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Clinical Microbiology and Infection :... Jul 2024Pneumocystis jirovecii pneumonia (PCP) is a common opportunistic infection among people living with HIV (PWH), particularly among new and untreated cases. Several... (Meta-Analysis)
Meta-Analysis Comparative Study Review
Comparative efficacy and safety of Pneumocystis jirovecii pneumonia prophylaxis regimens for people living with HIV: a systematic review and network meta-analysis of randomized controlled trials.
BACKGROUND
Pneumocystis jirovecii pneumonia (PCP) is a common opportunistic infection among people living with HIV (PWH), particularly among new and untreated cases. Several regimens are available for the prophylaxis of PCP, including trimethoprim-sulfamethoxazole (TMP-SMX), dapsone-based regimens (DBRs), aerosolized pentamidine (AP), and atovaquone.
OBJECTIVES
To compare the efficacy and safety of PCP prophylaxis regimens in PWH by network meta-analysis.
METHODS
DATA SOURCES: Embase, MEDLINE, and CENTRAL from inception to June 21, 2023.
STUDY ELIGIBILITY CRITERIA
Comparative randomized controlled trials (RCTs).
PARTICIPANTS
PWH.
INTERVENTIONS
Regimens for PCP prophylaxis either compared head-to-head or versus no treatment/placebo.
ASSESSMENT OF RISK OF BIAS
Cochrane risk-of-bias tool for RCTs 2.
METHODS OF DATA SYNTHESIS
Title or abstract and full-text screening and data extraction were performed in duplicate by two independent reviewers. Data on PCP incidence, all-cause mortality, and discontinuation due to toxicity were pooled and ranked by network meta-analysis. Subgroup analyses of primary versus secondary prophylaxis, by year, and by dosage were performed.
RESULTS
A total of 26 RCTs, comprising 55 treatment arms involving 7516 PWH were included. For the prevention of PCP, TMP-SMX was ranked the most favourable agent and was superior to DBRs (risk ratio [RR] = 0.54; 95% CI, 0.36-0.83) and AP (RR = 0.53; 95% CI, 0.36-0.77). TMP-SMX was also the only agent with a mortality benefit compared with no treatment/placebo (RR = 0.79; 95% CI, 0.64-0.98). However, TMP-SMX was also ranked as the most toxic agent with a greater risk of discontinuation than DBRs (RR = 1.25; 95% CI, 1.01-1.54) and AP (7.20; 95% CI, 5.37-9.66). No significant differences in PCP prevention or mortality were detected among the other regimens. The findings remained consistent within subgroups.
CONCLUSIONS
TMP-SMX is the most effective agent for PCP prophylaxis in PWH and the only agent to confer a mortality benefit; consequently, it should continue to be recommended as the first-line agent. Further studies are necessary to determine the optimal dosing of TMP-SMX to maximize efficacy and minimize toxicity.
Topics: Humans; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Network Meta-Analysis; Trimethoprim, Sulfamethoxazole Drug Combination; Pneumocystis carinii; HIV Infections; AIDS-Related Opportunistic Infections; Dapsone; Pentamidine; Atovaquone; Antifungal Agents; Treatment Outcome
PubMed: 38583518
DOI: 10.1016/j.cmi.2024.03.037 -
Pneumonia (Nathan Qld.) Apr 2024Leprosy reactions often require prolonged high-dose steroids or immunosuppressive drugs, putting patients at risk of Pneumocystis jirovecii pneumonia (PJP). However, no...
Leprosy reactions often require prolonged high-dose steroids or immunosuppressive drugs, putting patients at risk of Pneumocystis jirovecii pneumonia (PJP). However, no PJP cases are reported, possibly due to dapsone treatment for leprosy. In patients with leprosy reactions not receiving dapsone because of toxicity or resistance and requiring long-term immunosuppression, PJP prophylaxis should be considered.
PubMed: 38576014
DOI: 10.1186/s41479-024-00127-x -
Monaldi Archives For Chest Disease =... Apr 2024In this study, we compared the predisposing factors, key demographic and clinical characteristics, clinical outcomes, and factors associated with poor prognosis in...
In this study, we compared the predisposing factors, key demographic and clinical characteristics, clinical outcomes, and factors associated with poor prognosis in pneumocystis pneumonia (PCP) infection among the human immunodeficiency virus (HIV)-positive and non-HIV patient populations. This retrospective analysis was conducted at the Aga Khan University Hospital, Karachi, via the collection and analysis of patient records with a diagnosis of "pneumocystosis" between January 2015 and October 2020. Additionally, the laboratory database was evaluated, and patients with a laboratory-confirmed diagnosis of PCP were included. During the study period, 52 laboratory-confirmed hospitalized PCP patients were identified. Of these, 23 and 29 patients were diagnosed using microscopy and polymerase chain reaction, respectively. 34.6% of our patients were HIV positive, with a median CD4 count of 20.5 cells/mm3 (range: 10.7-50.5). Other conditions identified were corticosteroid use, autoimmune diseases, malignancy, radiation, and chemotherapy. On chest imaging, consolidation was found in 30%, ground-glass opacities in 24%, and nodular infiltrates in 20% of the cases. HIV-positive patients had a lower hemoglobin level and a higher level of β-D-glucan at the time of admission, whereas non-HIV patients were found to have more co-morbid conditions than HIV patients. We observed no difference in clinical outcomes between the two populations. Factors associated with a poor prognosis among our patients included concomitant infections at the time of diagnosis, the need for invasive mechanical ventilation, and a longer duration of stay in the hospital as well as the intensive care unit.
PubMed: 38572694
DOI: 10.4081/monaldi.2024.2810 -
Cleveland Clinic Journal of Medicine Apr 2024
Topics: Humans; Pneumonia, Pneumocystis; Adrenal Cortex Hormones
PubMed: 38561210
DOI: 10.3949/ccjm.91a.23082 -
ACG Case Reports Journal Apr 2024is an opportunistic fungus typically causing pulmonary infection in immunocompromised persons. We present a case of pneumonia (PJP) in a patient with alcoholic...
is an opportunistic fungus typically causing pulmonary infection in immunocompromised persons. We present a case of pneumonia (PJP) in a patient with alcoholic hepatitis and underlying cirrhosis. PJP in patients with alcoholic hepatitis or cirrhosis is sparsely reported in literature. This condition carries a poor prognosis and high mortality. Clinicians need to recognize alcohol use resulting in liver damage as a significant etiological risk factor for PJP.
PubMed: 38560014
DOI: 10.14309/crj.0000000000001316 -
Viruses Feb 2024The frequency of respiratory viruses in people living with HIV (PLHIV) and their impact on lung function remain unclear. We aimed to determine the frequency of...
The frequency of respiratory viruses in people living with HIV (PLHIV) and their impact on lung function remain unclear. We aimed to determine the frequency of respiratory viruses in bronchoalveolar lavage and induced sputum samples in PLHIV and correlate their presence with lung function. A prospective cohort of adults hospitalized in Medellín between September 2016 and December 2018 included three groups: group 1 = people diagnosed with HIV and a diagnosis of community-acquired pneumonia (CAP), group 2 = HIV, and group 3 = CAP. People were followed up with at months 1, 6, and 12. Clinical, microbiological, and spirometric data were collected. Respiratory viruses were detected by multiplex RT-PCR. Sixty-five patients were included. At least 1 respiratory virus was identified in 51.9%, 45.1%, and 57.1% of groups 1, 2 and 3, respectively. Among these, 89% of respiratory viruses were detected with another pathogen, mainly (40.7%) and (22.2%). The most frequent respiratory virus was rhinovirus (24/65, 37%). On admission, 30.4% of group 1, 16.6% of group 2, and 50% of group 3 had airflow limitation, with alteration in forced expiratory volume at first second in both groups with pneumonia compared to HIV. Respiratory viruses are frequent in people diagnosed with HIV, generally coexisting with other pathogens. Pulmonary function on admission was affected in patients with pneumonia, improving significantly in the 1st, 6th, and 12th months after CAP onset.
Topics: Adult; Humans; Prospective Studies; Follow-Up Studies; Pneumonia; Viruses; Lung; HIV Infections
PubMed: 38543710
DOI: 10.3390/v16030344 -
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 -
Journal of Fungi (Basel, Switzerland) Mar 2024Pet dogs are a valuable natural animal model for studying relationships between primary immunodeficiencies and susceptibility to and other opportunistic respiratory...
Pet dogs are a valuable natural animal model for studying relationships between primary immunodeficiencies and susceptibility to and other opportunistic respiratory pathogens. Certain breeds, such as the Cavalier King Charles Spaniel, are over-represented for pneumonia (PCP), suggesting the presence of a primary immunodeficiency in the breed. Here, we report the discovery of a nonsense variant in three Cavalier King Charles Spaniel dogs with either PCP (n = 2) or refractory pneumonia (n = 1). encodes a protein that plays critical roles in T-cell activation and other aspects of immune function. Deleterious variants have recently been reported in human patients with PCP and other recurrent pneumonias. In addition to opportunistic respiratory infection, the affected dogs also exhibited other clinical manifestations of CARMIL2 deficiencies that have been reported in humans, including early-onset gastrointestinal disease, allergic skin disease, mucocutaneous lesions, abscesses, autoimmune disorders, and gastrointestinal parasitism. This discovery highlights the potential utility of a natural canine model in identifying and studying primary immunodeficiencies in patients affected by PCP.
PubMed: 38535207
DOI: 10.3390/jof10030198 -
Medical Mycology Case Reports Mar 2024is a type of endophytic fungus that parasitizes monocotyledonous plants. Cases of humans and other mammals being infected by are very rare around the world. We report...
is a type of endophytic fungus that parasitizes monocotyledonous plants. Cases of humans and other mammals being infected by are very rare around the world. We report the first case of subcutaneous mycosis caused by in China. A kidney transplant recipient was admitted for pneumonia and subsequently developed left calf redness and swelling due to a infection. The patient was treated with sulfamethoxazole and voriconazole and underwent five surgical debridements and vacuum sealing drainage (VSD) applications with the left leg. The patient was eventually cured and discharged from the hospital.
PubMed: 38533460
DOI: 10.1016/j.mmcr.2023.100620 -
British Journal of Haematology Jun 2024Pneumocystis jirovecii can cause life-threatening pneumonia (PjP), and patients with haematological malignancies are at high risk of this infection. Prophylactic... (Randomized Controlled Trial)
Randomized Controlled Trial
Pneumocystis jirovecii can cause life-threatening pneumonia (PjP), and patients with haematological malignancies are at high risk of this infection. Prophylactic measures have significantly decreased morbidity and mortality, but there is a paucity of contemporary data on the incidence and clinical course of PjP in well-defined and homogenous patient populations, such as children suffering from acute lymphoblastic leukaemia (ALL). In the multi-international trial AIEOP-BFM ALL2009, PjP was diagnosed in six children (incidence 1/1000) and was associated with insufficient prophylaxis in five of them. Although none of the patients died of PjP, the long-term impact of the infection is unclear.
Topics: Humans; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Child; Pneumocystis carinii; Male; Female; Child, Preschool; Antineoplastic Combined Chemotherapy Protocols; Adolescent; Incidence
PubMed: 38527954
DOI: 10.1111/bjh.19382