ANTIMICROBIAL

RESISTANCE: CASEBASED REVIEW

Staci Lee, MD, MEHP

November 18, 2015
(Slide set courtesy of Dr. Michelle Iandiorio)

Learning Objective
To apply your knowledge of antimicrobial resistance to

clinical scenarios
To provide you a brief review of antimicrobial resistance

mechanisms

GET YOUR ICLICKERS

READY

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.

Which of the following is the correct explanation

for 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.

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

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.

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.

Which of the following is the mechanism by

which the infecting organism obtained the
genes to produce this toxin?

A.
B.
C.
D.

Conjugation
Transduction
Transformation
Transposition

Horizontal Gene Transfer

Case 3
An elderly chronic nursing home patient is brought to the

hospital with new onset confusion, low-grade fever,

tachycardia, and low blood pressure.
She was diagnosed with a urinary tract infection three

days 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 and
vancomycin.

What is the correct mechanism for the

resistance of Enterococcus to 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

Vancomycin-Resistant Enterococci (VRE)

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.

Case 4 continued
Purulence from the abscess area grows

Staphylococcus aureus.
The microbiology lab technician inoculates broth

bottles that contain various concentrations of

moxifloxacin.
You are asked to confirm the MIC report.

What is the Minimum Inhibitory

Concentration (MIC)?
Standard"inoculum"of"bacteria"

1"g/mL"of"
an,bio,c"

A.

2"g/mL"

4"g/mL"

B.

8"g/mL"

C.

16"g/mL"

32"g/mL"

64"g/mL"

D.

Case 5
A 56-year old man with morbid obesity and chronic

bilateral 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 no

wound cultures could be obtained but his blood cultures

grew Staph aureus.
Initial sensitivity testing shows resistance to erythromycin

and sensitivity to clindamycin.

This additional test identifies this stain of Staph

aureus as having:
A. Inducible resistance to
clindamycin in the lab
B. Reversion back to
erythromycin 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

Case 6
A 40-year old alcoholic man is seen in the ED with

fever, productive cough with current-jelly colored

sputum.
Sputum culture reveals Klebsiella pneumoniae.

Which plate demonstrates that the bacteria is

resistant to ceftriaxone tested by disc diffusion?

A.

B.

An ESBL is suspected. Which of the following

options is the mechanism for ESBL production
in GNR?
ESBL carried by plasmid!!!!
BUT

A. Induced production of ESBL that is

chromosomal
B. Induced production of ESBL that is
plasmid-mediated
C. Selection of ESBL-producing strain

Case 7
A 63-year old patient who has been in the TSI for the past

three 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.

A modified Hodge test is performed to see if this

Pseudomonas strain produces an enzyme that
degrades carbapenems.

this is what we test (the bug)

The image on the left shows the

results of the test.
You confirm that this
Pseudomonas strain:
A. Produces carbapenemase
B. Does not produce

carbapenemase
bacteria susceptible to carabepems

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 ganciclovirresistant CMV.

Which of the following is correct about

ganciclovir resistance in CMV?
A. Deletion of CMV thymidine kinase

acyclovir

B. Mutation in viral DNA polymerase causes

resistance to ganciclovir but not foscarnet

C. Point mutation in by CMV phosphotransferase

is encoded by UL97 gene

Case 9
A 45 year-old man with HIV since 1996 is seen for routine

care.
He has been taking tenofovir, emtricitabine, and

atazanavir/ritonavir for the past 4 years with good

tolerability 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

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

phenotype=

C. Order phenotype testing to see if there is a

significant drug-drug interaction

D. Stop current regimen and change to II-based

regimen.

How Drug Resistance Arises

No mutations if virus is not replicating

Richman, DD. How drug resistance arises. Scientific American , July 1998
AETC National Resource Center

Genotype Testing (GART)

Compares the genetic makeup of the patients HIV versus

the wild-type strain

Identifies known mutations which are associated with

resistance 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

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

stop all meds at the same time !!!

when you get better retake it again

C. Suboptimal adherence to HAART

D. Superinfection with resistant virus

Big problem

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

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

Case 10
A 33 year old man who emigrated to the U.S. from the

Phillippines 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.

Case 10, continued

Two months after completion of latent TB therapy and

initiation 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

Which of the following is the most likely cause for this

clinical syndrome?
for 9 months

A. Efflux pump leading to INH resistance

B. Enzyme degrading pyrazinamide
C. Mutation of gene encoding mycobacterial RNA

polymerase leading to rifampin resistance

D. Reduction of ergosterol leading to amphoteracin B

decreased activity

Mycobacterial Resistance
Naturally occurring mutations can confer resistance
On drug therapy, drug-susceptible organisms are killed,

selecting for 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 drug
resistant TB is prevalent
Treatment regimens can be changed once the results of

drug susceptibility testing are available

National Tuberculosis Center, Drug-Resistant Tuberculosis 2nd Edition.

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

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.

The mechanism of Cryptococcal resistance to

echinocandins has not yet been fully elucidated.
By which of the following mechanisms are
Candida species developing echinocandin
resistance?
A. Alteration of FKS1/FKS2 subunits of -1,3 D

glucan synthase
B. Increased expression of 14--demethylase
C. Alteration of the binding site of -1,6-D- glucan

synthase

cryptococcus

D. Replacement of ergosterol with other sterols for

membrane function

Case 12
A 72 year-old diabetic woman on HD for ESRD is seen

with right tibial osteomyelitis with VRE (vancomycinresistant Enterococcus).

Resistance testing shows resistance to:
Aminoglycosides
Ampicillin
Vancomycin
Linezolid

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

Case 13
A 21 year-old college football player is seen with multiple

skin abscesses.
His provider performs I&D and also sends a sample of the

purulent material to the lab for culture and sensitivities.

Culture grows Staphylococcus aureus that is resistant to

oxacillin.

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

MRSA is resistant to all -lactam antibiotics

except which of the following?
A. Ampicillin/sulbactam
B. Ceftriaxone
C. Ceftaroline
D. Imipenem
E. Nafcillin

Case 14
A 75 year old woman with recurrent UTIs is seen with

early right-sided pyelonephritis.

Urinalysis, urine culture and sensitivities are ordered.
Her provider prescribes ciprofloxacin, pending culture and

sensitivity testing.

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

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

CONTACT INFORMATION
Staci Lee, MD, MEHP
slee@salud.unm.edu
Office: UNMH 5ACC 5171
Phone 272-5666