Fluoroquinolone-resistant Streptococcus pneumoniae associated with levofloxacin therapy.
Fluoroquinolone-resistant cultures of Streptococcus pneumoniae were isolated from 2 patients who were treated for pneumonia with levofloxacin. Nucleotide sequence analysis of bacterial DNA showed that the isolates contained mutations in both parC (DNA topoisomerase IV) and gyrA (DNA gyrase), which were shown previously to confer fluoroquinolone resistance. With the resistant isolates, the MICs for ciprofloxacin, gatifloxacin, grepafloxacin, levofloxacin, and trovafloxacin were above the maximal serum drug concentrations reported for standard dosage regimens. In contrast, the MICs for gemifloxacin and moxifloxacin were below the maximal serum concentrations. Increased effectiveness at blocking the growth of resistant mutants should make gemifloxacin and moxifloxacin less likely to allow the enrichment of mutants within susceptible populations. Additional resistance mutations in the isolates were readily obtained by plating on gemifloxacin- or moxifloxacin-containing agar. Thus, neither compound is expected to halt further accumulation of resistance mutations once mutant enrichment has been initiated by less potent derivatives.
Urban
C
C
New York Hospital Medical Center of Queens, Flushing, NY 11355, USA. cmurban@nyp.org
Rahman
N
N
Zhao
X
X
Mariano
N
N
Segal-Maurer
S
S
Drlica
K
K
Rahal
J J
JJ
D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D000890:Anti-Infective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D027081:DNA Gyrase; D027101:DNA Topoisomerase IV; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D004352:Drug Resistance, Microbial; D006801:Humans; D064704:Levofloxacin; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D015242:Ofloxacin / Q000494:pharmacology / Q000627:therapeutic use*; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy*; D017354:Point Mutation; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification
D000890:Anti-Infective Agents; D064704:Levofloxacin; D015242:Ofloxacin; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase; D004250:DNA Topoisomerases, Type II