Cases Of Pneumocystis Carinii Pneumonia Research Articles

Efficacy and safety of carrimycin in ten patients with severe pneumonia following solid organ transplantation.

The number of patients undergoing solid organ transplantation has increased annually. However, infections in solid organ transplant recipients can have a severe effect on patient survival owing to the continued use of immunosuppressants. Carrimycin is a novel macrolide antibiotic produced by genetically engineered streptomyces spiramyceticus harboring a 4''-O-isovaleryltransferase gene (ist) from streptomyces thermotoleran. Carrimycin has good antibacterial and antiviral effects. However, no relevant studies have been conducted on the efficacy and safety of carrimycin in patients with severe pneumonia (SP) after solid organ transplantation. To explore the efficacy and safety of carrimycin in patients with SP after solid organ transplantation to provide a medication reference for clinical treatment. In March 2022, ten patients with SP following solid-organ transplantation were treated at our hospital between January 2021 and March 2022. When the condition was critical and difficult to control with other drugs, carrimycin was administered. These ten patients' clinical features and treatment protocols were retrospectively analyzed, and the efficacy and safety of carrimycin for treating SP following solid organ transplantation were evaluated. All ten patients were included in the analysis. Regarding etiological agent detection, there were three cases of fungal pneumonia, two cases of bacterial pneumonia, two cases of Pneumocystis pneumonia, and three cases of mixed infections. After treatment with carrimycin, the disease in seven patients significantly improved, the course of the disease was significantly shortened, fever was quickly controlled, chest computed tomography was significantly improved, and oxygenation was significantly improved. Finally, the patients were discharged after curing. One patient died of acute respiratory distress syndrome, and two patients discontinued treatment. Carrimycin is a safe and effective treatment modality for SP following solid organ transplantation. Carrimycin may have antibacterial and antiviral effects in patients with SP following solid organ transplantation.

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.

Mapping the Burden of Fungal Diseases in the United Arab Emirates.

The United Arab Emirates has very little data on the incidence or prevalence of fungal diseases. Using total and underlying disease risk populations and likely affected proportions, we have modelled the burden of fungal disease for the first time. The most prevalent serious fungal conditions are recurrent vulvovaginitis (~190,000 affected) and fungal asthma (~34,000 affected). Given the UAE's low prevalence of HIV, we estimate an at-risk population of 204 with respect to serious fungal infections with cryptococcal meningitis estimated at 2 cases annually, 15 cases of Pneumocystis pneumonia (PCP) annually, and 20 cases of esophageal candidiasis in the HIV population. PCP incidence in non-HIV patients is estimated at 150 cases annually. Likewise, with the same low prevalence of tuberculosis in the country, we estimate a total chronic pulmonary aspergillosis prevalence of 1002 cases. The estimated annual incidence of invasive aspergillosis is 505 patients, based on local data on rates of malignancy, solid organ transplantation, and chronic obstructive pulmonary disease (5.9 per 100,000). Based on the 2022 annual report of the UAE's national surveillance database, candidaemia annual incidence is 1090 (11.8/100,000), of which 49.2% occurs in intensive care. Fungal diseases affect ~228,695 (2.46%) of the population in the UAE.

Pneumocystis Pneumonia After Allogeneic Hematopoietic Cell Transplantation: A Case-Control Study on Epidemiology and Risk Factors on Behalf of the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation

Pneumocystis pneumonia (PCP) is a life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT). However, allo-HCT procedures have evolved toward older patients, unrelated donors, and reduced-intensity conditioning, possibly modifying the risks. Polymerase chain reaction (PCR), widely used nowadays, is more sensitive than microscopy diagnostic methods. This study aimed to assess the factors associated with PCP in allo-HCT recipients within 2 years of HCT and managed according to current procedures. This multicenter, nested case-control study included PCP cases diagnosed by PCR, cytology, or immunofluorescence on bronchoalveolar lavage fluid between 2016 and 2018. Two controls per case were selected from the ProMISe registry and matched for the center, transplant date, and underlying disease. Fifty-two cases and 104 controls were included among the 5452 patients who underwent allo-HCT in the participating centers. PCP occurred at a median of 11.5 months after transplantation. The mortality rate was 24% on day 30 after the PCP diagnosis and 37% on day 90. The clinical presentation and mortality rates of the 24 patients diagnosed using only PCR were not different from those diagnosed with microscopy methods. Our study demonstrates a substantial incidence of, and mortality from, PCP, after allogeneic HCT despite well-established prophylactic approaches. In our experience, PCP nowadays occurs later after transplant than previously reported, justifying the prolongation of prophylaxis after six months in many cases. Allo-HCT recipients diagnosed with PCR as the only PCP marker should benefit from specific treatment as for other patients.

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.

304 - A Case of Pneumocystis pneumonia in a patient with suspected hyper IGM syndrome

304 - A Case of Pneumocystis pneumonia in a patient with suspected hyper IGM syndrome

Post-COVID-19 Pneumocystis pneumonia cases from Pakistan: an observational study.

Background. Concurrent coronavirus disease 2019 (COVID-19) and Pneumocystis jirovecii pneumonia (PJP) has been described in various reports, with a recent study describing a 9.3 % P. jirovecii detection rate in critically ill COVID-19 patients. Methods. Patients with PCR-confirmed PJP following COVID-19 infection who were admitted to Aga Khan University Hospital, Karachi, Pakistan from March 2020-June 2021 were identified through a laboratory database. Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus was performed by RT-PCR Cobas SARS-CoV-2 qualitative assay. P. jirovecii PCR was performed using the RealStar Pneumocystis jirovecii PCR kit. Clinical, radiological and laboratory data for PJP patients were recorded. Results. During the study period, 3707 patients were admitted with COVID-19 at our hospital. P. jirovecii PCR was requested for 90 patients and was positive in 10 (11 %). Five out of 10 patients were discharged from the hospital and later developed cough and dyspnoea. Five patients remained hospitalized with severe COVID-19 and developed PJP. Eight patients in our study received systemic steroids. The trends of lymphocyte counts of all patients showed a lymphocyte count of <1000 mm-3 (<1.0×106 cells µl-1) in the week of PJP diagnosis. Four patients did not survive; one of these patients did not receive co-trimoxazole due to late diagnosis, one patient had concomitant nosocomial pneumonia and bacteraemia with multidrug-resistant Acinetobacter species, and two patients had concomitant aspergillosis. Conclusion. In summary, invasive fungal infections such as PJP should be considered as a complication in COVID-19 patients, with prompt evaluation and management.

Clinical cases of pneumocystis pneumonia in patients with HIV infection and underlying COVID-19

During the COVID-19 pandemic, additional difficulties have emerged in the differential diagnosis of interstitial pulmonary abnormalities, especially in patients with HIV infection, in whom this kind of injury can be caused by a wide range of pathogens, including opportunistic diseases. The high probability of an adverse outcome of pulmonary disease in patients with severe immunodeficiency requires an urgent choice of effective therapy.The article describes clinical cases of pneumocystis pneumonia in two COVID-19 patients with newly diagnosed HIV infection, illustrating the difficulties of differential diagnosis in these conditions.

S3237 Pneumocystis jirovecii Infection in Cirrhosis: A Case Report and Review of the Literature

Introduction: Pneumocystis jirovecii is a fungus that causes serious pneumonia in immunocompromised individuals most classically associated with AIDS or prolonged steroid use. Immune dysfunction is a well- nown complication of cirrhosis; however, Pneumocystis pneumonia (PCP) is not typically associated with cirrhosis as a common risk factor. We present a case of PCP in a patient with cirrhosis and review the existing cases in the literature. Case Description/Methods: A 59-year-old male with past medical history of alcoholic cirrhosis (MELD 30, Child Pugh Class C) presented with sepsis secondary to spontaneous bacterial peritonitis. He reported he was 6 months sober. He initially improved on ceftriaxone alone; he did not receive steroids. On hospital day five he developed dyspnea and hypoxia. CT-angiogram revealed extensive ground glass opacities. Despite broad spectrum antimicrobials, his condition deteriorated resulting in invasive ventilation. Bronchoalveolar lavage was significant for Pneumocystis jiroveci by polymerase chain reaction. HIV testing was negative. Due to renal impairment, therapy was initiated with clindamycin and primaquine before he expired (Figure). Discussion: This case was unique in that cirrhosis was the only identified risk factor for immunosuppression which predisposed to PCP. PCP is rare outside of risk factors including AIDS, prolonged systemic steroids and other immunosuppressive therapies, organ transplantation, hematologic malignancy, and solid tumors. There were 14 similar cases in the literature. Of the 15 total cases, 66% were male; the median age was 54. Eleven were in the setting of alcoholic hepatitis, and 9 of these received steroids. However, none of the steroid exposures were significant enough to be a classic risk factor for PCP. Common comorbidities included COPD and lymphopenia. CMV pneumonia was seen in 33% of cases. Esophageal candidiasis and Histoplasma capsulatum pneumonia were also recorded. Fatality in 87% of cases suggests that PCP in cirrhosis is associated with a poor prognosis. There are multiple possible mechanisms why these patients developed PCP. Systemic inflammation related to cirrhosis may dysregulate key inflammatory mediators required for immune response to Pneumocystis. Also, Low CD4 counts related to portal hypertension and splenic sequestration may play a role, although an effective immune response also requires interplay of B cells and natural killer cells. This case and review are important reminders of the severity of immunocompromise in cirrhosis.Figure 1.: CT-Angiogram with diffuse ground glass opacities. Table 1. - Author Date Age/sex Prior steroid exposure (duration if applicable) Etiology of cirrhosis Additional conditions Treatment for PCP Death (y/n) Ikawa 2001 40M Y (10 days and 22 days with a 7 day interim in between) alcohol abuse cytomegalovirus pneumonia, esophageal candidiasis, lymphopenia none Y Faria 2007 44F present in 6 of 7 cases (median duration: 16 days)* alcohol abuse cytomegalovirus isolated in 3 of 7 cases* trimethoprim/ sulfamethoxazole (TMP/SMX) Y 49M alcohol abuse TMP/SMX Y 50M alcohol abuse TMP/SMX Y 53M alcohol abuse TMP/SMX Y 56F alcohol abuse TMP/SMX Y 58F alcohol abuse TMP/SMX Y 61M alcohol abuse TMP/SMX Y Dodi 2010 54F Y (9 days) alcohol abuse cytomegalovirus pneumonia, hepatorenal syndrome TMP/SMX Y Yee 2017 52M N hepatitis c hepatitis c, lymphopenia primaquine, clindamycin, corticosteroids, TMP/SMX N Hadfield 2019 63M N alcohol abuse COPD TMP/SMX Y Akhter 2020 67F N hepatitis c COPD steroids, antibiotics (unspecified) N Dugan 2020 64M N NASH COPD, lymphopenia, histoplasma capsulatum pneumonia TMP/SMX Y Chung 2020 43M Y (26 days) alcohol abuse n/a TMP/SMX Y Meyers 2022 59M N alcohol abuse COPD, lymphopenia clindamycin, primaquine Y *Not specified which cases had the exposures and/or conditions.

Is Pneumocystis Jirovecii Transmitted by the Airborne Route?

<h3>Background</h3> Pneumocystis jirovecii (p.jirovecii) is a fungus responsible for causing opportunistic Pneumocystis pneumonia (PCP) in immunocompromised patients. Currently the Centers for Disease Control and Prevention (CDC) recommends following standard precautions while also avoiding placing a PCP patient in the same room with an immunocompromised patient. There has been recent scientific evidence that indicates P.jirovecii may be transmitted by the airborne route. The purpose of this literature review is to evaluate the recent research findings to assess whether escalating transmission-based precautions from droplet to airborne isolation is necessary to best prevent transmission of P.jirovecii in the immunocompromised oncologic patient population at a 514-bed inpatient comprehensive cancer center. <h3>Methods</h3> PubMed was utilized to identify articles describing PCP outbreaks, the fungal characteristics, and mode of transmission. The articles reviewed comprised of systematic reviews, case control, and case report studies published between years 2016 through 2021, with one influential case control study published in 2010. The patient population studied in the outbreaks included those with heart, kidney, or liver transplants and patient populations with other immunocompromising conditions. <h3>Results</h3> Nine articles, including 4 systematic reviews, 4 case control studies, and 1 case report were reviewed. The scientific evidence of the fungal characteristics, mode of transmission, and occurrence of clusters of PCP cases favored the hypothesis that airborne transmission is possible. There are still some unknowns including the length of time that the fungal cysts can remain in the air and if the cysts are spread via droplet or aerosolized route. <h3>Conclusions</h3> Despite the recent findings demonstrating possible airborne transmission, until further studies increase the strength of evidence for airborne transmission, droplet precautions should be considered for PCP patients to prevent transmission in the immunocompromised population.

#42 A Retrospective Study of Valganciclovir Discontinuation Due to Toxicity or Intolerance in Pediatric Solid Organ Transplant Patients

Abstract Background Cytomegalovirus (CMV) prevention strategies in pediatric solid organ transplantation (SOT) recipients include universal prophylaxis or pre-emptive therapy with valganciclovir (VGCV) based on CMV risk stratification. However, VGCV is associated with myelosuppresion and nephrotoxicity, which may result in premature termination or dose modifications of VGCV and/or discontinuation of Pneumocystis jirovecii pneumonia (PJP) prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX), which is also myelosupressive. There are no currently approved alternatives for CMV prevention in pediatric SOT patients. Thus, the specific aims of this study were to determine the frequency with which SOT recipients receiving VGCV develop neutropenia or lymphopenia, how often VGCV or TMP-SMX are discontinued or have a dose reduction, and whether changes in CMV prophylaxis are associated with increased rates of CMV DNAemia or disease. Method A retrospective, observational study of pediatric SOT recipients who were &amp;lt; 20 years old and who initiated VGCV prophylaxis, with the intent to receive at least 3 months of therapy, was conducted at 8 U.S. centers between January 2016 and December 2019. Each site abstracted demographic and clinical data for 1 year post-transplantation into a central REDCap electronic database hosted at St Jude. Patients with complete information as of December 2021 (n= 557) were included in this preliminary analysis. Results The cohort included 201 renal (36%), 101 cardiac (18%), 202 liver (36%), 34 lung (6%), 10 multivisceral (2%), 2 intestinal and 6 other SOT recipients. Median age at transplantation was 9.5 [IQR: 2.7- 14] years; 52% were male. VGCV was prematurely discontinued in 31 and the dose was adjusted in 168 resulting in changes in 199 (36%) recipients. TMP-SMX was discontinued prematurely in 61 and changed to an alternative therapy in 77 patients resulting in changes in 131 (24%) recipients. Seven patients discontinued both medications. No breakthrough cases of Pneumocystis pneumonia were documented. There were 119 (21%) patients with at least one episode of CMV DNAemia in the first year post-transplant, 54 (45%) of these occurred in patients who had changes to their VGCV prophylaxis. Conclusion Preliminary analysis of this large pediatric cohort suggests that CMV prophylaxis with VGCV is difficult to maintain and requires frequent dose adjustments and/or discontinuation of either VGCV and/or TMP-SMX for PJP prophylaxis. Despite alterations in PJP prophylaxis, no breakthrough infections were documented. These findings highlight the need to study the safety and efficacy of alternative prophylactic options for CMV in pediatric SOT recipients.

Evolving epidemiology of pneumocystis pneumonia: Findings from a longitudinal population-based study and a retrospective multi-center study in Germany.

SummaryBackgroundPneumocystis pneumonia (PCP) is a life-threatening opportunistic infectious disease of immunocompromised patients. Its incidence has decreased worldwide in the past, but data concerning its recent epidemiology are lacking.MethodsWe retrospectively analyzed all German inpatient cases from January 1, 2014 to December 31, 2019, to describe the recent epidemiology, incidence, clinical course, mortality and underlying diseases of PCP. Simultaneously, we conducted a retrospective multi-center study at two German university hospitals, and analyzed PCP cases treated there to gain deeper insights on the basis of primary patient data.FindingsThe incidence of PCP significantly increased from 2·3 to 2·6 per 100,000 population from 2014 to 2019 (1,857 to 2,172 cases, +17·0%, p < 0·0001), as well as PCP-related deaths (516 to 615 cases, +19·2%, p = 0·011). The spectrum of underlying diseases changed: Risk groups with established chemoprophylaxis for PCP based on international guidelines (HIV, hematologic malignancies, and transplantation) showed a significant decrease in PCP cases and deaths. Others, especially those with solid malignancies, and autoimmune and pulmonary diseases showed a significant increase in case numbers and deaths. Data from the retrospective multi-center study added information regarding prophylaxis and diagnostics of PCP.InterpretationThe incidence of PCP has reversed its trend, showing a significant increase in mortality on population level. Patients who were not previously considered in prophylactic measures are increasingly affected by PCP. This development deserves further investigation, and additional comprehensive guidelines for the use of chemoprophylaxis in new risk groups are needed.FundingDepartment of Nephrology and Hypertension, University Hospital Schleswig-Holstein, Kiel.

Pneumocystis in the era of prophylaxis: do the guidelines have to change?

In the era of effective prophylaxis, the objective of this study was to describe pneumocystis pneumonia (PCP) patients' profile and evaluate the consistency of clinical situations encountered with the recommended indications for prophylaxis. This was a single-centre, retrospective study. All adults (> 18years) with a definitive diagnosis of PCP were included. Data were collected from patients' electronic medical files. The study examined the medical files of 225 patients diagnosed with PCP and treated between 1 January, 2015, and 30 June, 2020. More than 95% of the patients were not on anti-PCP prophylaxis at the time of PCP diagnosis. There were 32 (14%) deaths before the end of PCP treatment, mainly in auto-immune disease (30%) and solid tumours (38%) groups unlike the solid-organ transplants group, among whom deaths were infrequent. Indeed, 48% of our cohort (n = 107) had both corticosteroid (CS) therapy, immunosuppressive or immunomodulatory treatment, and lymphopaenia and could have been considered at high risk for PCP. Trimethoprim/sulfamethoxazole was administered as first-line PCP curative treatment in 95% of the patients. Toxicities of this drug led to treatment interruption in 25% of the patients (except death). This study found a high number of PCP cases over 5years. Unsurprisingly, most of the patients were immunosuppressed, with risk factors for PCP already described in the literature. This large number of PCP cases should be avoidable and, consequently, questions arise. Faced with these data, prophylaxis should be common sense for immunocompromised patients with risk factors, even if formalised recommendations do not exist.

Genetic Polymorphisms of Pneumocystis jirovecii in HIV-Positive and HIV-Negative Patients in Northern China.

Pneumocystis jirovecii is an opportunistic fungus that can cause severe and potentially fatal Pneumocystis pneumonia (PCP) in immunodeficient patients. In this study, we investigated the genetic polymorphisms of P. jirovecii at eight different loci, including six nuclear genes (ITS, 26S rRNA, sod, dhps, dhfr and β-Tub) and two mitochondrial genes (mtLSU-rRNA and cyb) in three PCP cases, including two patients with HIV infection and one without HIV infection in Shanxi Province, P.R. China. The gene targets were amplified by PCR followed by sequencing of plasmid clones. The HIV-negative patient showed a coinfection with two genotypes of P. jirovecii at six of the eight loci sequenced. Of the two HIV-positive patients, one showed a coinfection with two genotypes of P. jirovecii at the same two of the six loci as in the HIV-negative patient, while the other showed a single infection at all eight loci sequenced. None of the three drug target genes (dhfr, dhps and cyb) showed mutations known to be potentially associated with drug resistance. This is the first report of genetic polymorphisms of P. jirovecii in PCP patients in Shanxi Province, China. Our findings expand our understanding of the genetic diversity of P. jirovecii in China.

Lung Segmentation in CT Images: A Residual U-Net Approach on a Cross-Cohort Dataset

Lung cancer is one of the most common causes of cancer-related mortality, and since the majority of cases are diagnosed when the tumor is in an advanced stage, the 5-year survival rate is dismally low. Nevertheless, the chances of survival can increase if the tumor is identified early on, which can be achieved through screening with computed tomography (CT). The clinical evaluation of CT images is a very time-consuming task and computed-aided diagnosis systems can help reduce this burden. The segmentation of the lungs is usually the first step taken in image analysis automatic models of the thorax. However, this task is very challenging since the lungs present high variability in shape and size. Moreover, the co-occurrence of other respiratory comorbidities alongside lung cancer is frequent, and each pathology can present its own scope of CT imaging appearances. This work investigated the development of a deep learning model, whose architecture consists of the combination of two structures, a U-Net and a ResNet34. The proposed model was designed on a cross-cohort dataset and it achieved a mean dice similarity coefficient (DSC) higher than 0.93 for the 4 different cohorts tested. The segmentation masks were qualitatively evaluated by two experienced radiologists to identify the main limitations of the developed model, despite the good overall performance obtained. The performance per pathology was assessed, and the results confirmed a small degradation for consolidation and pneumocystis pneumonia cases, with a DSC of 0.9015 ± 0.2140 and 0.8750 ± 0.1290, respectively. This work represents a relevant assessment of the lung segmentation model, taking into consideration the pathological cases that can be found in the clinical routine, since a global assessment could not detail the fragilities of the model.

Two Cases of Pneumocystis Pneumonia during the COVID-19 Outbreak

Two Cases of Pneumocystis Pneumonia during the COVID-19 Outbreak

Global prevalence, mortality, and main risk factors for COVID-19 associated pneumocystosis: A systematic review and meta-analysis

Objective: Pneumocystis pneumonia (PcP) is a life-threatening infection caused by the opportunistic fungi Pneumocystis jirovecii. The emergence of the COVID-19 pandemic forced the focus of attention of health policymakers on these two infections due to their clinical and paraclinical similarities, which cause diagnostic dilemmas. This study was undertaken to evaluate and estimate the global prevalence and main leading risk factors of coronavirus-associated pneumocystosis (CAP).Methods: We searched related databases between December 2019 and May 2022 for studies reporting CAP. Meta-analysis was performed using StatsDirect software (version 2.7.9) according to the DerSimonian and Laird method applying the random-effects model. We evaluated heterogeneity using the χ2-based Q statistic (significant for P<0.05) and the I2 statistic (>75% indicative of “notable” heterogeneity). Moreover, an odds ratio (OR) analysis was performed for eligible data.Results: Our meta-analysis included eight studies with 923 patients hospitalized with COVID-19; among them, 92 were PcP cases. The overall pooled prevalence of CAP was estimated at 11.5%. The mortality among CAP patients was lower than that of non-PcP patients (OR 1.93; 95% CI 0.86-4.31). Long-term corticosteroid therapy (OR 28.22; 95% CI 0.54-1 480.84) was the most predisposing factor for PcP among COVID-19 patients, followed by pulmonary diseases (OR 1.46; 95% CI 0.43-4.98), kidney diseases (OR 1.26; 95% CI 0.21-7.49), and acute respiratory destruction syndrome (OR1.22; 95% CI 0.05-29.28).Conclusions: The prevalence of PcP among the COVID-19 population is almost similar to the pre-COVID era. However, PcP-related mortality was decreased by the emergence of the COVID-19 pandemic. Women with COVID-19 are more susceptible to PcP than men. Acute respiratory distress syndrome, kidney diseases, pulmonary diseases, and long-term corticosteroid therapy increased the risk of PcP; however, transplantation and malignancy decreased the risk for PcP among COVID-19 patients. Further retrospective, case-control, prospective, and more precisely systematic review and meta-analysis studies are needed in this field.

CASE SERIES OF PNEUMOCYSTIS JIROVECII PNEUMONIA IN POST-COVID-19 DISEASE

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Pneumocystis carinii pneumonia (PCP) is an AIDS-defining illness, associated with significant morbidity and mortality. It is also found in patients with other immunosuppressive conditions such as organ transplant and malignancies (1). We present 4 cases of PCP in post-COVID 19 patients. All cases were HIV negative. CASE PRESENTATION: Case 1: A 30-year old female was admitted with a 1-month history of worsening shortness of breath (SOB) and productive cough. She had no known co-morbids and no history of corticosteroid use. Her oxygen saturation (SpO2) was 85% and respiratory rate (RR) was 35 breaths/minute (BPM). Chest examination revealed bibasilar crackles and CT scan showed bilateral (B/L) ground-glass haziness along with interlobular septal thickening. Patient's COVID-19 test was negative however her antibodies were reactive. Bronchoalveolar lavage (BAL) came back positive for PCP. Patient was managed with co-trimoxazole 48 hourly and prednisolone 25 mg BID.Case 2: A 70-year old male was admitted with high grade fever and SOB for 4 days. He was a known hypertensive, with a history of severe COVID-19 pneumonia 1.5 months back for which he was managed with IV tocilizumab and dexamethasone. His SpO2 was 63% and RR was 73 BPM. Chest examination revealed unilateral (U/L) reduced breath sounds. Chest X-ray showed U/L consolidation and sputum for PCP tested positive. Patient was shifted to the ICU and intubated for respiratory failure. He expired after 4 days of ICU stay.Case 3: A 71-year old male was admitted with SOB for 3 days. He was a known diabetic and hypertensive, with a history of severe COVID-19 pneumonia 1.5 months back, for which he was treated with IV tocilizumab and corticosteroids. His SpO2 was 93% and RR was 28 BPM. Chest examination revealed bibasilar crackles. His CT scan revealed B/L ground-glass haziness, and BAL was positive for PCP. Patient was managed with co-trimoxazole 8 hourly and prednisolone 20 mg BID.Case 4: A 28-year old female was electively admitted for induction chemotherapy. She was a known case of Acute Myeloid Leukemia with a history of COVID-19 infection 1 month back for which she was managed at home. During her hospital stay, she developed persistent cough and febrile neutropenia. Chest examination revealed bibasilar crackles and CT scan showed B/L ground-glass haze. BAL was positive for PCP. She was managed with co-trimoxazole 8 hourly and prednisolone 20 mg BID. DISCUSSION: A number of infectious sequelae have been described in post-COVID 19 patients. Few case reports of concurrent PCP and COVID-19 infection exist in literature (2), however there is only 1 case report of PCP as a post-COVID 19 sequela (3). CONCLUSIONS: This case series highlights the importance of being vigilant for infectious sequelae associated with SARS-CoV-2. REFERENCE #1: Schmidt, J.J., Lueck, C., Ziesing, S. et al. Clinical course, treatment and outcome of Pneumocystis pneumonia in immunocompromised adults: a retrospective analysis over 17 years. Crit Care 22, 307 (2018). REFERENCE #2: Bhat P, Noval M, Doub JB, Heil E. Concurrent COVID-19 and Pneumocystis jirovecii pneumonia in a severely immunocompromised 25-year-old patient. International Journal of Infectious Diseases. 2020 Oct 1;99:119-21. REFERENCE #3: Viceconte G, Buonomo AR, Lanzardo A, Pinchera B, Zappulo E, Scotto R, Schiano Moriello N, Vargas M, Iacovazzo C, Servillo G, Gentile I. Pneumocystis jirovecii pneumonia in an immunocompetent patient recovered from COVID-19. Infectious Diseases. 2021 May 4;53(5):382-5. DISCLOSURES: No relevant relationships by Maaha Ayub, source=Web Response No relevant relationships by Mustafa Bin Ali Zubairi, source=Web Response No relevant relationships by Ali Zubairi, source=Web Response

Updated estimated incidence and prevalence of serious fungal infections in Trinidad and Tobago

Objective: To estimate the incidence and prevalence of serious fungal infections in Trinidad and Tobago (T&T), with a population of 1 394 973 million. Methods: The medical literature was searched to obtain published data on the incidence and prevalence of fungal infections in the Caribbean. If data were unavailable, estimations were performed using the frequencies of fungal infection in populations at risk. Asthma and pulmonary tuberculosis rates were used to derive the prevalence of allergic bronchopulmonary aspergillosis (ABPA), severe asthma with fungal sensitization (SAFS), and chronic pulmonary aspergillosis (CPA). Results: The estimated annual burden of fungal infections was 46 156 persons (3.3% of the population), including 21 455 women with recurrent vulvovaginal candidiasis, 118 persons with invasive aspergillosis, 3637 adults with ABPA, 4800 with SAFS, and 178 with CPA. Annually, we estimated 70 cases of candidemia and 14 647 cases of tinea capitis in children. Of the 11 000 persons living with HIV/AIDS, it was estimated that there were 40 cases of cryptococcal meningitis, 88 cases of disseminated histoplasmosis, and 124 cases of Pneumocystis pneumonia. Conclusion: There seems to be an extensive burden of fungal infections in T&T. Hence, targeted interventions are required to improve clinical and laboratory diagnosis and a national surveillance system should be implemented.

Comparative effectiveness of trimethoprim-sulfamethoxazole versus atovaquone for the prophylaxis of pneumocystis pneumonia in patients with connective tissue diseases receiving prolonged high-dose glucocorticoids

We compared the prophylactic effect of trimethoprim-sulfamethoxazole (TMP-SMX) with atovaquone for pneumocystis pneumonia (PCP) in patients with connective tissue diseases (CTDs) receiving high-dose glucocorticoids. Patients with CTDs aged ≥ 18years who were treated with a prolonged course (≥ 4weeks) of glucocorticoids (≥ 20mg/day prednisone) in a Japanese tertiary center between 2013 and 2017 were included. The patients were categorized into two groups: TMP-SMX and atovaquone group. Adjusted cumulative incidence of PCP was compared between the two groups after propensity score weighting for differences in confounding factors. A total of 480 patients with a prolonged high-dose glucocorticoid treatment were identified. Out of 383 patients with TMP-SMX prophylaxis, 102 (26.8%) patients experienced adverse events leading to discontinuation within 4weeks of initiation, while no patient in the atovaquone discontinued the therapy. Two hundred eighty-one patients received TMP-SMX, while 107 received atovaquone for PCP prophylaxis. During a total of 397.0 person-years, 7 PCP cases (2 in the TMP-SMX, 5 in the atovaquone) occurred with a mortality rate of 54.5%. After adjusting for differences in baseline characteristics, the adjusted cumulative incidence of PCP was similar between the two group (HR 0.97, 95% CI 0.19-5.09, p = 0.97). Prophylactic effects for PCP in CTDs patients receiving prolonged high-dose glucocorticoids were similar between TMP-SMX and atovaquone. Atovaquone was well-tolerated with no side effects.