Colistin Therapy, Survival and Renal Replacement Therapy in Burn Patients: A 10-Year Single-Center Cohort Study

Abstract

Purpose Colistin is still a therapeutic cornerstone against multidrug-resistant gram-negative bacteria (MDRGN), mostly when other antibiotics do not gain adequate activity on these strains. In the present study, we evaluated in a cohort of burn patients the relationship between colistin therapy, survival and requirement of renal replacement therapy (CRRT). Patients and Methods Retrospective study of 133 burn patients treated with iv colistimethate sodium (loading dose 9.0 × 10 6 IU, maintenance dose 4.5 × 10 6 IU BID) and 35 treated with other antibiotics for MDRGN infection including Acinetobacter baumannii , Pseudomonas aeruginosa , and Klebsiella pneumoniae between January 2008 and December 2017. Multivariate analysis with logistic regression was used to determine the effect of the predictors such as age, total body surface area (TBSA), third-degree burn areas, Revised Baux score, Charlson comorbidity score, length of stay, colistin dose and duration of treatment, mechanical ventilation, and need of CRRT on in-hospital mortality. To investigate the relationship between colistin and renal function, we focused on survivor patients as the completion of the therapeutic course of colistin represented the basic requirement to analyze its impact on the kidney. Results Out of 133 colistin- and 35 other antibiotics-treated patients, 83 (62.4%) and 31 (88.6%) survived, and 53 (39.8%) and 3 (9.7%) required CRRT, respectively. The severity of burns, as well as CRRT requirement and mortality, was significantly higher in colistin-treated patients than in other antibiotics-treated patients. Age and TBSA% were the significant predictors of mortality. Out of 83 colistin-treated survivors, 19 (22.9%) required CRRT (9 before and 10 after the start of colistin), and 64 (77.1%) had a normal renal function. No difference about the colistin dose and baseline characteristics, but the revised Baux score was found between the 9 patients requiring CRRT before the colistin course and the 10 patients after. Similarly, among the 64 patients not undergoing CRRT, no difference was found between the patients treated with the cumulative dose of colistin <99.0 × 10 6 IU (n = 33, median daily dose of 4.0 × 10 6 IU) and >99.0 × 10 6 IU (n = 31, median daily dose of 9.0 × 10 6 IU) about the baseline characteristics and the daily median plasma creatinine over 24 days of therapy. Conclusion Colistin therapy was associated with more severe burns, mortality, and CRRT requirement. A short course therapy, at appropriate cumulative dosage, can lead to clinical success without a significant association with severe renal impairment.

Epidemiology and Early Bacteriology of Extremely Severe Burns from an LPG Tanker Explosion in Eastern China

“…Despite its potential adverse effects on renal function, colistin continues to play a key role as salvage treatment in burn patients. Mariano et al [21] reported…”

“…Despite its potential adverse effects on renal function, colistin continues to play a key role as salvage treatment in burn patients. Mariano et al [ 21 ] reported that colistin therapy can lead to clinical success without a significant association with severe renal impairment.…”

Pharmacokinetics and Nephrotoxicity of Polymyxin MRX-8 in Rats: A Novel Agent against Resistant Gram-Negative Bacteria

“…One study in rats showed that polymyxin=-induced nephrotoxicity was related to the frequency of dosing [28]. A 10-year cohort study found that nephrotoxicity is related to the dose and the number of days of administration [29]. In this study, the drug exposure of MRX-8 was approximately 1.5-fold and 1.3-fold higher than PMB at the dose of 8 mg/kg, while MRX-8 showed lower nephrotoxicity than PMB at the same dose.…”

Emergence of Multidrug Resistant Microbial Species in the Bacterial Profile of Burn Wounds: A Cohort Study from Pak Italian Modern Burn Center, Multan

“…Usage of Colistin is frequently associated with Nephrotoxicity and incidence of CRRT during or after completion of the therapeutic course however there are several studies that support the safety of Colistin Therapy. 13 Moreover, combination therapy e.g., Carbapenem with Colistin or Amikacin is routinely used in clinical practice to broaden the antimicrobial spectrum and reduce the risk of initial inappropriate therapy, although its potential for antimicrobial synergy and delaying or preventing antimicrobial resistance remains a subject of constant scrutiny and progressive research. 14 In our clinical setting, the problem of MRD and XDR is a nuisance in treatment of major burns which overlaps with overcrowding of patients and extended hospital stay.…”