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PubMed1986

Reactions of Escherichia coli TEM beta-lactamase with cephalothin and with C10-dipeptidyl cephalosporin esters.

Two novel C10-(dipeptidyl)cephalosporin esters (3-(beta-chloro-L-alanyl-beta-chloro-L-alanyloxymethyl)-7 beta-(2-thienylacetamido)-3-cephem-4-carboxylic acid (7) and sodium 3-(L-alanyl-L-alanyloxymethyl)-7 beta-(2-thienylacetamido)-3-cephem-4-carboxylate, toluene-sulfonic acid salt (18] were synthesized, and their reactions with Escherichia coli TEM beta-lactamase were examined. Kinetic parameters determined for the enzymatic reactions of 7 (Km = 0.32 mM; Vmax = 338 mumol min-1 (mg protein)-1) and of 18 (Km = 0.33 mM, Vmax = 338 mumol min-1 (mg protein)-1) demonstrate that both of the peptidyl esters are good substrates for the lactamase. In fact, the Vmax rates for 7 and 18 are each more than 4-fold greater than that obtained for cephalothin, 1 (Vmax = 78 mumol min-1 (mg protein)-1), a well characterized substrate for the lactamases. Analysis of the enzymatic reactions by high field (500 MHz) 1H NMR revealed similar patterns for fragmentation of the cephem nucleus of 1, 7, and 18. However, while hydrolysis of 1 produces acetate, cleavage of 7 and 18 releases beta Cl-LAla-beta Cl-LAla and LAla-LAla, respectively, from the dipeptidyl cephalosporin esters. Based on these findings, a strategy for co-opting the beta-lactamases of Gram-negative bacteria for "delivery" of bactericidal agents is described, and an explanation for the previously reported (Mobashery, S., Lerner, S.A., and Johnston, M. (1986) J. Am. Chem. Soc. 108, 1685) antibacterial activity of 7 is offered.

Cephalothin↗
PubMed1985

Comparison of Escherichia coli susceptibility to cephalothin, cefazolin, ceforanide, and cefamandole.

Twenty-seven Escherichia coli test strains that were not susceptible to cephalothin were tested for susceptibility to cefazolin, cefamandole, and ceforanide. By zone-size criteria (greater than or equal to 18 mm), 67% of E coli were susceptible to cefazolin and cefamandole, and 93% were susceptible to ceforanide. By microtiter assay (MIC less than or equal to 8 micrograms/ml), 88% were susceptible to cefazolin and cefamandole, and 94% were susceptible to ceforanide. The results support susceptibility testing of E coli with specific first- or second-generation cephalosporins rather than with class agents.

Cefamandole↗
PubMed1985

A prospective double-blind comparison of piperacillin, cephalothin and cefoxitin in the prevention of postoperative infections in patients undergoing intra-abdominal operations.

Piperacillin has been shown to be as safe and effective an agent as cephalothin and cefoxitin when used in patients undergoing elective intra-abdominal surgical procedures. Enterococcus species have been shown in other studies to be susceptible to piperacillin, perhaps making it the preferred antibiotic for prophylaxis in clinical settings when enteric flora will be encountered.

Abdomen↗
PubMed1985

[The pharmacokinetics of cephalothin following single and repeated administration in man].

The repeated administration of substances, which are mainly excreted by tubular secretion, can cause an increase of its own elimination. Because cephalothin is tubularly transported, it was of interest to prove, whether or not the repeated administration of therapeutic doses for 5 d produces an increases of renal elimination. Pharmacokinetic parameters show only small differences between the single and repeated dosing, caused by changes of volume of distribution. No stimulation of the carrier transport system was found. On the contrary, the renal elimination was reduced slightly after therapy for 5 d. Our results show that the present dosage recommendations are valid also for repeated administrations.

Adolescent↗
PubMed1977

[Clinical study on penetration of antibiotics into cerebrospinal fluid (second report),-Study on intravenous administration of sodium cephalothin with mannitol solution (author's transl)].

Penetration of Sodium Cephalothin (CET) into CSF follwing intravenous administration was studied in 23 patients with intracranial diseases excluding inflammation and severe subarachnoid hemorrhage. 1) After intravenous injection of 2 g of CET, ventricular CSF was obtained in 4 cases. All these 4 cases showed CET concentration in CSF to be below 0.1 mcg/ml. 2) After intravenous injection of 2 g of CET, lumbar CSF was obtained in 6 cases. In two cases out of these 6 cases, CET concentration in CSF was higher than 0.7 mcg/ml. 3) In 13 cases 2 g of CET with 200ml of 20% Mannitol was injected intravenously and lumbar CSF was examined. CET concentrations in CSF between 0.7 mcg/ml and 6.0 mcg/ml were observed in 9 cases of this group. 4) According to the results it is strongly suggested that the administration of Monnitol and CET is very effective for penetration of CET into CSF.

Adolescent↗
PubMed1979

Investigations on the potential nephrotoxicity of cefazedone and gentamicin and of their combination, in comparison with the combination of cefazolin and cephalothin with gentamicin.

The nephrotoxicity of (6R,7R)-7-(2-[3,5-Dichloro-4-oxo-1(4H)-pyridyl]-acetamido)-3-([(5-methyl-1,3,4-thiadiazol-2-yl)-thio]methyl)-8-oxo-5-thia-1-azabicyclo[4,2,0]oct-2-ene-2-carboxylic acid (cefazedone, Refosporen), cephalothin, cefazolin and gentamicin was investigated by the determination of alanine-amino-peptidase (AAP) in urine of healthy volunteers. The results were compared with those obtained by application of the respective combination. The beta-lactam antibiotics showed no effect on the elimination of the characteristic tubule enzyme, while gentamicin, as is known, induced a marked increase of the enzyme elimination. The results with cefazedone + gentamicin show that the determining component on the extent of AAP elimination is the aminoglycoside exclusively, where high and low responders can be observed. When the experiments with gentamicin and with the combination gentamicin and cefazedone were carried out with the same volunteers, no additive effects could be observed.

Adolescent↗
PubMed1984

[A comparison of the penetration characteristics of latamoxef and cephalothin into the right atrial appendage and pericardial fluid of adult patients undergoing open-heart surgery].

A comparative study of the serum, atrial muscle, and pericardial fluid concentrations of latamoxef (LMOX) and cephalothin (CET) was performed in 18 adult patients having cardiac surgery. Patients were randomly assigned to receive either a single dose of CET 30 mg/kg, LMOX 30 mg/kg, or LMOX 20 mg/kg. Each drug was administered intravenously soon after anesthetic maintenance was achieved. After each drug administration, serum samples were obtained at various time intervals before, during, and after extracorporeal circulation (ECC), and assayed for CET and LMOX concentration. A sample of pericardial fluid was collected immediately after the pericardium was opened. The right atrial appendage tissue samples were obtained at the time of heart cannulation. The pharmacokinetics and penetration characteristics of each drug were analysed by the method of two-compartment model. Serum concentrations of CET following a single intravenous injection of 30 mg/kg were the high values, 172.4 +/- 35.6 micrograms/ml at 5 minutes, and 92.9 +/- 33.8 micrograms/ml at 15 minutes after injection. The initial (before bypass) half-life was 0.22 +/- 0.11 hour (13.1 minutes) while half-lives during and after ECC were prolonged significantly. In the cases of CET group, the myocardial tissue concentration value of 4.86 micrograms/g was obtained in only 1 case. The mean pericardial fluid concentration was 4.69 +/- 3.35 micrograms/ml at 5 to 30 minutes after injection. Serum concentration of LMOX following a injection of 30 mg/kg were 253.6 +/- 67.4 micrograms/ml at 5 minutes, and 176.3 +/- 64.1 micrograms/ml at 15 minutes after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

[Pharmacodynamics of cephaloridine and cephalothin combined with sulfalene in rabbits].

The combined use of cephaloridin and cephalothin with sulfalen resulted in decreased binding of the cephalosporins by serum proteins and decreased rate of drug elimination in rabbits. It might be suggested that these two processes were interrelated. The decreased binding of the antibiotics by proteins in rabbits promoted an increase in the volume distribution of the drugs at the expense of a rise in the level of their penetration from the blood into the peripheral tissues.

Animals↗
PubMed1983

[Comparison of side effects of intravenous cephapirin and cephalothin with special reference to the incidence of phlebitis].

The frequency and severity of side effects, above all, phlebitis, associated with an intravenous use of cephapirin (CEPR) or cephalothin (CET) was compared in 69 patients with infections. Two grams of each drug were administered intravenously twice a day with a 21-G vein needle in one of the two arms of the patients. CEPR was administered to 32 patients, and CET to 37 patients respectively. After treatment, the status of the veins was checked, and laboratory findings and other side effects were evaluated daily. Each drug appeared to be equally efficacious in the treatment of infections. The administration of CEPR was associated with a slightly lower rate of phlebitis and other side effects, but the difference between the 2 drugs was not significant (0.05 less than P less than 0.10). Phlebitis was observed in 1 patient (3.1%) of CEPR group and in 3 patients (8.1%) of CET group. Side effects, including phlebitis, were observed in 4 patients (12.5%) of CEPR group and in 12 patients (32.4%) of CET group. In CET group, drug exanthema (3 cases), drug fever (3 cases), and abnormalities in liver function (4 cases) were observed. These findings, together with the results of other reports, suggest that CEPR is a safe and useful drug in the treatment of infection as compared with CET.

Adolescent↗
PubMed1978

[Microbiological evaluation of cefoxitin, a new beta-lactamase resistant cephamycin antibiotic, compared to cephalothin, cephaloridine and cefazolin].

Cefoxitin (Mefoxitin), Cephaloridin, Cephalothin and Cefazolin were tested in vitro against 380 clinical isolates of Staph. aureus and Enterobacteriaceae using the tube dilution procedure. Of the gramnegative microorganisms a selection of 150 strains was examined regarding susceptibility to the antibiotic combinations cefoxitin/gentamicin and cefoxitin/sisomicin in comparison to cephalothin/gentamicin and cephalothin/sisomicin. Cefoxitin has a broad antimicrobial spectrum and a high beta-lactamase-resistance. Cefoxitin was more active than the other antibiotics tested against E. coli, Klebsiella, Serratia, Enterobacter, indole-negative and -positive Proteus species. The high effectiveness of cefoxitin against anaerobic bacteria such as Bacteroides fragilis and Clostridium perfringens is discussed. Cefoxitin has an excellent bactericidal potency. Among the combinations tested cefoxitin/sisomicin was most active and obtained synergistic effects in most species. The resistance rate of cefoxitin of 8.7% was reduced to 0.7% with cefoxitin/sisomicin.

Cefazolin↗
PubMed1983

Renal function following cardiopulmonary bypass surgery in children: a randomized comparison of the effects of gentamicin and cloxacillin with cephalothin.

Renal function was studied in 36 children who were randomly allocated to receive either gentamicin and cloxacillin or cephalothin as prophylactic antibiotic cover for complex cardiopulmonary bypass surgery. Both groups of children developed a similar degree of impairment of glomerular function with significant elevations in plasma creatinine concentrations and urine albumin excretion compared to preoperative levels which tended to resolve by the 5th postoperative day. The urine excretion of N-acetyl-glucosaminidase increased in both groups postoperatively but remained significantly elevated only in those children who had received gentamicin. These findings suggest that whilst gentamicin exerts a demonstrable nephrotoxic effect on the proximal renal tubules it does not contribute significantly to either the incidence or severity of postoperative renal glomerular impairment.

Acute Kidney Injury↗
PubMed1981

Prospective, randomized, double-blind study using prophylactic cephalothin for major, elective, general thoracic operations.

A total of 211 patients were entered into a randomized, double-blind study of postoperative infection in which an antibiotic (cephalothin) and a placebo were used. The antibiotic was effective in reducing sleep wound infections (p less than 0.05) and superficial wound infections (p less than 0.01). The incidence of pulmonary infections was decreased, but the change was not statistically significant, and the incidence of empyema was unaffected.

Bacterial Infections↗
PubMed1981

[Synergistic effect of thiamphenicol and cephalothin on Bacterioides fragilis (author's transl)].

Synergistic effect of thiamphenicol (TP) and cephalothin (CET) on Bacteroides fragilis was proved in vitro. Especially its effect was much clear on B. fragilis which is possible to produce beta-lactamase. Synergistic bactericidal effect of TP and CET was proved. Chemotherapeutic effect of TP and CET against experimental mixed infectious mouse due to E. coli (beta-lactamase -) and B. fragilis (beta-lactamase +) was proved.

Animals↗
PubMed1978

Cephalothin-tobramycin as a preventive antibiotic combination.

Antimicrobial therapy should never be used indiscriminately, nor can it take the place of meticulous surgical technique. Appropriate antimicrobial agents administered within the critical time period and in the recommended dosage to achieve adequate serum concentrations effectively reduce the incidence of postoperative wound and other systemic infections. The low incidence of infection and virtual absence of adverse effects strongly suggest that cephalothin-tobramycine combination therapy is a valuable adjunct in emergency surgical procedures.

Adolescent↗
PubMed1980

Cephalothin and cefamandole penetration into bone, synovial fluid, and wound drainage fluid.

UNLABELLED: Concentrations of cephalothin or cefamandole were measured in serum, bone, synovial fluid, and wound drainage fluid in fifty-seven patients undergoing total hip or knee replacement after a two-gram intravenous bolus injection. The concentrations were similar in serum and synovial fluid for both antibiotics; however, in bone and drainage fluid the concentration of cefamandole was higher by a factor of three. Concentrations of the same antibiotic at the hip and knee were not significantly different even though a tourniquet was used for the knee replacement procedures. CLINICAL RELEVANCE: The antibiotics penetrate bone and enter synovial fluid so rapidly that it is unnecessary to administer prophylactic antibiotics prior to the time of surgery.

Body Fluids↗
PubMed1976

Phlebitis associated with the intravenous use of cephalothin and cephapirin.

The frequency and severity of phlebitis associated with cephalothin and cephapirin was compared in a double-blind study in 82 surgical patients with 149 different infusion sites. After treatment with the coded drug products, the status of each patient's veins was evaluated daily by i.v. therapists. Cephapirin was associated with a slightly lower rate of phlebitis, but the difference was not significant. For both drugs, the duration of therapy did not appear to have an effect on the rate of phlebitis. Scalp vein needles were associated with a lower rate of phlebitis than plastic catheters, but the difference was not significant.

Cephalosporins↗
PubMed1976

[Haemolytic anaemia and acute renal failure associated with cephalothin and furosemide therapy (author's transl)].

A case report is presented of a 79 year old patient with a bilateral brochopneumonia. Four days after beginning the therapy with cephalothin and furosemide an acute renal failure appeared and six days later a haemolytic anaemia was observed. The modificated Coombs test was positive. The post mortem histiological examination of the kidneys revealed cloudy swelling, necrosis of tubuli, containing protein cylinders ("chromoproteid kidney").

Acute Kidney Injury↗