الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 64 |  |  |
| | | from | 64 | | |
Abstract
Linezolid is antibiotic belonging to oxazolidinones group. It acts by protein synthesis inhibition and has clinical utility in the treatment of infections caused by resistant aerobic Gram-positive bacteria (as methicillin- resistant S. aureus (MRSA), Vancomycin Resistant Enterococci (VRE), and mycobacterial infections). LZD inhibits bacterial protein synthesis by binding to residues within the 23S ribosomal RNA of the 50S large subunit of bacterial ribosomes. Linezolid induced lactic acidosis is currently a documented adverse event associated with Linezolid treatment. The underlying mechanism may be related to mitochondrial dysfunction. LZD binds to mammalian ribosomes, leading to decrease in the activity of respiratory chain complexes containing mitochondrial DNA-encoded subunits and a decrease in the amount of protein of these complexes due to obvious similarities between bacterial ribosomes and mammalian cytoplasmic ribosomes.
The current study was conducted to evaluate the incidence of linezolid induced lactic acidosis in post GIT-operative patients. The study was carried on 150 patients admitted to ICU after gastro intestinal tract surgery. Patients were divided into two groups: those who used LZD and those who used vancomycin with 75 patients in each group. Patients with other risk factors for lactic acidosis were excluded from the study.
The results of arterial blood gases at day 0 before administration of drug, and daily after drug administration were recorded from patients’ charts. Daily hemodynamic measurements (blood pressure, pulse rate and temperature), fluid balance, urine output and CVP were also recorded daily.
Results revealed that, there was no statistically significant differences between the two groups as regards age, gender and comorbidities. Vital signs (including SBP, DBP, temperature and heart rate), CVP, UOP, fluid balance and basic initial biochemistry (including Na+, K+, HCO3-, lactate and pH) were comparable between LZD and VAN groups (all p >0.05). The mean duration of antibiotics use was statistically significantly shorter in the LZD group compared to the VAN group (p=0.009).
The incidence of lactic acidosis was statistically significantly higher in patients on LZD therapy than in those on VAN therapy (13.3% vs. 1.3 %, respectively, p=0.005). The mortality rate after antibiotic administration was higher (but doesn’t reach statistical significance) in patients on LZD therapy compared to those on VAN therapy (25.3% vs. 17.3 %, respectively, p=0.232). ‘Definite’ lactic acidosis occurred in three cases (4.0%) in LZD group, while none of the patients in the VAN group developed definite lactic acidosis However, this difference did not reach statistical significance (p=0.245). ‘Probable’ lactic acidosis occurred in seven cases (9.3%) in LZD group vs. one case (1.3%) in VAN group, which was statistically significant result (p=0.029). Definite lactic acidosis was defined as a serum pH of < 7.25 and serum lactate 4 mmol/L. Probable lactic acidosis was defined as lactic acid above 4 mmol/L or acidosis of below pH 7.25.
According to the Univariate Logistic regression analysis patients on LZD therapy were statistically significance more likely to have lactic acidosis than patients on VAN therapy by approximately 11 times (crude OR=11.385; 95% C. I=1.419-91.352; p=0.022), while age, gender, presence of comorbidity, duration, and mean fluid balance after drug intake were not statistically significance associated with a change in the probability of developing lactic acidosis. However, when these factors were entered together into a multivariate model, increase in mean fluid balance was statistically significance associated with reduced likelihood of developing lactic acidosis (adjusted OR=0.998, 95% C.I.= 0.996 - 1.000, p=0.047).
Conclusion, based on the results obtained by this study on post GIT -operative patients, we founded an increased incidence of LZD induced lactic acidosis that did not reach statistical significance. so LZD is not associated with significant higher incidence of lactic acidosis in comparison to vancomycin.