Is ranitidine necessary as premedication for regimens containing paclitaxel? A non-inferiority study.

BACKGROUND: Histamine type-2-receptor antagonist drugs (H2-antagonists) have been used as standard treatment to prevent hypersensitivity reactions (HRs) in paclitaxel-containing regimens, however, their use has been strongly questioned. Ranitidine has been the most widely used H2-antagonist. Therefore, especially after its withdrawal from the market, the objective of this study is to determine the impact of its elimination from premedication on HR incidence. METHODS: A cohort, multicenter, observational, prospective, and non-inferiority study, including paclitaxel-naïve cancer patients, designed to determine the incidence of HRs of any grade associated with paclitaxel administration and analyze non-inferiority against the incidence estimated in the literature (20%), with 5% as the maximum difference (Δ). Patients with a solid neoplasm of any type/stage, who initiated treatment with paclitaxel without H2-antagonists in the premedication regimen were enrolled. RESULTS: A total of 441 patients were included, of whom 50 presented 54 HRs of any grade. The cumulative incidence was 11.3% (95%CI 8.5-14.7), thus fulfilling the hypothesis of non-inferiority. Of the overall HRs detected, 15 were grade ≥ 3 with a cumulative incidence of 3.4% (95%CI 1.9-5.5). CONCLUSIONS: This study demonstrates that the elimination of ranitidine from paclitaxel premedication schedules is non-inferior in the development of HRs of any grade compared to the administration of H2-antagonists.

Caracterización del proceso de fermentación y del efecto de inhibición de Lactobacillus lactis en Staphylococcus aureus y Staphylococcus epidermidis / Characterization of the Fermentation Process and the Inhibition Effect of Lactobacillus lactis in Staphylococcus aureus and Staphylococcus epidermidis / Caracterização do processo de fermentação e do efeito de inibição de Lactobacillus lactis em Staphylococcus aureus e Staphylococcus epidermidis

Se evaluó el proceso fermentativo e inhibición in vitro de L. lactis en Staphylococcus aureus y Staphylococcus epidermidis; así mismo, el crecimiento de L. lactis a tres pH (2,5, 4,5 y 7), sales biliares (0,5, 1 y 2 %), bilis bovina (1 y 1,2 %) y dos temperaturas (38 y 45 °C). Se determinaron péptidos y ácidos orgánicos en sobrenadante de L. lactis por HPLC. Se hizo cinética de fermentación en la que se evaluó: pH, azúcar total, proteína y ácido láctico. Se realizó antibiograma de dicloxacilina, cefepime, penicilina y cefalotina. Se definió la inhibición de L. lactis y su sobrenadante en cepas patógenas. El mejor crecimiento fue a pH de 2,5 (3 x 10(12) UFC/ml); de 1 x 10(10) y 4 x 10(9) UFC/ml para 0,5 % de sales biliares y 1,2 % de bilis bovina, respectivamente; de 3,5 x 10(13) y 3,4 x 10(13) UFC/ml para 38 y 45 °C, respectivamente. El HPLC determinó los péptidos VAR-TIR-VAR y ácido láctico (83,11 %). La cinética de fermentación determinó la fase exponencial a 14:24 h con un valor 77 x 10(10) UFC/ml, valores de pH de 4,284, azúcar 2,33 mg/ml, proteína 1,44 mg/ml y acidez de 0,79 %. Se encontró que S. aureus y S. epidermidis fueron sensibles a todos los antibióticos. Las bacterias patógenas fueron resistentes a la cepa láctica, pero S. epidermidis fue sensible al sobrenadante de L. lactis. Se concluye que Lactobacillus lactis mostró adecuada capacidad de crecimiento, buenos parámetros de fermentación y efecto inhibitorio en cepas de S. aureus y S. epidermidis en condiciones in vitro.

The fermentative process and in vitro inhibition of L. lactis in Staphylococcus aureus and Staphylococcus epidermidis were assessed. The growth of L. lactis at three pH (2.5, 4.5 and 7), bile salts (0.5, 1 and 2 %), bovine bile (1 and 1.2 %) and two temperatures (38 and 45 °C) were evaluated. Peptides and organic acids in supernatant of L. lactis by HPLC were determined. Fermentation kinetics was carried out, evaluating: pH, total sugar, protein and lactic acid. An antibiogram of dicloxacilin, cefepime, penilicin and cefalotin was made. The inhibition of L. lactis and its supernatant were defined in pathogenic strains. The best growth was at a pH of 2.5 (3 x 10(12) UFC/ml); of 1 x 10(10) and 4 x 10(9) UFC/ml for 0.5 % of bile salts and 1.2 % of bovine bile, respectively; of 3.5 x 10(13) and 3.4 x 10(13) UFC/ml for 38 and 45 °C, respectively. The HPLC determined the peptides VAR-TIR-VAR and lactic acid (83.11 %). The fermentation kinetics determined the exponential phase at 14:24 h with a value of 77 x 10(10) UFC/ml, pH values of 4.284, 2.33 mg/ml sugar, 1.44 mg/ml protein and acidity of 0.79 %. It was found that S. aureus and S. epidermidis were sensitive to all antibiotics. The pathogenic bacteria were resistant to the lactic strain, but S. epidermidis was sensitive to the supernatant of L. lactis. The conclusion is that Lactobacillus lactis showed adequate growth capacity, good fermentation parameters and inhibitory effect in strains of S. aureus and S. epidermidis in in vitro conditions.

Avaliou-se o processo fermentativo e a inibição in vitro de L. lactis em Staphylococcus aureus e Staphylococcus epidermidis. Avaliou-se o crescimento de L. lactis a três pH (2,5, 4,5 e 7), sais biliares (0,5, 1 e 2 %), bílis bovina (1 e 1,2 %) e duas temperaturas (38 e 45 °C). Determinaram-se peptídeos e ácidos orgânicos em sobrenadante de L. lactis por HPLC. Fez-se cinética de fermentação, avaliando: pH, açúcar total, proteína e ácido láctico. Realizou-se antibiograma de dicloxacilina, cefepime, penicilina e cefalotina. Definiu-se a inibição de L. lactis e seu sobrenadante em cepas patógenas. o melhor crescimento foi a pH de 2,5 (3 x 10(12) UFC/ ml); de 1 x 10(10) e 4 x 10(9) UFC/ml para 0,5 % de sais biliares e 1,2 % de bílis bovina, respectivamente; de 3,5 x 10(13) e 3,4 x 10(13) UFC/ml para 38 e 45 °C, respectivamente. O HPLC determinou os peptídeos VAR-TIR-VAR e ácido láctico (83,11 %). A cinética de fermentação determinou a fase exponencial a 14h: 24m com um valor 77 x 10(10) UFC/ml, valores de pH de 4,284, açúcar 2,33 mg/ml, proteína 1,44 mg/ml e acidez de 0,79 %. Constatou-se que S. aureus e S. epidermidis foram sensíveis a todos os antibióticos. As bactérias patógenas foram resistentes à cepa láctica, mas S. epidermidis foi sensível ao sobrenadante de L. lactis. Conclui-se que Lactobacillus lactis mostrou uma adequada capacidade de crescimento, bons parâmetros de fermentação e efeito inibitório em cepas de S. aureus e S. epidermidis em condições in vitro.