Telithromycin-resistant Streptococcus pneumoniae

To the Editor: In recent years, antimicrobial drug resistance in Streptococcus pneumoniae has increased worldwide and is a major health concern. Resistance to β-lac-tams and macrolides, considered to be first-line therapeutic agents, is particularly high in France and many Asian countries (1–3). Resistance to new fluoroquinolones is reported with increasing frequency, which emphasizes the need for new effective drugs. Telithromycin, the first member of a new macrolide family, the ketolides, has been developed to overcome macrolide resistance. In vitro data have shown that telithromycin remains active against 98% to 100% of erythromycin-resistant strains (2,3). However, resistant mutants have been isolated in vitro, and a few poorly documented clinical failures have been reported in the treatment of pneumococcal infections. We report the first isolation of telithromycin-resistant S. pneumoniae from a blood culture after therapy. An 87-year-old woman was admitted on March 28, 2004, to St Joseph Hospital in Paris with typical upper left lobar pneumonia, as inferred from auscultatory results, radiologic findings , and laboratory data: leukocytes 37,300 cells/µL, C-reactive protein 455 mg/L, and positive urinary pneu-mococcal antigen (BinaxNOW, was not febrile. She had been followed for many years for chronic obstructive pulmonary disease (COPD), with acute exacerbation only in 2001. At that time, she was treated with the macrolide rox-ithromycin, without bacteriologic documentation, in addition to acetyl-cysteine (3 × 200 mg/d) and aerosolized terbutaline. On March 13, her COPD was exacerbated. On March 20, she visited her general practitioner and received 800 mg/day telithromycin for 5 days without improvement. Because of a cutaneous rash attributed to telithromycin, she received 20 mg prednisolone. After 48 hours, she was admitted to St Joseph Hospital because her respiratory syndrome was aggravated. A blood culture drawn on admission yielded a S. pneumoniae serotype 14 with decreased β-lactam susceptibility (MICs: penicillin G: 1 µg/mL; amoxicillin: 0.75 µg/mL; cefotaxime: 0.5 µg/mL, as determined by Etest). The strain was resistant to tetracy-clines, cotrimoxazole, macrolides, and lincosamides (erythromycin and clindamycin MIC >32 µg/mL). The MIC of telithromycin, performed on Mueller-Hinton agar + 5% horse blood by serial 2-fold dilution, was equal to 2 µg/mL in air and 8 µg/mL under CO 2 (0.01–0.03 µg/mL for control strains ATCC 49619 and 10 clinical isolates, including 5 that were MLSB [macrolide-lincosamide-strep-togramin B]–resistant). The patient was treated with 100 mg/kg/day intravenous amoxicillin and improved within 48 hours. She was discharged from the hospital 1 week later in good condition but remained …