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ANTIMICROBIAL RESISTANCEAMONG INTENSIVE CARE UNIT PATIENTS IN A TERTIARY CARE HOSPITAL OF BANGLADESH

Background: Antimicrobial resistance is a growing concern specially among the critically ill patients who are often treated by multiple antibiotics. But, the data regarding the pattern of antimicrobial resistance in this population are often insufficient. Objective: To observe the pattern of antimicrobial resistance among the patients admitted into the intensive care unit (ICU). Methodology: This prospective observational study was carried out in the ICU of a tertiary care hospital of Bangladesh over 6 months. Samples of blood, urine, tracheal aspirate, wound swab and pus were obtained from the patients, cultured and analyzed. Results: Among 100 subjects, the most common primary diagnoses were aspiration pneumonia (29%) and urinary tract infection (UTI) (24%). Out of 315 samples, microorganisms were isolated from 125 samples (39.68%). The most common sample yielding positive culture was tracheal aspirate (67.2%), and the most frequently isolated microorganisms were Pseudomonas spp. (35%), Escherichia coli (28%), Acinetobacterspp. (24%) andKlebsiellaspp. (18%). Acinetobacterspp., Pseudomonasspp. and Klebsiellaspp.were the commonest resistant organisms. Overall prevalence of resistance to antibiotics were: ceftriaxone 72%, ceftazidime 78.4%, ciprofloxacin 81.6%, gentamicin 84%, meropenem 49.6% andnetilmicin 39.2%. Meropenem was the most sensitive antibiotic against Klebsiellaspp.(66.67%) but Acinetobacterspp.was still resistant to meropenem and amikacin but sensitive to cotrimoxazole (66.67%). Multidrug resistant Pseudomonas, Acinetobacter and, Klebsiella species were found; piperacillin-tazobactam combination showed <40% resistance against them. No single antibiotic showed good efficacy against Acinetobacterspp. Conclusion: The prevalence of antibiotic resistance is high among the ICU patients, and the majority of the isolated organisms are resistant to conventional antibiotics.


Introduction
The intensive care unit (ICU) is often called the epicenter of infection due to its extremely vulnerable population. The risk of infection increasesbecause of multiple procedures and use of invasive devices e.g., intubation, mechanical ventilation, vascular access, central venous lines distorting the integrity of protective barriers. In addition, several drugs are often administered, which predispose to infections. For example sedatives, muscle relaxants precipitate pneumonia by reducing cough and swallow reflexes or stress ulcer prophylaxis predispose to infection by distorting the normal nonpathogenic bacterial flora. 1 Consequently, the ICU population has one of the highest occurrence rates of nosocomial infections (20-30% of all ICU-admissions) 2,3 , leading to an enormous impact on morbidity, hospital costs, and often, survival. [4][5][6] According to the Extended Prevalence of Infection in Intensive Care (EPIC) II 1-day prospective point-prevalence study in 1,265 participating ICUs in 75 countries worldwide, 51% of the 12,796 patients were considered infected, although no subdivision was made for hospitalacquired infections. 7 The patients in the ICU have a 5-to7-fold higher risk of nosocomial infection compared with the other patients due to underlying illness, suppressed immune systems and frequent use of invasive devices, exposure to broad spectrum antibiotics and the colonization of resistant microorganisms. Suspected infection may be pneumonia, meningitis, intra-abdominal infection, urinary tract infection and catheter-related infections. 8 Along with the problem of nosocomial infection, the ongoing emergence of resistance in the community and hospital is considered a major threat for public health. Due to the specific risk profile of its residents, the ICU is deemed the epicenter of resistance development, as well as, has even been described as a factory for creating, disseminating, and amplifying antimicrobial resistance. 9 Both infection and multidrug resistance (MDR) result in a considerable clinical and economic burden. As such, the presence of MDR boosts the deleterious impact of nosocomial infection. 10 Due to the specific risk of infection, the additional cost of MDR in hospitalized patients with infections has been estimated at $6,000 to $30,000 per patient. 11 This burden of resistance, however, is probably more due to higher rate of inappropriate empiric antimicrobial treatment associated with infections caused by MDR pathogens than with the virulence of particular MDR strains. 12 In a study in an Indian ICU, the most common organisms were Acinetobacter spp., Escherichia coli, Klebsiellaspp., Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pyogenes. 13 But in a European ICU, Staphylococcus aureus was found as the most frequently isolated organism (30.1%), followed by Pseudomonas aeruginosa (28.7%), Coagulase-negative Staphylococcus (19.1%) and Yeast (17.1%) 14 . In almost all cases, there is a need to initiate empirical antimicrobial treatment before obtaining the microbial culture results, but the situation is further complicated during the past decades, a shift in the MDR dilemma has been noted from gram-positive to gram-negative bacteria, especially due to the scarceness of new antimicrobial agents activeagainst resistant gramnegative microorganisms 15 . Among gram-positive organisms, the Staphylococcusaureus, and vancomycin-resistant enterococci are of great concern 15,16 . In gram-negative bacteria, the resistance is mainly due to the rapid increase of extendedspectrum beta-lactamases (ESBLs) in Klebsiella pneumonia, Escherichia coli, and Proteus mirabilis; high level third-generation cephalosporin beta-lactamase resistance among Enterobacter spp. AndCitrobacter spp., and MDR in Pseudomonas aeruginosa, Acinetobacterspp., and Stenotrophomonas maltophilia 16 . Several other types of infections become more difficult to treat like anaerobicClostridium difficile, and fungal species. Infections with resistant strains of microorganisms in the ICUs lead to increased mortality and cost. 17 All these major reports indicate the need for obtaining data on resistant strains in the ICU along with the susceptibility pattern, to help in revising antibiotic policy and guiding clinicians for the better management of patients. Prevalent flora and antimicrobial resistance pattern may vary from region to region depending upon the predominant antibiotic use in that locality. Standard treatment guidelines of different microbes in ICUs are not sufficient for the purpose. Therefore, the present study was designed to determine the pattern of antimicrobial resistance among the ICU patients.

Methodology
This observational study was carried out inthe ICU of Dhaka Medical College Hospital, Dhaka, Bangladesh in 2015 over a period of 6 months.The objective was to determine the antibiotic resistance pattern among the adult ICU patients. The patients of either sex ageing 18 years or more suffering from various medical conditions and being treated with broad-spectrum antibiotics were included. Samples of blood, urine, sputum/tracheal aspirate and pus/wound swabs were collected from consecutive patients. The collected samples were cultured in standard culture media for isolation of potential pathogens following standard methods. For each isolate, antibiotic susceptibility was performed by disc diffusion method. Isolates showing sensitivity to all antibiotics, isolates from repeat culture of previously recruited patients and isolate identified as commensals, colonization or contaminants were excluded. Isolates with intermediate susceptibility were considered resistant.
The study protocol was approved by the Bangladesh College of Physicians and Surgeons (BCPS), and the Ethical Review Committee of Dhaka Medical College.Informed written consent was obtained from the patients or their attendants.
For the study, data were collected in a pre-designed structured data collection form, analyzed using SPSS for windows version 16.0.

Discussion
This study provides an analysis of epidemiology and microbiology of infections in the ICU patients of DhakaMedical College Hospital. In this study, aspiration pneumonia, and UTI are the predominant infections; these findings are consistent with those of Kumari et al. 18 In recent years, a rising trend of infection by gram negative organisms and increase in their resistance pattern has been observed. 9 Theorganisms that have emerged as most problematic for patients within the ICU include Acinetobacter spp., Klebsiella spp., Pseudomonas spp., andEscherichia coli. 19  Our study has got some important limitations. The sample size is relatively small, and is a single-centre study. So, the findings may not be generalizable. Anaerobic cultures and cultures suitable for isolating the fastidious organisms were not done. Some antibiotics which are less commonly used but having increasing importance in concurrent patient management might have been omitted from the sensitivity study. Also, the disc diffusion method, not the broth dilution method was used to determine the antibiotic sensitivity, accordingly, information regarding the minimum inhibitory concentration of antibiotics is lacking.

Conclusion
Antibiotic resistance is common among the ICU patients. Gram negative organisms constitute a major portion of the antibiotic resistant organisms. Commonly isolated organisms are often resistant to the commonly available antibiotics. When possible, antibiotics selection should be used based on the results of culture and sensitivity testing. For empirical use, third generation cephalosporins or carbapenems (e.g., meropenem) may be the optimal initial choice. Colomycin (colistin) and piperacillintazobactamcombination should be kept preserved for further use. Antibiotic usage guidelines may be formulated according to the resistance pattern in individual institutions.These should be based on further, well-designed studies. Rational use of antibiotic is the key to combat Antimicrobial Resistance.

Conflict of interest:
We have no conflict of interest.