Gram Negative Resistance (L40)

CRAB stands for _________-__________ _________ _________

Carbapenem-resistant Acinetobacter baumannii

CRAB stands for Carbapenem-resistant Acinetobacter baumannii

Nearly all cases occur in patients with prior ___________ exposure

healthcare

CRAB stands for Carbapenem-resistant Acinetobacter baumannii

the most common infection types are _________ and/or wound infections (i.e. critically ill patients)

pneumonia

CRAB stands for Carbapenem-resistant Acinetobacter baumannii

this resistance is typically mediated by OXA-23, OXA-24, and OXA-40 ______________

carbapenemases

CRAB stands for Carbapenem-resistant Acinetobacter baumannii

this resistance is typically mediated by OXA-23, OXA-24, and OXA-40 carbapenemases

Carbapenemases are beta-lactamases that _________ carbapenems (like ESBLs but even worse)

hydrolyze

the preferred CRAB treatment for mild infections is Ampicillin/Sulbactam ________ given IV q_________ infused over ____________ (dosed based on the Sulbactam component)

3g IV q4 hours infused over 30 minutes

the preferred antibiotic to treat CRAB for both mild and moderate infections is ________________

Ampicillin/Sulbactam (Ampicillin alone is useless)

the preferred CRAB treatment for moderate infections is Ampicillin/Sulbactam ________ given IV q_________ infused over ____________ (dosed based on the Sulbactam component)

9g IV q8 hours infused over 4 hours

the preferred antibiotic to treat CRAB for both mild and moderate infections is Ampicillin/Sulbactam and it is dosed based on the __________ component

Sulbactam (Ampicillin is inactive against A. baumannii, but sulbactam has intrinsic activity)

Sulbactam/durlobactam recently got approved for HAP/VAP caused by CRAB

Sulbactam resistance is primarily caused by ESBLs (ex: TEM), ADC (ex: ampC), and carbapenems (ex: OXA-23)

Durlobactam is a broad spectrum inhibitor of ____________, which helps restore Sulbactam’s activity

those enzymes! (ESBLs, ampC, carbapenems)

Tetracyclines may be considered as monotherapy for mild CRAB infections or as combination therapy for moderate infections

but, caution use of tetracyclines in __________ and _________ infections due to suboptimal exposure (often doesn’t apply to CRAB cuz it’s mostly in the lungs🙂)

bloodstream and urinary

_______________ may be considered as monotherapy for mild CRAB infections or as combination therapy for moderate infections

but, caution use of _____________ in bloodstream and urinary infections due to suboptimal exposure (often doesn’t apply to CRAB cuz it’s mostly in the lungs🙂)

tetracyclines

Tetracyclines may be considered as monotherapy for mild CRAB infections or as combination therapy for moderate infections

the IDSA guidelines prefer ___________ as first-line, but they like _____________ too (Eravacycline not recommended until more clinical data is available)

Minocycline, Tigecycline

Tetracyclines may be considered as monotherapy for mild CRAB infections or as combination therapy for moderate infections

the IDSA guidelines prefer Minocycline as first-line, but they like Tigecycline too (Eravacycline not recommended until more clinical data is available)

Minocycline and Tigecycline dosing for CRAB infections is ___________ than the dose for non-CRAB infections

higher

Tetracyclines may be considered as monotherapy for mild CRAB infections or as combination therapy for moderate infections

Minocycline and Tigecycline dosing for CRAB infections is higher than the dose for non-CRAB infections

Minocycline is _______mg given ________ (route) every _________

200mg given PO or IV every 12 hours (i.e. BID)

Tetracyclines may be considered as monotherapy for mild CRAB infections or as combination therapy for moderate infections

Minocycline and Tigecycline dosing for CRAB infections is higher (2x) than the dose for non-CRAB infections

Tigecycline is _______mg given ______ (route) for one dose, followed by _______mg given ______ (route) every ___________

200mg IV for one dose, followed by 100mg IV every 12 hours (i.e. BID)

Tetracyclines may be considered as monotherapy for mild CRAB infections or as combination therapy for moderate infections

Minocycline and Tigecycline dosing for CRAB infections is higher (2x) than the dose for non-CRAB infections

____________ is 200mg IV for one dose, followed by 100mg IV every 12 hours (BID)

Tigecycline

Tetracyclines may be considered as monotherapy for mild CRAB infections or as combination therapy for moderate infections

Minocycline and Tigecycline dosing for CRAB infections is higher than the dose for non-CRAB infections

______________ is 20mg PO or IV every 12 hours (BID)

Minocycline

Cefiderocol displayed excellent in vitro activity against CRAB, however… high mortality was observed in phase 3 trials for pts with CRAB

therefore, IDSA recommends Cefiderocol be limited to CRAB infections ________________

refractory to other agents

_______________ displayed excellent in vitro activity against CRAB, however… high mortality was observed in phase 3 trials for pts with CRAB

therefore, IDSA recommends _____________ be limited to CRAB infections refractory to other agents

Cefiderocol

ESBL are enzymes that hydrolyze __________ and __________

penicillins and cephalosporins

ESBL are enzymes that hydrolyze penicillins and cephalosporins

treatment options are very limited and often require hospital admission for _______ therapy

IV

ESBL-producing Enterobacterales: uncomplicated cystitis (urinary tract) treatment

Preferred antibiotics are ______________ or ______________

Nitrofurantoin or Bactrim

ESBL-producing Enterobacterales: uncomplicated cystitis (urinary tract) treatment

Preferred antibiotics are Nitrofurantoin or Bactrim

___________________ and ___________ are NOT recommended, even if they are reported to be susceptible

Amox/Clav and Doxycycline

ESBL-producing Enterobacterales: uncomplicated cystitis (urinary tract) treatment

Preferred antibiotics are Nitrofurantoin or Bactrim

__________ and ____________ alternative antibiotics should be reserved for more serious infections

Fluoroquinolones and carbapenems (like complicated cystitis or pyelonephritis)

ESBL-producing Enterobacterales: complicated cystitis and pyelonephritis (urinary tract) treatment

Preferred antibiotics are ___________, ___________, and ____________

fluoroquinolones, carbapenems, Bactrim

ESBL-producing Enterobacterales: infections outside of the urinary tract (pneumonia, bacteremia, IAI, SSTIs, etc.)

the preferred antibiotic class is ________________

carbapenems (then step-down to PO therapy with FQ or Bactrim)

CRE stands for __________ ______________ ____________

Carbapenem-resistant Enterobacterales

CRE stands for Carbapenem-resistant Enterobacterales

Increasing resistance to BLs has led to increased use of Carbapenems over time

Carbapenem resistance may be caused by __________________ production or by ____-________ resistance mechanisms

carbapenemase, non-enzymatic (ex: porin mutations)

CRE stands for Carbapenem-resistant Enterobacterales

Increasing resistance to BLs has led to increased use of Carbapenems over time

Carbapenem resistance may be caused by carbapenemase production or by non-enzymatic resistance mechanisms (ex: porin mutations)

the most common carbapenemase in the US is _______________

KPC (followed by IMP/NDM/VIM, and OXA-48)

for carbapenemase-producing CRE, treatment is based on the specific _____________ present

carbapenemase (KPC, IMP, NDM, OXA-48 or VIM)

common CRE carbapenemases are KPC, IMP, NDM, OXA-48 and VIM

KPC can occur in any gram-negatives and the preferred treatments are ________________, ________________ or ________________

Ceftazidime-Avibactam (same for OXA-48), Imipenem-Relebactam, Meropenem-Vaborbactam (those last two are for KPC only! cannot be used for IMP/NDM/VIM or for OXA-48)

common CRE carbapenemases are KPC, IMP, NDM, OXA-48 and VIM

KPC shares one of its preferred antibiotics with OXA-48s only preferred antibiotic, which is _______________

Ceftazidime-Avibactam

common CRE carbapenemases are KPC, IMP, NDM, OXA-48 and VIM

OXA-48 preferred treatment is ________________

Ceftazidime-Avibactam (can also be used for KPC)

common CRE carbapenemases are KPC, IMP, NDM, OXA-48 and VIM

the preferred treatments for IMP/NDM/VIM are ________________ monotherapy, or ________________ + _______________ combination therapy

Cefiderocol (cannot be used for KPC or OXA-48), Ceftazidime-Avibactam + Aztreonam (Ceft/Avi is used for KPC and OXA-48 on its own, but for IMP/NDM/VIM it must be with Aztreonam)

common CRE carbapenemases are KPC, IMP, NDM, OXA-48 and VIM

the preferred treatments for ______________ are Cefiderocol monotherapy, or Ceftazidime-Avibactam + Aztreonam combination therapy

IMP/NDM/VIM

common CRE carbapenemases are KPC, IMP, NDM, OXA-48 and VIM

the preferred treatments for _____________ are Ceftazidime-Avibactam, Imipenem-Relebactam, or Meropenem-Vaborbactam

KPC (Imipenem-Rele & Meropenem-Vabor can only be used for KPC, not any other carbapenemases)

common CRE carbapenemases are KPC, IMP, NDM, OXA-48 and VIM

the preferred treatment for _____________ is Ceftazidime-Avibactam

OXA-48 (Ceft-Avi is also an option for KPC)

CRE uncomplicated cystitis (urinary tract) preferred treatments are __________, ___________, or ______________

fluoroquinolones, nitrofurantoin, or Bactrim

CRE complicated cystitis and pyelonephritis (urinary tract) preferred treatments if susceptibility is confirmed are ______________ or ___________

Flurorquinolones (Cipro or Levo) and Bactrim

CRE complicated cystitis and pyelonephritis (urinary tract) preferred treatments if susceptibility is confirmed are FQ (Cipro or Levo) and Bactrim

If susceptibility is pending or if FQs and TMP/SMA are resistant, we can use ____________, __________, ________________, or _____________

Cefiderocol (IMP/NDM/VIM), Ceftazidime-Avibactam (OXA-48 and KPC), Imipenem-Relebactam (KPC), or Meropenem-Varobactam (KPC)

so basically all of the carbapenemase treatments lol (and these are the same ones we would use for CRE infections outside of the urinary tract)

CRE infections outside of the urinary tract (in the bloodstream) preferred treatments are ____________, ____________, ____________, or ____________

Cefiderocol (IMP/NDM/VIM), Ceftazidime-Avibactam (OXA-48 and KPC) or Ceftazidime-Avibactam + Aztreonam (IMP/NDM/VIM), Imipenem-Relebactam (KPC), or Meropenem-Varobactam (KPC)

just reiterating all of the carbapenemases and their specifics, so just know which goes with which

Multi-Drug Resistant: non-susceptibility to at least one agent in at least _______ different classes out of PCNs, Cephalopsorins, FQs, AGs, and Carbapenems

3

Multi-Drug Resistant: non-susceptibility to at least 1 agent in at least 3 different classes out of PCNs, Cephalopsorins, FQs, AGs, and Carbapenems

MDR Pseudomonas is a result of multiple mechanisms like decreased ________ expression, upregulation of _______ ________, mutation of _________________, hyperproduction of AmpC enzymes, and/or ______________ production

porin, efflux pumps, PCN-Binding-Proteins, carbapenemase

Difficult-to-Treat Resistant Pseudomonas in uncomplicated cystitis (urinary tract) preferred treatments are _________, ____________, _________, or ______________

Cefiderocol, Ceftazidime-Avibactam, Ceftolozane-Tazobactam**, and Imipenem-Relebactam (straight to the big guns😎 these are the same abx used for complicated cystitis or for pyelonephritis)

**this is for PSAE only, not for KPC, IMP/NDM/VIM, OXA-48**

Difficult-to-Treat Resistant Pseudomonas in complicated cystitis or pyelonephritis (urinary tract) preferred treatments are _________, ____________, _________, or ______________

Cefiderocol, Ceftazidime-Avibactam, Ceftolozane-Tazobactam**, and Imipenem-Relebactam (these are the same abx used for uncomplicated cystitis)

**this is for PSAE only, not for KPC, IMP/NDM/VIM, OXA-48**

Difficult-to-Treat Resistant Pseudomonas outside of the urinary tract (in the bloodstream) preferred treatments are ____________, ___________, or ______________

Ceftazidime-Avibactam, Ceftolozane-Tazobactam**, and Imipenem-Relebactam

**this is for PSAE only, not for KPC, IMP/NDM/VIM, OXA-48**

which preferred antibiotic for Difficult-to-Treat Resistant Pseudomonas is ONLY for PSAE and cannot be used for KPC, IMP/NDM/VIM, or OXA-48?

Ceftolozone-Tazobactam

Stenotrophomonas maltophilia: produces biofilm and virulence factors that allow it to cause infection or colonization in vulnerable hosts

Treatment is complicated by the presence of numerous __________ resistance mechanisms

intrinsic (L1 and L2 beta-lactamases, AG-modifying enzymes, and numerous efflux pumps)

Stenotrophomonas maltophilia: treatment is complicated by the presence of numerous intrinsic resistance mechanisms (L1/L2 beta-lactamases, AG-modifying enzymes, & numerous efflux pumps)

Preferred treatment for moderate-severe S. maltophilia infections (in the bloodstream or lungs) is combination therapy with two of the following: _____________, __________, __________, ___________, or ____________

Cefiderocol, Levo, Minocycline, Tigecycline, Bactrim (must pick 2 of these)