cefamandole and ceforanide

Antistaphylococcal penicillins and first-generation cephalosporins have traditionally been the prophylactic antibiotics of choice for patients undergoing cardiothoracic operations. Recently published studies have claimed improved outcomes with respect to postoperative wound infection when second-generation cephalosporins were used for prophylaxis. The purpose of this study was to critically review the infectious outcomes of prospective, randomized, and controlled studies of cardiothoracic surgery prophylaxis by means of meta-analytic techniques. For each of 28 studies meeting the meta-analysis entry criteria, odds ratios with 95% confidence intervals were calculated to compare the prophylactic efficacy of the antibiotic regimens. Odds ratios were then pooled, and a summary odds ratio was calculated for each pairing of antibiotic treatments. Placebo-controlled trials of cardiothoracic prophylaxis demonstrated a consistent benefit to the administration of antibiotic prophylaxis, with an approximate fivefold reduction in wound infection rate. The second-generation cephalosporins, cefamandole and cefuroxime, performed better than cefazolin, with an approximate one and one-half-fold reduction in wound infection rate. Administration of prophylaxis beyond 48 hours was not associated with improved infectious outcomes.

Topics: Anti-Bacterial Agents; Cardiac Surgical Procedures; Cefamandole; Cefazolin; Ceftriaxone; Cefuroxime; Cephalosporins; Cephalothin; Cephradine; Clinical Trials as Topic; Humans; MEDLINE; Meta-Analysis as Topic; Penicillins; Postoperative Period; Premedication; Prospective Studies; Randomized Controlled Trials as Topic; Surgical Wound Infection; Thoracic Surgery

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.

Topics: Bacteria; Cefamandole; Humans; Infections; Microbial Sensitivity Tests

The new second-generation cephalosporins, cefonicid, ceforanide, and cefuroxime, have recently become available. These agents are generally less active against gram-positive cocci than first-generation cephalosporins and, at best, equal to cefoxitin and cefamandole against many gram-negative bacteria. Cefuroxime, however, is the most active cephalosporin for beta-lactamase-producing Haemophilus influenzae. These newer agents have superior pharmacokinetic characteristics over cefoxitin and cefamandole. Smaller doses, longer dosing intervals and, potentially, a reduction in total drug cost may be the real advantage of these agents. Open trials and a limited number of comparative studies have documented the effectiveness of cefonicid, ceforanide, and cefuroxime in the treatment of most mild-to-serious infectious diseases, although failures with cefonicid in the treatment of staphylococcal infections have been reported. Notably, cefuroxime has received approval for the treatment of common pediatric bacterial meningitis infections. Replacement of cefamandole or cefoxitin with one of these "longer-acting" agents may be cost-beneficial; however, clinicians must be on alert for the development of bacterial resistance or decreased efficacy.

Topics: Bacteria; Bacterial Infections; Cefamandole; Cefonicid; Cefuroxime; Cephalosporins; Costs and Cost Analysis; Humans; Kinetics

In vitro susceptibility of Streptococcus pyogenes, Staphylococcus aureus, Staphylococcus epidermidis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Serratia marcescens, Hemophilus influenzae, Bacteroides fragilis, and Neisseria gonorrhea to three new second-generation and eight third-generation cephalosporins is tabulated. In general, the newer cephalosporins have an extended spectrum of activity against gram-negative bacteria, including Serratia marcescens, Pseudomonas aeruginosa, and Neisseria gonorrhea. They also tend to be active against anaerobes, including Bacteroides fragilis. However, they generally have less activity against gram-positive bacteria when compared with the first- and second-generation cephalosporins. Clinical summaries are given for each of the cephalosporins, with emphasis on the results of comparative clinical trials. These cephalosporins may prove especially useful in nosocomial infections with resistant organisms, intraabdominal infections, febrile episodes in the granulocytopenic patient, and meningitis.

Topics: Bacteria; Bacterial Infections; Bacteroides fragilis; Cefamandole; Cefoperazone; Cefotaxime; Cefotiam; Cephalosporins; Enterobacteriaceae; Haemophilus influenzae; Humans; Moxalactam; Pseudomonas aeruginosa

Topics: Cefaclor; Cefadroxil; Cefamandole; Cefazolin; Cefmetazole; Cefonicid; Cefoperazone; Cefotaxime; Cefotiam; Cefsulodin; Ceftizoxime; Cephalexin; Cephalosporins; Cephamycins; Cephradine; Humans; Intestinal Absorption; Kinetics; Moxalactam; Tissue Distribution

We studied the effect of different time intervals between antibiotic administration and tourniquet inflation in 62 patients undergoing reconstructive surgery in the lower extremities. The in vivo concentrations in soft tissue and bone of 3 cephalosporins (ceftazidime, ceftriaxone and ceforanide) were determined. Our findings suggest that the highest tissue concentrations were achieved by administration 20 min before tourniquet inflation.

Topics: Adipose Tissue; Adult; Aged; Bone and Bones; Cefamandole; Ceftazidime; Ceftriaxone; Cephalosporins; Female; Humans; Knee Prosthesis; Male; Middle Aged; Muscle, Skeletal; Prospective Studies; Skin; Time Factors; Tissue Distribution; Tourniquets

One hundred one patients undergoing total hip and knee arthroplasty were randomly assigned to receive either two 1 gm doses of ceforanide or five doses of cephalothin perioperatively. Simultaneous plasma and cancellous bone specimens were obtained intraoperatively and assayed for antibiotic concentration. Ceforanide plasma and bone levels remained sustained over six hours. Cephalothin plasma and bone levels obtained three to four hours post administration were 91% lower than levels obtained one hour post-dose. Patients were examined for infection for up to 18 months following surgery. None of the patients developed an infected implant. The sustained plasma and bone levels achieved with ceforanide obviate the need for intraoperative dosing necessary with other agents.

Topics: Adult; Aged; Aged, 80 and over; Bacterial Infections; Cefamandole; Cephalothin; Clinical Trials as Topic; Hip Prosthesis; Humans; Knee Prosthesis; Middle Aged; Premedication; Random Allocation

A randomized, prospective, double-blind study was designed to compare intravenous administration with intrauterine irrigation using an extended half-life (t1/2 = three hours) cephalosporin, ceforanide. Patients included in the study had a nonelective cesarean section with rupture of membranes for three hours or longer. Sixty-four patients received a single dose of ceforanide immediately after clamping the umbilical cord. Patients were similar in both groups in age, weight, length of labor, and duration of ruptured membranes. The group receiving the intravenous ceforanide had a significantly shorter duration of surgery than the patients receiving the intrauterine ceforanide. Endometritis infection rates were similar, 11.8% (intravenous) versus 11.1% (intrauterine), P greater than .1. Serum levels were as much as tenfold higher in the intravenous group versus the intrauterine group. Intrauterine irrigation with an antimicrobial agent provided no advantage over systemic administration.

Topics: Adult; Cefamandole; Cesarean Section; Clinical Trials as Topic; Double-Blind Method; Endometritis; Female; Humans; Injections, Intravenous; Postoperative Complications; Pregnancy; Premedication; Random Allocation; Risk; Therapeutic Irrigation; Urinary Tract Infections; Uterus

The response of serious skin and skin structure infections to ceforanide 1 gm every twelve hours or cefazolin 1 gm every eight hours was evaluated in ninety-six patients hospitalized for treatment. Most of the patients had decubitus ulcers; predominant pathogens were Staphylococcus aureus, Escherichia coli, and Proteus mirabilis. Ceforanide produced a satisfactory clinical response in 89 percent (forty-eight of fifty-four) of the patients evaluated and eradicated 90 percent (seventy-four of eighty-two) of the pathogens. Although the clinical response of forty-two cefazolin-treated patients was similar (satisfactory response in 86 percent, thirty-six patients), only 81 percent (forty-eight of fifty-nine) of the pathogens were eradicated. Both ceforanide and cefazolin were very well tolerated systemically and locally.

Topics: Adult; Aged; Bacterial Infections; Cefamandole; Cefazolin; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Pressure Ulcer; Skin Diseases, Infectious

Topics: Adult; Bacteria; Bacterial Infections; Cefamandole; Child; Clinical Trials as Topic; Humans; Kinetics; Microbial Sensitivity Tests

Two hundred twenty patients were randomly assigned to receive either ceforanide or cephalothin as perioperative antibiotic prophylaxis during cardiovascular surgery. More infections were seen among cephalothin recipients (8 deep, 32 total) than among ceforanide recipients (1 deep, 17 total). Among patients who had only coronary artery bypass grafting, more cephalothin recipients had infection than did ceforanide recipients (19 of 82 as opposed to 7 of 83; p = 0.001; relative risk, 2.7; 95% confidence interval, 1.22 to 6.18). The difference between the two regimens was attributable to fewer blood, wound, and urinary tract infections. Among patients who had other procedures, there was no difference in the efficacy of the two regimens. Cephalothin recipients who developed wound or blood stream infections had lower antibiotic levels in their atrial appendages than recipients not developing such infections (p = 0.02). If one assumes that cephalothin does not increase the risk of infection, then these data show that antibiotic prophylaxis prevents infection after coronary artery bypass surgery, and, in the dosages used, that ceforanide is superior to cephalothin.

Topics: Cefamandole; Cephalothin; Clinical Trials as Topic; Coronary Artery Bypass; Double-Blind Method; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Myocardium; Postoperative Complications; Premedication; Random Allocation; Respiratory Tract Infections; Risk; Sepsis; Surgical Wound Infection; Urinary Tract Infections

Twice-daily intramuscular ceforanide therapy of Staphylococcus aureus endocarditis in parenteral drug abusers was compared in a randomized prospective trial with intravenous cephapirin therapy. Dosage regimens were ceforanide, 1 g every 12 h, and cephapirin, 2 g every 4 h. Mean minimal inhibitory and bactericidal concentrations of ceforanide for S. aureus treated with ceforanide were 0.78 and 1.56 microgram/ml compared to cephapirin for patient isolates of 0.08 and 0.14 microgram/ml, respectively. Serum killing levels with ceforanide were 1:5.7 and 1:1.5 at peak and trough levels, compared to 1:134 (peak) and 1:4.2 (trough) with cephapirin. Despite this apparent in vitro advantage of cephapirin, patients treated with ceforanide did as well as those with cephapirin. Of 16 ceforanide-treated patients, all responded initially to therapy, and 15 were cured with 28 days of therapy. One patient relapsed at the end of therapy. Of 16 cephapirin-treated patients, 1 was a clinical and microbiological failure, and 3 other relapsed at the end of therapy. In addition, one ceforanide-treated patient and two cephapirin-treated patients developed central nervous system abscesses. These were cured with drainage and continuation of antibiotic therapy. Ceforanide was well tolerated by the intramuscular route. Cost analysis suggests that therapy with intramuscular ceforanide would result in an approximate 70% decrease in drug therapy cost when compared to intravenous cephapirin. Ceforanide appears to be a safe, efficacious, convenient, and relatively inexpensive drug for treating staphylococcal endocarditis in parenteral drug abusers.

Topics: Adult; Cefamandole; Endocarditis, Bacterial; Female; Humans; Injections, Intramuscular; Male; Prospective Studies; Random Allocation; Staphylococcal Infections; Substance-Related Disorders

Eighty-five patients undergoing cardiac surgery with cardiopulmonary bypass were given either cephalothin or ceforanide perioperatively in randomized, blinded fashion. The incidence of surgically related, postoperative infections was 23% for the cephalothin- and 26% for the ceforanide-treated groups. There were no statistically significant differences that could be identified between patients who became infected and those who remained free of infections, although the time spent in the operating theater was longer for the former group. Ceforanide achieves adequate levels in plasma and myocardial tissue that are sustained several hours after a 0.5-g parenteral dose and allows a 12-h interval between doses. Other currently available agents would have to be administered more frequently to achieve similar results.

Topics: Cardiac Surgical Procedures; Cardiopulmonary Bypass; Cefamandole; Cephalothin; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Myocardium; Premedication; Random Allocation

Antibiotic prophylaxis in open-heart operations is a widely accepted practice. Introduction of new antibiotics with differences in tissue distribution, spectrum of activity and therapeutic index prompts their evaluation as possible effective prophylactic agents. We compared the distribution, clinical efficacy, and safety of ceforanide with cephalothin as a prophylactic agent in coronary artery bypass graft (CABG) procedures. The results indicated that the intravenous administration of ceforanide at the dose of 1 gm every 12 hours for 2.5 days was equivalent to cephalothin 1 gm every 6 hours for 2.5 days. Serum, muscle, and bone concentrations of ceforanide were significantly greater than those of cephalothin. These concentrations consistently exceeded the minimal inhibitory concentration for Staphylococcus aureus, the major pathogen implicated in wound infections. No toxicty was observed with either antibiotic. Ceforanide merits consideration as a prophylactic antibiotic in CABG operations.

Topics: Aged; Cefamandole; Cephalosporins; Cephalothin; Clinical Trials as Topic; Coronary Artery Bypass; Double-Blind Method; Humans; Middle Aged; Surgical Wound Infection; Tissue Distribution

Doses of 30 mg of ceforanide or cefamandole per kg were administered intravenously to 26 patients just before their chests were opened for coronary artery bypass or cardiac valve replacement surgery. Samples of right atrial appendage, pericardial fluid, plasma, aortic wall, intercostal muscle, and sternum were obtained at different times after the antibiotic was injected, and these samples were assayed for cephalosporin concentration. For ceforanide the pre-bypass plasma half-life was 2.5 h, and the atrial appendage half-life was 2.1 h; for cefamandole the pre-bypass plasma half-life was 0.75 h and the atrial appendage half-life was 0.72 h. At 3 h the concentrations of ceforanide and cefamandole in atrial appendages were 28.0 and 5.0 micrograms/g, respectively. Ceforanide achieved higher and more sustained concentrations in other tissues than cefamandole. Considering the minimal inhibitory concentrations of these drugs for staphylococci, cefamandole and ceforanide should provide adequate protection against infection by these organisms for the duration of the surgical procedure.

Topics: Cardiac Surgical Procedures; Cefamandole; Cephalosporins; Half-Life; Humans; Muscles; Myocardium; Pericardial Effusion; Pericardium; Premedication; Ribs; Staphylococcal Infections; Sternum

We compared the safety and efficacy of a six-dose regimen of cephalothin with a two-dose regimen of ceforanide for the prevention of infection after elective vaginal hysterectomy. A total of 150 patients were randomly assigned to either regimen. The overall incidence of documented pelvic infection was 5.3% and did not differ significantly between the prophylaxis groups when stratified by type of surgery. No serious adverse reactions were encountered in either group, but phlebitis was significantly more common in patients receiving cephalothin. We conclude that a two-dose regimen of ceforanide given intramuscularly is as effective as, and possibly better tolerated than, a six-dose regimen of cephalothin.

Topics: Cefamandole; Cephalosporins; Cephalothin; Female; Humans; Hysterectomy; Hysterectomy, Vaginal; Premedication; Risk; Urinary Tract Infections

Ceforanide is a new (parenteral) long-acting cephalosporin with antimicrobial activity comparable to those of other second-generation cephalosporins. In a randomized prospective study, patients with community-acquired bacterial pneumonia were treated with ceforanide at 0.5 g every 12 h (28 cases) or with cefazolin at 1.0 g every 8 h (26 cases). The study groups were comparable in clinical and laboratory findings, including etiological diagnosis. Streptococcus pneumoniae was isolated from the sputum of 38 patients, of whom 8 (21%) were bacteremic. Mean peak and trough serum levels of ceforanide drawn 1 and 11.5 h after the 0.5-g intravenous dose were 39.6 and 2.5 microgram/ml, respectively. Of the 50 patients evaluable for efficacy, all responded clinically with no serious adverse reactions. In spite of clinical improvement and in vitro susceptibility, Haemophilus influenzae persisted in the sputum of five of the eight cefazolin-treated patients and four of the five patients treated with ceforanide. Ceforanide appears to be as safe and effective as cefazolin for the therapy of pneumonia caused by S. pneumoniae or H. influenzae, but neither drug was effective in clearing H. influenzae from the sputum.

Topics: Adult; Cefamandole; Cefazolin; Cephalosporins; Clinical Trials as Topic; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Pneumonia; Pneumonia, Staphylococcal; Pneumonia, Viral; Sputum; Staphylococcus

While acknowledging carotid atherosclerosis (CAS) as a risk factor for ischemic stroke, reports on its pathogenesis are scarce. This study aimed to explore the potential mechanism of CAS through RNA-seq data analysis. Carotid intima tissue samples from CAS patients and healthy subjects were subjected to RNA-seq analysis, which yielded, 1,427 differentially expressed genes (DEGs) related to CAS. Further, enrichment analysis (Gene Ontology, KEGG pathway, and MOCDE analysis) was performed on the DEGs. Hub genes identified via the protein-protein interaction network (PPI) were then analyzed using TRRUST, DisGeNET, PaGenBase, and CMAP databases. Results implicated inflammation and immunity in the pathogenesis of CAS. Also, lung disease was associated with CAS. Hub genes were expressed in multiple diseases, mainly regulated by RELA and NFKB1. Moreover, three small-molecule compounds were found via the CMAP database for management of CAS; hub genes served as potential targets. Collectively, inflammation and immunity are the potential pathological mechanisms of CAS. This study implicates CeForanide, Chenodeoxycholic acid, and 0317956-0000 as potential drug candidates for CAS treatment.

Topics: Carotid Artery Diseases; Case-Control Studies; Cefamandole; Chenodeoxycholic Acid; Computational Biology; Datasets as Topic; Female; Gene Expression Regulation; Healthy Volunteers; Humans; Male; Middle Aged; Protein Interaction Maps; RNA-Seq; Tunica Intima

A sensitive, accurate, precise and the same time simple and rapid method for the colorimetric determination of some cephalosporins of the second and third generations, such as: cefoxitin sodium (CFXT), cefaclor (CFCL), cefamandole nafate (CFMD), ceforanide l-lysine (CFRN), cefotaxime sodium (CFTX), and cefurozime sodium (CFRX) was described. The new method proposed is based: a) On the reduction of Fe(III) to Fe(II) by the drug analysed and b) On complexation of Fe(II) formed with o-Phenanthroline (O-Phen) consistently the formation of the well known highly stable orange-red coloured chelate complex [Fe(II)-(o-Phen)3]2+ which exhibits an absorption maximum at lambda = 510 nm (pH 4.50 +/- 0.2). Beer's law is obeyed for: 1.0 - 37.5 microgram mL-1 for CFX, 1.0 - 25.0 microgram mL-1 for CFMD, CFRN, and CFTX and 2.0 - 37.5 microgram mL-1 for CFTX and CFCL, while the apparent molar absorptivity ( epsilon in L mol-1cm-1) and the Sandell's sensitivity in (ngcm-2) both referred to the drug analyzed, are 1.29 x 10(4); 34.7 (CFXT), 7.61 x 10(3); 50.7 (CFCL), 3.33 x 10(4); 15.4 (CFMD), 2.60 x 10(4); 17.6 (CFRN) respectively. The regression line equation for each one of the above studied cephalosporins were calculated with a correlation coefficient 0.9997 < r < 1.0000; the accuracy and the precision of the method was considered as very satisfactory, while the results of a statistical analysis by means of the Student's t-test and the variance ratio F-test prove that no significant difference was observed between the results of the proposed method and those of official one.

Topics: Cefaclor; Cefamandole; Cefotaxime; Cefoxitin; Cefuroxime; Cephalosporins; Colorimetry; Indicators and Reagents; Molecular Structure; Sensitivity and Specificity

Although there are reports that the addition of a beta-lactamase inhibitor to ampicillin or amoxicillin greatly improves their in vitro activity against M. tuberculosis, there are no written reports about the antituberculosis effects of beta-lactamase inhibitors in combination with cephalosporins against M. tuberculosis. In this report, we have determined the minimal inhibitory concentrations (MIC) of 5 cephalosporins with or without combination with beta-lactamase inhibitor against M. tuberculosis strains isolated from patients before antituberculosis treatment and checked the production of beta-lactamase by bacteria before this procedure. Four strains of M. tuberculosis were contaminated during the experiment, and all the other 16 strains hydrolyzed the nitrocefin disc, thus indicating a beta-lactamase producer. The MICs of cephalosporins alone against M. tuberculosis were 200-400 micrograms/ml for ceforanide, 100-400 micrograms/ml for cephapirin, 400-1600 micrograms/ml for cefamandole, 200-1600 micrograms/ml for cefotaxime, and 800-1600 micrograms/ml for ceftriaxone. After adding the equimolar concentrations of sulbactam, the MICs were reduced to 100-200 micrograms/ml for ceforanide, 12.5-100 micrograms/ml for cephapirin, 100-400 micrograms/ml for cefamandole, 25-200 micrograms/ml for cefotaxime, and 100-800 micrograms/ml for ceftriaxone. We concluded that sulbactam enhanced the antituberculosis effect of cephalosporins.

Topics: beta-Lactamase Inhibitors; Cefamandole; Cefotaxime; Ceftriaxone; Cephalosporins; Cephapirin; Drug Synergism; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Sulbactam

The use of molybdophosphoric acid as an oxidising agent for the spectrophotometric determination of four cephalosporin derivatives, viz., cefadroxil monohydrate (I), cefapirin sodium (II), ceforanide L-lysine (III) and cefuroxime sodium (IV), either in the pure form or in pharmaceutical formulations is described. Beer's law is obeyed up to 100 micrograms ml-1 for I, up to 60 micrograms ml-1 for II and IV and up to 80 micrograms ml-1 for III. The molar absorptivities were 4.58 X 10(3), 11.3 X 10(3), 9.8 X 10(3) and 10.9 X 10(3) l mol-1 cm-1 and the Sandell sensitivities were 83.3, 39.3, 53.0 and 41.0 ng cm-2 for I, II, III and IV, respectively. The slopes and intercepts of the equations of the regression line were calculated for each of these drugs with the following correlation coefficients: I, 0.9993; II, 0.9999; III, 1.000; and IV, 0.9999. These antibiotics were determined successfully both in the pure form and in pharmaceutical preparations. The results demonstrated that the proposed procedure is at least as accurate, precise and reproducible as the official methods, while being simpler and less time consuming. A statistical analysis indicated that there was no significant difference between the results obtained by the proposed procedure and those of the official methods.

Topics: Cefadroxil; Cefamandole; Cefuroxime; Cephalosporins; Cephapirin; Chemical Phenomena; Chemistry; Indicators and Reagents; Spectrophotometry, Ultraviolet

Isoniazid (INH) is said to inhibit tubercle bacilli equally well in vivo and in vitro, and to be mycobactericidal. Ceforanide (CEF) can inhibit tubercle bacilli in vitro but has been found ineffective clinically. These two drugs were tested against virulent tubercle bacilli in cultured human macrophages (MP), partly to compare the results with clinical experience, and partly for a better understanding of antituberculosis activities of these drugs in human beings. INH had the same minimal inhibitory concentration (MIC) against tubercle bacilli in MP as in 7H9 broth cultures. It killed multiplying bacilli in MP but not nonmultiplying bacilli, even at 100 times MIC. It killed both multiplying and nonmultiplying bacilli in broth cultures. It interfered with its own effectiveness against intra-MP bacilli by preventing nonmultiplying bacilli from beginning to multiply and thus become susceptible to killing. These findings help explain why this demonstrably mycobactericidal drug produces relapses of tuberculosis when used alone. It was confirmed that CEF is able to inhibit growth in broth cultures (MIC = 10 micrograms/ml). However, it was not effective against either multiplying or nonmultiplying bacilli in MP at concentrations up to 50 micrograms/ml. These results with the drugs INH and CEF support the good record of correlation between the human MP model of tuberculosis and clinical experience in antituberculosis chemotherapy.

Topics: Adult; Cefamandole; Cells, Cultured; Female; Humans; Isoniazid; Macrophages; Male; Microbial Sensitivity Tests; Middle Aged; Mycobacterium tuberculosis

Thirty-four women who underwent vaginal hysterectomy received either ceforanide or cefazolin as perioperative antimicrobial prophylaxis. Samples of plasma, myometrium, endometrium and fallopian tubes were obtained at various intervals after injection and were assayed for cephalosporin concentration. Following intramuscular injection approximately 1 h prior to surgery, both drugs provided adequate tissue levels at the time of the procedure. Although both antimicrobials achieved similar tissue concentrations, all tissue samples for ceforanide exceeded the MIC90 for Escherichia coli while in the cefazolin group 9/18 myometrial samples and 10/15 endometrial samples fell below the MIC90 for this organism.

Topics: Adult; Cefamandole; Cefazolin; Endometrium; Fallopian Tubes; Female; Humans; Hysterectomy; Hysterectomy, Vaginal; Injections, Intramuscular; Middle Aged; Myometrium; Premedication; Tissue Distribution; Uterus

In joints with bacterial arthritis, continuing prolonged destruction of cartilage may occur in spite of prompt, effective antibiotic therapy. We measured the extent to which early antibiotic therapy with ceforanide altered the degradation of the cartilage after arthritis due to Staphylococcus aureus had been produced in the knee joint in rabbits. Degradation of the cartilage was quantified by analyses for glycosaminoglycan and collagen. Three weeks after the infection was produced, the cartilage had lost more than half of its glycosaminoglycan whether the antibiotic therapy had been started at one, two, or seven days after infection. Beginning the antibiotic treatment one day after infection reduced over-all loss of collagen by 37 per cent and decreased the area of erosion of the infected articular surfaces. When antibiotic treatment was begun at four, eight, or twelve hours after infection, the loss of glycosaminoglycan averaged 18 per cent. Prophylaxis with antibiotics completely prevented any degradation of the cartilage.. The findings reported here show how rapidly cartilage loses glycosaminoglycan when it is involved by arthritis caused by staphylococci and how early treatment of the infection reduces the loss of collagen. There is less protection against loss of glycosaminoglycan. The results emphasize the need for early diagnosis and treatment of infectious synovitis and support the rationale for early administration of antibiotics without waiting for identification of the responsible bacteria.

Topics: Animals; Arthritis, Infectious; Cartilage, Articular; Cefamandole; Collagen; Glycosaminoglycans; Rabbits; Staphylococcal Infections; Staphylococcus aureus; Time Factors

Three patients with rhinoscleroma who presented with nasal and pharyngeal symptoms are described. Treatment with ceforanide, a new second-generation cephalosporin with high intrinsic activity against Klebsiella, and possessing a long half-life, was used as outpatient treatment. A total of 120 g of ceforanide was administered over a period of two months. All three patients showed signs of clinical improvement, but only two of three became bacteriologically sterile at the end of two months; one patient relapsed bacteriologically but not clinically, once the drug was discontinued. Second- and third-generation cephalosporins appear to have excellent activity against the causative pathogens of rhinoscleroma. Because of the impracticality of administering these agents parenterally over prolonged periods of time, there is a need for the development of an oral cephalosporin with similar intrinsic activity and beta-lactamase stability. Perhaps the novel beta-lactam antibiotics such as the penems and monobactams, some of which can be administered orally, will answer that need.

Topics: Adult; Cefamandole; Female; Humans; Injections, Intramuscular; Male; Rhinoscleroma

Five factorial experiments were conducted, each with 10 bulls, three extenders, and six antibiotic treatments to determine safe levels of new antibiotics to add to bull spermatozoa. Dicloxacillin, cephapirin, ceforanide, gentamicin, and minocin were added at five concentrations to whole milk, egg yolk-Tris, and egg yolk-Tris detergent (sodium triethanolamine lauryl sulfate) extenders with penicillin and streptomycin as a control. Semen was extended to 20 X 10(6) sperm/ml, packaged in .5-ml straws, frozen and stored in liquid nitrogen, and thawed at 35 degrees C for 30 s. Two people assessed postthaw percentage of motile spermatozoa from two straws per treatment. Bulls and extenders always affected sperm motility significantly. Percentage of intact acrosomes of spermatozoa was assessed in selected treatments but did not differ in any experiment. Sodium triethanolamine lauryl sulfate tended to improve cryopreservation of spermatozoa. Percentage of motile spermatozoa in milk declined when concentrations of dicloxacillin exceeded 200 micrograms/ml or when gentamicin, as Gentocin, exceeded 500 micrograms/ml. Minocin was toxic at all levels tested in egg yolk and was nontoxic to sperm in milk extender at concentrations less than or equal to 100 micrograms/ml. Cephapirin and ceforanide were innocuous at all concentrations tested (200 to 2000 micrograms/ml). Fertility with cephapirin (500 micrograms/ml) added to an extender containing control antibiotics resulted in a 56-d nonreturn rate of 75.5 versus 72.1% for the control.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cefamandole; Cephapirin; Dicloxacillin; Ethanolamines; Freezing; Gentamicins; In Vitro Techniques; Insemination, Artificial; Male; Sodium Dodecyl Sulfate; Sperm Motility; Spermatozoa; Surface-Active Agents; Tissue Preservation

Tests with 52 strains of Staphylococcus aureus compared ceforanide and cefonicid. Addition of 50% human serum to the test system reduced the bacteriostatic and bactericidal activities of cefonicid, but ceforanide was not affected as greatly.

Topics: Cefamandole; Cefonicid; Culture Media; Humans; Microbial Sensitivity Tests; Staphylococcus aureus; Temperature; Time Factors

Topics: Bacterial Infections; Cefamandole; Child; Humans; Injections, Intramuscular; Safety

Topics: Cefamandole; Half-Life; Humans

Twenty-seven Escherichia coli test strains that were not susceptible to cephalothin were tested for susceptibility to cefazolin, cefamandole, and ceforanide. By zone-size criteria (greater than or equal to 18 mm), 67% of E coli were susceptible to cefazolin and cefamandole, and 93% were susceptible to ceforanide. By microtiter assay (MIC less than or equal to 8 micrograms/ml), 88% were susceptible to cefazolin and cefamandole, and 94% were susceptible to ceforanide. The results support susceptibility testing of E coli with specific first- or second-generation cephalosporins rather than with class agents.

Topics: Cefamandole; Cefazolin; Cephalothin; Escherichia coli; Microbial Sensitivity Tests

Among eight cephalosporins and cephamycins tested in preliminary in vitro screening against Mycobacterium tuberculosis, the most promising for further study was found to be ceforanide, followed by ceftizoxime, cephapirin, and cefotaxime. Moxalactam, cefoxitin, cefamandole, and cephalothin were found to be not active enough against M. tuberculosis to be considered for further in vitro studies. The antibacterial activity of various ceforanide concentrations was investigated by three methods: (i) the dynamics of radiometric readings (growth index) in 7H12 broth; (ii) the number of CFU in the same medium; and (iii) the proportion method on 7H11 agar plates. There was a good correlation among the results obtained with these methods. The MIC for most strains ranged from 6.0 to 25.0 micrograms/ml. The BACTEC radiometric method is a reliable, rapid, and convenient method for preliminary screening and determination of the level of antibacterial activity of drugs not commonly used against M. tuberculosis.

Topics: Biotransformation; Cefamandole; Cephalosporins; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Radiometry

Topics: Cefamandole; Cefonicid; Cefuroxime; Cephalosporins; Half-Life; Humans; Premedication; Surgical Wound Infection

The pharmacokinetics and protein binding of ceforanide were studied in 15 patients undergoing cholecystectomies. Each patient received ceforanide (20 mg/kg) intravenously on arrival in the operating room, after which serial blood samples were collected during the elimination phase for determination of total and free ceforanide concentrations in the serum. A high-pressure liquid chromatography assay was used, with a centrifugal filtration system for free-drug determinations. Serum concentration data for each individual were subjected to linear regression to determine the elimination rate constants (total and free drug), volumes of distribution, and systemic clearances. The mean elimination rate constants were 0.41 and 0.50 h-1 for total and free ceforanide, respectively. The mean percentage of ceforanide bound to serum protein was 87.9%. The relationship of the free ceforanide concentration to the total concentration appeared to be linear. The data were fit to double-reciprocal and half-reciprocal relationships with good agreement, showing one binding site and an association constant range of 1.6 X 10(7) to 1.9 X 10(7) at these in vivo concentrations. The mean volume of distribution and mean systemic clearance of total drug were 100 ml/kg and 45.9 ml/min per 1.73 m2, respectively. Ceforanide consistently produced higher intraoperative total drug concentrations compared with those of cefazolin and cefoxitin from similar studies.

Topics: Adolescent; Adult; Aged; Cefamandole; Chromatography, High Pressure Liquid; Female; Humans; Injections, Intravenous; Intraoperative Period; Kinetics; Male; Middle Aged; Premedication; Protein Binding

The pharmacokinetics of cefaronide (16 gm/kg dose), ceftriaxone and cefoperazone (47 gm/kg dose), after intravenous (i.v.) administration were determined in six Merino ewes. The mean values for terminal half life, steady state volume of distribution Vd(ss), renal clearance (ClR) and total body clearance (ClB) for cefaronide were 1.5 h, 0.39 l/kg, 0.06 l/h/kg and 0.16 l/h/kg, for ceftriaxone; 1.7 h, 0.30 l/kg, 0.08 l/h/kg, and 0.22 l/h/kg, and 0.7 h, 0.16 l/kg, 0.02 l/h/kg and 0.16 l/h/kg for cefoperazone, respectively. After 5.5 h, approximately 42% cefaronide, and after 8 h, approximately 37% ceftriaxone and 13% cefoperazone, was excreted in urine. The non-renal elimination of ceftriaxone and cefoperazone appeared to be more rapid in sheep than is reported in man. Cefaronide was excreted largely unchanged in the urine of sheep. Therefore, the elimination of cefaronide in sheep was similar to that found in man. Cefaronide was well distributed in sheep, whereas ceftriaxone and cefoperazone appeared to be distributed to a lesser degree. These findings underline the different disposition of drugs in different species.

Topics: Animals; Cefamandole; Cefoperazone; Cefotaxime; Ceftriaxone; Cephalosporins; Chromatography, High Pressure Liquid; Female; Injections, Intravenous; Kinetics; Sheep; Spectrophotometry, Ultraviolet

Results of treatment of urinary tract infection in 110 patients using new beta-lactam antibiotics are presented in summary. While in the uncomplicated infections a cure rate approaching 100% was observed even with very small dosages, complicated cases required higher dosages to achieve satisfactory clinical cure rates and especially to achieve acceptable bacteriological cure rates. The continuous need for new, more potent antibiotics is becoming apparent due to the increasing resistance rates of pathogens to the existing agents. The group of beta-lactam antibiotics offers much hope due to the continuous development of numerous new compounds with better antibacterial and kinetic properties, offering at the same time a very high degree of safety, compared to aminoglycosides and most other antibiotic groups.

Topics: Anti-Bacterial Agents; Bacterial Infections; beta-Lactamase Inhibitors; Cefamandole; Ceftazidime; Humans; Penicillins; Urinary Tract Infections

Bone and serum concentrations of five cephalosporins were assayed in 92 patients undergoing elective hip or knee prosthetic joint arthroplasty. One hundred twenty-five bone samples were assayed. Although there was no direct relation between serum and bone antibiotic concentrations, a trend toward increased bone antibiotic concentration for drugs with higher serum levels and longer half-lifes (cefazolin and ceforanide) was noted. Bone antibiotic concentrations were maximal within 60 minutes of drug administration. Although bone antibiotic concentrations following 2-g doses were greater than those following 1-g doses, the differences were not statistically significant. A trend toward higher bone antibiotic concentrations at hip surgery was noted, and this difference achieved statistical significance (p less than 0.05) for cefazolin. As a result of analysis of bone antibiotic concentrations, antimicrobial sensitivities, and cost, administration of 2 g of cefazolin immediately prior to operation, followed by 1 g every eight hours for 24 hours, is recommended in elective prosthetic joint surgery.

Topics: Adolescent; Adult; Aged; Bone and Bones; Cefamandole; Cefazolin; Cefoxitin; Cephalosporins; Cephalothin; Hip Joint; Hip Prosthesis; Humans; Knee Joint; Knee Prosthesis; Middle Aged; Premedication

Total joint arthroplasty is a common orthopedic procedure and requires prophylactic antibiotic coverage to prevent infections in the operated joint. The antibiotics routinely used for prophylaxis are the cephalosporins. This study compared bone, synovial fluid, and plasma concentrations of ceforanide with cephalothin concentrations in 30 patients undergoing elective total hip or total knee arthroplasty. Ceforanide provided significantly higher plasma concentrations for 61-110 minutes postdose than did cephalothin (p less than 0.025 and p less than 0.005). No difference was noted between the two antibiotics for the bone concentrations in the total hip arthroplasty group; however, cephalothin concentrated to a greater degree in the bone of patients undergoing total knee arthroplasty (p less than 0.05). Cephalothin achieved higher concentrations in the synovial fluid than did ceforanide (p less than 0.05). Both antibiotics were well tolerated and no postoperative infections were noted in either group.

Topics: Aged; Bone and Bones; Cefamandole; Cephalothin; Female; Humans; Joint Prosthesis; Male; Middle Aged; Premedication; Synovial Fluid

Ceforanide levels in plasma, gallbladder bile, gallbladder tissue, and common bile duct were studied in 10 patients with normal biliary tracts and in 35 patients with biliary disease at various intervals after intravenous injection of 1 g of the drug. Peak blood levels were obtained within 1 h of administration (mean, 67 +/- 15 micrograms/ml). Patients with a normal bilary tract, as well as patients with chronic cholecystitis and a patent cystic duct, achieved high gallbladder bile levels of ceforanide within 2 h (mean, 76 +/- 25 micrograms/ml) and attained even higher levels by 4 h (mean, 182 +/- 51 micrograms/ml). However, all patients with chronic cholecystitis and an occluded cystic duct had very low drug concentrations in the gallbladder bile (14 +/- 7 micrograms/ml at 2 h). Despite this difference in gallbladder bile levels, ceforanide levels of 21 +/- 3 micrograms/g were achieved at 1 to 3 h in gallbladder tissue in both groups with chronic cholecystitis. The concentration of ceforanide in common bile duct was 149 +/- 59 micrograms/ml at 2 h after administration, with levels over 60 micrograms/ml present from 1 to 4 h after administration. These results indicate that ceforanide reaches high levels in the biliary tract. Its potential value in the prevention and treatment of biliary infections should be assessed.

Topics: Adult; Aged; Bile; Cefamandole; Cephalosporins; Humans; Infusions, Parenteral; Middle Aged; Time Factors

We studied the pharmacokinetics of intramuscular ceforanide in 46 infants, children, and adolescents, ranging in age from 1 month to 17 years. After the subjects were given 20-mg doses of ceforanide per kg, the mean peak plasma concentration was 56.3 microgram/ml (range, 27.0 to 95.0), the mean 8-h level was 5.9 microgram/ml (range, 1.5 to 13.5), and the mean 12-h level was 1.5 microgram/ml (range, 0.2 to 4.2). Ceforanide half-life varied with the ages of the patients: in 1- to 2-year-old children, in half-life was significantly shorter (1.5 h) than in younger or older children. Plasma concentrations at 8 and 12 h after a dose were lowest in 1- to 2-year-old children. There was no relationship between the area under the curve, the volume of distribution, or the body clearance of ceforanide to the ages of the patients. Within 6 h of administration of the drug, a mean of 77.5% of a dose was excreted in urine, and at the end of 12 h, virtually all (93.9%) of the administered dose was recovered in urine samples. The administration of ceforanide every 12 h did not result in drug accumulation. A dose of 20 mg of ceforanide per kg every 12 h is recommended for most pediatric patients. Dosage recommendations for 1- to 2 year-old children are presented.

Topics: Adolescent; Age Factors; Anti-Bacterial Agents; Bacterial Infections; Cefamandole; Cephalosporins; Child; Child, Preschool; Drug Administration Schedule; Female; Half-Life; Humans; Infant; Injections, Intramuscular; Kinetics; Male

The pharmacokinetic of ceforanide, a new parenteral cephalosporin antibiotic, were examined at intravenous and intramuscular doses of 250, 500, and 1,000 mg in healthy male volunteers. Over the above dosing range, ceforanide pharmacokinetics were essentially linear, with plasma clearances varying from 2.2 to 2.5 liters/h. The best present overall estimate of the drug's half-life was 2.9 h. Intramuscular ceforanide was 100% bioavailable, Peak intravenous serum levels were 39, 71, and 135 micrograms/ml at the end of 30-min infusions of 250, 500, and 1,000 mg; after intramuscular injections of 250, 500, and 1,000 mg, the respective peak serum levels were 21, 38, and 69 micrograms/ml. From 80 to 85% of the above doses were eliminated as unchanged.

Topics: Biological Availability; Cefamandole; Cephalosporins; Dose-Response Relationship, Drug; Half-Life; Humans; Injections, Intramuscular; Injections, Intravenous; Kinetics; Male

The pharmacokinetic properties of 10 antimicrobial agents were examined in sterile and infected encapsulated subcutaneous abscesses in mice. The inoculum for sterile abscesses was autoclaved cecal contents; that for infected abscesses was autoclaved cecal contents combined with Bacteroides fragilis. The antimicrobial agents examined were rosaramicin, clindamycin, chloramphenicol, metronidazole, and six beta-lactam antibiotics. All antimicrobial agents entered abscesses, produced peak levels of biological activity that were somewhat delayed in comparison to serum levels, and were present in negligible levels 8 hr after administration. The highest concentration in abscesses was achieved with rosaramicin and clindamycin, with peak levels of 43%--63% of the peak serum level. Peak levels of other antimicrobial agents in sterile abscesses were 13%--27% of the peak serum level. Levels of biologically active during were significantly lower in infected abscesses than in sterile abscesses for antimicrobial agents that are inactivated by B. fragilis beta-lactamase.

Topics: Abscess; Animals; Bacteroides fragilis; Cefamandole; Cefoperazone; Cefoxitin; Cephalosporins; Cephalothin; Chloramphenicol; Clindamycin; Dose-Response Relationship, Drug; Lactams; Male; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Skin

The comparative tissue distribution of ceforanide, cefazolin, and cefamandole was determined in rats after subcutaneous doses of 100 mg/kg. Ceforanide had the longest plasma half-life, 0.9 h, versus 0.5 h for cefazolin and 0.4 h for cefamandole, and the highest area under the plasma concentration time curve, 324 micrograms x h per ml, versus 184 micrograms x h per ml for cefazolin and 42 micrograms x h per ml for cefamandole. The peak plasma concentrations of ceforanide and cefazolin were 173 and 140 micrograms/ml, respectively, and were threefold higher than that of cefamandole (49 micrograms/ml). Measureable concentrations of the three compounds were found in the liver, kidneys, lungs, submaxillary glands, cervical lymph nodes, bones, heart, abdominal muscles, eyes, and testes, with cefamandole levels being generally lower and more variable. The peak tissue levels of ceforanide and cefazolin were comparable, within the limit of data variation, and were considerably higher than that of cefamandole. The tissue half-lives of these cephalosporins were similar to the respective plasma half-lives.

Topics: Animals; Cefamandole; Cefazolin; Cephalosporins; Kinetics; Male; Rats

Pharmacologic studies of the semisynthetic cephalosporin ceforanide were conducted in 29 cancer patients. Intravenous doses of 500 mg over 30 min every 6 hr to 10 patients induced mean peak serum concentrations between 44.7 and 51.5 micrograms/ml, while in 10 patients receiving 1 gm over 30 min every 12 hr mean peak serum concentrations varied from 73.4 to 91.8 micrograms/ml. Twelve hours after 1 gm of drug, mean serum concentrations varied between 5.6 and 6.5 micrograms/ml. After a 500-mg loading dose, continuous infusion of 500 mg every 4 hr, 10 patients maintained serum concentrations above 34.2 micrograms/ml for 7 or 8 days. Most of the drug was excreted in the urine in the initial 6 hr after administration and mean urinary concentration of 1,315 micrograms/ml were obtained during this time. Serum half-life ranged between 2.2 and 2.9 hr on all schedules and therefore wa longer than that of other cephalosporins. No serious toxicity was noted. The relatively broad spectrum of activity in addition to the long half-life suggests clinical utility for this drug.

Topics: Adolescent; Adult; Aged; Cefamandole; Cephalosporins; Half-Life; Humans; Injections, Intravenous; Kinetics; Middle Aged; Neoplasms; Time Factors

Ceforanide (500 mg) was infused intravenously over 30 min into six normal subjects, 10 nondialysis patients with renal insufficiency, and six hemodialysis patients. Dialysis patients received two ceforanide infusions, one immediately before dialysis and another during an interdialysis period. Sequential plasma samples over 24 to 72 hr were assayed for ceforanide. Peak ceforanide levels (mean = 69 +/- 12 micrograms/ml) and volumes of distribution did not vary with creatinine clearance (Clcr, ml/min/1.73 m2) and both plasma clearance and renal clearance decreased linearly as Clcr decreased. Mean nonrenal clearance (4.6 +/- 1.8 ml/min/1.73 m2) did not vary with Clcr. Mean half-life was 3 hr in the normal subjects, increasing to approximately 25 hr in patients with severe renal insufficiency. Hemodialysis resulted in a removal of approximately 21% of the dose of ceforanide. Dosing recommendations for patients with renal insufficiency are provided.

Topics: Adult; Aged; Cefamandole; Cephalosporins; Humans; Kidney Failure, Chronic; Kinetics; Male; Middle Aged

This investigation evaluated the effect of probenecid on ceforanide concentrations in eight healthy volunteers. Each volunteer was given 1 or 2 g of ceforanide either alone or with 1 g of probenecid. Concentrations of ceforanide in plasma, urine, and saliva were then measured. Probenecid did not alter the plasma concentrations of ceforanide, nor did it affect the urinary excretion of this agent. Ceforanide was not secreted into saliva in any detectable amount either when administered alone or with probenecid. It is not clear why probenecid has a negligible effect on ceforanide concentrations in plasma. It may be that tubular secretion plays less of a role in the excretion of ceforanide than expected, or that the physical properties of ceforanide prevent probenecid from affecting its excretion.

Topics: Adult; Cefamandole; Cephalosporins; Drug Interactions; Female; Humans; Male; Middle Aged; Probenecid; Saliva

Ceforanide administered parenterally twice daily was used as the sole agent to treat 17 patients with right-sided endocarditis due to Staphylococcus aureus or nonenterococcal streptococci. Fifteen patients were cured of their original infection. Two patients were withdrawn from the study. One patient was transferred to another hospital 4 days after ceforanide therapy was initiated, and the other was changed to a different antibiotic regimen when his viridans streptococcus proved tolerant to ceforanide. The intramuscular form of ceforanide was well tolerated. It was stopped in two patients after week 3 of therapy because of adverse effects, possibly related to the study drug. These findings resolved with discontinuation of the ceforanide, and no additional antimicrobial therapy was necessary. Two patients who continued to abuse drugs intravenously during the study developed bacteremia with new organisms and required additional antimicrobial therapy. Ceforanide proved to be a useful agent in the treatment of right-sided endocarditis due to susceptible S. aureus and nonenterococcal streptococci.

Topics: Adolescent; Adult; Cefamandole; Cephalosporins; Child; Endocarditis, Bacterial; Humans; Injections, Intramuscular; Microbial Sensitivity Tests; Staphylococcal Infections; Streptococcal Infections

The pharmacokinetics of the l-lysine salt of ceforanide were studied after intravenous administration of 1132 and 2264 mg as 30-min constant-rate infusions and after intramuscular administration of 556 and 1132 mg. The peak intravenous plasma concentrations were 136 and 222 microgram/ml at termination of infusion, and 12-hr trough concentrations were 5.9 and 9.0 microgram/ml, respectively. The peak intramuscular plasma concentrations were 38 and 74 microgram/ml at 1.0-1.3 hr after dosing, and 12-hr trough concentrations were 3.9 and 6.7 microgram/ml, respectively. When 19 successive intravenous and intramuscular doses at these levels were administered at 12-hr intervals, there was no tendency toward drug accumulation. The major drug elimination route was urinary excretion; 85% of the dose was excreted unchanged in the urine within 12 hr, and no metabolites with antibiotic activity were observed in urine. The mean terminal plasma half-life was 2.98 hr, the mean plasma protein binding was 80.6%, the steady-state volume of distribution was 12 liters, the plasma clearance was 45.9 ml/min/1.73 m2, and the renal clearance was 34.9 ml/min/1.73 m2. The pharmacokinetic properties and antibacterial activity spectrum indicate that this antibiotic should be effective in treating human bacterial infections when administered at 12-hr intervals. It is presently under clinical investigation.

Topics: Adult; Blood Proteins; Cefamandole; Cephalosporins; Humans; Injections; Kinetics; Male; Protein Binding; Time Factors

Ceforanide (BL-S786R) is a new, broad-spectrum, parenteral cephalosporin. Pharmacokinetic properties were determined in rats (100 mg/kg), rabbits (30 mg/kg), dogs (25 mg/kg), and humans (2 g or 30 mg/kg) and compared with equivalent single doses of cefazolin. Plasma half-lives for ceforanide and cefazolin were 1.1 and 0.5 h in the rat, 5 and 0.3 h in the rabbit, 1 and 0.8 h in the dog, and 2.6 and 2 h in humans, respectively. The slower elimination of ceforanide, as reflected by longer plasma half-life, larger area under the curve, and peak plasma concentrations, was due to slower body and renal clearances. The apparent volumes of distribution of ceforanide and cefazolin were comparable. Rats, dogs, and humans excreted 80 to 100% of the ceforanide dose in the 0- to 24-h urine; rabbits excreted only 50%. Tubular secretion constituted 50% of ceforanide renal excretion in rabbits, dogs, and humans and 90% in rats; the remainder was excreted by glomerular filtration. There was no apparent correlation between the extent of tubular secretion and degree of plasma protein binding in different species. There was no significant pharmacokinetic interaction between ceforanide and amikacin in the rat. The slower elimination kinetics of ceforanide are indicative of the potential for a longer dosing interval and more effective antibiotic therapy as compared with available cephalosporins.

Topics: Adult; Animals; Blood Proteins; Cefamandole; Cefazolin; Cephalosporins; Dogs; Half-Life; Humans; Kidney; Kinetics; Male; Rabbits; Rats; Species Specificity

The pharmacokinetics of ceforanide were evaluated in 11 patients with end stage renal disease (creatinine clearance less than 5 ml/min). A single intravenous dose of 750 mg/m2 produced peak plasma concentrations of 123 +/- 29 microgram/ml. The plasma half-life (T 1/2) of the drug was 19.1 +/- 2.5 h. A 5.5 h hemodialysis session removed 53% of the drug and reduced the T 1/2 to 5 +/- 0.7 h. Plasma concentrations greater than 10 microgram/m2 were maintained without adverse effects with a 1.5-g/m2 dose administered three times a week for 2 weeks.

Topics: Adult; Aged; Cefamandole; Cephalosporins; Female; Half-Life; Humans; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Renal Dialysis

Thirty-five patients with cellulitis were treated with ceforanide, 1 g every 12 h, intramuscularly. A good clinical response was observed in 33 cases. Drug failure in the remaining two patients was thought to be due to the lack of surgical debridement. Drug concentrations well in excess of inhibitory levels for Streptococcus pyogenes were generally present throughout the treatment period; although this was not true of ceforanide concentrations relative to inhibitory levels for Staphylococcus aureus, the clinical response in patients with staphylococcal infection still appeared to be entirely satisfactory. Killing of S. pyogenes by 5, 50, and 500X the minimum inhibitory concentration of ceforanide proceeded at the same rate in vitro as did killing by 5, 50, and 500X the minimum inhibitory concentration of penicillin.

Topics: Bacteria; Cefamandole; Cellulitis; Cephalosporins; Erysipelas; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Time Factors

Ceforanide (30 mg/kg) administered every 12 h, cefazolin (20 mg/kg) administered every 8 h and methicillin or nafcillin (40 mg/kg) administered every 6 h were equally effective in reducing the number of Staphylococcus aureus in vegetations in rabbits with endocarditis. These treatments were more effective than methicillin or nafcillin administered every 12 h. Ceforanide produced higher peak concentrations and greater bactericidal activity in serum than the other drugs and had the longest half-life (5.8 h, compared with 0.4 to 0.8 h for the other agents.

Topics: Animals; Anti-Bacterial Agents; Cefamandole; Cefazolin; Cephalosporins; Endocarditis, Bacterial; Female; Methicillin; Nafcillin; Rabbits; Staphylococcal Infections; Staphylococcus aureus

HR 756, a new parenteral cephalosporin that is beta-lactamase resistant, was tested against 271 bacterial isolates. Both agar and broth dilution testing were employed, using two media and two inoculum sizes of bacteria. Antibacterial activity of the drug was compared to that of cefamandole (CFM) and ceforanide (CFN). In agar, HR 756 was more active than CFM and CFN against all bacteria tested except isolates of Staphylococcus aureus, which were better inhibited by CFM. HR 756 exhibited some antipseudomonas activity in agar, although a marked inoculum effect was apparent. A comparison of median minimum inhibitory and bactericidal concentrations in broth showed again that HR 756 was the most active of these three drugs. HR 756 demonstrated enhanced antibacterial activity compared to CFM and CFN against bacteria sensitive to all three drugs as well as against more resistant isolates of Serratia marcescens, Enterobacter species, and indole-positive Proteus. As with other cephalosporins, results for most bacteria were affected by inoculum size, medium, and type of dilution test employed in in vitro studies.

Topics: Bacteria; Cefamandole; Cephalosporins; Enterobacter; Enterobacteriaceae; Proteus; Pseudomonas aeruginosa; Serratia marcescens

Ceforanide (BL-S 786) is a new long-acting parenteral cephalosporin which has the major pharmacologic advantage of requiring only twice a day dosage. We treated 28 adult patients with community-acquired bacterial pneumonia using doses of 500 or 1000 mg every 12 hours. Twenty-four of 28 infections were due to Streptococcus pneumoniae and/or Hemophilus influenzae, and all pathogens were susceptible in vitro to both cephalothin and ceforanide. Patients were treated for a mean of 7.5 days, and all showed a good clinical and radiographic response with no mortality. Of the 13 patients with H. influenzae, the organism could still be recovered during therapy in 9/12 and post therapy in 3/8. One clinical superinfection (sepsis due to Pseudomonas aeruginosa) occurred during therapy. Side effects with therapy included thrombocytosis (15), asymptomatic eosinophilia (5), and mild elevation of the serum transaminases (3). These studies suggest that ceforanide is a safe and effective agent for the treatment of adult patients with bacterial pneumonia due to S. pneumoniae; further experience in therapy of H. influenzae is needed because of frequent failure of ceforanide to eradicate this organism from the sputum.

Topics: Adult; Cefamandole; Cephalosporins; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Injections, Intramuscular; Injections, Intravenous; Male; Pneumonia; Pneumonia, Pneumococcal

The bactericidal activity of ceforanide was compared, in an in vitro kinetic model, with that of five other cephalosproins: cephalothin, cefazolin, cefamandole, cefuroxime, and cefoxitin. Cultures of various pathogens in 95% human serum were incubated for 12 hours in the presence of the cephalosporins whose concentrations were modified periodically-by addition of a concentrated solution of drug or dilution with unmedicated serum-in order to simulate the variation of antibiotic concentration in human blood after one-gram intramuscular dose. One Gram-positive strain and six Gram-negative strains were used. Bactericidal activity was assessed by monitoring changes in the number of colony-forming units. Tests showed that against Klebsiella pneumoniae, ceforanide was the most active of the six cephalosporins. Proteus mirabilis was more susceptible to ceforanide and cefuroxime than to the other compounds; Enterobacter cloacae to ceforanide, cefuroxime, and cefamandole; Escherichia coli to ceforanide, cefuroxime, cefamandole, and cefazolin. The number of viable cells of Staphylococcus aureus was reduced below detectable levels by all cephalosporins except cefoxitin. On the other hand, Providencia stuartii was virtually unaffected by all of the cephalosporins except cefoxitin.

Topics: Bacteria; Cefamandole; Cephalosporins; Drug Resistance, Microbial; Drug Stability; Enterobacter; Escherichia coli; Humans; In Vitro Techniques; Kinetics; Klebsiella pneumoniae; Models, Biological; Proteus mirabilis

BL-S786 (ceforanide) is a new cephalosporin which showed broad-spectrum activity in vitro against 453 clinical isolates. At a concentration of 3.12 mug/ml, it inhibited greater than 75% of isolates of Escherichia coli, Klebsiella spp., Proteus mirabilis, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. Essentially no activity was observed against isolates of Serratia marcescens, and only minimal activity was observed against Enterobacter spp. Its activity was directly related to the size of the inoculum. The minimal bactericidal concentrations were similar to the minimal inhibitory concentrations for isolates of all organisms except S. aureus and S. pyogenes. The minimal bactericidal concentrations were considerably higher than the minimal inhibitory concentrations for these organisms.

Topics: Bacteria; Cefamandole; Cephalosporins; Microbial Sensitivity Tests

Ceforanide, a new cephalosporin antibiotic with a long half-life (3 h), can be administered twice daily. We evaluated its antimicrobial activity, pharmacology, and clinical efficacy. Twenty-seven patients with infections due to susceptible organisms received ceforanide, 0.5, 1, or 2 g, intramuscularly or intravenously every 12 h for 6 to 28 days. In vitro studies with the clinical isolates from 27 patients treated plus 263 additional isolates showed that ceforanide was active against cephalothin-susceptible gram-positive and gram-negative microorganisms. In addition, ceforanide inhibited 65% of cephalothin-resistant Escherichia coli and 65% of Enterobacter spp. at

Topics: Adult; Bacteria; Bacterial Infections; Cefamandole; Cephalosporins; Humans; Microbial Sensitivity Tests; Time Factors

The pharmacokinetics and safety of ceforanide and cefazolin were compared in normal subjects after 30-min intravenous infusions of 2-, 3-, and 4-g single doses and 4-g twice-daily doses for 10 days. No significant differences were observed in plasma-renal pharmacokinetic parameters between single and multiple doses of ceforanide. Half-life (t((1/2)), 2.8 h), plasma clearance (Cl(p), 48 ml/min per 1.73 m(2)), and renal clearance (Cl(0-12h) (r), 47 ml/min per 1.73 m(2); tubular secretion, 44%, and glomerular filtration, 56%) did not change with increased dose or on multiple dosing. No significant change was observed in t((1/2)) (1.9 h), area under the plasma concentration-time curve, Cl(r) (60 ml/min per 1.73 m(2); tubular secretion, 80%, and glomerular filtration, 20%), or Cl(p) (75 ml/min per 1.73 m(2)) for 4-g single doses compared with twice-daily administration of cefazolin. A small increase in cefazolin clearance was observed when plasma concentrations were greater than 100 mug/ml, when the single dose was increased from 2 to 4 g; this was a result of the decrease in percentage of plasma protein binding and increased renal clearance due to increased glomerular filtration. The increase in renal clearance resulted in a lack of linear proportionality of the plasma area under the curve with dose over a range of 2 to 4 for both cephalosporins, although this effect was much less marked with ceforanide. Both compounds were well tolerated both locally and systemically. There was no evidence of any change in renal function based on clearances of drug, p-aminohippuric acid, or creatinine, and other standard clinical parameters.

Topics: Adult; Blood Proteins; Cefamandole; Cefazolin; Cephalosporins; Dose-Response Relationship, Drug; Half-Life; Humans; Kinetics; Male; Protein Binding

The in vitro antimicrobial activities of BL-S786, cefoxitin, and cefamandole against 90 isolates of Enterobacteriaceae, including Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae and E. aerogenes, were studied by using an agar dilution procedure. Comparison of geometric mean minimal inhibitory concentrations showed that BL-S786 was half as active as cefamandole against Enterobacter species, 2 to 4 times more active than cefamandole against all other species, and 4 to 25 times more active than cefoxitin against all species. In vivo experiments employed acute protection tests in infected mice, using five isolates each of the five genera. Drugs were administered intramuscularly in two doses 3 h apart at dosages of 2.5, 5, 10, 20, and 40 mg per mouse. In most instances, BL-S786 was the most efficacious drug, being some 1.3 to 9.1 times more active than cefoxitin in all experiments and 1.5 to 8.7 times more active than cefamandole in most experiments. BL-S786 and cefamandole were comparable in activity in experiments with E. aerogenes, whereas BL-S786 was superior in experiments with E. cloacae.

Topics: Animals; Cefamandole; Cefoxitin; Enterobacter; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Female; Klebsiella pneumoniae; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Proteus mirabilis