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 pharmacokinctic/phannacodynamic (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. R_e z sults: 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 mgxL(-1), patients suffering from complicated intra-abdominal infection (cIAI) with MICs <= 1 mgxL(-1), and patients suffering from hospital-acquired pneumonia (HAP) with MICs 0.5 mgxL(-1). 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 Gramnegative pathogens; the desired outcomes could be obtained for the increased-dose treatment; with increasing dose (100 mg every 12 hours), the average cumlative 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 Klebsiella pneumoniae (CRKP) and carbapenemresistant Entembacter spp. (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.What is known about this subject- The use of standard tigecycline dosing is predicted to have a good clinical outcome for cSSSI patients with MICs <= 0.25 mgxL(-1), cIAI patients with MICs <= 0.5 mgxL(-1), and HAP patients with MICs <= 1 mgxL(-1)- Gram-positive bacteria are highly sensitive to tigecycline, while Gram-negative bacteria are less sensitive: their mean level of susceptibility to tigecycline is 77.3% (except Proteus mirabilis and Pseudomonas aeruginosa).- This may also warn that resistance of CRKP to tigecycline is worrying: for patients with cIAI and cSSSI, doses of 50 mg and 100 mg every 12 hours (q12h) did not achieve desirable results. In comparison, the prediction results for CRE infection are slightly improved: the dosing simulations confirmed that the current treatment, 50 mg q12h, was considered sufficient to treat HAP caused byCRE in cIAI patients. 100 mg q12h is recommended in clinical settings; however, for cSSSI treatment, combination regimen or other options for target elimination may be suggested.What this study adds- This article simulates the efficacy of different doses of tigecycline in the treatment of different infection sites from the PK/PD perspective and focuses on the sensitivity of common pathogens and CRE. Furthermore, current controversies about the dosage of tigecycline are partly explained in this article. We believe that the results of this study can provide guidance for the efficient use of tigecycline in clinical practice.