Legionellaantibiotic susceptibility testing: is it time for international standardization and evidence-based guidance?

Abstract

Legionella pneumophila, a Gram-negative bacillus, is the causative agent of Legionnaire’s disease, a form of severe community-acquired pneumonia. Infection can have high morbidity, with a high proportion of patients requiring ICU admission, and up to 10% mortality, which is exacerbated by the lack of efficacy of typical empirical antibiotic therapy against Legionella spp. The fastidious nature of the entire Legionellaceae family historically required inclusion of activated charcoal in the solid medium to remove growth inhibitors, which inherently interferes with accurate antimicrobial susceptibility determination, an acknowledged methodological shortfall, now rectified by a new solid medium that gives results comparable to those of microbroth dilution. Here, as an international Legionella community (with authors representing various international reference laboratories, countries and clinical stakeholders for diagnosis and treatment of legionellosis), we set out recommendations for the standardization of antimicrobial susceptibility testing methods, guidelines and reference strains to facilitate an improved era of antibiotic resistance determination.

Antibiotic Susceptibility of Environmental Legionella pneumophila Strains Isolated in Northern Italy

“…Susceptibility to ciprofloxacin was also shown to be in keeping with that demonstrated in two of the previous studies in which this antimicrobial agent was evaluated, with only slightly higher MIC 90 values (MIC 90 = 0.06 mg/L compared to the previously reported value of 0.03 mg/L) [11,12]. For levofloxacin, MIC 50 and MIC 90 values were also overall concordant with those of previous studies, although Wilson Comparable MIC distributions and results achieved in studies using a common methodology, further support the indications by Portal et al who advocate the use of the BMD method in combination with BYEα medium for AST of Lp [41].…”

“…Moreover, the lack of standardized methods for L. pneumophila susceptibility testing has resulted in the failure to establish appropriate clinical MIC cut-off values, allowing to correlate in vitro results to clinical outcome. There is, therefore, presently a great quest among researchers, stakeholders, and reference laboratories for the standardization of antimicrobial susceptibility testing methods, as well as for new guidelines and reference strains to facilitate and improve the detection of antimicrobial resistance [41].…”

Antimicrobial susceptibility profiles and tentative epidemiological cutoff values of Legionella pneumophila from environmental water and soil sources in China

“…Given that charcoal in the BCYEα plate biases the MICs for many antibiotics, including RIF, macrolides, and tetracycline ( Bornstein et al, 1985 ), two or more folds of high MICs or ECOFFs in most of the antimicrobials could be obtained when compared with the BMD method ( Portal et al, 2021b ); however, this seemed not to hold for DOX. Thus, a standardized method for Legionella is urgent to ensure that the MIC data remain consistent ( Portal et al, 2021a ). Portal et al (2021b) obtained an ECOFF for AZI based on the BMD methods ( Portal et al, 2021b ).…”

Case report: A prosthetic valve endocarditis caused by Legionella bozemanae in an immunocompetent patient

“…When it comes to treatment, there are no randomized trials involving legionellosis with non-pneumophila species. For long, antimicrobial susceptibility testing (AST) for Legionella has been challenging and not standardized, until the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Legionella Infections recently issued a recommendation ( 25 ). In this case, AST was impossible due to lack of a positive culture.…”