-
Journal of Epidemiology and Global... Jun 2023Recurrent urinary tract infection (UTI) occurs in sizable percentages of patients after a single episode and is a frequent cause of primary healthcare visits and...
BACKGROUND
Recurrent urinary tract infection (UTI) occurs in sizable percentages of patients after a single episode and is a frequent cause of primary healthcare visits and hospital admissions, accounting for up to one quarter of emergency department visits. We aim to describe the pattern of continuous antibiotic prophylaxis prescription for recurrent urinary tract infections, in what group of adult patients they are prescribed and their efficacy.
METHODS
A retrospective chart review of all adult patients diagnosed with single and recurrent symptomatic urinary tract infection in the period of January 2016 to December 2018.
RESULTS
A total of 250 patients with a single UTI episode and 227 patients with recurrent UTI episodes were included. Risk factors for recurrent UTI included diabetes mellitus, chronic renal disease, and use of immunosuppressive drugs, renal transplant, any form of urinary tract catheterization, immobilization and neurogenic bladder. E. coli infections were the most prevalent organism in patients with UTI episodes. Prophylactic antibiotics were given to 55% of patients with UTIs, Nitrofurantoin, Bactrim or amoxicillin clavulanic acid. Post renal transplant is the most frequent reason to prophylaxis antibiotics (44%). Bactrim was more prescribed in younger patients (P < 0.001), in post-renal transplantation (P < 0.001) and after urological procedures (P < 0.001), while Nitrofurantoin was more prescribed in immobilized patients (P = 0.002) and in patients with neurogenic bladder (P < 0.001). Patients who received continuous prophylactic antibiotics experienced significantly less episodes of urinary tract infections (P < 0.001), emergency room visits and hospital admissions due to urinary tract infections (P < 0.001).
CONCLUSION
Despite being effective in reducing recurrent urinary tract infection rate, emergency room visits and hospital admissions due to UTI, continuous antibiotic prophylaxis was only used in 55% of patients with recurrent infections. Trimethoprim/sulfamethoxazole was the most frequently used prophylactic antibiotic. Urology and gynecological referral were infrequently requested as part of the evaluation process for patients with recurrent UTI. There was a lack of use of other interventions such as topical estrogen in postmenopausal women and documentation of education on non-pharmacological methods to decrease urinary tract infections.
Topics: Humans; Adult; Female; Antibiotic Prophylaxis; Nitrofurantoin; Trimethoprim, Sulfamethoxazole Drug Combination; Escherichia coli; Retrospective Studies; Urinary Bladder, Neurogenic; Urinary Tract Infections; Anti-Bacterial Agents; Escherichia coli Infections; Risk Factors
PubMed: 37273158
DOI: 10.1007/s44197-023-00105-4 -
Chest Jan 2024Trimethoprim-sulfamethoxazole (TMP-SMX) is an effective treatment for Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients with and without HIV... (Observational Study)
Observational Study
Low-Dose vs Conventional-Dose Trimethoprim-Sulfamethoxazole Treatment for Pneumocystis Pneumonia in Patients Not Infected With HIV: A Multicenter, Retrospective Observational Cohort Study.
BACKGROUND
Trimethoprim-sulfamethoxazole (TMP-SMX) is an effective treatment for Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients with and without HIV infection; however, a high incidence of adverse events has been observed. Low-dose TMP-SMX is a potentially effective treatment with fewer adverse events; however, evidence is limited.
RESEARCH QUESTION
What is the efficacy and safety of low-dose TMP-SMX for non-HIV PCP compared with conventional-dose TMP-SMX after adjusting for patient background characteristics?
STUDY DESIGN AND METHODS
In this multicenter retrospective cohort study, we included patients diagnosed with non-HIV PCP and treated with TMP-SMX between June 2006 and March 2021 at three institutions. The patients were classified into low-dose (TMP < 12.5 mg/kg/d) and conventional-dose (TMP 12.5-20 mg/kg/d) groups. The primary end point was 30-day mortality, and the secondary end points were 180-day mortality, adverse events grade 3 or higher per the Common Terminology Criteria for Adverse Events v5.0, and initial treatment completion rates. Background characteristics were adjusted using the overlap weighting method with propensity scores.
RESULTS
Fifty-five patients in the low-dose group and 81 in the conventional-dose group were evaluated. In the overall cohort, the average age was 70.7 years, and the proportion of women was 55.1%. The average dose of TMP-SMX was 8.71 mg/kg/d in the low-dose group and 17.78 mg/kg/d in the conventional-dose group. There was no significant difference in 30-day mortality (6.7% vs 18.4%, respectively; P = .080) or 180-day mortality (14.6% vs 26.1%, respectively; P = .141) after adjusting for patient background characteristics. The incidence of adverse events, especially nausea and hyponatremia, was significantly lower in the low-dose group (29.8% vs 59.0%, respectively; P = .005). The initial treatment completion rates were 43.3% and 29.6% in the low-dose and conventional-dose groups (P = .158), respectively.
INTERPRETATION
Survival was similar between the low-dose and conventional-dose TMP-SMX groups, and low-dose TMP-SMX was associated with reduced adverse events in patients with non-HIV PCP.
Topics: Humans; Female; Aged; Trimethoprim, Sulfamethoxazole Drug Combination; Pneumonia, Pneumocystis; Retrospective Studies; HIV Infections; Treatment Outcome
PubMed: 37574166
DOI: 10.1016/j.chest.2023.08.009 -
The Brazilian Journal of Infectious... 2023Nocardiosis is a rare bacterial infection caused by Nocardia spp. However, an increasing incidence has been described whereby data about epidemiology and prognosis are... (Review)
Review
INTRODUCTION
Nocardiosis is a rare bacterial infection caused by Nocardia spp. However, an increasing incidence has been described whereby data about epidemiology and prognosis are essential.
METHODS
A retrospective descriptive study was conducted among patients with positive Nocardia spp. culture, from January 2019 to January 2023, at a Terciary Hospital in Portugal.
RESULTS
Nocardiosis was considered in 18 cases with a median age of 63.8-years-old. At least one immunosuppressive cause was identified in 70% of patients. Five patients had Disseminated Nocardiosis (DN). The lung was the most common site of clinical disease (77.8%) and Nocardia was most commonly identified in respiratory tract samples. The most frequently isolated species were Nocardia nova/africana (n = 7) followed by Nocardia cyriacigeorgica (n = 3) and Nocardia pseudobrasiliensis (n = 3). The majority of the patients (94.4%) received antibiotic therapy, of whom as many as 55.6% were treated with monotherapy. The most frequently prescribed antibiotic was trimethoprim-sulfamethoxazole. Selected antimicrobial agents were generally effective, with linezolid and cotrimoxazole (100% Susceptibility [S]) and amikacin (94% S) having the most activity against Nocardia species. The median (IQR) duration of treatment was 24.2 (1‒51.4) weeks for DN; The overall one-year case fatality was 33.3% (n = 6) and was higher in the DN (66.7%). No recurrence was observed.
CONCLUSION
Nocardiosis is an emerging infectious disease with a poor prognosis, particularly in DN. This review offers essential epidemiological insights and underscores the importance of gaining a better understanding of the microbiology of nocardiosis. Such knowledge can lead to the optimization of antimicrobial therapy and, when necessary, guide appropriate surgical interventions to prevent unfavorable outcomes.
Topics: Humans; Middle Aged; Retrospective Studies; Nocardia; Nocardia Infections; Anti-Bacterial Agents; Trimethoprim, Sulfamethoxazole Drug Combination; Anti-Infective Agents
PubMed: 37802128
DOI: 10.1016/j.bjid.2023.102806 -
Microorganisms Sep 2023Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by a defect in the phagocytic function of the innate immune system owing to mutations in genes... (Review)
Review
Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by a defect in the phagocytic function of the innate immune system owing to mutations in genes encoding the five subunits of the nicotinamide adenine dinucleotide phosphatase (NADPH) oxidase enzyme complex. This review aimed to provide a comprehensive approach to the pathogens associated with chronic granulomatous disease (CGD) and its management. Patients with CGD, often children, have recurrent life-threatening infections and may develop infectious or inflammatory complications. The most common microorganisms observed in the patients with CGD are , spp., spp., spp., spp., spp., and spp. Antibacterial prophylaxis with trimethoprim-sulfamethoxazole, antifungal prophylaxis usually with itraconazole, and interferon gamma immunotherapy have been successfully used in reducing infection in CGD. Haematopoietic stem cell transplantation (HCT) have been successfully proven to be the treatment of choice in patients with CGD.
PubMed: 37764077
DOI: 10.3390/microorganisms11092233 -
Critical Care Medicine Dec 2023Trimethoprim-sulfamethoxazole (TMP-SMX)-associated severe acute respiratory distress syndrome (ARDS) has gone underrecognized. We propose the first disease definition...
OBJECTIVES
Trimethoprim-sulfamethoxazole (TMP-SMX)-associated severe acute respiratory distress syndrome (ARDS) has gone underrecognized. We propose the first disease definition and clinical evaluation for a novel adverse drug reaction (ADR) based on a series of recently identified rare cases of life-threatening ADRs.
DESIGN
A retrospective study was conducted. All medical records were evaluated. Available pathology samples were sent to Massachusetts General for clinical consultation. Blood samples from surviving patients were obtained and human leukocyte antigen (HLA) analysis was performed by the Children's Mercy Hospital Genomic Center and Vanderbilt University Medical Center.
SETTING
U.S. ICUs, 1996-2021.
PATIENTS
Nineteen young patients (10-37) were identified. Patients were previously healthy, with no preexisting pulmonary disease, no other cause for respiratory failure, and no chronic history of smoking/vaping.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
Through our retrospective analysis, we analyzed clinical characteristics associated with TMP-SMX. Pathology samples were reviewed, and HLA analysis was performed on available samples by the study team or as standard of care at treatment hospitals in some cases. In 19 critically ill patients, we identified a pattern of severe respiratory failure requiring ICU admission, mechanical ventilation, and frequent extracorporeal membrane oxygenation use. We describe the first three-part clinical diagnosis and evaluation strategy: 1) Clinical definition: Unexplained severe respiratory failure in a patient receiving greater than or equal to 6 days of TMP-SMX at treatment dose (not prophylaxis). TMP-SMX ARDS is a diagnosis of exclusion. 2) Genetic association: One hundred percent of currently available TMP-SMX respiratory failure patient genomic data, ( n = 11) have been carriers of both HLA-B*07:02 and HLA-C*07:02 alleles. HLA allele evaluation could be considered in patients with suspected TMP-SMX respiratory failure. 3) Lung pathology: A unique pulmonary pathologic pattern of lung injury termed diffuse alveolar injury with delayed epithelialization has been observed in these cases. In suspected cases, surgical lung biopsy early in the clinical course could be considered.
CONCLUSIONS
TMP-SMX is a commonly prescribed antibiotic. However, we find it imperative to share this relatively rare but life-threatening condition with clinicians as the mortality rate approaches 40%.
Topics: Child; Humans; Trimethoprim, Sulfamethoxazole Drug Combination; Retrospective Studies; Anti-Bacterial Agents; Respiratory Distress Syndrome; Respiratory Insufficiency
PubMed: 37449964
DOI: 10.1097/CCM.0000000000006002 -
Nature Communications Nov 2023Temporal control of protein levels in cells and living animals can be used to improve our understanding of protein function. In addition, control of engineered proteins...
Temporal control of protein levels in cells and living animals can be used to improve our understanding of protein function. In addition, control of engineered proteins could be used in therapeutic applications. PRoteolysis-TArgeting Chimeras (PROTACs) have emerged as a small-molecule-driven strategy to achieve rapid, post-translational regulation of protein abundance via recruitment of an E3 ligase to the target protein of interest. Here, we develop several PROTAC molecules by covalently linking the antibiotic trimethoprim (TMP) to pomalidomide, a ligand for the E3 ligase, Cereblon. These molecules induce degradation of proteins of interest (POIs) genetically fused to a small protein domain, E. coli dihydrofolate reductase (eDHFR), the molecular target of TMP. We show that various eDHFR-tagged proteins can be robustly degraded to 95% of maximum expression with PROTAC molecule 7c. Moreover, TMP-based PROTACs minimally affect the expression of immunomodulatory imide drug (IMiD)-sensitive neosubstrates using proteomic and biochemical assays. Finally, we show multiplexed regulation with another known degron-PROTAC pair, as well as reversible protein regulation in a rodent model of metastatic cancer, demonstrating the formidable strength of this system. Altogether, TMP PROTACs are a robust approach for selective and reversible degradation of eDHFR-tagged proteins in vitro and in vivo.
Topics: Animals; Tetrahydrofolate Dehydrogenase; Proteolysis Targeting Chimera; Escherichia coli Proteins; Escherichia coli; Trimethoprim; Proteomics; Ubiquitin-Protein Ligases; Proteolysis
PubMed: 37923771
DOI: 10.1038/s41467-023-42820-3 -
COVID-19 and Listeria Meningitis Treated by Ampicillin, Sulfamethoxazole/Trimethoprim and Meropenem.Infection and Drug Resistance 2023Secondary bacterial infection was initially rare in SARS-CoV-2 infectious disease (COVID-19) patients, but COVID-19-associated bacterial infectious diseases have...
BACKGROUND
Secondary bacterial infection was initially rare in SARS-CoV-2 infectious disease (COVID-19) patients, but COVID-19-associated bacterial infectious diseases have recently been increasing. Furthermore, it might be difficult to distinguish COVID-19 from bacterial meningitis by the symptoms, and one might be uncertain about antibiotic therapy for infection-typically caused by eating contaminated food-in elderly persons and pregnant women.
CASE REPORT
A 96-year-old woman who had been living alone was found to have SARS-CoV-2 infection in February 2023. She was admitted to our hospital with high fever and disturbance of consciousness and was started on treatment with remdesivir. Two days later, her consciousness was still disturbed, and she was found to have a stiff neck. In addition, increased white blood cell counts and C-reactive protein suggested bacterial infection. Therefore, a lumbar puncture was done, and was ultimately isolated from blood cultures and its genetic material was detected in cerebrospinal fluid. She had previously eaten refrigerated food and cheese products. Intravenous ampicillin 1.0 g 6×/day was started, but one week later, loss of consciousness continued, and the cerebrospinal findings were not improved, although nasal swab became negative for SARS-CoV-2. Intravenous sulfamethoxazole/trimethoprim (ST) 80/400 mg 3×/day was added, and her consciousness and fever improved by one week later. A drug rash appeared after ST was started, and she was switched to meropenem. Her condition finally improved.
CONCLUSION
COVID-19-associated secondary listeria infection was found in an elderly woman. She was treated with not only ampicillin, but also ST and meropenem. Meningitis caused by should be considered as a secondary complication and carefully treated with antibiotics during the period of the COVID-19 pandemic.
PubMed: 37424669
DOI: 10.2147/IDR.S414879 -
Journal of the International AIDS... Jun 2023Co-trimoxazole prophylaxis is recommended for children born to women with HIV to protect those who acquire HIV from opportunistic infections, severe bacterial infections... (Review)
Review
INTRODUCTION
Co-trimoxazole prophylaxis is recommended for children born to women with HIV to protect those who acquire HIV from opportunistic infections, severe bacterial infections and malaria. With scale-up of maternal antiretroviral therapy, most children remain HIV-exposed uninfected (HEU) and the benefits of universal co-trimoxazole are uncertain. We assessed the effect of co-trimoxazole on mortality and morbidity of children who are HEU.
METHODS
We performed a systematic review (PROSPERO number: CRD42021215059). We systematically searched MEDLINE, Embase, Cochrane CENTRAL, Global Health, CINAHL Plus, Africa-Wide Information, SciELO and WHO Global Index Medicus for peer-reviewed articles from inception to 4th January 2022 without limits. Ongoing randomized controlled trials (RCTs) were identified through registries. We included RCTs reporting mortality or morbidity in children who are HEU receiving co-trimoxazole versus no prophylaxis/placebo. The risk of bias was assessed using the Cochrane 2.0 tool. Data were summarized using narrative synthesis and findings were stratified by malaria endemicity.
RESULTS
We screened 1257 records and included seven reports from four RCTs. Two trials from Botswana and South Africa of 4067 children who are HEU found no difference in mortality or infectious morbidity in children randomized to co-trimoxazole prophylaxis started at 2-6 weeks of age compared to those randomized to placebo or no treatment, although event rates were low. Sub-studies found that antimicrobial resistance was higher in infants receiving co-trimoxazole. Two trials in Uganda investigating prolonged co-trimoxazole after breastfeeding cessation showed protection against malaria but no other morbidity or mortality differences. All trials had some concerns or a high risk of bias, which limited the certainty of evidence.
DISCUSSION
Studies show no clinical benefit of co-trimoxazole prophylaxis in children who are HEU, except to prevent malaria. Potential harms were identified for co-trimoxazole prophylaxis leading to antimicrobial resistance. The trials in non-malarial regions were conducted in populations with low mortality potentially reducing generalizability to other settings.
CONCLUSIONS
In low-mortality settings with few HIV transmissions and well-performing early infant diagnosis and treatment programmes, universal co-trimoxazole may not be required.
Topics: Infant; Female; Child; Humans; Trimethoprim, Sulfamethoxazole Drug Combination; HIV Infections; Malaria; Uganda; Anti-Infective Agents; World Health Organization; Randomized Controlled Trials as Topic
PubMed: 37292018
DOI: 10.1002/jia2.26079