In vitro activity of tigemonam against multiresistant nosocomial Enterobacteriaceae.

Tigemonam, an oral monobactam that exhibits beta-lactamase stability similar to that of aztreonam, was tested in vitro against 240 species of Enterobacteriaceae (50 Escherichia coli, 48 Klebsiella pneumoniae, 52 Enterobacter cloacae, 32 Proteus mirabilis, 22 Proteus indole-positive [Providencia sp.], 24 Serratia sp., and 12 Citrobacter sp. All strains were resistant to ampicillin and first-generation cephalosporins. In addition, 77.4% were resistant to amoxicillin plus clavulanic acid, 46.8% to cefuroxime, 23.3% to ceftriaxone, 22.2% to aztreonam, 46.9% to cotrimoxazole, and 0.9% to norfloxacin. Tigemonam at a concentration of 4 micrograms/mL or less inhibited 72.7% of the strains with minimum inhibitory concentrations ranging from 0.03 or less to more than 512 micrograms/mL. The highest intrinsic activity was observed against Proteus sp. Tigemonam proved to be a bactericidal antibiotic. Cross-resistance was chiefly observed with aztreonam and ceftriaxone. It is concluded that tigemonam should play an important role in the treatment of nosocomial infections that do not require parenteral therapy and in the treatment of multiresistant community-acquired infections.

Successful response of severe neonatal gram-negative infection to treatment with aztreonam.

Aztreonam was administered to 25 neonates (16 term, 9 premature) with clinically and bacteriologically proved gram-negative infections. Ten patients had meningitis, 9 had septicemia and 6 had urinary tract infections. Patients were between 1 and 28 days of age. Aztreonam was administered intravenously in doses ranging from 40 to 120 mg/kg/day for 10-30 days, depending on the causative organism. All CSF, blood and urine cultures were sterile 48 h after drug treatment had begun. There was no incidence of bacteriologic relapse. Body temperature returned to normal in 96% of patients within 3-4 days of therapy. Aztreonam was well tolerated. One infant experience nausea and vomiting, but no patient was withdrawn from therapy due to adverse reactions.

In Vitro Activity of Tigemonam Against Multiresistant Nosocomial Enterobacteriaceae.

Tigemonam, an oral monobactam that exhibits beta-lactamase stability similar to that of aztreonam, was tested in vitro against 240 species of Enterobacteriaceae (50 Escherichia coli, 48 Klebsiella pneumoniae, 52 Enterobacter cloacae, 32 Proteus mirabilis, 22 Proteus indole-positive [Providencia sp.], 24 Serrada sp., and 12 Citrobacter sp. All strains were resistant to ampicillin and first-generation cephalosporins. In addition, 77.4% were resistant to amoxicillin plus clavulanic acid, 46.8% to cefuroxime, 23.3% to ceftriaxone, 22.2% to aztreonam, 46.9% to cotrimoxazole, and 0.9% to norfloxacin. Tigemonam at a concentration of 4 µg/mL or less inhibited 72.7% of the strains with minimum inhibitory concentrations ranging from 0.03 or less to more than 512 µg/mL. The highest intrinsic activity was observed against Proteus sp. Tigemonam proved to be a bactericidal antibiotic. Cross-resistance was chiefly observed with aztreonam and ceftriaxone. It is concluded that tigemonam should play an important role in the treatment of nosocomial infections that do not require parenteral therapy and in the treatment of multiresistant community-acquired infections.

Evaluation of aztreonam in difficult-to-treat infections with prolonged posttreatment follow-up.

Aztreonam at doses of 1 or 2 g given intramuscularly or intravenously every 8 h for 7 to 42 days was given to 55 patients, most of them suffering from difficult-to-treat infections either because the isolated pathogens were multiresistant or because of the location of the infection. Infections included: urinary tract (23 cases), deep soft tissue phlegmon (12 cases), chronic osteomyelitis in exacerbation (7 cases), abscesses (7 cases), pneumonia (4 cases), and external otitis (2 cases). In culture specimens, Pseudomonas aeruginosa (24 isolates) and various Enterobacteriaceae species (37 isolates) were isolated with MICs ranging from 0.25 to 16 micrograms/ml. Clinically, at the completion of treatment and after a 6-week posttreatment follow-up, 45 (81.6%) patients were cured, 4 (7.2%) improved, 3 (5.6%) relapsed, and 3 (5.6%) failed to respond to therapy. Bacteriologically, at the end of treatment, the pathogen was eradicated in 50 patients (91%) and persisted in 5 (9%). After a 6-week follow-up, cultures remained sterile in 33 patients (60.0%), 16 (29.1%) relapsed, in 6 (10.9%) bacteria persisted, and superinfection was reported in 4 (7.3%) patients. No appreciable adverse effects or toxicity was observed. From the reported results, it is concluded that aztreonam is a valuable addition to the field of antimicrobial chemotherapy that can be used effectively and safely in the treatment of a variety of gram-negative infections.

Aztreonam versus cefamandole in the treatment of urinary tract infections.

The in vivo efficacy and safety of aztreonam compared to that of cefamandole was randomly and prospectively studied in the treatment of 30 patients suffering from recurrent urinary tract infections with a patient ratio of 2 aztreonam to 1 cefamandole. The mean age was 51.6 +/- 15.4 and 59.8 +/- 13 years respectively. Both antibiotics were given at a dose of 1 g, 8 hourly i.m. for 7-13 days. Sixty-seven percent versus 70% of the patients given aztreonam and cefamandole respectively were suffering from upper urinary tract infections. X ray abnormalities predisposing to relapse or reinfections were present in 88% vs 80% of the patients, while all patients had typical symptoms of urinary tract infections, with high fever (greater than or equal to 38.5 degrees C) reported in 70% and 60% of the patients in the two treatment groups respectively. Escherichia coli and Proteus mirabilis were the predominant isolates in urine cultures. During treatment all patients responded favourably both clinically and bacteriologically, while after a 6-week follow-up 20% versus 30% relapsed clinically with 15% vs 30% bacteriologic relapses in the two groups, but only in patients suffering from upper urinary tract infections. No development of bacterial resistance was observed in the relapses, while mainly Enterococcus spp was implicated in reinfections. No appreciable side effects of toxicity were observed. It was concluded that aztreonam is a promising new antibiotic that deserves further clinical trials in systemic infections.