Pharmacokinetics of cefonicid in lactating goats after intravenous, intramuscular and subcutaneous administration, and after a long-acting formulation for subcutaneous administration.

The single-dose disposition kinetics of cefonicid were determined in clinically normal lactating goats (n = 6) after intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration of a conventional formulation, and after subcutaneous administration of a long-acting formulation (SC-LA). Cefonicid concentrations were determined by high performance liquid chromatography with ultraviolet detection. The concentration-time data were analysed by noncompartmental pharmacokinetic methods. Steady-state volume of distribution (Vss ) and clearance (Cl) of cefonicid after IV administration were 0.14 ± 0.03 L/kg and 0.51 ± 0.07 L/h·kg, respectively. Following IM, SC and SC-LA administration, cefonicid achieved maximum plasma concentrations of 14.46 ± 0.82, 11.98 ± 1.92 and 17.17 ± 2.45 mg/L at 0.26 ± 0.13, 0.42 ± 0.13 and 0.83 ± 0.20 hr, respectively. The absolute bioavailabilities after IM, SC and SC-LA routes were 75.34 ± 11.28%, 71.03 ± 19.14% and 102.84 ± 15.155%, respectively. After cefonicid analysis from milk samples, no concentrations were found above LOQ at any sampling time. From these data, cefonicid administered at 20 mg/kg each 12 hr after SC-LA could be effective to treat bacterial infections in lactating animals not affected by mastitis problems.

Cephalosporin susceptibility of Staphylococcus aureus strains isolated from commercial rabbit and goats farms in Spain.

Antimicrobial drug resistance is an important problem that challenges veterinary clinicians to provide effective treatments without further spreading resistance to other animals and people. The most commonly used pharmacodynamic parameter to define potency of antimicrobial drugs is minimum inhibitory concentration (MIC). The aim of this study was to evaluate the antibiotic susceptibility of thirty-six strains of Staphylococcus aureus isolated from dairy goats with mastitis and rabbits with chronic staphylococcosis. Four cephalosporins were tested: cephalexin, cephalotin, cefonicid and ceftiofur. MIC tests were performed according to the microdilution broth method. The calculated values of sensitivity in goats and rabbits were 66.67% and 72.22% for cephalexin, 72.22 % and 94.44% for cefonicid, 77.78% and 94.44% for cephalotin and 77.78% and 100% for ceftiofur, respectively. For all antibiotics, MIC90 of S. aureus from rabbits were lower than MIC90 from goats. These data suggest that more antibiotics are used in goat milk production than in rabbit farming. According to MIC values obtained in this study, ceftiofur and cephalotin may be the best option for treating S. aureus infections in lactating goats. For rabbits, ceftiofur showed lowest MIC values, therefore, it could be an alternative to treatment the infections caused by S. aureus in this species.

Substitute technology for reference substances in the analysis of impurities in cefonicid for injection with HPLC using a diode array detector.

With HPLC using a diode array detector (DAD), a method of substitution for reference substances in impurity profiling control was developed that combined peak tracking by the correlation of spectra with application of correction factors for determination of each impurity. For qualitative analysis, two-dimensional (2D) standard spectrochromatographic data produced by HPLC-DAD were compared with sample data to develop 2D chromatographic spectral correlative maps so that the three target impurities were recognized without preparation and injection of reference solutions. For quantitative analysis, correction factors among cefonicid and the three impurities were established. The correction factors were 1.06 for 5-mercapto-1,2,3,4-tetrazole 1-methyl sulfonic acid detected at 255 nm, 0.77 for 7-aminocephalosporanic acid detected at 265 nm, and 0.97 for methoxycefonicid detected at 268 nm. The method could be used in analysis of related substances in cefonicid for injection without recourse to chemical reference standards of the three impurities.

Empiric treatment with once-daily cefonicid and gentamicin for febrile non-neutropenic pediatric cancer patients with indwelling central venous catheters.

SUMMARY: The approach to treating febrile non-neutropenic hematooncologic patients with central venous catheters varies. We recently introduced once-daily administration of cefonicid and gentamicin for such children who were in good clinical condition and without focal signs of infection. Our 2-year experience of 125 episodes in 54 children is hereby reported. Absolute neutrophil counts were 550 to 16,700/mm. Bacteremia occurred in 6.4% episodes: only in patients with Hickman/Broviac catheters and not in those with port-a-caths [8/37 (21.6%) vs. 0/17 patients, P=0.046; 8/86 (9.3%) vs. 0/39 episodes, P=0.056]. The pathogens were coagulase-negative staphylococci (3), Streptococcus pneumoniae (2), Pseudomonas aeruginosa and Klebsiella pneumoniae (1), methicillin-sensitive Staphylococcus aureus (1), and Streptococcus milleri (1). All patients remained in stable clinical condition and all, except for 2 who became neutropenic and 1 with S. aureus bacteremia who developed cellulitis, defervesced while on the empiric therapy. Three episodes could not be managed as outpatients. No adverse effects were observed. We conclude that our approach is efficacious and safe and, furthermore, that empiric antibiotic therapy may not be indicated for selected patients with port-a-caths. Future study of children with Hickman/Broviac catheters will evaluate the use of cefonicid alone.

A successful treatment of necrotizing fasciitis following the surgery of distal radius plate removal: A case report and literature review.

RATIONALE: Necrotizing fasciitis (NF) is defined as a rare, rapidly progressive, and highly lethal skin infection characterized by necrosis of the fascia and subcutaneous tissue. PATIENT CONCERNS: The present study aims to discuss the case of a 35-year-old man who developed NF following a routine sterile right distal radius bone plate removal surgery. DIAGNOSES: The patient was suspected of NF based on his clinical manifestations, laboratory tests, and imaging results. The diagnosis of NF was confirmed by histological examinations. INTERVENTIONS: Serial prompt and extensive debridement was performed during the rapid and aggressive extension of the skin infection, together with antibiotics and supportive treatments. OUTCOMES: The condition of the patient finally improved on the sixth day of disease progression. Skin grafting of his right forearm wound was performed successfully 2 months after the admission. LESSONS: NF can occur during the perioperative period for routine clean radius plate removal operation in patients with no risk factor for NF. The objective is to remind the physicians to stay aware of this disease, especially its early clinical signs and symptoms. Urgent subsequent treatment, including surgical debridement, antibiotic therapy, and supporting management, is the key to ensure the survival and better prognosis of patients.

Solid-state chemistry and particle engineering with supercritical fluids in pharmaceutics.

The present commentary aims to review the modern and innovative strategies in particle engineering by the supercritical fluid technologies and it is principally concerned with the aspects of solid-state chemistry. Supercritical fluids based processes for particle production have been proved suitable for controlling solid-state, morphology and particle size of pharmaceuticals, in some cases on an industrial scale. Supercritical fluids should be considered in a prominent position in the development processes of drug products for the 21st century. In this respect, this innovative technology will help in meeting the more and more stringent requirements of regulatory authorities in terms of solid-state characterisation and purity, and environmental acceptability.

Influence of the ischaemic tourniquet in antibiotic prophylaxis in total knee replacement.

OBJECTIVE: There is level iv evidence that the preoperative administration of antibiotics helps in the prevention of prosthetic infection. There is controversy on whether the ischemia applied during surgery may affect the minimum inhibitory concentration of the antibiotic in the peri-prosthetic tissues. The aim of this study is to review this phenomenon through the determination of antibiotic concentration in the synovial tissue. MATERIAL AND METHOD: A prospective observational clinical study was conducted on 32 patients undergoing total knee replacement. Cefonicid 2g was administered as prophylaxis, with a tourniquet used for all patients. The antibiotic concentration was quantified by high performance liquid chromatography in samples of synovial tissue collected at the beginning and at the end of the intervention. RESULTS: The mean concentration of antibiotic was 23.16 µg/g (95% CI 19.19 to 27.13) in the samples at the beginning of the intervention and 15.45 µg/g (95% CI 13.20 to 17.69) in the final samples, being higher than the minimum inhibitory concentration of cefonicid, set at 8 µg/g. These results were statistically significant for both concentrations (P<.00001). DISCUSSION: The antibiotic concentration throughout the standard total knee prosthesis surgery performed with tourniquet gradually decreases throughout the intervention. The concentration determined at the end of the intervention was higher than the minimum inhibitory concentration required for the antibiotic studied. In conclusion, the use of a tourniquet does not increase the risk of infection.

Cefonicid kinetics in subjects with normal and impaired renal function.

Cefonicid is a cephalosporin with a longer t1/2 than currently available cephalosporins. Cefonicid kinetics after an intravenous dose of 7.5 mg/kg were followed in four groups of subjects: group 1, four subjects with normal creatinine clearance (Clcr greater than 80 ml/min); group II, seven subjects with mild renal insufficiency (Clcr 50 to 80 ml/min); group III, five subjects with moderate to severe renal impairment (Clcr 8 to 49 ml/min); and group IV, five subjects with end-stage renal disease who were receiving maintenance hemodialysis (Clcr less than 8 ml/ml). Cefonicid volume of distribution ranged from 6.9% to 17.6% body weight but was not related to Clcr. Elimination t1/2 was 4.6 +/- 0.7 hr in group 1,6.0 +/- 2.7 hr in group II, 25.6 +/- 14.0 hr in group III, and 65.3 +/- 43.6 hr in group IV. There was a strong correlation between plasma cefonicid clearance and Clcr. Nonrenal clearance did not change with decreasing Clcr. Hemodialysis clearance calculated from plasma concentrations and recovery in dialysate was 2.5 +/- 0.9 ml/min. These kinetic parameters were used to formulate dosage regimens for patients with renal impairment.

Kinetics and renal handling of cefonicid.

Cefonicid kinetics were determined after intravenous and intramuscular injection and the renal handling of the drug was examined, including the effect of probenecid on its excretion. Peak serum levels after 1000 and 500 mg intravenously was 221 and 91 micrograms/ml. The half-life (t1/2) was the same for both regimens (3.5 hr). Intramuscular injection of the 1000- and 500-mg doses resulted in peak serum levels of 112 and 40 micrograms/ml. When probenecid was given with the 500-mg dose, the peak serum level was 61 micrograms/ml and the time to peak level rose from 1.3 to 2.5 hr. The t1/2 after 1000 and 500 mg alone was much the same at 4.8 and 4.9 hr. The addition of probenecid to the 500-mg dose extended the t1/2 and 7.5 hr. Renal clearance, excretion, and secretion rates for cefonicid were reduced by the addition of probenecid. Cefonicid's long t1/2 and high blood levels may provide clinical efficacy with a single daily dose.

Cefonicid. A review of its antibacterial activity, pharmacological properties and therapeutic use.

Cefonicid is a 'second generation' cephalosporin administered intravenously or intramuscularly. It is similar to cefamandole in its superiority to first generation cephalosporins against several enterobacteriaceae as well as its activity against Haemophilus influenzae, including beta-lactamase-producing strains. Its activity against Staphylococcus aureus is similar to that of cefoxitin and inferior to cefamandole and first generation cephalosporins. It has excellent in vitro activity against Neisseria gonorrhoeae, but is inactive against Pseudomonas, Acinetobacter, Serratia, and Bacteroides fragilis. Due to high achievable plasma concentrations and a relatively long half-life, in most clinical trials cefonicid has been administered once daily. It was comparable in efficacy with cefamandole or cefazolin in the treatment of patients with urinary tract, lower respiratory tract, and soft tissue and bone infections. It has also been compared with penicillin in the treatment of uncomplicated gonorrhoea. Results from a small series of patients with endocarditis appear to indicate that cefonicid should not be used in patients with serious staphylococcal infections. Single doses of cefonicid given preoperatively appear to offer a similar degree of protection against post-surgical infection as multiple doses of other antibiotics, but further data from studies involving larger numbers of patients are needed to confirm these impressions. Patients who require prolonged antibiotic therapy, such as those with osteomyelitis being treated as outpatients after a relatively short inpatient course, could benefit from the once daily dose regimen of cefonicid.

Postoperative mediastinitis: a comparison of two electrocautery techniques on presternal soft tissues.

Postoperative mediastinitis remains a serious surgical problem, complicating 0.4% to 5% of all cases. In an experiment designed to address this problem, 36 mongrel dogs underwent a median sternotomy incision. In group I (n = 18) all layers to the sternum were opened by a scalpel, and electrocautery was used only for pinpoint hemostasis. In group II (n = 18) the skin was opened by a scalpel and the remaining layers to the sternum were opened by electrocautery. Total kilojoules of electrical energy delivered to the tissues was 9.4 +/- 5.7 for group I and 44.1 +/- 7.0 for group II (p less than 0.001). Each group was randomly divided into three subgroups (n = 6): Ia and IIa were noninoculated controls; Ib and IIb were inoculated just before skin closure; Ic and IIc were inoculated and given one preoperative dose of cefonicid. The inoculum contained Staphylococcus intermedius in a 0.5 ml suspension of 10(8) organisms. Each animal was observed and the wounds were scored daily until death or until all survivors were put to death on the eighth postoperative day. Pleural fluid was cultured at autopsy. Ten dogs died of mediastinitis (four in IIa and six in IIb), but none from group I (p less than 0.01). Positive cultures from pleural fluid in matching subgroups (n = 6) occurred as follows: one in Ia and five in IIa (p less than 0.05); one in Ib and six in IIb (p less than 0.01); zero in Ic and two in IIc. We conclude that pinpoint hemostasis on the soft tissues of the sternotomy incision significantly reduces the severity and frequency of penetrating mediastinitis.

Preventive antibiotic usage in traumatic thoracic injuries requiring closed tube thoracostomy.

OBJECTIVE: To evaluate the safety and effectiveness of antibiotics in reducing the infectious complications following closed tube thoracostomy for isolated chest trauma. DESIGN: Double-blind, randomized clinical trial. SETTING: Medical school affiliated large urban teaching hospital and trauma center. PATIENTS: One hundred nineteen of 159 patients over 18 years old presenting to the emergency department requiring closed tube thoracostomy for isolated chest injuries (113 penetrating, 6 blunt). INTERVENTION: Patients received either placebo or 1 g cefonicid daily intravenously started at chest tube insertion and stopped within 24 h of removal. MEASUREMENTS AND RESULTS: The development of wound infections, pneumonia (CDC criteria), or empyema; the incidence of adverse events; length of hospitalization. One nonspecific infection was seen in the cefonicid group (1.6 percent) and six respiratory tract infections (10.7 percent) in the placebo group (three empyema, one empyema with pneumonia, two pneumonia) (p = 0.0505; p = 0.0094 [excluding nonspecific infection]). No significant differences with antibiotic use were seen in the duration of chest tube use (p = 0.766), peak WBC counts (p = 0.108), lower peak temperatures (p = 0.063), or length of hospitalization (p = 0.165). Patients who developed infectious complications averaged approximately 8 days longer hospitalization than those without (p < 0.0001). CONCLUSION: This study showed that patients receiving antibiotics had a significantly reduced rate of infection than did patients administered placebo. No significant adverse events were seen in either group.

Disposition of intramuscular cefonicid in elderly patients.

OBJECTIVE: To examine the disposition of intramuscular (IM) cefonicid in elderly patients with bacterial pneumonia. DESIGN: Pharmacokinetic study. SETTING: A 620-bed university-affiliated long-term care institution with its own 39-bed acute care unit. PATIENTS: Nine consecutive elderly patients with bacterial pneumonia treated with IM cefonicid. MEASUREMENTS: Blood samples were collected on the seventh day of therapy over a 24-hour period and analyzed by high performance liquid chromatography. Pharmacokinetics parameters (volume of distribution, half-life, and clearance) and protein binding were calculated. Clinical outcome of IM cefonicid therapy was also noted. RESULTS: The estimated creatinine clearance (CIcr) ranged from 32 to 145 mL/min. Peak cefonicid serum concentrations occurred at 0.5-1.5 hours, with a mean value of 118 +/- 41 micrograms/mL. Cefonicid concentrations declined monoexponentially to 57 +/- 16 micrograms/mL at 12 hours and 28 +/- 14 micrograms/mL at 24 hours. The mean apparent distribution volume was 0.2 +/- 0.07 L/kg, and the mean apparent total clearance was 15 +/- 12 mL/min. The half-life ranged from 3.1 to 38 hours. A linear correlation was noted between Clcr and cefonicid clearance (r = 0.99). CONCLUSIONS: Cefonicid absorption was variable among these patients, and the serum half-life was longer than previous values noted in younger patients with similar degree of renal dysfunction. Pharmacokinetic and clinical outcome data from our study group indicate the potential role of IM cefonicid in treating elderly patients with bacterial pneumonia.

Cefonicid concentrations in human aqueous humor.

One-gram doses of cefonicid sodium were given intravenously to patients prior to cataract surgery. Although serum levels were high, cefonicid levels in aqueous humor were low: mean peak concentrations of 0.25 and 0.27 mg/L were observed two and four hours after administration, respectively. The unusually high protein binding of cefonicid may explain these observations. The observed concentrations were not above the minimum inhibitory concentrations of cefonicid for those pathogens commonly involved in bacterial endophthalmitis.

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).

Single-dose cefazolin versus cefonicid for antibiotic prophylaxis in cesarean delivery.

The purpose of this prospective investigation was to compare a single intravenous dose of cefazolin to a single dose of cefonicid as prophylaxis for women having unscheduled cesarean delivery. In a double-blind, randomized design, 96 patients were assigned to receive a 1-g dose of cefazolin and 103 patients were designated to receive a 1-g dose of cefonicid. The antibiotics were administered after delivery of the infant. The two groups were comparable with respect to recognized risk factors for postcesarean infection. There were no statistically significant differences between the groups in the incidence of standard febrile morbidity, endomyometritis, urinary tract infection, wound infection, and bacteremia. There were also no significant differences between the groups in the fever index or the duration of hospitalization. We conclude that cefazolin and cefonicid provide a similar degree of prophylaxis against infection in patients having unscheduled cesarean delivery.

Single-dose antibiotic prophylaxis in women undergoing vaginal hysterectomy.

One hundred thirty-five patients undergoing vaginal hysterectomy were randomly assigned to one of three regimens of prophylactic antibiotics. There was no statistically significant difference among the three groups in the incidence of postoperative pelvic cellulitis, fever index, or duration of hospitalization. A single preoperative dose of cefazolin was as effective as three perioperative doses of cefazolin or a single dose of cefonicid in preventing postoperative infectious morbidity.

Duration of preventive antibiotic administration for open extremity fractures.

The necessary duration of antibiotic administration after open fracture has not been established. In a double-blind prospective trial we randomized 248 patients with open fractures to receive one or five days of cefonicid sodium therapy or five days of cefamandole nafate therapy as part of the initial treatment. Rates of fracture-associated infections in the three groups were ten (13%) of 79, ten (12%) of 85, and 11 (13%) of 84, respectively. The 95% confidence limit for the difference in infection rates between the one-day group and the combined five-day groups was 0% to 8.3%. The actual difference was 0.2%. A brief course of antibiotic administration is not inferior to a prolonged course of antibiotics for prevention of postoperative fracture-site infections.

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.

Cefamandole versus cefonicid prophylaxis in cardiovascular surgery: a prospective study.

We randomized 400 patients who were scheduled for an elective cardiovascular operation involving median sternotomy to receive cefamandole nafate or cefonicid in a prospective double-blind study. Three hundred fifty-seven patients were evaluable for prophylactic efficacy. Chest wound and donor site infections and early prosthetic valve endocarditis occurred more frequently with cefonicid (11 patients, 6.3%) than with cefamandole (4 patients, 2.2%) (p = 0.05). Three patients, all in the cefonicid group, required sternal debridement to control postoperative deep wound infections. Twenty-five miscellaneous postoperative infections (urinary tract infection, pneumonia, intravenous site infection, bacteremia, sepsis, Clostridium difficile diarrhea) occurred in 16 patients (9.19%) in the cefonicid group and four in 4 patients (2.19%) in the cefamandole group (p = 0.003). These data indicate that cefamandole is superior to cefonicid in preventing both surgical wound infections and miscellaneous nonsurgical infections after cardiovascular operations.