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PubMed1996

Analysis of binary mixtures of cephalothin and cefoxitin by using first-derivative spectrophotometry.

A method for the analysis of two-component mixtures of cephalothin and cefoxitin using zero-crossing first-derivative spectrophotometry is described. This technique permits the quantification of these drugs with closely overlapping spectral bands without any separation step. Linear calibration graphs of first-derivative values at 235.00 and 236.75 nm for cephalothin and cefoxitin, respectively, with negligible intercepts were obtained versus concentration in the range 4.0-32.0 micrograms ml-1 for both antibiotics. This paper presents a systematic examination of the experimental data by applying an exhaustive statistical analysis to demonstrate the validity of the method. The results of the determination of these antibiotics in mixtures of injectable dosage forms are also presented, together with their determinations in physiological serum and glucosed physiological serum.

Calibration↗
PubMed1995

Binding of cephalothin and cefotaxime to D-ala-D-ala-peptidase reveals a functional basis of a natural mutation in a low-affinity penicillin-binding protein and in extended-spectrum beta-lactamases.

Two clinically-important beta-lactam antibiotics, cephalothin and cefotaxime, have been observed by X-ray crystallography bound to the reactive Ser62 of the D-alanyl-D-alanine carboxypeptidase/transpeptidase of Streptomyces sp. R61. Refinement of the two crystal structures produced R factors for 3 sigma (F) data of 0.166 (to 1.8 A) and 0.170 (to 2.0 A) for the cephalothin and cefotaxime complexes, respectively. In each complex, a water molecule is within 3.1 and 3.6 A of the acylated beta-lactam carbonyl carbon atom, but is poorly activated by active site residues for nucleophilic attack and deacylation. This apparent lack of good stereochemistry for facile hydrolysis is in accord with the long half-lives of cephalosporin intermediates in solution (20-40 h) and the efficacy of these beta-lactams as inhibitors of bacterial cell wall synthesis. Different hydrogen binding patterns of the two cephalosporins to Thr301 are consistent with the low cefotaxime affinity of an altered penicillin-binding protein, PBP-2x, reported in cefotaxime-resistant strains of Streptococcus pneumoniae, and with the ability of mutant class A beta-lactamases to hydrolyze third-generation cephalosporins.

Amino Acid Sequence↗
PubMed1989

Potentiometric determination of cephalothin.

The composition of a pseudo-liquid potential-determining phase for the cephalothin-selective electrode has been determined and the following basic electrode parameters were examined: measurement range, slope, limit of detection, selectivity and lifetime. This paper discusses the effect of side-chain substituents on the electrode properties, the electrode having been used for cephalothin determination in the range 43-436.5 mg l-1 (standard deviation, 0.64-4.5 mg l-1).

Cephalothin↗
PubMed1975

Inactivation of cefazolin, cephaloridine, and cephalothin by methicillin-sensitive and methicillin-resistant strains of Staphylococcus aureus.

Cefazolin was more susceptible than cephaloridine and cephalothin to in vitro inactivation by coagulase-positive, penicillinase-producing strains of Staphylococcus aureus. Inactivation (which was greater with methicillin-resistant than with methicillin-sensitive strains) was demonstrated by assay of the antibiotics in broth cultures with simultaneous colony counts and by exposure of the antibiotics to penicillinase powders extracted from S. aureus. Cefazolin was destroyed to a greater extent than was cephaloridine, whereas cephalothin underwent little, if any, destruction. The clinical implications of this degradation, thought by some to be of importance for cephaloridine, might also apply to cefazolin.

Cefazolin↗
PubMed1977

Effect of hemoperfusion of clearance of gentamicin, cephalothin, and clindamycon from plasma of normal dogs.

Nine normal dogs were divided into three groups of three. Group 1 was given an overdose of gentamicin; group 2, cephalothin; and group 3, clindamycin. Group 1 had hemoperfusion with Amberlite XE-336, and groups 2 and 3 with Amberlite XAD-4 resin adsorbents, for 6 hr with a blood flow rate of 300 ml/min. The plasma clearance and removal rates of antibiotics by the hemoperfusion columns were high. The clearance rate of gentamicin from plasma (mean +/- standard deviation) ranged from 59 +/- 30 to 199 +/- 6 ml/min, of cephalothin from 66 +/- 14 to 157 +/- 8 ml/min, and of clindamycin from 55 +/- 9 to 125 +/- 16 ml/min. Of the total dose of antibiotic administered, the hemoperfusion columns removed 67% from theplasma in group 1, 41% in group 2, and 18% in group 3. The fact that antibiotics may be rapidly removed from the blood during hemoperfusion should be considered in calculation of the therapeutic dose of antibiotic required for patients who receive this preocedure. Also, hemoperfusion can effectively and rapidly remove certain antibiotics from the blood of patients who have had a potentially toxic overdose.

Animals↗
PubMed1978

Differential inactivation of cephapirin vs. cephalothin by penicillin-resistant strains of Staphylococcus aureus: a preliminary study.

The bactericidal effectiveness of cephapirin and cephalothin against small (approximately 10(5)) and large (approximately 10(8)) inocula of penicillin-resistant Staphylococcus aureus was evaluated. With the smaller inoculum, no differences in bactericidal activity between the two drugs (tested at 2 and 40 microgram/ml) were seen after incubation for 2, 4, 6, or 24 hr. Neither cephalosporin effectively killed a larger inoculum in a concentration of 250 times the minimal bactericidal concentration for selected strains. Total inactivation of cephapirin (40 microgram/ml) by eight of 13 strains was demonstrated with the larger inoculum. These preliminary studies indicate that inactivation of cephapirin is pH-dependent. No strain inactivated cephapirin in less than or equal to 4 hr. Inactivation was independent of temperature at 37 C and 42 C. Although cephalothin was resistant to inactivation under the same conditions, the inoculum required to inactivate cephapirin was not killed by 100 microgram of cephalothin/ml. Although strains of S. aureus that slowly inactivate cephapirin appear to be prevalent, no strain that rapidly inactivates this cephalosporin was identified.

Cephalosporins↗
PubMed1979

Penetration of cephapirin and cephalothin into the right atrial appendage and pericardial fluid of patients undergoing open-heart surgery.

To prevent infection in 27 patients who underwent coronary artery bypass or cardiac valve replacement surgery, each patient received a single 2-g dose of either cephalothin or cephapirin intravenously before the operation (prior to opening of the chest cavity). Samples of the right atrial appendage, pericardial fluid, and serum were obtained at various intervals after injection of the antibiotic and were assayed for cephalosporin concentrations. Cephapirin consistently reached higher levels than cephalothin in the right atrial appendage and pericardial fluid; both cephalosporins, however, reach concentrations in these sites well above their minimal inhibitory concentrations (MICs) for penicillin-resistant staphylococci. Of particular interest was the brevity of the period (about 100 min) during which levels of both antibiotics were maintained above the MIC in the right atrial appendage. This finding emphasizes the need for administration of these antibiotics shortly before surgery.

Adult↗
PubMed1979

Synergy of vancomycin plus cefazolin or cephalothin against methicillin-resistance Staphylococcus epidermidis.

The in vitro activity of cephalothin, cefazolin, and vancomycin against 25 isolates of methicillin-resistant Staphylococcus epidermidis was determined by means of a broth dilution technique with two sizes of inoculum. The size of the inoculum had a marked effect on the minimal inhibitory concentrations and the minimal bactericidal concentrations of all three antibiotics. With a small inoculum, 100% of the isolates were inhibited by 3.12 micrograms of vancomycin/ml, 76% by 12.5 micrograms of cephalothin/ml, and 64% by 12.5 micrograms of cefazolin/ml. With a large inoculum 100% of the isolates were inhibited by 200 micrograms of vancomycin/ml, 40% by 12.5 micrograms of cephalothin/ml, and 12% by 12.5 micrograms of cefazolin/ml. As determined by a tube dilution checkerboard technique for both sizes of inoculum, the combination of vancomycin plus cephalothin was synergistic against methicillin-resistant S. epidermidis in 45 of 50 cases, and the combination of vancomycin plus cefazolin was synergistic in 39 or 50 cases. These data from in vitro studies suggest that these antibiotic combinations should be evaluated clinically in patients with severe infections caused by methicillin-resistant S. epidermidis.

Cefazolin↗
PubMed1983

Early results of a comparative trial of ceftazidime versus cephalothin, carbenicillin and gentamicin in the treatment of febrile granulocytopenic patients.

Ceftazidime was compared with a combination of cephalothin, carbenicillin and gentamicin as empirical therapy for fever in granulocytopenic patients. Forty-eight patients were studied in this randomized trial. In the 44 evaluable cases, favourable clinical responses were seen in 9/21 ceftazidime-treated cases and 13/23 patients treated with the combination. Four of 5 bacteraemias were cured with ceftazidime and 3 of 4 with triple therapy. Comparable numbers of patients developed new fevers while on therapy. Five ceftazidime-treated patients developed documented superinfection compared to 6 patients in the other group. Five patients treated with ceftazidime died from the initial infection or a superinfection compared with 3 on the combination. The overall results appear to be similar at this time. However, remarkable differences were observed between the types of superinfecting organisms with the two regimens. If all 48 patients are considered the isolates were as follows: ceftazidime treatment--5 clostridia, 3 enterococci, 1 Staphylococcus epidermidis and 1 Citrobacter; cephalothin-carbenicillin-gentamicin treatment--4 Pseudomonas, 1 Escherichia coli, 1 Bacteroides fragilis and 2 Candida spp. These results suggest that Gram-positive coverage should be added to ceftazidime in the empirical treatment of febrile granulocytopenic patients.

Adult↗
PubMedDate not supplied

A randomized study of tobramycin plus ticarcillin, tobramycin plus cephalothin and ticarcillin, or tobramycin plus mezlocillin in the treatment of infection in neutropenic patients with malignancies.

Two hundred twenty-five patients with 358 febrile episodes were treated with tobramycin and ticarcillin (TT), tobramycin and mezlocillin (TM), or tobramycin, ticarcillin and cephalothin (TTC). There were no statistically significant differences in the response rates for patients who were proven to have infection (67% with TT, 69% with TTC and 53% with TM). Patients were more often cured of their infection if their neutrophil count rose during therapy. In this study, the addition of cephalothin to TT did not increase the frequency of azotemia (10% and 12%, respectively). Although mezlocillin has a broader spectrum of activity in vitro than ticarcillin, it was not more efficacious when combined with tobramycin than ticarcillin plus tobramycin for the treatment of infections in neutropenic patients.

Adult↗
PubMed1977

Effects of cephalothin and penicillin G on platelet function in vitro.

High concentrations of cephalothin or penicillin G inhibit a number of the functions of human or rabbit platelets in citrated platelet-rich plasma (PRP) and in suspensions of washed platelets. The reactions shown to be inhibited are: ADP-induced shape change and the primary and secondary phases of aggregation and release induced by ADP or adrenaline in human cirtated PRP; release and aggregation of washed human platelets exposed to collagen, thrombin, vasopressin, or the ionophore A 23,187; aggregation of washed human platelets exposed to phytohaemagglutinin from Phaseolus vulgaris (PHA) or polylysine; release induced by concanavalin A or PHA in suspensions of washed platelets from rabbits; platelet adherence to a collagen-coated surface or to the damaged intimal surface of the rabbit aorta; platelet factor 3 availability; lysis of rabbit platelets by an antiserum directed against them; and clot retraction. Neither antibiotic affected serotonin-induced aggregation; a high concentration of cephalothin slightly inhibited the initial rate of serotonin uptake. Penicilloic acid showed about half the inhibitory effect of penicillin G on ADP-induced aggregation. In citrated human platelet-rich plasma, ampicillin and oxacillin inhibited ADP-induced aggregation to the same extent as similar concentrations of penicillin G; in suspensions of washed platelets, however, ampicillin was less inhibitory than penicillin G or oxacillin. Platelet ultrastructure, assessed by transmission electron microscopy, was not visibly altered. Evidence that the antibiotics become bound to platelets is the finding that platelets incubated with the antibiotics ans resuspended in fresh media showed less response to aggregating agents compared with control platelets. Penicillin G and related antibiotics may be inhibitory because they coat the platelet surface. Their effects on platelet functions are probably responsible for excessive bleeding and increased bleeding times observed in patients and volunteers receiving high doses of these antibiotics.

Antibodies↗
PubMed1976

Comparative pharmacokinetics of cefamandole, cephapirin, and cephalothin in healthy subjects and effect of repeated dosing.

Cefamandole nafate, cephapirin, and cephalothin were administered intravenously in crossover fashion to 12 volunteers, in dosages of 2 g every 6 h for 16 doses. Mean peak levels of cefamandole were approximately 50% higher than those of the other agents. The serum concentration curves appeared to decline bi-exponentially, suggesting that a two-compartment model was most applicable for pharmacokinetic analysis; accordingly, the t((1/2)) of cefamandole was significantly longer when the serum peak was omitted from the analysis (0.86 versus 0.73 h, P < 0.05). The half-lives of cephalothin and cephapirin, 0.34 and 0.36 h, respectively, were probably underestimates reflecting the inclusion of distribution-phase values in the calculation. Repeated dosing had no effect on the peak serum levels, half-life, serum clearance, or apparent volume of distribution with one exception: peak serum levels of cephapirin were significantly lower after the sixteenth than after the first dose. Marked variations within a given subject were noted in the half-life and apparent volume of distribution of cefamandole in several instances. Renal clearances of cefamandole exhibited saturation kinetics similar to those of penicillin G.

Cephalosporins↗
PubMed1976

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.

Adult↗
PubMed1977

Amikacin and cephalothin: empiric regimen for granulocytopenic cancer patients.

Amikacin (15 mg/kg per day) was used in combination with cephalothin (7 g/m(2) per day) as an empiric regimen for de novo febrile (>101 degrees F [38.3 degrees C]) episodes in 93 granulocytopenic (<1,000/mm(3)) cancer patients. Both drugs were given intravenously in four equal doses every 6 h. The response rate for all documented infections was 83%, including 11 of 17 (65%) bacteremias. Escherichia coli (14 cases) was the most common pathogen, whereas Pseudomonas aeruginosa (2 cases) caused fewer infections. Mean amikacin serum levels were 8.7 mug/ml at 1 h and 2.2 mug/ml at 5 h. Failure of bone marrow recovery in association with a bacteremia was a bad prognostic sign (only two of eight improving). Ototoxicity occurred in two (2%) patients, whereas presumed antibiotic-induced nephrotoxicity developed in six (7%) patients. Surveillance cultures (nose, gums axilla, and rectum) of all hospitalized patients revealed no significant change in the incidence of amikacin resistance. The combination of amikacin and cephalothin in this dose and schedule was safe and efficacious in these granulocytopenic patients.

Adult↗
PubMed1978

Excretion of cefamandole, cefazolin, and cephalothin into T-tube bile.

The biliary tract excretion of cefamandole, cefazolin, and cephalothin was measured in eight patients with T-tubes inserted into their common ducts after ductal exploration for biliary tract stones. Each patient received 1.0 g intravenously of each cephalosporin on 3 separate days; T-tube bile and serum were collected at selected time intervals thereafter. In seven patients, bile and urine were collected for 6 h after the administration of each drug. Mean peak levels of cefamandole, cefazolin, and cephalothin in bile were 352, 46, and 12 mug/ml, respectively. The respective mean peak serum levels were 55.0, 92.8, and 32.4 mug/ml. Despite the fact that peak serum levels of cefazolin were 1.5 times those of cefamandole, levels in bile of cefamandole were about 8 times those of cefazolin. Over a 6-h period, almost three times as much cefamandole was excreted into bile as was cefazolin. Therefore, in those patients with biliary tract sepsis, in whom a cephalosporin is indicated for therapy, cefamandole appears to be the drug of choice.

Adult↗
PubMed1979

Bacampicillin, Ampicillin, Cephalothin, and Cephapirin levels in human blood and interstitial fluid.

The diffusibility of bacampicillin, ampicillin, cephalothin, and cephapirin into human interstitial fluid was investigated by using crossover studies. We compared bacampicillin with ampicillin and found that bacampicillin was better absorbed after oral administration. Blood, interstitial fluid, and urine levels were consistently higher in volunteers who received bacampicillin. We compared cephalothin with cephapirin and found that blood and interstitial fluid levels were comparable throughout the study.

Adult↗
PubMed1979

Effect of cephalothin on measurement of creatinine concentration.

Cephalothin, an antibiotic implicated as nephrotoxic, falsely elevates the creatinine concentration as determined by the Jaffé reaction in vitro. We studied this effect in vivo and demonstrated variable degrees of interference in determinations of plasma and urinary creatinine concentrations by two automated methods. Clinicians should be aware of this phenomenon in patients receiving cephalothin, both when monitoring renal function and when assessing patient reliability in the collection of timed urine specimens.

Cephalothin↗