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PubMed1987

Parenteral antibiotic therapy at home: experience with intramuscular cefonicid.

Patients with serious infections often remain hospitalized solely to continue parenteral antibiotic therapy although many who are afebrile and medically stable could complete treatment in an outpatient setting. Potential advantages of outpatient treatment include lower costs and greater efficiency in the use of hospital beds, and economic and psychological benefits to patients. Cefonicid, a parenteral cephalosporin with an extended antibacterial spectrum and a prolonged serum half-life, was used to treat 39 patients with serious infections, mostly those of bone or soft tissues. Staphylococcus aureus was the predominant pathogen isolated (18 patients); nine gram-negative aerobes were observed in single instances. After indicated surgical procedures and inpatient intravenous antibiotic therapy, the patients were discharged to continue parenteral therapy at home with once-daily intramuscular doses of cefonicid. Mean duration of outpatient therapy was 16 days. The clinical response was satisfactory in all but two patients, one with relapse of a S aureus wound infection, the second with a gram-negative reinfection at the site of a bone cyst. Systemic and local tolerability of cefonicid were good. It is concluded that outpatient antibiotic therapy with intramuscular cefonicid can benefit both patients and hospitals.

Adolescent↗

PubMed1987

A comparison of cefonicid with other beta-lactams regarding the effect of human and mouse sera on antibacterial activity.

The effect of the addition of 50% human or mouse serum on the antibacterial activity of cefonicid, three first generation cephalosporins and ampicillin was studied. Human serum added to the test system considerably reduced the activity of cefonicid against Staphylococcus aureus and Staphylococcus epidermidis strains, and to a lesser degree against Proteus mirabilis, Escherichia coli and Klebsiella pneumoniae strains. Human serum also reduced, albeit to a lesser extent, the activities of cephalothin, cefazolin, and ampicillin, whereas it increased the activity of cephaloridine. In contrast, mouse serum did not or only insignificantly reduced the activity of cefonicid against some of the bacterial isolates; this is reflected in the excellent protective effect of cefonicid in experimental mouse infections.

Animals↗

PubMed1983

Plasma and myocardial levels of cefonicid during open-heart surgery.

To minimize the incidence of postoperative infections in patients undergoing open-heart surgery, antibiotics should maintain tissue concentrations greater than the minimal inhibitory concentration (MIC) for potential pathogens (eg, Staphylococcus) for the duration of the operation. The ability of cefonicid, a new β-lactamase-resistant parenteral cephalosporin, to attain plasma and myocardial levels greater than the MIC (4.8 to 5.0 μg/mL) for penicillin-resistant Staphylococci was assessed in 13 patients. Six patients were administered 1 g and seven patients were administered 2 g of cefonicid IM one hour prior to surgery. In all patients the plasma concentrations of the drug were determined at the start of surgery, 15 minutes after the patient was placed on cardiopulmonary bypass (CPB), and at the completion of CPB. In addition, the concentration of cefonicid was determined in a right atrial biopsy. It was found that both 1 g and 2 g of cefonicid administered one hour prior to surgery resulted in plasma and myocardial levels greater than the MIC for the organisms most frequently implicated in postoperative infections.

Aged↗

PubMed1995

A double-blinded, randomized, controlled clinical trial to compare cefazolin and cefonicid for antimicrobial prophylaxis in clean orthopedic surgery.

A double-blind, prospective randomized study was performed to compare cefazolin and cefonicid given for prophylaxis to 102 patients undergoing orthopedic surgery. Risk factors (e.g., age, sex, type of operation performed) among the two groups were similar. All patients had foreign material (prosthesis or other hardware) inserted at operation. There was a total of 6 infections (3 wound and 3 urinary tract) in 6 patients among the 48 receiving cefazolin (12.5%), whereas no infections were observed among the 54 patients who received cefonicid. Cefonicid, given once daily, provides protection against postoperative infection that is not inferior to cefazolin. A larger study is needed to confirm whether cefonicid is indeed superior to cefazolin.

Adolescent↗

PubMedDate not supplied

Cefonicid: a long-acting, second-generation cephalosporin. Antimicrobial activity, pharmacokinetics, clinical efficacy and adverse effects.

Cefonicid is a new second-generation cephalosporin with a broad antimicrobial spectrum of activity and a prolonged serum elimination half-life. It has good in vitro activity against methicillin-sensitive Staphylococcus aureus, nonenterococcal streptococci, Hemophilus influenzae, Neisseria gonorrhoeae, Neisseria meningitidis and many of the commonly isolated Enterobacteriaceae. Organisms usually resistant to cefonicid include species of Pseudomonas, Serratia, Acinetobacter and Providencia, and Bacteroides fragilis. The drug is 98% protein bound in human serum, which probably contributes to its significant reduction of antimicrobial activity measured in serum. Limited clinical trials have demonstrated it to be effective for surgical prophylaxis and for treating infections of the urinary tract, lower respiratory tract and bone. Failures have been reported in treatment of soft tissue infections and endocarditis caused by S. aureus. A potential cost reduction may be achieved by administering a single daily dose of cefonicid for established infections or a single preoperative dose for effective surgical prophylaxis instead of multiple-dose regimens of other, similar agents.

Bacteria↗

PubMed2003

Determination of cefonicid in human urine by adsorptive square-wave stripping voltammetry.

The adsorption behavior of cefonicid on the hanging mercury drop electrode (HMDE) has been examined using cyclic voltammetry and square-wave voltammetry techniques in Britton-Robinson (B-R) buffers in the pH range of 2.0-11.0. The effect of different parameters on the accumulation behavior of the adsorbed species has been evaluated. Sensitive measurements can be achieved after controlled adsorption on the surface of HMDE followed by square-wave voltammetry. Under optimal conditions, a detection limit of 4.0 x 10(-8) M and a linear calibration graph in the range 1.0 x 10(-7)-1.0 x 10(-6) M were obtained. Direct simple determination of cefonicid in urine was established with no manipulation of urine sample other than dilution and subsequent adsorptive stripping voltammetric determination. The detection limit of the method was 1.0 microg x ml(-1) of cefonicid in urine.

Adsorption↗

PubMed1981

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.

Adult↗

PubMed1991

Penetration of cefonicid into serum, salpinges, cervix and vaginal tissue.

Cefonicid is a new cephalosporin that, given in adequate concentrations is able to kill some pathogens such as Gram-positive cocci and many Enterobacteriaceae. In this study we have evaluated 40 patients receiving 1 g of cefonicid i.m. at various times before abdominal or vaginal hysterectomy. The results of the present study indicate that a single dose of 1 g of cefonicid given intramuscularly is useful as prophylaxis and treatment of gynecological infections.

Cefonicid↗

PubMed1996

Failure of cefonicid prophylaxis for infectious complications related to endoscopic retrograde cholangiopancreatography.

We performed a controlled study to evaluate the role of cefonicid in preventing infectious complications related to retrograde cholangiopancreatography (ERCP). Consecutive patients were randomized to receive prophylaxis with cefonicid (1 g intravenously) 1 hour before the procedure or to be untreated controls. During a 26-month period, 179 ERCPs, including 93 therapeutic procedures, were performed on 164 patients. Prophylaxis was administered before 88 procedures (49%). The rate of bacteremia among treated patients was similar to that among controls (3% vs. 2%, respectively; P = .4). The rate of cholangitis was also similar among both groups (8% vs. 2%, respectively; P = .07). There were no episodes of sepsis, and none of the patients died. The rate of bacteremia was also similar among patients undergoing diagnostic procedures and patients undergoing therapeutic procedures, but all cases of cholangitis occurred in the latter group (0 vs. 10%, respectively; P = .002). Nevertheless, the rate of cholangitis was not significantly changed by the use of prophylaxis (14% among treated patients vs. 5% among controls, P = .12). Therefore, infectious complications could not be prevented by cefonicid prophylaxis.

Bacteremia↗

PubMedDate not supplied

Tissue penetration and half-life of cefonicid.

The pharmacokinetics of cefonicid in the serum and tissues of patients undergoing open heart surgery, vaginal hysterectomy, and hip replacement was studied and compared with that of cefazolin and cefoxitin. Cefonicid achieved serum and tissue concentrations that were higher and more prolonged than those of cefazolin and cefoxitin. For cefonicid parallelism was observed between the serum and tissue concentration-time curves. Correlations of these properties to clinical efficacy were not attempted.

Adult↗

PubMedDate not supplied

Single-dose regimen of cefonicid for the treatment of uncomplicated infections of the lower urinary tract.

Fifty-three women with symptoms of lower urinary tract infection were randomly assigned to treatment with cefonicid administered intramuscularly in a single 1-g dose or to treatment with 500 mg of amoxicillin administered orally three times a day for five to seven days. Urine cultures were obtained before therapy and again at five to 18 days and six to seven weeks after termination of therapy. Forty-one patients had greater than or equal to 2 X 10(4) colony-forming units (cfu)/ml of catheterized urine or greater than or equal to 10(5) cfu/ml of midstream urine. In the cefonicid-treated group, 19 (90%) of 21 patients demonstrated bacteriologic cure at early follow-up. Of the 18 patients seen at late follow-up, 15 were cured and three were reinfected. One patient was lost to late follow-up. In the amoxicillin-treated group, 16 (80%) of 20 patients demonstrated bacteriologic cure at early follow-up. Of the 15 patients available at late follow-up, 14 were cured and one was reinfected. One patient was lost to late follow-up. Cefonicid is an effective single-dose agent in uncomplicated lower urinary tract infection.

Adult↗

PubMedDate not supplied

Cefonicid in a once-daily regimen for treatment of osteomyelitis in an ambulatory setting.

Fifteen patients with bone joint infections were treated with 1.0 g of cefonicid administered intravenously or intramuscularly once daily. Single organisms isolated included Staphylococcus aureus (from six patients), Staphylococcus epidermidis (three), and Peptococcus species (one). For four patients infection was polymicrobial, and for one patient no organism was isolated. The mean duration of therapy was 40.4 days, only 10.9 days of which were spent in the hospital. The remainder of therapy was administered intramuscularly in an ambulatory setting. Therapy was successful in all 12 assessable patients. No clinical or bacteriologic relapse occurred in the follow-up period of three to 13 months. The occurrence of adverse effects prompted discontinuation of cefonicid therapy in three patients. Minimum savings in hospital-bed costs alone were $64,350, with 390 hospital days avoided. The minimum savings in work income were $10,010, with 182 days of absenteeism avoided. These data are preliminary but suggest efficacy of cefonicid in a mode of therapy that could have profound cost benefits.

Adult↗

PubMedDate not supplied

Failure of a once-daily regimen of cefonicid for treatment of endocarditis due to Staphylococcus aureus.

Cefonicid, a new long-acting cephalosporin, was evaluated for treatment of endocarditis due to Staphylococcus aureus. Four patients, all with infection of the tricuspid valve, were treated with a single daily injection. By the fifth day of therapy, three of the four patients continued to have spiking fevers and positive blood cultures, and treatment with cefonicid was discontinued. Even though peak concentrations of antibiotic in serum were greater than 20-40 times the minimum inhibitory concentration of the antibiotic for the infecting organism, serum bactericidal titers were less than 1:8 in three patients. Susceptibility testing of 52 clinical isolates in broth confirmed a marked difference between inhibitory and bactericidal concentrations for 40% of these strains. In addition, susceptibility testing performed in serum rather than broth resulted in a sixfold increase in the minimum inhibitory concentration, a result suggesting that protein binding may be in part responsible for these failures of treatment. Cefonicid administered as a single daily dose is inadequate for treatment of endocarditis due to S. aureus and should not be used for treatment of bacteremia or life-threatening infections known or suspected to be caused by this organism.

Adult↗

PubMed1983

Clinical trial of cefonicid for treatment of skin infections.

Twenty patients with skin and soft-tissue infections were treated with parenteral cefonicid. Cultures obtained in cellulitis cases from an aspirate of a leading edge of inflammation were positive in 42% of these patients. Pathogens isolated were Staphylococcus aureus (six strains), Proteus mirabilis (one strain), and Streptococcus agalactiae. Adverse effects were pain on intramuscular injection (two patients), rash (one patient), and positive Coombs test (one patient). All side effects were mild and none required discontinuing antibiotic therapy. A single treatment failure occurred in a patient with an undrained perirectal abscess. Cefonicid may be a useful drug in the treatment of skin and soft-tissue infections. The long half-life of cefonicid (4.8 h) is a valuable advantage and may facilitate patient compliance and convenience.

Adult↗

PubMed1986

Comparative in vitro evaluation of cefonicid, cefazolin, and penicillin against viridans group streptococci isolated from blood.

The in vitro activity of cefonicid against 60 strains of viridans group streptococci isolated from blood of patients with bacteremia and infective endocarditis was compared with those of cefazolin and penicillin. Cefonicid was less active than cefazolin, and both cephalosporins were less active than penicillin. The MIC50 and MIC90 for the strains tested were 0.06 and 1 microgram/ml for penicillin, 0.125 and 8 micrograms/ml for cefazolin, and 4 and 32 micrograms/ml for cefonicid.

Cefamandole↗

PubMed1987

Peritoneal transport of cefonicid.

The pharmacokinetic characteristics of cefonicid, a highly protein-bound expanded-spectrum cephalosporin, were examined in six noninfected, clinically stable patients undergoing continuous ambulatory peritoneal dialysis. After a 1.0-g intravenous dose of cefonicid, the mean concentrations in serum were 105 +/- 25 and 35.6 +/- 14.4 micrograms/ml at 3 and 72 h, respectively. Despite a prolonged half-life in serum of 49.7 +/- 18 h, the penetration into peritoneal fluid was low. The average concentration in dialysate over the 72-h study period was 2.7 micrograms/ml. The serum clearance was 2.6 +/- 1.0 ml/min, and the distribution volume was 0.14 +/- 0.02 liter/kg. Dosage recommendations and clinical considerations for cefonicid use in continuous ambulatory peritoneal dialysis patients are discussed.

Cefamandole↗

PubMed1987

Effects of cefonicid and other cephalosporin antibiotics on male sexual development in rats.

The purpose of this study was to determine whether cefonicid, a cephalosporin antibiotic with a modified N-methylthiotetrazole (MTT) side chain, caused testicular toxicity when subcutaneously administered to Sprague-Dawley male rats from days 6 to 36 postpartum at doses of 50 to 1,000 mg/kg per day. Moxalactam (a cephamycin antibiotic which will be referred to as a cephalosporin for convenience throughout), which contains the MTT side chain, was used as a positive control and was administered at 100 to 1,000 mg/kg per day, and cephalothin, which lacks an MTT side chain, was used as the negative control at 1,000 mg/kg per day. Moxalactam caused a significant reduction in testicular and seminal vesicle weights in 37-day-old animals, and histological examination revealed bilateral multifocal atrophy of the seminiferous tubules at all dose levels. Animals reared to reproductive maturity had significant deficits in fertility, and histological examination revealed multifocal or diffuse atrophy of the seminiferous tubules at all doses with a severity greater than that observed in the 37-day-old animals. The histological findings were confirmed by marked reductions in testicular sperm production rates and cauda epididymal sperm numbers. Cephalothin and cefonicid had no treatment-related adverse effects on the sexual maturation of prepubertal, juvenile, or adult males. The absence (in cephalothin) or modification (in cefonicid) of the MTT side chain was not associated with adverse reproductive effects. The relevance of these findings to humans in prenatal and prepubertal stages of life cannot be determined at this time.

Age Factors↗

PubMed1990

Randomized, double-blind trial of cefonicid and nafcillin in the treatment of skin and skin structure infections.

We compared treatment with one daily intravenous dose of cefonicid and multidose nafcillin in 65 patients with severe infections of the skin or skin structure. Clinical cure or improvement was achieved in 91% of the patients given cefonicid and in 87% of the patients given nafcillin (P = 0.97). The use of cefonicid may allow outpatient therapy of some severe infections.

Adolescent↗