Abstract

BackgroundIn the recent era, antimicrobial resistance has been identified as one of the most important threats to human health worldwide. The rapid emergence of antibiotic-resistant pathogens (ABRP) in the modern intensive care unit (ICU) also represents a “nightmare scenario” with unknown clinical consequences. In the Greek ICU, in particular, gram negative ABRPs are now considered endemic. However, the possible longitudinal impact of ABRPs on long-term outcomes of ICU patients has not yet been determined.MethodsIn this two-year (January 2014-December 2015) single-centre observational longitudinal study, 351 non-neurocritical ICU patients ≥ 18 year-old were enrolled. Patients’ demographic, clinical and outcome data were prospectively collected. Quality-adjusted life years (QALY) were calculated at 6, 12, 18 and 24 months after ICU admission.ResultsFifty-eight patients developed infections due to ABRP (ABRP group), 57 due to non-ABRP (non-ABRP group), and 236 demonstrated no infection (no-infection group) while in ICU. Multiple regression analysis revealed that multiple organ dysfunction syndrome score (OR: 0.676, 95%CI 0.584–0.782; P < 0.001) and continuous renal replacement therapy (OR: 4.453, 95%CI 1.805–10.982; P = 0.001) were the only independent determinants for ABRP infections in ICU. Intra-ICU, 90-day and 2-year mortality was 27.9%, 52.4% and 61.5%, respectively. Compared to the non-ABRP and no-infection group, the ABRP group demonstrated increased intra-ICU, 90-day and 2-year mortality (P ≤ 0.022), worse 2-year survival rates in ICU patients overall and ICU survivor subset (Log-rank test, P ≤ 0.046), and poorer progress over time in 2-year QALY kinetics in ICU population overall, ICU survivor and 2-year survivor subgroups (P ≤ 0.013). ABRP group was further divided into multi-drug and extensively-drug resistant subgroups [MDR (n = 34) / XDR (n = 24), respectively]. Compared to MDR subgroup, the XDR subgroup demonstrated increased ICU, 90-day and 2-year mortality (P ≤ 0.031), but similar 90-day and 2-year QALYs (P ≥ 0.549). ABRP infections overall (HR = 1.778, 95% CI 1.166–2.711; P = 0.008), as well as XDR [HR = 1.889, 95% CI 1.075–3.320; P = 0.027) but not MDR pathogens, were independently associated with 2-year mortality, after adjusting for several covariates of critical illness.ConclusionsThe present study may suggest a significant association between ABRP (especially XDR) infections in ICU and increased mortality and inability rates for a prolonged period post-discharge that requires further attention in larger-scale studies.

Highlights

  • In the recent era, antimicrobial resistance has been identified as one of the most important threats to human health worldwide

  • The present study may suggest a significant association between antibiotic-resistant pathogens (ABRP) infections in intensive care unit (ICU) and increased mortality and inability rates for a prolonged period post-discharge that requires further attention in larger-scale studies

  • A total of 373 ICU patients were assessed for eligibility to participate in the study during the study period (January 1, 2014 to December 31, 2015)

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Summary

Introduction

Antimicrobial resistance has been identified as one of the most important threats to human health worldwide. Critical illness may impair mental, physical and social health, limit patients’ mobility and independence, and damage self-confidence, sense of hope and positive outlook [2]. These devastating consequences of critical illness, of limited “clinical relevance”, are considered as “patient-important outcomes” (such as quality of life, functional/cognitive/neurological outcomes assessed after ICU discharge) and their role in clinical research is increasingly emphasized [3, 4]. Antibiotic resistant pathogens (ABRP) have been identified as one of the most important threats for the modern ICU, limiting treatment options and resulting in adverse clinical outcomes and excessive cost of care [6,7,8]. The impact of antimicrobial resistance on ICU mortality has been widely studied so far [9,10,11,12,13,14,15,16,17,18,19,20]; the putative influence of ABRP-induced ICU infections on post-ICU patient-important, intermediate and long-term outcomes remains largely undetermined so far

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