Sisomicin: an aminoglycoside antibiotic that is highly effective against Pseudomonas.
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Amikacin↗
Biomedical subjects
C C Sanders
Publications and source records attributed to C C Sanders.
Antagonism of cefamandole by cefoxitin in routine disk susceptibility tests.
Cefoxitin was found to antagonize cefamandole in standardized disk diffusion susceptibility tests. This antagonism increased as the distance between the two disks decreased, and was most frequently observed in tests with cephalothin-resistant Enterobacteriaceae. It occurred in tests with 68 of 98 (69%) cephalothin-resistant isolates, one of six (17%) cephalothin-intermediate isolates, and one of 40 (3%) cephalothin-susceptible isolates. Clinical laboratories that use both disks in routine susceptibility tests should be aware of this anatagonism and should ensure that the disks are not placed in proximity to each other.
Cefamandole↗
Inhibition of Streptococcus mutans by human plaque flora.
The ability of human oral bacteria to inhibit Streptococcus mutans was studied under a variety of in vitro conditions using an agar overlay assay. Extensive inherent variability in microbial antagonism by certain organisms was demonstrated. Antagonistic activity was also significantly influenced by changes in the assay conditions.
Bacterial Physiological Phenomena↗
In vitro activity of furazlocillin (Bay k 4999) compared with those of mezlocillin, piperacillin, and standard beta-lactam antibiotics.
The activity of furazlocillin (Bay k 4999) was compared with those of mezlocillin, piperacillin, and standard beta-lactam antibiotics against a number of gram-positive and gram-negative organisms. These new expanded-spectrum penicillins were less active than penicillin G against most gram-positive organisms. Furazlocillin, mezlocillin, and piperacillin showed activity comparable to ampicillin and penicillin G against Haemophilus influenzae and penicillin-susceptible neisseriae, respectively. None of the drugs tested was effective against penicillin-resistant gonococci. The activity of furazlocillin was greater than that of mezlocillin, piperacillin, ampicillin, or carbenicillin against many Enterobacteriaceae. However, certain beta-lactam-resistant strains among these organisms were not highly susceptible to any of the three new penicillins. Furazlocillin was less active than piperacillin against Pseudomonas aeruginosa but was more active than carbenicillin or mezlocillin. Inoculum effects and discrepancies between minimal inhibitory concentrations and minimal bactericidal concentrations were observed with furazlocillin, mezlocillin, and piperacillin against several genera. The kinetics of bacterial killing by the new penicillins were often slow and incomplete over 24 h, especially in tests with Enterobacter and P. aeruginosa. Synergy was demonstrated between furazlocillin and aminoglycosides against a variety of gram-negative bacilli and Streptococcus faecalis.
Aminoglycosides↗
Emergence of resistance to cefamandole: possible role of cefoxitin-inducible beta-lactamases.
Selection of resistance to cefamandole has been observed, and the drug has failed to protect animals lethally infected with certain Enterobacteriaceae that appeared to be highly susceptible in vitro. Using spectrophotometric assays, some of these organisms were found to produce beta-lactamases highly active against cefamandole. Cefoxitin, a poor enzyme substrate, was found to be superior to both cephalothin and cefamandole in induction of these enzymes. A simple disk induction test was developed and used to examine 147 Enterobacteriaceae for production of these beta-lactamases. The enzymes were found in 69% of cephalothin-resistant, cefamandole-susceptible strains and in only 3% of strains susceptible to both cephalothin and cefamandole. They were most prevalent among isolates of Enterobacter, indole-positive Proteus, and Serratia. Since selection of resistance and therapeutic failures have occurred most often among these genera, the relationship between presence of inducible enzymes and outcome of therapy should be examined further in humans.
Cefamandole↗
Toxicity of antibacterial agents: mechanism of action on mammalian cells.
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Aminoglycosides↗
In vitro studies with Sch 21420 and Sch 22591: activity in comparison with six other aminoglycosides and synergy with penicillin against enterococci.
In vitro tests were performed with Sch 21420 and Sch 22591 to determine (i) their activity in comparison to six other aminoglycosides against 343 clinical isolates, and (ii) whether synergy with penicillin G could be demonstrated with enterococci. In broth dilution tests, Sch 22591 was more active than the seven other aminoglycosides against Staphylococcus aureus, Enterobacteriaceae, and most nonfermenting gram-negative bacilli. Sch 22591 was as active as tobramycin against Pseudomonas aeruginosa. The activity of Sch 21420 was comparable to gentamicin, sisomicin, netilmicin, and tobramycin but greater than amikacin or kanamycin against S. aureus and most genera of Enterobacteriaceae. Sch 21420, amikacin, and kanamycin were (i) more active than the other five aminoglycosides against Proteus rettgeri and Providencia stuartii, but (ii) less active than the other five aminoglycosides against Neisseria gonorrhoeae, enterococci, most nonfermenting gram-negative bacilli, Proteus mirabilis, and Proteus morganii. Studies on the bactericidal activity of Sch 22591 with penicillin indicated a synergistic interaction against enterococci, including strains highly resistant to streptomycin and kanamycin. This could be demonstrated with combinations containing 3.0 to 6.0 mug of Sch 22591 per ml and was comparable to that observed with penicillin/gentamicin. Penicillin plus Sch 21420 (25 mug/ml) also demonstrated synergy against enterococci, including strains highly resistant to streptomycin. However, synergy did not occur against strains highly resistant to kanamycin. These latter results were similar to those obtained in tests with penicillin/kanamycin.
Aminoglycosides↗
Comparison of 5-episisomicin (Sch 22591), gentamicin, sisomicin, and tobramycin in treatment of experimental Pseudomonas infections in mice.
Sch 22591 (5-episisomicin), gentamicin, sisomicin, and tobramycin were compared for their ability to protect mice from lethal intraperitoneal challenge with 12 Pseudomonas strains, all susceptible to each of the aminoglycosides (minimal inhibitory concentrations and minimal bactericidal concentrations were </=6.2 mug/ml). Median 50% protective doses were 5.8, 6.4, 7.7, and 17.8 mg/kg for Sch 22591, tobramycin, sisomicin, and gentamicin, respectively. Those for Sch 22591 were significantly lower than gentamicin in five protection tests and significantly lower than both gentamicin and tobramycin in one test. Microbial analysis of the therapeutic effect indicated that protection from lethality by each of the four aminoglycosides was associated with either a complete eradication or a reduction in the number of challenge bacteria in both the heart blood and peritoneum. In rare instances, challenge isolates exhibiting decreased susceptibility to one or more of the aminoglycosides were recovered from animals. However, this in vivo selection of resistance did not appear related to either the aminoglycoside used in therapy or the outcome of therapy, and resistant isolates were recovered as frequently from untreated animals as from those receiving one of the four aminoglycosides.
Animals↗
Inhibition of Neisseria gonorrhoeae by aerobic and facultatively anaerobic components of the endocervical flora: evidence for a protective effect against infection.
The ability of aerobic and facultatively anaerobic endocervical flora to inhibit the growth of Neisseria gonorrhoeae in vitro was assayed. Factors influencing the occurrence of inhibitory components of the flora in vivo were evaluated. Endocervical swabs were obtained from 229 women at a local venereal disease clinic. Endocervical flora and N. gonorrhoeae were isolated and identified, and the ability of the flora to inhibit the growth of N. gonorrhoeae was determined by an agar overlay assay. Results revealed the most active inhibitors to be streptococci, staphylococci, and lactobacilli, in that order. Among only those women harboring inhibitory endocervical flora, inhibitory lactobacilli were recovered from fewer women infected with N. gonorrhoeae than uninfected women (P less than 0.05). Among women having contact with an infected partner, those who subsequently developed gonorrhea were less likely to have inhibitory lactobacilli than those who did not become infected (P less than 0.05). No other significant differences in the composition of the inhibitory flora were noted between infected and uninfected women. During the 2 weeks following menses, recovery of inhibitory lactobacilli on culture was highest, whereas recovery of N. gonorrhoeae was lowest. These observations suggest that the presence of certain lactobacilli may reduce risk of acquisition of N. gonorrhoeae following exposure to infected partners and that the potential protective effect may be greatest during the 2 weeks after menses.
Aerobiosis↗
Comparison of BL-S786 with cephalothin, cefamandole and cefoxitin in vitro and in treatment of experimental infections in mice.
The activity of BL-S786 was compared to that of cephalothin, cefamandole and cefoxitin in vitro and in treatment of experimental infections in mice. In broth dilution tests, the activity of BL-S786 was less than cephalothin or cefamandole against Staphylococcus aureus and less than cefamandole or cefoxitin against Haemophilus influenzae. BL-S786 and cefamandole were the two most active drugs against cephalothin-sensitive Enterobacteriaceae. In tests with cephalothin-resistant Enterobacteriaceae, BL-S786 was generally less active than cefamandole but more active than cefoxitin against all strains except Proteus and Providencia. Regardless of the comparative in vitro activity of the four drugs, BL-S786 was the most effective drug in treatment of mice lethally infected with Enterobacteriaceae. Protection from lethality was associated with clearance of bacteremia by each of the four drugs. In several tests where in vitro activity was not predictive of in vivo efficacy, selection of resistance in vivo was found to have occurred.
Animals↗
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↗
In vitro activity of rosamicin against Neisseria and Haemophilus, including penicillinase-producing strains.
Rosamicin was significantly more active against Haemophilus and Neisseria than are many antibiotics currently used to treat or prevent infection caused by these organisms. This enhanced activity was also observed against penicillinase-producing strains.
Anti-Bacterial Agents↗
Bacterial interference. IV. Epidemiological determinants of the antagonistic activity of the normal throat flora against group A streptococci.
A study was performed to identify epidemiological factors such as age, race, sex, and time of culture that might influence the ability of the normal pharyngeal flora to interfere with growth of group A streptococci. From March 1974 through February 1975, throat swabs were obtained from 952 individuals. Cultures were assayed by an agar overlay procedure for the presence of bacteria capable of inhibiting growth of group A streptococci. The observed inhibition was then determined to be bacteriostatic or bactericidal by use of a broth filtrate technique. Regardless of age, race, or sex, subjects were more likely to harbor interfering flora if cultured during the months of March and April, which coincided with the highest prevalence of group A streptococci in the community. Race and sex of subjects appeared not to influence the inhibitory activity of throat flora either quantitatively or qualitatively. However, among individuals with interfering flora, the prevalence of bactericidal organisms increased and bacteriostatic organisms decreased with advancing age. Since the presence of bactericidal, and not bacteriostatic, organisms has been associated with resistance to colonization of the throat by group A streptococci, this higher prevalence of bactericidal organisms in older individuals suggests that bacterial interference may be one of the mechanisms that account for the greater resistance of adults than children to streptococcal throat infection.
Adolescent↗
Selection and characterization of strains of Staphylococcus aureus displaying unusual resistance to aminoglycosides.
Susceptibility tests with aminoglycosides against Staphylococcus aureus have revealed discrepancies between the minimal inhibitory concentrations and the minimal bactericidal concentrations. To further evaluate these discrepancies, kill curves were performed against a susceptible strain of S. aureus with five different aminoglycosides (amikacin, kanamycin, tobramycin, gentamicin, sisomicin) at concentrations up to 16-fold above the minimal inhibitory concentration. Results revealed the presence of small subpopulations of cells capable of growth within 24 h in concentrations of aminoglycoside up to eightfold above the minimal inhibitory concentration for the parent strain. These subpopulations occurred at a frequency of >/=10(-7) parent cells, were not physiologically different from the susceptible parent strains, and were present in approximately one-half of 30 strains of S. aureus tested. The resistance of these subpopulations was approximately eightfold higher than that of the parent for all five aminoglycosides and was independent of concentration or type of aminoglycoside used to select them. This resistance was not due to extracellular degradation of drug and was stable over eight transfers in drug-free medium, except when selected by gentamicin or sisomicin.
Amikacin↗
Bacterial interference: effects of oral antibiotics on the normal throat flora and its ability to interfere with group A streptococci.
The effects of orally administered penicillin and tetracycline on the composition of the normal throat flora and its interference with the growth of group A streptococci were evaluated by throat culture and an agar overlay technique. Tetracycline caused only a slight, transient quantitative decrease in the composition of the flora and interference activity. Penicillin caused significant quantitative and qualitative decreases in both the composition of the flora and interference activity. The diminution in interference activity persisted up to 3 weeks after therapy. The differences observed between the antibiotic regimens correlated with differences in initial susceptibility of the flora to the antibiotic used and emergence of the resistance during therapy. Results indicated that although effects of antibiotics on the composition of the flora are transient, effects on its ability to interfere with group A streptococci may persist long after therapy is discontinued. It is thus possible that penicillin therapy may enhance susceptibility of certain individuals to subsequent infection with group A streptococci.
Administration, Oral↗
Effects of procedural variations on the activity of aminoglycosides in vitro.
Am J Clin Pathol 63:438-445, 1975. The effects of procedural variations on the activities of gentamicin, tobramycin, sisomicin, kanamycin, and amikacin in vitro were evaluated using 134 clinical isolates. In broth dilution studies, a change in assay medium from brain-heart infusion broth to Mueller-Hinton broth resulted in significant changes in minimal inhibitory concentrations in 36% (242 of 670) of assays. A change in the bacterial population size utilized in broth dilution studies resulted in significant changes in minimal inhibitory concentrations in 34% (155 of 456) of assays. These variations in activities appeared to depend more on the organism tested than on the particular aminoglycoside used; with strains of Staphylococcus aureus, Proteus, and Providenica being most affected. For all five aminoglycosides, minimal inhibitory concentrations determined by broth dilution, regardless of medium, showed poor correlation with zone sizes obtained by the Bauer-Kirby technic. These results suggest that unless some standard assay procedure for activity of aminoglycosides is adopted, meaningful comparison of results within and among laboratories will not be possible.
Aminoglycosides↗
BL-P1654: a bacteriostatic penicillin?
In tube dilution studies, large discrepancies between inhibitory and bactericidal concentrations of BL-P1654 against Pseudomonas were observed. To explain these discrepancies which were not observed with carbenicillin, the kinetics of bacterial killing by these two penicillins were evaluated and compared. The kinetics of bacterial killing by both antimicrobial agents were characteristic of a penicillin, with killing initiating simultaneously with growth. Kill curves revealed the presence of a small number of cells resistant to BL-P1654 which were not detectable macroscopically. Studies on microbial resistance also showed the presence of a small but consistent number of cells resistant to BL-P1654 over a broad range of concentrations above its minimal inhibitory concentration. This pattern of resistance was not observed with carbenicillin. Thus, the discrepancies between inhibitory and bactericidal concentrations of BL-P1654 were not due to any unusual bacteriostatic activity but rather due to a small number of resistant cells whose presence could be detected only by sensitive subculturing techniques.
Carbenicillin↗
Streptococcal pharyngitis: an old nemesis.
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Humans↗