Antimicrobial Susceptibility of Acinetobacter baumannii complex Isolated From Different Clinical Samples In A Tertiary Care Hospital

Introduction: Increasing resistance to antimicrobial agents used in the treatment of infections based on Acinetobacter baumannii complex strains has become an important health issue.

Aim: The aim in this study is to determine the antimicrobial resistance ratios in A. baumannii complex strains isolated from the patients staying at our hospital.

Methodology: Antibiotics resistance ratio of 163 A. baumannii complex strains isolated from the samples sent to our laboratory from different clinics between January 2012 and June 2015 were evaluated retrospectively in our study. Identification and antibiograms of A. baumannii complex isolates were determined by automized system VITEK2 (bioMerieux, France).

Result: For A. baumannii complex isolates, a resistance was determined in amikacin (35.2%), cefepime (93.7%), ceftazidime (96.8%), ciprofloxacin (97.3%), colistin (5.5%), gentamicin (77.2%), imipenem (89.1%), levofloxacin (95.2%), meropenem (90.3%), tigecycline (41.3%), netilmicin (19.5%), cefoperazone-sulbactam (79%) and trimethoprim sulfamethoxazole (68.9%) ratio.

Conclusion: As a result, as antibiotics resistance can change in different areas, the susceptibility ratios of this kind of resistant bacteria should be known in situation requiring empirical treatment especially. The antibiotics with highest effect on A. baumannii complex isolates isolated in our study are colistin, netilmicin and amikacin in order. On the other hand, the high resistance ratios to carbapenems and other antibiotics also draw attention.

Keywords: Acinetobacter baumannii complex; Antibiotic; MIC

An Acinetobacter bacterium has become the most commonly isolated factor in hospital infections, especially those in intensive care unit, in recent years [1,2]. Acinetobacter baumannii complex is mostly isolated from clinical samples among Acinetobacter types [3]. Ventilator-associated pneumonia, urinary tract infections, septicaemia and scar infections can be named among the severe nosocomial infection epidemia caused by A. baumannii complex [4,5]. Today, the increasing resistance to the antimicrobial agents used in the treatment of infections caused by A. baumannii complex isolates has become an important health problem as in the whole world [1,6]. As the antibiotic resistance rates change between hospitals, knowing the resistance of bacteria which is a problem in all hospitals is important in determining the antibiotic protocol appropriate for the treatment [7,8]. The aim of this study is to determine the antimicrobial resistance ratios in A. baumannii complex isolates isolated from the patients staying in our hospital and contributing to the studies made on this subject.

Antibiotics resistance ratios of 163 A. baumannii complex isolates isolated from the samples sent from different clinics to Sabuncuoglu Serefeddin Education and Research Hospital Medical Microbiology Laboratory between January 2012 and June 2015 were reviewed retrospectively. The hospital has 465 patients' beds capacity and catchment population of this region is three hundred thousand. This hospital consists of one main building. The samples were sent for culturing and inoculated to sheep blood agar and Eosin Methylene Blue Agar (EMB). At the end of 18-24 hour incubation at 37 °C, isolated microorganisms were identified and antibiograms were determined by automized system VITEK2 (bioMerieux, France).

Amikacin, netilmicin, colistin, gentamicin, trimethoprim-sulfamethoxazole, cefoperazone-sulbactam, meropenem, imipenem, levofloxacin, ciprofloxacin, cefepime and ceftazidime (Mast Diagnostics, Merseyside, UK) resistance rates of A. baumannii complex isolates were explored retrospectively and the results wereinterpreted according to CLSI 2013 standards. No tigecycline interpretative criteria universally accepted for Acinetobacter spp, therefore the Food and Drug Administration approved breakpoints for members of the family Enterobacteriaceae have been used. Pseudomonas aeruginosa ATCC 27853 has been used as control strain in laboratory.

Among 163 A. baumannii complex isolates, 86 (52.7%) were originated from respiratory tract, 45 (27.6%) from blood, 20 (12.3%) from surgical scars and 12 (7.4%) from urinary samples. Samples from which the strains were isolated from are shown in Table 1.

The samples which A. baumannii strains were isolated from were mostly from the samples sent from Intensive Care Units (139 patients 85.2%). The clinical distribution of the samples from which Acinetobacter strains were isolated is shown in Table 2.

The most effective antibiotics were colistin and netilmicin when the strains were evaluated. Their antibiotic resistance ratios were determined as 5.5% and 19.5% in order. Amikacin with a ratio of 35.2% and tigecycline with a resistance ratio of 41.3% followed. Resistance rates to other antibiotics changed between 68.9% and 96.8%. Antibiotic resistance of isolated strains is shown in Table 3.

When we compare year over year, there are some differences of antibiotic resistance especially during the 2012 and 2013. Resistance to cefoperazone-sulbactam, gentamicin, and carbapenems were very high in 2013. Resistance to amikacin, and netilmicin were very high in 2015. Resistance to trimethoprim-sulfamethoxazole was very high in 2012. Ceftazidim, resistance to ciprofloxacin, levofloxacin and cefepime became full resistance after 2012. Resistance to colistin changed from 6.2% to 9% from 2012 to 2015 (Table 3).

Acinetobacter strains which are among the most important nosocomial pathogens survive for a long time by colonization in different environments, on the surfaces of mechanical devices used in hospitals, patients and hospital staff [9]. Hospital infections are mostly observed in intensive care units. Acinetobacter infections are also most common in intensive care units [1]. Ozdem et al. [10] isolated 58.9%, Balci et al. [11] 63% and Dogan et al [12] 66.2% of A. baumannii complex isolates from the patients in intensive care units. Again in this study, A. baumannii complex isolates were isolated mostly from the intensive care unit patients (85.2% from General Intensive Care and Neurology Intensive Care).

There is a difference in the distribution of samples in which Acinetobacter strains were commonly isolated from. Although A. baumannii complex infections are observed in all body parts, they are mostly observed in the respiratory system and scar infections [3,13]. A. baumannii complex isolates were 43% in respiratory system, 24% in scars by Balci et al. [11], 30% in mucus, 29% in scar by Aral et al. [14], 48% in tracheal aspirate samples by Atasoy et al. [15]. Similar to other studies, A. baumannii complex was isolated mostly from respiratory tract samples (52.7%).

It was observed that the isolation of multi resistant strains and gradually increasing antibiotic resistance cause a decrease in empirical treatment options of clinicians on patients hospitalized with A. baumannii complex infection suspicion [16,17]. A. baumannii complex which causes infections with high mortality and is more resistant to many antibiotics [18]. Wide use of high spectrum antibiotics such as ureidopenicillins, fluoroquinolones and third generation cephalosporins resulted in Acinetobacter types being more resistant to antibiotics [19]. In different studies in Turkey, it was observed that quinolones and cephalosporin resistance rates were over 90% [12,20]. In our study the resistance rates were detected as 97.3% in ciprofloxacin, 95.2% in levofloxacin, 96.8% in ceftazidime and 93.7% in cefepime and the results were similar to the results of other recent studies in our country. This result might be construed to mean that neither third-generation cephalosporins nor quinolones appear suitable for A. baumannii complex infections.

Aminoglycosides are the antibiotics commonly used in A. baumannii complex infections. The resistance rates determined were Ozdemir et al.[21] gentamicin 82%, amikacin 76%, netilmicin 25%, Kurtoglu et al.[22] gentamicin 86%, amikacin 52%, İraz et al.[20] gentamicin 54%, amikacin 69%, netilmicin 15%. In our study, the resistance rates determined were gentamicin in 77.2%, amikacin in 35.2% and netilmicin in 19.5%. The most effective aminoglycoside derivative of netilmicin to A. baumannii complex types is antibiotic. Resistance to gentamicin, and was very high in 2013 but resistance to amikacin, and netilmicin were very high in 2015. This is because increasing prevalence of gentamicin resistance physicians used to prefer amikacin and netilmicin more after 2013.

Tigecycline is a tetracycline group glycilcyclin. It inhibits the protein synthesis in ribosome level. It was effective in bacterium including multi medicine resistant Acinetobacter and Pseudomonas strains [23]. Different results were observed in many tigecycline studies. In a study made by Alpat et al. [24] in 2010, no tigecycline resistance was determined and in the studies made in 2011, Ozdem et al.[10] determined tigecycline resistance as 5.5% and Kurtoglu et al.[22] as 16%. Tigecycline resistance was found 41% in our study. Because of high resistance of A. baumannii complex to other antibiotics physician began to use tigecycline from 2013. So tigecycline resistance demonstrated a tendency to increase over years.

With gradually increasing resistance rates against this antibiotic group, carbapenem is the primary antibiotic group which should be preferred in infections caused by Acinetobacter [25,26]. In 2005 Gazi et al. [27] detected meropenem resistance rate as 36.3% and imipenem resistance rate as 40.5% and in a study by Bacakoglu et al.[28] in 2009, imipenem resistance rate was 78%, meropenem resistance rate was 55% and in 2013 Gozutok et al. determined resistance rates in their study as 91% imipenem and meropenem. In this study, imipenem resistance was found 89.1% and meropenem resistance 90.3%. Resistance to carbapenems were very high in 2013. We think that the gradually increasing carbapenem resistance is due to its common use in empirical treatment.

Colistins are the most common polymyxin derivatives used in clinical practice. These antibiotics are effective against many gram-negative bacterium including Acinetobacter types P.aeruginosa, Klebsiella and Enterobacter [30]. While Ozdemir et al. [21] and Gozutok et al. [29] determined no resistance to colistin, Iraz et al. [20] determined a resistance rate of 1% and Dogan et al. [12] a resistance of 1.4%. The colistin resistance was found 5.5% in our study. As colistin was used more commonly but we can emphasize that resistance ratios would increase in time.

These results of resistance to antibiotic show us that we have to be careful when using antibiotics. We have documented that during the 2011-2013 study period the use of a large number of broad spectrum antibiotics used, the infection caused by Acinetobacter baumannii complex has become more serious with resistant to carbapenems. Also we demonstrated that these isolates were not genotypic similarity [31]. One of the limitation of this study is that we did not presented the clinical and demographic data of patients. But other information may help physician to use true antibiotic therapy and take care about the patients isolation.

As a results a high resistance ratio develops against imipenem, levofloxacin, meropenem and gentamicin which are the antibiotics commonly used until recent years for A. baumannii complex, with a resistance ratio increasing constantly in the whole world. The resistance to colistin which had a rare resistance in previous years was 5.5%. This demonstrated that a higher ratio of resistance might develop against colistin in the future. As antibiotic resistance increases, hardships will be experienced in A. baumannii complex treatment unless the necessary precautions are taken and new antibiotics are discovered. In order to prevent the spreading of resistant Acinetobacter strains, infection control measures should be taken, clinicians and laboratory workers should cooperate during antibiotic use and hospital hygienic rules should be observed.