-
Journal of Infection and Chemotherapy :... Feb 2024The development of pneumocystis pneumonia (PCP) has recently become a growing concern; thus, its prevention has become increasingly important....
Sulfamethoxazole-trimethoprim for pneumocystis pneumonia prophylaxis, causes of discontinuation and thrombocytopenia observed during administration: A single-center retrospective study.
INTRODUCTION
The development of pneumocystis pneumonia (PCP) has recently become a growing concern; thus, its prevention has become increasingly important. Sulfamethoxazole-trimethoprim (ST) is a cost-effective first-line and prophylactic treatment for PCP. However, ST administration criteria for PCP prophylaxis remain unclear and are often discontinued because of adverse events (AEs). In this study, we aimed to investigate the causes of ST discontinuation and the associated AEs using objective data.
METHODS
We retrospectively analyzed the data of 162 patients admitted to Kansai Medical University Hospital between January 2018 and December 2020, who received ST for PCP prophylaxis. We compared clinical characteristics, laboratory data, and incidence of AEs between ST non-discontinuation and ST discontinuation groups. Additionally, we divided the patients into non-developing and developing thrombocytopenia (≥ Grade 1) groups based on the investigation results.
RESULTS
No patients developed PCP while receiving ST. The most common causes of ST discontinuation were thrombocytopenia (37%), liver dysfunction (20%), and rash (18%). Multivariate analysis revealed thrombocytopenia (≥ Grade 1) as a factor significantly associated with ST discontinuation. Furthermore, we identified three factors correlated with thrombocytopenia (≥ Grade 1): age ≥50 years, lymphocyte count <1000/μL, and platelet count <180,000/μL.
CONCLUSIONS
Patients with the aforementioned factors are at higher risk of developing thrombocytopenia (≥ Grade 1) during ST administration for PCP prophylaxis. Therefore, platelet count monitoring is essential to enhance safety and efficacy of ST treatment. Nonetheless, further research is warranted to explore additional implications and interventions.
Topics: Humans; Middle Aged; Retrospective Studies; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Thrombocytopenia
PubMed: 37797822
DOI: 10.1016/j.jiac.2023.09.030 -
The American Journal of Case Reports Sep 2023BACKGROUND Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a form of vasculitis predominantly affecting small blood vessels and systemic...
BACKGROUND Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a form of vasculitis predominantly affecting small blood vessels and systemic organs, including the lungs and kidneys. The serum ANCA is an important diagnostic marker for AAV. However, ANCA levels can be nonspecifically elevated in autoimmune diseases like rheumatoid arthritis (RA) and some infectious diseases. Furthermore, RA and AAV can occur together. Therefore, when ANCA is detected in patients with RA, interpretation of the results is often difficult. CASE REPORT A 71-year-old woman with a 15-year history of RA was admitted to our hospital with a fever and anorexia. She was treated with prednisolone 5 mg/day and iguratimod 50 mg/day for the RA. She presented with bilateral frosted glass shadows in the lungs, acute kidney injury, positive myeloperoxidase (MPO)-ANCA results, and elevated ß-D-glucan levels, suggesting AAV or pneumocystis pneumonia. A renal biopsy and bronchoalveolar lavage ruled out AAV. A polymerase chain reaction of the bronchoalveolar lavage fluid was positive for Pneumocystis jirovecii DNA, leading to a diagnosis of pneumocystis pneumonia. After admission, the patient continued to receive intravenous supplemental fluids, and renal function improved. Based on her pathological test results and clinical course, acute kidney injury was diagnosed as prerenal failure due to dehydration in the background of chronic kidney disease. CONCLUSIONS Even if MPO-ANCA is positive in patients with RA, it is important to consider the possibility of a false-positive result and perform a thorough and aggressive examination.
Topics: Female; Humans; Aged; Antibodies, Antineutrophil Cytoplasmic; Peroxidase; Pneumonia, Pneumocystis; Arthritis, Rheumatoid; Acute Kidney Injury; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
PubMed: 37752696
DOI: 10.12659/AJCR.941306 -
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 -
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 -
Cancer Reports (Hoboken, N.J.) Oct 2023CD19-targeted chimeric antigen receptor (CAR)-T cell therapy involves administration of patient-derived T cells that target B cells, resulting in B-cell depletion and... (Review)
Review
Pneumocystis jirovecii pneumonia after CD4+ T-cell recovery subsequent to CD19-targeted chimeric antigen receptor T-cell therapy: A case report and brief review of literature.
BACKGROUND
CD19-targeted chimeric antigen receptor (CAR)-T cell therapy involves administration of patient-derived T cells that target B cells, resulting in B-cell depletion and aplasia. In immunity against Pneumocystis jirovecii (Pj), CD4+ T cells and, more recently, B cells, are generally considered important. Antigen presentation by B cells to CD4+ T cells is particularly important. Trimethoprim-sulfamethoxazole (TMP/SMX) for Pj pneumonia (PJP) prophylaxis is generally discontinued when the CD4+ T-cell count is >200/μL. Here we report the first case, to our knowledge, of PJP in a patient with a CD4+ T cell count of >200/μL after CAR-T cell therapy.
CASE
A 14-year-old girl developed hemophagocytic lymphohistiocytosis (HLH) after cord blood transplantation (CBT) for relapsed precursor B-cell acute lymphoblastic leukemia (B-ALL). Twenty-one months after CBT, she was diagnosed with combined second relapse in the bone marrow and central nervous system. The patient was treated with CD19-targeted CAR-T cell therapy for the relapse. After CAR-T cell therapy, the patient remained in remission and continued to receive TMP/SMX for PJP prophylaxis. Seven months after CAR-T cell therapy, CD4+ T cells recovered and TMP/SMX was discontinued. The B-cell aplasia persisted. Ten months after CAR-T cell therapy, the patient developed PJP. The patient was also considered to have macrophage hyperactivation at the onset of PJP. Treatment with immunoglobulin, TMP/SMX, and prednisolone was initiated, and the patient's symptoms rapidly ameliorated.
CONCLUSION
The patient in the present case developed PJP despite a CD4+ T-cell count of >200/μL after CAR-T cell therapy, probably because of inadequate CD4+ T-cell activation caused by B-cell depletion after CAR-T cell therapy and repeated abnormal macrophage immune responses after CBT. It is important to determine the duration of TMP/SMX for prophylaxis after CAR-T cell therapy according to each case, as well as the CD4+ T-cell count.
Topics: Female; Humans; Adolescent; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Receptors, Chimeric Antigen; CD4-Positive T-Lymphocytes; Retrospective Studies; Recurrence; Cell- and Tissue-Based Therapy
PubMed: 37563749
DOI: 10.1002/cnr2.1885 -
International Journal of Molecular... Mar 2024Inflammation and mucus production are prevalent characteristics of chronic respiratory conditions, such as asthma and chronic chronic obstructive pulmonary disease...
Inflammation and mucus production are prevalent characteristics of chronic respiratory conditions, such as asthma and chronic chronic obstructive pulmonary disease (COPD). Biological co-factors, including bacteria, viruses, and fungi, may exacerbate these diseases by activating various pathways associated with airway diseases. An example is the fungus , which is linked to severe COPD in human patients. Recent evidence has demonstrated that significantly enhanced inflammation and mucus hypersecretion in a rat model of elastase-induced COPD. The present study specifically aims to investigate two additional aspects associated with the pathology induced by infection: inflammation and collagen deposition around airways. To this end, the focus was to investigate the role of the IL-1β pro-inflammatory pathway during infection in COPD rats. Several airway pathology-related features, such as inflammation, mucus hypersecretion, and fibrosis, were evaluated using histological and molecular techniques. COPD animals infected with exhibited elevated inflammation levels, including a synergistic increase in IL-1β and Cox-2. Furthermore, protein levels of the IL-1β-dependent transcription factor cAMP response element-binding (CREB) showed a synergistic elevation of their phosphorylated version in the lungs of COPD animals infected with , while mucus levels were notably higher in the airways of COPD-infected animals. Interestingly, a CREB responsive element (CRE) was identified in the Muc5b promoter. The presence of CREB in the Muc5b promoter was synergistically increased in COPD animals infected with compared to other experimental groups. Finally, an increment of deposited collagen was identified surrounding the airways of COPD animals infected with compared with the other experimental animal groups and correlated with the increase of mRNA levels. These findings emphasize the role of as a potential biological co-factor in chronic respiratory diseases like COPD or asthma, warranting new perspectives in the treatment of chronic respiratory diseases.
Topics: Humans; Rats; Animals; Pneumocystis; Pancreatic Elastase; Pulmonary Disease, Chronic Obstructive; Lung; Asthma; Pneumonia, Pneumocystis; Mucus; Inflammation; Collagen
PubMed: 38542124
DOI: 10.3390/ijms25063150 -
IDCases 2023Trimethoprim-sulfamethoxazole (TMP-SMX), also referred to as co-trimazole, is a common antibiotic used to treat a wide range of infections ranging from simple skin and...
Trimethoprim-sulfamethoxazole (TMP-SMX), also referred to as co-trimazole, is a common antibiotic used to treat a wide range of infections ranging from simple skin and soft tissue infections to opportunistic infections such as Pneumocystis jirovecii. Generally, this medication is well-tolerated, but severe adverse reactions, such as myelosuppression and hepatitis, can occur, albeit rarely. In this case report, we describe a patient who presented to the hospital with symptoms of rash, elevated liver enzymes, thrombocytopenia, and acute kidney injury 2 weeks after completing a course of TMP-SMX for a skin infection. We highlight the difficulties in diagnosing adverse events associated with this drug due to the variability in its presentation and the unpredictable onset of symptoms. By excluding common differential diagnoses including thrombotic thrombocytopenic purpura (TTP) and glucose-6-phosphate- dehydrogenase (G6PD) deficiency, we concluded that the patient was suffering from TMP-SMX-induced multi-organ dysfunction and treated him supportively. Through this case report, we aim to elucidate the importance of early recognition and treatment of the adverse effects of TMP-SMX.
PubMed: 37954169
DOI: 10.1016/j.idcr.2023.e01917 -
The World Allergy Organization Journal Jan 2024Trimethoprim-sulfamethoxazole (TMP-SMX) is a broad spectrum antibiotic in use for more than 50 years. It has an important indication as first line agent in the... (Review)
Review
Trimethoprim-sulfamethoxazole (TMP-SMX) is a broad spectrum antibiotic in use for more than 50 years. It has an important indication as first line agent in the prophylaxis of opportunistic infections, particularly pneumonia (PJP), in immunosuppressed patients. For those who have a history of allergy or severe intolerance to TMP-SMX, pentamidine, dapsone or atovaquone may be substituted; however there is evidence that TMP-SMX offers superior coverage for PJP, toxoplasmosis, and nocardiosis. Compared to pentamidine, it has the added benefit of cost-effectiveness and self-administration as opposed to required hospital attendance for administration. Many patients who report a history of allergy or adverse reaction to TMP-SMX (or "sulfur allergy") will be found not to be allergic; and even those who are allergic may be able to be desensitized. The evaluation and, where appropriate, removal of TMP-SMX allergy label enables the use of TMP-SMX for prophylaxis against opportunistic infections. This is a cost-effective intervention to optimize antimicrobial prescribing and reduce the risk of opportunistic infections in immunosuppressed patients.
PubMed: 38235260
DOI: 10.1016/j.waojou.2023.100856 -
Infection and Drug Resistance 2024To investigate the value of metagenomic Next-Generation Sequencing (mNGS) in diagnosing pneumonia (PJP) in non-human immunodeficiency virus (HIV)-infected patients.
OBJECTIVE
To investigate the value of metagenomic Next-Generation Sequencing (mNGS) in diagnosing pneumonia (PJP) in non-human immunodeficiency virus (HIV)-infected patients.
METHODS
In this retrospective study, non-HIV-infected patients with PJP and those diagnosed with non-PJP from August 2022 to December 2024 were selected as subjects. The presence of (PJ) and other co-pathogens in bronchoalveolar lavage fluid (BALF) was analyzed, and the diagnostic efficacy of NGS, polymerase chain reaction (PCR) and serum 1,3-β-D-glucan (BDG) in PJP was compared with the reference standard of clinical compound diagnosis.
RESULTS
Eighty-nine non-HIV-infected patients were recruited, with dyspnea as the primary symptom (69.66%) and solid malignant tumor as the most common underlying disease (20.22%). Taking clinical compound diagnosis as the reference standard, the sensitivity, specificity, negative predictive value and positive predictive value of mNGS were higher than those detected by PCR and serum BDG. Among 42 non-HIV-infected patients with PJP who underwent mNGS and conventional pathogen detection of BALF, 6 had simple PJ infection and 36 had combined PJ infection. The detection rate of mNGS in mixed infections was significantly higher than that of conventional pathogen detection (85.71 vs 61.70%, = 0.012). A total of 127 pathogens were detected in BALF using mNGS, among which fungi had the highest detection rate (46.46%). The fungi, viruses and bacteria detected were mainly , human gammaherpesvirus 4 and .
CONCLUSION
mNGS is highly effective in diagnosing non-HIV-infected patients with PJP and exhibits ideal performance in the detection of co-pathogens. In addition, it has certain value for clinical diagnosis and guidance of targeted anti-infective drug treatment.
PubMed: 38628239
DOI: 10.2147/IDR.S450878 -
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