Clinical Feature, Therapy, Antimicrobial Resistance Gene Distribution, and Outcome of Nosocomial Meningitis Induced by Multidrug-Resistant Enterobacteriaceae-A Longitudinal Cohort Study From Two Neurosurgical Centers in Northern China

Abstract

Objectives: This is a comparative cohort study aiming to evaluate the mortality risk factors for patients with nosocomial meningitis (NM) induced by multidrug-resistant Enterobacteriaceae (MDRE) in China. The clinical features and therapies of patients and the resistance mechanisms of MDRE pathogens were also assessed.

Methods: MDRE-NM patients from two neurosurgical centers in China from 2014 to 2019 were included in this study. Clinical features were extracted from the medical record databases of the two centers. The molecular mechanisms underlying the microbiological resistance mechanisms of each MDRE pathogen were determined, Kaplan-Meier survival analysis was conducted, and multivariable analyses were performed using a Cox proportional hazard model.

Results: Ninety MDRE-NM patients were included in this study. Klebsiella pneumoniae accounted for the highest proportion of causative pathogens (46/90, 51.1%), and 40 causative pathogens (44.4%) were meropenem-resistant. blaKPC (27/40, 67.5%) was the predominant carbapenem resistance gene. Multivariate Cox analysis showed that external ventricular drainage (EVD) [hazard ratio (HR) = 2.524, 95% confidence interval (CI) = 1.101-5.787, p = 0.029] and a Glasgow Coma Scale (GCS) score ≤;8 (HR = 4.033, 95% CI = 1.526-10.645, p = 0.005) were mortality risk factors for patients with MDRE-NM. A total of 90.0%, 94.4%, and 97.8% of MDRE-NM patients received antibiotic prophylaxis (AP), antibiotic empirical therapy (AET), and antibiotic definitive therapy (ADT), respectively.

Conclusions: NM caused by MDRE is an important sign of the failure of neurosurgery. MDRE possesses multiple drug resistance genotypes, and EVD and a GCS score ≤;8 are independent mortality risk factors for patients with MDRE-NM, which deserve the attention of microbiologists and neurosurgical clinicians.

Keywords: MDRE; antimicrobial resistance genes; clinical feature; nosocomial meningitis; outcome.

Figure 1

Flowchart of patient inclusion. MDRE, multidrug-resistant Enterobacteriaceae; NM, nosocomial meningitis.

Figure 2

Distribution of bacteria isolated from the cerebrospinal fluid (CSF) of patients with nosocomial meningitis (NM).Outer ring: Distribution of bacteria. Middle ring: Distribution of multidrug-resistant (MDR) bacteria. Inner ring: Distribution of MDR bacteria causing NM mortality. CoNS, coagulase-negative staphylococci.

Figure 3

Number and distribution of NM caused by Enterobacteriaceae and MDRE. MDRE, multidrug-resistant Enterobacteriaceae; NM, nosocomial meningitis.

Figure 4

Distribution and AST of the MDRE group. (A) Year-by-year distribution of nosocomial meningitis (NM) caused by MDRE. (B) AST of MDRE. AST, antimicrobial resistance test; MDRE, multidrug-resistant Enterobacteriaceae.

Figure 5

Year-by-year distribution of patients dying due to MDRE-NM. MDRE, multidrug-resistant Enterobacteriaceae; NM, nosocomial meningitis.

Figure 6

Kaplan–Meier analysis of the 30-day mortality of patients who experienced nosocomial meningitis caused by multidrug-resistant Enterobacteriaceae (MDRE-NM). EVD, external ventricular drainage; GCS, Glasgow Coma Scale; ICU, intensive care unit; HAP, hospital-acquired pneumonia; AMV: assisted mechanical ventilation.