Elizabethkingia anophelis bacteremia is associated with clinically significant infections and high mortality

Abstract

Unlike Elizabethkingia meningoseptica, the clinical importance of E. anophelis is poorly understood. We determined the clinical and molecular epidemiology of bacteremia caused by Elizabethkingia-like species from five regional hospitals in Hong Kong. Among 45 episodes of Elizabethkingia-like bacteremia, 21 were caused by Elizabethkingia, including 17 E. anophelis, three E. meningoseptica and one E. miricola; while 24 were caused by other diverse genera/species, as determined by 16S rRNA gene sequencing. Of the 17 cases of E. anophelis bacteremia, 15 (88%) were clinically significant. The most common diagnosis was pneumonia (n = 5), followed by catheter-related bacteremia (n = 4), neonatal meningitis (n = 3), nosocomial bacteremia (n = 2) and neutropenic fever (n = 1). E. anophelis bacteremia was commonly associated with complications and carried 23.5% mortality. In contrast, of the 24 episodes of bacteremia due to non-Elizabethkingia species, 16 (67%) were clinically insignificant. Compared to non-Elizabethkingia bacteremia, Elizabethkingia bacteremia was associated with more clinically significant infections (P < 0.01) and positive cultures from other sites (P < 0.01), less polymicrobial bacteremia (P < 0.01), and higher complication (P < 0.05) and mortality (P < 0.05) rates. Elizabethkingia bacteremia is predominantly caused by E. anophelis instead of E. meningoseptica. Elizabethkingia bacteremia, especially due to E. anophelis, carries significant morbidity and mortality, and should be considered clinically significant unless proven otherwise.

Figure 1. Phylogenetic tree showing the relationship of the 45 Elizabethkingia-like blood culture isolates to related bacterial species using 16S rRNA gene sequence analysis.

The tree was constructed by maximum likelihood method using General Time Reversible model and Escherichia coli (CP010304) as the root. A total of 1325 nucleotide positions were included in the analysis. Bootstrap values were calculated from 1000 replicates. The scale bar indicates the number of substitutions per site. Names and accession numbers are given as cited in GenBank database.

Figure 2. Results of MALDI-TOF MS identification of the 21 Elizabethkingia strains.

In panel (A), representative MALDI-TOF MS spectra of the three Elizabethkingia species are shown. In panel (B), dendrogram was generated from hierarchical clustering of MALDI-TOF MS spectra of 21 Elizabethkingia isolates and reference strains of E. meningoseptica and E. miricola, using ClinProTools 3.0 (Bruker Daltonics, Germany). Distances are displayed in relative units.

Figure 3. Pulsed-field gel electrophoresis (PFGE) analysis of the 17 E. anophelis isolates and E. anophelis type strain R26^T.

(lane 1 = EA1, lane 2 = EA2, lane 3 = EA3, lane 4 = EA4, lane 5 = EA5, lane 6 = EA6, lane 7 = EA7, lane 8 = EA8, lane 9 = EA9, lane 10 = EA10, lane 11 = EA11, lane 12 = EA12, lane 13 = EA13, lane 14 = EA14, lane 15 = EA15, lane 16 = HKU38, lane 17 = HKU36, lane 18 = R26^T, M = lambda marker). In Panel (A), PFGE was performed using CHEF Mapper XA system (Bio-Rad) and restriction endonuclease XbaI. Results showed that the 17 isolates possessed distinct PFGE patterns. In Panel (B), dendrogram was constructed with PFGE data by similarity and clustering analysis using the Dice coefficient (1% tolerance and 0.5% optimization) and unweighted pair-group method using average linkages with GelCompar II.