Efficacy and Safety of Colistin in the Treatment of Infections Caused by Multidrug-resistant Pseudomonas aeruginosa in Patients with Hematologic Malignancy: A Matched Pair Analysis

Abstract

Objective A rise in infections with multidrug-resistant Pseudomonas aeruginosa (MDR-PA) is a significant contributor to increased morbidity and mortality of patients with hematologic malignancies. The aim of this study was to determine the efficacy and safety of colistin (colistimethate sodium) in the treatment of serious infections caused by MDR-PA in these patients. Patients and Methods A matched pair analysis of renal function, toxicities, and outcome of 26 patients receiving colistin and control subjects was done. All patients had clinical signs of sepsis; P. aeruginosa was isolated from blood in 69% of patients in colistin group and 84% in control group. Patients treated with colistin received 3 million units every 8 hours for a median duration of 13 days. Additionally, patients received at least two additional antimicrobial or antifungal drugs. Results Resolution of infection was achieved in twenty patients (76.9%) receiving colistin and in 17 (65.4%) control subjects. Mortality rate was 11% in both groups. There was no statistically significant difference in the level of serum creatinine, creatinine clearance, or potassium levels before and after treatment between groups. Only one patient receiving colistin developed de novo renal failure and one displayed transient neurologic toxicity. Conclusion Our results suggest that in patients with hematologic malignancies, colistin is effective in treating severe infections caused by MDR-PA while maintaining an acceptable toxicity profile. Prospective randomized studies comparing efficacy and safety of colistin with those of other antipseudomonal drugs are needed.

Targeted therapy against multi-resistant bacteria in leukemic and hematopoietic stem cell transplant recipients: guidelines of the 4th European Conference on Infections in Leukemia (ECIL-4, 2011)

“…5 The other study compared 26 patients (84% bacteremic) receiving colistin to 26 patients receiving antipseudomonal β−lactams and found similar rates of resolution of infection (77% vs. 65%) and mortality (11% in both groups). 61 Nephrotoxicity, which was reported in up to 50% of patients receiving colistin/polymyxin B in older studies, is much less frequent in newer studies, with rates ranging from 10-30%. 44 In the two Pseudomonas studies just cited, no significantly increased nephrotoxicity occurred in patients treated with colistin, as compared with other agents (including aminoglycosides), although one patient treated with colistin suffered from seizures.…”

“…3 Two retrospective analyses that included patients with (mainly hematological) malignancies who were treated with colistin for MDR P. aeruginosa infections obtained differing results. 5,61 In one study, 31-colistin-treated patients (45% with bacteremia, 55% with pneumonia) were compared to those (n= 64) treated with a non-colistin (β-lactam or quinolone) regimen. The colistin regimen achieved a higher rate of clinical response in multiple logistic regression analysis (P=0.026; odds ratio 2.9 (1.5, 7.6), whereas microbiological response (48% vs. 41%) and infection-related death rates (26% vs. 17%) were similar.…”

“…44 In the two Pseudomonas studies just cited, no significantly increased nephrotoxicity occurred in patients treated with colistin, as compared with other agents (including aminoglycosides), although one patient treated with colistin suffered from seizures. 5,61 Among another 38 colistin treatment courses in adults and children with hematological malignancy or HSCT, nephrotoxicity developed in only 11%. 62 The use of a 9-million-unit loading dose and high daily dosages (4.5 million units twice daily) of colistin 47 may help to overcome the problem of low blood levels that may have been responsible for the suboptimal efficacy of polymyxins in some studies, leading to increased mortality, as well as to the selection of resistant strain variants.…”

The prevention and management of infections due to multidrug resistant organisms in haematology patients

“…Despite renal toxicity (0-50%), it has been found to be safe in neutropenic patients. [104][105][106] and is recommended for treatment of carbapenemresistant Enterobacteriaceae and P. aeruginosa [102]. Successful treatment of MDR Pseudomonas has been demonstrated in bacteraemic haematology patients, predominately in conjunction with a beta-lactam agent.…”

Caracterización molecular de Pseudomonas aeruginosa resistentes a carbapenémicos provenientes de cuatro hospitales de Venezuela

“…Estudios previos refieren que colistina presenta una potente actividad frente a cepas de P. aeruginosa multiresistentes, por lo que ha surgido como una alternativa terapéutica para las infecciones causadas por este microorganismo 18,[20][21][22] . Sin embargo, se ha reportado resistencia a colistina en algunos aislados [23][24][25] .…”