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Healthcare-associated vancomycin resistant Enterococcus faecium infections in the Mansoura University Hospitals intensive care units, Egypt

Healthcare-associated vancomycin resistant Enterococcus faecium infections in the Mansoura... Vancomycin resistant Enterococcus faecium (VREF) ia an emerging and challenging nosocomial pathogen. This study aimed to determine the prevalence, risk factors and clonal relationships be- tween different VREF isolates in the intensive care units (ICUs) of the university hospitals in our geo- graphic location. This prospective study was conducted from July, 2012 until September, 2013 on 781 patients who were admitted to the ICUs of the Mansoura University Hospitals (MUHs), and ful- filled the healthcare-associated infection (HAI) criteria. Susceptibility testing was determined using the disk diffusion method. The clonal relationships were evaluated with pulsed field gel electropho- resis (PFGE). Out of 52 E. faecium isolates, 12 (23.1%) were vancomycin resistant. The significant risk factors for the VREF infections were: transfer to the ICU from a ward, renal failure, an extended ICU stay and use of third-generation cephalosporins, gentamicin, or ciprofloxacin. PFGE with the 12 isolates showed 9 different patterns; 3 belonged to the same pulsotype and another 2 carried a second pulsotypes. The similar pulsotypes isolates were isolated from ICUs of one hospital (EICUs); how- ever, all of the isolates from the other ICUs had different patterns. Infection control policy, in con- junction with antibiotic stewardship, is important to combat VREF transmission in these high-risk patients. Key words: Enterococcus faecium, ICU, vancomycin, risk factors, PFGE. In addition to this distinct resistance profile, genomic analyses have shown that hospital acquired E. faecium Introduction strains have a genetic repertoire that is distinct from that of Enterococci are opportunistic pathogens of the nor- community associated E. faecium strains that asympto- mal humans and animals intestinal microbiota. The most matically colonize the human gastrointestinal tract (van common Enterococcus species that is involved in noso- Schaik et al., 2010). This distinct genetic repertoire in- comial infections is Enterococcus faecium (E. faecium) cludes the enterococcal surface protein, Esp, which is a (Top et al., 2008; Arias and Murray, 2012). known virulence determinant (Heikens et al., 2007; 2011). Genomic islands that encode novel metabolic pathways E. faecium has become one of the most important, (Heikens et al., 2008), and insertion sequence elements emerging and challenging nosocomial pathogens (Arias (Leavis et al., 2007). It is now considered that these deter- and Murray, 2012). It is a difficult to treat this pathogen due minants may be adaptive elements that have improved the to its intrinsic resistance to cephalosporins, aminogly relative fitness of E. faecium subpopulations in the hospital cosides, clindamycin and trimethoprim-sulfamethoxazole environment (Willems and van Schaik, 2009). Due to the (Leclercq et al., 2013). Moreover, it has the ability to easily acquire antibiotic resistance genes trough transfer of plas- resistance of multiple antibiotics, the treatment of choice in serious E. faecium infections is glycopeptides. However, mids, chromosomal exchange or mutation (Jett et al., 1994). prudent use of vancomycin is needed as it is associated with Send correspondence to D. Moemen. Department of Medical Microbiology and Immunology, Faculty of Medicine, Mansoura University, Egypt. E-mail: dr_daliamoemen@yahoo.com. 778 Moemen et al. an increased risk for vancomycin resistant enterococci and C. children hospital ICUs, which included pediatric (VRE) colonization and infection (Tornieporth et al., (PICU), neonatal ICU (NICU) and surgical ICU (SICU). 1996). Study population In the last decades, the number of VRE infections has This study included 781 patients (who provided writ- increased (Grayson et al., 1991; Jones et al., 1995; Rice, ten consent) that were admitted to different MUHs ICUs 2001). The first VRE isolates were reported in the United and fulfilled the healthcare-associated infection (HAI) cri- Kingdom in the late 1980s (Uttley et al., 1988). In the United States, more than 80% of E. faecium isolates from teria. (Infections acquired  48 hours after admission that hospitals are vancomycin resistant (Hidron et al., 2008). were not present or incubating at the time of hospital admis- Vancomycin-resistant E. faecium (VREF) has been associ- sion). The infection types were documented with specific ated with outbreaks in hospitals worldwide (Arias and Mur- HAIs definitions, which were established by the Centers for ray, 2012). The VREF colonization and infection rates have Disease Control and Prevention (Horan et al., 2008). risen steadily, with most cases being caused by the VanA Data collection and definitions and VanB genotypes, which are the most commonly en- countered glycopeptide resistance forms (Coque et al., The following data were collected: demographic 1996; Rice, 2006; Deshpande et al., 2007). characteristics, ICU stay duration, transfer to the ICU from The clinical impacts of VRE include the limited avai- a ward, diagnosis at ICU admission, medical conditions lability of drugs to treat VRE infections and the ability of that may alter the patient’s immunity (comorbidity) (e.g. VRE to transfer the genetic determinant for vancomycin re- diabetes, malignancy, hepatic impairment, renal impair- sistance to other Gram-positive pathogens, such as Staphy- ment and chronic lung diseases), invasive devices or proce- lococcus aureus (Schooneveld et al., 2008; Noble et al., dures (e.g. surgical procedures, central venous catheter 1992). [CVC], peripheral venous catheter [PVC], mechanical ven- tilation, and total parenteral nutrition [TPN], drug therapy VREF is associated with hospital-acquired infections (e.g. antibiotics and their durations, prior antibiotic treat- such as urinary tract infections, wounds, bacteremia, endo- ment, which was defined as any antibiotic treatment during carditis and meningitis (Top et al., 2008; Arias and Murray, the two weeks preceding ICU admission), immunosup- 2012). Several studies have demonstrated that VRE bacte- pressive therapy (which included steroid therapy, cytotoxic raemia patients have a higher mortality rate than those in- chemotherapy or radiotherapy given within one month fected with vancomycin-susceptible enterococci (Vergis et prior to ICU admission), and neutropenia (less than 500 al., 2001; Edmond et al., 1996; Bhavnani et al., 2000). neutrophils per mm ) Information regarding the VRE Infections prevalence A “case patient” was defined as patient who was in- in Egypt indicates that there is an increasing VRE infection fected with VREF and was attending a Mansoura Univer- rate. Ghonaim et al. (2009) reported that VRE isolates con- sity ICU during the study period. A “control patient” was stituted 20.9% of hospital associated enterococcal infec- defined as a Vancomycin susceptible Enterococcus tions at the Egyptian National Liver Institute. faecium (VSEF) infected patient who was attending a To control the rapid spread of multidrug resistant or- Mansoura University ICU during the same period. The pa- ganisms, it is necessary to understand the risk factors for tients whose initial isolate was susceptible to vancomycin acquiring them. Therefore, the aim of this study was to but who subsequently had VREF isolates that were recov- identify the VREF prevalence and possible risk factors in ered were included as case patients. ICU patients who are at high risk of VREF infection. Addi- tionally, we aimed to identify the clonal relationship be- Microbiologic studies tween different isolates via pulsed-field gel electrophoresis The samples were processed in the Medical Diagnos- (PFGE). tics and Infection Control Unit (MDICU) laboratory using standard protocols. E. faecium laboratory identification Materials and Methods was performed by Gram stain, colonial morphology on blood agar, growth and blackening of bile esculin agar, the Patients and methods absence of catalase production, resistance to 6.5% sodium Study design chloride. The results were confirmed with the API 20 Strep (Biomerieux SA, Montalieu - Vercica and France) system. This was a prospective study, which was conducted in In vitro susceptibilities of the isolates to antimicrobials nine ICUs in three different MUHs, that were situated were determined with the disk diffusion method which was within the same geographical region over a 15 months pe- defined by the [CLSI] (Institute CaLS, 2011). The antibiot- riod from July, 2012 until September, 2013. The ICU bed ics that were tested included ampicillin (10 g), cipro- numbers range from 4 to 27, with a median of 10. They ICUs were categorized as: A. emergency hospital ICUs floxacin (5 g), high content gentamicin (120 g), erythro- (EICUs), B. specialized medical hospital ICUs (SMICUs) mycin (15 g), tetracycline (30 g), vancomycin (30 g), Vancomycin resistant E. faecium 779 All VREF isolates (100%) were resistant to ampicillin, teicoplanin (30 g), linezolid (30 g), and chloramphenicol gentamicin, and ciprofloxacin. Most of the isolates (92%) (30 g). Glycopeptide antibiotics MICs for: vancomycin were resistant to erythromycin (only one isolate was sensi- and teicoplanin against the E. faecium isolates were exam- tive), and 5 isolates were resistant to tetracycline (42%). All ined with the VITEK 2 system (bioMérieux). of the strains were sensitive to linezolid and chloram- PFGE phenicol. The clonal relationships between the vancomycin- The ICU-acquired VREF Risk factors resistant strains were studied by evaluating the genomic DNA with PFGE (Antonishyn et al., 2000). DNA that was Among the 52 E. faecium infected patients, 40 restricted with the SmaI enzyme was separated on an aga- (76.9%) had VSEF infections (control patients), and 12 rose gel using a CHEF DR III apparatus (Bio-Rad laborato- (23.1%) had VREF infections (case patients). The compar- ries). The running conditions were 6 V per cm, with pulses ative demographic and clinical features for both the case and controls patients are listed in Tables 1 and 2. The risk ranging from 2 to 15 s for 18 h at 14 C. The DNA banding factors that were significantly associated with the ICU- patterns were visualized under UV light after staining with acquired VREF infections were: transfer to the ICU from a ethidium bromide (0.5 mg/mL). The similarities between ward (p = 0.04), renal failure (p = 0.01), and longer ICU the isolates were determined by visual comparison of the stay duration (p = 0.018). Additionally, antibiotic use for a isolate band patterns. The interpretation of the PFGE re- long period of time and use of third-generation cepha- sults was carried out by eye according to the criteria de- losporins, gentamicin, or ciprofloxacin were also associ- scribed by Tenover et al. (1995). ated with VREF infections. Statistical analysis PFGE The SPSS software (SPSS Inc., Chicago, IL, USA) was used for data analyseis. Proportions were compared us- The restriction endonuclease patterns obtained with the PFGE following the SmaI treatment for the 12 VREF ing the 2 test and continuous variables were compared us- isolates are presented in Figure 1. In general, the 12 isolates ing Student’s t or Mann-Whitney U tests. The results are showed 9 different patterns. Three isolates belonged to the presented as numbers (percentages) for frequency and as same pulsotype and another 2 carried similar pulsotypes. the mean  standard deviation for quantitative variables. Of interest, the isolates with similar pulsotypes were iso- Odds ratios (OR) [95% confidence interval (CI)] were cal- lated from the ICUs of one hospital (EICUs); however, all culated for all significant (p < 0.05) qualitative variables in of the isolates from the other ICUs had different patterns. the univariate analyseis. Discussion Results E. faecium is a highly resistant nosocomial pathogen VREF Prevalence in the ICUs and has recently emerged as an important threat in hospitals During the study period, a total of 975 specimens worldwide (Arias and Murray, 2012). In this study, VREF were collected from 782 patients, with clinically suspected constituted 23.1% of the observed E. faecium isolates, a re- HAIs in MUHs ICUs. Out of 52 E. faecium isolates de- sult that was close to the Ghonaim et al. study observations, tected, 12 were VREF, which constituted (12/52) 23.1% of in which the VRE isolates constituted 20.9% of the hospi- the E. faecium isolates. tal-associated enterococcal infections at the National Liver Institute (Ghonaim et al., 2009), which indicated a big VREF isolates problem in Egypt. Similar studies from the United States Twelve VREF single-patient isolates (i.e., 1 isolate reported vancomycin resistance in up to 28% of all noso- per patient) were obtained from the following sites: urine (7 comial Enterococcus species (NNIS, 2004). However stud- isolates), blood (3 isolates) and wound (2 isolates). A total ies from India and South America showed much lower of of 12 infections were documented in 12 patients, including VRE infection prevalence ranging from 1- 8.7% (Mathur et urinary tract infection (7 patients), bacteremia instances (3 al., 2003; Taneja et al., 2004; Kapoor et al., 2005; Kaur et patients), and surgical site infection (2 patients). Of these al., 2009; Praharaj et al., 2003; Panesso et al., 2013). E. 12 patients, 6 isolates were obtained from the emergency faecium antibiotics sensitivity pattern in the present study is hospital ICUs, 4 were obtained from the ICUs of the spe- consistent with the concept that vancomycin resistance is cialized medical hospital and 2 were from PICUs. usually accompanied by resistance to other antimicrobial agents, such as penicillin, ampicillin, erythromycin, cipro- Antibiotic susceptibility testing of the VREF isolates floxacin and gentamicin. The objective of this study was to Twelve E. faecium isolates were resistant to both determine the risk factors for HAI that were associated with glycopeptides antibiotics (vancomycin and teicoplanin) VREF among the MUH ICU inpatients. We found that transfers to the ICU from a ward (p = 0.04) and renal fail- (with a vancomycin MIC  32 g/mL) (VanA phenotype). 780 Moemen et al. Table 1 - ICU-acquired VREF infection risk factors. Factor Patients with E. faecium infections p- value Odds ratio VREFn=12 VSEFn=40 No. (%) No. (%) Sex (male): 7 58.3 25 62.5 0.8 0.84 Diabetes mellitus 3 25.0 7 17.5 0.7 1.6 Neutropenia 4 33.3 10 25.0 0.7 1.5 Neoplastic disease 5 41.7 16 40.0 0.9 1.1 Transfer to the ICU from a ward 8 66.6 12 30.0 0.04* 4.7 Surgery 4 33.3 14 35.0 1 0.9 Immunosuppressive drugs 5 41.7 11 27.5 0.4 1.9 Prior antibiotic treatment 10 83.3 28 70.0 0.5 2.1 Organ failure: Respiratory 3 25 6 15 0.4 1.9 Cardiac 2 16.7 7 17.5 1 0.9 Renal 5 41.7 3 7.5 0.01* 8.8 Neurologic 1 8.3 6 15.0 1 0.5 Liver 3 25 5 12.5 0.4 2.3 During ICU hospitalization: Intravascular catheter 12 100 36 90 0.6 - Urinary catheter 12 100 37 92.5 1 - Mechanical ventilation 12 100 37 92.5 1 - ICU stay duration (days) 0.018* 0.47-5.06 12  5.51 9.23  4.86 * Significant, p-value  0.05; ICU, intensive care unit. Table 2 - Antibiotic use amongst the study patients during their ICU stays. Factor Patients with E. faecium infections p-value Odds ratio VREFn=12 VSEFn=40 No. (%) No. (%) Antibiotic treatment duration, days < 0.001** 8.09-13.91 16  11 5  6 Vancomycin use 5 41.7 12 30.0 0.45 1.66 Extended-spectrum penicillin use 7 58.3 19 47.5 0.5 1.6 Fluoroquinolone use 9 75 16 40.0 1 0.8 Carbapenem use 3 25.0 12 30.0 1 0.8 Aminoglycoside use 6 50.0 8 20.0 0.04* 4 First generation cephalosporin use 2 16.7 18 45.0 0.09 0.2 Second generation cephalosporin use 2 16.7 15 37.5 0.3 0.3 Third generation cephalosporin use 6 50.0 6 15.0 0.01* 5.7 *Significant, p-value  0.05; **highly significant, p-value  0.001. ures (P = 0.01) were associated with VREF infections. Intra ferent from other studies in which dialysis was not associ- hospital transfer was associated with VREF colonization or ated with the VREF infection incidences (Webb et al., infection in other studies (Tornieporth et al., 1996; Webb et 2001; Handwerger et al., 1993; Descheemaeker et al., al., 2001). The patients may have acquired E. facium during 2000). Patients who require hemodialysis often have com- their ward stay, which later caused infections during their plicated illnesses and may receive multiple antibiotic cour- ICU stays. However, our study showed that renal failure ses, including vancomycin, which places them at greater was a risk factor for VREF infection acquisition. This is dif- risk for VREF infection or colonization. Frequent hospital- Vancomycin resistant E. faecium 781 data show that all of the strains were not from the same clone, indicating multiple acquisitions of resistant isolates. However, the VREF infections within the ICUs of one hos- pital (the EICUs) may result from cross transmission of prevalent isolates. This shows that spread occurred within the ICUs of an individual hospital but not in the other hospi- tals. This might be because the EICUs have more critical care cases compared with the other ICUs (e.g., care for pa- tients with acute, life-threatening illnesses or injuries), in which VRE infection prevention measures are more impor- tant than in the other ICU type’s. Similarly other studies have documented the spread of VREF clones among hospi- tals (Sader et al., 1994; Fridkin et al., 1998; Nourse et al., 2000; Corso et al., 2007). The microorganism can be trans- mitted by health care workers in particular via their hands which are most likely the most common mode of noso- comial transmission (Boyce et al., 1994). VREF transmis- sion by way of contaminated medical equipment and health care carriers has been investigated and shown to occur in different hospitals sections especially in the dialysis ward Figure 1 - SmaI restriction endonuclease patterns obtained by PFGE: (Kalocheretis et al., 2004). Adherence to infection control Lane M marker; lane 1, patient 1 (SMICU); lanes 2, 3and 4 (EICUs); precautions by ICU staff members may also affect possible lane5, (PICU); lanes 6 and 7, (EICUs); lane 8, (PICU); lane 9, (SMICU); VREF transmission. Other distinct strains may come from lane 10, (SMICU); lane 11, (SMICU); lane 12, (EICU). intrinsic E. facium, which is selected for under selective pressure. Thus, infection control policy, in conjunction izations and cross-transmission can also contribute to with practices that control antimicrobial use, is important to VREF infection in patients undergoing hemodialysis combat VREF infection transmission in these high-risk pa- (Chow et al., 1993; Roghmann et al., 1998). The other risk tients. Moreover, our data ensure that standard efforts to re- factor for VREF infection in the ICU was longer ICU stay duce cross-transmission might be needed hospital-wide duration (p = 0.018). This result consistant with most previ- because the VREF rates outside of the ICUs greatly affect ous studies (Ostrowsky et al., 1999; Warren et al., 2003; Se the ICU- specific VREF rates. et al., 2009; Pan et al., 2012; Fridkin et al., 2001). Longer ICU stays can indicate a greater chance of receiving antibi- References otics and also a longer exposure time to possible pathogen Antonishyn NA, McDonald RR, Chan E et al. (2000) Evaluation transmission. Our study showed that patients who had a of fluorescence-based amplified fragment length polymor- prior exposure to broad-spectrum antibiotics and for a pro- phism analysis for molecular typing in hospital epidemiol- longed duration were at a higher risk of VREF infections ogy: comparison with pulsed-field gel electrophoresis for due to the selective pressure from prior antibiotics. Interest- typing strains of vancomycin resistant Enterococcus faecium. J Clin Microbiol 38:4058-4065. ingly, in this study, vancomycin use was not found to be a Arias CA, Murray BE (2012) The rise of the Enterococcus: be- risk factor for VREF infection, which is different from yond vancomycin resistance. Nat Rev Microbiol 10:266- other studies (Tornieporth et al., 1996; Fridkin et al., 2001). This can be explained by the theory that in medical settings Bhavnani SM, Drake JA, Forrest A et al. (2000) A nationwide, in which VREF infections are endemic, the patients with multicenter, case-control study comparing risk factors, treat- VREF colonization may serve as a source for already anti- ment, and outcome for vancomycin-resistant and -suscepti- biotic resistant E. faecium strains in patients who have not ble enterococcal bacteremia. Diagn Microbiol Infect Dis necessarily received glycopeptide antibiotics (Murray, 36:145-158. 2000; Hayden, 2000). According to the PFGE analysis, Boyce JM, Opal SM, Chow JW et al. (1994) Outbreak of multi- drug-resistant Enterococcus faecium with transferable vanB there were nine pulsotypes that were noted during the study class vancomycin resistance. J Clin Microbiol 32:1148- period. The PFGE analysis showed different patterns in the different ICUs of the three hospitals, except for the EICUs Chow JW, Kuritza A, Shlaes DM et al. (1993) Clonal spread of in the emergency hospital, in which the 6 VREF isolates vancomycin- resistant Enterococcus faecium between pa- showed 3 different patterns. Specifically, 3 isolates be- tients in three hospitals in two states. J Clin Microbiol longed to the same pulsotype and another 2 carried similar 31:1609-1611. pulsotypes, indicating that there was a spread within the Coque TM, Tomayko JF, Ricke SC et al. (1996) Vancomycin- ICUs of one hospital (the emergency hospital). Thus, our resistant enterococci from nosocomial, community, and ani- 782 Moemen et al. mal sources in the United States. Antimicrob Agents ria for specific types of infections in the acute care setting. Chemother 40:2605-2609. Am J Infect Control 36:309-332. Corso AC, Gagetti PS, Rodríguez MM et al. (2007) Molecular ep- Institute CaLS (2011) Performance standards for antimicrobial idemiology of vancomycin-resistant Enterococcus faecium susceptibility testing: 17th informational supplement, in Argentina. Int J Infect Dis 11:69-75. M100-S21. Wayne, PA.:Clinical and Laboratory Standards Descheemaeker P, Ieven M, Chapelle S et al. (2000) Prevalence Institute. and molecular epidemiology of glycopeptide-resistant Jett BD, Huycke MM, Gilmore MS (1994) Virulence of enterococci in Belgian renal dialysis units. J Infect Dis enterococci. Clin Microbiol Rev 7:462-478. 181:235-241. Johnson AP, Uttley AH, Woodford N et al. (1990) Resistance to Deshpande LM, Fritsche TR, Moet GJ et al. (2007) Antimicrobial vancomycin and teicoplanin: an emerging clinical problem. resistance and molecular epidemiology of vancomycin- Clin Microbiol Rev 3:280-291. resistant enterococci from North America and Europe: a re- Jones RN, Sader HS, Erwin ME et al. (1995) Emerging multiply port from the SENTRY antimicrobial surveillance program. resistant enterococci among clinical isolates. I. Prevalence Diagn Microbiol Infect Dis 58:163-170. data from 97 medical center surveillance study in the United Edmond MB, Ober JF, Dawson JD et al. (1996) Vancomy- States. Enterococcus Study Group. Diagn Microbiol Infect cin-resistant enterococcal bacteremia: Natural history and Dis 21:85-93. attributable mortality. Clin Infect Dis 23:1234-1239. Kalocheretis P, Baimakou E, Zerbala S et al. (2004) Dissemina- Fridkin SK, Edwards JR, Courval JM et al. (2001) Intensive Care tion of vancomycin-resistant enterococci among haemo- Antimicrobial Resistance Epidemiology (ICARE) Project dialysis patients in Athens, Greece. J Antimicrob Chemother and the National Nosocomial Infections Surveillance 54:1031-1034. (NNIS) System Hospitals. The effect of vancomycin and Kapoor L, Randhawa VS, Deb M (2005) Antimicrobial resistance third-generation cephalosporins on prevalence of vanco- of enterococcal blood isolates at a pediatric care hospital in mycin-resistant enterococci in 126 U.S. adult intensive care India. Jpn J Infect Dis 58:101-103. units. Ann Intern Med 135:175-183. Kaur N, Chaudhary U, Aggarwal R et al. (2009) Emergence of Fridkin SK, Yokoe DS, Whitney CG et al. (1998) Epidemiology VRE and their antimicrobial sensitivity pattern in a tertiary of a dominant clonal strain of vancomycin-resistant care teaching hospital. J Med Biol Sci 8:26-32. Enterococcus faecium at separate hospitals in Boston, Mas- Leavis HL, Willems RJ, van Wamel WJ et al. (2007) Insertion se- sachusetts. J Clin Microbiol 36:965-970. quence-driven diversification creates a globally dispersed Ghonaim M, Ghoniem E, Abdulaziz A et al. (2009) Enterococci emerging multiresistant subspecies of E. faecium. PLoS in Hospital Associated Infection in the National Liver Insti- Pathog 3:75-96. tute, Egypt. Egy J Med Microbiol 18:69-79. Leclercq R, Canton R, Brown DF et al. (2013) EUCAST expert Grayson ML, Eliopoulos GM, Wennersten CB et al. (1991) In- rules in antimicrobial susceptibility testing. Clin Microbiol creasing resistance to beta-lactam antibiotics among clinical Infect 19:141-160. isolates of Enterococcus faecium: a 22-year review at one Mathur P, Kapil A, Chandra R et al. (2003) Antimicrobial resis- institution. Antimicrob Agents Chemother 35:2180-2184. tance in Enterococcus faecalis at a tertiary care centre of Handwerger S, Raucher B, Altarac D et al. (1993) Nosocomial northern India. Indian J Med Res 118:25-28. outbreak due to Enterococcus faecium highly resistant to Murray BE (2000) Vancomycin-resistant enterococcal infections. vancomycin, penicillin, and gentamicin. Clin Infect Dis N Engl J Med 342:710-721. 16:750-755. NNIS (2004) National Nosocomial Infections Surveillance Hayden MK (2000) Insights into the epidemiology and control of (NNIS) System Report, data summary from January 1992 infection with vancomycin-resistant enterococci. Clin Infect through June 2004, issued October 2004. Am J Infect Con- Dis 31:1058-1065. trol 32:470-485. Heikens E, Bonten MJ, Willems RJ (2007) Enterococcal surface Noble WC, Virani Z, Cree RG (1992) Co-transfer of vancomycin protein Esp is important for biofilm formation of and other resistance genes from Enterococcus faecalis Enterococcus faecium E1162. J Bacteriol 189:8233-8240. NCTC 12201 to Staphylococcus aureus. FEMS Microbiol Heikens E, Singh KV, Jacques-Palaz KD et al. (2011) Contribu- Lett 72:195-198. tion of the enterococcal surface protein Esp to pathogenesis Nourse C, Byrne C, Kaufmann M et al. (2000) VRE in the Repub- of Enterococcus faecium endocarditis. Microbes Infect lic of Ireland: clinical significance, characteristics and mo- 13:1185-1190. lecular similarity of isolates. J Hosp Inf 44:288-293. Heikens E, van Schaik W, Leavis HL et al. (2008) Identification Ostrowsky BE, Venkataraman L, D’Agata EMC et al. (1999) of a novel genomic island specific to hospital-acquired Vancomycin-Resistant Enterococci in Intensive Care Units: clonal complex 17 Enterococcus faecium isolates. Appl En- High Frequency of Stool Carriage During a Non-Outbreak viron Microbiol 74:7094-7097. Period. Arch Intern Med 159:1467-1472. Hidron AI, Edwards JR, Patel J et al. (2008) NHSN annual up- Pan SC, Wang JT, Chen YC et al. (2012) Incidence of and risk date: antimicrobial-resistant pathogens associated with factors for infection or colonization of vancomycin-resistant healthcare-associated infections: annual summary of data enterococci in patients in the intensive care unit. PLoS ONE reported to the national healthcare safety network at the cen- 7:e47297. ters for disease control and prevention, 2006-2007. Infect Panesso D1, Reyes J, Rincón S et al. (2010) Molecular epidemiol- Control Hosp Epidemiol 29:996-1011. ogy of vancomycin-resistant Enterococcus faecium: a pro- Horan TC, Andrus M, Dudeck MA (2008) CDC/NHSN surveil- spective, multicenter study inSouth American hospitals. J lance definition of health care-associated infection and crite- Clin Microbiol 48:1562-1569. Vancomycin resistant E. faecium 783 Praharaj I, Sujatha S, Parija SC (2013) Phenotypic & genotypic Top J, Willems R, Bonten M (2008) Emergence of CC17 characterization of vancomycin resistant Enterococcus iso- Enterococcus faecium: from commensal to hospital-adapted lates from clinical specimens. Indian J Med Res 138:549- pathogen. FEMS Immunol Med Microbiol 52:297-308. 556. Tornieporth NG, Roberts RB, John J et al. (1996) Risk factors as- sociated with vancomycin-resistant Enterococcus faecium Rice LB (2001) Emergence of vancomycin-resistant enterococci. infection or colonization in 145 matched case patients and Emerg Infect Dis 7:183-187. control patients. Clin Infect Dis 23:767-772. Tornieporth NG, Roberts RB, John J et al. (1996) Risk factors as- Rice LB (2006) Antimicrobial resistance in gram-positive bacte- sociated with vancomycin-resistant Enterococcus faecium ria. Am J Med 119:11-19. Roghmann MC, Fink JC, Polish L infection or colonization in 145 matched case patients and et al. (1998) Colonization with vancomycin-resistant control patients. Clin Infect Dis 23:767-772. enterococci in chronic hemodialysis patients. Am J Kidney Uttley AH, Collins CH, Naidoo J et al. (1988) Vancomycin- Dis 32:254-257. resistant enterococci. Lancet 1:57-58. Sader HS, Pfaller MA, Tenover FC et al. (1994) Evaluation and van Schaik W, Top J, Riley DR et al. (2010) Pyrosequencing- characterization of multiresistant Enterococcus faecium based comparative genome analysis of the nosocomial from 12 U.S. medical centers. J Clin Microbiol 32:2840- pathogen Enterococcus faecium and identification of a large transferable pathogenicity island. BMC Genomics 11:239. Vergis EN, Hayden MK, Chow JW et al. (2001) Determinants of Schooneveld TV, Rupp ME (2010) Control of Gram-positive vancomycin resistance and mortality rates in enterococcal multidrug-resistant pathogens. In: Lautenbach E, Woeltje bacteremia. A prospective multicenter study. Ann Intern KF, Malani PN, editors. Practical healthcare epidemiology. Med 135:484-492. 3rd ed. Chicago, United States: The University of Chicago Warren DK, Kollef MH, Seiler S et al. (2003) The Epidemiology Press p. 197-208. of Vancomycin-Resistant Enterococcus Colonization in a Se YB, Chun HJ, Yi HJ et al. (2009) Incidence and risk factors of Medical Intensive Care Unit Infect Control Hosp Epidemiol infection caused by vancomycin-resistant enterococcus col- 24:257-263. Webb M, Riley LW, Roberts RB (2001) Cost of hospitalization onization in neuro- surgical intensive care unit patients. J for and risk factors associated with vancomycin-resistant Korean Neurosurg Soc 46:123-129. Enterococcus faecium infection and colonization. Clin In- Taneja N, Rani P, Emmanuel R et al. (2004) Significance of fect Dis 33:445-452. vancomycin resistant enterococci from urinary specimens at Willems RJ, van Schaik W (2009) Transition of Enterococcus a tertiary care centre in northern India. Indian J Med Res faecium from commensal organism to nosocomial pathogen. 119:72-74. Future Microbiol 4:1125-1135. Tenover FC, Arbeit RD, Goering RV et al. (1995) Interpreting Associate Editor: Roxane Maria Fontes Piazza chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain All the content of the journal, except where otherwise noted, is licensed under a typing. J Clin Microbiol 33:2233-2239. Creative Commons License CC BY-NC. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Brazilian Journal of Microbiology Pubmed Central

Healthcare-associated vancomycin resistant Enterococcus faecium infections in the Mansoura University Hospitals intensive care units, Egypt

Brazilian Journal of Microbiology , Volume 46 (3) – Jul 1, 2015

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Abstract

Vancomycin resistant Enterococcus faecium (VREF) ia an emerging and challenging nosocomial pathogen. This study aimed to determine the prevalence, risk factors and clonal relationships be- tween different VREF isolates in the intensive care units (ICUs) of the university hospitals in our geo- graphic location. This prospective study was conducted from July, 2012 until September, 2013 on 781 patients who were admitted to the ICUs of the Mansoura University Hospitals (MUHs), and ful- filled the healthcare-associated infection (HAI) criteria. Susceptibility testing was determined using the disk diffusion method. The clonal relationships were evaluated with pulsed field gel electropho- resis (PFGE). Out of 52 E. faecium isolates, 12 (23.1%) were vancomycin resistant. The significant risk factors for the VREF infections were: transfer to the ICU from a ward, renal failure, an extended ICU stay and use of third-generation cephalosporins, gentamicin, or ciprofloxacin. PFGE with the 12 isolates showed 9 different patterns; 3 belonged to the same pulsotype and another 2 carried a second pulsotypes. The similar pulsotypes isolates were isolated from ICUs of one hospital (EICUs); how- ever, all of the isolates from the other ICUs had different patterns. Infection control policy, in con- junction with antibiotic stewardship, is important to combat VREF transmission in these high-risk patients. Key words: Enterococcus faecium, ICU, vancomycin, risk factors, PFGE. In addition to this distinct resistance profile, genomic analyses have shown that hospital acquired E. faecium Introduction strains have a genetic repertoire that is distinct from that of Enterococci are opportunistic pathogens of the nor- community associated E. faecium strains that asympto- mal humans and animals intestinal microbiota. The most matically colonize the human gastrointestinal tract (van common Enterococcus species that is involved in noso- Schaik et al., 2010). This distinct genetic repertoire in- comial infections is Enterococcus faecium (E. faecium) cludes the enterococcal surface protein, Esp, which is a (Top et al., 2008; Arias and Murray, 2012). known virulence determinant (Heikens et al., 2007; 2011). Genomic islands that encode novel metabolic pathways E. faecium has become one of the most important, (Heikens et al., 2008), and insertion sequence elements emerging and challenging nosocomial pathogens (Arias (Leavis et al., 2007). It is now considered that these deter- and Murray, 2012). It is a difficult to treat this pathogen due minants may be adaptive elements that have improved the to its intrinsic resistance to cephalosporins, aminogly relative fitness of E. faecium subpopulations in the hospital cosides, clindamycin and trimethoprim-sulfamethoxazole environment (Willems and van Schaik, 2009). Due to the (Leclercq et al., 2013). Moreover, it has the ability to easily acquire antibiotic resistance genes trough transfer of plas- resistance of multiple antibiotics, the treatment of choice in serious E. faecium infections is glycopeptides. However, mids, chromosomal exchange or mutation (Jett et al., 1994). prudent use of vancomycin is needed as it is associated with Send correspondence to D. Moemen. Department of Medical Microbiology and Immunology, Faculty of Medicine, Mansoura University, Egypt. E-mail: dr_daliamoemen@yahoo.com. 778 Moemen et al. an increased risk for vancomycin resistant enterococci and C. children hospital ICUs, which included pediatric (VRE) colonization and infection (Tornieporth et al., (PICU), neonatal ICU (NICU) and surgical ICU (SICU). 1996). Study population In the last decades, the number of VRE infections has This study included 781 patients (who provided writ- increased (Grayson et al., 1991; Jones et al., 1995; Rice, ten consent) that were admitted to different MUHs ICUs 2001). The first VRE isolates were reported in the United and fulfilled the healthcare-associated infection (HAI) cri- Kingdom in the late 1980s (Uttley et al., 1988). In the United States, more than 80% of E. faecium isolates from teria. (Infections acquired  48 hours after admission that hospitals are vancomycin resistant (Hidron et al., 2008). were not present or incubating at the time of hospital admis- Vancomycin-resistant E. faecium (VREF) has been associ- sion). The infection types were documented with specific ated with outbreaks in hospitals worldwide (Arias and Mur- HAIs definitions, which were established by the Centers for ray, 2012). The VREF colonization and infection rates have Disease Control and Prevention (Horan et al., 2008). risen steadily, with most cases being caused by the VanA Data collection and definitions and VanB genotypes, which are the most commonly en- countered glycopeptide resistance forms (Coque et al., The following data were collected: demographic 1996; Rice, 2006; Deshpande et al., 2007). characteristics, ICU stay duration, transfer to the ICU from The clinical impacts of VRE include the limited avai- a ward, diagnosis at ICU admission, medical conditions lability of drugs to treat VRE infections and the ability of that may alter the patient’s immunity (comorbidity) (e.g. VRE to transfer the genetic determinant for vancomycin re- diabetes, malignancy, hepatic impairment, renal impair- sistance to other Gram-positive pathogens, such as Staphy- ment and chronic lung diseases), invasive devices or proce- lococcus aureus (Schooneveld et al., 2008; Noble et al., dures (e.g. surgical procedures, central venous catheter 1992). [CVC], peripheral venous catheter [PVC], mechanical ven- tilation, and total parenteral nutrition [TPN], drug therapy VREF is associated with hospital-acquired infections (e.g. antibiotics and their durations, prior antibiotic treat- such as urinary tract infections, wounds, bacteremia, endo- ment, which was defined as any antibiotic treatment during carditis and meningitis (Top et al., 2008; Arias and Murray, the two weeks preceding ICU admission), immunosup- 2012). Several studies have demonstrated that VRE bacte- pressive therapy (which included steroid therapy, cytotoxic raemia patients have a higher mortality rate than those in- chemotherapy or radiotherapy given within one month fected with vancomycin-susceptible enterococci (Vergis et prior to ICU admission), and neutropenia (less than 500 al., 2001; Edmond et al., 1996; Bhavnani et al., 2000). neutrophils per mm ) Information regarding the VRE Infections prevalence A “case patient” was defined as patient who was in- in Egypt indicates that there is an increasing VRE infection fected with VREF and was attending a Mansoura Univer- rate. Ghonaim et al. (2009) reported that VRE isolates con- sity ICU during the study period. A “control patient” was stituted 20.9% of hospital associated enterococcal infec- defined as a Vancomycin susceptible Enterococcus tions at the Egyptian National Liver Institute. faecium (VSEF) infected patient who was attending a To control the rapid spread of multidrug resistant or- Mansoura University ICU during the same period. The pa- ganisms, it is necessary to understand the risk factors for tients whose initial isolate was susceptible to vancomycin acquiring them. Therefore, the aim of this study was to but who subsequently had VREF isolates that were recov- identify the VREF prevalence and possible risk factors in ered were included as case patients. ICU patients who are at high risk of VREF infection. Addi- tionally, we aimed to identify the clonal relationship be- Microbiologic studies tween different isolates via pulsed-field gel electrophoresis The samples were processed in the Medical Diagnos- (PFGE). tics and Infection Control Unit (MDICU) laboratory using standard protocols. E. faecium laboratory identification Materials and Methods was performed by Gram stain, colonial morphology on blood agar, growth and blackening of bile esculin agar, the Patients and methods absence of catalase production, resistance to 6.5% sodium Study design chloride. The results were confirmed with the API 20 Strep (Biomerieux SA, Montalieu - Vercica and France) system. This was a prospective study, which was conducted in In vitro susceptibilities of the isolates to antimicrobials nine ICUs in three different MUHs, that were situated were determined with the disk diffusion method which was within the same geographical region over a 15 months pe- defined by the [CLSI] (Institute CaLS, 2011). The antibiot- riod from July, 2012 until September, 2013. The ICU bed ics that were tested included ampicillin (10 g), cipro- numbers range from 4 to 27, with a median of 10. They ICUs were categorized as: A. emergency hospital ICUs floxacin (5 g), high content gentamicin (120 g), erythro- (EICUs), B. specialized medical hospital ICUs (SMICUs) mycin (15 g), tetracycline (30 g), vancomycin (30 g), Vancomycin resistant E. faecium 779 All VREF isolates (100%) were resistant to ampicillin, teicoplanin (30 g), linezolid (30 g), and chloramphenicol gentamicin, and ciprofloxacin. Most of the isolates (92%) (30 g). Glycopeptide antibiotics MICs for: vancomycin were resistant to erythromycin (only one isolate was sensi- and teicoplanin against the E. faecium isolates were exam- tive), and 5 isolates were resistant to tetracycline (42%). All ined with the VITEK 2 system (bioMérieux). of the strains were sensitive to linezolid and chloram- PFGE phenicol. The clonal relationships between the vancomycin- The ICU-acquired VREF Risk factors resistant strains were studied by evaluating the genomic DNA with PFGE (Antonishyn et al., 2000). DNA that was Among the 52 E. faecium infected patients, 40 restricted with the SmaI enzyme was separated on an aga- (76.9%) had VSEF infections (control patients), and 12 rose gel using a CHEF DR III apparatus (Bio-Rad laborato- (23.1%) had VREF infections (case patients). The compar- ries). The running conditions were 6 V per cm, with pulses ative demographic and clinical features for both the case and controls patients are listed in Tables 1 and 2. The risk ranging from 2 to 15 s for 18 h at 14 C. The DNA banding factors that were significantly associated with the ICU- patterns were visualized under UV light after staining with acquired VREF infections were: transfer to the ICU from a ethidium bromide (0.5 mg/mL). The similarities between ward (p = 0.04), renal failure (p = 0.01), and longer ICU the isolates were determined by visual comparison of the stay duration (p = 0.018). Additionally, antibiotic use for a isolate band patterns. The interpretation of the PFGE re- long period of time and use of third-generation cepha- sults was carried out by eye according to the criteria de- losporins, gentamicin, or ciprofloxacin were also associ- scribed by Tenover et al. (1995). ated with VREF infections. Statistical analysis PFGE The SPSS software (SPSS Inc., Chicago, IL, USA) was used for data analyseis. Proportions were compared us- The restriction endonuclease patterns obtained with the PFGE following the SmaI treatment for the 12 VREF ing the 2 test and continuous variables were compared us- isolates are presented in Figure 1. In general, the 12 isolates ing Student’s t or Mann-Whitney U tests. The results are showed 9 different patterns. Three isolates belonged to the presented as numbers (percentages) for frequency and as same pulsotype and another 2 carried similar pulsotypes. the mean  standard deviation for quantitative variables. Of interest, the isolates with similar pulsotypes were iso- Odds ratios (OR) [95% confidence interval (CI)] were cal- lated from the ICUs of one hospital (EICUs); however, all culated for all significant (p < 0.05) qualitative variables in of the isolates from the other ICUs had different patterns. the univariate analyseis. Discussion Results E. faecium is a highly resistant nosocomial pathogen VREF Prevalence in the ICUs and has recently emerged as an important threat in hospitals During the study period, a total of 975 specimens worldwide (Arias and Murray, 2012). In this study, VREF were collected from 782 patients, with clinically suspected constituted 23.1% of the observed E. faecium isolates, a re- HAIs in MUHs ICUs. Out of 52 E. faecium isolates de- sult that was close to the Ghonaim et al. study observations, tected, 12 were VREF, which constituted (12/52) 23.1% of in which the VRE isolates constituted 20.9% of the hospi- the E. faecium isolates. tal-associated enterococcal infections at the National Liver Institute (Ghonaim et al., 2009), which indicated a big VREF isolates problem in Egypt. Similar studies from the United States Twelve VREF single-patient isolates (i.e., 1 isolate reported vancomycin resistance in up to 28% of all noso- per patient) were obtained from the following sites: urine (7 comial Enterococcus species (NNIS, 2004). However stud- isolates), blood (3 isolates) and wound (2 isolates). A total ies from India and South America showed much lower of of 12 infections were documented in 12 patients, including VRE infection prevalence ranging from 1- 8.7% (Mathur et urinary tract infection (7 patients), bacteremia instances (3 al., 2003; Taneja et al., 2004; Kapoor et al., 2005; Kaur et patients), and surgical site infection (2 patients). Of these al., 2009; Praharaj et al., 2003; Panesso et al., 2013). E. 12 patients, 6 isolates were obtained from the emergency faecium antibiotics sensitivity pattern in the present study is hospital ICUs, 4 were obtained from the ICUs of the spe- consistent with the concept that vancomycin resistance is cialized medical hospital and 2 were from PICUs. usually accompanied by resistance to other antimicrobial agents, such as penicillin, ampicillin, erythromycin, cipro- Antibiotic susceptibility testing of the VREF isolates floxacin and gentamicin. The objective of this study was to Twelve E. faecium isolates were resistant to both determine the risk factors for HAI that were associated with glycopeptides antibiotics (vancomycin and teicoplanin) VREF among the MUH ICU inpatients. We found that transfers to the ICU from a ward (p = 0.04) and renal fail- (with a vancomycin MIC  32 g/mL) (VanA phenotype). 780 Moemen et al. Table 1 - ICU-acquired VREF infection risk factors. Factor Patients with E. faecium infections p- value Odds ratio VREFn=12 VSEFn=40 No. (%) No. (%) Sex (male): 7 58.3 25 62.5 0.8 0.84 Diabetes mellitus 3 25.0 7 17.5 0.7 1.6 Neutropenia 4 33.3 10 25.0 0.7 1.5 Neoplastic disease 5 41.7 16 40.0 0.9 1.1 Transfer to the ICU from a ward 8 66.6 12 30.0 0.04* 4.7 Surgery 4 33.3 14 35.0 1 0.9 Immunosuppressive drugs 5 41.7 11 27.5 0.4 1.9 Prior antibiotic treatment 10 83.3 28 70.0 0.5 2.1 Organ failure: Respiratory 3 25 6 15 0.4 1.9 Cardiac 2 16.7 7 17.5 1 0.9 Renal 5 41.7 3 7.5 0.01* 8.8 Neurologic 1 8.3 6 15.0 1 0.5 Liver 3 25 5 12.5 0.4 2.3 During ICU hospitalization: Intravascular catheter 12 100 36 90 0.6 - Urinary catheter 12 100 37 92.5 1 - Mechanical ventilation 12 100 37 92.5 1 - ICU stay duration (days) 0.018* 0.47-5.06 12  5.51 9.23  4.86 * Significant, p-value  0.05; ICU, intensive care unit. Table 2 - Antibiotic use amongst the study patients during their ICU stays. Factor Patients with E. faecium infections p-value Odds ratio VREFn=12 VSEFn=40 No. (%) No. (%) Antibiotic treatment duration, days < 0.001** 8.09-13.91 16  11 5  6 Vancomycin use 5 41.7 12 30.0 0.45 1.66 Extended-spectrum penicillin use 7 58.3 19 47.5 0.5 1.6 Fluoroquinolone use 9 75 16 40.0 1 0.8 Carbapenem use 3 25.0 12 30.0 1 0.8 Aminoglycoside use 6 50.0 8 20.0 0.04* 4 First generation cephalosporin use 2 16.7 18 45.0 0.09 0.2 Second generation cephalosporin use 2 16.7 15 37.5 0.3 0.3 Third generation cephalosporin use 6 50.0 6 15.0 0.01* 5.7 *Significant, p-value  0.05; **highly significant, p-value  0.001. ures (P = 0.01) were associated with VREF infections. Intra ferent from other studies in which dialysis was not associ- hospital transfer was associated with VREF colonization or ated with the VREF infection incidences (Webb et al., infection in other studies (Tornieporth et al., 1996; Webb et 2001; Handwerger et al., 1993; Descheemaeker et al., al., 2001). The patients may have acquired E. facium during 2000). Patients who require hemodialysis often have com- their ward stay, which later caused infections during their plicated illnesses and may receive multiple antibiotic cour- ICU stays. However, our study showed that renal failure ses, including vancomycin, which places them at greater was a risk factor for VREF infection acquisition. This is dif- risk for VREF infection or colonization. Frequent hospital- Vancomycin resistant E. faecium 781 data show that all of the strains were not from the same clone, indicating multiple acquisitions of resistant isolates. However, the VREF infections within the ICUs of one hos- pital (the EICUs) may result from cross transmission of prevalent isolates. This shows that spread occurred within the ICUs of an individual hospital but not in the other hospi- tals. This might be because the EICUs have more critical care cases compared with the other ICUs (e.g., care for pa- tients with acute, life-threatening illnesses or injuries), in which VRE infection prevention measures are more impor- tant than in the other ICU type’s. Similarly other studies have documented the spread of VREF clones among hospi- tals (Sader et al., 1994; Fridkin et al., 1998; Nourse et al., 2000; Corso et al., 2007). The microorganism can be trans- mitted by health care workers in particular via their hands which are most likely the most common mode of noso- comial transmission (Boyce et al., 1994). VREF transmis- sion by way of contaminated medical equipment and health care carriers has been investigated and shown to occur in different hospitals sections especially in the dialysis ward Figure 1 - SmaI restriction endonuclease patterns obtained by PFGE: (Kalocheretis et al., 2004). Adherence to infection control Lane M marker; lane 1, patient 1 (SMICU); lanes 2, 3and 4 (EICUs); precautions by ICU staff members may also affect possible lane5, (PICU); lanes 6 and 7, (EICUs); lane 8, (PICU); lane 9, (SMICU); VREF transmission. Other distinct strains may come from lane 10, (SMICU); lane 11, (SMICU); lane 12, (EICU). intrinsic E. facium, which is selected for under selective pressure. Thus, infection control policy, in conjunction izations and cross-transmission can also contribute to with practices that control antimicrobial use, is important to VREF infection in patients undergoing hemodialysis combat VREF infection transmission in these high-risk pa- (Chow et al., 1993; Roghmann et al., 1998). The other risk tients. Moreover, our data ensure that standard efforts to re- factor for VREF infection in the ICU was longer ICU stay duce cross-transmission might be needed hospital-wide duration (p = 0.018). This result consistant with most previ- because the VREF rates outside of the ICUs greatly affect ous studies (Ostrowsky et al., 1999; Warren et al., 2003; Se the ICU- specific VREF rates. et al., 2009; Pan et al., 2012; Fridkin et al., 2001). Longer ICU stays can indicate a greater chance of receiving antibi- References otics and also a longer exposure time to possible pathogen Antonishyn NA, McDonald RR, Chan E et al. (2000) Evaluation transmission. Our study showed that patients who had a of fluorescence-based amplified fragment length polymor- prior exposure to broad-spectrum antibiotics and for a pro- phism analysis for molecular typing in hospital epidemiol- longed duration were at a higher risk of VREF infections ogy: comparison with pulsed-field gel electrophoresis for due to the selective pressure from prior antibiotics. Interest- typing strains of vancomycin resistant Enterococcus faecium. J Clin Microbiol 38:4058-4065. ingly, in this study, vancomycin use was not found to be a Arias CA, Murray BE (2012) The rise of the Enterococcus: be- risk factor for VREF infection, which is different from yond vancomycin resistance. Nat Rev Microbiol 10:266- other studies (Tornieporth et al., 1996; Fridkin et al., 2001). This can be explained by the theory that in medical settings Bhavnani SM, Drake JA, Forrest A et al. (2000) A nationwide, in which VREF infections are endemic, the patients with multicenter, case-control study comparing risk factors, treat- VREF colonization may serve as a source for already anti- ment, and outcome for vancomycin-resistant and -suscepti- biotic resistant E. faecium strains in patients who have not ble enterococcal bacteremia. Diagn Microbiol Infect Dis necessarily received glycopeptide antibiotics (Murray, 36:145-158. 2000; Hayden, 2000). According to the PFGE analysis, Boyce JM, Opal SM, Chow JW et al. (1994) Outbreak of multi- drug-resistant Enterococcus faecium with transferable vanB there were nine pulsotypes that were noted during the study class vancomycin resistance. J Clin Microbiol 32:1148- period. The PFGE analysis showed different patterns in the different ICUs of the three hospitals, except for the EICUs Chow JW, Kuritza A, Shlaes DM et al. (1993) Clonal spread of in the emergency hospital, in which the 6 VREF isolates vancomycin- resistant Enterococcus faecium between pa- showed 3 different patterns. Specifically, 3 isolates be- tients in three hospitals in two states. J Clin Microbiol longed to the same pulsotype and another 2 carried similar 31:1609-1611. pulsotypes, indicating that there was a spread within the Coque TM, Tomayko JF, Ricke SC et al. (1996) Vancomycin- ICUs of one hospital (the emergency hospital). Thus, our resistant enterococci from nosocomial, community, and ani- 782 Moemen et al. mal sources in the United States. Antimicrob Agents ria for specific types of infections in the acute care setting. Chemother 40:2605-2609. Am J Infect Control 36:309-332. Corso AC, Gagetti PS, Rodríguez MM et al. (2007) Molecular ep- Institute CaLS (2011) Performance standards for antimicrobial idemiology of vancomycin-resistant Enterococcus faecium susceptibility testing: 17th informational supplement, in Argentina. Int J Infect Dis 11:69-75. M100-S21. Wayne, PA.:Clinical and Laboratory Standards Descheemaeker P, Ieven M, Chapelle S et al. (2000) Prevalence Institute. and molecular epidemiology of glycopeptide-resistant Jett BD, Huycke MM, Gilmore MS (1994) Virulence of enterococci in Belgian renal dialysis units. J Infect Dis enterococci. Clin Microbiol Rev 7:462-478. 181:235-241. Johnson AP, Uttley AH, Woodford N et al. (1990) Resistance to Deshpande LM, Fritsche TR, Moet GJ et al. (2007) Antimicrobial vancomycin and teicoplanin: an emerging clinical problem. resistance and molecular epidemiology of vancomycin- Clin Microbiol Rev 3:280-291. resistant enterococci from North America and Europe: a re- Jones RN, Sader HS, Erwin ME et al. (1995) Emerging multiply port from the SENTRY antimicrobial surveillance program. resistant enterococci among clinical isolates. I. Prevalence Diagn Microbiol Infect Dis 58:163-170. data from 97 medical center surveillance study in the United Edmond MB, Ober JF, Dawson JD et al. (1996) Vancomy- States. Enterococcus Study Group. Diagn Microbiol Infect cin-resistant enterococcal bacteremia: Natural history and Dis 21:85-93. attributable mortality. Clin Infect Dis 23:1234-1239. Kalocheretis P, Baimakou E, Zerbala S et al. (2004) Dissemina- Fridkin SK, Edwards JR, Courval JM et al. (2001) Intensive Care tion of vancomycin-resistant enterococci among haemo- Antimicrobial Resistance Epidemiology (ICARE) Project dialysis patients in Athens, Greece. J Antimicrob Chemother and the National Nosocomial Infections Surveillance 54:1031-1034. (NNIS) System Hospitals. The effect of vancomycin and Kapoor L, Randhawa VS, Deb M (2005) Antimicrobial resistance third-generation cephalosporins on prevalence of vanco- of enterococcal blood isolates at a pediatric care hospital in mycin-resistant enterococci in 126 U.S. adult intensive care India. Jpn J Infect Dis 58:101-103. units. Ann Intern Med 135:175-183. Kaur N, Chaudhary U, Aggarwal R et al. (2009) Emergence of Fridkin SK, Yokoe DS, Whitney CG et al. (1998) Epidemiology VRE and their antimicrobial sensitivity pattern in a tertiary of a dominant clonal strain of vancomycin-resistant care teaching hospital. J Med Biol Sci 8:26-32. Enterococcus faecium at separate hospitals in Boston, Mas- Leavis HL, Willems RJ, van Wamel WJ et al. (2007) Insertion se- sachusetts. J Clin Microbiol 36:965-970. quence-driven diversification creates a globally dispersed Ghonaim M, Ghoniem E, Abdulaziz A et al. (2009) Enterococci emerging multiresistant subspecies of E. faecium. PLoS in Hospital Associated Infection in the National Liver Insti- Pathog 3:75-96. tute, Egypt. Egy J Med Microbiol 18:69-79. Leclercq R, Canton R, Brown DF et al. (2013) EUCAST expert Grayson ML, Eliopoulos GM, Wennersten CB et al. (1991) In- rules in antimicrobial susceptibility testing. Clin Microbiol creasing resistance to beta-lactam antibiotics among clinical Infect 19:141-160. isolates of Enterococcus faecium: a 22-year review at one Mathur P, Kapil A, Chandra R et al. (2003) Antimicrobial resis- institution. Antimicrob Agents Chemother 35:2180-2184. tance in Enterococcus faecalis at a tertiary care centre of Handwerger S, Raucher B, Altarac D et al. (1993) Nosocomial northern India. Indian J Med Res 118:25-28. outbreak due to Enterococcus faecium highly resistant to Murray BE (2000) Vancomycin-resistant enterococcal infections. vancomycin, penicillin, and gentamicin. Clin Infect Dis N Engl J Med 342:710-721. 16:750-755. NNIS (2004) National Nosocomial Infections Surveillance Hayden MK (2000) Insights into the epidemiology and control of (NNIS) System Report, data summary from January 1992 infection with vancomycin-resistant enterococci. Clin Infect through June 2004, issued October 2004. Am J Infect Con- Dis 31:1058-1065. trol 32:470-485. Heikens E, Bonten MJ, Willems RJ (2007) Enterococcal surface Noble WC, Virani Z, Cree RG (1992) Co-transfer of vancomycin protein Esp is important for biofilm formation of and other resistance genes from Enterococcus faecalis Enterococcus faecium E1162. J Bacteriol 189:8233-8240. NCTC 12201 to Staphylococcus aureus. FEMS Microbiol Heikens E, Singh KV, Jacques-Palaz KD et al. (2011) Contribu- Lett 72:195-198. tion of the enterococcal surface protein Esp to pathogenesis Nourse C, Byrne C, Kaufmann M et al. (2000) VRE in the Repub- of Enterococcus faecium endocarditis. Microbes Infect lic of Ireland: clinical significance, characteristics and mo- 13:1185-1190. lecular similarity of isolates. J Hosp Inf 44:288-293. Heikens E, van Schaik W, Leavis HL et al. (2008) Identification Ostrowsky BE, Venkataraman L, D’Agata EMC et al. (1999) of a novel genomic island specific to hospital-acquired Vancomycin-Resistant Enterococci in Intensive Care Units: clonal complex 17 Enterococcus faecium isolates. Appl En- High Frequency of Stool Carriage During a Non-Outbreak viron Microbiol 74:7094-7097. Period. Arch Intern Med 159:1467-1472. Hidron AI, Edwards JR, Patel J et al. (2008) NHSN annual up- Pan SC, Wang JT, Chen YC et al. (2012) Incidence of and risk date: antimicrobial-resistant pathogens associated with factors for infection or colonization of vancomycin-resistant healthcare-associated infections: annual summary of data enterococci in patients in the intensive care unit. PLoS ONE reported to the national healthcare safety network at the cen- 7:e47297. ters for disease control and prevention, 2006-2007. Infect Panesso D1, Reyes J, Rincón S et al. (2010) Molecular epidemiol- Control Hosp Epidemiol 29:996-1011. ogy of vancomycin-resistant Enterococcus faecium: a pro- Horan TC, Andrus M, Dudeck MA (2008) CDC/NHSN surveil- spective, multicenter study inSouth American hospitals. J lance definition of health care-associated infection and crite- Clin Microbiol 48:1562-1569. Vancomycin resistant E. faecium 783 Praharaj I, Sujatha S, Parija SC (2013) Phenotypic & genotypic Top J, Willems R, Bonten M (2008) Emergence of CC17 characterization of vancomycin resistant Enterococcus iso- Enterococcus faecium: from commensal to hospital-adapted lates from clinical specimens. Indian J Med Res 138:549- pathogen. FEMS Immunol Med Microbiol 52:297-308. 556. Tornieporth NG, Roberts RB, John J et al. (1996) Risk factors as- sociated with vancomycin-resistant Enterococcus faecium Rice LB (2001) Emergence of vancomycin-resistant enterococci. infection or colonization in 145 matched case patients and Emerg Infect Dis 7:183-187. control patients. Clin Infect Dis 23:767-772. Tornieporth NG, Roberts RB, John J et al. (1996) Risk factors as- Rice LB (2006) Antimicrobial resistance in gram-positive bacte- sociated with vancomycin-resistant Enterococcus faecium ria. Am J Med 119:11-19. Roghmann MC, Fink JC, Polish L infection or colonization in 145 matched case patients and et al. (1998) Colonization with vancomycin-resistant control patients. Clin Infect Dis 23:767-772. enterococci in chronic hemodialysis patients. Am J Kidney Uttley AH, Collins CH, Naidoo J et al. (1988) Vancomycin- Dis 32:254-257. resistant enterococci. Lancet 1:57-58. Sader HS, Pfaller MA, Tenover FC et al. (1994) Evaluation and van Schaik W, Top J, Riley DR et al. (2010) Pyrosequencing- characterization of multiresistant Enterococcus faecium based comparative genome analysis of the nosocomial from 12 U.S. medical centers. J Clin Microbiol 32:2840- pathogen Enterococcus faecium and identification of a large transferable pathogenicity island. BMC Genomics 11:239. Vergis EN, Hayden MK, Chow JW et al. (2001) Determinants of Schooneveld TV, Rupp ME (2010) Control of Gram-positive vancomycin resistance and mortality rates in enterococcal multidrug-resistant pathogens. In: Lautenbach E, Woeltje bacteremia. A prospective multicenter study. Ann Intern KF, Malani PN, editors. Practical healthcare epidemiology. Med 135:484-492. 3rd ed. Chicago, United States: The University of Chicago Warren DK, Kollef MH, Seiler S et al. (2003) The Epidemiology Press p. 197-208. of Vancomycin-Resistant Enterococcus Colonization in a Se YB, Chun HJ, Yi HJ et al. (2009) Incidence and risk factors of Medical Intensive Care Unit Infect Control Hosp Epidemiol infection caused by vancomycin-resistant enterococcus col- 24:257-263. Webb M, Riley LW, Roberts RB (2001) Cost of hospitalization onization in neuro- surgical intensive care unit patients. J for and risk factors associated with vancomycin-resistant Korean Neurosurg Soc 46:123-129. Enterococcus faecium infection and colonization. Clin In- Taneja N, Rani P, Emmanuel R et al. (2004) Significance of fect Dis 33:445-452. vancomycin resistant enterococci from urinary specimens at Willems RJ, van Schaik W (2009) Transition of Enterococcus a tertiary care centre in northern India. Indian J Med Res faecium from commensal organism to nosocomial pathogen. 119:72-74. Future Microbiol 4:1125-1135. Tenover FC, Arbeit RD, Goering RV et al. (1995) Interpreting Associate Editor: Roxane Maria Fontes Piazza chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain All the content of the journal, except where otherwise noted, is licensed under a typing. J Clin Microbiol 33:2233-2239. Creative Commons License CC BY-NC.

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Published: Jul 1, 2015

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