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OBJECTIVES: The objective of this review was to compare the effectiveness of Colistin monotherapy and combination therapy for the treatment of multidrug-resistant gram-negative bacterial infections. DATA SOURCES: PubMed, Cochrane Library. STUDY ELIGIBILITY INTERVENTIONS AND EXCLUSIONS: In this systematic review, we included all retrospective and prospective studies and randomized controlled trials (RCTs) that compared intravenous polymyxin monotherapy and combination therapy with any other antibiotic for treating multidrug-resistant infections. Studies using inhaled polymyxins with 5 or less than 5 patients were excluded. The primary outcome was 30-day all-cause mortality and if not reported at day 30 we extracted and documented the closest time point. Both crude outcome rates and adjusted effect estimates were extracted for mortality. STUDY APPRAISAL DATA EXTRACTION AND SYNTHESIS: Search string used was "(Colistin OR polymyxin) AND (Enterobacteriaceae OR Klebsiella OR Acinetobacter OR Escherichia coli OR Pseudomonas) AND (random OR prospective OR retrospective OR cohort OR observational OR blind)." Thirty-nine studies were included in our analysis; out of which 6 RCTs were included and 9 studies used carbapenem as the adjunctive antibiotic. Each study was screened and reviewed for eligibility independently by two authors and data extrapolated on an Excel sheet. RESULTS: The meta-analysis of polymyxin monotherapy vs. combination therapy in multidrug-resistant infections yielded an odds ratio (OR) of 0.81 (95% confidence interval [CI]: 0.65-1.01) with minimal heterogeneity (I 2 = 40%), whereas pooled analysis of this comparison in studies that included carbapenem as combination therapy yielded an OR of 0.64 (CI: 0.40-1.03; I 2 = 62%). Likewise, the pooled analysis of the RCTs yielded an OR of 0.82 (95% CI: 0.58-1.16, I 2 = 22%). All these showed no statistical significance. However, it was seen that polymyxin combination therapy was more effective in multidrug-resistant infections compared to polymyxin monotherapy. The effectiveness was more glaring when carbapenems were used as the combination drug instead of any other antibiotic and more so in many in vitro studies that used polymyxin combination therapy. CONCLUSION: Although statistically insignificant, it would be prudent to use polymyxin combination therapy to treat multidrug-resistant gram-negative bacilli (GNB) infection over monotherapy with preference to use carbapenem as the adjunct alongside polymyxins. HOW TO CITE THIS ARTICLE: Samal S, Mishra SB, Patra SK, Rath A, Dash A, Nayak B, et al. Polymyxin Monotherapy vs. Combination Therapy for the Treatment of Multidrug-resistant Infections: A Systematic Review and Meta-analysis. Indian J Crit Care Med 2021;25(2):199-206.
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INTRODUCTION: High utilization of antimicrobial agent (AMA) and inappropriate usage in an intensive care unit (ICU) intensifies resistant organism, morbidity, mortality, and treatment cost. Prescription audit and active feedback are a proven method to check the irrational prescription. To analyze and compare the utilization of drugs, the World Health Organization (WHO) proposed daily defined dose (DDD)/100 patient days and days of therapy (DOT)/100 patient days to measure utilization of AMAs. Data of AMAs utilization are required for planning an antibiotic policy and for follow-up of intervention strategies. MATERIALS AND METHODS: A prospective observational study was conducted for 1 year from July 2018 to June 2019 and the data obtained from ICU of a tertiary care hospital. The demographic data, the disease data, and the utilization of different classes of AMAs [WHO-Anatomical Therapeutic Chemical (ATC) classification] as well as their cost were recorded. Total number of patient days, DDD, DDD/100 patient days, and DOT/100 patient days were calculated as proposed by the WHO. Statistical analysis was performed using statistical software SPSS version 25.0. The descriptive analysis was performed using summary statistics median [interquartile range (IQR)]. RESULTS: A total 939 patients were included, out of them 332 (35.4%) were female. The median age of the total patients was 58 (45-70). The median length of stay in ICU was 3 days. Mortality rate during our study period was 38.6%. The highly utilized AMAs in our study was ceftriaxone (36.95 DDD/100 patient days) followed by piperacillin/tazobactam (31.57), meropenem (26.4), doxycycline (21.53), and polymyxin B (21.38). The association between APACHE II and SOFA score with use of restricted antibiotics found to be statistical significant (p value 0.018 and 0.000, respectively). The cost of antibiotics per patient and patient days were $449.97 and $93.77, respectively, while median value of total cost was $2,343.26. CONCLUSION: Ceftriaxone was the highest utilized AMA. The risk of receiving restricted antibiotics intensified with increasing prevalence of multidrug resistance bacteria and associated comorbidities. High treatment cost is responsible for higher utilization of restricted antibiotics in ICU. HOW TO CITE THIS ARTICLE: Patra SK, Mishra SB, Rath A, Samal S, Iqbal SN. Study of Antimicrobial Utilization and Cost of Therapy in Medicine Intensive Care Unit of a Tertiary Care Hospital in Eastern India. Indian J Crit Care Med 2020;24(10):938-942.
