cefoxitin and Bacteroides-Infections

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

A review is given of current antibiotic treatment of anaerobic infections. It is emphasized that infections with Bacteroides fragilis constitute the main problem, virtually all other anaerobe organisms of clinical significance are sensitive to penicillin. Particularly useful antibiotics for infections with B. fragilis are cefoxitin, chloramphenicol, clindamycin and the nitroimidazoles. Vancomycin is the drug of choice for pseudomembranous colitis provoked by Clostridium difficile.

Topics: Anaerobiosis; Anti-Bacterial Agents; Bacterial Infections; Bacteroides fragilis; Bacteroides Infections; Cefoxitin; Cephalosporins; Chloramphenicol; Clindamycin; Humans; Metronidazole; Penicillins; Tetracyclines; Tinidazole; Vancomycin

Perioperative antibiotics decrease surgical wound infection (SWI) in trauma patients requiring abdominal exploration. This investigation evaluated 24 hours of cefoxitin or ampicillin/sulbactam used for early therapy in such patients. Patients were randomly assigned to one of two treatment groups. The primary endpoint evaluated was SWI, which was defined as purulent drainage or active wound treatment. Five hundred ninety-two patients were evaluated: 283 received ampicillin/sulbactam and 309 received cefoxitin. The incidence of wound infection among the ampicillin/sulbactam patients was 2% and among cefoxitin patients it was 7% (p < 0.004). The cefoxitin patients with colon injuries were analyzed (p < 0.007). The major difference between the two groups was an increased incidence of enterococcal infections in the cefoxitin-treated patients. A single broad-spectrum antibiotic given for 24 hour perioperatively effectively controls SWI. Use of ampicillin/sulbactam results in a significantly lower SWI rate than use of cefoxitin, which may be a result of improved enterococcal and Bacteroides coverage.

Topics: Abdomen; Adolescent; Adult; Ampicillin; Bacteroides Infections; Cefoxitin; Drug Combinations; Enterococcus; Gram-Positive Bacterial Infections; Humans; Incidence; Middle Aged; Multivariate Analysis; Premedication; Sulbactam; Surgical Wound Infection

The efficacy and toxicity of moxalactam were compared with the efficacy and toxicity of cefoxitin given with or without tobramycin to 109 patients with surgical infections. A total of 66 patients could be assessed for efficacy (33 patients in each group); 13 of the cefoxitin-treated patients also received tobramycin for at least 72 h. Most patients had intraabdominal infections; 17 had peritonitis, 14 had intraabdominal abscesses, and 7 had perforation of a gangrenous appendix. There were 15 patients with necrotizing soft-tissue infections. The predominant pathogens were members of the Enterobacteriaceae and Bacteroides fragilis. The cure rates were 79% (26 of 33 patients) for moxalactam and 88% (29 of 33 patients) for cefoxitin; the difference in cure rates was not statistically significant. In several patients, cultures of purulent intraabdominal exudates were negative, although bacteria were observed after Gram staining; this presumably reflected the potent activity of the antibiotic therapy which had been started before surgical drainage could be carried out. Adverse effects were observed in 18 of 44 assessable patients (41%) in the cefoxitin group and in 12 of 36 patients (33%) in the moxalactam group; the difference in the rates of adverse effects was not statistically significant. Our results suggest that moxalactam is similar in efficacy and toxicity to cefoxitin given with or without tobramycin for the treatment of serious surgical sepsis caused by a mixture of anaerobic and aerobic pathogens.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Bacteroides fragilis; Bacteroides Infections; Cefoxitin; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Moxalactam; Prospective Studies; Random Allocation; Surgical Wound Infection; Tobramycin

A double-blind, randomized study of gentamicin and netilmicin, each in combination with cefoxitin, was done to compare their respective efficacy and toxicity in patients with serious systemic infection. Thirty-seven surgical patients were evaluated for efficacy and 46 patients were evaluated for toxicity. The most frequently cultured organisms were Escherichia coli (15), Klebsiella sp (9), Proteus sp (6), and Bacteroides sp (4). For 23 patients treated with gentamicin-cefoxitin (G-C), the clinical response was favorable in 20/21 (95.2%) evaluable cases, and elimination or marked reduction of 33/34 (97.1%) organisms was achieved. For 14 patients treated with netilmicin-cefoxitin (N-C), the clinical response was favorable in 13/13 (100%) evaluable cases, and 19/20 (95%) organisms were eliminated or markedly reduced. Nephrotoxicity was defined as an increase in serum creatinine to greater than 25% over baseline with an absolute rise of at least 0.5 mg/100 ml to a value greater than or equal to 1.3 mg/100 ml. Based on these criteria, nephrotoxicity was seen in 2/27 (7.4%) patients treated with G-C and in 3/19 (15.8%) patients treated with N-C. Ototoxicity was defined as a greater than 20 dB loss at any frequency. Based on these criteria, ototoxicity was seen in 5/27 (18.5%) patients treated with G-C and 2/19 (10.5%) patients treated with N-C. The data show no significant difference in toxicity and suggest that netilmicin and gentamicin are both highly effective in combination with cefoxitin in patients who have serious infections after surgery.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Bacteroides Infections; Cefoxitin; Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Enterobacteriaceae Infections; Female; Gentamicins; Hearing; Humans; Male; Middle Aged; Netilmicin; Random Allocation; Surgical Wound Infection; Vestibular Function Tests

We conducted a prospective, double-blind, randomized, placebo-controlled study of cefoxitin perioperative prophylaxis in 386 women having cesarean sections after labor or rupture of membranes. Private patients constituted 70% of subjects. Cefoxitin was chosen for its low toxicity and its broad spectrum against common obstetric pathogens including Bacteroides fragilis. Cefoxitin-treated women received 2 mg of drug intravenously at umbilical cord clamping and at 6 and 12 hours after surgery. Demographic and obstetric variables did not differ between the 190 placebo-treated women and the 196 cefoxitin-treated women. The morbidity rate from infection was significantly reduced by cefoxitin prophylaxis. Seven factors were significantly correlated with increased risk of infection after cesarean section: maternal age, socioeconomic status, race, gestational age, duration of internal fetal monitoring, use of intrauterine pressure catheter, and obesity. Cefoxitin prophylaxis resulted in significant decreases in infection incidence in women with one, two, and three risk factors, respectively, but the reduction was not significant in women with no risk factors. Length of hospital stay was not significantly reduced by cefoxitin prophylaxis but antibiotic use was decreased 24%.

Topics: Adult; Bacteroides fragilis; Bacteroides Infections; Cefoxitin; Cesarean Section; Double-Blind Method; Female; Humans; Postoperative Care; Prospective Studies; Random Allocation; Risk; Surgical Wound Infection

Topics: Bacterial Infections; Bacteroides fragilis; Bacteroides Infections; Cefoxitin; Cephalosporins; Clinical Trials as Topic; Female; Genital Diseases, Female; Humans; Injections, Intravenous; Pregnancy; Pregnancy Complications, Infectious

Antimicrobial susceptibilities of 4973 Bacteroides spp. isolates recovered from various sources of patients from 12 countries (99.6% from European countries) in the Antimicrobial Testing Leadership and Surveillance (ATLAS) programme, 2007-2020, were investigated. The minimum inhibitory concentrations (MICs) of the isolates with six commonly used agents were determined using the agar dilution method. Among the isolates, 10 Bacteroides spp. were included: B. fragilis (n=3180, 64.0%) was encountered most frequently, followed by B. thetaiotaomicron (n=675) and B. ovatus (n=409). During the 14 years, the proportion of B. fragilis declined, but the proportion of non-fragilis Bacteroides spp. increased. More than 90% of the isolates tested were susceptible to piperacillin-tazobactam, meropenem and tigecycline. Significantly lower susceptibility rates to cefoxitin (P<0.001), clindamycin (P<0.001), piperacillin/tazobactam (P<0.001) and tigecycline (P=0.006) were observed among non-fragilis Bacteroides spp. isolates than among B. fragilis isolates. Moreover, the susceptibility rates to clindamycin (P=0.003) and tigecycline (P=0.044) decreased significantly among non-fragilis Bacteroides spp. over time. Clindamycin susceptibility rates >80% were found in Greece (100%), Sweden (86.3%) and the UK (80.7%), and the lowest susceptibility rates were found in the USA (42.9%) and Japan (53.9%). In conclusion, the susceptibility of Bacteroides spp. to commonly used antibiotics varied geographically. Empirical antibiotic therapy for suspected anaerobic infections with clindamycin and cefoxitin should be avoided due to high resistance rates. Piperacillin-tazobactam, meropenem, metronidazole and tigecycline could be considered favourable options for the treatment of infections caused by Bacteroides spp.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Bacteroides fragilis; Bacteroides Infections; Cefoxitin; Clindamycin; Humans; Leadership; Meropenem; Microbial Sensitivity Tests; Piperacillin; Tazobactam; Tigecycline

Bacteroides fragilis is a part of the normal gastrointestinal flora, but it is also the most common anaerobic bacteria causing the infection. It is highly resistant to antibiotics and contains abundant antibiotic resistance mechanisms.. The antibiotic resistance pattern of 78 isolates of B. fragilis (22 strains from clinical samples and 56 strains from the colorectal tissue) was investigated using agar dilution method. The gene encoding Bacteroides fargilis toxin bft, and antibiotic resistance genes were targeted by PCR assay.. The highest rate of resistance was observed for penicillin G (100%) followed by tetracycline (74.4%), clindamycin (41%) and cefoxitin (38.5%). Only a single isolate showed resistance to imipenem which contained cfiA and IS1186 genes. All isolates were susceptible to metronidazole. Accordingly, tetQ (87.2%), cepA (73.1%) and ermF (64.1%) were the most abundant antibiotic-resistant genes identified in this study. MIC values for penicillin, cefoxitin and clindamycin were significantly different among isolates with the cepA, cfxA and ermF in compare with those lacking such genes. In addition, 22.7 and 17.8% of clinical and GIT isolates had the bft gene, respectively.. The finding of this study shows that metronidazole is highly in vitro active agent against all of B. fragilis isolates and remain the first-line antimicrobial for empirical therapy.

Topics: Anti-Bacterial Agents; Bacterial Toxins; Bacteroides fragilis; Bacteroides Infections; Cefoxitin; Clindamycin; Cross-Sectional Studies; DNA, Bacterial; Drug Resistance, Bacterial; Gastrointestinal Tract; Genes, Bacterial; Humans; Imipenem; Inpatients; Metalloendopeptidases; Metronidazole; Microbial Sensitivity Tests; Penicillin G; Polymerase Chain Reaction; RNA, Ribosomal, 16S; Tetracycline

Some strains of Bacteroides fragilis species are associated with diarrhea as a result of enterotoxin production (bft or fragilysin). Fragilysin is activated by C11 protease (fpn) and together with C10 protease (bfp) play a significant role in its invasiveness. The objectives of this study were to investigate the proportion of clinical isolates from extra-intestinal sources that are toxin producers and characterize the genes mediating toxin production. Clinical isolates submitted to our reference laboratory over the last 13 years were screened for toxin production using PCR technique. All stool isolates were excluded. The isolates were tested for their susceptibility to 8 antimicrobial agents by E test. Carbapenem resistance gene cfiA was detected by PCR.. A total of 421 B. fragilis isolates were viable. Out of these, bft was detected in 210 (49.9%) isolates. Of the 210 bft-positive isolates, 171 (81.4%), 33 (15.7%) and 6 (2.8%) harbored bft-1, bft-2, and bft-3 genes, respectively. Twenty (9.5%) of the bft-positive strains originated from bloodstream infections. Twenty-five, 20 and 9 strains harbored bfp-1, bfp-2 and bfp-3 gene, respectively. Two, 3, 4 bfp isotypes were detected simultaneously in some of strains. The resistance rates against amoxicillin-clavulanic acid was 32%, clindamycin 62%, cefoxitin 26%, imipenem 11%, meropenem 17%, metronidazole 4%, piperacillin 61% and tigecycline 14%. A chromosomally located cfiA gene that encode metallo-β-lactamase was identified in only 34 isolates (16.2%).. The prevalence of enterotoxin-producing B. fragilis was high among the extra-intestinal isolates. Metronidazole was the most active agent against all isolates. There was no statistically significance difference between resistance rates among bft-positive and bft-negative isolates except for clindamycin.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacterial Toxins; Bacteroides fragilis; Bacteroides Infections; Cefoxitin; Clindamycin; Drug Resistance, Bacterial; Feces; Female; Humans; Imipenem; Kuwait; Male; Meropenem; Metronidazole; Microbial Sensitivity Tests; Piperacillin; Prevalence; Prospective Studies; Respiratory Tract Infections; Sepsis; Tigecycline; Wound Infection

The changes in susceptibilities of Bacteroides fragilis group strains isolated in our hospital from 1997 to 2006 were studied. A total of 1,343 clinical strains were included. The study showed differences in the resistance rates in the different species of the group. Increasing resistance to clindamycin and moxifloxacin was observed. Susceptibility to imipenem, piperacillin-tazobactam, and metronidazole remained unchanged.

Topics: Anti-Bacterial Agents; Bacteroides; Bacteroides fragilis; Bacteroides Infections; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Spain; Species Specificity; Time Factors

Representing the major part of the human colon microflora, members of the Bacteroides fragilis group are frequently involved in mixed aerobic and anaerobic infections. Recent studies show an increased resistance of the B. fragilis group against several antimicrobial agents. The aim of the present study was to determine the susceptibility of 87 B. fragilis group strains isolated in 2003/2004 in Western Austria against eight antimicrobial agents by Etest. Furthermore, the resistance patterns were compared with those of 45 B. fragilis group strains isolated in 1992 and referred to the world wide trend towards increased resistance. In 1992 as well as in 2003/2004, all strains were susceptible against metronidazole and imipenem. However, comparing the MIC-values of the B. fragilis group strains collected 1992 with data from 2003/2004, a significant increase in resistance was found for clindamycin (p<0.01). Regarding cefoxitin, a similar trend could be observed. However, this difference was not yet significant (p=0.144). Our findings underline the emerging resistance of the B. fragilis group against antimicrobial agents and underscore the importance of susceptibility testing of anaerobes even in routine laboratories.

Topics: Anti-Bacterial Agents; Austria; Bacteroides fragilis; Bacteroides Infections; Cefoxitin; Clindamycin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests

Topics: Abscess; Ampicillin; Animals; Anti-Bacterial Agents; Bacteroides fragilis; Bacteroides Infections; Cefotetan; Cefoxitin; Cephamycins; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Male; Mice; Mice, Inbred C3H; Microbial Sensitivity Tests; Penicillins; Peritoneal Diseases; Sulbactam

The recovery of Candida albicans along with bacteria from the abdomen in the setting of peritonitis is becoming increasingly common. It is not known whether the interactions between the fungal and bacterial elements of these infections are synergistic, competitive, or neutral. To study this question, we have examined the effects of both the addition of C. albicans to a solely bacterial infection caused by Escherichia coli and Bacteroides fragilis, and the deletion of various components of this system using directed antimicrobial therapy. In a mixed infection, both C. albicans and bacteria contributed to mortality, since only the combination of cefoxitin and amphotericin B improved survival (from 50% to 90%). The addition of C. albicans to the bacterial inoculum increased the recovery of abscesses, but only to the number seen with fungal infection alone, implying two fairly independent processes. Although the number of bacteria recovered from abscesses at 10 days postinfection was unchanged with the addition of fungi, the deletion of the bacterial component of mixed infections led to the overgrowth of C. albicans. We conclude that this model of mixed C. albicans/E. coli/B. fragilis peritonitis is best characterized as two nonsynergistic, parallel infections with incomplete competition, allowing the survival of all three organisms to eventual abscess formation.

Topics: Abscess; Amphotericin B; Animals; Bacteroides fragilis; Bacteroides Infections; Candida albicans; Candidiasis; Cefotetan; Cefoxitin; Clindamycin; Colony Count, Microbial; Drug Combinations; Escherichia coli; Escherichia coli Infections; Male; Mice; Mice, Inbred BALB C; Peritoneal Diseases; Peritonitis; Survival Rate

Intra-abdominal abscess is seldom adequately treated by systemic antibiotics alone and often requires surgical or computed tomography-guided drainage for resolution. Abscess penetration of six currently used antibiotics was examined in a murine intra-abdominal abscess model. Ampicillin/sulbactam, cefmetazole, clindamycin, and trospectomycin penetrated intra-abdominal abscesses to a greater degree than cefoxitin and ceftriaxone. Abscess pus antibiotic levels were not significantly higher after multiple doses than after a single dose. Pus antibiotic levels below the MIC90 for Bacteroides and E. coli within intra-abdominal abscess were observed for most antibiotics with the doses used in this study. Selection of antibiotics with a greater ability to penetrate abscess may be important in optimally treating patients with abdominal infection.

Topics: Abdominal Abscess; Ampicillin; Animals; Anti-Bacterial Agents; Bacteroides fragilis; Bacteroides Infections; Cefmetazole; Cefoxitin; Ceftriaxone; Clindamycin; Drug Evaluation, Preclinical; Drug Therapy, Combination; Escherichia coli Infections; Hydrogen-Ion Concentration; Male; Mice; Microbial Sensitivity Tests; Spectinomycin; Sulbactam

The susceptibilities of 100 clinical isolates belonging to the Bacteroides fragilis group to 9 antibiotics, i.e. ampicillin, piperacillin, ceftriaxone, cefotaxime, cefoxitin, imipenem, erythromycin, clindamycin, and metronidazole, were tested using a standard agar dilution method and the E-test. Overall, 81% of the E-test MICs were within one log2 dilution step of the agar dilution MICs and 95% were within two log2 dilution steps. The E-test showed significantly lower MIC values than the agar dilution method for ampicillin, cefotaxime, and imipenem, and significantly higher MIC values for piperacillin, ceftriaxone, erythromycin, clindamycin, and metronidazole. However, this only resulted in minor discrepancies that did not change the susceptibility status. The E-test is easy to perform and read, and the MIC values correlated well with the MICs obtained by the agar dilution method when testing susceptibility of the Bacteroides fragilis group.

Topics: Ampicillin; Animals; Bacteroides fragilis; Bacteroides Infections; Cefoxitin; Culture Media, Conditioned; Disease Susceptibility; Erythromycin; Microbial Sensitivity Tests

The distributions of radiolabelled free cefoxitin (FC) and liposome-encapsulated cefoxitin (LC) were compared in an animal model of intra-abdominal sepsis. Intraperitoneally administered LC was initially retained in the peritoneal cavity with subsequent preferential drug targeting to the liver (14% injected LC) and spleen (6% injected LC) by 3 h post-injection. Differing patterns of liposomal drug and lipid retention indicated that drug release from the liposome complex occurred within the peritoneum, liver and spleen. Intraperitoneal FC was rapidly taken up into the systemic circulation, with peak recovery in the blood (9% injected FC) and liver (5% injected FC) at 1 h post-injection. FC was also rapidly eliminated; 7% of the injected drug was recovered in the kidney 1 h post-injection. A negligible amount of FC was recovered in the spleen and very little FC or LC was found in the lungs of treated animals. Unlike FC, LC was found to provide a sustained bactericidal drug level (> 40 micrograms mL-1) in the peritoneal fluid for up to 5 h post-injection. LC also achieved significantly higher drug levels, compared with FC, within the liver at 3 and 5 h post-injection. Since severe intra-abdominal sepsis is often characterized by the presence of intraphagocytic bacteria in hepatic and splenic reticuloendothelial systems, the enhanced delivery of liposome-encapsulated anti-microbial agents, such as cefoxitin, to the liver and spleen may provide a more effective treatment for the septic condition.

Topics: Abdomen; Animals; Bacterial Infections; Bacteroides fragilis; Bacteroides Infections; Cefoxitin; Drug Carriers; Drug Compounding; Enterococcus faecalis; Escherichia coli Infections; Freeze Drying; Gram-Positive Bacterial Infections; Injections, Intraperitoneal; Liposomes; Male; Rats; Rats, Sprague-Dawley; Tissue Distribution

Topics: Abdomen; Bacteroides fragilis; Bacteroides Infections; Cefotetan; Cefoxitin; Drug Resistance, Microbial; Humans; Surgical Wound Infection

Topics: Bacteria, Anaerobic; Bacterial Infections; Bacteroides; Bacteroides Infections; Cefotetan; Cefoxitin; Drug Resistance, Microbial; Humans; In Vitro Techniques; Microbial Sensitivity Tests

Topics: Abdomen; Abscess; Animals; Bacterial Infections; Bacteroides fragilis; Bacteroides Infections; Cefmetazole; Cefotetan; Cefoxitin; Drug Evaluation, Preclinical; Escherichia coli Infections; Male; Mice

Cefoxitin, cefotetan, and cefmetazole were compared in 10-day therapy of intra-abdominal and subcutaneous infections caused by three organisms: Bacteroides fragilis and Bacteroides thetaiotaomicron combined with either Escherichia coli or Staphylococcus aureus. Intra-abdominal infection was caused by B. fragilis plus B. thetaiotaomicron plus E. coli. Therapy was initiated immediately before inoculation or was delayed for 8 h. Mortality was 14 of 30 (47%) for saline-treated mice, and all survivors developed abscesses. Immediate therapy reduced mortality and the percentage of mice with abscesses (in survivors), respectively, to 17 and 20% with cefoxitin, 0 and 13% with cefotetan, and 0 and 17% with cefmetazole, and the numbers of all bacteria were reduced by all the cephalosporins. Delayed therapy reduced mortality and abscess formation, respectively, to 20 and 8% of mice with cefoxitin, 10 and 93% with cefotetan, and 7 and 96% with cefmetazole. B. thetaiotaomicron survived in all abscesses treated with cefotetan and cefmetazole. Subcutaneous abscesses were caused by each organism alone or in combinations of one aerobe (S. aureus or E. coli) and one or two Bacteroides species. Early therapy reduced the numbers of all bacteria independent of their in vitro susceptibility. All agents reduced the number of each Bacteroides species with either E. coli or S. aureus. However, when therapy was delayed, cefotetan and cefmetazole were less effective than cefoxitin against B. thetaiotaomicron. Cefotetan was the most active agent against E. coli, and cefmetazole was the most effective against S. aureus. These data illustrate the efficacy of all tested cephalosporins in the prophylaxis of polymicrobial infections.

Topics: Abdomen; Abscess; Animals; Bacterial Infections; Bacteroides fragilis; Bacteroides Infections; Cefmetazole; Cefotetan; Cefoxitin; Disease Models, Animal; Escherichia coli; Escherichia coli Infections; Male; Mice; Microbial Sensitivity Tests; Skin Diseases, Bacterial; Staphylococcal Infections; Staphylococcal Skin Infections; Staphylococcus aureus

The systemic tumor necrosis factor (TNF) response has been extensively studied during infection. In addition, antibiotics that cause cell-wall lysis have been associated with endotoxinemia and, therefore, could trigger TNF release. We studied the effects of pretreatment with cefoxitin and/or anti-TNF antibody on mortality and early (90 minutes) and delayed (6 hours) serum TNF levels in a murine model of mixed Escherichia coli/Bacteroides fragilis peritonitis. At low and intermediate inocula levels, cefoxitin, but not anti-TNF antibody, prevented death, and low serum TNF levels were noted in all groups. At the highest inoculum level, mortality was uniform in control, cefoxitin, and anti-TNF antibody groups, and a significant elevation in serum TNF levels was seen only at the 6-hour point in animals receiving cefoxitin. The addition of anti-TNF antibody to cefoxitin at this inoculum level abrogated the 6-hour rise in serum TNF levels and reduced mortality to 40%. These results emphasize that the cytokine response in disease is dependent on both the nature of the insult and other forms of therapeutic interventions.

Topics: Animals; Antibodies, Anti-Idiotypic; Bacteroides fragilis; Bacteroides Infections; Cefoxitin; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Therapy, Combination; Escherichia coli Infections; Immunoglobulin G; Injections, Intramuscular; Injections, Intraperitoneal; Male; Mice; Mice, Inbred BALB C; Peritonitis; Survival Rate; Tumor Necrosis Factor-alpha

Hemorrhagic shock has been shown to increase the susceptibility to infection despite the administration of conventionally accepted doses of antimicrobial drugs. The efficacy of increasing antibiotic dose in a model of mixed gram-negative infection, both with and without hemorrhagic shock, was examined. Shock was induced by bleeding rats to a mean arterial pressure of 45 millimeters of mercury for 45 minutes followed by resuscitation with shed blood and saline solution. One hour after shock or sham, the rats were inoculated with 1 x 10(8) Escherichia coli plus 1 x 10(9) Bacteroides fragilis in a fecal suspension subcutaneously. Rats were given either no antibiotic (CONTROL) or cefoxitin at 30 milligrams per kilogram (STANDARD) or 200 milligrams per kilogram (HIGH) intraperitoneally, 30 minutes before and at six and 12 hours after inoculation. Tissue cefoxitin concentrations were measured 30 minutes before and at six and 12 hours after inoculation. Tissue cefoxitin concentrations were measured 30 minutes after the initial dose. STANDARD reduced abscess diameter by 58 percent compared with CONTROL in rats that were not shocked, but only by 26 percent after shock (p < 0.05 shock versus sham). HIGH further decreased abscess diameter and weight (4 +/- 1 millimeter and 22 +/- 22 milligrams) after shock compared with STANDARD (9 +/- 1 millimeter and 230 +/- 90 milligrams; both p < 0.05). Peak tissue cefoxitin levels were greater than 19 times the minimal inhibitory concentration for each bacteria for HIGH compared with eight times for STANDARD. These data demonstrate that an increased dose of cefoxitin was superior to a conventional dose in controlling a mixed gram-negative infection after shock and suggest that altering traditional antibiotic use may decrease the incidence of infection after shock and hemorrhage.

Topics: Abscess; Animals; Bacteroides fragilis; Bacteroides Infections; Cefoxitin; Disease Susceptibility; Escherichia coli Infections; Female; Rats; Rats, Sprague-Dawley; Shock, Hemorrhagic; Wound Infection

beta-Lactamase production (nitrocefin disk method) and agar dilution susceptibility of amoxicillin, amoxicillin-clavulanate, ticarcillin, ticarcillin-clavulanate, cefoxitin, imipenem, and metronidazole were determined for 320 Bacteroides species (not Bacteroides fragilis group) and 129 fusobacteria from 28 U.S. centers. Overall, 64.7% of Bacteroides species and 41.1% of fusobacteria were beta-lactamase positive. Among the Bacteroides species, positivity rates were highest for B. bivius (85.0%), followed by B. splanchnicus (83.3%), B. eggerthii (77.8%), and B. oralis (77.1%); 54.5% of black-pigmented Bacteroides species were beta-lactamase positive. Among the fusobacteria, Fusobacterium mortiferum showed the highest rate of beta-lactamase positivity (76.9%). MICs of amoxicillin (128 micrograms/ml) and ticarcillin (64 micrograms/ml) for 90% of all beta-lactamase-positive strains were reduced to 4 and 2 micrograms/ml, respectively, with the addition of clavulanate. MICs of amoxicillin and ticarcillin for 90% of all beta-lactamase-negative strains were 1 and 4 micrograms/ml, respectively, and greater than or equal to 98.4% of the strains were susceptible to the beta-lactams tested. Of the beta-lactamase-producing strains, 45.9% were susceptible to amoxicillin at less than or equal to 4 micrograms/ml and 93.4% were susceptible to ticarcillin at less than or equal to 64 micrograms/ml; the addition of clavulanate raised the rates to 90.4 and 100%, respectively. All strains were susceptible to cefoxitin, imipenem, and metronidazole. The activity of amoxicillin against 29 beta-lactamase-producing strains (10 Bacteroides species and 19 fusobacteria) was not enhanced by the addition of clavulanate; however, 82.7% of these strains were susceptible to amoxicillin, and all were susceptible to ticarcillin. Although beta-lactamase positivity is on the increase in non-B. fragilis group Bacteroides species and fusobacteria, amoxicillin-clavulanate, ticarcillin, cefoxitin, imipenem, and metronidazole should be suitable for the treatment of infections with these strains. The addition of clavulanate does not appreciably improve the efficacy of ticarcillin against these organisms.

Topics: Amoxicillin; Anti-Bacterial Agents; Bacteroides; Bacteroides Infections; beta-Lactamase Inhibitors; beta-Lactamases; Cefoxitin; Clavulanic Acid; Clavulanic Acids; Fusobacterium; Fusobacterium Infections; Imipenem; Metronidazole; Microbial Sensitivity Tests; Ticarcillin; United States

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

The relationships between capsulate and non-capsulate Bacteroides fragilis strains and Escherichia coli, and between capsulate and non-capsulate strains of the B. melaninogenicus group and Streptococcus pyogenes, were studied in a subcutaneous abscess model in mice. Selective antimicrobial agents directed against either aerobic or anaerobic bacteria were used alone or in combination to explore the effect of eradication of one component of the mixed infection. Single agent therapy effective against both aerobic and anaerobic flora was also employed. Single therapy of mixed infection directed at the elimination of only one organism (S. pyogenes, E. coli or Bacteroides sp.) caused significant reductions in the numbers of sensitive organisms and also smaller yet significant decreases in the numbers of insensitive organisms. However, the abscesses were not eliminated after such therapy. Combination therapy or use of a single agent (cefoxitin) directed against the aerobic and anaerobic components of the infection was more effective. Non-capsulate Bacteroides spp. became capsulate after passage in mice mixed with either S. pyogenes or E. coli. Therapy directed at the elimination of S. pyogenes and E. coli did not prevent the emergence of capsulate Bacteroides spp. These data demonstrate the synergy between all members of the B. fragilis group and E. coli and between the B. melaninogenicus group and S. pyogenes, and reiterate the need to direct antimicrobial therapy at the eradication of the aerobic and anaerobic components of mixed infections.

Topics: Abscess; Aerobiosis; Anaerobiosis; Animals; Bacteroides; Bacteroides fragilis; Bacteroides Infections; Cefoxitin; Disease Models, Animal; Drug Resistance, Microbial; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Gentamicins; Leucomycins; Male; Metronidazole; Mice; Microbial Sensitivity Tests; Prevotella melaninogenica; Skin Diseases; Streptococcal Infections; Streptococcus pyogenes

The six species of the Bacteroides fragilis group are potent pathogens and commonly have different susceptibility patterns. We determined the relative annual isolation rate of anaerobic bacteria and the susceptibility of B. fragilis group species isolated during 1987 at two community hospitals. The relative frequencies of isolation of 261 strains were as follows: B. fragilis, 61%; B. thetaiotaomicron, 17%; B. distasonis, 7%; B. vulgatus, 6%; B. ovatus, 5%; and B. uniformis, 4%. A total of 234 recent clinical isolates were tested against cefmetazole, cefotetan, cefoxitin, ceftizoxime, clindamycin, imipenem, and piperacillin by a brucella agar dilution method. Imipenem was the most active agent tested with all but three isolates (two B. vulgatus and one B. distasonis) susceptible to less than 2 micrograms/ml. Of the cephalosporins tested, cefoxitin, cefotetan, and cefmetazole were relatively equal against B. fragilis, with 93 to 98% of strains susceptible to 32 micrograms/ml. Ceftizoxime was less active, with an MIC for 90% of strains tested of 128 micrograms/ml and only 75% of isolates susceptible to 32 micrograms/ml. Against B. ovatus, B. vulgatus, B. thetaiotaomicron, and B. uniformis, cefoxitin showed a two- to threefold-superior activity compared with that of cefotetan and cefmetazole. In general, ceftizoxime was much less active, except against B. distasonis, for which 78% of isolates were susceptible to 32 micrograms/ml compared with 68% for cefoxitin, 19% for cefmetazole, and 16% for cefotetan. Clindamycin and piperacillin showed activity similar to that of cefoxitin, except piperacillin was less active versus B. vulgatus and B. distasonis. We therefore suggest that clinical laboratories determine the species of B. fragilis group isolates as well as perform susceptibility studies on the isolates. Clinicians should be aware that while B. fragilis is the most frequent isolate, 38% of isolates are from other, more resistant B. fragilis group species.

Topics: Bacteroides fragilis; Bacteroides Infections; Cefmetazole; Cefotetan; Cefoxitin; Ceftizoxime; Humans; Microbial Sensitivity Tests; Periodicity

Resistance to cefoxitin among species of the Bacteroides fragilis group of organisms has remained low (8%-10%) in a multicenter nationwide survey. However, a statistically significant increase in the percentage of B. fragilis group organisms resistant to cefoxitin was found at Tufts-New England Medical Center from 1981 to 1982. Non fragilis species accounted for most of the resistance. The presence of cefoxitin resistance in B. fragilis isolates correlated with resistance to other antibiotics. The presence of cefoxitin-resistant B. fragilis group organisms also correlated with the presence of other cefoxitin-resistant bacteria. No difference could be detected in therapeutic outcome of patients with cefoxitin-sensitive or cefoxitin-resistant B. fragilis group organisms, regardless of treatment with cefoxitin or other antibiotics.

Topics: Age Factors; Bacteroides; Bacteroides fragilis; Bacteroides Infections; Cefoxitin; Drug Resistance, Microbial; Drug Utilization; Female; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors

Topics: Abscess; Bacteroides fragilis; Bacteroides Infections; Cefoxitin; Female; Humans; Infant

We inoculated 120 rats with 2 X 10(9) Escherichia coli or 2 X 10(9) Bacteroides fragilis suspended in normal saline solution or incorporated into fibrin clots. In the control group, all animals died after inoculation with E coli, but none died after the inoculation with B fragilis; both were suspended in normal saline solution. Escherichia coli entrapped in fibrin did not cause mortality but did result in abscess formation in all animals. Bacteroides fragilis incorporated into fibrin clots resulted in abscess formation in the majority of animals. Treatment with gentamicin sulfate, ampicillin sulfate, and cefoxitin sodium completely abolished the mortality secondary to E coli suspended in normal saline solution but did not influence the rate of abscess formation secondary to E coli incorporated into fibrin clots. Similarly, cefoxitin and clindamycin phosphate did not significantly change abscess formation secondary to B fragilis incorporated into fibrin clots. We conclude that systemic antibiotics are ineffective in the prevention of abscesses secondary to bacteria trapped in fibrin, either because they do not reach bactericidal levels in the fibrin clot, as in the case of gentamicin, ampicillin, and clindamycin, or, as in the case of cefoxitin, because of the inoculum effect caused by the high number of bacteria. Fibrinogen or fibrin itself do not afford any protection of bacteria against the action of antibiotics.

Topics: Abscess; Ampicillin; Animals; Anti-Bacterial Agents; Ascites; Bacteroides fragilis; Bacteroides Infections; Blood Coagulation; Cefoxitin; Clindamycin; Escherichia coli; Escherichia coli Infections; Fibrin; Gentamicins; Male; Rats; Rats, Inbred Strains

A new mouse model of anaerobic infection with Bacteroides fragilis alone or in a mixed infection with Escherichia coli is described. It is established by implantation under the skin of a filter paper disk saturated with the appropriate bacterial suspension. The penetration of antibiotics into the implantation site can be detected by assaying the disk. The local infection can be both standardized and evaluated by determining the bacterial count on the disk. The antimicrobial efficacy of ceftizoxime was compared with other commercially available antibiotics administered in a single dose, 40 mg/kg subcutaneously, one hour after implantation of the disk. Using such a regimen ceftizoxime was found to be superior to a clindamycin-gentamicin combination and equal to or superior to cefoxitin in these models.

Topics: Animals; Bacteroides fragilis; Bacteroides Infections; Cefotaxime; Cefoxitin; Ceftizoxime; Clindamycin; Cyclophosphamide; Escherichia coli Infections; Gentamicins; Mice

Topics: Abdomen; Abscess; Adult; Appendectomy; Appendicitis; Bacteroides fragilis; Bacteroides Infections; Cefoxitin; Diagnosis, Differential; Humans; Male; Pain

The efficacy of cefoxitin, mezlocillin, latamoxef and metronidazole in anaerobic lung infection was studied using a rabbit model. A mixture of Bacteroides fragilis, Peptococcus morbillorum, Eubacterium lentum and Fusobacterium nucleatum was inoculated transtracheally to produce infection within the lung. Mezlocillin was most effective, achieving bacteriologic cure in 5 out of 8 animals. With cefoxitin therapy, 4 out of 8 became bacteriologically sterile. Severe diarrhea with elevated titers of Clostridium difficile toxin was noted in most cefoxitin-treated animals. Latamoxef- and metronidazole-treated animals had apparently healed lesions, but cultures were positive in 6 and 7 out of 8 in each group, respectively. The commonest pathogen isolated in the last two groups was P. morbillorum. The therapeutic superiority of mezlocillin over metronidazole and latamoxef was statistically significant (p less than or equal to 0.05).

Topics: Animals; Anti-Bacterial Agents; Bacteria, Anaerobic; Bacteroides fragilis; Bacteroides Infections; Cefoxitin; Eubacterium; Fusobacterium Infections; Male; Metronidazole; Mezlocillin; Microbial Sensitivity Tests; Moxalactam; Peptococcus; Pneumonia; Rabbits

Our clinical experience with new antibiotics giving special consideration to the individual cephalosporin groups is discussed. Although newer cephalosporins from cefamandol and cefoxitin to cefotiam and cefoperazon already showed increased effectiveness (for example, cefoxitin in bacteroides infection) in comparison to older ones, the real breakthrough regarding enterobacteriaceae was only made with cephalosporins of the cefotaxime group. This group's main indication is non-specific initial therapy of severe nosocomial infections, especially processes in which the presence of resistant enterobacteriaceae must be assumed. Because of its broad spectrum of action, cefotaxime can to a large extent replace the combinations with aminoglycosides which were used previously. When required, cefotaxime proves to be a good partner for combinations with pseudomonas antibiotics.

Topics: Bacteroides Infections; Cefotaxime; Cefoxitin; Cephalosporins; Cross Infection; Drug Therapy, Combination; Enterobacteriaceae Infections; Gentamicins; Humans; Pseudomonas Infections; Staphylococcal Infections; Structure-Activity Relationship

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: Bacteroides Infections; Cefoxitin; Digestive System; Digestive System Surgical Procedures; Humans; Injections, Intramuscular; Premedication; Surgical Wound Infection

Topics: Aged; Bacterial Infections; Bacteroides fragilis; Bacteroides Infections; Cefoxitin; Diverticulitis; Female; Humans; Middle Aged

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

Cefoxitin (mefoxin), a new semisynthetic cephamycin antibiotic, resistant to degradation by beta-lactamase enzymes produced by bacteria. In vitro, cefoxitin is active against virtually all clinically important gram-negative facultative bacteria other than Pseudomonas and Enterobacter spp., gram-positive aerobic bacteria other than the enterococcus, and clinically important anaerobic organisms, including Bacteroides fragilis. This broad antibacterial spectrum suggested that cefoxitin might be an effective single antibiotic agent for the treatment of mixed aerobic-anaerobic infections in obstetric and gynecologic patients. In this investigation, the efficacy and safety of cefoxitin was evaluated in 109 patients--68 with salpingitis, 25 with endomyometritis, 9 with pelvic cellulitis, and 7 with pelvic abscesses. An average of 2.5 bacteria were isolated from each patient. Aerobic bacteria alone was isolated in 38% of patients, anaerobic bacteria alone in 25%, and a combination of aerobic and anaerobic bacteria was isolated in 37% of patients. Overall, 100 of 109 (92%) infections responded to treatment with cefoxitin alone. The major cause of treatment failure was the presence of abscesses requiring surgical drainage. In addition to being an effective single agent for the management of pelvic infections, cefoxitin proved to be safe and well tolerated by patients.

Topics: Abscess; Acute Disease; Adolescent; Adult; Aerobiosis; Anaerobiosis; Bacterial Infections; Bacteroides Infections; Cefoxitin; Cellulitis; Cephalosporins; Female; Gonorrhea; Humans; Middle Aged; Pelvis; Salpingitis

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

Cefoxitin, a beta-lactamase-resistant cephalosporin, was found to be more effective than cephalothin against an experimental mixed infection containing Bacteroides fragilis and Fusobacterium necrophorum.

Topics: Animals; Bacteroides fragilis; Bacteroides Infections; Cefoxitin; Cephalosporins; Cephalothin; Fusobacterium; Mice