Clinical and Molecular Characteristics of Neonatal Extended-Spectrum β-Lactamase-Producing Gram-Negative Bacteremia: A 12-Year Case-Control-Control Study of a Referral Center in Taiwan

Abstract

Extended-spectrum β-lactamase (ESBL)-producing Gram-negative bacteremia (GNB) in the neonatal intensive care unit was characterized by comparison with two control groups: a susceptible control group and a general base population group over 2001 to 2012. The influence of ESBL production on mortality was studied in all study subjects and ESBL-GNB isolates were microbiologically characterized. We identified 77 episodes of ESBL-GNB (14.2% of all neonatal late-onset GNB), which were caused by Klebsiella spp. (62.3%), E. coli (20.8%) and Enterobacter spp. (16.9%). Most ESBL-GNB strains were genetically unrelated and the SHV-type ESBLs were the most prevalent (67% of isolates). Comparison with both control groups disclosed previous usage of 3rd generation cephalosporin (odds ratio [OR], 4.72; 95% confidence interval [CI], 2.03–10.97; P < 0.001), and underlying renal disease (OR, 4.07; 95% CI, 1.10–15.08; P = 0.035) as independent risk factors for ESBL-GNB. Inadequate empiric antibiotics, a higher illness severity, higher rates of infectious complications and sepsis-attributable mortality were more frequently seen in neonates with ESBL-GNB than those with non-ESBL GNB (20.8% and 15.6% vs. 9.2% and 7.9%, respectively; P = 0.008 and 0.049, respectively). Neonates with underlying secondary hypertension (OR, 7.22; 95% CI, 2.17–24.06) and infectious complications after bacteremia (OR, 6.66; 95% CI, 1.81–19.31) were identified as independent risk factor for in-hospital mortality. ESBL-GNB accounted for one-seventh of all neonatal gram-negative bacteremia, especially in neonates exposed to broad-spectrum cephalosporins. Neonates with ESBL-GNB bacteremia more frequently received inadequate empirical antibiotic therapy, which were associated with a higher rate of infectious complications and an adverse outcome.

Risk factors for multidrug‐resistant Gram‐negative bacteria infection in intensive care units: A meta‐analysis

“…Nine studies (Alexiou et al, 2012;Fang et al, 2016;Katsaragakis et al, 2008;Michalopoulos et al, 2011;Tsai et al, 2016;Vasudevan et al, 2014;Vasudevan et al, 2015;Venkatachalam et al, 2014;Young et al, 2007) reported data on history of operative procedures in relation to MDR-GNB infection in this metaanalysis ( Figure 3). No substantial heterogeneity (I 2 = 0%, P>0.10) was observed.…”

“…Seventeen studies (Alexiou et al, 2012;Costa, Atta, & Silva, 2015;Fang, Chen, & Zhou, 2016;Katsaragakis et al, 2008;Liu et al, 2015;Lye et al, 2012;Marcos et al, 2011;Michalopoulos et al, 2011;Osthoff, Mcguinness, Wagen, & Eisen, 2015;Patel et al, 2014; Prata-Rocha, Gontijo-Filho, & Melo, 2012;Tsai et al, 2016;Vasudevan, Memon, Mukhopadhyay, Li, & Tambyah, 2015;Vasudevan, Mukhopadhyay, Li, Yuen, & Tambyah, 2014;Venkatachalam et al, 2014;Young, Sabel, & Price, 2007;Zhong et al, 2012) reported the correlation of gender and MDR-GNB infection ( Figure 2). The random effect model was used to pool results (I 2 = 75.4%, P < 0.001).…”

“…Five studies (Nseir et al, 2011;Prata-Rocha et al, 2012;Tsai et al, 2016;Vasudevan et al, 2014;Young et al, 2007) reported the association of central venous catheterisation and MDR-GNB infection ( Figure 4). The fixed effects model was used due to lack of heterogeneity in the meta-analysis (I 2 = 0%, P>0.10).…”

“…Seven studies (Fang et al, 2016;Michalopoulos et al, 2011;Nseir et al, 2011;Patel et al, 2014;Prata-Rocha et al, 2012;Tsai et al, 2016;Vasudevan et al, 2014) reported associations between mechanical ventilation and MDR-GNB infection ( Figure 5A). The fixed effects model was chosen due to lack of heterogeneity in the meta-analysis (I 2 = 0%, P>0.10).…”

Antimicrobial-resistant Gram-negative infections in neonates: burden of disease and challenges in treatment

“…The SHV-type ESBLs were the most prevalent among these patients (67% of ESBLs), with most strains being genetically unrelated. In this study, neonates infected with ESBL-GN strains had higher rates of infectious complications (p = 0.008) and adverse outcomes (p=0.049) compared to non-ESBLs [18].…”