Antimicrobial susceptibility testing of Kingella kingae with broth microdilution and disk diffusion using EUCAST recommended media

Abstract

Objectives: Increasing use of improved culture techniques and sensitive nucleic acid amplification assays have resulted in recognition of Kingella kingae as an important cause of invasive infections in young children, especially in septic arthritis, osteomyelitis, bacteraemia, and endocarditis. In 2016, EUCAST established clinical MIC breakpoints for K. kingae (published in EUCAST Clinical Breakpoint Tables v 7.0, 2017). The present study was carried out to produce MIC-zone diameter correlations for K. kingae on an international collection of isolates, with the aim of suggesting zone diameter breakpoints corresponding to the clinical MIC breakpoints. Methods: Antimicrobial susceptibility testing was performed for 18 clinically relevant agents on a collection of 159 clinical isolates of K. kingae. Broth microdilution MIC determination and disk diffusion were performed according to EUCAST recommendations for fastidious organisms. Results: The correlation between MICs and zone diameters was good for all agents with EUCAST breakpoints for K. kingae. b-lactamase was detected in 41 isolates (26%) and these isolates were resistant to aminopenicillins. These isolates were also resistant to trimethoprim-sulfamethoxazole. Resistance to tetracyclines was detected in 8% of all isolates. All resistant isolates were correctly categorized for these agents with the proposed zone diameter breakpoints. One isolate, resistant to erythromycin but susceptible to other macrolides, was categorized as susceptible with erythromycin disk diffusion. No resistance was detected for the cephalosporins, carbapenems, and fluoroquinolones tested. Conclusion: Based on the results in this study, zone diameter breakpoints for K. kingae calibrated to EUCAST clinical MIC breakpoints were proposed and approved by EUCAST.

Review highlights the latest research in Kingella kingae and stresses that molecular tests are required for diagnosis

“…As a measure of caution, this antibiotic class should be avoided whenever a beta-lactamase producer strain is isolated, as these strains remain fully susceptible to cephalosporin drugs. 60 Kingella kingae is intrinsically resistant to glycopeptides and clindamycin. This is an essential consideration in regions where community-associated methicillin-resistant Staphylococcus aureus infections are common and these antibiotics are empirically administered to children with skeletal system infections, pending culture results.…”

“…This is an essential consideration in regions where community-associated methicillin-resistant Staphylococcus aureus infections are common and these antibiotics are empirically administered to children with skeletal system infections, pending culture results. 60 With a few exceptions, K. kingae is susceptible to aminoglycosides, macrolides, tetracycline, co-trimoxazole and fluoroquinolones. 4,60 Because of the lack of studies that specifically addressed the antibiotic therapy of K. kingae infections, patients have been treated…”

<p>Acute Hematogenous Osteomyelitis in Children: Clinical Presentation and Management</p>

“…These isolates are universally resistant to vancomycin and frequently clindamycin but are typically susceptible to β-lactam antimicrobials; K. kingae may produce a β-lactamase in up to 26% of cases. 59 , 88 , 89 As antimicrobial susceptibility testing cannot frequently be performed in the clinical setting, use of a cephalosporin is often recommended. 21 Many strains of K. kingae are also susceptible to TMP-SMX, 59 , 89 potentially making this an attractive alternative to β-lactams.…”

Management of Pediatric Acute Hematogenous Osteomyelitis, Part I: Antimicrobial Stewardship Approach and Review of Therapies for Methicillin‐Susceptible Staphylococcus aureus, Streptococcus pyogenes, and Kingella kingae

“…In the treatment of K. kingae, first‐generation cephalosporins are preferred because they provide dual coverage against K. kingae and S. aureus and remain stable against the beta‐lactamases that K. kingae can produce . Limited data from 40 isolates suggest that K. kingae remains susceptible to cefazolin with an MIC range of 0.19–0.75 mg/L .…”

“…Intravenous ampicillin, ampicillin‐sulbactam, and the PO counterparts amoxicillin and amoxicillin‐clavulanate also demonstrate activity against K. kingae . While K. kingae can be susceptible to ampicillin or amoxicillin alone, 25% of isolates have been identified as beta‐lactamase producing …”