11.18.15 antimicrobial resistance vignettes review lee

7/25/2019 11.18.15 Antimicrobial Resistance Vignettes Review Lee

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ANTIMICROBIALRESISTANCE: CASE-

BASED REVIEW

Staci Lee, MD, MEHP

November 18, 2015

(Slide set courtesy of Dr. Michelle Iandiorio)


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Learning Objective

To apply your knowledge of antimicrobial resistance toclinical scenarios

To provide you a brief review of antimicrobial resistancemechanisms


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GET YOUR ICLICKERS

READY


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Case 1

A microbiologist is working with Staphylococcus

aureus in the lab, testing the activity of various

antimicrobial agents against its growth.

She notices that metronidazole does not have

any activity against the bacterial isolate, no matter

how high a concentration of drug she uses.


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Which of the following is the correct explanationfor why Staph aureus is resistant to

metronidazole?

A.

Alteration of metronidazole binding site in

MRSA.

B.

Decreased MSSA cell wall permeability to

metronidazole.

C. Enzymatic degradation of metronidazole by

Staph aureus.

D.

Innate ability of Staph aureus to resist the

activity of metronidazole.


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Mechanisms of Resistance

Intrinsic resistance

Innate ability of bacterial species to resist

activity of drug

Transfer of genetic material coding for resistance

Alteration of target of antibiotic

Enzymatic degradation of antibiotic

Changes in cell wall permeability

Production of efflux pumps


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Case 2

A 3-year old girl is brought in by her aunt for a

fever, sore throat, and neck swelling. The girl has

been unable to swallow any water today.

She has never had any significant illnesses.

Her parents did not have her vaccinated for

religious reasons.


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Case 2 continued

She is suspected of having an infection whose

symptoms result from a toxin which prevents

protein synthesis by catalyzing ADP-ribosylation

of elongation factor EF-2.


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Which of the following is the mechanism bywhich the infecting organism obtained the

genes to produce this toxin?

A. ConjugationB. Transduction

C. Transformation

D. Transposition


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Horizontal Gene Transfer


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Case 3

An elderly chronic nursing home patient is brought to thehospital with new onset confusion, low-grade fever,

tachycardia, and low blood pressure.

She was diagnosed with a urinary tract infection threedays before and given nitrofurantoin.

In the hospital, she is diagnosed with pyelonephritis and

urine cultures grew Enterococcus. Bacterial sensitivities

showed that the organism is resistant to ampicillin andvancomycin.


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What is the correct mechanism for the

resistance of Enterococcusto vancomycin?

A.Alteration in vancomycin binding site

B.

Enzymatic degradation of vancomycin.

C. Innate ability of Enterococcus to resist

the activity of vancomycin.

D. Thickened cell wall


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Vancomycin-Resistant Enterococci (VRE)


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Case 4

A 12-year old girl with Type I DM is seen

with an expanding are of erythema

surrounding an abscess at an injection site.


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Case 4 continued

Purulence from the abscess area grows

Staphylococcus aureus.

The microbiology lab technician inoculates brothbottles that contain various concentrations of

moxifloxacin.

You are asked to confirm the MIC report.


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What is the Minimum Inhibitory

Concentration (MIC)?

! #$%&' ()

*+,-.(,/

0 #$%&' 1 #$%&' 2 #$%&' !3 #$%&' 40 #$%&' 31 #$%&'

56*+7*87 .+(/9:9& () -*/6;8.*

A. B. C. D.


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Case 5

A 56-year old man with morbid obesity and chronicbilateral lower extremity lymphedema is seen for recurrent

lower extremity cellulitis.

He is allergic to penicillin (anaphylaxis)

He has no open wound on his lower extremities so nowound cultures could be obtained but his blood cultures

grew Staph aureus.

Initial sensitivity testing shows resistance to erythromycin

and sensitivity to clindamycin.


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This additional test identifies this stain of Staph

aureus as having:

A. Inducible resistance to

clindamycin in the lab

B.

Reversion back toerythromycin sensitivity in

the lab

C. Selected resistance to

clindamycin in vivo

D. Selective resistance to

erythromycin in vivo

D-Test= erythromycin is inducible resistace to clinda,ycin

resistance to clindamycin (postive Test)> report it


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Case 6

A 40-year old alcoholic man is seen in the ED withfever, productive cough with current-jelly colored

sputum.

Sputum culture reveals Klebsiella pneumoniae.


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Which plate demonstrates that the bacteria is

resistant to ceftriaxone tested by disc diffusion?

A. B.


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An ESBL is suspected. Which of the following

options is the mechanism for ESBL productionin GNR?

A. Induced production of ESBL that is

chromosomal

B. Induced production of ESBL that is

plasmid-mediated

C. Selection of ESBL-producing strain

ESBL carried by plasmid!!!!

BUT


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Case 7

A 63-year old patient who has been in the TSI for the pastthree months for complications related to bowel surgery

for colon cancer is seen for ventilator-associated

pneumonia (VAP) with Pseudomonas aeruginosa.

The patient is continues to have fever, productive sputum,

high ventilator settings and high oxygen requirement

despite treatment with meropenem.


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A modified Hodge test is performed to see if thisPseudomonasstrain produces an enzyme that

degrades carbapenems.

The image on the left shows theresults of the test.

You confirm that thisPseudomonasstrain:

A. Produces carbapenemase

B. Does not produce

carbapenemase

bacteria susceptible to carabepems

this is what we test (the bug)


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Case 8

A 32-year old man with AML s/p HSCT

has been chronically treated with

valganciclovir for CMV colitis.The patient is now seen with fever and

worsened bloody diarrhea.

You are concerned about ganciclovir-resistant CMV.


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Which of the following is correct about

ganciclovir resistance in CMV?

A. Deletion of CMV thymidine kinase

B. Mutation in viral DNA polymerase causesresistance to ganciclovir but not foscarnet

C. Point mutation in by CMV phosphotransferase

is encoded by UL97 gene

acyclovir


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Case 9

A 45 year-old man with HIV since 1996 is seen for routinecare.

He has been taking tenofovir, emtricitabine, and

atazanavir/ritonavir for the past 4 years with goodtolerability and good virologic response (undetectable VL).

His last two labs reveal a stable CD4 of 450 but

detectable HIV VL

1 month ago: HIV VL 250 Current: HIV VL 1000

viral load every 3 to 6 months

CD4 count does not change that much


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Which of the following is the most appropriate

next step?

A. Continue current regimen as VL is likely a blip

B. Order genotypic testing to determine if significant

resistance mutations are present

C. Order phenotype testing to see if there is asignificant drug-drug interaction

D. Stop current regimen and change to II-basedregimen.

phenotype=


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AETC National Resource Center

Richman, DD. How drug resistance arises. Scientific American , July 1998

How Drug Resistance Arises

No mutations if virus is not replicating


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Genotype Testing (GART)

Compares the genetic makeup of the patients HIV versusthe wild-type strain

Identifies known mutations which are associated withresistance to specific genes

When to order GART

At acute infection/entry into care

Suboptimal suppression of viral load after starting HAART Virologic failure during ART

Used to assist in selecting active drugs for a new regimen


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Which of the following is NOT a likely

cause of resistance?

A. Drug-drug interaction leading to reduced

level of ART

B. Missing all ART medications for the past 2

months

C. Suboptimal adherence to HAARTD. Superinfection with resistant virus

Big problem

stop all meds at the same time !!!

when you get better retake it again


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Causes of HIV Resistance

Inadequate drug therapy

Poor adherence causing subtherapeutic drug levels

Poor absorption causing subtherapeutic drug levels

Drug-drug interaction

Infected with resistant virus during initial infection

Superinfection with resistant virus


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Prevention of Resistance

!3 active ART medications from at least 2 different classes

Avoid drug interactions

Promote/ensure adherence

!95% adherence required

Note: No mutations if virus is not replicating


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Case 10

A 33 year old man who emigrated to the U.S. from thePhillippines was placed on TNF-alpha blocker therapy for

his ulcerative colitis.

He does have a history of reactive ppd 5 years previously

and completed 9 months of routine therapy for latent TB.


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Case 10, continued

Two months after completion of latent TB therapy andinitiation of TNF-alpha later, he is seen with a progressive

cough with hematemesis, fever, weight loss, and night

sweats.

Sputum AFB is positive

Sputum Cx: Mycobacterium tuberculosis


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Which of the following is the most likely cause for thisclinical syndrome?

A. Efflux pump leading to INH resistance

B. Enzyme degrading pyrazinamide

C. Mutation of gene encoding mycobacterial RNApolymerase leading to rifampin resistance

D. Reduction of ergosterol leading to amphoteracin B

decreased activity

for 9 months


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Mycobacterial Resistance

Naturally occurring mutations can confer resistance

On drug therapy, drug-susceptible organisms are killed,selectingfor drug-resistant mutants

Should be considered in patients:

Who remain culture positive after 2-4 months of treatment

Patients who have previously been treated for TB

Contacts of patients with drug-resistant TB

Patients born in countries or who reside in setting where drugresistant TB is prevalent

Treatment regimens can be changed once the results of

drug susceptibility testing are availableNational Tuberculosis Center, Drug-Resistant Tuberculosis 2ndEdition.


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Treatment Principles for Active TB

1. Empiric therapy consists of multiple drugs

Covers for the presence of resistant strains

Prevents selection of drug-resistant strains

De-escalate therapy once susceptibilities are known

2. Promote adherence

3.

Monitor for intolerance or toxicities

4. Never add a single drug to a failing regimen


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Case 11

A 56 year old woman with HIV (CD4 200, not on HAART)is seen with a 3 week history of progressive headache,

low-grade fever, unstable gait, and mild neck stiffness.

Lumbar puncture is performed and CSF analysis is

consistent with meningitis.

CSF Cryptococcal Ag is positive.


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The mechanism of Cryptococcal resistance to

echinocandins has not yet been fully elucidated.

By which of the following mechanisms areCandida species developing echinocandin

resistance?

A. Alteration of FKS1/FKS2 subunits of "-1,3 Dglucan synthase

B. Increased expression of 14-#-demethylase

C. Alteration of the binding site of "-1,6-D- glucansynthase

D. Replacement of ergosterol with other sterols formembrane function

cryptococcus


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Case 12

A 72 year-old diabetic woman on HD for ESRD is seenwith right tibial osteomyelitis with VRE (vancomycin-

resistant Enterococcus).

Resistance testing shows resistance to:

Aminoglycosides

Ampicillin

Vancomycin Linezolid


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Which of the following correctly describes the

mechanism of resistance to linezolid?

A. Alteration of 30S ribosomal subunit

B. Alteration of dihydrofolate reductase

C. Efflux pump

D. Mutation in DNA gyrase

E. Mutation in rRNA F. Thickened cell wall


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Case 13

A 21 year-old college football player is seen with multipleskin abscesses.

His provider performs I&D and also sends a sample of thepurulent material to the lab for culture and sensitivities.

Culture grows Staphylococcus aureus that is resistant to

oxacillin.


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MRSA has which mechanism(s) of

resistance?A. Altered PBP2a

B. $-lactamase

C. Carbapenemase

D. Thickened cell wall

E. A&B

F. B & D

G. A,B,C, & D


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MRSA is resistant to all "-lactam antibiotics

exceptwhich of the following?

A. Ampicillin/sulbactam

B. Ceftriaxone

C. Ceftaroline

D. Imipenem

E. Nafcillin


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Case 14

A 75 year old woman with recurrent UTIs is seen withearly right-sided pyelonephritis.

Urinalysis, urine culture and sensitivities are ordered.

Her provider prescribes ciprofloxacin, pending culture andsensitivity testing.


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Case 14, continued

U/A: LCE positive, nitrate positive, WBC>150, RBC 5,glucose 1+, ketones negative

Urine culture: Escherichia coli

Resistant to ampicillin, ciprofloxacin, nitrofurantoin, TMP/SMX


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Which of the following is the mechanism of

resistance to ciprofloxacin?

A. Efflux pump

B. Extended-spectrum B-lactamase production

C. Overproduction of dihydropteroate synthase

D. Methylation of 50S ribosomal unit

E. Mutation in DNA Gyrase


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CONTACT INFORMATION

Staci Lee, MD, [email protected]

Office: UNMH 5ACC 5171

Phone 272-5666

11.18.15 antimicrobial resistance vignettes review lee

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