208. Exposure-response relationship of ceftazidime/avibactam in adults with central nervous system infections caused by carbapenem-resistant <i>Klebsiella pneumoniae:</i> a prospective observational study

Abstract Background Central nervous system (CNS) infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) poses significant challenges for clinicians in ICU. Achieving optimal drug exposure in the cerebrospinal fluid (CSF) is crucial for good outcomes. This study aimed to evaluate the exposure-response relationship of ceftazidime/avibactam (CZA) in plasma and CSF. Methods All patients received CZA (2.5 g), IV infusion (over 2 hours), q8h. At steady-state after the fourth dose of CZA, the concentrations of CZA in the plasma and CSF were determined by ultra-performance liquid chromatography (UPLC) at 1, 2, 2.25, 2.5, 3, 4, 6, and 8 h post-dose. The PK/PD index of ceftazidime (CAZ) and avibactam(AVI) was calculated for each patient. Demographic, clinical efficacy, microbiological eradication, and 28-day mortality were reviewed. Blood and CSF samples were collected for calculation of PK parameters by non-compartmental pharmacokinetics (PK) modeling. The attainment of CAZ and AVI PK/PD targets in plasma and CSF was calculated to assess the exposure-response relationship of CZA and the corresponding clinical efficacy rate and bacterial eradication rate. Results CAZ and AVI demonstrated good penetration into CSF, evidenced by median CSF/plasma AUCtau ratio of 43.8 % and 55.8 %, respectively. CZA 2.5 g q8h achieved CAZ PK/PD target of 50%fT &amp;gt;MIC in both plasma and 50%T &amp;gt;MIC in CSF of all patients and reached AVI PK/PD target of 50%T &amp;gt;CT=1 mg/L in CSF of 80% (16/20) of patients. The dosing regimen also achieved CAZ PK/PD target of 100% fT &amp;gt;4MIC in plasma of 9 patients and 100% T &amp;gt;4MIC in CSF of 14 patients. At the end of the treatment, the overall clinical and microbiological efficacy rates were 80.0% and 100%, respectively. Only one case of CZA-related adverse event (Clostridioides difficile-associated diarrhoea) was reported. Conclusion The good CSF penetration of CZA enables the dosing regimen of CZA 2.5 g q8h a promising treatment option for CNS infections caused by CRKP. Disclosures Nanyang Li, Master of Medicine, TenNor Therapeutics (Suzhou) Ltd: Investigator Jing Zhang, Doctor of Medicine, TenNor Therapeutics (Suzhou) Ltd: Investigator