title: Daptomycin plus trimethoprim/sulfamethoxazole combination therapy in post-neurosurgical meningitis caused by linezolid-resistant Staphylococcus epidermidis.
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.
authors: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
authors: Antonio
authors: A
authors: Vena
authors: Marco
authors: M
authors: Falcone
authors: Emma
authors: E
authors: Comandini
authors: Marcello
authors: M
authors: Meledandri
authors: Andrea
authors: A
authors: Novelli
authors: Floriana
authors: F
authors: Campanile
authors: Stefania
authors: S
authors: Stefani
authors: Mario
authors: M
authors: Venditti
mesh_terms: D000081:Acetamides / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000187:drug effects; D017576:Daptomycin / Q000097:blood / Q000134:cerebrospinal fluid / Q000627:therapeutic use*; D005260:Female; D006020:Glycopeptides / Q000627:therapeutic use; D006801:Humans; D000069349:Linezolid; D008581:Meningitis / Q000188:drug therapy* / Q000601:surgery; D016106:Methicillin Resistance / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D023303:Oxazolidinones / Q000627:therapeutic use*; D016459:Prosthesis-Related Infections / Q000382:microbiology*; D013212:Staphylococcus epidermidis / Q000187:drug effects* / Q000302:isolation & purification; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000097:blood / Q000134:cerebrospinal fluid / Q000627:therapeutic use*
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D023303:Oxazolidinones; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D000069349:Linezolid; D017576:Daptomycin