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ORIGINAL ARTICLE  
Year : 2012  |  Volume : 5  |  Issue : 5  |  Page : 427-430
Prevalence of inducible clindamycin resistance in clinical isolates of coagulase negative staphylococci at a tertiary care hospital


1 Department of Microbiology, Government Medical College Hospital, Sector-32, Chandigarh, India
2 Department of Microbiology, Pt. B.D.S. University of Health Sciences, Rohtak, Haryana, India
3 Department of General Medicine, National Institute of Medical Sciences, Jaipur, India

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Date of Web Publication27-Dec-2012
 

   Abstract 

Background : Coagulase negative staphylococci (CoNS) are an important group of multi-drug resistant nosocomial pathogens. Clindamycin resistance in staphylococci can be either constitutive or inducible. Clindamycin has been used successfully to treat pneumonia, soft-tissue and musculoskeletal infections due to methicillin-resistant CoNS (MRCoNS) in adults and children, but this matter is complicated by the possibility of inducible macrolide-lincosamide streptogramin B resistance (MLSBi). Aims: The present study was aimed to determine the incidence of inducible clindamycin resistance in CoNS isolates in our hospital using D-test, relationship between MRCoNS and MLSBi isolates, association of MLSBi isolates with community or nosocomial setting and treatment options for these isolates. Materials and Methods : A total of 250 consecutive, non-duplicate strains of CoNS were isolated from various clinical specimens, both from indoor and outdoor patients. After determining methicillin resistance, D-test was performed on all erythromycin-resistant and clindamycin-sensitive isolates to detect inducible clindamycin resistance. Results : Among 250 CoNS isolates, 89 (35.6%) were found to be MRCoNS and 20% had MLSBi phenotype. MRCoNS showed higher inducible as well as constitutive resistance (p<0.0001) to clindamycin as compared to methicillin-sensitive CoNS (MSCoNS). All isolates having MLSBi phenotype were sensitive to vancomycin and linezolid. Conclusions : Clindamycin is a useful drug in the treatment of staphylococcal infections. Hence, routine testing of staphylococcal isolates for inducible clindamycin resistance is strongly recommended.

Keywords: D-test, inducible resistance, macrolide-lincosamide streptogramin B resistance phenotype, methicillin-resistant CoNS, staphylococci

How to cite this article:
Bansal N, Chaudhary U, Gupta V. Prevalence of inducible clindamycin resistance in clinical isolates of coagulase negative staphylococci at a tertiary care hospital. Ann Trop Med Public Health 2012;5:427-30

How to cite this URL:
Bansal N, Chaudhary U, Gupta V. Prevalence of inducible clindamycin resistance in clinical isolates of coagulase negative staphylococci at a tertiary care hospital. Ann Trop Med Public Health [serial online] 2012 [cited 2018 May 23];5:427-30. Available from: http://www.atmph.org/text.asp?2012/5/5/427/105124

   Introduction Top


Coagulase-negative staphylococci (CoNS) have been recognised worldwide as important causes of nosocomial and community-acquired infections. [1] The increasing prevalence of methicillin resistance among staphylococci is a therapeutic threat, and clindamycin is considered to be one of the alternative agents available to address this issue. [2] The macrolides, lincosamides and type B streptogramin agents (MLSB) are chemically distinct but exert similar action by binding to 50S ribosomal subunit inhibiting bacterial protein synthesis. In staphylococci, macrolide (erythromycin) resistance is usually caused either by an active efflux mechanism encoded by msrA gene (conferring resistance to macrolides and group B streptogramins only) or by ribosomal modification mediated by 23S rRNA methylases encoded by the erm genes. Methylases lead to MLSB resistance which can either be inducible (MLSBi resistance) or constitutive (MLSBc resistance). [3]

Staphylococcal isolates with MLSBc resistance are resistant to both erythromycin and clindamycin in vitro whereas strains with MLSBi resistance phenotype appear resistant to erythromycin but susceptible to clindamycin. [4] Thus standard methods for antimicrobial susceptibility tests do not recognize MLSBi resistance and this may lead to therapeutic failure when clindamycin is used. Disc diffusion induction methods (D-test) should be used routinely in microbiological laboratories to detect MLSBi resistance. This test involves the placement of an erythromycin disc close to a clindamycin disc. The diffusion of erythromycin induces resistance to clindamycin, giving a flattening zone of inhibition around the clindamycin disk adjacent to the erythromycin (D-shaped zone). [5] Although there is growing data regarding the prevalence of MLSBi resistance phenotypes among Staphylococcus aureus isolates from different regions of India, data in CoNS is still limited. The present study was undertaken to investigate the prevalence of inducible resistance to clindamycin in CoNS as these are now important emerging nosocomial pathogens.


   Materials and Methods Top


A total of 250 single-patient coagulase negative staphylococcal clinical isolates from inpatients or outpatients attending a North Indian hospital were prospectively collected during the period from March 2007-July 2008. These isolates were recovered from a wide range of infections, including skin surgical site infections (SSI), bloodstream infections (BSI), respiratory tract infections (RTI), urinary tract infections, ear infections, and ocular infections. The clinical isolates were identified as CoNS by performing standard microbiological procedures.

Resistance to oxacillin, erythromycin, and clindamycin was assessed based on the guidelines from the Clinical Laboratory Standards Institute (CLSI). [6] The resistance phenotypes of erythromycin-resistant isolates were determined by the double disc test with erythromycin (15μg) and clindamycin (2μg) discs placed at a distance of 15mm edge to edge. After 18 h incubation at 37°C, blunting of the clindamycin zone of inhibition proximal to the erythromycin disc indicated an inducible type of MLSB resistance and resistance to both erythromycin and clindamycin indicated constitutive MLSB resistance. Isolates which were resistant to erythromycin and remained sensitive to clindamycin (no induction) were defined as showing the MS phenotype. [6] All antibiotic discs used in the study were procured from Hi-media ® Laboratories, Mumbai, India. S. aureus American Type Culture Collection (ATCC) 25923 was used to achieve quality control (QC) for antibiotic sensitivity tests. Additional QC was performed with separate in-house selected CoNS strains that demonstrated positive and negative D-test reactions. All strains with MLSBi phenotype were further tested for antimicrobial susceptibility using Kirby-Bauer [7] disc diffusion method for the following antimicrobial agents with their disc content in brackets:- Cephalexin (30μg), amoxycillin/clavulanic acid (20/10μg), trimethoprim/sulfamethoxazole (1.25/23.75μg), linezolid (30μg), vancomycin (30μg), quinupristin-dalfopristin (15μg), ciprofloxacin (5μg), gatifloxacin (5μg).


   Results Top


Among 250 CoNS isolates studied, maximum isolation was from pus and pus swabs (37.2%) followed by urine (30.8%) and blood (25.2%). The rate of isolation from indoor patients was 70%. 35.6% isolates were found to be methicillin-resistant CoNS (MRCoNS). [Table 1] shows the distribution of MLSB resistance phenotypes (constitutive resistance, inducible resistance and MS phenotype) among MRCoNS and methicillin-sensitive CoNS (MSCoNS) isolates.
Table 1: Distribution of MLSB resistance phenotypes among MRCoNS and MSCoNS isolates


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A total of 45 (18%) isolates of CoNS were found to be D-test positive. Among MRCoNS isolates, 51.7% had the constitutive and 25.8% had the inducible clindamycin resistance. In MSCoNS isolates, 11.8% and 13.7% isolates exhibited the constitutive and inducible resistance phenotypes respectively. Thus, both the constitutive and inducible resistance phenotypes were found to be significantly higher in MRCoNS isolates compared to MSCoNS (P<0.0001and P<0.05 respectively by Chi-square test). Isolates with MS phenotype and sensitive to both erythromycin and clindamycin were predominant among MSCoNS.

Also, we found that out of 23 MRCoNS strains which had MLSBi phenotype, 18 (78.3%) were hospital-acquired and 5 strains (21.7%) were community-acquired. Similarly, among 22 MSCoNS strains with MLSBi phenotype, hospital-acquired strains (68.2%) were more as compared to community-acquired (31.8%).

[Table 2] shows the antibiotic profile of the isolates with MLSBi resistance. The isolates were found to be least sensitive to cotrimoxazole, ciprofloxacin and amoxycillin/clavulanic acid while no resistance was seen to vancomycin and linezolid.
Table 2: Sensitivity of isolates with MLSBi resistance phenotype (n=45) to various antimicrobial agents

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   Discussion Top


The increasing frequency of coagulase-negative staphylococcal infections and ever increasing problem of methicillin resistance among staphylococci have led to renewed interest in the use of clindamycin therapy to treat such infections. Clindamycin is a good alternative to vancomycin for the treatment of both meticillin-resistant and -susceptible staphylococcal infections. [1],[2] It's tolerability, cost, good oral absorption and excellent tissue penetration makes it an important option in outpatient therapy or as follow-up after intravenous therapy. [8] However, one important issue in clindamycin treatment is the risk of clinical failure during therapy. Therapeutic failures caused by MLSB inducible resistance phenotypes are being more commonly reported due to selection of constitutive mutants both in vitro and in vivo during clindamycin therapy. [9],[10],[11],[12],[13],[14] Conversely, labeling all erythromycin-resistant staphylococci as clindamycin resistant prevents the use of clindamycin in infections caused by truly clindamycin-susceptible staphylococcal isolates. A therapeutic decision is not possible without the relevant antibiotic susceptibility data. This is where the D-test becomes significant.

In our study we found that among 89 MRCoNS isolates, 51.7%, 25.8% and 12.4% isolates had the constitutive MLSB resistance, inducible clindamycin resistance and the MS phenotype respectively. But in our MSCoNS isolates, MS phenotype was predominant (27.3%), with 11.8% and 13.7% isolates having MLSBc and MLSBi resistance respectively. Both constitutive and inducible resistances were significantly higher in MRCoNS isolates in comparison to MSCoNS. Likewise, Azap et al and other researchers reported a higher percentage of constitutive and inducible clindamycin resistance in MRCoNS compared to MSCoNS isolates from a hospital in Turkey. [15],[16],[17] Lim et al,[18] reported inducible resistance in 9.6% CoNS isolates by the disc diffusion test whereas Schmitz et al,[19] documented a fairly high incidence of both constitutive (69%) and inducible (30%) resisatnce in CoNS. On the contrary Hamilton-Miller et al,[20] determined higher rates of inducible resistance compared to constitutive in CoNS. From India, Ciraj et al,[21] reported an incidence of 6.3% of inducible clindamycin resistance in CoNS which is significantly lower than our results. Similarly, Angel et al,[22] reported 19% MS phenotype and 10% MLSBi resisatnce but no MLSBc phenotype in their CoNS isolates. Pal et al,[23] from western India reported higher inducible resistance rates in MRCoNS than MSCoNS which is in accordance with our study. Possible variations in the prevalence of constitutive, inducible clindamycin resistance and MS phenotype could be explained due to differences in bacterial susceptibility in different geographical areas and also due to varying antimicrobial subscribing patterns of physicians. These differences highlight the significance of inducible clindamycin resistance in our geographical setting.

The presence of higher rate of inducible clindamycin resistance in hospital-acquired strains (33 isolates out of 45) is also a critical finding in the study. This is explained by the fact that nosocomial strains are often multi-drug resistant owing to injudicious use of all available effective antimicrobial agents. Also, low prevalence of MLSBi in community setting makes clindamycin a good therapeutic option.

Recent reports on surveillance data have indicated that CoNS are among the five most commonly reported pathogens (in fifth place at 9 to 9.7%, compared with 10 to 11.2% for  S.aureus Scientific Name Search ) in hospitals conducting hospital-wide surveillance. [1] Most noticeably, the shifts have been toward the more antibiotic resistant pathogens, of which the CoNS are a major group and clindamycin is an attractive therapeutic alternative to vancomycin in staphylococcal infections. [2] Hence, to conclude it is important for laboratories to be aware of the local prevalence of MLSBi resistance as the incidence is highly variable with regard to geographical area. The D-test is an easy, sensitive, and reliable means for detection of MLSBi strains in a clinical laboratory setting and should be performed routinely.

 
   References Top

1.Kloos WE, Bannerman TL. Update on clinical significance of coagulase-negative staphylococci. Clin Microbiol Rev 1994;7:117-40.  Back to cited text no. 1
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Correspondence Address:
Neha Bansal
Department of Microbiology, Government Medical College Hospital, Sector-32, Chandigarh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1755-6783.105124

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