Daptomycin plus trimethoprim/sulfamethoxazole combination therapy in post-neurosurgical meningitis caused by linezolid-resistant Staphylococcus epidermidis

Diagn Microbiol Infect Dis. 2013 May;76(1):99-102. doi: 10.1016/j.diagmicrobio.2013.01.021. Epub 2013 Feb 26.

Abstract

Post-neurosurgical infection is a serious complication that occurs in approx. 4% of all patients undergoing neurosurgical procedures and is associated with high morbidity and mortality rates and prolonged length of intensive care unit (ICU) stay. Coagulase-negative staphylococci (CoNS), especially methicillin-resistant Staphylococcus epidermidis (MRSE), are the most frequent pathogens involved in CNS post-neurosurgical meningitis. Treatment is challenging especially in patients with meningitis due to multidrug- resistant (MDR) CONS. Herein, we report a unique case of post-neurosurgical meningitis due to MRSE resistant to linezolid (a molecular analysis revealed the presence of the mutation G2576T on domain V of the 23S rRNA gene) and with reduced susceptibility to glycopeptides, successfully treated with a combination of daptomycin at 10 mg/kg daily plus trimethoprim/sulfamethoxazole (TMP/SMX). This antibiotic combination showed an indifferent interaction in in vitro studies. Daptomycin serum and cerebrospinal fluid (CSF) concentrations, determined through blood and CSF samples drawn just prior to and 4 h after the third dose, were 18.9-0.78 and 51.65-3.1 mg/L, respectively. These values allowed us to approximate a 5-6% penetration rate of the drug through an inflamed blood-brain barrier. In conclusion, although further studies are needed, combination of high-dose daptomycin plus TMP/SMX is a reasonable option for treatment of meningitis caused by multidrug-resistant S. epidermidis.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / therapeutic use*
  • Anti-Bacterial Agents / therapeutic use
  • Blood-Brain Barrier / drug effects
  • Daptomycin / blood
  • Daptomycin / cerebrospinal fluid
  • Daptomycin / therapeutic use*
  • Female
  • Glycopeptides / therapeutic use
  • Humans
  • Linezolid
  • Meningitis / drug therapy*
  • Meningitis / surgery
  • Methicillin Resistance / drug effects
  • Microbial Sensitivity Tests
  • Middle Aged
  • Oxazolidinones / therapeutic use*
  • Prosthesis-Related Infections / microbiology*
  • Staphylococcus epidermidis / drug effects*
  • Staphylococcus epidermidis / isolation & purification
  • Treatment Outcome
  • Trimethoprim, Sulfamethoxazole Drug Combination / blood
  • Trimethoprim, Sulfamethoxazole Drug Combination / cerebrospinal fluid
  • Trimethoprim, Sulfamethoxazole Drug Combination / therapeutic use*

Substances

  • Acetamides
  • Anti-Bacterial Agents
  • Glycopeptides
  • Oxazolidinones
  • Trimethoprim, Sulfamethoxazole Drug Combination
  • Linezolid
  • Daptomycin