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Predictors of insufficient amikacin peak concentration in critically ill
patients receiving a 25mg/kg total body weight regimen
Etienne de Montmollin, MD1; Lila Bouadma, MD, PhD1; Nathalie Gault, MD2, 3, 4; Bruno Mourvillier, MD1;
Eric Mariotte, MD1; Sarah Chemam, MD1; Laurent Massias, PharmD5; Emmanuelle Papy, PharmD5;
Florence Tubach, MD, PhD2, 3, 4; Michel Wolff, MD1; Romain Sonneville, MD1
1 Service de Réanimation Médicale et des Maladies infectieuse, Hôpital Bichat–Claude-Bernard, Assistance
Publique–Hôpitaux de Paris, Université Paris Diderot, PRES Sorbonne Paris Cité, Paris, France
2 Département d'Epidémiologie et Recherche Clinique, Hôpital Bichat–Claude-Bernard, Assistance Publique–
Hôpitaux de Paris, 75018 Paris, France
3 INSERM CIC 1425-EC, UMR 1123 ECEVE, 75018 Paris, France
4 Université Paris Diderot, PRES Sorbonne Paris Cité, UMR 1123 ECEVE, 75018 Paris, France
5 Pharmacie, Hôpital Bichat-Claude Bernard, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot,
PRES Sorbonne Paris cité, Paris, France.

Table 1s: Microbiological characteristics of the 181 episodes of amikacin initiation
Variable
n (%) or median [IQR]
Reason for antibiotherapy initiation
Severe sepsis/Septic shock
111 (61.3)
Acute respiratory failure
33 (18.2)
Others
37 (20.4)
Site of infection (n=181)
Pulmonary
120 (66.3)
Intra-abdominal
10 (5.5)
Urinary tract
11 (6.1)
Primary blood stream infection
8 (4.4)
Mediastinal
2 (1.1)
Skin and soft tissue
5 (2.8)
Others
3 (1.7)
Identified pathogens (n=114)*
Gram positive cocci
23 (20.2)
Staphylococcus aureus
8
Enterococcus sp
12
Streptococcus sp
3
Enterobacteriacae
67 (58.8)
Escherichia coli
19
Klebsiella sp
12
Enterobacter sp
17
Proteus sp
6
Serratia sp
6
Citrobacter sp
4
Morganella sp
3
Non-fermentive gram-negative bacilli
35 (30.7)
Pseudomonas aeruginosa
28
Acinetobacter sp
4
Stenotrophomonas maltophilia
3
Other pathogens
12 (10.5)
Duration of antibiotic therapy (days)
8 [3 – 8]
Number of amikacin infusions
1 [1 – 1]
Treatment failure (n=116)
7 (6.0)
* Total is more than 100% since more than one pathogen could be identified for a single patient.
Abbreviations: IQR, interquartile range

Table 2s: Univariate analysis of predictive factors of amikacin Cmax<60mg/L
Variable
n (%) or median [IQR]
Cmax<60mg/L
n=60
Cmax≥60mg/L
n=121
p
Demographic data at ICU admission
Male gender
44 (73.3)
87 (71.9)
0.84
Age (years)
61.5 [49.8-67.3]
62 [51-72]
0.60
BMI (kg/m2)
22.8 [20.3-26.5]
25.1 [23.1-30.1]
0.02*
Inclusion period, by quarter
<0.001*
1st
30 (50)
24 (19.8)
2nd
11 (18.3)
31 (25.6)
3rd
6 (10)
28 (23.1)
4th
13 (21.7)
38 (31.4)
Type of patient
0.44
Medical
48 (80)
90 (74.4)
Scheduled surgery
5 (8.3)
8 (6.6)
Unscheduled surgery
7 (11.7)
23 (19)
Reason for admission
0.40
Severe sepsis/septic shock
17 (28.3)
29 (24)
Cardiogenic shock
13 (21.7)
16 (13.2)
Acute respiratory distress
18 (30)
37 (30.6)
Cardiac surgery
10 (16.7)
24 (19.8)
Cardiac arrest
1 (1.7)
5 (4.1)
Acute renal failure
0
5 (4.1)
Comorbidities†
Chronic heart failure
24 (40)
44 (36.4)
0.63
Diabetes
9 (15)
31 (25.6)
0.11
Cirrhosis
8 (13.3)
4 (3.3)
0.03*
Terminal renal failure
5 (8.3)
10 (8.3)
0.79
COPD
8 (13.3)
11 (9.1)
0.38
HIV positive
7 (11.7)
9 (7.4)
0.35
Ongoing cancer
7 (11.7)
8 (6.6)
0.38
Chronic health status (Knaus scale)
0.59
Normal health status
13 (21.7)
36 (29.8)
Mild limitation
28 (46.7)
51 (42.1)
Important limitation
19 (31.7)
33 (27.3)
Major restriction
0
1 (0.8)
SAPS II
52 [37-66.3]
51 [41-68]
0.58
*: p<0.1.
† Total is more than 100% since patients could have more than one comorbidity
Abbreviations: IQR, Interquartile range; BMI, Body Mass Index; COPD, Chronic Obstructive
Pulmonary Disease; SAPS, Simplified Acute Physiology Score.

Table 2s (continued): Univariate analysis of predictive factors of amikacin Cmax<60mg/L
Variable
n (%) or median [IQR]
Cmax<60mg/L
n=60
Cmax≥60mg/L
n=121
p
Data at inclusion
Time between ICU admission and Cmax (days)
3 [0.8-15]
5 [1-13]
0.59
SOFA score at inclusion ≥ 8
35 (58.3)
69 (57)
0.87
Need for catecholamine
44 (73.3)
75 (62)
0.13
ECMO
8 (13.3)
20 (16.5)
0.58
Glasgow score <15
23 (38.3)
52 (43)
0.55
Mechanical ventilation
51 (85)
99 (81.8)
0.59
PEEP (cmH2O)
6 [5-8]
6 [5-8]
0.71
Plateau pressure (cmH2O)
24 [21-28]
22 [19-28]
0.34
DIC
8 (13.3)
11 (9.1)
0.38
GFR (mL/min)
0 [0-35.6]
0 [0-36.4]
0.94
RIFLE
0.83
Normal renal function
18 (30)
37 (30.6)
Risk
9 (15)
14 (11.6)
Injury
10 (16.7)
14 (11.6)
Failure
17 (28.3)
41 (33.9)
Loss
2 (3.3)
3 (2.5)
End stage
4 (6.7)
12 (9.9)
Ascites
8 (13.3)
6 (5)
0.09*
Biology
PaO2/FiO2 ratio
215 [134-302]
228 [141-322]
0.60
Albuminemia (g/L)
18.7 [16.2-21.7]
20.2 [16-24.5]
0.57
Lactates (mmol/L)
1.7 [1-2.6]
1.8 [1.2-3.2]
0.78
Hemodilution parameters
24-hour fluid balance (mL)
550 [-450 – 2450]
-500 [-1600 – 650]
<0.01*
24-hour fluid intake (mL)
1550 [500 – 3060]
950 [75 – 2000]
0.03*
6-hour fluid balance (mL)
300 [0 – 1025]
200 [-220 – 1000]
0.53
6-hour fluid intake (mL)
675 [220 – 1100]
500 [0 – 1500]
0.45
24-hour hematocrit delta (%)
-1.74 [-5.9 – 1.1]
-1.6 [-6.3 – 1.8]
0.79
24-hour proteinemia delta (%)
-1.6 [-7.3 – 0.8]
-1.4[-5.6 – 1.7]
0.19
Reason for antibiotherapy initiation
0.23
Severe sepsis/Septic shock
42 (70)
69 (57)
Acute respiratory failure
8 (13.3)
25 (20.7)
Others
10 (16.7)
27 (22.3)
Site of infection
0.90
Lung
40 (66.7)
80 (66.7)
Digestive
4 (6.7)
6 (5)
Urinary tract
3 (5)
8 (6.6)
Primary bacteremia
2 (3.3)
6 (5)

Mediastinum
1 (1.7)
1 (0.8)
Skin and soft tissue
2 (3.3)
3 (2.5)
Others
8 (13.3)
17 (14)
*: p<0.1.
Abbreviations: IQR, Interquartile range; SOFA, Sequential Organ Failure Assessment; ECMO, Extra Corporeal
Membrane Oxygenation; DIC, Disseminated Intravascular Coagulation; GFR, Glomerular Filtration Rate.