This document discusses the appropriate use of antibiotics in emergency settings. It begins with an introduction on the need for early empiric antibiotic therapy in some infections. It then outlines the indications and spectrum of activity of commonly used antibiotics for conditions like UTI, meningitis, pneumonia, and soft tissue infections. It emphasizes that delays in administering antibiotics in conditions like meningitis and sepsis are associated with worse outcomes.

1. Suad AL-Sulimani R3

2. Introduction : in the acute setting of the emergency department (ED), it is often necessary to make treatment decisions of infection without precise knowledge of infectious source or microbial species In certain cases (e.g., suspected meningitis, gram-negative sepsis, bacterial peritonitis, pneumonia), early empiric therapy may be lifesaving. Unnecessary use of Antibiotics in ED contribute in emerging new antimicrobial resistance

3. Outline Basic knowledge of Antimicrobial Spectrum of activity . Discuss the indications of frequently used antibiotics in Emergency . Antibiotics guideline use in (UTI ,Meningitis , CAP & soft tissue infection ) Evidence based Advances in Early ED Antibiotic use . Review the most common drug interactions of the most commonly used Antibiotics

4. Gram +ve bacteria Cocci : =Strept: pyogen ,pnumoniae , viridans =Staph : aureus ,epidermus , saprophyticus Bacilli : =clostridium =Bacillus = Listeria

5. Gram -ve bacteria Cocci : = Neisseria gonorrhea , Niesseria Meningitidis Bacilli : =Klebsella , Ecoli , Enterobacter ,Psudomonus aerogenosa CoccoBacilli : = H.influenzae , B.Pertussis

6. Spectrum of Activity Narrow-Spectrum Antimicrobial Wide-Spectrum Antimicrobial

7. ` St Re pt enterococcus Staph .aeru M R S A H.Influ morexella niesseria Psudomonus Gram –ve rods e.coli anaerob Penicillin Amoxacillin/Ampicillin + + 0 0 +/- 0 +(niesseria meningitis 0 0 0 Amoxicillin/calvu(oral + + + 0 + + + 0 + + Tazobactaum /Pipracellin (iv ) + + + 0 + + + + + + Carbapenums (imepenu meropenum + + e.fecalis only + 0 + + + + + +

8. ` cephalosporins strptococcus enterococcus Staph .aerus MRSA H.influ morexella niesseria Psudomonus Gram –ve rods ecoli 1 st generation Cephalexin + 0 + 0 + not cephalexin +/- 0 0 0 2 nd generation Cefuroxime , cefacolr + 0 + 0 + + cefacolr +/- +/- 0 +/- 3 rd generation Ceftriaxone ,cefexime + 0 + 0 + + + +/- + 3 rd generation (antipsudomonus Ceftazidine + 0 +/- 0 + + +/- + + 4 th generation cefepime + 0 + 0 + + + + +

9. */ Common antibiotics Spectrum of activities Macrolides (bacteriostatic) - Erythromycin (also azithromycin, clarithromycin) Gram-positive bacteria, Mycoplasma, Legionella Aminoglycosides (bactericidal) Streptomycin, kanamycin, gentamicin, tobramycin, amikacin, netilmicin and neomycin (topical) gram-negative and some gram-positive bacteria. They are not useful for anaerobic bacteria, Tetracyclines (bacteriostatic) Tetracycline, minocycline and doxycycline b. Spectrum of activity - These are broad spectrum antibiotics and are useful against intracellular bacteria Chloramphenicol, lincomycin, clindamycin (bacteriostatic) Chloramphenicol - Broad range Lincomycin and clindamycin - Restricted range Quinolones - nalidixic acid, ciprofloxacin, oxolinic acid (bactericidal) Gram-positive cocci , gram –ve bacteria

10. Oral Quinelones Flouroquinolones (cont.). Trovafloxacin. Covers Gm pos, neg, and anaerobes. Hepatotoxicity with prolonged use. Absorption delayed by morphine. Moxifloxacin. Covers Gm pos, neg, and anaerobes. Good vs. Clostridium and Bacteroides – same range as metronidazole, and superior to clindamycin. QD dosing. Gatifloxicin. Covers Gm pos, neg, and anaerobes. Very similar to moxifloxacin, but less expensive . QD dosing.

11. Urinary tract infection

12. CYSTITIS & UTI COMMON ORGANISM : - 80-85% E.COLI - 5-1-% STAPH SAPROPHYTICUS -KLEBSIELLA & POTEU CAUSE MINORITY OF CASE

13. Evedience based advances : Most of the b-lactams appear to be less effective may yield increased incidences of recurrences and of adverse effects . Amoxicillin is thus no longer recommended as empirical therapy for uncomplicated UTI (the sanford guide for antimicrobial therapy 2010) CHARACTER OF PATIENTS SUGGESTED NTIBIOTIC DURATION Uncomplicated acute bacterial cystitis 1)Trimethoprim-sulfamethoxazole or trimethoprim .(IA) 2)Fluoroquinolones, ofloxacin (IA) , norfloxacin ,(AII ciprofloxacin, AII and fleroxacin AII nitrofurantoin,) 3)b-lactams (E,I). 3 DAYS 3-7 DAYS

14. Antibiotic therapy for three days was similar to prolonged therapy (≥5 days) in achieving symptomatic cure, while prolonged treatment was more effective in obtaining bacteriologic cure. There is no apparent benefit in extending therapy with TMP-SMX or a fluoroquinolone past three days , and adverse reactions are more common in patients treated with longer regimens.

15. Evedience based advances : In randomized double-blind trial, bacteriologic and clinical success higher for 7 days of CIP than for 14 days of TMP-SMX; failures correlated with TMP-SMX in vitro resistance. Since CIP worked with 7-day rx, suspect other FQs effective with 7 days of therapy; Levo 750 mg FDA-approved for 5 days (the sanford guide for antimicrobial therapy 2010) CHARACTER OF PATIENTS SUGGESTED NTIBIOTIC DURATION Uncomplicated acute pyelonephritis Resistance of E. coli to TMP/SMX 13-45% in collaborative ER study (CID 47:1150, 2008). 1)oral fluoroquinolone , Levo 750 mg q24, Oflox 400 mg bid, Moxi NAI 400 mg q24h (A,II). 2) CIP 500 mg bid or CIP-ER(AII) 1000 mg q24hpossibly If a gram-positive bacterium is the likely causative organism, amoxicillin or amoxicillin/clavulanic acid may be used alone (B,III) 2 weeks 7 days

16. Common organisms: - Enterobacteriaceae, -P. aeruginosa, enterococci -rarely S. aureus (CID 42:46,2006) CHARACTER OF PATIENTS SUGGESTED NTIBIOTIC DURATION Complicated UTI/catheters Obstruction, reflux, azotemia, transplant, Foley catheterrelated, R/O obstruction (AMP + gent) or PIP-TZ (Tazocin ) or TC-CL ticarcillin-clavulanate or or IMP = imipenem- or MER meropenem (IV FQ: CIP, Gati, Levo) or Ceftaz or Cef 2-3weeks

17. Community Acquired Pneumonia (CAP )

18. Common organisms in CAP No co-morbidity : Most common organism strept.pnumonae 2/3 of the cases ,Atypicals—M. pneumoniae, , viral Co-morbidity: Alcoholism: S. pneumo,anaerobes, coliforms COPD: H. influenzae,M. catarrhalis, S. pneumo IVDU: Hematogenous S. aureus Post-CVA aspiration: Oral flora, incl. S. pneumo Post- influenza :S. pneumo. And S. aureus

19. Evidence based advances : There is abundant evidence that macrolide monotherapy is highly effective in the treatment of CAP in outpatients with mild to moderately severe disease For patients admitted through the emerg dose should be administered while still in the ED .(Moderate recommendation; level III ) Clinical Infectious Diseases 2000;31:383–421 © 2000 by the Infectious Diseases Society of America. Previously healthy and no risk factors for drug-resistant S. pneumoniae (DRSP) infection A macrolide (azithromycin, clarithromycin, or erythromycin) (strong recommendation; level I evidence) Doxycycline (weak recommendation; level III evidence)

20. Presence of comorbidities, - chronic heart, lung,liver, or renal disease - diabetes mellitus; ---alcoholism; malignancies; asplenia; immunosuppressing use of immunosuppressing drugs; use of antimicrobials within the previous 3 months (in which case an alternative from a different class should be selected) A respiratory fluoroquinolone (moxifloxacin, gemifloxacin,or levofloxacin (level I evidence) A b-lactam plus a macrolide (strong recommendation (level I evidence) alternatives include ceftriaxone, cefpodoxime, and cefuroxime [500 mg 2 times daily]; doxycycline [level II evidence]

21. Respiratory fluoroquinolones (levofloxacin, moxifloxacin or gemifloxacin were more likely to result in treatment success than the combination of a beta-lactam plus a macrolide for the treatment of CAP that was mostly mild to moderate in severity (odds ratio, OR 1.39, 95% CI 1.02-1.90)

22. Bacterial Meningitis

23. Empiric Therapy—immunocompetent Age: Preterm to <1 mo Group B strep 49%, E. coli 18%, listeria 7%, AMP + cefotaxime AMP + gentamicin Age: 1 mo– 50 yrs S. pneumo, meningococci, H. influenzae now very rare, listeria unlikely if young & immuno-competent (add ampicillin if suspect listeria: 2 gm IV q4h) Adult dosage: [( Cefotaxime 2 gm IV q4–6h OR ceftriaxone 2 gm IV q12h)] + ( dexamethasone) + Vanco [( MER 2 gm IV q8h) (Peds: 40 mg/kg IV q8h)] + IV dexamethasone + vanco

24. Age > 50 years or alcoholism or other deblitating illneesses , immunocompromized Strpt .Pnumoniae,listeria, gram –ve bacilli 1)AMP 2 gm IV q4h) + (ceftriaxone 2 gm IV q12h or cefotaxime 2 gm IV q6h) + vanco + IV Dexamethasone 2) MER 2 gm IV q8h + vanco + IV dexamethasone. Basilar skull fracture S. pneumoniae , H. influenzae , group A beta-hemolytic streptococci Vancomycin plus a third-generation cephalosporin•Δ Penetrating trauma Staphylococcus aureus , coagulase-negative staphylococci (especially Staphylococcus epidermidis ), aerobic gram-negative bacilli (including Pseudomonas aeruginosa ) Vancomycin plus cefepime; OR vancomycin plus ceftazidime; OR vancomycin plus meropenem

25. Delay in initial antibiotics in the emergency department (median delay of four hours) was associated with a worsening of hypotension, altered mental status, and seizures in about 15 percent of patients . Those patients whose delay in antibiotic therapy allowed their disease to advance from having zero or one to having two or three poor prognostic indicators had a significant increase in adverse outcomes.

26. patients with pneumococcal meningitis , a delay in antibiotic treatment of more than three hours after hospital admission was a strong and independent risk factor for mortality (OR 14.1; 95% CI: 3.9 to 50.9). Delayed therapy was a greater risk factor than the isolation of a penicillin-resistant strain (OR 6.83; 95% CI 2.94-20.8) or a higher disease severity (OR 1.12; 95% CI 1.07-1.15)

27. Fever Interval before Diagnosis, Prior Antibiotic Treatment, and Clinical Outcome for Young Children with Bacterial Meningitis Clinical Infectious Diseases 2001;32:566–572 retrospective chart review, we compared the fever interval that preceded diagnosis with the complication rate among 288 young children (age, 3–36 months ) Pneumococcus species were associated with the longest fever interval prior to diagnosis of meningitis, the highest frequency of contact with a clinician before hospitalization, and the highest rate of documented morbidity or mortality . For S. pneumoniae, there was an association between antibiotic treatment received at prior meetings with a clinician and a reduced rate of meningitis‐related complications (odds ratio, 0.14; ). Antibiotic treatment during such meetings is associated with a substantial reduction in disease‐related sequelae.

28. Skin and Soft-Tissue Infections inthe Era of Resistance: MRSA and More

29. CA-MRSA: The New Epidemic A global emerging health problem 8-12% of MRSA infections Most involve skin & soft-tissue structures Commonly presents with spontaneous abscess Reported in severe infections: Bacteremia, Pneumonia (often necrotizing) Osteomyelitis Bursitis, arthritis,Meningitis Fridkin SK, et al.N Engl J Med. 2005;352:1436-1444. Pannaraj PS, et al.Clin Infect Dis. 2006;43:953-960.

30. Risk factors to develop CAMRSA soft tissue infection : = Antibiotic use (particularly cephalosporin and fluoroquinolone use) strongly correlates with the risk for MRSA colonization and infectio = residents of long-term care facilities =Homeless =IV drug users =Prisoners =Military Personnel =HIV patients 60% are abscess, 40% cellulitis , small persentage as impetigo Clin Infect Dis. 2007;45 Suppl 3:S171-6

31. Antibiotics & Abscesses - Not required for simple, uncomplicated cases - Indications for addition of antibiotics:  Major surrounding cellulitis  Signs of systemic toxicity  Facial abscess  Immunocompromised  Recurrent abscesses  Large abscess (≥ 5 cm) - Typical duration: 7-10 days The Sanford Guide: 2008, page 47. Lee MC, et al. Pediatr Infect Dis J. 2004;23:123-127. Ruhe JJ, et al.Clin Infect Dis. 2007;44:777-784 .

32. Skin and soft tissue infections Parenteral therapy • Vancomycin (30 mg/kg IV every 24 hours in 2 equally divided doses; not to exceed 2 g/24 hours unless concentrations in serum are inappropriately low) • Daptomycin (4 mg/kg IV once daily) • Linezolid (600 mg IV twice daily) • Tigecycline (100 mg IV once, thereafter 50 mg IV every 12 hours) Oral therapy • TMP-SMX (2 double-strength tablets orally twice daily) • Doxycycline or minocycline (100 mg orally twice daily) • Clindamycin* (300 to 450 mg orally every 6 to 8 hours) • Linezolid (600 mg orally twice daily)

33. Sepsis

34. Cutoff time of <1 hr for early goal directed therapy & administration of appropriate antibiotics in severe sepsis & septic shock initiated in emergency department are primary determinant of mortality.

35. Effectivness of Antibiotic administration within 1 hr of hypotension was associated with better survival rate in septic shock

36. Antibiotics in sepsis if Pseudomonas is an unlikely pathogen vancomycin with one of the following: Cephalosporin, 3rd or 4th generation (eg, ceftriaxone or cefotaxime) or Beta-lactam/beta-lactamase inhibitor (eg, piperacillin-tazobactam, ticarcillin-clavulanate or Carbapenem (eg, imipenem or meropenem

37. + Pseudomonas is a possible pathogen, we combine vancomycin Antipseudomonal cephalosporin (eg, ceftazidime, cefepime, or Antipseudomonal carbapenem (eg, imipenem, meropenem), or Antipseudomonal beta-lactam/beta-lactamase inhibitor (eg, piperacillin-tazobactam,ticarcillin-clavulanate), or Fluoroquinolone with good anti-pseudomonal activity (eg, ciprofloxacin), or Aminoglycoside (eg, gentamicin, amikacin), or Monobactam (eg, aztreonam)

38. Common antibiotic drug interaction

40. Take home massages Basic knowledge of antibiotic spectrum of activity is required for infection management Advances in UTI treatment support using antibiotics for shorter course Oral Flurquinelones are supported by evedience to be effective in treatment of CAP Early AB in meningitis is proven to reduce complications & improve outcome

41. Take home massages MRSA soft tissue & wound infection is a newly emerging problem Early Antibiotics in sepsis is part of early goal directed therapy

42. THANK YOU

43. Pregnancy Aerobic Gm-neg. bacilli & Staph. hemolyticus Screen 1st trimester. If positive, rx 3–7 days with amox, nitrofurantoin, O Ceph, TMP-SMX, or TMP alone Screen monthly for recurrence. Some authorities treat continuously until delivery (stop TMP-SMX 2 wks before EDC). ↑ resistance of E. coli to TMP-SMX. Before and after invasive urologic intervention, e.g., Foley catheter Aerobic Gm-