Systematic review of the impact of appropriate versus inappropriate initial antibiotic therapy on outcomes of patients with severe bacterial infections

Highlights

• Systematic review and meta-analyses assessing impact of appropriate versus inappropriate antimicrobial therapy.

• Early administration of appropriate antimicrobial therapy significantly reduces mortality rate.

• Early administration of appropriate antimicrobial therapy significantly reduces hospital length of stay.

• Early initiation of appropriate antimicrobial therapy increases clinical cure rates and reduces hospital costs.

• Increasing the availability of rapid diagnostics is essential in order to improve patient outcomes.

ABSTRACT

We investigated the impact of appropriate versus inappropriate initial antimicrobial therapy on the clinical outcomes of patients with severe bacterial infections as part of a systematic review and meta-analyses assessing the impact of delay in appropriate antimicrobial therapy. Literature searches of MEDLINE and Embase, conducted on 24 July 2018, identified studies published after 2007 reporting the impact of delay in appropriate antibiotic therapy for hospitalised adult patients with bacterial infections. Results were statistically pooled for outcomes including mortality, hospital length of stay (LOS) and treatment failure. Subgroup analyses were explored by site of infection where data permitted. Inclusion criteria were met by 145 studies, of which 114 reported data on the impact of appropriate versus inappropriate initial therapy. In the pooled analysis, rates of mortality were significantly in favour of appropriate therapy [odds ratio (OR) = 0.44, 95% CI 0.38–0.50]. Across eight studies, LOS was shorter with appropriate therapy compared with inappropriate therapy [mean difference (MD) −2.54 days (95% CI −5.30 to 0.23)], but not significantly so. The incidence of treatment failure was significantly lower in patients who received appropriate therapy compared with patients who received inappropriate therapy (six studies: OR = 0.33, 95% CI 0.16–0.66) as was mean hospital costs (four studies: MD −7.38 thousand US$ or Euros, 95% CI −14.14 to −0.62). Initiation of appropriate versus inappropriate antibiotics can reduce mortality, reduce treatment failure and decrease LOS, highlighting the importance of broad‑spectrum empirical therapy and rapid diagnostics for early identification of the causative pathogen. [Study registration: PROSPERO: CRD42018104669]

Introduction

Severe bacterial infections are associated with considerable mortality, morbidity and healthcare costs [1], [2], [3], [4]. Assessment of the appropriateness of antibiotic therapy can be performed by evaluating cultures of causative pathogens and their antimicrobial susceptibility, which typically takes at least 48–72 h [5]. The adoption of rapid diagnostic techniques to determine antimicrobial susceptibility can reduce therapeutic delay but is not currently routine practice. Consequently, physicians initiate antibiotic treatment before test results have confirmed the causative pathogen and its drug resistance pattern. Initiation of inappropriate antibiotic treatment is associated with higher mortality and longer hospital length of stay (LOS) [4]. These results have been observed in patients with pneumonia, with appropriate initial therapy resulting in higher survival rates, shorter hospital stay and lower healthcare costs [6,7].

We performed a systematic review to assess the impact of delayed appropriate antibacterial therapy on clinical outcomes (i.e. mortality, LOS, cost and treatment failure) of patients with community- and hospital-acquired severe bacterial infections. Here we focus on the impact of appropriate versus inappropriate initial therapy.