NDLI: Pharmacodynamic Modeling of Clarithromycin against Macrolide-Resistant [PCR-Positive mef(A) or erm(B)] Streptococcus pneumoniae Simulating Clinically Achievable Serum and Epithelial Lining Fluid Free-Drug Concentrations

Content Provider	PubMed Central
Author	Noreddin, Ayman M. Roberts, Danielle Nichol, Kim Wierzbowski, Aleksandra Hoban, Daryl J. Zhanel, George G.
Copyright Year	2002
Abstract	The association between macrolide resistance mechanisms and clinical outcomes remains understudied. The present study, using an in vitro pharmacodynamic model, assessed clarithromycin (CLR) activity against mef(A)-positive and erm(B)-negative Streptococcus pneumoniae isolates by simulating free-drug concentrations in serum and both total (protein-bound and free) and free drug in epithelial lining fluid (ELF). Five mef(A)-positive and erm(B)-negative strains, one mef(A)-negative and erm(B)-positive strain, and a control [mef(A)-negative and erm(B)-negative] strain of S. pneumoniae were tested. CLR was modeled using a one-compartment model, simulating a dosage of 500 mg, per os, twice a day (in serum, free-drug Cp maximum of 2 μg/ml, t 1/2 of 6 h; in ELF, C ELF(total) maximum of 35μg/ml, t 1/2 of 6 h; CELF(free) maximum of 14 μg/ml, t 1/2 of 6 h). Starting inocula were 106 CFU/ml in Mueller-Hinton broth with 2% lysed horse blood. With sampling at 0, 4, 8, 12, 20, and 24 h, the extent of bacterial killing was assessed. Achieving CLR T/MIC values of ≥90% (AUC0-24/MIC ratio, ≥61) resulted in bacterial eradication, while T>MIC values of 40 to 56% (AUC0-24/MIC ratios of ≥30.5 to 38) resulted in a 1.2 to 2.0 log10 CFU/ml decrease at 24 h compared to that for the initial inoculum. CLR T/MIC values of ≤8% (AUC0-24/MIC ratio, ≤17.3) resulted in a static effect or bacterial regrowth. The high drug concentrations in ELF that were obtained clinically with CLR may explain the lack of clinical failures with mef(A)-producing S. pneumoniae strains, with MICs up to 8 μg/ml. However, mef(A) isolates for which MICs are ≥16 μg/ml along with erm(B) may result in bacteriological failures.
Related Links	http://dx.doi.org/10.1128/aac.46.12.4029-4034.2002
Ending Page	4034
Page Count	6
Starting Page	4029
File Format	PDF
ISSN	00664804
e-ISSN	10986596
Journal	Antimicrobial Agents and Chemotherapy
Issue Number	12
Volume Number	46
Language	English
Publisher	American Society for Microbiology
Publisher Date	2002-12-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Pharmacology (medical) Pharmacology Infectious Diseases Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Pharmacology Pharmacology (medical)

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Pharmacodynamic Activity of Telithromycin at Simulated Clinically Achievable Free-Drug Concentrations in Serum and Epithelial Lining Fluid against Efflux (mefE)-Producing Macrolide- Resistant Streptococcus pneumoniae for Which Telithromycin MICs Vary

Antimicrobial Susceptibility and Macrolide Resistance Inducibility of Streptococcus pneumoniae Carrying erm(A), erm(B), or mef(A)

Macrolide-Resistant Streptococcus pneumoniae in Canada during 1998–1999: Prevalence of mef(A) and erm(B) and Susceptibilities to Ketolides

Macrolide Resistance in Streptococcus pneumoniae

In vitro killing activities of antibiotics at clinically achievable concentrations in cerebrospinal fluid against penicillin-resistant Streptococcus pneumoniae isolated from children with meningitis.

Pharmacodynamics of Moxifloxacin and Levofloxacin at Simulated Epithelial Lining Fluid Drug Concentrations against Streptococcus pneumoniae

Clonal Spread of mef-Positive Macrolide-Resistant Streptococcus pneumoniae Isolates Causing Invasive Disease in Adults in Germany▿

Predominance of 23S rRNA Mutants among Non-Erm, Non-Mef Macrolide-Resistant Clinical Isolates of Streptococcus pneumoniae Collected in the United States in 1999-2000

Effects of Clarithromycin at Sub-Minimum Inhibitory Concentrations on Early ermB Gene Expression, Metabolic Activity and Growth of an erm(B)-Expressing Macrolide-Resistant Strain of Streptococcus pneumoniae

Pharmacodynamic Modeling of Clarithromycin against Macrolide-Resistant [PCR-Positive mef(A) or erm(B)] Streptococcus pneumoniae Simulating Clinically Achievable Serum and Epithelial Lining Fluid Free-Drug Concentrations

Similar Documents

Pharmacodynamic Activity of Telithromycin at Simulated Clinically Achievable Free-Drug Concentrations in Serum and Epithelial Lining Fluid against Efflux (mefE)-Producing Macrolide- Resistant Streptococcus pneumoniae for Which Telithromycin MICs Vary

Antimicrobial Susceptibility and Macrolide Resistance Inducibility of Streptococcus pneumoniae Carrying erm(A), erm(B), or mef(A)

Macrolide-Resistant Streptococcus pneumoniae in Canada during 1998–1999: Prevalence of mef(A) and erm(B) and Susceptibilities to Ketolides

Macrolide Resistance in Streptococcus pneumoniae

In vitro killing activities of antibiotics at clinically achievable concentrations in cerebrospinal fluid against penicillin-resistant Streptococcus pneumoniae isolated from children with meningitis.

Pharmacodynamics of Moxifloxacin and Levofloxacin at Simulated Epithelial Lining Fluid Drug Concentrations against Streptococcus pneumoniae

Clonal Spread of mef-Positive Macrolide-Resistant Streptococcus pneumoniae Isolates Causing Invasive Disease in Adults in Germany▿

Predominance of 23S rRNA Mutants among Non-Erm, Non-Mef Macrolide-Resistant Clinical Isolates of Streptococcus pneumoniae Collected in the United States in 1999-2000

Effects of Clarithromycin at Sub-Minimum Inhibitory Concentrations on Early ermB Gene Expression, Metabolic Activity and Growth of an erm(B)-Expressing Macrolide-Resistant Strain of Streptococcus pneumoniae

Pharmacodynamic Modeling of Clarithromycin against Macrolide-Resistant [PCR-Positive mef(A) or erm(B)] Streptococcus pneumoniae Simulating Clinically Achievable Serum and Epithelial Lining Fluid Free-Drug Concentrations