Analysis based on Monte Carlo simulation: How effective is tigecycline in routine antimicrobial therapy?

OBJECTIVE

This paper aims to assess the efficacy of tigecycline in the treatment of several different infections from a pharmacokinetic/pharmacodynamic (PK/PD) perspective.

MATERIALS AND METHODS

The minimum inhibitory concentration (MIC) test strip test was used to determine the MICs of clinical isolates of tigecycline. A 5,000-subjects simulation was performed by Crystal Ball software to calculate the probability of achieving the required PK/PD exposure.

RESULTS

The use of standard tigecycline dosing is predicted to have a good clinical outcome for patients suffering from complicated skin and skin structure infection (cSSSI) with MICs ≤ 0.25 mg×L, patients suffering from complicated intra-abdominal infection (cIAI) with MICs ≤ 1 mg×L, and patients suffering from hospital-acquired pneumonia (HAP) with MICs ≤ 0.5 mg×L. Generally, Gram-positive bacteria are highly sensitive to tigecycline, while Gram-negative bacteria are less sensitive: for patients with HAP and cIAI, the tolerable outcome was achieved using the standard regimen for most Gram-negative pathogens; the desired outcomes could be obtained for the increased-dose treatment; with increasing dose (100 mg every 12 hours), the average cumulative fractions of response (CFRs) markedly increased from 38.18 to 56.21% for cSSSI patients. When tigecycline, a standard regimen, was used to treat carbapenem-resistant (CRKP) and carbapenem-resistant . (CRE) infections, the cumulative response scores were 4.96 - 66.39% and 13.14 - 95.18%, respectively, and the CFRs of the increased dose also increased correspondingly.

CONCLUSION

Currently, the standard dose of tigecycline is feasible in the treatment of common bacterial infections, and PK/PD indexes are needed to optimize the regimens for refractory carbapenem-resistant bacterial infections.