The role of antimicrobial resistance on long-term mortality and quality of life in critically ill patients: a prospective longitudinal 2-year study

BACKGROUND: In 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. METHODS: In 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. RESULTS: Fifty-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. CONCLUSIONS: The 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.