Ceftazidime therapeutic drug monitoring in patients with melioidosis
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Background
Most patients with melioidosis receive prolonged intravenous ceftazidime during the intensive phase of their antibiotic therapy. Contemporary guidelines use weight and renal function to guide dosing, but therapeutic drug monitoring (TDM) might enable further individualisation of therapy.
Objective
To examine the potential utility of ceftazidime TDM in the management of melioidosis.
Methods
We reviewed consecutive serum free ceftazidime concentrations in patients with culture-confirmed melioidosis at an Australian referral hospital. We documented the minimum inhibitory concentration (MIC) for ceftazidime of the patients’ Burkholderia pseudomallei isolates. We then recorded the patients’ ceftazidime dosing regimen, their serum free ceftazidime concentration and if any adverse drug reactions occurred during their treatment.
Results
Trough concentrations were measured in 31 patients receiving intermittent ceftazidime dosing, while random concentrations were measured in 91 patients receiving a continuous infusion. The median (range) trough concentration:MIC ratio was 37.7 (2.7-156.6) in those receiving intermittent dosing and 47.5 (8.1-181.5) in those receiving a continuous infusion. Serum ceftazidime concentrations correlated with neurotoxicity, which was documented in 5/31 (16%) receiving intermittent dosing and in 4/91 (4%) receiving a continuous infusion. Serum ceftazidime concentrations were also higher in individuals who died from their infection than in those who survived. There was no association between ceftazidime concentrations and subsequent disease recurrence.
Conclusion
Current dosing recommendations for the treatment of melioidosis achieve serum ceftazidime concentrations that greatly exceed the MIC of B. pseudomallei in this region of Australia. TDM-guided reductions in the ceftazidime dose and/or dosing frequency may mitigate the risk of ceftazidime toxicity.
