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At least 19 recordsLinked to original sources
PubMed1975

[Experimental study in rats on the renal compatibility of cephalothin and cephalothin-aminoglycoside combinations (author's transl)].

The possible nephrotoxity of cephalothin and the antibiotic combinations cephalotin-gentamicin and cephalothin-tobramycin was investigated in standardized animal experiments. Toxicity parameters were blood-urea concentration, the urinary enzymes GOT, LDH, MDH and the cell excretion rate, supplemented by histological investigations of the kidneys. Compared with other cephalosporine derivates, the antibiotic cephalothin in a toxic threshold-dose of 3000 mg/kg/day proved to be realtively well tolerated by the kidneys. On comparison with the respective monotherapy, the renal tolerance for cephalothin-aminoglycoside combinations was reduced. The clinical value of these findings is discussed.

Aminoglycosides↗
PubMed1975

Empiric therapy for cancer patients: comparative study of ticarcillin-tobramycin, ticarcillin-cephalothin, and cephalothin-tobramycin.

Three combinations of antibiotics (cephalothin-tobramycin, cephalothin-ticarcillin, and ticarcillin-tobramycin) were administered empirically to 186 patients with cancer who were suspected of having a life-threatening infection. In approximately one-half of these patients, gram-negative infection was documented bacteriologically and consisted of septicemia in 50% of these patients. The three antimicrobial regimens were similarly effective and resulted in a favorable clinical response in approximately 55% of the patients. The administration of the cephalothin-tobramycin combination was associated with a significantly higher frequency of nephrotoxicity than that of the other two regimens.

Anti-Bacterial Agents↗
PubMed1978

Microbial degradation of cephalothin by cephalothin-susceptible Escherichia coli.

Cephalothin (CET)-susceptible Escherichia coli, which can degrade CET after prolonged incubation in broth containing a concentration of the drug greater than the minimum inhibitory concentration, was found in a clinical specimen. The substrate specificity of the partially purified enzyme to cephalosporin analogs strongly indicated the occurrence of CET-specific degradation. Nuclear magnetic resonance analysis of the degradation reaction demonstrated the appearance of two new signals attributed to deacetyl CET. This suggests the possibility of the presence of acylesterase.

Cephalothin↗
PubMed1977

Penetration of cefamandole, cephalothin, and desacetylcephalothin into fibrin clots.

The conversion of cephalothin into a less active metabolite (desacetylcephalothin) might influence its distribution in tissues. An experimental rabbit model devised to determine concentrations of antibiotics in subcutaneous fibrin clots was used in this study. Groups of five to six animals received 100-mg/kg intravenous injections of either cefamandole or cephalothin. One hour after the injection, the concentration of cefamandole in serum was 20 times higher than that of cephalothin. Whereas cephalothin was undetectable at 4 h, cefamandole was still detectable at the end of the experiment. The half-lives of cephalothin and cefamandole in serum were 16 and 27 min, respectively. The concentration of cefamandole found in fibrin clots was severalfold higher than that of cephalothin. The half-life of cefamandole in clots (81 min) was superior to that of cephalothin (38 min). Although concentrations of both antibiotics were higher in serum than in clots at 1 h, the concentrations of these drugs in the clots persisted at higher levels throughout the next 5 h of the experiment. The extent of binding of cefamandole (87%) to rabbit serum was greater than that of cephalothin (50%). At least 55% of cephalothin was metabolized in vivo into its less active metabolite desacetylcephalothin. This metabolite was found in higher proportion in the serum (75%) than in the clots (55%). Whereas only 12% of the free (unbound) cephalothin reached the clots, 78% of the free cefamandole was found in the clots. This lower level of penetration of unbound cephalothin might be explained by the short half-life of this antibiotic, not permitting equilibrium to occur.

Animals↗
PubMedDate not supplied

Penetration of cephalothin and cefoxitin into experimental infections with Bacteroides fragilis.

The in vitro activities of cephalothin and cefoxitin against Bacteroides fragilis were studied by time-kill curves and measurement of residual drugs in culture supernatants. Cefoxitin was bactericidal, causing a decrease of 10(7) in viable counts over 24 hr. Cephalothin caused an initial decrease of 10(2) B. fragilis at 2 hr; this change was followed by growth of the organism within 24 hr back to the number present before addition of cephalothin. The concentration of cephalothin in broth decreased rapidly within 2 hr and was undetectable within 24 hr, whereas the level of cefoxitin decreased only 25% over the 24-hr period. Penetration of these drugs into perforated ping pong balls implanted intraperitoneally in rabbits was studied. Three weeks after implantation the reservoirs were infected with B. fragilis. After intramuscular administration of five doses of antibiotic, the penetration of cephalothin, as measured by bioassay, in uninfected and infected capsules was 16% and 2%, respectively, of the peak serum concentration; similar findings were noted with cefoxitin. For determination of the rate of breakdown within the infected site, radiolabeled antibiotic was injected into the capsule, and the concentrations of bioactive and radioactive drug were determined. With radiolabeled cephalothin there was a rapid decrease in bioactivity during the initial 60 min, and no active drug was measurable after 2 hr. In contrast, only 40% of cefoxitin was inactivated at the end of 6 hr. The results indicate that levels of cephalothin and cefoxitin are reduced significantly in sites infected with B. fragilis. The decrease appears to be mediated by both a decrease in penetration and inactivation at the site of infection.

Animals↗
PubMedDate not supplied

Comparative studies of cefoxitin and cephalothin: an overview.

A comparative study of the efficacy and safety of cefoxitin and cephalothin in the treatment of serious infections was carried out by 21 investigators. A total of 320 patients were treated with cefoxitin, and 276 patients were treated with cephalothin. In each group 50% of patients could be evaluated. Patients were randomly allocated to groups in open fashion, and final analysis showed that the groups were comparable in terms of sex, age, severity of illness, and duration of therapy. The majority of pathogens isolated were susceptible to both agents, although 13% of gram-negative bacilli and anaerobes were susceptible to cefoxitin alone. The overall percentage of patients cured or improved by cephalothin was 93%; for cefoxitin the proportion was 91%. No statistical differences in response by type of organism or site of infection were shown. Cefoxitin was effective in treating infections and in eradicating the pathogenic bacteria. Cefoxitin was as well tolerated as cephalothin and produced no more adverse reactions or abnormal laboratory findings than did cephalothin. The results of this study demonstrate that cefoxitin is as effective in achieving bacteriologic and clinical cures as is cephalothin and also is effective in treatment of infections due to cephalothin-resistant bacteria.

Bacterial Infections↗
PubMed1978

Sodium clavulanate potentiation of cephalosporin activity against clinical isolates of cephalothin-resistant Klebsiella pneumoniae.

Plasmid-carrying Klebsiella pneunomiae clinical isolates with agar dilution minimum inhibitory concentrations (MIC) of 32 mug/ml or greater were tested for in vitro potentiation of cephalothin activity by clavulanic acid (BRL-14151), an inhibitor of beta-lactamases. The addition of 10 mug of clavulanate per ml caused greater than a 500-fold reduction in geometric mean cephalothin agar dilution MIC, with lesser but significant reductions resulting from clavulanate concentrations of 5 or 1 mug/ml. Clavulanate-potentiated reduction of cephalothin MICs in broth against resistant Klebsiella were comparable to reduction in agar dilution MICs as a rule. However, a low concentration (1 mug/ml) of clavulanate produced cephalothin MICs in broth several-fold higher than by the agar dilution method. Modest cephalothin-potentiating effects of clavulanate on cephalothin-susceptible strains and on cefoxitin against cephalothin-resistant Klebsiella strongly suggested that the major effect of clavulanate was beta-lactamase inhibition.

Amidohydrolases↗
PubMed1977

[Prevention using cephalothin in open-heart surgery].

To assay the efficiency of cephalothin prophylaxis in open-heart surgery, bacteriological examination of pressure-measurement units, intravenous catheter tips, and urine were made in 211 consecutive patients as well as blood cultures and sputum in suspected postoperative sepsis. Furthermore, cephalothin concentration in serum and tissue was determined in 12 consecutive adults with intact kidney function. Samples were taken before, during, and after the cardiopulmonary bypass, the tissue from the right atrium only before and after cardiopulmonary bypass. A high serum cephalothin level (80.04 +/- 23.35 microgram/ml) was measured 30 min after administration of 2 g cephalothin given as a 15-min-long i.v. infusion on induction of anesthesia. An antibiotic regimen - 4 X 2 g dose of cephalothin daily (first dose on induction of anesthesia) - provides a serum cephalothin level which is significantly higher than the cephalothin minimum inhibitory concentrations for most gram-positive organisms (0.475 microgram/ml) and so ensures an adequate antibiotic coverage throughout the surgical procedure and during the early postoperative phase of open-heart surgery.

Adult↗
PubMed1978

Gentamicin-cephalothin drug reaction.

A case report describing the occurrence of nephrotoxicity in a 26-year-old black male with sickle cell anemia after concurrent i.v. administration of gentamicin sulfate and cephalothin sodium is presented. Cephalothin 1 g.i.v. every six hours was given for three days for a Klebsiella infection demonstrated by urine and blood culture to be cephalosporin sensitive. Cephalothin was then discontinued and gentamicin, after an i.v. loading dose of 2.6 mg/kg, was given for 14 days in a dosage of 1.3 mg/kg every eight hours. After cultures of pus aspirated from the right thigh demonstrated Klebsiella, 2 g of cephalothin was administered i.v. every six hours and gentamicin sulfate was discontinued. Gentamicin therapy was reinstituted two days later, at a dosage of 5 mg/kg/day. The gentamicin-cephalothin therapy was continued for nine days. The gentamicin dosage interval was increased from every eight to every 16 hours when serum creatinine and gentamicin levels became elevated. Gentamicin was discontinued entirely two days later because serum gentamicin levels were not decreasing. Previous case reports and studies of nephrotoxicity associated with concurrent gentamicin-cephalothin therapy are reviewed. Pharmacists should be alert to the possible increased incidence of nephrotoxicity occurring with concurrent genticin-cephalothin therapy.

Adult↗
PubMed1976

Prophylactic cephalothin in gastrointestinal surgery.

A prospective study was carried out to evaluate the effect of a strictly standardized, short-term prophylactic treatment with cephalothin (Keflin) on the incidence of postoperative wound infections in gastrointestinal surgery. Achieved levels of cephalothin activity in serum and interstitial water were studied, and the sensitivity of isolated bacteria at the end of operation and from septic wounds was defined. Patients were divided at random into treatment and control groups. The treatment group received 2 g cephalothin at the induction of anesthesia and another 2 g, 5 and 10 hours after the primary infusion. The control group remained untreated. The rapid infusion of 2 g cephalothin resulted in high initial serum levels, which declined rapidly. Equilibration between intraand extravascular compartments occurred about 60-80 minutes after start of infusion. At that time the infused dose resulted in a cephalothin level of about 30 mug/ml in ECV and plasma, or about 30% of the initial concentration. Despite the prophylactic infusion of cephalothin, the frequency of wound infection in treated patients was the same as in the controls. Subdivision of the material according to type of surgery performed did not reveal any difference between untreated patients and controls. No shift towards cephalothin-resistant strains was observed in isolates from septic wounds in the treatment group.

Adolescent↗
PubMed1977

[In vitro susceptibility of bacteroidaceae to cefoxitin and cephalothin (author's transl)].

The activity of the new cephamycin C derivatives cefoxitin against 102 clinical isolates of Bacteroidaceae (95 Bacteroides strains and 7 Fusobacterium-Sphaerophorus cultures) was determined by tube dilution and standardized agar diffusion tests and compared to that of cephalothin. Cefoxitin was more active than cephalothin against 56 Bacteroides fragilis strains, 19 Bacteroides thetaiota-omicron strains and two Bacteroides splanchnicus strains. The difference seemed less pronounced with five Bacteroides vulgatus and four Bacteroides variabilis cultures. Three Bacteroides melaninogenicus and six Bacteroides oralis strains displayed similar sensitivity to both cephalosporins. At concentrations of 32 microng/ml or less, cefoxitin inhibited 91% and cephalothin 33% of the Bacteroides strains. Two strains of Sphaerophorus varius were likewise much more sensitive to cefoxitin than to cephalothin (MIC values 8 micron8/ml of cefoxitin and 256 microng/ml of cephalothin). Three other Sphaerophorus strains (the species necrophorus and freundii/mortiferum) and two of Fusobacterium fusiforme (Fusobacterium nucleatum) strains were very similar in their susceptibility to both cephalosporins. Statistical analysis of the relationship between MIC and zone size diameter showed relatively high correlation coefficients for cefoxitin and cephalothin (r=-0.741 and r=-0.703 respectively).

Bacteroidaceae↗
PubMedDate not supplied

Hemolysis induced by cefazolin and cephalothin in a patient with penicillin sensitivity.

A patient with penicillin sensitivity, who had never received a cephalosporin antibiotic previously, developed anemia and spherocytosis following the administration of cefazolin. Hemolysis abated when the drug was discontinued on the fourth day, and recurred on day six when cephalothin therapy was begun. IgG and complement components were present on the patient's erythrocytes, and IgG antibodies in her serum reacted with normal red blood cells which had been coated with benzylpenicillin, cefazolin or cephalothin. Antibodies to cephalothin-coated red blood cells were removed partially by incubating her serum with either benzylpenicillin or cefazolin. Complement-fixing IgG antibodies which reacted with red blood cells coated by cefazolin, cephalothin, and benzylpenicillin were considered to be responsible for hemolysis during the administration of cefazolin and, subsequently, cephalothin. The patient recovered completely following discontinuation of antibiotics, transfusion of red blood cells, and treatment with glucocorticoids. It is concluded that hemolysis may occur during therapy with cefazolin, as well as cephalothin, and may develop rapidly in a patient with penicillin sensitivity.

Adult↗
PubMed1978

Treatment of experimental Staphylococcus aureus endocarditis: comparison of cephalothin, cefazolin, and methicillin.

The effectiveness of cefazolin in Staphylococcus aureus endocarditis has been questioned because of in vitro inactivation by staphylococcal beta-lactamase. Cefazolin, although inactivated in vitro by S. aureus beta-lactamase, was as effective as cephalothin in the treatment of left-sided S. aureus endocarditis in rabbits. Cefazolin (20 mg/kg every 6 or 8 h), cephalothin (40 mg/kg every 6 h), and methicillin (40 mg/kg every 6 h), administered intramuscularly, were compared in the treatment of left-sided endocarditis caused in rabbits by a highly penicillin-resistant strain of S. aureus. The three antibiotics were all effective in reducing titers in vegetations. However, at the dose used, methicillin reduced the titers more rapidly than cephalothin or cefazolin. Cefazolin concentrations in serum were about double those achieved with cephalothin or methicillin. However, cefazolin was only half as active as methicillin and one-eighth as active as cephalothin in vitro in a serum assay. The half life in serum of cefazolin, cephalothin, and methicillin were each about 30 min. Serum bactericidal activities of the three antibiotics were very similar.

Animals↗
PubMed1976

Clinical pharmacology of cefamandole as compared with cephalothin.

We compared the pharmacology of cefamandole and cephalothin in six healthy adult male volunteers. After a 1-g, 20-min intravenous (i.v.) infusion, the average peak blood level of cefamandole was 87.6 versus 64.1 mug/ml for cephalothin. An i.v. infusion of 500 mg/h for 2 h (after a loading dose of 750 mg) gave an average steady-state blood level of 28.5 mug/ml for cefamandole and 18.2 mug/ml for cephalothin. Mean peak serum levels after 1 g intramuscularly were similar for the two antibiotics (about 21 mug/ml), but with cefamandole they persisted longer, and the area under the blood level curve was about 25% greater. The average t((1/2)) as determined from both i.v. studies was 34 min for cefamandole versus 30 min for cephalothin. The mean serum clearance for cephalothin, due to its partial conversion to a metabolite, was much greater than for cefamandole (425 versus 272 ml/min per 1.73 m(2)), but the renal clearances were similar for the two antibiotics (268 versus 257 ml/min per 1.73 m(2)). Other values for cefamandole and cephalothin were: 24-h urinary excretion, 80 and 66%; serum protein binding, 74 and 70%; and apparent volume of distribution, 12.8 and 18.5 liters/1.73 m(2), respectively. Thus, the pharmacology of the two antibiotics was similar. Blood levels were somewhat higher with cefamandole i.v., but the results suggest that dosage regimens should be the same for the two antibiotics.

Adult↗