Clinafloxacin versus Piperacillin-Tazobactam in Treatment of Patients with Severe Skin and Soft Tissue Infections

Abstract

Patients (n ‫؍‬ 409) with severe skin and soft tissue infections (SSTIs) were randomized to receive clinafloxacin or piperacillin-tazobactam (plus optional vancomycin for methicillin-resistant cocci), administered intravenously, with the option to switch to oral medication. Most patients had cellulitis, wound infections, or diabetic foot infections. Staphylococcus aureus, Enterococcus faecalis, and Pseudomonas aeruginosa were the most common baseline pathogens. Fewer baseline pathogens were resistant to clinafloxacin (1.8%) than to piperacillin-tazobactam (6.2%) (P ‫؍‬ 0.001). The clinafloxacin and piperacillin-tazobactam groups did not differ significantly in clinical cure rates (68.8 and 65.2%, respectively) or microbiologic eradication rates (61.5 and 57.2%). Clinafloxacin yielded higher eradication rates for all three of the most common pathogenic species, although no differences were statistically significant. Within the power of this study, the overall frequency of adverse events was similar (P ‫؍‬ 0.577) in the two treatment groups. Drug-associated adverse events (P ‫؍‬ 0.050) and treatment discontinuations (P ‫؍‬ 0.052) were marginally more frequent in the clinafloxacin group, primarily due to phototoxicity in outpatients receiving clinafloxacin. Although most cases of phototoxicity were mild to moderate, four cases were reported as severe. In summary, clinafloxacin monotherapy was equivalent in effectiveness to therapy with piperacillin-tazobactam plus optional vancomycin in the treatment of hospitalized patients with severe SSTIs.Skin and soft tissue infections (SSTIs), such as spontaneous lymphangitis or cellulitis, and especially complicated infections, such as wound and surgical infections or diabetic foot ulcers, often require hospitalization and intravenous (i.v.) antibacterial treatment. These infections are caused by a mixture of aerobic and anaerobic organisms and are responsible for increased morbidity, prolonged hospital stay, and increased health care costs (3,13,19).Staphylococcus aureus and streptococci; gram-negative bacteria such as Pseudomonas aeruginosa, Enterobacteriaceae, and Enterococcus spp.; and anaerobes such as Bacteroides fragilis are frequently isolated (8,12,13,18,32 Frequently used antimicrobial agents have included expandedspectrum cephalosporins (e.g., cefoxitin, cefotetan, cefmetazole), imipenem-cilastatin, ␤-lactam-␤-lactamase inhibitor combinations (e.g., piperacillin-tazobactam, ticarcillin-clavulanate), and fluoroquinolones (13,14,15,18,20,35). However, emerging resistance, particularly among S. aureus, P. aeruginosa, and enterococci, is making the choice of treatment increasingly more difficult (23).Clinafloxacin is an extended-spectrum fluoroquinolone antibacterial that is bactericidal against S. aureus, including methicillin-resistant strains, and most strains of ciprofloxacinresistant S. aureus (7,33). Like other fluoroquinolones, clinafloxacin has activity against Pseudomonas spp. and the Enterobacteriaceae; the MICs of clinafloxacin at which 90% of isolates are ...

Ertapenem Once Daily Versus Piperacillin‐Tazobactam 4 Times per Day for Treatment of Complicated Skin and Skin‐Structure Infections in Adults: Results of a Prospective, Randomized, Double‐Blind Multicenter Study

“…In this study of CSSSIs, the cure rates among patients who received ertapenem and among patients who received piperacillin-tazobactam were equivalent overall (82.4% vs. 84.4%) and similar to or somewhat higher than those reported in other, similarly designed clinical trials [15][16][17][18][19]. As shown by others, cure rates for foot infections associated with diabetes, which are often complicated by compromised vascularity, were lower for both treatment groups in this study.…”

Efficacy of ertapenem against methicillin-susceptible Staphylococcus aureus in complicated skin/skin structure infections: results of a double-blind clinical trial versus piperacillin-tazobactam

“…In the large pivotal skin/skin structure infection trial, ertapenem therapy had equivalent efficacy overall to piperacillin-tazobactam [3]. MSSA was the predominant pathogen in that trial, as has been reported in several similar trials [8][9][10][11][12]. The objective of this subgroup analysis of data from the pivotal skin/skin structure infection trial was to compare the efficacy of ertapenem with that of piperacillin-tazobactam in the treatment of serious staphylococcal infections and to examine the demographic and disease characteristics of patients with MSSA infection.…”

“…In two large studies comparing quinupristin/dalfopristin [11]. Additionally, in an open-label study of levofloxacin versus ticarcillin-clavulanate alone or followed by amoxicillin-clavulanate [12], clinical success rates for patients with S. aureus infection (presumably MSSA, since patients with infections caused by resistant bacteria were excluded) were 87.3% (48 of 55) for levofloxacin and 78% (39/50) for ticarcillin-clavulanate/amoxicillin-clavulanate 2-5 days post-therapy, an endpoint similar to the end of treatment assessment but considerably shorter than 10-21 days post-therapy test of cure assessment in the current report.…”

Incidence of Neutropenia during Treatment of Bone-Related Infections with Piperacillin-Tazobactam

“…However, the length of piperacillin-tazobactam treatment described in published studies does not usually surpass 2 weeks [3][4][5], including some recent trials dealing with patients with diabetic foot infection [19,20]. Ruiz-Irastorza et al [18] explain these apparent differences in the marrow toxicity of piperacillin and piperacillin-tazobactam by the difference in the amount of the usual daily dose (12 g, in the case of piperacillin, and 16 g, in the case of piperacillin-tazobactam).…”