EFFECT OF PATHOLOGICAL-CHANGES OF PH, PO2 AND PCO2 ON THE ACTIVITY OFANTIMICROBIAL AGENTS IN-VITRO

Since standard susceptibility tests reflect the physiological rather t han the pathological conditions prevailing within an infected abdomen, as recently documented, the effect of reduced pH and PO2 and increase d pCO2 on the activity of antibiotics in vitro was studied. MICs were determined in vitro under standard culture conditions (MIC(standard)) and modified conditions (MIC(modification)) simulating the previously determined pathological values. Various classes of antibiotics were af fected differently by the modified conditions. However, within an anti biotic class similar results were obtained for gram-negative and gram- positive pathogens. Median MIC(modification)/MIC(standard) ratios were 4 for aminoglycosides, 2 for quinolones and clindamycin, 1 for cephal osporins, and 0.5 for penicillins and vancomycin. Anaerobic conditions and a pH of 6.4 further increased the ratio of aminoglycosides to 8. Ratios were similar within an antibiotic class at inocula of 10(5) or 10(7) cfu/ml. All MICs determined in tests with imipenem against gram- negative and gram-positive bacteria and with vancomycin against gram-p ositive organisms were below the susceptibility breakpoint, whatever c onditions and inocula were employed. In contrast, the percentage of MI Cs in susceptibility range using high inocula and modified conditions decreased to 78 % for penicillins, 73 % for cephalosporins, 22 % for a minoglycosides, 11 % for quinolones and 0 % for clindamycin. In conclu sion, routine susceptibility testing may overestimate the activity of aminoglycosides and underestimate the activity of beta-lactams under t he conditions prevailing during abdominal infection.