Antibiotic Updates: Part I

Transcription

1 Antibiotic Updates: Part I Fredrick M. Abrahamian, DO, FACEP, FIDSA Health Sciences Clinical Professor of Emergency Medicine David Geffen School of Medicine at UCLA Los Angeles, California Financial Disclosures I have the following financial relationships to disclose: Commercial Interest What Was Received Role Allergan, Merck, Grifols, Seqirus Honoraria Speaker Paratek, Melinta, Nabriva Consulting Fee Consultant I do not intent to discuss an unapproved or investigative use of a commercial product or device in my presentation. Objectives Develop a basic understanding of the treatment of commonly encountered infectious diseases in the ED Develop an understanding of the limitations of common antibiotics used in the ED Become familiar with common drug interactions associated with antibiotics Understand the role of newer antibiotics in the treatment of infections in the ED 1

2 Discussion Points Recent FDA-approved antibiotics Decisions in selecting antibiotics Skin & soft-tissue infections Gonococcal infections Recent FDA-Approved Antibiotics 2014 Dalbavancin Acute bacterial skin & skin structure infections Oritavancin Acute bacterial skin & skin structure infections Tedizolid phosphate Acute bacterial skin & skin structure infections Ceftolozane-tazobactam Complicated intra-abdominal infections & UTIs 2015 Ceftazidime-avibactam Complicated intra-abdominal infections & UTIs 2016 Bezlotoxumab (human monoclonal antibody) Recurrent C. difficile infection 2017 Delafloxacin Acute bacterial skin & skin structure infections Meropenem-vaborbactam Complicated urinary tract infections 2

3 Decisions in Selecting Antibiotics Knowledge of causative organism(s) Resistance patterns Spectrum of activity Patient factors Community vs healthcare Age, co-morbidities, pregnancy Side-effects Drug-drug interactions Availability of drug & cost Skin & Soft-Tissue Infections TMP/SMX 1-2 DS PO bid Clindamycin mg PO tid Highly active against MRSA Clinically considered not effective for S. pyogenes Can also be given IV ( mg IV q8 hours) Covers staphylococci, streptococci, anaerobes Variable susceptibility (inducible resistance) Doxycycline or minocycline 100 mg PO bid Rifampin 300 mg PO bid Variable susceptibility Excellent tissue penetration Avoid during pregnancy or children 8 years Rapid emergence of resistance when used alone Penetrates mucosal tissue; best for decolonization N Engl J Med. 2016;374: [TMP/SMX vs placebo] Clin Infect Dis. 2016;62: [TMP/SMX vs Clindamycin] N Engl J Med. 2015;372: [TMP/SMX vs Clindamycin] Trimethoprim/Sulfamethoxazole Standard dose (160/800 mg) sufficient Category D Hyperkalemia with ACE inhibitors Thrombocytopenia with thiazide diuretics Elevates digoxin & phenytoin levels Potentiates effects of oral hypoglycemics Methotrexate & marrow suppression Increases activity of warfarin Antimicrob Agents Chemother. 2011;55: [TMP/SMX dose] 3

4 Warfarin & Antibiotics Interactions with Warfarin: TMP/SMX Metronidazole Fluoroquinolones (dysglycemia) Doxycycline (minor) Dicloxacillin (reduces INR) JAMA. 2015;314: [Dicloxacillin & INR] Clin Infect Dis. 2013;57: [Fluoroquinolones & blood glucose] Arch Intern Med. 2010;170: [TMP/SMX & warfarin] Rifampin & Drug Interactions Inducer of cytochrome-p450 system Decreases the effect or levels of: ß-blockers, digoxin, ACE-inhibitors Diltiazem, nifedipine Corticosteroids, methadone Oral anticoagulants Phenytoin, sulfonylureas Oral contraceptives Obstet Gynecol. 2001;98: [OCPs & antibiotics] Vancomycin 1 gram IV q12h Concern for emergence of VRE, VISA, VRSA Slow bactericidal activity; poor tissue penetration Linezolid 600 mg IV/PO q12h Oral form 100% bioavailable Different pharmacokinetics compared to Vanco Inhibits toxin production Daptomycin 4-6 mg/kg IV q24h Complicated SSTIs, S. aureus bacteremia, right sided endocarditis due to MSSA & MRSA Binds surfactant and gets inactivated Tigecycline 1 st dose 100 mg IV then 50 mg IV q12h Also covers Gram-negatives & anaerobes Does not cover Pseudomonas; ± Proteus Complicated SSTIs, intra-abdominal infections, CAP (not for DRSP) 4

5 Other FDA-Approved Antimicrobial Therapies for MRSA SSTIs Telavancin IV Lipoglycopeptide 10 mg/kg daily over 1 hr Ceftaroline IV Cephalosporins with MRSA activity 600 mg q12 hrs over 5-60 min Other Antimicrobials for MRSA SSTIs Dalbavancin Oritavancin Tedizolid Delafloxacin IV IV PO / IV PO / IV Lipoglycopeptide 1500 mg over 30 min Lipoglycopeptide Single dose of 1200 mg over 3 hrs Oxazolidinone 200 mg PO once daily for 6 days 200 mg IV infusion over 1 hr Fluoroquinolone 450 mg PO q12 hrs 300 mg IV over 1 hr q12 hrs 5

6 Drug Streptococci, Group A (B,C,G) MSSA MRSA Penicillin Dicloxacillin Amoxicillin Amox/clav Cephalexin Erythromycin +/- +/- - Azithromycin +/- + - Doxycycline +/- +/- + Minocycline TMP/SMX Clindamycin Ciprofloxacin +/- + - Levo / Moxifloxacin Complicated Infections More likely mixed aerobic & anaerobic infections Consider in patients with: Bite-related wounds Chronic infected wounds Deep peri-rectal infections Vascular insufficiency (venous stasis ulcers) Immunocompromising conditions Infected burns Deep post-operative intra-abdominal infections Infect Dis Clin North Am. 2008;22: Spectrum of Activity Vancomycin Ceftaroline Clindamycin Ertapenem Linezolid Daptomycin Tigecycline No Gram neg. & anaerobic coverage Does not cover Pseudomonas No Gram neg. coverage Does not cover Pseudomonas No Gram neg. & anaerobic coverage No Gram neg. & anaerobic coverage Does not cover Pseudomonas 6

7 Gonococcal Infections % Cefixime MIC 0.25, N Engl J Med. 2012;366: Cefixime MICs & Outcomes Retrospective cohort study Culture-positive N. gonorrhea infections Reduced susceptibility MIC 0.12 μg/ml 291 culture-positive cases; 133 returned 6.77% overall rate of clinical failure 25% clinical failure with cefixime MIC % clinical failure with cefixime MIC <0.12 Relative risk of JAMA. 2013;309: Treatment of Uncomplicated Gonococcal Infections of the Cervix, Urethra, & Rectum Ceftriaxone 250 mg IM x 1 PLUS Azithromycin 1 gram PO x 1 or Doxycycline 100 mg PO bid x 7 days Azithromycin preferred over doxycycline MMWR. 2015;64: [Practice guidelines] NEJM. 2015;373: [Azithro vs Doxy for Chlamydia] MMWR. 2012;61:

8 Gonorrhea Treatment Dose ceftriaxone at 250 mg Safeguard against decreased susceptibility Effective against pharyngeal infection; often asymptomatic, difficult to detect, & eradicate Dual treatment recommended whether or not chlamydial infection has been ruled out MMWR. 2015;64: [Practice guidelines] MMWR. 2012;61: Gonorrhea Treatment Regimens If ceftriaxone not available: Cefixime 400 mg PO x 1 If severe cephalosporin allergy: Gentamicin 240 mg IM x 1 or Gemifloxacin 320 mg PO x 1 PLUS Azithromycin 2 grams PO x 1 Monotherapy with azithromycin is no longer recommended MMWR. 2015;64: [Practice guidelines] Take Home Points TMP/SMX: Hyperkalemia with ACE inhibitors Increases activity of warfarin Utilize dual therapy for treatment of gonorrhea: Ceftriaxone 250 mg IM x 1 PLUS Azithromycin 1 gram PO x 1 or Doxycycline 100 mg PO bid x 7 days No azithromycin monotherapy 8