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Duration of antibiotic prophylaxis. An experimental study.

An animal wound model was used to evaluate single dose cefazolin, multiple dose cefazolin, and single dose cefonicid in the prevention of wound infection. Incisions made in Swiss-Webster mice were contaminated with either Staph. aureus (1.94 X 10(8) colony forming units) or E. coli (4.39 X 10(8) colony forming units). Five experimental groups were studied. Group I encompassed control animals given saline solution, Group II animals given 10 mg cefazolin preoperatively, Group III animals given 10 mg of cefazolin preoperatively and postoperatively, Group IV animals given 10 mg of cefonicid preoperatively, and Group V animals given 20 mg of cefonicid preoperatively. All medications were given by intraperitoneal injection. Antibiotics were given 1 hour before operation. Postoperative doses were given 4 hours after operation. Incisions were opened 48 hours after surgery and wound bacterial concentrations were determined. After both Staph. aureus and E. coli contamination, each of the four cephalosporin regimens significantly reduced the mean wound bacterial concentrations compared with that of the control animals (p less than 0.001). Each of the four cephalosporin regimens also significantly reduced the number of infected wounds compared with that of the control subjects (p less than 0.001). No significant differences were noted among the four antibiotic regimens with respect to mean wound bacterial concentration or infection rate. In the context of this model, a single dose of cefazolin seems to be equally effective as multiple doses of the drug for surgical prophylaxis. Extended half-life cephalosporins, like cefonicid, do not appear to be more effective than a single dose of cefazolin, which is a much less expensive antibiotic.

Animals↗

Effect of cephalosporins on fascial healing after celiotomy.

A 7 day course of either cefonicid or cefazolin significantly reduced mean wound breaking weight after midline celiotomy in Sprague-Dawley rats compared with control animals. This detrimental effect was not seen when each drug was administered as a single preoperative dose. Even a 3 day course of cefonicid was associated with a significant reduction in the weight required to disrupt a healing abdominal closure. An increased incidence of incisional hernias was also noted among animals treated for 7 days with cefonicid or cefazolin. Shorter antibiotic regimens were not associated with an increased frequency of incisional herniation.

Animals↗

Treatment of bacterial osteomyelitis and Staphylococcus aureus endocarditis and single-dose therapy for uncomplicated Neisseria gonorrhoeae infections: an overview.

Cefonicid is a new second-generation cephalosporin that has broad-spectrum antibacterial activity, achieves high peak serum concentrations, and has a long half-life. The high serum concentration and long half-life of cefonicid make it feasible to administer the drug once daily either intravenously or intramuscularly. For the treatment of bacterial osteomyelitis, a specific antibacterial agent is administered for four to eight weeks. Ideally, the optimal antibiotic should have good activity against organisms commonly implicated in bone infections, be easy to administer, be stable in inflammatory conditions, achieve good concentrations in bone, and have minimal toxicity. For treatment of Staphylococcus aureus endocarditis, the same criterion of minimal toxicity should be met for the agent used; in addition, it should have excellent antistaphylococcal activity in vivo and in vitro, be stable to beta-lactamase, and exhibit good bactericidal activity at trough serum levels. In uncomplicated Neisseria gonorrhoeae infections, the ideal antibiotic should be one that could be administered in a single dose in a small volume and would not be painful on intramuscular injection. The antibiotic should be nontoxic; stable to N. gonorrhoeae beta-lactamase; and reliably able to eradicate urethral, endocervical, rectal, and pharyngeal infections. Cefonicid may fulfill some of these criteria.

Animals↗

Effect of protein binding on drug penetration into blister fluid.

The effect of protein binding on drug penetration into blister fluid was evaluated by using cefonicid, ceftizoxime, and cefotaxime. Drug concentrations in a chamber with a high surface area/volume ratio (i.e., paper disk) follow changes in serum more closely than do those in a chamber with a low surface area/volume ratio. Both the area under the concentration-time curve ratio and the concentration ratio (by the disk method) for cefonicid were statistically lower than the ratios for ceftizoxime and cefotaxime. The high degree of protein binding of cefonicid results in the availability of less drug for diffusion to blister fluid than with the low-protein-binding ceftizoxime and cefotaxime.

Adult↗

Role of long-acting cephalosporins in ambulatory therapy.

Selected patients with community-acquired infections can be discharged from the hospital, when afebrile and stable, with parenteral antibiotic therapy continued on an ambulatory basis. This therapy is currently possible because of the availability of long-acting cephalosporins that can be administered once daily, often with substantial reductions in hospital costs. Cefonicid and ceftriaxone both have sufficiently long half-lives and either may be administered intramuscularly once daily. Their antibacterial spectra encompass many of the pathogens encountered in community-acquired infections of the lower respiratory tract, skin and soft tissue, bone, and urinary tract. Ceftriaxone, a third-generation cephalosporin, has a broader spectrum than the second-generation agent cefonicid. Ceftriaxone should generally be reserved for the treatment of gonococcal disease and of community- or hospital-acquired infections due to organisms resistant to the narrower-spectrum and less expensive long half-life agent cefonicid.

Ambulatory Care↗

Use of long half-life parenteral cephalosporins in ambulatory practice.

Cefonicid (Monocid) and ceftriaxone (Rocephin) are long half-life cephalosporins that may be used for serious infections in the outpatient setting. They may be used as an extension of initial hospital treatment, or therapy can be initiated and completed in many cases with the patient remaining at home. Sufficient clinical experience exists with both ceftriaxone and cefonicid to recommend these agents for selected patients having pyelonephritis, osteomyelitis, or soft tissue infections. Cefonicid, perhaps in combination with erythromycin, will provide excellent coverage for complicated community-acquired pneumonias. Ceftriaxone is effective as single-dose therapy for even complicated gonococcal infections. The use of long half-life cephalosporins in ambulatory practice may result in substantial cost savings for certain patients.

Ambulatory Care↗

The efficacy of a single dose antibiotic regimen in adults undergoing tonsillectomy.

Several studies have indicated that antibiotics given for 5-7 days post-tonsillectomy are beneficial. A prospective double blind randomized study was undertaken to evaluate the efficacy of a long-acting antibiotic (Cefonicid) given prophylactically at the time of tonsillectomy. Dependent variables were percent weight loss, number of doses of pain medications required postoperatively, the number of days required to resume a normal diet, and return to work. The results of all independent tests indicated that there were no statistically significant differences between the Cefonicid group and the placebo group. The results of this study indicate that single dose prophylactic application of Cefonicid is not effective in adults undergoing tonsillectomy.

Adolescent↗

In vitro susceptibilities of 176 clinical isolates of Streptococcus pneumoniae to 11 beta-lactams, erythromycin, and tetracycline.

One hundred seventy six consecutive, non-duplicate pneumococcal isolates from clinical specimens collected from November 1994 through February 1995 in nine general hospitals throughout Belgium were tested for their in vitro susceptibilities to penicillin, ampicillin, amoxycillin with and without clavulanate, cefaclor, cefuroxime, cefonicid, cefprozil, cefpodoxime, cefotaxime, imipenem, tetracycline, and erythromycin by means of the NCCLS microdilution test. The overall rate of decreased susceptibility to penicillin was 12.5%, including 6.3% of intermediately and 6.3% of fully resistant isolates. Penicillin, ampicillin amoxycillin, amoxycillin/clavulanate, cefuroxime, cefotaxime and imipenem had the highest activity on a weight basis (MIC50 < or = 0.008 microgram/ml), followed by cefpodoxime and erythromycin (MIC50 of 0.015 microgram/ml), cefprozil and tetracycline (MIC50 of 0.12 microgram/ml), and eventually, cefaclor and cefonicid (MIC50 of 0.5 microgram/ml). Aggregate rates of susceptible plus intermediately resistant isolates at NCCLS-recommended breakpoints, i.e. overall percentages of isolates likely to respond to increased antibiotic doses in vivo (except for meningitis), were 100.0% for imipenem and cefotaxime, 98.9% for amoxycillin with and without clavulanate, 93.8% for penicillin, and 90.9% for cefuroxime. Overall rates of susceptibility to erythromycin and tetracycline amounted to 78.4% and 72.7%, respectively. MIC values of all beta-lactams increased with those of penicillin. Ampicillin was equally active as penicillin against isolates with reduced susceptibility to the latter (MIC90 of 2 micrograms/ml); imipenem, cefotaxime, and amoxycillin with and without clavulanate however, were more active (MIC90 3, 1, and 1 doubling dilution, respectively, below that of penicillin), while cefpodoxime, cefuroxime, cefprozil, cefonicid, and cefaclor on the other hand, were less active (MIC90, 1, 1, 2, 5, and 5 doubling dilutions, respectively, above that of penicillin). In conclusion, the present data confirm that pneumococcal resistance to penicillin has increased in Belgium, suggest that resistance to erythromycin may have stabilised, and reveal an unexpectedly high rate of resistance to tetracycline. Imipenem was the most active antibiotic tested overall, and amoxycillin with or without clavulanate the most active oral antibiotic, with activity almost similar to that of cefotaxime.

Anti-Bacterial Agents↗

Ceforanide. A review of its antibacterial activity, pharmacokinetic properties and clinical efficacy.

Ceforanide is a 'second generation' cephalosporin administered intravenously or intramuscularly. It is similar to cefamandole and cefonicid in its in vitro superiority to 'first generation' cephalosporins against several species of Enterobacteriaceae as well as its activity against Haemophilus influenzae, including beta-lactamase-producing strains. Its activity against Staphylococcus aureus is less than that of cefamandole, cefuroxime and first generation cephalosporins. The in vitro activity against Neisseria gonorrhoeae is excellent. Pseudomonas, Acinetobacter and Serratia species, and Bacteroides fragilis are resistant, as are many strains of Proteus and Providencia species. The elimination half-life is relatively long, although shorter than that of cefonicid, and in most clinical trials ceforanide has been administered twice daily. It appeared to be comparable in therapeutic efficacy to procaine penicillin and cephazolin in the treatment of patients with community-acquired pneumonia, to cephazolin in the treatment of skin and soft tissue infections due to S. aureus or beta-haemolytic streptococci and to cefapirin in S. aureus endocarditis in parenteral drug abusers. Also, it was comparable in efficacy to cephalothin in the prophylaxis of infection in patients undergoing open heart surgery or vaginal hysterectomy, and to cephazolin in patients undergoing cholecystectomy. Thus, ceforanide is an alternative to first and certain other second generation cephalosporins in several important therapeutic and prophylactic situations. It has no advantage over other cephalosporins with regard to spectrum of antibacterial activity, but has a longer half-life than other second generation cephalosporins, except cefonicid, and can be administered according to a twice daily dosage schedule.

Bacteria↗

Fibrin glue-antibiotic suspension in the prevention of prosthetic graft infection.

UNLABELLED: The following study was done to assess whether fibrin glue-antibiotic suspension (FGAS) can prevent infection of a PTFE vascular graft in a contaminated wound. METHODS: FGAS was made by combining cryoprecipitate with a mixture of bovine thrombin, aminocaproic acid, and tobramycin (5 mg/cc thrombus). Antibiotic activity was documented by in vitro kinetics which revealed initial elutions to be greater than 8,000 mu gm/cc and elutions at 4 days to be greater than 2 mcg/cc. Twelve dogs had a 1-cm section of infrarenal aorta replaced with a PTFE graft that had been bathed in a 2-cc solution of E. coli 3 x 10(8) CFU/ml and S. aureus 3 x 10(8) CFU/ml. Both organisms were sensitive to tobramycin and cefonicid. Dogs were divided into three groups of four. Group I had a contaminated PTFE graft placed and no further therapy. Group II had a contaminated PTFE graft placed and sealed with fibrin glue. Group III had a contaminated PTFE graft placed and sealed with FGAS. All three groups received daily IV cefonicid. RESULTS: Group I: Four of four dogs were reoperated on the fourth day for suspected sepsis and all four had pseudoaneurysms (one ruptured). Three of four were culture positive for S. aureus and two of four positive for E. coli. Group II: Four of four died of anastomotic disruption by the third day. Four of four were culture positive for S. aureus and E. coli. Group III: All four dogs survived and were sacrificed on Day 17: all anastomoses were normal. Animal survival was significantly associated with the treatment given (p = 0.0025). Three of four tissue cultures of the grafts were weakly positive for S. aureus and one of four for E. coli and Pseudomonas. Serum tobramycin levels were negligible at 12, 24, 72, and 96 hours. CONCLUSIONS: The data show that FGAS was associated with a reduction in vascular graft infection and pseudoaneurysm formation after exposure to a standardized bacterial inoculum. Whether complete eradication of all organisms can be achieved with higher doses of tobramycin is as yet undetermined.

Aneurysm, Infected↗

Development of revised quality control limits for disk diffusion susceptibility tests of selected cephem antibiotics with Haemophilus influenzae and description of a new control strain.

Inconsistent quality control results in disk diffusion testing of cefaclor, cefamandole, cefonicid, and cefuroxime with Haemophilus influenzae ATCC 49247 and Haemophilus test medium (HTM) prompted a search for an alternative control strain that would provide more reliable results. A five-laboratory study was conducted to evaluate two candidate H. influenzae strains as possible alternatives to the aforementioned strain. Repetitive testing of the candidate strains and H. influenzae ATCC 49247 over several days with a total of six different lots of HTM documented consistent performance of the two candidate strains and confirmed inconsistent results for some of the antibiotics with H. influenzae ATCC 49247. In particular, certain lots of HTM failed to yield cefaclor and cefamandole zone sizes within the quality control range advocated by the National Committee for Clinical Laboratory Standards. Because of the greater consistency offered by the new strains, one was selected (now designated H. influenzae ATCC 49766) to be recommended for routine quality control testing of cefaclor, cefamandole, cefonicid, cefuroxime, and the related carbacephem loracarbef. The new control strain and zone size ranges proposed here have been approved by the National Committee for Clinical Laboratory Standards in place of the previously recommended strain and zone size limits for testing of these five cephem antibiotics.

Ampicillin↗

Comparative in-vitro activity of selected new beta-lactam antimicrobials against Neisseria gonorrhoeae.

Four new beta-lactam antimicrobials, ceftriaxone, cefotiam, cefonicid, and mecillinam, were evaluated in vitro against 72 beta-lactamase-negative and 26 beta-lactamase-positive isolates of Neisseria gonorrhoeae. Ceftriaxone was the most active of the antimicrobials tested. It inhibited all isolates, regardless of beta-lactamase activity, at a concentration of less than or equal to 0.015 microgram/ml. Cefotiam and cefonicid were also active against both groups but not as active as ceftriaxone. Both groups of N gonorrhoeae showed a high degree of resistance against mecillinam.

Amdinocillin↗

Antimicrobial prophylaxis in urologic surgery: does it give some benefit?

Three types of antibiotic prophylactic regimens were evaluated versus a control without prophylaxis (group A: 3,912 cases) in urologic surgery. The antibiotic regimens were: group B = cefazolin 1 g/12 h/3 days (3,660 cases); group C = cefonicid 1 g/24 h/3 days (2,076 cases), and group D = cefonicid 1 g single dose (3,169 cases). The parameters used were the comparison of the corresponding rates of postsurgical sepsis and operative wound infections. Numeric investigations for the validity of a retrospective study (unpaired data) were performed: homogenicity test, relative risk point estimate and confidence limits (95%), and etiological fraction point estimate and confidence limits (95%). Chi-square for other purposes were performed. Endoscopic handling was considered homogeneous (same infective risk), while open surgery was heterogeneous (p < 0.001). In order to avoid probable bias, a correction factor was used. Although in different degrees, prophylaxis significantly reduced the morbidity of surgical wound infections (p < 0.001; etiological fraction > 90%). The differences (p < 0.01) between groups B and C/D were attributed to pharmacokinetic causes (short T 1/2 of cefazolin). To obtain the maximum protective effect, the use of antibiotics with a T 1/2 of > 4 h is suggested. There was no resistant mutans in previously sensitive strains. However, a significant selection of intrinsically resistant strains was observed. Monodose offers at lest the same advantages as multiple-dose therapy. In addition, the monodose selected in a lesser proportion both the resistant strains (p < 0.001) and the number of microbial associations (p < 0.01).

Cefazolin↗

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.

Adolescent↗

Experimental tracheal revascularization with omentum.

We assessed omental revascularization of heterotopic tracheal implants in rats, and investigated the influence of factors that can enhance revascularization. The trachea of the donor animal was excised in two parts, and each tracheal allograft was implanted in the omentum of two recipients. The influence of mechanical factors was evaluated by applying traction at both ends of the graft with and without drainage of the tracheal lumen, and the influence of pharmacologic factors by giving cefonicid, hydrocortisone, cefonicid plus hydrocortisone, or cyclosporine and azathioprine during the postoperative period. Revascularization of the graft from the omentum with preservation of the tracheal structure was established. Graft viability showed significant differences between the tracheal implants to which no traction had been applied and those with traction at both ends. Tracheal allografts from animals receiving immunosuppressants were completely viable and no significant differences were found between the controls and animals in this group.

Animals↗

Impact of drug policy on the use of parenteral cephalosporins in Italy.

OBJECTIVE: To evaluate the effects of the 1998 revision of CUF Note 55 on doctors' prescribing behaviour and drug costs with regard to intramuscularly administered cephalosporins. METHOD: National data on drug use between January 1998 and June 2000 were provided by the Drug Utilisation Monitoring Centre of the Ministry of Health. The Anatomic Therapeutic Chemical classification and the Defined Daily Dose methodology, as well as population estimates obtained from the Italian National Statistics Institute were used to define consumption as the number of defined daily doses per 1000 inhabitants per day. The cost of these antibiotic medications was determined using the wholesale price reported in Informatore Farmaceutico. Italian inflation rates were used to annuitize the expenditure. "STATA 6.0" software was used for all statistical analyses. RESULTS: The use of cefonicid rose dramatically after the revision (+ 136.3%), whereas the utilisation of the other active ingredients decreased. A decrease of 5.6% in the expenditure for all parenteral cephalosporins was observed in this period while the same figure increased by 2.3% after one year. CONCLUSION: The exclusion of cefonicid from a restricted list appears to have significantly affected doctors' prescribing practices, while the effect on drug expenditure was contradictory.

Cephalosporins↗

In-vitro activities of trospectomycin, cefpodoxime, and second-generation cephalosporins against Haemophilus influenzae type b.

The in-vitro activities of trospectomycin, cefpodoxime, cefamandole, cefonicid, and cefuroxime against beta-lactamase-negative and -positive invasive clinical isolates of Haemophilus influenzae type b were determined by the agar dilution method. Trospectomycin and cefpodoxime inhibited 90% of the strains at concentrations of 5 and 0.06 mg/l, respectively, and no differences between the susceptibilities of the beta-lactamase-negative and -positive strains were noted. The activity of cefpodoxime was minimally affected by increased inoculum size, but significant inoculum effects were noted with cefamandole, cefonicid, and cefuroxime with beta-lactamase positive strains.

Anti-Bacterial Agents↗

Nationwide study of the susceptibility of the Bacteroides fragilis group in the United States.

A nationwide susceptibility survey of the Bacteroides fragilis group was continued at New England Medical Center in 1983. A total of 555 strains were obtained from eight centers in the United States. In addition to the nine antimicrobial agents studied in the two previous years, three other agents were added to the evaluation: cefamandole, cefuroxime, and cefonicid. The results for the strains tested with the original nine drugs in 1983 were compared with those for 1,292 isolates tested in 1981 and 1982. The most active beta-lactam drug was piperacillin, which had an 8% resistance rate. Cefoxitin resistance increased from 10% in 1982 to 16% in 1983. High rates of resistance to cefotaxime, cefoperazone, cefamandole, cefonicid, and cefuroxime were encountered. No metronidazole- or chloramphenicol-resistant isolates were found during the 3 years of the study. Susceptibility patterns varied at the eight hospitals: the outbreak of cefoxitin resistance reported in 1982 at New England Medical Center remitted, while a high clindamycin resistance rate was documented at one hospital in 1983. These data indicate the need for determining the susceptibility patterns for the B. fragilis group of organisms at each hospital.

Anti-Bacterial Agents↗