Using Therapeutic Drug Monitoring to Treat KPC-Producing Klebsiella pneumoniae Central Nervous System Infection With Ceftazidime/Avibactam

Abstract

This report describes the treatment of KPC-3 producing multidrug-resistant (MDR) K. pneumoniae with CAZ-AVI in a patient who developed post-neurosurgical meningitis and bacteremia. Therapeutic drug monitoring (TDM) of CSF and blood samples demonstrated CAZ-AVI concentration levels 20-fold greater than the minimum inhibitory concentration (MIC) in the first 60 minutes post-infusion, providing evidence for its utility in treating KPC-KP CNS infections.

Intraventricular Plus Systemic Antibiotic Therapy for Treating Polymyxin-Resistant Klebsiella pneumoniae Ventriculitis: A Case Report

“…CAZ/AVI is a combination of the third-generation cephalosporin ceftazidime and the novel non-β-lactam β-lactamase inhibitor avibactam, which has been approved for treating adults with complicated urinary tract infections, complicated intra-abdominal infections, hospital-acquired pneumonia, and other infections caused by aerobic gram-negative organisms in patients with limited treatment options [ 16 ]. However, only 6 adult cases of CNS infections caused by MDR/XDR K. pneumoniae were effectively treated using CAZ/AVI [ 17–21 ]. One case was treated with intravenous CAZ/AVI alone, and 5 cases were treated with CAZ/AVI IV combined with another antibiotic for CNS infection, including ventricular injection or intravenous antibiotic ( Table 5 ).…”

Ceftazidime-avibactam for the Treatment of Multidrug-resistant Pseudomonas aeruginosa Central Nervous System Infection in Pediatric Patient: A Case Report

“…Up to our knowledge, only 7 published reports have described CNS infections including meningitis, ventriculitis and brain abscess treated with ceftazidime-avibactam. 8,[15][16][17][18][19][20] Carbapenem-resistant K. pneumoniae was the etiologic pathogen in 3 cases, 8,15,16 extensively drug-resistant P. aeruginosa in 2 cases, 17,18 both carbapenem-resistant K. pneumoniae and P. aeruginosa in one case, 19 and Burkholderia multivorans in one case. 20 Duration of treatment ranged between 14 and 110 days.…”

“…20 Duration of treatment ranged between 14 and 110 days. Ceftazidime-avibactam was given as monotherapy in 2 cases, 16,17 with intrathecal aminoglycoside in 3 cases, 8,15,19 with IV colistin in one case, 18 and with combination of levofloxacin, meropenem and sulfamethoxazole-trimethoprim in one case. 20 All cases achieved successful outcomes.…”

A guide to therapeutic drug monitoring of β‐lactam antibiotics

“…63,64 The above clinical scenarios certainly merit consideration of β-lactam TDM. Other populations to consider may include pediatrics, 65 obesity, 66,67 transplant recipients, 68 central nervous system (CNS) infections (which can be directly sampled as opposed to using serum levels as a surrogate marker), 69 and patients with known multidrug resistant organisms with few other treatment regimens who require the administration of higher doses of β-lactams than FDA approved to reach clinically therapeutic exposures. 64 Select case reports utilizing TDM of β-lactams in complex patients are summarized in Table 2.…”