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6.  Comparative In Vitro Studies of Cinoxacin, Nalidixic Acid, and Oxolinic Acid 
Cinoxacin and nalidixic acid were found to be similar in in vitro activity against 138 Shigella isolates and somewhat less active than oxolinic acid on a weight basis. Cross-resistance developed when 10 shigellae were transferred on increasing amounts of the respective agent contained in Mueller-Hinton agar. Plate dilution studies of the effect of changes in agar pH on the minimum inhibitory concentration revealed that the antibacterial activity increased with decreasing pH. Protein binding investigations revealed a high degree of binding, with nalidixic acid > oxolinic acid > cinoxacin.
PMCID: PMC429866  PMID: 12717
7.  Medium for Use in Antibiotic Susceptibility Testing of Anaerobic Bacteria 
A medium is described which was designed for use in testing the minimal inhibitory concentration of antibiotics for anaerobic bacteria by agar dilution. It contains: Trypticase (1%), Gelysate (1%), yeast extract (0.5%), glucose (0.1%), pyruvate (0.1%), arginine (0.1%), NaCl (0.5%), hemin (5 μg/ml), vitamin K1 (0.5 μg/ml), agar (1.5%). The medium does not require the addition of blood to support growth of most clinical isolates of anaerobic bacteria.
PMCID: PMC429869  PMID: 1008552
8.  Chemically Defined Medium for Susceptibility Testing of Antimicrobial Agents 
A defined medium was developed that supports growth of many of the bacterial and fungal pathogens frequently isolated in clinics.
PMCID: PMC429868  PMID: 1008551
9.  Procedure for Expediting Determinations of Antibiotic Susceptibility of Gram-Negative, Urinary Tract Pathogens 
Standardized direct disk diffusion antibiotic susceptibility testing on monomicrobial urine specimens is compared with the Food and Drug Administration method. The direct procedure yields acceptable data and may conserve 24 h in reporting results.
PMCID: PMC429867  PMID: 1008550
10.  Cultivation of Staphylococcus aureus in a Synthetic Medium of Low Ultraviolet Absorptivity 
A new synthetic medium having negligible ultraviolet absorbance is described for growing staphylococci in experiments requiring ultraviolet spectrophotometry of cell-free portions of the culture.
PMCID: PMC429865  PMID: 1008549
11.  Bacteriocin Production by Group A Streptococcal L-Forms 
L-forms induced from a bacteriocin-producing strain of group A streptococcus retained both the ability to produce the streptococcin and producer strain immunity to the homologous bacteriocin. L-forms of a spontaneously cured (bacteriocin negative) derivative of this same strain failed to produce streptococcin but were sensitive to its action.
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PMCID: PMC429864  PMID: 795376
12.  Comparison of Josamycin and Erythromycin in the Therapy of Mycoplasma pneumoniae Pneumonia 
A controlled, double-blind study was performed to compare the efficacy of two macrolide antibiotics, erythromycin and josamycin, in the therapy of Mycoplasma pneumoniae pneumonia. Marine Corps recruit volunteers received one of the two antibiotics in a dosage of 2 g daily for 7 days. Twelve of 21 men treated with josamycin and 9 of 25 men treated with erythromycin had confirmed M. pneumoniae pneumonia. The josamycin-treated group remained hospitalized for 5.4 ± 1.2 days compared to 5.1 ± 2.0 days for the erythromycin-treated group (0.60 > P > 0.50). Fever days were similar for the josamycin-treated (1.4 ± 0.4) and erythromycin-treated (1.2 ± 0.3) groups (P = 0.95). There was no difference in resolution of signs and symptoms of illness in the two study populations. Thus, josamycin is as efficacious as erythromycin in the therapy of M. pneumoniae pneumonia.
PMCID: PMC429862  PMID: 795375
13.  Effect of Clindamycin on Aminoglycoside Activity in a Murine Model of Invasive Escherichia coli Infection 
Previous studies have demonstrated that the early in vitro bactericidal activity of gentamicin and amikacin is inhibited by clindamycin. To investigate the possible clinical implications of these findings, the effect of clindamycin in combination with gentamicin or amikacin was compared with that of the aminoglycoside alone in the treatment of normal and neutropenic mice with Escherichia coli peritonitis and bacteremia. Mice treated with saline or clindamycin alone experienced rapid multiplication of bacteria in the peritoneal cavity, bacteremia, and subsequent death. Gentamicin or amikacin given 2 h after E. coli inoculation significantly reduced the mortality and peritoneal bacterial counts in normal and neutropenic mice in comparison with untreated controls. Prior or simultaneous administration of clindamycin with either aminoglycoside did not inhibit survival or bacterial clearance from the peritoneum. The only clindamycin effect was slight enhancement of survival of neutropenic mice treated with multiple doses of amikacin and clindamycin in comparison to those treated with amikacin alone.
PMCID: PMC429861  PMID: 795374
14.  Antibiotic Synergy and Antagonism Against Clinical Isolates of Klebsiella Species 
Minimal inhibitory concentrations of kanamycin, gentamicin, amikacin, cephalothin, and chloramphenicol were determined in Trypticase soy broth for 70 clinical isolates of Klebsiella species. Gentamicin and amikacin were the most active on a weight basis. Chloramphenicol was more active than kanamycin, and cephalothin was the least active of all. Studies using a microtiter modification of the checkerboard technique were performed to evaluate the comparative activity of the three aminoglycosides in combination with either chloramphenicol or cephalothin. The cephalothin-aminoglycoside combinations demonstrated synergy in >80% of the isolates tested. No antagonism was noted. The chloramphenicol-aminoglycoside combinations showed antagonism in 35 to 45% of the isolates tested. The data suggest that the chloramphenicol-aminoglycoside combinations be used with caution when treating serious infections where Klebsiella is a potential pathogen.
PMCID: PMC429860  PMID: 1008547
15.  Effect of 9-β-d-Arabinofuranosyladenine 5′-Monophosphate and 9-β-d-Arabinofuranosylhypoxanthine 5′-Monophosphate on Experimental Herpes Simplex Keratitis 
Treatment of established experimental keratitis caused by herpes simplex virus with 9-β-d-arabinofuranosyladenine 5′-monophosphate (Ara-AMP) or 9-β-d-arabinofuranosylhypoxanthine 5′-monophosphate (Ara-HxMP) showed that the Ara-AMP, in a concentration of 2 or 20%, had a significant effect on the keratitis but that 0.4% Ara-HxMP showed only minimal activity. Ara-AMP was also effective in the treatment of idoxuridine-resistant keratitis. No local toxicity with a high concentration (20%) of Ara-AMP was seen, but the duration of therapy was brief.
PMCID: PMC429859  PMID: 1008546
16.  Reevaluation of the Disk Diffusion Method for Sulfonamide Susceptibility Testing of Neisseria meningitidis 
Lack of correlation between quantitative minimal inhibitory concentration (MIC) determinations and disk diffusion susceptibility tests in our laboratory prompted a study to reevaluate the use of the disk diffusion test for sulfonamide susceptibility testing of Neisseria meningitidis. One hundred and sixty-three recent clinical isolates of N. meningitidis were examined for sulfonamide susceptibility by the agar dilution and disk diffusion methods. Optimal inocula for each of the tests were determined, and thereafter all disk diffusion tests were compared with quantitative MICs as determined by the agar dilution method using sulfadiazine and an inoculum of 106 colony-forming units (CFU)/ml. The clearest and most reproducible zone diameters were obtained with a 107-CFU/ml inoculum in the disk diffusion test. There was complete correlation between the disk zone diameters for 300-μg disks of sulfadiazine and sulfathiazole and the agar dilution test MICs. All isolates with a zone diameter of <20 mm were resistant to sulfadiazine, whereas those with zone diameters of ≥30 mm were susceptible. False susceptible and false resistant readings were obtained with 300-μg sulfisoxazole disks. These data suggest that inocula and type of sulfonamide are critical factors in the disk diffusion test for meningococcal susceptibility testing. Sulfonamide disks are not interchangeable for susceptibility testing of meningococci.
PMCID: PMC429856  PMID: 827239
17.  Cephalosporin and Aminoglycoside Concentrations in Peritoneal Capsular Fluid in Rabbits 
To study the penetration of antibiotics into peritoneal tissue fluid, a subcutaneous tissue capsule model was modified by implanting multiple, perforated spherical capsules in the peritoneal cavity of rabbits. Capsules became vascularized, encased in connective tissue, and filled with fluid having a mean protein concentration of 3.6 g/100 ml. Capsular fluid was obtained by percutaneous needle aspiration and assayed for antibiotic by the disk plate bioassay technique. Cephalosporins were administered intramuscularly at a dose of 30 mg/kg. Mean peak concentrations of cephaloridine and cefazolin were significantly higher than cephalothin and cephapirin in capsular fluids, but the percent penetration (ratio of capsular mean peak to serum mean peak) ranged from 8.7 to 16.9% and was not significantly different among the cephalosporins. At 24 h the capsular concentration of cefazolin was significantly greater than for the other cephalosporins (P < 0.001). Lower rabbit serum protein binding observed at high in vivo concentrations may have enabled cefazolin to penetrate capsular fluid, but in vitro protein binding studies did not confirm a decrease in serum protein binding at high concentrations within the clinical range. Kanamycin and amikacin showed comparable capsular fluid peak concentrations as did gentamicin and tobramycin. The percent penetration ranged from 15.2 to 34.5% for the aminoglycosides. The only statistical difference was that amikacin penetration was significantly higher than that for tobramycin. Mean capsular concentrations of amikacin, cefazolin, and cephaloridine compared most favorably with the minimum inhibitory concentration of gram-negative bacilli at the dosages used in this study.
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PMCID: PMC429863  PMID: 1008548
18.  In Vitro Activity of Gentamicin, Amikacin, and Netilmicin Alone and in Combination with Carbenicillin Against Serratia marcescens 
The inhibitory and bactericidal effects of gentamicin, amikacin, netilmicin (Sch 20569), and carbenicillin were tested against 55 clinical isolates of Serratia marcescens that had been subtyped into 26 strains by biotyping and serotyping. Three major patterns of resistance to gentamicin, netilmicin, and carbenicillin were recognized among these isolates. (i) Most of the 27 isolates that were susceptible to gentamicin (minimal bactericidal concentration [MBC] ≤6.25 μg/ml) were susceptible to carbenicillin (MBC ≤125 μg/ml) and resistant to netilmicin (MBC ≥12.5 μg/ml). (ii) Most of the 11 isolates with moderate resistance to gentamicin (MBC of 12.5 to 25 μg/ml) were also susceptible to carbenicillin and resistant to netilmicin. (iii) The 17 isolates with high-level resistance to gentamicin (MBC ≥ 50 μg/ml) were all highly resistant to carbenicillin (MBC ≥8,000 μg/ml) but susceptible to netilmicin (MBC ≤6.25 μg/ml). The susceptibility to amikacin was unpredictable among these groups of isolates but, overall, 80% of the isolates were killed by 25 μg of amikacin/ml, which is within the range of peak serum concentrations used therapeutically. Clinically attainable subinhibitory concentrations of carbenicillin enhanced the activity of the three aminoglycosides against all isolates with MBCs of carbenicillin ≤2,000 μg/ml. The 17 isolates with high-level resistance to carbenicillin and gentamicin, as well as the four isolates with high-level resistance to carbenicillin but not to gentamicin, were not susceptible to such enhancement of aminoglycoside activity by carbenicillin.
PMCID: PMC429858  PMID: 795373
19.  Comparison of the Epidemiology of Bacterial Resistance to Mecillinam and Ampicillin 
Mecillinam is a new type of β-lactam antibiotic (an amidinopenicillanic acid) that is particularly active against Enterobacteriaceae and is taken orally as in the form of an ester, pivmecillinam. Assessment of any new antibiotic should include a survey of levels of bacterial resistance and investigation of its capacity to select resistant organisms or harm the commensal flora. Antibiotic resistance patterns of 2,000 Enterobacteriaceae isolated from the urine of patients with significant urinary tract infections were therefore determined. Mecillinam-resistant Enterobacteriaceae were found to be much less common than ampicillin-amoxycillin-resistant organisms both in the community and in hospital patients. Most ampicillin-resistant Enterobacteriaceae from infected urines were susceptible to mecillinam, but the relatively rare mecillinam-resistant organisms were usually resistant to ampicillin and cephaloridine. The fecal flora of 26 healthy volunteers who served as controls or were given repeated courses of therapeutic doses of either ampicillin or pivmecillinam was studied. Pivmecillinam had only a transient effect on the aerobic fecal flora and in contrast to ampicillin did not increase populations of resistant Enterobacteriaceae, which would be a potential hazard to the patient and contaminate the environment.
PMCID: PMC429857  PMID: 1051328
20.  Stability of Gentamicin in Serum 
Patients' sera were divided into three portions when the initial gentamicin level was determined and were stored at −20, 4, and 25°C in plastic or glass tubes. Gentamicin levels were repeated after 1 and 2 days of storage at the respective temperatures. There was no significant difference in gentamicin levels among portions, except those from a patient in renal failure with high serum concentrations of carbenicillin.
PMCID: PMC429851  PMID: 1008545
21.  Sisomicin Versus Netilmicin: In Vitro Susceptibility Testing 
Antimicrobial susceptibility to sisomicin and netilmicin (Sch 20569) was determined on 164 clinical isolates using a broth microdilution method. Sisomicin was active against 86.1%, and netilmicin against 96.4%, of the isolates. In addition, netilmicin was active against 93.7% of the strains that were resistant to gentamicin, kanamycin, tobramycin, and sisomicin.
PMCID: PMC429850  PMID: 827238
22.  Preparation of Isolated Intestinal Villi Useful for Studying Hydrolysis Rates of Penicillin and Cephalosporin Esters 
A method for the preparation of freeze-dried intestinal villi from hamsters and mice is described. The villi, consisting largely of epithelial cells rich in esterase activity, are useful for hydrolysis studies of penicillin and cephalosporin esters.
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PMCID: PMC429849  PMID: 1008544
23.  Antifungal Properties of Electrically Generated Metallic Ions 
A qualitative and quantitative investigation was undertaken to study the susceptibility of unicellular eucaryotic organisms (yeasts) to metallic cations generated by low levels of direct current. Results were characteristic of effects obtained previously using clinical and standard bacteria test organisms. The present study demonstrated that anodic silver (Ag+) at low direct currents had inhibitory and fungicidal properties. Broth dilution susceptibility tests were made on several species of Candida and one species of Torulopsis. Growth in all isolates was inhibited by concentrations of electrically generated silver ions between 0.5 and 4.7 μg/ml, and silver exhibited fungicidal properties at concentrations as low as 1.9 μg/ml. The inhibitory and fungicidal concentrations of electrically generated silver ions are lower than those reported for other silver compounds.
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PMCID: PMC429848  PMID: 1034467
24.  Comparative Nephrotoxicities of Netilmicin and Gentamicin in Rats 
The relative nephrotoxicities of netilmicin (Sch 20569) and gentamicin were compared in rats at doses of 30, 60, 90, and 120 mg/kg per day for 15 days. Both drugs caused proteinuria and a decrease in urine osmolality; however, netilmicin produced significantly less changes at all doses than gentamicin. Whereas gentamicin resulted in a decline in creatinine clearance at all doses, netilmicin failed to cause a decline in creatinine clearance. Renal-cortical concentrations of antibiotic at sacrifice were similar in animals receiving either drug. Light-microscopic changes were less severe with netilmicin than gentamicin. Cytosegresomes with myeloid bodies were identified electron microscopically in the kidneys of animals receiving either netilmicin or gentamicin at all doses. Electron-microscopic manifestations were similar. The data indicate that in the rat, netilmicin is distinctly less nephrotoxic than gentamicin.
PMCID: PMC429846  PMID: 1008542
25.  Ticarcillin in Combination with Cephalothin or Gentamicin as Empiric Antibiotic Therapy in Granulocytopenic Cancer Patients 
Ticarcillin was used in combination with either cephalothin or gentamicin as initial empiric antibiotic therapy for 127 patient trials of suspected infection in granulocytopenic cancer patients. Bacteremia was present in 20%, nonbacteremic microbiologically documented infections in 21%, clinically documented infections in 23%, and possible infections in 5%; infection was doubtful in 31%. Although Staphylococcus aureus was the most common single organism isolated (23%), gram-negative bacilli accounted for 54% of all pathogens. Both antibiotic regimens were highly efficacious, with complete resolution in 46% of bacteremias, 88% of nonbacteremic microbiologically documented infections, and 95% of clinically documented infections. Among bacteremias, 8 of 9 caused by S. aureus but only 4 of 15 (27%) caused by gram-negative bacilli were completely resolved with these antibiotic combinations. Reasons for nonresponse in bacteremias were persistent granulocytopenia, mixed infection and, in two patients, antibiotic-resistant organisms. Toxicities other than hypokalemia were minimal. Although the rate of further infections was high overall (18/127), only one occurred among the 39 patients with <4 days of antibiotic therapy. Ticarcillin in combination with either cephalothin or gentamicin was effective as initial empiric therapy of suspected infection in granulocytopenic cancer patients.
PMCID: PMC429845  PMID: 795372

Results 1-25 (362)