Emergence of resistance to daptomycin in a cohort of patients with methicillin-resistant Staphylococcus aureus persistent bacteraemia treated with daptomycin

4 Theoretically estimated AUC 24 /MIC ratios against VRE susceptible to linezolid, according to the EUCAST clinical breakpoint (MIC¼ 4 mg/L), 1 were in the recommended range for the effective treatment of severe infections with linezolid (AUC 24 /MIC ratio of 80 –120) 6 in both cases (.93.76 and .250.96, respectively). In addition , biliary trough levels (C min) of linezolid were above the EUCAST clinical breakpoint against VRE in both cases (7.42 and 37.53 mg/L, respectively), this ensuring a theoretical T .MIC of .100%. The wide interindividual pharmacokinetic variability of linezolid observed between the two patients (patient 1: V ss 31. 5 L, CL 4.2 L/h and t 1/2 5.2 h; patient 2: V ss 67.1 L, CL 1.6 L/h and t 1/2 29.1 h) confirmed previous observations in critically ill patients during treatment with linezolid. 8 This variability is expected to potentially impact more on tolerability than on efficacy. Notably, patient 2 experienced hyperlactacidaemia (an increase in lactate level of 6.2 mmol/L during linezolid treatment), which could have been related to drug overexposure potentially favoured by drug –drug interactions and renal impairment. 8 However, it should not be overlooked that linezolid has generally been shown to be safe and effective in LTx patients. 9 The therapeutic drug monitoring of plasma C min may represent a valuable tool for the optimal management of linezolid in these cases, 8 and has recently been shown to improve safety outcomes in long-term treatment. 10 We recognize that the absence of real biliary pharmacokinetic/ pharmacodynamic data may be a limitation. However, these data confirm the potentially valuable role of linezolid in the treatment of cholangitis due to multidrug-resistant Enterococcus in LTx patients, since they meet the recommendations of good biliary penetration that are given in the Tokyo guidelines. References 1 Asín E, Isla A, Canut A et al. Comparison of antimicrobial pharmacokinetic/pharmacodynamic breakpoints with EUCAST and CLSI clinical breakpoints for Gram-positive bacteria. 4 Cremaschi E, Maggiore U, Maccari C et al. Linezolid levels in a patient with biliary tract sepsis, severe hepatic failure and acute kidney injury on sustained low-efficiency dialysis (SLED). 5 Pea F, Viale P, Lugano M et al. Biliary penetration and pharmacodynamic exposure of linezolid in liver transplant patients. 6 Rayner CR, Forrest A, Meagher AK et al. Clinical pharmacodynamics of linezolid in seriously ill patients treated in a compassionate use programme. 7 Pea F, Viale P, Lugano M et …