Objectives The best therapeutic approach for treating MRSA endocarditis remains unknown, particularly in cases of high vancomycin MICs. We report here a case of daptomycin-non-susceptible, ceftaroline-resistant and fosfomycin-resistant MRSA native left valve endocarditis that was successfully treated with valve repair and a combination of high-dose daptomycin and ceftaroline. Methods Antimicrobial testing of the clinical strain was performed using Etest and microdilution broth methods. Time–kill and chequerboard methodologies were used to test the activity of antibiotic combinations. Results By Etest, the MIC of vancomycin was 2 mg/L, the MIC of daptomycin was 2 mg/L, the MIC of fosfomycin was 1024 mg/L and the MIC of ceftaroline was 1.5 mg/L. At the standard inoculum (105 cfu/mL), the three combinations of daptomycin plus ceftaroline, cloxacillin or fosfomycin were synergistic and bactericidal. However, when these combinations were tested using a higher inoculum (108 cfu/mL), all combinations were synergistic, but only daptomycin plus ceftaroline had bactericidal activity. Conclusions These results confirmed a synergistic effect between daptomycin plus ceftaroline and increased bactericidal activity against MRSA, suggesting that this combination may be effective for the treatment of invasive MRSA infection. Our experience highlights the potential clinical use of synergy testing to guide difficult treatment decisions in patients with MDR MRSA infection.

Our institution has performed microbiological diagnosis of Tropheryma whipplei since 2001, initially with a PCR targeting 16S rRNA before the development of a quantitative PCR in 2012. Here we report the clinical characteristics of a cohort of patients suffering from Whipple disease (WD) and evaluate the impact of these molecular techniques. Patients with a positive PCR for T. whipplei between 2001 and 2016 were retrospectively collected from microbiological databases. Two infectious diseases specialists reviewed their medical records and classified them as definite WD, probable WD or carriage of T. whipplei without disease. A total of 1153 samples were tested for T. whipplei; 76 samples taken from 36 patients were positive. Fifteen were considered as presenting a definite WD, seven as a probable WD and 14 as carriers. Median age was 56.4 years (extremes, 6.6e76.1). Median time from symptoms to diagnosis was 3 years (2.5 months to 13.3 years). About 60% were immunosuppressed. The most frequent clinical presentations were joint pain (16/22), weight loss (15/22) and/or digestive tract disorder (15/22); 41% had neurological manifestations, 32% pulmonary involvement and 32% lymphadenopathies. Bacterial load in faeces or saliva were 88 425 copies/mL (IQR 6175-292 725) in definite and probable WD and 311 copies/mL (IQR 253e2090) in carriers, respectively. We observed a 90% PPV above 32 200 copies/mL in faeces. WD is a chronic multisystemic disease with frequent pulmonary involvement. Underlying immunodeficiency is commonly observed leading to more complex clinical presentation. Positive T. whipplei PCR in both stool and saliva has a high positive predictive value. Moreover, patients with WD present higher bacterial load in faeces with a threshold of >32 200 copies/mL predicting ongoing infection.

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51 52 53 4 Dear Editor, 54 Common management options for Graves' disease (GD) include medical treatment, 55 radioactive iodine (RAI) ablation or surgery. Thionamides (carbimazole, methimazole and 56 propylthiouracil) are the first-line medical treatment of GD. Due to potential hepatotoxicity, their 57 use in the setting of underlying hepatic disease can be challenging. For such cases and if 58 thyroidectomy or RAI cannot be rapidly implemented, alternative medical strategies are not 59 well-established.60We report the case of a 28-year-old Caucasian female diagnosed with type I autoimmune 61 hepatitis (AIH) with severely altered liver function tests (alanine aminotransferase of 1437 U/l, 62 total bilirubin of 286 µmol/l).An undetectable TSH prompted a targeted history that revealed 63 recent restlessness, rapid heartbeat and increased stool frequency. Free thyroxine (fT4) and free 64 triiodothyronine (fT3) were more than 2-fold increased. Ultrasonography showed a normally 65 sized but heterogeneous thyroid with increased vascularity. Autoantibodies against the 66 thyrotropin receptor (TRAb) were strongly positive; a diagnosis of GD was made. Due to the 67 AIH, oral prednisone was started at 50 mg/day, with rapid improvement of hepatic function, 68 allowing for progressive tapering after 2 weeks with concomitant introduction of azathioprine. 69Given the severe hepatitis, thionamides were withheld in accordance with ATA guidelines 70 recommending caution in case of more than 5-fold transaminase elevation. Propranolol and low 71 dose cholestyramine were prescribed for 3 weeks. A rapid decrease of both fT4 and fT3 was 72 observed as soon as 48 hours after glucocorticoid (GC) initiation. After 1 month of 73 immunosuppressive treatment, liver function tests, fT4 and fT3 were normal. The TRAb titer 74 progressively decreased, becoming negative at 6 months of treatment (Fig. 1).

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