Acinetobacter Resistance in Turkish Tertiary Care Hospitals. Zeliha KOCAK TUFAN, MD, Assoc. Prof.

Acinetobacter Resistance in Turkish Tertiary Care Hospitals Zeliha KOCAK TUFAN, MD, Assoc. Prof.

Acinetobacter Problem Countries that have reported hospital outbreaks of carbapenem-resistant Acinetobacter highlighted in red, adapted from (Seifert 2005)

Turkish National Databases (ULAKBIM) 1996-2013 April Key word acinetobacter ---337 publications acinetobacter and resistance ---107 publications

140 126 120 104 100 86 80 60 40 20 21 0 1996-1999 2000-2004 2005-2009 2010-2013 The number of the publications on Acinetobacter in Turkey by years. (from 1996-2013 April)

1996

For Acinetobacter species, the levels of resistance were lowest for imipenem and meropenem. Recent reports of acquired carbapenemase activity in this species and among species of Enterobacteriaceae highlight the need to carefully monitor carbapenem susceptibility!!

For Acinetobacter species, the levels of resistance were lowest for imipenem and meropenem. 2000 Recent reports of acquired carbapenemase activity in this species and among species of Enterobacteriaceae highlight the need to carefully monitor carbapenem susceptibility!!

Guven et al. all Turkish studies on Acinetobacter resistance 1993 to 2009---17 years!! evaluated according to the date periods of the collection of the strains not the publication years of the studies Guven T et al. The increasing resistance in Nosocomial Acientobacter I solates in Turkey: 1993-2009. Poster presentation. EACID 2011

82 manuscripts The lowest resistance rates tigecycline (0.8%) colistin (2.4%) netilmycine (25%) cefaperazone-sulbactam (60%) Guven T et al. The increasing resistance in Nosocomial Acinetobacter Isolates in Turkey: 1993-2009. Poster presentation. EACID 2011

Growing carbapenem resistance: 33% to 80% for imipenem, 9% to 82% for meropenem, 64% to 90% for ciprofloxacin. Guven T et al. The increasing resistance in Nosocomial Acientobacter I solates in Turkey: 1993-2009. Poster presentation. EACID 2011

Antibiotics 1993-1997 1998-2002 2003-2007 2008-2009 n R (%) n R (%) n R (%) n R (%) Ampicillin-sulbactam 265 44,1 1296 69,5 1011 63,1 60 78,3 Piperacillin-tazobactam 243 87,2 1519 72,1 1836 78,5 347 89,9 Ceftazidime 870 80,8 2316 79,6 2121 84,5 675 88,3 Cefoperazone-sulbactam 352 30,7 822 65,7 791 43,5 217 59,9 Imipenem 930 33,1 2370 35,7 2314 40,6 675 79,7 Meropenem 90 8,8 956 38,7 1183 44,3 459 82,3 Netilmicin 116 4,3 1061 24 1006 28,6 217 24,9 Gentamicin 699 81,2 1791 72,1 1391 75,6 675 84,1 Amikacin 841 59,8 2319 59,2 2071 61,9 676 80,6 Ciprofloxacin 921 63,5 2391 61,2 2289 79,9 675 90 Tetracycline 23 52,2 254 68,9 208 65,8 140 86,4 Cefepime 213 75,6 1247 65,8 1808 73,5 663 81,3 Levofloxacin 0 --- 140 31,4 344 54,9 77 84,4 Colistin 0 --- 0 --- 294 2,7 293 2,4

Acinetobacter studies in Turkey: Resistant Acinetobacter percentages among other Gram negatives or within the all Acinetobacter species Clinical isolates of retrospective laboratory results Colonisation? Infection? Phenotypic and genotypic analysis----the real ongoing genotypes in the ICUs. ULAKBIM; ehis.ebscohost.com

Multidrug resistant A.baumannii resistance to more than two of the following five drug classes: antipseudomonal cephalosporins (ceftazidime or cefepime), antipseudomonal carbapenems (imipenem or meropenem), ampicillin-sulbactam, fluoroquinolones (ciprofloxacin or levofloxacin), aminoglycosides (gentamicin, tobramycin, or amikacin).

Resistance to carbapenem in Acinetobacter species the accumulation of various resistance mechanisms beta-lactamase production loss of outer-membrane porins over-expression of efflux pumps penicillin-binding protein alterations carbapenem-hydrolysing oxacillinases

metallobetalactamase ---not common in A.baumannii, oxacillinases --most commonly acquired carbapenem-hydrolyzing enzymes. blaoxa-58 A. baumannii- carbapenemase gene predominated among carbapenem-resistant isolates: Italy, Greece, Lebanon and Turkey. OXA-58 like and OXA-23-like carbapenemases :2000-2006 period strains in Turkey.

The subgroup 3 OXA-69 first reported from Singapore and Turkey was associated with an intermediate resistance to carbapenems in the absence of other apparent resistance factors. Brown S, Amyes SGB. Clin Microbiol Infect 2005; 11: 326 9. Jan Walther-Rasmussen, Niels Høiby JAC 2006;373-83

Altun et al Ankara T&R Hospital, MDR Acinetobacter species: blaoxa-23 -----32% blaoxa-58 -----2% blaoxa-48 none blandm none 100% resistance to piperacillin, ciprofloxacin, ceftazidime and cefepime. 100%susceptible to colistin (S. Altun, poster presentation, ECCMID 2013)

Resistance Rates and Comparison of Acinetobacter susceptibility by otomatised and manuel methods in a tertiary care hospital from Ankara Antibiotics Resistant n(%) Susceptible n(%) Intermediate n(%) Vitek 2 Manuel Vitek 2 Manuel Vitek 2 Manuel Amikasin 33 (75) 10 (27.7) 1 (2.3) Seftazidim 44 (100) 35 (81.4) 3 (7) 5 (11.6) Siprofloksasin 42 (100) 43 (100) Kolistin 41 (100) 43 (100) Gentamisin 21 (47.7) 12 (27.3) 11 (25) İmipenem 42 (95.5) 26(60.5) 2 (4.5) 6 (14) 11 (25.6) Levofloksasin 41 (95.5) 2 (4.5) Meropenem 42 (95.5) 40 (95.2) 2 (4.8) 2 (4.5) Netilmisin 5 (12.2) 23 (54.8) 23 (56.1) 19 (45.2) 13 (31.7) 32 (80) 20 (46.5) 3 (7.5) 4 (9.3) 5 (12.5) 19 (44.2) Tetrasiklin 32 (78) 7 (17.1) 2 (4.9) Sefoperazonsulbaktam Trimetoprimsulfometaksazol 20 (45.5) 21 (51.2) 24 (54.5) 20 (48.8)

First description of New Delhi metallo beta-lactamase (NDM-1)- carbapenemase from a novel Acinetobacter species (NB14) in Turkey P. Espinal*, N. Mosqueda, M. Telli, T. van der Reijden, L. Dijkshoorn, I. Roca, J. Vila (Barcelona, ES; Aydin, TR; Leiden, NL) From a female pediatric patient with pyelonephritis. Resistant to imipenem and meropenem (>32 mg/l), ceftazidime and piperacilline/tazobactam and susceptible to amikacin, ciprofloxacine and cephaperazone/sulbactam. MICs for colistin and tigecycline were (0.25 and 0.5 mg/l, respectively). PCR and sequencing identified the presence of blandm-1. Transferable antimicrobial resistance mechanisms ESCMID 2013

Carbapenem-resistance determinants in Acinetobacter baumannii isolates: CarO, AdeB, and blaoxa-24, blaoxa-58 type carbapenemases D. Guneser Merdan*, B. Aksu, G. Soyletir, J.M. Pages, M.U. Hasdemir (Istanbul, TR; Marseille, FR) Modifications in CarO porin protein, the production of various carbapenemases (VIM, IMP, OXA type carbapenemases) and/or overexpression of AdeABC efflux pump have been associated with the carbapenem resistance in A. baumannii. 4 multidrug resistant clinical strains of A. baumannii Carbapenemase activity was only detected in the two isolates and they gave positive PCR results for oxacillinase encoding genes, blaoxa-24 and blaoxa-58. All isolates displayed high level adeb transcripts in RT-PCR The alterations in CarO porin protein and the production of OXA-24 and OXA-58 type carbapenemases might be the main contributors of high level imipenem resistance. AdeABC efflux pump is another participant of carbapenem resistance in these isolates leading relatively low imipenem and meropenem MICs. ESCMID 2013

Increasing antimicrobial resistance in nosocomial pathogens; multidrugresistant (MDR) and pandrugresistant (PDR) Acinetobacter baumannii C. Celik, M.G. Gozel*, F. Dayi, M.Z. Bakici, N. Elaldi (Sivas, TR) 454 Acinetobacter spp. strains isolated from clinical specimens (165 respiratory tract, 99 urine, 76 blood, 70 wound, 14 cerebro spinal fluid and 30 others) of hospitalized patients diagnosed with nosocomial infection at Cumhuriyet University Research and Training Hospital during 2007-2011. Rate of MDR and PDR A. baumannii were detected as 57.3% and 14.0% respectively. ESCMID 2013

Tigecycline-sensitivity of multidrug-resistant Acinetobacter baumannii, comparison of Etest, Disc Diffusion and VITEK 2 S. Altun*, Z. Koçak Tufan, C. Bulut, U. Onde, S. Kinikli, A.P. Demiroz (Ankara, TR) Although e-test is recommended to detect sensitivity, otomatized system (VITEK 2, Biomerieux) results are used in routine work to start the therapy as soon as possible up to e-test results are available. Comparison of E-test, VITEK 2 and disc diffusion methods for tygecycline sensitivity of Acinetobacter baumannii. According to VITEK 2, E- test and disc diffusion results, resistance was detected in 1 (2%), 1 (2%) and 18 (40%) strains respectively. The only strain detected as resistant by E-test was found to be sensitive by VITEK 2 while the resistant strain by VITEK 2 was found to be intermediate sensitive by e- test. Eight of 26 (31%) sensitive strains by E-test were found to be intermediate sensitive by VITEK. A correlation of 46% was detected between E-test and VITEK2 (R=0.463, p=0.002). No correlation was detected between disc diffusion and other tests. Disc diffusion method seems to be not useful for detecting tygecycline sensitivity of Acinetobacter baumannii. E-test and VITEK 2 results are correlated and VITEK 2 results can be used when trying to make an alternative therapy with tygecycline for treating acinetobacter infections while waiting E-test results. ESCMID 2013

Guven et al, 2013 252 A. baumannii infection episodes ---229 hospitalized patients in ICUs in a tertiary care hospital from Ankara imipenem resistance 54%--2008 99%--2011 meropenem resistance 74%--2008 99%--2011 Guven T et al. Increasing resistance of nosocomial Acinetobacter baumannii: Are we going to be defeated? Turkish j Med Sci. 2013

The resistance rates of other antimicrobial agents from 2008 to 2011: 95.7% to 93.5% for ampicillin/sulbactam, 45.7% to 90.3% for cephoperazone/sulbactam, 41.7% to 53% for netilmicin, 96% to 87.2% for gentamicin, 91.7% to 72% for trimethoprim-sulfamethoxazole. Guven T et al. Increasing resistance of nosocomial Acinetobacter baumannii: Are we going to be defeated? Turkish j Med Sci. 2013

Colistin resistant four strains!!! Resistance rate to tigecycline increased to 81.3% (2011) from 12.5% (2008) Guven T et al. Increasing resistance of nosocomial Acinetobacter baumannii: Are we going to be defeated? Turkish j Med Sci. 2013

Are we in the post-antibiotic era?

Thank you for your attention.