Investigation of β-lactam antibiotic-induced vancomycin-resistant MRSA (BIVR)

Hanaki, Hideaki; Yamaguchi, Yoshio; Yanagisawa, Chie; Uehara, Kazuaki; Matsui, Hidehito; Yamaguchi, Yuuichi; Hososaka, Yasuko; Barada, Kazunari; Sakai, Fumiko; Itabashi, Yasuko; Ikeda, Shinsuke; Atsuda, Koichiro; Tanaka, Haruo; Igarashi, Takashi; Nagayama, Ariaki; Sunakawa, Keisuke

doi:10.1007/s10156-004-0371-x

Cited by 18 publications

(17 citation statements)

References 15 publications

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“…2), which is most probably due to activated cell wall synthesis (26)(27)(28). It has been reported that the simultaneous exposure of S. aureus to vancomycin and beta-lactams in vitro can lead to vancomycin resistance in certain strains, designated beta-lactam-induced vancomycin-resistant MRSA (BIVR) (29). The proposed mechanism was the linkage of the increase in cell wall precursors observed in the presence of beta-lactams to the vancomycin present in the medium, thus limiting vancomycin's availability for target inhibition (26).…”

Section: Discussionmentioning

confidence: 99%

Exposure of Staphylococcus aureus to Subinhibitory Concentrations of β-Lactam Antibiotics Induces Heterogeneous Vancomycin-Intermediate Staphylococcus aureus

Roch

Clair

Renzoni

et al. 2014

Antimicrob Agents Chemother

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h Glycopeptides are known to select for heterogeneous vancomycin-intermediate Staphylococcus aureus (h-VISA) from susceptible strains. In certain clinical situations, h-VISA strains have been isolated from patients without previous exposure to glycopeptides, such as cystic fibrosis patients, who frequently receive repeated treatments with beta-lactam antibiotics. Our objective was to determine whether prolonged exposure to beta-lactam antibiotics can induce h-VISA. We exposed 3 clinical vancomycin-susceptible methicillin-resistant Staphylococcus aureus (MRSA) strains to ceftazidime, ceftriaxone, imipenem, and vancomycin (as a control) at subinhibitory concentrations for 18 days in vitro. Population analyses showed progressive increases in vancomycin resistance; seven of the 12 derived strains obtained after induction were classified as h-VISA according to the following criteria: area under the curve (AUC) on day 18/AUC of Mu3 of >90% and/or growth on brain heart infusion (BHI) agar with 4 mg/liter vancomycin. The derived isolates had thickened cell walls proportional to the level of glycopeptide resistance. Genes known to be associated with glycopeptide resistance (vraSR, yvqF, SA1703, graRS, walKR, and rpoB) were PCR sequenced; no de novo mutations were observed upon beta-lactam exposure. To determine whether trfA, a gene encoding a glycopeptide resistance factor, was essential in the selection of h-VISA upon beta-lactam pressure, a trfA-knockout strain was generated by allelic replacement. Indeed, beta-lactam exposure of this mutated strain showed no capacity to induce vancomycin resistance. In conclusion, these results showed that beta-lactam antibiotics at subinhibitory concentrations can induce intermediate vancomycin resistance in vitro. This induction required an intact trfA locus. Our results suggest that prior use of beta-lactam antibiotics can compromise vancomycin efficacy in the treatment of MRSA infections.

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Section: Discussionmentioning

confidence: 99%

Exposure of Staphylococcus aureus to Subinhibitory Concentrations of β-Lactam Antibiotics Induces Heterogeneous Vancomycin-Intermediate Staphylococcus aureus

Roch

Clair

Renzoni

et al. 2014

Antimicrob Agents Chemother

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“…The clinically useful antibiotic arsenal available against them is limited, and new resistant mutants worsen the situation. MRSA strains with frank resistance to vancomycin (VRSA) have also been reported and may, together with the intermediate strains, soon become a serious problem (Centers for Disease Control and Prevention 2002;Bozdogan et al 2003;Hanaki et al 2005). Thus, new drugs active against VRE and MRSA are critically needed.…”

Section: Introductionmentioning

confidence: 99%

Potent activity of the lichen antibiotic (+)-usnic acid against clinical isolates of vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus

Elo

Matikainen

Pelttari

2007

Naturwissenschaften

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Vancomycin-resistant enterococci (VRE) and methicillin-resistant staphylococci, most notably methicillin-resistant Staphylococcus aureus (MRSA), are serious clinical problems. The antibiotic arsenal available against them is limited, and new mutants worsen the situation. We studied the activity of (+)-usnic acid, an old lichen-derived drug, and its sodium salt against clinical isolates of VRE and MRSA using the agar diffusion and minimal inhibitory concentration (MIC) methods. The acid and, especially, the sodium salt had potent antimicrobial activity against all clinical isolates of VRE and MRSA studied. The MIC values of the sodium salt against VRE strains ranged between 4 and 16 microg/ml (1-day test) and between 4 and 31 microg/ml (2-day test), being below 8 microg/ml for most strains. The salt had potent activity even against those strains that were not inhibited by ampicillin (125 microg/ml), and it never lost its activity after 24 h, in contrast to ampicillin. Thus, in spite of the fact that usnic acid can in some cases cause serious toxicity, it and its salts may be worth considering in clinical practice in cases where other therapies have failed or the microbe is resistant toward other agents.

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“…In fact, a synergistic effect of these drugs was previously reported (9,22). However, the combination therapy of VAN and a ␤-lactam antibiotic caused the emergence of VAN-resistant MRSA (15,26), designated ␤-lactaminduced VAN-resistant MRSA (BIVR) (12,14). Currently, about 20% of MRSA strains isolated from septicemia patients have been reported to be BIVR (13).…”

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confidence: 99%

Rapid Depletion of Free Vancomycin in Medium in the Presence of β-Lactam Antibiotics and Growth Restoration in Staphylococcus aureus Strains with β-Lactam-Induced Vancomycin Resistance

Yanagisawa

Hanaki

Matsui

et al. 2009

Antimicrob Agents Chemother

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Growth of the BIVR cells to an absorption level of ϳ0.3 at 578 nm required about 24 h in the presence of vancomycin alone at the MIC (4.0 g/ml). However, growth was achieved in only about 10 h when 1/1,000 to 1/2,000 the MIC of ␤-lactam antibiotic was added 2 h prior to the addition of vancomycin, suggesting that the ␤-lactams shortened the time to recovery from vancomycin-mediated growth inhibition. Free vancomycin in the culture medium decreased to 2.3 g/ml in the first 8 h in the culture containing vancomycin alone, yet cell growth was undetectable. When the vancomycin concentration dropped below ϳ1.5 g/ml at 24 h, the cells began to grow. In the culture supplemented with the ␤-lactam 2 h prior to the addition of vancomycin, the drug concentration continuously dropped from 4 to 0.5 g/ml in the first 8 h, and the cells began to grow at a vancomycin concentration of ϳ1.7 g/ml or at 4 h of incubation. The gene encoding the enzyme involved in D-Ala-D-lactate synthesis was undetectable. Based on these results, we concluded that BIVR is attributable mainly to a rapid depletion of vancomycin in the medium triggered or promoted by ␤-lactam antibiotics.

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Investigation of β-lactam antibiotic-induced vancomycin-resistant MRSA (BIVR)

Cited by 18 publications

References 15 publications

Exposure of Staphylococcus aureus to Subinhibitory Concentrations of β-Lactam Antibiotics Induces Heterogeneous Vancomycin-Intermediate Staphylococcus aureus

Exposure of Staphylococcus aureus to Subinhibitory Concentrations of β-Lactam Antibiotics Induces Heterogeneous Vancomycin-Intermediate Staphylococcus aureus

Potent activity of the lichen antibiotic (+)-usnic acid against clinical isolates of vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus

Rapid Depletion of Free Vancomycin in Medium in the Presence of β-Lactam Antibiotics and Growth Restoration in Staphylococcus aureus Strains with β-Lactam-Induced Vancomycin Resistance

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