Staphylococcus aureus (S.aureus) is recognised as one of the important organism causing hospital-acquired and community-acquired skin and soft tissue infections in most parts of the world. The increasing prevalence of methicillin resistance among Staphylococci is an important concern [1]. The emergence of resistance to methicillin in Staphylococcus aureus has left with very few therapeutic options. The macrolide – lincosamide – streptogramin B (MLS_B) family of antibiotic serves as one such alternative, with clindamycin being the preferred drug due to its excellent pharmacokinetic properties [2].

Clindamycin is considered a useful alternative in Penicillin allergic patients for the treatment of skin and soft tissue infections caused by S.aureus. It gets accumulated in abscesses and no renal dosage adjustment is required. It has excellent tissue penetration except into the central nervous system, where it does not cross the blood-brain barrier, even in the presence of inflamed meninges [3]. Good oral absorption makes it an attractive option for outpatient prescription or as a follow-up drug after intravenous therapy [4].

This helps in the early shift to outpatient management of susceptible infection without the need for continued intravenous access [5]. Widespread use of MLS_B antibiotics has led to an increase in the number of Staphylococcal strains acquiring resistance to MLS_B antibiotics [2,6]. The most common mechanism for such resistance is target site modification mediated by erm genes which can be expressed either constitutively (constitutive MLS_B phenotype) or inducibly (inducible MLS_B phenotype).

Strains with inducible resistance to clindamycin are difficult to detect in the routine laboratory as they appear erythromycin resistant and clindamycin sensitive in vitro when not placed adjacent to each other. In such cases, in vivo therapy with clindamycin may select constitutive erm mutants leading to clinical therapeutic failure.

In the case of another mechanism of resistance mediated through MSR A genes i.e. efflux of antibiotic, Staphylococcal isolates appear erythromycin resistant and clindamycin sensitive with both in vivo and in vitro and the strain does not typically become clindamycin resistant during therapy [7].

Fig 1. Showing D shaped zone around clindamycin when clindamycin and erythromycin are placed at a distance of 15mm indicating D test positive.

Three phenotypes were identified :

1. MS phenotype: Staphylococcal isolates exhibiting resistance to erythromycin (zone size ≤ 13mm) while sensitive to clindamycin (zone size ≥21 mm) and giving circular zone of inhibition around clindamycin was labelled as having MS phenotype.
2. Inducible MLS_B (iMLS_B) phenotype: Staphylococcal isolates sharing resistance to erythromycin (zone size ≤ 13mm) while being sensitive to clindamycin (zone size ≥ 21mm) and giving D shaped zone of Inhibition around clindamycin with flattening towards erythromycin disc was labelled as having iMLS_B phenotype.
3. Constitutive MLS_B (cMLS_B) phenotype: This phenotype was labelled for those Staphylococcal isolates which showed resistance to both erythromycin (zone size ≤ 13mm ) and clindamycin (zone size ≤14 mm) with a circular shape of the zone of inhibition around the discs.

Results were tabulated and analyzed statistically. One hundred and sixty-five Staphylococcus aureus isolates were tested for susceptibility to erythromycin and other antibiotics by routine disc diffusion testing.

Table-1: Susceptibility to Erythromycin and Clindamycin among Staphylococcus aureus isolates

ERY – Erythromycin, CL – Clindamycin, S – Sensitive, R – Resistant, cMLS_B – constitutive MLS_B phenotype, iMLS_B – inducible MLS_B phenotype, MS – MS phenotype.

It was also observed that percentages of inducible resistance and MS phenotype were higher amongst MRSA (21.42% and 40.47%) as compared to MSSA (7.40% and 30.86%). This was in concordance with a few of the studies reported earlier. Deotale v et al. found inducible resistance of 27.6% in MRSA and 1.6% in MSSA and MS phenotype were high amongst MRSA (24.3%) as compared to MSSA (4%) [2]. Yilmaz et al [1] found inducible resistance of 24.4% in MRSA and 14.8% in MSSA, Gadepalli et al. [6] showed it to be 30% in MRSA and 10% in MSSA, While Mohamed Rahabar et al. [15] reported 22.6% in MRSA and 4% in MSSA.

Constitutive resistance in our study was seen in 5 (5.95%) of MRSA isolates and 3 (3.70%) in MSSA isolates. This was in concordance with Kavitha Prabhu et al. where the percentages of constitutive resistance among MRSA and MSSA were (16.66%) and 6.15% respectively [16]. Also this was in concordance with a few of the studies reported earlier [1]. Some studies have shown a very high frequency of inducible resistance among MRSA [11]. On the contrary few studies have shown a higher percentage of inducible resistance in MSSA as compared to MRSA [17,18].

Because of a restricted range of antibiotics for the treatment of MRSA infection and the known limitations of vancomycin, Clindamycin should be considered for the management of serious skin and soft tissue infection with MRSA that are sensitive to clindamycin [19]. The true sensitivity to clindamycin can only be judged after performing a D test on erythromycin resistant isolates, as the prevalence of inducible clindamycin resistance (Macrolide resistance) in Staphylococcus aureus varies in different regions and from hospital to hospital.

From our study we can conclude that there is a fairly high percentage of inducible clindamycin resistance amongst the Staphylococcal isolates which shows erythromycin resistance.

So clinical Microbiology laboratories should report inducible clindamycin resistance in Staphylococcus aureus, and the D test can be used as a simple and reliable method to delineate inducible and constitutive clindamycin resistance in routine clinical laboratories.