Intravenous azithromycin plus ceftriaxone followed by oral azithromycin for the treatment of inpatients with community-acquired pneumonia: an open-label, non-comparative multicenter trial

Community-Acquired Pneumonia (CAP) is a major public health problem. In Brazil it has been estimated that 2,000,000 people are affected by CAP every year. Of those, 780,000 are admitted to hospital, and 30,000 have death as the outcome. This is an open-label, non-comparative study with the purpose of evaluating efficacy, safety, and tolerability levels of IV azithromycin (IVA) and IV ceftriaxone (IVC), followed by oral azithromycin (OA) for the treatment of inpatients with mild to severe CAP. Eighty-six patients (mean age 56.6 ± 19.8) were administered IVA (500mg/day) and IVC (1g/day) for 2 to 5 days, followed by AO (500mg/day) to complete a total of 10 days. At the end of treatment (EOT) and after 30 days (End of Study - EOS) the medication was evaluated clinically, microbiologically and for tolerability levels. Out of the total 86-patient population, 62 (72.1 percent) completed the study. At the end of treatment, 95.2 percent (CI95: 88.9 percent - 100 percent) reported cure or clinical improvement; at the end of the study, that figure was 88.9 percent (CI95: 74.1 percent - 91.7 percent). Out of the 86 patients enrolled in the study, 15 were microbiologically evaluable for bacteriological response. Of those, 6 reported pathogen eradication at the end of therapy (40 percent), and 8 reported presumed eradication (53.3 percent). At end of study evaluation, 9 patients showed pathogen eradication (50 percent), and 7 showed presumed eradication (38.89 percent). Therefore, negative cultures were obtained from 93.3 percent of the patients at EOT, and from 88.9 percent at the end of the study. One patient (6.67 percent of patient population) reported presumed microbiological resistance. At study end, 2 patients (11.11 percent) still reported undetermined culture. Uncontrollable vomiting and worsening pneumonia condition were reported by 2.3 percent of patients. Discussion and Conclusion Treatment based on the administration of IV azithromycin...

Mecanismos de ação e de resistência aos cetolídeos / Machanisms of action and resistence to ketolides

O aumento da resistência a múltiplas drogas em algumas linhagens de microorganismos tem sido registrado em todo o mundo. Consequentemente, os corriqueiros antibióticos orais estão perdendo sua eficácia no tratamento de infecções causadas por esses organismos. Nesse cenário, novos antimicrobianos, como os cetolídeos, estão emergindo. Eles representam uma nova geração da família dos macrolídeos, na qual o grupo 3-ceto substitui L-cladinose no anel de lactona. Cetolídeos mostraram-se mais ativos que outros macrolídeos contra várias bactérias gram-positivas, como Enterococcus sp. e Streptococcus sp. No entanto, algumas linhagens de Staphylococcus aureus resistentes à meticilina e à eritromicina parecem ser resistentes aos cetolídeos, como mutações estruturais no local de união do cetolídeos ao ribossomo, a existência de bombas de expulsão ativa, e a presença de enzimas inativantes. Algumas linhagens que apresentam o gene erm B ativo, como Streptococcus pyogenes, apresentam resistência aos cetolídeos.

The increase of multidrug resistance in some strains of microorganisms has beendocumented all over the world. Consequently, the current oral antibiotics arelosing their efficacy in the treatment of infections caused by these organisms. Inthis scenario, new antimicrobials, like ketolides, have emerged. They represent anew generation of the macrolides family, in which the 3-keto group replaces theL-cladinose in the lactone ring. Ketolides have shown to be more active thanother macrolides against many Gram-positive bacteria, like Enterococcus sp. andStreptococcus sp. However, some methicilin and erythromycin resistant strains ofStaphylococcus aureus seem to be resistant to ketolides. Some resistancemechanisms to ketolides have been identified, such as: the structural mutationsin binding sites of ketolides to ribosome; the existence of active efflux pump; andthe presence of inactivating enzymes. Some strains with the active gene erm B,such as the Streptococcus pyogenes, also present resistance to ketolides.