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Synergism of cefazolin-gentamicin against enterococci.

A miniaturized technique for detecting antibiotic synergy by using microliter volumes was perfected. With this microtiter serial dilution method, the effect of the previously untried combination of cefazolin and gentamicin on 10 strains of enterococci was evaluated. At clinically achievable concentrations, the combination of cefazolin and gentamicin was found to be synergistic against all 10 strains when the data were plotted in the form of an isobologram. These results were compared with the conventional method of detecting synergy in vitro, namely, the determination of the rate of killing of the microorganisms with the antibiotics, singly and in combination. Similar results were also observed. These findings indicate that the microtiter serial dilution technique is a useful method for the routine determination of drug synergy. Moreover, in a patient with penicillin hypersensitivity and enterococcal infection, the combination of cefazolin and gentamicin should be considered for possible therapy.

Cefazolin

Synergy of penicillin-netilmicin combinations against enterococci including strains highly resistant to streptomycin or kanamycin.

The in vitro activity of combinations of penicillin and netilimicin was determined against 20 clinical isolates of enterococci and compared with that obtained in simultaneous tests with penicillin/sisomicin, penicillin/streptomycin, and penicillin/kanamycin. Synergy between the two drugs in each combination was determined by the use of quantitative kill curves and was defined as a killing by the combination at least 100-fold greater than that produced by the most effective drug alone. Penicillin/netilmicin and penicillin/sisomicin combinations were found to be synergistic against the majority of isolates tested, including strains resistant to penicillin/streptomycin or penicillin/kanamycin combinations. This synergy with penicillin could be demonstrated at a concentration of </=7 mug/ml for either netilmicin or sisomicin. Studies on the kinetics of killing produced by these combinations showed the rate and extent of killing to be directly dependent upon the organism's relative susceptibility to the aminoglycoside alone and the aminoglycoside concentration in the combination. Results also indicated that the interaction between penicillin and netilmicin was true synergy; i.e., rapid and complete killing was produced by combinations containing each drug at concentrations insufficient to produce any killing alone, and the killing observed could not be produced by either drug alone at a concentration equivalent to the total drug concentration in the combination. The potential clinical application of this synergistic interaction should be investigated further, especially in view of recent reports showing netilmicin to be considerably less toxic than gentamicin in experimental animals.

Anti-Bacterial Agents

Simple technique for the assay of antibiotic synergism against enterococci.

A simple technique with antibiotic-impregnated disks has been developed to demonstrate the antibiotic synergism of penicillins and aminoglycosides against enterococci. The two antibiotic disks are placed on inoculated plates so that the distance between their centers is less than the sum of the two radii of their previously determined inhibitory zones. After 5 h of incubation, beta-lactamase powder is dusted onto the susceptibility plate with a sterile cotton swab. After overnight incubation, the synergistic effect of the antibiotics is demonstrated by a clear area of no growth in between the two disks. There is good correlation between the synergism determined by this procedure and the susceptibility of the organisms to 2 mg of streptomycin per ml. This technique is simple and can be employed by any laboratory which performs Kirby-Bauer susceptibility procedures.

Anti-Bacterial Agents

Action and interaction of penicillin and gentamicin on enterococci.

The action and interaction of benzylpenicillin and gentamicin on Streptococcus faecalis was studied using mainly turbidimetric methods. The minimum antibacterial concentration (MAC) of each antibiotic lay considerably below the conventionally determined minimum inhibitory concentration, and levels of the two agents exceeding the MAC were necessary in order to obtain a synergic interaction. Evidence was obtained that gentamicin interfered with bacterial lysis induced by penicillin, and this suggests that the aminoglycoside is responsible for the bactericidal activity of the combination, the role of the penicillin being solely to facilitate access of the aminoglycoside to its target site. Our findings do not, however, fully support the generally held view that the increased permeability of enterococci to aminoglycosides is due to penicillin-induced cell wall damage. 'Persisters'--cells surviving prolonged exposure to the optimum lethal concentration of penicillin--were not killed by subsequent exposure to gentamicin if the penicillin was removed but were killed if the penicillin remained present.

Dose-Response Relationship, Drug

[Isolation of enterococci from clinical materials and their susceptibility to antibiotics (author's transl)].

Three hundred and fifty-one strains of enterococci were isolated from 2,337 clinical materials including urine, blood, pus and other during 6 months of spring and summer in 1977. Urine was the most frequent source of the organism among them. As for species, S. liquefaciens was isolated most frequently (45.5%), being followed by S. zymogenes (26.5%) and S. faecalis (21.5%) in order. The susceptibility of the isolates was tested with 10 antibiotics. In general, the majority of the strains were resistant to several antibiotics, but almost all the strains were susceptible to ampicillin and benzylpenicillin. The susceptibility of S. liquefaciens, S. zymogenes and S. faecalis to 10 antibiotics was similar with each other in pattern, while that of S. faecium and S. durans was considerably lower.

Anti-Bacterial Agents

[Enterocin typing of enterococci].

The author worked out a method of enterocinotyping on enterococci. A possibility of enterococcus typing by means of a set of enterocinogenic enterococcus strains was shown. A mobile enterococcus 4 (10 p) strain, possessing a high antagonistic activity, is suggested for enterococcus identification. Differentiation of enterococcus species by the enterocine sensitivity proved to be impossible.

Anaerobiosis

[Sanitary-index significance of enterococci in the study of household articles].

A total of 670 washings from various household articles were studied in creches and kindergartens for fecal contamination with the aid of two bacteriological tests (coli and enterococal titres); the degree of their contamination with enterococci and E. coli differed. Strongly contaminated objects (diapers, swaddling tables) were revealed with equal frequency by both tests, but objects assessed as moderately contaminated were more frequently revealed by the enterococcus test (P less than 0.05) than by colimetry. Criteria of evaluation of the quality of washings by the data of enterococcometry are suggested.

Child Day Care Centers

[Study of enterococci in milk].

Studied were a total of 270 samples of raw and pasteurized milk taken during the various technologic states of pasteurized mild produced for consumption at the State Economic Enterprise "Serdica", establishing the enterococcus and coli titers. It was found that the enterococcus titer of the raw milk varies from 10(-3) up to 10(-6), and the titer of the pasteurized milk at the enterprise and upon delivery through its commercial channels is from 1 up to 10(-3). The enterococcus titer of milk that was pasteurized and was kept for 24 hours at 4-5 degrees C was found to range from 1 to 10(-3), and of milk kept at 18-22 degrees C --from (0(-1) to 10(-6). Full coincidence of the enterococcus titer with the values of the coli titer was found only for pasteurized milk kept under refrigerator conditions. Along with the coli titer the enterococcus one may be used as a subsidiary means in a more strict bacteriologic control, however, it may not be referred to as the only criterion replacing the coli values in the hygiene evaluation of milk. All species of enterococci in varying counts are established in both raw and pasteurized milk. Prevailing are the strains of the Str. faecium group -- 43.2 per cent, and those of the Str. faecalis group -- 24.6 per cent.

Animals

[Studies on the growth requirements of enterococci (author's transl)].

The growth requirements of biochemically defined strains of the enterococcus species Streptococcus faecium, S. faecalis, S. faecalis var. zymogenes and S. faecalis var. liquefaciens were compared. Arginine, glutamic acid, histidine, leucine, methionine and valine were essential and isoleucine, tryptophan, adenine and uracil were stimulatory to growth for all testes strains. Variation in the specific requirements occur for alanine, glycine, and serine representing strains differences. Threonine was essential for S. faecium strains but had no effect on the growth of strains of other species of enterococci.

Adenine