Respiratory tract infections remain a common cause of morbidity and mortality worldwide, and Haemophilus spp. have been the important pathogens causing respiratory tract infections (2, 3). Haemophilus parainfluenzae is one of the pathogens that are frequently isolated from respiratory specimens, but the clinical isolates are usually neglected as indigenous bacteria of the human respiratory tract. However, recent case reports have indicated that H. parainfluenzae might also be the causative organism of certain respiratory diseases, such as acute pneumonia (4, 7). We have focused on this bacterium by studying its prevalence in patients, as well as the antimicrobial susceptibilities of the clinical isolates. Furthermore, we identified some fluoroquinolone-resistant strains of H. parainfluenzae (FRHP) in our collection.
Respiratory specimens (e.g., sputum, pharyngeal swabs, and tonsillar swabs) were collected from patients visiting the outpatient departments of 382 facilities all over Japan in 1998 to 2000. H. influenzae (1,213 strains), H. parainfluenzae (920 strains), H. haemolyticus (232 strains), and H. parahaemolyticus (111 strains) were isolated from the samples collected in the 3 years. The MICs of some antimicrobial agents, including levofloxacin, were determined for all of the strains by the NCCLS standard broth microdilution method (5). Ampicillin was purchased from Wako Chemicals (Osaka, Japan), and all other antimicrobial agents were kindly provided by the corresponding manufacturers. We determined the fluoroquinolone-resistant strains of Haemophilus spp. with the NCCLS breakpoint of levofloxacin, >2 μg/ml (6). The numbers of FRHP isolates were 2 (2.4%), 16 (3.6%), and 13 (3.0%) in 1998, 1999, and 2000, respectively, while only one or two fluoroquinolone-resistant strains of the other Haemophilus spp. were isolated. The distributions of drug MICs for H. parainfluenzae, 20 fluoroquinolone-susceptible strains of H. parainfluenzae (FSHP), and 30 FRHP isolates are summarized in Table 1. All five fluoroquinolones exhibited excellent antimicrobial activity against FSHP (MICs for 90% of the strains tested [MIC90s], ≤0.015 to 0.06 μg/ml), whereas each MIC90 of fluoroquinolones for FRHP was more than 100-fold higher than that that for FSHP. Sitafloxacin exhibited a clearly lower MIC90 (1 μg/ml) than did the other fluoroquinolones. The susceptibilities of FRHP to other, nonfluoroquinolone antimicrobial agents were similar to those of FSHP, while two FRHP isolates exhibited lower susceptibilities to ampicillin (MIC, >32 μg/ml).
TABLE 1.
Distribution of the MICs of five fluoroquinolones and four nonfluoroquinolones for FSHP and FRHPa
| Antimicrobial agent | No. of strains for which the MIC (μg/ml) was:
|
||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ≤0.015 | 0.03 | 0.06 | 0.125 | 0.25 | 0.5 | 1 | 2 | 4 | 8 | 16 | 32 | >32 | |
| FSHP (n = 20) | |||||||||||||
| Ciprofloxacin | 17 | 20 | |||||||||||
| Levofloxacin | 10 | 18 | 20 | ||||||||||
| Moxifloxacin | 4 | 12 | 18 | 19 | 20 | ||||||||
| Sitafloxacin | 19 | 20 | |||||||||||
| Sparfloxacin | 13 | 19 | 20 | ||||||||||
| Ampicillin | 2 | 11 | 16 | 19 | 20 | ||||||||
| Cefotiam | 4 | 16 | 19 | 20 | |||||||||
| Imipenem | 1 | 5 | 15 | 18 | 20 | ||||||||
| Clarithromycin | 1 | 4 | 14 | 19 | 20 | ||||||||
| FRHP (n = 30) | |||||||||||||
| Ciprofloxacin | 2 | 5 | 16 | 24 | 28 | 30 | |||||||
| Levofloxacin | 19 | 28 | 30 | ||||||||||
| Moxifloxacin | 5 | 12 | 22 | 30 | |||||||||
| Sitafloxacin | 1 | 11 | 22 | 28 | 30 | ||||||||
| Sparfloxacin | 2 | 9 | 19 | 30 | |||||||||
| Ampicillin | 3 | 19 | 22 | 25 | 27 | 28 | 30 | ||||||
| Cefotiam | 2 | 15 | 27 | 29 | 30 | ||||||||
| Imipenem | 1 | 13 | 27 | 29 | 30 | ||||||||
| Clarithromycin | 3 | 7 | 16 | 29 | 30 | ||||||||
The values represent the cumulative number of strains for which the MICs were below the MICs indicated, and the underlined values represent the 90th percentile of the total number of strains.
To our knowledge, only a few studies previously examined the drug susceptibility of H. parainfluenzae. The recently reported surveillance studies in Europe (2) and the United States (3) indicated that most H. parainfluenzae isolates were susceptible to levofloxacin and other fluoroquinolones. This is the first report regarding clinical isolates of FRHP. It is conceivable that the fluoroquinolone resistance of FRHP described in this report is caused by genetic mutations in the gyrA and/or the parC gene which likely occur in some other bacteria, such as Streptococcus pneumoniae and H. influenzae (1, 8). This bacterial resistance might be related to the selective pressure derived from the prevalent use of fluoroquinolones in Japan (8). Careful monitoring of changes in the drug susceptibility pattern of H. parainfluenzae, as well as those of many other pathogens, is important.
(This study was previously presented in part [42nd Intersci. Conf. Antimicrob. Agents Chemother., abstr. C2-1994, p. 124].)
Acknowledgments
We thank Shinsuke Matsuki, Suntory Co., Ltd., for assistance with the collection of strains and Intetsu Kobayashi, Mitsubishi Kagaku Bio-Clinical Laboratories, for helpful assistance and suggestions.
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