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Transcript

Don't be so (gram) negative

start

Welcome to the gram negative escape room!

You will need to complete 5 tests to assess your bug-drug knowledge. Are you ready?!

Where are you?

Bug-Drug Basics

Pseudo-what?

HECK-YES

ESBL and CRE, oh my!

Will you be overcome with (gram) negativity?

Each of the following tests gives you the opportunity to escape the Gram Negative Room

1/3

Which of these is not a normal location for a member of the order Enterobacterales to colonize?

Urinary tract

Test 1

Gastrointestinal lumen

Skin

Correct!!

Enterobacterales (order) are aerobic (or "facultative anerobic") residents of the GI tract, and can colonize the urinary tract. They are often present on surfaces throughout the environment. The world is, most unfortunately, covered in a thin layer of excrement! Skin is not a normal place for Enterobacterales to reside, though chronic wounds, including diabetic wounds, may be colonized.

Onwards!

Next question:Pick the most likely pairing of organism and clinical syndrome!

2/3

Proteus mirabilis and pneumonia

STEC and acute diarrhea

Salmonella and UTI

Test 1

Correct!!

Various types of E. coli can cause acute diarrheal illness (STEC, EHEC, etc). Salmonella and shigella can cause diarrheal illness as well; illness outside of diarrheal presentations is much more rare for Salmonella/Shigella (e.g. UTI, bone/joint, etc). Given that nasopharyngeal colonization with Enterobacterales is rare, pneumonia is an uncommon infection for Enterobacterales to cause overall. However, they are occasionally implicated, particularly in hospital-acquired or ventilator-acquired pneumonias.Most times, Enterobacterales (E. coli, Klebsiella, Proteus, etc) are major causative agents in acute UTI and intra-abdominal infections. Our empiric antibiotic coverage should reflect that!

Onwards!

You're almost there.Which of the following would be the most likely patient to need empiric antibiotic coverage for Pseudomonas aeruginosa?

3/3

A 24 year old woman who resides in the community, being hospitalized for a UTI

A 55 year old man with cellulitis of his lower leg

A 72 year old woman who has a new ventilator-acquired pneumonia

An 87 year old woman who resides in a nursing home and has a new mild pneumonia, but has not been hospitalized or received IV antibiotics recently

Test 1

Correct!!

Pseudomonas can reside in water, soil, and plant matter in the environment, but its usual reservoir is health care environments, and patients with significant antibiotic use and health care exposure tend to show up with Pseudomonas infections more often.Our young woman with a UTI would not necessarily need empiric coverage for P. aeruginosa, as that's an uncommon pathogen for community-onset UTI.Our gentleman with cellulitis would not need coverage either, as P. aeruginosa is a rare cause of skin infections (it's more associated with specific scenarios such as diabetic foot infections in subtropical climates, and other chronic infected wounds). Our elderly lady from the nursing facility does not automatically warrant P. aeruginosa coverage for her pneumonia, either. She doesn't have any specific risk factors. We'll talk more about this when we talk about CAP and HAP/VAP.Our ventilator-associated pneumonia patient is the most logical candidate for empiric coverage, given P. aeruginosa featuring in VAP with some regularity. Hopefully we can get a respiratory culture and de-escalate her antimicrobials, if P. aeruginosa doesn't turn up!

Onwards!

Where are You?

Bug-Drug Basics

Pseudo-what?

HECK-YES

ESBL and CRE, oh my!

Will you be overcome with (gram) negativity?

Complete each test to beat the game: there is no other way to escape!

1/4

Let's talk bug/drug: which of the following provides the highest % susceptible for Enterobacterales?

Penicillins (e.g. penicillin G, amoxicillin)

Anti-pseudomonal penicillin/BL inhibitor (piperacillin-tazobactam)

Penicillin/BL inhibitor (e.g. ampicillin-sulbactam, amoxicillin/clavulanate)

Test 2

Correct!!

Enterobacterales have had waning susceptibilties to penicillins over time.Addition of a beta-lactamase inhibitor (e.g. ampicillin/sulbactam, amoxicillin/clavulanate) improves coverage, but only somewhat (55-80% S); not enough for us to rely on empirically in hospitalized, acutely ill patients with infections where we're suspecting Enterobacterales (UTI, IAI).The anti-Pseudomonal penicillin/BL inhibitor combination, piperacillin-tazobactam, maintains good activity against Enterobacterales. But we don't often need it since we have narrower options we can use.

Onwards!

Bug/drug, continued: which of the following would we potentially use empirically for Enterobacterales in an acutely ill hospitalized patient, based on antibiogram?

2/4

3rd generation cephalosporin

2nd generation cephalosporin

1st generation cephalosporin

Test 2

Correct!!

Cephalosporins are overall great for Enterobacterales. Gram negative activity generally tends to increase up the generations (1st<2nd<3rd<4th).Even first generation cephalosporins (e.g. cefazolin) have relatively good activity against E. coli/etc, but in our health system we don't test them against breakpoints that are relevant to most systemic infections.....so we can't recommend them empirically in the septic patient :(The 2nd generation cephalosporin that we test (cefuroxime) are only available PO, and the breakpoints are only relevant to uncomplicated UTI. Of note, clinically we do use cefotetan or cefoxitin in abdominal surgical prophylaxis.Our third generation IV cephalosporin of choice, ceftriaxone, provides excellent coverage of most Enterobacterales. Cefepime also does, but is often more broad than needed.

Onwards!

Which of the following is the best empiric choice for E. coli uncomplicated cystitis?

3/4

Levofloxacin

Trimethoprim-sulfamethoxazole

Nitrofurantoin

Test 2

Correct!!

E. coli susceptibilties to levofloxacin (fluoroquinolones in general) and trimethoprim/sulfamethoxazole have lagged in recent years. Maybe they'd still work for uncomplicated cystitis.....but there are better options. Please note, we also wouldn't want to use these agents empirically in acutely ill hospitalized patients with UTI or IAI and sepsis.Nitrofurantoin retains excellent activity against E. coli, and is a very appropriate first-line choice for uncomplicated cystitis.

Onwards!

4/4

1

2

3

4

5

continuE

A. Aztreonam

B. Meropenem

SOLUTION

C. Linezolid

D. Ciprofloxacin

E. Ceftriaxone

Rank the following antibiotics on the right, based on their relative % coverage of Enterobacterales (by tertiary references and our antibiogram) by dragging them to the bars on the left:

Test 2

Correct!!

Meropenem provides extremely robust coverage for Enterobacterales, however it is extremely broad spectrum, so we try to limit use for more resistant organisms.Aztreonam, the monobactam, provides excellent coverage for Enterobacterales, however it also covers Pseudomonas, so we try to use something more streamlined if we don't need coverage for that particular bug.Ceftriaxone provides great coverage of Enterobacterales in our region and health system, and is a good empiric choice for acutely ill hospitalized patients.Ciprofloxacin can cover Enterobacterales, but lately fluoroquinolone susceptibilities have lagged across the country/world.Linezolid only provides gram positive coverage; completely inactive against Enterobacterales.

Onwards!

Where are You?

Bug/Drug Basics

Pseudo-what?

HECK-YES

ESBL and CRE, oh my!

Will you be overcome with (gram) negativity?

Complete each test to beat the game: there is no other way to escape!

Which of the following is preferred empiric monotherapy coverage for Pseudomonas aeruginosa in our area?

1/3

Tobramycin

Meropenem

Test 3

Cefepime

Levofloxacin

Correct!!

By the end of rotation, you should be able to easily name drugs that cover Pseudomonas aeruginosa. Challenge yourself!Tobramycin, while it has a high %Susceptible, is not great monotherapy for P. aeruginosa (patients tend to have worse outcomes). Sometimes we use it in combination with other drugs (e.g. a beta-lactam) for "empiric double coverage".Levofloxacin isn't the best empiric choice, as susceptibilities are in the low-mid 80's.Cefepime has great susceptibilities (~90+%) and is a targeted choice.Meropenem has good susceptibilities, but we try to preserve meropenem for resistant infections with no other options.

Onwards!

True or False: Using 2 drugs active against Pseudomonas aeruginosa prevents antibiotic resistance from developing on treatment

2/3

False

True

We should double cover this patient!!

Test 3

Correct!!

There's very little evidence that using 2 active drugs ("double covering") against P. aeruginosa prevents resistance. Usually we are double-covering to improve the probability that one of the agents we use is active from the start. Once susceptibilities on the P. aeruginosa return, we can get rid of one of the drugs (or, if we don't grow P. aeruginosa we can de-escalate even further!)

Onwards!

Which of these agents would most likely be the best option for treatment of difficult-to-treat resistant Pseudomonas?

3/3

Test 3

Correct!!

Ceftolozane-Tazobactam (Zerbaxa) is tailor made for difficult-to-treat resistant P. aeruginosa. If the organism is susceptible, it's a great choice. There are other options if it's not susceptible, though.Meropenem-vaborbactam (Vabomere) is not designed for resistant P. aeruginosa. It's not going to be better than plain meropenem for that situation. It's more targeted toward the mechanisms responsible for carbapenem-resistant Enterobacterales (CRE). Tigecycline doesn't have any activity against P. aeruginosa at all, even if it's not considered difficult-to-treat resistant. :) (Of note, all three of these antibiotics are on our formulary, but with restrictions for use!)

Onwards!

Where are you?

Bug-Drug Basics

Psuedo-what?

HECK-YES

ESBL and CRE, oh my!

Will you be overcome with (gram) negativity?

Complete each test to beat the game: there is no other way to escape!

Which are the top 3 most common inducible AmpC producing organisms you need to be on the lookout for in clinical practice (i.e. that may require antibiotic therapy adjustments)?

1/2

1

2

3

continue

Solución

Solution

A. Citrobacter freundii

B. Klebsiella pneumoniae

C. Enterobacter cloacae

D. Klebsiella aerogenes

E. Serratia marsescens

Test 4

Which are the top 3 most common inducible AmpC producing organisms you need to be on the lookout for in clinical practice (i.e. that may require antibiotic therapy adjustments)?

1/2

continue

Test 4

Enterobacter cloacae and Klebsiella (formerly Enterobacter) aerogenes, as well as Citrobacter freundii, are the most common expressers of clinically relevant inducible AmpC enzymes. Serratia marsescens can also do this, but the frequency is low, such that it doesn't routinely prompt us to avoid specific antibiotics that are marked as susceptible.Klebsiella pneumoniae does not frequently produce inducible AmpC.

2/2

continuE

Drag the antibiotics to the correct category:

Retains good activity against AmpC producers :)

May be degraded by AmpC enzymes :(

1. Cefazolin

2. Ceftriaxone

3. Cefepime

Solución

4. Aztreonam

5. Ertapenem

SOLUTION

6. Levofloxacin

Test 4

Antibiotics against inducible AmpC producers

2/2

continue

Test 4

Our common AmpC producers (i.e. Enterobacter cloacae, Klebsiella aerogenes, Citrobacter freundii) will often be resistant to cefazolin at a baseline. Ceftriaxone may show as susceptible, but resistance may develop on treatment :( Aztreonam is also not robust against inducible AmpC enzymes.On the other hand, cefepime's zwitterion structure enables it to quickly scoot past any AmpC enzymes to produce robust bacterial killing. Carbapenems also withstand AmpC very well (but we should save these for more resistant organisms where possible). Don't forget, AmpC is a beta-lactamase, so it won't specifically inactivate levofloxacin (but the organism may have other mechanisms of resistance for fluroquinolones, so be sure to check the susceptibility profile!)

Where are you?

Bug-Drug Basics

Pseudo-what?

HECK-YES

ESBL and CRE, oh my!

Will you be overcome with (gram) negativity?

Complete each test to beat the game: there is no other way to escape!

1/3

Say you were looking at a susceptibility report on a culture. Which of the following would clue you in to a likely ESBL producing organism (specific to our health system)?

Lab reports an "ESBL: Positive" line on the susceptibility report

Test 5

An Enterobacter cloacae, Klebsiella aerogenes, or Citrobacter freundii that was ceftriaxone-R

An Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis that was ceftriaxone-R

Correct!!

Here within our health system, the lab does NOT report ESBL positive or negative via specific testing. Some health systems do this, however, so check to see what the practice is wherever you are.E. coli, P. mirabilis, or K. pneumoniae that are ceftriaxone-R are most likely ESBL producers.E. cloacae, K. aerogenes, or C. freundii that are ceftriaxone-R (or are marked by lab as such, even if the ceftriaxone MIC is low) are most likely AmpC producers.

Onwards!

What is/are the drug(s) of choice for serious ESBL-producing organism infections??

2/3

Carbapenems

Cefepime

Fluoroquinolones

Test 5

Correct!!

Carbapenems (e.g. meropenem, ertapenem) are the drugs of choice for serious infections with ESBL-producing organisms.Cefepime is less robust against ESBLs, and some retrospective literature suggests that outcomes are worse when using it, even if it's marked as susceptible.Fluoroquinolones may be active against ESBLs, and are sometimes used as oral step-down therapy. However, oftentimes, ESBLs have other resistance mechanisms on board that confer fluoroquinolone resistance as well :(

Onwards!

Which of the following groups of drugs is the best arsenal to potentially help treat carbapenem-resistant Enterobacterales?

3/3

Cefepime/enmetazobactam, ceftazidime/avybactam, ceftolozane/tazobactam

Cefiderocol, meropenem/vaborbactam, ceftazidime/avibactam

Ceftaroline, meropenem/vaborbactam, cefiderocol

Test 5

Correct!!

Out of all of the drugs listed, there are a few that aren't active against CREs, including ceftaroline (which is similar to ceftriaxone but with MRSA coverage), cefepime/enmetazobactam (which has ESBL coverage, but not CRE), and ceftolozane/tazobactam (which is designed for resistant Pseudomonas, not CRE). Ceftazidime/avibactam, meropenem/vaborbactam, and cefiderocol all have activity against CREs. Which one to choose? That will depend on the enzymatic mechanism (e.g. KPC, NDM, etc) and the susceptibility profile of the individual CRE! All of these are restricted antibiotics in our health system.

Onwards!

Congratulations!!!

You have escaped the (gram) negativitity and can use your knowledge to optimize ID care for our patients :) This concludes the game!

back

That answer is not correct...

But no need to be (gram) negative, continue on your way and try again!

Oh oh!

1 - B

2 - A

3 - E

4 - D

5 - C

1 - C

2 - D

3 - A

Good Activity :)

356

May be Degraded :(

124