Characterisation of a Staphylococcus aureus strain with progressive loss of susceptibility to vancomycin and daptomycin during therapy

Abstract

Following an initial response to vancomycin therapy, a patient with meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia developed endocarditis, failed a second course of vancomycin and then failed daptomycin therapy. An increase in the vancomycin minimum inhibitory concentrations of four consecutive MRSA blood isolates from 2 μg/mL to 8 μg/mL was shown by Etest. Population analysis of four successive blood culture isolates recovered over the 10-week period showed that the MRSA strain became progressively less susceptible to both vancomycin and daptomycin. Retrospectively, the macro Etest method using teicoplanin indicated a decrease in vancomycin susceptibility in the second blood isolate. The patient improved after treatment with various courses of trimethoprim/sulphamethoxazole, quinupristin/dalfopristin and linezolid. Early detection of vancomycin-heteroresistant S. aureus isolates, which appeared to have clinical significance in this case, continues to be a challenge for the clinical laboratory. Development of suitable practical methods for this should be given priority. Concurrent development of resistance to vancomycin and daptomycin, whilst rare, must be considered in a patient who is unresponsive to daptomycin following vancomycin therapy.

Reduced Vancomycin Susceptibility inStaphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications

“…As described above, in many cases, the hVISA or VISA phenotype is detected after a prolonged period of infection, which is associated with a failure of glycopeptide therapy (121,151,213,313,316,326,337,340,348,376). The testing of later clinical isolates from patients who have failed glycopeptide treatment appears more likely to yield a positive result for hVISA or VISA.…”

“…At Austin Health, we have detected high rates of hVISA (up to 50% of MRSA isolates) when all MRSA isolates are assessed in detail by PAP; however, a significant clinical impact of the hVISA phenotype has not been demonstrated for less severe infections such as superficial-wound infections (118). As highlighted in a recent case report of serious MRSA infection, the early detection of hVISA in a patient that subsequently failed vancomycin and then daptomycin therapy may have alerted the clinician to the potential for treatment failure and a possible alternate approach to therapy (348). At present, we favor the screening of isolates from high-risk patients (those with bacteremia or deep-seated infection) and patients who are failing vancomycin therapy, as indicated by persisting positive cultures upon therapy (Fig.…”

“…In some cases resistance appears to be associated with mutations in mprF and yycG, loci which have been implicated in reduced vancomycin susceptibility in some strains. There has been an association between hVISA and VISA and reduced susceptibility to daptomycin (61,222,243,348,388). It appears that vancomycin exposure per se can induce low-level daptomycin resistance or daptomycin heteroresistance (131,283,293,348); however, these changes appear to be strain specific and may be unstable (283).…”

“…There has been an association between hVISA and VISA and reduced susceptibility to daptomycin (61,222,243,348,388). It appears that vancomycin exposure per se can induce low-level daptomycin resistance or daptomycin heteroresistance (131,283,293,348); however, these changes appear to be strain specific and may be unstable (283). Data from in vitro and animal studies suggest that daptomycin may have a lower rate of in vitro killing of hVISA than against VSSA (175); however, daptomycin retains bactericidal activity against hVISA and VISA (2,40,196,283).…”

“…Thirty-two VISA strains from Israel had an MIC of daptomycin of Յ0.5 g per ml. Some case reports described the failure of daptomycin therapy after failed vancomycin therapy for serious MRSA infections (18,131,348), and in one case, persistent MRSA bacteremia was subsequently successfully cleared with linezolid and fusidic acid (131).…”