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Lysis if enterobacteria by cefoxitin, cefuroxime, and cephalothin.

Cefoxitin, cefuroxime, and cephalothin were added to dense populations of beta-lactamase-producing enterobacteria, and the subsequent turbidity changes were monitored continuously. Viable counts and antibiotic assays were made at intervals after the addition of antibiotic, and the morphological appearances of the organisms were observed. Cephalothin caused lysis of most of the organisms tested, but even at high concentrations, after a few hours the antibiotic was destroyed and the organisms recommenced logarithmic growth. Cefoxitin produced lysis of all the strains of Escherichia coli and Klebsiella species tested, with supression of regrowth. With cephalothin and cefoxitin the viable counts after the addition of antibiotic correlated with the turbidity measurements. Cefuroxime infrequently caused lysis that suppressed multiplication, and the organisms became long and filamentous while the turbidity readings increased; the viable counts did not correlate with the turbidity measurements. Cefuroxime and cefoxitin were not destroyed by the beta-lactamases of any of the strains of enterobacteria that were studied.

Bacteriolysis↗

Penetration of methicillin, oxacillin, and cephalothin into bone and synovial tissues.

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.

Bone and Bones↗

Effectiveness of nafcillin, methicillin, and cephalothin in experimental Staphylococcus aureus endocarditis.

Nafcillin, methicillin, and cephalothin (40 mg/kg every 6 h) were all effective in reducing the number of Staphylococcus aureus in vegetations in rabbits with endocarditis. Nafcillin and methicillin reduced the number of S. aureus at a significantly faster rate than did cephalothin. Nafcillin and methicillin also reduced titers of the S. aureus more rapidly than did cephalothin in vitro, both in broth and in rabbit serum.

Animals↗

Cefoperazone (T-1551), a new semisynthetic cephalosporin: comparison with cephalothin and gentamicin.

The in vitro activity of cefoperazone (T-1551) against almost 9,000 recent clinical isolates at six institutions was tested and compared with that of cephalothin and gentamicin. The modal minimum inhibitory concentrations of cefoperazone were 16- and 4-fold less than those of cephalothin and gentamicin, respectively, against 5,503 strains of Enterobacteriaceae. Species normally resistant to cephalothin, such as indole-positive protease and enterobacters, were almost universally susceptible to cefoperazone. Cefoperazone demonstrated activity comparable to gentamicin against Pseudomonas aeruginosa and other pseudomonads.

Bacteria↗

Chemoprophylaxis with cefoxitin and cephalothin in orthopedic surgery: a comparison.

Forty-eight patients who underwent elective hip or knee surgery were randomly divided into two groups. A total of 22 patients received a single 1-g preoperative bolus of cefoxitin, and 26 patients received a single 1-g preoperative dose of cephalothin. At various time intervals, serum and bone samples were taken during the operative procedure. Our data indicated that whereas serum levels of cefoxitin and cephalothin were maintained for at least 2h at levels capable of inhibiting most gram-positive cocci and many gram-negative rods, bone levels of cefoxitin rather rapid decay over a 2-h period. Moreover, in only 58% of the entire cephalothin-treated group were bone levels detectable and then only at a concentration that would inhibited gram-positive cocci. No significant morbidity was observed in either treatment group.

Bacterial Infections↗

Relative incidence of phlebitis caused by continuous intravenous infusion of cephapirin and cephalothin.

In a single-blinded study, two groups of 10 healthy subjects were given cephapirin or cephalothin by continuous intravenous infusion for 5 days, 0.5 g every 6 hr for the first day and then 1.0 g every 6 hr for 4 days. Eight of the cephalothin subjects and two of the cephapirin subjects developed phlebitis. Phlebitis was more severe in the cephalothin group and developed more rapidly, necessitating vein changes six times more often than in the cephapirin group. The less irritating properties of cephapirin demonstrated in this study indicate it may be the more useful cephalosporin analogue for intravenous therapy.

Acetamides↗

In vitro activity of ceftizoxime against Bacteroides fragilis: comparison with benzylpenicillin, cephalothin, and cefoxitin.

Minimum inhibitory concentrations of ceftizoxime for seven clinical isolates of Bacteroides fragilis were found to be markedly affected by inoculum size; the very low minimum inhibitory concentration values (less than or equal to 0.25 microgram/ml) obtained in tests with most strains were not sustained when the inoculum was raised 100-fold. Benzylpenicillin and cephalothin were also affected by inoculum size, but cefoxitin was not. Antibiotic assays showed that the strains inactivated ceftizoxime and cephalothin completely, benzylpenicillin partially, and cefoxitin not at all. Morphological investigations revealed that populations of B. fragilis responded differently to each of the four beta-lactam agents during the early stages of the encounter between B. fragilis and the antibiotic. Benzylpenicillin and cefoxitin induced spheroplast formation at lower concentrations than did ceftizoxime. Cephalothin evoked a novel morphological response that was not seen with other beta-lactam agents.

Anti-Bacterial Agents↗

Comparison of ceforanide and cephalothin prophylaxis for vaginal hysterectomies.

We compared the safety and efficacy of a six-dose regimen of cephalothin with a two-dose regimen of ceforanide for the prevention of infection after elective vaginal hysterectomy. A total of 150 patients were randomly assigned to either regimen. The overall incidence of documented pelvic infection was 5.3% and did not differ significantly between the prophylaxis groups when stratified by type of surgery. No serious adverse reactions were encountered in either group, but phlebitis was significantly more common in patients receiving cephalothin. We conclude that a two-dose regimen of ceforanide given intramuscularly is as effective as, and possibly better tolerated than, a six-dose regimen of cephalothin.

Cefamandole↗

Comparison of the chemotherapeutic and pharmacodynamic activities of cephradine, cephalothin, and cephaloridine in mice.

Cephradine, a new semisynthetic cephalosporin derivative, is 7[d(-)-2-amino-2-(1,4-cyclohexadien-1-yl) acetamido]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid hydrate. The compound has a broad spectrum of antimicrobial activity in vitro. When given subcutaneously to mice, cephradine was appreciably more effective than cephalothin against infections induced by penicillinase-producing Staphylococcus, Escherichia coli, Klebsiella pneumoniae, or Enterobacter cloacae strains. Cephradine and cephaloridine possessed equivalent activity in treating infections caused by these same three gram-negative bacteria. The mean total bioactivity of cephradine in the serum of mice peaked within 30 min (59 mug/ml) after parenteral administration and was approximately threefold that of cephalothin (20 mug/ml), but less than that of cephaloridine (83 mug/ml). Nearly all of the administered cephradine (84%) and cephaloridine (70%) were excreted in the urine as the parent compounds. In contrast, only 47% (total bioactivity) of administered cephalothin was recovered, an amount that represented only 15 to 20% of the parent substance.

Animals↗

Disk susceptibility studies with cefazolin and cephalothin.

Cefazolin and cephalothin disk susceptibility and minimal inhibitory concentration determinations were conducted on 591 clinical isolates. Cefazolin demonstrated superior activity, as shown by lower minimal inhibitory concentrations, and a greater percentage of isolates inhibited in the disk susceptibility test. The cephalothin antibiotic class disk by the standard Bauer-Kirby method failed to detect susceptibility to cefazolin in a significant percentage of Escherchia coli, Enterobacter species, and Enterococcus isolates. A separate cefazolin disk with a susceptibility cut-off point of 18 mm is recommended. An alternative to a separate cefazolin disk would be a reinterpretation of the cephalothin susceptibility disk zone diameters so that it would more adequately predict cefazolin activity.

Cephalosporins↗

Pharmacology of cephalothin in the biliary tract of humans.

Serum and biliary tract levels of cephalothin were determined in a large series of patients. Serum cephalothin levels in the therapeutic range were present at 1 h after a single dose of the antibiotic in only 4 of 39 (10.3%) subjects. Therapeutic bile cephalothin levels were achieved in only 2.4% of all subjects, and this occurred between 40 and 70 min after the administration of the antibiotic.

Adolescent↗

Studies of cephalothin: aminoglycoside synergism against enterococci.

Combinations of cephalothin and aminoglycoside antibiotics are not currently used in the therapy of serious enterococcal infections, because clinical trials of these combinations have been unsuccessful. Studies of 28 enterococci isolated from patients with enterococcal bacteremia suggested three possible mechanisms for this in vivo antibiotic failure: (i) a relatively high level of resistance to cephalothin among all enterococci and especially those characterized as Streptococcus faecium, (ii) a significant incidence of high-level resistance to the aminoglycosides among certain strains of enterococci, and (iii) a failure of synergism to occur when cephalothin concentrations fall below the minimal inhibitory concentration of the enterococcus, as occurs during the in vivo metabolism and excretion of this antibiotic when given in standard doses for endocarditis.

Aminoglycosides↗

Comparison of in vitro antimicrobial activity of cefamandole and cefazolin with cephalothin against over 8,000 clinical bacterial isolates.

Antimicrobial susceptibility to cefamandole versus cephalothin and cefazolin versus cephalothin was compared by the broth microdilution method against 3,000 and 5,895 clinical bacterial isolates, respectively. Cefamandole and, to a lesser degree, cefazolin showed greater activity than cephalothin against Enterobacteriaceae, but the three drugs were comparable against gram-positive cocci.

Bacteria↗

Cephalothin, a new cephalosporin with a broad antibacterial spectrum. I. In vitro studies employing the gradient plate technique.

Cephalothin is 7-(thiophene-2-acetamido) cephalosporanic acid; it was prepared by N-acylation of the nucleus of cephalosporin C, 7-aminocephalosporanic acid. Cephalothin had a broad spectrum of antibiotic activity that was essentially unaffected by human serum or inoculum level, the activity of penicillinase, or pH variation of the growth medium. In vitro development of resistance by staphylococci could not be demonstrated, but the gram-negative organisms did develop a stepwise type of resistance to the antibiotic. Staphylococci made resistant in vitro to 5-methyl-3-phenyl-4-isoxazole penicillin were also resistant to cephalothin and to 6-(2,6-dimethoxybenzamido) penicillin; however, the mechanism of resistance to each antibiotic may have differed. Some complications involved in the laboratory evaluation methods currently in use in the field of antibiotics are examined.

Anti-Bacterial Agents↗

Measurement of three antibiotics (penicillin, cephalothin, and chloramphenicol) when present together in mixtures.

Benzylpenicillin, cephalothin, and chloramphenicol were measured individually and quantitatively when present together in mixtures at concentrations found in patients. The assay depended on the selective inactivation of two of the antibiotics, permitting the third to be assayed as if present alone. Agar seeded with a chloramphenicol-resistant, penicillinase-negative Staphylococcus aureus was used for a cylinder-plate assay of appropriately diluted fluid to determine the activity of either benzylpenicillin or cephalothin after either beta-lactamase inactivation of the former or ultraviolet light inactivation of the latter. Chloramphenicol was assayed with Sarcina lutea after appropriate beta-lactamase inactivation of both cephalothin and benzylpenicillin. Fluids containing various amounts of the three antibiotics were assayed by this method with less than 8% error. Procedures that fail to measure each antibiotic individually may give larger errors.

Biological Assay↗

In vitro and in vivo laboratory evaluation of cephalothin, a new broad spectrum antibiotic.

Boniece, W. S. (Lilly Research Laboratories, Indianapolis, Indiana), W. E. Wick, D. H. Holmes, and C. E. Redman. In vitro and in vivo laboratory evaluation of cephalothin, a new broad-spectrum antibiotic. J. Bacteriol. 84:1292-1296. 1962.-Cephalothin, a new cephalosporin antibiotic, is the sodium salt of 7-(thiophene-2-acetamido) cephalosporanic acid. The activity of this antibiotic against a variety of gram-positive and gram-negative bacteria is described, as determined by the tube-dilution and disc-plate methods. Correlations of the results of the therapy of experimental infections in mice with in vitro sensitivity to cephalothin are presented. The data from the gram-negative bacterial infection tests suggest the following relationship on a within strain basis: ed(50) = C(i)ld(50) (bi), where the subscript i stands for the various strains.

Animals↗

Isolation and characterization of cephalothin-susceptible Campylobacter coli from slaughter cattle.

In a recent meat survey, 10 of 13 (77%) Campylobacter coli isolates were susceptible to cephalothin. These organisms were isolated from nine slaughter cattle from eight meat packing establishments. All 10 isolates grew at 43 degrees C but not at 25 degrees C, were catalase and oxidase positive, and were susceptible to nalidixic acid (30 micrograms) and cephalothin (30 micrograms). The cultures were subsequently identified as C. coli serogroup 20, biotype I (Lior scheme). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that protein and lipopolysaccharide profiles of whole cell preparations of the 10 cephalothin-susceptible strains and the reference strain for C. coli serogroup 20 were very similar. The plasmid profiles of these 11 strains were identical.

Abattoirs↗