Research on the use and side effects of the antibacterial medication colistin

Colistin is a kidney-damaging (nephrotoxic) antibacterial agent. It is currently used in several countries, including Latvia, for critically ill patients due to the spread of multidrug-resistant Gram-negative (Gr-) bacterial infections. Unfortunately, there are currently limited alternatives treating these severe infections. Therefore, special attention should be paid to the proper use of available agents, which includes correct dosing, to minimise the potential development of colistin resistance.

Pretrunīgi ieteikumi par kolistīna devas lielumu dažādos avotos, it īpaši pacientiem ar pavājināto nieru funkcionālo stāvokli, un kolistīna terapeitiskā zāļu monitoringa nepieejamība padara šo situāciju īpaši izaicinošu.

Data on colistin use in the Mediterranean region, the USA, and countries in Asia are available, but there has been no data on its use in the Baltic states so far.

Information on risk factors for colistin nephrotoxicity remains controversial. The aim of this study was to explore the practice of colistin use and nephrotoxicity risk factors at one of the largest hospitals in Latvia.

The study collected data on patients who received colistin for the treatment of multidrug-resistant Gr-bacterial infections for at least 72 hours. Patients were grouped according to their renal functional status at the time of initiation and during the colistin therapy and during the treatment. Patients who developed acute kidney injury (AKI) due to colistin use were compared with patients without AKI.

A total of 117 episodes of colistin use were analysed. Colistin is most commonly prescribed for the treatment of pneumonia caused by Acinetobacter baumannii. The most common duration of colistin therapy was 11 days. The generally recommended dosing regimen for colistin is a loading dose (first dose, which is usually higher than the maintenance dose in order to reach drug concentrations more quickly) equal to 9 million units (MU), followed by a daily dose of 9 MU divided into 2-3 administrations. Most patients received the recommended loading dose of 9 MU (63.2%), while the remaining patients received a reduced loading dose, e.g. 6 MU, or therapy started immediately with the maintenance dose to maintain the drug's concentration in the blood. Patients with impaired kidney function were most likely to miss the standard loading dose (17 out of 26 cases or 65%) compared to other groups (p = 0.013). The choice of maintenance dose was also related to the patient's renal functional status. Colistin dosing was consistent with recommended doses in 62% (1047/1697) of all days of colistin therapy. Potential overdose was most frequently observed in patients with moderate renal function (GFR 30-59 ml/min) when receiving the standard colistin dose of 9 MU per day instead of a reduced dose. In contrast, the lower colistin dose was present in almost all renal function status groups.

AKI was observed in 24 of 87 cases (27.6%) during colistin therapy (serum creatinine increases at least 1.5 times). Patients often received at least one potentially nephrotoxic drug simultaneously with colistin (69 out of 87 cases or 79%), which was torasemide, a non-steroidal anti-inflammatory drug or vancomycin. No association was found between the use of these agents and the risk of nephrotoxicity of colistin. After analysing potential risk factors for colistin-associated AKI, it was found that the loading dose of 9 MU increased the risk of AKI (OR = 4.31, p = 0.029), but considering the wide 95% confidence interval (1.16–16.0), this risk could be lower.

Aleksandra Bule will defend her doctoral thesis “Colistin Use Pattern and Nephrotoxicity in Critically Ill Patients with Carbapenem-Resistant Gram-Negative Bacterial Infections” on 21 December 2023. Read more

RSU dissertation database