Abstract
Staphylococcus aureus is a significant human pathogen and is the primary cause of skin and soft tissue infections. Antimicrobial resistance is an ongoing concern, with increasing reports of multi-resistant S. aureus infections which have limited options available for treatment. New Zealand has high incidence rates of infections caused by S. aureus, with the predominant circulating clone often being resistant to the topical antibiotics fusidic acid and mupirocin. Healthcare facilities have relied on chlorhexidine as the main antimicrobial agent used to prevent and control infections caused by common pathogens including S. aureus. Chlorhexidine resistance in S. aureus has been associated with qacA, a gene which encodes for a multi-drug efflux pump.
The objectives of this study were to (i) determine prevalence of qacA in New Zealand S. aureus; (ii) correlate prevalence of qacA gene in New Zealand S. aureus strains with clonal lineages, susceptibility profiles, and patient demographics; and (iii) examine the genetic context of the qacA gene in circulating S. aureus clones.
The qacA prevalence in New Zealand S. aureus isolates is 7%. Concerningly, presence of the qacA gene is associated with the predominant clonal lineage spa type t127 strain found in New Zealand. The predominant New Zealand t127 strain is synonymous with fusidic acid resistance and, in 45% of cases, mupirocin resistant. The combination of qacA with fusidic acid and mupirocin resistance in S. aureus has the theoretical potential of being resistant to the three most common topical treatment options used for skin and soft tissue infections.
We were unable to find a statistically significant difference in phenotypic susceptibility to chlorhexidine when testing isolates with and without qacA. Despite being unable to find reduced susceptibility in qacA carrying strains, these strains continue to be associated with failed decolonisation strategies in case control studies. Further work could look at the development of an assay in different milieu to detect phenotypic expression of qacA which leads to reduced susceptibility to chlorhexidine.
The qacA gene was found on a ~28 kb plasmid, co-located with genes that confer resistance to penicillins and mupirocin (mupA). The representative plasmid (pNZAK1) closely resembles the ubiquitous pMW2 plasmid. Interestingly, mupA and the qac operon are found on a ~7 kb insertion sequence. A nucleotide BLAST search of this sequence indicates that this genetic arrangement is specific to the ST1, t127 clonal lineage in New Zealand. Although not closely located in the genome, qacA and the fusidic acid resistance gene fusC are both associated with the predominant t127 clone. These findings suggest that the heavy use of topical antibiotics and amoxicillin consumption in New Zealand may have contributed to the marked prevalence of qacA in New Zealand S. aureus.
Taken together, antimicrobial use, including chlorhexidine, has the theoretical potential to select out multi-resistant S. aureus leading to the predominance and success of the t127 clone and consequently, to the high rates of infection found in New Zealand. Thus, consideration should be given to the widespread use of chlorhexidine and the unintended consequence this has on health-care related infections.