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Medical Mycology Nov 2020Pneumocystis jirovecii can cause life-threatening pneumonia in immunocompromised patients. Traditional diagnostic testing has relied on staining and direct visualization... (Review)
Review
Pneumocystis jirovecii can cause life-threatening pneumonia in immunocompromised patients. Traditional diagnostic testing has relied on staining and direct visualization of the life-forms in bronchoalveolar lavage fluid. This method has proven insensitive, and invasive procedures may be needed to obtain adequate samples. Molecular methods of detection such as polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), and antibody-antigen assays have been developed in an effort to solve these problems. These techniques are very sensitive and have the potential to detect Pneumocystis life-forms in noninvasive samples such as sputum, oral washes, nasopharyngeal aspirates, and serum. This review evaluates 100 studies that compare use of various diagnostic tests for Pneumocystis jirovecii pneumonia (PCP) in patient samples. Novel diagnostic methods have been widely used in the research setting but have faced barriers to clinical implementation including: interpretation of low fungal burdens, standardization of techniques, integration into resource-poor settings, poor understanding of the impact of host factors, geographic variations in the organism, heterogeneity of studies, and limited clinician recognition of PCP. Addressing these barriers will require identification of phenotypes that progress to PCP and diagnostic cut-offs for colonization, generation of life-form specific markers, comparison of commercial PCR assays, investigation of cost-effective point of care options, evaluation of host factors such as HIV status that may impact diagnosis, and identification of markers of genetic diversity that may be useful in diagnostic panels. Performing high-quality studies and educating physicians will be crucial to improve the rates of diagnosis of PCP and ultimately to improve patient outcomes.
Topics: Humans; Immunoassay; Immunocompromised Host; Microbiological Techniques; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Sensitivity and Specificity; Specimen Handling; Staining and Labeling
PubMed: 32400869
DOI: 10.1093/mmy/myaa024 -
International Journal of Environmental... Feb 2022(1) Background: pneumonia (PCP) has a substantial impact on the morbidity and mortality of patients, especially those with autoimmune disorders, thus requiring optimal... (Review)
Review
(1) Background: pneumonia (PCP) has a substantial impact on the morbidity and mortality of patients, especially those with autoimmune disorders, thus requiring optimal dosing strategies of Trimethoprim-Sulfamethoxazole (TMP-SMX). Therefore, to ensure the safety of TMP-SMX, there is a high demand to review current evidence in PCP patients with a focus on dose optimization strategies; (2) Methods: Various databases were searched from January 2000 to December 2021 for articles in English, focusing on the dose optimization of TMP-SMX. The data were collected in a specific form with predefined inclusion and exclusion criteria. The quality of each article was evaluated using a Newcastle-Ottawa Scale (NOS) for retrospective studies, Joanna Briggs Institute (JBI) critical checklist for case reports, and Cochrane bias tool for randomized clinical trials (RCTs); (3) Results: Thirteen studies met the inclusion criteria for final analysis. Of the 13 selected studies, nine were retrospective cohort studies, two case reports, and two randomized controlled trials (RCT). Most of the studies compared the high-dose with low-dose TMP-SMX therapy for PCP. We have found that a low dose of TMP-SMX provides satisfactory outcomes while reducing the mortality rate and PCP-associated adverse events. This strategy reduces the economic burden of illness and enhances patients' compliance to daily regimen plan; (4) Conclusions: The large-scale RCTs and cohort studies are required to improve dosing strategies to prevent initial occurrence of PCP or to prevent recurrence of PCP in immune compromised patients.
Topics: Cohort Studies; Humans; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 35270525
DOI: 10.3390/ijerph19052833 -
Expert Review of Anti-infective Therapy Oct 2019: pneumonia (PcP) has classically been described as a serious complication in patients infected with the human immunodeficiency virus (HIV). However, the emerging... (Review)
Review
: pneumonia (PcP) has classically been described as a serious complication in patients infected with the human immunodeficiency virus (HIV). However, the emerging number of conditions associated with immunosuppression has led to its appearance in other patient populations. : This article reviews the most recent publications on PcP in the HIV-infected and HIV-uninfected population, focusing on epidemiology, diagnostic, therapy and prevention. The data discussed here were mainly obtained from a non-systematic review using Medline and references from relevant articles including randomized clinical trials, meta-analyses, observational studies and clinical reviews. : The growing incidence of infection in the HIV-uninfected population suggests the need for new global epidemiological studies in order to identify the true scale of the disease in this population. These data would allow us to improve diagnosis, therapeutic strategies, and clinical management. It is very important that both patients and physicians realize that HIV-uninfected patients are at risk of PcP and that rapid diagnosis and early initiation of treatment are associated with better prognosis. Currently, in-hospital mortality rates are very high: 15% for HIV-infected patients and 50% in some HIV-uninfected patients. Therefore, adequate preventive measures should be implemented to avoid the high mortality rates seen in recent decades.
Topics: AIDS-Related Opportunistic Infections; Animals; HIV Infections; Humans; Immunocompromised Host; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic
PubMed: 31550942
DOI: 10.1080/14787210.2019.1671823 -
Current Opinion in Infectious Diseases Aug 2019Pneumocystis pneumonia (PCP) is a frequent opportunistic infection associated with a high mortality rate. PCP is of increasing importance in non-HIV immunocompromised... (Review)
Review
PURPOSE OF REVIEW
Pneumocystis pneumonia (PCP) is a frequent opportunistic infection associated with a high mortality rate. PCP is of increasing importance in non-HIV immunocompromised patients, who present with severe respiratory distress with low fungal loads. Molecular detection of Pneumocystis in broncho-alveolar lavage (BAL) has become an important diagnostic tool, but quantitative PCR (qPCR) needs standardization.
RECENT FINDINGS
Despite a high negative predictive value, the positive predictive value of qPCR is moderate, as it also detects colonized patients. Attempts are made to set a cut-off value of qPCR to discriminate between PCP and colonization, or to use noninvasive samples or combined strategies to increase specificity.
SUMMARY
It is easy to set a qPCR cut-off for HIV-infected patients. In non-HIV IC patients, a gain in specificity could be obtained by combining strategies, that is, qPCR on BAL and a noninvasive sample, or qPCR and serum beta-1,3-D-glucan dosage.
Topics: Bronchoalveolar Lavage Fluid; Coinfection; Disease Management; HIV Infections; Humans; Immunocompromised Host; Molecular Diagnostic Techniques; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Real-Time Polymerase Chain Reaction; Reproducibility of Results; Sensitivity and Specificity
PubMed: 31107250
DOI: 10.1097/QCO.0000000000000559 -
Cold Spring Harbor Perspectives in... Nov 2014Since its initial misidentification as a trypanosome some 100 years ago, Pneumocystis has remained recalcitrant to study. Although we have learned much, we still do not... (Review)
Review
Since its initial misidentification as a trypanosome some 100 years ago, Pneumocystis has remained recalcitrant to study. Although we have learned much, we still do not have definitive answers to such basic questions as, where is the reservoir of infection, how does Pneumocystis reproduce, what is the mechanism of infection, and are there true species of Pneumocystis? The goal of this review is to provide the reader the most up to date information available about the biology of Pneumocystis and the disease it produces.
Topics: Humans; Pneumocystis; Pneumocystis Infections; Pneumonia, Pneumocystis; Virulence Factors
PubMed: 25367973
DOI: 10.1101/cshperspect.a019828 -
Annals of the Rheumatic Diseases May 2018To investigate the efficacy and safety of trimethoprim/sulfamethoxazole (TMP-SMX) as primary prophylaxis for pneumocystis pneumonia (PCP) in patients with rheumatic...
OBJECTIVES
To investigate the efficacy and safety of trimethoprim/sulfamethoxazole (TMP-SMX) as primary prophylaxis for pneumocystis pneumonia (PCP) in patients with rheumatic diseases receiving high-dose steroids.
METHODS
The study included 1522 treatment episodes with prolonged (≥4 weeks) high-dose (≥30 mg/day prednisone) steroids in 1092 patients over a 12-year period. Of these, 262 treatment episodes involved TMP-SMX (prophylaxis group) while other episodes involved no prophylaxis (control group). Differences in 1-year PCP incidence and its mortality between the two groups were estimated using Cox regression. To minimise baseline imbalance, propensity score matching was performed and efficacy outcome was mainly assessed in the postmatched population (n=235 in both groups).
RESULTS
During a total of 1474.4 person-years, 30 PCP cases occurred with a mortality rate of 36.7%. One non-fatal case occurred in the prophylaxis group. TMP-SMX significantly reduced the 1-year PCP incidence (adjusted HR=0.07(95% CI 0.01 to 0.53)) and related mortality (adjusted HR=0.08 (95% CI 0.0006 to 0.71)) in the postmatched population. The result of the same analysis performed in the whole population was consistent with that of the primary analysis. Incidence rate of adverse drug reactions (ADR) related to TMP-SMX was 21.2 (14.8-29.3)/100 person-years. Only two serious ADRs (including one Stevens-Johnson syndrome case) occurred. The number needed to treat for preventing one PCP (52 (33-124)) was lower than the number needed to harm for serious ADR (131 (55-∞)).
CONCLUSION
TMP-SMX prophylaxis significantly reduces the PCP incidence with a favourable safety profile in patients with rheumatic disease receiving prolonged, high-dose steroids.
Topics: Adult; Antifungal Agents; Female; Glucocorticoids; Humans; Incidence; Male; Middle Aged; Pneumonia, Pneumocystis; Propensity Score; Retrospective Studies; Rheumatic Diseases; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 29092853
DOI: 10.1136/annrheumdis-2017-211796 -
Pulmonology 2022
Topics: Acrylamides; Aniline Compounds; Humans; Indoles; Leukopenia; Lymphopenia; Pneumonia, Pneumocystis; Pyrimidines
PubMed: 35701337
DOI: 10.1016/j.pulmoe.2022.04.005 -
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 -
British Medical Journal (Clinical... Feb 1983
Topics: Animals; Drug Combinations; Female; Humans; Infant; Male; Pentamidine; Pneumonia, Pneumocystis; Rats; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 6402123
DOI: 10.1136/bmj.286.6364.499 -
Journal of the Formosan Medical... Nov 2008Pneumocystis pneumonia (PcP) in humans is caused by Pneumocystis jirovecii, which has recently been reclassified as a fungus because its cell wall composition and... (Review)
Review
Pneumocystis pneumonia (PcP) in humans is caused by Pneumocystis jirovecii, which has recently been reclassified as a fungus because its cell wall composition and nucleotide sequences are more similar to those of fungi. PcP occurs only in immunocompromised individuals such as those with AIDS. Despite the use of highly active antiretroviral therapy, PcP remains the leading opportunistic infection in AIDS patients. Based on nucleotide sequence variations in the internal transcribed spacer region of rRNA genes, more than 60 different types of P. jirovecii have been identified. Although type differences do not appear to correlate with the clinical characteristics of PcP, nucleotide sequence variations of the organism have been useful in epidemiologic studies. As a result, some recurrent infections are found to be due to re-infection with new types, and outbreaks due to the same types of P. jirovecii have been identified. Initial diagnosis of PcP is usually based on symptoms and chest radiography. A characteristic histopathologic feature is the presence of acellular eosinophilic exudates and organisms in the alveoli. Ultimate diagnosis of PcP is achieved by demonstration of the organism in induced sputum or bronchoalveolar lavage fluid by tinctorial staining or polymerase chain reaction (PCR). Among the many different PCR methods, the nested PCR that targets the large subunit mitochondrial rRNA gene is the most sensitive and specific. Combination of trimethoprim and sulfamethoxazole is the first choice of drugs for both treatment and prophylaxis of PcP. Other drugs that can be used include a combination of primaquine and clindamycin, pentamidine, atovaquone, and a combination of dapsone and trimethoprim. Pneumocystis organisms have the ability to inactivate the phagocytic activity of alveolar macrophages and to induce them to undergo apoptosis. This apoptosis is due to activation of caspase 9 by polyamines that are present in high levels in the lung and alveolar macrophages during PcP.
Topics: Humans; Pneumonia, Pneumocystis
PubMed: 18971152
DOI: 10.1016/S0929-6646(08)60199-0