Colistin effective against nosocomial GNB infections in paediatric patients

Intravenous colistin therapy demonstrates acceptable efficacy in the treatment of nosocomial Gram-negative bacteria (GNB) infections in paediatric patients, reports a Thailand study.

In addition, the risk of clinical failure is higher in patients with at least two organ dysfunctions, those with septic shock, and those receiving chemotherapy or immunosuppressants.

“Nephrotoxicity should be extensively monitored and appropriately managed, especially in paediatric patients with hypoalbuminemia, using vasopressors, vancomycin, or amphotericin B,” the investigators said. [Pediatr Infed Dis J 2024;43:1054-1060]

Some 178 patients aged <18 years (median age 3.4 years) who received intravenous colistin between January 2014 and December 2018 were included in this retrospective study. The investigators reviewed clinical data and treatment outcomes, as well as assessed factors associated with treatment outcomes.

The mean dose of colistin given to patients without renal impairment was 5.1 mg/kg/day, and the clinical response rate in those receiving colistin for specific treatment was 70.8 percent. The rates of infection-related and crude mortality were 17.5 percent and 19.7 percent, respectively.

Additionally, the nephrotoxicity rate was 29.8 percent, and nearly 70 percent of episodes occurred between the third and seventh day of treatment.

Of note, the presence of two or more organ dysfunctions (adjusted hazard ratio [aHR], 7.17, 95 percent confidence interval [CI], 1.64‒31.40), septic shock (aHR, 2.69, 95 percent CI, 1.36‒5.32), and receiving chemotherapy/immunosuppressants (aHR, 2.68, 95 percent CI, 1.36‒5.25) predicted clinical failure.

Factors associated with nephrotoxicity were as follows: hypoalbuminemia (aHR, 2.93, 95 percent CI, 1.26‒6.78), receiving amphotericin B (aHR, 2.29, 95 percent CI, 1.16‒4.52), vancomycin (aHR, 3.36, 95 percent CI, 1.50‒7.56), and vasopressors (aHR, 2.57, 95 percent CI, 1.27‒5.21).

Paediatric studies

In paediatric studies, clinical responses ranged from 68.6 percent to 80.5 percent. Most patients had significant comorbidity and were admitted to a paediatric intensive care unit, diagnosed with pneumonia caused by A. baumanii and treated with colistin at about 5 CBA mg/kg/day. [J Infect Chemother 2018;24:370-375; Pediatr Infect Dis J 2014;33:e19-e24; Int J Antimicrob Agents 2012;40:140-144]

“In our study, A. baumannii was the most common pathogen (85.2 percent), and 65.4 percent of patients achieved a microbiologic response,” the investigators said. “Other paediatric studies, in which the major causative microorganism was A. baumannii, reported microbiological eradication rates ranging from 76.0 percent to 78.2 percent.” [Int J Antimicrob Agents 2012;40:140-144; Paediatr Drugs 2015;17:323-330]

The infection-related mortality rate of 17.5 percent was consistent with those seen in previous paediatric studies, which ranged from 11.5 percent to 26.3 percent. [Int J Antimicrob Agents 2012;40:140-144; Paediatr Drugs 2015;17:323-330]

The current study did not observe colistin-related neurotoxicity, which was described as seizures.  “The other neurotoxicity, that is, paresthesia, dizziness, muscle weakness, and confusion, is challenging to assess because sedative or neuromuscular blocking drugs can also cause the same neurotoxic effects,” the investigators said.

Earlier studies rarely reported neurotoxicity in paediatric patients receiving colistin, which ranged from 0 percent to 2.3 percent. [Int J Antimicrob Agents 2012;40:140-144]