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Pharmacokinetic Dat...
Pharmacokinetic Data Are Predictive of In Vivo Efficacy for Cefixime and Ceftriaxone against Susceptible and Resistant Neisseria gonorrhoeae Strains in the Gonorrhea Mouse Model
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- Connolly, Kristie L. (författare)
- Department of Microbiology and Immunology, Uniformed Services University of Health Sciences, Bethesda, MD, United States
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- Eakin, Ann E. (författare)
- Division of Microbiology and Infectious Diseases, National Institutes of Health, Rockville, MD, United States
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- Gomez, Carolina (författare)
- Department of Microbiology and Immunology, Uniformed Services University of Health Sciences, Bethesda, MD, United States
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- Osborn, Blaire L. (författare)
- Division of Microbiology and Infectious Diseases, National Institutes of Health, Rockville, MD, United States
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- Unemo, Magnus, 1970- (författare)
- Örebro universitet,Institutionen för medicinska vetenskaper,Region Örebro län,WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine, Clinical Microbiology
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- Jerse, Ann E. (författare)
- Department of Microbiology and Immunology, Uniformed Services University of Health Sciences, Bethesda, MD, United States
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(creator_code:org_t)
- American Society for Microbiology, 2019
- 2019
- Engelska.
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Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 63:3
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- There is a pressing need for drug development for gonorrhea. Here we describe pharmacokinetics/pharmacodynamics (PK/PD) analysis of extended-spectrum cephalosporins (ESC) against drug-susceptible and drug-resistant gonococcal strains in a murine genital tract infection model. PK determined in uninfected mice displayed a clear dose response in plasma levels following single doses of ceftriaxone (CRO) (intraperitoneal) or cefixime (CFM) (oral). The observed doses required for efficacy against ESCS strain FA1090 were 5 mg/kg (CRO) and 12 mg/kg (CFM); these doses had estimated therapeutic times (time of free drug above the MIC, fTMIC) of 24 h and 37 h, respectively. No single dose of CRO or CFM was effective against the ESCR strain H041. However, fractionation (TIDq8h) of a 120 mg/kg dose of CRO resulted in estimated therapeutic times in the range of 23 h and cleared H041 infection in a majority (90%) of mice, comparable to gentamicin. In contrast, multiple CFM doses of 120 or 300 mg/kg administered TIDq8h cleared infection in ≤ 50% of mice with therapeutic times estimated from single-dose PK data, of 13 and 27 h, respectively. This study reveals a clear relationship between plasma ESC levels and bacterial clearance rates in the gonorrhea mouse model. The PK/PD relationships in mice reflected that observed in humans with in vivo efficacy against an ESCS strain requiring doses that yielded an fTMIC in excess of 20-24 h. PK data also accurately predicted the failure of single doses of ESCs against an ESCR strain and were useful in designing effective dosing regimens.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
Nyckelord
- antibiotic resistance
- cefixime
- ceftriaxone
- clearance
- gonorrhea
- mouse model
- pharmacokinetics
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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