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In vitro synergistic effects of double combinations of β-lactams and azithromycin against clinical isolates of Neisseria gonorrhoeae

  • ORIGINAL ARTICLE
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Journal of Infection and Chemotherapy

Abstract

In Japan, Neisseria gonorrhoeae, a sexually transmitted pathogen, has recently shown significant resistance to various antimicrobial agents. In this study, a checkerboard method was utilized to investigate the in vitro activities of cefixime (CFIX), cefteram (CFTM), or amoxicillin (AMPC) in combination with azithromycin (AZM) against 25 clinical isolates of N. gonorrhoeae. Synergy, defined as a fractional inhibitory concentration (FIC) index of less than or equal to 0.50, was observed in 32% of isolates with CFIX+AZM, 12% of isolates with CFTM+AZM, and 4% of isolates with AMPC+AZM. Moreover, partial synergy, defined as an FIC index of greater than 0.50 and less than 1, was observed in 44% of isolates with CFIX+AZM, 68% of isolates with CFTM+AZM, and 52% of isolates with AMPC+AZM. In particular, as a result of the combination of CFIX and AZM, for all isolates, significant reductions were observed in the median CFIX minimum inhibitory concentration (MIC; from 0.25 to 0.008 µg/ml; P < 0.0001) and the median AZM MIC (from 0.12 to 0.03 µg/ml; P < 0.0001). However, antagonism, defined as an FIC index of greater than 1, was observed in only 4% of the isolates with both CFIX+AZM and CFTM+AZM, while it was seen in 12% of the isolates with AMPC+AZM. To our knowledge, this is the first study to demonstrate that the in vitro activity of CFIX against N. gonorrhoeae can be significantly enhanced in combination with AZM.

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References

  1. M Tanaka H Nakayama M Haraoka T Saika I Kobayashi S Naito (2000) ArticleTitleAntimicrobial resistance of Neisseria gonorrhoeae and high prevalence of ciprofloxacin-resistant isolates in Japan, 1993 to 1998 J Clin Microbiol 38 521–5 Occurrence Handle10655338 Occurrence Handle1:CAS:528:DC%2BD3cXht1aqtbo%3D

    PubMed  CAS  Google Scholar 

  2. M Tanaka H Nakayama T Notomi S Irie Y Tsunoda A Okadome et al. (2004) ArticleTitleAntimicrobial resistance of Neisseria gonorrhoeae in Japan, 1993 to 2002: continuous increasing of ciprofloxacin-resistant isolates Int J Antimicrob Agents 24S S15–S22 Occurrence Handle10.1016/j.ijantimicag.2004.02.005 Occurrence Handle1:CAS:528:DC%2BD2cXnsFSgurc%3D

    Article  CAS  Google Scholar 

  3. S Kamidono T Matsumoto (2004) ArticleTitleGonococcal infections, 2004 guidelines for diagnosis and treatment for sexually transmitted diseases Jpn J STD 15 IssueIDSuppl 8–13

    Google Scholar 

  4. InstitutionalAuthorNameCenters for Disease Control and Prevention (2002) ArticleTitleSexually transmitted diseases treatment guidelines 2002 Morb Mortal Wkly Rep 51 IssueIDRR-6 36–42

    Google Scholar 

  5. M Tanaka J Kumazawa T Matsumoto Y Kumamoto T Hirose T Saka et al. (1996) ArticleTitleBasic and clinical studies of azithromycin for the treatment of sexually transmitted male urethritis Jpn Arch STD 7 76–91

    Google Scholar 

  6. InstitutionalAuthorNameClinical and Laboratory Standards Institute (2005) Performance standards for antimicrobial susceptibility testing; fifteenth informational supplement CLSI document M100-S15 CLSI Wayne, PA

    Google Scholar 

  7. GM Eliopoulos RC Moellering (1996) Antimicrobial combinations V Lorian (Eds) Antibiotics in laboratory medicine EditionNumber4th ed Williams and Wilkins Baltimore, MD 330–96

    Google Scholar 

  8. Tanaka M, Huruya R, Nakayama H, Iyota T, Saika T, Kobayashi I. Antimicrobial resistance of Neisseria gonorrhoeae in Fukuoka city, Japan 2004. Jpn J STD 2005; A-02, 49

  9. MW Ruble DH Gilbert SH Zinner (1995) ArticleTitleIn-vitro interaction of azithromycin and fluoroquinolones against gram-positive and gram-negative bacteria Clin Microbiol Infect 1 183–9 Occurrence Handle10.1111/j.1469-0691.1996.tb00551.x

    Article  Google Scholar 

  10. F Fernandez-Cuenca L Martinez-Martinez A Pascual EJ Perea (2003) ArticleTitleIn vitro activity of azithromycin in combination with amikacin, ceftazidime, ciprofloxacin or imipenem against clinical isolates of Acinobacter baumannii Chemotherapy 49 24–6 Occurrence Handle12714805 Occurrence Handle1:CAS:528:DC%2BD3sXks1Ghu78%3D Occurrence Handle10.1159/000069774

    Article  PubMed  CAS  Google Scholar 

  11. SJ Martin SL Pendland C Chen P Schreckenberger LH Danziger (1996) ArticleTitleIn vitro synergy testing of macrolide-quinolone combinations against 41 clinical isolates of Legionella Antimicrob Agents Chemother 40 1419–21 Occurrence Handle8726012 Occurrence Handle1:CAS:528:DyaK28XjtlWmtLo%3D

    PubMed  CAS  Google Scholar 

  12. DH Martin TF Mroczkowski ZA Dalu J McCarty RB Jones SJ Hopkins et al. (1992) ArticleTitleA controlled trial of a single dose of azithromycin for the treatment of chlamydial urethritis and cervicitis. The Azithromycin for Chlamydial Infections Study Group N Engl J Med 327 921–5 Occurrence Handle1325036 Occurrence Handle1:STN:280:DyaK38zot1KisA%3D%3D Occurrence Handle10.1056/NEJM199209243271304

    Article  PubMed  CAS  Google Scholar 

  13. A Nilsen A Halsos A Johansen E Hansen E Torud D Moseng et al. (1992) ArticleTitleA double blind study of single dose azithromycin and doxycycline in the treatment of chlamydial urethritis in males Genitourin Med 68 325–7 Occurrence Handle1330880 Occurrence Handle1:STN:280:DyaK3s%2Flt1altw%3D%3D

    PubMed  CAS  Google Scholar 

  14. EM Thorpe SuffixJr WE Stamm EW Hook Suffix3rd SA Gall RB Jones K Henry et al. (1996) ArticleTitleChlamydial cervicitis and urethritis: single dose treatment compared with doxycycline for 7 days in community based practises Genitourin Med 72 93–7 Occurrence Handle8698374

    PubMed  Google Scholar 

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Correspondence to Masatoshi Tanaka.

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Furuya, R., Nakayama, H., Kanayama, A. et al. In vitro synergistic effects of double combinations of β-lactams and azithromycin against clinical isolates of Neisseria gonorrhoeae . J Infect Chemother 12, 172–176 (2006). https://doi.org/10.1007/s10156-006-0445-z

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  • DOI: https://doi.org/10.1007/s10156-006-0445-z

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