A retrospective study of Enterococcus faecalis infective endocarditis: comparison of clinical characteristics and outcomes associated with treatment.

Introduction: A synergistic antibiotic combination of a penicillin and gentamicin (AG) or ceftriaxone (AC) is used in the management of Enterococcus faecalis infective endocarditis (EFIE). We compare the treatment outcomes between AG and AC, including low and high dose ceftriaxone (1 and 2 g 12 hourly). Methods: A retrospective cohort study of patients treated for EFIE at single tertiary centre (2012-2019). Outcome measures examined were 90- and 180-day mortality, treatment associated adverse events and relapse of bacteraemia (within 1 year). Results: 39 patients were enrolled [61.6% given (AC) (n = 24), 24% received ACL (n = 10) and 34% received ACN (n = 14)], 38.4% received AG (n = 15). We noted a difference in the mortality outcomes at 90 and 180 days between those treated with AG and AC overall (6.7% and 33.3%, respectively) although this did not reach statistical significance (P = 0.114, P = 0.061). No significant difference was noted between these groups in incidence of relapsed bacteraemia with two cases noted in the AC cohort (8.3%, 2/24) and none observed (0/15) in the AG cohort (P = 0.662, P = 0.414). A greater number of adverse events was observed in the AG group (11/15, 73.3%) compared to the overall AC group (6/24, 25.0%) (P = 0.009), with no difference between the high and low dose ceftriaxone groups (P = 0.05). Conclusion: Combination treatment of EFIE with AC is associated with a reduced number of adverse events in comparison to AG groups. Although increased mortality was observed in the AC group, this did not reach statistical significance, and reflects the greater comorbidities and reduced capacity for surgical source control in this cohort.

Evaluation of the Haemophilus influenzae EUCAST and CLSI disc diffusion methods to recognize aminopenicillin and amoxicillin/clavulanate resistance.

OBJECTIVES: Implementation of EUCAST susceptibility testing in an Australian hospital laboratory demonstrated higher rates of aminopenicillin and amoxicillin/clavulanate resistance in Haemophilus influenzae than previously recognized. This study aimed to better define the variability in the detection of ß-lactam resistance based on EUCAST and CLSI disc diffusion (DD) methodology, by comparison with the recommended reference method, broth microdilution (BMD), and by concordance with genomic analysis. METHODS: A total of 100 random H. influenzae isolates were assessed for ampicillin and amoxicillin/clavulanate susceptibility by EUCAST and CLSI DD and BMD. WGS was used to analyse the ftsI gene of a subset of isolates with ß-lactam resistance, other than that due to isolated ß-lactamase production. RESULTS: Of the 100 isolates, 32 were categorized as either ß-lactamase negative, ampicillin resistant (BLNAR) (n = 18) or ß-lactamase positive, amoxicillin/clavulanate resistant (BLPACR) (n = 14) by EUCAST DD. All 18 EUCAST BLNAR isolates were genotypically confirmed by WGS. Five of 18 BLNAR isolates were concordant by CLSI DD, 12 by EUCAST BMD and 4 by CLSI BMD. Nine of 14 EUCAST BLPACR isolates were confirmed by WGS; the remaining 5 were 1 mm below the EUCAST DD breakpoint. Only one isolate was detected as BLPACR by CLSI DD. Group III mutations associated with high-level ampicillin resistance were identified in 10/32 isolates. CONCLUSIONS: The EUCAST DD susceptibility method is more reliable than either CLSI or BMD for the detection of genotypically defined BLNAR resistance. However, accurate categorization of amoxicillin/clavulanate resistance remains problematic. Continuous and reproducible surveillance of resistance is needed; for this to be possible, robust susceptibility methods are required.