Vol 43 # 2 June 2011 - Kma.org.kw

More documents

Recommendations

Info

106 Inducible Clindamycin Resistance in Staphylococcus Aureus: A Study from a Tertiary Care Hospital... June 2011 In the present study, the aim was to determine the incidence of methicillin resistance among S.aureus isolates from various clinical samples and to detect inducible MLSB resistant strains. Also, we tried to ascertain the relationship between MRSA and MLSBi isolates, association of MLSBi isolates with community or nosocomial setting and lastly, treatment options for these MLSBi isolates. MATERIALS AND METHODS Bacterial isolates This study included 250 consecutive, non-duplicate strains of Staphylococcus aureus isolated from various clinical specimens (pus, wound swabs, blood, respiratory tract, urine, high vaginal swabs and body fluids), derived from both outpatients and inpatients of our teaching and tertiary care hospital during March 2007- July 2008. S.aureus isolates were identified using standard microbiological procedures [6] . Detection of methicillin resistance All identified isolates of S. aureus were subjected to antibiotic susceptibility testing by Kirby-Bauer disc diffusion method based on guidelines from the Clinical Laboratory Standards Institute (CLSI) [7] . Methicillin resistance was detected by using oxacillin (1μg) disc on a swab inoculated Mueller-Hinton Agar (MHA) plate supplemented with 2% NaCl and incubating at 35 ºC for 24 hours [8] . Detection of inducible clindamycin resistance Inducible clindamycin resistance was detected by performing a disc approximation test, by placing a 2 μg clindamycin disc at a distance of 15 mm (edge to edge) from a 15 μg-erythromycin disc on the same plate as a part of the normal disc diffusion procedure [9] . 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 S.aureus strains that demonstrated positive and negative D-test reactions. Reporting Interpretation was done in accordance with CLSI guidelines. Isolates resistant to both erythromycin and clindamycin were defined as showing constitutive MLSB resistance (MLSBc phenotype). Those showing flattening or blunting of the clindamycin zone adjacent to the erythromycin disc (referred to as a “D” zone) were defined as having inducible clindamycin resistance (MLSBi phenotype), and those that were resistant to erythromycin and sensitive to clindamycin (no induction) were defined as showing the MS phenotype [9] . All strains with MLSBi phenotype were then tested for antimicrobial susceptibility using Kirby- Bauer disc diffusion method for the following antimicrobial agents with their disc content in brackets:- cephalexin (30 μg), amoxicillin / clavulanic acid (20 / 10 μg), trimethoprim / sulfamethoxazole (1.25 / 23.75 μg), linezolid (30 μg), vancomycin (30 μg), doxycycline (30 μg), quinupristin-dalfopristin (15 μg), ciprofloxacin (5 μg) and gatifloxacin (5 μg). Statistical analysis The results obtained were analyzed statistically using Chi-square test to compare differences between groups. All analyses were two tailed, and p < 0.05 was considered significant. RESULTS Among 250 S.aureus isolates studied, maximum isolation was from pus and pus swabs (60.8%), followed by blood (14.8%). The rate of isolation from inpatients was 69.2%. 44.8% isolates were found to be MRSA. Table 1 shows the distribution of MLSB resistance phenotypes (constitutive resistance, inducible resistance and MS phenotype) among MRSA and MSSA isolates. A total of 50 (20%) isolates of S.aureus were found to be D-test positive. Among MRSA isolates, 44.7% had the constitutive and 33.9% had the inducible clindamycin resistance. In MSSA isolates, 11.6% and 8.7% isolates exhibited the constitutive and inducible resistance phenotypes respectively. Thus, both the constitutive and inducible resistance phenotypes were found to be significantly higher in MRSA isolates compared to MSSA (p < 0.0001and p < 0.0001 respectively by Chi-square test). Isolates with MS phenotype and sensitive to both erythromycin and clindamycin were predominant among MSSA. Also, we found that out of 38 MRSA strains which had MLSBi phenotype, 24 (63.2%) were hospitalacquired and 14 strains (36.2%) were communityacquired. Similarly, among 12 MSSA strains with MLSBi phenotype, hospital-acquired strains (66.7%) were more as compared to community-acquired (33.3%). Susceptibility of the isolates with MLSBi resistance was cephalexin 48%, amoxyclav 44%, cotrimoxazole 24%, doxycycline 46%, quinopristin-dalfopristin 54%, ciprofloxacin 44%, gatifloxacin 64%, vancomycin 100% and linezolid 100%. DISCUSSION Clindamycin is a useful drug in the treatment of skin and soft-tissue infections and serious infections caused by staphylococcal species, as well as anerobes. It has excellent tissue penetration (except for the central nervous system), accumulates in abscesses, and no renal
June 2011 KUWAIT MEDICAL JOURNAL 107 Table 1: Distribution of MLSB resistance phenotypes among MRSA and MSSA isolates Isolates (n) MLSBc phenotype (%) MLSBi phenotype (%) MS phenotype (%) Sensitive to both ERY and CLI (%) MRSA (112) MSSA (138) Total (250) 50 (44.7) 16 (11.6) 66 (26.4) 38 (33.9) 12 (8.7) 50 (20.0) 11 (9.8) 27 (19.6) 38 (15.2) 13 (11.6) 83 (60.1) 96 (38.4) MRSA – Methicillin - resistant S.aureus, MSSA- Methicillin - sensitive S.aureus, MLSBc - Constitutive MLSB resistance, MLSBi - Inducible clindamycin resistance, MS phenotype - Resistant to erythromycin and sensitive to clindamycin but no induction, ERY- Erythromycin, CLI- Clindamycin dosing adjustments are needed. Good oral absorption makes it an important option in outpatient therapy or as follow-up after intravenous therapy. Clindamycin is also of particular importance as an alternative antibiotic in the penicillin-allergic patient [3] . For any clinical microbiology laboratory, the differentiation of erm-mediated inducible MLSB (MLSBi phenotype) isolates from isolates with msrAmediated (MS phenotype) resistance is a critical issue because of the therapeutic implications of using clindamycin to treat a patient with an inducible clindamycin-resistant S.aureus isolate [5] . Since the MLSBi resistance mechanism is not recognized by using standard susceptibility test methods and its prevalence varies according to geographic location, D-test becomes an imperative part of routine antimicrobial susceptibility test for all clinical isolates of S.aureus. Failure to identify MLSBi resistance may lead to clinical failure of clindamycin therapy. Conversely, labeling all erythromycin-resistant staphylococci as clindamycin-resistant prevents the use of clindamycin in infections caused by truly clindamycin-sensitive staphylococcal isolates. Hence, CLSI recommends routine testing of all staphylococcal isolates for MLSBi resistance [1,3] . In our study, we found that among 112 MRSA isolates, 44.7, 33.9 and 9.8% isolates had the constitutive MLSB resistance, inducible clindamycin resistance and the MS phenotype respectively. Both constitutive and inducible resistance was significantly higher in MRSA isolates in comparison to MSSA. These findings are in concordance with various studies reported by Azap et al, Schmitz et al, Fiebelkorn et al, and many more [2,3,10-14] . Likewise, from India, Gadepalli et al, Gupta et al, and Pal et al had similar findings [1,15,16] . Schreckenberger et al [17] and Levin et al [18] showed higher percentage of inducible resistance in MSSA as compared to MRSA which is contrary to our study. None of the above quoted studies found MS phenotype among MRSA isolates except those by Gupta et al and Pal et al [15,16] which is in accordance with our study. Similarly, Angel et al from India found that among the MRSA isolates 12% had the MS phenotype [19] . In our study, we found that among MSSA isolates, MS phenotype was predominant (19.6%), with 11.6 and 8.7% isolates having MLSBc and MLSBi resistance respectively. On the contrary, Deotale et al reported that only 1.6% of MSSA isolates had MLSBi phenotype and Gupta et al reported high level of inducible resistance (17.3%) compared to constitutive resistance (10%) in MSSA isolates [15,20] . However, Angel et al and Ciraj et al did not find constitutive MLSB resistance pattern in MSSA isolates [19,21] . 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 prescribing patterns of physicians. These differences highlight the significance of inducible clindamycin resistance in our geographical setting. The presence of a higher rate of inducible clindamycin resistance in hospital-acquired strains (36 isolates out of 50) 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. The treatment options recommended for serious infections due to MRSA are the glycopeptide antibiotics such as vancomycin or teicoplanin, linezolid, quinupristin-dalfopristin, trimethoprimsulfamethoxazole, clindamycin, doxycycline, fluoroquinolones or rifampicin [22] . In our study, we did not find any isolate showing resistance either to vancomycin or to linezolid. Recent reports of S. aureus isolates with intermediate or complete resistance to vancomycin portend a chemotherapeutic era in which effective bactericidal antibiotics against this organism may no longer be readily available. Clindamycin is a useful drug and is usually advocated in severe in-patient MRSA infections depending upon the antimicrobial susceptibility results [22] . Further, by using clindamycin, use of vancomycin can be avoided. However, expression of inducible resistance to clindamycin could limit the effectiveness of this drug. Hence, clinical laboratories should report in vitro inducible clindamycin resistance in S. aureus isolates and clinicians should be aware of the potential of clindamycin treatment failure in patients with infections caused by inducible resistant strains. In such cases, vancomycin and linezolid are the drugs which are considered for therapy [1] .
Page 1 and 2: VOLUME 43 NUMBER 2 KMJ KUWAIT MEDIC
Page 3 and 4: Kuwait Medical Journal (KMJ) Publis
Page 5 and 6: Instructions for Authors five), fol
Page 7 and 8: June 2011 KUWAIT MEDICAL JOURNAL 87
Page 25: June 2011 KUWAIT MEDICAL JOURNAL 10
Page 55 and 56: June 2011 and premature delivery, s
Page 77 and 78:
June 2011 KUWAIT MEDICAL JOURNAL 15
Page 79 and 80:
Page 81 and 82:
Page 83 and 84:
Page 85 and 86:
Page 87 and 88:
Page 89 and 90:
Page 91 and 92:
show all

Vol 43 # 2 June 2011 - Kma.org.kw

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?