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.