Antibiotic resistance rates among bacterial isolates from infected patients of intensive care unit over the period ( 2011-2016 ) in Bursa , Turkey

Background: The aims of this study were to evaluate the microbiological data for effective infection control and specific antimicrobial stewardship, and to report the epidemiology of intensive care unit (ICU)-acquired infections and the local antimicrobial resistance of pathogens Methods: Data were collected between January 2011 and October 2016 from the cardiology and cardiovascular surgery patients. The identification and antimicrobial susceptibility analyses of clinical pathogenic isolates were determined by the automatic device system. Results: Klebsiella pneumoniae was detected increasingly and significantly (p=0.048) resistant to imipenem (IMP). Acinetobacter baumanii was found increasingly and significantly (p=0.045, p=0.030, p=0.006, p=0.027) resistant to amikacin (AN), gentamicin (GN), trimethoprimsulfamethoxazole (SXT) and tetracycline (TE), respectively. There was a significantly decrease in the resistant rates of IMP, piperacillin-tazobactam (TPZ), meropenem (MEM) and ciprofloxacin (CIP) for Pseudomonas spp. (p=0.048). All gram-negative bacteria isolates showed significantly increasing resistance rates to cefepime (CEP) (p=0.015). Also, all gram-positive bacteria demonstrated significantly decreasing resistance rates to teicoplanin (TEC) (p=0.034). Conclusion: This study suggets that inadequacy of infection control measures such as hand hygiene and patient isolation may have contributed to increasing the rates of carbapenem-resistant K. pnemoniae (CR-KP) isolates in recent years. Antibiotic resistance rates among bacterial isolates from infected patients of intensive care unit over the period (2011-2016) in Bursa, Turkey Sanem Karadag Gecgel1, Necmiye Demircan2 1 Departments of Microbiology and Clinical Microbiology, University of Health Sciences, Yuksek Ihtisas Training and Research Hospital, Bursa, Turkey. 2 Departments of Infectious Diseases and Clinical Microbiology, University of Health Sciences, Yuksek Ihtisas Training and Research Hospital, Bursa, Turkey. Contact information: Sanem Karadag Gecgel.  sanemkaradag@yahoo.com


Introduction
The antimicrobial stewardship in intensive care unit (ICU) is highly important measurement to control antimicrobial resistance in most hospital.There are two main problems to this issue.Inappropriate usage of antibiotic therapy and poor concordance to the infection control policy.Both can lead to the occurrence of resistant pathogens by various molecular mechanisms such as mutation, gene transfer and selection of the resistant strains [1,2].Recently, most ICU-acquired infection are due to pathogens like methicillin-resistant Staphylococci, multidrug-resistant Pseudomonas aeruginosa and Acinetobacter species.Additionaly, carbapenem resistant K. pneumoniae (CR-KP) are detected more frequently in the recent years worldwide [3][4][5].Therefore, awareness about the current local epidemiology and antimicrobial susceptibility of bacterial isolates is an important factor in prescribing true empiric antibiothreapy in ICU [6,7].Despite this fact, medical treatment options of multidrug-resistant pathogens are limited [8].
The aim of this study is to report the epidemiology of ICU-acquired infections and the local antimicrobial resistance of microorganism isolates over a 6-year period.

Patients
Data were collected between January 2011-October 2016, retrospectively, from admitted adult cardiology and cardiovascular surgery (CVS) patients at Bursa Yuksek Ihtisas Training and Research Hospital, Turkey.This hospital is a tertiary care hospital serving a 3-million population region.ICU-acquired infections were diagnosed after 48 hours of ICU admission according to Centers for Disease Control and Prevention guidelines [9].Piperacillin-tazobactam, imipenem, meropenem antibiotics were frequently used in treatment of ICU-acquired infection caused by gram-negative bacteria and vancomycin, linezolid, daptomycin antibiotics were frequently used in treatment of ICU-acquired infection caused by gram-positive bacteria.

Statistical analyses
Data were analyzed by SPSS program version 21.0 with Fisher's exact chi-square test and Pearson chisquare test.Differences were accepted statistically significant at p<0.05.

Results
The distribution of recovered pathogens in ICUs over a 6-year period is demonstrated in Table 1.Acinetobacter baumanii and coagulase-negative Staphylococcus (CNS) were the most common pathogens recovered.The distribution of resistance rates of recoverd pathogens through three-year periods was determined.Antibiotic resistance rates of microorganisms between 2011-2012-2013 and 2014-2015-2016 were combined and the total resistance rates in both periods were compared.A comparison between resistance rates in gram-negative pathogens during a 6-year period is demonstrated in Table 2, 3.A second comparison between resistance rates in gram-positive bacteria over a 6-year period is shown in Table 4

Discussion
Hospitalization in ICU is an important risk factor to acquire infection with carbapenem resistant K. pneumoniae (CR-KP), because of usage of many invasive devices such as urinary catheters, central venous catheters, mechanical ventilation and the possibility of transmission infection between patients.Additionaly, broad-spectrum antimicrobial drugs such as carbapenems are frequently used in ICUs and these drugs are known to contribute for emergence of CR-KP [10][11][12].In our study, K. pneumoniae was detected increasingly and significantly resistant to imipenem, because our tertiary care hospital admitted cardiology and cardiovascular surgery patients (CVS) from referral hospitals to our ICUs.We suspect that these patients have contributed for spread of CR-KP in our ICUs.In addition, the insufficient isolation of infected patients and inadequate ventilation in our ICUs have increased rates of infection and isolation of resistant pathogens among patients during the two compared periods (2014-2016 versus 2011-2013) as shown in Table 2-4.Also, similar increasing rates were observed in relation to use of urinary catheterization and the length period of usage it.Both these two factors were most probably increased infection with CR-KP in our intensive care units.
In our study, multidrug-resistant A. baumanii isolates were the most common cause of infections among our patients in ICUs as it has been recoded worldwide [13][14][15][16].The increase in antibiotic resistance rates among A. baumanii isolates was significant (Table 2-3).It has been reported that carbapenem-resistant Acinetobacter isolates can be increased rapidly and become a significant problem in intensive care unit patients.Additionaly, rates of resistant Acinetobacter strains are observed to be higher in countries where carbapenems are intensely used [17,18].
Studies have also shown an increasing carbapenem-resistance in P. aeruginosa isolates from ICU-acquired infections [19][20][21].In our study, there was a significantly decrease in the resistant rates of Pseudomonas spp.and P. aeruginosa to IMP, TPZ, MEM and CIP, but both were not istatistically significant.In addition, decreased rates of resistance to IMP and MEM were detected in all gram-negative pathogens and these were not statistically significant (Table 2-3).The reason for this decrease may be due the fact that in our hospital, our physicians used less empirical treatment in ICU-acquired infections and they are preferring to apply mostly treatment based on culture results.This approach may has led to reduce the occcurrence of carbapenem-resistant pathogens in our hospital.It is also impotant to note that our hospital's microbiology laboratory provided 24-hour service, and offer a rapid assessment of positive blood cultures and the result of gram-staining.
In our hospital, physcians are prefering treatment of gram-positive bacterial infections with vancomycin, daptomycin and linezolid instead of teicoplanin.Despite this treatment approch, there was overall no change in rates of resistant among all gram-positive bacteria to these 3 drugs, but there was statistically significant decreased in resistant to TEC (Table 4).However, various studies have shown that teicoplanin could theoretically represent an acceptable alternative drug, since it has comparable efficacy compared to vancomycin in various disease conditions and excellant bone diffusion [22].Extensive use of teicoplanin in ICU patienst may result in development of increased resistance rates in gramposive bacteria, whereas the usage of vancomycin occasionally during empirical therapy, and according to MIC values were the main reasons for not increasing vancomycin resistance rates in gram-positive bacteria in this study [23][24][25][26].
In conclusion, this study showes that close cooperation between microbiology laboratory and physcians has been associated with decrease in carbapenem and vancomycin resistance rates in pathogens recovered from ICU's patients.

Table 2 .
Comparison of the antimicrobial resistance rates in different gram negative pathogens over two periods(2011-2013 versus 2014-2016).
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