Susceptibility Testing of Kingella Kingae to Cefazolin.

We read with great interest the article entitled 'Antimicrobial susceptibility testing of Kingella kingae with broth microdilution and disk diffusion using EUCAST recommended media' by Matuschek et al. [[1]Matuschek E. Åhman J. Kahlmeter G. Yagupsky P. Antimicrobial susceptibility testing of Kingella kingae with broth microdilution and disk diffusion using EUCAST recommended media.Clin Microbiol Infect. 2017; (S1198-743X(17)30403-2)Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar]. Kingella kingae is now recognized as the first pathogen causing septic arthritis and osteomyelitis in children between 6 months and 4 years of age in several countries, preceding Staphylococcus aureus [[2]Yagupsky P. Kingella kingae: carriage, transmission, and disease.Clin Microbiol Rev. 2015; 28: 54-79Crossref PubMed Scopus (123) Google Scholar]. Empiric treatment should therefore cover both pathogens, and amoxicillin plus clavulanate or second- or third-generation cephalosporins have been recommended [2Yagupsky P. Kingella kingae: carriage, transmission, and disease.Clin Microbiol Rev. 2015; 28: 54-79Crossref PubMed Scopus (123) Google Scholar, 3Paakkonen M. Peltola H. Management of a child with suspected acute septic arthritis.Arch Dis Child. 2012; 97: 287-292Crossref PubMed Scopus (38) Google Scholar]. Moreover, K. kingae is not fully susceptible to oxacillin (minimum inhibitory concentration (MIC) MIC50 = 3 mg/L and MIC90 = 6 mg/L) [[2]Yagupsky P. Kingella kingae: carriage, transmission, and disease.Clin Microbiol Rev. 2015; 28: 54-79Crossref PubMed Scopus (123) Google Scholar], which is frequently used as first-line treatment in some countries. First-generation cephalosporins such as cefazolin have long been recognized as curing bone and joint infections due to S. aureus and are even recommended in prosthetic joint infection treatment due to methicillin-susceptible S. aureus [[4]Osmon D.R. Berbari E.F. Berendt A.R. Lew D. Zimmerli W. Steckelberg J.M. et al.Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America.Clin Infect Dis. 2013; 56: e1-25Crossref PubMed Scopus (162) Google Scholar]. However, the susceptibility of K. kingae to this drug has not yet been investigated. Breakpoints were not provided in the recent publication of the European Committee on Antimicrobial Susceptibility Testing (EUCAST, Clinical Breakpoint Tables v7.1, March 2017, http://www.eucast.org/); nor was MIC distribution defined by Matuschek et al. [[1]Matuschek E. Åhman J. Kahlmeter G. Yagupsky P. Antimicrobial susceptibility testing of Kingella kingae with broth microdilution and disk diffusion using EUCAST recommended media.Clin Microbiol Infect. 2017; (S1198-743X(17)30403-2)Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar]. Forty clinical K. kingae isolates from various geographical locations and representative of the diversity of the species in terms of pathogenicity and genotypes, based on multilocus sequence typing analysis [[5]Basmaci R. Bidet P. Yagupsky P. Muñoz-Almagro C. Balashova N.V. Doit C. et al.Major intercontinentally distributed sequence types of Kingella kingae and development of a rapid molecular typing tool.J Clin Microbiol. 2014; 52: 3890-3897Crossref PubMed Scopus (25) Google Scholar], were selected for susceptibility testing. The reference type strain ATCC 23330 from Norway was also included. The 40 clinical isolates were from the United States (n = 5), Canada (n = 5), Spain (n = 6), Israel (n = 10), Iceland (n = 2) and France (n = 12). The major sequence type complexes STc-6, 14, 23, 25, 33 and 35 were represented with 11, eight, five, six, three and five strains respectively. Twenty-nine strains were involved in osteoarticular infections, four in occult bacteraemia, three in endocarditis, one in infection of unknown site and three from healthy carriers. Nine strains produced a penicillinase and were from the United States, Iceland, Israel and France [[6]Basmaci R. Bonacorsi S. Bidet P. Balashova N.V. Lau J. Muñoz-Almagro C. et al.Genotyping, local prevalence, and international dissemination of beta-lactamase-producing Kingella kingae strains.Clin Microbiol Infect. 2014; 20: O811-O817Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar]. Cefazolin MICs using the Etest method were determined on Müller-Hinton-F agar (bioMérieux, Marcy l'Étoile, France) with an inoculum of McFarland 0.5 (corresponding to 108 CFU/mL), as recommended by EUCAST. The reference strains Escherichia coli ATCC 25922 and S. aureus ATCC 29213 were used as controls. MIC50 and MIC90 were 0.38 and 0.5 mg/L respectively (range, 0.19–0.75 mg/L). The nine β-lactamase-producing K. kingae isolates had similar cefazolin MICs compared to their nonproducing counterparts (MIC50 = 0.50 mg/L (range, 0.25–0.75 mg/L) vs. MIC50 = 0.38 mg/L (range, 0.19–0.75 mg/L), respectively; p 0.31 by Mann-Whitney U test). The cefazolin MICs of the reference strains E. coli ATCC 25922 and S. aureus ATCC 29213 were 2 and 0.38 mg/L, respectively. All the K. kingae strains had a cefazolin MIC under the 'non-species-related' MIC breakpoints (1 mg/L) as proposed by EUCAST. Moreover the cefazolin MICs of the K. kingae isolates were lower than those of S. aureus, for which the epidemiologic cutoff is 2 mg/L. The recent description of penicillinase-producing K. kingae strains with the potential risk of a global emergence and dissemination [[6]Basmaci R. Bonacorsi S. Bidet P. Balashova N.V. Lau J. Muñoz-Almagro C. et al.Genotyping, local prevalence, and international dissemination of beta-lactamase-producing Kingella kingae strains.Clin Microbiol Infect. 2014; 20: O811-O817Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar], as well as the necessity to cover S. aureus in case of culture and PCR-negative septic arthritis, led us to reconsider the first-line treatment. Cefazolin appears active among K. kingae β-lactamase producers. Although β-lactamase-producing K. kingae strains remain uncommon, international collaboration to monitor their spread is crucial. The present study investigated a sample of K. kingae strains representative of the diversity of the species throughout the world. Our results indicate that in vitro susceptibility of K. kingae to cefazolin is compatible with the use of this drug in probabilistic treatment of bone and joint infections in infants. All authors report no conflicts of interest relevant to this article.