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Year : 2003  |  Volume : 21  |  Issue : 3  |  Page : 196-198

Emergence of low level vancomycin resistance in MRSA

Department of Clinical Microbiology, Sher-i-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir - 190 011, India

Correspondence Address:
Department of Clinical Microbiology, Sher-i-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir - 190 011, India

 ~ Abstract 

One hundred and twenty methicillin resistant Staphylococcus aureus (MRSA) strains were checked for minimum inhibitory concenteration (MIC) of vancomycin. The results showed that 98 strains (81.7 %) had MIC < 4g/mL, 18 strains (15 %) had MIC 8 g/mL, and 4 (03.3%) had MIC 16 g/mL which being borderline between sensitive (< 4g/mL) and resistant (>32g/mL) values points towards possible emergence of low level vancomycin resistance in the organisms and may explain the reasons of delayed therapeutic success of vancomycin in S.aureus bacteraemia in some situations.

How to cite this article:
Assadullah S, Kakru D K, Thoker M A, Bhat F A, Hussain N, Shah A. Emergence of low level vancomycin resistance in MRSA. Indian J Med Microbiol 2003;21:196-8

How to cite this URL:
Assadullah S, Kakru D K, Thoker M A, Bhat F A, Hussain N, Shah A. Emergence of low level vancomycin resistance in MRSA. Indian J Med Microbiol [serial online] 2003 [cited 2021 Mar 5];21:196-8. Available from:

Vancomycin, a glycopeptide, is the main antimicrobial agent available to treat serious infections with MRSA. Efficacy of this drug in treatment of such infections has contributed to the misconception that it is therapeutically equivalent to -lactam antibiotics. No clinical trial has compared vancomycin to -lactam antibiotics for the treatment of serious staphylococcal infections. However, evidence strongly suggests that for serious infections caused by MRSA vancomycin is less effective. The duration of bacteraemia in vancomycin treated cases is 6 to 9 days,[1] versus 2 to 4 days for patients treated with -lactams.[2]
An investigational carbapenem (a -lactam) antibiotic with in vitro activity against MRSA was more effective than vancomycin against both MSSA (methicillin sensitive S. aureus) and MRSA strains in a rabbit model of endocarditis.[3] As such vancomycin should be used to treat MRSA infections only to prevent loss of its activity as has been reported recently[4],[5],[6] in case of some isolates of S. aureus that showed decreased susceptibility to vancomycin in vivo after prolonged exposure to this drug. Now that VISA (vancomycin intermediate S. aureus) is a definite entity[7] this study was undertaken to find magnitude of this problem and make the clinicians aware of this impending public health disaster, if inappropriate use of this glycopeptide is continued.

 ~ Materials and methods Top

One hundred and twenty methicillin resistant stains of S. aureus were chosen for the study. These strains were isolated from different clinical samples received in the department of microbiology over a period of one year (1999). Identification of these strains was done by conventional methods.[8] The antimicrobial susceptibility testing was performed by disc diffusion method of Kirby-Bauer. In view of the fact that VISA are detected only by dilution-based susceptibility test methods[9] MIC of vancomycin for all the 120 strains was determined by tube dilution method (macrobroth dilution)[10] - two-fold dilutions of vancomycin (Sigma, USA) were prepared in Mueller-Hinton broth (HiMedia, Mumbai) ranging from 0.5-128g/mL. To each tube 1mL of actively growing suspension of MRSA was added; the inoculum was prepared adjusting the concentration of MRSA to 105 - 106 colony forming units (CFU)/mL using McFarland standard and the results recorded were after 24 hours of incubation at 35C . S. aureus NCTC 6571 Oxford strain was used as reference strain.

 ~ Results Top

All strains of MRSA were susceptible to vancomycin by disc diffusion method (30g/disc). Antimicrobial susceptibility testing of other drugs, also done by disc diffusion method showed varied results [Table - 1] with co-trimoxazole and ampicillin showing a very high percentage of resistance followed by gentamicin, cefotaxime and ciprofloxacin. In broth dilution method 81.7% of MRSA strains had MIC < 4g/mL, 15% had MIC 8g/mL, and 3.3% had MIC 16g/mL. None of the strains had MIC of 32g/mL [Table - 2].
Co : Co-trimoxazole, Am : Ampicillin, G : Gentamicin, Ct : Cefotaxime, Cf : Ciprofloxacin, Cp : Cefaperazone, Cx : Ceftriaxone

 ~ Discussion Top

Virtually every antibiotic introduced into clinical practice has encountered resistance at one level or other. S. aureus is one such pathogen that has shown disconcerting propensity to develop resistance to a number of antimicrobials and MRSA is one such group that has been a matter of concern since late 1970s. Vancomycin, a glycopeptide, is currently the main antimicrobial available to treat infections with these MRSA. Until recently vancomycin resistance among gram positive bacteria had been thought to be uncommon, but there are confirmed reports of vancomycin resistance in enterococcus species[11] and some coagulase negative staphylococci.[12] Resistance in enterococci has been shown to be plasmid mediated,[11] inducible and transferable,[13] and has been associated with the appearance of or increased synthesis of proteins of 39 kDa size which are cytoplasmic proteins,[14] though mechanism of induction of these proteins is not yet established.
Widespread use of vancomycin to treat infections caused by MRSA has been reported to result in the emergence of low level resistance. Though very few instances only, VISA are a definite entity now. But the large scale development, and subsequent spread of resistance to vancomycin is perceived as a fearsome threat to the already challenging therapy of MRSA. In our study, we found 4 (3.3%) strains having MIC 16g/mL which is border line between susceptible and resistant values. This may be a pointer towards emerging low level vancomycin resistance in S. aureus and the possible reason for this development can be inappropriate use of vancomycin especially in situations where an alternate antimicrobial like -lactam in reasonably higher dose can be more beneficial. Also patients colonized but not infected with MRSA should not be treated with vancomycin merely for the sake of eliminating carriage of this organism.
Decision to put a patient, infected with MRSA, on a glycopeptide should be vested in a clinical microbiologist who should make it mandatory to check MIC of such strains. Such studies should be carried out by more and more hospitals so that appropriate measures are taken whenever and wherever necessary. 

 ~ References Top

1.Levine DP, Fromm BS, Reddy BR. Slow response to vancomycin or vancomycin plus rifampin in MRSA endocarditis. Ann Intern Med 1991;115:674.  Back to cited text no. 1    
2.Korzeniowski O, Sande MA, and the National Collaborative Endocarditis Study Group : Combination antimicrobial therapy of S. aureus endocarditis in parenteral drug addicts and non-addicts. Ann Intern Med 1982;97:496.  Back to cited text no. 2    
3.Chambers HF. In vitro and in vivo anti-staphylococcal activities of L-695, 256, a carbapenem with high affinity for penicillin-binding protein 2a. Antimicrob agents Chemother 1995;39:462.  Back to cited text no. 3    
4.Centres for disease control and prevention. Reduced susceptibility of S. aureus to vancomycin - Japan, 1996. MMWR 1997;46:624-626.  Back to cited text no. 4    
5.Centres for disease control and prevention. S. aureus with reduced susceptibility to vancomycin - United States. MMWR 1997;46:765-766.  Back to cited text no. 5    
6.Hiramatsu K, Hanaki H, Ino T, Yabuta K, Oguri T, Tenover FC. MRSA clinical strain with reduced vancomycin susceptibility. J Antimicrob Chemother 1997;40:135-136.  Back to cited text no. 6    
7.Turco TF, Melko GP, Williams JR. Vancomycin intermedicate-resistant Staphylococcus aureus. Ann Pharmacother 1998;32(7-8):758-760.  Back to cited text no. 7    
8.Konemann EW, et al. Gram positive cocci part - I (Chapter on Staphylococci and related organisms), Diagnostic Microbiology, 4th ed., (JB Lippincott company) p.406-430.  Back to cited text no. 8    
9.Verbist L. Relevance of antibiotic susceptibility testing for clinical practice. Eur J Microbiol Infect Dis 1993;12(Suppl .1):2-5.  Back to cited text no. 9    
10.Ericsson. Antibiotic sensitivity testing, report of an international collaborative study. Acta Pathol Microbiol Scand Soet B Supple 1971;l217:3-9.  Back to cited text no. 10    
11.Leclerq R, Derlot E, Weber M, Duval J, Courvalin P. Plasmid mediated resistance to vancomycin and teichoplanin in Enterococcus faecium. New Eng J Med 1988;319:157-161.  Back to cited text no. 11    
12.Schwalbe rs, et al. Emergence of vancomycin resistance in Coagulase negative staphylococci. New England J Med 1987;316:927-929.  Back to cited text no. 12    
13.Leclerq R, Derlot E, Weber M, Duval J, Courvalin P. Transferable vancomycin and teichoplanin resistance in E. faecium. Antimicrob Agents Chemother 1989;33:10-15.  Back to cited text no. 13    
14.Al-Obeid, Cllatz S, Gutmann L. Mechanism of resistance to vancomycin in E. faecium D 366 and E. faecalis A 256. Antimicrob Agents Chemother 1990;34:252-256.  Back to cited text no. 14    
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2004 - Indian Journal of Medical Microbiology
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