Objectives: The purpose of this study was to identify clinically important risk factors that may predispose patients with appropriate vancomycin dosing to an unexpectedly-high trough concentration (C_min) and the occurrence of nephrotoxicity.

Methods: Patients treated with vancomycin and who were performed therapeutic drug monitoring were included in the study. Nephrotoxicity was defined as an increase of >0.5 mg/dL or a 50% increase in serum creatinine over the baseline. Multivariate analysis was performed to identify independent risk factors for C_min of ≥20 μg/mL and deterioration of renal function.

Results: One hundred and ninety-seven patients were analyzed. Nephrotoxicity occurred in 16.8% of patients during vancomycin therapy. C_min of ≥20 μg/mL was demonstrated in 17.8% of patients. Twenty-five of 35 patients demonstrated a C_min of ≥20 μg/mL at multiple TDM. C_min of ≥20 μg/mL and deterioration of renal function were closely correlated with one another. Additionally, an independent risk factor identified to be associated with C_min of ≥20 μg/mL was the ad_ministration of diuretics [odds ratio (OR) 3.21, 95% confidence interval (CI) 1.30–7.90]. Use of non-steroidal anti-inflammatory drugs (NSAIDs) (OR 3.22, 95% CI 1.09–9.57) and management with total parenteral nutrition (OR 3.64, 95% CI 1.33–10.00) were independent factors associated with nephrotoxicity during vancomycin therapy.

Conclusions: NSAIDs, diuretic drug use and total parenteral nutrition (TPN) were independent risk factors for a high C_min or nephrotoxicity. Limited use of these drugs is preferable to prevent adverse events during vancomycin therapy.

Background: Sodium mercaptoacetic acid double disk synergy test (SMA-DDSTs) is frequently used in Japan to detect metallo-β-lactamase (MBL) producer easily. In this study, we evaluated SMA-DDST at the points of the antimicrobial disk, and the distance between SMA and an antimicrobial disk.

Methods: Forty-one clinical isolates ceftazidime (CAZ)-resistant Enterobacteriaceae and 12 reference strains were tested. Those isolates included 17, 19, 4 and 13 of only IMP-, IMP with other classes of β-lactamases-, New Delhi MBL with other classes of β-lactamases- and non-MBL-producers, respectively. SMA-DDSTs were performed with CAZ, imipenem (IPM) and meropenem (MEPM)-containing disks with the distance between SMA and antimicrobial disk at 11 mm or 16 mm (centerto-center).

Results: The sensitivities were 27/40 (68%), 17/40 (43%), 35/40 (88%), 29/40 (73%), 25/40 (63%), and 39/40 (98%) for 16 mm CAZ-SMA-DDST, 16 mm IPMSMA-DDST, 16 mm MEPM-SMA-DDST, 11 mm CAZ-SMA-DDST, 11 mm IPMSMA- DDST, and 11 mm MEPM-SMA-DDST, respectively. CAZ and MEPM disk showed the highest sensitivity for only MBL-producing isolates and MBL with coproducing other classes of β-lactamases-producing isolates, respectively. Among any of antimicrobials used in this study, 11 mm SMA-DDSTs showed higher sensitivity than those 16 mm. The specificity was 100% for all SMA-DDSTs. However, the ambiguous false-expansion of growth inhibition zone was induced in 11 mm CAZ-SMA-DDST for non-MBL-producing isolates.

Conclusion: This study suggested that the combination of 16 mm CAZ-SMA-DDST and 11 mm MEPM-SMA-DDST is suitable for screening MBL-producing isolates.