Neisseria gonorrhoeae telithromycin in vitro
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1 THE JAPANESE JOURNAL OF ANTIBIOTICS ( 97 ) Neisseria gonorrhoeae telithromycin in vitro Neisseria gonorrhoeae 22 telithromycin (TEL) erythromycin (EM), clarithromycin (CAM), penicillin G (PCG), cefodizime (CDZM), cefixime (CFIX), levofloxacin (LVFX), minocycline (MINO) spectinomycin (SPCM) TEL MIC mg/ml MIC 50 MIC 90 mg/ml TEL MIC 50 MIC 90 EM CAM 8 MINO 4 2 LVFX 6 64 CFIX MIC 50 MIC 90 2 PCG.4% CDZM SPCM breakpoint MIC 32 mg/ml TEL mg/ml breakpoint MIC Telithromycin (TEL) erythromycin (EM) 8 ) TEL Streptococcus pneumoniae Haemophilus influenzae Moraxella catarrhalis 2,3) Mycoplasma pneumoniae 4), Chlamydia pneumoniae 5) Legionella pneumophila 6) TEL Neisseria gonorrhoeae
2 38( 98 ) THE JAPANESE JOURNAL OF ANTIBIOTICS 58 3 June cefodizime (CDZM), spectinomycin (SPCM) ceftriaxone (CTRX) ) TEL N. gonorrhoeae I N. gonorrhoeae ATCC49226 N. gonorrhoeae ID TEST HN-20 b-lactamase b-lactamase 8) PCR TEMtype b-lactamase 2. TEL EM penicillin G PCG, clarithromycin CAM, SPCM CDZM cefixime CFIX, levofloxacin LVFX, minocycline MINO, TEL EM CAM 90% LVFX 0. N NaOH CFIX 50 mm (ph 7.0) 3. MIC MIC National Committee for Clinical Laboratory Standards NCCLS Clinical and Laboratory Standards Institute 9) GC Agar Base (Becton Dickinson) 36 g/l IsovitalX enrichment (Becton Dickinson) % II % %, 0 9.3%, % % 2. Breakpoint MIC MORAN timetherapeutic t /2 /ln 2 ln(c max / 4 MIC 90 ) 3 4 MIC 7 0 0) 3 MIC, 7 MIC C max /3e (7 ln 2/t/2) ) MIC (Table ) 2 5) Breakpoint MIC SPCM MORAN Therapeutic time NCCLS Breakpoint MIC 6) PCG
3 THE JAPANESE JOURNAL OF ANTIBIOTICS ( 99 ) Table. Breakpoint MIC calculated by modified Moran s fomula. NCCLS Breakpoint MIC Breakpoint MIC Tables 2, 3 PCG 0.06 m g/ml, TEL 600 mg EM, CAM, CFIX m g/ml, TEL 800 mg MINO, LVFX mg/ml, CDZM 4 mg/ml, SPCM 32 m g/ml 3. N. gonorrhoeae 22 TEL EM CAM PCG CDZM CFIX LVFX MINO SPCM MIC range MIC 50 MIC 90 Table 2 b-lactamase 2 (0.94%) 2 PCR TEM type b-lactamase TEL MIC m g/ml EM CAM MIC 50 MIC 90 2 m g/ml 8 4 mg/ml TEL MIC 50 MIC 90 m g/ml m g/ml EM CAM 8 MINO MIC 50 MIC 90 mg/ml LVFX MIC 50 MIC mg/ml 32 mg/ml b-lactam PCG, CFIX, CDZM MIC 50 MIC 90 2,, 4,, mg/ml SPCM Breakpoint MIC 32 mg/ml MIC 28 m g/ml 6 N. gonorrhoeae 800
4 320(00) THE JAPANESE JOURNAL OF ANTIBIOTICS 58 3 June Table 2. Antibacterial activity of telithromycin and other agents against 22 Neisseria gonorrhoeae isolates in Japan. Table 3. Antibacterial activity of telithromycin and other agents against 70 levofloxacin-, minocycline, and cefixime-resistant Neisseria gonorrhoeae isolates. TEL CFIX, LVFX, MINO 70 Table 3 TEL 600 mg 77.%, TEL 800 mg 00% EM CAM 00% Fig. TEL MIC
5 THE JAPANESE JOURNAL OF ANTIBIOTICS (0) Fig.. Correlation between MICs of telithromycin and those of the other antimicrobials. clarithromycin MIC(µg/mL) R 2 =0.67 R 2 = minocycline MIC(µg/mL) telithromycin MIC(µg/mL) telithromycin MIC(µg/mL) levofloxacin MIC(µg/mL) R 2 =0.09 R 2 =0.03 cefixime MIC(µg/mL) telithromycin MIC(µg/mL) telithromycin MIC(µg/mL) The correlation coefficient between MICs of telithromycin and those of the compound by Spearman rank correlation analysis
6 322(02) THE JAPANESE JOURNAL OF ANTIBIOTICS 58 3 June Log 2 (MIC) Spearman EM CAM MIC R TEL EM 8, CAM 4 m g/ml TEL m g/ml TEL MINO, PCG, CDZM LVFX, CFIX SPCM 0. TEL 83.5% (8/97) CFIX mg/ml TEL m g/ml CFIX 52.9% (8/34) III. 8 7) aztreonam (AZT), SPCM TEM- b -lactamase PPNG (penicillinaseproducing Neisseria gnorrhoeae), PBP- PBP- 2 CMRNG (Chromosome-Mediated penicillin-resistant Neisseria gonorrhoeae) CMRNG cefmetazole (CMZ) cefotiam (CTM) AZT MIC 200 AKASAKA 8) cefdinir AZT AZT AZT CZRNG (cefozopran-resistant Neisseria gnorrhoeae) 9) PBP-2 PRSP (penicillin-resistant Streptococcus pneumoniae) Nesseira PBP 20,2) DNA topoisomerase gyra parc 22) ribosomal RNA methylase (ermf) 23), (meff, mtr) 24,25) (tetm) 26) SPCM 6S ribosomal RNA 27) Breakpoint MIC MORAN CFIX 400 mg Breakpoint MIC NCCLS Breakpoint MIC LVFX 500 mg NCCLS 2 Breakpoint MIC NCCLS Breakpoint MIC Breakpoint MIC MIC PCG, EM, CAM, LVFX
7 THE JAPANESE JOURNAL OF ANTIBIOTICS (03) 79 99% MINO CFIX 52 46% 4 SHIGEMURA 28) ) CTRX CDZM SPCM 3 TEL mg/ml Breakpoint MIC ciprofloxacin (CPFX) 0.06 mg/ml LVFX tetracycline (TC) mg/ml MORAN TEL 600 mg 800 mg Breakpoint MIC m g/ml 600 mg 84%, 800 mg 00% 20 30% C. trachomatis CDC ) N. gonorrhoeae C. trachomatis TEL C. trachomatis MIC m g/ml CAM EM, azithromycin (AZM) mg/ml 8 29) N. gonorrhoeae C. trachomatis TEL TEL ) BRYSKIER, A.: New research in macrolides and ketolides since 997. Expert Opin Investig. Drugs 8: 7 94, 999 2) BARRY, A. L.; P. C. FUCHS & S. D. BROWN: In vitro activities of the ketolide HMR 3647 against recent gram-positive clinical isolates and Haemophilus influenzae. Antimicrob. Agents Chemother. 42: , 998 3) Telithromycin in vitro 5(S-): 7 8, ) BEBEAR, C. M.; H. RENAUDIN, A. BRYSKIER, et al.: Comparative activities of telithromycin (HMR 3647), levofloxacin, and other antimicrobial agents against human mycoplasmas. Antimicrob. Agents Chemother. 44: , ) ROBLIN, P. M. & M. R. HAMMERSCHLAG: In vitro activity of a new ketolide antibiotic; HMR 3647, against Chlamydia pneumoniae. Antimicrob. Agents Chemother. 42: 55 56, 998
8 324(04) THE JAPANESE JOURNAL OF ANTIBIOTICS 58 3 June 6) EDELSTEIN, P. H. & M. A. C. EDELSTEIN: In vitro activity of the ketolide HMR 3647 (RU 66647) for Legionella spp., its pharmacokinetics in guinea pigs, and use of the drug to treat guinea pigs with Legionella pneumophila pneumonia. Antimicrob. Agents Chemother. 43: 90 95, 999 7) (Supplement): 8 3, ),,, b-lactamase Escherichia coli 52: , ) National Committee for Clinical Laboratory Standards: Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; Approved standard Sixth edition, M7 A6. National Committee for Clinical Laboratory Standards, Wayne, Pa. 23 (2), ) MORAN, J. S. & W. C. LEVINE: Related Articles. Drugs of choice for the treatment of uncomplicated gonococcal infections. Clin. Infect. Dis. 20 (Suppl. ): S47 65, 995 ) Centers for Disease Control and Prevention: 998 guidelines for treatment of sexually transmitted diseases. MMWR Recomm Rep 23; 47(RR-):, 998 2) ),,, Telithromycin 5(S-) 7 8, ) ) CHIEN, S. C.; M. C. ROGGE, L. G. GISCLON, et al.: Pharmacokinetic profile of levofloxacin following once-daily 500-milligram oral or intravenous doses. Antimicrob. Agents Chemother. 4: , 997 6) National Committee for Clinical Laboratory Standards Performance Standards for Antimicrobial Susceptibility Testing; 4th Informational Supplement. National Committee for Clinical Laboratory Standards. Wayne, Pa., M00-S4, 24(): 97, ),,, : : 7 45, ) AKASAKA, S.; T. MURATANI, Y. YAMADA, et al.: Emergence of cephems and aztreonam high-resistant Neisseria gonorrheae that does not produce b -lactamase. J. Infect. Chemother. 7: 49 50, 200 9) MURATANI, T.; S. AKASAKA, T. KOBAYASHI, et al.: Outbreak of cefozopran (penicillin, oral cephems, and aztreonam)-resistant Neisseria gonorrhoeae in Japan. Antimicrob. Agents Chemother. 45: , ) AMEYAMA, S.; S. ONODERA, M. TAKAHATA, et al.: Mosaiclike structure of penicillin-binding protein 2 Gene ( pena) in clinical isolates of Neisseria gonorrhoeae with reduced susceptibility to cefixime. Antimicrob. Agents Chemother. 46: , ) GenBank accession No. AY46782 AY ) TANAKA, M.; T. MATSUMOTO, M. SAKUMOTO, et al.: Reduced clinical efficacy of pazufloxacin against gonorrhea due to high prevalence of quinolone-resistant isolates with the GyrA mutation. Antimicrob. Agents Chemother. 42: , ) ROBERTS, M. C.; W. O. CHUNG, D. ROE, et al.: Erythromycin-resistant Neisseria gonorrhoeae and oral commensal Neisseria spp. carry known rrna methylase genes. Antimicrob. Agents Chemother. 43: , ) LUNA, V. A.; S. J. COUSIN, W. L. WHITTINGTON, et al.: Identification of the conjugative mef gene in clinical Acinetobacter junii and Neisseria gonorrhoeae isolates. Antimicrob. Agents Chemother. 44: , ) HAGMAN, K. E.; W. PAN, B. G. SPRATT, et al.: Resistance of Neisseria gonorrhoeae to antimicrobial hydrophobic agents is modulated by the mtrrcde efflux system. Microbiology 4: 6 622, ) MORSE, S. A.; S. R. JOHNSON, J. W. BIDDLE, et al.: Highlevel tetracycline resistance in Neisseria gonorrhoeae is result of acquisition of streptococcal tetm determinant. Antimicrob. Agents Chemother. 30: , ) GALIMAND, M.; G. GERBAUD & P. COURVALIN: Spectinomycin resistance in Neisseria spp. due to mutations in 6S rrna. Antimicrob. Agents Chemother. 44: , ) SHIGEMURA, K.; H. OKADA, S. KAMIDONO, et al.: Susceptibilities of Neisseria gonorrhoeae to fluoroquinolones and other antimicrobial agents in Hyogo and Osaka, Japan. Sex. Transm. Infect. 80: 05 07, ) Chlamydia trachomatis telithromycin 53: ,
9 THE JAPANESE JOURNAL OF ANTIBIOTICS (05) IN VITRO ANTIBACTERIAL ACTIVITIES OF TELITHROMYCIN AGAINST CLINICAL ISOLATES OF Neisseria gonorrhoeae TETSURO MURATANI and TETSURO MATSUMOTO Department of Urology, School of Medicine, University of Occupational and Environmental Health, - Iseigaoka, Yahatanishi-ku, Kitakyushu, , Japan SUSUMU ARAI Preclinical Development, Scientific Affairs, Sanofi-Aventis Group, Aventis Pharma, -3-2 Minamidai, Kawagoe, Saitama, , Japan In vitro antibacterial activity of telithromycin (TEL) against the isolates of Neisseria gonorrhoeae (22 isolates) derived from urine or genital secretion in 2002 (April to December) was examined in comparison with those of macrolides (erythromycin [EM], clarithromycin [CAM]), penicillins (penicillin G [PCG]), cephems (cefodizime [CDZM], cefixime [CFIX]), quinolones (levofloxacin [LVFX]), tetracyclines (minocycline [MINO]), and aminoglycosides (spectinomycin [SPCM]). The MIC of TEL was ranged from to m g/ml and the MIC 50 and MIC 90 of TEL were respectively and m g/ml, which were the lowest values compared with those of other oral antibacterial agents measured. When compared TEL with other agents in the order of the MIC 50 and MIC 90, TEL was more superior to EM and CAM (both eight times), MINO (four times and twice), and LVFX (6 and 64 times). The MIC 90 of TEL was superior in twice though the MIC 50 was the same in comparison with CFIX. The CDZM resistant strain did not exist and SPCM also inhibit growth with 32 m g/ml or less that was the breakpoint MIC excluding one stock though the PCG sensitive strain was only.4% in the injection drug. However, clinical breakpoint MIC is not established, but the efficacy of TEL is prospective because of its high antibacterial activity to inhibit growth of all stocks for gonococcus with m g/ml. It is expected that TEL can become an oral antibiotic recommended for treatment of gonococcus if dosage and administration are considered.
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