Therapeutic options among broad-spectrum β-lactams for infections caused by levofloxacin-nonsusceptible Streptococcus pneumoniae

Streptococcus pneumoniae has consistently become more resistant to primary, orally administered treatment regimens used for community-acquired respiratory tract infections (CARTI; sinusitis, bronchitis, pneumonia). As resistance rates approach 40-50% in the United States and North America for penicillin and macrolides, other agents also have exhibited coresistance rates of 10-20% (tetracycline, clindamycin, trimethoprim/sulfamethoxazole). These facts led to altered clinical treatment guidelines (IDSA) supporting the use of respiratory fluoroquinolones (levofloxacin, gatifloxacin, gemifloxacin, and moxifloxacin). This report from the SENTRY Antimicrobial Surveillance Program lists possible parenterally administered treatment alternatives for the fluoroquinolone (levofloxacin)-nonsusceptible pneumococci. The SENTRY Program isolates from CARTI (1997-2003), totaling 21 605 strains from Europe, Asia Pacific, and the Americas, were screened for fluoroquinolone-resistant S. pneumoniae. A total of 157 (0.7%) levofloxacin-nonsusceptible (MIC ≥ 4 μg/mL) strains were identified and tested by reference broth microdilution methods against 27 antimicrobials. Quinolone resistance-determining region (QRDR) mutations were determined by PCR amplification and gene sequencing. The entire population of S. pneumoniae had the following antibiogram demographics: penicillin-nonsusceptible (32%), macrolide resistance (24%), tetracycline resistance (21%), clindamycin resistance (11%), trimethoprim/sulfamethoxazole resistance (33%), and 6% of strains were resistant to all 5 drugs. Levofloxacin-resistant strains routinely had 2 or more QRDR mutations most frequently in gyrA at Ser81Phe or Tyr and in parC at Ser79Phe or Tyr and Lys137Asn. Four agents had extremely low rates of resistance when tested against the 157 levofloxacin-nonsusceptible strains (e.g., quinupristin/dalfopristin, 0% resistance; vancomycin, 0%; cefepime, 1%; ceftriaxone, 1%). Levofloxacin-nonsusceptible pneumococcal isolates remain uncommon, but are a growing problem in CARTI (1.4% in 2003), especially in previously fluoroquinolone-treated cases. Parenteral cephalosporins (cefepime or ceftriaxone) continue to be potent and safe for use in hospitalized patients with S. pneumoniae community-acquired pneumonia, used with or without co-drugs according to published guidelines.