1071. Efficacy of Anti-Staphylococcal Lysin, LSVT-1701, in Combination with Daptomycin in Experimental Left-Sided Infective Endocarditis (IE) Due to Methicillin-Resistant Staphylococcus aureus (MRSA)

Background Anti-staphylococcal phage lysins, such as LSVT-1701, represent important candidate adjunctive agents against invasive MRSA infections because of both their microbicidal and anti-biofilm properties. We, thus, sought to examine the in vivo efficacy of LSVT-1701 combination with daptomycin, a standard-of-care anti-MRSA agent with proven efficacy against bacteremia and IE in humans. Methods We utilized the rabbit model of aortic valve infective endocarditis (using the prototype MRSA strain, MW2) to examine the combined efficacy of LSVT-1701 plus daptomycin. We examined microbiologic outcomes in distinct target tissues (cardiac vegetations, spleen and kidney) in this model, as well as the pharmacokinetic and pharmacodynamic drivers and target attainment values most predictive of treatment outcomes. LSVT-1701 was given at two dose-regimens (32.5 mg/kg and 50 mg/kg) with different dose-durations (single dose vs daily dose for 2 d vs daily dose for 4 d); daptomycin was administered in combination with daptomycin at a sub-lethal daily dose of 4 mg/kg for 4 d to maximize potential synergistic interaction outcomes. Results The Table below shows all LSVT-1701 regimens in combination with daptomycin significantly reduced MRSA burdens in all target tissue as compared to untreated controls. The reduction in MRSA counts was statistically significant in instances of both increasing LSVT-1701 dose level (i.e., single doses of 50 mg/kg vs 32.5 mg/kg iv), as well as increased numbers of lysin doses (i.e., four daily doses vs a single-dose or two daily-doses) in combination with daptomycin. Of note, both the LSVT-1701 50 mg/kg and 32.5 mg/kg daily dose-strategies given for four days in combination with daptomycin sterilized all target tissues (i.e., quantitative cultures ≤ the lower limit of detection of 1 log10 CFU/g. tissue). MRSA bio-burdens in blood, vegetations, kidneys and spleen in rabbit IE model Conclusion LSVT-1701 administered at 32.5 or 50 mg/kg in a 4 d daily-dose regimen in combination with daptomycin resulted in microbiologic sterilization of all target organs in this MRSA IE model. These data support further clinical development of LSVT-1701 for the treatment of MRSA endovascular infections including IE. Disclosures David Huang, MD, PhD, Lysovant (Consultant) Eric Gaukel, BS, Lysovant (Employee) Katyna Borroto-Esoda, PhD, Lysovant (Consultant) Arnold Bayer, MD, PhD, Lysovant (Grant/Research Support)

Efficacy of Once Daily versus Divided Daily Administration of Low Daily Dosage (15 mg/Day) of Methimazole in the Induction of Euthyroidism in Graves’ Hyperthyroidism: A Randomized Controlled Study

Background. Previous studies used unequal or high daily dosages of methimazole (MMI) to compare the efficacy of once daily dose regimen (OD-MMI) with that of divided daily doses regimen (DD-MMI) in inducing euthyroidism. Objectives. To compare the efficacy of OD-MMI to that of DD-MMI using low daily dosage of MMI in inducing euthyroidism. Methods. Fifty patients with clinically nonsevere Graves’ hyperthyroidism were randomized to be treated with 15 mg/day OD-MMI or 15 mg/day DD-MMI. Results. 21 cases (84%) in OD-MMI and 23 cases (92%) in DD-MMI were eligible for analyses. During the treatment, there was no difference in baseline characteristics, serum FT3 and FT4 reductions, and cumulative rate of achieving euthyroidism (4.8% versus 4.3%, 28.6% versus 34.8%, 71.4% versus 82.6%, and 85.7% versus 87.0% at 2, 4, 8, and 12 weeks, resp.) between both regimens. Hypothyroidism developed in DD-MMI significantly more than in OD-MMI (17.4% versus 0%, p<0.05). Conclusions. Treatment with MMI at a low daily dosage of 15 mg/day OD-MMI is as effective as DD-MMI in the reduction of serum thyroid hormone levels and induction of euthyroidism. The OD-MMI regimen is preferable to the DD-MMI regimen in the treatment of clinically nonsevere Graves’ hyperthyroidism. This trial is registered with Thai Clinical Trials Registry: TCTR20170529001.

Aminoglycoside antibiotics and postantibiotic effect

Man has been fighting diseases for centuries. One of the major battles is against microorganisms and diseases they cause. A health education course was organized on prescribing aminoglycoside antibiotics and postantibiotic effect. The aim of the course was to change the prescription habits in our colleagues. The postantibiotic effect of aminoglycoside antibiotics as well as impact of subinhibiting doses on duration of postantibiotic effect requires modification of previous therapeutic protocols. Single daily dose has the same or even greater effect than multiple daily doses. The toxicity of aminoglycosides is not increased and remains the same or smaller in single daily regimens. Results The single daily dose regimen of aminoglycosides has been used in 63.6% of cases in Clinic for Infectious Diseases of the Clinical Center of Novi Sad, 41.2% in Outpatient Health Care Center of Novi Sad "Liman" and this regimen has not been used in General Practice Department, Children's Health Care Department and Ear, Nose and Throat Clinic at all. The twice daily regimen has been used instead. Conclusion Doctors are aware of the postantibiotic effect, but vast majority are still bound to their old habits in regard to prescribing antibiotics. Our educational course failed to achieve its goal.

Cefcanel Daloxate versus Penicillin in Acute Streptococcal Pharyngotonsillitis

Objective: To determine the efficacy, safety and tolerance of cefcanel daloxate and phenoxymethylpenicillin (PcV) in the treatment of acute pharyngotonsillitis caused by beta-hemolytic streptococci group A (bhsga).Patients and Methods: Randomized, double-blind, multicentre study with subjects randomized 1:1:1:1 to four parallel treatment groups: cefcanel daloxate 150 mg bid, 300 mg bid, 600 mg daily and PcV 300 mg tid. Patients were treated for 10 days with clinical, bacteriological and safety evaluation at inclusion, during therapy (day 5), early after completion of therapy (day 14) and two weeks later (day 28).Results: Of 340 subjects enrolled, 324 were valid for safety analysis and 249 for efficacy analysis. At the short term visit, clinical cure rates for cefcanel daloxate 300 mg bid and PcV groups were similar at approximately 70%. The cure rates for cefcanel daloxate 150 mg bid and 600 mg daily were significantly worse at 57.4 and 54.4%. Approximately 80% of all pretherapy throat swabs grewbhsga. Allbhsgawere susceptible or intermediately susceptible to PcV and cefcanel. The bacterial elimination rate for cefcanel daloxate was 82.8% and for PcV it was 89.8%. The elimination rate was significantly lower in the cefcanel daloxate 150 mg bid and 600 mg daily groups. The clinical cure rates and the bacteriological elimination rates increased by about 10% for cefcanel daloxate 300 mg bid and the PcV groups at the last valid visit and remained significantly better than the other two cefcanel daloxate doses. Adverse events were not significantly different among the four treatment groups.Conclusions: Cefcanel daloxate 300 mg bid was as effective and as well tolerated as PcV 300 mg tid in the treatment of acute pharyngotonsillitis. A lower dose or once-daily dose regimen of cefcanel daloxate was not as effective clinically or bacteriologically.