Intrathecal Antibacterial and Antifungal Therapies

Abstract

SUMMARY Intrathecal administration of anti-infectives is indicated in central nervous system infections by multiresistant pathogens when drugs that can reach adequate cerebrospinal fluid (CSF) concentrations by systemic therapy are not available. Antibiotics that readily pass the blood-brain and blood-CSF barriers and/or that have low toxicity allowing an increase in the daily dosage should not be used for intrathecal therapy. Intrathecal therapy is accompanied by systemic treatment. Antibacterials indispensable for intrathecal therapy include aminoglycosides, colistin, daptomycin, tigecycline, and vancomycin. Limited experience suggests the utility of the antifungals amphotericin B and caspofungin. Intraventricular administration ensures distribution throughout the CSF compartment, whereas intralumbar dosing often fails to attain adequate antibiotic concentrations in the ventricles. The individual dose is determined by the estimated size of the CSF space and by the estimated clearance from CSF. For moderately lipophilic anti-infectives with a molecular weight above approximately 1,000 g/mol, as well as for hydrophilic drugs with a molecular weight above approximately 400 g/mol, one daily dose is normally adequate. The ventricular drain should be clamped for 15 to 120 min to facilitate the distribution of the anti-infective in the CSF space. Therapeutic drug monitoring of the trough levels is necessary only in cases of therapeutic failure.

Different influences on mitochondrial function, oxidative stress and cytotoxicity of antibiotics on primary human neuron and cell lines

“…SH‐SY5Y is the most commonly used model to study human neuron cells whereas PC12 and N27 are rat dopaminergic neural cell lines and CAD is a murine neuron cell line . The antibiotics used in our study are those that can penetrate blood brain barrier from six different classes: metronidazole (a nitroimidazole), tigecycline (a glycylcycline), azithromycin (a macrolide), clindamycin (a lincosamide), ampicillin (a β‐lactam) and sulfamethoxazole (a sulphonamide) . At clinically relevant concentrations, we found that metronidazole, tigecycline, clindamycin and azithromycin induced apoptosis of human primary neuron as assessed by flow cytometry of Annexin V (Figure A‐D).…”

Treatment options for K. pneumoniae, P. aeruginosa and A. baumannii co-resistant to carbapenems, aminoglycosides, polymyxins and tigecycline: an approach based on the mechanisms of resistance to carbapenems

“…For example, a case of meningitis by pandrug-resistant P. aeruginosa (with amikacin MIC 32 mg/L) was successfully treated with intraventricular amikacin [ 195 ]. PK/PD considerations for intrathecal administration of antibiotics are discussed in detail in a recent review [ 196 ]. Intravesical administration of antibiotics (e.g., colistin or aminoglycosides [ 197 , 198 ]) may also be an option for lower urinary tract infections, but clinical data against CAPT-resistant GNB are lacking.…”

Intrathecal tobramycin and pausing induction chemotherapy for pediatric acute lymphoblastic leukemia facilitate successful management of disseminated Pseudomonas aeruginosa infection and meningitis

“…7 Intrathecal and intraventricular antimicrobial therapy have been recommended by the Infectious Diseases Society of America in the treatment of adult health care-associated meningitis when the infection responds poorly to intravenous antibiotics, but evidence on intrathecal antimicrobial therapy in the pediatric population is scarce. 8,9 We present a case of pediatric standard-risk ALL with an unusually difficult P. aeruginosa infection, as well as a rationale for administering intrathecal antibiotics and pausing induction chemotherapy in the rare situation of an excellent day 15 minimal residual disease (MRD) response and persistent P. aeruginosa meningitis. Parental consent was obtained for the publication of this report.…”