Acinetobacter baumannii: assessing susceptibility patterns, management practices, and mortality predictors in a tertiary teaching hospital in Lebanon.

BACKGROUND: Acinetobacter baumannii is a major nosocomial pathogen capable of causing life-threatening infections. This bacterium is highly resistant to antibiotics and associated with high mortality rates. Therefore, this study aimed to evaluate A. baumannii's susceptibility patterns to antimicrobials, assess the appropriateness of the initiated antimicrobial therapy, determine the mortality rate, and identify predictors associated with mortality. METHODS: A retrospective observational study was conducted among patients infected with A. baumannii at a university hospital in Lebanon through the revision of medical records. Kaplan-Meier survival analysis and log-rank tests were used to analyze time-to-mortality. Binary logistic regression was performed to identify predictors of mortality. RESULTS: The records of 188 patients were screened, and 111 patients with A. baumannii infection were enrolled. Almost all isolates were resistant to carbapenem, and 43% of the isolates were extensively-drug resistant. Almost half of the patients received initial inappropriate antimicrobial therapy (n = 50, 45.1%). The 30-day mortality rate associated with A. baumannii infection was 71.2% (79/111). The time to mortality in patients who received inappropriate antimicrobial therapy (5.70 ± 1.07 days) was significantly shorter than in those who received appropriate antimicrobial therapy (12.43 ± 1.01 days, P < 0.01). Binary logistic regression revealed that inappropriate antimicrobial therapy (adjusted odds ratio [AOR] = 16.22, 95% CI 2.68-9.97, P = 0.002), mechanical ventilation (AOR = 14.72, 95% CI 3.27-6.61, P < 0.001), and thrombocytopenia (AOR = 8.82, 95% CI 1.12-9.75, P = 0.003) were more likely associated with mortality. CONCLUSIONS: A. baumannii exhibits an alarming mortality rate among infected patients. Thrombocytopenia, mechanical ventilation, and inappropriate antibiotic administration are associated with mortality in patients infected with A. baumannii. The prompt initiation of appropriate antimicrobial therapy, infection control measures, and effective stewardship program are crucial to reduce the incidence of A. baumannii and improve the treatment outcomes.

Cigarette smoke interacts with amiodarone toxicity in Saccharomyces cerevisiae.

Amiodarone (AMD) is an antiarrhythmic drug prescribed to treat ventricular tachycardia and fibrillation. However, it causes an unpredictable toxicity (idiosyncratic), which may depend on co-exposure to pollutants. AMD toxicity involves calcium homeostasis alteration and oxidative stress, which are also affected by cigarette smoke (CS). We investigated the interaction of CS-condensate (CSC), phenanthrene, and benzo(a)pyrene with AMD toxicity on Saccharomyces cerevisiae. AMD toxicity was reduced by CSC or phenanthrene. Benzo(a)pyrene mildly decreased AMD toxicity on the wild-type strain, but not on the catalase-CTT1 mutant. This latter and other mutants in glucose receptor-GPR1 or calcium transporter-PMR1 showed lower antagonistic effect to AMD by CSC or phenanthrene relative to the wild type, suggesting roles of oxidative stress, calcium homeostasis, and hexose-sensing in this interaction.

Dose-dependent interaction of two heavy metals with amiodarone toxicity in Saccharomyces cerevisiae.

Amiodarone (AMD) is an antiarrhythmic drug that induces idiosyncratic toxicity. Environmental pollutants, including heavy metals, could interact with its toxicity by affecting pharmacokinetics and pharmacodynamics. Other levels of interaction could exist in yeast, such as oxidative stress and the general stress response. In this study, we investigated the interaction of mercury chloride (HgCl2) and cadmium chloride (CdCl2) with AMD toxicity on Saccharomyces cerevisiae. Interaction type - synergistic, additive, or antagonistic - was determined by median drug effect analysis using "CompuSyn". HgCl2 potentiated AMD toxicity at high doses (≥ 71.4 µm, which yielded more than 60% inhibition). CdCl2 acted similarly at high doses (≥ 57.9 µm). An antagonistic effect appeared at lower doses with both heavy metals (≤ 49.4 µm for HgCl2 and AMD; ≤ 18.9 µm for CdCl2 and AMD). The threshold concentrations (HgCl2 or CdCl2 combined with AMD) that switched the interaction from antagonistic to additive, and then to synergistic, were decreased in the yeast strain mutant in catalase (CTT1), suggesting an important role for this enzyme. Moreover, mutation of the nutrient sensing receptor gene GPR1 caused the synergistic interaction of CdCl2, but not HgCl2, with AMD to occur at the lowest tested concentrations (1.2 µm). The reverse was obtained with the mutant strain in calcium-manganese transporter gene PMR1, where the synergistic interaction of HgCl2 with AMD occurred at concentrations (20.7 µm) lower than that of the wild type (71.4 µm). These results demonstrated a dose-dependent interaction between the two heavy metals with AMD toxicity, and the involvement of oxidative stress, calcium homeostasis, and nutrient sensing in the observed interaction.