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PubMed1989

Effect of age and renal function on cefonicid pharmacokinetics.

Cefonicid (15 mg/kg) was administered intravenously at a constant rate of infusion over 15 min to 10 geriatric patients (mean age, 77 years) and to 4 young subjects (mean age, 35 years). Model-dependent and noncompartmental pharmacokinetic parameters were calculated and found to be congruous; noncompartmental data are reported. Significant differences in the values for area under the curve, mean residence time, total body clearance, and renal clearance were observed between the geriatric and young groups. Mean elimination half-life values were 9.59 and 4.88 h for the geriatric and young groups, respectively. Total body and renal clearances were inversely correlated to age and directly correlated to creatinine clearance. Free fraction was not correlated to albumin concentration but was correlated exponentially to total cefonicid concentration. Despite the prolonged half-life values observed in our geriatric patients, the difference in mean trough concentrations was slight. Daily administration of a 15-mg/kg dose should provide adequate concentrations in serum and should not produce appreciable accumulation in geriatric patients.

Adult↗
PubMed1988

Compatibility of clindamycin phosphate with aztreonam in polypropylene syringes and with cefoperazone sodium, cefonicid sodium, and cefuroxime sodium in partial-fill glass bottles.

The stability and compatibility of clindamycin phosphate admixed with four beta-lactams, an experimental monobactam (aztreonam), and three cephalosporins (cefoperazone sodium, cefonicid sodium, and cefuroxime sodium), were studied. Aztreonam alone and the combination of clindamycin phosphate-aztreonam were prepared in duplicate polypropylene syringes. Each cephalosporin antibiotic as well as the three clindamycin phosphate-cephalosporin combinations were admixed in duplicate 100 ml partial-fill glass bottles containing either dextrose 5% in water or NaCl 0.9%. All solutions were examined, antibiotic concentrations were determined, and pH was measured at the time of admixture and 1, 4, 8, 12, 24, and 48 hours later. The solutions were maintained at room temperature under fluorescent lighting for the length of the study. Antibiotic concentrations were determined by drug-specific high performance liquid chromatographic assays. Significant instability or incompatibility was defined as a decrease in concentration of greater than ten percent relative to the initial concentration measured at the time of admixture. All antibiotics were stable for 48 hours. In the combination studies, clindamycin was stable for 48 hours, both in partial-fill glass bottles and syringes. Aztreonam, cefoperazone, cefonicid, and cefuroxime were also stable for 48 hours.

Aztreonam↗
PubMed1991

Prophylaxis against infection. Single-dose cefonicid compared with multiple-dose cefamandole.

A total of 1489 patients were included in a prospective, randomized study that compared the efficacy of a single dose of cefonicid in 474 patients (Group I) with that of three doses of cefamandole in 510 patients (Group II) and five doses of cefamandole in 505 patients (Group III), for prophylaxis against infection after an operation on bone. The operations involved the insertion of a Moore prosthesis, an Ender and Küntscher nail, a bone-plate, or another device for internal fixation. Patients who had an open fracture or a total joint replacement were not included in the study. The three groups were similar with regard to mean age, sex ratio, duration of preoperative hospitalization, underlying risk factors, and type of operation. The rates of wound infection were not significantly different in the three groups (p = 0.8) or when the rates were stratified according to the type of operation (p greater than 0.3). Staphylococcus aureus and gram-negative bacilli were the most common infecting microorganisms. The rate of mortality related to infection was similar in all three groups (p = 0.2). No adverse side-effects of drugs were encountered. A single preoperative dose of cefonicid, three doses of cefamandole, and five doses of cefamandole were equally effective prophylaxis against infection of the wound in these patients.

Aged↗
PubMed1991

[Short term post-surgical prophylaxis in gynecology. Use of cefonicid].

In this study the Authors have evaluated the use of cefonicid in "short-term" post-surgical prophylaxis in gynecology. No effects, nor alteration to hematochemical parameters related to the administration of this medicine have been observed and the analysis of data shows that the use of cefonicid contributes to reducing the incidence of post-surgical infections in hospital in a cure group compared to a control group.

Cefonicid↗
PubMed1990

[Disulfiram-like effect of cefonicid: first observation].

The disulfiram-like reaction is linked to the assumption of ethyl alcohol during therapy with the cephalosporin latamoxef, cefamandole and cefoperazone. The reaction is commonly ascribed to the methyl-thiotetrazole group, resembling part of the disulfiram molecule. We describe the case of a patient who experienced on two different occasions a disulfiram-like effect during therapy with cefonicid. This cephalosporin contains the methylsulphothiotetrazole group in place of the methylthiotetrazole group. Our observation is the first related to cefonicid.

Aged↗
PubMed1989

Cortical and medullary kidney tissue levels of cefonicid in human beings.

Cefonicid concentration has been determined microbiologically in cortical and medullary tissue in 30 patient undergoing surgery because of neoplastic disease localized within the kidney. Each subject received 1 g of cefonicid intramuscularly in a single administration. The patients were divided into six groups, from which samples of blood and tissue were collected 2, 4, 6, 8, 12, 24 h respectively after treatment with the drug. The mean peak serum levels appeared at the second hour (74.96 +/- 8.14 mcg/ml) and the decay shows a monoexponential behaviour, reaching a minimum value of 5.4 +/- 2.33 mcg/ml at the 24th hour. In the cortical tissue of the kidney the peak levels appeared at the fourth hour (26.22 +/- 8.87 mcg/g), while at the 24th hour levels were about 3.08 +/- 0.81 mcg/g. A very similar behaviour could also be observed in the medullary tissue of the kidney with peak levels at the fourth hour (25.82 +/- 10.06 mcg/g) and levels of 3.48 +/- 0.85 mcg/g at the 24th hour. A delay in the decay of tissue levels in comparison with the decay of blood levels could be observed from the eighth hour.

Adult↗
PubMedDate not supplied

[Cefonicid toxicity. I. Effects on the reactivity of the specific immune system].

The degree of toxicity of the antibiotic Cefonicid on the cellular reactivity of the immune system was evaluated. The effects on some lymphokine (IL-2 and IFN-gamma) production and the degree of proliferation of splenic lymphocytes following mitogen stimulation have been considered. Our results show that Cefonicid does not impair the immune response, except at very high doses (500 micrograms/ml).

Animals↗
PubMed1987

Penetration of cefonicid in skin suction blister fluid in healthy volunteers.

A new cephalosporin, cefonicid (1 g) was given intramuscularly to six healthy volunteers 12 h after induction of skin suction blister. Serum and blister fluid were collected during a 24 h period. Antibiotic assay was made by a microbiological method. The data were analysed by a one-compartment kinetic model. Despite the high protein binding, cefonicid penetrated in microbiologically effective concentration into blister fluid. Blister fluid concentrations were higher than the serum concentrations at 24 h.

Adult↗
PubMedDate not supplied

Bioavailability in human volunteers of three intramuscular formulations of cefonicid: a long-acting cephalosporin.

Three different intramuscular formulations of cefonicid (a new long acting cephalosporin) have been tested for bioavailability in 12 healthy volunteers, using a triple crossover design. No significant differences were detectable between the bioequivalence of the three formulations in terms of area-under-curve and 24-h urinary excretion. However, one of the formulations (A) was absorbed significantly more rapidly from the site of injection, causing higher serum levels for up to 1.5 h after administration. A significantly greater urinary excretion was also found up to 8 h after administration of formulation A. All three formulations were well tolerated, and no side-effects or significant changes in laboratory tests were observed.

Adult↗
PubMed1991

Interference of cephalosporins with immune response: effects of cefonicid on human T-helper cells.

To determine the immunosuppressive effect(s) of cephalosporin cefonicid (CEFO) on human T-helper cells (Th), we exposed human peripheral blood mononuclear cells (PBMC) to various concentrations of CEFO during in vitro stimulation with a panel of T-lymphocyte stimulators that activate different Th/antigen presenting cell (APC) pathways. We evaluated the proliferation and IL-2 production induced by influenza virus (FLU), allogeneic lymphocytes (ALLO), xenogeneic mouse splenocytes (XENO) or phytohemagglutinin (PHA). The proliferative responses to FLU and XENO were much more depressed by CEFO than those to ALLO or PHA. After 7 days of culture with the highest dose of CEFO tested (200 mg/l) the stimulation index (stimulated/unstimulated culture) was near to 0 in FLU and XENO treated cultures, indicating that the response against these antigens was completely abrogated. The responses to ALLO and PHA were also impaired, but not abrogated (stimulation index greater than 1). Since FLU and XENO utilize the CD4+ Th/self-APC pathway our data suggested that this pathway was extremely sensitive to CEFO-induced inhibition both when the response requires memory Th cells (FLU) and virgin Th cells (XENO). The incubation with CEFO (200 mg/l) reduced the IL-2 production by XENO, FLU and ALLO to less than 20% of control cultures, while paradoxically increases to 120% the production by PHA.

Antigens↗
PubMed1987

Quality control limits for microdilution susceptibility tests with aztreonam, imipenem, ceftriaxone, ceftazidime, ceftizoxime, cefuroxime, and cefonicid.

A six-laboratory collaborative study was performed in order to define quality control limits for microdilution tests with seven new beta-lactams (aztreonam, imipenem, ceftriaxone, ceftazidime, ceftizoxime, cefuroxime, and cefonicid). Four standard control strains were tested and the expected MIC limits for each of the appropriate drug-microorganism combinations were defined.

Anti-Bacterial Agents↗
PubMed1982

Pharmacokinetics of cefonicid, a new broad-spectrum cephalosporin.

This study determined the pharmacokinetic disposition of cefonicid. A single dose of 7.5 mg/kg of body weight was administered to five healthy volunteers as a 5-min intravenous infusion. Multiple plasma and urine samples were collected for 48 h. Peak plasma concentrations ranged from 95 to 156 micrograms/ml and fell slowly (mean plasma half-life, 4.4 +/- 0.8 h), so that levels after 12 h were in the range of 6 to 12 micrograms/ml. Urinary concentrations were high but variable and ranged from 100 to 1,000 micrograms/ml for the first 12 h after the dose and averaged 84 micrograms/ml between 12 and 24 h. Plasma and renal clearances were 0.32 +/- 0.06 and 0.29 +/- 0.05 ml/min per kg, respectively. An average of 88 +/- 6% of the dose was excreted unchanged in the urine over 48 h. The mean steady-state volume of distribution was found to be 0.11 +/- 0.01 liters/kg.

Biological Assay↗
PubMed1984

Azlocillin and cefonicid penetration into bone enhanced by probenecid.

Azlocillin (AZL) and cefonicid (CFD) penetration into rabbit humerus and scapula was evaluated with and without concomitantly administered probenecid. Groups of animals received either 70 mg of AZL intravenously or 20 mg of CFD intramuscularly per kg of body weight; other groups were pretreated with 40 mg of probenecid per kg before the administration of antibiotics. Peak levels of AZL in the sera of animals not receiving probenecid were 76.0 micrograms/ml at 30 min and declined to 7.7 micrograms/ml by 2.0 h. Maximum concentrations in bone were 2.7 micrograms/g in the humerus and 7.1 micrograms/g in the scapula at 1 h. Pretreatment with probenecid significantly elevated levels of AZL in both serum and bone while increasing the half-life in serum from 0.44 to 0.65 h. Maximum drug concentrations in bones of probenecid-pretreated animals were 3.9 and 11.7 micrograms/g in the humerus and scapula, respectively, with detectable levels persisting in bone for up to 4 h. The peak level of CFD alone in serum was 36.7 micrograms/ml at 30 min and declined to 0.86 micrograms/ml at 8 h. Maximum concentrations in bone were 0.66 micrograms/g in the humerus at 1 h and 1.8 micrograms/g in the scapula at 2 h. Pretreatment with probenecid significantly elevated levels of CFD in both serum and bone while increasing the half-life in serum from 1.4 to 2.94 h. Pretreatment with probenecid achieved maximum concentrations of 1.7 and 2.8 micrograms/g in the humerus and scapula, respectively. Detectable levels of CFD persisted in the humerus for up to 4 h and in the scapula for 8 h.

Animals↗
PubMed1991

Therapeutic efficacy and renal effects of cefonicid in the treatment of difficult urinary tract infections.

UNLABELLED: EFFICACY, renal effects and nephrotoxicity of the cephalosporin cefonicid (CEF) were evaluated in 11 adult patients with urinary tract infection and varying renal function (creatinine cl 19-161 ml/min, mean 75). CEF was administered i.m. for 7 days at a daily dose adjusted to renal function of the patients. EFFICACY: At the 4th day and at the end of the treatment urine cultures were negative in all cases; a recurrence of the infection was observed in 4 patients 10 days after completion of therapy. Renal effects and nephrotoxicity: CEF neither modified plasma creatinine, urea, uric acid and their renal clearances nor glomerular filtration rate. Only the urinary enzyme activity of alanine aminopeptidase increased slightly at the end of the therapy. It returned to basal values in the post-treatment period. Urinary enzyme activities of gamma-glutamyltransferase, alkaline phosphatase, N-acetyl-beta-D-glucosaminidase and lysozyme were unmodified during and after treatment with CEF. These results indicate that CEF is an effective antimicrobial agent which does not influence renal function, nor cause nephrotoxic effects.

Adult↗
PubMed1990

Single-dose antibiotic prophylaxis in patients at high risk for infection in biliary surgery: a prospective and randomized study comparing cefonicid with mezlocillin.

The usefulness of antibiotic prophylaxis in biliary surgery is well established. When antibiotic prophylaxis is not used, wound infection rates after biliary surgery range from 10% to 25%. With antibiotic prophylaxis, the rates can be reduced to less than 5%. Three questions are still controversial: Do all patients undergoing biliary surgery require antibiotic prophylaxis? What is the ideal antibiotic for use in biliary surgery? What should be the duration of antibiotic prophylaxis? In this study we prospectively evaluated the efficacy of a single dose of antibiotic prophylaxis in biliary surgery, administered to patients at high risk for infection, in a trial comparing cefonicid (a cephalosporin with a long half-life) with mezlocillin (a broad-spectrum ureidopenicillin).

Adult↗
PubMed1990

Cefonicid distribution into tonsillar tissue.

The kinetic profile in tonsils of cefonicid has been studied in 30 patients who underwent tonsillectomy after administration of a single intramuscular dose of 1 g. Blood and tissue samples were withdrawn 1, 2, 3, 6, 12 and 24 h after administration of the drug. The analytical determination was performed employing a microbiological method. Peak serum levels appeared at the first hour (94.2 +/- 9.83 mg/l), while peak tissue values were determined in samples collected at the third hour (11.9 +/- 3.68 mg/kg). Serum levels at the 24th hour were 3.82 +/- 1.25 mg/l. Levels in the tonsils were 7.54 +/- 2.96 mg/kg at the sixth hour, 3.34 +/- 1.42 mg/kg at the twelfth hour and 0.40 +/- 0.31 mg/kg at the 24th hour.

Adolescent↗
PubMed1995

[Excretion of cefonicid and ceftriaxone into the saliva].

The serum and saliva levels of cefonicid (Monocid) and ceftriaxon (Rocephin) were studied after iv. administration on mice. It was found that both of the antibiotics were secreted well into saliva and their therapeutic values remained for 4-5 hours.

Animals↗