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Antimicrobial resistance profile of methicillin resistant staphylococcal aureus from skin and soft tissue isolatesAntimicrobial resistance profile of methicillin resistant staphylococcal aureus from skin and soft tissue isolatesFaiza IdreesAga Khan University Kauser JabeenAga Khan University Muhammad Shoaib KhanAga Khan University Afia ZafarAga Khan University Follow this and additional works at: Recommended Citation
Idrees, F., Jabeen, K., Khan, M., Zafar, A. (2009). Antimicrobial resistance profile of methicillin resistant staphylococcal aureus from
skin and soft tissue isolates. Journal of the Pakistan Medical Association, 59(5), 266-9.
Antimicrobial resistance profile of Methicil in Resistant Staphylococcal
Aureus from skin and soft tissue isolates
Faiza Idrees, Kauser Jabeen, Muhammad Shoaib Khan, Afia Zafar Department of Pathology & Microbiology, Aga Khan University Hospital, Karachi, Pakistan.
Objectives: To evaluate resistance rates in methicillin resistant Staphylococcus aureus (MRSA) against
clindamycin, cotrimoxazole, tetracycline, fusidic acid, rifampicin and chloramphenicol isolated from skin and soft tissue infections (SSTI).
Methods: Descriptive analysis of SSTI samples yielding MRSA in clinical laboratory of a tertiary care center;
receiving specimens across Pakistan from January 2005 to June 2007.
Microbiological Methods: MRSA were identified using standard microbiological techniques. Susceptibility
testing was performed by disc diffusion according to Clinical Laboratory Standards Institute (CLSI) against fusidic acid, tetracycline, cotrimoxazole, clindamycin, rifampicin and chloramphenicol. Minimum inhibitory concentrations (MIC) of rifampicin were determined using agar dilution method according to CLSI.
Results: During the study period 501 MRSA were isolated from SSTI. Overall variable susceptibility pattern with
high resistance rates to tetracycline (82%), clindamycin (79%), cotrimoxazole (59%), and rifampicin (50%) were observed. Resistance to chloramphenicol (10%) and fusidic acid (9%) was low.
Conclusion: There is a strong need in resource limited countries to review the utility of conventional antibiotics
for the management of MRSA SSTI as new agents are expensive and not available. High resistance rates were observed against cotrimoxazole, tetracycline and clindamycin. Resistance to fusidic acid, rifampicin and Chloramphenicol was low (JPMA 59:266; 2009).
requires hospitalization.3 Final y, it is a nephrotoxic drug and Staphylococcus aureus causes skin and soft-tissue requires monitoring of renal function and drug levels that lead infections (SSTIs) that range from fol iculitis to life- to increased morbidity and costs for the patient.
threatening conditions, such as necrotizing fasci tis.1 Alternate options for the MRSA infections include Emerging methicil in resistance among Staphylococcus newer agents like linezolid, daptomycin, tigecycline, and aureus initial y in nosocomial and recently in community quinupristin/dalfopristin.3 However, these agents are either isolates is problematic because empirical choice of very expensive or not available in Pakistan.3 Guidelines for antimicrobials must include agents with activity against the treatment of skin and soft tissue infections published by resistant strains.2 Management of MRSA infections is CDC in 2005 have also recommended the use of macrolides, chal enging as these strains are resistant to al beta lactam antibiotics. In contrast to health care associated MRSA doxycycline or minocycline in minor MRSA infections.4 isolates that are resistant to multiple antibiotics, community- In addition, many studies from different regions of associated MRSA isolates tend to be resistant to fewer the world have reported efficacy of fusidic acid, rifampicin, antibiotics and often remain susceptible to non-beta lactam antibiotics, such as clindamycin, sulfonamides, and chloramphenicol in skin and soft tissue infections with MRSA.5,6 All of these antibiotics are potent Vancomycin has excel ent efficacy in skin and soft- antistaphylococcal agents with good tissue penetration, tissue infections in general and specifical y against those due cheaper as compared to glycopeptides and are also available to MRSA.3 However, for various reasons these agents should in both oral and parenteral formulations.4 However, their use be reserved for patients who have severe infections requiring is limited in developed countries due to their potential hospitalization or who have not responded to at empts to adverse effects.
eradicate the infection. Firstly, excessive use of vancomycin There is a strong need in resource limited countries would result in emergence of vancomycin resistance.2,3 like Pakistan to review the utility of conventional antibiotics Secondly, vancomycin is expensive and available only in effective for the management of skin and soft tissue infections parenteral form and most of the times its administration caused by MRSA. However, published data in Pakistan is limited in this regard. Therefore, this study was conducted to explore the cheaper and easy to administer drugs for soft tissue infections by MRSA. The susceptibility pat ern of MRSA strains were evaluated against fusidic acid, cotrimoxazole, rifampicin, chloramphenicol, clindamycin and tetracycline isolated from SSTIs. Moreover, studies from Pakistan that reported susceptibility pat ern of MRSA were reviewed and their findings were correlated with our results. Material and Methods
This study was conducted at the Clinical Microbiology Laboratory of Aga Khan University Hospital that receives specimens from across Pakistan via its col ection points. Skin (FD= Fusidic acid, 10µg; C=Chloramphenicol, 25µg; R=Rifampicin; TE= Tetracycline,
and soft tissue samples yielding growth of S.aureus from 30µg; SXT= Cotrimoxazole, 30µg; DA= Clindamycin, 2µg)
January 2005 to June 2007 were included. Organisms were Figure: Resistance pattern of MRSA.
identified as S.aureus by Gram stain, catalase and coagulase test.7 Other supplemental tests were DNAse, phosphatase and chloramphenicol (C) (10%) and fusidic acid (FA) (9%) was mannitol fermentation.7 Antimicrobial sensitivities against oxacil in (1 g), fusidic acid (10 g), cotrimoxazole (30µg), Analysis of data from the studies done in various tetracycline (30µg), clindamycin (2µg) and chloramphenicol regions of Pakistan is shown in Table.
(25 µg) were performed by Kirby Bauer method according to Clinical Laboratory Standards Institute (CLSI).8 Methicil in resistance was confirmed by oxacil in screen agar containing Increasing antimicrobial resistance has emerged 6 g/ml oxacil in and incubation at 30 C for 24 hours.8 globally as one of the paramount microbial threats of the Sensitivities against rifampicin were determined by minimum 21st century.9 Infections due to MRSA are the significant inhibitory concentration (MIC) method using agar dilution cause of morbidity and mortality worldwide. Incidence of according to CLSI.8 MRSA is increasing worldwide, and is escalating in Literature review was done using Pubmed, google, Pakistan.10-13 Previously MRSA infections were a concern medscape and Pakmedinet using different terms "MRSA and only in hospitals but now MRSA is isolated frequently from susceptibility pat ern", "MRSA and skin and soft tissue" etc.
the infections acquired in the community.14 Skin and soft Al the information was recorded on a standard questionnaire. tissue infections are the major manifestations of community-acquired MRSA strains. During the past 15 years emergence and dissemination of these strains had led During the study period a total of 501 MRSA strains to major therapeutic and infection control related problems.
were isolated from skin and soft tissue specimens. Overall, Methicil in resistance in Staphylococcus aureus variable susceptibility pat ern was observed in MRSA restricts therapeutic options for clinical isolates; especially strains, with high resistance rates to tetracycline (TE) those isolated from SSTIs. Alternative treatment options (82%), clindamycin (DA) (79%), cotrimoxazole (SXT) include fusidic acid, cotrimoxazole, clindamycin, (59%), and rifampicin (R) (50%). Resistance to tetracycline, rifampicin, quinolones, and chloramphenicol.
Table: Percentage resistance in MRSA isolates reported in various studies from Pakistan.
No. of MRSA Isolates
Emerg Infect Dis24 J Pak Med Assoc25 Vol. 59, No. 5, May 2009 Prediction of sensitivity to these drugs requires knowledge infection is yet to be defined. There are certain trials of of antibiotic susceptibility pattern of MRSA from a usage of chloramphenicol in multi-drug resistant gram- particular region. Our MRSA strains from both hospital and positive organisms like MRSA, vancomycin-intermediate community showed low resistance to fusidic acid that is comparable with studies reported from USA,9,14 Australia5 Staphylococcal.aureus (VRSA) and vancomycin-resistant and South Africa.15 Fusidic acid is available in intravenous, enterococcus (VRE).20 Chloramphenicol is routinely used oral, and topical preparations and when given systemically for the management of VRE infections at our institute. Data is widely distributed throughout the body, including areas for use of this antibiotic for the management of MRSA such as bone, joint fluid, prostate and large abscesses.16 infections is limited; however, it should be reserved for Therefore, it can be particularly useful in treating MRSA.16 cases when there are very limited therapeutic options.
However, it is well recognized that use of fusidic acid, as Further clinical trials are needed before its routine use is monotherapy, is associated with increased resistance as indicated for the treatment of MRSA infections.
compared to combination therapy.16 Therefore, combination In this study, all the strains showed susceptibility to treatment with rifampicin or cotrimoxazole is advisable and vancomycin. Vancomycin is a glycopeptide and is currently proven to be beneficial in treatment and eradication of a drug of choice for MRSA infections.4 Since there is MRSA stains.5,9 Recent studies from different parts of the recognition of VRE, the emergence of VRSA has been world indicate increase in the usage of fusidic acid as anticipated in future. There are few reports of VRSA/VISA topical monotherapy for the treatment of skin infections cases from US.21 One of the common risk factor for especially in Europe.17 Such topical therapy has proven acquiring VISA is the long-term use of vancomycin.22 It is effective but has also been associated with significant therefore important to consider alternate treatment options emergence of resistance.17 Thus, clinicians should for MRSA infections to prevent the VISA/VRSA reconsider the use of topical fusidic acid monotherapy especially for prolonged periods.
acquisition. The emergence of S.aureus with reduced susceptibility to Vancomycin presents the potential for The resistance to rifampicin (50%) was relatively infection with a virulent organism for which therapeutic better as compared to other agents. Rifampicin is another options are severely limited.
oral antimicrobial agent with good tissue penetration. This agent could be used to treat MRSA infections in our setting.
Comparison of our study results with other However, as Pakistan is a high burden Mycobacterium published studies of Pakistan from Lahore,23 Rawalpindi24 tuberculosis (TB) country, increased usage of rifampicin is and Karachi25 revealed resistance rates against clindamycin, not advisable as a routine for the management of MRSA tetracycline and cotrimoxazole similar to our study.
SSTI because of potential development of resistance in TB.
Likewise, rifampicin sensitivity results and fusidate However, its use is justified in certain difficult clinical sensitivity from a previous study done in Karachi25 situations when treatment options are very limited.
correlated with our findings.
We observed high resistance rates to clindamycin, tetracycline and cotrimoxazole in our MRSA isolates. A MRSA is a major pathogen in skin and soft tissue higher rate of clindamycin resistance in endemic isolates is infections worldwide. One of the limitations of this study is disappointing as this drug has a very good efficacy in the lack of differentiation between hospital acquired and community associated strains. Therefore, no comments can Cotrimoxazole has also been used in clinical studies be made on the difference in susceptibility pattern of with a cure rate of 86-90% in MRSA SSTI18 Likewise, community and hospital acquired strains. High resistance tetracycline derivatives, doxycycline and minocycline also rates against cotrimoxazole, tetracycline and clindamycin have excellent tissue penetration, and demonstrate good were observed. Therefore, empirical therapy with these antistaphylococcal activity at clinically achievable levels agents at our centre is not recommended; however, these with a reported cure rate of 83% in MRSA skin and soft agents could be used after the sensitivity results are tissue infections.19 However, high resistance rates to this available. Resistance to fusidic acid and rifampicin was drug were observed in our study probably due to irrational low; however, as monotherapy with these agents could lead use of this antibiotic by general practitioners in Pakistan.
to resistance, therefore, combination therapy should always Another concern is the toxicity that is associated with be used. Resistance to chloramphenicol was very low but clinical trials recommending its use in MRSA skin and soft Resistance to chloramphenicol was low (10%); tissue infections are limited and further evidence is required however, its role in management of MRSA soft tissue before its routine use. community- acquired infections.Pak J Pharm Sci 2007; 20:299-304. Frazee BW, Lynn J, Charlebois ED, Lambert L, Lowery D, Perdreau- John CC, John RS. Therapies and vaccines for emerging bacterial infections: Remington F. High prevalence of methicillin resistant Staphylococcus aureus Learning from Methicillin resistant Staphylococcus aureus. Pediatr Clin N in skin and soft tissue infections. Annals of Emergency Medicine 2005; Am 2006; 53:699-713.
Deresinski S. Methicillin resistant Staphylococcus aureus: An evolutionary, Shittu AO, Lin J. Antimicrobial susceptibility patterns and characterization of epidemiologic and therapeutic odyssey Clin Infect Dis 2005; 40: 562-73. clinical isolates of Staphylococcus aureus in KwaZulu-Natal province, South Micek ST. Alternatives to vancomycin for the treatment of methicillin Africa. BMC Infect Dis 2006; 6:125. resistant Staphylococcus aureus infections Clin Infect Dis 2007; 45: S184-90.
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Vol. 59, No. 5, May 2009
Target cell availability and the successful suppression of HIV by hydroxyurea and didanosine Rob J. De Boer AIDS 1998, 12:1567–1570 Keywords: Hydroxyurea, immunosuppression, target cell availability, 72 weeks of ddI–HU treatment, three out of sixpatients had no detectable plasma virus, and that there