High-dose, extended-interval colistin administration in critically ill patients: is this the right dosing strategy? A preliminary study

Lidia Dalfino, Filomena Puntillo, Adriana Mosca, Rosa Monno, Maria Luigia Spada, Sara Coppolecchia, Giuseppe Miragliotta, Francesco Bruno, Nicola Brienza, Lidia Dalfino, Filomena Puntillo, Adriana Mosca, Rosa Monno, Maria Luigia Spada, Sara Coppolecchia, Giuseppe Miragliotta, Francesco Bruno, Nicola Brienza

Abstract

Background: Gram-negative bacteria susceptible only to colistin (COS) are emerging causes of severe nosocomial infections, reviving interest in the use of colistin. However, consensus on the most effective way to administer colistin has not yet been reached.

Methods: All patients who had sepsis due to COS gram-negative bacteria or minimally susceptible gram-negative bacteria and received intravenous colistimethate sodium (CMS) were prospectively enrolled. The CMS dosing schedule was based on a loading dose of 9 MU and a 9-MU twice-daily fractioned maintenance dose, titrated on renal function. For each CMS course, clinical cure, bacteriological clearance, daily serum creatinine clearance, and estimated creatinine clearance were recorded.

Results: Twenty-eight infectious episodes due to Acinetobacter baumannii (46.4%), Klebsiella pneumoniae (46.4%), and Pseudomonas aeruginosa (7.2%) were analyzed. The main types of infection were bloodstream infection (64.3%) and ventilator-associated pneumonia (35.7%). Clinical cure was observed in 23 cases (82.1%). Acute kidney injury developed during 5 treatment courses (17.8%), did not require renal replacement therapy, and subsided within 10 days from CMS discontinuation. No correlation was found between variation in serum creatinine level (from baseline to peak) and daily and cumulative doses of CMS, and between variation in serum creatinine level (from baseline to peak) and duration of CMS treatment.

Conclusions: Our study shows that in severe infections due to COS gram-negative bacteria, the high-dose, extended-interval CMS regimen has a high efficacy, without significant renal toxicity.

Figures

Figure 1.
Figure 1.
Estimated median creatinine clearance values on the first day of colistin treatment (baseline), at the lowest value reached (worst), on discontinuation of colistimethate sodium (CMS) treatment (stop CMS), and at the end of follow-up (final), in patients without (white box plots) and those with (gray box plots) acute kidney injury (AKI). *P < .05 versus baseline. Abbreviations: AKI, acute kidney ijury; CMS, colistimethate sodium.
Figure 2.
Figure 2.
Correlation between serum creatinine variation (from baseline to peak values) and daily colistimethate sodium doses (A) and between serum creatinine variation (from baseline to peak values) and treatment duration (B). Abbreviation: CMS, colistimethate sodium.

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