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Antibiotic Pearls in the Emergency DepartmentDIANE LUM, PHARMD, BCACP

EMERGENCY MEDICINE CLINICAL PHARMACIST

STONY BROOK UNIVERSITY HOSPITAL

EMAIL: DIANE.LUM@STONYBROOKMEDICINE.EDU

PHONE: 631-885-0842

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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?

3Hospital 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

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HCAP Risk Factors for MDR Pathogens

Immune suppression

Hospitalization in last 90 days

Poor functional status

Antibiotic use within the past 6 months

CID, 2013;57(10):1373-83

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Empiric Therapy for HCAP

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Results

30 day mortality HCAP 0-1 vs MDR >2 risk factors (8.6% vs18.2%, P <0.012)

CID, 2013;57(10):1373-83

Pathogens >2 MDR risk factors (%)

0-1 risk factor (%) P-value

S. Aureus 17.6 4.6 <0.001

MRSA 12.9 0 <0.001

P. Aeruginosa 11.2 2 0.001

MDR Pathogens 27.1 2 <0.001

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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)

CID. 2010;51:S48-S53

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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

9Cefepime vs. Piperacillin/Tazobactam vs. Meropenem

Cefepime: 89% susceptible to PseudomonasPiperacillin/Tazobactam: 85% susceptible to PseudomonasMeropenem: 68% susceptible to Pseudomonas

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

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Double Coverage

Beta-lactams Plus Either Aminoglycoside or Fluoroquinolone

Meropenem Amikacin

Piperacillin/Tazobactam Tobramycin

Cefepime Gentamicin

Ceftazidime Levofloxacin

Aztreonam Ciprofloxacin

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Antibiogram

Antibiotic Percent susceptible to Pseudomonas (%)

Cefepime 89

Ceftazadime 87

Piperacillin/tazobactam 85

Meropenem 68

Aztreonam 57

Ciprofloxacin 58

Levofloxacin 52

Amikacin 95

Tobramycin 89

Gentamicin 76

12Cephalosporin 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

Jemergmed. 2012;42:612-620

13Carbapenem 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;59:1113-1122J Allergy Clin Immunol, 2015;135:972-6

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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. 1250 mg, 1500 mg, 1750 mg)

CID. 2011:52Am J Health-Syst Pharm. 2009;56

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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. 2011:52Am J Health-Syst Pharm. 2009;56CID. 2011;53:164-166

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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

J Emerg Med, 2013;44(5):910-918

17Empiric 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)

CID, 2007;44:S27-72

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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):1312-23

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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):1312-23

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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

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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

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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

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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

CID, 2011;52(5):e103

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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):132-173

25Mild 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):132-173

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Mild Diabetic Foot Infection

Pathogen Antibiotic

Staphylococcus aureus (MSSA), Streptococcus

Clindamycin

Cephalexin

Levofloxacin

Methicillin Resistant S. aureus (MRSA)

Doxycycline

Sulfamethoxazole/Trimethoprim

CID, 2012;54(12):132-173

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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

CID, 2012;54(12):132-173

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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):132-173

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Antibiotic Pearls in the Emergency DepartmentDIANE LUM, PHARMD, BCACP

EMERGENCY MEDICINE CLINICAL PHARMACIST

STONY BROOK UNIVERSITY HOSPITAL

EMAIL: DIANE.LUM@STONYBROOKMEDICINE.EDU

PHONE: 631-885-0842