Repaglinide induced acute hepototoxicity.

Repaglinide is considered a safe drug; adverse events are mild to moderate which includes hypoglycemia, headache, nausea, vomiting, diarrhea and dyspepsia as similar to sulphonylureas. This case report describes a rare side effect of repaglinide. In rare cases, elevated liver enzymes have been noted. We report a case of acute hepatotoxicity in a 78-year-old woman who developed acute hepatotoxicity while taking repaglinide.

Enteritis necroticans with midgut necrosis caused by Clostridium perfringens.

Enteritis necroticans is a necrotizing process manifesting as segmental gangrene of the bowel, triggered by Clostridium perfringens toxins under specific dietary conditions. It is a rare disease in developed countries and is probably underdiagnosed. A case of enteritis necroticans presenting with midgut necrosis with sepsis and hemolysis is reported herein. Bacteriologic culture of blood and peritoneal content revealed C perfringens. Dietary history, including the ingestion of meat together with sweet potatoes, should increase clinical suspicion of enteritis necroticans. Early recognition and timely surgical intervention are required for successful treatment. Clinicians are encouraged to be aware of this clinically fulminant yet rarely recognized surgical entity.

Correlation of predicted serum bactericidal activities and values measured in volunteers.

A method was devised for predicting the serum bactericidal activity of new drugs. Six healthy volunteers received 2 g moxalactam, cefoperazone and cefotaxime, respectively, as 30-min infusions in a crossover manner at one-week intervals. The pharmacokinetics of each drug was characterized and the bactericidal activity of the serum 1 h after infusion was measured against panels of six strains of Pseudomonas aeruginosa, six strains of Escherichia coli, six strains of Staphylococcus aureus, and four strains of Klebsiella pneumoniae. The minimum bactericidal concentration of each antibiotic was determined for each organism by the standard NCCLS reference method and the method of Stratton and Reller. On the basis of these values and a serum concentration-time curve constructed from individual patient pharmacokinetic parameters, the bactericidal activity of the serum 1 h after infusion was predicted. These predictions showed a 90% agreement with measured values calculated according to the method of Stratton and Reller, whereas an agreement of 74% was obtained with the reference method. This difference was statistically significant (p less than 0.001).

The serum bactericidal activity of latamoxef (moxalactam), cefoperazone and cefotaxime.

We determined the serum bactericidal activity 1 h after the end of 2 g, 30 min infusions of latamoxef, cefoperazone and cefotaxime in six volunteers against six strains each of Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Pseudomonas aeruginosa. All produced excellent serum bactericidal activity against E. coli. Latamoxef and cefotaxime were superior for K. pneumoniae. Cefoperazone produced the highest titres against Staph. aureus. None of these agents produced sufficient bactericidal activity against Ps. aeruginosa to be useful in initial single agent therapy for the septic, granulocytopenic cancer patient.

Single-dose regimen of cefonicid for the treatment of uncomplicated infections of the lower urinary tract.

Fifty-three women with symptoms of lower urinary tract infection were randomly assigned to treatment with cefonicid administered intramuscularly in a single 1-g dose or to treatment with 500 mg of amoxicillin administered orally three times a day for five to seven days. Urine cultures were obtained before therapy and again at five to 18 days and six to seven weeks after termination of therapy. Forty-one patients had greater than or equal to 2 X 10(4) colony-forming units (cfu)/ml of catheterized urine or greater than or equal to 10(5) cfu/ml of midstream urine. In the cefonicid-treated group, 19 (90%) of 21 patients demonstrated bacteriologic cure at early follow-up. Of the 18 patients seen at late follow-up, 15 were cured and three were reinfected. One patient was lost to late follow-up. In the amoxicillin-treated group, 16 (80%) of 20 patients demonstrated bacteriologic cure at early follow-up. Of the 15 patients available at late follow-up, 14 were cured and one was reinfected. One patient was lost to late follow-up. Cefonicid is an effective single-dose agent in uncomplicated lower urinary tract infection.

Reactogenicity, immunogenicity, and efficacy of a chick embryo cell-derived vaccine for Rocky Mountain spotted fever.

A new formalin-inactivated vaccine prepared by sucrose density gradient centrifugation of tissue culture-grown Rickettsia rickettsii was evaluated for safety and immunogenicity in a placebo-controlled, double-blind study. Most of the 52 seronegative adult vaccinees, 88% after the first and 66% after the second dose, experienced brief, mild (mostly local) reactions, but only 50% exhibited a systemic immune response to vaccination. Six unvaccinated volunteers (controls) and 16 of these vaccinees were challenged with R rickettsii one month after vaccination. Vaccine efficacy was 25%; all six controls and 12 of 16 vaccinees developed typical Rocky Mountain spotted fever. The incubation period was longer, the duration of constitutional symptoms shorter, and the height of fever lower in ill vaccinees than in controls. The vaccine provided only partial protection against Rocky Mountain spotted fever but ameliorated the illness.

Single-dose cefonicid therapy for urinary tract infections.

The efficacy of single-dose therapy with cefonicid (1 g intramuscularly) and multidose therapy with amoxicillin (500 mg orally three times a day for 7 days) was compared for the treatment of uncomplicated lower urinary tract infection in women. Of 50 patients with symptoms of lower urinary tract infection randomized to receive either cefonicid or amoxicillin, 39 were infected with greater than or equal to 10(5) bacteria per ml. At early posttherapy follow-up (5 to 18 days), 19 of 21 (90%) cefonicid-treated patients and 16 of 18 (89%) amoxicillin-treated patients were cured. At late posttherapy follow-up (6 to 7 weeks), 16 of 18 (89%) cefonicid-treated patients and 14 of 15 (93%) amoxicillin-treated patients were cured. One patient was lost to follow-up in each late follow-up group. There were fewer side effects in the cefonicid-treated group. There were significantly more organisms resistant to amoxicillin than to cefonicid in the study population. Considering the small size of the series, single-dose therapy with cefonicid for lower urinary tract infection in women appears to be as safe and effective as conventional multidose therapy with amoxicillin.

Comparative pharmacokinetics of moxalactam, cefoperazone, and cefotaxime in normal volunteers.

The pharmacokinetic parameters of moxalactam were compared with those of cefoperazone and cefotaxime in normal volunteers in a crossover manner. Following 30-min intravenous infusions of 2 g of each of the three antibiotics, serum levels at 1 hr were slightly lower for moxalactam (88 micrograms/ml) than for cefoperazone (112 micrograms/ml) but more than three times those obtained for cefotaxime (29 micrograms/ml). By 8 hr, levels of moxalactam (9.2 micrograms/ml) were slightly higher than those of cefoperazone (6.5 micrograms/ml), and levels of cefotaxime in serum were unmeasurable (less than 1 micrograms/ml). These values reflect differences in half lives of the three agents. Peak serum levels following intramuscular injection and serum levels during constant intravenous infusion were similar for moxalactam and cefoperazone because of counterbalancing differences in the apparent volume of distribution and rates of elimination of the two antibiotics. Serum levels of cefotaxime were much lower than those of the other two antibiotics primarily because of the rapid elimination of cefotaxime from the body. The kidney was the major route of excretion of moxalactam, whereas extrarenal mechanisms were more important for elimination of cefoperazone. These differences in pharmacokinetics may have significant implications for the clinical use of these new antibiotics.