Comparative in vitro activity of a pharmacokinetically enhanced oral formulation of amoxicillin/clavulanic acid (2000/125 mg twice daily) against 9172 respiratory isolates collected worldwide in 2000.
OBJECTIVE
A new, pharmacokinetically enhanced, oral formulation of amoxicillin/clavulanic acid has been developed to overcome resistance in the major bacterial respiratory pathogen Streptococcus pneumoniae, while maintaining excellent activity against Haemophilus influenzae and Moraxella catarrhalis, including beta-lactamase producing strains. This study was conducted to provide in vitro susceptibility data for amoxicillin/clavulanic acid and 16 comparator agents against the key respiratory tract pathogens.


METHODS
Susceptibility testing was performed on 9172 isolates collected from 95 centers in North America, Europe, Australia, and Hong Kong by broth microdilution MIC determination, according to NCCLS methods, using amoxicillin/clavulanic acid and 16 comparator antimicrobial agents. Results were interpreted according to NCCLS breakpoints and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints based on oral dosing regimens.


RESULTS
Overall, 93.5% of Streptococcus pneumoniae isolates were susceptible to amoxicillin/clavulanic acid at the current susceptible breakpoint of < or =2 microg/mL and 97.3% at the PK/PD susceptible breakpoint of < or =4 microg/mL for the extended release formulation. Proportions of isolates that were penicillin intermediate and resistant were 13% and 16.5%, respectively, while 25% were macrolide resistant and 21.8% trimethoprim/sulfamethoxazole resistant. 21.9% of Haemophilus influenzae were beta-lactamase producers and 16.8% trimethoprim/sulfamethoxazole resistant, >99% of isolates were susceptible to amoxicillin/clavulanic acid, cefixime, ciprofloxacin and levofloxacin at NCCLS breakpoints. The most active agents against Moraxella catarrhalis were amoxicillin/clavulanic acid, macrolides, cefixime, fluoroquinolones, and doxycycline. Overall, 13% of Streptococcus pyogenes were resistant to macrolides.


CONCLUSIONS
The extended release formulation of amoxicillin/clavulanic acid has potential for empiric use against many respiratory tract infections worldwide due to its activity against species resistant to many agents currently in use.
Koeth
Laura M
LM
Laboratory Specialists, Inc., 1651 A. Crossings Parkway, Westlake, OH, USA. amdlmk@aol.com
Jacobs
Michael R
MR
Good
Caryn E
CE
Bajaksouzian
Saralee
S
Windau
Anne
A
Jakielaszek
Charles
C
Saunders
Kay A
KA
D000284:Administration, Oral; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001315:Australia; D024881:Drug Resistance, Bacterial; D005060:Europe; D006193:Haemophilus influenzae / Q000187:drug effects* / Q000302:isolation & purification; D006723:Hong Kong; D006801:Humans; D008826:Microbial Sensitivity Tests; D001936:Moraxella catarrhalis / Q000187:drug effects* / Q000302:isolation & purification; D009656:North America; D011159:Population Surveillance; D012141:Respiratory Tract Infections / Q000382:microbiology*; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000302:isolation & purification
D000900:Anti-Bacterial Agents; D019980:Amoxicillin-Potassium Clavulanate Combination