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The substantial decline in the Pneumocystis jirovecii pneumonia (PCP) incidence in HIV-infected patients after the introduction of antiretroviral therapy (ART) in resource-rich settings and the growing number of non-HIV-infected immunocompromised patients at risk leads to considerable epidemiologic changes with clinical, diagnostic, and treatment consequences for physicians. HIV-infected patients usually develop a subacute course of disease, while non-HIV-infected immunocompromised patients are characterized by a rapid disease progression with higher risk of respiratory failure and higher mortality. The main symptoms usually include exertional dyspnea, dry cough, and subfebrile temperature or fever. Lactate dehydrogenase may be elevated. Typical findings on computed tomography scans of the chest are bilateral ground-glass opacities with or without cystic lesions, which are usually associated with the presence of AIDS. Empiric treatment should be initiated as soon as PCP is suspected. Bronchoalveolar lavage has a higher diagnostic yield compared to induced sputum. Immunofluorescence is superior to conventional staining. A combination of different diagnostic tests such as microscopy, polymerase chain reaction, and (1,3)-β-D-glucan is recommended. Trimeth­oprim/sulfamethoxazole for 21 days is the treatment of choice in adults and children. Alternative treatment regimens include dapsone with trimethoprim, clindamycin with primaquine, atovaquone, or pentamidine. Patients with moderate to severe disease should receive adjunctive corticosteroids. In newly diagnosed HIV-infected patients with PCP, ART should be initiated as soon as possible. In non-HIV-infected immunocompromised patients, improvement of the immune status should be discussed (e.g., temporary reduction of immunosuppressive agents). PCP prophylaxis is effective and depends on the immune status of the patient and the underlying immunocompromising disease.

PurposeSevere Pneumocystis jirovecii pneumonia (PJP) requiring intensive care has been the subject of few prospective studies. It is unclear whether delayed curative antibiotic therapy may impact survival in these severe forms of PJP. The impact of corticosteroid therapy combined with antibiotics is also unclear.MethodsThis multicentre, prospective observational study involving 49 adult intensive care units (ICUs) in France was designed to evaluate the severity, the clinical spectrum, and outcomes of patients with severe PJP, and to assess the association between delayed curative antibiotic treatment and adjunctive corticosteroid therapy with mortality.ResultsWe included 158 patients with PJP from September 2020 to August 2022. Their main reason for admission was acute respiratory failure (n = 150, 94.9%). 12% of them received antibiotic prophylaxis for PJP before ICU admission. The ICU, hospital, and 6-month mortality were 31.6%, 35.4%, and 40.5%, respectively. Using time-to-event analysis with a propensity score-based inverse probability of treatment weighting, the initiation of curative antibiotic treatment after 96 h of ICU admission was associated with faster occurrence of death [time ratio: 6.75; 95% confidence interval (95% CI): 1.48–30.82; P = 0.014]. The use of corticosteroids for PJP was associated with faster occurrence of death (time ratio: 2.48; 95% CI 1.01–6.08; P = 0.048).ConclusionThis study showed that few patients with PJP admitted to intensive care received prophylactic antibiotic therapy, that delay in curative antibiotic treatment was common and that both delay in curative antibiotic treatment and adjunctive corticosteroids for PJP were associated with accelerated mortality.

There are no definitive clinical practice guidelines regarding the necessity and dosage of trimethoprim–sulfamethoxazole (TMP/SMX) prophylaxis for Pneumocystis jirovecii pneumonia (PJP) in individuals undergoing rituximab therapy. This retrospective study evaluated the effectiveness and safety of various TMP–SMX prophylactic dosing regimens over a 1-year period in 690 patients with non-Hodgkin lymphoma treated with rituximab at a university hospital in Thailand from 2013 to 2022. Out of these patients, 622 (90.1%) received TMP/SMX, with a mean duration of prophylaxis of 265.7 days (SD 85.66). The overall incidence of PJP was 1% (7 patients), which was significantly higher in the non-prophylaxis group (5.8%, 4 patients) compared to the prophylaxis group (0.6%, 3 patients). No cases of PJP occurred among those receiving standard prophylaxis or a single-strength tablet every other day, three times a week. However, instances in the prophylaxis cohort were reported in patients who took two single-strength tablets twice daily, twice a week. Prophylaxis resulted in a significant reduction in the one-year incidence of PJP, with a hazard ratio of 0.105 (95% CI: 0.023–0.469). Mild adverse reactions were noted in 3.05% of patients, all of whom recovered. These findings suggest that TMP/SMX prophylaxis was associated with a lower incidence of PJP and was well tolerated. Future studies should explore optimal dosing strategies while considering patient selection bias and concurrent immunosuppressive therapy.

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. 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. 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. 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. 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.

This report details the case of a 77-year-old female with Mycobacterium intracellulare pulmonary disease and history of bladder tumor surgery. The patient initially presented to our hospital with a one-day history of fever. After receiving antibiotic and anti-nontuberculous mycobacterial therapy for three days, the patient remained febrile. The patient’s white blood cell and neutrophil counts were within normal range, while the lymphocyte count was decreased. Chest computed tomography (CT) revealed diffuse ground-glass opacities in the lungs. Further investigations demonstrated a significantly reduced CD4 + T-lymphocyte count. Mycobacterium intracellulare and Pneumocystis jirovecii (PJ) were identified in the bronchoalveolar lavage fluid (BALF) specimen. The patient was treated with oral trimethoprim-sulfamethoxazole (TMP-SMZ) and intravenous caspofungin. Following treatment, the patient’s symptoms improved, and she was discharged. This study reports the first documented case of rare Pneumocystis jirovecii pneumonia (PJP) complicating nontuberculous mycobacterial lung disease. It underscores the importance of monitoring immune function and facilitating the early recognition of secondary infections in such patients.

Introduction Nephrotic syndrome (NS) is a common chronic kidney disease that is often accompanied by a state of immunodeficiency. Immunosuppression increases the risk of infections, with Pneumocystis jirovecii and Nocardia brasiliensis being two opportunistic pathogens that can cause severe infections in patients with compromised immune function. This study presents a case of a middle-aged male patient with NS concurrently infected with Pneumocystis jirovecii and Nocardia brasiliensis. It aims to synthesize the pertinent diagnostic approaches and treatment experiences. Notably, there have been no reported cases of NS occurring simultaneously with both Pneumocystis jirovecii pneumonia and Nocardia pneumonia. Case presentation A 58-year-old male farmer presented to the hospital with a one-week history of persistent fever, cough, and sputum production. His maximum body temperature was recorded at 39 °C, and he produced yellow viscous sputum. This patient had a one-year history of NS, managed with long-term oral corticosteroid and cyclophosphamide therapy. Admission chest computed tomography displayed interstitial changes in both lungs. After failing to detect any pathogens through routine etiological tests, we successfully identified Nocardia brasiliensis, Pneumocystis jirovecii, and Lodderomyces elongisporus using bronchoscopy-guided sputum samples through metagenomic next-generation sequencing (mNGS) technology. Subsequently, we initiated a combined treatment regimen for the patient using trimethoprim-sulfamethoxazole, meropenem, and moxifloxacin, which yielded remarkable therapeutic outcomes. Conclusion The adoption and promotion of mNGS technologies have significantly resolved the difficulty in early pathogen detection, guiding clinicians from empirical to genomic diagnosis, achieving prevention before treatment, and thereby enhancing patient survival rates.

ObjectivePneumocystis jirovecii pneumonia (PJP) is a serious opportunistic infection mainly diagnosed in patients with rheumatic conditions. However, PJP in anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5 + DM) patients remains poorly understood. We aimed to investigate the 6-month PJP risk in newly diagnosed MDA5 + DM patients.MethodsA retrospective observational study of 105 inpatients with newly diagnosed MDA5 + DM was conducted at Renji Hospital from January 2018 to November 2019. Demographic information, clinical characteristics, and treatment data were recorded. The primary outcome was PJP incidence within 6 months after a MDA5 + DM diagnosis.ResultsThe analysis included 105 patients, including 13 patients diagnosed with PJP during the observation period. The median time from the MDA5 + DM diagnosis to PJP was 89 ± 38 days. Compared with the PJP − patients, the PJP + patients had a significantly greater risk of mortality (69.2% vs. 13.0% P < 0.001). Regarding the baseline comorbidities, hypertension (P = 0.013) and cancer (P = 0.02) were more common in the PJP + group. Additionally, a larger proportion of the PJP + patients received prolonged high-dose steroid therapy (≥ 60 mg/day and ≥ 1 month) (P = 0.022) and double or triple immunosuppressant therapy (P = 0.013). The multivariate analysis showed that PJP was independently associated with lymphopenia (ALC < 500 cells/µl) (OR: 5.434, 95% CI: 2.074–55.155; P = 0.012) and the combined use of cyclophosphamide (CTX) and tacrolimus (TAC) (OR: 10.695, 95% CI: 1.440–20.508; P = 0.005).ConclusionThere was a high incidence and mortality in the MDA5 + DM patients with PJP, with patients on combined immunosuppressive treatments, particularly CTX and TAC, being at a higher risk. Prolonged high-dose steroid therapy (≥ 60 mg/day and ≥ 1 month) was another risk factor for PJP. Key Points• There was a high incidence and mortality in the MDA5 + DM patients with PJP.• Most PJP cases occurred within 3 months after the MDA5 + DM diagnosis. • The 6-month infection risk of PJP increased with the administration of multiagent immunosuppression, especially the combination of CTX and TAC. • Prolonged high-dose steroid therapy (≥ 60 mg/day and ≥ 1 month) was another risk factor for PJP.

Key Points Pneumocystis pneumonia (PCP) remains the most prevalent opportunistic infection in patients with AIDS and is a significant cause of severe pneumonia in immunocompromised patients with cancer, organ transplant recipients or those receiving immunosuppressant medications. Pneumocystis is an intractable fungal pathogen classified phylogenetically with the Ascomycetes. Pneumocystis has pathways involved in cell-cycle control, signal transduction and metabolism that are analogous to the pathways in these yeast. Pneumocystis has a unique life cycle alternating between small trophic forms and cysts, which contain 2, 4 or 8 intracystic bodies. The airborne route of transmission is currently the favoured model for the spread of infection. Pneumocystis interacts with the lung epithelium and immune cells of the lower respiratory tract, resulting in inflammation, which is hazardous to the host. This is a complex interaction involving surface antigens of the organism and host surfactant proteins, adhesion molecules, macrophages, neutrophils, lymphocytes, and cytokine and chemokine responses. Drug targets for the treatment of PCP include metabolic pathways for dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR), DNA and protein synthesis inhibition, sterol metabolism, cytochrome b complex and cell-wall construction through inhibition of the GSC1 glucan synthetase. Mutations in DHPS, DHFR, and cytochrome b have raised the concern of emerging resistance to the medications currently in use. The efforts of the Pneumocystis research community have contributed substantially to the current understanding of the complex biology of Pneumocystis and the intricate association with the host. Continued research is essential to continue investigating the biology of this organism in the hope of developing novel treatment strategies for PCP. Pneumonia caused by the fungus Pneumocystis is the most prevalent opportunistic infection in patients with AIDS. Here, Charles Thomas and Andrew Limper review the latest knowledge on the biology and pathogenesis of this opportunistic fungal pathogen. The fungal infection Pneumocystis pneumonia is the most prevalent opportunistic infection in patients with AIDS. Although the analysis of this opportunistic fungal pathogen has been hindered by the inability to isolate it in pure culture, the use of molecular techniques and genomic analysis have brought insights into its complex cell biology. Analysis of the intricate relationship between Pneumocystis and the host lung during infection has revealed that the attachment of Pneumocystis to the alveolar epithelium promotes the transition of the organism from the trophic to the cyst form. It also revealed that Pneumocystis infection elicits the production of inflammatory mediators, culminating in lung injury and impaired gas exchange. Here we discuss these and other recent findings relating to the biology and pathogenesis of this intractable fungus.

Ectopic adrenocorticotropic hormone syndrome is a distinct subtype of endogenous Cushing’s syndrome characterized by excessive cortisol secretion, which increases susceptibility to opportunistic infections. Herein, we present the case of a male patient in his early 40s who was admitted with fatigue and bilateral lower-extremity edema. Laboratory tests revealed markedly elevated serum adrenocorticotropic hormone and cortisol levels. Ectopic adrenocorticotropic hormone syndrome was confirmed via dexamethasone suppression testing and somatostatin receptor–targeted positron emission tomography–computed tomography, which localized an ectopic adrenocorticotropic hormone–secreting right pulmonary carcinoid tumor (a neuroendocrine tumor). During hospitalization, the patient was diagnosed with concurrent Pneumocystis jirovecii pneumonia and pulmonary cryptococcosis, and he responded favorably to trimethoprim–sulfamethoxazole and fluconazole. This case, supported by a review of the relevant literature, highlights the importance of early infection diagnosis, prompt management, and appropriate prophylaxis in patients with ectopic adrenocorticotropic hormone syndrome to improve prognosis.

Pneumocystis jirovecii pneumonia (PJP) constitutes a significant clinical burden even in patients without HIV infection, but the role of corticosteroids in such population remained controversial. The multicenter retrospective study aimed to evaluate the impact of adjunctive corticosteroids on outcomes in non-HIV patients with PJP. The primary outcome was all-cause mortality at 60 days. Among 334 enrolled subjects, 251 (75.1%) received adjunctive corticosteroids. Kaplan-Meier analysis showed higher 60-days mortality rate in patients with adjunctive corticosteroids (log-rank P  < 0.001). However, corticosteroid-treated patients showed more shock (43.0% vs. 25.3%; P  = 0.002) and worse PaO2/FiO2 (183.3 vs. 290.3; P  < 0.001). By multivariable and 1:1 propensity score matching analysis, adjunctive corticosteroid therapy was not associated with higher mortality (log-rank P  = 0.13). Subgroup analyses were conducted to explore potential effect modifiers. Among the subgroup of patients without shock, we found adjunctive corticosteroids were associated with higher mortality (odds ratio 2.72, 95% confidence interval 1.11–6.66; P  = 0.03). The observed association between adjunctive corticosteroids and higher 60-day mortality in non-HIV PJP might primarily relate to underlying indications for corticosteroid use rather than direct therapeutic effects. Adjunctive steroid used in patients with low disease severity should therefore be reconsidered.