Bayhan Bektöre

Increasing number of drug resistant tuberculosis (TB) cases, observed in recent years, is an important public health problem. Extensively drug resistant TB (XDR-TB) is the development of resistance against any fluoroquinolones and at least one of the injectable second line anti-TB drugs in addition to resistance against isoniazide and rifampicin which are the first line anti-TB drugs [definition of multidrug resistant TB (MDR-TB)]. Anti-TB therapy failed with first-line anti-TB drugs due to MDR-TB cases is being planned according to second-line anti-TB drug susceptibility test results if available and if not, standart treatment protocols are used. Although it is recommended that individual anti-TB therapy should be designed according to the isolate's susceptibility test results, standart therapeutic protocols are always needed since second-line anti-TB drug susceptibility testing generally could not be performed in developing countries like Turkey. For this reason, nationwide and regional surveillance studies to determine the resistance patterns are always needed to make decisions about the standard therapy algorithms. In this study, it was aimed to investigate the presence of extensive drug resistance among 81 MDR-TB isolates obtained from various health care facilities from Istanbul, Izmir and Manisa and to determine the XDR-TB incidence in Marmara and Aegean regions. Furthermore, we aimed to provide epidemiological data to clinicians to support their choice of second-line anti-TB drugs for MDR-TB infections. Susceptibility testing of isolates for the first and the second-line anti-TB drugs were performed by using modified Middlebrook 7H9 broth in fluorometric BACTEC MGIT 960 system (Becton Dickinson, USA). Eighty-one MDR-TB isolates included in this study were isolated from 43 (53.1%) patients residing in Istanbul, 26 (32.1%) in Izmir and 12 (14.8%) in Manisa provinces. We could not find any isolate consistent with XDR-TB definition in this study. Second-line drug resistance rates of MDR-TB isolates to amikacin and kanamycin were 1.2%, ofloxacin and levofloxacin were 2.5%, capreomycin was 14.8%, ethionamide was 37% whereas linezolid resistance was not detected. Statistically significant correlation was detected between resistance rates of these antibiotic pairs; levofloxacin-ofloxacin (p< 0.01), amikacin-kanamycin (p= 0.01) and streptomycin-ethionamide (p= 0.04). In our study, extensive drug resistance was not encountered in any MDR-TB isolates while high resistance rates was observed against ethionamide and capreomycin. It can be concluded that parenteral aminoglycosides amikasin and kanamycin, fluoroquinolones and linezolid seemed to be reliable anti-TB agents in MDR-TB treatment, however, further larger scale studies are needed.

Increasing multidrug resistance in nosocomial Enterococcus strains from all over the world recently enhances the need for further investigation of enterococci, especially their virulence factors. There are still many lacking parts about virulence factors of clinical enterococcus isolates. In this study, it was aimed to investigate the antibiotic resistance and the presence of potential virulence factors of 91 Enterococcus strains (59 E.faecalis, 31 E.faecium and 1 E.gallinarum) isolated from urine cultures of inpatients between January 2008-June 2010 in our hospital and also to evaluate whether a correlation existed between antibiotic resistance and potential virulence factors. The genes which encoded virulence factors of enterococci; aggregation substance (AS), enterococcal surface protein (ESP) and hyaluronidase (HYL) (asa1, esp, hyl respectively) were studied by molecular methods and haemolysin production and gelatinase activity were studied by phenotypic methods. Vancomycin resistant strains were checked for the presence of vanA and vanB genes. Eight (25.8%) E.faecium isolates were found glycopeptide resistant. In seven of these isolates resistance type was vanA and in one it was neither vanA nor vanB. High-level gentamicin and high-level streptomycin resistance rates were 74.2% and 61.3% in E.faecium strains and were 22% ve 27.1% in E.faecalis strains, respectively. Beta-lactamase production and linezolid resistance were not detected in any of the strains. E.faecium isolates were more resistant (p< 0.001-0.013) than E.faecalis isolates to all tested antibiotics except tetracycline, minocycline, doxycycline and streptogramin (p< 0.001). hyl gene positivity (p< 0.001) was found higher in E.faecium isolates whereas esp (p= 0.003) and asa1 (p< 0.001) gene positivity, haemolysin production (p=0.014) and gelatinase activity (p= 0.029) were higher in E.faecalis isolates. AS and ESP were the most frequent virulence factors, with the rates of 26.7% and 25.6%, respectively. There were 32 (35.6%) strains without any of the investigated virulence factors. We have also detected that asa1 gene positive E.faecalis isolates were more resistant to ciprofloxacin (p= 0.001), norfloxacin (p= 0.006) and levofloxacin (p= 0.001) than asa1 gene negative isolates; esp gene positive E.faecalis isolates were more resistant to doxycycline (p= 0.043) than esp gene negative isolates and hyl gene positive E.faecium isolates were more resistant to nitrofurantoine (p= 0.011) than hyl gene negative isolates. This was the first clinical sample originated study, investigating the corelation between antibiotic resistance and virulence factors in urinary Enterococcus isolates in Turkey.

An extended-spectrum B-lactamase (ESBL)-producing Providencia stuartii isolate was studied. A qnrA1 gene co-expressing blaVEB-1 gene was detected. Both genes were transferred to the recipient strain. The ciprofloxacin MIC of recipient strain increased tenfold. The blaVEB-1 gene persisted in microorganisms in Turkey but it also spread with PMQR genes to other species. The combination of PMQR with multidrug resistant isolates producing ESBLs may compromise the use of valuable antibiotics. Serious efforts are necessary to detect PMQR determinants not only with common B-lactamases in widespread pathogens but also with uncommon forms that are encountered infrequently.

Although in certain countries in Europe fosfomycin trometamol (FT) has been used for many years, in Turkey FT has become available in recent years. FT has a broad-spectrum activity against most of gram-positive and gram-negative bacteria. In this study, we aimed to evaluate the effect of FT, a new alternative antimicrobial agent in the treatment of patients with Escherichia coli related uncomplicated lower urinary tract infection (UTI). For this purpose, between May 2007-July 2008, FT susceptibility of 771 nonduplicate E. coli strains, isolated from urine samples of patients with uncomplicated lower UTI (bacteria > or = 10(5) cfu/mL), was determined by disk diffusion method according to Clinical and Laboratory Standarts Institute (CLSI) criteria. Simultaneously, extended-spectrum beta-lactamase (ESBL) detection was performed by double disk synergy test in all isolates. Among all E. coli isolates, FT resistance rate was 0.4% (3/771) and ESBL positivity was 19.5% (150/771). The rates of ESBL producing strains isolated from inpatients and outpatients were 34.1% (70/205) and 14.1% (80/566), respectively, and the difference was found statistically significant (p = 0.0001). Although resistance to FT was not detected in non-ESBL producing E. coli isolates (n = 621), FT resistance rate was 2% (3/150) in ESBL producers. As far as the current literature was concerned this was the largest scale study investigating the activity of FT in Turkey. Resistance to antimicrobials that had been used frequently as therapeutic options for the treatment of E. coli related UTIs, has been increasing. In the present study high susceptibility rates to FT was determined for urinary E. coli isolates. In conclusion, these data suggest that FT may be a good alternative for the treatment of uncomplicated UTIs as a first line antimicrobial agent.