cefamandole and Endocarditis--Bacterial

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

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

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

Seventy-nine patients about to undergo cardiac operations were randomly allocated to two treatment groups in an attempt to reduce postoperative chest infections. The group receiving a short peroperative course of cefamandole, an antibiotic effective against both the pneumococcus and Haemophilus influenzae, had a significantly lower postoperative chest infection rate than the group receiving a 3-day course of cephradine, an antibiotic previously chosen to prevent intracardiac infection during the operation. By selecting an appropriate antibiotic it is possible, using a short peroperative course, to reduce the postoperative chest infection rate in patients undergoing cardiac operations.

Topics: Adult; Cardiac Surgical Procedures; Cefamandole; Cephalosporins; Cephradine; Endocarditis, Bacterial; Humans; Intraoperative Period; Postoperative Complications; Respiratory Tract Infections; Surgical Wound Infection; Urinary Tract Infections

Cefamandole nafate (CM) and cephalothin sodium (CP) were administered as prophylaxis in a randomized, prospective study to 30 consecutive patients undergoing prosthetic cardiac valve insertion. A single dose of 20 mg/kg was given intramuscularly during anesthesia induction, and serial plasma antibiotic concentrations, atrial muscle and cardiac valve tissue antibiotic levels, plasma bactericidal activity against pathogenic staphylococci, and infectious complications were determined and compared for the two drugs. Both antibiotics produced high plasma levels (>20 mug/ml 30 min after injection) which fell less than 25% during the period of cardiopulmonary bypass. However, CM levels were significantly higher at most time periods (P<0.05) than CP levels. CP levels were undetectable in atrial muscle from 14 of 15 patients and in valves from 10 of 15 patients. In contrast, CM bioactivity was found in all tissues. Differences in tissue antibiotic concentration could not be accounted for by differences in plasma concentrations or by CP tissue binding and were assumed to be caused by differences in penetration. Plasma bactericidal activity against staphylococci was equal for the two drugs (median titer, 1:16). No infections were seen in either group. CM appeared to be an effective and perhaps preferable prophylactic antibiotic for use during cardiac surgery.

Topics: Adolescent; Adult; Aged; Blood Bactericidal Activity; Cefamandole; Cephalosporins; Cephalothin; Clinical Trials as Topic; Drug Evaluation; Endocarditis, Bacterial; Female; Heart Valve Prosthesis; Humans; Male; Middle Aged; Myocardium; Postoperative Complications

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

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

Topics: Aged; Aged, 80 and over; Cefamandole; Cefonicid; Endocarditis, Bacterial; Female; Haemophilus Infections; Humans; Microbial Sensitivity Tests

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

Topics: Cefamandole; Cefazolin; Cefonicid; Endocarditis, Bacterial; Humans; Microbial Sensitivity Tests; Penicillins; Sepsis; Streptococcal Infections; Streptococcus

Cephalosporin-aminoglycoside therapy of human enterococcal endocarditis has been associated with a high incidence of clinical failure. The comparative efficacy of three cephalosporin antibiotics (cefamandole, cefazolin, and cephalothin), in combination with gentamicin, was studied in a rabbit model of enterococcal endocarditis. The cefamandole-gentamicin combination produced higher rates of cure, despite the administration of comparatively lower doses. Studies of antibiotic penetration into a fibrin thrombus indicated that cefamandole penetrated the thrombus readily. The greater efficacy of the cefamandole-gentamicin combination may be related to the superior penetration of cefamandole into the fibrin-rich vegetations of endocarditis.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Cefamandole; Cephalosporins; Drug Therapy, Combination; Endocarditis, Bacterial; Male; Microbial Sensitivity Tests; Rabbits; Streptococcal Infections; Time Factors

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

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

The experience with the cefamandole prophylaxis in 244 patients with open heart-surgery, and another 84 patients operated upon on prosthetic vascular reconstruction was evaluated. No case of endocarditis, sepsis or massive wound infection with infected prosthesis was found in the reviewed patients. Considering the fact that patients undergoing open heart-surgery and prosthetic vascular reconstruction are subjected to much more bacterial contamination than patients undergoing any other surgical procedure, the cephalosporin treatment (in our study cefamandole) should be considered the antibiotic of choice in preventing of infection during and after such surgical intervention.

Topics: Adult; Aged; Bacterial Infections; Cardiac Surgical Procedures; Cefamandole; Cephalosporins; Endocarditis, Bacterial; Female; Heart Valve Prosthesis; Humans; Male; Middle Aged; Postoperative Complications; Surgical Wound Infection