Washington, John A.

The activities of Sch 21420 and amikacin were compared in vitro against 448 clinical bacterial isolates and against 82 gentamicin-resistant isolates of gram-negative bacilli. At 1 μg/ml, Sch 21420 was more active than amikacin against most Enterobacteriaceae but less active against Pseudomonas aeruginosa . Activity of these antibiotics against gentamicin-resistant organisms varied according to the species examined.

Inhibitory activity of cephalexin, cephradine, and cefaclor was compared by the WHO-ICS agar dilution technique. Cefaclor was substantially more active against staphylococci, streptococci, gonococci, meningococci, Haemophilus, Escherichia coli, Klebsiella pneumoniae, Citrobacter diversus, Proteus mirabilis , salmonellae, and shigellae than was cephalexin, which in turn was more active than cephradine. Cefaclor appeared to be less resistant to staphylococcal penicillinase than did the other two agents. None of these cephalosporins was active against Enterobacter, Serratia , indole-positive Proteeae, Pseudomonas , or Bacteroides fragilis .

In an effort to determine the feasibility and accuracy of performing direct susceptibility tests from positive blood cultures, minimal inhibitory concentrations (MICs), determined by the agar dilution method, of direct and standardized tests with seven antibiotics were compared. Results were analyzed as to the number of very major (change in MIC from susceptible in preliminary direct testing to resistant in final standardized testing), major (change in MIC from resistant to susceptible), and minor (change in MIC without change in interpretation) discrepancies. The results for gram-positive cocci and for gram-negative bacilli were 5, 6, and 82 of 162 strains tested and 3, 12, and 79 of 90 strains tested, respectively. Of the total number of susceptibility tests compared, major and very major discrepancies occurred in only 1 and 2.4% of instances with gram-positive and -negative isolates, respectively. The majority of discrepancies were noted with Staphylococcus epidermidis (four very major, five major), Klebsiella (two very major, four major), and Alcaligenes (five major). The antibiotics most often exhibiting discrepancies were penicillin, ampicillin, and cephalothin. The results indicate that preliminary susceptibility testing directly from positive blood culture bottles is generally both feasible and accurate.

The minimal inhibitory concentrations of 601 clinical isolates of anaerobic bacteria to 10 different antimicrobial agents were determined by an agar-dilution technique. Nearly all strains were resistant to kanamycin and gentamicin, although moderate activity to both drugs was noted with Fusobacterium sp., anaerobic cocci, some strains of Bacteroides melaninogenicus , and nonsporeforming gram-positive bacilli. Chloramphenicol at 12.5 μg/ml inhibited all but three of the strains tested. Tetracycline at 6.25 μg/ml had high activity against all groups tested, with the exception that only 39% of strains of Bacteroides fragilis were inhibited at this concentration. Excluding certain species of Bacteroides , the majority of anaerobes were inhibited by penicillin at 3.1 μg/ml or less and by cephalothin at 12.5 μg/ml or less. Lincomycin at 6.2 μg/ml or less was active against nearly all strains. Erythromycin at a concentration of 3.1 μg/ml was active against B. fragilis ; however, erythromycin was less active against the other groups. Most of the minimal inhibitory concentrations of lincomycin exceeded those of clindamycin by fourfold. Rifampin inhibited virtually all strains at 3.1 μg/ml.

Since the microbiological assay of the antibiotic content of serum generally requires 18 to 24 hr of incubation, results of such procedures may not become available in time to make appropriate adjustments in subsequent dosages of antibiotic. A 4-hr bioassay for determining concentrations of gentamicin in serum has been developed in which Staphylococcus aureus ATCC 6538P is used as the test organism. Poured plates have yielded satisfactory results after storage at 4 C for 5 days. Results of the 4-hr procedure agree closely with those of a conventional 18-hr disc-plate assay performed with the same test organism.