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PubMed1976

Clinical pharmacology of cefamandole as compared with cephalothin.

We compared the pharmacology of cefamandole and cephalothin in six healthy adult male volunteers. After a 1-g, 20-min intravenous (i.v.) infusion, the average peak blood level of cefamandole was 87.6 versus 64.1 mug/ml for cephalothin. An i.v. infusion of 500 mg/h for 2 h (after a loading dose of 750 mg) gave an average steady-state blood level of 28.5 mug/ml for cefamandole and 18.2 mug/ml for cephalothin. Mean peak serum levels after 1 g intramuscularly were similar for the two antibiotics (about 21 mug/ml), but with cefamandole they persisted longer, and the area under the blood level curve was about 25% greater. The average t((1/2)) as determined from both i.v. studies was 34 min for cefamandole versus 30 min for cephalothin. The mean serum clearance for cephalothin, due to its partial conversion to a metabolite, was much greater than for cefamandole (425 versus 272 ml/min per 1.73 m(2)), but the renal clearances were similar for the two antibiotics (268 versus 257 ml/min per 1.73 m(2)). Other values for cefamandole and cephalothin were: 24-h urinary excretion, 80 and 66%; serum protein binding, 74 and 70%; and apparent volume of distribution, 12.8 and 18.5 liters/1.73 m(2), respectively. Thus, the pharmacology of the two antibiotics was similar. Blood levels were somewhat higher with cefamandole i.v., but the results suggest that dosage regimens should be the same for the two antibiotics.

Adult↗
PubMed1963

IN VITRO BIOLOGICAL ACTIVITY OF CEPHALOTHIN.

Chang, Te-Wen (Tufts University School of Medicine, Boston, Mass.) and Louis Weinstein. In vitro biological activity of cephalothin. J. Bacteriol. 85:1022-1027. 1963.-Cephalothin is a "broad-spectrum" antibiotic active, in low concentrations, against Diplococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus. Shigella, Salmonella, and Proteus mirabilis were the most sensitive of the gram-negative organisms. Escherichia coli and Aerobacter aerogenes were suppressed to a lesser degree, whereas Pseudomonas aeruginosa and Herellea were highly resistant. Penicillin-sensitive and -resistant strains of S. aureus were equally susceptible to cephalothin. Exposure to increasing concentrations of the drug very frequently led to the development of resistance in gram-negative organisms; this was observed less often with S. aureus. Cephalothin stimulated the production of penicillinase by staphylococci, which remained sensitive to the cephalosporanic acid derivatives despite repeated subculture in increasing concentrations of the agent. Cephalothin was not inhibited by penicillinase. This antibiotic was more toxic to cultures of human amnion and mouse embryo cells than benzyl penicillin G but was less injurious than oxytetracycline, chlortetracycline, and demethylchlortetracycline; tetracylcine produced about the same degree of cellular damage as cephalothin.

Acinetobacter↗
PubMed1980

IgE antibodies produced in mice instrumental in analyses of antigenicity of cephalothin preparation.

IgE antibodies to a cephalothin preparation were produced in mice which had been immunized with cephalothin-Ascaris extract conjugate mixed with Al(OH)3 gel plus Bordetella pertussis. Mice which had been irradiated just before receiving the booster injection wtih the conjugate showed higher IgE antibody levels against the preparation in comparison with unirradiated mice. The specificities of IgE antibodies against the preparation were examined with an inhibition test of passive cutaneous anaphylactic (PCA) reaction. The intensity of the PCA reaction evoked by the cephalothin preparation in the rats was substantially or partially reduced by a pretreatment of the animals with an injection of a cephalothin preparation from another source or a cephaloridine preparation. Meanwhile, a prior injection of a cefazolin, a 7-aminocephalosporanic acid, a benzylpenicillin (PcG) preparation, or an aminobenzylpenicillin preparation into the animals showed only weak or no influence on the PCA reaction. These results suggest that the acyl side chain of cephalothin plays an important role as eliciting antigenic determinant in the PCA reaction. The difference in the antigenic specificity between the cephalothin and PcG preparation is also discussed.

Animals↗
PubMedDate not supplied

Comparative efficacy and tolerance of cefamandole and cephalothin as prophylaxis for open heart surgery: a randomized double-blind study.

Cephalothin, a common used agent for antimicrobial prophylaxis, was compared with cefamandole, a second generation semi-synthetic cephalosporin having a somewhat broader antimicrobial spectrum, in a randomized, double-blind clinical trial of 201 patients undergoing elective open heart surgery. Cephalothin was administered to 101 patients and 100 received cefamandole. The protocol was not followed in 23 patients, 11 of whom received cephalothin and 12 cefamandole. Of 90 patients who could be evaluated for efficacy of cephalothin, two developed superficial wound infections and one developed an asymptomatic urinary tract infection. Five of 88 patients who received cefamandole developed infections; urinary tract infections in two, mediastinitis in one, a superficial wound infection in one, and pneumonia in one after prolonged endotracheal ventilation. Both were well tolerated with no adverse reactions attributed to either antibiotic. Cephalothin and cefamandole appear to provide similar efficacy and patient tolerance in open heart surgery; however, the drug regimen for cefamandole cost $83, whereas it was $58 for cephalothin.

Adult↗
PubMed1980

Phlebitis associated with the intravenous use of cephapirin and cephalothin in the combination therapy of antibiotics.

Phlebitis related to antibiotic infusion is one of the most frequent causes of morbidity in the debilitated patients with severe infection. There are a number of causes of infusion-induced phlebitis such as pH of intravenous fluid, needle used, and contamination of venipuncture site. Vein used to play an important role, particularly in patients with granulocytopenia receiving intravenous infusion. Cephalothin is an effective antibiotic in the treatment of granulocytopenic infection and is widely used currently. When cephalothin was introduced commercially, the frequency of phlebitis was as high as 50%. The main reason was thought to be acidity of the antibiotic solution. The cephalothin solution used currently is neutral in pH, but prevention of phlebitis is still not perfect. In contrast, cephapirin recently developed cephalosporin antibiotic, which resembles cephalothin in the antimicrobial activity and pharmacological properties caused less phlebitis than cephalothin in initial clinical studies. The patients receiving chemotherapy for malignant diseases frequently die of infections. A cephalosporin antibiotic is administered intravenously for a prolonged time in the presence of thrombocytopenia, and under such circumstances, other antibiotics such as carbenicillin (CBPC) and aminoglycoside are usually used in combination. The influence of these antibiotics injected through the same vein must be considered, but the possibility of phlebitis due to CBPC and aminoglycoside is negligible. In the present clinical study, 24 granulocytopenic patients were treated with the combination of antibiotics, cephapirin-carbenicillin-amikacin and cephalothin-carbenicillin-amikacin. Besides the clinical effect of the antibiotics, the incidence and severity of phlebitis were studied.

Agranulocytosis↗
PubMed1970

Relationship Between beta-Lactamase Activity and Resistance of Enterobacter to Cephalothin.

The relationship between cephalosporin beta-lactamase activity and resistance to cephalothin was investigated in strains of Enterobacter cloacae and E. aerogenes. beta-Lactamase activity was detected in all strains, but a quantitative correlation between amount of beta-lactamase activity and level of resistance to cephalothin was not observed. Permeability barriers to cephalothin were observed and varied from strain to strain. beta-Lactamase activity was increased by growing organisms in the presence of penicillin G. These enzymes hydrolyzed cephalosporins more rapidly than penicillins. Penicillinase-resistant penicillins, especially those of the isoxazolyl series, effectively inhibited Enterobacter beta-lactamase. A synergistic antibacterial effect was observed when organisms were exposed to cephalothin and oxacillin in combination, and the resistance of even very small inocula to cephalothin was reduced by addition of oxacillin. Oxacillin probably exerts its effect by inhibiting beta-lactamase at an intracellular site. Intracellular beta-lactamase may make an important contribution to the resistance of even small inocula of gram-negative bacilli to cephalosporin and penicillin antibiotics. Although beta-lactamase plays a significant role in the resistance of Enterobacter to cephalothin, other factors, such as permeability barriers, also participate in determining the level of resistance.

Journal Article↗
PubMed1977

A trial of cephalothin sodium in colon surgery to prevent wound infection.

A double-blind trial of preoperative and perioperative cephalothin sodium in patients undergoing colonic surgery was carried out to test the value of this drug in reducing wound infection rates. Two studies were performed. In the first trial, 1 gm of cephalothin sodium or a placebo was given intravenously at the beginning of operation, and 1 gm one hour later. In the second trial, the dose of cephalothin or placebo was increased to 2 gm. There was no significant reduction in wound infections in either study in the groups receiving cephalothin, although over two thirds of the organisms cultured from the infected wounds were sensitive to cephalothin. It is suggested that meticulous attention to technique to avoid gross contamination remains the most important factor in the prevention of wound infections after colon surgery.

Cephalothin↗
PubMedDate not supplied

Pharmacokinetics of amikacin and cephalothin in bedridden elderly patients.

The pharmacokinetics of amikacin (5.5 mg/kg intramuscularly) and cephalothin (1000 mg/body intravenously) in bedridden elderly patients were studied in comparison with those in healthy volunteers. The eliminations of amikacin and cephalothin from the plasma followed the course of a one-compartment open model. For amikacin, five healthy volunteers, elimination rate constant Kel was 0.396 hr-1, biologic half-life t1/2 was 1.80 hour, volume of distribution Vd was 0.201 l./kg; in five bedridden elderly patients, Kel was 0.208 hr-1, t1/2 was 3.55 hours, Vd was 0.376 l./kg. Cumulative renal excretion of amikacin in 8 hours was 44 per cent of the total dose in bedridden elderly patients and 69 per cent in healthy volunteers. For cephalothin, in seven healthy volunteers, Kel was 0.0353 min-1, t1/2 was 19.7 min, Vd was 0.176 l./kg; in four bedridden elderly patients, Kel was 0.0127 min-1, t1/2 was 56.4 min, Vd was 0.283 l./kg. Cumulative renal excretion of cephalothin reached a plateau by 4 hours of 40.8 per cent of the total dose in bedridden elderly patients and of 56.7 per cent in healthy volunteers. These results suggest that in bedridden elderly patients decreased renal excretion of amikacin and cephalothin is related to decreased renal function and an increased Vd.

Adult↗
PubMed1990

Antibiotic prophylaxis in lower-extremity amputations due to ischemia. A prospective, randomized trial of cephalothin versus methicillin.

The efficiency of prophylactic antibiotic therapy in amputation surgery was studied in a prospective, randomized trial of a first-generation cephalosporin (cephalothin) compared with a narrow-spectrum beta-lactam stable penicillin (methicillin). Eighty-eight patients received cephalothin 2 g X 4 on the day of operation, while 86 patients received methicillin 1 g X 4. The patients were followed up for 21 days. Infected wounds occurred in 14.8% of the patients in the cephalothin group, compared with 14% in the methicillin group. The frequency of deep infections was 10.2% versus 4.7% (P = 0.1611). The reamputation frequency was 18.2% in the cephalothin group compared with 12.8% in the methicillin group; the frequency of below-knee reamputation was 18.4% versus 7.7% (P = 0.1469). No clostridial infections were found. The study did not demonstrate any significant difference between cephalothin and methicillin in the prophylaxis for lower-extremity amputations, although the latter drug tended to be the best choice.

Adult↗
PubMed1978

Cephalothin plus an aminoglycoside is more nephrotoxic than methicillin plus an aminoglycoside.

In a prospective, randomised, double-blind trial to determine if cephalothin plus an aminoglycoside is more nephrotoxic than methicillin plus an aminoglycoside, patients were assigned to one of four treatment groups: cephalothin and gentamicin (C.G.), cephalothin and tobramycin (C.T.), methicillin and gentamicin (M.G.), or methicillin and tobramycin (M.T.). The incidence of definite nephrotoxicity was: C.G., 7/23 (30.4%); C.T., 5/24 (20.8%); M.G., 2/20 (10%); and M.T., 1/23 (4.3%). There was no statistically significant difference in nephrotoxicity between the combined gentamicin groups (C.G. and M.G.) and the combined tobramycin groups (C.T. and M.T.). Definite nephrotoxicity developed in 12/47 (25.5%) of the combined cephalothin groups (C.G. and C.T.) and in only 3/43 (7%) of the combined methicilllin groups (M.G. and M.T.). The combination of cephalothin plus an aminoglycoside is therefore more nephrotoxic than the combination of methicillin plus an aminoglycoside.

Acute Kidney Injury↗
PubMed1978

Reassessment of the "class" concept of disk susceptibility testing. Cephalothin disks versus minimal inhibitory concentrations with eleven cephalosporins.

Reassessment of the "class" concept of disk susceptibility testing. Cephalothin disks versus minimal inhibitory concentrations with eleven cephalosporins. Am J Clin Pathol 70: 909--913, 1978. Studies were carried out to determine whether susceptibility or resistance to 11 cephalosporins could be predicted reliably from the results of tests with a single cephalothin disk. The cephalosporins were tested with a microdilution technic and with a standardized disk test. Strains susceptible to a cephalothin disk were predictably susceptible to all other cephalosporins. However, 2--12% of the strains were resistant to cephalothin disks but were susceptible to the more active parenteral drugs cefoxitin, cephamandole, cefuroxime, and BL-S786. Because of differences in antimicrobial activities, the cephalosporins could be divided into three subgroups for purposes of susceptibility testing: one subgroup includes the majority of cephalosporins and may be represented by tests with cephalothin, the second subgroup inclues three active parenteral drugs (cephamandole, cefuroxime, and BL-S786) and may be represented by tests with cefuroxime, and the third subgroup consists of cefoxitin, a cephamycin with a unique broad spectrum of activity. Until the drugs in the second and third subgroups are released for general therapeutic use, the practice of testing only one cephalosporin disk appears to be a reasonably reliable procedure.

Bacteria↗
PubMed1985

Reliability of cefaclor, cefazolin, cefamandole, and cephalothin disks to predict susceptibility of Enterobacteriaceae, Staphylococcus species, and Haemophilus influenzae.

Interpretive zone-size standards currently used for cephalothin and cefamandole disk tests also may be applied to tests with disks containing 30 micrograms of cefaclor or cefazolin. Against 627 representative isolates, susceptibility to cefaclor and cefazolin could be predicted by testing cephalothin. However, cefazolin is more active than cephalothin against isolates of Escherichia coli with a TEM beta-lactamase plasmid. The expanded spectrum of cefamandole continues to necessitate separate testing. Against methicillin-resistant staphylococci, cefaclor disks were more reliable than cephalothin or cefamandole, but false-susceptible results were seen with all four disks. For testing Haemophilus influenzae, the cefazolin disks were not reliable; cephalothin or cefaclor disks could predict susceptibility to either drug.

Cefaclor↗
PubMed1976

Induction of resistance in Staphylococcus aureus and Klebsiella pneumoniae by exposure to cephalothin and cefoxitin.

Six strains each of Staphylococcus aureus and Klebsiella pneumoniae were exposed to subinhibitory, but serially incremental, concentrations of cephalothin and cefoxitin in a totally defined liquid culture medium. After exposure to cephalothin, the level of resistance to both drugs increased; the gain was greater against cephalothin and among the strains of K. pneumoniae. After exposure to cefoxitin, resistance to both drugs developed; this resistance was greater against cefoxitin and among the strains of K. pneumoniae. Acquired resistance was not lost after serial subculture in drug-free medium. Qualitative tests revealed no cephalosporinase activity in the resistant straphylococci and in four of the strains of K. pneumoniae. Two strains of K. pneumoniae, which had been isolated from a patient before and after failure of treatment with cephalothin, respectively, had no demonstrable cephalosporinase activity as isolated but developed activity after exposure to cephalothin in vitro.

Cefoxitin↗
PubMed1987

Cephalothin clearance of Staphylococcus aureus from two experimental infection sites in the presence and absence of local phagocytic cells.

The clearance of Staphylococcus aureus from perforated peritoneal capsules which are accessible to phagocytic cells, and subcutaneous Visking chambers which exclude phagocytes, was studied simultaneously in eight rabbits implanted with both devices. Animals were treated with cephalothin, 100 mg/kg im every 8 h for sixteen doses, beginning 24 h after inoculation of the infection sites with S. aureus (cephalothin MIC 0.125 mg/l, MBC 0.5 mg/l). At the start of cephalothin, subcutaneous chambers contained a higher concentration of S. aureus (8.4 log10 cfu/ml) than peritoneal capsules (6.8 log10 cfu/ml, P less than 0.001). There was a significant bactericidal effect in subcutaneous chambers on both the third and sixth day of treatment (P less than 0.002), whereas in peritoneal capsules this did not occur until day six. The total reduction in bacterial count in subcutaneous chambers (7.0 log10 cfu/ml) was significantly greater than in capsules (4.4 log10 cfu/ml, P less than 0.002). The mean concentration of cephalothin in subcutaneous chambers (10.7 mg/l) was significantly higher than in peritoneal capsules (6.1 mg/l, P less than 0.02), but no difference in in-vitro killing of S. aureus was detected at these concentrations. We conclude that cephalothin clearance of S. aureus from a site accessible to phagocytes was delayed when compared to a phagocyte-inaccessible site.

Animals↗
PubMed1982

Chemoprophylaxis in cardiac and orthopedic surgery: comparison of cephalothin and cephapirin.

In a retrospective sequential study we determined the rate of infection occurring despite cephalothin or cephapirin chemoprophylaxis in orthopedic and cardiac surgery done from 1973 to 1977. The incidence of infection after prosthetic hip placement or open reduction of hip fracture was 3.4% and 1.0% in patients receiving cephalothin or cephapirin, respectively. The infection rate after prosthetic heart valve implantation was 3.5% in those receiving cephalothin and 1.6% in those receiving cephapirin. There was no significant difference in infection rate, duration of fever greater than or equal to 38.0 C, or length of postoperative hospitalization. The efficacy of selected antistaphylococcal antibiotics in preventing colonization of human fibrin clots by staphylococci was studied. Although cephapirin was effective at lower concentration, the activity of cephalothin and cephapirin was comparable. Cephalothin and cephapirin have equivalent chemoprophylactic activity by clinical and microbiological criteria, permitting cost to be used as a basis for choosing between these antibiotics.

Cardiac Surgical Procedures↗
PubMedDate not supplied

Cephalothin and cefazolin in vitro antibacterial activity and pharmacokinetics in dogs.

The periods of time that cephalothin and cefazolin serum concentration remained above minimum inhibitory concentration (MIC) for beta hemolytic, coagulase positive staphylococcal, and Escherichia coli clinical isolates were compared. Cephalothin and cefazolin were similarly very effective in vitro against staphylococcal isolates, with an MIC90 of 0.12 microgram/mL and 0.25 microgram/mL, respectively. In contrast, cefazolin was more effective than cephalothin against E coli isolates; the cefazolin MIC90 for E coli was 16 micrograms/mL and for cephalothin 64 micrograms/mL. Cefazolin (20 mg/kg intravenously [i.v.]) serum concentration remained more than MIC90 for E coli isolates significantly longer than serum concentration of cephalothin (40 mg/kg i.v.) (P < .001).

Animals↗
PubMed1977

Cefuroxime, a new parenteral cephalosporin: collaborative in vitro susceptibility comparison with cephalothin against 5,887 clinical bacterial isolates.

Cefuroxime, a new parenteral cephalosporin was compared with cephalothin by broth microdilution susceptibility testing against 5,887 routine clinical bacterial isolates in four large clinical laboratories. The minimal inhibitory concentrations (MICs) of cefuroxime against the Enterobacteriaceae were consistently lower than those of cephalothin. This was most striking among the Enterobacter species, which were generally susceptible to cefuroxime (MIC </= 8 mug/ml), but resistant to cephalothin. Similar results occurred with Haemophilus species, Acinetobacter anitratus, meningococci, and Aeromonas hydrophilia, but Pseudomonas species and enterococci were resistant to high concentrations of both drugs. Streptococci showed slightly greater susceptibility to cefuroxime than to cephalothin. By contrast, staphylococci were more susceptible to cephalothin. Bacteroides fragilis was resistant to cefuroxime, but other anaerobes were generally susceptible.

Bacteria↗
PubMed1979

Protection from gentamicin nephrotoxicity by cephalothin and carbenicillin.

In rats, cephalothin exerts a protective effect upon the nephrotoxicity of gentamicin. To examine the possibility that this effect is also observed with carbenicillin, we gave the following (milligrams per kilogram) to rats daily for 14 days: gentamicin alone, 60; gentamicin plus cephalothin, 100, 500, or 1,000; gentamicin plus carbenicillin, 50, 100, 250, 500, or 1,000. A 500-mg/kg dose of cephalothin afforded significant partial protection from gentamicin nephrotoxicity, as did a 100-mg/kg dose of carbenicillin. Increasing doses of either drug failed to increase protection. The data suggest that in rats not only does carbenicillin afford some protection from gentamicin nephrotoxicity, but also that it does so at a lower dose than cephalothin. These findings may in part explain the divergent observations regarding the nephrotoxicity of cephalothin-gentamicin combination therapy in rats and humans.

Animals↗