Risk Factors of Initial Inappropriate Antibiotic Therapy and the Impacts on Outcomes of Neonates with Gram-Negative Bacteremia

Abstract

Background: Timely appropriate empirical antibiotic plays an important role in critically ill patients with gram-negative bacteremia. However, the relevant data and significant impacts have not been well studied in the neonatal intensive care unit (NICU). Methods: An 8-year (1 January 2007–31 December 2014) cohort study of all NICU patients with gram-negative bacteremia (GNB) in a tertiary-care medical center was performed. Inadequate empirical antibiotic therapy was defined when a patient did not receive any antimicrobial agent to which the causative microorganisms were susceptible within 24 h of blood culture sampling. Neonates with GNB treated with inadequate antibiotics were compared with those who received initial adequate antibiotics. Results: Among 376 episodes of Gram-negative bacteremia, 75 (19.9%) received inadequate empirical antibiotic therapy. The cause of inadequate treatment was mostly due to the pathogen resistance to prescribed antibiotics (88.0%). Bacteremia caused by Pseudomonas aeruginosa (Odds ratio [OR]: 20.8, P < 0.001) and extended spectrum β-lactamase (ESBL)-producing bacteria (OR: 18.4, P < 0.001) had the highest risk of inadequate treatment. Previous exposure with third generation cephalosporin was identified as the only independent risk factor (OR: 2.52, 95% CI: 1.18–5.37, P = 0.018). Empirically inadequately treated bacteremias were significantly more likely to have worse outcomes than those with adequate therapy, including a higher risk of major organ damage (20.0% versus 6.6%, P < 0.001) and infectious complications (25.3% versus 9.3%, P < 0.001), and overall mortality (22.7% versus 11.0%, P = 0.013). Conclusions: Inadequate empirical antibiotic therapy occurs in one-fifth of Gram-negative bacteremias in the NICU, and is associated with worse outcomes. Additional prospective studies are needed to elucidate the optimal timing and aggressive antibiotic regimen for neonates who are at risk of antibiotic-resistant Gram-negative bacteremia.

Clinical Impact and Risk Factors of Nonsusceptibility to Third-Generation Cephalosporins Among Hospitalized Adults with Monomicrobial Enterobacteriaceae Bacteremia in Southern Taiwan: A Multicenter Study

“…The higher nonsusceptible rates toward antimicrobial agents among Enterobacteriaceae bacteremia isolates in recent years led clinicians more difficulty in selecting appropriate empirical antimicrobial agents, especially for extended-spectrum β-lactamase (ESBL)-producing bacteria. 28 Though ESBL-producing phenotype was not examined, the high 3GC-NS rate among our Enterobacteriaceae isolates might partly be contributed by the presence of ESBL-producing isolates. In the era of reduced susceptibility to 3GCs among Enterobacteriaceae isolates, the information of the clinical parameters predictive of 3GC-NS identified in our study is helpful to select appropriate antimicrobial agents.…”

Neonatal Paenibacilliosis:Paenibacillus thiaminolyticusas a Novel Cause of Neonatal Sepsis with High Risk of Sequelae in Uganda

“…Inappropriate empirical antibiotic therapy has been associated with worse outcomes for neonatal sepsis. [55][56][57] These studies assume that an appropriate antibiotic is ultimately administered within 1-3 days of symptom onset. 58 Unfortunately, P. thiaminolyticus can be difficult to recover using culture and will be consistently missed in Uganda and other parts of the world where neonatal sepsis is common.…”

Machine Learning Approaches to Predict In-Hospital Mortality among Neonates with Clinically Suspected Sepsis in the Neonatal Intensive Care Unit

“…We found that the model developed using ML algorithms has much better predictive power than the traditional neonatal severity scoring systems, which are limited by the inability to fully consider integrated variables [ 13 , 14 , 15 ]. In the NICU, an episode of clinically suspected sepsis rarely directly causes mortality but is often associated with antibiotic exposure, infectious complications, prolonged ventilation and hospitalization and sometimes surgical intervention [ 22 , 23 , 24 ]. After neonates survive the most critically ill perinatal period, the combination of multiple factors, chronic comorbidities and subsequent nosocomial infections usually contributes to ultimate in-hospital mortality [ 25 , 26 ].…”