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1.  Analysis of the Interactions Between Piperacillin, Ticarcillin, or Carbenicillin and Aminoglycoside Antibiotics 
Enhanced activity against clinical isolates of Pseudomonas aeruginosa was demonstrated with piperacillin, ticarcillin, and carbenicillin in combination with gentamicin, tobramycin, and amikacin.
PMCID: PMC352492  PMID: 101133
2.  In Vitro Susceptibility of 30 Strains of Chlamydia trachomatis to Rosamicin 
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.
PMCID: PMC352488  PMID: 708027
3.  Polymyxin B-Penicillin Antagonism in Proteus Mirabilis 
Polymyxin B protects Proteus mirabilis from usually lethal penicillin concentrations.
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PMCID: PMC352579  PMID: 217303
4.  Proposed Ticarcillin Disk Control Values for Escherichia coli and Pseudomonas aeruginosa: Multicenter Cooperative Study 
In a multicenter cooperative controlled study, individual test, accuracy, and precision control values were determined for 75-μg ticarcillin disks with Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853.
PMCID: PMC352493  PMID: 101134
5.  In Vitro Evaluation of a Semisynthetic Derivative of Gentamicin B (SCH 21420) 
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.
PMCID: PMC352351  PMID: 666309
6.  Comparative In Vitro Activity of Five Cephalosporin Antibiotics Against Salmonellae† 
The in vitro activities of five cephalosporin antibiotics against 121 strains of salmonellae were compared. Cefamandole and cefaclor were more potent than cefazolin, and these three drugs were more active than cephalothin and cephalexin.
PMCID: PMC352198  PMID: 626485
7.  Method for Qualitative Determination of 2-Deoxystreptamine 
We have developed a qualitative method to assay for the presence of 2-deoxystreptamine in hydrolysates of crude aminoglycoside preparations using a 2-deoxystreptamine-requiring idiotrophic mutant. The assay involves (i) incubation of a 2-deoxystreptamine-requiring mutant with 1 mg of a hydrolyzed preparation from a crude unknown antibiotic mixture per ml, and (ii) examination of the resultant incubation mixture for production of antibiotic(s) by disk assay.
PMCID: PMC352421  PMID: 686706
8.  Haemophilus influenzae Susceptibility Testing Within Four Hours by a Modification of the Autobac I System 
By adding an XV strip to the eugonic broth or substituting Levinthal broth, the standard Autobac I susceptibility testing system may be used to determine susceptibility of Haemophilus influenzae to antimicrobial agents. Complete concordance was attained in testing 30 strains (5 resistant) by Autobac I, disk diffusion, and broth dilution methods. Autobac I results were available within 4 h after isolation of the organism.
PMCID: PMC352353  PMID: 307368
9.  Comparative Activities of Selected Beta-Lactam Antibiotics Against Haemophilus influenzae 
The comparative activities of ampicillin, cefamandole, cefoxitin, cefaclor, and cefatrizine against both beta-lactamase-producing and non-beta-lactamase-producing isolates of Haemophilus influenzae were determined by using an agar dilution susceptibility test procedure. Ampicillin was the most active drug tested against non-beta-lactamase-producing isolates, whereas cefamandole was most active against beta-lactamase-producing strains.
PMCID: PMC352238  PMID: 306221
10.  Acidometric Agar Plate Method for Ampicillin Susceptibility Testing of Haemophilus influenzae 
The need for an accurate and rapid method of testing ampicillin susceptibility of Haemophilus influenzae, especially strains isolated from patients with meningitis and septicemia, is indisputable. Various methods have been employed for this purpose. Each has advantages and disadvantages. This report describes a modification of the capillary acidometric procedure in which an agar plate is substituted for a tube. All beta-lactamase results obtained by this modified technique correlated with minimal inhibitory concentrations determined in liquid media and the chromogenic cephalosporin substrate method. This modified acidometric agar procedure is a simple, inexpensive, accurate, and rapid way to determine H. influenzae susceptibility to ampicillin.
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PMCID: PMC352233  PMID: 306220
11.  Pharmacokinetics of Mezlocillin in Healthy Volunteers 
Mezlocillin in doses of 1.0, 2.0, and 5.0 g and carbenicillin in doses of 2.0 g were given as bolus injections intravenously to 10 healthy volunteers. For mezlocillin, dose-dependent pharmacokinetics was detected. This is reflected by a more than proportional rise in serum concentrations and a decreased total body clearance as doses were increased. Per dose unit, the areas under serum concentration curves to infinity were 33.5 μg·h/ml for the 1.0-g dose, 47.2 μg·h/ml for the 2.0-g dose, and 54.8 μg·h/ml for the 5.0-g dose. The body clearance fell from 31.2 liters/h with the 1.0-g dose to 17.0 liters/h with the 5.0-g dose. This can be explained mainly by a marked depression of nonrenal clearance, which fell from 12.2 to 3.8 liters/h, compared with a parallel change in renal clearance from 19.0 to 13.2 liters/h. Contributing to the non-linearity may be biotransformation, evacuation via bile, or another process. With dose increments, rising amounts are recovered unchanged in the urine—61% after a 1.0-g dose compared with 69% after a 5.0-g dose. This clearly defines metabolism as a major factor of elimination. Carbenicillin, for which the first-order, two-compartment open model was applicable here as in previous studies, had a longer serum half-life than did mezlocillin. For the 2.0-g doses, the former had a half-life of 1.4 h, compared with 0.8 h for the latter (calculated as if the two-compartment model were fully valid). The relative area under the curve (see above) was 76.1 μg·h/ml after the 2.0-g dose.
PMCID: PMC352560  PMID: 742869
12.  Activity of Derivatives and Analogs of Dapsone Against Mycobacterium leprae 
Of 25 dapsone derivatives and analogs screened for activity against Mycobacterium leprae in the mouse footpad system, only 7 were active. All seven were metabolized to or contaminated with dapsone.
PMCID: PMC352553  PMID: 727767
13.  SCE-963, a New Broad-Spectrum Cephalosporin: In Vitro and In Vivo Antibacterial Activities 
SCE-963 {7β-[2-(2-aminothiazol-4-yl)acetamido]-3-[({1-(2-dimethylaminoethyl)- 1H-tetrazol-5-yl}thio)methyl]-ceph-3-em-4-carboxylic acid}, a new semisynthetic cephalosporin, showed excellent antibacterial activity against gram-positive and gram-negative bacteria, including Haemophilus influenzae, indole-positive Proteus, Enterobacter species, and Citrobacter freundii. The minimum inhibitory concentrations of SCE-963 against most strains of clinically isolated Escherichia coli, Klebsiella pneumoniae, H. influenzae, and Proteus mirabilis were within the range of 0.2 to 0.78 μg/ml. These activities were about 10 times more potent than those of cefazolin, cephaloridine, and cephalothin. Variations in pH, addition of horse serum, and type of growth medium had no significant effect on the activity of the cephalosporin, but the inoculum size elicited a considerable effect on the activity of β-lactamase-producing strains of bacteria. SCE-963 exerted bactericidal and bacteriolytic effects on Staphylococcus aureus and E. coli. The pronounced in vitro activity was reflected in the remarkable protection in mice infected with a wide range of gram-negative bacteria, such as E. coli, K. pneumoniae, P. mirabilis, Proteus vulgaris, Proteus morganii, and Proteus rettgeri. The protective effects of SCE-963 in mice infected with E. coli, K. pneumoniae, and P. vulgaris varied according to the challenge dose. The activity of SCE-963 was far more potent when the drug was administered parenterally rather than orally.
PMCID: PMC352508  PMID: 718154
14.  Quantitation of Imidazoles by Agar-Disk Diffusion 
A simple, reliable, and inexpensive assay for quantitation of the imidazole drugs miconazole, RV 40,500, and RV 41,400 was tested. The assay, similar to a Kirby-Bauer test, was sensitive to less than or equal to 0.2 μg of drug per ml and linear from less than or equal to 0.2 to 10.0 μg/ml. Concentration of inoculum and agar depth in test plates was not as critical as the type of medium, amount of inoculum, or type of drug used.
PMCID: PMC352494  PMID: 568452
15.  UK-18892, a New Aminoglycoside: An In Vitro Study 
UK-18892 is a new aminoglycoside antibiotic, a derivative of kanamycin A structurally related to amikacin. It was found to be active against a wide range of pathogenic bacteria, including many gentamicin-resistant strains. The spectrum and degree of activity of UK-18892 were similar to those of amikacin, and differences were relatively minor. UK-18892 was about twice as active as amikacin against gentamicin-susceptible strains of Pseudomonas aeruginosa. Both amikacin and UK-18892 were equally active against gentamicin-resistant strains of P. aeruginosa. There were no appreciable differences in the activity of UK-18892 and amikacin against Enterobacteriaceae and Staphylococcus aureus. Cross-resistance between these two antimicrobials was also apparent.
PMCID: PMC352438  PMID: 100050
16.  In Vitro Susceptibility Studies with Netilmicin: Comparison of a 10-μg Netilmicin Disk with a Standardized 10-μg Gentamicin Disk 
Netilmicin is a new, semisynthetic aminoglycoside antibiotic active against some gentamicin-resistant gram-negative bacteria. In this study we compared a 10-μg netilmicin disk with the standardized 10-μg gentamicin disk in terms of their abilities to predict probable clinical susceptibility to netilmicin. The agar dilution procedure of the International Collaborative Study of the World Health Organization and the U.S. Food and Drug Administration standardized disk test procedure were used. The gentamicin disk failed to predict the clinical susceptibility to netilmicin of 26 of 118 isolates previously shown by the agar dilution technique to to be netilmicin susceptible. The netilmicin disk correctly predicted probable susceptibility of all 26 isolates, including 20 shown by the agar dilution procedure to be resistant to gentamicin. These studies demonstrate the need for a separate netilmicin disk for use in agar diffusion disk susceptibility tests.
PMCID: PMC352388  PMID: 98106
17.  Activity of Three 8-Hydroxyquinoline Derivatives Against In Vitro Dental Plaque 
Three 8-hydroxyquinoline derivatives, assessed using an in vitro preformed dental plaque model system, were differentially inhibitory for four plaque-forming microorganisms.
PMCID: PMC352387  PMID: 98105
18.  In Vitro Antibacterial Activity of Amikacin and Ticarcillin, Alone and in Combination, Against Pseudomonas aeruginosa 
In vitro antimicrobial susceptibility studies using amikacin and ticarcillin, alone and in combination, were performed on 20 strains of Pseudomonas aeruginosa. All strains were susceptible to amikacin, and ticarcillin was active against 16 of the 20 strains. Enhanced anti-pseudomonas activity could be demonstrated with the combination of amikacin and ticarcillin.
PMCID: PMC352379  PMID: 98109
19.  Effect of N′-Methylnicotinamide on the Renal Accumulation and Reabsorption of Gentamicin in Rats 
N′-methylnicotinamide, a substrate of the organic base transport system, reduced renal accumulation of [14C]gentamicin in rats by 15% and increased clearance by 25%, suggesting that gentamicin is not secreted by this mechanism.
PMCID: PMC352352  PMID: 149514
20.  Isolation and Characterization of Multiply Antibiotic-Resistant Clostridium perfringens Strains from Porcine Feces 
Multiply antibiotic-resistant strains of Clostridium perfringens were isolated from porcine feces. Strains that were resistant to tetracycline, erythromycin, clindamycin, and lincomycin were isolated, but no penicillin- or chloramphenicol-resistant strains were obtained. Typical minimal inhibitory concentrations for resistant strains were 16 to 64 μg of tetracycline per ml, 64 to >128 μg of erythromycin per ml, ≥128 μg of lincomycin per ml, and 16 to 128 μg of clindamycin per ml. Resistance to erythromycin was always associated with resistance to lincomycin and clindamycin. Minimal inhibitory concentrations were determined for 258 strains from six farms that used antibiotics in their feeds and 240 strains from five farms that did not use antibiotics. The results show that 77.9 and 22.7% of the strains from the former farms were resistant to tetracycline and erythromycin-clindamycin-lincomycin, respectively. The comparable data from the latter farms were 25.0 and 0.8%, respectively. Agarose gel electrophoresis failed to reveal a plasmid band that was common to the resistant strains but absent in the susceptible strains. Attempts to transfer tetracycline, erythromycin, and clindamycin resistance from one strain, CW459, were not successful. Antibiotic-susceptible mutants were not isolated from this strain, despite the use of a variety of curing agents.
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PMCID: PMC352347  PMID: 208463
21.  Synergy of Azlocillin and Mezlocillin Combined With Aminoglycoside Antibiotics and Cephalosporins 
Synergistic activity between both azlocillin and mezlocillin and aminoglycosides or cefazolin could be demonstrated by checkerboard dilution, isobologram, and killing curve techniques. Azlocillin and mezlocillin combined with gentamicin, netilmicin, or amikacin were synergistic against Escherichia coli, Klebsiella, Citrobacter, Enterobacter, Serratia, and indole-positive Proteus. Synergy was observed with isolates that were susceptible or resistant to azlocillin or mezlocillin. Synergy was seen most often when azlocillin or mezlocillin were combined with amikacin, gentamicin, or netilmicin against Pseudomonas aeruginosa. The combination of mezlocillin and an aminoglycoside produced synergy more often than did carbenicillin plus an aminoglycoside. No antagonism was seen when aminoglycoside antibiotics were combined with azlocillin or mezlocillin. Cefazolin was synergistic against Pseudomonas, Providencia, P. mirabilis, indole-positive Proteus, Citrobacter, Klebsiella, and Escherichia coli, when combined with azlocillin or mezlocillin. However, the combination of either agent with cefazolin was antagonistic when tested against selected indole-positive Proteus and Enterobacter isolates.
PMCID: PMC352336  PMID: 666302
22.  Activity of Azlocillin and Mezlocillin Against Gram-Negative Organisms: Comparison with Other Penicillins 
The activities of azlocillin and mezlocillin were compared with those of carbenicillin, ticarcillin, and pirbenicillin against a wide range of gram-negative organisms. The two new drugs were considerably more active than carbenicillin against Klebsiella species and Escherichia coli. Carbenicillin was twice as active against Proteus mirabilis as mezlocillin and four times as active as azlocillin. Against Pseudomonas aeruginosa, azlocillin was eight times as active as carbenicillin. Azlocillin and mezlocillin were twice as active as carbenicillin against Bacteroides fragilis, and these drugs showed a high degree of activity against Haemophilus influenzae and Neisseria gonorrhoeae.
PMCID: PMC352288  PMID: 96726
23.  Accumulation Pharmacokinetics of Tobramycin 
Tobramycin pharmacokinetics is usually described by a one-compartment model, but this model fails to account for both the incomplete urinary recovery and prolonged post-treatment persistence noted with this drug. We examined the multiple-dose behavior of tobramycin in 35 treated patients with stable renal function, using peak and trough serum concentrations, urine recovery, and postmortem tissue analysis. Serum concentrations rose slowly throughout treatment and declined in two phases after the drug was stopped. The first-phase half-life correlated well with renal function, but the second averaged 146 h and was poorly related to creatinine clearance. A two-compartment model was used to describe the biphasic decline in serum concentrations and to calculate the amount of drug in the tissue compartment at all times during and after treatment. Predicted tissue amounts rose continually throughout treatment in all study patients. In 5 patients, the total amount of tobramycin in the body after the final dose was recovered in the urine, but urine had to be collected for 10 to 20 days to achieve complete recovery of the drug. In four patients, the predicted tissue amount was recovered from postmortem tissues. Regardless of the dose, tobramycin accumulated in the tissues of all patients receiving this antibiotic. The two-compartment pharmacokinetic model explains both the rising peak and trough concentrations during treatment and the detection of the drug in serum and urine long after the last dose.
PMCID: PMC352305  PMID: 666293
24.  Beta-Lactamases: Determination of Their Isoelectric Points 
Important discrepancies in isoelectric points (pI) of β-lactamases were observed depending on the experimental procedure used for their determination: isoelectric focusing (IEF) in sucrose density gradients or analytical IEF in thin-layer polyacrylamide gels (PA). The variations, negligable in the case of TEM-like β-lactamases, appeared to be important in the case of cephalosporinases and are related to an artifact which appears in PA-IEF. This has been clearly shown with β-lactamase preparations from the following bacterial strains: Pseudomonas aeruginosa NCTC 8203 (pI = 8.7), P. aeruginosa NCTC 10701 (pI = 9.4), and Proteus morganii NCTC 235 (pI = 8.3). The data previously obtained by PA-IEF were much lower.
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PMCID: PMC352312  PMID: 96731
25.  Chloramphenicol Resistance in Streptococcus pneumoniae: Enzymatic Acetylation and Possible Plasmid Linkage 
Clinical isolates of Streptococcus pneumoniae resistant to chloramphenicol were observed in France for the first time in 1973. During a 4-year survey, these strains were found to represent 6% of a total of 564 isolates of S. pneumoniae in a general hospital and to belong to 13 different serotypes. One such strain, referred to as BM 6001, was shown to inactivate chloramphenicol, and the process was found to be inducible. The inactivated products were demonstrated to be O-acetoxy esters of chloramphenicol. The synthesis of an inducible chloramphenicol acetyltransferase was shown to be responsible for the inactivation of the drug. The resistant strain was able to transfer the chloramphenicol marker by transformation to competent strains of pneumococci at a frequency of 1% of that observed for control chromosomal markers. The loss of resistance was enhanced by ethidium bromide treatment, but no chloramphenicol-resistant mutant was isolated by mutagenesis of a “cured” clone or naturally susceptible isolates. All attempts to isolate plasmid deoxyribonucleic acid as covalently closed circular molecules from strain BM 6001 have been unsuccessful, but epidemiological evidence and the fact that the genes specifying chloramphenicol acetyltransferase synthesis are usually located on plasmids suggest that this marker may be plasmid-borne in S. pneumoniae.
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PMCID: PMC352291  PMID: 27138

Results 1-25 (369)