1. Introduction
Multidrug-resistant acinetobacter baumannii (MDRAB) is an intractable pathogen which is intrinsically resistant to penicillins, cephalosporins, and fluoroquinolones. The treatment of MDRAB infection is a clinical challenge due to the limit of clinical antibacterial choices [1]. Nosocomial central nervous system infection (CNSI) due to drug-resistant strains had substantially increased over recent years. Owning to multiple drug-resistant and the poor drug penetration through the blood brain barrier (BBB), CNSI caused by MDRAB after neurosurgical procedure could result in longer hospitalization duration, serious neurologic dysfunction and even death[2, 3].
Tigecycline (TGC) is a novel glycyclcycline with broad-spectrum antibiotic activity against multiple pathogens, including Gram-positive pathogenic bacteria, Gram-negative bacteria, atypical pathogens and anaerobe. TGC also plays an important role in the treatment of multidrug-resistant strains infection including vancomycin-resistant enterococci, methicillin-resistant staphylo-cocci, and acinetobacter baumannii. Therefore, TGC is considered as a therapeutic option for MDRAB infection [4, 5]. TGC has been approved for the treatment of complicated skin and skin-structure infections, complicated intra-abdominal infections and community-acquired pneumonia because of the widely distribution in tissue after intravenous infusion[6]. And considering of high sensitivity to MDRABin vitro , TGC is also used for nosocomial pneumonia caused by MDRAB off-label [7].
Generally, the ability of TGC to penetrate through the BBB into cerebrospinal fluid (CSF) was quite weak based on the pharmacokinetic data acquired from health adults without intracranial infection[8]. Poor BBB permeability limits the use of TGC to treat CNSI caused by MDRAB. However, intracranial diseases such as cerebritis would facilitate the permeability of the BBB[9], and this might increase the CSF-to-serum ratio of TGC. To evaluate the CSF-to-serum ratio of TGC at steady-state when patients were diagnosed with CNSI is important for the treatment of MDRAB CNSI. Up to now, reports to evaluate the penetration of TGC into CSF of patients with CNSI was always based on single case[6, 10]. And some of the reports didn’t provide accurate data due to the insensitivity of methods. The lack of data on the ability of TGC to penetrate the BBB of patients with intracranial infection made controversy exist widely about using TGC to treat CNSI caused by MDRAB.
In this study, we established a sensitive, effective and rapid method to analyze TGC in CSF and serum. This method could quantify TGC in CSF or serum ranged from the concentration of 5 ng/mL to 2000 ng/mL in 2.5 min. Depending on this method, concentration of TGC at steady-state in serum and CSF from 12 patients with MDRAB CNSI was determined to evaluate the penetration ratio of TGC into CSF. Correlation of the concentration of TGC in CSF and serum from CNSI patients could be evaluated by quantification of the trough concentration of TGC at steady-state in serum and CSF.