Antibiotic Updates: Part II 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
Discussion Points Intra-abdominal infections Febrile neutropenia Urinary tract infections Clostridium difficile infection Intra-Abdominal Infections In general, direct empiric therapy towards: Enterobacteriaceae & anaerobes Anaerobic therapy not indicated for acute uncomplicated cholecystitis Reserve anti-pseudomonal coverage for: Severe infections, immunocompromised, or advanced age No need for routine MRSA coverage Intra-Abdominal Infections Ampicillin-sulbactam not recommended High rates of resistance among E. coli Cefotetan & clindamycin not recommended High rates of resistance among B. fragilis Reserve aminoglycosides for patients allergic to ß-lactams & quinolones 2
Intra-Abdominal Infections Mild diverticulitis, drained peri-rectal abscess TMP/SMX DS plus Metronidazole Amoxicillin/clavulanate (2 grams bid) Cipro or Levofloxacin plus Metronidazole Moxifloxacin Treat for 7-10 days 4-day course of therapy with source control for complicated infections has been advocated N Engl J Med. 2015;372:1996-2005. [Shorter course of therapy] Antimicrob Agents Chemother. 2007;51:1649-55. [Anaerobes susceptibility trends] Community-Acquired Intra-Abdominal Infections in Adults Mild-to-Moderate Severity Cefoxitin Moxifloxacin Ticarcillin / clavulanic acid Ertapenem Tigecycline Cefazolin, cefuroxime, ceftriaxone, or cefotaxime plus metronidazole Ciprofloxacin or levofloxacin plus metronidazole Community-Acquired Intra-Abdominal Infections in Adults High Risk or Severe Imipenem-cilastatin Meropenem Doripenem Piperacillin-tazobactam Cefepime or ceftazidime plus metronidazole Ciprofloxacin or levofloxacin plus metronidazole 3
Empiric Rx of Neutropenic Fever Piperacillin-tazobactam Imipenem; Meropenem; Doripenem Cefepime Ceftazidime Poor activity against many gram-positives Penicillin-allergy: Ciprofloxacin plus Clindamycin Aztreonam plus Vancomycin J Clin Oncol. 2018. [Febrile neutropenia guideline update] Clin Infect Dis. 2011;52:e56-e93. [IDSA guidelines] Additional Antibiotics Add vancomycin if: Hemodynamic instability Pneumonia Catheter-related infection Skin & soft-tissue infection Known history of MRSA Add metronidazole if using cefepime/ceftazidime: Oral mucositis Perirectal & intra-abdominal infections J Clin Oncol. 2018. [Febrile neutropenia guideline update] Clin Infect Dis. 2011;52:e56-e93. [IDSA guidelines] Acute Cystitis Amoxicillin & ampicillin High rates of E. coli resistance Short half-life; rapidly excreted Lower eradication rates Amox-clavu (58%) vs. Ciprofloxacin (77%) Cefpodoxime (82%) vs. Ciprofloxacin (93%) Not very effective in clearing vaginal E. coli J Clin Microbiol. 2015;53:2686-92. JAMA. 2012;307:583-89. [Cefpodoxime for cystitis] 4
Acute Cystitis Nitrofurantoin 100 mg bid x 5 days TMP/SMX DS bid x 3 days Fosfomycin 3 grams single dose Avoid fluoroquinolones as first-line agents Avoid oral ß-lactams as first-line agents Avoid amoxicillin & ampicillin JAMA. 2012;307:583-89. [Cefpodoxime for cystitis] Antimicrob Agents Chemother. 2012;56:2181-3. [Resistance trends] Clin Infect Dis. 2011;52:e103-e20. [IDSA UTI guidelines] Arch Intern Med. 2007;167:2207-12. [Short course nitrofurantoin] Nitrofurantoin 100 mg PO bid x 5 days Efficacy compared to TMP/SMX x 3 days Not for Proteus or Pseudomonas; ± Klebsiella Category B; not near term (hemolytic anemia) Not in children 12 years Not for pyelonephritis Interaction with Mg-containing antacids Arch Intern Med. 2007;167:2207-12. [TMP/SMX vs. Nitrofurantoin] Acute Pyelonephritis Obtain urine culture & susceptibility testing Oral fluoroquinolones x 5-7 days No difference in 7 vs. 14 day course of Cipro Levofloxacin 750 mg FDA-approved for 5 days Other oral agents longer duration: 14 days Other agents: 3 rd /4 th generation cephalosporins; anti-pseudomonal penicillins; carbapenems Emerg Infect Dis. 2016;22:1594-1603. [Resistant E. coli & pyelonephritis] Clin Infect Dis. 2011;52:e103-e20. [IDSA UTI guidelines] 5
Complicated UTIs Ceftolozane-tazobactam Also for IAB infections with metronidazole 1.5 gram IV over 1 hr q8 hrs if CrCl > 50 Ceftazidime-avibactam Also for IAB infections with metronidazole 2.5 grams IV over 2 hrs q8 hrs if CrCl > 50 Meropenem-vaborbactam 4 grams IV over 3 hrs q8 hrs if CrCl 50 C. difficile: Assessing Severity Non-severe Leukocyte count <15,000 cells/ml Creatinine <1.5 mg/dl Severe Leukocyte count 15,000 cells/ml Creatinine >1.5 mg/dl Fulminant Hypotension, shock, ileus, megacolon Clin Infect Dis. 2018. [Practice guidelines] Am J Gastroenterol. 2013;108:478-98. [Practice guidelines] Infect Control Hosp Epidemiol. 2010;31:431-55. [Practice guidelines] C. difficile Antimicrobial Therapy Initial episode, non-severe Initial episode, severe Initial episode, fulminant Vancomycin 125 mg qid Fidaxomicin 200 mg bid Metronidazole 500 mg tid Vancomycin 125 mg qid Fidaxomicin 200 mg bid Vancomycin 500 mg qid plus Metronidazole 500 mg IV tid Clin Infect Dis. 2018. [Practice guidelines] Am J Gastroenterol. 2013;108:478-98. [Practice guidelines] Infect Control Hosp Epidemiol. 2010;31:431-55. [Practice guidelines] 6
C. difficile Therapy Chance of 1 st recurrence: 10-20% Chance of recurrence after 1 st : 40-65% Fidaxomicin Minimal systemic absorption Bezlotoxumab (in conjunction with antibiotic) Human monoclonal antibody; binds to toxin B Single dose of 10 mg/kg IV over 1 hr N Engl J Med. 2017;376:305-17. [C.diff & bezlotoxumab] Clin Infect Dis. 2012;55(S2):S154-61. [C.diff & fidaxomicin] Take Home Points Anti-pseudomonal agents: Avoid routine use for intra-abdominal infections Initiate in febrile neutropenic patients Do not use nitrofurantoin for pyelonephritis Severity assessment of C. difficile infection: Utilize WBC count & creatinine 7