Can Macrolide Antibiotics Prevent Hospital Readmissions?
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ABSTRACT:
SUBMITTER: Wedzicha JA
PROVIDER: S-EPMC6812442 | biostudies-literature | 2019 Oct
REPOSITORIES: biostudies-literature
Publications
Can Macrolide Antibiotics Prevent Hospital Readmissions?
Wedzicha Jadwiga A JA Ritchie Andrew I AI Martinez Fernando J FJ
American journal of respiratory and critical care medicine 20191001 7
Similar Datasets
Project description: Not available
| S-EPMC6494352 | biostudies-literature
Project description:Macrolides are clinically important antibiotics thought to inhibit bacterial growth by impeding the passage of newly synthesized polypeptides through the nascent peptide exit tunnel of the bacterial ribosome. Recent data challenged this view by showing that macrolide antibiotics can differentially affect synthesis of individual proteins. In order to understand the general mechanism of macrolide action, we used genome-wide ribosome profiling and analyzed the redistribution of ribosomes translating highly expressed genes in bacterial cells treated with high concentrations of macrolide antibiotics. The metagene analysis indicated that inhibition of early rounds of translation, which would be characteristic of the conventional view of macrolide action, occurs only at a limited number of genes. Translation of most genes proceeds past the 5' proximal codons and can be arrested at more distal codons when the ribosome encounters specific short sequence motifs. The sequence motifs enriched in the sites of arrest are confined to the nascent peptide residues in the peptidyl transferase center but not to the peptide segments that contact the antibiotic molecule in the exit tunnel. This led to the conclusion that the general mode of macrolide action involves selective inhibition of peptide bond formation between specific combinations of donor and acceptor substrates. Additional factors operating in the living cell but not during in vitro protein synthesis may modulate site-specific action of macrolide antibiotics.
2014-11-03 | GSE61619 | GEO
Project description:BackgroundThe increased risk of cardiovascular events in patients prescribed macrolides has been subject to debate for decades.MethodsMedline, EMBASE databases and ClinicalTrials.gov were searched from inception until August 31, 2022 for studies investigating the link between macrolides and cardiovascular risk. A meta-analysis was performed using a random-effects model.ResultsA total of 80 studies involving 39,374,874 patients were included. No association was found between macrolides and all-cause death. However, compared with the non-macrolide group, macrolides were associated with a significantly increased risk of ventricular arrhythmia or sudden cardiac death (VA or SCD) (azithromycin, relative ratio [RR]: 1.53; 95% confidence interval [CI]: 1.19 to 1.97; clarithromycin, RR: 1.52; 95% CI: 1.07 to 2.16). Besides, administration of macrolides was associated with a higher risk of cardiovascular disease (CVD) death (azithromycin, RR: 1.63; 95% CI: 1.17 to 2.27) and a slightly increased risk of myocardial infarction (MI) (azithromycin, RR: 1.08; 95% CI: 1.02 to 1.15). Interestingly, no association was observed between roxithromycin and adverse cardiac outcomes. Increased risk of VA or SCD was observed for recent or current use of macrolides, MI for former use, and CVD death for current use.ConclusionAdministration of macrolide antibiotics and timing of macrolide use are associated with increased risk for SCD or VTA and cardiovascular death, but not all-cause death.
| S-EPMC9996752 | biostudies-literature
Project description:80S ribosomes of S.cerevisiae carry G2400A mutation in the 25S rRNA which makes them sensitive to macrolide antibiotics
2021-05-25 | GSE164275 | GEO
Project description:Macrolides, one of the most commonly used class of antibiotics, are a group of drugs produced by Streptomyces species. They belong to the polyketide class of natural products. Their activity is due to the presence of a large macrolide lactone ring with deoxy sugar moieties. They are protein synthesis inhibitors and broad-spectrum antibiotics, active against both gram-positive and gram-negative bacteria. Different analytical techniques have been reported for the determination of macrolides such as chromatographic methods, flow injection methods, spectrofluorometric methods, spectrophotometric methods, and capillary electrophoresis methods. Among these methods, spectrophotometric methods are sensitive and cost effective for the analysis of various antibiotics in pharmaceutical formulations as well as biological samples. This article reviews different spectrophotometric methods for the determination of macrolide antibiotics.
| S-EPMC4644142 | biostudies-literature
Project description:Macrolide resistance mechanisms can be target-based with a change in a 23S ribosomal RNA (rRNA) residue or a mutation in ribosomal protein L4 or L22 affecting the ribosome's interaction with the antibiotic. Alternatively, mono- or dimethylation of A2058 in domain V of the 23S rRNA by an acquired rRNA methyltransferase, the product of an erm (erythromycin ribosome methylation) gene, can interfere with antibiotic binding. Acquired genes encoding efflux pumps, most predominantly mef(A) + msr(D) in pneumococci/streptococci and msr(A/B) in staphylococci, also mediate resistance. Drug-inactivating mechanisms include phosphorylation of the 2'-hydroxyl of the amino sugar found at position C5 by phosphotransferases and hydrolysis of the macrocyclic lactone by esterases. These acquired genes are regulated by either translation or transcription attenuation, largely because cells are less fit when these genes, especially the rRNA methyltransferases, are highly induced or constitutively expressed. The induction of gene expression is cleverly tied to the mechanism of action of macrolides, relying on antibiotic-bound ribosomes stalled at specific sequences of nascent polypeptides to promote transcription or translation of downstream sequences.
| S-EPMC5046686 | biostudies-literature
Project description:Macrolides are clinically important antibiotics thought to inhibit bacterial growth by impeding the passage of newly synthesized polypeptides through the nascent peptide exit tunnel of the bacterial ribosome. Recent data challenged this view by showing that macrolide antibiotics can differentially affect synthesis of individual proteins. In order to understand the general mechanism of macrolide action, we used genome-wide ribosome profiling and analyzed the redistribution of ribosomes translating highly expressed genes in bacterial cells treated with high concentrations of macrolide antibiotics. The metagene analysis indicated that inhibition of early rounds of translation, which would be characteristic of the conventional view of macrolide action, occurs only at a limited number of genes. Translation of most genes proceeds past the 5' proximal codons and can be arrested at more distal codons when the ribosome encounters specific short sequence motifs. The sequence motifs enriched in the sites of arrest are confined to the nascent peptide residues in the peptidyl transferase center but not to the peptide segments that contact the antibiotic molecule in the exit tunnel. This led to the conclusion that the general mode of macrolide action involves selective inhibition of peptide bond formation between specific combinations of donor and acceptor substrates. Additional factors operating in the living cell but not during in vitro protein synthesis may modulate site-specific action of macrolide antibiotics. Comparing ribosome distribution in bacterial cells treated with macrolide antibiotics against the control cells.
2014-11-03 | E-GEOD-61619 | biostudies-arrayexpress
Project description:New tools to accurately identify potentially preventable 30-day readmissions are needed. The HOSPITAL score has been internationally validated for medical inpatients, but its performance in select conditions targeted by the Hospital Readmission Reduction Program (HRRP) is unknown.Retrospective cohort study.Six geographically diverse medical centers.All consecutive adult medical patients discharged alive in 2011 with 1 of the 4 medical conditions targeted by the HRRP (acute myocardial infarction, chronic obstructive pulmonary disease, pneumonia, and heart failure) were included. Potentially preventable 30-day readmissions were identified using the SQLape algorithm. The HOSPITAL score was calculated for all patients.A multivariable logistic regression model accounting for hospital effects was used to evaluate the accuracy (Brier score), discrimination (c-statistic), and calibration (Pearson goodness-of-fit) of the HOSPITAL score for each 4 medical conditions.Among the 9181 patients included, the overall 30-day potentially preventable readmission rate was 13.6%. Across all 4 diagnoses, the HOSPITAL score had very good accuracy (Brier score of 0.11), good discrimination (c-statistic of 0.68), and excellent calibration (Hosmer-Lemeshow goodness-of-fit test, P=0.77). Within each diagnosis, performance was similar. In sensitivity analyses, performance was similar for all readmissions (not just potentially preventable) and when restricted to patients age 65 and above.The HOSPITAL score identifies a high-risk cohort for potentially preventable readmissions in a variety of practice settings, including conditions targeted by the HRRP. It may be a valuable tool when included in interventions to reduce readmissions within or across these conditions.
| S-EPMC5309170 | biostudies-other
Project description:Hospital readmission rates are increasingly used to assess quality. Little is known, however, about potential preventability of readmissions among children. Our objective was to evaluate potential preventability of 30-day readmissions using medical record review and interviews.A cross-sectional study in 305 children (<18 years old) readmitted within 30 days to a freestanding children's hospital between December 2012 and February 2013. Interviews (N = 1459) were conducted with parents/guardians, patients (if ≥13 years old), inpatient clinicians, and primary care providers. Reviewers evaluated medical records, interview summaries, and transcripts, and then rated potential preventability. Multivariate regression analysis was used to identify factors associated with potentially preventable readmission. Adjusted event curves were generated to model days to readmission.Of readmissions, 29.5% were potentially preventable. Potentially preventable readmissions occurred sooner after discharge than non-potentially preventable readmissions (5 vs 9 median days; P < .001). The odds of a readmission being potentially preventable were greatest when the index admission and readmission were causally related (adjusted odds ratio [AOR]: 2.6; 95% confidence interval [CI]: 1.0-6.8) and when hospital (AOR: 16.3; 95% CI: 5.9-44.8) or patient (AOR: 7.1; 95% CI: 2.5-20.5) factors were identified. Interviews provided new information about the readmission in 31.2% of cases.Nearly 30% of 30-day readmissions to a children's hospital may be potentially preventable. Hospital and patient factors are associated with potential preventability and may provide targets for quality improvement efforts. Interviews contribute important information and should be considered when evaluating readmissions.
| S-EPMC5557411 | biostudies-other
Project description: Not available
| S-EPMC5862720 | biostudies-literature