1. Antibiotic Pearls in the Emergency Department
Diane lum, pharmd, bcacp
Emergency medicine clinical pharmacist
Stony brook university hospital
Phone:

2. Case 1
AB is a 70 year old male from NH with h/o DM, HTN, COPD, HIV and recently hospitalized for 10 days two weeks ago. Pt presents with SOB and fever for 2 days
Vitals: Temp 101°F, HR 108, RR 24, BP 90/60, Wt 110 kg
Labs: WBC 20, Scr 1.6
Allergies: Penicillin (rash)
Dx: HCAP and sepsis
What antibiotics would you give this patient?

3. Hospital Acquired Pneumonia and Health Care Acquired Pneumonia
Hospital acquired pneumonia (HAP)
Occurs >48 hours after admission
Health care acquired pneumonia (HCAP)
Hospitalized >2 days within 90 days
Nursing home or long term care facility
Received IV antibiotics, chemotherapy or wound care in past 30 days
Hemodialysis
Am J Respir Crit Care Med. 2005;171

4. HCAP Risk Factors for MDR Pathogens
Immune suppression
Hospitalization in last 90 days
Poor functional status
Antibiotic use within the past 6 months
Prospective multicenter study in Japan in Journal CID
CID, 2013;57(10):

5. Empiric Therapy for HCAP

6. Results
30 day mortality HCAP 0-1 vs MDR >2 risk factors (8.6% vs18.2%, P <0.012)
Pathogens
>2 MDR risk factors (%)
0-1 risk factor (%)
P-value
S. Aureus
17.6
4.6
<0.001
MRSA
12.9
P. Aeruginosa
11.2 2
0.001
MDR Pathogens
27.1
CID, 2013;57(10):

7. Empiric Therapy HAP Potential Pathogens Antibiotics
Pseudomonas, Klebsiella, Acinetobacter
Cefepime, ceftazadime, meropenem, or piperacillin/tazobactam
PLUS
Antipseudomonal fluoroquinolone (ciprofloxacin or levofloxacin) or Aminoglycoside (amikacin, gentamicin, tobramycin)
MRSA
Vancomycin or linezolid*(only if risk factors present)
Legionella pneumophila
Azithromycin, ciprofloxacin, or levofloxacin (Use instead of aminoglycoside if Legionella suspected)
Legionella: immunocompromised pts, NH or LTC, or hospital with water supply with ongoing construction
CID. 2010;51:S48-S53

8. Empiric Therapy HAP/HCAP
Antibiotic
Dose
Cefepime
1 to 2 grams
Meropenem
1 gram
Piperacillin/tazobactam
4.5 grams
Gentamicin/tobramycin
7 mg/kg (Ideal body weight)
Amikacin
20 mg/kg (Ideal body weight)
Levofloxacin
750 mg
Ciprofloxacin
400 mg
Linezolid
600 mg
Vancomycin
15 to 20 mg/kg (actual body weight)
Am J Respir Crit Care Med. 2005;171

9. Cefepime vs. Piperacillin/Tazobactam vs. Meropenem
Broad spectrum beta-lactams
Gram positives (MSSA, Strep), gram negatives including Pseudomonas
Cefepime has NO anaerobic or enterococcus coverage
Piperacillin/tazobactam covers anaerobes and enterococcus
NO ESBL coverage
Meropenem covers anaerobes, enterococcus and ESBL
Add antibiogram to this slide
Cefepime: 89% susceptible to Pseudomonas
Piperacillin/Tazobactam: 85% susceptible to Pseudomonas
Meropenem: 68% susceptible to Pseudomonas

10. Double Coverage
Beta-lactams Plus Either Aminoglycoside or Fluoroquinolone
Meropenem
Amikacin
Piperacillin/Tazobactam
Tobramycin
Cefepime
Gentamicin
Ceftazidime
Levofloxacin
Aztreonam
Ciprofloxacin
Insert antibiogram, double coverage data mostly aminoglycoside and betalactam. Mostly for bacteremia and critically ill pts

11. Antibiogram Antibiotic Percent susceptible to Pseudomonas (%) Cefepime89
Ceftazadime 87
Piperacillin/tazobactam 85
Meropenem 68
Aztreonam 57
Ciprofloxacin 58
Levofloxacin 52
Amikacin 95
Tobramycin
Gentamicin 76

12. Cephalosporin in Patients with Penicillin Allergy
Cross sensitivity is 1% using a 1st and 2nd generation cephalosporin
Aminopenicillins (ampicillin, amoxicillin) have similar side chain to 1st and 2nd generation cephalosporin
Try to avoid 1st and 2nd generation cephalosporins due to similar side chain
Can use 3rd and 4th generation cephalosporins
Ceftriaxone and cefepime
Until the mid-1980s, many penicillins were produced by fermentation from a cephalosporin mold and not from a penicillin mold. The drugs were thereafter synthetically modified to create the penicillin structure but were contaminated with cephalosporin-type products until approximately With improvements in the manufacturing process, more cross-reactivity exists currently among cephalosporins than between cephalosporins and penicillins.
Cross sensitivity from R1 side chain off beta lactam ring. Before 1980s, cephalosporin manufacturing process contaminiated
Jemergmed. 2012;42:

13. Carbapenem and monobactam in Patients with Penicillin Allergy
Carbapenem (meropenem, ertapenem): <1% cross sensitivity
Monobactam (aztreonam): Can be safely given with patients with penicillin allergy
May cross react with ceftazadime due to similar side chain
CID, 2014;59:
J Allergy Clin Immunol, 2015;135:972-6

14. Vancomycin Dosing: 15 to 20 mg/kg per dose (Use actual body weight)
Maximum initial dose: 2000 mg
25 to 30 mg/kg per dose in critically ill patients
Septic shock, meningitis, osteomyelitis, endocarditis, HAP
Round to nearest 250 mg (i.e mg, 1500 mg, 1750 mg)
Renal tox with earlier formulations due to impurities, Mississippi mud
CID. 2011:52
Am J Health-Syst Pharm. 2009;56

15. Vancomycin and special populations
Renal impairment: Same initial dose (15 to 20 mg/kg)
Dialysis: 15 to 20 mg/kg
SBUH dosing guidelines: Load 15 to 20 mg/kg x1 then give 10 mg/kg after 1st dialysis
Obesity: Same initial dose15 to 20 mg/kg actual body weight
CID. 2011:52
Am J Health-Syst Pharm. 2009;56
CID. 2011;53:

16. Vancomycin Dosing and Outcomes
Single center retrospective cohort study of vancomycin in ED
Correct dose 980 times (22.1%), 3143 (70.7%) underdosed, 318(7.2%) overdosed
Overdosing vancomycin doses resulted in increased length of stay and underdosing resulted in sub-therapeutic troughs
Add literature
J Emerg Med, 2013;44(5):

17. Empiric Therapy Community Acquired Pneumonia
Ceftriaxone 1 to 2 grams
PLUS
Azithromycin 500 mg OR Doxycycline 100 mg (Option for patients with QTc prolongation) OR
Levofloxacin 750 mg (Option for patients with penicillin allergy)
Talk about coverage, doxy option for QTc prolongation
CID, 2007;44:S27-72

18. Community Acquired Pneumonia
Randomized cross over trial tested non-inferiority of beta-lactam versus beta-lactam plus macrolide versus fluoroquinolone (FQ)
Primary outcome: 90 day mortality
Patient population: median age 70 years old, patients not admitted to the ICU
NEJM. 2015;372(14):

19. Community Acquired Pneumonia
Results:
Risk of death 1.9% higher (CI -0.6 to 4.4) with beta-lactam plus macrolide group than beta-lactam monotherapy
Risk of death 0.6% lower (CI -2.8 to 1.9) with the FQ group than beta-lactam monotherapy
Conclusion:
In patients with CAP admitted to non-ICU wards, empiric treatment with beta- lactam monotherapy was non-inferior to beta-lactam plus macrolide and FQ
NEJM. 2015;372(14):

20. Empiric Therapy Uncomplicated UTI
Nitrofurantoin 100 mg BID for 5 days
Do not use in patients with CrCl <60 mL/min
Sulfamethoxazole/trimethoprim DS BID for 3 days
Avoid if resistance prevalence is known to exceed 20%
Fosfomycin 3 g PO one dose
(slightly less efficacious compared to other therapies)
CID, 2011;52(5):e103

21. Empiric Therapy Uncomplicated UTI
FQ (levofloxacin or ciprofloxacin for 3 days)
Avoid if possible to minimize drug-resistant organisms
Beta lactams (cefpodoxime, cefdinir, cefaclor, amoxicillin-clavulanate)
Inferior to other regimens
Cephalexin less studied
CID, 2011;52(5):e103

22. Empiric Oral Therapy Pyelonephritis
Ciprofloxacin 500 mg oral BID for 7 days +/- ciprofloxacin 400 mg IV x1
If resistance >10% to FQ give one time IV dose of ceftriaxone 1 g IV or aminoglycoside first
If <10% resistance give Levofloxacin 750 mg oral once daily for 5 days for outpatient management
Sulfamethoxazole/trimethoprim DS oral BID for 14 days only if pathogen is susceptible
If susceptibility unknown give initial dose ceftriaxone 1 g or aminoglycoside first
CID, 2011;52(5):e103

23. Empiric IV Therapy Pyelonephritis
Beta-lactams for 10 to 14 days
Give 1 time dose of ceftriaxone 1 g IV or aminoglycoside first
Patients with history of extended spectrum beta-lactamase (ESBL) producing gram negative rods: Use carbapenem
Pts with resistance to FQ and TMX
CID, 2011;52(5):e103

24. Diabetic Foot Infection
Clinical Severity
Infection Severity
Clinical Manifestations
Uninfected
No purulence or inflammation
Mild
Presence of purulence + >1 sign of inflammation and cellulitis (if present)< 2 cm around ulcer limited to skin or superficial subcutaneous tissue
Moderate
Same as mild PLUS at least one of the following:>2 cm of cellulitis, lymphangitic streaking, spread beneath superficial fascia, deep tissue abscess, gangrene, involvement of muscle, tendon, joint or bone
Severe
Any of the above PLUS systemic toxicity or metabolic instability
CID, 2012;54(12):

25. Mild and Moderate Diabetic Foot Infection
Choose an antibiotic to cover gram positive cocci
Do not need to cover Pseudomonas unless patient has risk factors
Consider covering for MRSA in patients with prior history
CID, 2012;54(12):

26. Mild Diabetic Foot Infection
Pathogen
Antibiotic
Staphylococcus aureus (MSSA), Streptococcus
Clindamycin
Cephalexin
Levofloxacin
Methicillin Resistant S. aureus (MRSA)
Doxycycline
Sulfamethoxazole/Trimethoprim
Only 57% susceptible to staph (levoflox), talk about clindamycin MRSA and D test
CID, 2012;54(12):

27. Moderate Diabetic Foot Infection
Pathogen
Antibiotic
MSSA, Streptococcus, enterobacteriaceae, anaerobes
Cefoxitin
Ampicillin/sulbactam
Ertapenem
Levofloxacin or ciprofloxacin + clindamycin
Ceftriaxone (no anaerobic coverage)
MRSA (only if suspected)
Vancomycin, linezolid, or daptomycin
Risk factors: IV drug user, h/o of MRSA, NH, hospitalization w/in 3 months or prolonged hosp >2 weeks
CID, 2012;54(12):

28. Severe Diabetic Foot Infection
Start broad spectrum antibiotics
Pathogen
Antibiotic
Pseudomonas and anaerobes
Piperacillin/tazobactam
Meropenem
Cefepime, Ceftazadime, aztreonam or ciprofloxacin + metronidazole
MRSA
Vancomycin, linezolid or daptomycin
CID, 2012;54(12):

29. Antibiotic Pearls in the Emergency Department
Diane lum, pharmd, bcacp
Emergency medicine clinical pharmacist
Stony brook university hospital
Phone: