Association of kidney function with effectiveness of procalcitonin-guided antibiotic treatment: apatient-level meta-analysis from randomized controlled trials.

Eva Heilmann,Claudia Gregoriano,Albertus Beishuizen,Michel Wolff,Lila Bouadma,Dylan W Delange,Djillali Annane,Armand R.J Girbes,Michael Tamm,Pierre Damas,Yahya Shehabi,Jean Chastre,Evelien De Jong,Vandack Nobre,Alessia Verduri,Philipp Schuetz,Yannick Wirz,Daiana Stolz,Florence Tubach,Konrad Reinhart,Maarten W N Nijsten ,Carolina Oliveira ,Beat Müeller ,Jos A H Van Oers ,Charles‐Édouard Luyt ,Kristina B Kristoffersen ,Mirjam Christ‐Crain

doi:10.1515/cclm-2020-0931

Abstract

Patients with impaired kidney function have a significantly slower decrease of procalcitonin (PCT) levels during infection. Our aim was to study PCT-guided antibiotic stewardship and clinical outcomes in patients with impairments of kidney function as assessed by creatinine levels measured upon hospital admission. We pooled and analyzed individual data from 15 randomized controlled trials who were randomly assigned to receive antibiotic therapy based on a PCT-algorithms or based on standard of care. We stratified patients on the initial glomerular filtration rate (GFR, ml/min/1.73m2) in three groups (GFR >90 [chronic kidney disease; CKD 1], GFR 15-89 [CKD 2-4] and GFR<15 [CKD 5]). The main efficacy and safety endpoints were duration of antibiotic treatment and 30-day mortality. Mean duration of antibiotic treatment was significantly shorter in PCT-guided (n=2,492) compared tocontrol patients (n=2,510) (9.5-7.6days; adjusted difference in days-2.01 [95% CI,-2.45 to-1.58]). CKD 5 patients had overall longer treatment durations, but a 2.5-day reduction in treatment duration was still found in patients receiving in PCT-guided care (11.3 vs. 8.6days [95% CI-3.59 to-1.40]). There were 397 deaths in 2,492 PCT-group patients (15.9%) compared to 460 deaths in 2,510 control patients (18.3%) (adjusted odds ratio, 0.88 [95% CI 0.78 to 0.98)]. Effects of PCT-guidance on antibiotic treatment duration and mortality were similar in subgroups stratified by infection type and clinical setting (pinteraction >0.05). This individual patient data meta-analysis confirms that the use of PCT in patients with impaired kidney function, as assessed by admission creatinine levels, is associated with shorter antibiotic courses and lower mortality rates.

Highlights

Antibiotic stewardship has become an international priority to reduce risk of multi-resistant organisms and potential drug-related side effects for patients [1]
Mean duration of antibiotic treatment was significantly shorter in PCT-guided (n=2,492) compared to control patients (n=2,510) (9.5–7.6 days; adjusted difference in days −2.01 [95% confidence intervals (CIs), −2.45 to −1.58])
A total of 990 records were identified in the initial search, of which 71 were assessed for eligibility and a total of 32 trials were potentially eligible for analysis

Summary

Introduction

Antibiotic stewardship has become an international priority to reduce risk of multi-resistant organisms and potential drug-related side effects for patients [1]. Among different other clinical and laboratory markers, procalcitonin (PCT) has emerged as an adjunct to clinical judgement to assess the risk for bacterial infection and treatment response to antibiotic therapy [2,3,4]. PCT is released by different tissues in the body in response to systemic inflammation caused by bacterial infections through cytokine stimulation (e.g., interleukin [IL)-1β, IL-6 or tumor necrosis factor [TNF]-α) [5,6,7]. Multiple randomized studies found that antibiotic stewardship based on clinical judgement and PCT levels results in reduced antibiotic exposure, lower risk for side-effects and improvements in clinical outcomes including overall survival [11,12,13]. Still it is important to understand that PCT should be used only as an adjunct to clinical decision making since several factors and conditions may cause false positive and false negative results [16]

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