Severe Pneumocystis Carinii Pneumonia Research Articles

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

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. 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. 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). 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]). CXR evaluation alongside bedside clinical information offers good accuracy for discriminating definite PCP from other HIV-associated respiratory diseases.

B-204 A Real-time Probe-based PCR Assay for Detection of Pneumocystis Pneumonia

Abstract Background Pneumocystis jirovecii is an atypical opportunistic fungus with lung tropism and worldwide distribution that continues to be one of the major opportunistic pathogens causing severe Pneumocystis pneumonia (PcP) in individuals with acquired immune deficiency syndrome (AIDS) and patients with immunosuppression due to other causes. Widespread prophylaxis and treatment for P. jirovecii with sulfa drugs have decreased the incidence of PcP, but concerns have been raised about the possible emergence of P. jirovecii isolates resistant to these drugs. Point mutations in this gene have been associated with prior exposure to sulfa drugs in other microorganisms, the polymorphic positions 165 and 171, which lead to an amino acid change at positions 55 (Thr55Ala) and 57 (Pro57Ser) of the polypeptide chain, respectively. Fluorescent PCR technology can detect the nucleic acid fragments of P. jirovecii in patients' serum, alveolar perfusion fluid (BALF) and tissue samples, and further identify drug-resistant mutations, which is of great significance for early clinical and accurate initiation of antifungal therapy. MycoMDx Pneumocystis Jirovecii PCR Assay is the use of PCR-fluorescence probe method, combined with other methods to achieve the auxiliary diagnosis of P. jirovecii infection and resistance to sulfonamides (Fig. 1). Methods In this study, we did a performance evaluation of the MycoMDx Pneumocystis Jirovecii PCR Assay (CE-approved), including diagnostic sensitivity and specificity, the limit of detection (LoD), precision and stability. The above PCR assay reagents were developed and produced by Dynamiker Biotechnology (Tianjin) Co., Ltd. Results The sensitivity and specificity of the PCR assay reagents were above 90%, the LoD was 1000 copies/mL, and the precision and stability were in accordance with the requirements (CV≤5%). Conclusions The MycoMDx Pneumocystis Jirovecii PCR Assay has great clinical value by providing a rapid and reliable test to aid in early diagnosis.

Pneumocystis pneumonia in French intensive care units in 2013-2019: mortality and immunocompromised conditions.

The recent epidemiology of Pneumocystis pneumonia (PCP) requiring intensive care unit (ICU) admission and the associated spectrum of immunocompromising conditions are poorly described. We analyzed all adult PCP cases admitted to French ICUs via the French medical database system (PMSI), over the period from 2013 to 2019. French ICUs admitted a total of 4055 adult patients with PCP. Among all hospitalized PCP cases, the proportion requiring ICU admission increased from 17.8 in 2014 to 21.3% in 2019 (P < 0.001). The incidence of severe PCP rose from 0.85 in 2013 to 1.32/100,000 adult inhabitants in 2019 (P < 0.0001), primarily due to the proportion of HIV-negative patients that increased from 60.6% to 74.4% (P < 0.0001). Meanwhile, the annual number of severe PCP cases among patients with HIV infection remained stable over the years. In-hospital mortality of severe PCP cases was 28.5% in patients with HIV infection and 49.7% in patients without. Multivariable logistic analysis showed that patients with HIV infection had a lower adjusted risk of death than patients without HIV infection (Odds Ratio [OR]: 0.30, 95% confidence interval [95CI]: 0.17-0.55). Comorbidities or conditions strongly associated with hospital mortality included the patient's age, Simplified Acute Physiologic Score II, congestive heart failure, coagulopathy, solid organ cancer, and cirrhosis. A vast array of autoimmune inflammatory diseases affected 19.9% of HIV-negative patients. The number of PCP cases requiring ICU admission in France has risen sharply. While the yearly count of severe PCP cases in HIV-infected patients has remained steady, this rise predominantly affects cancer patients, with a recent surge observed in patients with autoimmune inflammatory diseases, affecting one in five individuals.

A RARE COMPLICATION: ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS) INDUCED BY SEVERE PNEUMOCYSTIS CARINII PNEUMONIA (PCP)

Introduction: Pneumocystis pneumonia (PCP) represents a prevalent opportunistic infection among individuals with HIV, posing a significant risk of mortality. The occurrence of acute respiratory distress syndrome (ARDS) as a consequence of PCP further accentuates the gravity and intricacy of this pulmonary infection. Objective: This case report aims to discuss the management of the rare complication of ARDS induced by severe PCP in a 36-year-old man with HIV. Case Presentation: A 36-year-old male teacher, presented with worsening dyspnea, intermittent fever, and a productive cough persisting for two weeks, along with weight loss and fatigue. Initial diagnostic impressions included pulmonary tuberculosis with pneumonia. Treatment involved oxygen therapy, fluid administration, and medication. Laboratory tests showed leukocytosis, elevated blood glucose, and abnormal liver function. Subsequent investigations confirmed HIV infection. Chest X-ray revealed severe bilateral pneumonia and possible ARDS, leading to transfer to the Intensive Care Coronary Unit for further management. Discussion: The diagnosis of severe Pneumocystis jirovecii pneumonia (PCP) underscores the importance of recognizing PCP as a significant clinical concern, especially in HIV patients. Diagnostic challenges, such as late HIV diagnosis, highlight the need for timely screening and intervention. Management involved a multidisciplinary approach, including pulmonologists and cardiologists. Despite treatment adjustments, some patients experience clinical deterioration, necessitating careful management strategies like antiretroviral (ARV) therapy and respiratory support. This case underscores the complexity of managing PCP-related ARDS and the crucial role of timely intervention and comprehensive care. Conclusion: Severe PCP led to ARDS in an HIV-infected patient due to inflammation and lung damage, exacerbated by the immunocompromised state. Timely diagnosis and treatment are crucial to prevent complications and improve outcomes in such cases.

The Development and Evaluation of a Prediction Model for Kidney Transplant-Based Pneumocystis carinii Pneumonia Patients Based on Hematological Indicators.

This study aimed to develop a simple predictive model for early identification of the risk of adverse outcomes in kidney transplant-associated Pneumocystis carinii pneumonia (PCP) patients. This study encompassed 103 patients diagnosed with PCP, who received treatment at our hospital between 2018 and 2023. Among these participants, 20 were categorized as suffering from severe PCP, and, regrettably, 13 among them succumbed. Through the application of machine learning techniques and multivariate logistic regression analysis, two pivotal variables were discerned and subsequently integrated into a nomogram. The efficacy of the model was assessed via receiver operating characteristic (ROC) curves and calibration curves. Additionally, decision curve analysis (DCA) and a clinical impact curve (CIC) were employed to evaluate the clinical utility of the model. The Kaplan-Meier (KM) survival curves were utilized to ascertain the model's aptitude for risk stratification. Hematological markers, namely Procalcitonin (PCT) and C-reactive protein (CRP)-to-albumin ratio (CAR), were identified through machine learning and multivariate logistic regression. These variables were subsequently utilized to formulate a predictive model, presented in the form of a nomogram. The ROC curve exhibited commendable predictive accuracy in both internal validation (AUC = 0.861) and external validation (AUC = 0.896). Within a specific threshold probability range, both DCA and CIC demonstrated notable performance. Moreover, the KM survival curve further substantiated the nomogram's efficacy in risk stratification. Based on hematological parameters, especially CAR and PCT, a simple nomogram was established to stratify prognostic risk in patients with renal transplant-related PCP.

Meta-Analysis and Systematic Literature Review of the Genus Pneumocystis in Pet, Farm, Zoo, and Wild Mammal Species.

A systematic literature search on Pneumocystis in 276 pet, farm, zoo, and wild mammal species resulted in 124 publications originating from 38 countries that were analyzed descriptively and statistically, for which inclusion and exclusion criteria were exactly defined. The range of recorded Pneumocystis prevalence was broad, yet in half of the citations a prevalence of ≤25% was documented. Prevalence was significantly dependent on the method used for Pneumocystis detection, with PCR revealing the highest percentages. Pet animals showed the lowest median Pneumocystis prevalence, followed by farm, wild, and zoo animals. In contrast, pet and farm animals showed higher proportions of high-grade infection levels compared to zoo and wild mammals. Only in individual cases, all of them associated with severe Pneumocystis pneumonia, was an underlying immunosuppression confirmed. Acquired immunosuppression caused by other diseases was frequently discussed, but its significance, especially in highly immunosuppressive cases, needs to be clarified. This meta-analysis supported a potential influence of the social and environmental factors of the host on Pneumocystis transmission in wildlife, which must be further elucidated, as well as the genetic diversity of the fungus.

Features of clinical manifestations and diagnosis of comorbidity of disseminated pulmonary tuberculosis, coronavirus, pneumocystis and pneumococcal pneumonia in patients with late stages of HIV infection with immunodeficiency

Aim. To study the features of clinical manifestations and diagnosis of comorbidity of disseminated pulmonary tuberculosis, coronavirus, pneumocystis and pneumococcal pneumonia in patients with late stages of HIV infection with immunodeficiency.&#x0D; Materials and methods. The prospective study included 120 newly identified patients with disseminated pulmonary tuberculosis with Mycobacterium tuberculosis, stage IVB of HIV infection, in the phase of progression and in the absence of antiretroviral therapy, aged 2953 years, who were randomized into 1A and 2A main groups and 1B and 2B comparison groups. Group 1A included 29 patients with comorbidity and pneumocystis pneumonia and group 2A 31 patients with comorbidity of disseminated pulmonary tuberculosis, coronovirus pneumococcal pneumonia, and group 1B and 2B comprised 29 and 31 similar patients, but without coronovirus pneumonia. To diagnose coronavirus pneumonia, PCR of SARS-CoV-2 RNA was used in smears from the nasopharynx and oropharynx, in sputum or in endotracheal aspirate. To detect Pneumocystis jirovecii, the causative agent of pneumocystis pneumonia, a microscopic examination of diagnostic material from the respiratory tract with RomanovskyGiemse and GrokottGmri coloration was carried out, and to detect Streptococcus pneumoniae, the causative agent of pneumococcal pneumonia, the diagnostic material was seeded on special nutrient media with determination of the drug resistance of the resulting culture to broad-spectrum antibiotics. Statistical data processing was carried out using the Microsoft Office Excel 2019 program with the calculation of the average in the group and the standard error of the average, confidence interval.&#x0D; Results. The comorbidity of disseminated pulmonary tuberculosis, coronavirus, pneumocystis and pneumococcal pneumonia in patients in the late stages of HIV infection, in the phase of progression and in the absence of antiretroviral therapy was characterized by severe immunodeficiency, generalization of tuberculosis with multiple extrapulmonary lesions and severe pneumonia. This determines the similarity of clinical manifestations and respiratory symptoms, and also makes it difficult to visualize computed tomographic changes consisting of a complex simultaneous combination of four pathological syndromes: dissemination, pleural pathology, increased pulmonary pattern and adenopathy. Simultaneous layering of several pathologies with the same type of clinical manifestations and computed tomographic changes requires a comprehensive etiological diagnosis of specific diseases to prescribe timely comprehensive treatment and reduce the lethality of this heavy contingent of patients.&#x0D; Conclusion. Patients with disseminated pulmonary tuberculosis and HIV infection who are registered in the office of tuberculosis care for HIV-infected in the tuberculosis dispensary represent a high risk group of COVID-19 infection and the development of coronavirus pneumonia, and with severe immunodeficiency, pneumocystis and pneumococcal pneumonia, should be regularly subjected to preventive studies for timely detection of COVID-19, coronavirus, pneumocystis and pneumococcal pneumonia for the purpose of their emergency isolation and timely treatment.

Axenic Long-Term Cultivation of Pneumocystis jirovecii.

Pneumocystis jirovecii, a fungus causing severe Pneumocystis pneumonia (PCP) in humans, has long been described as non-culturable. Only isolated short-term experiments with P. jirovecii and a small number of experiments involving animal-derived Pneumocystis species have been published to date. However, P. jirovecii culture conditions may differ significantly from those of animal-derived Pneumocystis, as there are major genotypic and phenotypic differences between them. Establishing a well-performing P. jirovecii cultivation is crucial to understanding PCP and its pathophysiological processes. The aim of this study, therefore, was to develop an axenic culture for Pneumocystis jirovecii. To identify promising approaches for cultivation, a literature survey encompassing animal-derived Pneumocystis cultures was carried out. The variables identified, such as incubation time, pH value, vitamins, amino acids, and other components, were trialed and adjusted to find the optimum conditions for P. jirovecii culture. This allowed us to develop a medium that produced a 42.6-fold increase in P. jirovecii qPCR copy numbers after a 48-day culture. Growth was confirmed microscopically by the increasing number and size of actively growing Pneumocystis clusters in the final medium, DMEM-O3. P. jirovecii doubling time was 8.9 days (range 6.9 to 13.6 days). In conclusion, we successfully cultivated P. jirovecii under optimized cell-free conditions in a 70-day long-term culture for the first time. However, further optimization of the culture conditions for this slow grower is indispensable.

Machine Learning Models for Prediction of Severe Pneumocystis carinii Pneumonia after Kidney Transplantation: A Single-Center Retrospective Study.

The objective of this study was to formulate and validate a prognostic model for postoperative severe Pneumocystis carinii pneumonia (SPCP) in kidney transplant recipients utilizing machine learning algorithms, and to compare the performance of various models. Clinical manifestations and laboratory test results upon admission were gathered as variables for 88 patients who experienced PCP following kidney transplantation. The most discriminative variables were identified, and subsequently, Support Vector Machine (SVM), Logistic Regression (LR), Random Forest (RF), K-Nearest Neighbor (KNN), Light Gradient Boosting Machine (LGBM), and eXtreme Gradient Boosting (XGB) models were constructed. Finally, the models' predictive capabilities were assessed through ROC curves, sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and F1-scores. The Shapley additive explanations (SHAP) algorithm was employed to elucidate the contributions of the most effective model's variables. Through lasso regression, five features-hemoglobin (Hb), Procalcitonin (PCT), C-reactive protein (CRP), progressive dyspnea, and Albumin (ALB)-were identified, and six machine learning models were developed using these variables after evaluating their correlation and multicollinearity. In the validation cohort, the RF model demonstrated the highest AUC (0.920 (0.810-1.000), F1-Score (0.8), accuracy (0.885), sensitivity (0.818), PPV (0.667), and NPV (0.913) among the six models, while the XGB and KNN models exhibited the highest specificity (0.909) among the six models. Notably, CRP exerted a significant influence on the models, as revealed by SHAP and feature importance rankings. Machine learning algorithms offer a viable approach for constructing prognostic models to predict the development of severe disease following PCP in kidney transplant recipients, with potential practical applications.

Efficacy of initial caspofungin plus trimethoprim/sulfamethoxazole for severe PCP in patients without human immunodeficiency virus infection

BackgroundThe number of pneumocystis pneumonia (PCP) cases is increasing in immunocompromised patients without human immunodeficiency virus infection (HIV), causing serious morbidity with high mortality. Trimethoprim/sulfamethoxazole (TMP/SMZ) monotherapy has limited effectiveness in the treatment of PCP. Clinical data on whether initial caspofungin plus TMP/SMZ for this disease is superior to monotherapy in non-HIV-infected patients are limited. We aimed to compare the clinical effectiveness of these regimens for severe PCP in non-HIV patients.MethodsA retrospective study reviewed 104 non-HIV-infected patients with confirmed PCP in the intensive care unit between January 2016 and December 2021. Eleven patients were excluded from the study because TMP/SMZ could not be used due to severe hematologic disorders or clinical data were missing. All enrolled patients were divided into three groups according to different treatment strategies: Group 1 received TMP/SMZ monotherapy, Group 2 received caspofungin combined with TMP/SMZ as first-line therapy, and Group 3 initially received TMP/SMZ monotherapy and later received caspofungin as salvage therapy. The clinical characteristics and outcomes were compared among the groups.ResultsA total of 93 patients met the criteria. The overall positive response rate of anti-PCP treatment was 58.06%, and the overall 90-day all-cause mortality rate was 49.46%. The median APACHE II score was 21.44. The concurrent infection rate was 74.19%, among whom 15.05% (n = 14) of those patients had pulmonary aspergillosis, 21.05% (n = 20) had bacteremia, and 23.65% (n = 22) had CMV infections. The patients who received initial caspofungin combination with TMP/SMZ had the best positive response rate (76.74%) compared to others (p = 0.001). Furthermore, the group that received initial caspofungin combined with TMP/SMZ had a 90-day all-cause mortality rate (39.53%) that was significantly different from that of the shift group (65.51%, p = 0.024), but this rate showed no statistically significant difference compared with that in the monotherapy group (48.62%, p = 0.322). None of the patients had serious adverse events from caspofungin therapy.ConclusionsFor non-HIV-infected patients with severe PCP, initial combination therapy with caspofungin and TMP/SMZ is a promising first-line treatment option compared with TMP/SMZ monotherapy and combination therapy as salvage therapy.

Metagenomic next-generation sequencing performed on blood samples for the early recognition of severe Pneumocystis pneumonia in critical hematological patients

Severe Pneumocystis pneumonia (PCP) has a poor prognosis, and its early and precise diagnosis is difficult in immunocompromised individuals. Therefore, this study explored the diagnostic value of metagenomic next-generation sequencing (mNGS) of peripheral blood in diagnosing severe PCP in patients with hematological diseases. This prospective study analyzed the clinical manifestations, mNGS results (from the peripheral blood), traditional pathogen detection results, laboratory test results, chest computed tomography (CT) images, treatments, and outcomes of severe PCP in hematological patients who were hospitalized in the 2 centers of the Affiliated Hospital of Soochow University between September 2019 and October 2021. A total of 31 cases of hematological diseases complicated with pulmonary infections, including 7 cases of severe PCP diagnosed by mNGS performed on peripheral blood samples, were analyzed. Traditional pathogen detection methods for PCP cannot be used. In contrast, the laboratory readings for Pneumocystis jirovecii (Pj) detected within 48 hours of symptom onset by mNGS on the 7 blood samples ranged from 12 to 5873, with a median value of 43. Under the guidance of the mNGS results, preemptive antimicrobial therapy with trimethoprim/sulfamethoxazole alone or in combination with caspofungin was administered to treat Pj. After treatment, 4 patients recovered, and 3 patients died of acute respiratory failure and acute respiratory distress syndrome (ARDS). MNGS performed on peripheral blood samples is optional but can provide early recognition of severe PCP and help guide empirical treatment in critical hematological patients.

Severe Pneumocystis Pneumonia Associated with Ulcerative Colitis

A 56-year-old woman with a 9-month history of ulcerative colitis (UC) who had been treated with prednisolone (PSL) 40 mg/day and azathioprinefor 2 months was referred to our hospital because of fever and dyspnea. Computed tomography (CT) of the chest revealed diffuse ground-glass opacities in both lungs and consolidation in both lower lobes. PCR of the patient's bronchoalveolar lavage fluid was positive for pneumocystis jirovecii, and she was diagnosed with pneumocystis pneumonia (PCP). The patient developed refractory respiratory failure that required invasive mechanical ventilation. After sulfamethoxazole-trimethoprim administration and methyl prednisolone pulse therapy, her clinical condition improved dramatically. Few reports are available on severe PCP associated with UC. It is important to keep in mind the possibility of complication by PCP in UC patients.

Risk factors for Pneumocystis pneumonia with acute respiratory failure among kidney transplant recipients

PurposeOne of the rare life-threatening fungal infections is pneumocystis pneumonia (PCP). Immunocompromised patients are the main vulnerable population. We investigate the risk factors associated with the development of severe PCP infection with acute respiratory failure after kidney transplantation.Materials and methodsThis is a retrospective, single-center, case-control study. PCP patients who are kidney transplant recipients and required high-flow oxygen support or mechanical ventilation between March 2009 and February 2017 were included in the study. The comparison was conducted between the non-severe and severe PCP groups. To identify associated risk factors, we performed univariate and multivariate logistic regression.ResultsAmong the total 2,330 kidney transplant recipients, 50 patients (2.1%) were diagnosed with PCP. Of these, 27 patients (54.0%) had severe PCP and 7 patients (14.0%) died, all of them were severe PCP patients. In the severe PCP group, the time from transplantation to PCP diagnosis (23.4 ± 24.9 months vs. 13.7 ± 9.9 months, p = 0.090) was insignificantly faster than in the non-severe PCP group. According to multiple logistic regression analysis, the significant risk factors associated with severe PCP were as follows, age (odds ratios (OR) 1.07; 95% confidence intervals (CI): 1.01–1.13; p = 0.027), time from transplantation to PCP diagnosis (odds ratios (OR) 0.92; 95% confidence intervals (CI): 0.86–0.99; p = 0.024), lymphopenia (OR 6.48; 95% CI: 1.05–40.09; p = 0.044), and history of acute rejection within 1 year (OR 8.28; 95% CI: 1.29–53.20; p = 0.026).ConclusionPatients who have lymphopenia at the time of hospital admission or have been recently treated with acute rejection are more likely to progress to severe PCP, requiring intensive monitoring and aggressive treatment.

Detection of Pneumocystis and Morphological Description of Fungal Distribution and Severity of Infection in Thirty-Six Mammal Species

Pneumocystis spp. are thought to adapt to the lungs of potentially all mammals. However, the full host range, fungal burden and severity of infection are unknown for many species. In this study, lung tissue samples originating from 845 animals of 31 different families of eight mammal orders were screened by in situ hybridization (ISH) using a universal 18S rRNA probe for Pneumocystis, followed by hematoxylin and eosin (H&E) staining for determining histopathological lesions. A total of 216 (26%) samples were positive for Pneumocystis spp., encompassing 36 of 98 investigated mammal species, with 17 of them being described for the first time for the presence of Pneumocystis spp. The prevalence of Pneumocystis spp. as assessed by ISH varied greatly among different mammal species while the organism load was overall low, suggesting a status of colonization or subclinical infection. Severe Pneumocystis pneumonia seemed to be very rare. For most of the Pneumocystis-positive samples, comparative microscopic examination of H&E- and ISH-stained serial sections revealed an association of the fungus with minor lesions, consistent with an interstitial pneumonia. Colonization or subclinical infection of Pneumocystis in the lung might be important in many mammal species because the animals may serve as a reservoir.

Initiating antiretroviral therapy within 2 weeks of anti-Pneumocystis treatment does not increase mortality or AIDS-defining events in patients with HIV-associated moderate to severe Pneumocystis pneumonia: results of a prospective observational multicenter study

BackgroundThe mortality rate remains high among patients with coinfection with Pneumocystis pneumonia (PCP) and HIV. The timing for initiation of antiretroviral therapy (ART) after a diagnosis of moderate to severe PCP remains controversial, however. We therefore designed the present study to determine the optimal timing for ART initiation in AIDS-associated PCP (AIDS/PCP) patients.MethodsThis was a multicenter, observational, prospective clinical trial. Eligible participants were recruited from 14 hospitals in mainland China, and assigned to an Early ART arm (initiation of ART ≤ 14 days after PCP diagnosis) and a Deferred ART arm (initiation of ART > 14 days after PCP diagnosis). The primary outcomes were death and the incidence of AIDS-defining events at week 48. The secondary outcomes were the changes in CD4+ T-cell counts from baseline values at weeks 12, 24, and 48, the virological suppression rate at week 24 and week 48, the rate of development of PCP-associated immune reconstitution inflammatory syndrome (PCP/IRIS), and the rate of adverse events over 48 weeks.ResultsThe present study was performed using the data of 363 participants, with 169 participants in the Early ART arm, and 194 participants in the Deferred ART arm. Immunological and virological outcomes were found to be similar in both treatment arms. At week 48, there were no significant differences for the incidence of mortality (20 vs. 26, p = 0.860), and AIDS-defining events (17 vs. 26, p = 0.412). Over 48 weeks, the rates of PCP/IRIS (2 vs. 3, p = 1.000), adverse events (70 vs. 72, p = 0.465), and grade 3 or 4 adverse events (28 vs. 34, p = 0.919) did not reach statistical significance. A significant difference observed between two study arms was that 11 participants (55.0%) in the Early ART arm compared to 23 participants (88.5%) in the Deferred ART arm (p = 0.026) succumbed before ART had ever been started.ConclusionsEarly ART initiation results in no increase in mortality, AIDS-defining events, IRIS, adverse events, and immunological or virological outcomes. These results support the early initiation of ART in patients with moderate to severe AIDS/PCP.Clinical trial registrationThe present trial was registered at Chinese Clinical Trial Registry (ChiCTR1900021195). Registered 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362.

Extracorporeal membrane oxygenation rescue for severe pneumocystis pneumonia with the Macklin effect: a case report

BackgroundPneumocystis jirovecii pneumonia (PJP) in an immunocompromised host is often associated with the Macklin effect, which can progress to spontaneous pneumomediastinum (SPM), subcutaneous emphysema (SCE), and pneumothorax (PNX). Diagnosing the causative organism of these conditions in non-HIV infected patients and treating hypoxemia while preventing further lung damage can be challenging. This study examines the case of a non-HIV infected male with SPM, SCE, and PNX secondary to severe Pneumocystis jirovecii (PJ) infection.Case presentationA 53-year-old male with pure red cell aplasia (PRCA) was admitted with fever, dry cough, and shortness of breath. His respiratory function progressively deteriorated due to the development of SPM, SCE, and PNX, eventually requiring endotracheal intubation and invasive ventilation. As a result of high pressure in his airways occasioned by lung recruitment maneuvers, his pulmonary parameters worsened, necessitating veno-venous (VV) extracorporeal membrane oxygenation (ECMO) therapy. The early initiation of VV-ECMO facilitated ultra-protective lung ventilation and prevented the progression of SPM, SCE, and PNX. Traditional diagnostic assays were unrevealing, whereupon the patient resorted to the metagenomic next-generation sequencing technology for uncovering potential pathogens. Consequently, we detected a significantly higher infection by PJ in the patient’s bronchoscopy lavage fluid. Finally, the patient was successfully treated with appropriate antimicrobials and was decannulated after nine days of ECMO support.ConclusionsSPM, SCE, and PNX are rare clinical manifestations of PJP. However, they can be considered as poor prognostic factors of the infection. Physicians should, therefore, be alert to the possibility of PJP in immunocompromised patients.

Preliminary Study on the Combination Effect of Clindamycin and Low Dose Trimethoprim-Sulfamethoxazole on Severe Pneumocystis Pneumonia After Renal Transplantation.

ObjectiveEvaluate the effect of the combination of clindamycin with low-dose trimethoprim-sulfamethoxazole (TMP/SMX) regimen on sever Pneumocystis pneumonia (PCP) after renal transplantation.Method20 severe PCP patients after renal transplantation were included in this historical-control, retrospective study. A 10 patients were treated with the standard dose of TMP/SMX (T group), the other 10 patients were treated with the combination of clindamycin and low dose TMP/SMX (CT group).ResultsAlthough there was no significant difference in the hospital survival between the two groups, the CT protocol improved the PaO2/FiO2 ratio more significantly and rapidly after the 6th ICU day (1.51 vs. 0.38, P = 0.014). CT protocol also ameliorated the pulmonary infiltration and the lactate dehydrogenase level more effectively. Moreover, the CT protocol reduced the incidence of pneumomediastinum (0 vs. 50%, P = 0.008), the length of hospital staying (26.5 vs. 39.0 days, P = 0.011) and ICU staying (12.5 vs. 22.5 days, P = 0.008). Furthermore, more thrombocytopenia (9/10 vs. 3/10, P = 0.020) was emerged in the T group than in the CT group. The total adverse reaction rate was much lower in the CT group than in the T group (8/80 vs. 27/80, P < 0.001). Consequently, the dosage of TMP/SMX was reduced in 8 patients, while only 2 patients in the CT group received TMP/SMX decrement (P = 0.023).ConclusionThe current study proposed that clindamycin combined with low-dose TMP/SMX was more effective and safer the than single use of TMP/SMX for severe PCP patients after renal transplantation (NCT 04328688).

No Statistically Apparent Difference in Antifungal Effectiveness Observed Among Trimethoprim/Sulfamethoxazole Plus Clindamycin or Caspofungin, and Trimethoprim/Sulfamethoxazole Monotherapy in HIV-Infected Patients with Moderate to Severe Pneumocystis Pneumonia: Results of an Observational Multicenter Cohort Study.

IntroductionPneumocystis pneumonia is a common opportunistic infection in patients with HIV/AIDS, and is a leading cause of death in this population. Early selection of effective treatment is therefore critical to reduce mortality. We conducted a clinical trial to compare the effectiveness and safety of three different antifungal treatment regimens in HIV-infected patients with moderate to severe PCP.MethodsOur study was a multicenter, observational prospective clinical trial. We recruited 320 HIV-infected patients with moderate to severe PCP, and stratified these subjects into a trimethoprim/sulfamethoxazole (TMP-SMX) monotherapy group, a TMP-SMX plus clindamycin group, and a TMP-SMX plus caspofungin group. Patients were invited to participate in 12 weeks of follow-up. Outcomes included the difference in overall mortality and the proportion of overall positive response to treatment in the three groups at weeks 4 and 12, the difference in treatment duration, and the proportion of adverse events among the three groups during the study period.ResultsThe probability of survival not statistically different among three treatment groups. Mortality in the TMP-SMX monotherapy group (group 1) was 15/115 (13.04%) vs. 20/83 (24.10%) in the TMP-SMX plus clindamycin group (group 2) vs. 24/107 (22.43%) in the TMP-SMX plus caspofungin group (group 3) at week 12 (p = 0.092). The overall positive response rate to treatment in the three groups was 24.14%, 34.94%, and 38.32%, respectively, at week 4, and 33.91%, 38.55%, and 44.86%, respectively, at week 12. No significant difference in the overall positive response rate to treatment at either week 4 or week 12 was noted (p = 0.061, p = 0.246). Rates of changes to therapy were 6.50% (8/123) in group 1, 3.40% (3/87) in group 2, and 2.70% (3/110) in group 3, and did not differ significantly among the three groups (p = 0.376). There were also no significant differences in adverse events among the three treatment groups of patients with moderate to severe PCP.ConclusionsOur results indicate that there are no significant statistical differences among the three studied treatment regimens in terms of antifungal effectiveness in HIV-infected patients with moderate to severe PCP. TMP-SMX monotherapy is a convenient, cheap, and effective therapeutic drug regimen to treat HIV-infected patients with moderate to severe PCP, and is an appropriate treatment strategy in resource-limited settings.Clinical Trial Registrationwww.ClinicalTrials.gov, ID: ChiCTR1900021195. Registered on February 1, 2019.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00586-5.

Prevalence of Pneumocystosis in Sub-Saharan Africa and Helminth Immune Modulation.

Sub-Saharan Africa is the region of the world with the highest prevalence of helminth infections. To protect themselves from the defensive mechanisms of their respective hosts, helminths modulate their immune responses. This modulation has relevant clinical and epidemiological consequences, including the inhibition of inflammatory processes that characterize infection by other microorganisms. Severe Pneumocystis pneumonia is characterized by an intense inflammatory reaction that can lead to death. Acquired immunodeficiency syndrome is the main predisposing factor to the development of pneumocystosis. Although the introduction of highly active antiretroviral therapy has led to a notable decline in the incidence of acquired immunodeficiency syndrome-associated complications, pneumocystosis continues to be an important global health problem. Despite the high incidence of human immunodeficiency virus infection in the sub-Saharan region, the prevalence of Pneumocystis pneumonia there has been lower than expected. Several factors, or combinations thereof, may contribute to this evolution. Here, we hypothesize the possible role of helminth immune modulation as an important issue at play. On the other hand, and looking ahead, we believe that the immune modulation achieved by helminths may be an important factor to consider during the design and evaluation processes of vaccines against Pneumocystis jirovecii to be used in Sub-Saharan Africa. The requirements of a balanced triggering of different types of immune responses for controlling the infection produced by this microorganism, as observed during experiments in animal models, support this final consideration.

First case of low-dose umbilical cord blood therapy for pediatric acute respiratory distress syndrome induced by Pneumocystis carinii pneumonia

ObjectiveThis study aimed to present the case of a boy with acute distress syndrome (ARDS) treated with low-dose umbilical cord blood (UCB) therapy and explore the underlying possible mechanism.MethodsA 7-year-old boy with severe Pneumocystis carinii pneumonia and severe ARDS was treated with allogeneic UCB as salvage therapy.ResultsThe patient did not improve after being treated with lung protective ventilation, pulmonary surfactant replacement, and extracorporeal membrane oxygenation (ECMO) for 30 days. However, his disease reversed 5 days after allogeneic UCB infusion, and he weaned from ECMO after 7 days of infusion. Bioinformatics confirmed that his Toll-like receptor (TLR) was abnormal before UCB infusion. However, after the infusion, his immune system was activated and repaired, and the TLR4/MyD88/NF-κB signaling pathway was recovered.ConclusionAllogenic UCB could treat ARDS by repairing the TLR4/MyD88/NF-κB signaling pathway, thereby achieving stability of the immune system.