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Ceforanide vs. cephalothin concentrations in total joint arthroplasty.

Total joint arthroplasty is a common orthopedic procedure and requires prophylactic antibiotic coverage to prevent infections in the operated joint. The antibiotics routinely used for prophylaxis are the cephalosporins. This study compared bone, synovial fluid, and plasma concentrations of ceforanide with cephalothin concentrations in 30 patients undergoing elective total hip or total knee arthroplasty. Ceforanide provided significantly higher plasma concentrations for 61-110 minutes postdose than did cephalothin (p less than 0.025 and p less than 0.005). No difference was noted between the two antibiotics for the bone concentrations in the total hip arthroplasty group; however, cephalothin concentrated to a greater degree in the bone of patients undergoing total knee arthroplasty (p less than 0.05). Cephalothin achieved higher concentrations in the synovial fluid than did ceforanide (p less than 0.05). Both antibiotics were well tolerated and no postoperative infections were noted in either group.

Aged↗

Use of selective media for detection of cephalothin-resistant bacteria in surgical patients.

Bacterial colonization in hospitalized patients is an important step in nosocomial infections. Frequent employment of antimicrobials can modify patients' normal microbiota, favoring colonization and infection by antimicrobial-resistant microorganisms. First-generation cephalosporins are frequently used as prophylactic antibiotics in surgery. Intestinal, oropharyngeal and skin colonization by cephalothin-resistant microorganisms were studied in 60 pre-operative patients at the Hospital Universitário Pedro Ernesto. Feces were cultured in Eosin-methylene blue medium containing 32 microg/mL of cephalothin. Swabs obtained from the oropharynx and from skin were inoculated in cistein-lactose electrolytes-deficient medium containing 32 microg/mL of cephalothin. Isolated strains were identified and tested for susceptibility to antimicrobials by disk diffusion. Cephalothin-resistant strains were isolated from the feces of 59 patients (98%), from the oropharynx of 13 patients (22%) and from skin in 10 patients (17%). Enterobacter cloacae was predominant in feces (68% of the patients) and oropharynx (13%). Acinetobacter spp. was the most frequent microorganism isolated from the skin (10%). Antimicrobial multiresistant strains were isolated from at least one of the sites in 38 patients (63%). The employment of selective medium containing antimicrobials is a relatively simple and efficient method, being useful to evaluate microorganisms from hospitalized patients' microbiota that are relevant as potential pathogens in nosocomial infections.

Anti-Bacterial Agents↗

Comparison of BL-S786 with cephalothin, cefamandole and cefoxitin in vitro and in treatment of experimental infections in mice.

The activity of BL-S786 was compared to that of cephalothin, cefamandole and cefoxitin in vitro and in treatment of experimental infections in mice. In broth dilution tests, the activity of BL-S786 was less than cephalothin or cefamandole against Staphylococcus aureus and less than cefamandole or cefoxitin against Haemophilus influenzae. BL-S786 and cefamandole were the two most active drugs against cephalothin-sensitive Enterobacteriaceae. In tests with cephalothin-resistant Enterobacteriaceae, BL-S786 was generally less active than cefamandole but more active than cefoxitin against all strains except Proteus and Providencia. Regardless of the comparative in vitro activity of the four drugs, BL-S786 was the most effective drug in treatment of mice lethally infected with Enterobacteriaceae. Protection from lethality was associated with clearance of bacteremia by each of the four drugs. In several tests where in vitro activity was not predictive of in vivo efficacy, selection of resistance in vivo was found to have occurred.

Animals↗

Evaluation of antibacterial activities of cephalosporin antibiotics: cefazolin, cephaloridine, cephalothin, and cephalexin.

The antibacterial activities of 4 cephalosporin antibiotics, cefazolin, cephaloridine, cephalothin and cephalexin, against 330 isolates of bacteria from patients at National Taiwan University Hospital, were determined by an agar plate dilution technique. Cephalosporins possess strong antibacterial activity against gram-positive bacteria except Enterococci. Staphylococcus aureus is the most susceptible among the organisms tested. More than 90% of Staphylococcus aureus strains are suppressed by cefazolin, cephaloridine and cephalothin at the concentrations of 3.13 mug/ml or less, except that 49.1% are suppressed by cephalexin. The relative potency of cephalosporins against Staphylococcus aureus in decreasing order is cephaloridine, cephalothin, cefazolin, and cephalexin. The gram-negative bacilli, Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis are less susceptible to cephalosporins than the gram-positive cocci. Among the cephalosporins, cefazolin is the most active against the gram-negative pathogens tested. The relative potency of antibacterial activity of cephalosporins against E. coli in decreasing order is cefazolin, cephaloridine, cephalexin, and cephalothin. One hour after the intramuscular injection of 500 mg of cefazolin, the maximum concentration of 33.3 mug/ml is reached in the serum. The sufficient high levels are sustained for 8 hours. Very high concentrations of cefazolin are also found in the urine.

Adult↗

Human myocardial responses to antibiotics: gentamicin, tobramycin and cephalothin.

Although myocardial toxicity of certain antibiotics has been suggested by animal studies, their effects on human cardiac muscle has not been established. Accordingly, human right atrial trabeculae contracting isometrically in vitro were exposed to increasing doses of the antibiotics gentamicin, tobramycin and cephalothin. Contractile responses were measured and dose-response curves calculated by a polynomial regression analysis. All three antibiotics demonstrated a dose-related decrease in relative developed force although resting force remained constant. Concentrations of gentamicin, tobramycin and cephalothin that caused 50% depression of developed force were 1.97, 1.92 and 52.75 mg/mL, respectively. These doses were 200, 200 and 2600 times the accepted serum toxic concentrations for gentamicin, tobramycin and cephalothin, respectively. The depression caused by cephalothin is probably related to ionic changes within the bath solution. In conclusion, gentamicin and tobramycin have myocardial toxicity at high concentrations which should not occur clinically when used judiciously.

Anti-Bacterial Agents↗

Utilization of cephalothin by Yersinia enterocolitica as sole carbon and energy source.

Two Yersinia enterocolitica strains were able to utilize the products of cephalothin degradation. The utilization of these products was shown by an increase of oxygen uptake by Y. enterocolitica with cephalothin as the only substrate, and by the growth of both strains with the hydrolysis products of cephalothin as sole energy and carbon sources. Nuclear magnetic resonance analysis of the cephalothin degradation reaction demonstrated the progressive disappearance of hydrolysis products. However, the products of benzylpenicillin degradation could not be utilized by Y. enterocolitica.

Biotransformation↗

Cephalothin prophylaxis in cardiac valve surgery. A prospective, double-blind comparison of two-day and six-day regimens.

A prospective, double-blind study comparing a 6 day with a 2 day regimen of cephalothin prophylaxis was conducted among 200 patients undergoing prosthetic valve replacement. No cases of endocarditis occurred during the 2 month follow-up. Sternal wound infection developed in 2.8 per cent of the 6 day group and 2.1 per cent of the 2 day group. Pneumonia developed in 8.5 per cent of the 6 day and 5.3 per cent of the 2 day group; most of the bacteria isolated were susceptible to cephalothin. Urinary tract infection developed more frequently in the 2 day group (17.0 versus 8.5 per cent), particularly during the first 6 postoperative days. Three of 11 patients with no detectable cephalothin in their sera at the close of operation developed staphylococcal wound infections, compared with 2 of 175 patients whose sera contained cephalothin at the close of surgery (p = 0.002, Fisher's exact test). A short course of prophylactic antibiotics is prudent, but there is no justification for prolonging their administration.

Cephalothin↗

Empiric therapy for infections in granulocytopenic cancer patients: continuous infusion of amikacin plus cephalothin.

A combination of amikacin sulfate given by continuous infusion (800 mg/sq m/24 hr) plus cephalothin sodium (2 g every four hours) was used as initial empiric therapy for the treatment of 65 evaluable febrile (greater than 38.5 degrees C) episodes in 54 granulcoytopenic (neutrophils, less than 1,000/microliter) adult cancer patients. Carbenicillin disodium (5 g every four hours) was substituted for cephalothin in patients with Pseudomonas infections and in patients in whom the initial regimen was unsuccessful. Thirty-two of the 38(84%) identifiable infections responded to therapy, including all of the eight septicemias and eight of 11 pneumonias. Three additional infections responded to the substitution of carbenicillin for cephalothin, for a total response rate of 92% (35/38). Nephrotoxicity occurred in five patients (7.1%), most commonly in patients over 60 years of age. Ototoxicity, highly correlated with a duration of greater than 19 days and a total dosage of greater than 25 g of amikacin sulfate, occurred in four patients (5.6%). Amikacin given by continuous infusion plus cephalothin is a safe and efficacious empiric therapy for infections in granulocytopenic cancer patients.

Acute Disease↗

Cephalothin. Its in vitro antibacterial spectrum as studied in a diagnostic laboratory.

Of 655 bacterial strains isolated in a routine clinical diagnostic laboratory, 564 (86 per cent) were found sensitive to cephalothin by disk sensitivity test. However, the fraction of sensitive Gram-negative bacilli and enterococci declined sharply at concentrations approximating those obtained in serum after the usual recommended dosages. Gram-positive bacteria remained sensitive throughout the entire range of testing concentrations. Unless very high dosages are used, cephalothin cannot be considered a broad-spectrum antibacterial agent for use while cultures are pending. Even with very high dosages all strains of Pseudomonas spp. and significant fractions of other Gram-negative bacillary species remain resistant to cephalothin. If used alone, the high potency cephalothin disk may yield inadequate information and should be supplemented by a lower potency disk, standardized measurements of zone diameters, or a screening plate.

Cephalothin↗

Liposome-encapsulated cephalothin in the treatment of experimental murine salmonellosis.

The effectiveness of liposome-encapsulated cephalothin was compared with free cephalothin for the treatment of mice experimentally infected with Salmonella typhimurium. Compared with free cephalothin, following intravenous administration, liposome-encapsulated cephalothin was cleared from the circulation more rapidly and concentrated in the liver and spleen. Treatment of infected mice with the liposome antibiotic complex was more efficacious in terms of reducing the number of S. typhimurium in these organs as compared with the free antibiotic. The results suggest that liposome-encapsulated antimicrobial agents may possess a therapeutic advantage in the treatment of diseases caused by facultative intracellular bacteria since this manipulation favors delivery of the entrapped antibiotic to intracellular sites occupied by S. typhimurium.

Animals↗

Acute renal failure after cis-dichlorodiammineplatinum(II) and gentamicin-cephalothin therapies.

Combined gentamicin-cephalothin therapy in four patients after treatment with cis-dichlorodiammineplatinum(II) (CPDD) for advanced solid tumors was complicated by severe acute renal failure. The total dose of gentamicin varied from 240 to 945 mg and that of cephalothin varied from 28 to 48 g. Low-dose (0.5 mg/kg x 8) CPDD was given to one patient, high-dose (3 mg/kg) CPDD was given to two patients, and very high-dose (5 mg/kg) CPDD was given to one patient. The high and very high doses of CPDD were given with concomitant mannitol diuresis. CPDD therapy was complicated by mild transient azotemia in three patients and by severe acute renal failure in one. In the latter, the azotemia began to improve on Day 7 after CPDD treatment. Following gentamicin-cephalothin therapy, all patients developed severe acute renal failure which persisted until death. At autopsy, all patients had extensive renal tubular necrosis at various stages. These findings indicate that gentamicin-cephalothin therapy after treatment with CPDD can be severely nephrotoxic, and that this antibiotic combination should be given with great caution, if at all, to patients receiving CPDD treatment for malignancy.

Acute Kidney Injury↗

[Experimental studies on the passage of antibiotics into cerebrospinal fluid in staphylococcal meningitis in rabbits. II. Cephaloridine, cephalothin and cefazolin (author's transl)].

Passage of cephaloridine, cephalothin and cefazolin into cerebrospinal fluid (CSF) was evaluated in Staphylococcus aureus meningitis in rabbits and the following results were obtained. 1. Concentration in CSF (microgram/ml) [CSF/serum ratio (%)] was determined 1/2, 1 and 2 hours after a single intravenous injection of 100 mg/kg of each antibiotic, respectively; cephaloridine-7.5 [8.9], 9.7 [13.8], 9.1 [22.6]; cephalothin-0.42 [3.6], 0.23 [6.4], not detectable [0]; cefazolin-7.5 [11.8], 5.2 [19.3], 2.0 [17.5]. 2. When results with cefazolin after an intravenous injection 100 mg/kg and 200 mg/kg were compared, a definite dose response was noted in blood concentration but not in CSF concentration. 3. A standard error of CSF concentrations of each antibiotic was larger than that of penicillins, and "Unpredictability" of their passage into CSF was considered to be one of the characteristics common to these three drugs in respect of their passage into CSF. 4. There was no significant difference noted in antibiotic passage into CSF between cephaloridine of low protein binding rate and cefazolin of very high binding rate. Cephalothin, of which binding rate was intermediate, showed a remarkably lower passage into CSF. These results indicate that a correlation does not always exist between protein binding rate of the antibiotics and their passage into CSF. 5. Based on the above results, a review of the literature was made on clinical applicability of these three antibiotics in the treatment of bacterial meningitis. Low transport rate of cephalothin into CSF and nephrotoxicity of cephaloridine make them to be unsuitable for bacterial meningitis. Cefazolin is considered to be suitable in the treatment of ampicillin-resistant Escherichia coli meningitis and Gram-positive coccal meningitis in which penicillins are not applicable.

Animals↗

Pharmacokinetics of cephalothin and cephalexin in selected avian species.

Plasma concentrations and the biological half-lives of cephalothin and cephalexin in avian species of a variety of body sizes and metabolic rates were studied. The species chosen were eastern bobwhite quail (Colinus v virginianus), pigeons (Columba livia), hybrid rosybill ducks (Netta sp), greater sandhill cranes (Grus canadensis tabida), and emus (Dromiceius novaehollandiae). In the 1st phase of the study, cephalothin sodium was given IM in a dose of 100 mg/kg of body weight. Plasma concentrations reached peak (av 18 micrograms/ml) at 0.5 hour and were measurable 2.5 to 5.5 hours after drug administration. The biological half-life of cephalothin was 16 to 54 minutes; the half-life varied directly with increased species body weight, with the exception of the ducks studied. In the 2nd phase, cephalexin monohydrate was given orally in doses of 25, 35, and 50 mg/kg of body weight. Plasma concentrations reached peak (av 20 micrograms/ml) at 0.5 to 1 hour and were measurable 2.5 to 5.5 hours after drug administration. The biological half-life of cephalexin was 36 to 126 minutes. In the 3rd phase, differences in plasma concentrations and the half-lives of cephalexin between fed quail and fasted quail were insignificant. Dosage regimens for cephalothin of 100 mg/kg 4 times a day and for cephalexin of 35 to 50 mg/kg 4 times a day would be expected to establish and maintain therapeutic plasma concentrations in large birds (pigeons, cranes, and emus). These same doses, administered every 2 to 3 hours, would be expected to establish and maintain therapeutic plasma concentrations in smaller birds (quail, ducks).

Animals↗

Double-blind comparison of phlebitis associated with cefazolin and cephalothin.

In a double-blind, crossover study in 28 patients having infections susceptible to cephalosporins (mostly Staphylococcus or Streptococcus), phlebitis developed in twice as many patients (46.4%) receiving intravenous cephalothin within 48 hours, as in patients (21.4%) receiving intravenous cefazolin over the same time period. Likewise, drug therapy had to be discontinued more frequently with cephalothin (39%) than with cefazolin (21%), and the percentage of patients reporting pain or discomfort scores of 1+ or higher was greater with cephalothin (46.4%) than with cefazolin (21.4%). In our study, the intravenous administration of cefazolin was associated with a lower incidence of phlebitis than was cephalothin.

Adult↗

Cephalothin kinetics: before, during, and after cardiopulmonary bypass surgery.

Cephalothin kinetics was studied in 5 patients the day before (PREOP), during (SURG), and the day after (POSTOP) cardiopulmonary bypass surgery. The PREOP (114 ml/min) and SURG (94 ml/min) renal clearances were of the same order but both were less than POSTOP renal clearance (248 ml/min). Cephalothin total body clearance during operation was lower (p less than 0.01) than PREOP or POSTOP clearance, with decreased metabolic clearance the primary cause. There was reduction in cephalothin elimination throughout the surgical procedure, not only in the period of extracorporeal circulation, indicating that general anesthesia had a significant influence on drug disposition. The metabolite deacetylcephalothin was rapidly formed on all 3 days and its kinetic behavior paralleled that of the parent drug.

Adult↗

Quantitation of carbenicillin disodium, cefazolin sodium, cephalothin sodium, nafcillin sodium, and ticarcillin disodium by high-pressure liquid chromatography.

High-pressure liquid chromatographic (HPLC) methods for the quantitation of carbenicillin, cefazolin, cephalothin, nafcillin, and ticarcillin were developed. The stability of 2% solutions of the antibiotics in normal saline and in 5% dextrose in water were studied at 24 and 5 degrees. The assays were conducted using a previously reported colorimetric method, and some assays also were performed using HPLC. For discolored solutions of cephalothin, the colorimetric method was not stability indicating. The percent relative standard deviations by HPLC based on six injections were 1.69, 0.94, 1.30, 1.59, and 1.6 for carbenicillin, cefazolin, cephalothin, nafcillin, and ticarcillin, respectively. Both carbenicillin and ticarcillin apparently may be mixtures of two isomers at equilibrium with each other. The shelflives recommended by the manufacturers at 5 degrees may be too conservative.

Carbenicillin↗

Zero-crossing derivative spectrophotometry for the determination of mixtures of cephaloridine and cephalothin in pure and dosage forms.

First- and second-derivative spectrophotometry, with a zero-crossing technique of measurement, has been used for the quantitation of two-component mixtures of cephaloridine and cephalothin Na, which are cephalosporins with closely overlapping spectral bands. Beer's Law is followed for up to 28 and 36 micrograms/mL of cephaloridine in the first- and second-derivative modes, respectively, and up to 36 micrograms/mL of cephalothin Na in both modes. Detection limits at the 0.05 level of significance were calculated to be 0.13 and 0.37 micrograms/mL of cephaloridine and cephalothin Na, respectively, in the first-derivative mode, and 0.25 and 0.29 micrograms/mL, respectively, in the second-derivative mode. The recovery of these antibiotics in mixtures of injectable dosage forms is also reported.

Cephaloridine↗

Amdinocillin pharmacokinetics. Simultaneous administration with cephalothin and cerebrospinal fluid penetration.

In the treatment of serious infections, combinations of beta-lactam antibiotics are being utilized in order to avoid aminoglycoside toxicity and to achieve antibacterial synergy. The pharmacokinetic disposition of amdinocillin and cephalothin was determined, when administered alone or in combination to healthy volunteers, as well as the penetration of amdinocillin into human cerebrospinal fluid. Six subjects received, on separate occasions, single intravenous doses of amdinocillin 10 mg/kg, cephalothin 15 mg/kg, or a combination of the two in the same doses. The elimination half-lives of amdinocillin and cephalothin are increased when these drugs are given simultaneously, compared with when they are administered alone. However, no significant differences were observed. When they were given in combination, no significant changes in plasma clearance, renal clearance, or steady-state volume of distribution were found. Eight patients undergoing lumbar puncture for various neurologic disorders without inflamed meninges received a single dose of 10 mg/kg amdinocillin intravenously. One to two hours later, simultaneous plasma and cerebrospinal fluid samples were obtained. The concentration of amdinocillin in the cerebrospinal fluid ranged from approximately 1 to 10 percent of concomitant plasma concentrations. Thus, amdinocillin penetrates in the cerebrospinal fluid in marginal amounts in the absence of meningeal inflammation.

Adult↗