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Biomedical subjects

H Thadepalli

Publications and source records attributed to H Thadepalli.

At least 55 records · Page 3Linked to original sources

Therapeutic evaluation of difloxacin (A-56619) and A-56620 for experimentally induced Bacteroides fragilis-associated intra-abdominal abscess.

Difloxacin (A-56619) and A-56620, two novel fluoroquinolones, were tested in comparison with ciprofloxacin, cefoxitin, and combined clindamycin and gentamicin in the treatment of experimentally induced intraabdominal abscess associated with Bacteroides fragilis. Difloxacin was found to be as effective as clindamycin-gentamicin. A-56620, despite achieving subtherapeutic levels in serum, was found to be as effective as cefoxitin. Both difloxacin and A-56620 were effective in vivo against experimentally induced intra-abdominal abscess in rats.

Abscess↗

Antibiotic levels in the small intestine.

It is unknown if parenteral antibiotics commonly used for prophylaxis reach adequate therapeutic levels in the intestinal tissue to inhibit the growth of bacteria, such as Escherichia coli and Bacteroids fragilis, commonly associated with injury to the gastrointestinal tract. We have designed an experiment using dogs to study this problem. We considered an antibiotic to be effective if a single dose reached increased levels in the intestinal tissue to inhibit the growth of the majority of Escherichia coli and Bacteroides fragilis strains isolated from the gastrointestinal tract. Of 14 different antibiotics studied, we conclude that carbenicillin, mezlocillin, piperacillin, cefbuperazone and cefoxitin as single drugs and Timentin (ticarcillin with clavulanic acid) and clindamycin with gentamicin and co-trimoxazole (trimethoprium and sulfamethoxazole) achieved therapeutic levels. Azlocillin, cefoperazone, cefmenoxime and minocycline failed to achieve significant concentrations. This experiment using dogs was extremely useful to determine the pharmacokinetics of antibiotics in the small intestine and to predict the efficacy of antibiotics considered for prophylaxis.

Animals↗

In vitro activity and in vivo evaluation of ticarcillin plus clavulanic acid against aerobic and anaerobic bacteria.

The efficacy of ticarcillin plus clavulanic acid was compared with that of certain broad-spectrum antibiotics such as ticarcillin, azlocillin, and piperacillin against blood culture isolates of aerobic bacteria obtained from seriously ill patients and anaerobic bacteria obtained from other miscellaneous infections. Ticarcillin plus clavulanic acid was found to be as effective as other broad-spectrum antibiotics against most of the 285 septicemic isolates tested. Ticarcillin plus clavulanic acid was most effective against 351 anaerobic bacteria, including B. fragilis. Further, 32 strains of B. fragilis that were relatively resistant to ticarcillin and azlocillin were tested with a mixture of ticarcillin or azlocillin, each in combination with clavulanic acid. Ticarcillin plus clavulanic acid inhibited all 32 strains of B. fragilis. Addition of clavulanic acid to cephalothin, penicillin, or azlocillin also augmented the antibiotic activity against B. fragilis by 4- to 64-fold. These in vitro data suggest that ticarcillin plus clavulanic acid may be used as a single antibiotic in the cases of bacterial septicemias and that the combination may be used in the treatment of multiple-antibiotic-resistant bacterial strains. In a related study, the augmentation activity of clavulanic acid with penicillin or ticarcillin was evaluated against B. fragilis in a rat intra-abdominal abscess model. Gelatin capsules filled with a mixture of B. fragilis and Escherichia coli were implanted intraperitoneally in male Wistar rats. Four different groups of animals with appropriate controls were treated with penicillin or ticarcillin alone or in combination with clavulanic acid. Treatment was started immediately or delayed for 48 hours after peritoneal soilage. The mortality rate decreased by almost one half when antibiotic therapy was started immediately. Treatment with ticarcillin plus clavulanic acid resulted in a cure in 70 to 89 percent of animals, showing that this combination is the most effective regimen in the treatment of rats with experimental intra-abdominal abscesses caused by B. fragilis and E. coli.

Abscess↗

Ticarcillin plus clavulanic acid versus moxalactam in the treatment of skin and soft tissue infections.

A formulation of 3.0 g of ticarcillin and 0.1 g of clavulanic acid was evaluated in the treatment of skin and soft tissue infections, and its efficacy was compared with that of moxalactam in a randomized open study. Thirty-three patients received 3.1 g of ticarcillin plus clavulanic acid every six hours via intravenous infusion, and 36 patients received 2.0 g of moxalactam every eight hours via intravenous infusion. Diagnostic categories included intramuscular abscesses, cellulitis, skin ulcers, gangrene, and perirectal abscesses. The average age of the patients and the duration of therapy were similar in both groups. Overall, 45 aerobic and 25 anaerobic bacteria were isolated from the ticarcillin plus clavulanic acid-treated patients; 58 aerobic and 24 anaerobic bacteria were isolated from the moxalactam-treated patients. Thirty of 33 patients in the ticarcillin plus clavulanic acid-treated group had a satisfactory response; a skin rash developed in one patient; therapy failed in one patient with Staphylococcus aureus infection; and one patient died as a result of a bleeding peptic ulcer. In the moxalactam-treated group, 32 of 36 patients had a satisfactory response; a skin rash developed in one patient; therapy failed in a patient with Pseudomonas aeruginosa infection; and two patients were unevaluable. Ticarcillin plus clavulanic acid as a single agent was found to be as effective as moxalactam in the treatment of skin and soft tissue infections.

Adolescent↗

Prophylactic antibiotics and no antibiotics compared in penetrating chest trauma.

Conflicting data exist concerning the value of antimicrobial prophylaxis in chest trauma. In a prospective and randomized study, we assessed the value of antibiotic prophylaxis in 80 consecutive relatively young, predominantly male patients admitted for gunshot or knife injuries of the chest. Forty patients received intravenous doxycycline and 40 received no antibiotic. Between the two groups we found no difference in the incidence of postoperative infections: we conclude that routine antibiotic prophylaxis is not recommended in penetrating chest trauma in patients such as ours.

Adolescent↗

In vitro activity of cefbuperazone, a new cephamycin, against anaerobic bacteria.

The 90% MIC of cefbuperazone (BMY 25182) was 32 micrograms/ml for Bacteroides fragilis and Bacteroides spp., 128 micrograms/ml for Fusobacterium and Clostridium spp., 64 micrograms/ml for Eubacterium and Peptococcus spp., 8 micrograms/ml for Actinomyces spp., and 32 micrograms/ml for Peptostreptococcus spp. The level of activity of cefbuperazone was higher against B. fragilis and lower against anaerobic cocci than those of related cephalosporins, i.e., cefoxitin, cefoperazone, cefotaxime, ceftizoxime, and cefmenoxime. However, the activity of cefbuperazone was comparable to that of moxalactam against all groups tested. Size of inoculum and type of media used did not alter the MICs of cefbuperazone for B. fragilis. Cefbuperazone showed synergistic activity when combined with cefoxitin against resistant strains of B. fragilis.

Anti-Bacterial Agents↗

Augmentation effect of clavulanic acid with penicillin, cephalothin and ticarcillin against Bacteroides fragilis.

The effect of clavulanic acid on the in vitro activity of beta-lactam antibiotics against Bacteroides fragilis (154 strains) was tested. The MIC90 on 154 strains of B. fragilis tested was greater than 64 micrograms/ml for penicillin and cephalothin, and greater than 128 for ticarcillin alone. 32 strains of B. fragilis relatively resistant to the test beta-lactam antibiotics (most of them beta-lactamase producers) were retested with the addition of clavulanic acid. 90% of the strains were then inhibited by less than or equal to 8 micrograms/ml of penicillin and cephalothin, and by 32 micrograms/ml of ticarcillin. The strongest beta-lactamase producers were the most susceptible, and this was not influenced by change in pH of the diluent for clavulanic acid from 6.0 to 7.4. Both penicillin and cephalothin when combined with clavulanic acid were highly effective against B. fragilis but the therapeutic relevance of these combinations remains to be evaluated.

Bacteroides fragilis↗

Cefmenoxime therapy for gynecologic and obstetric infections.

Cefmenoxime, a new third-generation cephalosporin, was used as a single drug in the therapy for female genital tract infections. Therapeutic response was considered satisfactory in 21 of 22 cases of pelvic inflammatory disease, six of nine tuboovarian abscesses, two of three severe wound infections, and all five cases of endometritis. Overall, 34 of 39 patients responded. The peak serum antibiotic levels in this study ranged from 15.8 to 64 (average 48.7) micrograms/mL, and the trough level ranged from 0.9 to 4 (average 3.1) micrograms/mL. Cefmenoxime was tested in vitro against 424 isolates of anaerobes including 208 strains of bacteroides of which 80 were Bacteroides fragilis. Cefmenoxime inhibited the growth of 90% or greater of the organisms (minimal inhibitory concentration 90) at less than or equal to 64 micrograms/mL. The minimal inhibitory concentration for 75% of B fragilis was 32 micrograms/mL. This study suggests that cefmenoxime as a single-drug therapy is effective in the treatment of female genital tract infections caused by aerobic (including the gonococcus) and anaerobic bacteria.

Abscess↗

Comparison of cefamandole and carbenicillin in preventing sepsis following penetrating abdominal trauma.

One hundred and five patients with penetrating abdominal injuries were treated with single-antibiotic regimens. Forty-seven patients were treated with intravenous (IV) cefamandole and for comparison 58 patients were treated with IV carbenicillin previously shown to be effective against postoperative infections associated with abdominal trauma. The overall incidence of deep infection on a single antibiotic therapy was 8.6 per cent, including two patients on cefamandole alone (4.3%) and seven (12.1%) on carbenicillin alone. One in each antibiotic group died of sepsis with a total mortality of 1.9 per cent. The authors concluded that cefamandole when used alone was found to be safe and more effective than carbenicillin alone in preventing sepsis in patients with abdominal trauma.

Abdominal Injuries↗

Newer beta-lactam antibiotics in the treatment of experimental Staphylococcus aureus endocarditis.

Antistaphylococcal activity of three beta-lactam antibiotics, i.e. cefmenoxime, cefotaxime and latamoxef (moxalactam) was compared with that of nafcillin by studying cure rates of aortic valvular endocarditis caused by one of three clinical isolates of Staphylococcus aureus in New Zealand white male rabbits. The animals were randomly allocated to a control and four antibiotic treatment groups. Each animal except the controls received 60 mg/kg of one antibiotic intramuscularly twice daily for two weeks, beginning 24 h after induction of endocarditis. The aortic valve was sterilized in 11 of 15 (73%) animals treated with cefmenoxime, nine of 13 (69%) treated with cefotaxime, 11 of 13 (85%) treated with latamoxef and 12 of 15 (80%) treated with nafcillin. All nine animals in the control group developed aortic valvular vegetations with an average of 2.4 X 10(9) cfu/g. The differences in sterility rates resulting from treatment with the four antibiotics were not statistically significant (P greater than 0.70).

Animals↗

Augmentation of the in vitro activity of azlocillin against Bacteroides fragilis by clavulanic acid.

Azlocillin was active against 90% of 154 strains of Bacteroides fragilis at a concentration of 64 micrograms/ml. Twenty-eight strains of B. fragilis with an azlocillin MIC of greater than or equal to 8 micrograms/ml were retested with a combination of azlocillin plus clavulanic acid. Of these strains, 71% showed a 4- to 32-fold decrease in the MIC of azlocillin plus clavulanic acid.

Azlocillin↗

In vitro susceptibility of anaerobic bacteria to ciprofloxacin (Bay o 9867).

About 80% of 70 clinical isolates of Bacteroides fragilis were inhibited by 4 micrograms of ciprofloxacin (Bay o 9867) per ml. The 90% MIC of ciprofloxacin was 8 micrograms/ml for other Bacteroides species, 2 micrograms/ml for Peptococcus species, 8 micrograms/ml for Peptostreptococcus species, and 16 micrograms/ml for Clostridium and Eubacterium species.

Animals↗

Susceptibility of intestinal anaerobes to new beta-lactam antibiotics.

In vitro susceptibility of 473 isolates of anaerobic bacteria derived from patients hospitalized for treatment of abdominal trauma was tested against third-generation cephalosporins--moxalactam, cefotaxime, ceftizoxime, cefmenoxime--and a penicillin--N-formimidoyl thienamycin--by serial agar dilution method in the anaerobic glove box. There were 208 Bacteroides isolates including 80 Bacteroides fragilis and 100 peptococci and peptostreptococci. The minimal inhibitory concentration (MIC) 75% of B. fragilis was less than or equal to 32 micrograms/ml for the cephalosporins tested and less than or equal to 8 micrograms/ml for thienamycin. The MIC of B. fragilis and Bacteroides vulgatus was not much influenced by increased inoculum size. Characteristically, peptostreptococci and peptococci were resistant to all four cephalosporins tested with MIC 75% being 32-64 micrograms/ml. All five antibiotics in this study appear suitable for therapy of intraabdominal suppurative infections, but the poor activity of third-generation cephalosporins on anaerobic cocci can be a cause of concern.

Anti-Bacterial Agents↗

In vitro activity of cefmenoxime, cefotaxime, latamoxef, cefazolin, nafcillin and vancomycin against 53 endocarditis and bacteremic strains of Staphylococcus aureus.

Antistaphylococcal activity of newer beta-lactam antibiotics, cefmenoxime, cefotaxime and latamoxef was compared with that of the more conventional antistaphylococcal agents, nafcillin, cefazolin and vancomycin. 53 strains of Staphylococcus aureus, 40 from patients with endocarditis and 13 from patients with bacteremia from other causes were tested in vitro against each antibiotic using agar dilution methods. Minimal concentration of antibiotic to inhibit 90% of strains tested was 2 micrograms/ml for cefmenoxime and cefotaxime, 8 micrograms/ml for latamoxef and only 0.5 microgram/ml for nafcillin, cefazolin and vancomycin. The newer beta-lactam antibiotics may not be preferred to nafcillin, cefazolin or vancomycin in the treatment of serious staphylococcal infections.

Anti-Bacterial Agents↗

Minocycline prophylaxis in elective hysterectomy.

Minocycline prophylaxis was compared with a placebo in 126 consecutive patients undergoing hysterectomy. The double-blind nature of this study was guarded until the study was completed. Of 95 patients who had abdominal hysterectomies, 32.7% on minocycline and 39.1% on placebo developed infectious complications. Of 31 vaginal hysterectomy patients, 20% on minocycline and 37.5% on the placebo developed septic complications (p less than 0.05). Although minocycline inhibited B. fragilis and E. coli effectively, those organisms colonized increasingly during the postoperative period with similar frequency in both the minocycline- and placebo-treated groups. Minocycline did not produce antibiotic-resistant strains. In our study the parenteral and oral forms of minocycline were found to be safe, and vestibular symptoms were no more common than in the placebo group. These data suggest that antibiotic prophylaxis with minocycline is safe and well tolerated. In addition, minocycline is effective in lowering the infection rate in vaginal, but not abdominal, hysterectomies.

Bacterial Infections↗

Evaluation of antibiotic therapy and surgical techniques in cases of homicidal wounds of the colon.

Infectious morbidity associated with colonic trauma was evaluated with respect to the specific site of the colonic injury, the surgical method used, and the antibiotic treatment prescribed. Septic complications were more frequent among patients who had left-sided colon injuries (P = less than 0.01) and among those who received antibiotics known to be ineffective against anaerobic bacteria (P = less than 0.01). A statistical analysis of the different surgical methods used, i.e., primary repair of the colon, primary repair with loop exteriorization, or colostomy, was indeterminable.

Anti-Bacterial Agents↗