Methicillin resistance & inducible clindamycin resistance in Staphylococcus aureus

Infection with methicillin resistant Staphylococcus aureus (MRSA) has emerged as a major problem of public health importance. Methicillin resistance is usually conferred by altered penicillin binding protein (PBP-2a) that causes resistance to all ß-lactam antimicrobial agents1. Clindamycin is not recommended for any infection caused by an inducible resistant isolate. MRSA isolates with inducible clindamycin resistance (iCR) are resistant to erythromycin and sensitive to clindamycin on routine testing. D-test can help to determine whether clindamycin could be used as a therapeutic option2. Sedighi et al3 have recommended) to use D-test routinely in all microbiologic laboratories and not to apply clindamycin in patients with infections caused by inducible resistant S. aureus. They also suggested to avoid switch therapy from erythromycin to clindamycin3. We undertook this study to investigate the presence of methicillin resistance and inducible clindamycin resistance, to estimate any existing relation between these two variables and to test the effectiveness of commonly used antibiotics on MRSA.

Material & Methods

The present study was conducted during May-July 2013 at the Microbiology department of Nilratan Sircar Medical College and Hospital, Kolkata, West Bengal, India. A total of 46 non-duplicate S. aureus isolates selected consecutively (23 pus, 6 blood, 17 wound swab samples) were subjected to Kirby-Bauer's disk diffusion method4. D-test for detecting iCR was employed on all specimens.

The antibiotic susceptibility test (AST) was done using Mueller-Hinton agar plate and evaluated using Clinical and Laboratory Standards Institute (CLSI) guidelines5. The isolates were tested for cefoxitin (30 μg), clindamycin (2 μg), azithromycin (15 μg), erythromycin (15 μg), co-trimoxazole (1.25/23.75 μg), ciprofloxacin (5 μg), vanocomycin and linezolid (30 μg) each. For D-test standard procedure as depicted by Seifi et al6 was followed. Chi-square test of significance for antibiotic effect on MRSA and methicillin sensitive S. aureus (MSS) and Karl-Pearson's correlation coefficient (r) for correlating methicillin resistance in S. aureus and iCR were employed.

Results & Discussion

Of the 46 isolates tested, 11 (23.9%) were MRSA, and 35 (76.1%) were MSSA. Six of 17 (35.3%) isolates from wound swab specimens were MRSA while five of six (83.3%) isolates from blood samples were MSSA. Nineteen of 46 isolates (41.3%) showed iCR.

Wound swab and blood specimens exhibited the highest (10 of 17, 58.82%) and lowest (1 of 6, 16.67%) iCR, respectively. Six of eleven (54.54%) MRSA and 13 of 35 (37.14%) MSSA isolates showed iCR. Ten of 17 (58.8%) erythromycin-resistant and clindamycin-sensitive isolates showed positive D-test.

All isolates were sensitive to vancomycin and linezolid. Co-trimoxazole followed vancomycin and linezolid in effectiveness among the antibiotics tested against MRSA (45.5%), and a similar percentage of MSSA (40%) was sensitive to co-trimoxazole (Table). Nine of the 11 MRSA (81.82%) isolates, 22 of the 35 MSSA (62.86) isolates and all 19 iCR isolates were resistant to azithromycin. A study in the UK underlines the futility of using macrolides in MRSA infections7. Six of the MRSA (54.54%) and 21 of the MSSA (60%) isolates were resistant to co-trimoxazole. The correlation coefficient between MRSA and iCR in S. aureus was 0.89.

Table Isolates showing resistance and sensitivity to different antibiotics tested

The findings on MRSA in our study was similar to that reported by Mehdinejad et al8. In a study by Prabhu et al9, 20 per cent MRSA and six per cent MSSA showed iCR contributing to an overall ten per cent prevalence of iCR. In the present study, about 40 per cent isolates showed iCR.

The relationship between MRSA and iCR appears to be clinically insignificant despite a high positive correlation coefficient.

MRSA is a growing public health problem globally. In our hospital 23.9 per cent of the tested isolates were MRSA. Higher prevalence of antibiotic resistance was noted among MRSA when tested for azithromycin and ciprofloxacin as compared to cotrimoxazole. Vancomycin and linezolid were found to be effective in all MRSA infected cases. A significant correlation could not be found between methicillin resistance and iCR.