Abstract
A direct relationship between inoculum size and in vitro antibiotic susceptibility is readily apparent in the response of Haemophilus influenzae to beta-lactamase antibiotics. We studied three strains of H. influenzae, (AmpS ChloroS, AmpR ChloroS, and AmpR ChloroR) in parallel under varying inocula conditions against Moxalactam and Ampicillin. The AmpS strain showed little or no inoculum effect with Moxalactam or Ampicillin while the AmpR strains showed dramatic differences in response to Ampicillin but not Moxalactam as demonstrated by broth dilution, agar dilution, and disk diffusion techniques. The inoculum effect was found to be independently related to the total number of colony-forming units (CFU) inoculated as well as the density of organisms (CFU/ml). Kinetic studies demonstrated significant differences between conventional broth growth curves and a continuous antibiotic flow system. Beta-lactamase producing H. influenzae reduced Ampicillin concentrations in “stagnant” in vitro systems but not in dynamic systems more analogous to the steady state of patients. Extrapolation from in vitro susceptibility studies to therapeutic decision-making requires knowledge beyond the MIC of an organism at a standard inoculum size, including: the total number of organisms in a patient, the maximum concentration of organisms in a patient, antibiotic tissue penetration, antibiotic turnover, and the effect of host defenses.
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Parmelee, S., Todd, J. & Kempe, C. 1054 INFLUENCE OF INOCULUM SIZE ON INTERPRETATION OF SUSCEPTIBILITY TESTING OF HAEMOPHILUS INFLUENZAE: MOXALACTAM VS. AMPICILLIN. Pediatr Res 15 (Suppl 4), 618 (1981). https://doi.org/10.1203/00006450-198104001-01080
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DOI: https://doi.org/10.1203/00006450-198104001-01080