis to evaluate the efficacy and safety of low-dose TMP-SMX regimens (<15 mg/kg/d of TMP) compared with the standard regimen in patients with PJP.MethodsWe searched PubMed, Embase, and the Cochrane database for relevant articles from inception to 10 March 2024. Studies were included if they focused on PJP patients receiving a low-dose TMP-SMX regimen compared with a standard regimen. The primary outcome was mortality. We assessed study quality and performed subgroup analysis and sensitivity analysis to explore potential heterogeneity among the included studies.ResultsSeven studies were included. Overall, the low-dose regimen significantly reduced the risk of mortality (odds ratio [OR] = 0.49; 95% CI, 0.30–0.80; I2 = 16%; P = 004). This finding was confirmed in further sensitivity and subgroup analyses. The low-dose regimen also significantly reduced total AEs (OR = 0.43; 95% CI, 0.29–0.62; I2 = 0%; P < 0.0001), and improved the incidence of most specific AEs (ORs ranged from 0.13 to 0.89). In addition, the low-dose regimen had significantly more patients completing the initial regimen (P = 0.002), fewer patients requiring dose reductions (P = 0.04), and almost significantly fewer patients requiring a switch to a second-line regimen (P = 0.06).ConclusionThe limited available evidence suggests that a low-dose TMP-SMX regimen significantly reduced mortality and total AEs in PJP patients. Thus, it is one of the potentially promising therapies to PJP and more high-quality and multi-center randomized trials should be conducted in the future.

Clinical practice pattern of Pneumocystis pneumonia prophylaxis in systemic lupus erythematosus: a cross-sectional study from lupus registry of nationwide institutions (LUNA).

Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in patients undergoing immunosuppressive therapy, such as glucocorticoid (GC) medication, for systemic autoimmune diseases like systemic lupus erythematosus (SLE). Despite the confirmed effectiveness of PCP prophylaxis, its clinical administration, especially in conjunction with GC dosage, remains unclear. We aimed to describe the clinical practice of PCP prophylaxis in association with SLE in Japan, evaluate the relationship between GC dosage and PCP prophylaxis, and explore the practice patterns associated with PCP prophylaxis. This cross-sectional study used data from the Lupus Registry of Nationwide Institutions in Japan from 2016 to 2021 and included patients diagnosed with SLE. Using descriptive statistics, multivariate analysis, and decision tree analysis, we examined the prevalence of PCP prophylaxis and its association with the GC dosage. Out of 1,460 patients, 21% underwent PCP prophylaxis. The frequency of prophylaxis decreased with a decrease in GC dosage. After adjusting for confounders, logistic regression revealed the odds ratio of PCP prophylaxis increased with higher prednisolone (PSL) doses: 3.7 for 5 ≤ PSL < 7.5mg, 5.2 for 7.5 ≤ PSL < 10mg, 9.0 for 10 ≤ PSL < 20mg, and 43.1 for PSL ≥ 20mg, using PSL < 5mg as the reference. Decision tree analysis indicated that a PSL dosage of < 11mg/day and immunosuppressant use were key determinants of PCP prophylaxis. This study provides valuable insights into PCP prophylaxis practices in patients with SLE in Japan, underscoring the importance of GC dosage and concomitant immunosuppressant use.

DDDR-11. INHIBITING OXIDATIVE PHOSPHORYLATION AND HYPOXIA WITH ATOVAQUONE – A STRATEGY TO RADIOSENSITIZE DIFFUSE MIDLINE GLIOMA

Abstract Diffuse midline glioma (DMG) is a uniformly fatal paediatric brainstem tumour with median survival of less than 1 year. Radiotherapy has been the only effective treatment for decades, but most DMGs recur within several months due to radioresistance. The hypoxic tumour microenvironment is a main feature of solid tumours including gliomas and a major contributor to radioresistance. Therefore, alleviating tumour hypoxia to enhance the effectiveness of radiotherapy is a potential therapeutic strategy to improve the survival outcomes of DMG patients. We found evidence suggesting increased mitochondrial oxidative phosphorylation (OXPHOS) in DMG. Hence, we aimed to target OXPHOS by decreasing the oxygen consumption rate (OCR) of DMG cells, which in turn will alleviate hypoxia by sparing more oxygen and subsequently improve the radiosensitivity of DMG cells. We performed a high-throughput screening to identify potent OCR inhibitors from a library of 1963 FDA-approved drugs. The most promising OCR inhibitor identified was atovaquone, a drug used for treatment of pneumocystis pneumonia and malaria. We found that atovaquone inhibited mitochondrial metabolism of DMG cells by specifically targeting the mitochondrial complex III. Increased mitochondrial reactive oxygen species after exposure to atovaquone suggested that it increases oxidative stress. The treatment alleviated hypoxia and decreased the expression of hypoxia-inducible factor-1a in 3-dimensional DMG neurospheres and improved the radiosensitivity in several DMG cultures. To overcome the poor bioavailability of commercially available atovaquone that results in low therapeutically effective brain concentrations, we tested its efficacy against the amorphous solid dispersion (ASD) atovaquone formulation which appears to enhance atovaquone levels in the brain. We found that both the formulations inhibited OCR and hypoxia at similar doses and enhanced DMG radiosensitivity. The combination of ASD atovaquone and radiation significantly improved survival in orthotopic DMG mouse model. Collectively, this data provides evidence of atovaquone as a potential radiosensitizer for DMG.

Radiological predictors of PCP in HIV-positive adults in South Africa: A matched case-control study

Background: Definition of chest X-ray (CXR) features associated with laboratory-confirmed pneumocystis pneumonia (PCP) among HIV-positive adults is needed to improve diagnosis in high-burden settings.Objectives: Our primary objective was to identify CXR features associated with confirmed PCP diagnosis and severe PCP (defined by hypoxia, intensive care unit referral/admission, and/or in-hospital death). We also explored the performance of logistic regression models, incorporating selected clinical and CXR predictors, for PCP diagnosis and severe PCP.Method: We conducted a case-control study involving HIV-positive adults with laboratory-confirmed PCP and a matched cohort with non-PCP respiratory presentations at regional hospitals in Cape Town, South Africa (2012–2020).Results: Records from 104 adults (52 PCP cases and 52 non-PCP controls) were included. Diffuse versus patchy ground-glass opacification was associated with increased odds of PCP diagnosis (adjusted odds ratio [aOR]: 6.2, 95% confidence interval [CI]: 1.6–28.9, P = 0.01) and severe PCP (aOR: 4.5, 95% CI: 1.6–14.4, P = 0.008). Consolidation was associated with severe PCP (aOR: 3.3, 95% CI: 1.2–11.0, P = 0.03) as was increasing ground-glass zone involvement (aOR: 2.1 for each one-unit increase in involved zone; 95% CI: 1.4–3.2, P = 0.0004). Models incorporating hypoxia (hypoxia model) or tachypnoea (respiratory rate model) with diffuse ground-glass opacities, absence of pleural effusion or reticular/reticulonodular changes on CXR performed well in predicting PCP (area under the receiver operating characteristic curve 0.828 [hypoxia model] and 0.857 [respiratory rate model]).Conclusion: CXR evaluation alongside bedside clinical information offers good accuracy for discriminating definite PCP from other HIV-associated respiratory diseases.

Variable reliability of the (1,3)-β-d-glucan test for screening Pneumocystis pneumonia in HIV-negative patients depending on the underlying condition.

(1,3)-β-d-Glucan (BG) assay is a non-invasive test commonly used in the diagnostic of invasive fungal diseases. Given its high sensitivity, it was suggested that a negative BG result is sufficient for excluding the diagnosis of Pneumocystis pneumonia (PCP). However, suboptimal performance has been described in human immunodeficiency virus (HIV)-negative patients, particularly those with haematological malignancies. We aimed to assess the sensitivity of the BG assay for diagnosing PCP in HIV-negative patients based on their underlying PCP risk factors. We conducted a single-center, retrospective study (2009-2021) enrolling HIV-negative patients diagnosed with PCP and who underwent BG testing. Patients colonized with Pneumocystis jirovecii were included as a control group. In all, 55 PCP patients and 61 colonized patients met the inclusion criteria. Patients were further categorized according to the underlying condition that exposes patients to PCP. Median BG concentration was significantly higher in the PCP group than in the colonization group (500 vs. 31 pg/ml; P<10-4, Mann-Whitney test) and the BG assay demonstrated a sensitivity of 85% and a specificity of 82% for PCP diagnosis. Notably, sensitivity was significantly higher in non-cancer patients (100%) compared to those with solid cancer (72%) and haematologic cancer (79%) (P<.05, Fischer's exact test). These findings strengthen the high performance of BG testing for screening PCP in non-cancer patients, comparable to that observed in HIV-infected individuals. In contrast, they highlight its low reliability in patients with malignancies, emphasizing the importance of considering underlying conditions when interpreting BG results and refining the role of the test in PCP diagnosis.

Effectiveness of pulse methylprednisolone in patients with non-human immunodeficiency virus pneumocystis pneumonia: a multicentre, retrospective registry-based cohort study

BackgroundA recent database study and meta-analysis reported that adjunctive glucocorticoid therapy reduces mortality in patients with non-human immunodeficiency virus-associated (non-HIV) Pneumocystis jirovecii pneumonia (PCP), having hypoxemia. However, the optimal glucocorticoid dose remains unclear. Our study aimed to evaluate the effectiveness of pulse methylprednisolone compared with mild-to-moderate steroid doses in patients with non-HIV PCP.MethodsThis multicentre retrospective cohort study included adults with non-HIV PCP receiving adjunctive steroids at three Japanese tertiary care hospitals from June 2006 to March 2021. Patients were categorised into pulse methylprednisolone and mild-to-moderate dose groups. Pulse methylprednisolone involved an initial intravenous infusion of 500–1000 mg methylprednisolone daily, while the mild-to-moderate dose was lower. Primary and secondary outcomes were 30-day and 180-day mortality from treatment initiation. Patient characteristics were adjusted using propensity score analysis with overlap weighting. Subgroup analysis focused on patients with respiratory failure.ResultsThe study included 139 patients with non-HIV PCP: 55 in the pulse methylprednisolone group and 84 in the mild-to-moderate dose group. After adjusting for patient background, 30-day mortality (14.2% vs. 15.5%, P = 0.850) and 180-day mortality (33.5% vs. 27.3%, P = 0.516) did not differ significantly between groups. Subgroup analysis revealed no significant associations among patients with respiratory failure.ConclusionsAfter adjusting for patient characteristics, no difference in prognosis was observed between pulse methylprednisolone and mild-to-moderate dose groups in patients with non-HIV PCP. A mild-to-moderate dose of adjunctive corticosteroid may suffice for treating non-HIV PCP.

Incidence of Pneumocystis jirovecii Pneumonia and Prophylaxis-Associated Adverse Events Among Patients with Systemic Lupus Erythematosus.

Pneumocystis jirovecii Pneumonia (PJP) is an opportunistic infection that may affect patients with systemic lupus erythematosus (SLE). The objective of this project was to describe the incidence of PJP among patients with SLE. A retrospective cohort analysis of the TriNetX database. Included patients had ≥2 ICD9- CM/ICD10-CM codes for SLE separated by at least 30 days and were new users of mycophenolate mofetil or cyclophosphamide. The incidence of PJP over the first six months of therapy was calculated; adverse events were assessed using incident rate ratios (IRR) and Cox proportional hazards regressions. A total of 6,017 patients with SLE were identified. Most were female (5,176, 86%) and Black or African American (2,138, 35.5%). Induction medications included mycophenolate mofetil (5,208, 86.6%), cyclophosphamide (505, 8.4%), or both (304, 5.1%); the most common PJP prophylaxis was trimethoprim/sulfamethoxazole (1,126, 18.7%). Five PJP cases were identified over 2,752 person years, one of whom received PJP prophylaxis, for an incidence rate of 1.8 cases per 1000 person years. In adjusted analysis, patients who received prophylaxis had a higher risk of neutropenia (hazard ratio (HR) 2.5, CI 1.4-4.4), leukopenia (HR 1.9, CI 1.3-2.8), nephropathy (HR 1.7, CI 1.4-2.1), and hyperkalemia (HR 1.4, CI 0.9-2.0). PJP rarely affects patients with SLE undergoing therapy with mycophenolate mofetil or cyclophosphamide; prophylaxis against PJP is associated with adverse events. The majority of patients with SLE and PJP had structural lung disease. These data do not support universal prescribing of PJP prophylaxis for patients with SLE without lung disease.

Clinical Pharmacist Involved in the Treatment of Pneumocystis carinii Pneumonia: A Case Report

Clinical Pharmacist Involved in the Treatment of Pneumocystis carinii Pneumonia: A Case Report

Impact of Extracorporeal Membrane Oxygenation (ECMO) on Serum Concentrations of Cefepime

ECMO is becoming widely used as a life-saving measure for critically ill patients. However, there is limited data on pharmacokinetics and the dosing of beta-lactam antibiotics in ECMO. In this study, we evaluated the serum concentrations of cefepime in patients on ECMO to determine the impact of ECMO circuitry and to guide therapeutic dosing. Methods: Patients 19 years or older admitted to the ICU, treated with ECMO and beta-lactam antibiotics for presumed or documented infection, were enrolled. Three blood samples (peak, midpoint, trough) were obtained before ECMO (pre-ECMO) and during ECMO (intra-ECMO) at a steady state. Results: Eight patients met inclusion criteria; six received cefepime. All patients were male. Average ± SD age was 45.8 ± 14.7. Four patients received ECMO for severe SARS-CoV-2 infection, and one each for Pneumocystis pneumonia and influenza A infection. Mean ± SD APACHE II and SOFA scores prior to ECMO were 24.6 ± 7.1 and 11.0 ± 3.9, respectively. All but one of the patients received venovenous (VV) ECMO. Cefepime 1 g every 6 h intravenously over 2 min was administered to all patients before and during ECMO. Cefepime concentrations were fit to non-compartment analysis (NCA) and area under the serum concentration–time curve averaged ± SE 211.9 ± 29.6 pre-ECMO and 329.6 ± 32.3 mg*h/L intra-ECMO, p = 0.023. No patients displayed signs of cefepime neurotoxicity. Patients received ECMO for 43.1± 30 days. All patients expired. Cefepime dosed at 1 g every 6 h intravenously appears to achieve therapeutic levels for critically ill patients on ECMO.

COMPREENDENDO A INTERSEÇÃO ENTRE HIV/AIDS E PNEUMONIA: UMA ANÁLISE ABRANGENTE DA LITERATURA

INTRODUCTION: The relationship between HIV/AIDS and pneumonia is complex and multifaceted. Individuals infected with HIV have a significantly higher risk of developing pneumonia, caused by both bacterial and viral agents, due to immune suppression from the virus. OBJECTIVE: To identify in the literature the relationship between HIV/AIDS and pneumonia in the context of nursing care. MATERIALS AND METHODS: This is an integrative literature review conducted in the MEDLINE, LILACS, and BDENF databases, using the descriptors: “HIV seropositivity,” “Pneumonia,” and “nursing care.” The descriptors were combined using the boolean operator AND, covering the period from 2018 to 2024. RESULTS: The study found that HIV-positive patients tend to experience a subacute progression of Pneumocystis jirovecii pneumonia (PCP), while immunocompromised patients without HIV face rapid progression, with a higher risk of respiratory failure and mortality. CT scans showed ground-glass opacities and elevated lactate dehydrogenase levels. Non-HIV patients had longer treatment delays and higher hospitalization and mortality rates. Lymphopenia, steroid use, and pneumothorax were associated with 60-day mortality. The incidence of bacterial pneumonia in people living with HIV decreased, linked to improved CD4 counts. Children with HIV showed higher mortality from coronavirus-related pneumonia. CONCLUSIONS: Future research should expand epidemiological surveillance, explore new therapies, and investigate co-infections in at-risk groups, particularly children. Additionally, strengthening public health policies and promoting prevention education are essential to improve clinical outcomes in vulnerable populations.

Risk factors for identifying pneumocystis pneumonia in pediatric patients.

This study aimed to identify the risk factors and construct the diagnostic model associated with pneumocystis pneumonia (PCP) in pediatric patients. This retrospective observational study analyzed 34 cases of PCP and 51 cases of other types of pneumonia treated at Children's Hospital Affiliated to Shandong University between January 2021 and August 2023. Multivariate binary logistic regression was used to identify the risk factors associated with PCP. Receiver operating characteristic curves and calibration plots were constructed to evaluate the diagnostic model. Twenty clinical variables significantly differed between the PCP and non-PCP groups. Multivariate binary logistic regression analysis revealed that dyspnea, body temperature>36.5°C, and age<1.46 years old were risk factors for PCP. The area under the curve of the diagnostic model was 0.958, the P-value of Hosmer-Lemeshow calibration test was 0.346, the R2 of the calibration plot for the actual and predicted probability of PCP was 0.9555 (P<0.001), and the mean Brier score was 0.069. In addition, metagenomic next-generation sequencing revealed 79.41% (27/34) and 52.93% (28/53) mixed infections in the PCP and non-PCP groups, respectively. There was significantly more co-infection with cytomegalovirus and Streptococcus pneumoniae in the PCP group than that in the non-PCP group (p<0.05). Dyspnea, body temperature>36.5°C, and age<1.46 years old were found to be independent risk factors for PCP in pediatric patients. The probability of co-infection with cytomegalovirus and S. pneumoniae in the PCP group was significantly higher than that in the non-PCP group.

Effectiveness and safety of lower dose sulfamethoxazole/trimethoprim for Pneumocystis jirovecii pneumonia prophylaxis in patients with systemic rheumatic diseases receiving moderate-to high-dose glucocorticoids

ObjectivesTo compare the effectiveness and safety of low-dose sulfamethoxazole/trimethoprim (SMX/TMP) for Pneumocystis jirovecii pneumonia (PCP) prophylaxis in patients with systemic rheumatic disease (SRD) who were receiving glucocorticoids. MethodsWe retrospectively analyzed data obtained from Japanese patients with SRD who received glucocorticoids between January 2006 and April 2024. Patients were divided into two groups based on the initial dose of SMX/TMP: low-dose (one tablet twice weekly on non-consecutive days); conventional-dose (one tablet per day). The primary endpoint was the incidence of PCP after 1 year since the initiation of SMX/TMP. Secondary endpoints were discontinuation rates of SMX/TMP therapy and severe adverse drug reactions (ADRs) after 1 year since the initiation of SMX/TMP in both groups, before and after adjusting for patient characteristics. ResultsA total of 186 patients were included in this study: 60 in the low-dose group and 126 in the conventional-dose group. No patients developed PCP within one year after starting SMX/TMP; however, two patients in the low-dose group required escalation of the SMX/TMP dose to the conventional dose due to subclinical PCP. In the adjusted analysis, the low-dose group had a significantly lower discontinuation rate and a lower incidence rate of severe ADRs than the conventional-dose group. ConclusionsLower-dose SMX/TMP therapy was as effective as conventional therapy for PCP prophylaxis and was associated with lower discontinuation rates in patients with SRD receiving glucocorticoids.

The role of trimethoprim/sulfamethoxazole in preventing opportunistic infections in systemic lupus erythematosus patients receiving low-level immunosuppressive treatment: an open-label, randomized, controlled trial

Objective: Systemic lupus erythematosus (SLE) patients receiving immunosuppressive therapy are at risk for opportunistic infections (OIs), particularly Pneumocystis pneumonia (PCP). This study aimed to evaluate the effectiveness of trimethoprim/sulfamethoxazole (TMP/SMX) as primary prophylaxis against OIs and its adverse effects in SLE patients receiving low-level immunosuppressive treatment in a real-world setting. Methods: This open-label randomized controlled trial enrolled SLE patients receiving low-level immunosuppressive treatment at Ramathibodi Hospital between May 2021 and December 2022. Patient demographics and relevant clinical data were collected. Participants were randomized 1:1 to receive TMP/SMX or no prophylaxis, with dose adjustments according to renal function. The incidences of TMP/SMX-sensitive OIs and adverse events were monitored for 12 months post-enrollment. Results: The trial was terminated early due to a high rate of adverse drug reactions (ADRs) associated with TMP/SMX. In total, 138 SLE patients receiving low-level immunosuppressive treatment were enrolled. Most patients (98.4%) were in disease remission. No TMP/SMX-sensitive OIs were observed in either group during the 12-month follow-up period. Among individuals receiving TMP/SMX, 10/70 (14.3%) developed ADRs. Of these 10 patients, eight experienced grade 1 ADRs, and two had grade 3 ADRs; all declined to resume prophylaxis. There were no deaths in the study. Conclusions: During the 12-month follow-up period, no TMP/SMX-sensitive OIs occurred in SLE patients receiving low-level immunosuppressive therapy, suggesting that primary prophylaxis with TMP/SMX may not significantly benefit this population. The high rate of ADRs observed underscores the need for clinicians to carefully consider the risks and benefits of TMP/SMX prophylaxis in these patients.

Application of the estimand framework for an emulated trial using reference based multiple imputation to investigate informative censoring

BackgroundThe ICH E9 (R1) addendum on Estimands and Sensitivity analysis in Clinical trials proposes a framework for the design and analysis of clinical trials aimed at improving clarity around the definition of the targeted treatment effect (the estimand) of a study.MethodsWe adopt the estimand framework in the context of a study using “trial emulation” to estimate the risk of pneumocystis pneumonia, an opportunistic disease contracted by people living with HIV and AIDS having a weakened immune system, when considering two antibiotic treatment regimes for stopping antibiotic prophylaxis treatment against this disease. A “while on treatment” strategy has been implemented for post-randomisation (intercurrent) events. We then perform a sensitivity analysis using reference based multiple imputation to model a scenario in which patients lost to follow-up stop taking prophylaxis.ResultsThe primary analysis indicated a protective effect for the new regime which used viral suppression as prophylaxis stopping criteria (hazard ratio (HR) 0.78, 95% confidence interval [0.69, 0.89], p < 0.001). For the sensitivity analysis, when we apply the “jump to off prophylaxis” approach, the hazard ratio is almost the same compared to that from the primary analysis (HR 0.80 [0.69, 0.95], p = 0.009). The sensitivity analysis confirmed that the new regime exhibits a clear improvement over the existing guidelines for PcP prophylaxis when those lost to follow-up “jump to off prophylaxis”.ConclusionsOur application using reference based multiple imputation demonstrates the method’s flexibility and simplicity for sensitivity analyses in the context of the estimand framework for (emulated) trials.

Infection image: cystic pneumocystis jirovecii pneumonia - forgotten?

A 43-year-old male patient presented to the emergency department with progressive dyspnea. CT scan showed pronounced cystic lesions and ground glass opacitiy in both lungs and diagnosis of HIV infection was established. Bronchoscopy confirmed diagnosis of pneumocystis jirovecii pneumonia (PCP). The radiological presentation with perihilar large cysts is typical for PCP in HIV-infected patients, but rarely encountered today.

Outcome of Pneumocystis Jirovecii pneumonia (PcP) in post-CAR-T patients with hematological malignancies

BackgroundPneumocystis jirovecii pneumonia (PcP) is an opportunistic infection associated with immunocompromised patients. The development of novel immunotherapies has promoted the incidence of PcP. This study describes the clinical course and outcome of PcP in chimeric antigen receptor (CAR) T cell recipients with hematological malignancies.MethodsThis is a retrospective case series of CAR-T recipients diagnosed with PcP in our center. The cases were all confirmed by metagenomic next-generation sequencing of clinical samples. The demographic, clinical, and outcome data were retrieved from the patients’ medical charts and electronic medical record system.ResultsIn total, 8 cases of PcP were identified. The underlying malignancies included T-acute lymphoblastic leukemia (ALL) (n = 1), diffuse large B cell lymphoma (DLBCL) (n = 4), and B-ALL (n = 3). One patient received short-term sulfamethoxazole-trimethoprim (SMZ-TMP) while the others had no prophylaxis. Four patients had neutropenia/lymphopenia at the diagnosis of PcP, and two patients had immunosuppressants within one month before PcP manifestation. The median time from CAR-T infusion to PcP diagnosis was 98.5 days (range 52–251). Seven patients recovered from PcP after proper management while one died of septic shock.ConclusionPcP can occur after different CAR-T product, and the long-term depletion of immune cells seems to be related to PcP. SMZ-TMP is effective in this setting. More real-world experience of CAR-T therapy is required to assess the incidence and outcome of PcP in this population.

Pneumocystis jirovecii pneumonia in hemato-oncological patients; 10 years of experience at Hospital Infantil Teletón de Oncología

Abstract Background Pneumocystis jirovecii pneumonia is an opportunistic infection that most frequently affects immunocompromised people, especially patients with HIV; clinical presentation is nonspecific and mortality rate in patients without HIV ranges are between 30% and 75%. In the international literature, there are few case reports of pediatric oncology patients. A series of cases is presented with the objective of describing the epidemiological characteristics, clinical presentation, treatment, and outcomes of Pneumocystis jirovecii pneumonia in this population group. Methods An observational, descriptive, and retrospective study was carried out in cancer patients under 18 years, with clinically compatible symptoms, an imaging study suggestive of the pneumonia, and identification of P. jirovecii using a PCR test of bronchial aspirate at Hospital Infantil Teletón de Oncología in Querétaro Mexico, since November 2014 to June 2023. Results A total of 17 events were reported with a median age of 9.8 years, 14/17 (82%) with a diagnosis of acute leukemias, 1/17 (6%) Ewing sarcoma, 1/17 (6%) lymphoma large cell anaplastic and 1/17 (6%) neuroblastoma. Regarding their therapeutic phases, 7/17 (41%) were in consolidation, 4/17 (23%) induction, 3/17 (18%) allogeneic HSCT (Hematopoietic stem-cell transplantation), 2/17 (12%) in surveillance, and 1/17 (6%) in maintenance. The clinical presentation in our patients was characterized by the presence of fever in 15/17 (88%), dry cough in 10/17 (59%) and 17/17 (100%) developed acute respiratory distress syndrome, which was classified as mild in 7/17 (41%), moderate in 5/17 (29%) and severe in 5/17 (29%). 13/17 (75%) presented distributive shock. All our patients underwent chest x-rays, 12/17 (70.5%) presented bilateral interstitial infiltrate, 4/17 (23.5%) consolidation, and 1/17 (6%) pleural effusion. Lung CT (computed tomography) was performed in 4/17 (23.5%), and 4/4 (100%) presented ground glass opacities. All of our patients were admitted to the PICU (Pediatric intensive care unit) and 16/17 (94%) required invasive mechanical ventilation. All receive treatment with TMP-SMX (Trimethoprim-sulfamethoxazole). 4/17 patients died (23%) of whom none received prophylaxis. 3/17 patients (18%) received prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX). Conclusion The present study is the first study in Mexico that compiles cases of Pneumocystis Jirovecii pneumonia in pediatric oncology patients. P. jirovecii pneumonia remains a rare cause, but represents a potentially fatal cause in oncology patients, so it is important to have a high clinical suspicion during the evaluation of an immunocompromised patient with evidence of pneumonia during all treatment phases with chemotherapy, in order to start treatment promptly. Thus, we also emphasize the importance of adequate prophylaxis as the most important preventive measure.

Survival status and influencing factors of death risk of HIV-infected patients in Hangzhou, 2004-2023

Objective: To analyze the survival status and death factors of confirmed HIV-infected patients in Hangzhou to provide a basis for the formulation of AIDS prevention and treatment strategies. Methods: A retrospective cohort study was conducted. The data were from the HIV/AIDS Comprehensive Response Information Management System of the Chinese Disease Control and Prevention Information System.Epidemiological characteristics of HIV-infected patients were comparied in Hangzhou City from 2004 to 2023 by using chi-square Test. The survival rate of HIV-infected patients in Hangzhou was calculated by the life table method, the survival curves of different subgroups were described by the Kaplan-Meier method, and the Cox proportional hazard regression model was used to analyze the influencing factors of death risk. The SPSS 26.0 software was used for statistical analysis. Results: Among the 9 457 subjects, the total follow-up time was 58 004.18 person-years, 494 patients died, fatality rate of all-cause cases was 0.85 per 100 person-years.The average survival time was 18.59 (95%CI:18.40-18.78) years. Malignant neoplasms and pneumocystis pneumonia were the first (14.37%,71/494) and second (10.73%, 53/494) causes of death, respectively. Death within 6 months after diagnosis accounted for 42.51% (210/494), and suicide accounted for 4.25% (21/494). Multivariate Cox regression analysis showed that compared with those who received antiviral treatment (ART) within 3 months of diagnosis, those who received ART outside 3 months and those who did not receive ART had a 1.65 (95%CI:1.25-2.19) and 20.68 (95%CI:15.80-27.06) times risk of death, respectively. The HIV-infected patients with high CD4+T lymphocytes (CD4) counts for the first time had a lower risk of death. The risk of death of patients with baseline CD4 counts of 200-349 cells/µl, 350-499 cells/µl, and ≥500 cells/µl was 0.38 (95%CI:0.29-0.49), 0.26 (95%CI:0.19-0.36), 0.21 (95%CI:0.14-0.31) times higher than that of baseline CD4 counts <200 cells/µl, respectively. Conclusions: The overall survival of the HIV-infected patients was good in Hangzhou from 2004 to 2023. Early detection of HIV infection and timely mobilization to participate in ART was the key to improving the survival rate of patients. At the same time, given the suicide problem of HIV-infected patients, suicide surveillance and depression and anxiety screening of HIV-infected patients should be further strengthened, and targeted psychological intervention policies should be implemented.

Evaluating the Efficacy of a Polymerase Chain Reaction Assay for Pneumocystis carinii Detection in Respiratory Samples

Abstract Introduction: Accurately identifying patients with pneumocystis pneumonia (PCP) presents considerable challenges, primarily relying on clinical suspicion. The manifestations of PCP lack specificity, encompassing symptoms such as cough, dyspnoea, fever, hypoxaemia, malaise and weight loss. Therefore, this study assesses the efficacy of a polymerase chain reaction (PCR) assay intended for use in clinical microbiology laboratories for the identification of Pneumocystis carinii from respiratory specimens. Materials and Methods: In this retrospective study, the medical records of patients aged 18 years and above were examined, focusing on those assessed using pneumocystis PCR-based tests. The study spanned from 2019 to 2022 in our tertiary care centre at Max Hospital, Saket. In this study, sputum and bronchoalveolar lavage (BAL) samples were proceeded for both staining and PCR for multi-copy mtLSU gene and single-copy dihydropteroate synthase polymorphisms (DHPS) fas gene of P. jirovecii. Results: In the analysis of 112 BAL specimens, 17 were identified as positive for P. carinii through both Grocott-Gomori’s Methenamine Silver Staining (GMS) staining and PCR. In addition, two BAL specimens were negative through GMS staining but showed positive results with PCR. On reviewing the clinical details of the patients associated with these two specimens, it was discovered that both individuals were under systemic steroid treatment, yet neither exhibited clinical signs of pneumocystis pneumonia (PCP). Consequently, these instances were classified as false positives by PCR. In comparison to GMS, the PCR assay demonstrated a sensitivity of 100% and specificity of 98% for detecting P. carinii in BAL specimens. Conclusions: The study underscores the necessity for individualised approaches, with each laboratory assessing the positive and negative predictive values based on their specific prevalence rates. In the ongoing pursuit of improving PCP diagnosis, PCR emerges as a promising screening tool that when used judiciously in conjunction with confirmatory measures, can enhance diagnostic precision in immunosuppressed populations.