It’s Arrived—The Vancomycin-Resistant MRSA . . . or Has it?


Synopsis: A 4-month old baby became infected with MRSA, which exhibited reduced susceptibility to vancomycin, and only responded to vancomycin treatment after an aminoglycoside was added.

Source Hiramatsu K, et al. Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. J Antimicrob Chemother 1997;40:135-146.

In may 1996, a 4-month old japanese baby boy became infected with MRSA two weeks after thoracic surgery. He was treated with 45 vancomycin mg/kg for four weeks to no avail, as he remained febrile with an elevated CRP of 40 mg/L and the wound continued to discharge pus. The aminoglycoside arbekacin was added to vancomycin to good effect and the wound began to heal, the purulent discharge subsided, and the CRP dropped to 9 mg/L. Both drugs were discontinued after 12 days treatment, but 12 days later an abscess became manifest, accompanied by recurred sudden fever and a CRP of 35 mg/L.

Treatment was restarted with arbekacin and ampicillin plus sulbactam rather than vancomycin. The baby became afebrile after six days, although the CRP fluctuated between 3 and 10 mg/L, which was interpreted as a sign of persistent infection. The abscess was finally debrided and treatment continued for a further 17 days, after which the baby was well enough to go home.


The minimum inhibitory concentration of vancomycin for the MRSA labelled Mu50 was determined to be 8 mg/L, and neither the vanA nor vanB genes were detected. Thus, it was not the fearsome "omniresistant MRSA" reported by the popular magazine New Scientist in May of this year. Had it been, it would have carried the vanA gene, which is highly mobile and confers high-level resistance to both vancomycin and teicoplanin. (See Table.)


Glycopeptide resistance

Genotype vanA vanB vanC unknow

Resistance acquired acquired intrinsic intrinsic Phenotype vanA vanB vanC vanC MIC (mg/L):

vancomyci64-1000+ 4-1000 2-32 2-32

teicoplani16-512 0.5-1 0.5-1 0.5-1

Conjugative transfer + + - - Source E. faecium E. faecium E. gallinarium E. casseliflavus E. faecalis E. faecalis

Rather, no specific mechanism for resistance could be identified. However, augmented cell wall synthesis was suggested as a possible mechanism of resistance since Mu50 produced three times the normal amount of penicillin-binding proteins PBP2 and PBP2+ (the latter is responsible for methicillin resistance) and cell wall precursors, giving it a doubly thick cell wall.

Irrespective of the in vitro susceptibility, which would be judged as low-level resistance, the Mu50 was clearly resistant clinically to vancomycin. This will doubtless give the hospital cause for concern since 2% of the MRSA isolates appear identical to the Mu50 strain. Moreover, prolonged treatment with vancomycin alone or in combination seems the only choice for treating infection; so, the more patients become infected, the greater the selective pressure placed on the MRSA. Not only do Staphylococcus aureus thrive under such circumstances but they are extraordinarily adept at spreading themselves about and passing on their capacity for resistance to other strains, whether close relatives or not. We can therefore be sure that this is not the last we will hear from this particular MRSA and that sooner, rather than later, the "reduced susceptibility to vancomycin" may well change to high-level resistance.