Changing Italian nosocomial-community trends and heteroresistance in Staphylococcus aureus from bacteremia and endocarditis

Abstract

Bloodstream infections due to Staphylococcus aureus (BSI) are serious infections both in hospitals and in the community, possibly leading to infective endocarditis (IE). The use of glycopeptides has been recently challenged by various forms of low-level resistance. This study evaluated the distribution of MSSA and MRSA isolates from BSI and IE in 4 Italian hospitals, their antibiotic susceptibility—focusing on the emergence of hVISA—and genotypic relationships. Our results demonstrate that the epidemiology of MRSA is changing versus different STs possessing features between community-acquired (CA)- and hospital-acquired (HA)-MRSA groups; furthermore, different MSSA isolated from BSI and IE were found, with the same backgrounds of the Italian CA-MRSA. The hVISA phenotype was very frequent (19.5%) and occurred more frequently in isolates from IE and in both the MSSA and MRSA strains. As expected, hVISA were detected in MRSA with vancomycin minimum inhibitory concentrations (MICs) of 1–2 mg/l, frequently associated with the major SCCmec I and II nosocomial clones; this phenotype was also detected in some MSSA strains. The few cases of MR-hVISA infections evaluated in our study demonstrated that 5 out of 9 patients (55%) receiving a glycopeptide, died. Future studies are required to validate these findings in terms of clinical impact.

Antimicrobial Heteroresistance: an Emerging Field in Need of Clarity

“…While some reports question the clinical significance of heteroresistance (51,63,76,148), others argue that there is a deterioration in clinical outcomes due to heteroresistant bacteria (46,50,64,71,77,78,(149)(150)(151)(152). Lack of a standard definition of heteroresistance may lead to misidentification of homogeneous strains as heteroresistant, hindering proper assessment of its clinical relevance.…”

“…Heteroresistance may also be misinterpreted when only a single colony, picked from primary bacterial populations isolated from patients, is analyzed for susceptibility to antibiotics (86). Heteroresistance has been relevant in recurrent infections (46,71), chronic infections (78), and infections with increased mortality rates (64,77,150,151). Underlying mechanisms for these therapeutic failures may have been antibiotic selection for the more resistant cells within the bacterial population and chemical communication of resistance, as described in more detail below.…”

Screening for Intermediately Vancomycin-Susceptible and Vancomycin-Heteroresistant Staphylococcus aureus by Use of Vancomycin-Supplemented Brain Heart Infusion Agar Biplates: Defining Growth Interpretation Criteria Based on Gold Standard Confirmation

“…It is cumbersome and not practical for routine use. Several screening methods have been proposed, but their sensitivity and specificity vary, and often confirmation with PAP-AUC is considered necessary (2,4,7,12,15,17). In previous PAP-AUC studies, we noted that the growth on agar plates supplemented with vancomycin concentrations of 4 and 3 mg/liter correlated well with the VISA and hVISA phenotype, respectively (11).…”

“…Etest methods, including the Macromethod and glycopeptide resistance detection (GRD), have been suggested, but their sensitivity and specificity are variable and confirmation with the gold standard population analysis profile is considered necessary (2,4,7,10,12,15,17). Several agar screening methods that utilize brain heart infusion (BHI) agar or Mueller-Hinton (MH) agar supplemented with vancomycin or teicoplanin at various concentrations have been proposed (1,4,6,11,13,14,16).…”

“…everal methods of screening for vancomycin intermediately susceptible Staphylococcus aureus (VISA) and heteroresistant (hVISA) strains among clinical isolates exist, but the optimal method has not been clearly defined (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Etest methods, including the Macromethod and glycopeptide resistance detection (GRD), have been suggested, but their sensitivity and specificity are variable and confirmation with the gold standard population analysis profile is considered necessary (2,4,7,10,12,15,17).…”