New and Emerging Therapy Cutaneous Infectious Diseases
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1 New and Emerging Therapy Cutaneous Infectious Diseases Ted Rosen, MD Professor of Dermatology Baylor College of Medicine Houston, Texas Disclosure S062 New and Emerging Therapies Conflict of Interest: Consultant for Medimetriks DRUG APPROVAL DATE Crisaborole (Eucrisa ) Dec 14, 2016 Dupilumab (Dupixent ) Mar 28, 2017 Guselkumab (Tremfya ) July 13, 2017 Brodalumab (Siliq ) Feb 15, 2017 Delafoxaciin (Baxdela ) June 19, 2017 Benznidazole (Not branded) Aug 29, 2017 Ozenoxacin (Xepi ) Dec 14, 2017 Oxymetazoline (Rhofade ) Jan 19, 2017 Avelumab (Bavencio ) Mar 23, 2017 H2O2 40% (Eskata ) Dec 17, 2017 HZ/suVaccine (Shingrix ) Oct 20, 2017 Blue Control Device July 13, 2017 dermapace Device Dec 28, 2017 DRUG APPROVAL DATE Crisaborole (Eucrisa ) Dec 14, 2016 Dupilumab (Dupixent ) Mar 28, 2017 Guselkumab (Tremfya ) July 13, 2017 Brodalumab (Siliq ) Feb 15, 2017 Delafoxaciin (Baxdela ) June 19, 2017 Benznidazole (Not branded) Aug 29, 2017 Ozenoxacin (Xepi ) Dec 14, 2017 Oxymetazoline (Rhofade ) Jan 19, 2017 Avelumab (Bavencio ) Mar 23, 2017 H2O2 40% (Eskata ) Dec 17, 2017 HZ/suVaccine (Shingrix ) Oct 20, 2017 Blue Control Device July 13, 2017 dermapace Device Dec 28, 2017 New Antibiotic: Delafloxacin (Baxdela ) Fluorinated quinolone MOA: Inhibits bacterial DNA replication Wide spectrum activity Gr+ and Gr- organisms Includes: MRSA, MSSA, Strep pyogenes, E. coli, Pseudomonas aeruginosa, Enterobacter, Klebsiella Approved ABSSSI in June, 2017 Available IV (unit dose 300mg) and Oral (unit dose 450mg) Ann Clin Microbiol Antimicrob. 2016;15(1):34-40 J Antimicrob Chemother. 2017;72: New Antibiotic: Delafloxacin (Baxdela ) Tested IV (300mg Q12h) or oral (450mg Q12h) (Oral followed 3 days IV loading dose) Active comparator: Vancomycin + Aztreonam N = 1510 in both studies combined Statistically non-inferior to combination AEs: Nausea, vomiting, diarrhea, headache, LFTs BLACK BOX: Tendinitis and tendon rupture, Peripheral neuropathy, CNS effects Ann Clin Microbiol Antimicrob. 2016;15(1):34-40 J Antimicrob Chemother. 2017;72:
2 Utility? Ozenoxacin (Xepi ): Approved Non-fluorinated quinolone Developed as 1% ointment for impetigo Dosed: BID x 5 days Wide spectrum activity against relevant Gram+ microbes, including MSSA, MRSA, mupirocin and ciprofloxacin resistant Staphylococci, Strep. Pyogenes Superior to placebo, and non-inferior retapamulin N=875 in two international studies, age > 2 months Future Microbiol. 2014;9(8 Suppl):S33-40 Future Microbiol. 2014;9(9): Skinmed Feb 1;15(1):57-59 Why Is New Impetigo Drug Important? High level resistance to mupirocin reported Conjugative (mupa) and nonconjugative (mupb) genes in Streptococci & Staphylococci confer resistance (encode for alternate isoleucyl-trna synthetases) Mupirocin resistance is a worldwide phenomenon: recent papers from China, France, India, Chicago Chagas Disease American trypanosomiasis T. cruzi Spread by reduviid bugs 10-30% risk progressive dis Megacolon Megaesophagus Cardiomyopathy Rarely dementia Microbiol Spectr Jan;6(1). doi: /microbiolspec Chagas Disease in USA? Rare indigenous cases 6 US Reduviid (Triatome) species T. gerstaeckeri, T. lecticularia, T. sanguisuga, T. indictiva, T. rubida, and T. protracta Survey pf 1510 vectors, 54.4% harbored T. cruzi, including subtypes known to cause Chagas disease Texas, LA, FL, NM, AZ Infect Genet Evol. 2017;58: Infect Genet Evol. 2017;58:
3 Benznidazole (No brand name) Rx children 2-12 (and adults) w/ Chagas disease (acute or chronic) Parasitological cure better: younger age and acute disease (vrs chronic) 60-90% Destroys parasite DNA 5-8 mg/kg/d (divided doses) x60d 12.5 and 100mg tablets Peripheral neuropathy Bone marrow depression Hypersensitivity reactions New Zoster Vaccine (Shingrix ) VZV subunit vaccine for shingles (not live attenuated) Glycoprotein E antigen + adjuvant TWO doses, 0, and then 2-6mo ACIP voted (8-7) to FAVOR new over existing HZ vaccine Indicated for > 50 EVEN if given prior vaccine, recommend to revaccinate 91-97% effective; ALL AGES; 4 year study (9 yr immunity) 88% effective reduction of PHN Use in HIV+ inconclusive, although appears positive N Engl J Med 2015; 372: N Engl J Med 2016; 375: Med Lett Drugs Ther. 2017;59: Hum Vaccin Immunother. 2017;13: Problem with HZ/su Vaccine Risk of AE s Injection site reactions Systemic side effects Either, within one week: 55-90% Grade 3 AE s: 5-17% Vaccine. 2018;36: J Infect Dis. 2017;216: Expert Rev Vaccines Jul;16(7):1-10 N Engl J Med. 2016;375: Emerging Therapies 3
4 J Am Acad Dermatol Jun;62(6): Br J Dermatol. 2017;176: Hyperthermia and Molluscum HPV Vaccine: Therapy for Common/Planter Warts? Small (n=21) Chinese prospective study Patented IR heating unit (We would use heating pad) 44 0 C (111 0 F) for 30 minutes, Weekly x 12 weeks 13 children, 8 sexually active adults (ages 21-28) Average # lesions = 59 (ie. Bad molluscum) 12/21 complete clearance 12 weeks (children and adults) Facial lesions more resistant Message: Thermotherapy non-invasive MC Rx Br J Dermatol. 2017;176: Acta Derm Venereol. 2015;95(8): HPV Vaccine: Therapy for Common/Planter Warts? Acta Derm Venereol. 2015;95(8): Clin Exp Dermatol Apr;42(3):
5 Louis Pasteur, 1884 When meditating on a disease, I never think of finding a remedy for it, but instead, a means of preventing it. Hurricane Harvey Hurricane Irma Hurricane Maria HOUSTON Hurricanes and Floods! Int J Environ Res Public Health Jun 3;14(6). pii: E594. Leptospirosis: Chemoprophylaxis Comprehensive review and meta-analysis Doxycycline most widely used drug Single dose 200mg OR 200mg/week for 2-4 weeks PRE-exposure dosage significantly reduces morbidity and mortality POST-exposure dosage trends toward benefit but often not statistically significant Int J Environ Res Public Health Jun 3;14(6). pii: E594. Flood coming? Take 200mg Doxycycline! Lancet Infect Dis Dec 8. pii: S (17) Road to my office! 5
6 Post-Exposure Bacterial Prophylaxis? French study; MSM who have condomless sexual contact All receiving PRE-exposure HIV prophylaxis w/ antiretroviral Randomized: Single dose doxycycline 200mg within 24 hours versus no antibiotic within 24 hours of sexual contact (n=116 per group) Followup: 10 months; Occurrence of chlamydia, GC, syphilis 22% presented with bacterial STD in prophylaxis group 42% presenting with bacterial STD in NO prophylaxis group (p =0.007) Adverse GI events: 53% PEP vs. 41% NO PEP (not stat signif) Lancet Infect Dis Dec 8. pii: S (17) Lancet Infect Dis Nov 6. pii: S (17) Lancet Infect Dis Dec;17(12): Lancet Feb 4;389(10068): New and Emerging Therapies for Cutaneous Infectious Disease THANKS FOR YOUR ATTENTION Ted Rosen, MD Baylor College of Medicine Houston, Texas J Infect Dis Dec 16;216(suppl_10):S957-S963 6
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