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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↗
PubMed1999

Transferability of cephalothin to the alveolar cavity in thoroughbreds.

Five Thoroughbreds were classified into 4 groups according to the administration method used for saline solution (saline), ambroxol, and cephalothin sodium (cephalothin). In group A, cephalothin was injected intravenously after oral administration of ambroxol. In group B, cephalothin was injected intravenously after oral administration of saline. Groups C and D were used as control groups. The dose of cephalothin or ambroxol was clinically administrated. Venous blood and bronchoalveolar lavage fluid (BALF) were sampled from each group. In groups A and B, cephalothin concentrations in plasma reached their maximum level 5 min after cephalothin administration and then declined over time. In plasma obtained from groups A and B, there were no significant differences in pharmacokinetic parameters (T1/2, Kel, Vd). By contrast, cephalothin concentrations in BALF reached their peak at 180 min after cephalothin administration in both groups A and B and maintained a relatively high level even after 300 min. These findings indicate that cephalothin requires a relatively long period of time to move from the blood stream to the alveolar cavity, but once transferred to the alveolar cavity, it is preserved for a long time. In groups A and B, cephalothin concentrations in BALF were approximately at the same level. However, in group A, total protein in BALF was lower at 60, 180, and 300 min than the other groups. Then, cephalothin concentration was adjusted to total protein in BALF. After adjustment to total protein in BALF, group A showed a concentration level of cephalothin approximately 1.5-fold higher than that of group B. This suggests that the transferability of cephalothin to the alveolar cavity improves as a result of the oral administration of ambroxol.

Ambroxol↗
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↗
PubMed1999

Clinical outcome of cephalothin versus vancomycin therapy in the treatment of coagulase-negative staphylococcal septicemia in neonates: relation to methicillin resistance and mec A gene carriage of blood isolates.

OBJECTIVE: Coagulase-negative staphylococci (CONS) are the most common causative agents in neonatal nosocomial septicemia. Because of widespread methicillin resistance among CONS, empiric therapy with vancomycin is recommended as the primary antibiotic regimen for these infections. In our unit, empiric treatment of nosocomially acquired septicemia consists of cephalothin and gentamicin, which are adjusted subsequently according to the determined bacterial susceptibility profile. Vancomycin is initiated only when the patient has been treated recently with cephalothin or when intravascular lines or endotracheal tube are colonized with oxacillin/cephalothin-resistant CONS strains. The aim of the present study was to evaluate the efficacy of our antibiotic regimen for CONS septicemia, in relation to methicillin-resistance and the carriage of mec A gene, encoding methicillin resistance, among CONS blood isolates from our unit. METHODS: Clinical symptoms of septicemia, clinical outcome, and laboratory parameters of septicemia (C-reactive protein) were studied retrospectively in 66 patients with CONS septicemia. The diagnosis of septicemia was made by the attending neonatologist and was defined by clinical symptoms of septicemia in the presence of a positive finding of a blood culture test, which was performed using a defined protocol. All CONS blood isolates were included to determine mec A gene carriage. RESULTS: In the 66 patients, three treatment categories were distinguished: treatment with cephalothin (25 patients, 38%); with vancomycin (15 patients, 23%); and primary treatment with cephalothin, switched subsequently to vancomycin (26 patients, 39%). It was found that 92% of all CONS blood isolates (61/66) were mec A-positive. Concordance of mec A gene carriage with methicillin/oxacillin resistance was found in 56 of 66 isolates (85%); 10 of 61 (16%) isolates that were mec A-positive were determined as oxacillin-susceptible. Although 22 of the 25 blood isolates of the cephalothin-treated patients were mec A-positive, clinical recovery was uneventful. In the 26 patients in whom antibiotic therapy was switched from cephalothin to vancomycin, two strains were cephalothin-susceptible and 8 patients already had recovered clinically before the switch, which was based solely on susceptibility test results. CONCLUSIONS: Cephalothin was found to be clinically efficacious in the treatment of neonatal CONS septicemia, despite a steadily increasing mec A gene carriage of CONS blood isolates in our neonatal intensive care unit and a corresponding high methicillin/oxacillin resistance. Hence, cephalothin remained the antibiotic of first choice in the treatment of CONS septicemia in our unit, with vancomycin selected exclusively for cases not responding to initial cephalothin treatment, or for patients developing CONS septicemia during or after recent cephalothin treatment. By applying this approach in our unit, we were able to reduce vancomycin use from 62% in 1994 to 1995 to 21% in 1997. This shows that such a policy may result in an important reduction of vancomycin use, which may aid in postponing the threatening emergence of vancomycin resistance among Gram-positive cocci.

Anti-Bacterial Agents↗
PubMed1980

Application of cephalosporins to obstetrics and gynecology: transfer of cefazolin and cephalothin to uterine tissue.

Antibiotics should be administered so as to maintain effective therapeutic levels in target organs. In routine clinical treatment, however, doses of antibiotics are determined on the basis of their achievable concentrations in blood. To determine the optimum doses of antibiotics against obstetric and gynecologic infections, the authors gave a single intravenous dose of 2 gm of cefazolin or cephalothin to 51 patients before hysterectomy and measured the levels of the antibiotics in uterine tissues and compared them with corresponding serum levels. The maximum tissue levels of cefazolin were generally about 6 to 7 times higher than those of cephalothin: In tthe perimetrium, levels were 154 microgram/gm for cefazolin and 24.1 microgram/gm for cephalothin; in the myometrium, 109.5 microgram/gm for cefazolin, and 15.5 microgram/gm for cephalothin; and in the endometrium, 98.9 microgram/gm for cefazolin and 10.4 microgram/gm for cephalothin. In the tissues, however, cephalothin reached peak levels more rapidly than cefazolin. Comparisons of the tissue levels and MIC of cefazolin and cephalothin revealed that cefazolin was maintained at over 12.5 microgram/gm for at least 150 minutes in the perimetrium, myometrium, and endometrium, whereas cephalothin was maintained at these levels for 40 to 50 minutes only in the perimetrium and myometrium. The ratio of tissue levels to serum levels was 40-70 to 100 for cefazolin and about 30 or less to 100 for cephalothin.

Adult↗
PubMed2001

Another look at differences in the susceptibility of Escherichia coli and Klebsiella pneumoniae to cephalothin and cefazolin.

The significance of in vitro susceptibility tests on Enterobacteriaceae to cephalothin and cefazolin has not been exactly defined in the guidelines of the National Committee for Clinical Laboratory Standards. In the hope of clarifying this confusion, we provide additional information from an ancillary study of the Taiwan Surveillance of Antimicrobial Resistance 1998 (TSAR I). There were 505 Escherichia coli and 227 Klebsiella pneumoniae isolates susceptible to cephalothin, reported by 42 participating hospitals. The susceptibility of these isolates were re-tested at the Microbial Infections Reference Laboratory using cefazolin, with the result that 72% of the 252 cephalothin-resistant E. coli isolates and 24% of the 41 cephalothin-resistant K. pneumoniae isolates were found to be susceptible to cefazolin. We further surveyed the availability of cephalothin and cefazolin in Pharmacy Departments; all of the TSAR I hospitals had cefazolin available in their pharmacies. The resistance rate of E. coli was significantly lower for 12 hospitals that had cefazolin in both pharmacy and laboratory compared with 11 hospitals that had cefazolin available in pharmacy but cephalothin in laboratory. In addition, for all the hospitals that had cephalothin available for clinical use, the resistance rate was twice as low in two hospitals reporting cefazolin susceptibility as in the seven hospitals reporting cephalothin susceptibility. Our findings suggest that inappropriate selection of cephalothin and cefazolin for susceptibility testing contribute to inaccurate indications of in vivo activity for first generation cephalosporins in the treatment of E. coli infections.

Cefazolin↗
PubMed1985

Pharmacokinetics and bioavailability of cephalothin in horse mares.

The pharmacokinetics and bioavailability of cephalothin given to 6 horse mares at a dosage level of 11 mg/kg of body weight IV or IM were investigated. The disposition of cephalothin given IV was characterized by a rapid disposition phase with a mean half-life of 2.89 minutes and a subsequent slower elimination phase with a mean half-life of only 14.7 minutes. The mean residence time of cephalothin was 10.6 +/- 2.11 minutes. The total plasma clearance of cephalothin averaged 13.6 ml/min/kg and was caused by metabolism and renal elimination. Renal clearance of cephalothin averaged 1.32 ml/min/kg and accounted for elimination of about 10.1% of the administered dose. The volume of distribution at steady state averaged 151 mg/kg. Plasma protein binding of cephalothin at a concentration of 10 micrograms/ml averaged 17.9 +/- 2.5%. Cephalothin was rapidly metabolized to desacetylcephalothin. Maximum plasma desacetylcephalothin concentrations were observed in the blood samples collected 5 minutes after IV doses and averaged 22.9 micrograms/ml. The apparent half-life of desacetylcephalothin in plasma was 41.6 minutes and its renal clearance averaged 4.49 +/- 2.43 ml/min/kg. An average of 33.9% of the dose was recovered in the urine as desacetylcephalothin. The maximum plasma cephalothin concentration after IM administration was 11.3 +/- 3.71 micrograms/ml. The terminal half-life was 47.0 minutes and was longer than the half-life after IV administration. The bioavailability of cephalothin given IM ranged from 38.3% to 93.1% and averaged 65.0 +/- 20.5%.

Animals↗