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Year : 2015  |  Volume : 141  |  Issue : 4  |  Page : 483-486

Antimicrobial susceptibility pattern of vancomycin resistant enterococci to newer antimicrobial agents

Department of Microbiology, Government Medical College Hospital, Sector 32, Chandigarh 160 030, India

Date of Web Publication24-Jun-2015

Correspondence Address:
Varsha Gupta
Department of Microbiology, Government Medical College Hospital, Sector 32, Chandigarh 160 030
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0971-5916.159309

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How to cite this article:
Gupta V, Singla N, Behl P, Sahoo T, Chander J. Antimicrobial susceptibility pattern of vancomycin resistant enterococci to newer antimicrobial agents. Indian J Med Res 2015;141:483-6

How to cite this URL:
Gupta V, Singla N, Behl P, Sahoo T, Chander J. Antimicrobial susceptibility pattern of vancomycin resistant enterococci to newer antimicrobial agents. Indian J Med Res [serial online] 2015 [cited 2020 May 31];141:483-6. Available from:


Enterococci are recognized as opportunistic pathogens and are natural inhabitants of the oral cavity, gastrointestinal tract (GIT) and the female genital tract in both humans and animals [1] . They have emerged as important nosocomial pathogens [2] . There are two main species - Enterococcus faecalis and E. faecium responsible for human enterococcal infections [3] . The most frequent infections caused by these organisms include urinary tract infections, intra-abdominal and intra-pelvic abscesses. These are increasingly being isolated from bacteraemia and meningitis cases mainly from hospitalized patients [4] .

The emergence of resistance to the most common anti-enterococcal antibiotics which include the β-lactam antibiotics like ampicillin, aminoglycosides and most importantly glycopeptides like vancomycin besides being inherently resistant to many others like cephalosporins and clindamycin has made the treatment of these infections a real challenge for clinicians [5] .

With the increase in emergence of resistance in enterococci to vancomycin, treatment of these infections has become difficult especially in serious infections [6] . Since options for the treatment of patients with vancomycin resistant enterococci (VRE) are very limited, this study was aimed to assess the potential usefulness of compounds, which have come into recent use.Newer antibiotics such as linezolid, daptomycin and tigecycline have shown good in vitro activity against VRE [7] . Quinupristin-dalfopristin (Q/D) is another agent that has potent in vitro activity against E. faecium but poor activity against E. faecalis[8] .

This study was conducted in the department of Microbiology, Government Medical College and Hospital, Chandigarh, India. In this study, the in vitro activity of vancomycin, teicoplanin, tigecycline, daptomycin, linezolid and quinupristin/dalfopristin has been evaluated against 75 non-repeat clinical isolates of vancomycin resistant E. faecalis (60) and E. faecium (15) by MIC (minimum inhibitory concentration) testing with Epsilometer test (E-test) method (E-test, AB Biodisk, Solna, Sweden). These 75 VRE isolates were obtained over a period of three years (2009-2011) from various samples namely, urine (56), blood (8) and pus (11). All these isolates were identified as Enterococcus according to standard methods and species identification was done using the conventional test scheme [9] . Initially the vancomycin resistant isolates were collected based on disc diffusion results as per Clinical and Laboratory Standards Institute (CLSI) guidelines using vancomycin disc (30 µg) [10] . All culture media, antibiotics discs and standard strains of bacteria used in this study were procured from Hi-media Laboratories Pvt. Ltd., Mumbai, India.

E. faecalis ATCC 29212 and E. faecalis ATCC 51299 were used for quality control. E-test strips of vancomycin, teicoplanin, tigecycline, daptomycin, linezolid and quinupristin/dalfopristin were obtained from AB BioDisk, Solna, Sweden. E-test to daptomycin was done on Mueller-Hinton agar supplemented with 50 mg/l calcium (Difco, USA) due to daptomycin's dependence on calcium. MIC values were interpreted according to the CLSI guidelines [10] except for tigecycline for which EUCAST was followed [11] .

Based on the MIC values for glycopeptides - vancomycin and teicoplanin, in our study majority of strains (49 E. faecalis and 15 E. faecium) belonged to the vanA resistance phenotype having high level vancomycin and teicoplanin resistance (MIC values being in the range of 64 to 256 µg/ml). We had eight E. faecalis isolates of van B type having variable levels of vancomycin resistance but were susceptible to teicoplanin (MIC values being in the range of 64 to 128 µg/ml for vancomycin and 0.064-0.50 µg/ml for teicoplanin). Three E. faecalis isolates had vancomycin MIC as 64 and teicoplanin MIC to be 4.0, 4.0, and 8.0 µg/ml, so probably these were van D type. Van D-type strains are characterized by moderate levels of resistance to both vancomycin and teicoplanin. Earlier reports from India have shown mainly vanA and vanB phenotypes [12] .The phenotypic classification of VRE in to various types is solely based on the vancomycin and teicoplanin breakpoints and is not a reliable method, and has some limitations also. Earlier report has shown that mutations in van B strains can exhibit resistance to teicoplanin and such strains become phenotypically indistinguishable from van A resistant phenotypes [13] . These strains need to be confirmed by molecular characterization.

A number of relatively new agents that possess clinical data and ultimately clinical utility in the treatment of more serious infections due to VRE have been studied [7] . There is limited information reported from India [14] . In our study, all our isolates had MIC for linezolid within susceptibility range, MIC values

≤ 2 µg/ml except for one E. faecium showing linezolid MIC to be 4 µg/ml which is intermediate susceptibility. A study from India has shown 100 per cent susceptibility of VRE to linezolid [14] . Yasliani et al[15 ] reported two isolates of E. faecium resistant to linezolid from Tehran with MIC 32 µg/ml. Susceptibility of VRE to linezolid was shown to decrease to 83 per cent six months after inclusion of linezolid on the hospital antibiotic policy [16] . A study from India showed daptomycin to be the most active agent against VRE, highlighting the importance of the drug as an excellent therapeutic option [17] . We also found all VREs to be 100 per cent susceptible to daptomycin (MIC ≤ 4.0 µg/ml). A surveillance of US hospitals showed that more than 99.5 per cent of VRE isolates were susceptible to daptomycin [18],[19],[20],[21] . But empiric daptomycin therapy for VRE infections should be used with caution and be based on susceptibility data [19] . Daptomycin resistance in enterococci was observed in a previously sensitive E. faecalis isolate, while on therapy [21],[22] . Quinupristin-dalfopristin is a streptogramin antibiotic active only against E. faecium. Resistance to quinupristin/dalfopristin has been reported in 1.3-2.4 per cent of patients with VRE [23] . We found three isolates of E. faecium resistant to Q/D(MIC=4.0 µg/ml) [Table 1]. Quinupristin/dalfopristin is advocated for vancomycin-resistant E. faecium infections in critically ill patients with serious underlying diseases [23] . In our study, all enterococcal isolates were found to be susceptible to tigecycline (MIC≤ 0.25 µg/ml), which was in agreement with a study from south India [24] . Cases of E. faecalis isolates with MIC 6 µg/ml for tigecycline have also been described [25] . A study from Korea showed high resistance to all the newer drugs and out of all tigecycline was found to be an effective drug [26] . Of all these antibiotics considered, daptomycin is the only bactericidal drug while linezolid, tigecycline and quinupristin/dalfopristin are bacteriostatic drugs. All have their side effects also [27] . Further, linezolid, tigecycline, and daptomycin, have activity against both vancomycin-resistant E. faecalis and E. faecium, whereas quinupristin-dalfopristin has activity against E. faecium only. Daptomycin is found to be inhibited by pulmonary surfactant so should not be used for pneumonias [28] .
Table 1: Distribution of MIC values for various antibiotics in vancomycin resistant enterococci isolates

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Vancomycin still remains the mainstay of treatment for serious enterococcal infections, if the strain is found susceptible. However, with the emergence of resistance to vancomycin other antibiotics like linezolid, quinupristin-dalfopristin, tigecycline and daptomycin can also be considered. The data on local patterns of susceptibility of VRE to newer antimicrobial agents can help in guiding the treatment of these pathogens.

   References Top

Murray BE, Weinstock GM. Enterococci: new aspects of an old organism. Proc Assoc Am Physicians 1999; 111 : 328-34.   Back to cited text no. 1
Arias CA, Murray BE. The rise of the Enterococcus: beyond vancomycin resistance. Nat Rev Microbiol 2012; 10 : 266-78.   Back to cited text no. 2
Jett BD, Huycke MM, Gilmore MS. Virulence of enterococci. Clin Microbiol Rev 1994; 7 : 462-78.  Back to cited text no. 3
Low DE, Keller N, Barth A, Jones RN. Clinical prevalence, antimicrobial susceptibility, and geographic resistance patterns of enterococci: results from the SENTRY Antimicrobial Surveillance Program, 1997-1999. Clin Infect Dis 2001; 32 (Suppl 2): S133-45.   Back to cited text no. 4
Sood S, Malhotra M, Das BK, Kapil A. Enterococcal infections & antimicrobial resistance. Indian J Med Res 2008; 128 : 111-21.   Back to cited text no. 5
Karmarkar MG, Gershom ES, Mehta PR. Enterococcal infections with special reference to phenotypic characterization & drug resistance. Indian J Med Res 2004; 119 (Suppl) : 22-5.  Back to cited text no. 6
Rivera AM, Boucher HW. Current concepts in antimicrobial therapy against select Gram-positive organisms: methicillin-resistant Staphylococcus aureus, penicillin-resistant pneumococci, and vancomycin-resistant enterococci. Mayo Clin Proc 2011; 86 : 1230-43.  Back to cited text no. 7
Jones RN, Ballow CH, Biedenbach DJ, Deinhart JA, Schentag JJ. Antimicrobial activity of quinupristin-dalfopristin (RP 59500, synercid) tested against over 28,000 recent clinical isolates from 200 medical centers in the United States and Canada. Diagn Microbiol Infect Dis 1998; 31 : 437-51.  Back to cited text no. 8
Teixeira LM, Carvalho MGS, Facklam RR. Enterococcus. In: Murray BE, Baron EJ, Jorgensen JH, Landry ML, Pfaller MA, editors. Manual of clinical microbiology. Washington (DC): American Society for Microbiology; 2007 Press. p. 430-42.  Back to cited text no. 9
Clinical and Laboratory Standards Institute (CLSI). Performance standards for antimicrobial susceptibility testing; 20 [th] Informational Supplement, vol. 30, M100-S20. Wayne, Pa, USA: CLSI; 2010.  Back to cited text no. 10
European c0 ommittee on a0 ntimicrobial Susceptibility t0 esting (EUCAST). Breakpoint tables for interpretation of MICs and zone diameters, version 1.1. Stockholm, Sweeden: Eucast0 ; 2010.   Back to cited text no. 11
Khudaier BY, Tewari R, Shafiani S, Sharma M, Emmanuel R, Sharma M, et al. Epidemiology and molecular characterization of vancomycin resistant Enterococci isolates in India. Scand J Infect Dis 2007; 39 : 662-70.  Back to cited text no. 12
Hayden MK, Trenholme GM, Schultz JE, Sahm DF. In vivo development of teicoplanin resistance in a VanB Enterococcus faecium isolate. J Infect Dis 1993; 167 : 1224-7.  Back to cited text no. 13
Chitnis S, Katara G, Hemvani N, Pareek S, Chitnis DS. In vitro activity of daptomycin & linezolid against methicillin resistant Staphylococcus aureus & vancomycin resistant enterococci isolated from hospitalized cases in Central India. Indian J Med Res 2013; 137 : 191-6.  Back to cited text no. 14
Yasliani S, Mohabati Mobarez A, Hosseini Doust R, Satari M, Teymornejad O. Linezolid vancomycin resistant Enterococcus isolated from clinical samples in Tehran hospitals. Indian J Med Sci 2009; 63 : 297-302.  Back to cited text no. 15
Raad II, Hanna HA, Hachem RY, Dvorak T, Arbuckle RB, Chaiban G, et al. Clinical-use-associated decrease in susceptibility of vancomycin-resistant Enterococcus faecium to linezolid: a comparison with quinupristin-dalfopristin. Antimicrob Agents Chemother 2004; 48 : 3583-5.  Back to cited text no. 16
Dhawan B, Gadepalli R, Kapil A .In vitro activity of daptomycin against Staphylococcus aureus and vancomycin-resistant Enterococcus faecium isolates associated with skin and soft tissue infections: first results from India. Diagn Microbiol Infect Dis 2009; 65 : 196-8.  Back to cited text no. 17
Sader HS, Jones RN. Antimicrobial susceptibility of gram-positive bacteria isolated from US medical centers: results of the Daptomycin Surveillance Program (2007-2008). Diagn Microbiol Infect Dis 2009; 65 : 158-62.  Back to cited text no. 18
Kamboj M, Cohen N, Gilhuley K, Babady NE, Seo SK, Sepkowitz KA .Emergence of daptomycin-resistant VRE: experience of a single institution. Infect Control Hosp Epidemiol 2011; 32 : 391-4.  Back to cited text no. 19
Humphries RM1, Pollett S, Sakoulas G. A current perspective on daptomycin for the clinical microbiologist. Clin Microbiol Rev 2013; 26 : 759-80.  Back to cited text no. 20
Arias CA, Panesso D, McGrath DM, Qin X, Mojica MF, Miller C, et al. Genetic basis for in vivo daptomycin resistance in Enterococci. N Engl J Med 2011; 365:892-900.   Back to cited text no. 21
Linden PK. Optimizing therapy for vancomycin-resistant enterococci (VRE). Semin Respir Crit Care Med 2007; 28 : 632-45.  Back to cited text no. 22
Winston DJ, Emmanouilides C, Kroeber A, Hindler J, Bruckner DA, Territo MC, et al. Quinupristin/Dalfopristin therapy for infections due to vancomycin-resistant Enterococcus faecium. Clin Infect Dis 2000; 30 : 790-7.   Back to cited text no. 23
Manoharan A, Chatterjee S, Madhan S, Mathai D. Evaluation of tigecycline activity in clinical isolates among Indian medical centers. Indian J Pathol Microbiol 2010; 53 : 734-7.  Back to cited text no. 24
Cordina C, Hill R, Deshpande A, Hood J, Inkster T. Tigecycline-resistant Enterococcus faecalis associated with omeprazole use in a surgical patient. J Antimicrob Chemother 2012; 67 : 1806-7.  Back to cited text no. 25
Lee do K, Kim Y, Park KS, Yang JW, Kim K, Ha NJ. Antimicrobial activity of mupirocin, daptomycin, linezolid, quinupristin/dalfopristin and tigecycline against vancomycin-resistant enterococci (VRE) from clinical isolates in Korea (1998 and 2005). J Biochem Mol Biol 2007; 40 : 881-7.  Back to cited text no. 26
Rubinstein E, Keynan Y. Vancomycin-resistant enterococci. Crit Care Clin 2013; 29 : 841-52.  Back to cited text no. 27
Pertel PE, Bernardo P, Fogarty C, Matthews P, Northland R, Benvenuto M, et al. Effects of prior effective therapy on the efficacy of daptomycin and ceftriaxone for the treatment of community-acquired pneumonia. Clin Infect Dis 2008; 46 : 1142-51.  Back to cited text no. 28


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