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PubMed1980

Single-dose and multidose prophylaxis in vaginal hysterectomy: a comparison of sodium cephalothin and metronidazole.

A total of 79 patients underwent vaginal hysterectomy and were randomly assigned to three regimens of prophylactic antibiotics: multidose intravenous sodium cephalothin, single-dose intravenous sodium cephalothin, and single-dose oral metronidazole. Control groups were selected from two previous studies conducted at our institution. The incidence rates of infectious morbidity following all three regimens of antibiotics were substantially lower than in the control groups. There was no statistically significant difference in the incidence of standard febrile morbidity and serious pelvic infections among the three groups. The fever index was lowest in the single-dose sodium cephalothin group.

Adult↗
PubMed1986

Per-operative antibiotic treatment in cardiovascular surgery: the influence of methicillin versus cephalothin on post-operative infections and bacterial colonization.

This paper reports the results of a prospective study of antibiotic prophylaxis in 543 patients undergoing open-heart surgery. All patients were given per-operatively either methicillin, 1 g four times a day, or cephalothin, 1 g four times a day. There was no significant difference in the frequency of postoperative infections between the two groups. It was established that per-operative antibiotic prophylaxis selected resistant coagulase-negative staphylococci (CNS) in the nasal flora of cardiac surgery patients, that this change occurred to the same degree whether methicillin or cephalothin was used, that cephalothin favoured colonization with antibiotic resistant species other than CNS. It was found that the staff of the intensive care unit formed a reservoir of multi-resistant CNS.

Anti-Bacterial Agents↗
PubMed2004

Electrochemical determination of Cephalothin antibiotic by adsorptive stripping voltammetric technique.

A sensitive and reliable stripping voltammetric method was developed to determine Cephalothin antibiotic drug. This method is based on the adsorptive accumulation of the drug at a hanging mercury drop electrode and then a negative sweep was initiated, which yield a well defined cathodic peak at -625 mV versus Ag/AgCl reference electrode. To achieve high sensitivity, various experimental and instrumental variables were investigated such as supporting electrolyte, pH, accumulation time and potential, drug concentration, scan rate, convection rate and working electrode area. The monitored adsorptive current was directly proportional to the concentration of Cephalothin and it shows a linear response in the range from 4 x 10(-7) to 1.2 x 10(-6) mol l(-1) (correlation coefficient=0.9995) and the detection limit (S/N=3) is 3.3 x 10(-9) mol l(-1) at an accumulation time of 3 min. The developed AdSV procedure shows a good reproducibility, the relative standard deviation R.S.D.% (n=10) at a concentration level of 5 x 10(-7) mol l(-1) was 0.94%. Possible interferences by other pharmaceutical drugs and surfactants have been also evaluated. The applicability of this approach was illustrated by the determination of Cephalothin in pharmaceutical preparation and biological fluids such as serum and urine.

Anti-Bacterial Agents↗
PubMed1981

A comparison of the penetration characteristics of cephapirin and cephalothin into right atrial appendage, muscle, fat, and pericardial fluid of pediatric patients undergoing open-heart operation.

Thirty-two pediatric patients having open-heart operation received a single dose of either cephalothin or cephapirin intravenously, 30 mg per kilogram of body weight, in the operating room, for prophylaxis before the chest cavity was opened. Samples of right atrial appendage, pericardial fluid, muscle, fat, and plasma were obtained at various time intervals after injection of the antibiotics, and assayed for cephalosporin concentration. The concentration-time profiles of cephalothin and cephapirin in atrial appendage, muscle, fat, and plasma were identical. Cephapirin produced higher total and free concentrations in pericardial fluid compared with cephalothin. This presumably was due to the lower protein binding of cephapirin. Antibiotic concentrations above the minimal inhibitory concentration for Staphylococcus aureus and S. epidermidis were present in myocardial tissue for at least 90 minutes after the dose was administered. These data support the need to administer these antibiotics shortly before surgical intervention and, if the operation is prolonged, the need to administer a second dose of antibiotic.

Adipose Tissue↗
PubMed1982

A comparison of the safety, efficacy, and distribution of ceforanide and cephalothin in coronary artery bypass graft surgery.

Antibiotic prophylaxis in open-heart operations is a widely accepted practice. Introduction of new antibiotics with differences in tissue distribution, spectrum of activity and therapeutic index prompts their evaluation as possible effective prophylactic agents. We compared the distribution, clinical efficacy, and safety of ceforanide with cephalothin as a prophylactic agent in coronary artery bypass graft (CABG) procedures. The results indicated that the intravenous administration of ceforanide at the dose of 1 gm every 12 hours for 2.5 days was equivalent to cephalothin 1 gm every 6 hours for 2.5 days. Serum, muscle, and bone concentrations of ceforanide were significantly greater than those of cephalothin. These concentrations consistently exceeded the minimal inhibitory concentration for Staphylococcus aureus, the major pathogen implicated in wound infections. No toxicty was observed with either antibiotic. Ceforanide merits consideration as a prophylactic antibiotic in CABG operations.

Aged↗
PubMed1978

Parenteral cephalothin therapy for pelvic gonococcal infections.

The efficacy of intravenous cephalothin was studied prospectively in 20 patients with acute pelvic inflammatory disease, all of whom presented with lower abdominal pain, cervical and adnexal tenderness, fever, and leukocytosis. Blood, cervical, and cul-de-sac cultures were obtained on admission. The latter was transported anaerobically and inoculated in routine and prereduced medium. Transgrow medium with trimethoprim was used for endocervical cultures. Neisseria gonorrhoeae was isolated from the endocervix in 15 patients and from the cul-de-sac in four patients. All received intravenous cephalothin, 2 gm every four hours for seven days. Clinical improvement was observed in 48 to 78 hours. The cervical cultures were negative for N. gonorrhoeae after 48 hours, at the completion of treatment, and two weeks post-treatment. The drug was well tolerated. It was concluded that cephalothin intravenously is an acceptable alternative antibiotic for the treatment of gonococcal pelvic infection.

Cephalothin↗
PubMed2002

Structural milestones in the reaction pathway of an amide hydrolase: substrate, acyl, and product complexes of cephalothin with AmpC beta-lactamase.

Beta-lactamases hydrolyze beta-lactam antibiotics and are the leading cause of bacterial resistance to these drugs. Although beta-lactamases have been extensively studied, structures of the substrate-enzyme and product-enzyme complexes have proven elusive. Here, the structure of a mutant AmpC in complex with the beta-lactam cephalothin in its substrate and product forms was determined by X-ray crystallography to 1.53 A resolution. The acyl-enzyme intermediate between AmpC and cephalothin was determined to 2.06 A resolution. The ligand undergoes a dramatic conformational change as the reaction progresses, with the characteristic six-membered dihydrothiazine ring of cephalothin rotating by 109 degrees. These structures correspond to all three intermediates along the reaction path and provide insight into substrate recognition, catalysis, and product expulsion.

Amides↗
PubMed1988

Coupling products of amino acids to penicillin V and cephalothin: synthesis and susceptibility to carboxypeptidases and lysosomal enzymes.

Amino acids have been coupled to the carboxyl group of penicillin V and cephalothin by methods that keep the beta-lactam ring intact. Derivatives were successfully obtained with both neutral (Leu, Val, Ala, Ile, Trp, Tyr, Gly) and one acidic (Glu) amino acids. The new compounds were inactive in vitro against Staphylococcus aureus or Micrococcus luteus. Incubation in the presence of purified carboxypeptidases (A, B), soluble lysosomal fractions from liver, or cellular homogenates from liver, kidney, fibroblasts, and macrophages did not allow recovery of the antibacterial activity. Injection in mice also failed to cause liberation of microbiologically active compounds. HPLC studies confirmed that the amide linkage between the antibiotic and the amino acid was not hydrolyzed in the presence of soluble lysosomal fractions from liver. However, conversion of cephalothin and cephalothin-leucine to desacetyl derivatives was observed in the presence of soluble lysosomal fractions and extracts from liver and semipurified orange peel acetylesterase(s). It is concluded that amino acid derivatives of beta-lactam antibiotics do not offer potential chemotherapeutic use as prodrugs.

Amino Acids↗
PubMed1979

In-vitro activities of cefamandole and cephalothin against 1,881 clinical isolates. A multi-center study.

By use of an agardilution technic, 1,881 clinical isolates were tested against cefamandole and cephalothin. The isolates represented 18 genera, recovered in five geographically separate centers within the United States. The majority of strains were susceptible (MICs less than or equal to 8 micrograms/ml) to both drugs. Cefamandole showed greater activity against most of the bacterial pathogens. Enterococci, Serratia spp., and Acinetobacter spp. were resistant to both drugs. Cephalothin was more active against Staphylococcus aureus, and both cephalosporins were relatively inactive against methicillin-resistant strains of S. aureus. Enterobacter spp. and indole-positive Proteus spp. were susceptible to cefamandole but resistant to cephalothin.

Bacteria↗
PubMed1983

Cefuroxime, cefamandole, cefoxitin, and cephalothin in vitro susceptibility tests: reassessment of the "class representative" concept, confirmation of disk interpretive criteria, and proposed quality control guidelines.

The relationship of cefuroxime in vitro susceptibility tests to similar cephalosporins (cefamandole, cefoxitin, and cephalothin) was evaluated using 396 recent clinical isolates. The previously published interpretive criteria of greater than or equal to 18 mm (less than or equal to 8.0 micrograms/mL) = susceptible and less than or equal to 14 mm (greater than or equal to 32 micrograms/mL) = resistant for each drug were considered appropriate. The results of all study methods demonstrated cefuroxime to be slightly less active than cefamandole against most species, yet both drugs possessed nearly identical antimicrobial spectra. Cephalothin and cefoxitin were confirmed to have spectra significantly different from cefamandole and from each other, thus requiring separate testing. The application of the "class representative" concept to cefuroxime and cefamandole seems justified. Use of a 30-micrograms cefuroxime disk yielded the best predictive results and minimized the number of false-susceptible (very major) interpretive errors. Quality control guidelines are presented in a tentative form for cefuroxime, and modifications in the cephalothin and cefamandole zone limits are suggested.

Bacteria↗
PubMed1978

Differences between cephalothin and newer parenterally absorbed cephalosporins in vitro: a justification for separate disks.

The activities of cefamandole and cefoxitin in vitro were compared with that of cephalothin against staphylococci and gram-negative bacilli. Cephalothin was the most active agent against staphylococci. Cefamandole exhibited the greatest activity against the Enterobacteriaceae, with the exceptions of Serratia marcescens and indole-positive Proteeae, against which cefoxitin was the most active antibiotic. The activity of newer cephalosporins that are resistant to the beta-lactamases of gram-negative bacteria renders untenable the status of cephalothin as the class representative of the cephalosporins for susceptibility testing.

Acinetobacter↗
PubMed1986

Pharmacokinetics and protein binding of cefazolin and cephalothin in patients with cirrhosis.

The effects of liver disease on the pharmacokinetics and protein binding of cefazolin and cephalothin were studied in patients with cirrhosis, chronic active hepatitis or normal liver function. The T1/2 and mean residence time of cefazolin were significantly shorter in cirrhosis. Cephalothin clearance was decreased by cirrhosis. Plasma protein binding of cefazolin, but not cephalothin was significantly reduced in cirrhosis. It is suggested that no dose reduction is necessary for either drug in severe hepatic impairment.

Adult↗
PubMed1986

Relationship between penicillinase production and the in-vitro activity of methicillin, oxacillin, cloxacillin, dicloxacillin, flucloxacillin, and cephalothin against strains of Staphylococcus aureus of different phage patterns and penicillinase activity.

A total of 157 strains of Staphylococcus aureus of different phage patterns and penicillinase production were investigated for their susceptibility to methicillin, oxacillin, cloxacillin, dicloxacillin, flucloxacillin and cephalothin by an agar dilution method. Only strains of the 52, 52A, 80, 81 complex had significantly higher IC-50 values than the rest of the strains. No correlation was found between penicillinase production and the IC-50 values. Penicillinase susceptibility divided the antibiotics into two groups: one including methicillin, oxacillin and cephalothin, and the other included dicloxacillin, cloxacillin and flucloxacillin. Nineteen strains of S. aureus which existed in both a penicillinase producing and a penicillinase non-producing form were examined for susceptibility to the six antibiotics. The difference between penicillinase positive and penicillinase negative variants was especially marked for flucloxacillin and cephalothin. Methicillin induction prior to susceptibility testing had only a minor influence on the results. Investigation of the stability of methicillin and the four isoxazolyl penicillins against penicillinase production by 37 strains of S. aureus showed methicillin to be the most stable antibiotic. This was followed by dicloxacillin, cloxacillin, flucloxacillin, and oxacillin in that order. The order of stability was identical and independent of phage pattern and quantitative penicillinase production.

Bacteriophage Typing↗
PubMed1988

In-vitro activity and beta-lactamase stability of methicillin, isoxazolyl penicillins and cephalothin against coagulase-negative staphylococci.

Forty-nine clinical strains of coagulase-negative staphylococci were investigated for susceptibility to methicillin, oxacillin, cloxacillin, dicloxacillin, flucloxacillin and cephalothin. The highest level of resistance was found to methicillin and the lowest to cephalothin. The resistance-level of the isoxazolyl penicillins showed a high degree of uniformity. However more strains were resistant to cloxacillin and oxacillin than to dicloxacillin and flucloxacillin. Only a weak correlation was found between beta-lactamase production, and resistance to the six antibiotics. Methicillin was the most stable. The inactivation of cephalothin differed from that of the other antibiotics.

Cephalothin↗
PubMed1988

Effect of the combination of clavulanic acid and cephalothin on an experimental infection with Yersinia enterocolitica in iron-overloaded mice.

Iron-overloaded mice were infected with a virulent strain of Yersinia enterocolitica by the oral route to study the effect of antimicrobial treatments. The effects of therapy were assessed by enumeration of viable yersiniae in Peyer's patches and in ileal contents. Combinations of cephalothin and clavulanic acid showed therapeutic effects, which were interpreted as in-vivo synergism, since each component alone was ineffective. Ceftazidime, which is relatively beta-lactamase resistant, showed in-vivo activity similar to that of the combination of cephalothin and clavulanic acid. These results suggest that clavulanic acid is able to protect cephalothin against Y. enterocolitica beta-lactamases in vivo, as has been shown previously in vitro.

Animals↗
PubMed1977

Nephrotoxicity in combined cephalothin and gentamicin therapy.

Thirty-two series of treatment with cephalothin and gentamicin for 5-10 days have been administered to 26 patients. An increase in serum creatinine occurred in 6 series. Important factors for the renal damage were elevated pretreatment serum creatinine, elevated serum gentamicin and probably a high serum cephalothin. In 2 patients the nephrotoxicity was fully reversible; the others died before a dicisive improvement in renal function could be expected. In 11 out of 28 treatment series there was a transient drop in serum potassium. Since the combination of cephalothin and gentamicin as the primary treatment of life-threatening infection has often proved effective, and since short-lasting treatment seems to entail only a minute risk of nephrotoxicity in patients with normal pretreatment serum creatinine, we still prefer this treatment in such cases.

Adolescent↗
PubMedDate not supplied

Effects of cephalothin, cefazolin, and cefmetazole on the hemostatic mechanism in normal dogs: implications for the surgical patient.

Twenty-six female beagles were used to evaluate the effects of intravenous and long-term subcutaneous administration of cephalothin, cefazolin, and cefmetazole on platelet function and the coagulation cascade. Platelet aggregation in response to an adenosine diphosphate (ADP) agonist, bleeding time, platelet count, platelet size, prothrombin time (PT), and activated partial thromboplastin times (aPTT) were evaluated before and 90 minutes after two intravenous doses (22 mg/kg) of cephalothin, cefazolin, and cefmetazole given at 90-minute intervals. Dogs given saline injections were used as controls. Platelet count, platelet size, PT, and aPTT were evaluated after 7 days of subcutaneous administration of saline, cefazolin, and cefmetazole (22 mg/kg every 8 hours). A significant decrease in platelet aggregation in response to ADP was detected 90 minutes after intravenous administration of cephalothin. Bleeding time was increased significantly 90 minutes after intravenous administration of cefmetazole. Platelet size was decreased significantly 24 hours after onset of the study in all animals, including controls. No significant changes in platelet count, platelet size, PT, or aPTT were detected after 7 days of subcutaneous administration. Cefazolin had no adverse effects on platelet aggregation in response to ADP, bleeding time, platelet count, platelet size, PT, or aPTT. Therefore, cefazolin should be considered as a perioperative antibiotic in dogs with conditions predisposing to hemostatic complications.

Animals↗
PubMed1984

Single-strain regression analysis for quality control of cephalothin-susceptibility testing and determination of interpretive breakpoints.

Histogram analysis of inhibition zone diameters around the 30 micrograms cephalothin disk for E. coli, P. mirabilis, and K. pneumoniae in samples from 1975 to 1982 showed a marked reproducibility of the disk-diffusion antibiotic-susceptibility test in the routine laboratory. A comparison of interpretive breakpoints with histograms for E. coli, P. mirabilis, K. pneumoniae, S. aureus, coagulase-negative staphylococci, and S. faecalis showed a higher proportion of possible misinterpretations using the breakpoints of the Swedish Reference Group, SRG, as compared to international (NCCLS) breakpoints. Further analysis using single-strain regression analysis revealed two major causes of interpretive errors. Firstly, the laboratory-related regression line for a bacterial species can be different from the general regression line of the reference laboratory. This difference has to be corrected by using species-related breakpoints. For E. coli, a species-specific breakpoint was determined to R = greater than 13 mm. Secondly, MIC limits recommended for the susceptibility categories of cephalothin by SRG are lower than the international limits and close to the true MIC values of many bacterial isolates, leading to misinterpretations due to the methodological variation. These studies suggest an adoption of international MIC limits for the susceptibility categories of cephalothin in Scandinavia. The "I" category should denote an indeterminate zone. A multi-laboratory quality control assessment using histogram analysis is recommended with optional single-strain regression analysis to determine breakpoints for problem combinations of bacterial species and antibiotics.

Bacteria↗