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BMC Infectious Diseases Jul 2023Pneumocystis jirovecii pneumonia (PJP) can be a life-threatening opportunistic infection. We aimed to evaluate the diagnostic accuracy of metagenomic next-generation... (Review)
Review
OBJECTIVE
Pneumocystis jirovecii pneumonia (PJP) can be a life-threatening opportunistic infection. We aimed to evaluate the diagnostic accuracy of metagenomic next-generation sequencing (mNGS) for PJP.
METHODS
A comprehensive electronic literature search of Web of Knowledge, PubMed, Cochrane Library, CNKI and Wanfang data was performed. Bivariate analysis was conducted to calculate the pooled sensitivity, specificity, diagnostic odds ratio (DOR), the area under the summary receiver operator characteristic (SROC) curve and the Q-point value (Q*).
RESULTS
The literature search resulted in 9 studies with a total of 1343 patients, including 418 cases diagnosed with PJP and 925 controls. The pooled sensitivity of mNGS for diagnosis of PJP was 0.974 [95% confidence interval (CI), 0.953-0.987]. The pooled specificity was 0.943 (95% CI, 0.926-0.957), the DOR was 431.58 (95% CI, 186.77-997.27), the area under the SROC curve was 0.987, and the Q* was 0.951. The I test indicated no heterogeneity between studies. The Deek funnel test suggested no potential publication bias. Subgroup analyses showed that the area under the SROC curve of mNGS for diagnosis of PJP in immunocompromised and non-HIV patients was 0.9852 and 0.979, respectively.
CONCLUSIONS
Current evidence indicates that mNGS exhibits excellent accuracy for the diagnosis of PJP. The mNGS is a promising tool for assessment of PJP in both immunocompromised and non-HIV patients.
Topics: Humans; Correlation of Data; High-Throughput Nucleotide Sequencing; Immunocompromised Host; Knowledge; Pneumonia, Pneumocystis
PubMed: 37430211
DOI: 10.1186/s12879-023-08440-4 -
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 -
European Journal of Pediatrics Sep 2023This study aims to provide practical recommendations on prophylaxis for infection in pediatric patients with immune-mediated rheumatic diseases receiving/scheduled to... (Review)
Review
Position statement on infection screening, prophylaxis, and vaccination in pediatric patients with rheumatic diseases and immunosuppressive therapies, part 2: infection prophylaxis.
This study aims to provide practical recommendations on prophylaxis for infection in pediatric patients with immune-mediated rheumatic diseases receiving/scheduled to receive immunosuppressive therapy. A qualitative approach was applied. A narrative literature review was performed via Medline. Primary searches were conducted using MeSH terms and free text to identify articles that analyzed data on infections and vaccinations in pediatric patients with immune-mediated rheumatic diseases receiving immunosuppressive therapy. The results were presented and discussed in a nominal group meeting comprising a committee of 12 pediatric rheumatologists from the Prevention and Treatment of Infections Working Group of the Spanish Society of Pediatric Rheumatology. Several recommendations were generated. A consensus procedure was implemented via a Delphi process that was extended to members of the Spanish Society of Pediatric Rheumatology and the Vaccine Advisory Committee of the Spanish Association of Pediatrics. Participants produced a score ranging from 0 (completely disagree) to 10 (completely agree). Agreement was considered to have been reached if at least 70% of participants voted ≥ 7. The literature review included more than 400 articles. Overall, 63 recommendations were generated (23 on infection prophylaxis) and voted by 59 pediatric rheumatologists and other pediatric specialists, all of whom achieved the pre-established level of agreement. The recommendations on prophylaxis of infection cover vaccination and prophylaxis against varicella zoster virus, tuberculosis, Pneumocystis jiroveccii, and invasive fungal infections in pediatric patients with immune-mediated rheumatic diseases receiving/scheduled to receive immunosuppressive therapy. Conclusion: Based on current evidence and a Delphi process, we provided consensus and updated recommendations on prophylaxis and treatment of infections to guide those caring for pediatric rheumatology patients. What is Known: •Data largely derived from adults find that infectious diseases and related complications are a major cause of morbidity and mortality in patients with immune-mediated rheumatic diseases. •It is crucial to be aware of the preventive measures that should be implemented to prevent these infections in children, although most guidelines are often extrapolated from adult cases. What is New: •In the absence of evidence, a literature review and a Delphi survey were conducted to establish a series of expert recommendations that could prove useful in clinical practice, providing a practical and simple day-to-day approach to be used by pediatric rheumatologists. •The recommendations focus on tuberculosis, herpes zoster virus, fungal infections, and Pneumocystis jirovecii.
PubMed: 37439850
DOI: 10.1007/s00431-023-05080-3 -
Chest Jun 2024Pneumocystis jirovecii pneumonia (PcP) remains associated with high rates of mortality, and the impact of immunocompromising underlying disease on the clinical... (Observational Study)
Observational Study
BACKGROUND
Pneumocystis jirovecii pneumonia (PcP) remains associated with high rates of mortality, and the impact of immunocompromising underlying disease on the clinical presentation, severity, and mortality of PcP has not been adequately evaluated.
RESEARCH QUESTION
Does the underlying disease and immunosuppression causing PcP impact the outcome and clinical presentation of the disease?
STUDY DESIGN AND METHODS
In this multicenter retrospective observational study, conducted from January 2011 to December 2021, all consecutive patients admitted with a proven or probable diagnosis of PcP according to the European Organisation for Research and Treatment of Cancer consensus definitions were included to assess the epidemiology and impact of underlying immunosuppressive diseases on overall and 90-day mortality.
RESULTS
Overall, 481 patients were included in the study; 180 (37.4%) were defined as proven PcP and 301 (62.6%) were defined as probable PcP. Patients with immune-mediated inflammatory diseases (IMIDs) or solid tumors had a statistically poorer prognosis than other patients with PcP at day 90. In multivariate analysis, among the HIV-negative population, solid tumor underlying disease (OR, 5.47; 95% CI, 2.16-14.1; P < .001), IMIDs (OR, 2.19; 95% CI, 1.05-4.60; P = .037), long-term corticosteroid exposure (OR, 2.07; 95% CI, 1.03-4.31; P = .045), cysts in sputum/BAL smears (OR, 1.92; 95% CI, 1.02-3.62; P = .043), and SOFA score at admission (OR, 1.58; 95% CI, 1.39-1.82; P < .001) were independently associated with 90-day mortality. Prior corticotherapy was the only immunosuppressant associated with 90-day mortality (OR, 1.67; 95% CI, 1.03-2.71; P = .035), especially for a prednisone daily dose ≥ 10 mg (OR, 1.80; 95% CI, 1.14-2.85; P = .010).
INTERPRETATION
Among patients who were HIV-negative, long-term corticosteroid prior to PcP diagnosis was independently associated with increased 90-day mortality, specifically in patients with IMIDs. These results highlight both the needs for PcP prophylaxis in patients with IMIDs and to early consider PcP curative treatment in severe pneumonia among patients with IMIDs.
Topics: Humans; Pneumonia, Pneumocystis; Male; Female; Retrospective Studies; Middle Aged; Prognosis; Aged; Pneumocystis carinii; Immunocompromised Host; Risk Factors
PubMed: 38215935
DOI: 10.1016/j.chest.2024.01.015 -
Infection and Drug Resistance 2024Pneumocystis pneumonia (PJP) is a severe respiratory infection caused by Pneumocystis in immunocompromised hosts. The role of P. colonization in the development or...
OBJECTIVE
Pneumocystis pneumonia (PJP) is a severe respiratory infection caused by Pneumocystis in immunocompromised hosts. The role of P. colonization in the development or progression of various pulmonary diseases has been reported. Our aim was to explore serial change in serum biomarkers and the independent risk factors for mortality in patients with and without chronic pulmonary diseases who developed PJP.
METHODS
We performed a retrospective study to select patients with Pneumocystis pneumonia between January 1, 2012, and December 31, 2021. Information regarding demographics, clinical characteristics, underlying diseases, laboratory tests, treatment, and outcomes was collected. Univariate and multivariate logistic regression analyses were used to identify independent predictors of in-hospital mortality.
RESULTS
A total of 167 patients diagnosed with PJP were included in the study: 53 in the CPD-PJP group and 114 in the NCPD-PJP group. The number of patients with PJP showed an increasing trend over the 10-year period. A similar trend was observed for in-hospital mortality. Independent risk factors associated with death in the NCPD-PJP group were procalcitonin level (adjusted OR 1.08, 95% CI 1.01-1.16, P=0.01), pneumothorax (adjusted OR 0.07, 95% CI 0.01-0.38, P=0.002), neutrophil count (adjusted OR 1.27, 95% CI 1.05-1.53, P=0.01) at 14 days, and hemoglobin level (adjusted OR 0.94, 95% CI 0.91-0.98; P=0.002) at 14 days after admission. The risk factor associated with death in the CPD-PJP group was neutrophil count (adjusted OR 1.19, 95% CI 0.99-1.43; P=0.05) at 14 days after admission.
CONCLUSION
The risk factors for death were different between patients with PJP with and without chronic pulmonary disease. Early identification of these factors in patients with PJP and other underlying diseases may improve prognosis.
PubMed: 38832106
DOI: 10.2147/IDR.S456716 -
BioRxiv : the Preprint Server For... Feb 2024pneumonia (PjP) poses a serious risk to individuals with compromised immune systems, such as individuals with HIV/AIDS or undergoing immunosuppressive therapies for...
pneumonia (PjP) poses a serious risk to individuals with compromised immune systems, such as individuals with HIV/AIDS or undergoing immunosuppressive therapies for cancer or solid organ transplants. Severe PjP triggers excessive lung inflammation, resulting in lung function decline and consequential alveolar damage, potentially culminating in acute respiratory distress syndrome. Non-HIV patients face a 30-60%mortality rate, emphasizing the need for a deeper understanding of inflammatory responses in PjP. Prior research emphasized macrophages in infections, neglecting neutrophils' role in tissue damage. Consequently, the overemphasis on macrophages led to an incomplete understanding of the role of neutrophils and inflammatory responses. In the current investigation, our RNAseq studies on a murine surrogate model of PjP revealed heightened activation of the NLRP3 inflammasome and NETosis cell death pathways in their lungs. Immunofluorescence staining confirmed Neutrophil Extracellular Trap (NET) presence in the lungs of the -infected mice, validating our findings. Moreover, isolated neutrophils exhibited NETosis when directly stimulated with . While isolated NETs did not compromise viability, our data highlight the potential role of neutrophils in promoting inflammation during pneumonia through NLRP3 inflammasome assembly and NETosis. These pathways, essential for inflammation and pathogen elimination, bear the risk of uncontrolled activation leading to excessive tissue damage and persistent inflammation. This pioneering study is the first to identify the formation of NETs and inflammasomes during infection, paving the way for comprehensive investigations into treatments aimed at mitigating lung damage and augmenting survival rates for individuals with PjP.
PubMed: 38405901
DOI: 10.1101/2024.02.16.580773 -
Annals of Medicine Dec 2023To evaluate diagnostic performance of metagenomic next-generation sequencing (mNGS) for pneumonia (PCP), in comparison with polymerase chain reaction (PCR), Gomori...
AIM
To evaluate diagnostic performance of metagenomic next-generation sequencing (mNGS) for pneumonia (PCP), in comparison with polymerase chain reaction (PCR), Gomori methenamine silver (GMS) staining and serum 1,3-β-d-Glucan (BG) assay.
METHODS
52 PCP patients and 103 patients with non-pneumocystic jirovecii pneumonia (non-PCP) were enrolled, and comparative analysis was conducted of different diagnostic tests. Clinical features and co-pathogen characteristics were reviewed.
RESULTS
The diagnostic sensitivity (92.3%) and specificity (87.4%) of mNGS did not show significant differences compared with that of PCR while mNGS had the advantage over PCR in the detection of co-pathogens. Despite its excellent specificity, the sensitivity of GMS staining (9.3%) was inferior to that of mNGS ( < .001). The combination of mNGS with serum BG statistically outperformed mNGS or serum BG alone in the areas under the receiver operating characteristic curves (AUCs, = .0013 and = .0015, respectively). Notably, all the blood samples showing positive mNGS for came from PCP patients. The leading co-pathogens among patients with PCP were cytomegalovirus, Epstein-Barr virus and Torque teno virus.
CONCLUSIONS
mNGS shows superiority over several common clinical methods in the diagnosis of suspected PCP. Serum BG in conjunction with mNGS further improved the diagnostic efficacy of mNGS.
Topics: Humans; Pneumonia, Pneumocystis; Epstein-Barr Virus Infections; Sensitivity and Specificity; Herpesvirus 4, Human; High-Throughput Nucleotide Sequencing; Respiratory System
PubMed: 37403381
DOI: 10.1080/07853890.2023.2232358 -
Journal of Medical Case Reports Feb 2024Pneumocystis jirovecii (PJP) pneumonia is a serious life-threatening condition in immunocompromised individuals and is often associated with human immunodeficiency virus...
INTRODUCTION AND IMPORTANCE
Pneumocystis jirovecii (PJP) pneumonia is a serious life-threatening condition in immunocompromised individuals and is often associated with human immunodeficiency virus (HIV) + patients. We describe a case of PJP pneumonia which provided a diagnostic challenge in a patient who presented with no known risk factors leading to a delay in initiation of appropriate antibiotic therapy.
CASE PRESENTATION
A 71-year-old previously healthy white/Caucasian male presented with subacute hypoxic respiratory failure due to multifocal pneumonia with diffuse bilateral ground glass opacities with consolidations despite prior treatment with antibiotics and steroids. He was admitted and started on intravenous broad-spectrum antibiotics but continued to deteriorate, eventually requiring intubation and transfer to the ICU. Bronchoscopy revealed PJP and treatment was initiated, but the patient developed refractory shock and multiorgan failure, and ultimately died. It was later discovered that he was HIV-1 positive.
CLINICAL DISCUSSION
PJP, as a potential cause of his presentation, was not considered given that our patient lacked any overt risk factors for PJP pneumonia. He continued to worsen despite broad spectrum antibiotic therapy and hence bronchoscopy was pursued. His clinical profile, in hindsight, was suspicious for PJP pneumonia and early PJP-directed antibiotic therapy may have prevented a fatal outcome, as in this case. There was an element of cognitive bias across multiple providers which may have contributed to the delay in treatment despite his rapid clinical decline while on conventional pneumonia treatment protocol. His diagnosis was later evident when his BAL-DFA grew PJP in addition to his low levels of CD4 and CD8 cells. He was found to be HIV-1 positive five days after his death; there was a delay in this diagnosis since all positive HIV tests from the hospital are reported as 'pending' until the presumptive positive sample goes to the Connecticut Department of Public Health State laboratory for the confirmatory test. PJP-targeted therapies were initiated later in our patient's hospital course when the infection had progressed to refractory septic shock with multiorgan failure and eventual death.
CONCLUSION
PJP pneumonia is a fatal disease if not recognized early in the course of illness, and the patient usually undergoes multiple antibiotic regimens before they are diagnosed and receive appropriate clinical care. The gold standard of diagnostic testing for PJP is by obtaining bronchial washings through a flexible bronchoscopy and the turnaround time for such results may take a few days to result. A significant proportion of patients may not have any overt risk factors of immunosuppression and early empiric treatment for PJP may be clinically appropriate as the delay in diagnosis may be associated with significant morbidity and mortality risk.
Topics: Humans; Male; Aged; Pneumonia, Pneumocystis; Pneumocystis carinii; Risk Factors; Anti-Bacterial Agents; HIV Infections
PubMed: 38342895
DOI: 10.1186/s13256-024-04350-4 -
PLoS Neglected Tropical Diseases Sep 2023Fungal diseases are associated with high morbidity and mortality, yet their epidemiology and burden are not well addressed. While deaths probably exceed 1.5 million per...
Fungal diseases are associated with high morbidity and mortality, yet their epidemiology and burden are not well addressed. While deaths probably exceed 1.5 million per year, many cases remain undiagnosed and underreported. Estimating the burden of these diseases is needed for prioritization and implementation of effective control programs. Here we used a model based on population at risk to estimate the burden of serious fungal infections in Sudan. The prevalence of the susceptible population including HIV, TB, cancer, asthma, and COPD was obtained from the literature. Incidence and prevalence of fungal infections were calculated using local data when applicable and if not available then regional or international figures were used. In total, the estimated number of Sudanese suffering from fungal disease is 5 M (10% of the total population). Tinea capitis, recurrent vulvovaginitis and keratitis are estimated to affect 4,127,760, 631,261, and 6,552 patients, respectively. HIV-related mycosis is estimated to affect 5,945 oral candidiasis, 1,921 esophageal candidiasis, 571 Pneumocystis pneumonia, and 462 cryptococcal meningitis cases. Aspergillus infections are estimated as follow: 3,438 invasive aspergillosis, 14,950 chronic pulmonary aspergillosis, 67,860 allergic bronchopulmonary aspergillosis cases, while the prevalence of severe asthma with fungal sensitization and fungal rhinosinusitis was 86,860 and 93,600 cases, respectively. The neglected tropical disease eumycetoma was estimated to affect 16,837 cases with a rate of 36/100,000. Serious fungal infections are quite common in Sudan and require urgent attention to improve diagnosis, promote treatment, and develop surveillance programs.
Topics: Female; Humans; Sudan; Mycoses; Candidiasis; Asthma; HIV Infections
PubMed: 37656764
DOI: 10.1371/journal.pntd.0011464 -
Cureus Dec 2023Objective To investigate the predisposing factors, disease course, potential complications, role of primary prophylaxis, and overall outcomes of pneumonia (PJP) in...
Objective To investigate the predisposing factors, disease course, potential complications, role of primary prophylaxis, and overall outcomes of pneumonia (PJP) in cancer patients. Methods The study was conducted at Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore, Pakistan. We analyzed the medical records of cancer patients diagnosed with PJP from January 2018 to December 2022 and collected data about demographic characteristics, clinical presentation, predisposing factors, treatment, complications, and mortality rates. We used SPSS 20 (IBM Corp., Armonk, NY, USA) for data analysis. Results Out of 84 patients, 59.5% (n=50) were males and most of the patients belonged to the age group 41 to 65 years. Sixty-seven point nine percent (67.9%; n=57) of patients had underlying hematological malignancy, including three bone marrow transplant recipients while 32.2% (n=27) of patients had underlying solid organ malignancy. We also observed the use of corticosteroids, rituximab, and fludarabine as predisposing factors in 15% (n=13), 27% (n=23), and 3.7%(n=03) of patients, respectively. The most common symptoms were dyspnea (88%; n=74), followed by fever (69%; n=58) and cough (69%; n=58). The former one was more prevalent in hematological malignancy patients as compared to the solid organ tumor group (p-value 0.001). We noted respiratory failure (45.2%; n=38), ICU stay (52.38%; n=44), death (32%; n=27), and shock (10.7% n=9) as the most common PJP-related complications. Moreover, all these complications were more frequent in hematological malignancy patients. We also observed that only three patients developed PJP while on adequate primary prophylaxis for this condition. The overall all-cause one-month mortality was 32% (n=27). Conclusion Cancer patients, especially those with hematological malignancies presenting with symptoms suggestive of PJP, need careful evaluation and preemptive treatment as PJP-related mortality is higher in cancer patients. Early diagnosis and treatment in this population can be lifesaving. Moreover, all cancer patients should receive PJP prophylaxis when indicated.
PubMed: 38283518
DOI: 10.7759/cureus.51291