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Microbiology Spectrum Feb 2024spp. are host obligate fungal pathogens that can cause severe pneumonia in mammals and rely heavily on their host for essential nutrients. The lack of a sustainable...
spp. are host obligate fungal pathogens that can cause severe pneumonia in mammals and rely heavily on their host for essential nutrients. The lack of a sustainable culture system poses challenges in understanding their metabolism, and the acquisition of essential nutrients from host lungs remains unexplored. Transmission electron micrographs show that extracellular vesicles (EVs) are found near spp. within the lung. We hypothesized that EVs transport essential nutrients to the fungi during infection. To investigate this, EVs from - and -infected rodents were biochemically and functionally characterized. These EVs contained host proteins involved in cellular, metabolic, and immune processes as well as proteins with homologs found in other fungal EV proteomes, indicating that may release EVs. Notably, EV uptake by indicated their potential involvement in nutrient acquisition and a possibility for using engineered EVs for efficient therapeutic delivery. However, EVs added to did not show increased growth or viability, implying that additional nutrients or factors are necessary to support their metabolic requirements. Exposure of macrophages to EVs increased proinflammatory cytokine levels but did not affect macrophages' ability to kill or phagocytose . These findings provide vital insights into and host EV interactions, yet the mechanisms underlying 's survival in the lung remain uncertain. These studies are the first to isolate, characterize, and functionally assess EVs from -infected rodents, promising to enhance our understanding of host-pathogen dynamics and therapeutic potential.IMPORTANCE spp. are fungal pathogens that can cause severe pneumonia in mammals, relying heavily on the host for essential nutrients. The absence of an culture system poses challenges in understanding their metabolism, and the acquisition of vital nutrients from host lungs remains unexplored. Extracellular vesicles (EVs) are found near spp., and it is hypothesized that these vesicles transport nutrients to the pathogenic fungi. proteins within the EVs showed homology to other fungal EV proteomes, suggesting that spp. release EVs. While EVs did not significantly enhance growth , displayed active uptake of these vesicles. Moreover, EVs induced proinflammatory cytokine production in macrophages without compromising their ability to combat . These findings provide valuable insights into EV dynamics during host-pathogen interactions in pneumonia. However, the precise underlying mechanisms remain uncertain. This research also raises the potential for engineered EVs in therapeutic applications.
Topics: Rats; Animals; Pneumocystis carinii; Proteome; Pneumonia, Pneumocystis; Pneumocystis; Macrophages; Mammals; Cytokines; Extracellular Vesicles
PubMed: 38236033
DOI: 10.1128/spectrum.03653-23 -
Epidemiology and Infection Oct 2023Secondary pneumonia occurs in 8-24% of patients with Coronavirus 2019 (COVID-19) infection and is associated with increased morbidity and mortality. Diagnosis of...
Secondary pneumonia occurs in 8-24% of patients with Coronavirus 2019 (COVID-19) infection and is associated with increased morbidity and mortality. Diagnosis of secondary pneumonia can be challenging. The purpose of this study was to evaluate the use of plasma microbial cell free DNA sequencing (mcfNGS) in the evaluation of secondary pneumonia after COVID-19. We performed a single-center case series of patients with COVID-19 who underwent mcfNGS to evaluate secondary pneumonia and reported the organisms identified, concordance with available tests, clinical utility, and outcomes. In 8/13 (61%) cases, mcfNGS detected 1-6 organisms, with clinically significant organisms identified in 4 cases, including , and spp. Management was changed in 85% (11/13) of patients based on results, including initiation of targeted therapy, de-escalation of empiric antimicrobials, and avoiding contingent escalation of antifungals. mcfNGS may be helpful to identify pathogens causing secondary pneumonia, including opportunistic pathogens in immunocompromised patients with COVID-19. However, providers need to carefully interpret this test within the clinical context.
Topics: Humans; Pneumonia, Pneumocystis; COVID-19; Pneumocystis carinii; Anti-Infective Agents; High-Throughput Nucleotide Sequencing
PubMed: 37886888
DOI: 10.1017/S0950268823001711 -
International Journal of Clinical... Nov 2023At our institution, patients with hematological disease who require pneumonia (PJP) prophylaxis were administered atovaquone at a low dose (750 mg/day). However, there...
OBJECTIVE
At our institution, patients with hematological disease who require pneumonia (PJP) prophylaxis were administered atovaquone at a low dose (750 mg/day). However, there have been few reports on the efficacy of low-dose atovaquone administration, and the purpose of this study is, therefore, to investigate its effectiveness.
MATERIALS AND METHODS
We investigated the expression of PJP in patients with hematological disease who received atovaquone administration. Atovaquone was administered at a low dose of 750 mg once daily, and the follow-up time was the period of PJP prophylaxis that included atovaquone administration.
RESULTS
85 patients were included in the study. The median age of the study population was 72 years (range: 33 - 97). The duration of atovaquone treatment and follow-up time were 150 days (22 - 1,018) and 258 days (22 - 1,457), respectively. In hematologic diseases, multiple myeloma was high in 31 patients and malignant lymphoma in 28 patients. No patients exhibited PJP during the observation period.
CONCLUSION
In hematological disease patients with relatively low risk of PJP, low-dose atovaquone may prevent the onset of PJP.
Topics: Humans; Adult; Middle Aged; Aged; Aged, 80 and over; Pneumonia, Pneumocystis; Atovaquone; Pneumocystis carinii; Trimethoprim, Sulfamethoxazole Drug Combination; Hematologic Diseases; Retrospective Studies
PubMed: 37622674
DOI: 10.5414/CP204368 -
Internal Medicine (Tokyo, Japan) Mar 2024
Topics: Humans; Pneumonia, Pneumocystis; Immunosuppressive Agents; Cytomegalovirus; Cytomegalovirus Infections; Immunocompromised Host; Pneumocystis carinii
PubMed: 37438137
DOI: 10.2169/internalmedicine.2026-23 -
Clinical Transplantation Sep 2023Pneumocystis jirovecii pneumonia (PJP) is a potentially fatal infection afflicting the immunocompromised population, including solid organ transplant (SOT) recipients....
BACKGROUND
Pneumocystis jirovecii pneumonia (PJP) is a potentially fatal infection afflicting the immunocompromised population, including solid organ transplant (SOT) recipients. Several risk factors have been described; however, little is known regarding the risk of PJP in SOT recipients with posttransplant lymphoproliferative disorder (PTLD).
METHODS
We performed a nested case-control study of SOT recipients diagnosed with PJP from 2000 to 2020. PJP was defined as positive microscopy or polymerase chain reaction testing with compatible symptoms and radiographic findings. Control patients were matched 2:1 by year of first transplant, first transplanted organ, transplant center, and sex. Multivariable conditional logistic regression was performed to test associations with PJP and Cox regression analyzed post-PJP outcomes.
RESULTS
Sixty-seven PJP cases were matched to 134 controls. The most common transplant was kidney (55.2%). Fourteen patients had a history of PTLD, 12 of whom developed PJP. After adjusting for age, acute rejection, cytomegalovirus infection, PJP prophylaxis, and lymphopenia (lymphocyte count < .5 × 10 /L), PTLD was independently associated with PJP (OR 14.0, 95% CI 1.7-114.5; p = .014). Lymphopenia was also a significant association (OR 8.2, 95% CI 3.2-20.7; p < .001). PJP was associated with mortality within 90 days of diagnosis (p < .001), but not after 90 days (p = .317). PJP was also associated with 90-day death-censored renal allograft loss (p = .026).
CONCLUSIONS
PTLD is independently associated with PJP after adjustment for recognized risk factors. This is likely influenced by PTLD-directed chemotherapy, particularly rituximab-containing regimens. PJP is associated with early mortality, but this effect is not persistent after 90 days. PJP prophylaxis should be considered in SOT recipients with PTLD.
Topics: Humans; Pneumonia, Pneumocystis; Kidney Transplantation; Case-Control Studies; Pneumocystis carinii; Risk Factors; Transplant Recipients; Lymphoproliferative Disorders; Lymphopenia
PubMed: 37195184
DOI: 10.1111/ctr.15021 -
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 -
BioRxiv : the Preprint Server For... Sep 2023spp. are host obligate fungal pathogens that can cause severe pneumonia in mammals and rely heavily on their host for essential nutrients. The lack of a sustainable...
spp. are host obligate fungal pathogens that can cause severe pneumonia in mammals and rely heavily on their host for essential nutrients. The lack of a sustainable culture system poses challenges in understanding their metabolism and the acquisition of essential nutrients from host lungs remains unexplored. Transmission electron micrographs show Extracellular Vesicles (EVs) are found near spp. within the lung. We hypothesized that EVs transport essential nutrients to the fungi during infection. To investigate this, EVs from and infected rodents were biochemically and functionally characterized. These EVs contained host proteins involved in cellular, metabolic, and immune processes as well as proteins with homologs found in other fungal EV proteomes, indicating may release EVs. Notably, EV uptake by indicated their potential involvement in nutrient acquisition and indicate a possibility for using engineered EVs for efficient therapeutic delivery. However, EVs added to , did not show increased growth or viability, implying that additional nutrients or factors are necessary to support their metabolic requirements. Exposure of macrophages to EVs increased proinflammatory cytokine levels, but did not affect macrophages' ability to kill or phagocytose . These findings provide vital insights into and host EV interactions, yet the mechanisms underlying 's survival in the lung remain uncertain. These studies are the first to isolate, characterize, and functionally assess EVs from -infected rodents, promising to enhance our understanding of host-pathogen dynamics and therapeutic potential.
PubMed: 37786700
DOI: 10.1101/2023.09.19.558454 -
Cureus Oct 2023pneumonia (PCP) is a rare, life-threatening opportunistic fungal infection that rarely occurs with CD4 counts greater than 200 cells/mm3. We present a case of PCP in a...
pneumonia (PCP) is a rare, life-threatening opportunistic fungal infection that rarely occurs with CD4 counts greater than 200 cells/mm3. We present a case of PCP in a young male who presented with fever, weakness, dyspnea, and a non-productive cough. He was initially treated for community-acquired pneumonia but was then noted to be HIV positive with signs of immunosuppression such as oral thrush. The CD4 count was found to be very high, at 646 cells/mm3 and 281 cells/mm3 on repeat. The patient was treated with trimethoprim/sulfamethoxazole (TMP/SMX) and fluconazole and further started on highly active antiretroviral therapy (HAART) with TMP/SMX as a means of secondary prophylaxis in the outpatient setting.
PubMed: 37942381
DOI: 10.7759/cureus.46680 -
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