Ceftazidime-Avibactam for the Treatment of Post-Neurosurgical Meningitis Caused by a Klebsiella pneumoniae carbapenemase (KPC)-Producing Klebsiella pneumoniae

Abstract

Background. Infections of the central nervous system (CNS) caused by multidrug-resistant Gram-negative organisms are difficult to treat due to limited CNS penetration of antimicrobials, Treatment of such infections often requires intraventricular and systemic administration of antibiotics. Here, we describe a case of meningitis caused by a KPC-producing K. pneumoniae successfully treated with ceftazidime-avibactam monotherapy. Case presentation: A 27-year old man was admitted to the hospital after sustaining severe traumatic brain injury undergoing left-sided hemicraniectomy. Two weeks after hospitalization, the patient was noted to have an extra-axial fluid collection underneath his surgical site. The patient was taken to the operating room for a wash-out of the hemicraniectomy site. K. pneumoniae was isolated from his cerebrospinal fluid which exhibited a multidrug resistance phenotype including resistance to carbapenems. Due to the complex nature of the patient's skull fractures, poor wound healing at the hemicraniectomy site and the possibility of disseminating the infection into the deep ventricular system, the patient was deemed to be a poor candidate for an external ventricular drain (EVD). Patient was started on ceftazidime-avibactam 2.5 g given intravenously every 6 h monotherapy for the treatment of meningitis. Methods. Antimicrobial susceptibilities were determined by broth microdilution and ceftazidime-avibactam MIC was determined by Etest. Detection of genes coding for the most common carbapenemases (blaKPC, blaNDM, blaVIM,blaIMPand blaOXA-48) was performed by PCR. Strain typing was performed by multilocus sequence typing (MLST) and capsular polysaccharide characterization was carried out by sequencing of the wzi gene. Results. The patient was treated successfully with systemic ceftazidime-avibactam for 14 days. The organism was highly resistant to β-lactams and aminoglycosides while retaining susceptibility to colistin (MIC 0.25 µg/ml) and ceftazidime-avibactam (MIC 1 µg/ml). The isolate was found to be strain type 307 (ST307) with wzi-173 capsular polysaccharide harboring the blaKPC-2 gene embedded in Tn4401a. Conclusion. Ceftazidime-avibactam may be a promising option for CNS infections caused by KPC-producing Enterobacteriaceae. ST 307 maybe a novel emerging strain type in the US. Disclosures. R. A. Bonomo, Merck: Grant Investigator and Scientific Advisor, Consulting fee and Research grant. Actavis: Invited Speaker, Speaker honorarium. Allergan: Grant Investigator, Research grant. Wockhardt: Grant Investigator, Research grant. GlaxoSmithKline: Grant Investigator, Research grant. AstraZeneca: Grant Investigator, Research grant