Antibiotics and Resistance: New Drugs to Help Combat the ......cUTI, cIAI December 2014 Ceftazidime/Avibactam (Avycaz®) cUTI,cIAI February 2015 Bezlotoxumab(Zinplava

7/24/2018

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ANTIBIOTICS AND RESISTANCE: NEW DRUGS TO HELP COMBAT THE

PROBLEM

Anna-Kathryn Burch, M.D.

Medical Director, Pediatric Antimicrobial Stewardship

Palmetto Health Children’s Hospital

PHUSC

DISCLOSURES

• I have nothing to disclose.

CLINICAL CASE

• Patient is a 17 year old with history of interstitial nephritis, etiology unknown.

• required a cadaveric renal transplant at MUSC 7/2/14

• Patient was doing well until March 2018 when she began to experience kidney rejection

• Kidney Bx 3/9/18 for pathology to prove GVHD

• Oh by the way, she admits she quit taking her immunosuppressive drugs after the biopsy proved she was in rejection.

• Patient had large hematoma in the bladder s/p kidney biopsy.

• 3/10/18 clot removed via large bore foley

CLINICAL CASE

• In the background…Patient is receiving plasmapheresis and increased immunosuppression

• thymoglobulin, rituximab and abatacept per peds Nephrology

• 3/15-3/30/18: Urosepsis #1 with ESBL E.coli., Blood and Urine culture positive.

• Tx x 10 days with Ertapenem after clearing blood culture.

• 4/4-4/17/18: Urosepsis #2 with ESBL E.coli (stable susceptibilities), blood and urine culture positive.

• Patient had a PICU stay.

• 4/4 ECHO neg, 4/8 RUS neg, 4/9 thoracic/lumbar MRI neg.

• Tx x 14 days with Ertapenem after clearing blood culture.

CLINICAL CASE

• readmitted 4/20/18 for line placement and plasmapheresis.

• 4/22-5/21/18: Urosepsis #3 with ESBL E.coli (stable susceptibilities), blood culture

only positive as urine culture unfortunately no performed.

• 4/24 ECHO neg

• 4/26 MRI abdomen and pelvis showed subtle areas of delayed-diminished

enhancement involving mid and lower aspect of left kidney which can be seen in

the setting of pyelonephritis.

• Tx x 4 weeks of IV ertapenem after clearing blood culture.

CLINICAL CASE

• 5/29-6/18/18: Patient admitted with fever-dx with ESBL E.coli in urine and

C.diff colitis.

• Patient tx with Ertapenem and Fidaxomicin x 14 days.

• 5/31 MRI abd/pelvis was negative.

• Because ESBL E.coli and C.diff found in stool, patient underwent FMT 6/13/18.

• Repeat urine culture 6/15/18 was negative.

• 6/22/18: Stool culture and stool c.diff s/p FMT performed. Stool is c.diff and ESBL

E.coli positive.

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CLINICAL CASE

• 6/24/18: Urosepsis #4 with ESBL E.coli (stable susceptibilities) in blood and

urine cultures.

• Patient has been started on Ceftazidime/Avibactam for urosepsis and oral vancomycin

for c.diff colitis as she is now symptomatic.

•WHAT DO YOU DO WITH THIS

PATIENT?????

ANTIBIOTIC RESISTANCE

ANTIMICROBIAL HISTORY

• Ancient Egyptians used honey as a wound dressing

• Contains hydrogen peroxide and the stickiness of honey provided a wound dressing

• Ancient Serbia:

• old bread was pressed on wounds to help prevent infection

• many of the molds on the bread contained early, raw forms of penicillin

• 1640:

• John Parkington wrote about mold's effectiveness as an antibiotic

• 1877:

• Louis Pasteur determined that cultures of bacillus anthracis specked with penicillium notatum could not easily sustain growth

World Health Organization Report on Infectious Diseases, 2000

ANTIMICROBIAL HISTORY

• 1927:

• German Gerhard Domagk found that an industrial dye, prontosil rubrum, had antibacterial action against staphylococci and hemolytic streptococci

• Sulfonamide was the first antimicrobial

• Received Nobel Prize

• 1928:

• British Alexander Fleming observed the antibiotic effects of penicillin

• Penicillium notatum had destroyed staphylococcus bacteria in culture

• Penicillin was finally isolated in 1939

• early 1940s large scale fermentation processes were developed for the production of penicillin


WHAT IS ANTIMICROBIAL RESISTANCE?

• Ability of organisms to resist the effects of an antimicrobial

• Organisms change in some way that reduces or eliminates the effectiveness of drugs,

chemicals, or other agents designed to cure or prevent infections

• The microbes have a better survival rate

• continue to multiply causing more harm

http://www.cdc.gov/drugresistance/community/anitbiotic-resistance-faqs.htm

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ANTIMICROBIAL RESISTANCE

• Selected Pressure

• Susceptible microbes are killed easily with antimicrobials leaving organisms that are resistant

• They can then pass on their resistance genes

• Replication

• Conjugation

• Plasmids carrying the genes jump from one organism to another

• “This process is a natural, unstoppable phenomenon exacerbated by the abuse, overuse and misuse of antimicrobials in the treatment of human illness and in animal husbandry, aquaculture and agriculture.”




• Abuse, Overuse and Misuse of Antimicrobials• Increase in drug-resistant organisms

• Primary cause is repeated and improper uses of antimicrobials

• Increased pressure on physicians inevitably leads to "defensive" and unnecessary prescribing as a means of forestalling potential complications

• In North America it is estimated that physicians in both Canada and the United States over-prescribe antibiotics by

50%


“… the microbes are educated to resist

penicillin and a host of penicillin-fast

organisms is bred out… In such cases the

thoughtless person playing with penicillin is

morally responsible for the death of the

man who finally succumbs to infection with

the penicillin-resistant organisms. I hope

this evil can be averted.”

- Sir Alexander Fleming, NY Times June 1945


• Causal associations between antimicrobial use and the

emergence of antimicrobial resistance

• Changes in antimicrobial use are paralleled by changes in prevalence of resistance

Dellit TH et al. CID 2007

Fluoroquinolone Use and Resistance Rates in PSA and Gram-

Negative Bacilli

Neuhauser, M. M. et al. JAMA 2003


• Causal associations between antimicrobial use and the emergence of antimicrobial resistance (cont)

• Resistance is more prevalent in health care-associated bacterial infections

• Patients with health care-associated infections caused by resistant strains are more likely than control patients to have prior antibiotic exposure

• Areas within hospitals with the highest rates of antimicrobial resistance also have the highest rates of antimicrobial use

• Increased length of exposure to antimicrobials increases the likelihood of colonization with resistant organisms


• There is an association between development of antimicrobial resistance and

mortality

• Cosgrove et al CID 2003: Meta-analysis

• Patients with MRSA bacteremia had an increased risk of mortality compared to

patients with MSSA bacteremia

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ANTIMICROBIAL DEVELOPMENT VS. RESISTANCE

1st case MRSA reported 1961

FEWER DRUGS CREATED TO COMBAT ANTIBIOTIC RESISTANCE

WHAT ARE WE DOING ABOUT RESISTANCE

NEW DRUGS 2014-2017

Drug Indications Approval Date

Dalbavancin (Dalvance®) ABSSSI May 2014

Tedizolid (Sivextro®) ABSSSI June 2014

Oritavancin (Orbactiv®) ABSSSI August 2014

Ceftolozane/Tazobactam

(Zerbaxa®)

cUTI, cIAI December 2014

Ceftazidime/Avibactam

(Avycaz®)

cUTI, cIAI February 2015

Bezlotoxumab (Zinplava®) C.difficile Infection October 2016

Delafloxacin (Baxdela®) ABSSSI June 2017

Meropenem/Vaborbactam

(Vabomere®)

cUTI September 2017

Plazomicin (Zemdri®) cUTI June 2018

NEW GRAM-POSITIVE AGENTS

• Dalbavancin (Lipoglycopeptide – think long acting Vancomycin)

• Oritavancin (Lipoglycopeptide – think long acting Vancomycin)

• Tedizolid (Oxazolidinone – think Linezolid like)

• Delafloxacin (Fluoroquinolone – think ciprofloxacin like)

DALBAVANCIN (DALVANCE®)

• Lipoglycopeptide

• Mechanism of Action

• Inhibits cross-linking of peptidoglycans

• Destabilizes cell wall, causing cell death

• Concentration dependent, bactericidal

• FDA approved indications: acute bacterial skin and skin structure infections (ABSSSI)

Roberts KD, et al. Pharmacotherapy 2015;35(10):935-948

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• ABSSSI recommended Adult dose:

• Single-dose regimen:

• 1500mg IV x 1 dose

• Two-dose regimen:

• 1000mg IV day 1, followed by 500mg IV day 8

• Effective half-life: 8.5 hours

• No dose adjustment necessary with hemodialysis

• No adjustment for mild liver dysfunction

• Infused over 30 minutes

• Cost around $4500/course

• No home health, No PICC line



• Pediatric Dosing:

• phase 1, open-label, multicenter study to investigate the pharmacokinetics (PK) and safety of a single dose of intravenous dalbavancin in hospitalized pediatric subjects 3 months to 11 years of age

• the following age-dependent dosing regimen was found to achieve similar dalbavancin exposure to that in adults administered a 2-dose regimen:

• 6 to <18 years of age, 12 mg/kg (1000 mg maximum) on day 1, 6 mg/kg (500 mg maximum) on day 8

• 3 months to <6 years of age, 15 mg/kg (1000 mg maximum) on day 1, 7.5 mg/kg (500 mg maximum) on day 8

• following age-dependent regimen was found to match adult exposure after a single-dose (1500 mg):

• 6 to <18 years of age, 18 mg/kg (1500 mg maximum) on day 1

• 3 months to <6 years of age, 22.5 mg/kg (1500 mg maximum) on day 1

Pediatr Infect Dis J. 2017 Jul;36(7):645-653.

ORITAVANCIN (ORBACTIV®)

• Lipoglycopeptide

• Multiple Mechanisms of Action

• Inhibits cross-linking of peptidoglycans

• Destabilizes cell wall, causing cell death

• Disruption of bacterial membrane integrity

• Leads to depolarization, permeabilization and cell death

• Concentration dependent, bactericidal

• Only lipoglycopeptide that can cover VRE

• FDA approved indications: ABSSSI



• ABSSSI recommended adult dose:

• 1200 mg IV once

• Terminal half-life: 8-10 days

• No adjustment for renal or hepatic impairment

• Infused over 3 hours

• Cost around $2900 per dose

• No home health, No PICC line



https://clinicaltrials.gov/ct2/show/NCT02134301

DALBAVANCIN/ORITAVANCIN STEWARDSHIP

• Formulary should choose only one if possible simplify for practitioners

• Possible uses:

• If patient isn’t an ideal candidate for oral antibiotics

• Key Patient groups: lack of transportation, live to far from infusion center, poor follow

up

https://www.ncbi.nlm.nih.gov/pubmed/28060045

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TEDIZOLID (SIVEXTRO®)

• Member pf oxazolidinone class (similar to Linezolid)

• Prodrug: tedizolid phosphate—converted to in vivo active form by phosphatases

• Active against VRE


• Inhibits protein synthesis by binding to the 23S ribosomal RNA of the 50S subunit, preventing the formation of 70S complex

• Why its unique:

• More potent activity against MDR gram-positive pathogens allows for lower amounts of drug to be given

• Phase 3 trial compared 6 days of tedizolid vs 10 days of linezolid

• May have less risk of adverse effects:

• MAO inhibition, bone marrow effects


Kisgen JJ, et al. Am J Health Syst Pharm. 2014 Apr 15;71(8):621-33

TEDIZOLID (SIVEXTRO®)

• ABSSSI recommended adult dose:

• 200 mg IV/PO daily for 6 days

• Adolescent Dosing:

• multicenter, open-label study, a single IV infusion (N = 10) or oral dose (N = 10) of

200 mg tedizolid phosphate was administered to adolescents already receiving

antibacterial treatment for presumed or documented infection.

• Overall pharmacokinetics of tedizolid was similar after administration of a single oral

or IV 200 mg dose, and bioavailability was high.

• Exposure profiles were similar to those in adults.

Pediatr Infect Dis J. 2016 Jun;35(6):628-33

Kisgen JJ, et al. Am J Health Syst Pharm. 2014 Apr 15;71(8):621-33

TEDIZOLID STEWARDSHIP

• last-line treatment of ABSSSI when other options are not feasible

• Especially in patients who would otherwise be given PO linezolid but are restricted

due to drug interactions

• Will have a minimum role most likely

DELAFLOXACIN (BAXDELATM)

• Anionic fluoroquinolone

• Concentration-dependent bactericidal activity

• Mechanism of action

• Equally potent activity against topoisomerase IV and DNA gyrase

• More potent activity in acidic environments due to molecule having a weak acid

property


Cho JC, et al. Pharmacotherapy 2017 Oct 23

DELAFLOXACIN (BAXDELATM)

• Why its unique:

• Broad spectrum of activity against gram-negative, atypical, anaerobic and gram-positive

bacteria

• MRSA, PSA

• No QTc prolongation found in initial studies

• ABSSI recommended adult dose:

• 300 mg IV q 12 hours or 450 mg PO q 12 hours

• No pediatric clinical trials currently…

Cho JC, et al. Pharmacotherapy 2017 Oct 23

DELAFLOXACIN STEWARDSHIP

• Treatment of polymicrobial ABSSSI when all other IV or PO options are not

feasible (in adolescent populations)

• Will have a minimum role most likely

https://www.ncbi.nlm.nih.gov/pubmed/26910588

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NEW GRAM-NEGATIVE AGENTS

• Ceftolozane/Tazobactam (think cephalosporin with a friend—help against

Enterobacteriaceae ESBLs and resistant PSA)

• Ceftazidime/Avibactam (think cephalosporin with a friend—help against

Enterobacteriaceae KPCs and ESBLs)

• Meropenem-Vaborbactam (think help against Enterobacteriaceae KPCs and

ESBLs)

BETA-LACTAM RESISTANCE

Peds ASP conference June 1, 2017

CEFTOLOZANE/TAZOBACTAM (ZERBAXA®)

• Ceftolozane

• Cephalosporin with potent anti-pseudomonal activity

• Similar to ceftazidime--with a different side chain

• Destroyed by ESBLs and Carbapenemases

• Relatively stable vs Amp C

• Tazobactam

• Protects ceftolozane from many ESBLs and Cephalosporinases

• Not active against AmpC beta-lactamases or Carbapenemases

Zhanel GG et al. Drugs 2014;74:31-51.


• Spectrum of Activity:

• Strong Against:

• Pseudomonas aeruginosa, including ceftazidime- and carbapenem-resistant strains

• Enterobacteriaceae, including many ESBL-producing strains

• Weak Against:

• Ceftazidime-resistant Enterobacter spp

• Carbapenemase-producing Enterobacteriaceae

• Gram-positive anything

• Gram-negative anaerobes

• Tazobactam does add anaerobic coverage, but it is weaker

Zhanel GG et al. Drugs 2014;74:31-51.


• Pediatric Dosing at PHR:

• Neonatal: 18 mg/kg IV q 8 hours

• Each 18 mg/kg ceft/taz=12 mg ceftolozane/kg per dose

• General: 27 mg/kg IV q 8 hours


• CF: 54 mg/kg IV q 8 hours


CEFTOLOZANE/TAZOBACTAM STEWARDSHIP

• Helpful against ESBL Enterobacteriaceae and Resistant PSA

• Has not been very helpful in our CF population

• Will have a moderate/major role most likely in GNR Infections

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CEFTAZIDIME/AVIBACTAM (AVYCAZ®)

• Ceftazidime

• Third-generation antipseudomonal cephalosporin

• Susceptible to ESBL and KPC enzymes, but not porin channel changes that affect

carbapenems

• Avibactam

• Novel beta-lactamase inhibitor not based on beta-lactam structure

• Active against ESBLs, KPC-type and OXA-48 carbapenemases

• Not active against metallo-beta lactamases



• Strong Against:

• Many gram-negative bacilli

• PSA

• Enterobacteriaceae producing KPC and ESBL enzymes

• Weak Against:

• Gram-positive organisms

• GNRs producing metallo-beta-lactamases (NDM)

• Gram-negative anaerobes

• Avibactam does not add anaerobic coverage (unlike tazobactam)

• Doesn’t help with Acinetobacter


• Pediatric Dosing at PHR:

• 62.5 mg/kg IV q 8 hours

• Each 62.5 mg/kg ceftaz/avi=50 mg ceftaz/kg per dose

CEFTAZIDIME/AVIBACTAM STEWARDSHIP

• Helpful against ESBL and KPC producing Enterobacteriaceae

• Has been very helpful in our CF population

• Will have a major future role most likely in GNR Infections

MEROPENEM/VABORBACTAM (VABOMERE®)

• Meropenem

• Potent antipseudomonal carbapenem with broad spectrum

• Resistant to destruction from ESBLs, cephalosporinases

• Vaborbactam

• Boronic acid beta-lactamase inhibitor

• Active against ESBLs, KPCs but not metallo-beta-lactamases (NDM)

• Doesn’t add activity against resistant PSA

Toussaint K, Gallagher JC. Ann Pharmacother 2015;49:86-98



• Strong Against:

• Many gram-negative bacilli

• Carbapenem-susceptible Pseudomonas aeruginosa

• Enterobacteriaceae producing KPC and ESBL enzymes

• Weak Against:

• Carbapenem-resistant PSA

• GNRs producing metallo-beta-lactamases (NDM) or OXA-enzymes

Shaeles DM. Ann NY Acad Sci 2013;1277:105-114

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• Pediatric Dosing:

• In trials for PK/PD data in children

MEROPENEM/VABORBACTAM STEWARDSHIP

• Helpful against ESBL and KPC producing Enterobacteriaceae

• Hopefully will be helpful in our CF population but we have not used this at

PHR yet

PLAZOMICIN (ZEMDRITM)

• Neoglycoside

• next-generation aminoglycoside


• Inhibits bacterial protein synthesis

• Exhibits dose-dependent bactericidal activity

• Activity against:

• ESBL Enterobacteriaceae

• fluoroquinolone-resistant and aminoglycoside-resistant GNB

• GNB-expressing Amp C cephalosporinases, carbapenemases, and metallo-beta-lactamases (NDM)

• not Proteus species or strains with aminoglycoside-resistant methylase genes (eg, ArmA, RmtC)

• Activity against P. aeruginosa and Acinetobacter baumannii remains limited

Clinical Infectious Diseases, Volume 56, Issue 12, 15 June 2013, Pages 1685–1694

Expert Review of Anti-infective Therapy, 10:4,459-473

OTHER AGENTS IN GNR PIPELINE

Agent Class Company Notes

Imipenem/Relebactam Carbapenem-beta-

lactamase Inhibitor

Merck

Cefiderocol Siderophore

Cephalosporin

Shionogi Novel mechanism

that relies on active

iron transport

“Trojan Horse”

CEFIDEROCOL:USING IRON AS A TROJAN HORSE

NON-ANTIBIOTIC OPTIONS FOR TREATMENT OF MDR ORGANISMS

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FECAL MICROBIOTA TRANSPLANT (FMT)

• FMT has been used in adults (and children) for c.diff colitis with very good

cure rates

• Can FMT be used to help eradicate MDR GNR that colonize the GI tract???


• 34 year old had recurrent UTI preventing her from receiving a kidney/pancreas transplant.

• Combined fecal microbiota transfer and antibiotic treatment prevented recurrences of urinary tract infections with multidrug-resistant (MDR) Pseudomonas aeruginosa, but it failed to eradicate intestinal colonization with MDR Escherichia coli.


• Treated 15 patients carrying ESBL-producing Enterobacteriaceae(ESBL-EB) with FMT.

• Seven patients underwent a second FMT after 4 weeks when ESBL-EB remained

• total number of 22 transplants

• The objective was decolonization of ESBL-EB.

• Three out of 15 (20%) patients were ESBL-negative at 1, 2 and 4 weeks after the first transplant

• Six out of 15 (40%) were negative after the second transplant.

• Comparison of fecal microbiota at baseline and 4 weeks after FMT revealed restoration of microbial diversity after FMT and a microbial shift towards donor composition.

BMC Res Notes. 2018; 11: 190.


• Twenty-five FMTs were performed in 20 participants who were colonized by a median of 2 (range, 1–4) strains of antibiotic resistant bacteria (ARB).

• 40% had neutropenia

• The primary endpoint was reached in 15/25 (60%) of the FMTs and more frequently in cases in which there was no periprocedural use of antibiotics (79% vs 36%, P < .05).

• 15/20 (75%) participants experienced complete ARB decolonization.

• There were no severe adverse events.

• The microbiota composition analysis revealed higher abundance of Barnesiellaspp., Bacteroides, and Butyricimonas and greater bacterial richness in the fecal material, resulting in eradication of Klebsiella pneumoniae compared with nonresponders.


• Palmetto Health Children’s Hospital:

• N=1

• FMT 6/13/18 for ESBL E.coli colonization and C.diff infection

• 6/22/18: Stool culture and stool c.diff s/p FMT performed.

• Stool is c.diff and ESBL E.coli positive.

• Patient started on antibiotics 2 days later for urosepsis #4

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863815/

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PHAGE THERAPY

• 2015, 69 year old male on vacation in Egypt developed pancreatitis (with pseudocyst) with a MDR Acinetobacter

• Treated with meropenem, tigecycline and colistin

• Airlifted home to UCSD—bacteria is now resistant to all antimicrobials

• His wife (an infectious disease epidemiologist and director of the UC San Diego Global Health Institute) searched for a way to save him.

• A colleague mentioned a friend had traveled to Tblisi, Georgia to undergo “phage therapy” for a difficult condition and had been “miraculously cured.”

• 3 Research teams in the US had phages that matched his Acinetobacter

• eIND from FDA

https://medschool.ucsd.edu/som/medicine/divisions/infectious-diseases/research/center-innovative-phage-applications-and-therapeutics/Pages/default.aspx https://medschool.ucsd.edu/som/medicine/divisions/infectious-diseases/research/center-innovative-phage-applications-and-therapeutics/Pages/default.aspx

PHAGE THERAPY

• Phages (Bacteriophages) are viruses that solely and selectively target and kill

bacteria.

• Have been shown to effectively fight off and kill multi-drug resistant bacteria

• In theory, when all antibiotic medication fails, bacteriophages could still

succeed in killing the bacteria before the infection could kill the person.

https://medschool.ucsd.edu/som/medicine/divisions/infectious-diseases/research/center-innovative-phage-applications-and-therapeutics/Pages/default.aspx

PHAGE THERAPY HISTORY

• Frederick Twort

• 1915

• bacteriologist from England

• first to suggest that it was a virus that was responsible for previous observations of a "factor" that killed bacteria

• Felix d'Herelle

• 1917

• microbiologist at the Institut Pasteur in Paris

• picked up where Twort left off and first proposed phages as a therapy for human infections



• The first known therapeutic use of phages occurred in 1919

• d'Herelle and several hospital interns ingested a phage cocktail to check its safety

• gave it to a 12-year-old boy with severe dysentery

• symptoms cleared up after a single dose

• he fully recovered within a few days

• d'Herelle didn't publish findings until 1931


• Eli Lilly produced phages for human use in the US

• In the 1940s

• marketed to treat a range of bacterial infections

• Invention of antibiotics = Phage therapy fell out of favor in the U.S. and most of Europe

• Russia, Poland and the Republic of Georgia —

• antibiotics not as easily accessed

• phage therapy and commercial production continued

• phage studies continued to be non-randomized and uncontrolled

• data was lacking to show that phage therapy was effective


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• Western scientists "re-discovered" phage therapy in the 1980s.

• Growing threat of antibiotic-resistant bacterial strains has continued to further

interest in phage therapy as a potential alternative


PHAGE THERAPY

• Benefits

• Very specific about the bacteria they infect

• Damage to other bacteria or human cells is minimal

• Risk of resistance is low

• Bacteria can eventually shed the surface receptors that phages use to dock and enter the cells

• If resistance occurs, researchers can find new phages that work

• nearly inexhaustible supply of phages in nature


PHAGE THERAPY

• Risks

• phage therapy testing has largely been observational, or conducted in small, non-

randomized trials

• What are the short and long term side effects???

• Septic shock due to bacteria releasing endotoxins when broken up by phages

• not widely reported through the many decades of phage therapy in Eastern

Europe


PHAGE THERAPY

• Risks continued

• Transduction: phages are able to transfer DNA from one bacterium to another

• Phage manipulation and engineered introduction could theoretically introduce new

virulence factors or toxins to already pathogenic bacteria, or convert non-

pathogenic bacteria into pathogens.

• pre-selecting phages that have been carefully screened for toxins and virulence

factors


PHAGE THERAPY IN USA

• IPATH-Center for Innovative Phage

Applications and Therapeutics

• first bacteriophage therapy center in North

America

• UCSD

• https://medschool.ucsd.edu/som/medicine/d

ivisions/infectious-diseases/research/center-

innovative-phage-applications-and-

therapeutics/Pages/default.aspx


PHAGE THERAPY

• Palmetto Health Children’s Hospital:

• N=1 (hopefully)

• Patient’s strain of ESBL E.coli has been sent to Adaptive Phage Therapeutics (APT)

• If phage cocktail is identified, it will take 4+ weeks to make

• Then we will have to have to be approved by the FDA via an eIND

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SUMMARY

• Antibiotic Resistance is real

• At least 50% of antimicrobials prescribed in North America are unnecessary

• 80% of all antibiotics used in the US are given to animals

• Antimicrobial Stewardship is here to stay

• JCAHO, CDC, President Executive Order

• Not a lot of new antibiotics are coming out of the drug pipeline

• We are turning to century old treatments for pan resistant bacteria

Documents

Antibiotics and Resistance: New Drugs to Help Combat the ......cUTI, cIAI December 2014 Ceftazidime/Avibactam (Avycaz®) cUTI,cIAI February 2015 Bezlotoxumab(Zinplava