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At least 19 recordsLinked to original sources
PubMed1983

Therapy of staphylococcal infections with cefamandole or vancomycin alone or with a combination of cefamandole and tobramycin.

Eighty adult patients with microbiologically demonstrated staphylococcal infections were included in a comparative trial of cefamandole and cefamandole plus tobramycin. Patients with cefamandole-resistant pathogens were treated with vancomycin, if the initial therapy consisted of cefamandole, but were continued on cefamandole plus tobramycin if already started on that combination. Of the patients infected with cefamandole-susceptible strains, 91% (20/22) responded favorably to treatment with cefamandole alone, and 88% (30/34) responded favorably to cefamandole plus tobramycin. Of the patients infected with cefamandole-resistant staphylococci, 70% (7/10) responded to treatment with cefamandole plus tobramycin, and 86% (12/14) responded to treatment with vancomycin, even though vancomycin therapy was started 24 to 48 h later than cefamandole-plus-tobramycin therapy. No major side effects were observed; however, cefamandole plus tobramycin was associated with a rise in the serum creatinine level in 11% (4/44) of the patients. The bactericidal activity of the serum in cefamandole-treated patients and in cefamandole-plus-tobramycin-treated patients was identical against cefamandole-susceptible strains. Against cefamandole-resistant strains, 87% of the vancomycin-containing sera were bactericidal at a dilution of 1:8, whereas only 57% of the cefamandole-plus-tobramycin-containing sera were active at that dilution.

Anti-Bacterial Agents↗
PubMed1977

Delineation of the relative antibacterial activity of cefamandole and cefamandole nafate.

By conventional laboratory evaluation procedures, the in vitro antibacterial activities of cefamandole and its O-formyl ester, cefamandole nafate, appear virtually identical. When the activities of these two compounds were examined for their ability to lyse log-phase cultures of susceptible bacteria, however, cefamandole was found to be about 10 times more active than cefamandole nafate. Cefamandole nafate was shown to be rapidly converted to cefamandole in bacteriological media, with a half-life of less than 1 h at a pH of 7.0 or above. At pH 6.0, in log-phase inhibition experiments, however, cefamandole nafate is more stable, allowing delineation of the activity between cefamandole and cefamandole nafate. The efficacy of cefamandole was identical to that of cefamandole nafate in treating experimental animal infections, indicating that rapid conversion of cefamandole nafate to cefamandole occurs in vivo.

Animals↗
PubMed1978

Hydrolysis of cefamandole nafate to cefamandole in vivo.

The hydrolysis of cefamandole nafate, and the O-formyl ester of cefamandole, to cefamandole was studied in vivo in dogs and normal human subjects. After administration of cefamandole nafate to dogs or humans, the parent compound disappeared rapidly from plasma. Disappearance was slightly faster in dogs (half-life [t1/2], 4--6 min) than in humans (t1/2, 6--9 min). The calculated rate constant for hydrolysis of cefamandole nafate was also higher in dogs than in humans, yielding t1/2 values of 6--7 min and 10--17 min, respectively. The rapid hydrolysis of cefamandole nafate to cefamandole in vivo, combined with the partial hydrolysis of cefamandole nafate in vitro before administration (caused by Na2CO3 in the formulation), resulted in circulating levels of cefamandole nafate lower than those of cefamandole. In humans the disappearance of cefamandole nafate was not significantly altered after administration of large (4.0 g) or multiple (4.0g every 6 hr) doses of cefamandole nafate.

Animals↗
PubMed1978

A comparative study of the activity of cefamandole and other cephalosporins and analysis of the beta-lactamase stability and synergy of cefamandole with aminoglycosides.

The antibacterial activity of cefamandole against 445 clinical isolates was investigated and compared with the activity of other known cephalosporins (cephalothin, cephaloridine, cephalexin, and cefazolin) and of two penicillins (ampicillin and carbenicillin). Cefamandole was the most active antibiotic against isolates of Citrobacter, Enterobacter, and Shigella, and its activity against Staphylococcus aureus, Bacteroides, and some members of the Enterobacteriaceae was comparable to that of the other antibiotics tested. The stability of cefamandole with respect to beta-lactamase was investigated and compared with that of cephalothin, cefazolin, and cephalexin. Cefamandole was stable with respect to the beta-lactamases of Enterobacter and some other members of the Enterobacteriaceae. No significant correlation was found between the antibacterial activity and the beta-lactamase stability of cefamandole, except with Enterobacter. The synergistic activity of cefamandole combined with gentamicin or amikacin was demonstrated by killing-curve techniques, isobolograms, and susceptibility data. Although 12%--46% of the isolates were synergistically inhibited by either combination, antagonism was not observed. No correlation between the hydrolysis of cefamandole by beta-lactamase and the synergistic activity of cefamandole combined with amikacin was demonstrated.

Acinetobacter↗
PubMed1983

Randomized trial of cefamandole plus amdinocillin versus cefamandole in serious pediatric infections.

In a randomized, prospective clinical trial cefamandole therapy was compared with cefamandole plus amdinocillin in infants and children with suspected bacterial infections. Fifty-two infections in 50 patients with bone and joint (19 infections), pulmonary (19 infections), soft tissue (eight infections), and urinary tract (6 infections) diseases were treated. Bacterial infection was documented in 31 patients. All isolates were susceptible to cefamandole except one strain of Serratia marcescens, which was susceptible to the combination. In vitro synergy was demonstrated in all coliform bacilli, in three of seven Haemophilus strains, and in six of 16 gram-positive cocci. No correlation between degree of serum bactericidal activity and presence or absence of synergy could be demonstrated. One patient treated with cefamandole died; all other patients responded promptly to therapy without serious adverse drug effects.

Amdinocillin↗
PubMed1990

Simultaneous determination of cefamandole and cefamandole nafate in human plasma and urine by high-performance liquid chromatography with column switching.

A high-performance liquid chromatographic method with column switching has been developed for the simultaneous determination of cefamandole and cefamandole nafate in plasma and urine. The plasma and urine samples were injected onto a precolumn packed with Corasil RP C18 (37-50 microns) after simple dilution with an internal standard solution in 0.05 M phosphoric acid. Polar plasma and urine components were washed out using 0.05 M phosphoric acid. After valve switching, the concentrated drugs were desorbed in back-flush mode and separated by a reversed-phase C8 column with methanol-5 mM tetrabutylammonium bromide (45:55, v/v) as the mobile phase. The method showed excellent precision with good sensitivity and speed, and a detection limit of 0.5 microgram/ml. The total analysis time per sample was less than 30 min, and the mean coefficients of variation for intra- and inter-assay were both less than 4.9%. The method has been successfully applied to plasma and urine samples for human volunteers after intravenous injection of cefamandole nafate.

Cefamandole↗
PubMedDate not supplied

[Cefamandole as prophylactic A.B. in abdominal surgery. Comparative study of cefamandole versus clindamycin/tobramycin (author's transl)].

A prospective, randomized and controlled study of prophylactic A.B. was made in 100 patients prior to abdominal surgery. Fifty patients received 3 x 2 g of cefamandole I.V. within 24 hrs, the first dose being given at the time of anesthetic induction. Postoperative infections occurred in 2% of this group. Fifty patients received the association Clindamycin-Tobramycin (clindamycin 600 mg - tobramycin 80 mg/8 hrs) for 24 hrs, the first dose also at the induction of anesthesia. The complication rate in this group was 18%. The difference between those 2 groups is statistically significant (p less than 0.01). Cefamandole used as a prophylactic antibiotic in abdominal surgery reduces the incidence of postoperative wound infections when compared to the association clindamycin-tobramycin.

Adolescent↗
PubMed1976

Conversion of cefamandole nafate to cefamandole sodium.

The rate of hydrolysis of the formyl moiety of cefamandole nafate was determined as a function of pH, temperature, and concentration of added sodium carbonate or tromethamine. The reaction rate was sensitive to hydroxide ion in the pH 5.5-8.0 range with half-life values of hours to minutes. Hydrolysis was rapid upon the addition of sodium carbonate or tromethamine. Chirality in the 7-D-mandelamido side chain was unaffected by hydrolysis.

Carbonates↗
PubMed1993

[The effect of different autotransfusion procedures on the antibiotic picture. A study on cephalosporin cefamandole].

Infection after open heart surgery is a serious complication since eradication of infection in these cases is difficult even with appropriate antibiotic therapy. In the attempt to avoid this problem, prophylactic administration of antibiotics is common. Their relative safety and their broad spectrum of activity make cephalosporin antibiotics popular choices for prophylaxis prior to and during operations, including cardiovascular procedures. METHODS. Preoperative antibiotic prophylaxis with 2 g cefamandole was performed in a prospective randomized study including 62 male patients divided into three groups. All patients gave informed consent, and the study was approved by the ethics committee of the hospital. Patients in group 1 (n = 21) and group 2 (n = 21) underwent aortocoronary bypass (ACVB) with extracorporeal circulation (ECC), while patients in group 3 (n = 20) had carotid surgery. Anaesthesia, coronary-bypass procedures and infusion regime were standardized. The flow rate during ECC was maintained at 2.41/min/m2 and the rectal temperature between 33 degrees and 34 degrees C. Arterial and urine specimens for the determination of plasma and urine levels of cefamandole were taken at definite times. Autologous blood salvage during operation was performed with haemofiltration techniques (HF) in group 1 (HF 80, Fresenius, Bad Homburg, Germany) and with cell separation techniques (CS) in group 2 (Hemonetics III, Hemonetics). Plasma and urine cefamandole levels were measured by high-pressure liquid chromatography (HPLC). RESULTS. After administration of 2 g cefamandole mean peak levels of 404.6 +/- 141.7 micrograms/ml were seen. Because of haemodilution at the beginning of extracorporeal circulation, group 1 and 2 showed much lower cefamandole plasma levels, 22.1 +/- 11.6 micrograms/ml and 24.3 +/- 14.4 micrograms/ml, than group 3 (after the same time course), with 47.4 +/- 19.1 micrograms/ml. For all patients in group 1 and 2 prebypass time (70.3 +/- 22.4 min) and the duration of the ECC (72.3 +/- 17.7 min) were comparable. There was a significant correlation between prebypass time and cefamandole plasma levels at the beginning of extracorporeal circulation (P < 0.001). No correlation could be seen for the plasma concentration after discontinuation of the extracorporeal circulation and the duration of extracorporeal circulation. The volume of autologous red packed cells and the enclosed amount of cefamandole showed a significant difference (P < 0.001) between group 1 (1120.0 +/- 296.8 ml, 27.5 +/- 17.1 mg) and group 2 (734.3 +/- 186.6 ml, 2.9 +/- 3.2 mg). The plasma cefamandole level after transfusion of autologous blood displayed a significant correlation (p < 0.01) with cefamandole concentration in the autologous red packed cells. Transfusion of the autologous blood produced no significant increase in plasma cefamandole levels. With an operation time of more than 2.5 h during ECC the cefamandole plasma level decreased below the necessary minimal inhibitory concentration (MIC90), particularly for gram-negative bacteria. CONCLUSION. Additional administration of 1 g cefamandole shortly before the beginning of cardiopulmonary bypass is recommended, particularly for surgical procedures with ECC of more than 2.5 h. Adjustment of drug dosage prior to or during surgery may be required to optimize therapy, but before this can be achieved precisely, more information on drug disposition during the operative procedures is needed.

Aged↗
PubMed1985

Extravascular hemolysis following the administration of cefamandole.

Hemolytic anemia occurred in a 70-year-old female after a five-day course of intravenous cefamandole. The patient's serum contained an IgG antibody which was reactive with red blood cells which had been coated in vitro with cefamandole but not with uncoated cells. An in vitro assay of allogeneic mononuclear phagocytosis of cefamandole-coated red cells sensitized with the patient's anti-cefamandole indicated that the anti-cefamandole could induce significant phagocytosis. The anti-cefamandole was easily inhibited in vitro by cefamandole as well as by a variety of related cephalosporins indicating broad cross-reactivity, with the antigenic site primarily the 7-amino-cephalosporanic acid nucleus. Penicillins could inhibit the anti-cefamandole but only when using concentrations 3-10 X those of cephalosporins. Eleven examples of anti-penicillin tested failed to react with cefamandole-coated red cells. Screening of 344 random sera from hospitalized patients found only five (1.5%) reactive with cefamandole-coated red cells; three of these sera were also reactive with penicillin-coated red cells. The patient's hemolysis subsided following cessation of the drug. This is the first report of anti-cefamandole-induced hemolytic anemia.

Aged↗
PubMed1980

[Double-blind comparison of cefamandole and cefazolin in the therapy of respiratory tract infections (author's transl)].

A cooperative study in 46 institutions and clinics in Tohoku and Hoddaido districts in Japan was carried out to compare the efficacy, usefulness and safety of cefamandole and cefazolin in treatment of repiratory tract infections by randomized double blind technique. Two grams of either of the two cephalosporins were given by intravenous drip infusion to the two groups of patients aged over 16 years twice a day for 14 days. Of a total of 232 patients included in the study, 120 patients were treated with cefamandole and 122 patients with cefazolin. Of these patients treated with either of the both drugs, 27 patients were excluded from evaluation for efficacy. All 232 patients were adopted for analysis of side effects. Characteristics of the population, sex and age distribution, severity of infections and infecting organisms before treatment were similar in each treatment group and no statistically significant differences could be found between the two groups. Both groups included nearly equal numbers of patients with underlying diseases or with complications. The patients pre-treated with other antibiotics before the start of the study or treated simultaneously with anti-inflammatory drugs were equally distributed in the both treatment groups. Clinical cure rate was 69.2% in groups of the patients treated with cefamandole, whereas that in cefazolin treatment group was 62.2%. Thus, there was a difference of 7% in clinical cure rate between two treatment groups, though it was not statistically significant. In groups of patients with acute bacterial pneumonia or lung abcess, clinical cure rate with cefamandole was 76.7%, whereas that with cefazolin was 67.7%. Thus, the clinical cure rate was 9% higher in the group of patients treated with cefamandole, though the difference was again statistically not significant. In the group of patients with infections associated with chronic respiratory diseases, cefamandole cured 50% of the patients treated, whereas cefazolin cured 48.1%. Comparison of the curves of cumulative distribution of MICs of cefamandole and cefazolin proved the superiority of cefamandole to cefazolin in antimicrobial activities against strains of various species isolated from the patients in the study. Rate of eradication of potential pathogenic microorganisms was 82.4% in the patients with pneumonia or lung abscess who were treated with cefamandole, whereas that with cefazolin was 83.3%. Taking efficacy and adverse effects into consideration, usefulness of the two cephalosporins in the treatment of respiratory tract infections was evaluated by doctors in charge. In 33.3% of patients treated, cefamandole was evaluated as quite useful in the treatment of pneumonia or lung abscess. In contrast, cefazolin was evaluated as quite useful in only 18.3% of patient treated. This difference was statistically significant (P smaller than 0.1). In treatment of patients with infections associated with chronic respiratory disease, cefamandole and cefazolin were evaluated as quite useful or useful in 53.1% and in 51...

Adult↗
PubMed1981

Pharmacology of ceftizoxime compared with that of cefamandole.

The pharmacokinetics of ceftizoxime, a new beta-lactam antibiotic, were studied in normal, male volunteers and compared with the pharmacokinetics of cefamandole. After administration of 500 mg intramuscularly, ceftizoxime produced a peak level of 13.7 +/- 1 microgram/ml, compared with 13.2 +/- 1.6 microgram/ml for cefamandole. At 4 h, the serum level of ceftizoxime was 4.8 micrograms/ml, and that of cefamandole was 1.9 microgram/ml. At 8 h, ceftizoxime was still detected at 0.73 microgram/ml, whereas cefamandole was not. The half-life of ceftizoxime after intramuscular administration was 1.7 h, compared with 1 h for cefamandole. Serum levels of ceftizoxime and cefamandole after 1 g infused over 30 min were 84 and 88 micrograms/ml, respectively. At 5 h cefamandole was not detectable, whereas ceftizoxime had a serum level of 4.5 micrograms/ml and, at 7 h, 2.1 micrograms/ml. The half-life of ceftizoxime was 1.9 h, compared with 0.78 h for cefamandole. Urinary recovery of ceftizoxime after intramuscular and intravenous administration was 70 and 80%, respectively, compared with 78 and 73% for cefamandole.

Adult↗
PubMed1975

In vitro activity and pharmacokinetics in patients of cefamandole, a new cephalsoporin antibiotic.

Cefamandole nafate, a new cephalosporin for parenteral use, was evaluated in vitro against 231 recent clinical isolates and in 12 patients. Cefamandole had activity equivalent to cefazolin against Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae. Cefamandole was more active than cephalothin or cefazolin against Proteus mirabilis. Both cefamandole and cefazolin were as active as cephalothin against S. aureus, were slightly more active against K. pneumoniae, and were considerably more active against E. coli. All strains of indole-positive Proteus sp. were inhibited by 6.3 mug of cefamandole per ml but only 20% were inhibited by 25 mug of cefazolin or cephalothin per ml. Eighty-eight percent of Enterobacter sp. was inhibited by 25 mug of cefamandole per ml, but only 20 and 5% were inhibited by the same concentration of cefazolin and cephalothin, respectively. Peak levels of cefamandole ranged from 6.0 to 110 mug/ml in serum and levels ranged from 440 to 16,800 mug/ml in a 4- to 6-h collection of urine after a 500-mg or 1-g intramuscular dose (6.1 to 17.3 mg/kg) in patients with endogenous creatinine clearances of >/=31 ml/min. These levels were done after the first dose, at mid-therapy, and at the end of therapy. There was no evidence of accumulation with the 500-mg or 1-g dose given every 4 to 6 h. The percentage of the dose excreted in the urine within the first 4 to 6 h after administration of cefamandole was >/=43%. The half-life of cefamandole in serum was 49 to 126 min.

Bacteria↗
PubMed1978

Comparison of the pharmacokinetics of cefamandole and other cephalosporin compounds.

The pharmacokinetic properties of cefamandole were determined and compared with the properties of other cephalosporin agents. Cefamandole was found to be approximately 70% bound to protein. The mean peak concentration in serum after intramuscular (im) injection of 1 g of cefamandole was 20 microgram/ml at 0.5 hr, whereas the level at 6 hr was 1 microgram/ml. After intravenous (iv) infusion of 1 g of cefamandole, levels in serum ranged from 68 to 147 microgram/ml depending on the period of infusion. At 4 hr after infusion, levels were less than 1 microgram/ml. Probenecid elevated serum levels and prolonged excretion. The half-life (t1/2) of cefamandole after im injection ranged from 1 to 1.5 hr and from 0.45 to 1.2 hr after iv injection. Rates of serum and renal clearance of cefamandole ranged from 210 to 300 microliter/min per 1.73 m2. The apparent volume of distribution ranged from 12.4 to 17.9 liters/1.73 m2. Urinary excretion was rapid, with 60% of a dose excreted in the first 2 hr after injection. In 6 hr 90% of a dose was excreted. The pharmacokinetic properties of cefamandole were similar to those of cephalothin and cefoxitin, but the serum t1/2 was shorter than that reported for cefazolin and cefuroxime. Correlation of in vitro studies with pharmacokinetic properties revealed that cefamandole would inhibit most susceptible gram-positive and gram-negative bacteria if given by suggested im or iv regimens.

Bacterial Infections↗
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↗
PubMed1979

Clinical and laboratory evaluation of cefamandole in the therapy of Haemophilus spp. Bronchopulmonary infections.

A prospective, randomized, single-blind comparison of parenteral cefamandole and ampicillin was conducted in 27 hospitalized adult patients with pneumonia or purulent tracheobronchitis due to Haemophilus spp. Patients received either parenteral cefamandole or ampicillin in a dose of 1 g every 6 h. Cefamandole was as effective and safe as ampicillin. Of the 14 patients treated with cefamandole, 13 were considered cured, as were 12 of the 13 treated with ampicillin. One patient in each treatment group improved clinically but did not clear his sputum of Haemophilus spp. One patient treated with cefamandole had a recurrence of Haemophilus spp. bronchitis 9 days after cure. Adverse effects were more common in the cefamandole-treated group (50% versus 15%), but were mild and did not require discontinuation of therapy in any patient. The in vitro susceptibilities of 64 clinical isolates of Haemophilus spp. to 10 antibiotics were determined. Cefamandole was the most active of the cephalosporin-cephamycin antibiotics tested, inhibiting 98% of 61 non-beta-lactamase-producing isolates at 2 mug/ml and 100% at 4 mug/ml. Cefamandole inhibited the three ampicillin-resistant isolates at 2 mug/ml or less. Cephapirin, cefoxitin, and cephalothin were the next most active, whereas cefazolin and cephradine were the least active.

Adult↗