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Recent clinical data on vancomycin pharmacokinetics and pharmacodynamics suggest a reevaluation of current dosing and monitoring recommendations. The previous 2009 vancomycin consensus guidelines recommend trough monitoring as a surrogate marker for the target area under the curve over 24 hours to minimum inhibitory concentration (AUC/MIC). However, recent data suggest that trough monitoring is associated with higher nephrotoxicity. This document is an executive summary of the new vancomycin consensus guidelines for vancomycin dosing and monitoring. It was developed by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists vancomycin consensus guidelines committee. These consensus guidelines recommend an AUC/MIC ratio of 400–600 mg*hour/L (assuming a broth microdilution MIC of 1 mg/L) to achieve clinical efficacy and ensure safety for patients being treated for serious methicillin-resistant Staphylococcus aureus infections.

Drug dosage adjustment for patients with acute or chronic kidney disease is an accepted standard of practice. The challenge is how to accurately estimate a patient's kidney function in both acute and chronic kidney disease and determine the influence of renal replacement therapies on drug disposition. Kidney Disease: Improving Global Outcomes (KDIGO) held a conference to investigate these issues and propose recommendations for practitioners, researchers, and those involved in the drug development and regulatory arenas. The conference attendees discussed the major challenges facing drug dosage adjustment for patients with kidney disease. In particular, although glomerular filtration rate is the metric used to guide dose adjustment, kidney disease does affect nonrenal clearances, and this is not adequately considered in most pharmacokinetic studies. There are also inadequate studies in patients receiving all forms of renal replacement therapy and in the pediatric population. The conference generated 37 recommendations for clinical practice, 32 recommendations for future research directions, and 24 recommendations for regulatory agencies (US Food and Drug Administration and European Medicines Agency) to enhance the quality of pharmacokinetic and pharmacodynamic information available to clinicians. The KDIGO Conference highlighted the gaps and focused on crafting paths to the future that will stimulate research and improve the global outcomes of patients with acute and chronic kidney disease.

Antibiotic renal dose adjustments are determined in subjects with stable chronic kidney disease and may not translate to patients in late phase trials and practice. Ceftolozane/tazobactam, ceftazidime/avibactam, and telavancin all carry precautionary statements for reduced clinical response in patients with baseline creatinine clearance 30 - 50 mL/min, potentially due to unnecessary dose reduction in the setting of acute kidney injury (AKI). In this review, we discuss the regulatory landscape for antibiotics eliminated by the kidney and highlight the importance of the first 48 hours of therapy. Using a clinical database, we identify AKI on admission in a substantial proportion of patients with pneumonia (27.1%), intra-abdominal (19.5%), urinary tract (20.0%), or skin and skin structure infections (9.7%) that resolved by 48 hours in 57.2% of cases. We suggest that deferred renal dose reduction of wide therapeutic index antibiotics could improve outcomes in patients with infectious diseases.

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