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Inducible clindamycin resistance among clinical isolates of staphylococci Ciraj A M, Vinod P, Sreejith G, Rajani K - Indian J Pathol Microbiol
Indian Journal of Pathology and Microbiology
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ORIGINAL ARTICLE Table of Contents   
Year : 2009  |  Volume : 52  |  Issue : 1  |  Page : 49-51
Inducible clindamycin resistance among clinical isolates of staphylococci


Department of Microbiology, Melaka Manipal Medical College, Manipal University, Manipal, Karnataka 576 104, India

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   Abstract  

Introduction: Clinical failure of clindamycin therapy has been reported due to multiple mechanisms that confer resistance to macrolide, lincosamide and streptogramin antibiotics. This study was undertaken to detect the presence of inducible clindamycin resistance among clinical isolates of staphylococci. Materials and Methods: The detection of inducible clindamycin resistance was performed by D-test using erythromycin and clindamycin discs as per CDC guidelines. Results: Among the 244 clinical isolates of staphylococci studied, 32 (13.1%) showed inducible clindamycin resistance and belonged to the MLSBi phenotype. Among the MLS B i phenotypes, 10 isolates were methicillin-resistant Staphylococcus aureus (38.4% of the total MRSA), 16 were methicillin-sensitive Staphylococcus aureus (12.9% of the total MSSA) and 6 were coagulase-negative staphylococci (6.3% of the total CONS). Conclusion: The test for inducible resistance to clindamycin should be included in the routine antibiotic susceptibility testing, as it will help in guiding therapy.

Keywords: Inducible clindamycin resistance, MLS B i phenotype, Staphylococcus aureus

How to cite this article:
Ciraj A M, Vinod P, Sreejith G, Rajani K. Inducible clindamycin resistance among clinical isolates of staphylococci. Indian J Pathol Microbiol 2009;52:49-51

How to cite this URL:
Ciraj A M, Vinod P, Sreejith G, Rajani K. Inducible clindamycin resistance among clinical isolates of staphylococci. Indian J Pathol Microbiol [serial online] 2009 [cited 2014 Mar 6];52:49-51. Available from: http://www.ijpmonline.org/text.asp?2009/52/1/49/44963



   Introduction   Top


Macrolides, lincosamides and streptogramin (MLS) antibiotics are structurally unrelated; however, they are related microbiologically because of their similar mode of action. MLS antibiotics inhibit bacterial protein synthesis by binding to 23s rRNA, which is a part of the large ribosomal subunit. They have a spectrum of activity directed against Gram-positive cocci, Gram-negative cocci and intra-cellular bacteria such as chlamydiae and rickettsiae.

Resistance to MLS antibiotics occur either through target site modification, efflux of antibiotics, or drug modification. [1] In target-site modification, methylation of the A2058 residue, located in the conserved domain V of 23s rRNA, takes place, which leads to cross resistance and results in the formation of the phenotype of resistance pattern known as MLSB. [2] This phenotype is encoded by erythromycin ribosome methylases( erm ) genes that have been reported from a wide variety of microorganisms. [3]

Clindamycin is used in the treatment of skin and soft-tissue infections, caused by the staphylococcal species. Good oral absorption makes this drug an important option in outpatient therapy or as a follow-up after intravenous therapy. Clindamycin is also used as an alternative for patients who are allergic to penicillin. [4]

The expression of the MLS B phenotype can be constitutive (MLS B c) or inducible (MLS B i). Inducible resistance is observed when the inactive mRNA produced by the production of methylases becomes active in the presence of an inducer, while active methylase mRNA is produced in strains where constitutive expression is seen. [1] The strains carrying the inducible erm gene are resistant to the inducer and remain susceptible to non inducer macrolides and lincosamides. Low levels of erythromycin is an inducer of the MLS B i phenotype, which forms the basis of the D-test. [5]

Treatment of an infection using clindamycin or any non inducer macrolide, caused by a strain carrying inducible erm gene, can lead to clinical failure. [6],[7],[8] Constitutive mutants can be selected in vitro in the presence of clindamycin or any other non inducer macrolide as they are widespread among methicillin-resistant strains. [1] The present study was designed to detect the presence of inducible clindamycin resistance among clinical isolates of staphylococci.


   Materials and Methods   Top


A total of 244 strains of staphylococci, isolated from various clinical samples at our institution, were used in this study. The isolates were identified using conventional methods. [9] Erythromycin (15 µg) and clindamycin (2 µg) discs were procured from Himedia India Ltd. Isolates were initially screened for erythromycin resistance using the Kirby Bauer method.[10] The isolates that were found to be erythromycin resistant were further studied for inducible clindamycin resistance.

The detection of inducible clindamycin resistance was performed using the D-test. [4],[11] Briefly, an erythromycin disk was placed 15 mm (edge to edge) from a clindamycin disk in a standard disk diffusion test. A flattening of the zone of inhibition in the area between the disks where both drugs have diffused after 18-24 hours of incubation was considered to be inducible clindamycin resistance.

Quality control of the erythromycin and clindamycin disks was performed with Staphylococcus aureus Scientific Name Search  ATCC 25923 [Figure 1].[11]


   Results   Top


Among the 244 isolates studied, 150 (61.5%) were S. aureus and 94 (38.5%) were coagulase-negative staphylococci (CONS). Categorization of the isolates along with sources is depicted in [Table 1].

Among the 150 S. aureus strains, 26 (17.3%) were methicillin-resistant S. aureus (MRSA) and 124 (82.6%) were methicillin-sensitive S. aureus (MSSA). Among the CONS, 90 were methicillin-sensitive and 4 were methicillin-resistant [Table 2].

Of the 244 clinical isolates, 78 (32%) showed erythromycin resistance. Among the erythromycin-resistant isolates, 42 (53.8%) were S. aureus among which 14 were MRSA and the rest were MSSA (n = 28). Erythromycin resistance was seen in 36 (46.1%) strains of CONS. Of the 78 erythromycin-resistant isolates, 32 (13.1% of the total isolates) belonged to the MLSBi phenotype and showed inducible clindamycin resistance [Figure 1]. The isolation rates of MLS B i phenotypes from clinical samples are provided in [Table 2]. Among them, 16 isolates were MSSA (12.9%), 6 isolates were CONS (6.3%) and 10 isolates were MRSA (38.4%). Eight isolates showed constitutive resistance to clindamycin, of which 4 were MRSA and the rest were MRCONS. Resistance phenotypes of the isolates are provided in [Table 3].


   Discussion   Top


Accurate drug susceptibility data of the infecting microbe is an essential factor in making appropriate therapeutic decisions. The multiplicity of mechanisms, which confer resistance to MLS antibiotics, reflects the complexity of the resistant phenotypes as well as the clinical situation. The most widespread and clinically important resistance mechanisms encountered with Gram-positive organisms are the production of methylases and efflux proteins. The clinical failure of clindamycin therapy has been reported before. [6],[7],[8] Hence, there is a need to identify the mechanisms that confer resistance to MLS antibiotics with regard to clindamycin therapy of staphylococcal infections.

The emergence of resistance to multiple antibiotics among Gram-positive cocci has left very few therapeutic options for clinicians. Though 50% of our isolates were resistant phenotypes, the other 50% were sensitive to clindamycin, against which it would be safe and appropriate to use clindamycin or other macrolides. Therefore, using in vitro erythromycin resistance as a surrogate marker for all the MLS antibiotics and thereby avoiding them as a treatment option, would be inappropriate. A therapeutic decision is not possible without the relevant antibiotic susceptibility data. This is where the D-test becomes significant.

There have been a number of reports on the pattern of macrolide resistance in staphylococci. [12],[13],[14],[15],[16],[17] Characteristically, each report from different regions has shown a different pattern of resistance. Some reports have indicated a higher prevalence of inducible phenotypes, while others have indicated the frequency of incidence shifting from inducible to constitutive type in S. aureus. [12] Indian reports on inducible clindamycin resistance are scanty. [13],[14],[15]

Previous studies have reported 57% of susceptibility towards clindamycin among the MRSA strains. [16] MLSBi and MLSBc phenotypes were 5.4% and 43.7%, respectively in this study. In an European study, 93% of erythromycin-resistant MRSA and 44% of erythromycin-resistant MSSA exhibited constitutive resistance. [17]

In our study, the scenario was different; 38% of strains were MLSBi phenotype and 15.3% were MLS B c phenotype among the MRSA strains. Results with regard to the MSSA group are similar to the studies from Turkey, where no constitutive resistance was reported and inducible resistance to clindamycin was approximately 11%. [16]

The D-test is an easy test to perform along with routine susceptibility testing. The incidence of resistance is highly variable with regard to geographic locality, hence the local data regarding inducible clindamycin resistance is helpful in guiding anti-staphylococcal therapy.

 
   References   Top

1. Leclercq R. Mechanisms of resistance to macrolides and lincosamides: Nature of the resistance elements and their clinical implications. Clin Infect Dis 2002;34:482-92.  Back to cited text no. 1    
2. Weisblum B. Erythromycin resistance by ribosome modification. Antimicrob Agents Chemother 1995;39:577-85.   Back to cited text no. 2    
3. Roberts MC, Sutcliffe J, Courvalin P, Jensen LB, Rood J, Seppala H. Nomenclature for macrolide and macrolide-lincosamide-streptogramin B resistance determinants. Antimicrob Agents Chemother 1999;43:2823-30.  Back to cited text no. 3    
4. Fiebelkorn KR, Crawford SA, McElmeel ML, Jorgensen JH. Practical disk diffusion method for detection of inducible clindamycin resistance in Staphylococcus aureus and coagulase-negative staphylococci. J Clin Microbiol 2003;41:4740-4.  Back to cited text no. 4    
5. Weisblum B, Demohn V. Erythromycin-inducible resistance in Staphylococcus aureus : Survey of antibiotic classes involved. J Bacteriol 1969;98:447-52.   Back to cited text no. 5    
6. Watanakunakorn C. Clindamycin therapy of Staphylococcus aureus endocarditis: Clinical relapse and development of resistance to clindamycin, lincomycin and erythromycin. Am J Med 1976;60:419-25.   Back to cited text no. 6    
7. Drinkovic D, Fuller ER, Shore KP, Holland DJ, Ellis-Pegler R. Clindamycin treatment of Staphylococcus aureus expressing inducible clindamycin resistance. J Antimicrob Chemother 2001;48:315-6.  Back to cited text no. 7    
8. Siberry GK, Tekle T, Carroll K, Dick J. Failure of clindamycin treatment of methicillin-resistant Staphylococcus aureus expressing inducible clindamycin resistance in vitro. Clin Infect Dis 2003;37:1257-60.   Back to cited text no. 8    
9. Kloos WE, Banerman TL. Staphylococcus and Micrococcus. In: Chapter 22, Manual of clinical Microbiology 7th ed. In: Murray PR, Baron EJ, Pfaller MA, Tenover FC, Yolken RH, editors. Washington DC: ASM Press; 1999. p. 264-82.  Back to cited text no. 9    
10. Bauer AW, Kirby WM, Sherris JC, Turck M. Antibiotic susceptibility testing by a standardized single disk method. Am J Clin Pathol 1966;45:493-6.  Back to cited text no. 10    
11. CDC Appendix (to Routine Disk Diffusion test). Clindamycin disk induction test for Staphylococcus spp. [cited 2004 Jan 15]. Available from: http://www.phppo.cdc.gov/nltn/pdf/2004/2_Hindler_D-Test.pdf.  Back to cited text no. 11    
12. Jenssen WD, Thakker-Varia S, Dubin DT, Weinstein MP. Prevalence of macrolides-lincosamides-streptogramin B resistance and erm gene classes among clinical strains of staphylococci and streptococci. Antimicrob Agents Chemother 1987;31:883-8.  Back to cited text no. 12    
13. Gadepalli R, Dhawan B, Mohanty S, Kapil A, Das BK, Chaudhry R Inducible clindamycin resistance in clinical isolates of Staphylococcus aureus . Indian J Med Res 2006;123:571-3.  Back to cited text no. 13    
14. Navaneeth BV. A preliminary in vitro study on inducible and constitutive clindamycin resistance in Staphylococcus aureus from a South Indian tertiary care hospital. Int J Infect Dis 2006;10:184-5.  Back to cited text no. 14    
15. Angel MR, Balaji V, Prakash J, Brahmadathan KN, Mathews MS. Prevalence of inducible clindamycin resistance in gram positive organisms in a tertiary care centre. Indian J Med Microbiol 2008;26:262-4.  Back to cited text no. 15  [PUBMED]  Medknow Journal
16. Delialioglu N, Aslan G, Ozturk C, Baki V, Sen S, Emekdas G. Inducible clindamycin resistance in staphylococci isolated from clinical samples. Jpn J Infect Dis 2005;58:104-6.  Back to cited text no. 16    
17. Schmitz FJ, Sadurski R, Kray A, Boos M, Geisel R, Kφhrer K, et al . Prevalence of macrolide-resistance genes in Staphylococcus aureus and Enterococcus faecium isolates from 24 European university hospitals. J Antimicrob Chemother 2000;45:891-4.  Back to cited text no. 17    

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Correspondence Address:
A M Ciraj
Melaka Manipal Medical College, Manipal Academy of Higher Education, Manipal, Karnataka - 576 104
India
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DOI: 10.4103/0377-4929.44963

PMID: 19136780

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    Tables

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