Antibiotic de-escalation (ADE) was first implemented to reduce exposition to broad-spectrum antibiotics in the ICU. It is now part of the antimicrobial stewardship and is recommended in international guidelines. |
This systematic review aimed to evaluate the level of evidence regarding the safety of ADE (mortality, superinfections and duration of antimicrobial therapy) and the emergence of antibiotic resistance. |
Data related to safety showed with a low evidence level to support the safety of ADE. No conclusion can be drawn on the level of resistance after de-escalation. |
The reviewers recommend de-escalating antimicrobial treatment in patients requiring long-term antibiotic therapy and discussing the need for de-escalation for patients requiring short-term treatments.
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Introduction
Method
Principles
The goals of therapy are theoretically [3] |
Broadening the spectrum of antimicrobial therapy by administering different agents acting on different families of pathogens. This increases the likelihood that any responsible pathogen will be susceptible to at least one of the administered agents |
Improving the lethality of the treatment on the basis of a possible synergistic effect |
Preventing or delaying the emergence of resistance |
A large number of actions can be considered ADE, making it challenging to reach a consensus |
Narrowing the spectrum of the pivotal antimicrobial |
Early discontinuation of one or several antimicrobials of a combination therapy |
Early discontinuation of antimicrobial treatment. This has been excluded from the definition of ADE in the last consensus statement [1] |
Weiss et al. | Agent | Madaras-Kelly et al. | ||
---|---|---|---|---|
Rank | Similar response (%)a | Spectrum score | Rank | |
1 | 100 | Amoxicillin | 13.5 | 1 |
2 | 88 | Amoxicillin/clavulanate | 29.5 | 3 |
3 | 81 | 3rd-generation cephalosporin | 25.5 | 2 |
4 | 71 | Piperacillin/tazobactam | 42.25 | 7 |
4th-generation cephalosporin | 33.25 | 5 | ||
5 | 81 | Ertapenem | 30.25 | 4 |
6 | 85 | Imipenem | 41.5 | 6 |
Definition
Patient Perspective: Safety of Antimicrobial De-escalation
Studies | Study quality grade (mean) | No. patients | Mortality (%) | Length of stay (days) | Superinfections % | Severity score | AMR emergence % | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
ADE | No ADE | p | ADE | No ADE | p | ADE | No ADE | p | ADE | No ADE | p | ADE | No ADE | p | |||
Alvarez-Lerma 2006 [5] | 5 | 14.5% | 20% | – | 23.7 | 25.4 | 0.46 | – | – | – | 16.0a | 17.4a | – | – | – | – | |
Giantsou 2007 [6] | 4 | 113 | 12.0% | 43.5% | < 0.05 | 17.2 (1.2)d | 22.7 (6.3)d | < 0.05 | – | – | – | 7.1 (1.09)c | 7.1 (1.1)c | 0.9 | – | – | – |
Eachempati 2009 [17] | 4 | 138 | 33.8% | 42.1% | 0.324 | – | – | – | 27.30% | 35.10% | 0.34 | 79.8 (3.2)a | 85.5 (3.1)a | 0.223 | – | – | – |
De Waele 2010 [18] | 5 | 113 | 7%d | 21%d | 0.12 | – | – | – | – | – | – | 19(6.8)a | 18 (5.0)a | 0.87 | – | – | – |
Morel 2010 [19] | 6 | 116 | 18.3% | 24.6% | NS | 28 (33) | 24 (23) | 0.38 | 5% | 19% | 0.01 | 41(15)b | 40 (16)b | 0.68 | 10% | 19.1% | 0.10 |
Joung 2011 [20] | 6 | 137 | 2.3% | 14.0% | 0.03 | – | – | – | – | – | – | 15.6 (5.5)a | 15.3 (5.3)a | 0.90 | – | – | – |
Heenen 2012 [21] | 5 | 169 | 16% | 26% | 0.20e | – | – | – | – | – | – | – | – | – | – | – | – |
Gonzalez 2013 [22] | 7 | 229 | 17.1%d | 18.7%d | 0.5 | 12.9 (15.6)d | 10 (12.9)d | 0.12 | 2.50% | 5.30% | 0.15 | 7.8 (4.6)c | 7.2 (4.5)c | 0.32 | 15.30% | 10.70% | 0.1 |
Knaak 2013 [23] | 5 | 113 | 15%f | 39%f | < 0.01 | 15.4 (15.3)f | 18.0 (12.9)f | 0.35 | – | – | – | 5.7(3.3)c | 5.3 (3.7)c | 0.44 | – | – | – |
Mokart 2013 [24] | 6 | 101 | 18.18% | 26.32% | 0.57 | – | – | – | – | – | – | 8.5 [6;10.25]c | 7 [5;10]c | 0.37 | – | – | – |
Garnacho-Montero 2013 [7] | 7 | 628 | 28.3% | 34.1% | 0.001 | 26 (15–40)f | 24 (15–38)f | 0.015 | – | – | – | 7(4–10)c | 7 (4–10)c | 0.60 | – | – | – |
Paskovaty 2015 [8] | 5 | 101 | 24 (39%) | 15 (34%) | 0.68 | 17.1 (22.9)f | 23.4 (17.6)f | 0.005 | – | – | – | 7.2 (± 3.3)c | 8 (± 3.4)c | 0.18 | – | – | – |
Moraes 2016 [9] | 4 | 224 | 56.8% | 56.10% | 0.99 | 21 (10–37) | 19.5 (10–40) | > 0.05 | – | – | – | 7.9 ( 3.6)c | 7.3 (3.8)c | > 0.05 | – | – | – |
Weiss 2016 [10] | 5 | 182 | 31% | 26% | 0.53 | 16 (10.21) | 18 (12.21) | 0.82 | – | – | – | 6 [3;9]c | 5 [3;8]c | 0.46 | 14.30% | 21.30% | 0.32 |
De Bus 2016 [11] | 5 | 418 | 22.4%d | 21.3%d | 0.84 | 11 [6;19]d | 8 [5;15]d | 0.001 | 38.80% | 33% | 0.34 | 23 [18;30]a | 22 [17;28]a | 0.31 | 28.20% | 27.60% | 0.91 |
32.9%f | 33%f | 0.99 | |||||||||||||||
Turza 2016 [12] | 4 | 2658 | 6% | 9% | 0.002 | – | – | – | – | – | – | 15 (8)a | 14 (8)a | 0.02 | – | – | – |
Trupka 2017 [13] | 4 | 283 | 16.4%f | 43.3%f | < 0.001 | 11.0 [6.0;22.0]f | 12.0 [6.0;20]f | 0.918 | 8.3%g | 8.6%g | 0.92 | 22.7 (7.3)a | 21.7 (7.8)a | 0.262 | 6.3%h | 4.3%h | 0.468 |
Khan 2017 [14] | 5 | 108 | 21.9%d | 23.7%d | NS | 10.1 (4.6)d | 10.3 (9.1)d | NS | – | – | – | 10 (3.3)c | 9.8 (2.8)c | NS | – | – | – |
Li 2018 [15] | 6 | 156 | 28.6% | 23.80% | 0.620 | 19 [15;23] | 19 [15;26] | 0.764 | – | – | – | 16 [14;20] | 15.5 [14;19] | 0.346 | 31.0% | 40.5% | 0.36 |
Cowley 2019 [16] | 4 | 279 | 22.8% | 28.3% | 0.39 | 10 (5.24)d | 13 (8.23)d | Sig | – | – | – | 13 [10;18]a | 13 [9;17]a | NS | – | – | – |
15 [8;30]f | 20 [11;34]f | Sig | – | – | – |