|Year : 2014 | Volume
| Issue : 2 | Page : 71-74
A systemic review of antimicrobial resistance pattern of methicillin-resistant Staphylococcus aureus
Tewelde Tesfaye Gebremariam1, Yibrah Berhe Zelelow2
1 Department of Medical Microbiology and Immunology, Institute of Bio-medical Sciences, College of Health Sciences, Mekelle University, Mekelle, Ethiopia
2 Department of Gynecology and Obstetrics, School of Medicine, College of Health Sciences, Mekelle University, Mekelle, Ethiopia
|Date of Web Publication||20-Jun-2014|
Tewelde Tesfaye Gebremariam
Department of Medical Microbiology and Immunology, Institute of Bio Medical Sciences, College of Health Sciences, Mekelle University, P.O.Box: 1168, Mekelle
Source of Support: None, Conflict of Interest: None
Antimicrobial resistance of methicillin-resistant Staphylococcus aureus (MRSA) continues to be a problem for clinicians worldwide. It poses a serious therapeutic problem, leading to prolonged hospital stay and increased health-care costs. Current therapeutic options for MRSA are limited few expensive drugs. This study is a systematic review of published studies on MRSA and evaluates their antibiotic resistance pattern, and major finding as related to the objective of the study. Antimicrobial resistance of MRSA is based on CSLI guidelines-either disc diffusion or MIC methods. MRSA detection is either by classical methods for determining MICs (disc diffusion, Etest, or broth dilution), or screening techniques with solid culture medium containing oxacillin/cefoxitin and methods that detect the mecA gene or its protein product (PBP20 protein); S. aureus isolation should be based on standard bacteriological procedures: Tube/slide coagulase test or specific test like Pastorex or StaphID. A total of 33 studies were identified investigating the antimicrobial resistance of MRSA; of which 19 were included in the review. The majority of studies reported high levels of MRSA resistance against different antimicrobials. However, low levels of vancomycin resistance have been reported. Therefore, the knowledge of antimicrobial resistance of MRSA becomes necessary in the selection of appropriate empirical treatment of these infections. In addition, by employing a variety of prevention strategies, marked progress can be achieved in the control of drug-resistant pathogens, which can translate into more effective antimicrobial therapy.
Keywords: Antimicrobial resistance, empirical treatment, methicillin-resistant Staphylococcus aureus
|How to cite this article:|
Gebremariam TT, Zelelow YB. A systemic review of antimicrobial resistance pattern of methicillin-resistant Staphylococcus aureus. Saudi J Health Sci 2014;3:71-4
| Introduction|| |
Staphylococcus aureus is a common cause of hospital and community-acquired infections worldwide, manifesting from minor skin diseases to life-threatening infections. ,, The ability of the organism to cause a multitude of infections is probably due to the expression of myriads of different toxins, virulence factors and also cell wall adhesion proteins and Staphylococcal superantigen like proteins involved in immune evasion.  Infections caused by methicillin-resistant S. aureus (MRSA) are mainly nosocomial and are increasingly reported from many countries worldwide. , MRSA poses a serious therapeutic problem, leading to prolonged hospital stay and increased healthcare costs. ,,
There are two distinct types of MRSA: The hospital-acquired MRSA (HA-MRSA) and community-acquired MRSA (CA-MRSA). CA-MRSA originated with individuals in the community who had no risk factors from exposure to hospital environment and had distinctly different antibiotic sensitivities than the HA-MRSA which infected hospitalized patients with specific risks of infections. Currently, CA-MRSA has infiltrated the hospitals and is replacing HA-MRSA mainly in countries where the prevalence of CA-MRSA is high.  Five major lineages of MRSA (CC5, CC8, CC22, CC45, and CC30) circulate internationally and cause most nosocomial MRSA infections worldwide.  MRSA is of serious concern not due to its sole resistance to methicillin, but also because of its resistance to many other antimicrobials that are used on a regular basis in hospitals. Current therapeutic options for MRSA are a limited few expensive drugs like vancomycin, linezolid, teicoplanin, daptomycin, and streptogramins.  Another alarming sign is that emergence of resistance to Vancomycin, although at a low level has been reported. ,, Glycopeptides and linezolid continue to remain the mainstay of treatment for MRSA.  Since MRSA strains are often multi-drug resistance; there is a possibility of causing extensive outbreaks which may be difficult to control. ,,,,,
The degree of resistance MRSA toward commonly used antibiotics is recognized to be diverse from region to region. , MRSA is considered to have emerged from S. aureus through the acquisition of Staphylococcal cassette chromosome mec (SCCmec),  which carries the mecA gene for methicillin resistance which encodes the penicillin-binding protein 2a (PBP2a), ,,,,, resulting in reduced affinity for the β- lactam antibiotics including the penicillinase-resistant penicillin.  The mecA gene complex also contains insertion sites for plasmids and transposons that facilitate acquisition of resistance to other antibiotics. Another gene involved in penicillin resistance in Staphylococci is blaZ which encodes β-lactamase. 
Prolonged hospital stays, indiscriminate use of antibiotics, excessive antibiotic usage, lack of awareness, intravascular catheterization, hospitalization in intensive care unit, the presence of invasive devices and proximity to an already infected or colonized patient and receipt of antibiotics before coming to the hospital are some of the possible predisposing factors of MRSA emergence. ,, The emergence of these resistant strains represents a consequential response to selective pressures imposed by antimicrobial chemotherapy and once established; they are difficult to control and eradicate. 
The emergence of antimicrobial resistance in MRSA needs to be viewed in light of current evidence-based practice. Evidence emanating from research of low methodological quality is more likely to over- or underestimates the antimicrobial resistance of MRSA, giving an inaccurate description of the magnitude of the problem. Thus, the aim of this systematic review, using the available evidences was to determine the of antimicrobial-resistance pattern of MRSA.
| Materials and methods|| |
A literature search was performed to identify published studies between November 2001 and March 2013. Published studies were identified using an initial search of the MEDLINE/Index Medicus Database, PubMed, PMC, Google scholar, Science Direct, IDSOSI database, BioMed Central, Index Copernicus and Academic Journals database. The reference lists and bibliographies of all articles were then cross-checked for additional published and unpublished studies. The following keywords were used separately and combined in all databases and search engines: Methicillin-resistant Staphylococcus aureus, Staphylococcus aureus, MRSA infection, antimicrobial susceptibility, β-lactamase detection, antibiotic resistance, methicillin resistance, community-associated MRSA, MRSA infections, prevalence, susceptibility pattern, current susceptibility, antimicrobial susceptibility, and S. aureus.
Studies were included in the systematic review if they met the following criteria:
- Observational studies using standard, valid and reliable microbiological techniques in identifying MRSA isolates from different clinical samples; i. e. antimicrobial resistance of MRSA is based on CSLI guidelines-either disc diffusion or MIC methods. MRSA detection is either by classical methods for determining MICs (disc diffusion, Etest, or broth dilution), or screening techniques with solid culture medium containing oxacillin/cefoxitin and methods that detect the mecA gene or its protein product (PBP20 protein); S. aureus isolation should be based on standard bacteriological procedures: Tube/slide coagulase test or specific test like Pastorex or StaphID
- Full-text articles in English, published between November 2001 and March 2013.
| Results and discussion|| |
Assessment of methodological quality was carried out in two steps. Firstly, each study was ranked according to the hierarchy of evidence developed.  Studies were then reviewed critically using an adapted form of the quantitative appraisal tool.  This tool allowed both observational and repeated measures designs to be evaluated. The tool was adapted to make criteria specific to microbiological techniques. This included a section on microbiological methods such as times and temperatures relevant to incubation procedures, times, and days of the week when the sample was taken, method used to collect samples and the time lapse before collected samples were incubated. These criteria were included to evaluate the use of standard and therefore valid and reliable, microbiological techniques in each study.
The criterion concerning sample size was also expanded to include the random selection of subjects, and adequate inclusion/exclusion criteria. The critical appraisal tool assessed nine domains; including study purpose, study design, sample, and methodology and data analysis. Each of the nine domains had one or more criteria. All criteria answered with a 'yes' scored the full number of points, while criteria answered with a 'no' or which were not addressed scored zero. The maximum score that could be reached was 14 for observational studies.
The systematic literature search resulted in the identification of 33 studies; of which 19 were included in the review. Eleven studies not relating to antimicrobial-resistance pattern of MRSA and not using standard, valid, and reliable microbiological techniques were excluded. Thus, 19 studies were included in this review and all of them had observational designs examining antimicrobial-resistance pattern of MRSA.
To ensure the reliability of the scoring system, 10 papers selected at random were reviewed independently by two assessors. Following this review, a Pearson's correlation coefficient was calculated demonstrating 96% agreement between the two assessors (r = 0.98). A two-tailed paired t-test returned a P value of 0.34 (t = 1), demonstrating no significant difference between the two assessors and hence the absence of any systematic bias in scoring.
Methodological quality ranged from 6.5 to 9.5 out of 14 for observational studies. The 11 papers with observational designs returned a mean (standard deviation) quality score of 7.9 (1.1).
The pooled ranges and means for each outcome measure evaluated are presented in [Table 1]. The pooled mean of resistance of the included studies in this review indicated that more than 70% of MRSA were resistance to penicillin (95.6%), erythromycin (83.1%), and oxacillin (77.6%). However, low resistances have been reported to clindamycin (45.8%), amikacin (42.3%), and vancomycin (0.4%).
|Table 1: Pooled range and mean of antimicrobial resistance of methicillin-resistant S. aureus|
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In conclusion, the majority of studies reported high levels of MRSA resistance against different antimicrobials. However, low levels of vancomycin resistance against MRSA have been reported. Therefore, the knowledge of antimicrobial resistance of MRSA becomes necessary in the selection of appropriate empirical treatment of these infections. In addition, by employing a variety of prevention strategies, including proper personal hygiene, prescreening for carrier status before hospital admission, disinfection of hospital rooms, and careful monitoring of antimicrobial prescribing, marked progress can be achieved in the control of drug-resistant pathogens, which can translate into more effective antimicrobial therapy.
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