Determination of tolerance to antibiotic bactericidal activity on Kirby-Bauer susceptibility plates.

A rapid method utilizing Kirby-Bauer susceptibility plates was developed to determine bacterial tolerance to antibiotic bactericidal activity. After completion of initial antibiotic disk susceptibility testing, the disks containing cephalothin, cefazolin, nafcillin, oxacillin, and methicillin were removed and replaced with disks containing a potent beta-lactamase. The plates were reincubated for 18-24 hours and examined for regrowth of organisms within the original zone of inhibition. For 15 of 16 patients who had serious Staphylococcus aureus infections, the method correlated with clinical outcome of antibiotic chemotherapy. Broth dilution tests for bactericidal activity only correlated with clinical response for 11 of 16 patients. One hundred consecutive clinical S. aureus isolates tested with the new method demonstrated tolerance in 27% of strains to cephalothin, 15% to cefazolin, 1% to oxacillin, and 2% of nafcillin.

Serious staphylococcal infections with strains tolerant to bactericidal antibiotics.

The clinical response in 20 cases of serious staphylococcal infection was compared with the in vitro resistance or "tolerance" of the infecting Staphylococcus to killing by antibiotics used in treatment. Cases were divided into two groups: (1) patients who initially received nonbactericidal antibiotics (ten cases), and (2) patients who initially received bactericidal antibiotics with or without nonbactericidal antibiotics. Mortality due to uncontrolled staphylococcal infection was 40% (4/10) in group 1 as compared with no mortality (1/10) in group0) in group 1 as compared with no mortality (0/10) in group 2. The duration of positive cultures after start of therapy in group 1 (mean, 6.1 days) was significantly longer than that in group 2 (mean, 1.3 days). The duration of fever after start of therapy in group 1 was not significantly different when compared with group 2.