The Newest Methicillin-resistant Staphylococcus: MRSP

Abstract & Commentary

By Ellen Jo Baron, PhD, D(ABBM), Professor of Pathology and Medicine; Stanford University; Medical School Director, Clinical Microbiology Laboratory, Stanford University Medical Center, is Associate Editor for Infectious Disease Alert.

Dr. Baron reports no financial relationships relevant to this field of study.

Companion animals have been carrying a secret around for years. Maybe that is why my sister's golden retriever is always smiling. Methicillin-resistant coagulase-positive staphylococci are not exclusively Staphylococcus aureus. Our laboratory recently performed molecular identification tests on a large group of staphylococci to help develop a reliable method for rapid characterization of S. lugdunensis, and found three isolates mistakenly reported originally by our clinical laboratory scientists as Staphylococcus aureus. Like S. aureus, these isolates were able to coagulate rabbit plasma (the tube coagulase test), and displayed beta hemolysis on sheep blood agar; although in retrospect, we found that the hemolysis was most apparent on the second day, much like that of S. lugdunensis. Their antimicrobial resistance pattern resembled those of healthcare-associated MRSA, with several antimicrobial agents showing resistance. The most recent of these unique strains was found both in the blood and a colonized catheter tip from one patient. It was identified as S. pseudintermedius by 16S rRNA sequencing; our MicroScan (Dade Behring) biochemical Staphylococcus panel called it S. intermedius. As occasionally happens, the newer species name was not even in the database for the instrument. The two species are so closely related that there is still some controversy over whether they should be two species or lumped together into one species designation; although they do have both phenotypical and molecular differences that seem to warrant independent species names.

S. intermedius has long been recognized as a S. aureus-like microbe most likely to be encountered in a dog bite wound infection. Dogs and other animals carry S. intermedius as normal oral and skin flora. Like S. aureus, S. intermedius is beta hemolytic, produces DNase and can be confused with S. aureus in the laboratory, except that it is not gold pigmented and may not be positive in the slide coagulase test for clumping factor. Similar to S. lugdunensis, S. intermedius is pyrrolidonyl aminopeptidase (PYR) positive, which also distinguishes it from S. aureus (PYR negative). It is now thought that most animal infections previously ascribed to S. intermedius were actually caused by S. pseudintermedius.

The first human case of S. pseudintermedius infection was reported in late 2006.1 The patient was a 60-year-old male with an infected implantable cardioverter-defibrillator (ICD). Both the ventricular lead and the pus drained during surgical removal of the ICD yielded the organism.1 The authors did not report whether the patient had a pet. Before that report, the organism was thought to be restricted to animals. S. pseudintermedius was itself only named in 2005.2 Dogs and cats can become infected with S. pseudintermedius, which causes dermatitis, ear infections, and other syndromes often previously associated with S. aureus.

Workers recently reported that a small number of staphylococci isolated from numerous species of animals whose cultures were sent to veterinary laboratories were methicillin-resistant S. pseudintermedius.3 They not only carry the mecA gene (responsible for production of the penicillin-binding protein 2a enzyme that confers beta-lactam resistance), but the gene is situated in a mobile chromosomal element virtually identical to that carried by human isolates of MRSA — the staphylococcal cassette chromosome mec (in this case SCCmec type III).

Why will this fact become more important in the future? At this time, the two FDA-cleared molecular tests for detection of MRSA in human patient samples (BD GeneOhm and Cepheid GeneXpert), and potential future molecular tests, are based on detection of the mecA gene and a linker gene that is part of the SCCmec element. Thus the potential for false-positive molecular results (false-positive detection of MRSA) exists. Right now the prevalence of these strains in humans is unknown. Our own lab's experience would suggest less than 0.5%. A large study of > 16,000 German veterinary samples found the prevalence of MRSP to be only 0.45%, with most isolates originating in dogs, a few in cats, and very rarely in horses or donkeys.3 Even more potentially confusing for future molecular tests, the spa gene (encoding staphylococcal protein A), thought to be a unique marker for S. aureus and also used in molecular tests for S. aureus and MRSA, was also found as tandem repeats in a number of isolates of S. pseudintermedius from animals in both Europe and California.4 Bannoer et al reported that the recent widespread emergence of methicillin-resistant strains was due to independent acquisitions of the mecA gene by different S. pseudintermedius clones found on different continents. I guess those dogs really get around.

References

  1. Van Hoovels L, et al. First case of Staphylococcus pseudintermedius infection in a humans. J Clin Microbiol. 2006;44:4609-4612.
  2. Devriese LA, et al. Staphylococcus pseudintermedius sp. nov., a coagulase-positive species from animals. Int J Syst Evol Microbiol. 2005;55:1569-1573.
  3. Ruscher C, et al. Prevalence of methicillin-resistant Staphylococcus pseudintermedius isolated from clinical samples of companion animals and equidaes. Vet Microbiol. 2008 Oct 31. [Epub ahead of print].
  4. Moodley A, et al. Tandem repeat sequence analysis of staphylococcal protein A (spa) gene in methicillin-resistant Staphylococcus pseudintermedius. Vet Microbiol. 2008 Sep 30. [Epub ahead of print].
  5. Bannoehr J, et al. Population genetic structure of the Staphylococcus intermedius group: insights into agr diversification and the emergence of methicillin-resistant strains. J Bacteriol. 2007;189:8685-8692.