Antibiotic Use in the Emergency Department

Transcription

1 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 View-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: II think I was bitten by a spider. 1

2 Prevalence of MRSA in Purulent Skin Infections, August 2008 (n=619) 38% 59% 40% 44% 53% 63% 58% 48% 57% 72% 56% 62% 84% MSSA 16% Preliminary data. EMERGEncy ID Net. Organism by Infection Type MRSA MSSA Strep Other No growth 100% 80% 60% 40% 20% % Abscess (n=527) Infected wound (n=55) Cellulitis (n=37) Preliminary data. 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 Non-randomized design, small numbers Selection bias, vague outcome definitions Non-standardized drainage Inappropriate antibiotic choices Hankin A, Everett WW. Ann Emerg Med. 2007;50: Duong M, et al. Ann Emerg Med. 2010;55:

3 3

4 Antibiotics & Abscesses Not for simple, 1 st time, single, uncomplicated cases Indications for antibiotics: Surrounding cellulitis Signs of systemic toxicity Immunocompromised host High-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: Ruhe JJ, et al. Clin Infect Dis. 2007;44: Hepburn MJ, et al. Arch Intern Med. 2004;164: In vitro CA-MRSA Antimicrobial Susceptibility Patterns Resistant: All penicillins Cephalosporins Susceptible: TMP/SMX Rifampin Vancomycin Linezolid Variable : Clindamycin: 94% (2% inducible) Doxycycline: 100% Levofloxacin: 45% Erythromycin: 10% Susceptibility patterns are dynamic & vary geographically Preliminary data. EMERGEncy ID Net. Antimicrobial Therapy for CA-MRSA TMP/SMX 1-22 DS tablets PO bid Clindamycin mg PO tid or qid High rates of susceptibility Resistance rates to S. pyogenes is unknown Do not use near term (2 weeks before EDC) Can also be given IV ( mg IV q8 hours) Covers staphylococci, streptococci, anaerobes Inducible resistance Doxycycline or minocycline 100 mg PO bid Variable rates of susceptibility Excellent tissue penetration Avoid during pregnancy or children 8 years Rifampin 300 mg PO bid Risk-to-benefit ratio does not justify routine use Best reserved for decolonization purposes Numerous drug-drug interactions 4

5 Antimicrobial Therapy for CA-MRSA Vancomycin 1 gram IV q12h Linezolid (Zyvox ) 600 mg IV/PO q12h Daptomycin (Cubicin ) 4-66 mg/kg IV q24h Tigecycline (Tygacil TM ) st dose 100 mg IV then 50 mg IV q12h 1 st Concern for emergence of VRE, VISA, VRSA Slow bactericidal activity; poor tissue penetration 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 Also covers Gram-negatives & anaerobes Does not cover Pseudomonas; ± Proteus Complicated SSTIs, intra-abdominal abdominal infections, CAP (not for DRSP) Potential Future MRSA Therapies Quinupristin- dalfopristin (Synercid ) Dalbavancin Telavancin Oritavancin Ceftaroline Ceftobiprole Iclaprim IV IV IV IV/PO Two antibiotics acting synergistically Protein synthesis inhibitor Cell wall synthesis inhibitors Cephalosporins with MRSA activity Dihydrofolate reductase inhibitor Boucher HW, et al. Clin Infect Dis. 2009;48: Potential Future MRSA Therapies Tomopenem PZ-601 IV Carbapenems with MRSA activity RX-1741 PO TD-1792 IV PTK-0796 IV/PO RX-3341 IV 2 nd generation oxazolidinone Multivalent cephalosporin Protein synthesis inhibitor Quinolone with MRSA activity Boucher HW, et al. Clin Infect Dis. 2009;48:

6 MRSA & Cellulitis Role of MRSA not clear Cellulitis with purulence: MRSA 47% MSSA 34% Streptococci 13% Expert recommendation cover for MRSA TMP/SMX DS tablets bid plus Cephalexin 500 mg qid Clindamycin 300 mg qid Moran GJ, et al. N Engl J Med. 2006;355: Complicated Infections More likely mixed aerobic & anaerobic infections Consider in patients with: Chronic infections Peri-rectal rectal infections (consider deep abscess) Wounds involving lower extremities (e.g., feet) Vascular insufficiency (venous stasis ulcers) Immunocompromising conditions (e.g., DM) Bite-related wounds, IV drug use Post-operative operative wounds, infected burns Abrahamian FM, et al. Infect Dis Clin North Am ;22:

7 Complicated Infections Knowledge of emerging resistance & spectrum of activity of antimicrobials Cefoxitin Ampicillin/sulbactam Clindamycin Fluoroquinolones Daptomycin Tigecycline Vancomycin, Linezolid B. fragilis resistance E. coli resistance No Gram neg. coverage E. coli resistance No Gram neg. & anaerobic coverage Does not cover Pseudomonas 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: SSTIs Pneumonia Bacteremia My opinion: Do not advocate 1 dose IV & dispo home on PO meds 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: Maor Y, et al. Clin Infect Dis. 2009;199: Chang FY, et al. Medicine. 2003;82:

8 New Adult Vancomycin Dosing Regimen A loading dose of mg/kg actual body weight (ABW) over 2 hrs for critically ill patients Subsequent doses: 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: Clenched-Fist Injury 8

9 What Works on Pasteurella or E corrodens Yes Penicillin, amoxicillin, ampicillin 2 nd nd, 3 rd, 4 th gen. cephalosporins Carbapenems Fluoroquinolones Doxycycline Azithromycin Trimethoprim/sulfamethoxazole No 1 st gen. cephalosporins Dicloxacillin Erythromycin Nafcillin Clindamycin Aminoglycosides Metronidazole Abrahamian FM, et al. Animal & Human Bites. Therapy of Infectious Diseases, Abrahamian FM, et al. Bites. Infectious Diseases, 3rd ed Empiric Abx for Dog, Cat, & Human Bite Infections Antibiotic (s) Past/Eikenella Staph/Strep Anaerobes Amox-clav/Amp clav/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, Abrahamian FM, et al. Bites. Infectious Diseases, 3rd ed Forbes CD, et al. A Color Atlas & Text of Clinical Medicine,

10 Necrotizing Skin Infections Various classification systems Hemodynamic stabilization plus antibiotics: Vancomycin plus clindamycin plus piperacillin/tazobactam Linezolid plus piperacillin/tazobactam Early surgical consultation / exploration Hyperbaric oxygen therapy never 1 st line treatment Anaya DA, et al. Clin Infect Dis. 2007;44: 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:e

11 Predominant Aerobes in DFIs (406 pts) Staphylococcus species MSSA MRSA S. epidermidis Streptococcus species Enterococcus species Enterobacteriaceae Corynebacterium species Pseudomonas aeruginosa 81% 40% 12% 20% 41% 36% 35% 28% 9% Citron DM, et al. J Clin Micrbiol. 2007;45: 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

12 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: Neutropenic Fever: Decision-Making Process High risk (Consider age 16 high risk) Low risk Admit IV antibiotics No Outpatient therapy Single vs. dual therapy? Yes Decide if need to add Vancomycin & Metronidazole Always involve Heme/Onc Cipro plus amox-clav Hughes WT, et al. Clin Infect Dis. 2002;34:

13 Choices of IV Antibiotics Monotherapy (uncomplicated) Dual Therapy (complicated i.e., ICU admission) Cefepime Ceftazidime Imipenem Meropenem Piperacillin-tazobactam Ticarcillin-clavulanate Cefepime or Ceftazidime Imipenem or Meropenem plus Gentamicin, Tobramycin, or Amikacin Hughes WT, et al. Clin Infect Dis. 2002;34: Bow EJ, et al. Clin Infect Dis. 2006;43: 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 < 6 months 6 mo 2 yrs 2 yrs Certain Dx Antibiotics Antibiotics Abxs if severe Observe if not Uncertain Dx Antibiotics 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: Spiro DM, et al. JAMA. 2006;296: Stevanovic T, et al. Int J Pediatr Otorhinolaryngol. 2010;74:

14 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: The Sanford Guide: 2010, pages Pharyngitis: Modified Centor Criteria Criteria Temperature 38ºC Absence of cough Swollen, tender anterior cervical nodes Tonsillar swelling or exudate Age 3-14 years years 45 years Points McIsaac WJ, et al. JAMA. 2004;291: Pharyngitis: Modified Centor Criteria Score Risk of Strep 1% - 2.5% 5% - 10% 11% - 17% 28% - 35% 51% - 53% Therapy No further testing or antibiotic Culture Treat only + cultures Treat with antibiotics McIsaac WJ, et al. JAMA. 2004;291:

15 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: Green M, et al. Antimicrob Agents Chemother ;48: Take Home Points MRSA common in purulent skin infections High dose vanco for complicated infections Avoid routine use of rifampin 1 st 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