Levofloxacin-Resistant Streptococcus pneumoniae: Second Look

Jorgensen et al. have recently reported on the activities of four quinolones against a selected group of Streptococcus pneumoniae isolates resistant to levofloxacin (3). This report raised several important issues regarding the current status of quinolone resistance among pneumococci. Specific issues include, first, the current prevalence of fluoroquinolone resistance among pneumococci and, second, whether some fluoroquinolones can serve as therapeutic alternatives for infections caused by strains resistant to other fluoroquinolones.

Although Jorgensen et al. correctly state that quinolone resistance in S. pneumoniae has been described, it is important to note that recent studies have clearly established that this resistance continues to be a rare occurrence (2, 5, 7, 8; L. J. Selman, D. C. Mayfield, C. Thornsberry, Y. R. Mauriz, and D. F. Sahm, Abstr. 40th Intersci. Conf. Antimicrob. Agents Chemother., abstr. 1800, p. 111, 2000). For example, among 17,943 isolates of S. pneumoniae collected from more than 200 institutions per year (from 1997 to 2000) as part of the TRUST surveillance initiative, only 83 levofloxacin-resistant isolates (0.5%) and 20 levofloxacin- and penicillin-resistant isolates (0.1%) were encountered (Selman et al. 40th ICAAC). In addition, Chen et al. reported that only 0.3% of their pneumococcal isolates (25 of 7,551) were resistant to levofloxacin (1).

Chen et al. also reported that ciprofloxacin resistance had increased in their study population, but that has also raised some questions. For example, in one study the rate of ciprofloxacin nonsusceptibility among 5,640 recent clinical isolates from across the United States was only 0.3% (i.e., ciprofloxacin MICs were ≥4 μg/ml), and the current ciprofloxacin MIC distributions were essentially unchanged from those reported at the time ciprofloxacin became available for clinical use in the United States in the 1980s (6). Also of interest is a recent report from Japan in which levofloxacin resistance in S. pneumoniae isolates was <1% even though levofloxacin has been used extensively in Japan since the early 1990s (8). Clearly, the preponderance of current research suggests that current levels of pneumococcal resistance to currently available fluoroquinolones remain quite low (1, 2, 4, 5; Selman et al., 40th ICAAC), and at this time there seems to be very little if any clear association between fluoroquinolone use and resistance. Although regional or institutional differences may occur, e.g., the report of Chen et al., large surveillance studies yield a truer picture of the overall occurrence of resistance.

Finally, the suggestion by Jorgensen et al. that the greater potency of some quinolones could provide improved clinical efficacy against levofloxacin-resistant pneumococcal strains is premature. While it is true that some of the newer quinolones (including some not tested in this study) have lower MICs than the MIC of levofloxacin for S. pneumoniae, this alone does not indicate that they will be superior in treating respiratory tract infections. Such conclusions must await appropriate pharmacodynamic and clinical studies, as the authors state. This is especially important to note since mutations in the quinolone resistance-determining region of S. pneumoniae have resulted in decreased activities of all quinolones tested (3).

In this “era of antibiotic resistance,” with all its attendant concerns, overstating resistance can have as negative an impact as understating it. Although the Jorgensen report adds yet another piece to the puzzle of fluoroquinolone resistance and its causes—particularly their evaluation of zone diameter breakpoints to detect fluoroquinolone resistance among pneumococci—each new study must be interpreted within the context of the larger picture. Local resistance data should be used to guide local therapy, but general conclusions for national or international dissemination should be based on national and international surveillance data.