By Dr Abiola Senok (MBBS, PhD, FRCPath), Associate Professor, Microbiology and Infectious Diseases, Department of Basic Science, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
Staphylococcus aureus is a ubiquitous pathogen and persistent colonisation of the anterior nares by this organism occurs in about 20-30% of the population. Methicillin resistant S. aureus (MRSA) was first identified in the 1960s and it has now become established as a major cause of nosocomial infections globally. MRSA strains harbour the mecA gene on complex mobile genetic elements which are known as staphylococcal cassette chromosome (SCCmec). The mecA gene encodes for an altered penicillin binding protein (PBP2a). The expression of PBP2a results in loss of target affinity for beta lactam antibiotics. In addition to the mecA gene, the SCCmec elements also comprise of recombinase genes and regulatory elements. Additional antimicrobial resistance genes including those encoding resistance for aminoglycosides, macrolides and heavy metal ions may also be harboured.
Evolution of MRSA
In the early days of MRSA emergence, infections caused by these strains occurred in the healthcare setting, causing a spectrum of invasive disease in patients with underlying morbidities. The hospital-acquired MRSA (HA-MRSA) strains associated with these infections usually exhibited a multidrug resistance phenotype. However, in the last few decades, the emergence of community-acquired MRSA (CA-MRSA) strains has dramatically changed the landscape of MRSA epidemiology. These CA-MRSA strains were typically associated with infections originating in the community occurring in young healthy patients without the “classic” predisposing risk factors for MRSA infection. CA-MRSA strains are characterised by carriage of the smaller sized type IV or V SCCmec (in contrast to the larger sized SCCmec types I – III seen in HA-MRSA strains). Many CA-MRSA strains also harboured the Panton Valentine leucocidin (pvl) gene. However, the molecular epidemiology of MRSA continues to evolve. Increasing numbers of CA-MRSA clones are being reported and although some MRSA clones show a geographical predominance, others tend to have a more global distribution. Furthermore, CA-MRSA lineages are now displacing HA-MRSA strains as the dominant aetiological agents of nosocomial MRSA infections.
MRSA in the Arabian Gulf region
In the Arabian Gulf region, MRSA colonisation and infections are prevalent with CA-MRSA strains contributing significantly to the burden of MRSA infections. Emerging data on the genetic characterisation of isolates is now shedding light on the population structure of MRSA in the region. Similar to observations from other geographical regions, there is an increasing trend of CA-MRSA lineages being identified as aetiological agents of nosocomial infection in the Arabian Gulf region. It also appears that there is a wide clonal diversity with a large number of MRSA clonal complexes (CC) identified in single centre studies in the region. The CC80-MRSA-IV [PVL+] (the so-called “European CA-MRSA”) has been shown to be the predominant MRSA strain circulating in the region. The CC80-MRSA-IV [PVL+] strain is also predominant in North Africa. It has been suggested that this strain emerged in Europe and then spread into North Africa and the Middle East. Conversely, it could be hypothesised that these strains originated in the Middle East and disseminated into Europe via Turkey and North Africa. This is plausible as Europe is home to large immigrant communities from Turkey and North Africa. Furthermore, holiday travel from Europe to these regions is very popular.
Strains belonging to CC6, CC5 and CC22 have also been shown to occur with high frequency in the region. Interestingly, in Oman, ST-6-IV CA-MRSA has been shown to be the predominant MRSA strain. The first observation of nosocomial infections by highly successful pandemic clones (CC8, USA300 and CC22-MRSA-IV) and one rare MRSA clone (CC15-MRSA) in Saudi Arabia was reported recently. Thus, the pandemic USA300 which is the dominant MRSA strain in the United States has been now been described in four countries in the region, namely Saudi Arabia, United Arab Emirates and Qatar.
The CC22-MRSA-IV (UK-EMRSA-15/Barnim EMRSA), is a common and pandemic MRSA strain which is predominant in Western Europe. Recently, characterisation of CC22-MRSA strains from Saudi Arabia, Kuwait and UAE by microarray hybridisation was reported. The findings revealed the presence of six distinct ‘strains’ of CC22-MRSA-IV which were distinguishable on the basis of SCCmec IV subtypes and virulence factors. The “classic” European UK-EMRSA-15/Barnim EMRSA strains which have SCCmec IV h/j elements and lack tst1 or pvl genes were identified in UAE and Kuwait, however none was detected in Saudi Arabia. Indeed, all the CC22-MRSA-IV strains from Saudi Arabia were linked to epidemic strains from the Middle East and India. These include the “Gaza epidemic strain’ CC22-MRSA-IV strain which harbours the tst1 (encoding for toxic shock toxin) gene and those positive for the pvl gene.
CC-15-methicillin sensitive S. aureus (MSSA) is ubiquitous among healthy carriers and has been described as a predominant MSSA associated with nasal colonisation in Saudi Arabia. In contrast CC15-MRSA has only been described sporadically in the literature. It is however interesting that in the past couple of years, CC15-MRSA has been reported from nasal colonisation, clinical infection and retail meat products in Saudi Arabia. Close monitoring of this emerging MRSA strain in the region is needed.
While no MRSA strains harbouring vancomycin resistance genes have been described from the region, carriage of resistance genes for mupirocin and quaternary ammonium compounds has been identified. Virulence genes commonly identified include Panton-Valentine leucocidin (pvl), staphylococcal complement inhibitor (scn) and staphylokinase (sak) genes. Indeed, both scn and sak genes have also been shown to be prevalent in MSSA strains associated with nasal colonisation in Saudi Arabia.
Curtailing the trend
The increasing occurrence of community-acquired MRSA lineages as well as the emergence of pandemic and rare MRSA strains in the region is a cause for concern. The Arabian Gulf region is home to a large number of expatriates with many more visiting for business or tourism. Saudi Arabia hosts millions of pilgrims annually. This dynamic influx of people from across the globe might explain the wide diversity in the population structure of MRSA in the region. Strict infection control practices are critical if we are to stem the dissemination of these MRSA strains in the region. Continuous surveillance using sensitive molecular approaches such as high-resolution typing methods to monitor transmission routes and differentiate closely related strains is advocated.
Dr Abiola Senok is a Speaker at the Infection Control Conference held as part of Patient Safety Exhibition in Dubai, on 24th October, 2017.