Estudo comparativo do aztreonam com um regime terapêutico incluindo um aminoglicosídeo no tratamento da pneumonia Gram-negativa / Comparative study of aztreonam in Gram-negative pneumonia versus a therapeutic regimen that includes an aminoglycoside

A pneumonia Gram-negativa é uma complicaçäo frequente em pacientes hospitalizados, particularmente quando suas defesas estäo diminuídas. A severidade dessas infecçöes exige que seja iniciada imediatamente uma terapia antimicrobiana empírica, que geralmente utiliza uma combinaçäo de um antibiótico beta-lactâmico de amplo espectro com um aminoglicosídeo (AMG), apesar da toxicidade potencial desse regime. Comparamos a eficácia de um novo antibiótico beta-lactâmico, o aztreonam, que apresenta um espectro específico de atividade contra bactérias Gram-negativas e uma excelente difusäo no tecido pulmonar, com a de outro regime antibiótico que incluía um AMG. De um total de 69 pacientes, 43 foram tratados com aztreonam e os restantes com um AMG. Ambos os grupos eram equivalentes com relaçäo à severidade da infecçäo e à patologia subjacente. A eficácia clínica foi semelhante nos dois regimes (81 por cento com aztreonam, 62 por cento com AMG). A eficácia antimicrobiana porém, foi superior no grupo de aztreonam (88 por cento com aztreonam, 65 por cento com AMG), embora essas diferenças tenham desaparecido nos pacientes do grupo de AMG tratados com uma combinaçäo de amicacina e cefoxima ou ticarcilina. Os índices de colonizaçäo/superinfecçäo também foram semelhantes em ambos os grupos, embora a seleçäo de bactérias Gram-negativas tenha sido mais frequente no grupo de AMG. Nossos resultados sugerem que a monoterapia com aztreonam é uma alternativa útil no tratamento da pneumonia Gram-negativa

Ensaio comparativo milticêntrico do aztreonam no tratamento de infecçöes Gram-negativas em pacientes comprometidos sob tratamento intensivo / A multicenter comparative trial of aztreonam in the treatment of Gram-negative infections in compromised intensive-care patients

Um ensaio comparativo multicêntrico foi realizado em 4 hospitais universitários para avaliar a eficácia do aztreonam, um novo antibiótico monobactâmico. Todos os pacientes incluídos no estudo haviam sido admitidos à unidade de tratamento intensivo hospitalar com distúrbios subjacentes severos. No total, foram documentadas 167 infecçöes em 157 pacientes (78 pneumonias, 26 infecçöes do trato urinário, 23 peritonites e 40 septicemias). O estudo foi realizado em duas fases. Na fase 1, 49 pacientes que receberam aztreonam foram comparados a 26 que receberam amicacina. Ambas as drogas foram administradas como cobertura única contra bacilos Gram-negativos. Na fase 2, 48 pacientes tratados com aztreonam foram comparados a 34 que receberam uma combinaçäo sinérgica de amicacina e um beta-lactâmico de amplo espectro. Os resultados sugerem que o aztreonam pode ser adotado como monoterapia no tratamento de infecçöes Gram-negativas sistêmicas, com uma eficácia comparável à do tratamento antimicrobiano convencional. O aztreonam provavelmente é mais eficaz que a amicacina no tratamento de infecçöes do trato respiratório e pelo menos täo eficaz quanto à combinaçäo de beta-lactâmicos e aminoglicosídeos. Pode-se estabelecer uma dose-padräo adequada de 3-4 g/dia de aztreonam em pacientes comprometidos, devendo ser combinada a uma cobertura Gram-positiva quando o tratamento for prescrito empiricamente

A multicenter comparative trial of aztreonam in the treatment of gram-negative infections in compromised intensive-care patients.

A multicenter comparative trial was conducted in 4 university hospitals to evaluate the efficacy of aztreonam, a new monobactam antibiotic. All patients enrolled in the study were admitted to the intensive-care unit with severe underlying conditions. A total of 167 infections were documented in 157 patients (78 pneumonia, 26 urinary tract infection, 23 peritonitis, and 40 septicemia). The study was performed in 2 phases. In phase 1, 49 patients receiving aztreonam were compared with 26 receiving amikacin. These two drugs were administered as the sole coverage against gram-negative bacilli. In phase 2, 48 patients treated with aztreonam were compared with 34 who received a synergistic combination of amikacin and a broad-spectrum beta-lactam. The results suggest that aztreonam can be used as monotherapy in the treatment of systemic gram-negative infections with an efficacy comparable with that of standard antimicrobial therapy. Aztreonam is probably more effective than amikacin in treating respiratory tract infections and it is at least as effective as a beta-lactam-aminoglycoside combination. An adequate standard dosage of aztreonam could be established as 3-4 g/day in compromised patients, and it should be combined with gram-positive coverage when used empirically.

Therapeutic efficacy of the combination of aztreonam with cefotaxime in the treatment of severe nosocomial pneumonia. Comparative study against amikacin combined with cefotaxime.

The combination aztreonam + cefotaxime (AZ + CE) was compared to amikacin + cefotaxime (AM + CE) in the treatment of nosocomial pneumonia acquired at the intensive-care unit. This study included a total of 33 patients fulfilling criteria for nosocomial pneumonia. 16 of them were randomly allocated to the AZ + CE group and 17 to the AM + CE group. The empirical treatment was effective for 78% of AZ + CE cases and 92% of AM + CE cases (p = NS). Clinical care was observed in 77% of cases (10 out of 13 evaluable) in the AZ group and in 75% of the group treated with AM (12 cases out of 16 evaluable; p = NS). In the evaluable cases, treatment failure was associated with injections due to the following organisms: Acinetobacter calcoaceticus (1) and Pseudomonas aeruginosa (1) in the AZ group and A. calcoaceticus (1) in the AM group. Superinfections were observed only in the AM group P. aeruginosa. A. calcoaceticus, Streptococcus viridans, Candida albicans, Aspergillus fumigatus and Serratia marcescens. Both the peak and through serum concentrations of AZ and AM were maintained within normal ranges. Finally, an impairment of renal tubular function was observed in the group of patients treated with AM, as measured by urinary levels of N-acetyl-beta-D-glucosaminidase and leucine aminopeptidase sequentially during the treatment. These changes in renal functions alterations mentioned were not observed in the AZ group. It is concluded that the AZ + CE combination is an effective empirical and active antibiotic treatment against severe nosocomial pneumonia. Aztreonam has no renal toxicity, which is an advantage to take into account in patients with altered renal function.

Comparative study of aztreonam in gram-negative pneumonia versus a therapeutic regimen that includes an aminoglycoside. Spanish Study Group.

Gram-negative pneumonia is a frequent complication in hospitalized patients, particularly in those with diminished defenses. The severity of the infections makes it necessary to start immediately an empirical antimicrobial therapy that usually combines a broad-spectrum beta-lactam antibiotic with an aminoglycoside (AMG), despite the potential toxicity of this regimen. We have compared the efficacy of a new beta-lactam antibiotic, aztreonam, which shows both a specific spectrum of activity against gram-negative bacteria and a very good diffusion into pulmonary tissue, with that of another antibiotic regimen including an AMG. Of a total of 69 patients, 43 were treated with aztreonam and the remaining patients with an AMG. Both groups were comparable with respect to the severity of infection and underlying pathology. Clinical efficacy was similar in the two regimens (81% aztreonam, 62% AMG). However, antimicrobial efficacy was superior in the aztreonam group (88% aztreonam, 65% AMG), although differences disappeared in patients treated with the combination amikacin + cefotaxime or ticarcillin in the AMG group. Colonization/superinfection was also similar in both groups, although the selection of gram-negative bacteria occurred more frequently in the AMG group. Our results suggest that aztreonam, in monotherapy, may be a useful alternative for the treatment of gram-negative pneumonia.

Neurohormonal responses to antihypertensive treatment with captopril or hydrochlorothiazide.

In order to assess the neurohormonal responses to oral administration of two drugs with different antihypertensive mechanisms, and their implications for long-term efficacy, we studied the changes in plasma renin activity, aldosterone, catecholamines and blood pressure after two cross-over periods of treatment with captopril and hydrochlorothiazide for three months in 14 patients with moderate essential hypertension. Similar levels of plasma renin activity were achieved with both but plasma levels of noradrenaline and aldosterone rose with hydrochlorothiazide (P less than 0.005 and P less than 0.05). Dopamine levels decreased with captopril. Six patients on hydrochlorothiazide had potassium levels under 3.5 mmol/l. Captopril and hydrochlorothiazide were effective in controlling blood pressure in 78% and 50% of the patients respectively, but in cases where noradrenaline was significantly increased after treatment, the effect on diastolic blood pressure was less (P less than 0.05). These data suggest that captopril is highly effective for blood pressure control and that the neurohormonal responses to the drug probably provide additional benefits for long-term therapy in hypertension.