Bactericidal activity of oxacillin and glycopeptides against Staphylococcus aureus in patients with endocarditis: Looking for a relationship between tolerance and outcome

Abstract

BackgroundThere is no clear relationship between in vitro bactericidal activity tests and clinical outcome. We studied bactericidal activity of oxacillin, vancomycin and teicoplanin against Staphylococcus aureus isolates in patients with endocarditis and then we sought to determine if there was a relationship between in vitro bactericidal activity and clinical outcome.MethodsMinimal bacteriostatic and minimal bactericidal concentrations were determined for Staphylococcus aureus strains isolated from patients with endocarditis following standardized methods. Medical records were reviewed retrospectively to collect data on antimicrobial susceptibility at admission, antimicrobial therapy, need for surgery, embolic events and outcome.Results and DiscussionSixty-two Staphylococcus aureus strains were studied in 62 patients with endocarditis. Overall, 91.9% definite, 21% methicillin resistant and 72.6% cured. Surgery was performed in 32.3% and embolic events were documented in 64.5%. Tolerance to oxacillin and teicoplanin was more common than vancomycin tolerance among methicillin susceptible Staphylococcus aureus. Among methicillin resistant Staphylococcus aureus teicoplanin was shown to have a higher rate of tolerance than vancomycin. No statistically significant differences on clinical outcome between oxacillin tolerant and oxacillin non tolerant Staphylococcus aureus infections were observed. Tolerance to oxacillin did not adversely affect clinical outcomes of patients with methicillin susceptible Staphylococcus aureus endocarditis treated with a combination of antimicrobials including oxacillin. The cure rate was significantly lower among patients with methicillin resistant Staphylococcus aureus endocarditis.ConclusionsIn vitro bactericidal test results were not valid predictors of clinical outcome. Physicians need to use additional parameters when treating patients with staphylococcal endocarditis.

An Experimental Framework for Quantifying Bacterial Tolerance

“…Its definition as a duration is natural, as tolerance is the ability to survive transient exposure to stress. Therefore, the MDK has an inherent advantage over minimum bactericidal concentration/MIC ratios ( 23 ), which have been shown to be poorly correlated with tolerance ( 6 , 24 , 25 , 26 ) (minimum bactericidal concentration—the concentration required to kill ≥99.9% of a culture, typically after 24 h incubation). Another option typically used to evaluate tolerance is time-kill curve analysis.…”

Influence of teicoplanin MICs on treatment outcomes among patients with teicoplanin-treated methicillin-resistant Staphylococcus aureus bacteraemia: a hospital-based retrospective study

“…15 However, there are limited studies evaluating the relationship between teicoplanin MIC values and outcomes among patients with serious MRSA infections. 16,17 Thus, we conducted a retrospective cohort study to examine MRSA isolates obtained from patients with MRSA bacteraemia over a 13 month period, testing their susceptibility to teicoplanin by Etest w and identifying the breakpoint of teicoplanin MICs influencing treatment outcomes.…”

Relationship between vancomycin tolerance and clinical outcomes inStaphylococcus aureusbacteraemia

“…While previous researchers have evaluated the impact of bactericidal activity in SAB, data supporting the clinical relevance of this activity as measured by MBC/MIC ratio are limited. 13,[28][29][30] The most recent study evaluated S. aureus endocarditis (n ¼ 62) and was underpowered to detect an association between VT and clinical outcomes. 29 Data on the influence of b-lactam tolerance on Vancomycin tolerance in Staphylococcus aureus bacteraemia JAC clinical outcomes in MSSA infections are conflicting as well.…”

“…13,[28][29][30] The most recent study evaluated S. aureus endocarditis (n ¼ 62) and was underpowered to detect an association between VT and clinical outcomes. 29 Data on the influence of b-lactam tolerance on Vancomycin tolerance in Staphylococcus aureus bacteraemia JAC clinical outcomes in MSSA infections are conflicting as well. One study failed to find an association between oxacillin tolerance and clinical outcomes, while another found nafcillin tolerance was associated with increased duration of clinical symptoms of infection.…”