Time-kill curve analysis and pharmacodynamic modelling for in vitro evaluation of antimicrobials against Neisseria gonorrhoeae.

Förster, Sunniva; Unemo, Magnus; Hathaway, Lucy J.; Low, Nicola; Althaus, Christian L. (2016). Time-kill curve analysis and pharmacodynamic modelling for in vitro evaluation of antimicrobials against Neisseria gonorrhoeae. BMC microbiology, 16, p. 216. BioMed Central 10.1186/s12866-016-0838-9

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BACKGROUND Gonorrhoea is a sexually transmitted infection caused by the Gram-negative bacterium Neisseria gonorrhoeae. Resistance to first-line empirical monotherapy has emerged, so robust methods are needed to evaluate the activity of existing and novel antimicrobials against the bacterium. Pharmacodynamic models describing the relationship between the concentration of antimicrobials and the minimum growth rate of the bacteria provide more detailed information than the MIC only. RESULTS In this study, a novel standardised in vitro time-kill curve assay was developed. The assay was validated using five World Health Organization N. gonorrhoeae reference strains and a range of ciprofloxacin concentrations below and above the MIC. Then the activity of nine antimicrobials with different target mechanisms was examined against a highly antimicrobial susceptible clinical strain isolated in 1964. The experimental time-kill curves were analysed and quantified with a previously established pharmacodynamic model. First, the bacterial growth rates at each antimicrobial concentration were estimated with linear regression. Second, we fitted the model to the growth rates, resulting in four parameters that describe the pharmacodynamic properties of each antimicrobial. A gradual decrease of bactericidal effects from ciprofloxacin to spectinomycin and gentamicin was found. The beta-lactams ceftriaxone, cefixime and benzylpenicillin showed bactericidal and time-dependent properties. Chloramphenicol and tetracycline were purely bacteriostatic as they fully inhibited the growth but did not kill the bacteria. We also tested ciprofloxacin resistant strains and found higher pharmacodynamic MICs (zMIC) in the resistant strains and attenuated bactericidal effects at concentrations above the zMIC. CONCLUSIONS N. gonorrhoeae time-kill curve experiments analysed with a pharmacodynamic model have potential for in vitro evaluation of new and existing antimicrobials. The pharmacodynamic parameters based on a wide range of concentrations below and above the MIC provide information that could support improving future dosing strategies to treat gonorrhoea.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Förster, Sunniva; Hathaway, Lucy Jane; Low, Nicola and Althaus, Christian

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services

ISSN:

1471-2180

Publisher:

BioMed Central

Language:

English

Submitter:

Beatrice Minder Wyssmann

Date Deposited:

22 Sep 2016 11:50

Last Modified:

22 Sep 2016 14:02

Publisher DOI:

10.1186/s12866-016-0838-9

PubMed ID:

27639378

Uncontrolled Keywords:

Antimicrobial resistance Gonorrhoea Neisseria gonorrhoeae Pharmacodynamics Time-kill curves

BORIS DOI:

10.7892/boris.88638

URI:

https://boris.unibe.ch/id/eprint/88638

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