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ANTIMICROBIALRESISTANCEANDAPPROPRIATEANTIBIOTICSELECTIONMARI T. GALANG, MSN, RN, AGACNP

• This is for educational purposes only. This does not constitute giving advice or informal consultation regarding specific cases. Ultimately the treating provider is responsible for assessing the patient, the nature and extent of the infection and prescribing appropriate therapy.

• Be cautious with “curbside” consults

• Alexander Fleming’s Nobel Prize Acceptance speech• Moral: If you use Penicillin, use enough.

• CDC 2013 Antibiotic Resistance Threat paper:• 2,049,442 illnesses and 23,000 deaths due to antimicrobial resistance

"Sir Alexander Fleming - Nobel Lecture: Penicillin". Nobelprize.org. Nobel Media AB 2014. Web. 29 May 2017. <http://www.nobelprize.org/nobel_prizes/medicine/laureates/1945/fleming-lecture.htmlCenters for Disease Control. 2013. Antibiotic Resistance Threats in the United States, 2013. p13.

This Photo by Unknown Author is licensed under CC BY-SA

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CORE ACTIONS TO PREVENT RESISTANCE

• Prevent Infections

• Immunization, Hand washing, food preparation

• Tracking

• CDC’s National Healthcare Safety Network

• Emerging Infections Program

• Improving Antibiotic Prescribing/Stewardship

• Developing new drugs and diagnostic tests

MECHANISMS OF ACTION

1. Interfere with cell wall synthesis

1. Beta lactams, Glycopeptides

2. Inhibition of protein synthesis1. Macrolides, Linezolid, Clindamycin, Tetracycline, Aminoglycosides

3. Interference with nucleic acid synthesis1. Fluoroquinolones, Rifampin

4. Inhibition of a metabolic pathway

1. Sulfonamides

Tenover, F. 2006. Mechanisms of Antimicrobial Resistance in Bacteria. The American Journal of Medicine. Volume 119 (6A), S3-10.

HOW TO CIRCUMVENT GETTING KILLED

• Acquisition of resistant genes (horizontal evolution)

• Efflux pumps

• Downregulation of porins

• Change the target protein in the cell wall

• Vertical Evolution (selecting out through antimicrobial exposure)

• “what doesn’t kill you makes you stronger”

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•MRSA, MSSA, AmpC, ESBL, KPC, CRE, mcr

COAGULASE NEGATIVE STAPHYLOCOCCUS (CONS)

• Gram positive organism

• Naturally living on our skin

• Advent of modern medicine (venous lines, invasive procedures)

• Grouping of staphylococci that is coagulase negative (as opposed to S. aureus which is coagulase positive)

• Epidermidis, lugdunensis, etc.

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STAPHYLOCOCCUS AUREUS

• Gram positive organism

• Estimated no. of annual cases: 80,000 with 11,000 deaths

• “sticky”, high morbidity and mortality

• MSSA – Methicillin Susceptible Staphylococcus aureus

• MRSA – Methicillin Resistant Staphyloccus aureus• [mecA] resistance gene

Centers for Disease Control. 2013. Antibiotic Resistance Threats in the United States, 2013.

Clinical Infectious Diseases, 2011.

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STREPTOCOCCUS PNEUMONIAE

• “Pneumococcus”

• Part of the causative differential for Community Acquired Pneumonia

• Ceftriaxone, Levofloxacin/Moxifloxacin, Azithromycin

• Multiple serotypes• Pneumococcal Polysaccharide Vaccine (PPSV23)/Brand name Pneumovax 23

• 13-valent pneumococcal conjugate vaccine/Brand name: Prevnar 13

ENTEROCOCCUS

• Part of the Streptococus family (Group D)

• Enteric Flora

• Enterococcus species:

• Faecalis

• Faecium

• vanA resistance gene

• Ampicillin, Linezolid, Daptomycin, Vancomycin, Imipenem/Cilastatin

• Intrinsically resistant to vancomycin:• Enterococcus gallinarum

• Enterococcus casseliflavus

• Enterococcus flavescens

Bennett, John E.; Dolin, Raphael; Blaser, Martin J.. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases (Kindle Location 28446). Elsevier Health Sciences. Kindle Edition.

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PSEUDOMONAS AERUGINOSA

• Enteric Flora

• Gram negative rod• Non-Lactose Fermenter

• Gastrointestinal/Genitonurinary Infections

• Ceftazidime, Cefepime, Meropenem, Imipenem/Cilastatin, Piperacillin/Tazobactam,

• ceftazidime/avibactam, ceftolozane/tazobactam

• Ciprofloxacin, Levofloxacin

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INDUCIBLE RESISTANCE

• ampC resistance gene that is inducible when exposed to narrow cephalosporins• Enterobacter, Citrobacter, Serratia, Morganella, Providencia

Bennett, John E.; Dolin, Raphael; Blaser, Martin J.. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases (Kindle Location 28446). Elsevier Health Sciences. Kindle Edition.

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EXTENDED SPECTRUM BETA-LACTAMASE (ESBL)

• Multiple genes discovered that confer resistance• TEM, SHV, ampC, CTX to name a few

• Clinical implications?• Limited antimicrobial options

KLEBSIELLA PRODUCING CARBAPENAMASE (KPC)

• Carbapenam resistance (ertapenem, meropenem, imipenem, doripenem)• [KPC] – can be acquired by multiple gram negatives

• Metallo-beta-lactamases: uses zinc ion to hydrolyze betalaca• Resistant to clavulanic acid, tazobactam, sulbactam

• VIM, SPM, GIM, SIM, NDM

• NDM – New Delhi Metallo Beta-Lactamase

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ESCHERICHIA COLI

• Gram negative enteric organism

• First described in 1885

• Lactose Fermenter, motile

• Very versatile

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KLEBSIELLA PNEUMONIAE

• Gram negative enteric flora

• Urinary Tract infection, Liver abscesses and pneumonia

• Polysaccharide capsule >>mucoid colony

• Intrinsically resistant to Ampicllin

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ADDITIONAL REFERENCES

• Bennett, John E.; Dolin, Raphael; Blaser, Martin J.. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. Elsevier Health Sciences. Kindle Edition.