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 Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 17  |  Issue : 1  |  Page : 3-6

Determination of Vancomycin, Teicoplanin and Linezolid resistance among Staphylococcal isolates from a tertiary care hospital


Department of Microbiology, Seven Hills Hospital, Mumbai, Maharashtra, India

Date of Web Publication16-Jun-2015

Correspondence Address:
Shashikala Shivaprakasha
Department of Microbiology, Seven Hills Hospital, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0972-1282.158766

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  Abstract 

Background and Objectives: Increasing reports of Vancomycin creep have been observed in both Methicillin sensitive and Methicillin resistant staphylococcal isolates. The objective of this study was to determine the sensitivity pattern among clinical isolates of Methicillin sensitive and Methicillin resistant Staphylococcus aureus (MRSA), S. epidermidis, S. haemolyticus, to Vancomycin, Teicoplanin and Linezolid. Materials and Methods: A total of 82 S. aureus, 34 S. epidermidis and 26 S. haemolyticus isolated during Jan 2011 to Dec 2011 were included in the study. None of the S. aureus isolates were resistant to Vancomycin and Linezolid. Only one MRSA isolate was resistant to Teicoplanin. Vancomycin resistant strains among Methicillin resistant S. epidermidis was one (4.3%) and among S. haemolyticus was two (8.3%) respectively. Teicoplanin resistant strains among Methicillin resistant S. epidermidis was six (26.1%) and among S. haemolyticus was two (8.3%). Linezolid resistant strains among Methicillin resistant S. epidermidis was two (8.7%) and among S. haemolyticus was one (4.2%). Conclusion: Emergence of Vancomycin, Teicoplanin and Linezolid resistance among Methicillin resistant coagulase negative staphylococci (CoNS) is alarming limiting the therapeutic options.

Keywords: CoNS glycopeptides resistance, CoNS Linezolid, Teicoplanin resistance, CoNS Vancomycin, S. epidermidis, S. aureus, S. haemolyticus


How to cite this article:
Shivaprakasha S. Determination of Vancomycin, Teicoplanin and Linezolid resistance among Staphylococcal isolates from a tertiary care hospital. J Acad Clin Microbiol 2015;17:3-6

How to cite this URL:
Shivaprakasha S. Determination of Vancomycin, Teicoplanin and Linezolid resistance among Staphylococcal isolates from a tertiary care hospital. J Acad Clin Microbiol [serial online] 2015 [cited 2021 Jan 17];17:3-6. Available from: https://www.jacmjournal.org/text.asp?2015/17/1/3/158766


  Introduction Top


Increasing resistance to Vancomycin is a challenge in the management of S. aureus infections. Vancomycin creep has been observed in both Methicillin sensitive and Methicillin resistant staphylococcal isolates. [1] Among coagulase negative staphylococci it is commonly observed with S. haemolyticus & S. epidermidis.[2]

Though emergence of Vancomycin resistance is not a major problem in India, recent reports from Southern and Northern parts of India have documented the emergence of Vancomycin intermediate and resistant strains among staphylococcal isolates. [3],[4],[5],[6],[7] Data from the western part of India is scarce. It is postulated that the shift in Vancomycin MIC values may be associated with a concurrent rise in MIC values of other anti-MRSA agents. Hence we, analysed the data from our centre to find out the emergence of resistance to Vancomycin, Teicoplanin and Linezolid among Methicillin resistant and Methicillin sensitive staphylococal isolates.


  Materials and methods Top


All S. aureus, S. epidermidis and S. haemolyticus isolated during Jan 2011 to Dec 2011 at Seven Hills Hospital, Mumbai, India were included. Only non repetitive clinical isolates were included in the study. This study was undertaken to determine the sensitivity pattern among clinical isolates of Methicillin sensitive and Methicillin resistant S. aureus, S. epidermidis, S. haemolyticus to Vancomycin, Teicoplanin and Linezolid.

Identification and susceptibility testing was done by automated Phoenix (Becton-Dickinson) system. Staphylococcus aureus ATCC 29213 was used as control strain. Minimum inhibitory concentration (MIC) interpretation criteria was as per Clinical Laboratory Standards Institute (CLSI) [Table 1]a. [8]
Table 1:

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  Results Top


A total of 142 staphylococci were isolated during the study period. Of these, there were 82 S. aureus, 34 S. epidermidis and 26 S. haemolyticus isolates from various clinical samples like pus, endotracheal secretions, catheter tip, blood and semen. Coagulase negative staphylococci represented either pathogen/colonisation. None of these isolates were part of surveillance screening. Distribution of MIC for different staphylococci is shown in [Table 1]. Percentage susceptibility among Methicillin resistant and Methicillin sensitive staphylococci to Vancomycin, Teicoplanin, Linezolid is shown in [Table 2].
Table 2: Vancomycin, Teicoplanin, Linezolid percent susceptibility

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A total of 23 (28.05%) isolates out of 82 S. aureus strains were MRSA. The Vancomycin MIC was ≤1 mg/L for 80 S. aureus isolates and only two isolates showed an MIC of 2 mg/L [Table 1]b. One isolate was from pus specimen of an inpatient and the other was a betalactamase producing isolate from a pus specimen of an outpatient which was also Teicoplanin resistant. Both the isolates were community acquired MRSA (CA-MRSA). None of the S. aureus isolates were resistant to Vancomycin [Table 3]. All the S. aureus isolates were sensitive to Linezolid.
Table 3: Distribution of Methicillin resistant isolates among the various specimens and their MIC to Vancomycin, Teicoplanin and Linezolid

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Of the 34 S. epidermidis isolates, 23 (67.65%) were Methicillin resistant and 11 were Methicillin sensitive. Only one (0.03%) Methicillin resistant isolate was resistant to Vancomycin with an MIC >16 mg/L. This was also resistant to Teicoplanin and Linezolid. Teicoplanin resistance was seen in six isolates. MIC values of three isolates were not available. Only two (0.06%) Methicillin resistant isolates were resistant to Linezolid of which one was resistant to Vancomycin and had intermediate sensitivity to Teicoplanin. Among Methicillin sensitive isolates only one isolate had intermediate sensitivity to Teicoplanin with MIC 16 mg/L [Table 3].

Of the 26 S. haemolyticus isolates, 24 (92.31%) isolates were Methicillin resistant and two were Methicillin sensitive. Of the 24 Methicillin resistant isolates, two (0.08%) isolates were resistant to Vancomycin with MIC >16 mg/L and one had only intermediate sensitivity to Teicoplanin. There were two isolates resistant to Teicoplanin. Only one out of 24 (0.04%) isolates tested was resistant to Linezolid with MIC >4mg/L [Table 3].


  Discussion Top


After the emergence of Vancomycin-resistant enterococci in the 1980s, significant concern existed with regard to the potential for large outbreaks of Vancomycin-resistant S. aureus (VRSA) due to the acquisition of the vanA gene from enterococci. Fully Vancomycin-resistant strains of S. aureus (VRSA) due to the acquisition of the vanA gene from Vancomycin-resistant enterococci were first reported from the United States in 2002. [9]

In our study Vancomycin resistance was not noted among S. aureus isolates. In our study, only two (2.4%) S. aureus isolates showed increase in MIC for Vancomycin and one (1.2%) was MRSA, while other was MSSA. Though this constitutes a very small percentage, close monitoring to note the creep in MIC is warranted due to therapeutic implications. hVISA (heteroresistant VISA) is defined as a Vancomycin susceptible S. aureus (VSSA) strain with MIC ≤ 2 on routine testing, that upon subculture produces sub-colonies with MIC in the VISA/VRSA range at the frequency of ≥1x10^6 according to population analysis profile (PAP). Though we did not note a creep in the Vancomycin MIC value, hVISA prevalence was not looked into and this was a limitation to our study. However, it is difficult to confirm the presence of heteroresistance in clinical practice because conventional microbiological methods, including MIC determination, cannot detect hVISA. Therefore, if hVISA infection is strongly suspected based on clinical features, population analysis has to be performed at a reference laboratory. Heteroresistance has also been observed in coagulase-negative staphylococci. [10]

Elevated Vancomycin MIC in S. aureus has been associated with increased mortality in patients with Methicillin-susceptible S. aureus infections when they are treated with either Vancomycin or Flucloxacillin. Based on neutropenic mouse models, in vitro studies and limited data from human studies, the AUC/MIC ratio has been used as a preferred parameter for measuring the effectiveness of Vancomycin in treating S. aureus infections. A specific AUC/MIC threshold of 400 has been advocated as a target to achieve clinical effectiveness with Vancomycin, based on the initial clinical data from pneumonia and more recent data from bacteremia. Using Monte Carlo simulations, it has been suggested that the probability of attaining this ratio is approximately 100% in isolates with MIC ≤ 0.5 mg/L and the probability falls to 0% in isolates with MIC of 2 mg/L. Based on simulated models, it has further been reported that a daily dose of 3-4 gm of Vancomycin will be required to provide 90% probability of attaining the target AUC/MIC of 400 for an isolate with MIC 1 mg/L. One needs to consider alternate antibiotics for MRSA isolates especially for respiratory isolates if MIC >1mg/L. [1] In our study both the isolates with MIC 2 mg/L were from non respiratory specimens. Only one MRSA isolate was resistant to Teicoplanin indicating low prevalence of resistance and all isolates were sensitive to Linezolid.

Coagulase-negative staphylococci (CoNS), especially Staphylococcus epidermidis, are major nosocomial pathogens causing a variety of device-related infections in humans. Infections caused by coagulase negative staphylococci are mainly from indwelling foreign bodies, and their role as agents of osteomyelitis following cardiothoracic, ophthalmic and neurosurgical procedures and in immunocompromised patients have been well established.

Unlike that of Staphylococcus aureus, CoNS resistance to glycopeptides applies almost exclusively to Teicoplanin. The mechanisms involved are unclear, but CoNS with decreased susceptibility to glycopeptides show cell wall thickening and tend to form cellular aggregates. [9] In our study Vancomycin, Teicoplanin and Linezolid resistance was noted among Methicillin resistant CoNS. Reports on Teicoplanin susceptibility among CONS are scarce from India. [10],[11],[12] In our study Teicoplanin resistance that was limited to Methicillin resistant isolates among CoNS is consistent with other reports. There have been reports of S. haemolyticus resistant to Teicoplanin but sensitive to Vancomycin. Similar findings were observed in our study. [13],[14] Two pus isolates were resistant to Vancomycin, Teicoplanin and Linezolid. Both these isolates showed sensitivity to Tetracycline and Trimethoprim-Sulphamethaxazole. The appropriate antibiotics were selected based on antibiogram to treat such patients.

Recent epidemiological data show that Linezolid resistance occurs in ≤1% of S. aureus isolates and ≤0.1% of CoNS in the US. Staphylococcal Linezolid resistance is rare from India and is limited to case reports and is observed only among CoNS isolates. In our study also, Linezolid resistance that was observed among Methicillin resistant CoNS is consistent with Indian reports. [10],[11],[12]


  Conclusion Top


Prevalence of Vancomycin, Teicoplanin and Linezolid resistance among S. aureus isolates has not yet been detected in isolates from our hospital and no such reports are available from the western part of India. Vancomycin resistant coagulase negative staphyloccal isolates are also resistant to Teicoplanin and associated with a creep in Linezolid MICs, limiting the therapeutic options for CoNS infections. Though coagulase negative staphylococcal infections are limited to an immunocompromised host, emergence of Vancomycin, Teicoplanin and Linezolid resistance among Methicillin resistant coagulase negative staphylococci is alarming as this can spread to coagulase positive staphylococci in the future, limiting the therapeutic options. The only way out is to rationalise the use of these antibiotics.

 
  References Top

1.
Dhand A, Sakoulas G. Reduced vancomycin susceptibility among clinical Staphylococcus aureus isolates (′the MIC Creep′): Implications for therapy. F1000 Med Rep 2012;4:4.  Back to cited text no. 1
    
2.
Menezes GA, Harish BN, Sujatha S, Vinothini K, Parija SC. Emergence of vancomycin-intermediate Staphylococcus species in southern India. J Med Microbiol 2008;57:911-2.  Back to cited text no. 2
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Dhawan B, Gadepalli R, Rao C, Kapil A, Sreenivas V. Decreased susceptibility to vancomycin in meticillin-resistant Staphylococcus aureus: A 5 year study in an Indian tertiary hospital. J Med Microbiol 2010;59:375-6.  Back to cited text no. 3
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Ramana BV, Chaudhury A. Rising incidence of high MIC for vancomycin among Staphylococcus aureus strains at a Tertiary Care Hospital in South India. J Pharm Bioallied Sci 2012;4:173.  Back to cited text no. 4
    
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Tiwari HK, Sen MR. Emergence of vancomycin resistant Staphylococcus aureus (VRSA) from a Tertiary Care Hospital from northern part of India. BMC Infect Dis 2006;6:156.  Back to cited text no. 5
    
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Bhakta A, Bhattacharyya M, Todi S. A creep in the vancomycin minimum inhibitory concentration for Staphylococcus aureus in a Tertiary Care Hospital in India. Crit Care 2011;15:P232.  Back to cited text no. 6
    
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Reddy CM, Thati V, Shivannavar CT, Gaddad S. Vancomycin resistance among methicillin resistant Staphylococcus sureus isolates in Rayalseema region Andhra Pradesh, South India. World J Sci Technol 2012;2:06-08.  Back to cited text no. 7
    
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Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing; Twenty First Informational Supplement. M100-S17. Wayne, PA: CLSI; 2011.  Back to cited text no. 8
    
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Sujatha S, Praharaj I. Glycopeptide resistance in gram-positive cocci: A review. Interdiscip Perspect Infect Dis 2012;2012:781679.  Back to cited text no. 9
    
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Song JH, Hiramatsu K, Suh JY, Ko KS, Ito T, Kapi M, et al. Emergence in Asian countries of Staphylococcus aureus with reduced susceptibility to vancomycin. Antimicrob Agents Chemother 2004;48:4926-8.  Back to cited text no. 10
    
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Kalawat U, Sharma KK, Reddy S. Linezolid-resistant Staphylococcus spp. at a Tertiary Care Hospital of Andhra Pradesh. Indian J Med Microbiol 2011;29:314-5.  Back to cited text no. 11
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Peer MA, Nasir RA, Kakru DK, Fomda BA, Bashir G, Sheikh IA. Sepsis due to linezolid resistant Staphylococcus cohnii and Staphylococcus kloosii: First reports of linezolid resistance in coagulase negative staphylococci from India. Indian J Med Microbiol 2011;29:60-2.  Back to cited text no. 12
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Fajardo Olivares M, Hidalgo Orozco R, Rodríguez Garrido S, Gaona Álvarez C, Sánchez Silos RM, Hernández Rastrollo R, et al. Activity of vancomycin, teicoplanin and linezolid in methicillin resistant coagulase-negative staphylococci isolates from paediatric blood cultures. Rev Esp Quimioter 2012;25:25-30.  Back to cited text no. 13
    
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Ahlstrand E, Svensson K, Persson L, Tidefelt U, Söderquist B. Glycopeptide resistance in coagulase-negative staphylococci isolated in blood cultures from patients with hematological malignancies during three decades. Eur J Clin Microbiol Infect Dis 2011;30:1349-54.  Back to cited text no. 14
    



 
 
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