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Clinical Microbiology and Infection :... Jul 2024Pneumocystis jirovecii pneumonia (PCP) is a common opportunistic infection among people living with HIV (PWH), particularly among new and untreated cases. Several... (Meta-Analysis)
Meta-Analysis Comparative Study Review
Comparative efficacy and safety of Pneumocystis jirovecii pneumonia prophylaxis regimens for people living with HIV: a systematic review and network meta-analysis of randomized controlled trials.
BACKGROUND
Pneumocystis jirovecii pneumonia (PCP) is a common opportunistic infection among people living with HIV (PWH), particularly among new and untreated cases. Several regimens are available for the prophylaxis of PCP, including trimethoprim-sulfamethoxazole (TMP-SMX), dapsone-based regimens (DBRs), aerosolized pentamidine (AP), and atovaquone.
OBJECTIVES
To compare the efficacy and safety of PCP prophylaxis regimens in PWH by network meta-analysis.
METHODS
DATA SOURCES: Embase, MEDLINE, and CENTRAL from inception to June 21, 2023.
STUDY ELIGIBILITY CRITERIA
Comparative randomized controlled trials (RCTs).
PARTICIPANTS
PWH.
INTERVENTIONS
Regimens for PCP prophylaxis either compared head-to-head or versus no treatment/placebo.
ASSESSMENT OF RISK OF BIAS
Cochrane risk-of-bias tool for RCTs 2.
METHODS OF DATA SYNTHESIS
Title or abstract and full-text screening and data extraction were performed in duplicate by two independent reviewers. Data on PCP incidence, all-cause mortality, and discontinuation due to toxicity were pooled and ranked by network meta-analysis. Subgroup analyses of primary versus secondary prophylaxis, by year, and by dosage were performed.
RESULTS
A total of 26 RCTs, comprising 55 treatment arms involving 7516 PWH were included. For the prevention of PCP, TMP-SMX was ranked the most favourable agent and was superior to DBRs (risk ratio [RR] = 0.54; 95% CI, 0.36-0.83) and AP (RR = 0.53; 95% CI, 0.36-0.77). TMP-SMX was also the only agent with a mortality benefit compared with no treatment/placebo (RR = 0.79; 95% CI, 0.64-0.98). However, TMP-SMX was also ranked as the most toxic agent with a greater risk of discontinuation than DBRs (RR = 1.25; 95% CI, 1.01-1.54) and AP (7.20; 95% CI, 5.37-9.66). No significant differences in PCP prevention or mortality were detected among the other regimens. The findings remained consistent within subgroups.
CONCLUSIONS
TMP-SMX is the most effective agent for PCP prophylaxis in PWH and the only agent to confer a mortality benefit; consequently, it should continue to be recommended as the first-line agent. Further studies are necessary to determine the optimal dosing of TMP-SMX to maximize efficacy and minimize toxicity.
Topics: Humans; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Network Meta-Analysis; Trimethoprim, Sulfamethoxazole Drug Combination; Pneumocystis carinii; HIV Infections; AIDS-Related Opportunistic Infections; Dapsone; Pentamidine; Atovaquone; Antifungal Agents; Treatment Outcome
PubMed: 38583518
DOI: 10.1016/j.cmi.2024.03.037 -
Cureus Aug 2022pneumonia (PCP) is one of the most common opportunistic infections worldwide that affects the lung. leads to pneumonia, caused by , formerly known as . In recent... (Review)
Review
pneumonia (PCP) is one of the most common opportunistic infections worldwide that affects the lung. leads to pneumonia, caused by , formerly known as . In recent decades, PCP has been a major health problem for human immunodeficiency virus (HIV) patients and is responsible for most of mortality and morbidity. However, the increasing number of immunosuppressive-related diseases has led to outbreaks in other patient populations, raising the concern for PCP as it becomes a major concern among those patients. These changes led to marked changes in the prevalence and mortality rates of PCP. Huge variations in those parameters among HIV and non-HIV patients have been seen also. Historically, the diagnosis was made by staining and direct visualization of the organism within the bronchoalveolar lavage (BAL) fluid. The diagnosis is now made by microscopic examination and a real-time polymerase chain reaction (PCR) of BAL. Serum (1,3)-β-D-glucan, which is a component of the cell wall that distinguishes it from other fungi, has become an important diagnostic tool. Early diagnosis and treatment play a vital role in the patient's survival and in the infection outcome; hence, empirical PCP therapy should be started immediately when the infection is suspected without waiting for the results of the diagnostic test. Steroids play an important role in the treatment of HIV patients, especially patients who present with hypoxia and respiratory failure. Prophylaxis is very effective and should be given to all patients at high risk of PCP. Antiretroviral therapy (ART) should be started as soon as possible in newly diagnosed HIV-infected patients with PCP, and the immune status of immunocompromised patients with PCP should be improved by temporarily withholding immunosuppressive drugs or reducing their doses.
PubMed: 36106266
DOI: 10.7759/cureus.27727 -
Iranian Journal of Microbiology Aug 2021pneumonia (PJP) is a serious infection that usually affects those with a weak immune system. Since the prevalence of this infection in Iran and in the world is not...
BACKGROUND AND OBJECTIVES
pneumonia (PJP) is a serious infection that usually affects those with a weak immune system. Since the prevalence of this infection in Iran and in the world is not clearly defined, the present study aimed to evaluate the incidence, clinical spectrum, and demographic characteristics of PJP among HIV and non-HIV immunocompromised patients.
MATERIALS AND METHODS
Bronchoalveolar Lavage (BAL) specimens were obtained from 3 groups of immunocompromised patients, including acquired immunodeficiency syndrome (AIDS) patients, diabetic patients, and patients receiving immunosuppressive therapies. All were hospitalized in pulmonary units. The specimens were examined using microscopic methods (Giemsa and calcofluor white staining) and the nested-PCR technique based on mtLSU-rRNA gene.
RESULTS
A total of 120 BAL samples were collected. From 12.5% (5 from 40) of HIV-infected patients, 5% (2 from 40) of patients receiving immunosuppressive therapies, and 2.5% (1 from 40) of diabetic patients was isolated. There was not any association between the prevalence of PJP and the patient's gender (= 0.557) and age (= 0.681). Fever and dyspnea (n=7, 87.5%), nonproductive cough and abnormal auscultation sound (n=5, 62.5%), and also chills and weight loss (n=2, 25%) were the documented clinical symptoms of PJP. Also, the results showed that none of the samples had positive results for with microscopic tests while using the nested-PCR method 8 samples had positive results.
CONCLUSION
Since PJP often causes symptoms that are similar to other illnesses, such as the flu or tuberculosis, clinical and laboratory findings should be used simultaneously for making the final decision on drug administration.
PubMed: 34557281
DOI: 10.18502/ijm.v13i4.6977 -
Frontiers in Immunology 2021Pneumocystis jiroveci pneumonia (PJP) is the most common opportunistic infection in immunocompromised patients. The accurate prediction of PJP development in patients...
BACKGROUND
Pneumocystis jiroveci pneumonia (PJP) is the most common opportunistic infection in immunocompromised patients. The accurate prediction of PJP development in patients undergoing immunosuppressive therapy remains challenge.
METHODS
Patients undergoing immunosuppressive treatment and with confirmed pneumocystis jiroveci infection were enrolled. Another group of matched patients with immunosuppressant treatment but without signs of infectious diseases were enrolled to control group.
RESULTS
A total of 80 (40 PJP, 40 non-PJP) participants were enrolled from Tongji Hospital. None of the patients were HIV positive. The routine laboratory indicators, such as LYM, MON, RBC, TP, and ALB, were significantly lower in PJP patients than in non-PJP patients. Conversely, LDH in PJP patients was significantly higher than in non-PJP controls. For immunological indicators, the numbers of T, B, and NK cells were all remarkably lower in PJP patients than in non-PJP controls, whereas the functional markers such as HLA-DR, CD45RO and CD28 expressed on CD4 or CD8 T cells had no statistical difference between these two groups. Cluster analysis showing that decrease of host immunity markers including CD3, CD4 and CD8 T cells, and increase of tissue damage marker LDH were the most typical characteristics of PJP patients. A further established model based on combination of CD8 T cells and LDH showed prominent value in distinguishing PJP from non-PJP, with AUC of 0.941 (95% CI, 0.892-0.990).
CONCLUSIONS
A model based on combination of routine laboratory and immunological indicators shows prominent value for predicting the development of PJP in HIV-negative patients undergoing immunosuppressive therapy.
Topics: Adult; Aged; Biomarkers; Computational Biology; Disease Susceptibility; Female; Humans; Immunocompromised Host; Immunophenotyping; Immunosuppressive Agents; Male; Middle Aged; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Prognosis; ROC Curve; T-Lymphocyte Subsets
PubMed: 33912176
DOI: 10.3389/fimmu.2021.652383 -
Frontiers in Cellular and Infection... 2020pneumonia (PCP) is an AIDS-defining illness. In patients with HIV, the benefit of PCP prophylaxis is well-defined when the CD4 T-cell count decreases below 200...
pneumonia (PCP) is an AIDS-defining illness. In patients with HIV, the benefit of PCP prophylaxis is well-defined when the CD4 T-cell count decreases below 200 cells/μL. In other immunocompromised patients, the value of PCP prophylaxis is not always as well-established. This study aimed to describe the epidemiology of PCP in recent years and assess how many patients with PCP did or did not receive prophylaxis in the month preceding the infection. A multicenter retrospective study was performed in 3 tertiary care hospital. A list of patients that underwent broncho-alveolar lavage sampling and (PJ) PCR testing was retrieved from the microbiology laboratories. An in-house PJ quantitative PCR (qPCR) was used in each center. A cycle threshold (Ct) value of ≤ 28.5-30 was considered a probable PCP. For patients with a positive PJ qPCR but above this threshold, a predefined case definition of possible PCP was defined as a qPCR Ct value ≤ 34-35 and both of the following criteria: 1. Clinical and radiological features compatible with PCP and 2. The patient died or received PCP therapy and survived. Patient files from those with a qPCR Ct value ≤ 35 were reviewed to determine whether the patient fulfilled the case definition and if PCP prophylaxis had been used in the weeks preceding the PCP. Disease-specific guidelines, as well as hospital-wide guidelines, were used to evaluate if prophylaxis could be considered indicated. From 2012 to 2018, 482 BAL samples were tested. Two hundred and four had a qPCR Ct value ≤ 35 and were further evaluated: 90 fulfilled the definition of probable and 63 of possible PCP while the remaining 51 were considered colonized. Seventy-four percentages of the patients with PCP were HIV-negative. Only 11 (7%) of the 153 patients had received prophylaxis, despite that in 133 (87%) cases prophylaxis was indicated according to guidelines. In regions where HIV testing and treatment is available without restrictions, PCP is mainly diagnosed in non-HIV immunocompromised patients. More than four out of five patients with PCP had not received prophylaxis. Strategies to improve awareness of antimicrobial prophylaxis guidelines in immunocompromised patients are urgently needed.
Topics: Humans; Immunocompromised Host; Pneumocystis carinii; Pneumonia, Pneumocystis; Real-Time Polymerase Chain Reaction; Retrospective Studies
PubMed: 32500040
DOI: 10.3389/fcimb.2020.00224 -
The Journal of Infectious Diseases Jul 2019Glucan is the major cell wall component of Pneumocystis cysts. In the current study, we have characterized Pneumocystis Bgl2 (EC 3.2.1.58), an enzyme with...
Glucan is the major cell wall component of Pneumocystis cysts. In the current study, we have characterized Pneumocystis Bgl2 (EC 3.2.1.58), an enzyme with glucanosyltransferase and β-1,3 endoglucanase activity in other fungi. Pneumocystis murina, Pneumocystis carinii, and Pneumocystis jirovecii bgl2 complementary DNA sequences encode proteins of 437, 447, and 408 amino acids, respectively. Recombinant P. murina Bgl2 expressed in COS-1 cells demonstrated β-glucanase activity, as shown by degradation of the cell wall of Pneumocystis cysts. It also cleaved reduced laminaripentaose and transferred oligosaccharides, resulting in polymers of 6 and 7 glucan residues, demonstrating glucanosyltransferase activity. Surprisingly, confocal immunofluorescence analysis of P. murina-infected mouse lung sections using an antibody against recombinant Bgl2 showed that the native protein is localized primarily to the trophic form of Pneumocystis in both untreated mice and mice treated with caspofungin, an antifungal drug that inhibits β-1,3-glucan synthase. Thus, like other fungi, Bgl2 of Pneumocystis has both endoglucanase and glucanosyltransferase activities. Given that it is expressed primarily in trophic forms, further studies are needed to better understand its role in the biology of Pneumocystis.
Topics: Amino Acid Sequence; Animals; Antifungal Agents; CD40 Ligand; COS Cells; Caspofungin; Cell Wall; Chlorocebus aethiops; Glucan Endo-1,3-beta-D-Glucosidase; Glucans; Lung; Mice; Mice, Inbred C57BL; Mice, Knockout; Pneumocystis; Pneumonia, Pneumocystis; Recombinant Proteins; Sequence Alignment
PubMed: 31100118
DOI: 10.1093/infdis/jiz172 -
Clinical and Experimental Rheumatology May 2022Giant cell arteritis (GCA) afflicts older adults who may have age- and comorbidity-related risks for infection and is treated with immunosuppressants that increase risk...
OBJECTIVES
Giant cell arteritis (GCA) afflicts older adults who may have age- and comorbidity-related risks for infection and is treated with immunosuppressants that increase risk of infection. We examined GCA treatment patterns and rates of serious infections in two real-world cohorts in the U.S.
METHODS
We identified two GCA cohorts using two U.S. health insurance databases, Medicare (public, 2007-2017) and MarketScan (commercial, 2015-2019), by applying a validated claims-based algorithm with positive predictive value 79.0% for GCA. We required age ≥50 years and assessed baseline comorbidities, dispensing of immunosuppressants and prophylactic antibiotics, and vaccine administration. We calculated incidence rates (IR) of serious infections, defined as bacterial or viral infections requiring hospitalisation based on primary inpatient diagnosis code. Multivariable Cox proportional hazards models estimated hazard ratios for risk of serious infection for prespecified covariates.
RESULTS
The Medicare cohort included 734 patients, 28% male, mean age 77.1; the MarketScan cohort included 1022 patients, 30% male, mean age 68.4. More than 85% used prednisone ≥60mg daily at index date and <10% used tocilizumab. Serious infections developed in 27.9% of Medicare and 7.2% of MarketScan patients: IR per 100 person-years = 10.7 (95% CI 9.3, 12.2) in Medicare and 6.3 (95% CI 5.0, 7.9) in MarketScan. Older age and higher frailty score were significantly associated with increased risk for serious infection.
CONCLUSIONS
In these two U.S. GCA cohorts, high-dose glucocorticoids were the most common initial treatment, and over 25% of Medicare and 7% of MarketScan patients developed serious infection during follow-up. Older age and higher frailty score were associated with higher risk of serious infections, though maximum daily prednisone dose was not. Pneumocystis jiroveci pneumonia was rare in two GCA cohorts despite infrequent use of prophylactic antibiotics.
Topics: Aged; Anti-Bacterial Agents; Female; Frailty; Giant Cell Arteritis; Humans; Immunosuppressive Agents; Male; Medicare; Middle Aged; Prednisone; United States
PubMed: 34905480
DOI: 10.55563/clinexprheumatol/uonz1p -
Frontiers in Cellular and Infection... 2020pneumonia (PCP) remains the most frequent AIDS-defining illness in developed countries. This infection also occurs in non-AIDS immunosuppressed patients, e.g., those... (Review)
Review
pneumonia (PCP) remains the most frequent AIDS-defining illness in developed countries. This infection also occurs in non-AIDS immunosuppressed patients, e.g., those who have undergone an organ transplantation. Moreover, mild infections related to low pulmonary fungal burden, frequently designated as pulmonary colonization, occurs in patients with chronic pulmonary diseases, e.g., cystic fibrosis (CF). Indeed, this autosomal recessive disorder alters mucociliary clearance leading to bacterial and fungal colonization of the airways. This mini-review compiles and discusses available information on and CF. It highlights significant differences in the prevalence of pulmonary colonization in European and Brazilian CF patients. It also describes the microbiota associated with in CF patients colonized by . Furthermore, we have described genomic diversity in colonized CF patients. In addition of pulmonary colonization, it appears that PCP can occur in CF patients specifically after lung transplantation, thus requiring preventive strategies. In other respects, primary infection is a worldwide phenomenon occurring in non-immunosuppressed infants within their first months. The primary infection is mostly asymptomatic but it can also present as a benign self-limiting infection. It probably occurs in the same manner in CF infants. Nonetheless, two cases of severe primary infection mimicking PCP in CF infants have been reported, the genetic disease appearing in these circumstances as a risk factor of PCP while the host-pathogen interaction in older children and adults with pulmonary colonization remains to be clarified.
Topics: Adult; Brazil; Child; Cystic Fibrosis; Humans; Infant; Lung; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 33117730
DOI: 10.3389/fcimb.2020.571253 -
PloS One 2024Pneumocystis 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...
INTRODUCTION
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.
OBJECTIVE
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.
METHODS
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.
EXPECTED RESULTS
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.
CONCLUSIONS
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.
Topics: Humans; Immunocompromised Host; Pneumonia, Pneumocystis; Systematic Reviews as Topic; Pneumocystis carinii
PubMed: 38722952
DOI: 10.1371/journal.pone.0302055 -
CytoJournal 2021Many types of elective ancillary tests may be required to support the cytopathologic interpretations. Most of these tests can be performed on cell-blocks of different... (Review)
Review
Many types of elective ancillary tests may be required to support the cytopathologic interpretations. Most of these tests can be performed on cell-blocks of different cytology specimens. The cell-block sections can be used for almost any special stains including various and for including fungi, Pneumocystis jirovecii (carinii), and various organisms including acid-fast organisms similar to the surgical biopsy specimens. Similarly, in addition to , different can be performed on cell-blocks. Molecular tests broadly can be divided into two main types and .
PubMed: 33880127
DOI: 10.25259/Cytojournal_3_2021