Selection of high-level oxacillin resistance in heteroresistant Staphylococcus aureus by fluoroquinolone exposure

Venezia, Richard A.; Domaracki, Beth E.; Evans, Ann M.; Preston, Karen E.; Graffunder, Eileen

doi:10.1093/jac/48.3.375

Cited by 82 publications

(57 citation statements)

References 25 publications

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“…42 Fluoroquinolones might influence oxacillin resistance by selective inhibition or by killing of the more susceptible subpopulations in heteroresistant S. aureus. 43 In our study, 120/127 (94.49%) and 122/127 (96.1%) of the MRSA strains had intermediate sensitivity or frank resistance to at least one member of the fluoroquinolone and aminoglycoside classes respectively, while the respective numbers for the MSSA group were 32/70 (45.71%) and 44/70 (62.85%) (data not shown in table).…”

Section: Resultsmentioning

confidence: 45%

Length of exposure to the hospital environment is more important than antibiotic exposure in healthcare associated infections by methicillin-resistant Staphylococcus aureus: a comparative study

Baraboutis¹,

Tsagalou²,

Papakonstantinou³

et al. 2011

Braz J Infect Dis

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Objectives: Both total antimicrobial use and specific antimicrobials have been implicated as risk factors for healthcare-associated methicillin-resistant Staphylococcus aureus (HCA-MRSA) infection. The aims of this study were: (I) to explore predictors of a new HCA-MRSA infection in comparison with a new healthcare-associated methicillin-sensitive Staphylococcus aureus (HCA-MSSA); (II) to thoroughly assess the role of recent antibiotic use qualitatively and quantitatively. Methods: The time-period for our study was from October 1997 through September 2001. Through applying strict criteria, we identified two groups of inpatients, one with a new HCA-MRSA infection and one with a new HCA-MSSA infection. We recorded demographic, clinical and antibiotic use-related data up to 30 days before the positive culture date. Results: We identified 127 and 70 patients for each group, respectively. Two logistic regression models were carried out to assess the role of antimicrobial use (qualitatively and quantitatively). In model I, duration of hospital stay, presence of chronic wounds, aminoglycoside and fluoroquinolone use retained statistical significance. In model II, duration of hospital stay and history of intubation during the last month stood out as the only significant predictors of a subsequent HCA-MRSA infection. No significant differences in outcome were noted. Conclusions: The length of exposure to the hospital environment may be the best predictor of a new HCA-MRSA infection. Use of aminoglycosides and fluoroquinolones may also stand independently along with presence of chronic ulcers and surgical procedures. No independent association between quantitative antibiotic use and subsequent HCA-MRSA infection was documented. Keywords: methicillin-resistant Staphylococcus aureus; Staphylococcus aureus; antibacterial agents; fluoroquinolones. significant risk factor for MRSA acquisition and infection from most, but not all, case-control and cohort studies. 4,[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] Both total antimicrobial use as well as specific antimicrobial classes have been implicated. [11][12][13][14][15][16][17][18]24,25 Included in these classes are β-lactamic antibiotics, 14,26-33 cephalosporins, 11,12,16,22,29 aminoglycosides, 22,33,34 macrolides, 27 glycopeptides 15,[27][28][29]34 and fluoroquinolones (FQs). 6,11,12,14,[26][27][28][29][35][36][37] A relatively recently published meta-analysis detected a clear association between exposure to antibiotics and MRSA isolation. Significant risk ratios were found for FQs, glycopeptides, cephalosporins and other β-lactams. 38 A prediction model, aimed at identifying MRSA bacteremia, predicted that 80% of the nosocomial bacteremias would be resistant to methicillin if patients had experienced antimicrobials prior to the onset. This model also indicated that there were no differences between antibiotics in the prediction of MRSA. 29

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Section: Resultsmentioning

confidence: 45%

Length of exposure to the hospital environment is more important than antibiotic exposure in healthcare associated infections by methicillin-resistant Staphylococcus aureus: a comparative study

Baraboutis¹,

Tsagalou²,

Papakonstantinou³

et al. 2011

Braz J Infect Dis

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“…The magnitude of the association appears to exceed what would be expected through simple selection pressure (most methicillin-resistant S. aureus are also fluoroquinolone resistant), since other agents that lack activity versus methicillin-resistant S. aureus do not show the same degree of association (158). In vitro studies have subsequently suggested that fluoroquinolones may have unique effects on expression of adherence determinants and resistance factors in staphylococci (14,155). It remains to be seen whether control of fluoroquinolone use will aid in reducing the growth of methicillin-resistant S. aureus in health care institutions.…”

Section: Association Between Antimicrobial Use and Resistancementioning

confidence: 99%

Antimicrobial Stewardship Programs in Health Care Systems

2005

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SUMMARY Antimicrobial stewardship programs in hospitals seek to optimize antimicrobial prescribing in order to improve individual patient care as well as reduce hospital costs and slow the spread of antimicrobial resistance. With antimicrobial resistance on the rise worldwide and few new agents in development, antimicrobial stewardship programs are more important than ever in ensuring the continued efficacy of available antimicrobials. The design of antimicrobial management programs should be based on the best current understanding of the relationship between antimicrobial use and resistance. Such programs should be administered by multidisciplinary teams composed of infectious diseases physicians, clinical pharmacists, clinical microbiologists, and infection control practitioners and should be actively supported by hospital administrators. Strategies for changing antimicrobial prescribing behavior include education of prescribers regarding proper antimicrobial usage, creation of an antimicrobial formulary with restricted prescribing of targeted agents, and review of antimicrobial prescribing with feedback to prescribers. Clinical computer systems can aid in the implementation of each of these strategies, especially as expert systems able to provide patient-specific data and suggestions at the point of care. Antibiotic rotation strategies control the prescribing process by scheduled changes of antimicrobial classes used for empirical therapy. When instituting an antimicrobial stewardship program, a hospital should tailor its choice of strategies to its needs and available resources.

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“…Ciprofloxacin is a better MRSA selector than levofloxacin. Aminoglycosides and tobramycin in particular are unlikely to be effective because the aadD gene, encoding 4=,4Љ-adenylyltransferase, conferring tobramycin resistance is present within SCCmec (255)(256)(257)(258). Aztreonam selects for aminoglycoside resistance in an MRSA background (259).…”

Section: Emergence Of Resistance In Pk/pd Studies and In Cf Patientsmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Aerosolized Antibacterial Agents in Chronically Infected Cystic Fibrosis Patients

Dalhoff¹

2014

Clin Microbiol Rev

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SUMMARY Bacteria adapt to growth in lungs of patients with cystic fibrosis (CF) by selection of heterogeneously resistant variants that are not detected by conventional susceptibility testing but are selected for rapidly during antibacterial treatment. Therefore, total bacterial counts and antibiotic susceptibilities are misleading indicators of infection and are not helpful as guides for therapy decisions or efficacy endpoints. High drug concentrations delivered by aerosol may maximize efficacy, as decreased drug susceptibilities of the pathogens are compensated for by high target site concentrations. However, reductions of the bacterial load in sputum and improvements in lung function were within the same ranges following aerosolized and conventional therapies. Furthermore, the use of conventional pharmacokinetic/pharmacodynamic (PK/PD) surrogates correlating pharmacokinetics in serum with clinical cure and presumed or proven eradication of the pathogen as a basis for PK/PD investigations in CF patients is irrelevant, as minimization of systemic exposure is one of the main objectives of aerosolized therapy; in addition, bacterial pathogens cannot be eradicated, and chronic infection cannot be cured. Consequently, conventional PK/PD surrogates are not applicable to CF patients. It is nonetheless obvious that systemic exposure of patients, with all its sequelae, is minimized and that the burden of oral treatment for CF patients suffering from chronic infections is reduced.

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Selection of high-level oxacillin resistance in heteroresistant Staphylococcus aureus by fluoroquinolone exposure

Cited by 82 publications

References 25 publications

Length of exposure to the hospital environment is more important than antibiotic exposure in healthcare associated infections by methicillin-resistant Staphylococcus aureus: a comparative study

Length of exposure to the hospital environment is more important than antibiotic exposure in healthcare associated infections by methicillin-resistant Staphylococcus aureus: a comparative study

Antimicrobial Stewardship Programs in Health Care Systems

Pharmacokinetics and Pharmacodynamics of Aerosolized Antibacterial Agents in Chronically Infected Cystic Fibrosis Patients

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