Pharmacokinetics of colistin in critically ill patients with multidrug-resistant Gram-negative bacilli infection

Authors:
  • SJSonali P. Jadhav
    Sonali P. Jadhav
  • PKPrashant P. Kadam
    Prashant P. Kadam
  • RNRaghu K. Naidu
    Raghu K. Naidu
  • RNRahul D. Namjoshi
    Rahul D. Namjoshi
  • VGVishal Gupta
    Vishal Gupta
  • MGMangesh S. Gore
    Mangesh S. Gore
  • PSPallavi V. Surase
    Pallavi V. Surase
  • PMPreeti R. Mehta
    Preeti R. Mehta
  • JGJaideep A. Gogtay
    Jaideep A. Gogtay
  • UTUrmila M. Thatte
    Urmila M. Thatte
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Abstract
Colistin, which had not been used widely because of nephrotoxicity and neurotoxicity, has gained clinical importance in recent times due to the resurgence of multidrug-resistant Gram-negative bacilli. Very few studies, especially pharmacokinetic studies, have been performed with intravenous colistimethate sodium, and none in India. The aim of our study was to study the single-dose and steady-state pharmacokinetics of colistin in patients with multidrug-resistant Gram-negative bacilli infections. This was a prospective open-label pharmacokinetic study done in an intensive care unit in a tertiary care hospital on 15 critically ill patients with proven multidrug-resistant Gram-negative bacilli infection. Colistimethate sodium was injected as intermittent intravenous infusions in accordance with the recommendations on the package insert. For patients weighing ≥ 60 kg with a normal renal function or with a creatinine clearance (CL(CR)) of between 20 and 50 ml/min, the drug was administered at 2 million international units (MIU) every 8 h; for those with a CL(CR) of 10-20 ml/min, the dose was 2 MIU every 12 h. Those patients who weighed 8 was achieved in seven of nine patients after the single dose and in seven of eight patients at steady-state. For those patients whose cultures grew Pseudomonas spp, only one patient after the single dose and one patient at steady-state achieved a C(max)/MIC ratio of >8. A significant association was noted between dose and survival, and a trend was observed with patients weighing ≤ 60 kg (who received 50,000 IU/kg/day instead of 6 MIU/day for those >60 kg) having an increased mortality. The pharmacokinetic parameters of colistin were comparable to those reported in previous studies in critically ill patients. However, the recommended dose may be inadequate to maintain the C(max)/MIC ratio to an optimal level-at least in patients infected with Pseudomonas spp. The dose recommendation should be based only on creatinine clearance and not body weight.

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