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International Journal of Antimicrobial... May 2024American guidelines recommend trimethoprim-sulphamethoxazole (TMP-SMX) for preventing Pneumocystis jirovecii pneumonia (PJP) in paediatric patients at doses of 5-10...
Evaluation of effectiveness, hyperkalaemia, and hepatotoxicity of trimethoprim-sulphamethoxazole prophylaxis for Pneumocystis jirovecii pneumonia in paediatric patients: A single-centre retrospective study.
BACKGROUND
American guidelines recommend trimethoprim-sulphamethoxazole (TMP-SMX) for preventing Pneumocystis jirovecii pneumonia (PJP) in paediatric patients at doses of 5-10 mg/kg/d of the TMP component, administered either daily, three times weekly, or twice weekly. However, limited studies describe the effectiveness and safety of these prophylactic regimens. Our study aimed to assess the clinical effectiveness and incidence of adverse events associated with each TMP-SMX regimen in paediatric patients, and to identify risk factors for adverse events.
METHODS
We collected data regarding the onset of PJP, hyperkalaemia, and hepatotoxicity in patients aged 0-18 years who underwent prophylaxis with TMP-SMX from July 2018 to June 2023.
RESULTS
A total of 215 paediatric patients met the inclusion criteria. No patients developed PJP. Hyperkalaemia occurred in 14.7%, patients receiving TMP-SMX daily, 15.4% receiving it three times weekly, and 15.5% receiving it twice weekly. Hepatotoxicity was most frequent in patients receiving TMP-SMX twice weekly (19%), followed by those receiving it three times weekly (7.7%), and daily (5.9%). Younger patients were significantly more prone to developing hyperkalaemia or hepatotoxicity. Patients aged <1 year had the highest incidences of hyperkalaemia (56.5%), and those aged 1-2 years had the highest incidence of hepatotoxicity (25%).
CONCLUSIONS
No patient developed PJP under various dosage prophylactic regimens of TMP-SMX. However, our findings suggest the need to monitor potassium levels and hepatic function in patients undergoing any of the three TMP-SMX regimens. In particular, patients aged <1 year old and 1-2 years old face a higher risk of hyperkalaemia and hepatotoxicity, respectively.
Topics: Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Hyperkalemia; Child; Child, Preschool; Retrospective Studies; Infant; Male; Female; Adolescent; Pneumocystis carinii; Infant, Newborn; Chemical and Drug Induced Liver Injury; Anti-Bacterial Agents; Antibiotic Prophylaxis
PubMed: 38508538
DOI: 10.1016/j.ijantimicag.2024.107151 -
Microbiology and Molecular Biology... Jun 2024SUMMARYEvery human being is presumed to be infected by the fungus at least once in his or her lifetime. This fungus belongs to a large group of species that appear to... (Review)
Review
SUMMARYEvery human being is presumed to be infected by the fungus at least once in his or her lifetime. This fungus belongs to a large group of species that appear to exclusively infect mammals, with being the only one known to cause disease in humans. The mystery of origin and speciation is just beginning to unravel. Here, we provide a review of the major steps of evolution. The genus likely originated from soil or plant-associated organisms during the period of Cretaceous ~165 million years ago and successfully shifted to mammals. The transition coincided with a substantial loss of genes, many of which are related to the synthesis of nutrients that can be scavenged from hosts or cell wall components that could be targeted by the mammalian immune system. Following the transition, the genus cospeciated with mammals. Each species specialized at infecting its own host. Host specialization is presumably built at least partially upon surface glycoproteins, whose protogene was acquired prior to the genus formation. appeared at ~65 million years ago, overlapping with the emergence of the first primates. and its sister species , which infects macaques nowadays, may have had overlapping host ranges in the distant past. Clues from molecular clocks suggest that did not cospeciate with humans. Molecular evidence suggests that speciation involved chromosomal rearrangements and the mounting of genetic barriers that inhibit gene flow among species.
Topics: Humans; Animals; Pneumocystis carinii; Phylogeny; Pneumocystis Infections; Pneumocystis; Evolution, Molecular; Host Specificity; Pneumonia, Pneumocystis; Genome, Fungal; Mammals; Biological Evolution
PubMed: 38587383
DOI: 10.1128/mmbr.00202-22 -
Mycopathologia May 2024To describe the epidemiology of Pneumocystis jirovecii pneumonia and colonization diagnosed by next-generation sequencing (NGS) and explore the usefulness of the number...
OBJECTIVES
To describe the epidemiology of Pneumocystis jirovecii pneumonia and colonization diagnosed by next-generation sequencing (NGS) and explore the usefulness of the number of P. jirovecii sequence reads for the diagnosis of P. jirovecii pneumonia.
METHODS
We examined the NGS results for P. jirovecii in respiratory samples collected from patients and analysed their clinical, radiological and microbiological characteristics.
RESULTS
Among 285 respiratory samples collected over a 12-month period (January to December 2022), P. jirovecii sequences were detected in 56 samples from 53 patients. Fifty (94.3%) of the 53 patients were HIV-negative. Following our case definitions, 37 (69.8%) and 16 (30.2%) of the 53 patients had P. jirovecii infection and colonization respectively. P. jirovecii infection was associated with presence of underlying disease with immunosuppression (94.6% vs 18.8%, P < 0.05), positive serum 1,3-β-D-glucan (41.2% vs 0%, P < 0.01) and higher number of P. jirovecii sequence reads (P < 0.005). In contrast, P. jirovecii colonization was associated with the male sex (93.8% vs 54.1%, P < 0.01), another definitive infectious disease diagnosis of the respiratory tract (43.8% vs 2.7%, P < 0.001) and higher survival (100% vs 67.6%, P < 0.01). Although P. jirovecii pneumonia was associated with higher number of P. jirovecii reads in respiratory samples, only a sensitivity of 82.14% and a specificity of 68.75% could be achieved.
CONCLUSION
Detection of P. jirovecii sequences in respiratory samples has to be interpreted discreetly. A combination of clinical, radiological and laboratory findings is still the most crucial in determining whether a particular case is genuine P. jirovecii pneumonia.
Topics: Humans; Pneumonia, Pneumocystis; Male; High-Throughput Nucleotide Sequencing; Pneumocystis carinii; Female; Middle Aged; Aged; Adult; Aged, 80 and over; Respiratory System; Young Adult; Molecular Diagnostic Techniques
PubMed: 38704795
DOI: 10.1007/s11046-024-00849-y -
BMC Pulmonary Medicine Jan 2024Pneumocystis jirovecii pneumonia (PCP) could be fatal to patients without human immunodeficiency virus (HIV) infection. Current diagnostic methods are either invasive or... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Pneumocystis jirovecii pneumonia (PCP) could be fatal to patients without human immunodeficiency virus (HIV) infection. Current diagnostic methods are either invasive or inaccurate. We aimed to establish an accurate and non-invasive radiomics-based way to identify the risk of PCP infection in non-HIV patients with computed tomography (CT) manifestation of pneumonia.
METHODS
This is a retrospective study including non-HIV patients hospitalized for suspected PCP from January 2010 to December 2022 in one hospital. The patients were randomized in a 7:3 ratio into training and validation cohorts. Computed tomography (CT)-based radiomics features were extracted automatically and used to construct a radiomics model. A diagnostic model with traditional clinical and CT features was also built. The area under the curve (AUC) were calculated and used to evaluate the diagnostic performance of the models. The combination of the radiomics features and serum β-D-glucan levels was also evaluated for PCP diagnosis.
RESULTS
A total of 140 patients (PCP: N = 61, non-PCP: N = 79) were randomized into training (N = 97) and validation (N = 43) cohorts. The radiomics model consisting of nine radiomic features performed significantly better (AUC = 0.954; 95% CI: 0.898-1.000) than the traditional model consisting of serum β-D-glucan levels (AUC = 0.752; 95% CI: 0.597-0.908) in identifying PCP (P = 0.002). The combination of radiomics features and serum β-D-glucan levels showed an accuracy of 95.8% for identifying PCP infection (positive predictive value: 95.7%, negative predictive value: 95.8%).
CONCLUSIONS
Radiomics showed good diagnostic performance in differentiating PCP from other types of pneumonia in non-HIV patients. A combined diagnostic method including radiomics and serum β-D-glucan has the potential to provide an accurate and non-invasive way to identify the risk of PCP infection in non-HIV patients with CT manifestation of pneumonia.
TRIAL REGISTRATION
ClinicalTrials.gov (NCT05701631).
Topics: Humans; Pneumonia, Pneumocystis; Retrospective Studies; Pneumocystis carinii; Radiomics; beta-Glucans; HIV Infections; Glucans; Tomography
PubMed: 38167022
DOI: 10.1186/s12890-023-02827-4 -
The Pediatric Infectious Disease Journal Dec 2023
Topics: Humans; Child; Pneumonia, Pneumocystis; Neoplasms; Pneumocystis carinii
PubMed: 37773627
DOI: 10.1097/INF.0000000000004102 -
Diagnostic Microbiology and Infectious... Mar 2024Accurate differentiation between Pneumocystis jirovecii (Pj) infection and colonization is crucial for effective treatment.
BACKGROUND
Accurate differentiation between Pneumocystis jirovecii (Pj) infection and colonization is crucial for effective treatment.
METHODS
From September 2016 to June 2022, 89 immunocompromised patients with unexplained lung infiltrates and clinical suspicion of Pj pneumonia were enrolled at Peking University People's Hospital. Bronchoalveolar lavage fluid (BALF) of these patients were detected by quantitative PCR (qPCR) and droplet digital PCR (ddPCR).
RESULTS
The performance of ddPCR was superior to qPCR in detecting Pj infection. Area under the curve was 0.97 (95 %CI: 0.94-1) for ddPCR of the BALF in all patients. The optimal threshold value for discriminating Pj infection from colonization by ddPCR was 13.98 copies/test, with a sensitivity of 97.96 %, specificity of 85.71 %. No obvious correlation between ddPCR copy number and disease severity was observed.
CONCLUSION
BALF ddPCR exhibits robust potential in detecting Pj and effectively discriminating colonization and infection.
Topics: Humans; Pneumonia, Pneumocystis; Pneumocystis carinii; Bronchoalveolar Lavage Fluid; Diagnosis, Differential; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity
PubMed: 38184984
DOI: 10.1016/j.diagmicrobio.2023.116168 -
Nature Communications Nov 2023Surface antigenic variation is crucial for major pathogens that infect humans. To escape the immune system, they exploit various mechanisms. Understanding these...
Surface antigenic variation is crucial for major pathogens that infect humans. To escape the immune system, they exploit various mechanisms. Understanding these mechanisms is important to better prevent and fight the deadly diseases caused. Those used by the fungus Pneumocystis jirovecii that causes life-threatening pneumonia in immunocompromised individuals remain poorly understood. Here, though this fungus is currently not cultivable, our detailed analysis of the subtelomeric sequence motifs and genes encoding surface proteins suggests that the system involves the reassortment of the repertoire of ca. 80 non-expressed genes present in each strain, from which single genes are retrieved for mutually exclusive expression. Dispersion of the new repertoires, supposedly by healthy carrier individuals, appears very efficient because identical alleles are observed in patients from different countries. Our observations reveal a unique strategy of antigenic variation. They also highlight the possible role in genome rearrangements of small imperfect mirror sequences forming DNA triplexes.
Topics: Humans; Mosaicism; Pneumocystis carinii; Antigenic Variation; DNA, Fungal
PubMed: 37919276
DOI: 10.1038/s41467-023-42685-6 -
Transplant Infectious Disease : An... Oct 2023Among lung transplant recipients, serial bronchoscopies are performed frequently. Often, serial galactomannan (GM), 1,3-β-d-glucan (BDG), and Pneumocystis jirovecii...
BACKGROUND
Among lung transplant recipients, serial bronchoscopies are performed frequently. Often, serial galactomannan (GM), 1,3-β-d-glucan (BDG), and Pneumocystis jirovecii (PJ) testing is performed with these broncho-alveolar lavages (BALs) as standard of care with limited data to support their routine use.
METHODS
After Institutional Review Board approval, we retrospectively collected all blood and BAL GM, BDG, and PJ test results from January 2015 to July 20, 2022. Primary data collection from the Northwestern Medicine EDW was supplemented by manual chart review.
RESULTS
During the study period, 236 lung transplant recipients were cared for by our center. Of these patients, 217 (91.9%) had 1418 GM tests performed; 61 (4.3%) were positive (index ≥1). Fungal cultures were requested for most BAL-GM (90.7%). Out of duplicates in same BAL, results discrepancy was minimal (3.4%). 172 (72.9%) had BDG tests were performed; 25.6% were positive. Thirteen patients had multiple BDG during one hospitalization (mean 2.3 tests); none of the negative test repeated became positive. Eleven negative BDG were seen in patients with invasive aspergillosis (IA). Note that, 577 PJ testing were performed (direct fluorescent antibody [n = 494] or polymerase chain reaction [PCR] [n = 80], or both [n = 3]) in 174 different patients. None were positive.
CONCLUSION
Despite supplemental GM, BDG, and Pneumocystis jirovecii pneumonia PCR being performed routinely on lung transplant recipients undergoing BAL at our center, the data suggests a more tailored approach may be appropriate. There is no role for routine serial testing with these assays during a single hospitalization. BDG confers no added-value over GM with cultures for IA diagnosis.
Topics: Humans; Retrospective Studies; Transplant Recipients; Sensitivity and Specificity; Lung; Aspergillosis; Polymerase Chain Reaction; Pneumocystis carinii; Invasive Fungal Infections; Biomarkers; beta-Glucans; Mannans
PubMed: 37608632
DOI: 10.1111/tid.14136 -
PloS One 2024Pneumocytis jirovecii infection in preterm newborns has recently been associated with neonatal respiratory distress syndrome and bronchopulmonary dysplasia. Changes in...
BACKGROUND
Pneumocytis jirovecii infection in preterm newborns has recently been associated with neonatal respiratory distress syndrome and bronchopulmonary dysplasia. Changes in the bacterial microbiota of the airways have also been described in infants with bronchopulmonary dysplasia. However, until now there has been no information on the airway mycobiota in newborns. The purpose of this study was to describe the airway mycobiota in term and preterm newborns and its possible association with respiratory distress syndrome.
METHODS
Twenty-six matched preterm newborns with and without respiratory distress syndrome were studied, as well as 13 term babies. The identification of the fungal microbiota was carried out using molecular procedures in aspirated nasal samples at birth.
RESULTS
The ascomycota phylum was identified in 89.7% of newborns, while the basidiomycota phylum was found in 33.3%. Cladosporium was the predominant genus in both term and preterm infants 38.4% vs. 73% without statistical differences. Candida sake and Pneumocystis jirovecii were only found in preterm infants, suggesting a potential relationship with the risk of prematurity.
CONCLUSIONS
This is the first report to describe the fungal microbiota of the airways in term and preterm infants with and without respiratory distress syndrome. Although no differences have been observed, the number of cases analyzed could be small to obtain conclusive results, and more studies are needed to understand the role of the fungal microbiota of the airways in neonatal respiratory pathology.
Topics: Infant; Infant, Newborn; Humans; Infant, Premature; Bronchopulmonary Dysplasia; Mycobiome; Respiratory Distress Syndrome, Newborn; Pneumocystis carinii
PubMed: 38598489
DOI: 10.1371/journal.pone.0302027 -
Zhonghua Jie He He Hu Xi Za Zhi =... Dec 2023Pneumocystis pneumonia (PCP) is an opportunistic infection caused by and is the most common fungal infection in HIV/AIDS patients. With the routine use of...
Pneumocystis pneumonia (PCP) is an opportunistic infection caused by and is the most common fungal infection in HIV/AIDS patients. With the routine use of antiretroviral therapy (ART), the incidence of PCP infection in HIV/AIDS patients has decreased and the prognosis has improved significantly. On the other hand, the use of chemoradiotherapy and immunotherapy in patients with cancer, post-transplantation and autoimmune diseases are increasing dramatically, which has led to a similar increase in the incidence of PCP in these non-HIV/AIDS patients. There is a global shift in research on PCP from HIV-infected co-infected PCP (HIV-PCP) to non-HIV-infected co-infected PCP. The clinical course of non-HIV-PCP is rapid and severe, and the morbidity and mortality rates are higher than those of HIV-PCP. Studies have shown that 90% of non-HIV-PCP patients have a history of glucocorticoid use prior to infection, such as in patients with hematologic malignancies, solid organ transplants, and rheumatic diseases, and that long-term high-dose glucocorticoid use is an important risk for PCP susceptibility. Clinical practice has shown that PCP often occurs during the tapering of glucocorticoids, and a higher proportion of patients develop diffuse pulmonary lesions and, in more severe cases suffer from life-threatening acute respiratory failure. The pathogenesis of non-HIV infections associated with PCP is not yet clarified, and there is a lack of effective therapeutic practices that require further investigation.
Topics: Humans; Acquired Immunodeficiency Syndrome; Pneumonia, Pneumocystis; Glucocorticoids; AIDS-Related Opportunistic Infections; HIV Infections
PubMed: 38044054
DOI: 10.3760/cma.j.cn112147-20230826-00108