Beta-lactamase production by Kingella kingae in Israel is clonal and common in carriage organisms but rare among invasive strains

Abstract

The purpose of this study was to investigate the prevalence of β-lactamase and the genomic clonality of a large collection of Kingella kingae isolates from Israeli patients with a variety of invasive infections and asymptomatic pharyngeal carriers. β-lactamase production was studied by the nitrocefin method and the minimum inhibitory concentrations (MICs) of penicillin and amoxicillin-clavulanate were determined by the epsilon (Etest) method. The genotypic clonality of isolates was investigated by pulsed-field electrophoresis (PFGE). β-lactamase was found in 2 of 190 (1.1 %) invasive isolates and in 66 of 429 (15.4 %) randomly chosen carriage organisms (p < 0.001). Overall, 73 distinct PFGE clones were identified (33 among invasive organisms and 56 among carriage isolates). β-lactamase production was found to be limited to four distinct PFGE clones, which were common among carriage strains but rare among invasive strains, and all organisms in the collection belonging to these four clones expressed β-lactamase. The penicillin MIC of β-lactamase-producing isolates ranged between 0.094 and 2 mcg/mL (MIC50: 0.25 mcg/mL; MIC90: 1.5 mcg/mL) and that of amoxicillin-clavulanate between 0.064 and 0.47 mcg/mL (MIC50: 0.125 mcg/mL; MIC90: 0.125 mcg/mL). The penicillin MIC of β-lactamase non-producing isolates ranged between <0.002 and 0.064 mcg/mL (MIC50: 0.023 mcg/mL; MIC90: 0.047 mcg/mL). Although β-lactamase production is prevalent among K. kingae organisms carried by healthy carriers, the low invasive potential of most colonizing clones results in infrequent detection of the enzyme in isolates from patients with clinical infections. The exceptional presence of β-lactamase among invasive organisms correlates with the favorable response of K. kingae infections to the administration of β-lactamase-susceptible antibiotics.

Kingella kingae: Carriage, Transmission, and Disease

“…Production of ␤-lactamase among Israeli isolates was found to be limited to four distinct PFGE clones, and all members of these clones expressed the enzyme (60). A recent study confirmed the clonality of the trait in isolates from Reykjavik (Iceland) and Minneapolis, MN (USA) (61).…”

“…In a large study in which ␤-lactamase production and genomic clonality were investigated in a large sample of K. kingae isolates from Israeli individuals with clinical infections and asymptomatic pharyngeal carriers, the enzyme was detected in only 2 of 190 (1.1%) invasive isolates from patients with bacteremia, arthritis, osteomyelitis, or endocarditis and in 68 of 428 (15.9%) randomly chosen carriage organisms (P Ͻ 0.001), suggesting that the K. kingae strains that express ␤-lactamase are less capable of invading the bloodstream and deep host tissues and confirming that improved colonization ability does not necessarily imply enhanced virulence (60). These findings also imply that antibiotic resistance may confer a biological advantage to K. kingae organisms inhabiting in the pharynx in early childhood, overlapping the period in life of enhanced prevalence of oropharyngeal colonization and highest antimicrobial drug consumption (18,85,101,310).…”

“…The SCVs of K. kingae belong to several pulsed-field gel electrophoresis (PFGE) clones, of which clone T is the most commonly carried by the healthy pediatric population in southern Israel and is associated with ␤-lactamase production (60). Although clone T isolates are readily identified as K. kingae by MALDI-TOF technology and share alleles of the rtxA and por genes (encoding the RTX toxin and the porin protein, respectively) found in some other K. kingae clones, attempts to type clone T strains by multilocus sequence typing (MLST) failed, because even when diverse couples of primers were employed, amplification succeeded for only three housekeeping genes (abcZ, adk, and cpn60) (61).…”

Major Intercontinentally Distributed Sequence Types of Kingella kingae and Development of a Rapid Molecular Typing Tool

“…The typing results revealed noticeable genomic heterogeneity in the species. To date, 40 MLST sequence types (STs) and 73 PFGE clones have been identified, as well as 18 rtxA and 12 different por alleles (13)(14)(15)(16)(17)(18). Remarkable congruence has been observed between the results obtained using different typing methods (16,18).…”

First Identification of a Chromosomally Located Penicillinase Gene in Kingella kingae Species Isolated in Continental Europe

“…Plasmid-borne TEM-1 penicillinase production has been sporadically detected in a few countries but not in continental Europe, despite a high prevalence of K. kingae infections (2)(3)(4)(5)(6)(7)(8)(9).…”