cefamandole and Staphylococcal-Infections

The pharmacokinetics and intramuscular (i.m.) bioavailability of cefoperazone and cefamandole (20mg/kg) were investigated in dogs and the findings related to minimal inhibitory concentrations (MICs) for 90 bacterial strains isolated clinically from dogs. The MICs of cefamandole for Staphylococcus intermedius (MIC(90) 0.125 microg/mL) were lower than those of cefoperazone (MIC(90) 0.5 micro/mL) although the latter was more effective against Escherichia coli strains (MIC(90) 2.0 microg/mL vs. 4.0 microg/mL). The pharmacokinetics of the drugs after intravenous administrations were similar: a rapid distribution phase was followed by a slower elimination phase (t((1/2)lambda2) 84.0+/-21.3 min for cefoperazone and 81.4+/-9.7 min for cefamandole). The apparent volume of distribution and body clearance were 0.233 L/kg and 1.96 mL/kg/min for cefoperazone, 0.190 L/kg and 1.76 mL/kg/min for cefamandole. After i.m. administration the bioavailability and peak serum concentration of cefamandole (85.1+/-13.5% and 35.9+/-5.4 microg/mL) were significantly higher than cefoperazone (41.4+/-7.1% and 24.5+/-3.0 micog/mL), but not the serum half-lives (t(1/2el) 134.3+/-12.6 min for cefoperazone and 145.4+/-12.3 min for cefamandole). The time above MIC(90) indicated that cefamandole can be administered once daily to dogs for the treatment of staphylococcal infections (T>MIC for S. intermedius 23.8+/-0.3 and for Staphylococcus aureus 21.6+/-0.6h).

Topics: Animals; Anti-Bacterial Agents; Biological Availability; Cefamandole; Cefoperazone; Dogs; Female; Infusions, Intravenous; Injections, Intramuscular; Male; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus

A controlled randomized trial was carried out in 324 patients with inguinal hernia. Efficacy was evaluated of a single injection of cefamandole (n = 162) administered at operative site during local anesthesia, using an untreated group as control (n = 162), as prophylaxis against post-operative local infection. Seven patients in the control group developed abscesses at the operative site after discharge, 6 of the 7 during one-month follow up, compared with none in the treated group (n = 0.07). No side effects were reported due to the antibiotic therapy. The cost of the antibiotic treatment was 10 times less than that for treating the suppurations in the control group.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anesthesia, Local; Bacteremia; Cefamandole; Child; Drug Evaluation; Escherichia coli Infections; Female; Hernia, Inguinal; Humans; Male; Middle Aged; Postoperative Complications; Staphylococcal Infections; Streptococcal Infections

Recent studies of perioperative antimicrobial prophylaxis have indicated an improved efficacy of beta-lactamase-stable cephalosporins compared with cefazolin, the most commonly used prophylactic agent. Previous studies in our institution have revealed a superiority of cefamandole to cefazolin in patients undergoing heart surgery, although there was no difference between cefazolin and cefuroxime in patients undergoing peripheral vascular surgery. This study was therefore designed to compare cefamandole with cefazolin in wound infection prophylaxis in clean vascular surgery.. The study was conducted from August 1990 through May 1992 and consisted of 893 patients with aortic or infrainguinal arterial procedures randomized to receive either cefamandole or cefazolin.. The difference in infection rates associated with cefamandole versus cefazolin prophylaxis (3.2% vs 1.9%, respectively) was not significant (p = 0.42). A cost savings of approximately $95,000 per year at our institution favors the continued use of cefazolin over cefamandole. Risk factor analysis was carried out for preoperative and postoperative events that might have predisposed to infection. Only preoperative use of aspirin and the postoperative finding of a lymphocele correlated with a higher infection rate.. Cefazolin continues to be the most cost-effective antibiotic for prophylaxis in clean vascular surgical procedures.

Topics: Adult; Aged; Cefamandole; Cefazolin; Cost-Benefit Analysis; Humans; Middle Aged; Premedication; Risk Factors; Staphylococcal Infections; Surgical Wound Infection; Vascular Surgical Procedures

Infection following prosthetic joint implant jeopardizes the prosthesis and may lead to long-term locomotor disability. Interoperative antimicrobial prophylaxis can reduce the incidence of infectious complications. The comparative safety and efficacy of single-dose teicoplanin and four doses of cephamandole over a 24-hour period is currently being assessed in a single-blind, randomized concurrent study of patients who undergo first time hip or knee arthroplasty. Of 660 evaluated patients, 352 have received cephamandole and 308 teicoplanin. Two patients in each group had a surgical wound infection at 1 week after surgery. Reassessment 30 days postoperatively showed resolution of the infection in both of the teicoplanin patients and in one of the cephamandole patients. Proven or suspected infection involving other body systems occurred in 30 teicoplanin and 38 cephamandole patients at 1 week postoperatively and in 5 teicoplanin and 3 cephamandole patients 1 month after surgery. Adverse events occurred in 20 (5.1%) teicoplanin patients and 29 (7.1%) cephamandole patients. These preliminary results suggest that single-dose teicoplanin is a safe and effective prophylactic agent in prosthetic joint implant surgery.

Topics: Adolescent; Anti-Bacterial Agents; Cefamandole; Glycopeptides; Hip Prosthesis; Humans; Incidence; Joint Prosthesis; Knee Prosthesis; Single-Blind Method; Staphylococcal Infections; Surgical Wound Infection; Teicoplanin

Between 1986 and 1988, 450 adults undergoing coronary artery bypass, cardiac valve replacement, or both were enrolled into a prospective, randomized, comparative trial of cephalothin versus cefamandole as perioperative prophylaxis. They were assessed during their hospitalization and at 6 weeks and 6 months after discharge for postoperative infectious complications. Eleven patients had major postoperative infections including 5 with sternal wound infections (three bacteremic), 6 with bacteremia, 1 with prosthetic valve endocarditis, and 3 with severe venous donor graft site infections. Eight major infections occurred in patients receiving cephalothin prophylaxis and three in patients receiving cefamandole, with all five sternal wound infections occurring in the cephalothin group. Postoperative pathogens responsible for the major infections included gram-negative aerobes in 5 patients, Staphylococcus aureus in 4, and Staphylococcus epidermidis in 2. Preoperative colonizing staphylococcal isolates were not predictive of postoperative staphylococcal pathogens. Although there was no statistically significant difference in rate of major postoperative infectious complications using either cephalothin or cefamandole prophylaxis, there was a trend in favor of cefamandole. Gram-negative aerobes are becoming increasingly important pathogens in this setting.

Topics: Aged; Cardiac Surgical Procedures; Cefamandole; Cephalothin; Coronary Artery Bypass; Female; Humans; Incidence; Length of Stay; Male; Middle Aged; Premedication; Prospective Studies; Staphylococcal Infections; Surgical Wound Infection; Survival Rate

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

Topics: Cardiac Surgical Procedures; Cefamandole; Cefonicid; Double-Blind Method; Endocarditis, Bacterial; Enterobacteriaceae Infections; Heart Valve Prosthesis; Humans; Premedication; Prospective Studies; Random Allocation; Staphylococcal Infections; Surgical Wound Infection

The changes in coagulase-negative staphylococcal flora induced by cefamandole prophylaxis were compared with those induced by pefloxacin prophylaxis among patients undergoing heart valve surgery. Twenty-five patients (15 receiving cefamandole prophylaxis and 10 receiving pefloxacin prophylaxis) were included in the study. In the pefloxacin group, colonization rates in anterior nares and in chest skin or wound that were 60% and 50% respectively before surgery, became 50% and 20% respectively after surgery. In the cefamandole group, colonization rates in anterior nares and chest skin or wound were 53.3% and 60% respectively before surgery and became 53.3% and 40% respectively after surgery. Cefamandole did not appear to induce the emergence of oxacillin or pefloxacin resistant coagulase-negative staphylococcal colonization in any cultured site. On the other hand pefloxacin appeared somewhat more efficacious than cefamandole in eradicating staphylococcal flora of anterior nares and chest skin or wound. Pefloxacin and oxacillin resistant strains were found in the perianal area in 0% of patients before pefloxacin prophylaxis and in 70% of patients after pefloxacin prophylaxis. However, further studies are necessary to confirm the emergence of antibiotic resistant coagulase-negative staphylococci in the intestinal microflora after quinolone administration. The clinical implications of such apparently disturbing phenomenon remain to be evaluated.

Topics: Cefamandole; Coagulase; Heart Valve Prosthesis; Humans; Nose; Pefloxacin; Postoperative Care; Premedication; Randomized Controlled Trials as Topic; Skin; Staphylococcal Infections; Staphylococcus

Topics: Adult; Cefamandole; Clinical Trials as Topic; Endocarditis, Bacterial; Female; Humans; Male; Middle Aged; Penicillins; Shock, Cardiogenic; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis

A double-blind, multicenter trial compared cefonicid and cefazolin for prophylaxis against postoperative infection in 117 patients undergoing joint replacement. Cefonicid, which has an extended serum half-life, was administered once daily, while cefazolin was given every eight hours. The drug was administered one half to one hour before surgery and continued for up to 72 hours. Patients were observed throughout their hospitalization period and followed for 30 days after discharge. No evidence of wound or joint infection was observed in any of the patients who met the criteria for evaluation. Adverse reactions consisted mainly of infrequent gastrointestinal symptoms and laboratory abnormalities. Three patients died from causes unrelated to study medication. No differences between the two regimens were found with respect to safety or efficacy in the prevention of postoperative infection after arthroplasty. The effectiveness of once-daily administration should make cefonicid a highly cost-effective alternative to many of the more expensive first- and second-generation cephalosporin antibiotics currently used in hospital practice.

Topics: Adult; Aged; Aged, 80 and over; Arthroplasty; Cefamandole; Cefazolin; Cefonicid; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Escherichia coli Infections; Female; Humans; Male; Middle Aged; Random Allocation; Staphylococcal Infections

Forty-seven adults with infected cutaneous lesions including decubitus ulcers, leg ulcers, cellulitis, pyoderma, and infected dermatitis were treated in a randomized single-blind study with ceftizoxime (2 gm/day, administered intravenously) or cefamandole (4 gm/day, administered intravenously). The duration of treatment ranged from five to 17 days with ceftizoxime and from six to 14 days with cefamandole. Both gram-positive cocci (mostly Staphylococcus sp) and gram-negative bacilli were cultured from the infected areas before treatment. Clinical and bacteriological responses to both drugs were excellent. Ceftizoxime at a dosage of 1 gm twice daily proved to be at least as effective as 1 gm of cefamandole given four times daily. Both drugs were well tolerated, effective, and safe in the treatment of skin and skin-structure infections. Neither drug therapy had to be discontinued because of adverse effects.

Topics: Adult; Aged; Cefamandole; Cefotaxime; Ceftizoxime; Cellulitis; Clinical Trials as Topic; Dermatitis; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pressure Ulcer; Proteus Infections; Proteus mirabilis; Psoriasis; Pyoderma; Random Allocation; Skin Diseases, Infectious; Staphylococcal Infections; Time Factors

Three hundred patients were included in a prospective randomized double-blind trial comparing the efficacy of cefamandole with that of a placebo for prophylaxis of sepsis in operations using Ender or Küntscher nails, bone plates, or other internal fixation devices. Patients with an open fracture, total joint replacement, or direct operation on the hip were not included in the study. Sixteen patients were excluded because the trial protocol was not followed exactly, so a total of 284 patients participated, 134 of whom were given cefamandole and 150, a placebo. The two groups were similar in terms of mean age, sex ratio, duration of preoperative hospital stay, underlying risk factors, and type of surgical procedure. A superficial wound infection developed in none of the 134 patients who were given cefamandole and in seven of those in the control group (p less than 0.05). Two deep-wound infections developed in the cefamandole-treated group and four, in the control group (p greater than 0.05). Staphylococcus aureus, Staphylococcus epidermidis, and gram-negative bacilli were the most common infecting organisms. The rates of infection-related mortality and abscopal infection were similar in both groups. No adverse side effects of the drug were encountered.

Topics: Bone Nails; Bone Plates; Bone Screws; Cefamandole; Clinical Trials as Topic; Double-Blind Method; Follow-Up Studies; Humans; Orthopedics; Premedication; Staphylococcal Infections; Surgical Wound Infection

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

A randomized, prospective study of 200 consecutive established hand infections was designed to compare the efficacy of two antibiotics, cefamandole and nafcillin. Bacteriologic data revealed 63.5% of the patients grew multiple organisms (2.3 organisms per culture) and 26% of the patients had anaerobic infections. Complications were noted in 13% of all patients--26% in patients who grew aerobes and anaerobes and 9.8% in patients who grew aerobes alone (p less than 0.05). Despite the fact that 95% of all organisms were sensitive in vitro to cefamandole whereas only 67% of organisms were sensitive to nafcillin (p less than 0.01), complications occurred more frequently in patients treated with cefamandole. We conclude that the empirical selection of a broad-spectrum antibiotic is reasonable based on in vitro sensitivity studies; however, other factors such as treatment delay, initial extent of infection, anatomic location of infection, cause of infection, and extent of surgical debridement are important in the development of complications.

Topics: Adolescent; Adult; Aged; Bacteria, Anaerobic; Bacterial Infections; Cefamandole; Clinical Trials as Topic; Female; Hand Dermatoses; Humans; Male; Middle Aged; Nafcillin; Prospective Studies; Random Allocation; Skin Diseases, Infectious; Staphylococcal Infections; Streptococcal Infections

Eighty adult patients with microbiologically demonstrated staphylococcal infections were included in a comparative trial of cefamandole and cefamandole plus tobramycin. Patients with cefamandole-resistant pathogens were treated with vancomycin, if the initial therapy consisted of cefamandole, but were continued on cefamandole plus tobramycin if already started on that combination. Of the patients infected with cefamandole-susceptible strains, 91% (20/22) responded favorably to treatment with cefamandole alone, and 88% (30/34) responded favorably to cefamandole plus tobramycin. Of the patients infected with cefamandole-resistant staphylococci, 70% (7/10) responded to treatment with cefamandole plus tobramycin, and 86% (12/14) responded to treatment with vancomycin, even though vancomycin therapy was started 24 to 48 h later than cefamandole-plus-tobramycin therapy. No major side effects were observed; however, cefamandole plus tobramycin was associated with a rise in the serum creatinine level in 11% (4/44) of the patients. The bactericidal activity of the serum in cefamandole-treated patients and in cefamandole-plus-tobramycin-treated patients was identical against cefamandole-susceptible strains. Against cefamandole-resistant strains, 87% of the vancomycin-containing sera were bactericidal at a dilution of 1:8, whereas only 57% of the cefamandole-plus-tobramycin-containing sera were active at that dilution.

Topics: Anti-Bacterial Agents; Cefamandole; Cephalosporins; Drug Therapy, Combination; Humans; Methicillin; Penicillin Resistance; Sepsis; Staphylococcal Infections; Staphylococcus; Tobramycin; Vancomycin

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

The clinical efficacy and tolerance of cefamandole, a new cephalosporin antibiotic effective against indole-positive strains of Proteus, and cefazolin were studied after intramuscular administration of 500 mg of either of the two cephalosporins every 8 hr for seven days in a prospective, randomized study of 65 elderly male patients with complicated urinary tarct infections. Both antibiotics were effective in eradicating the infections, and there was no significant difference between the two groups in regard to tolerance and cure rate, as defined by a negative urine culture one week and four to six weeks following discontinuation of the treatment. Because of its broader antibacterial spectrum, cefamandole appears to represent an improvement over previously available cephalosporin antibiotics.

Topics: Aged; Cefamandole; Cephalosporins; Enterobacteriaceae Infections; Escherichia coli Infections; Humans; Klebsiella Infections; Male; Proteus Infections; Staphylococcal Infections; Streptococcal Infections; Urinary Tract Infections

Methicillin (meticillin)-susceptible Staphylococcus aureus (MSSA) strains producing large amounts of type A beta-lactamase (Bla) have been associated with cefazolin failures, but the frequency and impact of these strains have not been well studied. Here we examined 98 MSSA clinical isolates and found that 26% produced type A Bla, 15% type B, 46% type C, and none type D and that 13% lacked blaZ. The cefazolin MIC(90) was 2 microg/ml for a standard inoculum and 32 microg/ml for a high inoculum, with 19% of isolates displaying a pronounced inoculum effect (MICs of >or=16 microg/ml with 10(7) CFU/ml) (9 type A and 10 type C Bla producers). At the high inoculum, type A producers displayed higher cefazolin MICs than type B or C producers, while type B and C producers displayed higher cefamandole MICs. Among isolates from hemodialysis patients with MSSA bacteremia, three from the six patients who experienced cefazolin failure showed a cefazolin inoculum effect, while none from the six patients successfully treated with cefazolin showed an inoculum effect, suggesting an association between these strains and cefazolin failure (P = 0.09 by Fisher's exact test). In summary, 19% of MSSA clinical isolates showed a pronounced inoculum effect with cefazolin, a phenomenon that could explain the cases of cefazolin failure previously reported for hemodialysis patients with MSSA bacteremia. These results suggest that for serious MSSA infections, the presence of a significant inoculum effect with cefazolin could be associated with clinical failure in patients treated with this cephalosporin, particularly when it is used at low doses.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Cefamandole; Cefazolin; Humans; Methicillin; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus aureus; Treatment Failure

Quinupristin-dalfopristin (Q-D) is an injectable streptogramin active against most gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). In experimental endocarditis, however, Q-D was less efficacious against MRSA isolates constitutively resistant to macrolide-lincosamide-streptogram B (C-MLS(B)) than against MLS(B)-susceptible isolates. To circumvent this problem, we used the checkerboard method to screen drug combinations that would increase the efficacy of Q-D against such bacteria. beta-Lactams consistently exhibited additive or synergistic activity with Q-D. Glycopeptides, quinolones, and aminoglycosides were indifferent. No drugs were antagonistic. The positive Q-D-beta-lactam interaction was independent of MLS(B) or beta-lactam resistance. Moreover, addition of Q-D at one-fourth the MIC to flucloxacillin-containing plates decreased the flucloxacillin MIC for MRSA from 500 to 1,000 mg/liter to 30 to 60 mg/liter. Yet, Q-D-beta-lactam combinations were not synergistic in bactericidal tests. Rats with aortic vegetations were infected with two C-MLS(B)-resistant MRSA isolates (isolates AW7 and P8) and were treated for 3 or 5 days with drug dosages simulating the following treatments in humans: (i) Q-D at 7 mg/kg two times a day (b.i.d.) (a relatively low dosage purposely used to help detect positive drug interactions), (ii) cefamandole at constant levels in serum of 30 mg/liter, (iii) cefepime at 2 g b.i.d., (iv) Q-D combined with either cefamandole or cefepime. Any of the drugs used alone resulted in treatment failure. In contrast, Q-D plus either cefamandole or cefepime significantly decreased valve infection compared to the levels of infection for both untreated controls and those that received monotherapy (P < 0.05). Importantly, Q-D prevented the growth of highly beta-lactam-resistant MRSA in vivo. The mechanism of this beneficial drug interaction is unknown. However, Q-D-beta-lactam combinations might be useful for the treatment of complicated infections caused by multiple organisms, including MRSA.

Topics: Animals; Anti-Bacterial Agents; Cefamandole; Cefepime; Cephalosporins; Disease Models, Animal; Drug Resistance, Microbial; Drug Resistance, Multiple; Drug Therapy, Combination; Endocarditis, Bacterial; Humans; Lincosamides; Macrolides; Microbial Sensitivity Tests; Rats; Staphylococcal Infections; Staphylococcus aureus; Time Factors; Virginiamycin

The aim of this work was to determine whether erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and alpha-1-antitrypsin (A1AT) levels are correlated significantly with early postoperative infectious complications after hip prosthetic surgery.. This prospective study was conducted on 100 total hip replacements performed between 1994 and 1995. ESR, CRP and A1AT were obtained before surgery then at 1, 2 and 6 weeks after surgery.. Seven bacteriologically proven cases of infection were reported. Infection was considered to be superficial if it did not extend deeper than the muscles fascia. There was a strong statistical correlation between A1AT level and infection for all postoperative times (p<0.0001). A1AT was highly sensitive (87.5 p. 100) and specific (85.8 p. 100) for infection compared with ESR (sensibility 70 p. 100 and specificity 65.9 p. 100) and CRP (sensitivity 63.6 p. 100 and specificity 80.1 p. 100).. In our hands, A1AT can be a most useful diagnostic tool for infection after prosthesis hip surgery. Although not totally specific, it is highly sensitive for infection compared with other tools such as ESR and CRP more frequently used. These findings suggest an avenue of research on the role of A1AT in infectious complications after prosthetic joint surgery.

Topics: Acinetobacter Infections; Adult; Aged; Aged, 80 and over; alpha 1-Antitrypsin; Anti-Bacterial Agents; Antibiotic Prophylaxis; Blood Sedimentation; C-Reactive Protein; Cefamandole; Cephalosporins; Clinical Enzyme Tests; Data Interpretation, Statistical; Female; Hip Prosthesis; Humans; Male; Middle Aged; Nephelometry and Turbidimetry; Postoperative Care; Prospective Studies; Prosthesis-Related Infections; Sensitivity and Specificity; Staphylococcal Infections; Staphylococcus epidermidis; Time Factors; Tobramycin; Vancomycin

Beta-lactams active against methicillin-resistant Staphylococcus aureus (MRSA) must resist penicillinase hydrolysis and bind penicillin-binding protein 2A (PBP 2A). Cefamandole might share these properties. When tested against 2 isogenic pairs of MRSA that produced or did not produce penicillinase, MICs of cefamandole (8-32 mg/L) were not affected by penicillinase, and cefamandole had a > or =40 times greater PBP 2A affinity than did methicillin. In rats, constant serum levels of 100 mg/L cefamandole successfully treated experimental endocarditis due to penicillinase-negative isolates but failed against penicillinase-producing organisms. This suggested that penicillinase produced in infected vegetations might hydrolyze the drug. Indeed, cefamandole was slowly degraded by penicillinase in vitro. Moreover, its efficacy was restored by combination with sulbactam in vivo. Cefamandole also uniformly prevented MRSA endocarditis in prophylaxis experiments, a setting in which bacteria were not yet clustered in the vegetations. Thus, while cefamandole treatment was limited by penicillinase, the drug was still successful for prophylaxis of experimental MRSA endocarditis.

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Carrier Proteins; Cefamandole; Cephalosporins; Endocarditis; Hexosyltransferases; Methicillin Resistance; Microbial Sensitivity Tests; Muramoylpentapeptide Carboxypeptidase; Penicillin-Binding Proteins; Penicillinase; Peptidyl Transferases; Rats; Staphylococcal Infections; Staphylococcus aureus

The purpose of this prospective study was to evaluate the effect of prophylactic antibiotic treatment on postoperative antibiotic spinal wound infection after spinal surgery with instrumentation. Subjects consisted of 110 successive patients that underwent instrumented fusion with Cotrel-Dubousset (CD) or Miami Moss instrumentation. In 56 cases, the indication for surgery was painful spondylolisthesis. The remaining 54 patients were treated for idiopathic scoliosis. In total, 172 spinal procedures were performed and included in the study. Preoperative infection prophylaxis consisting of 2 g cefamandole was administered to all patients. Patients received three doses of 2 g/day cefamandole after surgery for 3 days. Follow-up ranged from 1 to 4 years. The study revealed an early infection in one (0.6%) of the 172 procedures in a patient with spondylolisthesis. A late infection occurred in one (0.6%) patient with the diagnosis of idiopathic scoliosis. In both cases, cultures were positive for Staphylococcus aureus.

Topics: Adolescent; Adult; Antibiotic Prophylaxis; Cefamandole; Cephalosporins; Child; Female; Humans; Male; Middle Aged; Prospective Studies; Spinal Fusion; Staphylococcal Infections; Staphylococcus aureus; Surgical Wound Infection

The susceptibility of clinical isolates of methicillin-susceptible and -resistant staphylococci from cancer patients with central venous catheter bacteremia to quinupristin/dalfopristin, a semisynthetic streptogramin, was determined in vitro. Susceptibility of these isolates to nine other antistaphylococcal antibiotics was also determined for comparison. A total of 197 staphylococcal strains were tested from 1983 to 1992. Quinupristin/dalfopristin was bactericidal against all isolates, independent of their resistance to methicillin. Its activity was similar to that of vancomycin but superior to that of teicoplanin. Quinupristin/dalfopristin may prove to be an important addition to our armamentarium against catheter-related staphylococcal infections.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antitubercular; Bacteremia; Catheterization, Central Venous; Cefamandole; Cephalosporins; Ciprofloxacin; Clindamycin; Daptomycin; Humans; Methicillin; Methicillin Resistance; Microbial Sensitivity Tests; Neoplasms; Novobiocin; Oxacillin; Penicillins; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Teicoplanin; Vancomycin; Virginiamycin

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Cefamandole; Imipenem; Male; Methicillin Resistance; Mice; Mice, Inbred ICR; Staphylococcal Infections; Staphylococcus aureus

To determine the incidence, the mortality, the risk factors and the most appropriate method for treatment of sternal infections, 9,742 charts were reviewed retrospectively of patients having undergone a sternotomy for cardiac surgery at the Montreal Heart Institute. One hundred and eleven sternal infections (1.1%) were identified: 55 (0.57%) superficial, 56 (0.57%) profound (mediastinitis). The treatment for these profound infections was either debridement, open or closed with drainage irrigation, pectoral flap closure-repair, or epiplooplasty closure. The risk factors for those patients experiencing profound infections were diabetes, obesity, length of the surgical intervention, the time spent in the operating room, and the duration of endotracheal intubation. Eleven of the 111 patients died. The average length of hospitalization were similar for those patients treated by pectoral flap repair and by the epiplooplasty closure. All patients (100%) treated by the epiplooplasty closure developed an epigastric hernia. Six cases of recurrent infection were observed in the group treated by debridement. The average hospital stay was shortened for those patients benefiting from the pectoral flap and epiplooplasty closures. A high incidence of mortality is associated with profound sternal infection. The methods of treatment are various. We recommend as treatment of choice, the pectoral flap closure because there is relatively low risks with this procedure, little to no recurrence of infection, a shorter hospital stay and this procedure does not provoke epigastric hernia.

Topics: Adult; Aged; Cefamandole; Drainage; Female; Heart Diseases; Humans; Incidence; Male; Mediastinitis; Middle Aged; Multivariate Analysis; Osteotomy; Postoperative Complications; Preoperative Care; Retrospective Studies; Staphylococcal Infections; Sternum; Surgical Flaps

LY 146032, teicoplanin, vancomycin, oxacillin, cephalothin, cefamandole, ampicillin plus sulbactam, and cefoperazone plus sulbactam were studied against six isolates of staphylococci (including both Staphylococcus aureus and coagulase negative staphylococci) using in vivo and in vitro methods. In vitro susceptibility measurements demonstrated that all six isolates were sensitive to LY 146032 and vancomycin and that five of six isolates were sensitive to tiecoplanin, cefamandole, ampicillin plus sulbactam, and cefoperazone plus sulbactam. Comparison of antimicrobial therapy in an in vivo rabbit model demonstrated that cefoperazone plus sulbactam was active against the greatest number of isolates (five of six) based on a reduction of greater than or equal to 5.0 log10 colony forming units per milliliter (CFU/ml) from growth control at the end of the animal treatment study. Vancomycin and oxacillin were equal in achieving reductions of greater than or equal to 5.0 log10 CFU/ml in four of the six isolates. Comparing each isolate's in vivo outcome to in vitro data shows that in vitro susceptibility tests overpredict the sensitivity of these six isolates to LY 146032 and vancomycin, are variable for teicoplanin, cefamandole, ampicillin plus sulbactam, and cefoperazone plus sulbactam, and underpredict for oxacillin.

Topics: Ampicillin; Animals; Anti-Bacterial Agents; Cefamandole; Cefoperazone; Cephalothin; Daptomycin; Disease Models, Animal; Female; Glycopeptides; Oxacillin; Peptides; Rabbits; Staphylococcal Infections; Sulbactam; Teicoplanin; Vancomycin

Approximately 35,000 Staphylococcus aureus surgical wound infections occur annually in the United States. To investigate why S aureus causes infection despite the perioperative administration of cephalosporins, we compared 35 methicillin-susceptible isolates recovered from deep wound infections that complicated cefazolin prophylaxis (18 of 1650 patients) and cefamandole prophylaxis (17 of 3702 patients) with 64 colonizing isolates from presurgical patients. Compared with both colonizing and cefamandole-associated isolates, S aureus isolates from cefazolin-associated infections were more resistant to cefazolin by specialized assays. Staphylococcus aureus isolates that produced the A and C variants of staphylococcal beta-lactamase were associated with infections following cefazolin and cefamandole prophylaxis, respectively. These isolates hydrolyze the respective cephalosporins rapidly, suggesting that staphylococcal survival after perioperative prophylaxis may be mediated by in vivo degradation of the prophylactically administered cephalosporin. These data indicate that some S aureus wound infections occur because of deficiencies in antimicrobial effectiveness that are not detectable by routine susceptibility tests. This finding has important implications for the therapy and prevention of S aureus infection.

Topics: beta-Lactamases; Cefamandole; Cefazolin; Cephalosporins; Double-Blind Method; Humans; Methicillin; Microbial Sensitivity Tests; Premedication; Prospective Studies; Random Allocation; Staphylococcal Infections; Staphylococcus aureus; Surgical Wound Infection

We evaluated under controlled conditions the efficacy of topical and systemic antibiotics, alone and in combination, in the prevention of wound infection and measured serum and tissue antibiotic levels in the wound and distant tissue after administration of antibiotics topically, systemically, and in combination. Adult Sprague-Dawley rats were contaminated on the dorsal paravertebral muscles with a preset standardized inoculum of Staphylococcus aureus, Escherichia coli, and Bacteroides fragilis. A second-generation cephalosporin was used; systemic administration was given intramuscularly and topically in powder form. Wound infection was confirmed by the recovery of the organism by culture. Prophylactic antibiotics were effective in preventing wound infection in all groups. Topical antibiotic and a combination (topical/systemic) antibiotic were significantly more effective than was systemic antibiotic alone in preventing wound infection. Adequate levels of antibiotic were achieved in serum and tissue with both topical and systemic antibiotics. Wound tissue concentration of antibiotic was significantly higher when topical antibiotic was used.

Topics: Administration, Topical; Animals; Bacteroides Infections; Cefamandole; Escherichia coli Infections; Injections, Intramuscular; Rats; Rats, Inbred Strains; Staphylococcal Infections; Wound Infection

The pathophysiologic mechanism of acute hematogenous osteomyelitis in children has been further elucidated. Investigations revealed, that certain strains of staphylococcus aureus, responsible for the majority of infections, can resist intracellular killing after phagocytosis. Beta-lactam-antibiotics don't penetrate well into phagocytes and are unable to eradicate staphylococci surviving intracellularly. Fosfomycin, clindamycin and combinations of these antibiotics with beta-lactam-antibiotics are able to eradicate staphylococci also in phagocytic vacuoles. In a therapeutic investigation 36 patients have been treated with fosfomycin in combination with cefamandole intravenously for 10-14 days followed by clindamycin orally for 3-6 weeks. With this treatment schedule the therapeutic outcome was superior to previously employed therapeutic regimen.

Topics: Cefamandole; Child; Clindamycin; Drug Therapy, Combination; Fosfomycin; Humans; Macrophages; Osteomyelitis; Oxacillin; Phagocytosis; Sepsis; Staphylococcal Infections; Staphylococcus aureus

Hemorrhagic shock has been associated with an increased risk of infection after injury. The immediate and long term effects of hemorrhagic shock without tissue injury on the susceptibility of an animal to infection and the efficacy of antibiotic prophylaxis to prevent infection in this setting were examined. Sprague-Dawley rats were subjected to hemorrhagic shock (LD15) by bleeding to a mean arterial pressure of 45 millimeters of mercury for 45 minutes and were resuscitated with shed blood and normal saline solution. In one experiment, dorsal wounds were inoculated one hour before or after shock with either 10(6), 10(8) or 10(10) Staphylococcus aureus. In a second experiment, rats were infected at one hour, or one, three or five days after shock with 10(6), 10(7) or 10(8) S. aureus. Equivalent numbers of rats received cefamandole nafate prior to bacterial challenge. Hemorrhagic shock increased the susceptibility to wound infection at all inocula. Infection increased whether rats were wounded before or after shock, and this effect was sustained for up to three days. Antibiotic prophylaxis was of limited value in reducing the incidence of wound infection after shock.

Topics: Animals; Cefamandole; Disease Models, Animal; Disease Susceptibility; Female; Rats; Rats, Inbred Strains; Shock, Hemorrhagic; Staphylococcal Infections; Time Factors; Wound Infection

To assess the predictive value of preoperative surveillance cultures for the postoperative development of Staphylococcus aureus wound infection, the findings in 563 patients who underwent elective cardiac surgery were evaluated. One hundred and forty-seven (26%) were found to be S. aureus carriers preoperatively. Postoperatively, 11 S. aureus wound infections developed, 4 in patients whose cultures were positive preoperatively and 7 in patients whose cultures were negative preoperatively. The patient's endogenous flora appears to be the source of only a minority of such postoperative infections. The authors conclude that preoperative surveillance cultures are not of value in predicting patients at risk for wound infection after elective cardiac surgery.

Topics: Adolescent; Adult; Cefamandole; Cephalothin; Child; Child, Preschool; Female; Follow-Up Studies; Heart Diseases; Humans; Infant; Male; Middle Aged; Premedication; Preoperative Care; Staphylococcal Infections; Staphylococcus aureus; Surgical Wound Infection

To determine whether a slime-producing strain of Staphylococcus epidermidis was capable of producing acute infection of a prosthetic vascular graft, 5 cm segments of knitted Dacron were implanted in the infrarenal aortic position of dogs in three groups of animals. These included a control group (no graft contamination), a contaminated group that received a graft soaked in an S. epidermidis solution (untreated group), and a contaminated group in which perioperative antibiotics (three doses of cefamandole, 100 mg/kg) were administered (prophylaxis group). In all the animals reexploration and graft removal were performed at 10 days, with replacement of the defect being achieved with a new uncontaminated graft. These animals underwent exploration a third time after an additional 10-day period. S. epidermidis was not grown from the control animals (n = 7) but was cultured in 44% of the prophylaxis group (n = 9) and 88% of the untreated group (n = 16) during at least one of the operative procedures (chi 2 = 15.859; p less than 0.001). The pathologic features of acute S. epidermidis infection were best seen in the untreated animals and included anastomotic disruption (56%), periaortic hematoma, and lymphadenopathy (94%). Microscopic examination of the aortic tissues revealed extensive infiltrates of leukocytes, macrophages, and foreign body giant cells with aortic necrosis. These features were less prominent in the prophylaxis animals. We conclude that S. epidermidis is capable of producing acute graft infection with perigraft inflammation and anastomotic disruption. The administration of perioperative antibiotics reduced but did not abolish these effects of bacterial contamination of prosthetic vascular grafts.

Topics: Animals; Aorta, Abdominal; Blood Vessel Prosthesis; Cefamandole; Dogs; Female; Microscopy, Electron, Scanning; Premedication; Staphylococcal Infections; Staphylococcus epidermidis; Surgical Wound Infection

We evaluated antibiotic prophylaxis in the rabbit model of experimental endocarditis with three strains of Staphylococcus epidermidis of differing susceptibility patterns. For the first strain, which was highly susceptible to methicillin and cephalosporins, vegetations grew S. epidermidis for all 15 untreated rabbits compared with 1 of 20 rabbits receiving cefazolin, 3 of 20 receiving cefamandole, none of 20 receiving vancomycin, and none of 20 receiving LY146032. For the second strain, which was methicillin resistant but cephalosporin susceptible, vegetations were positive for 14 of 15 untreated controls, 4 of 20 receiving cefazolin, 5 of 22 receiving cefamandole, none of 20 receiving vancomycin, and none of 20 receiving LY146032. For the third strain, which was methicillin resistant and only intermediately susceptible to cephalosporin antibiotics, vegetation cultures were positive for 15 of 17 untreated controls, 14 of 21 receiving cefazolin, 11 of 20 receiving cefamandole, 5 of 20 receiving vancomycin, and 0 of 22 receiving LY146032. In conclusion, these studies in the endocarditis model indicate that cefazolin and cefamandole have some protective value against certain strains of S. epidermidis. Vancomycin and LY146032, however, were more active than cephalosporins for all three strains included in this analysis. These findings support the need for trials of vancomycin and LY146032 prophylaxis in patients undergoing placement of prosthetic heart valves.

Topics: Animals; Anti-Bacterial Agents; Cefamandole; Cefazolin; Cephalosporins; Daptomycin; Drug Resistance, Microbial; Endocarditis, Bacterial; Methicillin; Penicillin Resistance; Peptides; Rabbits; Staphylococcal Infections; Staphylococcus epidermidis; Vancomycin

Hemorrhagic shock increases the susceptibility to infection in both clinical and laboratory settings. Hemorrhagic shock also is associated with a decreased production of interferon-gamma (IFN-gamma), a potent modulator of immune function. We investigated the effect of IFN-gamma both alone and in addition to antibiotic prophylaxis upon infection following hemorrhagic shock. Sprague-Dawley rats were bled to a mean arterial pressure of 45 mm Hg for 45 min and then were resuscitated with shed blood and normal saline. Abscess formation was induced 1 hr later by subcutaneous injection of 1 X 10(8) Staphylococcus aureus. Four treatments were investigated: (1) control; (2) recombinant rat IFN-gamma, 7500 units, 30 min after inoculation and daily for 3 days; (3) cefamandole (CEF) nafate, 30 mg/kg, 30 min before and 4 hr after inoculation; and (4) IFN-gamma + CEF as in (2) and (3). Abscess size, weight, and quantitative bacterial counts were measured 7 days after inoculation. Hemorrhagic shock increased mean abscess size from 11.7 +/- 2.8 to 14.1 +/- 1.9 mm (P less than 0.05), in untreated rats. IFN-gamma alone resulted in minor changes in abscess formation in both shocked and unshocked animals. Shock rendered CEF ineffective in reducing abscess size. IFN-gamma + CEF significantly reduced abscess size (14.1 +/- 1.9 to 8.1 +/- 1.8 mm) and weight (771 +/- 214 to 252 +/- 132 mg) and decreased bacterial count after shock to 12% of control (all P less than 0.05). These data demonstrate that hemorrhagic shock impairs antibiotic efficacy; however, the addition of IFN-gamma restores the ability of host defenses to combat bacterial infection.

Topics: Abscess; Animals; Cefamandole; Immunity; Interferon-gamma; Shock, Hemorrhagic; Staphylococcal Infections

The efficacy of cefamandole and cefuroxime in preventing postoperative wound infections was compared in 3037 patients undergoing open-heart surgery. Antibiotic prophylaxis in 1467 patients having coronary artery bypass and valve replacement surgery was cefamandole 2 g iv preoperatively followed by 2 g q6h for five days postoperatively; 1570 patients received cefuroxime 1.5 g iv preoperatively then 1.5 g iv q 12h for three days postoperatively. Postoperative wound infections (sternal and leg wounds) were studied in each treatment group. In the cefamandole study group, 27 patients (1.8 percent) developed postoperative wound infections (9 sternal and 18 leg wounds). In the cefuroxime treatment group, 19 patients (1.2 percent) developed postoperative wound infections (9 sternal and 10 leg wounds). Overall, no statistical difference was found between the two antibiotics in preventing postoperative wound infections. However, in patients having valve replacement surgery, cefuroxime was found statistically more effective than cefamandole prophylaxis in preventing sternal wound infections (no infections in 284 patients compared with five infections in 205 patients, respectively, p = 0.01). The most common organism isolated from infected wounds with cefamandole was Staphylococcus aureus followed by S. epidermidis compared with cefuroxime which had S. epidermidis followed by S. aureus. Cefuroxime was found to be as effective as cefamandole and considerably less expensive in preventing postoperative wound infections in patients undergoing open-heart surgery.

Topics: Cardiac Surgical Procedures; Cefamandole; Cefuroxime; Cephalosporins; Coronary Artery Bypass; Heart Valve Prosthesis; Humans; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Surgical Wound Infection

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

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.

Topics: Ambulatory Care; Bacterial Infections; Cefamandole; Cefonicid; Ceftriaxone; Cellulitis; Cephalosporins; Gonorrhea; Half-Life; Humans; Injections, Intramuscular; Osteomyelitis; Pyelonephritis; Respiratory Tract Infections; Staphylococcal Infections; Streptococcal Infections

Plasma levels of antibiotics often do not correlate well with their tissue levels. To determine optimal antibiotic coverage for prophylactic effect in vascular surgery, we studied the tissue pharmacokinetics of four cephalosporins in dogs: cefazolin, cefoxitin, cefamandole, and moxalactam for 3 hours after a single (25 mg/kg) intravenous injection. The minimal inhibitory concentration (MIC) of these antibiotics for the three most common pathogens involved in graft infections (Staphylococcus aureus, S. albus, and Escherichia coli) and their tissue concentration (TC) in the plasma, muscle, subcutaneous tissue, and aortic wall were assayed. The data are presented as TC/MIC ratio. Cefoxitin and moxalactam failed to achieve an effective therapeutic TC/MIC ratio (greater than 10) for S. aureus and S. albus in all the tissues studied whereas cefoxitin and cefamandole were above therapeutic levels. All antibiotics achieved an effective therapeutic ratio against E. coli, but cefamandole performed better (p less than 0.05) than cefoxitin; the latter reached effective levels at 3 hours. Cefamandole attained the most effective bioactive aortic tissue levels when the three most common pathogens were considered together and should therefore be considered as an antibiotic agent of choice for prophylaxis in vascular surgery.

Topics: Animals; Aorta; Bacterial Infections; Cefamandole; Cefazolin; Cefoxitin; Cephalosporins; Dogs; Escherichia coli Infections; Kinetics; Moxalactam; Muscles; Staphylococcal Infections; Time Factors; Tissue Distribution; Vascular Surgical Procedures

Coagulase-negative staphylococci (S. epidermidis, 43 strains; S. warneri, 16 strains; S. haemolyticus, five strains; and others, four strains) were tested by the agar dilution method for nafcillin susceptibility: 53 were susceptible with a minimal inhibitory concentration (MIC) of less than or equal to 2 micrograms/ml; four were of indeterminate susceptibility, MIC = 4-16 micrograms/ml; and 11 were resistant, MIC greater than or equal to 32 micrograms/ml. The bactericidal activities from 0 to 24 hr for nafcillin, vancomycin, cephalothin, cefazolin, and cefamandole, each at 16 micrograms/ml in broth, were determined for all the isolates. The data indicate that a nafcillin agar dilution susceptibility test result of resistance does not consistently predict lack of killing activity by the cephalosporins. It is likely that each cephalosporin would have to be tested against individual coagulase-negative staphylococci in order to determine a suitable therapeutic or prophylactic cephalosporin, if a cephalosporin were to be used. Vancomycin was bactericidal for all the nafcillin-resistant coagulase-negative organisms tested.

Topics: Cefamandole; Cefazolin; Cephalosporins; Cephalothin; Coagulase; Humans; Microbial Sensitivity Tests; Nafcillin; Penicillin Resistance; Regression Analysis; Staphylococcal Infections; Staphylococcus; Staphylococcus epidermidis; Vancomycin

Ninety-two microbiologically documented staphylococcal infections were treated with cefamandole in an open comparative study on the clinical efficacy of this cephalosporin in the therapy of infections caused by both methicillin-susceptible and methicillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus spp. The majority of the episodes (86 of 92) were treated with cefamandole alone, and six were treated with cefamandole in association with other antibiotics. In the evaluable S. aureus infections, 34 of 46 (73.9%) due to methicillin-susceptible strains and 12 of 16 (75%) due to methicillin-resistant strains responded to therapy. In particular, among the patients infected by methicillin-susceptible S. aureus 6 of 9 cases of septicemia, 0 of 2 cases of endocarditis, 2 of 2 cases of pneumonia, 2 of 3 osteoarticular infections, 8 of 12 cases of peritonitis in patients with chronic renal failure in continuous ambulatory peritoneal dialysis (CAPD), 13 of 15 skin-soft tissue infections, and 3 of 3 urinary tract infections responded to therapy. Among those due to methicillin-resistant strains, cure was achieved in 2 of 4 cases of septicemia, 0 of 1 case of endocarditis, 9 of 10 skin-soft tissue infections, and 1 of 1 urinary tract infection. In the evaluable infections caused by coagulase-negative staphylococci, 9 of 11 (81.8%) due to methicillin-susceptible and 15 of 17 (88.2%) due to methicillin-resistant strains responded to therapy. In particular, among patients infected by methicillin-susceptible, coagulase-negative staphylococci, 4 of 4 cases of septicemia, 0 of 1 case of endocarditis, 1 of 1 case of pneumonia, 1 of 1 case of peritonitis in CAPD, 2 of 3 infections of skin-soft tissue, and 1 of 1 urinary tract infection responded to therapy. Among patients infected by methicillin-resistant, coagulase-negative staphylococci were cured 5 of 6 cases os septicemia, 6 of 6 cases of peritonitis (in CAPD), 4 of 4 infections of skin-soft tissue, and 0 of 1 urinary tract infection.

Topics: Adult; Aged; Cefamandole; Coagulase; Female; Humans; Male; Methicillin; Middle Aged; Penicillin Resistance; Sepsis; Staphylococcal Infections

An experimental wound model was used to evaluate the effectiveness of cefazolin, cefamandole, and cefotaxime in the prevention of wound infection. Incisions were contaminated with Staphylococcus aureus, Escherichia coli, or a standardized fecal suspension. Regardless of the contaminant employed, the prophylactic use of either cefazolin, cefamandole, or cefotaxime yielded lower concentrations of bacteria in the wounds and fewer infections compared with treatment with saline solution. Within the context of this experimental model, cefazolin proved equally as effective as the newer and more expensive cephalosporins, cefamandole and cefotaxime.

Topics: Animals; Cefamandole; Cefazolin; Cefotaxime; Cephalosporins; Escherichia coli Infections; Feces; Female; Mice; Staphylococcal Infections; Surgical Wound Infection

Cefonicid is a parenteral cephalosporin with a half-life of 4.5 hours, which permits once-daily dosing. The efficacy of cefonicid in the treatment of established staphylococcal infections was reviewed in all patients with infections due to staphylococci who were treated with cefonicid during the US clinical development program. Two hundred evaluable cases were identified, of which 95 had other pathogens as well. Cefonicid was clinically effective in 92% of skin and soft tissue infections, 74% of bone and joint infections, 83% of respiratory tract infections, and 95% of urinary tract infections. None of the three evaluable patients with Staphylococcus aureus endocarditis responded to cefonicid. Thus, based on current evidence, cefonicid is not effective in the treatment of established staphylococcal endocarditis. However, for the treatment of staphylococcal infections at other sites, cefonicid is comparable to other cephalosporins, most of which must be administered more frequently than cefonicid and thus are less cost-effective.

Topics: Cefamandole; Cefonicid; Drug Evaluation; Female; Humans; Male; Staphylococcal Infections

Topics: Adult; Aged; Cefamandole; Female; Heroin Dependence; Humans; Male; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus aureus

Topics: Ampicillin; Cefamandole; Cloxacillin; Drug Therapy, Combination; Humans; Skin Diseases, Infectious; Staphylococcal Infections

An investigation was carried out into the effectiveness of cefamandole as compared to that of cephalothin against methicillin-sensitive and methicillin-resistant strains of Staphylococcus aureus both in vitro and in mice with the experimental peritonitis-induced septicaemia as a model for a generalized infection. In the agar-diffusion test 95% of 118 and in the broth-dilution test 80% of 30 methicillin-resistant strains were sensitive to cefamandole. In experimental infections the ED50 with methicillin-resistant strains was 20 times greater than that required for the methicillin-sensitive strain although the MIC was only twice that for the latter. Doses of cephalothin required for treatment of infections due to methicillin-resistant strains were also twenty times greater than for those due to the methicillin-sensitive strain. But these differences were consistent with those in MIC (by factors of 16-32). Thus, the results of in-vitro testing of cefamandole are not predictive for its therapeutic efficacy in staphylococcal infections with methicillin-resistant strains. Therefore, rather than relying on inhibition zone diameter and MIC, the information that a staphylococcal strain is methicillin-resistant should be used as an indication not to choose cefamandole for chemotherapy.

Topics: Animals; Cefamandole; Male; Methicillin; Mice; Microbial Sensitivity Tests; Oxacillin; Penicillin Resistance; Peritonitis; Staphylococcal Infections; Staphylococcus aureus

Hand lacerations, especially when inadequately treated, may result in infections caused by aerobic or anaerobic bacteria. Anaerobic infections most commonly result from human bite injuries in which there is contact between hand and mouth. The search continues for an ideal antibiotic to employ when anaerobic organisms are suspected. In this study cefamandole, a new cephalosporin antibiotic, was employed whenever anaerobic hand infections were suspected following trauma. In each patient quantitative cultures for both aerobic and anaerobic organisms were obtained. All organisms isolated were tested by standard susceptibility assays for both aerobes and anaerobes. In the case of anaerobes, minimum inhibitory concentration assays were also performed. After the initial culture was obtained, each patient received approximately 1.5 gm of cefamandole every 6 hours for a period of 5 days. This therapy was changed only if susceptibility studies indicated resistance to cefamandole. In our patients, 58% of the infectious organisms were aerobic and facultative anaerobic and 42% were obligate anaerobes. The predominant organisms isolated were Staphylococcus aureus and Peptostreptococcus anaerobius, which accounted for 42% of the infections. In most of the aerobic infections a single organism was isolated, whereas multiple organisms were identified in the anaerobic infections. All but one of the infections responded to cefamandole; the one that didn't was caused by Enterobacter cloacae and required treatment with an aminoglycoside. Because of its broad-spectrum coverage, which includes both aerobes and anaerobes, cefamandole is useful in treating infections, especially those resulting from human bites.

Topics: Adolescent; Adult; Bacterial Infections; Cefamandole; Enterococcus faecalis; Female; Hand Dermatoses; Humans; Male; Peptostreptococcus; Skin Diseases, Infectious; Staphylococcal Infections; Streptococcal Infections

Topics: Animals; Cefamandole; Cephalosporins; Cephalothin; Microbial Sensitivity Tests; Osteomyelitis; Rabbits; Staphylococcal Infections; Staphylococcus aureus

Topics: Anti-Bacterial Agents; Cefamandole; Cephalosporins; Drug Therapy, Combination; Humans; Oxacillin; Penicillin Resistance; Sepsis; Staphylococcal Infections; Tobramycin; Vancomycin

Cefoperazone (10 mg/kg) and cephalothin (20 mg/kg) administered intramuscularly every 6 h were both effective in reducing the number of Staphylococcus aureus cells in vegetations in rabbits with endocarditis. Cefoperazone produced higher peak concentrations and greater bactericidal activity in serum than did cephalothin. Cefoperazone (40 mg/kg) administered every 6 h was significantly more effective than cefamandole (40 mg/kg) administered every 6 h in reducing the number of Enterobacter aerogenes cells in vegetations. Although cefamandole produced higher peak concentrations in serum, the serum bactericidal activity was greater with cefoperazone. The half-lives in serum were 0.64 h for cefoperazone and 0.46 h for cephalothin and cefamandole.

Topics: Animals; Cefamandole; Cefoperazone; Cephalosporins; Cephalothin; Endocarditis, Bacterial; Enterobacter; Enterobacteriaceae Infections; Female; Half-Life; Rabbits; Staphylococcal Infections

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

In 24 patients undergoing open-heart operation, 2 gm of cefamandole was administered intravenously by bolus technique at various time intervals prior to operation. Samples of pericardial fluid, atrial appendage tissue, and serum were obtained simultaneously in order to compare antibiotic levels in these sites as a function of time. All samples were microbiologically assayed by disc diffusion. Using linear regression analysis, the atrial appendage and serum half-lives for cefamandole were 36 and 38 minutes, respectively. At 40 minutes, peak levels of cefamandole were observed both in pericardial fluid and in atrial appendage tissue. The peak concentrations of cefamandole were 50 micrograms/gm in atrial appendage and 25 micrograms/ml for free drug content in pericardial fluid. These amounts were appreciably above the mean minimum inhibitory concentration of cefamandole for penicillin-resistant staphylococci, the usual pathogens grown in infections following implant operation.

Topics: Aged; Cefamandole; Cephalosporins; Coronary Artery Bypass; Half-Life; Heart Atria; Heart Valve Prosthesis; Humans; Microbial Sensitivity Tests; Middle Aged; Pericardial Effusion; Staphylococcal Infections; Surgical Wound Infection

Sixty women with endometritis following cesarean section were treated with cefamandole (12 gm/day) alone. Specimens for culture were obtained by endometrial lavage and from peripheral blood. Minimum inhibitory concentrations were performed on anaerobes and enterococci by an agar dilution technique. Anaerobic organisms were isolated in 55 of 60 (91.7%) endometrial specimens. Bacteremia was documented in 12 patients (20%). Of 387 isolates from uterine cultures, 20 (5%) were resistant or had MIC's greater than or equal to 32 micrograms/ml. Ten patients (17%) were judged clinical failures and responded to additional antibiotics. Of 19 patients with Bacteroides fragilis or related species isolates in the uterus, three (15%) were judged as failures. Cefamandole was well tolerated and appears to be useful in the initial treatment of endomyometritis.

Topics: Adult; Bacterial Infections; Bacteroides fragilis; Bacteroides Infections; Cefamandole; Cephalosporins; Cesarean Section; Endometritis; Enterobacteriaceae Infections; Female; Humans; Postoperative Complications; Pregnancy; Staphylococcal Infections; Streptococcal Infections

Therapy with cephamandole (1.0 g, every eight hours) for five days was effective in eliminating cephamandole-sensitive microorganisms from the urinary tract. A 75% cure rate was achieved in a group of 20 patients, 45% of whom had abnormalities of the urinary tract. Local pain (despite addition of lignocaine) was sufficiently prolonged and severe to make multiple-dose intramuscular administration unacceptable. No other toxic effects were encountered.

Topics: Anti-Infective Agents, Urinary; Cefamandole; Cephalosporins; Enterobacteriaceae Infections; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Pain; Staphylococcal Infections; Urinary Tract Infections

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

Antibiotic prophylaxis for the prevention of endocarditis due to methicillin-resistant Staphylococcus epidermidis (MRSE) was evaluated in a modified rabbit endocarditis model and compared with results obtained with methicillin-sensitive S. epidermidis (MSSE). One dose of nafcillin, cefamandole, cephalothin, or vancomycin neither prevented endocarditis nor sterilized the blood of rabbits challenged with each of two MRSE or two MSSE isolates. One dose of gentamicin protected greater than or equal to 80% of animals challenged with three of the four isolates, and one dose of rifampin protected greater than or equal to 90% challenged with any of the four isolates. Multiple doses of any of the antibiotics prevented endocarditis in greater than or equal to 80% of rabbits challenged with MSSE, and four doses of vancomycin protected rabbits challenged with MRSE. However, MRSE endocarditis was prevented in less than or equal to 25% of animals given six doses of nafcillin or cephalosporins. Thus, nafcillin and cephalosporins were ineffective prophylaxis for MRSE endocarditis, whereas vancomycin, gentamicin, and rifampin were effective.

Topics: Animals; Anti-Bacterial Agents; Cefamandole; Cephalothin; Endocarditis, Bacterial; Female; Gentamicins; Male; Methicillin; Nafcillin; Penicillin Resistance; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus; Vancomycin

We compared the intraocular pharmacokinetics of cefazolin with those of cefamandole, a recently marketed cephalosporin with enhanced activity against gram-negative bacilli. Following subconjunctival injection of 12.5 mg into infected eyes (S. aureus endophthalmitis) of pigmented rabbits, both drugs reached peak concentrations greater than 100 microgram/gm in cornea, sclera, and choroid-retina. The half-life was markedly shorter in sclera and choroid-retina than in cornea. Levels in the aqueous humor rose and fell more slowly than those in ocular tissues, reaching a maximum of only 5 to 10 microgram/ml. The pharmacokinetics of the two drugs were virtually identical in most intraocular sites. When cefazolin, which was less irritating than cefamandole by the subconjunctival route, was given in a dosage of 100 mg, levels in ocular tissues were increased by twofold to fourfold and in aqueous humor by 15-fold, compared to the concentrations produced by the 12.5 mg dosage. Levels in the vitreous humor were exceedingly low with both drugs; mean peak concentrations were 0.24 microgram/ml after the 12.5 mg dosage of cefamandole and less than 1.6 microgram/ml after the 100 mg dose of cefazolin.

Topics: Animals; Aqueous Humor; Cefamandole; Cefazolin; Cephalosporins; Conjunctiva; Dose-Response Relationship, Drug; Endophthalmitis; Eye; Half-Life; Injections; Kinetics; Rabbits; Staphylococcal Infections

Topics: Animals; Cefamandole; Cephalosporins; Injections, Intravenous; Meningitis; Meningitis, Haemophilus; Rabbits; Staphylococcal Infections

Cefamandole, a new parenteral cephalosporin antibiotic, was administered to 23 newborn infants with pustular skin infection due to Staphylococcus aureus for an average duration of 7.5 days. All the patients improved clinically. Elevation of serum glutamic oxaloacetic transaminase and eosinophilia were observed in nine infants each transiently during treatment. There were no abnormalities of renal functions and Coombs' test results remained negative. The levels of cefamandole in serum after either intravenous or intramuscular administration were higher and the mean life was longer than those previously reported in older infants, children, and adults.

Topics: Cefamandole; Cephalosporins; Female; Half-Life; Humans; Infant, Newborn; Infant, Newborn, Diseases; Kinetics; Male; Skin Diseases, Infectious; Staphylococcal Infections

Fifty-three infants and children, aged three months to 15 years, were treated with an average daily dose of 100 mg of cefamandole/kg intravenously. Of these patients, 47 had soft tissue cellulitis and six had pneumonia. Primary pathogens, including Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, and Haemophilus influenzae, were isolated from 43 of the 53 patients. Bacteremia was documented in six of the 53 patients. A satisfactory clinical and bacteriologic response to cefamandole was achieved in all cases except on (98%). The only treatment failure occurred in an infant with both periorbital cellulitis and bacteremia due to H. influenzae who developed meningitis while receiving cefamandole; no extravasation of the drug across the blood-brain barrier could be detected in spite of inflamed meninges. In general, the only aberrant effects of cefamandole were the appearance of eosinophilia in 28% of patients and a positive indirect Cooms' test without hemolysis in one patient. Cefamandole showed excellent in vitro activity against 87 ampicillin-resistant strains of H. influenzae. Because it has greater activity than any of the other cephalosporins against this important pediatric pathogen, cefamandole may have particular pertinence in the treatment of infections in infants and young children.

Topics: Adolescent; Bacterial Infections; Cefamandole; Cellulitis; Cephalosporins; Child; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Pneumonia; Pneumonia, Pneumococcal; Staphylococcal Infections; Streptococcal Infections

Cefamandole nafate was effective in the treatment of a variety of infections caused by Staphylococcus aureus, Streptococcus pyogenes group A, Streptococcus pneumoniae, and Haemophilus influenzae in infants and children. The infections included periorbital cellulitis and ethmoiditis, bacteremia, cellulitis, pneumonia, and lymphadenitis. In vitro, cefamandole was effective in inhibiting the growth of H. influenzae isolated from blood or cerebrospinal fluid of patients with meningitis or sepsis. In two patients rash developed and cefamandole was discontinued. Other significant adverse effects were not noted.

Topics: Adolescent; Bacterial Infections; Cefamandole; Cellulitis; Cephalosporins; Child; Child, Preschool; Ethmoid Sinus; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Microbial Sensitivity Tests; Pneumonia, Pneumococcal; Sinusitis; Staphylococcal Infections; Streptococcal Infections; Streptococcus pyogenes

Forty-four patients with serious bacterial infections were treated with cefamandole in a dose 1--2 g every four to six hours. Thirty-two patients were cured and six were markedly improved. Three of six failures were due to superinfection with cephalothin-resistant microorganisms. The over-all bacteriologic response was 80%. In 12 of 13 patients with bacteremia the blood was sterilized. Ten of 14 patients with gram-negative bacillary infections responded to treatment. Six of these were due to cephalothin-resistant microorganisms, three of which responded. Fifteen patients who were treated had a history of penicillin allergy. There were no serious reactions although skin rash did develop. Phlebitis was uncommon.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Cefamandole; Cephalosporins; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Middle Aged; Sepsis; Staphylococcal Infections; Streptococcal Infections

Topics: Adult; Bacterial Infections; Cefamandole; Cellulitis; Cephalosporins; Enterobacteriaceae Infections; Enterococcus faecalis; Haemophilus Infections; Humans; Pneumococcal Infections; Respiratory Tract Infections; Skin Diseases, Infectious; Staphylococcal Infections; Streptococcal Infections; Streptococcus pyogenes

Cefamandole was evaluated as the sole antimicrobial agent used to treat bacterial peritonitis in 113 patients. Dosage varied between 1 and 2 g given intravenously every 6 hr. Laparotomy for excision of infected or gangrenous tissues, closure of gastrointestinal perforations, or drainage of an established abscess was required in 99 of the cases. A good clinical response was obtained in 107 patients, or 95% of the total group. Of the six deaths only one could be attributed to infection. No evidence of renal, hepatic, or hematopoietic toxicity was noted. There were no allergic reactions, although 13 patients (12%) developed phlebitis in a vein used for antibiotic administration. Bacteriological studies revealed aerobic peritonitis in 99% of the patients, with anaerobe participation in 60% of these cases. Sensitivity testing by the disk diffusion and tube dilution methods confirmed the appropriateness of cefamandole therapy; 91% of the gram-negative rods and 61% of the anaerobes were susceptible. From results of this study, it would appear that cefamandole is a reliably effective antibiotic for use in treatment of most forms of acute peritonitis. Its role in surgical prophylaxis may be even more promising.

Topics: Adult; Aged; Bacterial Infections; Bacteroides Infections; Cefamandole; Cephalosporins; Child, Preschool; Drug Resistance, Microbial; Enterobacteriaceae Infections; Female; Humans; Male; Peritonitis; Staphylococcal Infections

The safety and efficacy of treatment with cefamandole were evaluated in 30 patients (from 18 institutions) with serious bone and joint infections. Five of the subjects were children. The antibiotic was given intramuscularly or intravenously in doses ranging from 2 to 12 g daily for five to 44 days. Twenty-six of the 30 patients responded satisfactorily. Fourteen of the fifteen infections due to Staphylococcus aureus were among the successful cases. Other pathogens were streptococci, Escherichia coli, Proteus mirabilis, and Bacteroides fragilis. The drug was well tolerated in patients in this series. Studies indicated that cefamandole penetrated the bones and joints. Further investigation of cefmandole in the treatment of bone and joint infections is warranted.

Topics: Adolescent; Adult; Aged; Arthritis, Infectious; Bacterial Infections; Bacteroides Infections; Bursitis; Cefamandole; Cephalosporins; Child; Child, Preschool; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Osteomyelitis; Pseudomonas Infections; Staphylococcal Infections; Streptococcal Infections; Surgical Wound Infection

Topics: Cefamandole; Cephaloridine; Cephalosporins; Half-Life; Humans; Staphylococcal Infections