Methicillin-resistant S. aureus infections among patients in the emergency department.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is increasingly recognized in infections among persons in the community without established risk factors for MRSA. METHODS: We enrolled adult patients with acute, purulent skin and soft-tissue infections presenting to 11 university-affiliated emergency departments during the month of August 2004. Cultures were obtained, and clinical information was collected. Available S. aureus isolates were characterized by antimicrobial-susceptibility testing, pulsed-field gel electrophoresis, and detection of toxin genes. On MRSA isolates, we performed typing of the staphylococcal cassette chromosome mec (SCCmec), the genetic element that carries the mecA gene encoding methicillin resistance. RESULTS: S. aureus was isolated from 320 of 422 patients with skin and soft-tissue infections (76 percent). The prevalence of MRSA was 59 percent overall and ranged from 15 to 74 percent. Pulsed-field type USA300 isolates accounted for 97 percent of MRSA isolates; 74 percent of these were a single strain (USA300-0114). SCCmec type IV and the Panton-Valentine leukocidin toxin gene were detected in 98 percent of MRSA isolates. Other toxin genes were detected rarely. Among the MRSA isolates, 95 percent were susceptible to clindamycin, 6 percent to erythromycin, 60 percent to fluoroquinolones, 100 percent to rifampin and trimethoprim-sulfamethoxazole, and 92 percent to tetracycline. Antibiotic therapy was not concordant with the results of susceptibility testing in 100 of 175 patients with MRSA infection who received antibiotics (57 percent). Among methicillin-susceptible S. aureus isolates, 31 percent were USA300 and 42 percent contained pvl genes. CONCLUSIONS: MRSA is the most common identifiable cause of skin and soft-tissue infections among patients presenting to emergency departments in 11 U.S. cities. When antimicrobial therapy is indicated for the treatment of skin and soft-tissue infections, clinicians should consider obtaining cultures and modifying empirical therapy to provide MRSA coverage.

Extended-release ciprofloxacin (Cipro XR) for treatment of urinary tract infections.

Symptomatic urinary tract infections (UTIs) constitute a major health problem throughout the Western world. In the USA, UTIs are responsible for 7-8 million outpatient visits each year and for over one-third of all hospital-acquired infections. Empiric antimicrobial therapy for UTIs, which are primarily caused by Escherichia coli, is increasingly being complicated by the emergence of resistance to the most widely used agents. Recent studies indicate that the prevalence of E. coli resistance to trimethoprim/sulphamethoxazole (TMP/SMX), the current first-line therapy for UTIs, exceeds 20% in many North American regions. Importantly, antibiotic resistance often translates into clinical failure. The use of antibiotics with favourable pharmacokinetic/pharmacodynamic profiles and convenient dosing schedules, which effectively increase bacterial eradication and patient compliance, can help to curb the current epidemic of resistance and reduce the rate of clinical failure associated with resistance. Fluoroquinolones have well-established efficacy in the treatment of multiple bacterial infections and, over the years, the rates of resistance to these antibiotics have remained very low. Fluoroquinolones are currently recommended for therapy of uncomplicated UTIs when the local incidence of TMP/SMX resistance is >or=10-20%, as well as for the treatment of complicated UTIs and acute pyelonephritis. Ciprofloxacin, one of the most widely used fluoroquinolones, has a potent bactericidal effect across the full spectrum of uropathogens, as well as a long and excellent efficacy and safety record in the management of UTI and other infections. A recently developed extended (modified)-release formulation of ciprofloxacin (Cipro XR or Cipro XL) provides higher maximum plasma concentrations with lower inter-patient variability than the conventional, immediate-release, twice-daily formulation. Additionally, therapeutic drug levels with extended-release ciprofloxacin are achieved rapidly and maintained over the course of 24 h, allowing once-daily dosing. Clinical trials in patients with cystitis and those with complicated UTIs or acute uncomplicated pyelonephritis indicate that extended-release ciprofloxacin is at least as effective as the immediate-release formulation. These studies have also confirmed good tolerability and safety of extended-release ciprofloxacin, similar to the immediate-release formulation. Therefore, extended-release ciprofloxacin is a convenient, well-tolerated and effective therapy for UTIs that may improve patients' compliance with treatment and thus decrease the risk of treatment failure and the spread of antibiotic resistance.

Once-daily, high-dose levofloxacin versus ticarcillin-clavulanate alone or followed by amoxicillin-clavulanate for complicated skin and skin-structure infections: a randomized, open-label trial.

This study tested whether levofloxacin, at a new high dose of 750 mg, was effective for the treatment of complicated skin and skin-structure infections (SSSIs). Patients with complicated SSSIs (n=399) were randomly assigned in a ratio of 1:1 to 2 treatment arms: levofloxacin (750 mg given once per day intravenously [iv], orally, or iv/orally) or ticarcillin-clavulanate (TC; 3.1 g given iv every 4-6 hours) followed, at the investigator's discretion, by amoxicillin-clavulanate (AC; 875 mg given orally every 12 hours). In the clinically evaluable population, therapeutic equivalence was demonstrated between the levofloxacin and TC/AC regimens (success rates of 84.1% and 80.3%, respectively). In the microbiologically evaluable population, the overall rate of eradication was 83.7% in the levofloxacin treatment group and 71.4% in the TC/AC treatment group (95% confidence interval, -24.3 to -0.2). Both levofloxacin and TC/AC were well tolerated. These data demonstrate that levofloxacin (750 mg once per day) is safe and at least as effective as TC/AC for complicated SSSIs.