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Frontiers in Cellular and Infection... 2022Due to the inability to be cultured , the biological characteristics and pathogenicity of remain unclear. Intestinal microflora disorder is related to the occurrence...
BACKGROUND
Due to the inability to be cultured , the biological characteristics and pathogenicity of remain unclear. Intestinal microflora disorder is related to the occurrence and development of various pulmonary diseases. This work explores the pathogenesis of pneumocystis pneumonia (PCP) in acquired immune deficiency syndrome (AIDS) patients from a microbiome perspective, to provide better strategies for the diagnosis, treatment, and prevention of PCP.
METHODS
Subjects were divided into three groups: human immunodeficiency virus (HIV)-infected patients combined with PCP, HIV-infected patients without PCP, and HIV-negative. Stool and bronchoalveolar lavage fluid (BALF) samples were collected, total DNA was extracted, and 16S rRNA high-throughput sequencing was performed using an Illumina MiSeq platform. PICRUSt and BugBase were used to predict microflora functions, and correlation analysis of intestinal and lung bacterial flora was conducted.
RESULTS
Compared with the HIV- group, prevotella and another 21 genera in the intestinal microbiome were statistically different in the HIV+ group; 25 genera including Escherichia-Shigella from HIV+PCP+ group were statistically different from HIV+PCP- group. The abundance of Genera such as Porphyromonas was positively or negatively correlated with CD16/CD56+ (μL). Compared with the HIV- group, identification efficiency based on area under the curve (AUC) >0.7 for the HIV+ group identified seven genera in the gut microbiota, including Enterococcus (total AUC = 0.9519). Compared with the HIV+PCP- group, there were no bacteria with AUC >0.7 in the lung or intestine of the HIV+PCP+ group. The number of shared bacteria between BALF and fecal samples was eight species in the HIV- group, 109 species in PCP- patients, and 228 species in PCP+ patients, according to Venn diagram analysis. Changes in various clinical indicators and blood parameters were also closely related to the increase or decrease in the abundance of intestinal and pulmonary bacteria, respectively.
CONCLUSIONS
HIV infection and PCP significantly altered the species composition of lung and intestinal microbiomes, HIV infection also significantly affected intestinal microbiome gene functions, and PCP exacerbated the changes. The classification model can be used to distinguish HIV+ from HIV- patients, but the efficiency of bacterial classification was poor between PCP+ and PCP- groups. The microbiomes in the lung and gut were correlated to some extent, providing evidence for the existence of a lung-gut axis, revealing a potential therapeutic target in patients with HIV and PCP.
Topics: Humans; Pneumonia, Pneumocystis; Gastrointestinal Microbiome; Acquired Immunodeficiency Syndrome; HIV Infections; RNA, Ribosomal, 16S; Lung; Microbiota
PubMed: 36339339
DOI: 10.3389/fcimb.2022.1033427 -
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 -
Clinical Infectious Diseases : An... Mar 2022Pneumocystis jirovecii is an opportunistic fungus that causes Pneumocystis pneumonia (PCP) in immunocompromised hosts. Over an 11-month period, we observed a rise in...
BACKGROUND
Pneumocystis jirovecii is an opportunistic fungus that causes Pneumocystis pneumonia (PCP) in immunocompromised hosts. Over an 11-month period, we observed a rise in cases of PCP among kidney-transplant recipients (KTR), prompting an outbreak investigation.
METHODS
Clinical and epidemiologic data were collected for KTR diagnosed with PCP between July 2019 and May 2020. Pneumocystis strain typing was performed using restriction fragment length polymorphism analyses and multilocus sequence typing in combination with next-generation sequencing. A transmission map was drawn, and a case-control analysis was performed to determine risk factors associated with PCP.
RESULTS
Nineteen cases of PCP in KTR were diagnosed at a median of 79 months post-transplantation; 8 received monthly belatacept infusions. Baseline characteristics were similar for KTR on belatacept versus other regimens; the number of clinic visits was numerically higher for the belatacept group during the study period (median 7.5 vs 3). Molecular typing of respiratory specimens from 9 patients revealed coinfection with up to 7 P. jirovecii strains per patient. A transmission map suggested multiple clusters of interhuman transmission. In a case-control univariate analysis, belatacept, lower absolute lymphocyte count, non-White race, and more transplant clinic visits were associated with an increased risk of PCP. In multivariate and prediction power estimate analyses, frequent clinic visits was the strongest risk factor for PCP.
CONCLUSIONS
Increased clinic exposure appeared to facilitate multiple clusters of nosocomial PCP transmission among KTR. Belatacept was a risk factor for PCP, possibly by increasing clinic exposure through the need for frequent visits for monthly infusions.
Topics: Disease Outbreaks; Humans; Kidney Transplantation; Multilocus Sequence Typing; Pneumocystis carinii; Pneumonia, Pneumocystis; Transplant Recipients; United States
PubMed: 34017984
DOI: 10.1093/cid/ciab474 -
Frontiers in Fungal Biology 2021species (spp.) are host-obligate fungal parasites that colonize and propagate almost exclusively in the alveolar lumen within the lungs of mammals where they can cause...
species (spp.) are host-obligate fungal parasites that colonize and propagate almost exclusively in the alveolar lumen within the lungs of mammals where they can cause a lethal pneumonia. The emergence of this pneumonia in non-HIV infected persons caused by (PjP), illustrates the continued importance of and the need to understand its associated pathologies and to develop new therapies and preventative strategies. In the proposed life cycle, spp. attach to alveolar type 1 epithelial cells (AEC1) and prevent gas exchange. This process among other mechanisms of spp. pathogenesis is challenging to observe in real time due to the absence of a continuous or culture system. The study presented here provides a proof-of-concept for the development of murine lung organoids that mimic the lung alveolar sacs expressing alveolar epithelial type 1 cells (AEC1) and alveolar type 2 epithelial cells (AEC2). Use of these 3-dimensional organoids should facilitate studies of a multitude of unanswered questions and serve as an improved means to screen new anti- PjP agents.
PubMed: 37744131
DOI: 10.3389/ffunb.2021.740845 -
Journal of Fungi (Basel, Switzerland) Jul 2021The host immune response is critical in pneumonia (PCP). Immunocompetent hosts can eliminate the fungus without symptoms, while immunodeficient hosts develop PCP with... (Review)
Review
The host immune response is critical in pneumonia (PCP). Immunocompetent hosts can eliminate the fungus without symptoms, while immunodeficient hosts develop PCP with an unsuitable excessive inflammatory response leading to lung damage. From studies based on rodent models or clinical studies, this review aimed to better understand the pathophysiology of infection by analysing the role of immune cells, mostly lymphocytes, according to the immune status of the infected host. Hence, this review first describes the immune physiological response in infected immunocompetent hosts that are able to eliminate the fungus. The objective of the second part is to identify the immune elements required for the control of the fungus, focusing on specific immune deficiencies. Finally, the third part concentrates on the effect of the different immune elements in immunocompromised subjects during PCP, to better understand which cells are detrimental, and which, on the contrary, are beneficial once the disease has started. This work highlights that the immune response associated with a favourable outcome of the infection may differ according to the immune status of the host. In the case of immunocompetency, a close communication between B cells and TCD4 within tertiary lymphocyte structures appears critical to activate M2 macrophages without much inflammation. Conversely, in the case of immunodeficiency, a pro-inflammatory response including Th1 CD4, cytotoxic CD8, NK cells, and IFNγ release seems beneficial for M1 macrophage activation, despite the impact of inflammation on lung tissue.
PubMed: 34436164
DOI: 10.3390/jof7080625 -
Journal of Fungi (Basel, Switzerland) Mar 2023Trimethoprim-sulfamethoxazole (TMP-SMX) is a first-line pneumonia (PCP) prophylaxis agent, but monthly intravenous pentamidine (IVP) is used in immunocompromised hosts... (Review)
Review
BACKGROUND
Trimethoprim-sulfamethoxazole (TMP-SMX) is a first-line pneumonia (PCP) prophylaxis agent, but monthly intravenous pentamidine (IVP) is used in immunocompromised hosts without human immunodeficiency virus (HIV) infection because IVP is not associated with cytopenia and delayed engraftment.
METHOD
We performed a systematic review and meta-analysis to estimate breakthrough PCP incidence and adverse reactions in HIV-uninfected immunocompromised patients receiving IVP. MEDLINE, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched from their inception until 15 December 2022.
RESULTS
The pooled incidence of breakthrough PCP with IVP was 0.7% (95% CI, 0.3-1.4%, 16 studies, 3025 patients) and was similar when used as first-line prophylaxis (0.5%; 95% CI, 0.2-1.4%, 7 studies, 752 patients). The pooled incidence of adverse reactions was 11.3% (95% CI, 6.7-18.6%, 14 studies, 2068 patients). The pooled adverse event-related discontinuation was 3.7% (95% CI, 1.8-7.3%, 11 studies, 1802 patients), but was lower in patients receiving IVP monthly (2.0%; 95% CI 0.7-5.7%, 7 studies, 1182 patients).
CONCLUSION
Monthly IVP is an appropriate second-line agent for PCP prophylaxis in certain non-HIV immunocompromised hosts, especially in patients with hematologic malignancies and hematopoietic stem cell transplant recipients. Using IVP for PCP prophylaxis as an alternative to oral TMP-SMX while patients are unable to tolerate enteral medication administration is feasible.
PubMed: 37108861
DOI: 10.3390/jof9040406 -
Folia Parasitologica Jul 2021Pulmonary pathology is common in HIV-infected individuals, but the possible role of the parasitic protist Toxoplasma gondii (Nicolle et Manceaux, 1908) is not completely...
Pulmonary pathology is common in HIV-infected individuals, but the possible role of the parasitic protist Toxoplasma gondii (Nicolle et Manceaux, 1908) is not completely known. The present account reports result of a retrospective cohort study. Medical cards of 907 HIV-positive people, which included 120 deceased patients, were analysed. During a three-year follow-up, the pulmonary pathology was diagnosed in 306 patients (33.7 ± 1.6%): pneumocystis pneumonia in 124 (13.7 ± 1.1%), primary pulmonary tuberculosis in 113 (12.5 ± 1.1%), bacterial pneumonia in 58 (6.4 ± 0.8%) toxoplasmosis pneumonia in two (0.2 ± 0.2%), and others. All patients were divided into two cohorts: 531 individuals seropositive for T. gondii and 376 seronegative ones. It has been found out that general lung pathology is more common in patients with seropositivity to T. gondii than in seronegative ones (43.3 ± 2.2% vs. 20.1 ± 2.0%, p < 0.001). The diagnosis of pneumocystis pneumonia was made ten times more often in the cohort of seropositive patients than in the cohort of seronegative ones (21.9 ± 1.8% vs. 2.1 ± 0.7%, respectively, p < 0.001) and in deceased patients of these cohorts it was 5.5 times more (45.1 ± 5.9% vs. 8.2 ± 3.9, respectively, p < 0.001). In patients with fatal outcome and seropositivity to T. gondii, the incidences of pneumocystis pneumonia increased by 23.2% (p < 0.001) and bacterial pneumonia by 12.4% (p < 0.05), whereas in seronegative individuals only pulmonary tuberculosis increased by 13.1% (p < 0.05) сompared with corresponding whole cohorts. Pearson's contingency coefficient showed the mean strength association between infection with T. gondii and incidence of pneumocystis pneumonia both in whole cohort (C = 0.272) and in patients with fatal outcomes (C = 0.368). In сonclusion, significantly increasing rate of pneumocystis pneumonia in patients with HIV/AIDS and T. gondii infection can be caused by certain synergism between T. gondii and Pneumocystis jirovecii and in some cases overdiagnosis pneumocystis pneumonia due to undiagnosed toxoplasmosis pneumonia.
Topics: Adult; Female; HIV Infections; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Toxoplasma; Toxoplasmosis; Young Adult
PubMed: 34279242
DOI: 10.14411/fp.2021.018 -
Immunity, Inflammation and Disease Jan 2022Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in organ transplant recipients that may be prevented by antibiotic prophylaxis. We aimed to...
BACKGROUND
Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in organ transplant recipients that may be prevented by antibiotic prophylaxis. We aimed to investigate the incidence rate (IR) of PCP and the related hospitalization and mortality rates in liver transplant recipients in an era of routine prophylaxis.
METHODS
We included all adult liver transplant recipients transplanted at Rigshospitalet between January 1, 2011 and October 1, 2019. Microbiology data were obtained from the Danish Microbiology Database (MiBa), a national database containing all data from all Departments of Clinical Microbiology in Denmark receiving samples from both hospitals and general practices. According to local guidelines, PCP prophylaxis was initiated 1 week posttransplantation and discontinued after 6 months or sooner in patients experiencing side effects.
RESULTS
We included 343 liver transplant recipients with 1153 person-years of follow-up (PYFU), of which 269 (78%) received PCP prophylaxis during the first 6 months posttransplantation. Seven (2%) recipients were diagnosed with PCP during follow-up. In the first 6 months posttransplantation and in 269 transplant recipients who received prophylaxis there were zero PCP events while the IR was 32 (95% confidence interval [CI] 2.9-148) per 1000 PYFU in 74 recipient who did not receive prophylaxis. During 7th to 12th month posttransplantation the IR was 20 (95% CI: 5.5-53) per 1000 PYFU. All seven (100%) recipients diagnosed with PCP were hospitalized, however none died.
CONCLUSIONS
PCP was not detected in liver transplant recipients while on prophylaxis. Though, it worth mentioning that two out of the seven PCP patients received high-dose prednisolone before the PCP event. All liver transplant recipients with PCP were hospitalized, but none died. Randomized clinical trials to determine the optimal duration of prophylaxis are warranted.
Topics: Adult; Antibiotic Prophylaxis; Humans; Liver Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 34713963
DOI: 10.1002/iid3.546 -
The Journal of Infectious Diseases Jul 2019Glucan is the major cell wall component of Pneumocystis cysts. In the current study, we have characterized Pneumocystis Bgl2 (EC 3.2.1.58), an enzyme with...
Glucan is the major cell wall component of Pneumocystis cysts. In the current study, we have characterized Pneumocystis Bgl2 (EC 3.2.1.58), an enzyme with glucanosyltransferase and β-1,3 endoglucanase activity in other fungi. Pneumocystis murina, Pneumocystis carinii, and Pneumocystis jirovecii bgl2 complementary DNA sequences encode proteins of 437, 447, and 408 amino acids, respectively. Recombinant P. murina Bgl2 expressed in COS-1 cells demonstrated β-glucanase activity, as shown by degradation of the cell wall of Pneumocystis cysts. It also cleaved reduced laminaripentaose and transferred oligosaccharides, resulting in polymers of 6 and 7 glucan residues, demonstrating glucanosyltransferase activity. Surprisingly, confocal immunofluorescence analysis of P. murina-infected mouse lung sections using an antibody against recombinant Bgl2 showed that the native protein is localized primarily to the trophic form of Pneumocystis in both untreated mice and mice treated with caspofungin, an antifungal drug that inhibits β-1,3-glucan synthase. Thus, like other fungi, Bgl2 of Pneumocystis has both endoglucanase and glucanosyltransferase activities. Given that it is expressed primarily in trophic forms, further studies are needed to better understand its role in the biology of Pneumocystis.
Topics: Amino Acid Sequence; Animals; Antifungal Agents; CD40 Ligand; COS Cells; Caspofungin; Cell Wall; Chlorocebus aethiops; Glucan Endo-1,3-beta-D-Glucosidase; Glucans; Lung; Mice; Mice, Inbred C57BL; Mice, Knockout; Pneumocystis; Pneumonia, Pneumocystis; Recombinant Proteins; Sequence Alignment
PubMed: 31100118
DOI: 10.1093/infdis/jiz172 -
PloS One 2021Pneumocystis jirovecii pneumonia (PCP) is a fatal respiratory infection, mostly associated with immunocompromised conditions. Several reports have described PCP...
OBJECTIVE
Pneumocystis jirovecii pneumonia (PCP) is a fatal respiratory infection, mostly associated with immunocompromised conditions. Several reports have described PCP development in patients who were not immunocompromised, but the clinical course and prognosis of PCP are not well understood. We compared the clinical characteristics and prognoses between patients with and without immunocompromised conditions who developed PCP.
METHODS
We retrospectively analyzed patients who had been treated for PCP from three hospitals. We defined immunocompromised (IC) status as following: human immunodeficiency virus (HIV) infection; hematological malignancy; solid organ tumor under chemotherapy; rheumatic disease; medication with immunosuppressive agents. Patients without immunocompromised status were defined as being non-immunocompromised (non-IC).
RESULTS
The IC and non-IC groups comprised 173 and 14 patients. The median ages were 62.0 and 74.0 years in the IC and the non-IC group, respectively. The median interval between admission and anti-PCP treatment was significantly longer for patients in the non-IC group than that for patients in the IC group (7 vs. 2 days). The in-hospital mortality rates were significantly higher for patients in the non-IC group than that for patients in the IC group (71.4% vs. 43.9%; P = 0.047). A longer interval between admission and anti-PCP therapy was associated with increased 90-day mortality rate in patients with PCP (hazard ratio, 1.082; 95% confidence interval, 1.015-1.153; P = 0.016).
CONCLUSIONS
Patients with PCP with no predisposing illnesses were older and had higher mortality rates than IC patients with PCP. Delayed anti-PCP treatment was associated with increased 90-day mortality.
Topics: Aged; Female; Hospital Mortality; Humans; Immunocompromised Host; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Prognosis; Proportional Hazards Models; Republic of Korea; Retrospective Studies
PubMed: 33539407
DOI: 10.1371/journal.pone.0246296