Prevalence of first-step mutants among levofloxacin-susceptible isolates of Streptococcus pneumoniae in north Lebanon

Resistance of Streptococcus pneumoniae to fluoroquinolones arises by stepwise accumulation of spontaneous point mutations in the quinolone- resistance determining regions (QRDRs). Fluoroquinolones treatment of infections caused by first- step mutants (pre-resistant) can lead to the selection of resistant isolates, resulting in treatment failure. First-step mutants cannot however be reliably detected by routine resistance testing. Levofloxacin has been used as a surrogate marker to predict fluoroquinolone susceptibility in clinical laboratories. By use of a PCR followed by pyrosequencing, we examined 45 levofloxacin-susceptible pneumococcal strains [minimal inhibitory concentration (MIC), 0.5 mg/ ml] for first- step parC and parE mutations in the QRDR: 51.2% of isolates were recovered from pulmonary and nasal secretions, 22.2% from blood, 24.4% from ear and eye discharge, and 2.2% from cerebrospinal fluid. The results showed that three strains (6.6%) had first-step parC (Asp83-Asn) or parE (Asp435-Asn) mutations. This test could be useful for some high- risk patients or in national surveys.