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

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Foerster, SunnivaInstitute for Infectious Diseases, University of Bern, Bern, Switzerland; WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Faculty of Medicine and Health, Örebro University Hospital, Örebro, Sweden; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland (författare)

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

Artikel/kapitelEngelska2016

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2016-09-17
London, United Kingdom :BioMed Central,2016
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LIBRIS-ID:oai:DiVA.org:oru-52414
https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-52414URI
https://doi.org/10.1186/s12866-016-0838-9DOI

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Språk:engelska
Sammanfattning på:engelska

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Funding Agencies:SystemsX.ch (Swiss Initiative for Systems Biology)Swiss Platforms for Translational Medicine initiative, SwissTransMed 25/2013
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.

Ämnesord och genrebeteckningar

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Infektionsmedicin hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Infectious Medicine hsv//eng
NATURVETENSKAP Biologi Mikrobiologi hsv//swe
NATURAL SCIENCES Biological Sciences Microbiology hsv//eng
Neisseria gonorrhoeae
Gonorrhoea
Antimicrobial resistance
Time-kill curves
Pharmacodynamics

Biuppslag (personer, institutioner, konferenser, titlar ...)

Unemo, Magnus,1970-Örebro universitet,Institutionen för hälsovetenskaper,WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sweden(Swepub:oru)muo (författare)
Hathaway, Lucy J.Institute for Infectious Diseases, University of Bern, Bern, Switzerland (författare)
Low, NicolaInstitute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland (författare)
Althaus, Christian L.Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland (författare)
Institute for Infectious Diseases, University of Bern, Bern, Switzerland; WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Faculty of Medicine and Health, Örebro University Hospital, Örebro, Sweden; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, SwitzerlandInstitutionen för hälsovetenskaper (creator_code:org_t)

Sammanhörande titlar

Ingår i:BMC MicrobiologyLondon, United Kingdom : BioMed Central161471-2180

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Av författaren/redakt...: Foerster, Sunniv ...; Unemo, Magnus, 1 ...; Hathaway, Lucy J ...; Low, Nicola; Althaus, Christi ...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Infektionsmedici ...

NATURVETENSKAP: NATURVETENSKAP; och Biologi; och Mikrobiologi

Artiklar i publikationen: BMC Microbiology

Av lärosätet: Örebro universitet

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