Efficacy Assessment of High Dose Colistin against Carbapenem-Resistant Gram-Negative Bacteria (CR-GNB) in Critically Ill Patients: A Retrospective Non-Inferiority Trial
Basheer Abdel Rahman, Ahmed F. Mady, Noor Monther Ali, Abdulrahman Alharthy, Waleed Tharwat, Shahzad Ahmad, Rehab Eltreafi, Anas Mady, Arwa Alotaibi, Sajedah Almarzooq, Ali Omrani, Alyaa Elhazmi, Saad M Altamimi
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ABSTRACT
Background: Colistin is an effective
treatment option, recommended for carbapenem resistant gram-negative bacilli
(CR-GNB) in critically ill patients. Due to high nephrotoxicity, dose
management of Colistin is a tough decision to make. At standard dosage the
efficacy of Colistin is not well defined. Consequently, strategies involving
higher dosages were suggested.
Objective:
To evaluate the high dose of Colistin as non-inferior to standard dose in the
treatment of CR-GNB in critically ill patients.
Study
Design: Retrospective comparative study
Place and
Duration of Study: Intensive Care Unit, King Saud
Medical City Riyadh, Saudi Arabia from 1st January 2015 to 31st
December 2017.
Methodology: One hundred and ninety two
patients that met the inclusion criteria from all participants were further
divided into two groups. Group H (High dose) given the high dose of Colistin (9
million units intravenously (IV) loading dose, and then 9 million units/day in
2 or three divided doses) whereas group S was administered with standard dose
(no loading dose, 6 million units/day). The primary endpoint of the study was
the assessment of nephrotoxicity after the start of Colistin and secondary
endpoints were the mortality within 14 days of commencing Colistin along with
clinical effects and microbial clearance upon completion of treatment.
Results: The results of the study
established the non-inferiority of high dose of Colistin for the renal safety
and also showed significant improvement in microbial clearance and length of
ICU stay as compared to the standard dose. The other secondary end points such
as mortality (p = 0.99), length of hospital stay (p = 0.39), and global
improvement (p value of 0.06) revealed no significant difference between the
two groups.
Conclusion: The high dose of Colistin for
the treatment of carbapenem resistance gram negative bacilli (CR-GNB) was as
safe as the standard dose for renal safety. But we also found that it also
accelerates microbial clearance and reduces the time spent in the intensive
care unit.
Key words: Colistin, Colestimethate sodium,
Gram negative bacteraemia, Sepsis, Multi-drug resistant organisms, Acute kidney
injury