Understanding the Activity of Antibiotics in Cerebrospinal Fluid in vitro

Abstract

Background: In vitro studies suggest that antimicrobial activity of antibiotics meant to treat central nervous system infections such as meningitis or ventriculitis may be altered by cerebrospinal fluid (CSF). This could explain the reason behind the often observed discrepancies between the activity of antibiotics determined in artificial growth media in vitro, and their sometimes reduced clinical efficacy in CSF in vivo. If conducted in CSF, in vitro microbiological investigations might predict the ability of antibiotic drugs to treat CSF infections better than experiments in artificial growth media. In addition, they are less expensive, critical and time consuming than animal studies, and might potentially be appreciated in drug development as a rapid and cost-effective means to gain valuable information on drugs meant to treat infections residing in CSF. Summary: Data from microbiological in vitro experiments performed in CSF were compiled for fosfomycin, rifampicin, cefepime, cefotaxime, ceftriaxone, ciprofloxacin, gentamicin and vancomycin. Where possible, correlations between in vitro data and evidence from in vivo studies were established. Key Messages: As discussed in the text, no clear correlations between in vitro studies in CSF and clinical outcomes could be identified. Methodological recommendations derived from the collected studies are summarized in order to optimize future research on the topic.

Cdk8 and Ssn801 Regulate Oxidative Stress Resistance and Virulence in Cryptococcus neoformans

“…To test this, we performed in vitro growth curves in artificial CSF but found no difference between growth of cdk8 and control strains (Fig. 9B) (30).…”

“…For all studies, cryptococcal strains were grown overnight in YPD medium (1% [wt/vol] Bacto yeast extract, 2% [wt/vol] d -glucose, 2% [wt/vol] Bacto Peptone in ddH 2 O) at 30°C in room air with shaking at 230 rpm. For growth curves, cells were sedimented at 1,000 × g (25°C, 3 min), washed with phosphate-buffered saline (PBS), and adjusted to 1 × 10 5 cells/ml before growth at 30°C in room air in YPD or at 37°C, 5% CO 2 in DMEM, RPMI, or sterile artificial cerebrospinal fluid (ACSF) (124 mM NaCl, 2.5 mM KCl, 2 mM MgSO 4 , 1.25 mM KH 2 PO 4 , 26 mM NaHCO 3 , 10 mM d -glucose, 4 mM sucrose, 2.5 mM CaCl 2 , 360 mg/liter sterile BSA, 100 mM creatinine, 6 mM urea) (30). Cell counts were measured at the indicated time points, and growth curves were performed twice.…”

Review on Usage of Vancomycin in Livestock and Humans: Maintaining Its Efficacy, Prevention of Resistance and Alternative Therapy

“…Furthermore, it has been shown in a rabbit model that a high concentration of vancomycin is present in the cerebral spinal fluid of inflamed meninges [ 20 ]. Therapeutic concentrations of vancomycin in ascitic, pericardial, pleural, and synovial fluids are greater than 2.5 mg/L in humans [ 21 ].…”

Use of Supplemented or Human Material to Simulate PD Behavior of Antibiotics at the Target Site In Vitro

“…Cerebrospinal fluid (CSF) might also act as an important environment for antibiotic activity, especially in the treatment of central nervous infections, such as meningitis or ventriculitis. Concerns over equality of the antibiotic activity in vitro and its clinical efficacy have been discussed in the review by Matzneller et al [ 11 ]. Indeed, one study showed that rifampicin concentrations above the MIC were required to achieve bacterial killing of S. aureus in CSF (with CO 2 ) compared to pure MHB.…”