Background: Bacterial skin and soft tissue infections (SSTIs) have traditionally responded well to treatment with beta-lactam antibiotics (e.g., penicillin derivatives, first- or second-generation cephalosporins) or macro-lides. However, there has been concern whether they are still effective given the emerging resistance of Staphylococcus and Streptococcus species. Consequently, physicians have started using broader-spectrum beta-lactams (e.g., third-generation cephalosporins) or fluoroqui-nolones to treat SSTIs in the belief that they may be more effective, despite limited evidence to support this approach. Falagas and colleagues conducted a meta-analysis of studies comparing the beta-lactams with fluoro-quinolones in the empiric treatment of SSTIs.
The Study: The PubMed and Cochrane databases were used to identify relevant studies published between Janu-ary 1980 and February 2006. To be included, studies had to be randomized controlled trials that examined the clinical or microbiologic effectiveness of the medications. Studies using febrile neutropenic patients were excluded, as were those evaluating nonclinical markers of effectiveness (e.g., pharmacokinetic analysis). Trials also were excluded if they involved antibiotics that had been withdrawn from the market.
Results: Twenty studies involving 4,817 patients were reviewed. The beta-lactam agents included in the studies were extended-spectrum agents (amoxicillin/clavula-nate [Augmentin], ampicillin/sulbactam [Unasyn], and piperacillin/tazobactam [Zosyn]); first-generation ceph-alosporins (cephalexin [Keflex]); and third-generation cephalosporins (cefotaxime [Claforan] and ceftazidime [Fortaz]). Fluoroquinolones included were ofloxacin (Floxin), ciprofloxacin (Cipro), fleroxacin (not available in the U.S.), levofloxacin (Levaquin), and moxifloxacin (Avelox).
Overall, fluoroquinolones were more effective than beta-lactam antibiotics for empirically treating SSTIs, but the difference was small (90.4 versus 88.2 percent resolution). Fluoroquinolones also were more effective in treating mild to moderate SSTIs. However, both of these advantages disappeared when third-generation cephalosporins were excluded from the analysis. There also was no difference between the antibiotic classes in the treatment of moderate to severe infections.
Fluoroquinolones were no more effective than beta-lactam antibiotics in the treatment of abscesses and wound infections, nor were they more effective in treating patients hospitalized for SSTIs. Microbiologically, eradication rates of S. aureus and streptococci infections were the same for the two groups of medications. However, fluoroquinolones were more effective where gram-negative or anaerobic infections were identified.
No difference in mortality rates was found between the groups. Although most medication-related adverse events were mild and involved the gastrointestinal tract, fluoroquinolones were associated with a significantly higher rate of adverse events compared with beta-lactam antibiotics (19.2 and 15.2 percent, respectively).
Conclusion: The authors concluded that although fluo-roquinolones were slightly more effective in treating SSTIs compared with beta-lactam antibiotics, this difference disappeared when third-generation cephalosporins were excluded. When the greater adverse effect profile of fluoroquinolones was also considered, there was no substantial advantage to using them over beta-lactam agents for the empiric treatment of SSTIs. Although third-generation cephalosporins often are used to treat SSTIs, they appear to be less effective than extended-spectrum penicillins and first-generation cephalosporins.