TABLE 1.
Summary of polymyxin B-associated nephrotoxicity literature included in the pharmacometric nephrotoxicity meta-analysisa
| Author (yr) (reference) | No. of subjects receiving PMBb | Institution PMB dosing recommendations (mg/kg/day) | Daily PMB dose (mg/day) | Wt (kg) | Nephrotoxicity definition | % nephrotoxicity incidence (no. of patients affected/total no.) |
|---|---|---|---|---|---|---|
| Ouderkirk et al. (2003) (32) | 50 | 1.5–2.5 | Mean, 110 | NA | 2-fold ↑ in SCr to ≥2 mg/dl | 14 (7/50) |
| Holloway et al. (2006) (33) | 31 | NA | Median, 130 | NA | 1.5-fold ↑ in SCr, ↑ in SCr of ≥0.5 mg/dl, or 50% reduction in CLCR | 22.5 (7/31) |
| Teng et al. (2007) (21) | 27 | NA | Mean, 62.9 | NA | 1.5-fold ↑ in SCr, ↑ in SCr of ≥0.5 mg/dl, or 50% reduction in CLCR | 18.5 (5/27) |
| Pastewski et al. (2008) (20) | 11 | 1.5–2, 1.25 if CLCR is 30–80 ml/min, 0.5 if CLCR is <30 ml/min | Mean, 84 | NA | ↑ in SCr of ≥0.5 mg/dl or 50% reduction in CLCR | 54.5 (6/11) |
| Ramasubban et al. (2008) (34) | 45 | 1.5–2 | Mean, 120 | NA | ↑ in SCr by 0.5 mg/dl | 8.89 (4/45) |
| Mendes et al. (2009) (35) | 114 | NA | Mean, 96.7 | NA | If baseline SCr is <1.5 mg/dl, SCr ↑ to ≥1.8; if baseline SCr is >1.5 and <4, 1.5-fold ↑in SCr | 21.9 (25/114) |
| Oliveira et al. (2009) (36) | 30 | NA | Median, 100 | NA | 2-fold ↑ in SCr or ↑ in SCr of ≥1 mg/dl if initial SCr is >1.4 mg/dl | 27 (8/30) |
| Elias et al. (2010) (19) | 235 | NA | Median, 150 | NA | Mild, 50–100% ↑ in SCr; moderate, ≥100% ↑ in SCr but no dialysis; severe, need for dialysis | Mild, 13.6; moderate, 26.4; severe, 21.9 |
| Kvitko et al. (2011) (37) | 45 | NA | Mean, 141 | NA | Stage 1, 1.5- to 2-fold ↑ in SCr; stage 2, ≥2-fold ↑ in SCr | Stage 1, 11 (4/45); stage 2, 24 (11/45) |
| Esaian et al. (2012) (38) | 115 | 1.5–2.5, adjust for renal dysfunction | Median, 100 | Median, 69 | Meeting any of the RIFLE criteria | Risk, 48 (55/115), injury, 31 (36/115); failure, 17 (19/115) |
| Kubin et al. (2012) (39) | 73 | 2.5–3, 1–1.5 if CLCR is <80 ml/min | Median, 180 | Median, 76.4 | Meeting any of the RIFLE criteria | Risk, 27.4 (20/73); injury or failure, 20 (24/73) |
| Tuon et al. (2013) (9) | 96 | NA | Median, 200 | NA | Stage 1, 1.5- to 2-fold ↑ in SCr or SCr ↑ of 0.3 mg/dl; stage 2, 2- to 3-fold ↑ in SCr; stage 3, >3-fold ↑in SCr or SCr of ≥4 mg/dl with acute rise of ≥0.5 mg/dl | Stage 1, 11.5 (11/96); stage 2, 8.33 (8/96); stage 3, 1.04 (1/96) |
| Nandha et al. (2013) (40) | 32 | 1.5–2.5 | Mean, 111 | NA | Meeting any of the RIFLE criteria | Risk, 18.8 (6/32); injury, 15.6 (5/32); failure, 3.13 (1/32) |
| Akajagbor et al. (2013) (8) | 67 | 1.5–2 | Median, 123 | Median, 74 | Meeting any of the RIFLE criteria | Risk, 13.4 (9/67); injury, 19.4 (13/67); failure, 8.96 (6/67) |
| Phe et al. (2014) (10) | 104 | Mean, 104 | Mean, 72 | Meeting any of the RIFLE criteria | Risk, 4.8 (5/104); injury, 6.7 (7/104); failure, 11.5 (12/104) | |
| Rigatto et al. (2016) (11) | 410 | 1.5–3 | Median, 150 | Mean, 66 | Meeting any of the RIFLE criteria | Risk, 22.4 (92/410); injury, 9 (45/410); failure, 12.7 (52/410) |
| Crass et al. (2017) (41) | ||||||
| Non-cystic fibrosis patients | 49 | NA | Mean, 200.9 | Mean, 83 | Meeting any of the RIFLE criteria | Risk, 28.6 (14/49); injury, 12.2 (6/49); failure, 2.0 (1/49) |
| Cystic fibrosis patients | 29 | NA | Mean, 124.4 | Mean, 55 | Meeting any of the RIFLE Criteria | Risk, 24.1 (7/29); injury, 10.3 (3/29); failure, 0 (0/29) |
a
PMB, polymyxin B; CLCR, creatinine clearance (ml/min); SCr, serum creatinine (mg/dl); NA, not applicable; ↑, increase.
b
Patients receiving polymyxin B who were also evaluated for nephrotoxicity.