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PubMed1995

Synergistic enhancement of in vitro antimicrobial activity of imipenem and cefazolin, cephalothin, cefotiam, cefamandole or cefoperazone in combination against methicillin-sensitive and -resistant Staphylococcus aureus.

Synergistic enhancement of the in vitro antimicrobial activity of imipenem combined with cephalosporins against methicillin-resistant Staphylococcus aureus (MRSA) has been reported. In order to investigate which cephalosporin is more effective in enhancing the activity of imipenem against MRSA, the in vitro antimicrobial activities of imipenem, cefazolin, cephalothin, cefotiam, cefamandole and cefoperazone, alone and in combination, against methicillin-sensitive Staphylococcus aureus (MSSA) and MRSA were assessed. Using the checkerboard Mueller-Hinton agar dilution method, strong synergy was found in 97% to 100% of MRSA strains for imipenem and all tested cephalosporins except cefoperazone; fractional inhibitory concentration (FIC) indices were < or = 0.5. Among the cephalosporins studied, cefamandole most markedly increased the activity of imipenem against MRSA, followed, in order of decreasing effect, by cefotiam, cephalothin, cefazolin, and cefoperazone. The synergistic effect of imipenem combined with cefamandole or cefotiam was confirmed using the broth dilution method with 2% of NaCl.

Cefamandole↗
PubMed1967

Metabolism of oral cephalothin and related cephalosporins in the rat.

The fate of orally administered [(14)C]cephalothin has been studied in the rat. This antibiotic undergoes degradation in the gut followed by the subsequent absorption of a portion of the degradation products. About 50% of the administered radioactivity appears in the urine as a mixture of thienylacetylglycine, thienylacetamidoethanol and an unidentified polar metabolite. Evidence is presented indicating that thienylacetamidoethanol arises by the enzymic reduction of a metabolic intermediate, thienylacetamidoacetaldehyde. The metabolic fate of cephalothin is very similar to that of cephaloram reported earlier. The fate of [(14)C]cephaloridine and 7-phenoxy[1-(14)C]acetamidocephalosporin was also investigated. In addition to the expected metabolites, about 5% of the cephaloridine dose is absorbed unchanged. With 7-phenoxy[1-(14)C]acetamidocephalosporin, 15% of the dose is recovered in urine as deacetyl-7-phenoxy[1-(14)C]acetamidocephalosporin.

Journal Article↗
PubMed1978

Comparison of the in vitro activities of HR756 with cephalothin, cefoxitin, and cefamandole.

The in vitro activity of HR756, a new semisynthetic cephalosporin, was compared with the activities of cephalothin, cefoxitin, and cefamandole against 1,535 isolates of gram-positive and gram-negative bacteria. HR756 was less active than cephalothin and cefamandole and twofold more active than cefoxitin against Staphylococcus. All four of the antibiotics were inactive against the enterococcus group of Streptococcus; however, HR756 was the most active antibiotic against the other isolates of Streptococcus. HR756 was also more active against isolates of Enterobacteriaceae, including 84 to 95% of the isolates resistant to one or more of the other three antibiotics. HR756, at a concentration of 12.5 mug/ml, inhibited 86, 75, and 100% of the isolates of Pseudomonas aeruginosa, other Pseudomonas species, and Acinetobacter, respectively. The minimal inhibitory concentrations and minimal bactericidal concentrations of HR756 were within one twofold dilution for 11 of 21 gram-positive cocci and 119 of 125 gram-negative bacilli tested.

Bacteria↗
PubMed1964

INHIBITION OF SYNTHESIS OF THE CELL WALL OF STAPHYLOCOCCUS AUREUS BY CEPHALOTHIN.

Cephalothin, 7-(thiophene-2-acetamido)-cephalosporanic acid, suppresses synthesis of the cell of Staphylococcus aureus. Exposure to this agent led to a reduction in the degree of incorporation of carbon-14-lysine into the mucopeptide of the cell wall material and to an accumulation of N-acetyl glucosamine in the cell. The intensity of the lesions was comparable to that produced by penicillin.

Anti-Bacterial Agents↗
PubMed1976

Indirect method for assessing the penetration of beta-lactamase-nonsusceptible penicillins and cephalosporins in Escherichia coli strains.

Escherichia coli UB1005 and two mutants of this strain (DC2 and DC3) have been used to assess indirectly the relative ability of various beta-lactam antibiotics to penetrate the outer layers of E. coli. Benzylpenicillin, ampicillin, methicillin, cloxacillin, cephaloridine, cephalothin, and cephalexin have been examined. The results confirm those obtained with other methods and show that, among the compounds studied here, cephalosporins seem to penetrate more readily than penicillins.

Cephalosporinase↗
PubMed1976

Susceptibility of Streptococcus mutans to antimicrobial agents.

Fifty strains of Streptococcus mutans, including defined strains and clinical isolates, were tested for susceptibility to 20 different antimicrobial agents. Minimal inhibitory concentrations were determined by a liquid microtiter procedure. Antibiotics that were most effective in concentrations below 0.1 mug/ml included penicillin, ampicillin, erythromycin, cephalothin, and methicillin. Antibiotics effective in concentrations between 0.1 mug and 10 mug/ml included rifampin, lincomycin, thiostrepton, spiromycin, vancomycin, streptolydigan, novobiocin, tetracycline, chloramphenicol, spectinomycin, and gentamicin. Antibiotics effective at higher concentrations ranging from 10 mug/ml to 400 mug/ml included the aminoglycosides kanamycin, neomycin, streptomycin, and kasugamycin. Although most antibiotics exhibited inhibitory effects in a narrow range of concentrations, antibiotics such as tetracycline, thiostrepton, and spiromycin had a 1,000-fold range from the lowest to highest concentrations required for growth inhibition.

Anti-Bacterial Agents↗
PubMed1978

Fanconi syndrome associated with cephalothin and gentamicin therapy.

A case is reported of Fanconi syndrome and nonliquric renal failure, following a brief course of cephalothin and gentamicin, in a patient with diffuse histiocytic lymphoma. These drugs, especially when used in combination, have been associated with nephrotoxicity manifested as acute tubular necrosis and altered proximal tubular function, but biochemical evidence for generalized proximal tubular dysfunction has not been accurately defined. Thus far, only two other antibiotics, degraded tetracycline and streptozotocin, have been implicated in producing an acquired Fanconi syndrome.

Bacterial Infections↗
PubMed1987

Azlocillin, cephalothin, and tobramycin therapy in febrile solid tumor patients with chemotherapy-induced leukopenia.

Although the semisynthetic broad-spectrum acylureido-penicillin, azlocillin has been demonstrated to have significant antibiotic activity in leukemic patients, its role in combination therapy of febrile granulocytopenic patients with chemotherapy-treated solid tumors has not been clearly delineated. Thirty-five solid tumor patients with chemotherapy-induced absolute granulocytopenia (less than 1000 granulocytes/ml) associated with fever (greater than 38.3 degrees C) were treated on a prospective study with a combination of azlocillin 4 g intravenously (IV) every 6 hours, cephalothin 2 g IV every 6 hours, and tobramycin 80 to 100 mg IV every 8 to 12 hours. Prior chemotherapy included doxorubicin combinations in 18 patients and other combinations in 17 patients. Granulocyte counts preantibiotic therapy were greater than 100 granulocyte/ml in 14 patients, 100 to 499 in nine patients, and 500 to 1000 in 12 patients. Granulocyte nadirs were less than 100 in 20 patients, 100 to 499 in nine patients, and 500 to 1000 in six patients. Times for granulocytes to rise towards normal were 1 to 3 days in eight patients, 4 to 6 days in 18 patients, and 7 or more days in nine patients. Tobramycin levels were primarily in the peak range of 3 to 6 micrograms/ml and trough range of 0 to 1.9 micrograms/ml. The site and pathogen were identified in nine patients, the infection site clinically documented without isolated pathogen in three patients, and no site or pathogen identified in 23 patients. Of the 35 patients, 34 had good responses to the antibiotic combination (complete disappearance of fever and other evidence of infection). Serum creatinine rose 0.4 to 0.6 mg/dl in nine patients, 0.7 to 1.5 in four patients, and 1.5 in one patient (obstructive uropathy). The only other noted antibiotic-related side effect was hypokalemia. This antibiotic combination had little toxicity with marked efficacy.

Adult↗
PubMed1975

[Studies on the in vitro effects of cephalothin and gentamicin, alone and in combination, on proteus mirabilis and enterococci (author's transl)].

A combined antibiotic therapy is only useful in a few precisely defined clinical pictures where testing of the chemotherapeutics administered is required to determine their characteristics of action (antagonism, indifference, synergism) on the isolated organism. For the initial therapy of critical acute infections, simultaneous administration of cephalothin and gentamicin proved to be valuable. In the present study, the efficiency of these chemotherapeutics alone and in combination was investigated in a quantitative serial dilution test and with the membrane-filtration method. Thirty strains of Proteus mirabilis and enterococci showed only low sensitivity to the antibiotic alone. In combination, whereby gentamicin was at a constant level comparable to in vivo serum levels, an increase of bacteriostatic and bactericidal action could be demonstrated, especially for Proteus mirabilis. The antibacterial spectrum, the molecular-biological mode of action, clinical experience and possible side-effects of the cephalotin-gentamicin combination are discussed.

Cephalothin↗
PubMed2005

Crystallization of cephalothin sodium during lyophilization from tert-butyl alcohol-water cosolvent system.

PURPOSE: Because cephalothin sodium (I) does not crystallize readily when freeze-dried from aqueous solutions, organic cosolvents were used to increase the crystallinity of lyophilized I. METHODS: Compound I was lyophilized from water-organic cosolvent (5% w/w) systems of each ethanol, ispropanol, and tert-butyl alcohol (TBA). RESULTS: When frozen solutions of I (10% w/w) in each of these cosolvent systems was characterized by DSC, the presence of cosolvent in the freeze-concentrate was evident. Moreover, the presence of the cosolvent accelerated the solute crystallization. This observation was based on the XRD of these systems during the various stages of freeze-drying. High initial solute concentration and annealing of frozen solutions facilitated the formation of a highly crystalline lyophile. The accelerated crystallization is attributed to supersaturation in cosolvent systems, facilitating nucleation during freezing with subsequent growth during annealing. Lyophiles obtained from water-isopropanol and water-ethanol systems collapsed, while the use of TBA as a cosolvent yielded a friable and pharmaceutically elegant cake, containing fine needle-shaped crystals of I. Gas chromatography revealed a residual TBA concentration of approximately 0.001% w/w in the crystalline lyophiles. In general, residual cosolvent levels were higher in lyophiles with lower crystallinity. CONCLUSIONS: TBA-water was found to be a suitable freeze-drying medium to promote crystallization of I and yielded a lyophile with desirable product characteristics.

Cephalothin↗
PubMed1979

Comparative efficacy of prophylactic cephalothin and cefamandole for elective colon surgery: results of a prospective, randomized, double-blind study.

Thirty-four patients undergoing elective colon resection or anastomosis received either intravenous cephalothin or cefamandole prophylactically and were observed for evidence of intraabdominal or wound infection, or both, postoperatively. The infection rates were 31 and 33 per cent, respectively. Infections were caused predominantly by cephalosporin resistant aerobes and anaerobes. All four bacteremias were caused by members of the B. fragilis group. The overall infection rate (32 per cent) and the frequency of anaerobic bacteremia (12 per cent) observed in this study were much higher than previously reported after cephalosporin prophylaxis for colorectal surgery.

Adenoma↗
PubMed1977

The simultaneous quantitative determination of cephalothin and cefazolin in serum by high pressure liquid chromatography.

Conventional microbiological assay procedures for cephalosporins in serum do not allow the determination of serum concentrations if more than one cephalosporin is present in a single sample. An HPLC procedure has been developed which permits the simultaneous quantitative determination of cefazolin sodium and cephalothin sodium in serum. Reverse phase chromatography using methanol in 0.2 M ammonium acetate as the mobile phase was employed to separate and quantitate the two cephalosporins in a trichloroacetic acid supernatant solution prepared from serum.

Cefazolin↗
PubMed1984

Cefotaxime, cephalothin, and cephapirin: antimicrobial activity and synergy studies of cephalosporins with significant in vivo desacetyl metabolite concentrations.

The desacetyl metabolites of cefotaxime, cephalothin, and cephapirin were 5-55% as active as the parent drug, depending upon the bacterial species tested. Synergy or partial synergy was demonstrated in 64% of 25 strains of Enterobacteriaceae and Staphylococcus aureus tested against cephalothin/desacetylcephalothin and cephapirin/desacetylcephapirin combinations. Some species variations were identified that influenced synergy rates, particularly among the S. aureus strains (for example, highest rates for cephapirin).

Bacteria↗
PubMed1977

Cephalothin Prophylaxis and valve replacement.

In a study of antibiotic prophylaxis in adults undergoing heart valve replacement, we found that a 2 gm dose of cephalothin given intraoperatively produced adequate antimicrobial activity in the bloodstream throughout the period of cardiopulmonary bypass. A dosage of 1 gm every four hours postoperatively did not lead to significant accumulation of the antibiotic. With prophylaxis restricted to the intraoperative and early postoperative period, adverse drug reactions and superinfections were not a problem. Further, no cases of prosthetic valvulitis were encountered.

Aortic Valve↗
PubMed1988

Nitrogen losses and cephalothin absorption in peritonitis treated by hourly peritoneal dialysis.

The effects of peritonitis on dialysate nitrogen losses were investigated. Eight patients who developed peritonitis while undergoing peritoneal dialysis were compared to seven noninfected dialysis patients. Dialysate protein losses increased during peritonitis, but nitrogen losses into the dialysate did not increase. These findings were caused by reduced urea nitrogen losses in the peritonitis group, which proportionately, more than made up for the increased nitrogen losses from protein. We speculate that the smaller loss of urea nitrogen was due to diminished intake of food. Cephalothin uptake from the peritoneal cavity was unaltered by peritonitis and a dialysate flow rate of 2 L/hour averaged 26 +/- 2 mL/minute and 27 +/- 2 mL/minute in the noninfected and infected groups, respectively.

Absorption↗
PubMed1981

Tobramycin-clindamycin versus cephalothin-cephalexin in the treatment of appendicular peritonitis.

Forty-seven children, ages 1 to 14 years, with appendicular peritonitis were randomly divided into two groups: 27 were treated with the combination tobramycin-clindamycin and 20 with cephalothin followed by cephalexin. The overall rate of complications was 32%. Patients who had had their symptoms for less than 48 hours before being admitted to hospital had significantly fewer complications than those whose symptoms had lasted longer. Patients treated with tobramycin-clindamycin had significantly fewer wound infections. As clindamycin is effective against anaerobes this observation supports the view that anaerobes play an important role in the infectious complications in peritonitis. In this series, 12 species of aerobes and eight species of anaerobes were cultured from peritoneal fluid. In eight patients only one species was isolated; in the remaining 39 patients 29 different combinations of bacteria were encountered. Early diagnosis and administration of antibiotics preoperatively or during surgery, including clindamycin, metronidazol or tinidazol is recommended in the treatment of children with appendicular peritonitis.

Adolescent↗
PubMed2002

Acyl-intermediate structures of the extended-spectrum class A beta-lactamase, Toho-1, in complex with cefotaxime, cephalothin, and benzylpenicillin.

Bacterial resistance to beta-lactam antibiotics is a serious problem limiting current clinical therapy. The most common form of resistance is the production of beta-lactamases that inactivate beta-lactam antibiotics. Toho-1 is an extended-spectrum beta-lactamase that has acquired efficient activity not only to penicillins but also to cephalosporins including the expanded-spectrum cephalosporins that were developed to be stable in former beta-lactamases. We present the acyl-intermediate structures of Toho-1 in complex with cefotaxime (expanded-spectrum cephalosporin), cephalothin (non-expanded-spectrum cephalosporin), and benzylpenicillin at 1.8-, 2.0-, and 2.1-A resolutions, respectively. These structures reveal distinct features that can explain the ability of Toho-1 to hydrolyze expanded-spectrum cephalosporins. First, the Omega-loop of Toho-1 is displaced to avoid the steric contacts with the bulky side chain of cefotaxime. Second, the conserved residues Asn(104) and Asp(240) form unique interactions with the bulky side chain of cefotaxime to fix it tightly. Finally, the unique interaction between the conserved Ser(237) and cephalosporins probably helps to bring the beta-lactam carbonyl group to the suitable position in the oxyanion hole, thus increasing the cephalosporinase activity.

Amino Acid Sequence↗
PubMed1976

Tobramycin and cephalothin sodium in treatment of infected patients with acute leukemia.

Tobramycin has been shown to be safe and effective when given intravenously in combination antibiotic therapy for infected patients with acute leukemia or other profound pancytopenic states. Tobramycin in combination with one or more antibiotics (usually cephalothin) produced satisfactory clinical results in 21 of 30 episodes of fever. Toxic effects were minimal and were limited to occasional mild thrombophlebitis.

Acute Disease↗