active against Bordetella pertussis and Bordetella parapertussis. (6, 7). Therefore, we compared the susceptibilities of these. Bordetella species (34 clinical ...
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Vol. 42, No. 7
In Vitro Susceptibilities of Bordetella pertussis and Bordetella parapertussis to BAY 12-8039, Trovafloxacin, and Ciprofloxacin that the new fluoroquinolones should have good in vivo efficacy against pertussis and parapertussis (6). However, clinical trials have not yet been performed. The use of fluoroquinolones in children is contraindicated for toxicity reasons, but these agents might play a role in the treatment of adult patients with pertussis. For the novel compounds BAY 12-8039 and trovafloxacin, data on the concentrations achievable in bronchial secretions or sputum are not yet available.
BAY 12-8039 is a new 8-methoxyquinolone with activity against gram-positive bacteria that is significantly better than that of ciprofloxacin and activity against gram-negative bacteria comparable to that of ciprofloxacin (4). Trovafloxacin (formerly CP-99,219) is a novel fluoronaphthyridone related to the fluoroquinolones with excellent activity against both gram-positive and gram-negative organisms (3). Ciprofloxacin is very active against Bordetella pertussis and Bordetella parapertussis (6, 7). Therefore, we compared the susceptibilities of these Bordetella species (34 clinical isolates each) to BAY 12-8039 and trovafloxacin to their susceptibilities to ciprofloxacin. The agar dilution test procedure with Mueller-Hinton agar supplemented with 5% horse blood was very similar to that used in our previous studies (6, 7). Staphylococcus aureus ATCC 29213 served as the control strain. Table 1 shows the results of the MIC determinations. The
Thanks are due to W. Grotz for excellent technical assistance. This study was supported by financial grants and donation of the antimicrobial agents by Bayer AG and Pfizer GmbH. REFERENCES 1. Appleman, M. E., T. L. Hadfield, J. K. Gaines, and R. E. Winn. 1987. Susceptibility of Bordetella pertussis to five quinolone antimicrobic drugs. Diagn. Microbiol. Infect. Dis. 8:131–133. 2. Asahara, M., A. Tsuji, S. Goto, K. Masuda, and A. Kiuchi. 1989. In vitro and in vivo activities of QA-241, a new tricyclic quinolone derivative. Antimicrob. Agents Chemother. 33:1144–1152. 3. Briggs Gooding, B., and R. N. Jones. 1993. In vitro antimicrobial activity of CP-99,219, a novel azabicyclo-naphthyridone. Antimicrob. Agents Chemother. 37:349–353. 4. Dalhoff, A., U. Petersen, and R. Endermann. 1996. In vitro activity of BAY 12-8039, a new 8-methoxyquinolone. Chemotherapy 42:410–425. 5. Gerding, D. N., and J. A. Hitt. 1989. Tissue penetration of the new quinolones in humans. Rev. Infect. Dis. 11(Suppl. 5):S1046–1057. 6. Hoppe, J. E., and C. G. Simon. 1990. In vitro susceptibilities of Bordetella pertussis and Bordetella parapertussis to seven fluoroquinolones. Antimicrob. Agents Chemother. 34:2287–2288. 7. Hoppe, J. E., E. Rahimi-Galougahi, and G. Seibert. 1996. In vitro susceptibilities of Bordetella pertussis and Bordetella parapertussis to four fluoroquinolones (levofloxacin, d-ofloxacin, ofloxacin, and ciprofloxacin), cefpirome, and meropenem. Antimicrob. Agents Chemother. 40:807–808. 8. Kurzynski, T. A., D. M. Boehm, J. A. Rott-Petri, R. F. Schell, and P. E. Allison. 1988. Antimicrobial susceptibilities of Bordetella species isolated in a multicenter pertussis surveillance project. Antimicrob. Agents Chemother. 32:137–140.
TABLE 1. Activities of three fluoroquinolones against 34 isolates each of B. pertussis and B. parapertussis Organism
B. pertussis B. parapertussis
MIC (mg/ml)a
Antimicrobial agent
Range
50%
90%
BAY 12-8039 Trovafloxacin Ciprofloxacin BAY 12-8039 Trovafloxacin Ciprofloxacin
0.03 0.03–0.06 0.03–0.06 0.06–0.125 0.125 0.06
0.03 0.06 0.06 0.06 0.125 0.06
0.03 0.06 0.06 0.06 0.125 0.06
a 50% and 90%, MICs at which 50 and 90% of the isolates are inhibited, respectively.
results with ciprofloxacin are in good agreement with those of previous studies by our group (6, 7) and by others (1, 2, 8). The MICs of BAY 12-8039 and trovafloxacin against B. pertussis in the present study were essentially similar to those of ciprofloxacin (Table 1), thus confirming the results found with other species of gram-negative bacteria (3, 4). Similarly, the MICs of the three agents against B. parapertussis were all within one log2 dilution of each other (Table 1). The data on the in vitro activities of these agents against the two Bordetella species have to be interpreted in relation to the concentrations achievable in respiratory secretions. Such concentrations have been reported for ciprofloxacin (0.27 to 3.6 mg/ml [5]). A comparison of these concentrations and the MICs of all three agents against the Bordetella species suggests
Jo ¨rg E. Hoppe University Children’s Hospital Rumelinstrasse 23 D-72070 Tu ¨bingen Germany Axel Dalhoff Bayer AG Institut fu ¨r Chemotherapie D-42096 Wuppertal Germany Dietmar Pfru ¨nder Pfizer GmbH D-76032 Karlsruhe Germany
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