Multidrug-resistant organisms: what to treat with

It is culture-directed: the organism and its resistance mechanism are known, and the agent must test susceptible. It does not choose empiric therapy, separate infection from colonization, or set durations beyond what the cited guidance states. Adults only.

No doses, except where the dose is part of the recommendation (high-dose ampicillin–sulbactam, 9 g/day of the sulbactam component, Q5.2; high-dose daptomycin, recs 19–20 and 72). Dose every agent from its label or your pharmacy and adjust for kidney function (kidney function tool). IDSA 2026 Table 1 gives adult doses for normal kidney and liver function; several differ from the label.

Order. IDSA 2026 lists preferred and alternative agents alphabetically. Where its rationale ranks them (KPC: meropenem–vaborbactam, then ceftazidime–avibactam, then imipenem–relebactam; DTR P. aeruginosa pneumonia: ceftolozane–tazobactam), the list follows that ranking and the headline names the top agent. Otherwise the headline says "Options (unranked)", and agents IDSA asks to reserve (cefiderocol for DTR P. aeruginosa, Q4.2) go last. With pregnancy ticked, an agent carrying a pregnancy label warning is never the headline.

Grades. IDSA 2026 AMR guidance does not use GRADE, so its lines carry no grade. MRSA lines carry the 2011 letter grades (A–C strength, I–III evidence) or the GRADE strength from the 2014 SSTI and 2016 HAP/VAP guidelines; SAB 2026 statements are "consensus".

Gram-negatives (IDSA 2026). Cystitis and complicated UTI have their own questions. For infections outside the urinary tract the guidance is not site-specific, so the same suggestion is shown for bloodstream, pneumonia, intra-abdominal, skin/soft tissue and bone/joint infection. CNS infection is not addressed (drug penetration differs) and goes to ID consult; see the IDSA 2017 healthcare-associated ventriculitis and meningitis guideline. CRAB and S. maltophilia sections address invasive infection only, so urinary sites are not covered.

MRSA. Skin/soft tissue, bloodstream, pneumonia, bone/joint and CNS (MRSA 2011, SSTI 2014, HAP/VAP 2016, SAB 2026). Urinary and intra-abdominal MRSA are not addressed.

VRE. No current IDSA or ESCMID VRE treatment guideline exists. Only catheter-related bacteremia is covered, from the IDSA 2009 catheter guideline (listed as archived on idsociety.org). Bacteremia from another source, endocarditis (see the AHA 2015 and ESC 2023 endocarditis guidance; not reviewed here), cystitis and every other site go to ID consult.

β-lactam allergy has three answers, applied to every line by one exclusion rule:

• Unverified, non-anaphylactic penicillin allergy: penicillins (including sulbactam products) and penems are removed pending evaluation. Cephalosporins, carbapenems and aztreonam stay: the practice parameter suggests a cephalosporin may be given without testing in this situation (conditional, moderate certainty; secondary summary).
• Immediate or anaphylactic reaction to a penicillin, or to a cephalosporin other than ceftazidime: penicillins (including sulbactam products), cephalosporins (including cefiderocol and ceftaroline) and penems are removed by default; the parameter suggests a dissimilar-R1-side-chain cephalosporin may be given after penicillin anaphylaxis (conditional), so an allergist-cleared cephalosporin is an option. Carbapenems (including meropenem–vaborbactam and imipenem–relebactam) and aztreonam (including aztreonam–avibactam) stay: the 2022 drug-allergy practice parameter suggests a carbapenem, and aztreonam unless there is ceftazidime allergy, may be given without testing (both conditional; read via a secondary summary).
• Ceftazidime allergy: ceftazidime, ceftazidime–avibactam, aztreonam and aztreonam–avibactam are removed (shared side chain), and so is cefiderocol (side chain not verified safe). Other penicillins and cephalosporins are also removed pending allergy evaluation (conservative). Carbapenems stay.
• Severe delayed reaction (SJS/TEN, DRESS): every β-lactam is removed, including carbapenems and aztreonam, and the result asks for an allergy consult.

The penicillin allergy topic covers risk stratification and cross-reactivity.

Pregnancy. None of the guidance used here gives pregnancy-specific agent choices. Label warnings are tagged on the agent wherever it appears: aminoglycosides (fetal harm), tetracycline class (tooth discoloration, last half of pregnancy), TMP-SMX (possible malformation association; IDSA 2014 SSTI: avoid in third trimester), nitrofurantoin (contraindicated at term), polymyxin B (safety not established), telavancin (boxed developmental warning), tedizolid (may cause fetal harm), gepotidacin (fetal weight and mortality findings in mice and rats, §8.1), colistimethate (talipes varus in rabbit fetuses), fluoroquinolones (IDSA 2014 SSTI: relative contraindication).

Off-label tags are shown for agents approved since 2014 whose labels name specific infections (the newer β-lactam combinations, cefiderocol, eravacycline, tigecycline, daptomycin, linezolid, telavancin, gepotidacin, pivmecillinam, sulopenem, IV fosfomycin). Older generics have broad organism-based labels; check them.

US availability (checked 21 Oct 2026). Cefepime–enmetazobactam (Exblifep) and plazomicin (Zemdri) are named by IDSA but listed as discontinued in Drugs@FDA, so they never appear as an option. Cefepime–taniborbactam is not FDA-approved. Cefmetazole is not available in the US (IDSA Q1.6). Sulbactam–durlobactam (2023), aztreonam–avibactam (Feb 2025), IV fosfomycin (Oct 2025), gepotidacin (Mar 2025), pivmecillinam (Apr 2024) and oral sulopenem (Oct 2024) are marketed.

• Children and neonates.
• Empiric therapy before the organism is known.
• CNS infection by any gram-negative organism; VRE outside catheter-related bacteremia; MRSA urinary or intra-abdominal infection.
• Endocarditis and prosthetic-device infection details (prosthetic valve, prosthetic joint, spinal hardware).
• MSSA, VISA management beyond "use an alternative", and organisms not listed.
• Exact durations and doses, including dose changes for kidney or liver impairment.