Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
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On Aug 2018




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An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



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Aug 2018




Dr. Rajendra Kumar Ghritlaharey

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Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
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Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
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Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011

Important Notice

Original article / research
Year : 2009 | Month : June | Volume : 3 | Issue : 3 | Page : 1513 - 1518

Inducible Clindamycin Resistance In Staphylococcus Aureus-A Therapeutic Challenge

Mallick SK*, BasakS**, Bose S***

*(M.B.B.S)P.G. Student (M.D. Microbiology), **(M.D) Professor of Microbiology, ***( M.D) Professor of Microbiology, Jawaharlal Nehru Medical College , Sawangi (M) Wardha (M.S)

Correspondence Address :
Dr. Silpi Basak, (M.D),
Prof., Dept. of Microbiology,
Jawaharlal Nehru Medical College ,
Sawangi (M) Wardha, Ph: (07152) 287765,
09421726385. E-mail: drsbasak1@yahoo.com

Abstract

In modern medical practice, multidrug resistant Staphylococcus aureus isolates have limited therapeutic options. Clindamycin is a useful drug in treating Staphylococcal infection. This study was undertaken to determine the prevalence of inducible clindamycin resistance in clinical isolates of Staphylococcus aureus.

Inducible clindamycin resistance was tested by the clindamycin disc induction test (D-zone test) as recommended by the Clinical and Laboratory Standards Institute (CLSI) (previously known as NCCLS), 2004 guidelines.

18.6% of Staphylococcus aureus isolates were positive for inducible clindamycin resistance and belonged to the iMLSB phenotype. All iMLSB phenotypes (100%) were sensitive to vancomycin and linezolid, Moreover, all iMLSB phenotypes were methicillin resistant Staphylococcus aureus (MRSA).

We conclude that the clindamycin disc induction test (D-zone test) is easy, which should be performed routinely by all clinical microbiology laboratories to guide the clinicians about the iMLSB phenotype of Staphylococcus aureus to prevent misuse of antibiotics.

Keywords

Staphylococcus aureus, Inducible clindamycin resistance, D-zone test.

How to cite this article :

Mallick SK, Basak S, Bose S . INDUCIBLE CLINDAMYCIN RESISTANCE IN STAPHYLOCOCCUS AUREUS-A THERAPEUTIC CHALLENGE. Journal of Clinical and Diagnostic Research [serial online] 2009 June [cited: 2019 Aug 23 ]; 3:1513-1518. Available from
http://www.jcdr.net/back_issues.asp?issn=0973-709x&year=2009&month=June&volume=3&issue=3&page=1513-1518&id=525

Introduction
Antibiotic resistance in Staphylococcus aureus has become an ever-increasing problem. In Staphylococcus, penicillin resistance was recognized first in 1944 and methicillin resistance was recognized first in 1961 (1). In 1997, the intermediate susceptibility to vancomycin (VISA), heteroVISA and vancomycin resistant Staphylococcus aureus (VRSA) had been reported (2).

The increasing frequency of Methicillin resistant Staphylococcus aureus (MRSA) infections and the changing patterns of antibiotic resistance have led to renewed interest in macrolides, lincosamides and streptograminB (MLSB) antibiotics, especially in patients who are allergic to penicillin.

Clindamycin, a semisynthetic derivative of lincomycin has excellent tissue penetration (except for the central nervous system), rapid oral absorption, no requirement of dosage adjustment in the presence of renal disease and it is one of the most efficient antibiotics in treating Staphylococcal skin and soft tissue infections, including osteomyelitis.

The chemical structures of macrolides, lincosamides and streptogramin B are very different, but their mechanism of action is identical (3). All 3 antibiotics block protein synthesis by inhibiting peptidyltransferase. Bacteria develop cross resistance quite often to MLSB due to overlapping binding sites in 23SrRNA. Three types of MLSB resistance can be observed- i) Constitutive (c MLSB), ii)Inducible (iMLSB) and iii) MSB Phenotype.

Most commonly, the resistance to MLSB antibiotics occurs from the acquisition of the erm genes which encode enzymes that methylate 23SrRNA (3).

In constitutive MLSB resistance, active methylase mRNA is produced in absence of an inducer and the strains show a high level of cross-resistance to MLSB drugs. In inducible MLSB resistance, the bacteria produce inactive mRNA which is unable to encode methylase. The mRNA becomes active only in the presence of a macrolide inducer. Bacterial strains having an inducible erm gene are resistant to the inducer but appear to be susceptible to clindamycin by the disc diffusion method, thereby confusing Microbiologists. On getting the report as ‘Clindamycin sensitive’, clinicians have only two options, either to avoid prescribing a useful drug such as clindamycin or to lead to a therapeutic failure by using it. Inducible clindamycin resistance is not detected by standard broth microdilution testing, automated susceptibility testing devices, the standard disc diffusion test or the E-test (AB Biodisk) (4).

The issues of the detection and the reporting of inducible MLSB in Staphylococci have been addressed in 2004 at the Clinical and Laboratory Standards Institute (CLSI) guidelines, formerly known as the National Committee for Clinical Laboratory Standards (NCCLS) guidelines for antibiotic susceptibility testing (5). The CLSI has described the test methods that can routinely detect inducible clindamycin resistance.

In the MSB phenotype, a fully operational efflux pump that has specificity for 14- and 15-membered macrolides and streptogramin B, is responsible for MSB resistance. The efflux system involves the msr(A) and chromosomal genes to constitute the operational efflux pump(6). Clindamycin is neither an inducer nor a substrate for the pump and the strains are fully sensitive to clindamycin.

Aims And Objectives
The present study was undertaken
>> To determine the prevalence of inducible clindamycin resistance in the clinical isolates of Staphylococcus aureus.
>> To study the antibiotic sensitivity pattern of Staphylococcus aureus strains having the iMLSB phenotype.

Material and Methods

This study was conducted for a period of 10 months from September 2007 to June 2008. A total number of 366 Staphylococcus aureus strains were isolated and identified from clinical specimens such as pus, blood, body fluids, drain fluids, sputum, throat swab etc. following standard procedures (7) in the department of Microbiology, Jawaharlal Nehru Medical College, Sawangi (M), Wardha.

Antibiotic susceptibility tests were performed by the Kirby-Bauer disc diffusion method (8). Methicillin resistance was detected, based on CLSI recommendations, using a 1µg oxacillin disc(9) Staphylococcus aureus ATCC 25923 was used as control strain for the disc diffusion method.

D-zone test: The Erythromycin and Clindamycin double disc susceptibility test (D-zone test) was performed as per NCCLS guideline 2004 (5). A disc containing erythromycin (15 µg) was placed 15mm from centre to centre of a clindamycin (2 µg) disc. Inducible resistance to clindamycin is manifested by flattening or blunting of the clindamycin zone of inhibition adjacent to the erythromycin disc, giving a D-shape to the zone of inhibited growth. (Table/Fig 1)

Strains resistant to both erythromycin and clindamycin were defined as showing a constitutive MLSB (cMLSB) phenotype. Strains that were resistant to erythromycin and sensitive to clindamycin (no induction) were defined as showing the MSB phenotype (10).

Results

Among the 366 Staphylococcus aureus strains studied, 68 (18.6%) strains were D zone positive i.e. of the inducible MLSB (iMLSB) phenotype, which were resistant to erythromycin and sensitive to clindamycin by routine antibiotic sensitivity tests.

Out of 68 iMLSB phenotype Staphylococcus aureus strains, 48 (70.6%) strains were isolated from pus, followed by 9 (13.2%) strains which were isolated from blood culture (Table/Fig 2). All 68 (100%) iMLSB phenotype Staphylococcus aureus strains were sensitive to vancomycin and linezolid and 23 (33%) strains were sensitive to gattifloxacin (Table/Fig 3) .

In our study, the inducible MLSB (iMSLB) phenotype of Staphylococcus aureus strains were 68 (18.6%) as compared to the 14 (3.8%) constitutive MLSB (cMLSB) phenotypic strains and the 3 (0.8%) MSB phenotypic strains(Table/Fig 4). Out of 366 Staphylococcus aureus strains, 189 (51.6%) strains were Methicillin resistant Staphylococcus aureus (MRSA) and 177 (48.3%) strains were Methicillin sensitive Staphylococcus aureus. (MSSA) (Table/Fig 5). Out of 177 MSSA strains, 2(1.1%) were of the cMLSB phenotype. In the present study, out of 189 MRSA strains, 80 (42.3%) were clindamycin resistant and 109 (57.7%) were clindamycin sensitive (Table/Fig 6).

Discussion

In our study, 68 (18.6%) Staphylococcus aureus strains were of the iMLSB phenotype, whereas Angel et al from CMC, Vellore, reported that 23.2% strains were of the iMLSB phenotype (11) and Fiebelkorn et al reported that 28% (10) and Dizbay et al reported that 90% (12) of their Staphylococcus aureus strains were of the iMLSB phenotype. No MSSA strain was of the iMLSB phenotype in the present study. But other workers have found that 4% to 15% of their MSSA strains were of the iMLSB phenotype. (13), (14), (15) Out of 189 MRSA strains, 68 (36%) were of the iMLSB phenotype, though several studies from different parts of India have reported that 30% to 64% of their MRSA strains were of the iMLSB phenotype (11), (13), (15), (16), (17).

Though the incidence of the cMLSB phenotype is quite high outside India, (10), (13) Angel et al have not found any cMLSB resistance in Staphylococcus aureus strains.(11) We found 14 (3.8%) Staphylococcus aureus strains with the cMLSB phenotype, out of which 12 (6.3%) were MRSA strains and 2 (1.1%) were MSSA strains. Gadepalli et al had reported 12% strains of the MSB phenotype among the Staphylococcus aureus strains (17) but in our study, only 3 (0.8%) strains were of the MSB phenotype.

In the present study, the prevalence of the MRSA strains were 51.6%, which is somewhat similar to the results obtained by S. Anuprabha et al (MRSA strains were 54.8% ) (19) . Our hospital is a tertiary care hospital situated in a rural set up and caters to patients from villages of Vidarbha and the adjoining areas of Madhya Pradesh and Andhra Pradesh. Lack of awareness and the indiscriminate and the improper use of antibiotics before coming to the hospital might be the contributory factors for the high prevalence of MRSA in our study.

The true incidence of the iMLSB phenotype of Staphylococcus aureus depends on the patient population studied, the geographical region, the hospital characteristics and methicillin susceptibility (MRSA or MSSA) (13). The data from India is scanty (11), (16), (17).This is the first report from central India for MLSB resistance.

Though the confirmation of the iMLSB phenotype can be done by detecting the erm gene, the D-test is an easy test to perform for the detection of the iMLSB phenotype. All of our 68 iMLSB phenotype Staphylococcus aureus strains showed a false sensitivity zone by the routine Kirby-Bauer disc diffusion method. There are a few reports of clindamycin treatment failure in infections with Staphylococcus aureus strains with inducible clindamycin resistance (20), (21).

Methicillin resistant Staphylococcus aureus (MRSA) has been identified as one of the clinically important multidrug resistant organisms (MDRO) and therapeutic options for it are limited significantly. In a previous study conducted in our laboratory, we have already reported that 16.8% MRSA strains were resistant to 10 commonly used antibiotics including gentamicin, ciprofloxacin, erythromycin etc. in 1997. (22) But in that study, linezolid and vancomycin were not included.

In the present study, 47(24.9%) strains were resistant to all commonly used antibiotics (Table/Fig 3). But all MRSA strains were sensitive to linezolid and vancomycin. For MRSA strains, clindamycin is commonly used to treat skin and bone infections because of its tolerability and excellent tissue penetration and also, no renal adjustments are needed. Good oral absorption makes it an important option in outpatient therapy or as follow-up after intravenous therapy (15). But without the D-zone test, our 68 Staphylococcus aureus isolates with inducible clindamycin resistance would have been misclassified as Clindamycin sensitive, resulting in therapeutic failure. This is where the D-zone test becomes significant and important.

As clindamycin is one of the most commonly used antibiotics for MRSA strains, the increasing clindamycin resistance in the form of iMLSB and cMLSB, limits the therapeutic options for MRSA to the antibiotics like linezolid and vancomycin.

Conclusion

We hereby conclude that without the D-zone test, all Staphylococcus aureus isolates with inducible clindamycin resistance would have been misidentified as clindamycin susceptible by routine antibiotic susceptibility testing methods, resulting in the misuse of clindamycin and treatment failure.

Hence, all clinical microbiology laboratories should perform the D-zone test as per the CLSI guidelines 2004, which is simple and inexpensive, when Staphylococci appear to be erythromycin resistant and clindamycin susceptible by routine tests.

Acknowledgement

The authors highly acknowledge the Datta Meghe Institute of Medical Sciences University for funding this project.

References

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. Dowling H.F. The newer penicillins, Clinic. Pharmacol. Ther. 1961: 2:572-80.
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. Hiramastsu K., Hankaki H., Ino T., Yabuta K., Oguri T. Tenover F.C. Methicillin-resistant Staphylococcus aureus Clinical strain with reduced vancomycin susceptibility. J. Antimicrob. Chemother. 1997; 40: 135-6.
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. Roberts, M. C., J. Sutcliffe, P. Courvalin, L. B. Jensen, J. Rood, and H. Seppala. Nomenclature for macrolide-lincosamide-streptogramin B resistance determinants. Antimicrob. Agents Chemother. 1999; 43: 2823-2830.
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. Jorgensen JH, Crawford SA, McElmeel ML, Fiebelkorn KR. Detection of inducible clindamycin resistance of Staphylococci in conjunction with performance of automated broth susceptibility testing. J. Clin. Microbiol 2004; 42: 1800-2.
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. NCCLS. Performance standards for antimicrobial susceptibility testing; 14th informational supplement. M100-S14. Wayne,PA:NCCLS 2004.
6.
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