Emerging Antibiotic Resistance In Psedomonas And Acinetobacter Strains Isolated From ICU Patients: Comparison Of Years 1999, 2006 And 2009

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1 Article ID: WMC ISSN Emerging Antibiotic Resistance in Psedomonas and Acinetobacter Strains Isolated from ICU Patients: Comparison of Years 1999, 2006 and 2009 Corresponding Author: Dr. Kadriye Kart Yasar, M.D., Haseki Training and Research Hospital,Clinical Microbiology and Infectious Disesases, Turkey Submitting Author: Dr. Kadriye Kart Yasar, M.D., Clinical Microbiology and Infectious Disesases, Haseki Training and Research Hospital, Turkey Article ID: WMC Article Type: Original Articles Submitted on:24-apr-2011, 06:17:17 PM GMT Article URL: Subject Categories:INFECTIOUS DISEASES Keywords:ICU, Acinetobacter, Pseudomonas, Antimicrobial Resistance Published on: 26-Apr-2011, 07:33:49 PM GMT How to cite the article:kart Yasar K, Pehlivanoglu F, Sengoz G. Emerging Antibiotic Resistance in Psedomonas and Acinetobacter Strains Isolated from ICU Patients: Comparison of Years 1999, 2006 and WebmedCentral INFECTIOUS DISEASES 2011;2(4):WMC Source(s) of Funding: No source of funding Competing Interests: No competing interests. Additional Files: Manuscript Title page Webmedcentral > Original Articles Page 1 of 12

2 Emerging Antibiotic Resistance In Psedomonas And Acinetobacter Strains Isolated From ICU Patients: Comparison Of Years 1999, 2006 And 2009 Author(s):Kart Yasar K, Pehlivanoglu F, Sengoz G Abstract Objectives: Pseudomonas and Acinetobacter spp. which are usually resistant to many antibiotics, are the most important infectious pathogens in intensive care units (ICUs). The aim of this study was to determine the antibiotic resistance patterns of these agents and to follow variation in resistance among the years of 1999, 2006 and Methods: The resistance rates of various antibiotics for 21, 38 and 54 acinetobacter and 26, 44 and 66 pseudomonas bacteria which were isolated from blood cultures of ICU patients in years 1999, 2006 and 2009 respectively were compared with Fischer s qui square test statistically. Results: The most effective antibiotics were amikacin (88%), cephaperazone-sulbactam (85%), piperacillin-tazobactam (85%), ceftazidim (75%) and imipenem (75%) for Pseudomonas spp. and imipenem (76%),cephaperazone-sulbactam (71%), ciprofloxacin (52%) and amikacin (48%) for Acinetobacter spp. in Decreasing sensivities to amikacin (76%), cephaperazone-sulbactam (53%), piperacillin-tazobactam (71%), ceftazidim (53%) and imipenem (64%) for Pseudomonas spp. and decreasing sensivities to imipenem (28%), cephaperazone-sulbactam (37%), ciprofloxacin (13%) and amikacin (17%), piperacillin for Acinetobacter spp in 2009 were significant (p<0,05). Conclusions: These results suggested that significant resistance development for imipenem, cephaperazone-sulbactam and ciprofloxacin occurred against acinetobacter strains and for cephaperazone-sulbactam, amikacin and ceftazidime against pseudomonas strains. Increased resistance in our ICU is significant in Acinetobacter spp. The usage of some antibiotics have been limited and multidrug-resistant or pan-resistant strains have been monitorized by infection control committee of our hospital. Protective measures like good hand hygiene, strict contact isolation and control strategies for rational antibiotic usage may be effective factors for infection control caused by these pathogens in ICUs. Introduction Antibiotic-resistant bacteria are an emerging problem in intensive care units (ICUs). Infections caused by multidrug-resistant organisms may result in prolonged hospitalization, increased mortality rates and costs. Pseudomonas aeruginosa is a certain nosocomial pathogen with notable virulence factors and the ability to exhibit antibiotic resistance. Acinetobacter species have been associated with numerous ourbreaks of infection, especially in ICUs (1). Multidrug resistant P.aeruginosa and Acinetobacter species shows an increased risk of infection in patients in ICUs and clonal dissemination of multidrug-resistant strains occurs commonly (1). In addition, Fagon et al (2) reported that pneumonia with Acinetobacter spp. or P.aeruginosa was related with increased mortality rates (40%). Similarly, Blot et al (3) reported a crude hospital mortality rate of 42% for patients with A.baumannii bacteraemia. The use of broad spectrum antibiotics may lead the colonization with these pathogens and consequently to serious infections. The most important determinants for reduction of incidence of infections caused by Pseudomonas and Acinetobacter species in ICUs are rational antibiotic management, investigation of environmental sources of infection and strict contact isolation procedures. Optimizing empirical therapy requires knowledge of antimicrobial resistance patterns. The aim of this study was to determine the antibiotic resistance patterns of Pseudomonas and Acinetobacter species and to follow variation in resistance among the years of 1999, 2006 and Methods Settings Our hospital, is a 550-bed tertiary hospital. The adult internal and surgical ICU was founded with six beds in 1999 and 16 beds were added in There is an Webmedcentral > Original Articles Page 2 of 12

3 infection control committee and with two infection control nurses. The infection control nurses inform and liaise with the ward staff for isolation procedures and infection control measures based on microbiological results. Universal precautions are practiced by all health care workers. Infection control problems are also discussed in clinical meetings. Laboratory procedures The resistance rates of various antibiotics for 21, 38 and 54 acinetobacter and 26, 44 and 66 pseudomonas bacteria which were isolated from blood cultures of ICU patients in years 1999, 2006 and 2009 respectively were compared with Fischer s qui square test statistically. Blood cultures processed by automated BacT/Alert 3D system (Bio Merieux, France) and only one sample was studied from each patient. Positive signaled samples in BacT/Alert were cultured to choclate agar and after hours of incubation at 37 C, suspected colonies for Pseudomonas and Acinetobacter species identified with conventional biochemical procedures. The antimicrobial susceptibilities of ampicillin-sulbactam (SAM), gentamicin (GN), amikacin (AK), ceftriaxone (CRO), ciprofloxacin (CIP), cefoperazone-sulbactam (CFP), meropenem (MEM), piperacillin-tazobactam (TZP), cefepime (FEP) and ceftazidime (CAZ) were investigated by Kirby Bauer disc diffusion method on Mueller Hinton agar plates according to Clinical Laboratory Standard Institution (CLSI) recommendations (4). Results A total of 136 Pseudomonas spp. And 113 Acinetobacter spp. strains were evaluated for susceptibility to different antibiotics i.e. SAM, GN, AK, CRO, CIP, CFP, MEM, TZP, FEP and CAZ. Out of 136 pseudomonas strains, 26 were isolated in 1999, 44 were in 2006 and 66 were in Of all acinetobacter strains, 21 were isolated in 1999, 38 were in 2006 and 54 were in The most effective antibiotics were AK (88%), CFP (85%), TZP (85%), CAZ (75%) and MEM (75%) for Pseudomonas spp. and MEM (76%), CFP (71%), CIP (52%) and AK (48%) for Acinetobacter spp. in (Table 1 and 2). Table 1: Antimicrobial resistance rates of 136 Pseudomonas spp. isolates Table 2: Resistance rates of 113 Acinetobacter spp. isolates Decreasing sensivities to AK (76%), CFP (53%), TZP (71%), CAZ (53%) and MEM (64%) for Pseudomonas spp. in 2009 were significant (p<0,05). For Acinetobacter strains, there were significant decreasing sensivities to MEM (28%), CFP (37%), CIP (13%) and AK (17%), in 2009 too (p<0,05) (Figure 1 and 2). Figure 1. Resistance patterns of Pseudomonas spp. by years 1999, 2006 and Figure 2. Resistance patterns of Acinetobacter spp. by years 1999, 2006 and Discussion Pseudomonas and Acinetobacter species have emerged as the major causes of nosocomial infections, particularly in ICUs. Despite advances in sanitation and hygiene facilities and the introduction of new antimicrobial agents for management of nosocomial infections, Acinetobacter and pseudomonas infections still remains as a major factor related with hospital mortality and threats in critically ill patients. Unfortunately, many of infectious disease physicians have recently been confronted with multidrug-resistant P.aeruginosa and Acinetobacter isolates which are resistant to all beta-lactams and quinolones. In fact, inadequate empirical treatment has been related with mortality exceeding 30% (5) and delays in initiation of appropriate antimicrobial agent contribute prolonged hospitalization and persistence of infection (6). The prediction and selection of appropriate antimicrobials require active surveillance of emerging resistance trends. Obritsch et al (7) reported that significant increase in resistance rates of pseudomonas strains obtained from ICU patients from 1993 to 2002 for ciprofloxacin, imipenem, tobramycin and aztreonam. They also found that multidrug-resistance rates had increased from 4% in 1993 to 14% in Similarly, multi-drug resistant acinetobacter strains have been detected in recent years in our ICU. These multi-drug resistant acinetobacter strains could disseminate after contamination of the hospital environment and by nosocomial transmission especially by the hands of hospital staff among critically ill patients in our ICU. The infection control nurses of our hospital inform and liaise with the ward staff for isolation procedures and infection control measures when multi-drug resistant acineobacter strains isolated in the ICU. These problems are also discussed in clinical meetings. However, dissemination of these pathogens in the ICU could not be prevented despite regular training of personnel, due to inadequate number of staff, frequent staff changes and ward staff with low compliance to the preventive measures for infections in our hospital. Webmedcentral > Original Articles Page 3 of 12

4 Dual resistance rates for beta-lactams and quinolones were the highest among all antibiotics in this study (7). It is noticeable in our study that the sensitivity to quinolones and aminoglycosides also decreased remarkably beside the sensitivity to carbapenem and beta-lactam antibiotics decreased in particularly acinetobacter strains. In a review that analyzed the risk factors associated with development of multi-drug resistant A.baumannii and P.aeruginosa, deficiencies in the implementation of infection control guidelines and the use of broad-spectrum antibiotics were determined to be the most important risk factors (8). It has been found that use of carbapenems and third-generation cephalosporins appear to be associated with the development of an MDR phenotype by A. baumannii, while carbapenems and fluoroquinolones are implicated in MDR P. aeruginosa. As though, the antibiotic treatment is regulated by the infectious disease physicians and use of redundant antibiotics is avoided carefully in our ICU, nevertheless, the decrease in the antibiotic sensitivities of the acinetobacter and pseudomonas strains isolated in our ICU couldn t have been prevented until Beside the use of redundant antibiotics, it has also been demonstrated that the factors associated with patients such as hospitalization at ICU and bad general conditions have been suggested to be the facilitating factors for the resistant acinetobacter infections (9). In the recent years, hospital infections and ICU outbreaks such as primarily VIP due to multi-drug resistant A.baumannii have been reported (10-2). In fact, increased resistance in our ICU is significant in Acinetobacter spp. between years of 1999 and In compliance with our results, there are many reports from Turkey and other countries mentioned about increased antimicrobial resistance in Acinetobacter spp. A.baumannii has been one of the most frequently detected pathogens and the approximately half of the strains were found resistant to carbapenem in a multi-center study that has been conducted in Turkey and that investigated the infectious factors at ICU (13). In the MYSTIC Study that investigated the antimicrobial sensitivities of the nosocomial Gram negative pathogens, the sensitivities of P.aeruginosa strains to ceftazidime, cefepime and tobramycin were found 48%, 41% and 35% respectively, whereas 67% of the A.baumannii strains were found multi-drug resistant and those sensitivities of A.baumannii strains to carbapenem, tobramycin, cefepime, ciprofloxacin and ceftazidime were detected to be 53%, 44%, 37%, 29% and 22%, respectively (14). The resistance change rates of the ICU-sourced P.aeruginosa and A.baumannii strains between the years 2003 to 2006 was analyzed in another study conducted in Turkey and a significant decrease has been found in the sensitivity of the pseudomonas strains to carbapenem, beta-lactam and quinolone. The sensitivity of the A.baumannii isolates to carbapenem, beta-lactam antibiotics, quinolones and aminoglycosides significantly decreased in the year 2006 (15). In a multi-center study performed by participitation of 13 different ICUs that investigated device-associated hospital-acquired infection rates, the resistance rates of the P.aeruginosa strains to ciprofloxacin and ceftazidime, imipenem, piperacillin/tazobactam were found 51%, 38% and 30%, respectively, whereas the resistance rate of A.baumannii to piperacillin/ tazobactam was detected to 87% (16). Also, The 2009 Report of the International Nosocomial Infection Control Consortium (INICC) has reported according to the surveillance results with the participation of 173 ICUs in Latin America, Europe, Asia and Africa that device-associated infection rates were remarkably higher than the US ICU infection rates, rate of imipenem resistant acinetobacter was 46,3% and rate of quinolone-resistant pseudomonas was 50% (17). In another study that analyzed the episodes of the ICU-sourced 96 nosocomial bacteremia developed by A.baumannii, use of central venous catheter and ventilator, previous colonization with A.baumannii, respiratory-cardiovascular deficiency were determined to be a risk factor for A.baumannii bacteremia in univariate analysis. In the multivariate analyses of the same study; previous colonization and cardiovascular deficiency were demonstrated to be independent risk factors. The cumulative survival curves of A.baumannii bacteremia showed no difference when compared with control group, hospitalization duration and cost were found significant (18). In conclusion, resistance development for commonly used antibiotics against acinetobacter and pseudomonas strains in the ICU has been increased between years of 1999 and Increased resistance in our ICU is significant in Acinetobacter spp. Regular surveillance of ICU infections and adopting basic infection control practices that have been shown to prevent healthcare associated infections are very important steps towards the reduction of these infections (16). Improving hand hygiene practices of healthcare workers, strict contact isolation procedures and aceptic care of vascular catheters are important measures to prevent pseudomonas and acinetobacter colonisation and may provide decrease in the incidence of related bacteremia. In addition, there is a need to emphasize on the rational use of antimicrobials and strictly adhere to the concept of reserve drugs to minimize the misuse of available antimicrobials. Therefore, Webmedcentral > Original Articles Page 4 of 12

5 restricted antibiotic policies, antibiotic cycling and shorter antibiotic usage may be effective in reducing antibiotic resistance. References 1. Paterson D. The epidemiological profile of infections with multidrug-resistant Pseudomonas areruginosa and Acinetobacter species. Clin Infect Dis 2006; 43(suppl 2):s Fagon JY, Chastre J, Hance AJ, Montravers P, Novava A, Gibert C. Nosocomial pneumoniae in ventilated patients: a cohort study evaluating attr?butable mortality and hospital stay. Am J Med 1993; 94: Blot S, Vandewwoude K, Colardyn F. Nosocomial bacteremia involving Acinetobacter baumannii in critically ill patients: a matched cohort study. Intensive Care Med 2003; 29: Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility tests, 17th ed, M100-S18. Wayne, PA: CLSI; Ibrahim EH, Sherman G, Ward S, Fraser VJ, Kollef MH. The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting. Chest 2000; 118: Kollef MH. Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest 1999; 115: Obritsch MD, Fish DN, MacLaren R, Jung R. National surveillance of antimicrobial resistance in Pseudomonas aeruginosa?solates obtained from intensive care unit patients from 1993 to Antimicrob Agents and Chemother 2004; 48: Falagas ME, Kopterides P. Risk factors for the isolation of multi-drug resistant Acinetobacter baumannii and Pseudomonas aeruginosa: a systematic review of the literature. J Hosp Infect 2006;64: Poutanen SM, Louie M, Simor AE. Risk factors, clinical features and outcome of Acinetobacter bacteremia in adults. Eur J Clin Microbiol Dis 1997; 16: Corbella X, Montero A, Pujol M, Dominguez MA, Ayats J, Argerich MJ, et al. Emergence and rapid spread of carbapenem resistance during a large and sustained hospital outbreak of multiresistant Acinetobacter baumannii. J Clin Microbiol 2000;38: Roberts SA, Findlay R, Lang SDR. Investigation of an outbreak of multiüdrug resistant Acinetobacter baumannii in an intensive care burns unit. J Hosp Infect 2001; 48: Aygun G, Demirkiran O, Utku T, Mete B, Urkmez S, Yilmaz M, et al. Environmental contamination of during a carbapenem-resistant an Acinetobacter baumannii outbreak in an intensive care unit. J Hosp Infect 2002; Yucesoy M, Yulug N, Kocagoz S, Unal S, Cetin S, Calangu S, et al. Antimicrobial resistance of gram-negative isolates from intensive care units in Turkey: comparison to previous threevyrars. J Chemother 2000; 12: Zarakolu P, Hascelik G, Unal S. Antimicrobial susceptibility pattern of nosocomial gram negative pathogens: results from MYSTIC study in Hacettepe University Adult Hospital ( ). Mikrobiyol Bul 2006; 40: Aliskan H, Colakoglu S, Turunc T, Demiroglu YZ, Erdogan F, Akin S, et al. Four years of monitoring of antibiotic sensitivity rates of Pseudomonas aeruginosa and Acinetobacter baumannii strains isolated from patients in intensive care unit and inpatient clinics. Mikrobiyol Bul 2008; 42: Leblebicioglu H, Rosenthal VD, Arikan OA, Ozgultekin A, Yalcin AN, Koksal I, et al. Deviceüassociated hospital-acquired infection rates in Turkish intensive care units. Findings of the International Nosocomial Infection Control Concortium (INICC) J Hosp Infect 2007; 65: Rosenthal VD, Maki DG, Jamulitrat S, Mederios E, Kumar Todi S, Gomez DY, et al. International Nosocomial Infection Control Contortium (INICC) report, data summary for , issued June Am J Infect Control 2010; 38: Jang TN, Lee SH, Huang CH, Lee CL, Chen WY. Risk factors and impact of nosocomial Acinetobacter baumannii bloodstream infections in the adult intensive care unit: a case-control study. J Hosp Infect 2009; 73: Webmedcentral > Original Articles Page 5 of 12

6 Illustrations Illustration 1 Table 1: Antimicrobial resistance rates of 136 Pseudomonas spp. isolates Years CN AK CAZ CIP CFP MEM TZP FEP 1999 (n:26) 53 11, ,1 15, ,3 34, (n:44 ) 61,3 31, ,3 18,1 20,4 22,7 29, (n:66) 59,1 24,2 46, ,9 36,4 28,8 45,5 SAM: Ampicillin-sulbactam, CN: gentamicin, AK: amikacin, CIP: ciprofloxacin, CFP: cefoperazone-sulbactam, MEM: meropenem, TZP: piperacillin-tazobactam, FEP: cefepime, CAZ: ceftazidime. Webmedcentral > Original Articles Page 6 of 12

7 Illustration 2 Table 2: Resistance rates of 113 Acinetobacter spp. Isolates Years SAM CN AK CRO CIP CFP MEM TZP FEP 1999 (n:21) 66,6 80,9 52,3 71,4 47,6 28,5 23,8 66, (n:38) 52,6 76,3 55,2 92,1 78,4 23, ,4 42, (n:54) 61 90,7 83,3 94, ,2 90,7 79,6 SAM: Ampicillin-sulbactam, CN: gentamicin, AK: amikacin, CRO: ceftriaxone, CIP: ciprofloxacin, CFP: cefoperazone-sulbactam, MEM: meropenem, TZP: piperacillin-tazobactam, FEP: cefepime, CAZ: ceftazidime. Webmedcentral > Original Articles Page 7 of 12

8 Illustration 3 Figure 1. Resistance patterns of Pseudomonas spp. by years 1999, 2006 and Webmedcentral > Original Articles Page 8 of 12

9 Illustration 4 Figure 2. Resistance patterns of Acinetobacter spp. by years 1999, 2006 and Webmedcentral > Original Articles Page 9 of 12

10 Reviews Review 1 Review Title: Emerging Antibiotic Resistance in Pseudomonas and Acinetobacter Strains Isolated from ICU Patients Posted by Dr. Thomas Herchline on 04 Oct :09:24 PM GMT 1 Is the subject of the article within the scope of the subject category? Yes 2 Are the interpretations / conclusions sound and justified by the data? Yes 3 Is this a new and original contribution? Yes 4 Does this paper exemplify an awareness of other research on the topic? Yes 5 Are structure and length satisfactory? Yes 6 Can you suggest brief additions or amendments or an introductory statement that will increase the value of this paper for an international audience? 7 Can you suggest any reductions in the paper, or deletions of parts? No 8 Is the quality of the diction satisfactory? Yes 9 Are the illustrations and tables necessary and acceptable? Yes 10 Are the references adequate and are they all necessary? Yes 11 Are the keywords and abstract or summary informative? Yes Rating: 4 Comment: This study largely confirms the findings of many other publications on this topic. The tables do not reproduce well in the pdf format. It would be preferred if findings were consistently represented as percent resistant OR percent susceptible. Competing interests: None Invited by the author to make a review on this article? : No Experience and credentials in the specific area of science: Infectious Diseases physician Publications in the same or a related area of science: No How to cite: Herchline T.Emerging Antibiotic Resistance in Pseudomonas and Acinetobacter Strains Isolated from ICU Patients[Review of the article 'Emerging Antibiotic Resistance in Psedomonas and Acinetobacter Strains Isolated from ICU Patients: Comparison of Years 1999, 2006 and 2009 ' by ].WebmedCentral 2011;2(10):WMCRW00988 No Webmedcentral > Original Articles Page 10 of 12

11 Review 2 Review Title: Emerging Antibiotic Resistance in Psedomonas and Acinetobacter Strains Isolated from ICU Patients: Comparison of Years 1999, 2006 and 2009 Posted by Dr. Semsinur Karabela on 09 Jun :15:15 AM GMT 1 Is the subject of the article within the scope of the subject category? Yes 2 Are the interpretations / conclusions sound and justified by the data? Yes 3 Is this a new and original contribution? Yes 4 Does this paper exemplify an awareness of other research on the topic? Yes 5 Are structure and length satisfactory? Yes 6 Can you suggest brief additions or amendments or an introductory statement that will increase the value of this paper for an international audience? 7 Can you suggest any reductions in the paper, or deletions of parts? No 8 Is the quality of the diction satisfactory? Yes 9 Are the illustrations and tables necessary and acceptable? Yes 10 Are the references adequate and are they all necessary? Yes 11 Are the keywords and abstract or summary informative? Yes Rating: 8 Comment: This article is a valuable article that pointed out the emerging antimicrobial resistance of nonfermenters in ICUs. It is important to monitorize the resistance patterns of these agents in ICUs and in hospitals. Competing interests: No Invited by the author to make a review on this article? : Yes Experience and credentials in the specific area of science: Yes. I have a similar study. Publications in the same or a related area of science: Yes References:?eng?z, G.,?. Karabela, Y. Durdu, et al. Determination of isepamicin resistance in Pseudomonas strains and comparison with other aminoglycosides. Klimik Dergisi 2005; 18(1): How to cite: Karabela S.Emerging Antibiotic Resistance in Psedomonas and Acinetobacter Strains Isolated from ICU Patients: Comparison of Years 1999, 2006 and 2009[Review of the article 'Emerging Antibiotic Resistance in Psedomonas and Acinetobacter Strains Isolated from ICU Patients: Comparison of Years 1999, 2006 and 2009 ' by ].WebmedCentral 2011;2(6):WMCRW00813 No Webmedcentral > Original Articles Page 11 of 12

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