Antibiotic Use in the Emergency Department Fredrick M. Abrahamian, D.O., FACEP Associate Professor of Medicine UCLA School of Medicine Director of Education Department of Emergency Medicine Olive ViewView-UCLA Medical Center Sylmar, California Decisions in Selecting Antibiotics Knowledge of causative organism(s) Spectrum of activity Susceptibility pattern Patient factors  Community-acquired vs healthcare  Age, co-morbidities, pregnancy, etc  Drug-drug interactions Side-effects & “collateral damage” profiles Availability of drug & cost Chief complaint: “I think I was bitten by a spider.” spider.” 1 Prevalence of MRSA in Purulent Skin Infections, August 2008 (n=619) 38% 40% 44% 59% 63% 53% 72% 58% 48% 62% 57% 84% 56% MSSA 16% Preliminary data. EMERGEncy EMERGEncy ID Net. Organism by Infection Type MRSA MSSA Strep Other No growth 100% 80% 60% 40% 63 20% 42 38 Infected wound (n=55) Cellulitis (n=37) 0% Abscess (n=527) Preliminary data. EMERGEncy EMERGEncy ID Net. Should We Routinely Give Antibiotics After Abscess I&D? Many studies have shown no benefit However, studies have numerous limitations  Done before emergence of MRSA  NonNon-randomized design, small numbers  Selection bias, vague outcome definitions  NonNon-standardized drainage  Inappropriate antibiotic choices Hankin A, Everett WW. Ann Emerg Med. 2007;50:49-51. Duong M, et al. Ann Emerg Med. 2010;55:401-407. 2 3 Antibiotics & Abscesses Not for simple, 1st time, single, uncomplicated cases Indications for antibiotics:  Surrounding cellulitis  Signs of systemic toxicity  Immunocompromised host  HighHigh-risk locations (hands, face)  Recurrent abscesses or lack of response to I&D  Large abscess (≥ (≥ 5 cm) Duration: 5-10 days The Sanford Guide. 2010, page 49. Lee MC, et al. Pediatr Infect Dis J. 2004;23:123-127. Ruhe JJ, et al. Clin Infect Dis. 2007;44:777-784. Hepburn MJ, et al. Arch Intern Med. 2004;164:1669-1674. In vitro CACA-MRSA Antimicrobial Susceptibility Patterns Resistant: Variable :  All penicillins  Clindamycin: 94%  Cephalosporins (2% inducible) Susceptible:  Doxycycline: 100%  TMP/SMX  Levofloxacin: 45%  Rifampin  Erythromycin: 10%  Vancomycin Susceptibility patterns are  Linezolid dynamic & vary geographically Preliminary data. EMERGEncy EMERGEncy ID Net. Antimicrobial Therapy for CACA-MRSA TMP/SMX 1-2 DS tablets PO bid  High rates of susceptibility Clindamycin 300300-600 mg PO tid or qid  Can also be given IV (600(600-900 mg IV q8 hours)  Resistance rates to S. pyogenes is unknown  Do not use near term (2 weeks before EDC)  Covers staphylococci, streptococci, anaerobes  Inducible resistance Doxycycline or  Variable rates of susceptibility minocycline  Excellent tissue penetration 100 mg PO bid  Avoid during pregnancy or children ≤ 8 years  Risk-to-benefit ratio does not justify routine use Rifampin  Best reserved for decolonization purposes 300 mg PO bid  Numerous drugdrug-drug interactions 4 Antimicrobial Therapy for CACA-MRSA Vancomycin  Concern for emergence of VRE, VISA, VRSA 1 gram IV q12h  Slow bactericidal activity; poor tissue penetration Linezolid (Zyvox®) 600 mg IV/PO q12h Daptomycin (Cubicin®) 4-6 mg/kg IV q24h  Oral form 100% bioavailable  Different pharmacokinetics compared to Vanco  Inhibits toxin production  Complicated SSTIs, S. aureus bacteremia, right sided endocarditis due to MSSA & MRSA  Binds surfactant and gets inactivated Tigecycline  Also covers GramGram-negatives & anaerobes (TygacilTM)  Does not cover Pseudomonas; ± Proteus st 1 dose 100 mg  Complicated SSTIs, intra--abdominal infections, intra IV then 50 mg CAP (not for DRSP) IV q12h Potential Future MRSA Therapies QuinupristinQuinupristindalfopristin (Synercid®) IV Two antibiotics acting synergistically Protein synthesis inhibitor Dalbavancin Telavancin Oritavancin IV Cell wall synthesis inhibitors Ceftaroline Ceftobiprole IV Cephalosporins with MRSA activity Iclaprim IV/PO Dihydrofolate reductase inhibitor Boucher HW, et al. Clin Infect Dis. 2009;48:12009;48:1-12. Potential Future MRSA Therapies Tomopenem PZPZ-601 IV Carbapenems with MRSA activity RXRX-1741 PO 2nd generation oxazolidinone TDTD-1792 IV Multivalent cephalosporin PTKPTK-0796 IV/PO Protein synthesis inhibitor RXRX-3341 IV Quinolone with MRSA activity Boucher HW, et al. Clin Infect Dis. 2009;48:12009;48:1-12. 5 MRSA & Cellulitis Role of MRSA not clear Cellulitis with purulence:  MRSA 47%  MSSA 34%  Streptococci 13% Expert recommendation cover for MRSA TMP/SMX DS 11-2 tablets bid plus Cephalexin 500 mg qid Clindamycin 300 mg qid Moran GJ, et al. N Engl J Med. 2006;355:666-674. Complicated Infections More likely mixed aerobic & anaerobic infections Consider in patients with:  Chronic infections  PeriPeri-rectal infections (consider deep abscess)  Wounds involving lower extremities (e.g., feet)  Vascular insufficiency (venous stasis ulcers)  Immunocompromising conditions (e.g., DM)  BiteBite-related wounds, IV drug use  PostPost-operative wounds, infected burns Abrahamian FM, et al. Infect Dis Clin North Am. Am. 2008;22:892008;22:89-116. 6 Complicated Infections Knowledge of emerging resistance & spectrum of activity of antimicrobials Cefoxitin B. fragilis resistance Ampicillin/sulbactam E. coli resistance Clindamycin No Gram neg. coverage Fluoroquinolones E. coli resistance Daptomycin No Gram neg. & anaerobic coverage Tigecycline Does not cover Pseudomonas Vancomycin, Linezolid No Gram neg. & anaerobic coverage Vancomycin & Clinical Uses Bactericidal for most gram-positive organisms Primarily for treatment of MRSA infections Also for PCN-R S. pneumoniae & C. difficile Uses: My opinion: Do not advocate  SSTIs 1 dose IV & dispo home on  Pneumonia PO meds  Bacteremia  Endocarditis, meningitis, osteomyelitis  Hospital-acquired infections  Severe C. difficile infection Vancomycin & New Problems Variable tissue penetration Slow bactericidal activity Increasing MBCs and MICs among staphylococci  Failure rate increases with MICs ≥ 1.5 mg/L Emergence of hVISA  Not detected by standard susceptibility testing Not best for MSSA endocarditis, bacteremia, or pneumonia Lodise TP, et al. Antimicrob Agents Chemother. 2008;52:3315-3320. Maor Y, et al. Clin Infect Dis. 2009;199:619-624. Chang FY, et al. Medicine. 2003;82:333-339. 7 New Adult Vancomycin Dosing Regimen A loading dose of 25-30 mg/kg actual body weight (ABW) over 2 hrs for critically ill patients Subsequent doses: 15-20 mg/kg ABW q8-12 hrs Indicated for complicated infections:  Bacteremia  Endocarditis  Osteomyelitis  Meningitis  Hospital-acquired pneumonia Rybak M, et al. Am J Health Syst Pharm. 2009;66:82-98. ClenchedClenched-Fist Injury 8 What Works on Pasteurella or E corrodens Yes No Penicillin, amoxicillin, ampicillin 1st gen. cephalosporins 2nd, 3rd, 4th gen. cephalosporins Dicloxacillin Carbapenems Erythromycin Fluoroquinolones Nafcillin Doxycycline Clindamycin Azithromycin Aminoglycosides Trimethoprim/sulfamethoxazole Metronidazole Abrahamian FM, et al. Animal & Human Bites. Therapy of Infectious Diseases, 2003. Abrahamian FM, et al. Bites. Infectious Diseases, 3rd ed. 2004. Empiric Abx for Dog, Cat, & Human Bite Infections Antibiotic (s) Past/Eikenella Staph/Strep Anaerobes AmoxAmox-clav/Ampclav/Amp-sulb + + + +/+/- Cefoxitin + + Carbapenems + + + Azithromycin + + +/+/- Levofloxacin + + +/+/- Moxifloxacin + + + PCN + cephalexin + + +/+/- Cipro + Clinda + + + TMP/SMX + Clinda + + + Abrahamian FM, et al. Animal & Human Bites. Therapy of Infectious Diseases, 2003. Abrahamian FM, et al. Bites. Infectious Diseases, 3rd ed. 2004. Forbes CD, et al. A Color Atlas & Text of Clinical Medicine, 1993. 9 Necrotizing Skin Infections Various classification systems Hemodynamic stabilization plus antibiotics: ntibiotics:  Vancomycin plus clindamycin plus piperacillin/tazobactam  Linezolid plus piperacillin/tazobactam Early surgical consultation / exploration Hyperbaric oxygen therapy never 1st line treatment Anaya DA, et al. Clin Infect Dis. 2007;44:705-710. Microbiology of Diabetic Foot Infections (DFIs) Dependent on various factors:  Chronicity  Severity  Prior antibiotic exposure Current view of chronic or mod-severe DFIs:  Symbiotic pathogenic bacterial community  Biofilm formation Dowd SE, et al. PLoS ONE. 2008;3:e3326. 10 Predominant Aerobes in DFIs (406 pts) Staphylococcus species MSSA MRSA 81% 40% 12% S. epidermidis Streptococcus species Enterococcus species Enterobacteriaceae Corynebacterium species Pseudomonas aeruginosa 20% 41% 36% 35% 28% 9% Citron DM, et al. J Clin Micrbiol. 2007;45:2819-2828. Antimicrobial Therapy of DFIs Mild infection: Ulcer < 2 cm superficial inflammation Micro: Staphylococci (& MRSA) & streptococci Pen VK + TMP/SMX DS (minocycline) Oral 2nd/3rd gen. ceph. + TMP/SMX DS (minocycline) Fluoroquinolone + TMP/SMX DS (minocycline) The Sanford Guide: 2010, page 14. Other options: Diclox. or Cephalexin ± TMP/SMX DS (doxy, minocycline) Moderate infection: Ulcer > 2 cm of inflammation with extension to fascia Micro: Staph, strep, gram-negatives, & anaerobes; less likely Pseudomonas TMP/SMX DS + Amoxicillin/clavulanate (2 gm bid) Fluoroquinolone + Linezolid May need adding metronidazole The Sanford Guide: 2010, page 14. Other options: Clindamycin + Ciprofloxacin Ceftriaxone ± Metronidazole ± Vancomycin Ertapenem ± Vancomycin 11 Severe: Extensive inflammation, systemic toxicity Staph, strep, gram-negatives (Pseudomonas), anaerobes Vancomycin + ß-lactam/ß-lactamase inhibitor Pip/tazo, Ticarcillin/clav: Cover Pseudomonas Amp/sulbactam: Does not cover Pseudomonas Vancomycin + Metronidazole + Fluoroquinolone Ciprofloxacin most active against Pseudomonas Vancomycin + Carbapenem Meropenem, Imipenem, Doripenem: + Pseudomonas Ertapenem: Does not cover Pseudomonas The Sanford Guide: 2010, page 14. Neutropenia & Fever Bacterial Microbiology Majority: Gram-positive organisms  Staphylococcus & streptococcus species  Enterococcus faecalis / faecium  Corynebacterium species (PICC lines) Gram-negative organisms  E. coli, Klebsiella species, P. aeruginosa Anaerobes uncommon, unless:  Oral mucositis, perirectal, intra-abd source Hughes WT, et al. Clin Infect Dis. 2002;34:730-751. Neutropenic Fever: Decision-Making Process High risk (Consider age ≤ 16 high risk) Admit IV antibiotics No Single vs. dual therapy? Decide if need to add Vancomycin & Metronidazole Low risk Outpatient therapy Yes  Always involve Heme/Onc  Cipro plus amox-clav Hughes WT, et al. Clin Infect Dis. 2002;34:730-751. 12 Choices of IV Antibiotics Monotherapy (uncomplicated) Cefepime Ceftazidime Imipenem Meropenem Dual Therapy (complicated i.e., ICU admission) Piperacillin-tazobactam Ticarcillin-clavulanate Cefepime or Ceftazidime Imipenem or Meropenem plus Gentamicin, Tobramycin, or Amikacin Hughes WT, et al. Clin Infect Dis. 2002;34:730-751. Bow EJ, et al. Clin Infect Dis. 2006;43:447-450. Additional Antibiotics Add vancomycin if:  Septic shock  Catheter-related infection (bacteremia, cellulitis)  Known history of MRSA  On prophylactic therapy with quinolones Add metronidazole if using cefepime/ceftazidime:  Oral mucositis  Perirectal infection  Intra-abdominal infection Acute Otitis Media in Children Age Certain Dx Uncertain Dx < 6 months Antibiotics 6 mo – 2 yrs Antibiotics Antibiotics Abxs if severe Observe if not ≥ 2 yrs Abxs if severe Observe if not Observe Severe illness is defined as temperature ≥ 39°C in the past 24 hours or moderate-severe otalgia. Clinical Practice Guidelines. Pediatrics. 2004;113:14512004;113:1451-1465. Spiro DM, et al. JAMA. 2006;296:12352006;296:1235-1241. Stevanovic T, et al. Int J Pediatr Otorhinolaryngol. 2010;74:9302010;74:930-933. 13 Urinary Tract Infections Resistance correlates with clinical failure Acute cystitis, consider:  Nitrofurantoin 100 mg PO bid x 5 days Treat acute cystitis in pregnant patients for 7 days Outpatient pyelonephritis duration of therapy:  Cipro x 7 days (Levofloxacin 750 mg x 5 days)  Amox/clavulanate, cephalosporins x 14 days Obtain urine cultures for all patients with pyelo Gupta K, et al. Arch Intern Med. 2007;167:2207-2212. The Sanford Guide: 2010, pages 29-30. Pharyngitis: Modified Centor Criteria Criteria Temperature ≥ 38ºC Absence of cough Swollen, tender anterior cervical nodes Tonsillar swelling or exudate Age  3-14 years  15-44 years  ≥ 45 years Points 1 1 1 1 1 0 -1 McIsaac WJ, et al. JAMA. 2004;291:15872004;291:1587-1595. Pharyngitis: Modified Centor Criteria Score Risk of Strep Therapy ≤0 1% - 2.5% 1 5% - 10% 2 11% - 17% 3 28% - 35% Culture Treat only + cultures ≥4 51% - 53% Treat with antibiotics No further testing or antibiotic McIsaac WJ, et al. JAMA. 2004;291:15872004;291:1587-1595. 14 Acute Streptococcal Pharyngitis Treatment Pearls Penicillin is the drug of choice  Benzathine PCN G 1.2 million units IM x 1  Be cautious of mixture formulations Extended-release once daily amoxicillin Reports of macrolide-resistant strep Treatment up to 9 days after onset of Sxs is still effective for prevention of rheumatic fever Bisno AL, et al. Clin Infec Dis. 2002;35:1132002;35:113-125. Green M, et al. Antimicrob Agents Chemother. Chemother. 2004;48:4732004;48:473-476. Take Home Points MRSA common in purulent skin infections High dose vanco for complicated infections Avoid routine use of rifampin 1st gen. ceph. inactive against Pasteurella Neutropenia + ICU = Dual anti-pseudomonal Treat acute cystitis in pregnancy for 7 days AOM ≥ 6 mo: Observe non-severe illness Pharyngitis: Use modified Centor criteria 15