Cureus · 2026
Higher Loading Dose of Colistin for the Treatment of Ventilator-Associated Pneumonia in Critically Ill Children: A Retrospective Comparative Study at Queen Rania Abdullah Hospital for Children.
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Shweiyat Shadi H, Banikhaled Nasser, Haddadin Yacoub M, Alhajaj Hala, Alsaryrah Shaden, Abulannaz Amjed, Hjazeen Anees, Aldwan Adnan
Аннотация
BACKGROUND: Ventilator-associated pneumonia (VAP) remains a significant cause of morbidity and mortality in pediatric intensive care units (PICUs), particularly when caused by multidrug-resistant (MDR) Gram-negative organisms. Colistin has re-emerged as a last-line antibiotic for these infections; however, optimal dosing strategies remain inadequately studied in children.
OBJECTIVE: This retrospective study evaluates the association between a higher loading dose of colistin (9 mg/kg colistin base activity (CBA)) compared to the standard loading dose (5 mg/kg CBA) and clinical outcomes in children with VAP caused by carbapenem-resistant organisms.
METHODS: A retrospective comparative study was conducted at the PICU, Queen Rania Abdullah Hospital for Children, Royal Medical Services, Amman, Jordan, covering a three-year period from January 2023 to January 2026. Medical records of 80 children aged one month to 14 years with confirmed VAP caused by colistin-susceptible MDR Gram-negative organisms were reviewed. Patients were categorized according to colistin loading dose into group A, which received a standard loading dose of 5 mg/kg CBA (n = 40), and group B, which received a higher loading dose of 9 mg/kg CBA (n = 40). Both groups received a maintenance dose of 2.5 mg/kg CBA every 12 hours.
RESULTS: Among 80 children (mean age = 4.8 ± 3.6 years, range = 1 month to 12 years; 45/80 (56.3%) male), the higher loading dose group demonstrated significantly higher microbiological eradication at day 7 (33/40 (82.5%) vs. 24/40 (60.0%), p = 0.028). The clinical cure rate was also higher in the higher dose group (31/40 (77.5%) vs. 22/40 (55.0%), p = 0.034). Median time to clinical response was shorter in the higher dose group (4 vs. 6 days, p = 0.018). Colistin trough levels on day 2 were significantly higher in the higher dose group (2.8 ± 0.9 vs. 1.6 ± 0.6 µg/mL, p < 0.001), with a higher proportion achieving therapeutic levels (≥2 µg/mL) (29/40 (72.5%) vs. 14/40 (35.0%), p = 0.001). Duration of mechanical ventilation was shorter in the higher dose group (median = 12 vs. 16 days, p = 0.042). PICU length of stay was also reduced (median = 18 vs. 24 days, p = 0.038). Nephrotoxicity incidence was similar between groups (9/40 (22.5%) vs. 7/40 (17.5%), p = 0.58). In multivariate analysis, a higher loading dose was independently associated with microbiological eradication (adjusted odds ratio (aOR) = 3.24, 95% CI: 1.28-8.20, p = 0.013) and clinical cure (aOR = 2.86, 95% CI: 1.12-7.30, p = 0.028).
CONCLUSIONS: A higher loading dose of colistin (9 mg/kg CBA) in children with VAP caused by carbapenem-resistant organisms was associated with improved microbiological eradication, faster clinical response, and shorter duration of mechanical ventilation and PICU stay, while nephrotoxicity did not differ significantly between groups. These findings are hypothesis-generating and require confirmation in larger, prospective, preferably multicenter randomized studies.
OBJECTIVE: This retrospective study evaluates the association between a higher loading dose of colistin (9 mg/kg colistin base activity (CBA)) compared to the standard loading dose (5 mg/kg CBA) and clinical outcomes in children with VAP caused by carbapenem-resistant organisms.
METHODS: A retrospective comparative study was conducted at the PICU, Queen Rania Abdullah Hospital for Children, Royal Medical Services, Amman, Jordan, covering a three-year period from January 2023 to January 2026. Medical records of 80 children aged one month to 14 years with confirmed VAP caused by colistin-susceptible MDR Gram-negative organisms were reviewed. Patients were categorized according to colistin loading dose into group A, which received a standard loading dose of 5 mg/kg CBA (n = 40), and group B, which received a higher loading dose of 9 mg/kg CBA (n = 40). Both groups received a maintenance dose of 2.5 mg/kg CBA every 12 hours.
RESULTS: Among 80 children (mean age = 4.8 ± 3.6 years, range = 1 month to 12 years; 45/80 (56.3%) male), the higher loading dose group demonstrated significantly higher microbiological eradication at day 7 (33/40 (82.5%) vs. 24/40 (60.0%), p = 0.028). The clinical cure rate was also higher in the higher dose group (31/40 (77.5%) vs. 22/40 (55.0%), p = 0.034). Median time to clinical response was shorter in the higher dose group (4 vs. 6 days, p = 0.018). Colistin trough levels on day 2 were significantly higher in the higher dose group (2.8 ± 0.9 vs. 1.6 ± 0.6 µg/mL, p < 0.001), with a higher proportion achieving therapeutic levels (≥2 µg/mL) (29/40 (72.5%) vs. 14/40 (35.0%), p = 0.001). Duration of mechanical ventilation was shorter in the higher dose group (median = 12 vs. 16 days, p = 0.042). PICU length of stay was also reduced (median = 18 vs. 24 days, p = 0.038). Nephrotoxicity incidence was similar between groups (9/40 (22.5%) vs. 7/40 (17.5%), p = 0.58). In multivariate analysis, a higher loading dose was independently associated with microbiological eradication (adjusted odds ratio (aOR) = 3.24, 95% CI: 1.28-8.20, p = 0.013) and clinical cure (aOR = 2.86, 95% CI: 1.12-7.30, p = 0.028).
CONCLUSIONS: A higher loading dose of colistin (9 mg/kg CBA) in children with VAP caused by carbapenem-resistant organisms was associated with improved microbiological eradication, faster clinical response, and shorter duration of mechanical ventilation and PICU stay, while nephrotoxicity did not differ significantly between groups. These findings are hypothesis-generating and require confirmation in larger, prospective, preferably multicenter randomized studies.