cefamandole and Bacteroides-Infections

Topics: Bacterial Infections; Bacteroides Infections; Cefamandole; Cefazolin; Cefonicid; Cefoxitin; Cefuroxime; Cephalosporins; Gonorrhea; Haemophilus Infections; Humans; Respiratory Tract Infections; Structure-Activity Relationship

Thirty-one adult patients with infections due to anaerobic bacteria were treated with cefamandole. Bacteroides fragilis group (17) and Bacteroides melaninogenicus (13) were the most frequent anaerobes isolated. Duration of therapy varied from 2 to 49 days. Results were judged satisfactory in 26 cases, and unsatisfactory in 1 case. Four cases could not be evaluated. Adverse reactions occurred in 16 patients and included positive direct Coomb's test without hemolysis, transient liver function abnormalities, phlebitis, reversible neutropenia, fever, eosinophilia, and toxic epidermal necrolysis. The more significant reactions were associated with prolonged therapy. None was lethal. These data suggest that cefamandole is effective in treatment of most anaerobic infections.

Topics: Aerobiosis; Anaerobiosis; Bacteria; Bacterial Infections; Bacteroides Infections; Cefamandole; Cephalosporins; Clinical Trials as Topic; Humans

Topics: Anaerobiosis; Bacterial Infections; Bacteroides Infections; Cefamandole; Cephalosporins; Clinical Trials as Topic; Female; Humans

Cefamandole, cefoxitin, cefotetan, ceftizoxime, imipenem plus cilastatin, and ampicillin plus sulbactam were compared in the eradication of subcutaneous abscess in mice caused by Bacteroides fragilis group organisms and Escherichia coli alone or in combination. The abscesses were examined 5 d after inoculation. B. fragilis group reached log10.1-11.0 organisms per abscess and E. coli log11.6-12.5. Imipenem plus cilastatin significantly reduced (in 6.9-10.6 logs) the number of E. coli and all members of B. fragilis group alone or in all combinations. Ampicillin plus sulbactam reduced the numbers of all B. fragilis group (in 4.2-7.2 logs) but was less effective against E. coli (reduction of 1.8-4.2 logs). Cefoxitin was effective in significantly reducing (in 4.9-6.2 logs) the number of E. coli and all members of B. fragilis group alone or in all combinations. Cefotetan was effective against B. fragilis (reduction of 5.1-6.6 logs) and E. coli alone or in combination but did not reduce the number of Bacteroides thetaiotaomicron, Bacteroides vulgatus, and Bacteroides ovatus. Ceftizoxime was effective against only B. ovatus (reduction of 3.7-5.8) and E. coli (reduction of 6.0-8.1 logs); it did not reduce the number of other organisms. Cefamandole was effective against only E. coli and was not effective against any member of the B. fragilis group. These in vivo data confirm the in vitro activity of these antimicrobials.

Topics: Abscess; Ampicillin; Animals; Anti-Bacterial Agents; Bacteroides fragilis; Bacteroides Infections; Cefamandole; Cefotetan; Cefoxitin; Ceftizoxime; Cilastatin; Cilastatin, Imipenem Drug Combination; Disease Models, Animal; Drug Combinations; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Imipenem; Male; Mice; Skin Diseases; Sulbactam

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 relationships between resistant pathogens, serum levels of gentamicin, and the outcomes of gangrenous or perforated appendicitis were analyzed in 147 patients. Failure to cure the infection occurred significantly more frequently among patients treated with cefoperazone or cefamandole than among those treated with clindamycin and gentamicin in combination. The failures were associated with recovery of resistant Bacteroides fragilis from intraoperative cultures. Pseudomonas species were also associated with failures, their in vitro susceptibility not correlating with clinical cure. Patients with gentamicin peak serum levels of less than 6 micrograms/ml in the first three days were not more likely to be associated with failure than were patients with higher levels. These clinical observations indicate that antibiotic therapy of intra-abdominal sepsis should include antibiotics with in vitro activity against B fragilis and that precise adjustments of gentamicin levels may not improve outcome. In addition, Pseudomonas species may play a significant role in some of these infections.

Topics: Anti-Bacterial Agents; Appendicitis; Bacteroides fragilis; Bacteroides Infections; Cefamandole; Cefoperazone; Cephalosporins; Clindamycin; Drug Therapy, Combination; Female; Gangrene; Gentamicins; Humans; Male; Pseudomonas; Pseudomonas Infections; Rupture, Spontaneous

The correlation between in vitro antimicrobial activity and the in vivo response to antimicrobial therapy is affected by multiple host factors, the site and nature of the infection, and the pharmacokinetics of the antimicrobial and its penetration into areas of infection. In certain instances, discrepancies are also caused by methodologically-related variables of in vitro susceptibility tests. Examples of discrepancies between in vitro and in vivo response to antimicrobial are discussed.

Topics: Anti-Bacterial Agents; Bacteria; Bacteria, Anaerobic; Bacteroidaceae; Bacteroides; Bacteroides Infections; Cefamandole; Chloramphenicol; Clindamycin; Enterobacter; Enterobacteriaceae; False Positive Reactions; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Sepsis; Staphylococcus; Sulfamethoxazole; Trimethoprim

Strains of Bacteroides fragilis group isolated from peritoneal pus were tested for susceptibility to cefalotin, cefamandole, cefoxitin, clindamycin and metronidazole. Clindamycin and metronidazole were found to display the lowest MIC and MBC values. The median serum level of these antimicrobials was 2-4 times as high as the MIC effective against 100% of strains. The most active cephalosporin was the cephamycin derivative cefoxitin that inhibited 98% of strains at 16 mg/l which corresponds with the usual median serum level achieved at commonly recommended treatment regimens. The MICs of 16 mg/l to cefalotin and cefamandole were found in 9.8% and 3.7% of strains, respectively. These findings are consistent with data reported in the literature. Attention is also centered on the mode of antimicrobial action, principles of bacterial resistance and on factors which are co-responsible for the therapeutic effectiveness of the antimicrobials studied.

Topics: Abscess; Bacteroides; Bacteroides Infections; beta-Lactamases; Cefamandole; Cefoxitin; Cephalosporins; Cephalothin; Clindamycin; Humans; Metronidazole; Peritoneal Diseases

Cefamandole resistance in five patients was studied. Microorganisms emerged resistant to cefamandole during therapy with the drug in three patients with complicated infections. This resistance was associated with an enhanced production of beta-lactamase and/or with a change in the substrates and the isoelectric focusing patterns of the enzymes. Cross-resistance to other beta-lactam antibiotics developed concurrently in isolates from these patients. Disk diffusion tests did not detect resistance to cefamandole in the pretreatment isolate from the fourth patient; this isolate produced inactivating enzymes, and resistance was detected only in broth dilution tests. In the fifth patient, infection with a cefamandole-resistant Enterobacter developed during postoperative therapy with the drug. Resistance to cefamandole in the isolate from this patient was unstable and was associated with inducible beta-lactamase activity. These examples emphasize the need for close monitoring of patients who are given cefamandole and for thorough in vitro evaluation of isolates from the patients both before and after treatment.

Topics: Adult; Aged; Bacteroides Infections; beta-Lactamases; Cefamandole; Cefotaxime; Cefoxitin; Cephalosporins; Cephamycins; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Humans; Isoelectric Focusing; Male; Middle Aged; Moxalactam; Penicillin Resistance; Penicillins

Topics: Adult; Bacteroides fragilis; Bacteroides Infections; Cefamandole; Cephalosporins; Female; Humans; Male; Sepsis

An experimental model, where fibrin clots were inserted subcutaneously in rabbits, was adapted to study the in vivo efficacy of two cephalosporins against Bacteroides fragilis. The respective MIC's of cefamandole and cefoxitin against the microorganism were 16 microgram/ml and 1 microgram/ml. The clots were infected with 10(7) B. fragilis. Groups of seven animals received an intravenous bolus injection (100 mg/kg) of either drug. The serum levels of both drugs were similar to those seen in humans. The peak concentrations of cefamandole (40 microgram/mg) in the clots were found to be ten times higher than those of cefoxitin (4 microgram/mg). The log number of colony forming units in the clots averaged 7.5 at 0 h. At 6 hours, this number reached 8 in the untreated animals, 1.5 after cefoxitin, and 1.7 after cefamandole. The apparent in vitro superiority of cefoxitin against B. fragilis could not be demonstrated in vivo. This discrepancy between in vitro and in vivo data can be explained by the high degree of penetrance of cefamandole into the infected fibrin loci. In this animal system, both cefoxitin and cefamandole had similar in vivo activity against B. fragilis.

Topics: Animals; Bacteroides fragilis; Bacteroides Infections; Cefamandole; Cefoxitin; Cephalosporins; Fibrin; Half-Life; Kinetics; Rabbits

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

Increased understanding of bacterial infections of the pelvis has led to the frequent administration of double and triple antimicrobial chemotherapy for polymicrobial infections in hospitalized patients. This study evaluated the use of high-dose cefamandole as a single agent in the treatment of obstetric and gynecologic infections. Cefamandole was administered by intravenous infusion of 2 gm every 4 hours or, less often, every 3 hours. Twenty patients were entered into the study, 11 with postpartum endometritis and nine with pelvic inflammatory disease. Seventeen of the 20 patients (85%) were successfully treated; all failures were in the endometritis group. The aerobic organisms and the gram-positive anaerobic organisms isolated from these infections were susceptible in vitro to cefamandole at attainable serum concentrations. The bacteroides isolated were more resistant. The data suggest that high-dose cefamandole therapy is effective as a single agent for the majority of moderate obstetric and gynecologic infections.

Topics: Bacteria; Bacterial Infections; Bacteroides Infections; Cefamandole; Cephalosporins; Drug Resistance, Microbial; Endometritis; Female; Humans; Pelvic Inflammatory Disease

Cefamandole nafate is a derivative of 7-aminocephalosporanic acid which has been shown to have good in vitro activity against aerobes traditionally susceptible to cephalosporins as well as many anaerobes, including B. fragilis. One hundred women with obstetric or gynecologic infections completed treatment with cefamandole: 53 had post-cesarean section infections: 24, acute pelvic inflammatory disease: 16, posthysterectomy cuff cellulitis/abscess; and seven, vulvar or abdominal wound abscess. Almost 90% of these women had either polymicrobial aerobic/anaerobic bacterial infections or an anaerobic infection alone. Ninety women responded to cefamandole alone; in 10 cases chloramphenicol was added, but in addition five of these women required surgical therapy for eradication of infection. Mild to severe phlebitis at the infusion site that responded to conservative therapy was demonstrated in 14 women. Of 312 bacterial isolates from these women, 89% were sensitive to cefamandole at 32 microgram/ml, an easily achievable serum level; 93% of anaerobic streptococci, the most common isolates, were sensitive at 32 microgram/ml. Also, 90% of all Bacteroides species were susceptible at 32 microgram/ml; 82% of B. fragilis were susceptible at this concentration. These data indicate that cefamandole is safe and effective for treatment of women with polymicrobial pelvic infections but that approximately 5% of these women will require surgical exploration in addition to antimicrobial administration.

Topics: Abscess; Acute Disease; Bacterial Infections; Bacteroides Infections; Cefamandole; Cellulitis; Cephalosporins; Cesarean Section; Clostridium Infections; Endometritis; Enterobacteriaceae Infections; Female; Genital Diseases, Female; Humans; Hysterectomy; Peptococcus; Peptostreptococcus; Peritonitis; Pregnancy; Streptococcal Infections; Surgical Wound Infection; Vulvitis

Bacteroides fragilis is responsible for most anaerobic infections in man. Most isolates of B. fragilis show resistance to beta-lactam antibiotics. This resistance might be due to beta-lactamase production or permeability barrier in the cell wall. B. fragilis produce beta-lactamase with mainly cephalosporinase activity. Other Bacteroides species such as B. clostridiformis, B. melaninogenicus and B. oralis also produce beta-lactamase but with different biochemical characteristics.

Topics: Amidohydrolases; Anti-Bacterial Agents; Bacteriological Techniques; Bacteroides; Bacteroides fragilis; Bacteroides Infections; beta-Lactams; Cefamandole; Cefoxitin; Cell Wall; Cephalosporinase; Cephalosporins; Furans; Humans; Isoelectric Focusing; Penicillin G; Penicillin Resistance; Penicillinase; Penicillins; Prevotella melaninogenica; Species Specificity

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