Infectious diseases and impaired renal function often occur in critically ill patients, and delaying the start of appropriate empiric antimicrobial therapy or starting inappropriate therapy has been associated with poor outcomes. Our primary objective was to critically review and discuss the influence of chronic kidney disease (CKD) and acute kidney injury (AKI) on the clinical pharmacokinetic and pharmacodynamic properties of antimicrobial agents. The effect of continuous renal replacement therapies (CRRTs) and intermittent hemodialysis (IHD) on drug disposition in these two populations was also evaluated. Finally, proposed dosing strategies for selected antimicrobials in critically ill adult patients as well as those receiving CRRT or IHD have been compiled. We conducted a PubMed search (January 1980-March 2008) to identify all English-language literature published in which dosing recommendations were proposed for antimicrobials commonly used in critically ill patients, including those receiving CRRT or IHD. All pertinent reviews, selected studies, and associated references were evaluated to ensure their relevance. Forty antimicrobial, antifungal, and antiviral agents commonly used in critically ill patients were included for review. Dosage recommendations were synthesized from the 42 reviewed articles and peer-reviewed, evidence-based clinical drug databases to generate initial guidance for the determination of antimicrobial dosing strategies for critically ill adults. Because of the evolving process of critical illness, whether in patients with AKI or in those with CKD, prospective adaptation of these initial dosing recommendations to meet the needs of each individual patient will often rely on prospectively collected clinical and laboratory data.

Objective: To summarize current antibiotic dosing recommendations in critically ill patients receiving intermittent hemodialysis (IHD), prolonged intermittent renal replacement therapy (PIRRT), and continuous renal replacement therapy (CRRT), including considerations for individualizing therapy. Data Sources: A literature search of PubMed from January 2008 to May 2019 was performed to identify English-language literature in which dosing recommendations were proposed for antibiotics commonly used in critically ill patients receiving IHD, PIRRT, or CRRT. Study Selection and Data Extraction: All pertinent reviews, selected studies, and references were evaluated to ensure appropriateness for inclusion. Data Synthesis: Updated empirical dosing considerations are proposed for antibiotics in critically ill patients receiving IHD, PIRRT, and CRRT with recommendations for individualizing therapy. Relevance to Patient Care and Clinical Practice: This review defines principles for assessing renal function, identifies RRT system properties affecting drug clearance and drug properties affecting clearance during RRT, outlines pharmacokinetic and pharmacodynamic dosing considerations, reviews pertinent updates in the literature, develops updated empirical dosing recommendations, and highlights important factors for individualizing therapy in critically ill patients. Conclusions: Appropriate antimicrobial selection and dosing are vital to improve clinical outcomes. Dosing recommendations should be applied cautiously with efforts to consider local epidemiology and resistance patterns, antibiotic dosing and infusion strategies, renal replacement modalities, patient-specific considerations, severity of illness, residual renal function, comorbidities, and patient response to therapy. Recommendations provided herein are intended to serve as a guide in developing and revising therapy plans individualized to meet a patient’s needs.

Enterococci are a common cause of urinary tract infections (UTIs) among hospitalized patients. The rising prevalence of vancomycin-resistant enterococci (VRE) is of particular concern within many institutions because of its association with increased mortality and health care costs, as well as limited treatment options. Clinicians need to differentiate between VRE-associated urinary colonization, asymptomatic bacteriuria, and UTIs in order to determine the need for treatment, optimal therapeutic options, and length of therapy. Unnecessary use of antibiotics in patients simply colonized and not infected with VRE in the urine has become a large problem in both hospitals and long-term care facilities. A PubMed-MEDLINE search was conducted to identify all English-language literature published between January 1975 and March 2010 in order to summarize diagnostic criteria and treatment options for VRE UTIs. Several antimicrobials are discussed, with the specific focus on those with the potential to treat VRE UTIs and susceptibility patterns of VRE from urinary sources: ampicillin, amoxicillin, daptomycin, doxycycline, fosfomycin, imipenem-cilastatin, linezolid, nitrofurantoin, penicillin, piperacillin, quinupristin-dalfopristin, tetracycline, and tigecycline. Recommendations for empiric treatment of enterococcal UTIs and definitive treatment of VRE UTIs, including an evidence-based treatment algorithm, are proposed. Ampicillin generally is considered the drug of choice for ampicillin-susceptible enterococcal UTIs, including VRE. Nitrofurantoin, fosfomycin, and doxycycline have intrinsic activity against enterococci, including VRE, and are possible oral options for VRE cystitis. Linezolid and daptomycin should be reserved for confirmed or suspected upper and/or bacteremic VRE UTIs among ampicillin-resistant strains. Use of other antimicrobials, such as quinupristin-dalfopristin and tigecycline, should be evaluated on a case-by-case basis due to concerns of toxicity, resistance, and insufficient supportive data. Additional clinical data are needed to determine the optimal management and duration of therapy for VRE UTIs.