Bulletin of the World Health Organization

Antibiotics in severely malnourished children: systematic review of efficacy, safety and pharmacokinetics

Marzia Lazzerini & David Tickell

Volume 89, Number 8, August 2011, 594-607

Table 4. Pharmacokinetics of second-line parenteral antibiotics in children with severe acute malnutrition

Reference Drug, dose (per kg), route No. of children Cmax (μg/ml) and Tmax (min)
Vd (l/kg)
Clearance (ml/kg/h)
Half life (min)
AUC (μg.min/ml)
Malnourished Eutrophic Malnourished Eutrophic Malnourished Eutrophic Malnourished Eutrophic Malnourished Eutrophic
Bolme et al. 199530 Benzylpenicillin, 30 mg, IV 29 U: 1.47
K: 1.18
M: 0.91
MK: 0.93
1.39 CL U: 15.1*
CL K: 16.9*
CL M: 14.0*
CL MK: 11.6*
CL 22.2 U: 67.8
K: 44.8
M: 44.8
MK: 55.7
43.4 U: 1993.3
K: 1 769.2
M: 2 138.2
MK: 2 594.4
1351.3
Procaine penicillin G, 30 mg, IM 18 Tmax same in all groups (30–60 min) M: 139.1
MK: 264.9
177.4 Same in all groups (no values given)
Bolme et al. 198032 Benzylpenicillin, 50 000 IU, IV 16 K Cmax at 2 h: 3.1
M Cmax at 2 h: 4.1
MK Cmax at 2 h: 10.2
N Cmax at 2 h: 1.4** Trend to slower CL in malnourished
Benzylpenicillin, 16 000 IU, IM 13 Tmax < 30 m all groups
Cmax > 10 μg all groups
Trend to slower CL in malnourished
Buchanan et al. 197935 Penicillin G, 25 000 IU, IV 8 Day 0: 1.6
Day 21: 1.4
D0: 183*
D21: 286*
D0: 57*
D21: 32*
Seaton et al. 200736 Gentamicin, 7.5 mg, IM 34 100% > 8.0 μg/ml at 2 hour
76% > 12.0 μg/ml at 2 hour
0.67 CL 1.67a
Trough level: 98% < 1.0 mg/l at 20 ha
84
Samotra et al. 198537 Gentamicin, 4.0 mg, IM 10 Cmax 8.9 at 30 min Cmax 10.02 at 30 min 373 199 22.40 22.32
Khan et al. 200638 Gentamicin, 5.0 mg, IM 310 od: Cmax 11.7 at 60 min*
tds: Cmax 4.7 at 60 min*
Trough level at 24 h:
od: 0.29 mg/l*
tds: 0.48 mg/l
Bravo et al. 198239 Gentamicin, 3.5 mg, IV 18 Cmax 6.31 at 29.67 min* Cmax 8.39 at 24 min 0.46* 0.39 CL 3.99 CL 3.57 82 75 No difference (no values given)
Buchanan et al. 197940 Gentamicin, 2.4 mg, IV 6 D0: 3.9
D21: 4.36*
D0: CL 13.6 ml/kg
D21: CL 28.7 ml/kg*
D0: 229
D21: 179*

AUC, area under the plasma concentration time curve; CL, clearance; Cmax, maximum concentration; D0, day 0 (admission); D21, day 21 (recovery); IM, intramuscular; IU, international units; IV, intravenous; K, kwashiorkor; M, marasmus; MK, marasmic kwashiorkor; N, normal (controls); od, once daily dosing; tds, three times daily dosing; Tmax, time to maximum concentration; U, underweight; Vd, volume of distribution.* P < 0.05; **P-value not specified.

a One child who was in shock had a trough level of 5.5 μg/ml; longer clearance was noted in children with hypothermia, high serum creatinine or large base excess.