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1.
Eur Rev Med Pharmacol Sci ; 25(2): 1016-1023, 2021 01.
Article in English | MEDLINE | ID: mdl-33577057

ABSTRACT

OBJECTIVE: Colistin is a potent antibiotic which is mainly preferred in the treatment of multidrug-resistant (MDR) gram-negative bacilli. However, due to the increased risk of acute kidney injury following its use, the clinical application is limited. This nephrotoxicity is known to be induced by oxidative stress and related inflammation. In this study on rats, potent antioxidants Dexpanthenol (DEX) and Ascorbic acid (Vit C) have been administered in combination with Colistin to find out whether they would weaken Colistin's nephrotoxic effects. MATERIALS AND METHODS: Inflammation biomarkers were studied with enzyme-linked immunosorbent assay (ELISA) kits, and oxidative stress biomarkers were studied with different photometric methods in blood and tissue samples taken after treatment with DEX and Vit C in rats with colistin nephrotoxicity. In addition, inflammation and necrosis in the kidney tissues were examined pathologically. RESULTS: It has been observed in the serum and tissue samples that DEX and Vit C decrease oxidative stress and inflammation biomarkers, therefore acting as nephroprotective agents. CONCLUSIONS: These compounds have been found to ameliorate the nephrotoxic effects of Colistin, which were demonstrated in the rats treated with Colistin, as well as the combinations.


Subject(s)
Acute Kidney Injury/drug therapy , Ascorbic Acid/pharmacology , Inflammation/drug therapy , Neuroprotective Agents/pharmacology , Pantothenic Acid/analogs & derivatives , Acute Kidney Injury/chemically induced , Acute Kidney Injury/metabolism , Animals , Ascorbic Acid/administration & dosage , Colistin/administration & dosage , Disease Models, Animal , Inflammation/chemically induced , Inflammation/metabolism , Injections, Intraperitoneal , Male , Neuroprotective Agents/administration & dosage , Oxidative Stress/drug effects , Pantothenic Acid/administration & dosage , Pantothenic Acid/pharmacology , Rats , Rats, Sprague-Dawley
2.
Eur J Clin Microbiol Infect Dis ; 33(8): 1311-22, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24532009

ABSTRACT

The purpose of this investigation was to compare the efficacy of colistin-based therapies in extremely drug-resistant Acinetobacter spp. bloodstream infections (XDR-ABSI). A retrospective study was conducted in 27 tertiary-care centers from January 2009 to August 2012. The primary end-point was 14-day survival, and the secondary end-points were clinical and microbiological outcomes. Thirty-six and 214 patients [102 (47.7%): colistin-carbapenem (CC), 69 (32.2%): colistin-sulbactam (CS), and 43 (20.1%: tigecycline): colistin with other agent (CO)] received colistin monotherapy and colistin-based combinations, respectively. Rates of complete response/cure and 14-day survival were relatively higher, and microbiological eradication was significantly higher in the combination group. Also, the in-hospital mortality rate was significantly lower in the combination group. No significant difference was found in the clinical (p = 0.97) and microbiological (p = 0.92) outcomes and 14-day survival rates (p = 0.79) between the three combination groups. Neither the timing of initial effective treatment nor the presence of any concomitant infection was significant between the three groups (p > 0.05) and also for 14-day survival (p > 0.05). Higher Pitt bacteremia score (PBS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Charlson comorbidity index (CCI), and prolonged hospital and intensive care unit (ICU) stay before XDR-ABSI were significant risk factors for 14-day mortality (p = 0.02, p = 0.0001, p = 0.0001, p = 0.02, and p = 0.01, respectively). In the multivariable analysis, PBS, age, and duration of ICU stay were independent risk factors for 14-day mortality (p < 0.0001, p < 0.0001, and p = 0.001, respectively). Colistin-based combination therapy resulted in significantly higher microbiological eradication rates, relatively higher cure and 14-day survival rates, and lower in-hospital mortality compared to colistin monotherapy. CC, CS, and CO combinations for XDR-ABSI did not reveal significant differences with respect to 14-day survival and clinical or microbiological outcome before and after propensity score matching (PSM). PBS, age, and length of ICU stay were independent risk factors for 14-day mortality.


Subject(s)
Acinetobacter Infections/drug therapy , Acinetobacter baumannii/drug effects , Bacteremia/drug therapy , Carbapenems/therapeutic use , Colistin/therapeutic use , Sulbactam/therapeutic use , Acinetobacter baumannii/isolation & purification , Adult , Aged , Carbapenems/pharmacology , Colistin/pharmacology , Drug Resistance, Multiple, Bacterial , Drug Therapy, Combination , Female , Humans , Length of Stay , Male , Microbial Sensitivity Tests , Middle Aged , Retrospective Studies , Risk Factors , Sulbactam/pharmacology , Treatment Outcome
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