Supplemental Table 1. Overview of the Organisms Isolated by Blood

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Supplemental Table 1. Overview of the organisms isolated by blood culture N of deaths in children with N of multidrug- multidrug- N of infections N of patients (% resistant resistant Organism (% of total) of total) N of deaths infections (%) infections Coagulase negative staphylococcus (CNS) 62 (15.0) 61 (18.9) 19 Staphylococcus aureus 61 (14.8) 60 (18.6) 9 8 (13.1) 0 Enterobacter cloacae 30 (7.3) 30 (7.3) 7 15 (50.0) 4 Escherichia coli 24 (5.8) 24 (7.4) 8 2 (8.3) 0 Pseudomonas aeruginosa 23 (5.6) 23 (7.1) 9 6 (26.1) 3 Streptococcus spp. 22 (5.3) 17 (5.3) 3 Klebsiella pneumoniae 20 (4.9) 20 (6.2) 8 5 (25.0) 3 Candida albicans 18 (4.4) 18 (5.6) 7 Enterococcus faecalis 17 (4.1) 17 (5.3) 7 Klebsiella oxytoca 13 (3.2) 13 (4.0) 3 2 (15.4) 1 Serratia spp. 10 (2.4) 10 (3.1) 1 2 (20.0) 0 Streptococcus pneumoniae 10 (2.4) 10 (3.1) 0 Other Candida spp. 10 (2.4) 9 (2.8) 3 Acinetobacter baumannii complex 8 (1.9) 8 (2.5) 2 6 1 Haemophilus influenzae (not type b) 7 (1.7) 7 (2.2) 1 Other Enterococcus spp. 6 (1.5) 6 (1.9) 3 2 1 Other Fungi 5 (1.2) 5 (1.5) 3 Alpha haemolytic Streptococcus 5 (1.2) 5 (1.5) 1 Beta haemolytic streptococcus 5 (1.2) 5 (1.5) 0 Neisseria spp. 5 (1.2) 5 (1.5) 0 Bacillus cereus 5 (1.2) 5 (1.5) 0 Other Enterobacter spp. 4 4 2 1 1 Pantoea spp. 4 4 1 2 1 Stenotrophomonas maltophilia 4 4 0 Burkholderia cepacia complex 3 3 2 Other Acinetobacter spp. 3 3 1 1 0 Gram positive bacilli 3 3 1 Lactobacillus spp. 3 3 1 Rothia dentocariosa 2 2 1 Stomatococcus mucilaginosus 2 2 1 Aspergillus spp. 1 1 1 Flavimonas oryzihabitans 1 1 1 Gram negative bacilli 1 1 1 Massilia spp. 1 1 1 Raoultella ornithinolytica 1 1 1 Wautersia paucula 1 1 1 Aeromonas sobria 1 1 0 Brevundimonas vesicularis 1 1 0 Citrobacter freundii 1 1 0 Clostridium perfringens 1 1 0 Dermabacter hominis 1 1 0 Granulicatella adiacens 1 1 0 Other haemophilus spp. 1 1 0 Kocuria rosea 1 1 0 Leuconostoc spp. 1 1 0 Proteus mirabilis 1 1 0 Other Pseudomonas spp. 1 1 0 Sphingomonas paucimobilis 1 1 0 Total BLCU results 412 52 Total patients 323 86 14

Supplemental Table 2. Overview of the organisms isolated by BAL N of deaths in children with N of multidrug- multidrug- N of infections N of patients (% resistant resistant Organism (% of total) of total) N of deaths infections (%) infections Staphylococcus aureus 247 (21.7) 240 (35.7) 28 10 (4.0) 2 Haemophilus influenzae (not type b) 141 (12.4) 139 (20.7) 7 Moraxella catarrhalis 112 (9.9) 108 (16.1) 8 Candida albicans 105 (9.2) 104 (15.5) 21 Pseudomonas aeruginosa 78 (6.9) 69 (10.3) 12 9 (11.5) 1 Enterobacter cloacae 65 (5.7) 64 (9.5) 13 16 (24.6) 1 Streptococcus pneumoniae 61 (5.4) 60 (8.9) 1 Escherichia coli 44 (3.9) 42 (6.3) 10 4 (9.1) 1 Klebsiella pneumoniae 38 (3.3) 38 (5.7) 8 5 (13.2) 3 Other Candida spp. 31 (2.7) 25 (3.7) 8 Acinetobacter baumanii complex 27 (2.4) 27 (4.0) 6 19 (70.4) 5 Klebsiella oxytoca 24 (2.1) 24 (3.6) 8 5 (20.8) 1 Stenotrophomonas maltophilia 22 (1.9) 22 (3.3) 5 2 (9.1) 1 Aspergillus spp. 19 (1.7) 19 (2.8) 5 Serratia spp. 17 (1.5) 16 (2.4) 3 Enterococcus faecalis 16 (1.4) 16 (2.4) 7 Other Haemophilus spp. 13 (1.1) 13 (1.9) 3 1(7.7) 0 Beta haemolytic Streptococcus 12 (1.1) 12 (1.8) 1 Other Enterobacter spp. 9 9 (1.3) 5 3 2 Gram negative bacilli 6 6 0 Proteus mirabilis 5 5 3 Burholderica cepacia complex 5 5 3 2 1 Other Streptococcus spp. 3 3 1 Aeromonas spp. 3 3 0 Other Fungi 3 3 0 Coagulase Negative Staphylococcus (CNS) 2 2 2 Chryseobacterium meningosepticum 2 2 1 1 1 Raoultella spp. 2 2 1 Other Acinetobacter spp. 2 2 1 2 1 Citrobacter spp. 2 2 0 1 0 Neisseria spp. 2 2 0 Achromobacter xylosoxidans 1 1 1 1 1 Chryseomonas indologenes 1 1 1 Elizabethkingia meningoseptica 1 1 1 1 1 Sphingomonas paucimobilis 1 1 1 1 1 Eikenella corrodens 1 1 0 Hafnia alvei 1 1 0 Pantoea spp. 1 1 0 Other Pseudomonas spp. 1 1 0 Ralstonia pickettii 1 1 0 Rhodococcus spp. 1 1 0 Total BAL results 1137 83 Total patients 672 100 18

Supplemental Table 3. Bacteraemia and pneumonia rates per 1000 admissions in PICU from 2002 to 2012. Total infection rate Gram negative Gram positive Fungal infection Year [95% CI] infection rate [95% CI] infection rate [95% CI] rate [95% CI] 2002 74.9 (61.6-90.1) 31.7 (23.1-42.3) 36.0 (26.9-47.2) 7.2 (3.5-13.2) 2003 87.5 (73.1-103.6) 43.4 (33.3-55.5) 30.4 (22.0-40.8) 13.7 (8.3-21.4) 2004 103.5 (88.3-120.2) 53.8 (42.8-66.6) 36.8 (27.7-47.7) 12.9 (7.8-20.1) 2005 99.9 (84.8-116.6) 50.6 (39.8-63.3) 41.5 (31.7-53.2) 7.7 (3.9-13.8) 2006 109.8 (94.3-127.0) 57.3 (46.0-70.5) 43.0 (33.2-54.7) 9.5 (5.2-16.0) 2007 113.0 (96.2-131.5) 61.1 (48.7-75.6) 41.8 (31.6-54.2) 10.1 (5.4-17.1) 2008 112.6 (95.3-131.9) 47.5 (36.2-61.2) 46.7 (35.5-60.2) 18.3 (11.5-27.6) 2009 117.8 (100.6-136.8) 65.2 (52.3-80.2) 33.0 (23.9-44.3) 19.6 (12.7-28.9) 2010 116.9 (100.2-135.2) 63.6 (51.2-78.0) 37.0 (27.6-48.5) 16.3 (10.2-24.5) 2011 69.1 (56.2-83.9) 41.9 (31.9-54.0) 18.4 (11.9-27.0) 8.8 (4.6-15.4) 2012 84.1 (70.0-99.9) 42.4 (32.4-54.3) 27.3 (19.4-37.3) 14.4 (8.8-22.1)

Supplemental Table 4. Multidrug-resistant infection rates per 1000 admissions in PICU from 2002 until 2012. Total multidrug-resistant ESBL producing infection rate Year infection rate (95% CI) (95% CI) 2002 7.2 (3.5-13.2) 6.5 (3.0-12.2) 2003 6.5 (3.0-12.3) 5.8 (2.5-11.7) 2004 9.5 (5.2-15.9) 8.8 (4.7-15.1) 2005 6.3 (2.9-12.0) 4.2 (1.6-9.2) 2006 6.1 (2.8-11.6) 4.1 (1.5-8.9) 2007 7.7 (3.7-14.2) 7.0 (3.2-13.2) 2008 9.2 (4.6-16.4) 5.0 (1.8-10.9) 2009 11.0 (6.0-18.4) 9.4 (4.9-16.4) 2010 16.3 (10.2-24.5) 14.8 (9.1-22.8) 2011 8.1 (4.0-14.4) 6.6 (3.0-12.5) 2012 7.2 (3.5-13.2) 6.5 (3.0-12.2)

Supplemental Table 5. Bacteraemia rates per 1000 admissions in PICU from 2002 to 2012 Total infection rate Gram negative Gram positive Fungal infection Year [95% CI] infection rate [95% CI] infection rate [95% CI] rate [95% CI] 2002 46.8 (36.3-59.3) 9.3 (5.0-16.0) 36.0 (26.9-47.2) 1.4 (0.2-5.2) 2003 47.0 (36.5-59.5) 11.6 (6.6-18.7) 34.0 (25.1-44.9) 1.4 (0.2-5.2) 2004 53.1 (42.2-65.8) 12.9 (7.8-20.1) 34.7 (26.0-45.4) 4.8 (1.9-9.8) 2005 54.1 (43.0-67.2) 14.8 (9.1-22.5) 38.0 (28.7-49.3) 1.4 (0.2-5.1) 2006 53.2 (42.3-66.0) 10.2 (5.7-16.8) 42.3 (32.6-53.9) 0.6 (0.0-3.8) 2007 48.8 (37.7-62.0) 8.5 (4.3-15.2) 39.5 (29.5-51.6) 0.8 (0.0-4.3) 2008 45.9 (34.7-59.3) 10.8 (5.8-18.5) 30.9 (21.8-42.3) 4.2 (1.4-9.7) 2009 52.6 (41.0-66.4) 8.6 (4.3-15.4) 40.8 (30.6-53.2) 3.1 (0.9-8.0) 2010 45.1 (34.7-57.6) 17.8 (11.4-26.3) 25.1 (17.5-35.0) 2.2 (0.4-6.5) 2011 37.5 (28.0-49.0) 9.6 (5.1-16.3) 26.5 (18.6-36.5) 1.5 (0.2-5.3) 2012 42.4 (32.4-54.3) 10.1 (5.5-16.8) 29.5 (21.2-39.7) 2.9 (0.8-7.3)

Supplemental Table 6. Pneumonia rates per 1000 admissions in PICU from 2002 to 2012 Total infection rate Gram negative Gram positive Fungal infection Year [95% CI] infection rate [95% CI] infection rate [95% CI] rate [95% CI] 2002 49.7 (38.9-62.5) 23.1 (15.8-32.4) 20.9 (14.0-29.9) 5.8 (2.5-11.3) 2003 59.3 (47.4-73.1) 33.3 (24.5-44.1) 13.7 (8.3-21.4) 12.3 (7.2-19.6) 2004 77.6 (64.4-92.5) 44.9 (34.9-56.8) 25.2 (17.8-34.6) 7.5 (3.7-13.4) 2005 76.7 (63.4-91.7) 42.2 (32.4-54.0) 28.1 (20.2-38.1) 6.3 (2.9-12.0) 2006 83.9 (70.2-99.3) 48.4 (38.0-60.7) 26.6 (19.0-36.2) 8.9 (4.7-15.1) 2007 92.1 (76.9-109.2) 55.7 (43.9-69.7) 26.3 (18.3-36.6) 10.1 (5.4-17.1) 2008 85.9 (70.7-103.2) 37.5 (27.5-49.9) 32.5 (23.2-44.2) 15.8 (9.6-24.6) 2009 97.4 (81.7-115.0) 58.1 (45.9-72.4) 22.0 (14.7-31.6) 17.3 (10.9-26.0) 2010 95.4 (80.3-112.3) 51.8 (40.6-65.0) 28.8 (20.6-39.2) 14.8 (9.1-22.8) 2011 50.0 (39.0-63.0) 33.1 (24.2-44.0) 9.6 (5.1-16.3) 7.4 (3.5-13.5) 2012 63.2 (51.0-77.3) 33.8 (24.9-44.6) 18.0 (11.7-26.4) 11.5 (6.6-18.6)