Abstract
BackgroundThe widespread use of antibiotics has led to the emergence of multidrug-resistant (MDR) bacteria such as multidrug-resistant Acinetobacter baumannii (AB). Tigecycline (TGC), as the first glycylcycline antibiotic approved by FDA, is a broad-spectrum antibiotic which remains highly effective to treat AB infections.ObjectiveTo confirm the TGC treatment dosage and effectiveness to treat AB infections in the Chinese population by performing therapeutic drug monitoring (TDM).MethodsThis study was performed from October 2018 through March 2019 at the PLA General Hospital. A high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was validated and employed to determine the plasma concentrations of TGC in patients with infectious diseases. The minimum inhibitory concentration (MIC) of TGC to clinically isolated AB was determined by broth microdilution method, agar dilution method, and disk diffusion method. Moreover, a model of population pharmacokinetics/pharmacodynamics (PPK/PD) was constructed.ResultsA total of 186 plasma samples from 67 patients were detected by the validated HPLC-MS/MS method. The MIC values determined by the broth microdilution method were more sensitive and accurate than the other two methods. The microbial and clinical PK/PD breakpoints were reached when the maintenance dose of TGC was 100 mg.ConclusionOur study established a validated HPLC-MS/MS method to monitor the plasma concentrations of TGC. In view of the MIC range to AB isolates in our hospital and the PPK/PD modeling results, we recommend a relatively high dose of 100 mg q12h regimen to achieve the optimal clinical efficacy and antimicrobial response.
Highlights
The emergence of multidrug-resistant (MDR) or extensively drug-resistant (XDR) gram-negative bacteria has been increasing worldwide, especially in critically ill patients
Patients recruited were over 18 years old diagnosed with hospital-acquired pneumonia (HAP), complicated skin and skin structure infections (cSSSI), or cIAI and were treated with TGC
A total of 67 patients were enrolled in this study which consisted of 50 males and 17 females
Summary
The emergence of multidrug-resistant (MDR) or extensively drug-resistant (XDR) gram-negative bacteria has been increasing worldwide, especially in critically ill patients. Tigecycline (TGC), the first example of glycylcyclines, can block the protein synthesis of bacteria via binding with the 30S subunit of the ribosome It shows high in vitro activity against a broad spectrum of gram-positive and gram-negative bacteria, especially a variety of MDR pathogens (Boucher et al, 2000; Edlund and Nord, 2000). TGC has been approved by FDA for treating complicated skin and skin structure infections (cSSSI), intra-abdominal infections (cIAI), and communityacquired pneumonia (CAP) in patients over 18 years old (FDA, 2005) It is often prescribed off-label (over dose, over indications) for treating hospital-acquired pneumonia (HAP) caused by Acinetobacter spp. in China. Tigecycline (TGC), as the first glycylcycline antibiotic approved by FDA, is a broadspectrum antibiotic which remains highly effective to treat AB infections
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