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Colistin Dosing Regimens against Pseudomonas aeruginosa in Critically Ill Patients: An Application of Monte Carlo Simulation
| Content Provider | MDPI |
|---|---|
| Author | Nguyen, Van Montakantikul, Preecha Tragulpiankit, Pramote Houngsaitong, Jantana Shuib, Mohd |
| Copyright Year | 2021 |
| Description | Our aims are to assess various colistin dosing regimens against Pseudomonas aeruginosa (P. aeruginosa) infection in critically ill patients and to propose an appropriate regimen based on microbiological data. A Monte Carlo simulation was performed using the published colistin’s pharmacokinetic parameters of critically ill patients, the published pharmacodynamic target from a mouse thigh infection model, and the minimum inhibitory concentration (MIC) results from a Vietnamese hospital. The probability of target attainment (PTA) of 80% and cumulative fraction of response (CFR) of 90% were used to evaluate the efficacy of each regimen. Of 121 P. aeruginosa laboratory datasets, the carbapenem-resistant P. aeruginosa (CRPA) and the colistin-resistant P. aeruginosa rates were 29.8% and 0.8%, respectively. $MIC_{50,90}$ were both 0.5 mg/L. The simulated results showed that at MIC of 2 mg/L, most regimens could not reach the PTA target, particularly in patients with normal renal function (Creatinine clearance (CrCl) ≥ 80 mL/min). At MIC of 0.5 mg/L and 1 mg/L, current recommendations still worked well. On the basis of these results, aside from lung infection, our study recommends three regimens against P. aeruginosa infection at MIC of 0.5 mg/L, 1 mg/L, and 2 mg/L. In conclusion, higher total daily doses and fractionated colistin dosing regimens could be the strategy for difficult-to-acquire PTA cases, while a less aggressive dose might be appropriate for empirical treatment in settings with low $MIC_{50/90}$. |
| Starting Page | 595 |
| e-ISSN | 20796382 |
| DOI | 10.3390/antibiotics10050595 |
| Journal | Antibiotics |
| Issue Number | 5 |
| Volume Number | 10 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2021-05-17 |
| Access Restriction | Open |
| Subject Keyword | Antibiotics Pharmacology and Pharmacy Colistin Pseudomonas Aeruginosa Critically Ill Patients Pk/pd Monte Carlo Simulation |
| Content Type | Text |
| Resource Type | Article |
