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BMC Pulmonary Medicine Nov 2023Pneumocystis pneumonia (PCP) is a life-threatening pulmonary fungal infection that predominantly affects immunocompromised individuals, including kidney transplant...
BACKGROUND
Pneumocystis pneumonia (PCP) is a life-threatening pulmonary fungal infection that predominantly affects immunocompromised individuals, including kidney transplant recipients. Recent years have witnessed a rising incidence of PCP in this vulnerable population, leading to graft loss and increased mortality. Immunosuppression, which is essential in transplant recipients, heightens susceptibility to viral and opportunistic infections, magnifying the clinical challenge. Concurrently, the global impact of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been profound. Kidney transplant recipients have faced severe outcomes when infected with SARS-CoV-2, often requiring intensive care. Co-infection with COVID-19 and PCP in this context represents a complex clinical scenario that requires precise management strategies, involving a delicate balance between immunosuppression and immune activation. Although there have been case reports on management of COVID-19 and PCP in kidney transplant recipients, guidance on how to tackle these infections when they occur concurrently remains limited.
CASE PRESENTATIONS
We have encountered four kidney transplant recipients with concurrent COVID-19 and PCP infection. These patients received comprehensive treatment that included adjustment of their maintenance immunosuppressive regimen, anti-pneumocystis therapy, treatment for COVID-19 and other infections, and symptomatic and supportive care. After this multifaceted treatment strategy, all of these patients improved significantly and had favorable outcomes.
CONCLUSIONS
We have successfully managed four kidney transplant recipients co-infected with COVID-19 and PCP. While PCP is a known complication of immunosuppressive therapy, its incidence in patients with COVID-19 highlights the complexity of dual infections. Our findings suggest that tailored immunosuppressive regimens, coupled with antiviral and antimicrobial therapies, can lead to clinical improvement in such cases. Further research is needed to refine risk assessment and therapeutic strategies, which will ultimately enhance the care of this vulnerable population.
Topics: Humans; Pneumonia, Pneumocystis; COVID-19; Kidney Transplantation; Retrospective Studies; Transplant Recipients; SARS-CoV-2; Immunosuppressive Agents; Pneumocystis carinii
PubMed: 37990199
DOI: 10.1186/s12890-023-02764-2 -
Indian Journal of Pediatrics Aug 2023
Topics: Humans; Pneumocystis carinii; SARS-CoV-2; Coinfection; X-Linked Combined Immunodeficiency Diseases; COVID-19; Pneumonia, Pneumocystis
PubMed: 37249831
DOI: 10.1007/s12098-023-04661-2 -
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 -
Diagnostic Microbiology and Infectious... Jan 2024Asthma is characterized by chronic airway inflammation. In addition to allergens, microorganisms can affect the clinical course of asthma. It has been shown that some...
Asthma is characterized by chronic airway inflammation. In addition to allergens, microorganisms can affect the clinical course of asthma. It has been shown that some fungi play an important role in the progression of asthma. However, the effects of Pneumocystis jirovecii and Cryptosporidium spp., on the disease are little known. We investigated P. jirovecii and Cryptosporidium spp. in the sputum and stool sample of patients with asthma (n = 40) by microscopy and PCR compared to the healthy group (n = 40). P. jirovecii (12.5 %), and Cryptosporidium spp. (12.5 %) were detected in the sputum samples of only asthmatic patients (p = 0.029 and 0.029 respectively). However, Crpytosporidium spp. was detected equally in stool samples of both groups (p = 0.682). Our results indicate that P. jirovecii and Cryptosporidium spp. should be considered in patients with asthma and molecular screening of these neglected eukaryotes in respiratory tract samples may be beneficial in the clinical management of the disease.
Topics: Humans; Pneumocystis carinii; Prevalence; Cryptosporidium; Cryptosporidiosis; Asthma; Pneumonia, Pneumocystis
PubMed: 37913698
DOI: 10.1016/j.diagmicrobio.2023.116124 -
Respiratory Research Mar 2024Increasing evidence revealed that lung microbiota dysbiosis was associated with pulmonary infection in lung transplant recipients (LTRs). Pneumocystis jirovecii (P.... (Observational Study)
Observational Study
BACKGROUND
Increasing evidence revealed that lung microbiota dysbiosis was associated with pulmonary infection in lung transplant recipients (LTRs). Pneumocystis jirovecii (P. jirovecii) is an opportunistic fungal pathogen that frequently causes lethal pneumonia in LTRs. However, the lung microbiota in LTRs with P. jirovecii pneumonia (PJP) remains unknow.
METHODS
In this prospective observational study, we performed metagenomic next-generation sequencing (mNGS) on 72 bronchoalveolar lavage fluid (BALF) samples from 61 LTRs (20 with PJP, 22 with PJC, 19 time-matched stable LTRs, and 11 from LTRs after PJP recovery). We compared the lung microbiota composition of LTRs with and without P. jirovecii, and analyzed the related clinical variables.
RESULTS
BALFs collected at the episode of PJP showed a more discrete distribution with a lower species diversity, and microbiota composition differed significantly compared to P. jirovecii colonization (PJC) and control group. Human gammaherpesvirus 4, Phreatobacter oligotrophus, and Pseudomonas balearica were the differential microbiota species between the PJP and the other two groups. The network analysis revealed that most species had a positive correlation, while P. jirovecii was correlated negatively with 10 species including Acinetobacter venetianus, Pseudomonas guariconensis, Paracandidimonas soli, Acinetobacter colistiniresistens, and Castellaniella defragrans, which were enriched in the control group. The microbiota composition and diversity of BALF after PJP recovery were also different from the PJP and control groups, while the main components of the PJP recovery similar to control group. Clinical variables including age, creatinine, total protein, albumin, IgG, neutrophil, lymphocyte, CD3CD45, CD3CD4 and CD3CD8 T cells were deeply implicated in the alterations of lung microbiota in LTRs.
CONCLUSIONS
This study suggests that LTRs with PJP had altered lung microbiota compared to PJC, control, and after recovery groups. Furthermore, lung microbiota is related to age, renal function, nutritional and immune status in LTRs.
Topics: Humans; Pneumonia, Pneumocystis; Transplant Recipients; CD8-Positive T-Lymphocytes; Pneumocystis carinii; Microbiota; Lung
PubMed: 38486264
DOI: 10.1186/s12931-024-02755-9 -
Frontiers in Cellular and Infection... 2023Pneumonia are the leading cause of death worldwide, and antibiotic treatment remains fundamental. However, conventional sputum smears or cultures are still inefficient...
INTRODUCTION
Pneumonia are the leading cause of death worldwide, and antibiotic treatment remains fundamental. However, conventional sputum smears or cultures are still inefficient for obtaining pathogenic microorganisms.Metagenomic next-generation sequencing (mNGS) has shown great value in nucleic acid detection, however, the NGS results for lower respiratory tract microorganisms are still poorly studied.
METHODS
This study dealt with investigating the efficacy of mNGS in detecting pathogens in the lower respiratory tract of patients with pulmonary infections. A total of 112 patients admitted at the First Affiliated Hospital of Zhengzhou University between April 30, 2018, and June 30, 2020, were enrolled in this retrospective study. The bronchoalveolar lavage fluid (BALF) was obtained from lower respiratory tract from each patient. Routine methods (bacterial smear and culture) and mNGS were employed for the identification of pathogenic microorganisms in BALF.
RESULTS
The average patient age was 53.0 years, with 94.6% (106/112) obtaining pathogenic microorganism results. The total mNGS detection rate of pathogenic microorganisms significantly surpassed conventional methods (93.7% vs. 32.1%, P < 0.05). Notably, 75% of patients (84/112) were found to have bacteria by mNGS, but only 28.6% (32/112) were found to have bacteria by conventional approaches. The most commonly detected bacteria included (19.6%), (17.9%), (14.3%), (12.5%), (12.5%), and (11.6%). In 29.5% (33/112) of patients, fungi were identified using mNGS, including 23 cases of (20.5%), 18 of (16.1%), and 10 of (8.9%). However, only 7.1 % (8/112) of individuals were found to have fungi when conventional procedures were used. The mNGS detection rate of viruses was significantly higher than the conventional method rate (43.8% vs. 0.9%, P < 0.05). The most commonly detected viruses included Epstein-Barr virus (15.2%), cytomegalovirus (13.4%), circovirus (8.9%), human coronavirus (4.5%), and rhinovirus (4.5%). Only 29.4% (33/112) of patients were positive, whereas 5.4% (6/112) of patients were negative for both detection methods as shown by Kappa analysis, indicating poor consistency between the two methods (P = 0.340; Kappa analysis).
CONCLUSION
Significant benefits of mNGS have been shown in the detection of pathogenic microorganisms in patients with pulmonary infection. For those with suboptimal therapeutic responses, mNGS can provide an etiological basis, aiding in precise anti-infective treatment.
Topics: Humans; Middle Aged; Retrospective Studies; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Pneumonia; High-Throughput Nucleotide Sequencing; Respiratory System
PubMed: 38264726
DOI: 10.3389/fcimb.2023.1291980 -
Emerging Microbes & Infections Dec 2023AIDS: acquired immune deficiency syndrome; CI: confidence interval; EPHI: Ethiopian Public Health Institute; HAART: highly active antiretroviral therapy; HIV: human...
AIDS: acquired immune deficiency syndrome; CI: confidence interval; EPHI: Ethiopian Public Health Institute; HAART: highly active antiretroviral therapy; HIV: human immunodeficiency virus; HR: hazard ratio; Mg/dl: milligram per deciliter; TB: tuberculosis; PCP: pneumocystis carinii pneumonia; ZJU: Zhejiang University.
Topics: Humans; Female; Ethiopia; AIDS-Related Opportunistic Infections; HIV Infections; Acquired Immunodeficiency Syndrome; Neoplasms; Antiretroviral Therapy, Highly Active
PubMed: 37824698
DOI: 10.1080/22221751.2023.2271065 -
Medical Mycology Jun 2024This systematic review evaluates the current global impact of invasive infections caused by Pneumocystis jirovecii (principally pneumonia: PJP), and was carried out to...
Features and global impact of invasive fungal infections caused by Pneumocystis jirovecii: A systematic review to inform the World Health Organization fungal priority pathogens list.
This systematic review evaluates the current global impact of invasive infections caused by Pneumocystis jirovecii (principally pneumonia: PJP), and was carried out to inform the World Health Organization Fungal Priority Pathogens List. PubMed and Web of Science were used to find studies reporting mortality, inpatient care, complications/sequelae, antifungal susceptibility/resistance, preventability, annual incidence, global distribution, and emergence in the past 10 years, published from January 2011 to February 2021. Reported mortality is highly variable, depending on the patient population: In studies of persons with HIV, mortality was reported at 5%-30%, while in studies of persons without HIV, mortality ranged from 4% to 76%. Risk factors for disease principally include immunosuppression from HIV, but other types of immunosuppression are increasingly recognised, including solid organ and haematopoietic stem cell transplantation, autoimmune and inflammatory disease, and chemotherapy for cancer. Although prophylaxis is available and generally effective, burdensome side effects may lead to discontinuation. After a period of decline associated with improvement in access to HIV treatment, new risk groups of immunosuppressed patients with PJP are increasingly identified, including solid organ transplant patients.
Topics: Humans; Pneumocystis carinii; Invasive Fungal Infections; World Health Organization; Immunocompromised Host; Risk Factors; Global Health; Pneumonia, Pneumocystis; Antifungal Agents; Incidence
PubMed: 38935910
DOI: 10.1093/mmy/myae038 -
BMC Infectious Diseases Jan 2024Pneumocystis jirovecii pneumonia (PJP) is a life-threatening and severe disease in immunocompromised hosts. A synergistic regimen based on the combination of...
A regimen based on the combination of trimethoprim/sulfamethoxazole with caspofungin and corticosteroids as a first-line therapy for patients with severe non-HIV-related pneumocystis jirovecii pneumonia: a retrospective study in a tertiary hospital.
BACKGROUND
Pneumocystis jirovecii pneumonia (PJP) is a life-threatening and severe disease in immunocompromised hosts. A synergistic regimen based on the combination of sulfamethoxazole-trimethoprim (SMX-TMP) with caspofungin and glucocorticosteroids (GCSs) may be a potential first-line therapy for PJP. Therefore, it is important to explore the efficacy and safety of this synergistic therapy for treating non-HIV-related PJP patients.
METHODS
We retrospectively analysed the data of 38 patients with non-HIV-related PJP at the First Affiliated Hospital of Xi'an Jiaotong University. Patients were divided into two groups: the synergistic therapy group (ST group, n = 20) and the monotherapy group (MT group, n = 18). All patients were from the ICU and were diagnosed with severe PJP. In the ST group, all patients were treated with SMX-TMP (TMP 15-20 mg/kg per day) combined with caspofungin (70 mg as the loading dose and 50 mg/day as the maintenance dose) and a GCS (methylprednisolone 40-80 mg/day). Patients in the MT group were treated only with SMX-TMP (TMP 15-20 mg/kg per day). The clinical response, adverse events and mortality were compared between the two groups.
RESULTS
The percentage of patients with a positive clinical response in the ST group was significantly greater than that in the MT group (100.00% vs. 66.70%, P = 0.005). The incidence of adverse events in the MT group was greater than that in the ST group (50.00% vs. 15.00%, P = 0.022). Furthermore, the dose of TMP and duration of fever in the ST group were markedly lower than those in the MT group (15.71 mg/kg/day vs. 18.35 mg/kg/day (P = 0.001) and 7.00 days vs. 11.50 days (P = 0.029), respectively). However, there were no significant differences in all-cause mortality or duration of hospital stay between the MT group and the ST group.
CONCLUSIONS
Compared with SMZ/TMP monotherapy, synergistic therapy (SMZ-TMP combined with caspofungin and a GCS) for the treatment of non-HIV-related PJP can increase the clinical response rate, decrease the incidence of adverse events and shorten the duration of fever. These results indicate that synergistic therapy is effective and safe for treating severe non-HIV-related PJP.
Topics: Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Caspofungin; Retrospective Studies; Tertiary Care Centers; Pneumocystis carinii; Adrenal Cortex Hormones
PubMed: 38297200
DOI: 10.1186/s12879-024-09031-7 -
BMC Infectious Diseases Nov 2023Cancer case during pregnancy is rare, but it is the second leading cause of maternal mortality. (Review)
Review
BACKGROUND
Cancer case during pregnancy is rare, but it is the second leading cause of maternal mortality.
CASE PRESENTATION
A-32-year old pregnant woman with a gestational age of 37 weeks was admitted to the hospital due to repeated coughing for 5 months. She received Veno-Venous Extracorporeal Membrane Oxygenation (V-V ECMO) treatment for severe hypoxemia after delivery. She was diagnosed with non-small cell lung cancer (NSCLC) with bone metastasis and pneumocystis pneumonia (PCP). She subsequently received anti-tumor therapy and anti-infective therapy. After treatment, her condition improved and she was weaned from ECMO. Two weeks after weaning ECMO, her condition worsened again. Her family chose palliative treatment, and she ultimately died.
CONCLUSIONS
NSCLC is rare during pregnancy. At present, there is still a lack of standardized methods to manage these cases. For theses cases, the clinician should be wary of opportunistic infections, such as pneumocystis jirovecii (P. jirovecii) and Elizabethkingia spp. Specialized medical teams with abundant experience and multidisciplinary discussions from the perspectives of the patient's clinical characteristics as well as preferences are crucial for developing individualized and the best approach.
Topics: Humans; Pregnancy; Female; Infant, Newborn; Pneumonia, Pneumocystis; Carcinoma, Non-Small-Cell Lung; Pregnant Women; Lung Neoplasms; Pneumocystis carinii
PubMed: 37964211
DOI: 10.1186/s12879-023-08790-z