Introduction
Methods
Data sources and search strategy
Eligibility criteria
Study design
Patients
Intervention
Outcome
Study appraisal
Data extraction
Study characteristics
Definition and measuring incidence of (I)AAT
Measurement of the dependent variable
Data analysis
Results
Results of the search
Study characteristics
Reference
|
Study year(s)
|
Location
|
Design
|
Center
|
Number of patients
|
Outcome
|
Main type of infection
|
Severity index scale and significance difference
| |
---|---|---|---|---|---|---|---|---|---|
Number
|
Type
| ||||||||
Kim et al. [21]a
| 1998-2001 | Korea | R | 1 | U | 127 | M | MRSA bacteremia | McCabe’s classification, Jackson: NS |
Kang et al. [12]a
| 1998-2002 | Korea | R | 2 | U, G | 286 | M | Antibiotic-resistant Gram-negative Bacilli BSI | APACHE II: NS |
Micek et al. [33]a
| 1997-2002 | USA | R | 1 | U | 305 | M |
Pseudomonas aeruginosa BSI | SAPS II: NC |
Luna et al. [34] | 1999-2003 | Argentina | P | 6 | NM | 76 | M | Pneumonia (VAP) | APACHE II: NS |
Kim et al. [8] | 1998-2001 | South Korea | R | 1 | U | 238 | M | SAB | McCabe’s classification, Jackson: NS |
Scarsi et al. [22]a
| 2001-2003 | USA | R | 1 | U | 884 | M | Gram-negative BSI | Charlson index: NS |
Marschall et al. [36]a
| 2006-2007 | USA | P | 1 | T | 250 | M LOS | Gram-negative bacteremia | Charlson index, McCabe’s classification: NS |
Shorr et al. [37]a
| 2002-2004 | USA | R | 1 | U | 291 | M LOS C | MRSA infection | NM |
Rodríguez-Baño et al. [38]a
| 2003 | Spain | P | 59 | U, G | 209 | M | Sepsis | Charlson index: NC |
Ammerlaan et al. [39]a
| 2007 | West European countries | R | 60 | T, G | 334 | M | SAB | Modified Charlson index: NS |
Erbay et al. [19]a
| 2005-2008 | Turkey | R | 1 | U | 103 | M | Acinetobacter baumannii bacteremia | APACHE II: NC |
Kumar et al. [40]a
| 1996-2005 | Canada, USA, Saudi Arabia | R | 22 | U | 5,715 | M | Septic shock | APACHE II: NC |
Tseng et al. [41]a
| 2005-2007 | Taiwan | R | 1 | T | 163 | M | Pneumonia | Charlson index: NC |
Micek et al. [42]a
| 2002-2007 | USA | R | 1 | U | 760 | M | Gram-negative sepsis | APACHE II, Charlson index: NS |
Paul et al. [43]a
| 1999-2007 | Israel | R | 1 | NM | 510 | M | MRSA bacteremia | NM |
Joung et al. [44]a
| 2000-2006 | Korea | R | 1 | U | 116 | M | Pneumonia (HAP) Acinetobacter baumannii | APACHE II: NS |
Shorr et al. [45] | 2002-2007 | USA | R | 1 | U | 760 | LOS | Gram-negative sepsis | APACHE II, Charlson index: NS |
Suppli et al. [46]a
| 2002-2005 | Denmark | R | 1 | T | 196 | M | Enterococcal BSI | Charlson index: NS, except score 0 (P = 0.04) |
Reisfeld et al. [47]a
| 2005-2007 | Israel | R | 1 | G | 378 | M | Gram-negative bacteremia | NM |
Wilke et al. [48]a
| 2007 | Germany | R | 5 | T | 221 | M LOS C | Pneumonia (VAP, HAP) | NM |
Lye et al. [50]a
| 2007-2009 | Singapore | R | 2 | G | 675 | M | Gram-negative bacteremia | APACHE II <0.001; Charlson index: NS |
Tseng et al. [51] | 2007-2008 | Taiwan | R | 1 | U | 163 | M | Pneumonia (VAP) | APACHE II, Charlson index, SOFA: NC |
Chen et al. [52] | 2006-2011 | China | R | 1 | T | 118 | M | SAB | APACHE II: NC |
Labelle et al. [54]a
| 2002-2007 | USA | R | 1 | T | 436 | M | Septic shock | APACHE II, Charlson index: NC |
Chen et al. [55] | 2008-2009 | Taiwan | P | 1 | U | 937 | M, LOS | BSI | MEDS, Charlson index: NC |
Frakking et al. [56]a
| 2008-2010 | The Netherlands | R | 8 | U | 232 | M | ESBL bacteremia | Pitt bacteremia score: NS |
Tumbarello et al. [57]a
| 2008-2010 | Italy | R | 1 | U | 110 | M |
Pseudomonas aeruginosa pneumonia | SAPS II, SOFA: NS |
Data on definition and measurement of (I)AAT
Reference
|
Appropriate empiric antibiotic therapy
|
Inappropriate empiric antibiotic therapy
| |||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Aspects of appropriate antibiotic therapy
|
Aspects of inappropriate antibiotic therapy
| ||||||||||||||||||
Definition
|
According to the culture
|
Timing
|
Dose
|
According to guidelines
|
Route
|
Indication
|
Duration
|
No known contraindication
|
Frequency
|
Number of items
|
Definition
|
Intermediate or full
in vitro
resistance
|
Timing
|
Omission
|
Indication
|
Route
|
Number of items
|
% IAAT
| |
Kim et al. [21]a
|
Y
| Y | Y | N | N | Y | N | N | N | N |
3
|
N
| 76.38 | ||||||
Kang et al. [12]a
|
N
|
Y
| Y | Y | Y | N | N |
3
| 52.80 | ||||||||||
Micek et al. [33]a
|
N
|
Y
| Y | N | Y | N | N |
2
| 24.59 | ||||||||||
Luna et al. [34] |
Y
| Y | N | N | Y | N | N | N | N | N |
2
|
Y
| Y | Y | N | N | N |
2
| 68.42 |
Kim et al. [8] |
Y
| Y | Y | N | N | Y | N | N | N | N |
3
|
N
| 49.16 | ||||||
Scarsi et al. [22]a
|
Y
| Y | Y | Y | Y | N | N | N | N | N |
4
|
Y
| Y | Y | N | N | N |
2
| 14.14 |
Marschall et al. [36]a
|
Y
| Y | Y | N | N | N | N | N | N | N |
2
|
Y
| Y | N | Y | N | N |
2
| 31.6 |
Shorr et al. [37]a
|
Y
| Y | Y | N | N | N | N | N | N | N |
2
|
N
| 76.98 | ||||||
Rodriguez-Bano et al. [38]a
|
Y
| Y | Y | Y | N | Y | N | N | N | N |
4
|
N
| 78.95 | ||||||
Ammerlaan et al. [39]a
|
Y
| Y | Y | N | N | Y | N | N | N | N |
3
|
Y
| Y | Y | Y | Y | Y |
5
| 28.14 |
Erbay et al. [19]a
|
Y
| Y | Y | Y | Y | Y | N | N | N | N |
5
|
N
| 58.25 | ||||||
Kumar et al. [40]a
|
Y
| Y | Y | N | N | N | N | N | N | N |
2
|
Y
| Y | Y | N | N | N |
2
| 19.88 |
Tseng et al. [41]a
|
Y
| Y | N | N | N | N | Y | N | N | N |
2
|
Y
| Y | N | N | Y | N |
2
| 49.26 |
Micek et al. [42]a
|
Y
| Y | Y | N | N | N | Y | Y | N | N |
4
|
N
| 31.32 | ||||||
Paul et al. [43]a
|
Y
| Y | Y | N | N | N | N | N | N | N |
2
|
N
| 67.06 | ||||||
Joung et al. [44]a
|
Y
| Y | Y | Y | N | Y | N | N | N | N |
4
|
Y
| Y | Y | N | N | N |
2
| 57.76 |
Shorr et al. [45] |
N
|
Y
| Y | Y | Y | N | N |
3
| 31.30 | ||||||||||
Suppli et al. [46]a
|
Y
| Y | Y | Y | Y | N | Y | Y | Y | N |
7
|
N
| 25.51 | ||||||
Reisfeld et al. [47]a
|
Y
| Y | N | Y | N | N | N | N | N | Y |
3
|
N
| 39.95 | ||||||
Wilke et al. [48]a
|
Y
| N | N | N | Y | N | N | N | N | N |
1
|
N
| 51.58 | ||||||
Lye et al. [50]a
|
Y
| Y | N | Y | Y | N | N | N | N | N |
3
|
N
| 43.56 | ||||||
Tseng et al. [51] |
Y
| N | N | N | N | N | Y | N | N | N |
1
|
N
| 56.44 | ||||||
Chen et al. [52] |
Y
| Y | Y | N | N | N | N | N | N | N |
2
|
N
| 38.98 | ||||||
Labelle et al. [54]a
|
Y
| Y | Y | N | N | N | N | N | N | N |
2
|
N
| 51.88 | ||||||
Chen et al. [55] |
Y
| Y | Y | Y | Y | Y | N | N | N | N |
5
|
N
| 27.21 | ||||||
Frakking et al. [56]a
|
Y
| Y | Y | N | N | N | N | Y | N | N |
3
|
N
| 63.36 | ||||||
Tumbarello et al. [57]a
|
N
|
Y
| Y | N | N | N | N |
1
| 50.91 | ||||||||||
Total |
23
|
21
|
17
|
8
|
7
|
7
|
4
|
3
|
1
|
1
|
11
|
11
|
7
|
5
|
2
|
1
|
Measurement of the dependent variable
Mortality
Reference
|
Time of mortality assessment
|
AAT mortality rate, %
|
IAAT mortality rate, %
|
P
value
|
---|---|---|---|---|
Kim et al. [21] | 30 | 36.67 | 41.24 | 0.36 |
Kang et al. [12] | 30 | 27.41 | 38.41 | 0.049 |
Micek et al. [33] | IHM | 17.83 | 30.67 | 0.018 |
Scarsi et al. [22] | IHM | 16.07 | 13.60 | 0.48 |
Marschall et al. [36] | IHM | 14.03 | 13.92 | 1.0 |
Shorr et al. [37] | IHM | 11.94 | 19.64 | 0.15 |
Rodríguez-Baño et al. [38] | 30 | 18.18 | 24.24 | 0.3 |
Ammerlaan et al. [39] | 30 | 25.00 | 21.27 | NS |
Erbay et al. [19] | 30 | 39.53 | 65.00 | 0.011 |
Kumar et al. [40] | IHM | 48.00 | 89.70 | <0.0001 |
Tseng et al. [41] | IHM | 35.44 | 50.00 | OR 2.17 (1.4-3.38) 0.001 |
Micek et al. [42] | IHM | 36.40 | 51.68 | <0.001 |
Paul et al. [43] | 30 | 33.33 | 49.12 | 0.001 |
Joung et al. [44] | 30 | 22.45 | 49.25 | <0.0001 |
Suppli et al. [46] | 30 | 20.55 | 40.00 | 0.009 |
Reisfeld et al. [47] | 30 | 33.48 | 46.36 | OR 1.4 (0.86-2.29) (NS) |
Wilke et al. [48] | IHM | 14.02 | 26.32 | 0.021 |
Lye et al. [50] | IHM | 19.16 | 26.19 | OR 0.67 (0.46-0.96) 0.03 |
Labelle et al. [54] | IHM | 51.38 | 68.30 | <0.001 |
Frakking et al. [56] | 30 | 18.82 | 20.41 | NS |
Tumbarello et al. [57] | IHM | 24.07 | 64.29 | <0.001 |
Reference
|
Time of mortality assessment
|
AAT mortality rate
|
IAAT mortality rate
|
Significant differences
|
---|---|---|---|---|
Luna et al., 2006 [34] | 28 days | 29.17 | 63.46 | 0.007 |
Chen et al., 2013 [55] | 28 days | 9.09 | 38.04 | 0.001 |
Tseng et al., 2012 [51] | 60 days | 28.17 | 55.43 | 0.023 |
Kim et al., 2006 [8] | 12 weeks | 28.10 | 38.46 | NS |
LOS and costs
Discussion
Conclusions
Key messages
-
The definitions of IAAT varied. Nevertheless, almost every definition included the element ‘matching with the in vitro susceptibility’ or ‘intermediate or full in vitro resistance’.
-
This systematic review demonstrates a very high incidence of empiric IAAT in patients with severe infection, such as BSI, pneumonia, sepsis, or septic shock.
-
Meta-analysis provides evidence that empiric IAAT increases 30-day and in-hospital mortality in patients with a severe infection.
-
Clinicians should be aware of this problem, and further improvement actions should be taken. Further computerized decision support needs to be developed.