Strategies to control antibiotic resistance.

Antibiotic resistance is becoming a worldwide concern. Antibiotic resistance may be caused by sporadic mutations, which are not important unless spread clonally. Clonal resistance may disseminate a highly resistant clone to widespread geographic areas. The most effective interventions to limit the clonal spread of resistant organisms are effective infection control measures. Hospital antibiotic formulary restriction is the only control measure with proven effectiveness to control resistance related to antibiotic use. Hospital formularies should eliminate or restrict antibiotics with a high-resistance potential (eg, ceftazidime, ciprofloxacin, and imipenem), and should be replaced with equivalent antibiotics with a low-resistance potential (eg, cefe-pime, levofloxacin, and meropenem). Such low-resistance-potential antibiotics can either prevent or eliminate resistance problems associated with Klebsiella pneumoniae, Enterobacter species, or Pseudomonas aeruginosa. High-resistance-potential antibiotics, particularly ciprofloxacin and ceftazidime, also may indirectly increase the prevalence of highly resistant organisms (eg, methicillin-resistant Staphylococcus aureus [MRSA], vancomycin-resistant enterococci [VRE]). Vancomycin use should be restricted, not because it increases enterococcal resistance per se, but because it selects out naturally resistant enterococcal strains (eg, Enterococcus faecium that are vancomycin resistant). Linezolid does not increase the prevalence of VRE. Clinicians in the outpatient setting should also preferentially use oral antibiotics with a low-resistance potential (eg, clindamycin, metronidazole, doxycycline, minocycline, fluoroquinolones except ciprofloxacin, linezolid, and oral cephalosporins) in preference to their high-resistance-potential counterparts. For antibiotic resistance control interventions to be effective, they must be applied simultaneously to all antibiotics with activity against the specific resistance pathogen at the hospital formulary level. Multiple antibiotic substitutions are usually necessary to eradicate resistance problems caused by a particular pathogen. Multiple drugs of the same spectrum and low-resistance potential are necessary to eliminate resistance problems; single antibiotic substitutions are not effective.