Efficacy and safety of tigecycline monotherapy compared with vancomycin plus aztreonam in patients with complicated skin and skin structure infections: Results from a phase 3, randomized, double-blind trial.

OBJECTIVES: To compare the effect of tigecycline monotherapy, a first-in-class, expanded broad spectrum glycylcycline, with the combination of vancomycin and aztreonam (V + A) in the treatment of complicated skin and skin structure infections (cSSSI). METHODS: A phase 3, double-blind study conducted in 8 countries enrolled adults with cSSSI who required intravenous (IV) antibiotic therapy for > or =5 days. Patients were randomly assigned (1:1) to receive either tigecycline or V + A for up to 14 days. Primary endpoint was the clinical cure rate at the test-of-cure visit. Secondary endpoints included microbiologic efficacy and in vitro susceptibility to tigecycline of bacteria that cause cSSSI. Safety was assessed by physical examination, laboratory analyses, and adverse event reporting. RESULTS: A total of 596 patients were screened for enrollment, 573 were analyzed for safety, 537 were included in the clinical modified intent-to-treat (c-mITT) population, 397 were clinically evaluable (CE), and 228 were microbiologically evaluable (ME). At test-of-cure, cure rates were similar between tigecycline and V + A groups in the CE population (82.9% versus 82.3%, respectively) and in the c-mITT population (75.5% versus 76.9%, respectively). Microbiologic eradication rates (subject level) at test-of-cure in the ME population were also similar between tigecycline and V + A. Frequency of adverse events was similar between groups, although patients receiving tigecycline had higher incidence of nausea, vomiting, dyspepsia, and anorexia, while increased ALT/SGPT, pruritus, and rash occurred significantly more often in V + A-treated patients. CONCLUSIONS: This study demonstrates that the efficacy of tigecycline monotherapy for the treatment of patients with cSSSI is statistically noninferior to the combination of V + A.

Estudo comparativo entre as associaçöes aztreonam/clindamicina e tobramicina/clindamicina no tratamento de infecçöes intra-abdominais / Comparison of aztreonam plus clindamycin with tobramycin plus clindamycin in the treatment of intra-abdominal infections

Este estudo avaliou a atividade do aztreonam (um antibiótico ß-lactâmico com atividade específica contra bactérias Gram-negativas), comparando-a com a da tobramicina, em pacientes hospitalizados com infecçöes intra-abdominais severas causadas por patógenos Gram-negativos isoladamente ou associados a outras bactérias. O estudo incluiu no total 156 pacientes, dos quais 76 receberam aztreonam + clindamicina e 80 foram tratados com tobramicina + clindamicina. Os pacientes foram submetidos a diversos procedimentos cirúrgicos envolvendo a cavidade peritoneal. A avaliaçäo clínica final revelou percentagens semelhantes de resultados satisfatórios: 86,5% nos pacientes tratados com aztreonam e 86.2% no grupo tratado com tobramicina. Entre os pacientes que tiveram maus resultados observou-se que em 50% dos casos as infecçöes eram causadas por Gram-negativos isoladamente ou associados a miciroorganismos Gram-positivos, no grupo tratado com aztreonam; esta percentagem subiu para 82% quando se avaliou o mesmo subgrupo entre os pacientes tratados com tobramicina. A incidência de efeitos adversos e de alteraçöes dos parâmetros laboratoriais näo foi significante e semelhante nos dois grupos. Os resultados deste estudo sugerem que o aztreonam pode ser uma droga eficaz e segura para o tratamento de infecçöes causadas por bactérias Gram-negativas

Aztreonam in the treatment of bacterial meningitis.

The monobactam aztreonam was used to treat 22 young patients with meningitis caused by gram-negative bacilli. Haemophilus influenzae was isolated from the CSF of 21 patients and Salmonella heidelberg from the CSF of 1. Dosages ranged from 100 to 200 mg/kg/day in 4 doses at 6-hour intervals. Minimal inhibitory concentrations were determined by the broth dilution method for all isolated strains, and values ranged from 0.05 to 2.0 micrograms/ml. Blood and CSF drug levels were determined by a microbiologic plate diffusion method, and mean values for CSF and blood were 1.4 and 14.9 micrograms/ml, respectively. The outcome was good in 21 patients; 1 patient died. Complications were mild; subdural effusion occurred in 6 cases and was managed clinically; asymptomatic hydrocephalus was seen in 4; seizure during the acute phase occurred in 6 cases; hypoacusis was noted in 2, and motor impairment was detected at the follow-up in 1 case. Aztreonam achieved good blood and CSF penetration and performed well in the treatment of 20 cases of H. influenzae meningitis and in the one case of S. heidelberg meningitis.