by Arulkumaran, Nishkantha; Khpal, Muska; Tam, Karen;
Baheerathan, Aravindhan; Corredor, Carlos; Singer, Mervyn
Critical Care Medicine: May 2020 -
Volume 48 - Issue 5 - p 757-764
Abstract
Objective: To
investigate methods of antibiotic duration minimization and their effect on
mortality and infectious complications in critically ill patients.
Data Sources: A
systematic search of PubMed, Embase (via Ovid), clinicaltrials.gov, and the
Cochrane Central Register of Controlled Trials (via Wiley) (CENTRAL, Issue 2,
2015).
Study Selection:
Randomized clinical trials comparing strategies to minimize antibiotic duration
(days) for patients with infections or sepsis in intensive care.
Data Extraction:
A systematic review with meta-analyses and trial sequential analyses of
randomized clinical trials. Dichotomous data are presented as relative risk
(95% CIs) and p value, and continuous data are presented as mean difference
(CI) and p value.
Data Synthesis:
We included 22 randomized clinical trials (6,046 patients). Strategies to
minimize antibiotic use included procalcitonin (14 randomized clinical trials),
clinical algorithms (two randomized clinical trials), and fixed-antibiotic
duration (six randomized clinical trials). Procalcitonin (–1.23 [–1.61 to
–0.85]; p < 0.001), but not clinical algorithm–guided antibiotic therapy
(–7.41 [–18.18 to 3.37]; p = 0.18), was associated with shorter duration of
antibiotic therapy. The intended reduction in antibiotic duration ranged from 3
to 7 days in fixed-duration antibiotic therapy randomized clinical trials.
Neither procalcitonin-guided antibiotic treatment (0.91 [0.82–1.01]; p = 0.09),
clinical algorithm–guided antibiotic treatment (0.67 [0.30–1.54]; p = 0.35),
nor fixed-duration antibiotics (1.21 [0.90–1.63]; p = 0.20) were associated
with reduction in mortality. Z-curve for trial sequential analyses of mortality
associated with procalcitonin-guided therapy did not reach the trial sequential
monitoring boundaries for benefit, harm, or futility (adjusted CI, 0.72–1.10).
Trial sequential analyses for mortality associated with clinical algorithm and
fixed-duration treatment accumulated less than 5% of the required information
size. Despite shorter antibiotic duration, neither procalcitonin-guided therapy
(0.93 [0.84–1.03]; p = 0.15) nor fixed-duration antibiotic therapy (1.06
[0.74–1.53]; p = 0.75) was associated with treatment failure.
Conclusions:
Although the duration of antibiotic therapy is reduced with
procalcitonin-guided therapy or prespecified limited duration, meta-analysis
and trial sequential analyses are inconclusive for mortality benefit. Data on
clinical algorithms to guide antibiotic cessation are limited.
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