Clinical Cure of a Difficult-to-Treat Resistant Pseudomonas aeruginosa Ventriculitis Using Cefiderocol: A Case Report and Literature Review

Abstract

Ventriculitis are a complication of meningitis (community-acquired or nosocomial) or another central nervous system infections as brain abscess. They are associated to a different spectrum of microorganisms from resistant gram-negative bacilli to staphylococci that can lead serious illness with high mortality. Difficult-to-treat resistance Gram-negative bacilli may increase to 20% deaths respect susceptible isolates of the same bacteria. We present the first report of a clinical cured case of difficult-to-treat resistant Pseudomonas aeruginosa (DTR-P) ventriculitis in which cefiderocol penetration into the central nervous system (CNS) has been confirmed in blood and cerebrospinal fluid (CSF). Cefiderocol might be considered for difficult-to-treat CNS infections in view of the recent new cases published together our one.

Cefiderocol and Intraventricular Colistin for Ventriculitis due to an Extensively Drug-Resistant Pseudomonas Aeruginosa

“…Cefiderocol stands out as a new siderophore cephalosporin for the treatment of carbapenem-resistant gram-negative bacterial infections, including carbapenemase-resistant Enterobacterales and nonfermentative gram-negative bacilli such as Acinetobacter spp, Pseudomonas spp, and Stenotrophomonas spp. Cefiderocol enters using the bacteria's iron uptake system [11,12]. The European Medicines Agency has approved the administration of cefiderocol for patients with limited treatment options.…”

Extensively drug-resistant Pseudomonas aeruginosa panophthalmitis from contaminated artificial tears

“…The authors utilized a combination of cefiderocol and IV colistin due to the lack of data for blood-brain barrier penetration of cefiderocol. Based on levels drawn from CSF and serum samples, they noted that cefiderocol achieved 4% drug concentration in the CSF compared to the serum [15] . Other case reports describing the use of cefiderocol for ventriculitis have shown similar CSF to serum drug concentrations, albeit while using different dosing schemes [16] , [17] .…”

Pharmacokinetic/Pharmacodynamic Analysis of Continuous-Infusion Fosfomycin in Combination with Extended-Infusion Cefiderocol or Continuous-Infusion Ceftazidime-Avibactam in a Case Series of Difficult-to-Treat Resistant Pseudomonas aeruginosa Bloodstream Infections and/or Hospital-Acquired Pneumonia

“…Administration of fosfomycin by CI could be the best strategy for both maximizing PK/PD target attainment and preventing resistance emergence among MDR Gram-negative infections [ 17 , 18 , 19 ]. In this regard, we showed in a previous case of carbapenem-resistant PA ventriculitis treated with CI fosfomycin in combination with CI ceftazidime/avibactam that the penetration rate of fosfomycin into the CSF was as high as 50% and that attaining optimal joint PK/PD targets at the infection site was fundamental for granting microbiological eradication and clinical success [ 20 , 21 , 22 , 23 , 24 , 25 ].…”

“…A therapeutic drug monitoring (TDM)-guided personalized antimicrobial dosing with expert clinical pharmacological interpretation could represent a useful tool for promptly maximizing the attainment of optimal PK/PD targets in this challenging scenario. To this regard, different real-world studies recently highlighted the clinical relevance of a TDM-guided approach for personalized tailored therapy with novel BLs and/or BL/BLIc in deep-seated infections [ 20 , 21 , 22 , 23 , 24 , 25 ]. However, real-world data testing of the effectiveness of fosfomycin in combination with novel BLs or BL/BLIc in DTR-PA infections in relation to PK/PD target attainment is currently lacking [ 5 , 6 ].…”