First Detection of an Invasive
            <i>Staphylococcus aureus</i>
            Strain (D958) with Reduced Susceptibility to Glycopeptides in Saudi Arabia

Intensive use of antimicrobial agents in health care settings not only leads to the selection of multiresistant nosocomial isolates of Staphylococcus aureus but may also promote endogenous, resistance-conferring mutations in bacterial genes that encode drug targets. We evaluated the spectrum of rifampin resistance-conferring mutations in cultures of methicillin-susceptible S. aureus (MSSA) or methicillin-resistant S. aureus (MRSA) strains exposed in vitro to sub-MICs of ciprofloxacin. Growth of ciprofloxacin-susceptible MRSA strain MRGR3 and ciprofloxacin-resistant MSSA strain RA1 (a NCTC 8325 derivative) in the presence of 1/2؋ or 1/4؋ MIC of ciprofloxacin led to higher frequencies of rifampin-resistant mutants on agar supplemented with rifampin (0.25 mg/liter) than under ciprofloxacin-free conditions. While rifampin-resistant mutants from ciprofloxacin-free cultures essentially showed single-amino-acid substitutions, a significant proportion of rifampin-resistant mutants from ciprofloxacin-exposed cultures displayed in-frame deletions or insertions in the rpoB gene at several positions of the rifampin resistance cluster I. In-frame deletions or insertions were also recorded in rpoB cluster I of rifampin-resistant mutants from ciprofloxacin-exposed cultures of mutS and mutL DNA repair mutants of ciprofloxacin-resistant S. aureus strain RA1. Frequencies of rifampin-resistant mutants grown under ciprofloxacin-free medium were higher for mutant strains RA1 mutS2 and RA1 mutL, but not RA1 recA, than for their parent RA1. In conclusion, ciprofloxacin-mediated DNA damage in S. aureus, as exemplified by the wide diversity of deletions or insertions in rpoB, suggests the occurrence of major, quinolone-mediated disturbances in DNA fork progression and replication repair. Besides promoting antibiotic resistance, accumulation of unrepaired DNA replication errors, including insertions and deletions, may also contribute to potentially lethal mutations.

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“…Strain MRGR3 belongs to a different clonal family (sequence type 239 [ST239], clonal complex 5 [CC5]) than strains ISP794 and RA1 (ST8) (1).…”

Section: Methodsmentioning

confidence: 99%

Impact of Ciprofloxacin Exposure on Staphylococcus aureus Genomic Alterations Linked with Emergence of Rifampin Resistance

Didier

Villet

Huggler

et al. 2011

Antimicrob Agents Chemother

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“…Since their first description in Japan in 1997, GISA and hGISA have been progressively reported worldwide [5,[8][9][10]. These strains have been previously associated with prolonged antibiotic therapy, prolonged hospitalization, treatment failure, increased mortality and epidemic episodes with cross-contamination between patients [11].…”

Section: Discussionmentioning

confidence: 99%

Staphylococcus aureus with decreased susceptibility to glycopeptides in cystic fibrosis patients

Filleron

Chiron

Reverdy

et al. 2011

Journal of Cystic Fibrosis

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We report the isolation of Staphylococcus aureus with decreased susceptibility to glycopeptides in five CF patients and review the clinical and microbiological features of these cases. Three patients presented with pulmonary exacerbation that may be attributed to these strains and two of them were successfully treated using linezolid therapy. Glycopeptide-intermediate S. aureus (GISA) strains isolated in two patients were susceptible to methicillin, while the three other patients harbored methicillin-resistant GISA. Rarely reported in CF, GISA may remain underestimated due to the difficulty of detection, and both clinicians and microbiologists should be aware of the GISA emergence in CF patients' population.

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“…Failure with empiric vancomycin treatment in a Saudi 69-year-old male patient, for example, prompted physicians to obtain more accurate susceptibility data on the pathogen isolated from blood. This led to the discovery of the first heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA), a threatening signal to the effectiveness of empiric vancomycin treatment in hospitalized patients with severe infections [37].…”

Section: Overview Of Testing Methodologymentioning

confidence: 99%

Susceptibility Testing and Reporting of New Antibiotics with a Focus on Tedizolid: An International Working Group Report

et al. 2017

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Inappropriate use and overuse of antibiotics are among the most important factors in resistance development, and effective antibiotic stewardship measures are needed to optimize outcomes. Selection of appropriate antimicrobials relies on accurate and timely antimicrobial susceptibility testing. However, the availability of clinical breakpoints and in vitro susceptibility testing often lags behind regulatory approval by several years for new antimicrobials. A Working Group of clinical/medical microbiologists from Brazil, Canada, Mexico, Saudi Arabia, Russia and the UK recently examined issues surrounding antimicrobial susceptibility testing for novel antibiotics. While commercially available tests are being developed, potential surrogate antibiotics may be used as marker of susceptibility. Using tedizolid as an example of a new antibiotic, this special report makes recommendations to optimize routine susceptibility reporting.

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First Detection of an Invasive Staphylococcus aureus Strain (D958) with Reduced Susceptibility to Glycopeptides in Saudi Arabia

Cited by 21 publications

References 62 publications

Impact of Ciprofloxacin Exposure on Staphylococcus aureus Genomic Alterations Linked with Emergence of Rifampin Resistance

Impact of Ciprofloxacin Exposure on Staphylococcus aureus Genomic Alterations Linked with Emergence of Rifampin Resistance

Staphylococcus aureus with decreased susceptibility to glycopeptides in cystic fibrosis patients

Susceptibility Testing and Reporting of New Antibiotics with a Focus on Tedizolid: An International Working Group Report

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