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Infectious disease

Multidrug-resistant organisms

AmpC (HECK-Yes: Hafnia, E. cloacae complex, C. freundii, K. aerogenes, Yersinia): can derepress. Serious infections: cefepime (MIC ≤2) or carbapenem. Avoid CTX even if ‘S’.

Dan Rubin5 min6 questions2 trials

AmpC, ESBL, CRE

Gram-negative resistance is a mechanism problem, not a “broaden everything” problem. Name AmpC vs ESBL vs carbapenemase before you reach for a new BL/BLI ().

Three β-lactamase stories

  • AmpC

    Cephalosporinase

    Inactivates 3rd-generation cephalosporins and pip-tazo. Can be constitutive or inducible as cell-wall fragments accumulate. HECK-Yes: Hafnia, Enterobacter cloacae complex, Citrobacter freundii, Klebsiella aerogenes, Yersinia enterocolitica.

  • ESBL

    Plasmid-mediated

    Knocks out penicillins, cephalosporins, and aztreonam. Klebsiella > E. coli > Proteus, then other GNR. Lab flag at many hospitals: ceftriaxone-resistant GNR.

  • CRE

    Carbapenemase, porin, efflux

    Suspicious when imipenem / meropenem / ertapenem MIC >2. Cephalosporin or carbapenem in 3 months is a risk — penem exposure is not required. Care in India or Pakistan raises metallo-β-lactamase odds.

Organism / mechanismDo notCystitisInvasive / sick
High-risk AmpC — E. cloacae, K. aerogenes, C. freundii (~20% resistance). Serratia, M. morganii, Providencia are lower risk (~5%); treat off AST.Ceftriaxone even if reported “S.” That susceptibility is a trap.TMP-SMX or nitrofurantoin. Alts: fosfomycin (E. coli), single-dose aminoglycoside, or a FQ.Cefepime if MIC ≤2, TMP-SMX, or FQ. Critically ill: a carbapenem. Cefepime is noninferior to meropenem when source control is real ().
ESBL — CTX-R E. coli / Klebsiella / Proteus. Risks: antibiotics in 6 months, long stay, nursing home, age >65, lines, TPN, dialysis.Penicillins and cephalosporins, including pip-tazo, even if “S” (MERINO, ).TMP-SMX or nitrofurantoin. Alts: fosfomycin (E. coli), single-dose AG, or FQ.Complicated UTI: TMP-SMX or FQ if susceptible; carbapenem otherwise. Non-UTI: imipenem or meropenem. Skip ertapenem in critical illness and hypoalbuminemia.
CRE — carbapenemase vs porin/efflux. Call ID.Hope. Mechanism decides the drug.FQ, TMP-SMX, or single-dose AG if susceptible.Usually ceftazidime-avibactam; add aztreonam if India/Pakistan care (MBL). Meropenem-vaborbactam, imipenem-relebactam, cefiderocol also active. Extended-infusion meropenem only if MIC ≤1. Tigecycline is not for UTI or bacteremia.

CRAB, DTR Pseudomonas, MRSA, VRE

BugDefinition / cluePreferred
CRABCarbapenem-resistant A. baumanniiSulbactam-durlobactam plus meropenem or imipenem. Alt: high-dose amp-sulbactam plus a second agent. ID on the call.
DTR-PsANonsusceptible to pip-tazo, ceftazidime, cefepime, aztreonam, FQ, meropenem, and imipenemCeftolozane-tazobactam first. Ceftazidime-avibactam or cefiderocol are backups. Call ID.

MRSA

  • Community: no healthcare exposure; SSTI in the young and healthy. Risks: HIV, PWID, prior antibiotics; outbreaks in jails, barracks, sports, shared needles/razors.
  • Healthcare: >48 h into a stay, or within 12 months of healthcare. Risks: recent hospitalization or surgery, dialysis, LTC.
  • Nasal PCR NPV in CAP ~96.5–98% (). A negative swab is how you stop empiric vancomycin. NPV at other sites is emerging ().
  • Vancomycin MIC ≤2 is “S,” but failure and death rise at MIC = 2. VISA 4–8; VRSA ≥16.

Serious MRSA (bacteremia)

  • Vancomycin (AUC dosing; trough ~15–20) plus ID consult (J Infect 2016;72:19).
  • Persistent bacteremia or MIC ≥2: switch to daptomycin (not pneumonia, not meningitis), add ceftaroline, or both.
  • Daptomycin is inactivated by pulmonary surfactant — never for MRSA pneumonia. Use vancomycin or linezolid.

Mild MRSA (SSTI)

  • TMP-SMX or doxycycline >> clindamycin (resistance is up).
  • Linezolid when the oral β-lactam-adjacent option is gone.

VRE

  • E. faecium: often resistant, generally less virulent. E. faecalis: more virulent, still ampicillin-S in most hospitals — use ampicillin.
  • Risks: prior antibiotics, Foley, lines, nearby VRE patients, long stay / SNF, immunocompromise.
  • Sites: urine (often colonization), CLABSI, intra-abdominal / pelvic, prosthetic-valve endocarditis, meningitis (immunocompromise or VP shunt).