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RAMA Univ. J. Med Sci 2015;1(2): 35-42 Singh DN et al

Original Research

CAN CLINDAMYCIN ALSO BE USED AS AN EFFECTIVE DRUG INMETHICILLIN RESISTANT STAPHYLOCOCCI AS AN ALTERNATIVE

TO VANCOMYCIN

Singh DN1, Sujatha R2, Yadav S 3, Pal N3

1-Assistant Professor, Department of Microbiology, RMCH&RC, Kanpur2- Professor, Department, Department of Microbiology, RMCH&RC, Kanpur3- Tutor, Department of Microbiology, RMCH&RC, Kanpur

Abstract

Introduction: Staphylococcus is one of the most common bacteria causing hospital-acquiredinfections, increasing cost of treatment and hospital stay. Antibiotic resistance in Staphylococcushas become a big problem among hospitalized patients. Vancomycin and L inezolid is the onlytherapeutic option in Methicillin resistant Staphylococcus infections but there are some adverseeffects of these drugs. Therefore it is necessary to find out the most effective antibiotic other thanvancomycin against methicillin resistant Staphylococci. Aims and Objectives: To evaluate theutility of commonly used drugs against Staphylococcus and also investigated the prevalence oferythromycin-induced clindamycin resistance along with antibiotic resistant pattern ofStaphylococcus. Material and Methods: Total 450 non repeated Staphylococcus strains wereisolated from different clinical samples and S.aureus identified by specific biochemical tests andAntibiotic susceptibility testing and D- zone test were carried out as per CLSI guidelines.Result: Among 450 Staphylococcus strains, 360 were S.aureus and 90 were coagulase negativeStaphylococcus (CONS) in which 58.33% were MRSA 68.89% were MR-CONS. 99.04%MRSA and 100% MR-CONS were ciprofloxacin resistant and only 4% and 3.22% wereMethicillin sensitive S.aureus and CONS respectively. Total 168 (46.67%) S. aureus and 47(52.22%) CONS were clindamycin resistant out of which 92 (25.56 %) S. aureus and 3 (3.33 %)CONS were detected as inducible clindamycin Resistant. All inducible clindamycin resistantisolates were also resistant to cefoxitin (methicillin resistance) and ciprofloxacin anderythromycin. All staphylococcus were also sensitive to tigecycline, vancomycin and linezolid.All cefoxitin (methicillin) sensitive were sensitive to amikacin, gentamicin, tobramycin,netilmycin, tigecycline and vancomycin. Conclusion: Clindamycin and ciprofloxacin are highlyresistance to Staphylococcus not suitable alternative drugs for the treatment of hospital acquiredStaphylococcus infections because of high level resistance. Tigecycline, Amikacin andNetilmycin was found the most effective alternative drug for treatment

Key Words: Clindamycin, Methicillin Resistant Staphylococci, Vancomycin

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Introduction

Staphylococcus is group of gram positivebacteria causing a number of diseases,ranging from mild skin infection to seriousendocarditis.1 It is the most commonbacteria causing hospital-acquiredinfections, increasing cost of treatment andhospital stay. Antibiotic resistance inStaphylococcus has become a big problemamong hospitalized patients. The increasingprevalence of methicillin resistance amongStaphylococci has limited the use ofpenicillins and cephalosporins for thetreatment. There is limited option for thetreatment of methicillin resistantStaphylococci with vancomycin andlinezolid, however their high cost, intra-venous drug administration and adversedrug reaction limit the use. 2

Fluoroquinolone antibiotics could be analternative to vancomycin for the treatmentof methicillin resistant Staphylococci as thisgroup of antibiotic has low cost and goodoral absorption. Increasing number ofFluoroquinolone resistance amongmethicillin resistant Staphylococcus forcedthe investigators to look for antibiotics.3,4

Clindamycin could be an alternative toVancomycin as it has good oral absorptionand accumulation in abscesses.Staphylococcus can be resistant toErythromycin through either erm or msrAgene. Staphylococcus having erm gene maypossess inducible Clindamycin resistance. Indisc diffusion antibiotic susceptibility testinginducible Clindamycin may appearsusceptible to Clindamycin. Routinedetection of inducible Clindamycin

resistance in clinical isolates can decrease

the cost of treatment and prevent theunnecessary use of antibiotics.5

Erythromycin resistant in Staphylococcus isdue to either erm or msrA genes.Staphylococcus with erm-mediatederythromycin resistance may possessinducible clindamycin resistance but mayshow susceptiblity to clindamycin by discdiffusion method. Inducible clindamycinresistance can be detected by a simple D-zone test. If this test is come in routinelaboratory test, clindamycin can be safelyand effectively used in only trulyclindamycin susceptible cases.6

Emergence of resistance amongStaphylococci to various antibiotics hascreated problem to choose appropriateantibiotic for empirical treatment. Study onantibiotic resistance among methicillinresistant Staphylococci along with detectionof inducible clindamycin has not been donein Kanpur. Therefore, the present study wasundertaken to find out the most effectiveantibiotic other than vancomycin againstmethicillin resistant Staphylococci.

In this study we investigated the prevalenceof erythromycin-induced clindamycinresistance along with antibiotic resistantpattern of Staphylococcus isolated fromclinical samples.

Aims and ObjectivesThis study aimed to evaluate the utility ofcommonly used drugs againstStaphylococcus.

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Materials and Methods

SpecimenA total of 450 Staphylococcus strains wereobtained from pus, blood, CSF, sputum andurine sample from different clinicaldepartments of Rama Medical College andHospital between July 2014 and January2015.Specimen processingAll samples except blood were inoculated inThioglycolate media, incubated for 4-6 hrsand subculture on Blood agar andMacConkey’s agar.Identification of organism The obtainedorganisms were identified by observingcolony character, by microscopy using gramstain and by using specific biochemical tests(catalase test and slide coagulase test, tubecoagulase and mannitol fermentation test).7

Antibiotic sensitivity testAntibiotic susceptibility test and D- zonetest were carried out as per CLSI guidelines.The D-zone test was performed by doubledisk diffusion method, placing erythromycin(15 g) and clindamycin (2 g)μ μ disks 15 mmapart on the same plate [Fig.1].Staphylococcus aureus American TypeCulture Collection (ATCC) BAA-977(having inducible ermA gene; inducibleclindamycin resistance) and S. aureus ATCCBAA-976 (having inducible msrA gene;efflux erythromycin resistance) were used asquality control strain. For antibioticsusceptibility test 0.5 MacFarland bacterialsuspension was prepared and performed byKirby- Bauer disk diffusion method onMueller-Hinton agar. Methicillin resistancedetection was done in Staphylococcus by

cefoxitin (30µg) disk diffusion method. Allstaphylococcus were tested for penicillin,oxacillin, cefoxitin, ciprofloxacin,tetracycline doxycycline, tigecycline,amikacin, gentamicin, tobramycin,netilmycin, erythromycin resistance.6,7

Result

A total of 450 Staphylococcus strains wereisolated from various clinical samplesamong which 360 were identified asStaphylococcus aureus in which 210(58.33%) were MRSA and 90 as CoagulaseNegative Staphylococcus (CONS) in which62 (68.89%) were Methicillin resistantCONS(MR-CONS).[Fig 2- Fig 3] Out of210 MRSA isolates, ciprofloxacin resistancewas seen in 208 (99.04%) isolates. All 62(100 %) methicillin resistant CONS werealso resistant to ciprofloxacin. Resistance tociprofloxacin was seen in only 6 (4.00 %)Methicillin sensitive Staphylococcusaureus(MSSA) and 2 (3.22%) Methicillinsensitive Coagulase NegativeStaphylococcus(MS-CONS).[Fig 4] Total168 (46.67%) S. aureus and 47 (52.22%)CONS were resistant to clindamycin out ofwhich 92 (25.56 %) S. aureus and 3 (3.33%) CONS were detected as inducibleclindamycin Resistant. All inducibleclindamycin resistant isolates were alsoresistant to cefoxitin (methicillin resistance),ciprofloxacin and erythromycin. Allstaphylococcus were sensitive to tigecycline,vancomycin and linezolid. Resistance toaminoglycoside was seen in only cefoxitin(methicillin) resistant staphylococcus Out of210 MRSA, 17 (8.50%) were resistant toamikacin, 19 (9.04%) were resistant to

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observed in 23%, which is more than otherstudies, reported from different part of India.Inducible clindamycin resistance wasobserved significantly more in methicillin-resistant Staphylococcus isolates.12,13

The increased number of multiple antibiotic-resistant in methicillin resistantStaphylococcus have gained much attentionover the years.10 Fluoroquinolonecompounds such as ciprofloxacin, firstsynthesized in the 1980s, were found to haveextended antimicrobial spectra that includedgram-positive bacteria, and were hoped tobe useful in eradicating methicillin resistantStaphylococcus.4 However, since thesecompounds became available for clinicaluse, resistance among methicillin resistantStaphylococcus has been reported fromdifferent parts of the world.

In this study, significantly higher percentage(92.5%) of MRSA isolates showedresistance to ciprofloxacin. Similar results ofover 90% resistance have been reported insome studies reported from India. 12 NeetaD Gade et al. reported that maximumresistance (92.5 %) to ciprofloxacin wasobserved in MRSA.1 Resistance tociprofloxacin had steadily increased from39% in 1992 to 68% in 1996 reported byMehata AP et al.14 In such conditionsciprofloxacin may not be useful drug forempirical treatment of nosocomial infection.

In the present study, 80.4% MRSA showedresistance to ciprofloxacin. This differentpatterns and levels of resistance may arisefollowing exposure to differentfluroquinolones, and different strains may

produce different types of resistance.15

Methicillin and ciprofloxacin resistantStaphylococcus are also resistance to otherantibiotics, like aminoglycosides.16,17 Insuch situations clindamycin may be betteroption, as it is available in both intravenousand oral formulations and drug distributeswell into the tissue except central nervoussystem.18 Clindamycin is also cost effectivethan some of the other antibiotics.19

In the present study, tigecycline,vancomycin and linezolid were found to beuseful drugs in treating methicillin resistantStaphylococcal infections. None of theMRSA isolates showed resistance totigecycline, vancomycin as well as tolinezolid.

In the present study, 3.7% methicillinresistant Staphylococcus isolates wereresistant to Amikacin, 2.3% resistant togentamicin, 2.4% resistant to netilmycin and3.5% resistant to tobramycin. Many studiesreported different range of resistance toaminogycosides ranging from 41-54%.20

Typing of MRSA strains is necessary forthorough epidemiological investigations ofsources and modes of spread of these strainsin hospitals and to design appropriatecontrol measures.21

Conclusion

We concluded that Clindamycin andFluroquinolone (ciprofloxacin) are notsuitable alternative drugs for the treatmentof hospital acquired Staphylococcusinfections because of high level resistance.

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Tigecycline was found as the most effectivealternative drug followed by amikacin andnetilmycin.

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CORRESPONDING AUTHOR:Mr. Desh Nidhi SinghAssistant Professor, Department of Microbiology, Rama Medical College Hospital &ResearchCentre, Kanpur. EmailID: deshnidhisingh@gmail.com