Bacteremia Caused by Staphylococci with Inducible Vancomycin Heteroresistance

Abstract

The clinical significance of bacteremia due to vancomycin-heteroresistant staphylococci and a rapid laboratory screening method were examined; 203 strains of staphylococci isolated from patients with clinically significant bacteremia were screened by the disk-agar method with use of vancomycin-salt agar to demonstrate satellitism around an aztreonam disk as well as by conventional population screening. Eighteen isolates (three Staphylococcus aureus and 15 coagulase-negative staphylococci) were shown to be heteroresistant to vancomycin. A case-control clinical study showed that the interval between admission and bacteremia, admission to the intensive care unit, prior use of vancomycin and/or beta-lactams, and isolation of methicillin-resistant staphylococci were significantly more common among patients with bacteremia due to staphylococci with heteroresistance to vancomycin; these patients had an overall mortality of 44.4%. The use of vancomycin and admission to the intensive care unit were independently significant risk factors on multivariate analysis. Vancomycin heteroresistance is inducible by salt and beta-lactams. Indiscriminate sequential use of beta-lactams and glycopeptides may facilitate the emergence of glycopeptide resistance.

Heterogeneous resistance to vancomycin and teicoplanin among Staphylococcus spp. isolated from bacteremia

“…Wong and coworkers [31] also found a similar rate (7.4%) of CNS strains with reduced susceptibility to glycopeptides isolated from bloodstream among 203 patients analyzed. If we considered only bacteremias by CNS the prevalence found in our study would increase for 18.37% (9/49 patients).…”

“…Thus, our results may also reflect the severity of the patients admitted in this hospital. Wong and coworkers [31] in a case-control study showed that the admission to the intensive care unit, prior use of vancomycin and/or β-lactams and isolation of methicillin-resistant staphylococci were common characteristics among patients with bacteremia due to staphylococci with heteroresistance to vancomycin.…”

Hetero-resistance: an under-recognised confounder in diagnosis and therapy?

“…The disk diffusion test and several automated methods of susceptibility testing failed to detect glycopeptide-intermediate, possibly hetero-resistant S. aureus [9]. As vancomycin hetero-resistance appears to be inducible by salt and probably by â-lactam antibiotics [5], a screening method was proposed that looked for satellitism on Mueller-Hinton agar supplemented with vancomycin 4 mg=L and NaCl 4%, around an aztreonam disk, which, in contrast to other â-lactam antibiotics, has no inhibitory effect on gram-positive bacteria [5].…”

“…In contrast, vancomycin (intermediate) resistance is still extremely rare in S. aureus, but hetero-resistance to this drug has already been reported in as many as 9% of 129 MRSA isolates in a survey of seven Japanese university hospitals [3], in a case report from the UK [4], and in three MRSA cases from Hong Kong [5]. Recently, hetero-resistance has also been reported for teicoplanin [6].…”

“…It has been suggested that previously reported vancomycin heteroresistant S. aureus merely represent one end of a spectrum of low-level vancomycin resistance expression [7]. However, heterogeneous populations from which subclones could be generated with a vancomycin MIC of up to 16 mg=L for S. aureus and up to 64 mg=L for coagulase-negative staphylococci have been reported [5].…”