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

Shih-Ming Chu,Hsuan-Rong Huang,Ming-Chou Chiang,Ming-Horng Tsai,Ren-Huei Fu,Mei-Yin Lai,Jen-Fu Hsu

doi:10.3390/antibiotics9040203

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.

Highlights

Appropriate empirical antibiotic plays an important role in critically ill patients with gram-negative bacteremia
We reviewed the medical records of the neonates with initial inadequate antibiotics and compared them with those who received appropriate initial antimicrobial therapy
A total of 333 neonates with 395 episodes of Gram-negative bacteremia were identified; 19 of them were the recurrent episodes which occurred within one month after the first episode and were excluded, leaving a total of 333 neonates with 376 episodes of Gram-negative bacteremia for analysis (Table 1)

Summary

Introduction

Appropriate empirical antibiotic plays an important role in critically ill patients with gram-negative bacteremia. 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. Appropriate initial antibiotic therapy has been demonstrated as the key independent factor of treatment outcomes in patients with Gram-negative bacteremia in previous studies from the adult ICUs or wards [11,12,13,14]. This issue has not been fully studied in the NICU, except for a small sample size, case-control study found in the literature [15]. MDR GNB accounts for nearly one-fifth of all neonatal GNBs, or

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