Fluoroquinolone-resistant Streptococcus pneumoniae

To the Editor: In pneumococci, resistance to fluoroquinolones is associated with chromosomal mutations in the quinolone-resistance–determining regions (QRDR) of type II topoiso-merase enzymes, predominantly gyrA and parC. Several mutations have been described in these enzymes, but only a few have been shown by in vitro studies to confer resistance: S81F or Y, C, or I and E85K in gyrA; E474K in gyrB; A63T, S79F or Y or L and D83G or N in parC; and E474K and D435N or H in parE (1–5). Other frequently described mutations are K137N in parC and I460V in parE, which appear to not contribute to flu-oroquinolone resistance because they are commonly found in susceptible strains, and no evidence exists for their conferring fluoroquinolone resistance in vitro. We describe here a pneumococcal strain that was isolated from a 66-year-old white man with chronic obstructive pulmonary disease (COPD). The patient was admitted to the hospital with a presumed exacerba-tion of COPD. He had been discharged from the hospital 2 days earlier , having recovered from a similar manifestation of this disease. His treatment history was 250 mg/day oral levofloxacin for 7 days while in the hospital and levofloxacin for 10 days as an outpatient for a similar lower respiratory tract infection 3 months earlier. On this second admission he was given levofloxacin, 250 mg intravenously , once a day. He was treated with a low dosage because he was in renal failure. The patient continued to worsen and was transferred to the intensive care unit, where ceftriaxone, 1 g intravenously once a day, was given along with levofloxacin. He improved on the combination therapy and was discharged without sequelae. Cultures of the patient's blood and sputum grew Streptococcus pneumo-niae. The isolate from blood was resistant to levofloxacin (MIC 8 mg/L) and ciprofloxacin (MIC 8 mg/L), yet susceptible to gatifloxacin (MIC 1 mg/L) and ceftriaxone (MIC 0.38 mg/L), with intermediate resistance to penicillin (MIC 1.5 mg/L). The resistant isolate was of serotype 6A and of multilocus sequence type 376, which is the North Carolina 6A-23 clone Efflux testing that compared the ciprofloxacin MICs in the presence and absence of reserpine (10mg/L) showed no evidence of an overex-pressed efflux pump. We sequenced the QRDRs (gyrA, gyrB, parC, parE) and the entire gyrA and parC genes of the resistant strain isolated from blood by using previously described primers (2). Sequencing showed a S79Y mutation in parC and a Q118K …