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In Vitro Selection of High-Level Beta-Lactam Resistance in Methicillin-Susceptible Staphylococcus aureus.

ABSTRACT: Selective pressure of beta-lactams is thought to be responsible for mutation selection in methicillin-susceptible Staphylococcus aureus (MSSA). We used next-generation sequencing to compare the genomes of beta-lactamase-positive (SA0707) and -negative (SA0937) MSSA isolates with their derivatives obtained after selection with oxacillin, ceftaroline, or meropenem. Selection with oxacillin and ceftaroline caused a rapid and significant (6-8 times) increase in the minimum inhibitory concentration (MICs) of oxacillin, penicillin, amoxicillin/clavulanate, and ceftaroline against the derivatives of both isolates, associated with growth impairment. Selection with meropenem caused a limited increase in the MICs of all beta-lactams against both isolates. During the initial stages of selection (after 5-15 passages), mutations were detected only in some reads, which indicated the heterogeneity of the population; however, during the later stages, either the population reversed to the wild type or fixation of the mutation was observed in the entire population. Selection with different beta-lactams caused diverse mutational events, but common mutations were detected in gdpP, all penicillin-binding proteins, cell wall regulators (vraST, graR), and deletions in the promoter region of pbp4. Therefore, the disk diffusion test with cefoxitin does not reveal resistance associated with these mechanisms in some cases, which can lead to the failure of beta-lactam therapy.

SUBMITTER: Gostev V

PROVIDER: S-EPMC8227848 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Teicoplanin versus β-lactam for febrile patients with Staphylococcus-like bacteremia: focus on methicillin-susceptible Staphylococcus aureus bacteremia.

Project description:BackgroundMany studies have shown that vancomycin is inferior to β-lactam antibiotics in terms of effectiveness in the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. However, limited data are available regarding the comparison of clinical outcomes between patients receiving initial teicoplanin and those receiving β-lactam antibiotics for MSSA bacteremia.MethodsEighty-four adults with MSSA bacteremia were included: initial teicoplanin treatment group (n = 28) and β-lactam treatment group (n = 56). The two groups were further stratified based on propensity score matching according to the outcome analysis using a logistic regression model. We investigated the clinical outcomes between the groups before and after propensity score matching after treatment completion.ResultsPittsburgh bacteremia score ≥ 4 (odds ratio, 60.6; 95%CI, 7.4-496.8) was an independent risk factor for unfavorable outcome. After propensity score matching, the initial teicoplanin treatment group and the β-lactam treatment group consisted of 28 patients each. No statistically significant differences were observed in the proportions of patients with favorable outcomes and 30-day overall mortality rates between the groups before and after propensity score matching after the completion of teicoplanin or β-lactam treatment. The Kaplan-Meier 30-day survival curve also showed no significant difference between the patients receiving initial teicoplanin treatment and those receiving β-lactam treatment before and after matching (hazard ratio, 1.84, 95%CI, 0.60-5.64; and 3.12, 95%CI, 0.98-9.99, respectively).ConclusionsThere were no significant difference in clinical outcomes between initial teicoplanin treatment and β-lactam treatment among patients with MSSA bacteremia. Pittsburgh bacteremia score ≥ 4 was a significant risk factor for mortality.

| S-EPMC8117599 | biostudies-literature

RelQ Mediates the Expression of β-Lactam Resistance in Methicillin-Resistant Staphylococcus aureus.

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| S-EPMC6421274 | biostudies-literature

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| S-EPMC5819674 | biostudies-literature

Bicarbonate Resensitization of Methicillin-Resistant Staphylococcus aureus to β-Lactam Antibiotics.

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