Effect of Antibiotic Discontinuation Strategies on Mortality and Infectious Complications in Critically Ill Septic Patients: A Meta-Analysis and Trial Sequential Analysis*

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.

Infectious Disease Team Review Using Antibiotic Switch and Discharge Criteria Shortens the Duration of Intravenous Antibiotic: A Single-Center Cluster-Randomized Controlled Trial in Thailand

“…A duration of ATB therapy of 7–10 days is generally adequate for sepsis patients, and longer courses are necessary only in some patients, such as those with slow clinical response or with undrainable foci [ 18 ]. A shorter duration of ATB therapy even in sepsis patients is safe without affecting treatment success [ 19 ]. Decisions on the duration of ATB should be considered depending on patient-related factors and the type of infection [ 20 ].…”

Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021

“…The undesirable effects of using procalcitonin along with clinical evaluation to decide when to discontinue antimicrobials are considered minimal, and do not outweigh the potential benefits [ 322 ]. Limited data on the cost-effectiveness are available, although a single centre study reported decreased hospital costs associated with PCT-guided antibiotic in medical ICU patient with undifferentiated sepsis [ 323 ].…”

“…Neutropenia [204,208] Surrogate markers such as Serum or Bronchoalveolar Lavage Galactomannan Assay [209][210][211] Haematopoietic stem cell transplantation [204,208,212] Solid organ transplantation [202,[212][213][214] High dose corticosteroid therapy [215,216] Certain biologic response modifiers [206,217,218] outweigh the potential benefits [322]. Limited data on the cost-effectiveness are available, although a single centre study reported decreased hospital costs associated with PCT-guided antibiotic in medical ICU patient with undifferentiated sepsis [323].…”

Prognostic Value of Procalcitonin, C-Reactive Protein, and Lactate Levels in Emergency Evaluation of Cancer Patients with Suspected Infection

“…However, procalcitonin is more helpful in identifying Gram-negative bacterial systemic infections [25], and the accuracy of procalcitonin in predicting Gram-negative bacteremia in leukemia patients is quite good (area under the receiver operating characteristic curve (AUROC) = 0.779) [26]. Longitudinal assessment using serial procalcitonin measurements can predict prognosis and treatment efficacy in infections [27], and this assessment is used in antibiotic stewardship [28][29][30]. Procalcitonin is also used as an independent predictor of clinical deterioration in ED patients with suspected sepsis [31].…”