Citations

ABSTRACT Beta‐lactam antibiotics (beta‐lactams) are first‐line treatments for most major infectious syndromes in acutely ill patients, with in vitro activity against common pathogens, demonstrated efficacy in trials, and a perceived low risk of adverse effects. The current dosing approach, informed by population‐level data, tends to be simplistically reduced to a “one size fits all” dosing method which only accounts for body weight (i.e., in pediatrics) and end organ function to estimate drug clearance (e.g., estimated glomerular filtration rate); this approach results in substantial variability in observed serum concentrations in acutely ill patients, which can compromise real‐world effectiveness and safety. Beta‐lactam dose individualization, therefore, defined as a dosing regimen for one patient informed by measured concentrations from that patient, has been recommended in international clinical guidelines. Comprehensive guidance on best practices for beta‐lactam dose individualization is lacking. To address this knowledge gap and develop guidance, a multidisciplinary panel of international experts was assembled from the disciplines of infectious diseases, critical care, pharmacometrics, and laboratory medicine, representing both adults and pediatrics. The panel systematically evaluated the literature, using the GRADE approach where feasible, to address broad thematic questions pertaining to whether beta‐lactam dose individualization should be pursued, for what indications beta‐lactam dose individualization is warranted, and the most critical considerations and best practices for implementation of beta‐lactam individualization. The resultant consensus recommendations will equip healthcare professionals caring for acutely ill patients treated with beta‐lactam therapy with the evidence and tools necessary to guide optimal use of beta‐lactam dose individualization.

Abstract Background These recommendations provide guidance on the optimal timing for transitioning from intravenous to oral antibiotics in patients with complicated urinary tract infection (cUTI), especially in presence of associated Gram-negative bacteremia. Methods The panel's recommendations are based upon evidence derived from systematic literature reviews which focused on comparative benefits and harms of transitioning to oral therapy versus continuing parenteral therapy of the total duration of treatment, including publications since 2000. These recommendations adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Results The guidelines panel suggests transitioning to oral antibiotics in patients with cUTI who are clinically improving, able to take medication, and for whom an effective oral option is available, rather than continuing parenteral therapy for the remaining treatment duration, regardless of the presence of associated Gram-negative bacteremia. An effective oral option needs to be active against the causative pathogen and achieve therapeutic levels in the urine and relevant tissue. Conclusions Parenteral and oral antibiotics used to complete treatment courses for cUTI provide similar efficacy and adverse events, especially in the context of shorter duration of therapy. This recommendation places a high value on reducing avoidable intravenous catheter-related adverse events, costs, and resources, as well as taking into account practical aspects of antibiotic administration.

Abstract Background These recommendations provide guidance on the optimal duration of antibiotics in patients with complicated urinary tract infection (cUTI), especially in presence of associated Gram-negative bacteremia. Methods The panel's recommendations are based upon evidence derived from systematic literature reviews which focused on comparative benefits and harms of shorter (5–7 days) vs prolonged (10–14 days) duration of antibiotics, including publications since 2000. These recommendations adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Results The guidelines panel suggests that patients with cUTI who are improving on effective therapy can be treated with shorter duration of antimicrobials (either 5–7 days of a fluoroquinolone or 7 days of a non-fluoroquinolone) rather than longer courses of antibiotics, regardless of the presence of associated Gram-negative bacteremia. An effective antimicrobial agent achieves therapeutic levels in the urine and relevant tissue and is active against the causative pathogen. However, men with febrile UTI in whom acute bacterial prostatitis is suspected may benefit from a longer treatment duration (10–14 days), and a short courses of oral beta lactams may require higher doses for efficacy. Conclusions Shorter durations of antibiotics for cUTI provide similar efficacy as longer courses, except in men with febrile UTI in whom acute bacterial prostatitis is suspected. This recommendation places a high value on antibiotic stewardship considerations as well as reducing the burden of antimicrobial administration from a healthcare perspective and reducing the burden of taking antibiotics from a patient perspective.

Abstract Background These recommendations address the empiric choice of antibiotics in suspected complicated urinary tract infection (cUTI). Issues to balance include the need for appropriate initial empiric antimicrobial therapy, the patient's severity of illness, and antimicrobial stewardship concerns. Methods The panel's recommendations are based upon evidence derived from systematic literature reviews that focused on comparative benefits and harms of classes of antibiotics approved for cUTI, starting with publications from 2008 onwards, and our review of predictors of resistance in uropathogens included references identified since 2000. These recommendations adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Results The guidelines panel suggests initially selecting among preferred empiric antibiotic choices rather than alternative options, stratified for the patient's severity of illness and antimicrobial stewardship considerations. When choosing among these antibiotics for a specific patient, the guideline panel suggests a 4-step process to account for changing resistance patterns and individualized patient needs. The steps are: (1) assess the severity of illness (for initial prioritization of antibiotics), (2) consider patient-specific risk factors for resistant uropathogens (for optimization of coverage), (3) evaluate other patient-specific considerations (to reduce the risk of adverse events), and (4) for patients with sepsis, consult a relevant local antibiogram if available (to further improve the likelihood of giving appropriate empiric therapy). Lastly, the guideline panel suggests selecting definitive effective therapy with a targeted spectrum based on the result of the urine culture. Conclusions Many of the classes of antibiotics approved to treat cUTI demonstrate similar efficacy as other classes of antibiotics in randomized controlled trials. Bacterial resistance prevalence is always changing, and new antibiotics will be developed. In this context, the guidelines panel provides recommendations for choosing empiric antibiotic therapy for cUTI that will help clinicians decide among available antibiotic options at the point of care.