BOSTON – Despite limited data on the safety and efficacy of colistin in children, the polymyxin antimicrobial has been used increasingly in high-risk pediatric patients as salvage therapy for serious infections caused by multidrug-resistant gram-negative bacteria, according to Dr. Pia S. Pannaraj.
"The escalating impact of antimicrobial selective pressure in high-risk pediatric populations has limited the therapeutic options available for the treatment of multidrug-resistant [MDR] gram-negative bacilli, which in turn has led to renewed interest in colistin, despite the known nephrotoxic and neurotoxic risks," she reported at the annual meeting of the Infectious Diseases Society of America.
In a study designed to review risk factors for acquiring multidrug-resistant gram-negative bacteria requiring colistin treatment and the adverse effects of such treatment in pediatric patients, Dr. Pannaraj of Children’s Hospital Los Angeles and colleagues reviewed their experience with colistin in pediatric patients admitted to their hospital between Jan. 1, 2005, and Oct. 31, 2010. Based on pharmacy records for that period, 53 children were treated with intravenous or nebulized colistin for treatment or suppressive therapy of an infection caused by MDR bacteria. Of the 53 children, 14 received 18 courses of the drug and were included in the analysis, she said. For comparison, the investigators chose control patients from the medical records database who had matching underlying conditions and the similar dates of birth and admission dates to the colistin patients, she said.
Multidrug resistance was defined as resistance to at least three classes of antibiotics, Dr. Pannaraj said. The underlying conditions reported in the 14 study patients included cystic fibrosis in 8, non–cystic fibrosis chronic lung disease in 3, and malignancy in 1, she said, noting that "2 of the patients were previously healthy."
"Nephrotoxicity and neurotoxicity remain a concern with colistin use in children."
The investigators performed chi-square analysis and independent and paired t-tests to compare between-group differences for dichotomous and continuous variables. According to the analysis, the children with an MDR isolate requiring colistin had more hospital days during the previous calendar year, compared with their matched controls, at 101.0 days vs. 27.2 days, respectively, Dr. Pannaraj reported. Those with MDR isolates also received more types of antibiotic than did the matched controls (6.6 vs. 4.2) for longer durations (191.0 vs. 53.8 antibiotic days), she said. The percentage of children on daily antibiotic prophylaxis was similar in the colistin and control groups, at 55.6% and 58.3%, respectively.
Four gram-negative bacteria were isolated, including 16 Pseudomonas aeruginosa, 6 Acinetobacter baumannii, 3 Klebsiella pneumoniae, and 1 Alcaligenes species, with more than one pathogen isolated in seven of the children, Dr. Pannaraj said. The indications for treatment with colistin included pulmonary exacerbation in nine patients, wound infection in four patients, and bacteremia/sepsis in four patients. The mean colistin dosage was 5.9 mg/kg per day, divided into two or three daily doses. Mean treatment duration was 13.5 days for respiratory infection, 20.8 days for wound infection, and 18.0 days for bacteremia, she reported.
Creatinine levels doubled in two children, including one who had been receiving concomitant aminoglycoside. The patient on aminoglycoside stopped both antimicrobials, while the second patient completed her course uninterrupted, Dr. Pannaraj reported. Two of the children developed neurologic symptoms, including perioral tingling at a dose of 7.6 mg/kg per day in one and headache at a dose of 5.9 mg/kg per day in another; symptoms resolved after the drug course was completed.
Of 36 control patients, 5 developed adverse events attributable to antibiotics, including neutropenia, rash, diarrhea, and vaginal itch. "The percentage of adverse events was not significantly different between colistin and control patients, at 22.2% compared with 13.9%," Dr. Pannaraj said.
The findings underscore the effect of antimicrobial selective pressure in high-risk pediatric patients and suggest that "nephrotoxicity and neurotoxicity remain a concern with colistin use in children," Dr. Pannaraj said. "We need more studies on the dosing and safety of colistin to optimize it for the treatment of high-risk children."
Dr. Pannaraj had no financial conflicts of interest to disclose.