Intravenous colistin use for infections due to MDR Gram-negative bacilli in critically ill paediatric patients: a systematic review and meta-analysis

Abstract

Background Data are limited regarding the clinical effectiveness and safety of intravenous colistin for treatment of infections due to MDR Gram-negative bacilli (GNB) in paediatric ICUs (PICUs). Methods Systematic review of intravenous colistin use in critically ill paediatric patients with MDR-GNB infection in PubMed, Scopus and EMBASE (up to 31 January 2018). Results Out of 1181 citations, 7 studies were included on the use of intravenous colistin for 405 patients in PICUs. The majority of patients were diagnosed with lower respiratory tract infections, Acinetobacter baumannii being the predominant pathogen. Colistin dosages ranged between 2.6 and 18 mg/kg/day, with only one case reporting a loading dose. Emergence of colistin resistance during treatment was reported in two cases. Nephrotoxicity and neurotoxicity were reported in 6.1% and 0.5%, respectively, but concomitant medications and severe underlying illness limited our ability to definitively associate use of colistin with nephrotoxicity. Crude mortality was 29.5% (95% CI = 21.7%–38.1%), whereas infection-related mortality was 16.6% (95% CI = 12.2%–21.5%). Conclusions While the reported incidence of adverse events related to colistin was low, reported mortality rates for infections due to MDR-GNB in PICUs were notable. In addition to severity of disease and comorbidities, inadequate daily dosage and the absence of a loading dose may have contributed to mortality. As the use of colistin for treatment of MDR-GNB infections increases, it is imperative to understand whether optimal dosing of colistin in paediatric patients differs across different age groups. Thus, future studies to establish the pharmacokinetic properties of colistin in different paediatric settings are warranted.

Cryptococcal infection in HIV-infected patients with CD4+ T-cell counts under 100/μL diagnosed in a high-income country: a multicentre cohort study

“…In this study, meta-analyses showed that older age increases the risk of nephrotoxicity (OR 1.85 (95% CI 1.33e2.57)), and the rate of nephrotoxicity was found to be 50.6% (95% CI 38.2e62.9) in older adult patients (lower limit 51e65 years across studies). Consistent with our results, previous meta-analyses in paediatric and infant populations have shown low AKI rates during colistin therapy of 6.2% and 5.8% [259,260]. It should be noted that although very small numbers of studies in neonatal and paediatric patients were included in the secondary analysis, this was primarily because few studies in these populations used internationally recognized criteria for nephrotoxicity.…”

Effectiveness and Nephrotoxicity of Intravenous Polymyxin B in Carbapenem-Resistant Gram-Negative Bacterial Infections Among Chinese Children

“…A review and meta-analysis conducted by Falagas and his coworkers showed that the all-cause nephrotoxicity of 2994 adult patients (from 28 studies) treated with intravenous polymyxin B was 40.7% ( Falagas et al, 2021 ), and our study showed a lower incidence of AKI in children with polymyxin B than in adult patients at 27.3%, closer to the data reported by Siddiqui et al on children (21.4% incidence of nephrotoxicity) ( Siddiqui et al, 2014 ). However, a meta-analysis of the clinical data of 405 children treated with colistin showed that the incidence of nephrotoxicity in children treated with colistin was 6.1% ( Karageorgos et al, 2019 ), much lower than that in our study. This may be related to the different criteria used to determine nephrotoxicity in our study, as two of the studies on colistin ( Falagas et al, 2009 ; Kapoor et al, 2013 ) used an increase in creatinine greater than two times the baseline as a criterion for AKI, and our study used the maximum creatinine level during dosing to determine the occurrence of AKI (may amplify the potential nephrotoxicity of polymyxin B).…”

<p>Antimicrobial Resistance and Resistance Determinant Insights into Multi-Drug Resistant Gram-Negative Bacteria Isolates from Paediatric Patients in China</p>

“…The emergence of infectious diseases caused by multi-drug-resistant (MDR) pathogens is a major problem in the community, especially in children 1,2. MDR or extreme drug-resistant (XDR) GNB contributes to global infectious diseases in paediatric patients 3. Recent reports have shown that the rate of resistance in GNB increases periodically worldwide 4.…”