Antibiotic Abyss. Discussion Points. MRSA Treatment Guidelines

Transcription

1 Antibiotic Abyss Fredrick M. Abrahamian, D.O., FACEP, FIDSA Professor of Medicine UCLA School of Medicine Director of Education Department of Emergency Medicine Olive View-UCLA Medical Center Sylmar, California Discussion Points Skin & soft-tissue infections Pneumonia Diabetic foot infections Intra-abdominal infections Urinary tract infections Acute otitis media Acute uncomplicated rhinosinusitis MRSA Treatment Guidelines Skin & soft-tissue infections Including recurrent infections Pneumonia New vancomycin dosing Bacteremia & infective endocarditis Bone & joint infections CNS infections 1

2 Prevalence of MRSA in Acute, Purulent Skin Infections, August 2008 (n=619) 38% 59% 40% 44% 53% 63% 58% 48% 57% 72% 56% 62% 84% MSSA 16% Clin Infect Dis ;53: [Prevalence study] 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) Clin Infect Dis ;53: [Prevalence study] CA-MRSA Susceptibility Patterns Resistant: All penicillins Cephalosporins Susceptible: TMP/SMX Doxycycline Rifampin Vancomycin Linezolid Variable : Clindamycin: 94% (2% inducible resistant) Levofloxacin: 45% Erythromycin: 10% Susceptibility patterns are dynamic, vary geographically & in patient populations. Clin Infect Dis ;53: [Prevalence study] 2

3 MRSA SSTIs Clinical Guidelines Simple abscess: I&D alone likely to be enough Indications for antibiotics with abscesses: Severe or extensive disease (multiple sites) Rapid progression with cellulitis Signs & symptoms of systemic illness Extremes of age; co-morbidities Difficult to drain areas (hand, face, genitalia) Associated septic phlebitis Lack of response to I&D alone MRSA SSTIs Clinical Guidelines Outpatients with purulent cellulitis & no associated abscess: Empirical therapy for CA-MRSA is recommended Empirical therapy for ß-hemolytic streptococci likely unnecessary 5-10 days of therapy is recommended MRSA SSTIs Clinical Guidelines Outpatients with nonpurulent cellulitis & no associated abscess: Empirical therapy for ß-hemolytic streptococci is recommended Role of MRSA unknown Empirical coverage for MRSA in those who do not respond to ß-lactam therapy or those with systemic toxicity 3

4 MRSA SSTIs Clinical Guidelines Oral antibiotic options for CA-MRSA: TMP/SMX or clindamycin or linezolid alone Doxycycline or minocycline Coverage for ß-hemolytic strep & CA-MRSA: Clindamycin or linezolid alone TMP/SMX or doxycycline or minocycline with a ß-lactam (e.g., amoxicillin) Use of rifampin is not recommended Antimicrob Agents Chemother. 2011;55: [Dose of TMP/SMX] MRSA SSTIs Clinical Guidelines For hospitalized patients with csstis, empirical IV therapy for MRSA should be considered pending culture results: Vancomycin; Linezolid; Daptomycin Telavancin; Clindamycin ß-lactam may be considered in hospitalized patients with nonpurulent cellulitis 7-14 days of therapy MRSA SSTIs Clinical Guidelines Wound cultures are recommend: In patients treated with antibiotics Severe local infection Signs of systemic illness No response to initial therapy Concern for a cluster or outbreak 4

5 MRSA SSTIs Clinical Guidelines Decolonization may be considered: Recurrent SSTIs Infection among household members Nasal decolonization: Mupirocin bid x 5-10 days Mupirocin bid for 5-10 days plus chlorhexidine body wash for 5-14 days or dilute bleach baths Oral antibiotics not routinely recommended for decolonization CAP & CA-MRSA Has emerged as a cause of severe CAP Empirical therapy for MRSA is recommended: Severe illness (i.e., ICU admission) Necrotizing or cavitary infiltrates Empyema Antimicrobial choices include: Vancomycin; Linezolid; Clindamycin Clin Infect Dis. 2012;54: [Prevalence of MRSA pneumonia] New Adult IV Vancomycin Dosing Regimen Traditional dosing is adequate for most SSTIs: 1 gram or 15 mg/kg q12 hrs New regimen: mg/kg/dose ABW q8-12 hrs Not to exceed 2 grams per dose A loading dose of mg/kg ABW in seriously ill patients Extend infusion period to 2 hrs if dose > 1 g Am J Health Syst Pharm. 2009;66:82-8. [New vancomycin dosing regimen] 5

6 Take Home Points Non-purulent cellulitis: Cover for MRSA in those with systemic toxicity Routine wound cultures not recommended Routine decolonization not recommended Traditional vancomycin dosing is adequate for most SSTIs Cover for MRSA in severe pneumonia 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

7 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% J Clin Micrbiol. 2007;45: [Microbiology of DFIs] 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) Other options: Diclox. or Cephalexin ± TMP/SMX DS (doxy, minocycline) The Sanford Guide: Clin Infect Dis. 2012;54: [IDSA DFI guidelines] 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: Other options: Clindamycin + Ciprofloxacin Ceftriaxone ± Metronidazole ± Vancomycin Ertapenem ± Vancomycin 7

8 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: Take Home Point Diabetic foot infections: Avoid routine use of anti-mrsa & antipseudomonal agents Intra-Abdominal Infections In general, direct empiric therapy towards: Enterobacteriaceae & anaerobes Anaerobic therapy not indicated for acute cholecystitis Reserve anti-pseudomonal coverage for: Severe infections, immunocompromised, or advanced age No need for routine MRSA coverage Clin Infect Dis. 2010;50: [2010 IDSA guidelines] 8

9 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 Clin Infect Dis. 2010;50: [2010 IDSA guidelines] Intra-Abdominal Infections Outpatient Antimicrobial Therapy Mild diverticulitis, drained peri-rectal abscess TMP/SMX DS plus Metronidazole Amoxicillin/clavulanate (2 grams bid) Cipro or Levofloxacin plus Metronidazole Moxifloxacin High-degree of clinda resistance to B. fragilis Treat for 7-10 days The Sanford Guide: Antimicrob Agents Chemother. 2007;51: [Anaerobes susceptibility trends] Community-Acquired Intra-Abdominal Infections in Adults Mild-to-Moderate Severity Cefoxitin Ertapenem Moxifloxacin Tigecycline Ticarcillin / clavulanic acid Cefazolin, cefuroxime, ceftriaxone, or cefotaxime plus metronidazole Ciprofloxacin or levofloxacin plus metronidazole Clin Infect Dis. 2010;50: [2010 IDSA guidelines] 9

10 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 Clin Infect Dis. 2010;50: [2010 IDSA guidelines] Take Home Point Intra-abdominal infections: Avoid routine use of anti-pseudomonal agents UTI Clinical Practice Guidelines 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 Arch Intern Med. 2007;167: [Short course nitrofurantoin] Clin Infect Dis. 2011;52:e103-e20. [IDSA UTI guidelines] JAMA. 2012;307: [Cefpodoxime for cystitis] Antimicrob Agents Chemother. 2012;56: [Resistance trends] 10

11 UTI Clinical Practice Guidelines Acute Pyelonephritis Obtain urine culture & susceptibility test Oral fluoroquinolones x 5-7 days Consider initial IV dose in ED Fluoroquinolones; Ceftriaxone Aminoglycosides; Ertapenem TMP/SMX DS bid x 14 days Avoid oral ß-lactams as first-line agents Clin Infect Dis. 2011;52:e103-e20. [IDSA UTI guidelines] Take Home Points Use nitrofurantoin for 5 days as first-line agent for treatment of acute cystitis Use oral fluoroquinolones for 5-7 days as first-line agents for outpatient treatment of acute pyelonephritis Obtain urine culture & susceptibility testing in all patients with pyelonephritis Treatment of Acute Otitis Media Randomized, double-blind, placebo-controlled Amox-clavulanate vs placebo x 10 days 291 patients 6-23 months of age Initial resolution of symptoms by day 2: 35% amox-clavulanate vs 28% placebo Resolution of symptoms by day 7: 67% with amox-clavulanate vs 53% placebo More diarrhea in abxs group: 25% vs 15% N Engl J Med ;364: [RCT AOM] 11

12 Treatment of Acute Otitis Media Randomized, double-blind, placebo-controlled Amox-clavulanate vs placebo x 7 days 319 patients 6-35 months of age Treatment failure: 19% abx vs 45% placebo More diarrhea in abxs group: 48% vs 27% Antibiotics reduced risk of treatment failure by 62% & need for rescue treatment by 81% N Engl J Med ;364: [RCT AOM] 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. Pediatrics. 2004;113: [Clinical[ practice guidelines] JAMA. 2006;296: [Wait-and and-see approach] Int J Pediatr Otorhinolaryngol ;74: [Wait[ Wait-and-see approach] Take Home Points Antibiotics are recommended for patients less than 2 years of age with definite diagnosis of acute otitis media Treat acute otitis media at any age with temperature 39 C or moderate-severe otalgia 12

13 Acute Rhinosinusitis Randomized, placebo-controlled trial 166 adults with uncomplicated infections Amoxicillin vs. placebo x 10 days Primary outcome: Improvement of quality-of-life (QoL) scores after 3-4 days of therapy JAMA :307; [RCT Acute Rhinosinusitis] Acute Rhinosinusitis No significant differences in QoL scores or reported symptom improvement at day 3 & day 10 QoL scores or reported symptom improvement at day 7 favoring amoxicillin (NNT=6) Only symptom that showed benefit with antibiotic was nasal obstruction JAMA :307; [RCT Acute Rhinosinusitis] Take Home Point Treatment with antibiotics offers little clinical benefit for most patients with uncomplicated acute rhinosinusitis 13