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Daniel C. DeSimone, MDAssistant Professor of Medicine

DeSimone.Daniel@mayo.edu

Faculty photo will be placed here

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Antibiotic Update

Wednesday-Saturday, October 19-22, 2016Sawgrass Marriott Hotel Ponte Vedra Beach, Florida

Mayo School of Continuous Professional Development

2nd Annual InpatientMedicine for NPs & Pas:

Hospital Care from Admission to Discharge

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Disclosures for speaker:Date of presentation: 10/19/2016

• No relevant financial disclosures:• Daniel C. DeSimone, MD

• Reference to off-label/investigational use(s) of pharmaceuticals or devices:

• None

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Learning Objectives• Upon conclusion of this activity, participants

should be able to:• 1. Develop a strategy for selecting an antibiotic

based on the microorganism• 2. Determine the appropriate use of antibiotics

for multi-drug resistant organisms

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Pre-Test QuestionWhich antibiotic would you use to cover both methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa infection?1. Ceftolozane/tazobactam2. Dalbavancin3. Meropenem4. Linezolid5. No such antibiotic exists

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Spectrum of Microorganisms

MRSAVREVISAVRSA

Pseudomonas aeruginosa

Gram positive Gram negative

Anaerobes

StreptococciEnterococciTreponemaCONS

EnterobacteriaceaeKlebsiellaE. ColiAcinetobacter

No single antibiotic covers the entire spectrum

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Antibiotic “Arsenal”• Penicillins

• Cephalosporins

• Carbapenems

• Fluoroquinolones

• Aminoglycosides

• Macrolides

• Tetracyclines

• Metronidazole

• Clindamycin

• Trimethoprim/Sulfamethoxazole

• Vancomycin

• Daptomycin

• Linezolid, Tedizolid

• Telavancin

• Dalbavancin, Oritavancin

• Tigecycline

• Quinupristin/dalfopristin

• Aztreonam

• Ceftolozane/tazobactam

• Ceftazidime/avibactam

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Penicillins• Penicillin G (IV)

• Streptococci, Listeria, Neisseria, Enterococci

• Oxacillin/Nafcillin (IV) (anti-Staphylococcal)• Methicillin-susceptible S. aureus (MSSA)

• Ampicillin (IV), Amoxicillin (PO)• Gram positive and Gram negative coverage• E. coli, Proteus, Salmonella, Shigella, H. flu

• Augmentin (PO), Ampicillin/Sulbactam (IV)• GP and GN, and anaerobes

• Piperacillin/Tazobactam, Ticarcillin/Clavulanate (IV)• Anaerobes, GP, GN including Pseudomonas aeruginosa

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Cephalosporins• *None of the cephalosporins cover Enterococci• Cefazolin (IV), Cephalexin (PO)

• GP including MSSA• Cefotaxine (IV), Ceftriaxone (IV)

• Broad spectrum—GP, GN, except Pseudomonas• Ceftazidime, Cefepime (IV)

• Broad spectrum, including Pseudomonas• Ceftaroline (IV)

• MRSA and limited GN coverage

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Carbepenems• Meropenem, Imipenem, Doripenem

• Broad spectrum—GP, GN including Pseudomonas, and anaerobes

• Ertapenem• Does not cover Pseudomonas; once daily

dosing• All have seizure-inducing potential with

Imipenem having highest risk• Restrictions due to risk of carbapenemase

resistant enterobacteriaceae

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Quinolones• Levofloxacin, Ciprofloxacin, Moxifloxacin

• Greatest activity against GN bacilli—Enterobacteriaceae, Haemophilus, Neisseria, Moraxella catarrhalis, and Pseudomonas aeruginosa

• Avoid use in pregnancy and nursing mothers (category C), children for arthropathy with erosion of cartilage

• Risk of tendon rupture, prolongation of QT interval• FDA restriction—avoid use in uncomplicated UTI,

acute sinusitis/bronchitis. Risks>Benefits

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Aminoglycosides• Gentamicin, tobramycin, amikacin

• Used in combination to treat GNB infections especially Pseudomonas and multi-drug resistant Tuberculosis

• Limited by its toxicities• Nephrotoxicity: as high as 20%• Ototoxicity: vestibular or cochlear damage;

often irreversible

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Macrolides• Azithromycin, Clarithromycin, Erythromycin

• Streptococci, Haemophilis, Moraxella, and atypical organisms (Legionella, Mycoplasma, Chlamydia)

• Increasing resistance rates globally• Adverse reactions

• QT prolongation• GI side effects

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Tetracyclines• Doxycycline, Minocycline

• Broad spectrum (GP & GN), drug of choice for Rickettsia, Lyme disease, Brucella, Chlamydia, Coxiella

• Photosensitivity, “Blue-berry muffin” with minocycline long-term use

• Avoid in pregnancy and children <8 years of age

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Metronidazole• Treatment of choice for C. difficile infection,

then oral Vancomycin• >95% of anaerobes are susceptible• Active against anaerobes, protozoa,

microaerophilic bactereia—Bacteroides, Clostridium, Fusobacterium

• Peripheral neuropathy with long-term use, disulfiram-like reactions, nausea/vomiting, GI upset

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Clindamycin• Active against MRSA, Streptococci, and

anaerobes• Propensity to cause C. difficile infection

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Trimethoprim/Sulfamethoxazole• Active against GP including MRSA, GN,

Pneumocystis jirovecii, and protozoa• Nephrotoxicity is unommon; but decreases the

tubular secretion of creatinine—increase in serum creatinine that is not reflective of a true reduction in GFR

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Vancomycin (IV)• Primary use is for MRSA infections• Goal trough level 15-20 mcg/mL for CNS and

pulmonary infections (“Brain and Breathing”)• Goal trough level 10-15 mcg/mL for all other

infections• Red man syndrome: histamine-mediated

flushing during infusion—prolong infusion time, anti-histamine; not an allergic reaction

• Nephrotoxicity due to high levels of Vancomycin, closely monitor trough levels

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Daptomycin• Primarily used for MRSA and VRE (vancomycin

resistant enterococci) infections• Do not use for MRSA pneumonia (surfactant

inactivates Daptomycin)• Monitor creatine kinase levels, stop statins

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Linezolid, Tedizolid• Primarily treats MRSA and VRE infections• IV and PO formulations available• Limitations of extended use include

pancytopenia, peripheral neuropathy, serotonin syndrome (in combination of SSRI therapy), and ocular toxicity

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Telavancin• Activity against MRSA, VISA, VRSA• High rate of renal toxicity, and GI upset• Approved for use in complicated skin/soft tissue

infections and hospital-acquired pneumonias

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Dalbavancin, Oritavancin• Used for the treatment of skin/soft tissue

infections caused by GP bacteria including MRSA; limited data for more invasive infections

• Long half-life• *Once weekly dosing• High costs, ?allergic reactions• Oritavancin can artificially prolong aPTT, PT,

and INR

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Tigecycline• Active against MRSA, VRE, anaerobes,

Mycobacteria, and GN (except Pseudomonas)• Increased mortality risk associated with

Tigecycline in patients with bacteremia due to poor serum drug concentration levels

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Quinupristin/dalfopristin• Activity against VISA, VRSA, VRE, GN (except

Pseudomonas)• Adverse effects limit its use

• Myalgias• Arthralgias• Nausea• Hyperbilirubinemia

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Aztreonam• Use in patients with penicillin allergy• Active against Pseudomonas and

Enterobacteriaceae• No activity against GP organisms

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Ceftolozane-tazobactam• Novel cephalosporin• Broad-spectrum activity against Pseudomonas

aeruginosa, ESBL Enterobacteriaceae• Limited GP activity• Indications for complicated UTI and complicated

intra-abdominal infections when combined with Metronidazole

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Ceftazidime/avibactam• Avibactam is a novel broad-spectrum beta-

lactamase inhibitor• Activity against P. aeruginosa,

Enterobacteriaceae, some Klebsiellapneumoniae carbapenemases (KPC)

• Indication for use in complicated UTI and complicated intra-abdominal infections when combined with Metronidazole

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Post-Test QuestionWhich antibiotic would you use to cover both methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa infection?1. Ceftolozane/tazobactam2. Dalbavancin3. Meropenem4. Linezolid5. No such antibiotic exists

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Questions & Discussion

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References• http://www.uptodate.com/contents/antimicrobial-

stewardship?source=search_result&search=antibiotics&selectedTitle=1~150

• http://www.uptodate.com/contents/beta-lactam-antibiotics-mechanisms-of-action-and-resistance-and-adverse-effects?source=search_result&search=antibiotics&selectedTitle=2~150

• http://www.uptodate.com/contents/methicillin-resistant-staphylococcus-aureus-mrsa-in-adults-treatment-of-skin-and-soft-tissue-infections?source=search_result&search=mrsa+antibiotics&selectedTitle=1~150

• http://www.uptodate.com/contents/antimicrobial-approach-to-intra-abdominal-infections-in-adults?source=search_result&search=antibiotics&selectedTitle=5~150

• Antibiotic and Chemotherapy, Ninth Edition, Chapter 13, 170-199, Beta-Lactam Antibiotics. David Greenwood.