Colistin monotherapy versus combination of colistin with a β-lactam or rifampicin for the treatment of serious infections in the ICU due to multidrug-resistant Gram-negative bacteria

Introduction

The resistance of Gram-negative strains in the ICU is a growing problem. Recent studies suggest in-vitro synergy of colistin with β-lactams and colistin with rifampicin against these strains. However, there is controversy on the efficacy of the drug provided either as monotherapy or in combination with these drugs in critically ill patients.

Aim

To determine the clinical and microbiological efficacy of intravenouscolistin as monotherapy or in combination with β-lactams or rifampicin.

Methods

Sixteen patients admitted to a medical ICU between March 2005 and December 2005 who grew multiple-resistant strains of Pseudomonas aeruginosa (three patients), Acinetobacter baumanii (eight patients), Klebsiella pneumoniae (one patient) or mixed organisms (four patients) were included in the study. Fourteen patients had ventilator-associated pneumonia, one abdominal sepsis and one catheter-related sepsis. These patients were allocated to treatment: with colistin monotherapy in a dose of 3 million units three times daily adjusted for creatinine clearance (group 1: six patients), with colistin in the same dose and β-lactams (group 2: eight patients), and with the combination of rifampicin (600 mg/day) with colistin (group 3: two patients). Follow-up cultures and clinical evaluation were performed 5 days after the initiation of treatment. Clinical success was defined as a lessening of the signs and symptoms of infection, while microbiologic success was defined as eradication of the pathogen in follow-up qualitive cultures or as a 2-log decrease in bacterial load in quantitive cultures (BAL). The outcome of patients (discharged from the ITU or died) was also determined.

Results

In group 1, three patients (50%) showed clinical improvement and three did not improve (50%). In group 2, four patients improved (50%) and four did not (50%). In group 3, one patient improved (50%) and one deteriorated (50%). Microbiological improvement occurred in two out of six (33.3%) in group 1, five out of seven (71.4%) in group 2 and one out of two (50%) in group 3. Favorable outcome (discharged to the ward) occurred in one patient out of six (16.6%) in group 1, two out of seven (28.5%) in group 2 and one out of two (50%) in group 3. There is no statistically significant difference in clinical, microbiological or final outcome between the groups (P > 0.05). Three patients (18.75%) had significant side-effects (two renal impairment and one thrombocytopenia).

Conclusion

Patients that received the combination of colistin with β-lactams and colistin with rifampicin had higher rates of microbiological response and better outcome than patients in the colistin monotherapy group. The difference is not statistically significant, which is probably due to the small number of patients, especially in the rifampicin group, and the study is continuing with the recruitment of more patients.