PI-06. Successful use of hydroxymethylquinoxalindexide in complex antimicrobial therapy treating patients with Gram-negative fulminant infectious complications during induced hematopoesis aplasia

Summary

Systemic infectinos caused by polyresistant gram-negative micro-organisms are a pressing issue in treatment polychemotherapy (PCT) and hematopoietic stem cell transplants (HSCT) recipients as their clinical course is often fulminant and they are highly lethal in patients with aplasia. One of antimicrobial treatment strategies is the systematic use of 0.5% hydroxymethylquinoxalixide (dioxidine) solution as a part of complex antibacterial therapy in patients with severe infectious complications. The drug has bactericidal properties and is characterized by a wide spectrum of antibacterial activity. Our aim was to demonstrate feasibility of systematic use of hydroxymethyloxalinyxide (0.5% dioxide solution) in patients with resistant infections caused by Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter cloacae, Stenotrophomonas maltophilia, and Achromobacter xylosoxidans developing during chemotherapy-induced aplasia.

Materials and methods

In the Department of Bone Marrow Transplantation and Department of Hematology and Chemotherapy №1 (Russian Children’s Clinical Hospital of N. I. Pirogov Russian National Medical Research University), 18 patients with verified Gram-negative infection were administered 0.5% hydroxymethylquinoxalidioxide solution as part of combination antimicrobial therapy. The average age of patients was 6.9 years (6 months to 16 years). Pathogen verification and microbiological control of the infection process were carried out using blood, bronchoalveolar lavage, and wound drainage cultures, as well as swabs from mucous cavities and feces. All cancer patients have obtained a remission at the time of the study. The children had at least one site of verified Gram-negative infection, which progressed in spite of antibacterial therapy combination employed.

Results

In 11 patients was reported bacteriemia, in 4 cases associated with Ps. aeruginosa, and in 5 patients with Kl. pneumoniae, one with E. cloacae, one with S.maltophilia. Damage to oral mucosa associated with P. aeruginosa have been reported in 7 patients. In 2 cases, the infection was complicated by deep necrosis, in one patient K.pneumoniae culture was obtained. Five patients had ulcerative necrotic damage of perineum, in 3 cases caused by P. aeruginosa. In 2 patients, K. pneumoniae was found. Enterocolitis with K. pneumoniae colonization has been reported in 6 patients. In other cases the revealed pathogens were: P. aeruginosa (in 1 patient), A. xylosoxidans (in 1 patient), S. maltophilia (in 1 patient). Gram-negative infection lesions (P. aeruginosa, K. pneumoniae, S. maltophilia) in subcutaneous fat were observed in 6 patients. Pleuro-pneumonia associated with P. aeruginosa has been diagnosed in 4 patients. In one child, there were also multiple abscesses in the liver, spleen, pancreas, kidneys, lymph nodes detected by CT-scans. One patient had infection of soft tissues in the area of the ventricular bypass with inflammatory changes of the brain membranes caused by P. Aeruginosa. All the patients received 0.5% dioxin solution injection based on medical commission decision. The 0.5% solution of hydroxymethyloxalinide oxide was used at a daily dose <10 mg/kg. The dose was divided into 2-3 injections. Prior to application the 0.5% solution as diluted to 0.1-0.2% by sterile saline. The average treatment duration was 17.9 days (5-67 days). The hydroxymethylquinoxalidixide therapy allowed obtaining complete control of fulminant polyresistant Gram-negative infections in all patients. The pathogen eradication was in all cases confirmed by microbiological study. The drug remained effective throughout all treatment period, no cases of newly formed resistance were observed. In our study, none of the patients showed side effects.

Conclusion

Based on experience presented, the 0.5% dioxidine solution can be used as a reserved treatment in young immunocomputed patients as it is effective in most severe forms of infections of different localizations caused by polyresistant strains of gram-negative microorganisms. The timely prescription of dioxidine can significantly reduce infections mortality in children with progressive resistant Gram-negative infections.

Keywords

Sepsis, hydroxymethylquinoxalinoxide (dioxidine), Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter cloacae, Stenotrophomonas maltophilia, children.