Francis P. Tally

Aerobic and Anaerobic Bacteria in Diabetic Foot Ulcers

Twenty diabetic foot ulcers were cultured using optimal microbiologic techniques. Anaerobic bacteria coexisted with the more commonly recognized aerobic bacteria in 18 specimens. There were a total of 116 isolates with an average of 5.8 species per specimen (3.2 aerobes and 2.6 anaerobes). The principal isolates were Bacteroides species (sp.) (17 strains), peptococci (16), Proteus sp. (11), enterococci (9), Staphylococcus aureus (7), clostridia (7), and Escherichia coli (6). When antimicrobial therapy is indicated the selection of agents should consider the likelihood of a complex aerobic-anaerobic flora.

Beta-lactamase-mediated imipenem resistance in Bacteroides fragilis.

Imipenem has excellent antimicrobial activity owing in part to beta-lactamase stability. We found that only 2 of over 350 Bacteroides fragilis group clinical isolates were resistant to imipenem, with an MIC of more than 16 micrograms/ml. These two isolates from the Tufts Anaerobe Laboratory (TAL) were resistant to all other beta-lactam agents tested. The organisms were able to inactivate imipenem in broth cultures and contained similar beta-lactamases that were able to hydrolyze carbapenems, cephamycins, cephalosporins, and penicillins. The molecular sizes of the beta-lactamases in TAL2480 and TAL3636 were estimated to be 44,000 daltons. The novel beta-lactamase contained Zn2+ as a cofactor. An additional factor contributing to resistance was determined. The outer membranes of these two organisms were found to limit free diffusion of the drugs into the periplasm. This novel beta-lactamase, associated with a barrier to drug permeation, resulted in high-grade beta-lactam drug resistance.

Management of Anaerobic Infections

Anaerobic infections are reviewed with emphasis on management. Most anaerobic pulmonary infections respond to penicillin G, even when Bacteroides fragilis (penicillin-resistant) is present. Clindamycin is suitable in penicillin-sensitive patients. Intraabdominal infections have a complex flora usually involving anaerobes, especially B. fragilis. It is desirable to use antimicrobial therapy to cover potential pathogens of all types. Surgical drainage and debridement are extremely important considerations. Anaerobic bacteria were found in 72% of 200 patients with female genital tract infections and were the exclusive isolates in 30%. Surgical therapy is primary, but antimicrobial and anticoagulant therapy are also important. A variety of soft-tissue infections involve anaerobes. Surgery is the major therapeutic approach. Anaerobic endocarditis is uncommon but may be difficult to manage. Chloramphenicol is ordinarily the drug of choice for brain abscess. New antimicrobial agents, which are under investigation and are promising, include new penicillins, new cephalosporins, new tetracyclines, and metronidazole.

Susceptibility of the Bacteroides fragilis group in the United States: analysis by site of isolation.

An ongoing survey of the susceptibility of the Bacteroides fragilis group of bacteria was continued at New England Medical Center in 1984 and 1985. A total of 1,229 strains were obtained from eight centers in the United States. These results were compared with those for 1,847 isolates tested in 1981 through 1983. The most active beta-lactam drugs were imipenem and ticarcillin-clavulanic acid (Timentin), which had a less than 1% resistance rate. No metronidazole- or chloramphenicol-resistant isolates were found during the 5 years of the study. Isolates obtained from blood, perinatal, and bone sites of infection were more resistant to a variety of antimicrobial agents. Susceptibility patterns of the members of the B. fragilis group varied at the eight hospitals and among species. These data indicate the need for determining the susceptibility patterns for the B. fragilis group of organisms at each hospital.

A randomized comparison of cefoxitin with or without amikacin and clindamycin plus amikacin in surgical sepsis.

The efficacy of cefoxitin, either alone or in combination with an aminoglycoside was compared with clindamycin plus (+), an aminoglycoside for the treatment of mixed aerobic-anaerobic surgical infections, in a prospective randomized single blinded study. One hundred patients were entered into the study; 37 patients were assessable for clinical outcome in both groups, while toxicity could be assessed in 46 patients in the cefoxitin group and 47 in the clindamycin group. The groups were evenly matched considering age, sex, and type of infection. Favorable clinical responses were achieved in 34 of 37 patients treated with cefoxitin amikacin, and 29 of 37 patients treated with clindamycin + amikacin; there was no statistical difference between the groups (p > 0.1). The incidences of toxicity were the same. Our study has demonstrated that cefoxitin with or without an aminoglycoside is as effective as clindamycin plus an aminoglycoside in the therapy of serious mixed infections in surgical patients.

Treatment of Anaerobic Infections with Metronidazole

The results of treatment of 10 patients with anaerobic infections with metronidazole are presented. Six patients were cured, three showed initial good response but circumstances required a change to another drug, and one patient did not respond. The unique spectrum of the drug, its pharmacology, and limitations are discussed. The results indicate that further clinical trials to determine the efficacy of metronidazole in the treatment of anerobic infections are indicated.

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

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

Susceptibility of Anaerobes to Cefoxitin and Other Cephalosporins

The in vitro susceptibility of 155 strains of anaerobic bacteria to five cephalosporin antibiotics was tested. Cefoxitin was the most active against 33 isolates of Bacteroides fragilis; 82% of the strains were sensitive at 16 μg/ml. At 64 μg/ml cefazolin and cephaloridine were also generally effective. Cephalothin and cephalexin were relatively inactive versus B. fragilis. Cefoxitin, cephaloridine, cefazolin, and cephalothin showed comparable activity against 122 strains of anaerobes other than B. fragilis. More than 90% of the strains were sensitive to each of these antimicrobials at 16 μg/ml. Cephalexin was the least effective cephalosporin against all species tested.

Susceptibility of the Bacteroides fragilis group in the United States in 1981.

The minimal inhibitory concentrations of nine antimicrobial agents was determined for over 750 clinical isolates of the Bacteroides fragilis group of anaerobic bacteria collected from nine centers in the United States during 1981. High resistance rates were documented for cefoperazone, cefotaxime, and tetracycline. Cefoxitin had the best activity of the beta-lactam antibiotics, whereas moxalactam and piperacillin had good activities. The resistance rate for clindamycin was 6%. There were no metronidazole- or chloramphenicol-resistant isolates encountered. There were significant differences in susceptibility among the various species of the B. fragilis group, particularly with moxalactam, cefoxitin, and clindamycin. Clustering of clindamycin-, piperacillin-, and cefoxitin-resistant isolates was observed at different hospitals. The variability of resistance rates with the beta-lactam antibiotics and clindamycin indicates that susceptibility testing of significant clinical isolates should be performed to define local resistance patterns.

Amikacin Therapy for Severe Gram-Negative Sepsis: Emphasis on Infections with Gentamicin-Resistant Organisms

Amikacin (BB-K8) is a semisynthetic derivative of kanamycin which is active in vitro against many gentamicin-resistant Gram-negative bacilli. Twenty-three patients with 25 serious Gram-negative infections were treated with this new aminoglycoside. Twelve infections involved organisms that were resistant to gentamicin. Twenty patients satisfied the criteria for bacteriological and clinical cure. This included 11 of the 12 infections involving gentamicin-resistant Gram-negative bacilli. In 4 urinary tract infections there was a good clinical response, but routine follow-up urine cultures at 30 days were positive. One patient failed on amikacin therapy. Eighth nerve toxicity was detected in two patients. These results indicate that amikacin is effective in the treatment of serious Gram-negative infections and is particularly useful in those involving resistant organisms. Further studies are indicated to evaluate ototoxic potential.