Citations

Kanamycin, BB-K8, and gentamicin were tested in parallel against 1,037 bacterial strains isolated from clinical material. The activity of BB-K8 at 20 μg/ml was comparable to that of gentamicin at 8 μg/ml against Pseudomonas aeruginosa and against Enterobacteriaceae , with the exception of gentamicin-resistant strains of Proteus rettgeri and Providencia stuartii , in which case the activities of BB-K8 and kanamycin were the same. BB-K8 exhibited little or no activity against streptococci. The activity of BB-K8 was affected by pH and inoculum size. A regression graph for inhibition data with a 10-μg disk of BB-K8 was developed, and synergistic activity of penicillin and BB-K8 against Streptococcus faecalis was tested.

The in vitro inhibitory and bactericidal activities of spectinomycin hydrochloride were tested against a variety of bacteria. The antibiotic was inhibitory at 31.2 μg/ml to most strains of Escherichia coli, Klebsiella, Enterobacter , and Staphylococcus epidermidis . Concentrations of antibiotic exhibiting bactericidal activity exceeded the inhibitory concentration by at least fourfold. Regression graphs were plotted for results obtained with 30-, 100-, 200-, and 300-μg spectinomycin discs; tentative interpretative standards are proposed.

Thirty-two clinical isolates of Ureaplasma urealyticum were inhibited by 0.036 μg of rosaramicin per ml, whereas 25 (78%) and 13 (41%) of the strains were inhibited by this concentration of minocycline and tetracycline, respectively. These results suggest that rosaramicin may be useful for the treatment of U. urealyticum infections.

In a 1964 study of the pharmacokinetic determinants of penicillin cure of gonococcal urethritis, 45 male prisoner volunteers were experimentally infected with strains of Neisseria gonorrhoeae having known in vitro penicillin susceptibility. After developing urethritis, subjects received intramuscular penicillin G and had serum samples obtained serially to determine penicillin concentration. Using a multiple regression technique, we studied patient-associated parameters and parameters of the serum penicillin curves to determine the best predictors of treatment results. Cure was best predicted by the time the serum penicillin concentration remained above three to four times the penicillin minimum inhibitory concentration of the infecting strain (probability of correct classification, >0.80). Those cured had serum penicillin concentrations which remained in this range for means of 7 to 10 h. Our findings confirm principles of antimicrobial therapy derived from animal models and may have application in studying therapy of gonorrhea and other infectious diseases.

Because excessively high rates of false resistance have been encountered with the 10-μg amikacin disk in diffusion susceptibility tests, a study was performed to examine existing zone diameter interpretative criteria and to compare the accuracy of 10- and 30-μg amikacin disks by the error rate-bounded classification scheme. Although current zone diameter interpretative criteria eliminate false susceptibles, there is an unacceptably high rate of false resistants. This problem can be resolved in most instances by revising the zone diameter interpretative criteria for the 10-μg disk (resistant, ≤9 mm; indeterminate, 10 to 11 mm; susceptible, ≥12 mm) or, preferably, by replacing the 10-μg disk with a 30-μg disk and adopting new interpretative criteria (resistant, ≤14 mm; indeterminate, 15 to 16 mm; susceptible, ≥17 mm). Because of significant differences in performance among media, it is necessary to include Pseudomonas aeruginosa ATCC 27853 among controls routinely tested and to exclude from use lots of Mueller-Hinton agar yielding results outside the 75% tolerance (90% confidence) limits for amikacin.

Susceptibility tests using 7 antimicrobial agents (carbenicillin, chloramphenicol, clindamycin, penicillin, cephalothin, metronidazole, and tetracycline) were run against 35 anaerobes including Bacteroides fragilis (17), other gram-negative bacilli (7), clostridia (5), peptococci (4), and eubacteria (2). Results in triplicate obtained by the microbroth dilution method and the aerobic modification of the broth disk method were compared with those obtained with an agar dilution method using Wilkins-Chalgren agar. Media used in the microbroth dilution method included Wilkins-Chalgren broth, brain heart infusion broth, brucella broth, tryptic soy broth, thioglycolate broth, and Schaedler's broth. A result differing by more than one dilution from the Wilkins-Chalgren agar result was considered a discrepancy, and when there was a change in susceptibility status this was termed a significant discrepancy. The microbroth dilution method using Wilkins-Chalgren broth and thioglycolate broth produced the fewest total discrepancies (22 and 24, respectively), and Wilkins-Chalgren broth, thioglycolate, and Schaedler's broth had the fewest significant discrepancies (6, 5, and 5, respectively). With the broth disk method, there were 15 significant discrepancies, although half of these were with tetracycline, which was the antimicrobial agent associated with the highest number of significant discrepancies (33), considering all of the test methods and media.

A multi-center study of 1,838 clinical isolates established the accuracy of diffusion susceptibility tests with 30-μg cephalothin disks and 30-μg cefamandole disks. The same interpretive zone standards can be applied to tests with either disk but the two drugs cannot be tested interchangeably.

The penetrations of methicillin, oxacillin, and cephalothin into cortical bone and synovial tissues were studied 1 h after their intravenous administration in 105 patients having arthroplasty of the hip. Although the lowest serum levels were noted with cephalothin ( P < 0.01), more patients receiving cephalothin achieved osseous drug levels inhibitory to staphylococci ( P < 0.01). Differences in the penetration of the three agents into synovial tissues were not statistically significant.

The effect of combinations of gentamicin with trimethoprim or sulfamethoxazole-trimethoprim against clinical isolates of Escherichia coli (11 strains) and Klebsiella pneumoniae (12 strains) was examined by using a microdilution checkerboard technique. All isolates were susceptible to each antimicrobial agent. Synergism, defined as at least a 2-log 2 -dilution lowering of the minimal inhibitory concentration of either antibiotic in the combination compared with the minimal inhibitory concentration of the antibiotic alone, was observed with 15 of 23 (65%) isolates tested against trimethoprim and gentamicin and 14 of 23 (61%) isolates tested against sulfamethoxazole-trimethoprim and gentamicin. A 3-log 2 -dilution lowering of the minimal inhibitory concentration of either antibiotic was observed in 7 of 23 (30%) trimethoprim and gentamicin trials and 3 of 23 (13%) sulfamethoxazole-trimethoprim and gentamicin trials. Antagonism was observed in 3 of 46 combination trials and only with strains of K. pneumoniae .

A total of 13 of 30 clinical isolates of Chlamydia trachomatis were susceptible in vitro to 0.01 μg of rosamicin per ml. Only two of these strains were susceptible to tetracycline or erythromycin at this level. The results suggest that rosamicin may be useful for the treatment of chlamydial urethritis.