targeted antibiotic therapy by pathogen
in review
8 min read
Updated 2026-09-29
targeted antibiotic therapy by pathogen
Once an organism and susceptibilities are back, switch to the narrowest active agent — usually at 48–72 h. This table gives the preferred agent, alternatives, and oral step-down per organism, plus the traps where the lab report misleads: AmpC organisms reported ceftriaxone-susceptible, pip-tazo for ESBL bacteraemia, vancomycin continued for MSSA. Empiric choices before cultures: empiric antibiotic quick reference.
never a contaminant
S. aureus, S. lugdunensis, Candida, Gram-negative rods, S. pneumoniae, GAS, or Listeria in blood → treat, repeat blood cultures, find the source. Single-bottle CoNS, Cutibacterium, Corynebacterium, Micrococcus, or Bacillus (non-anthracis) → usually contaminant.
local antibiogram
Susceptibility report overrides this table. New β-lactam/β-lactamase-inhibitor combinations (ceftazidime-avibactam, meropenem-vaborbactam, cefiderocol) have restricted or variable Canadian availability — ID-directed.
Gram stain → likely organism → empiric step
Preliminary blood culture Gram stain, before identification:
| Gram stain | likely organisms | empiric step |
|---|---|---|
| GPC in clusters | S. aureus, CoNS | vancomycin until identified (1 of 2 bottles CoNS → likely contaminant) |
| GPC in pairs/chains | streptococci, pneumococcus (lancet diplococci), Enterococcus | ceftriaxone; + ampicillin or vancomycin if Enterococcus likely (GU/biliary source, prosthetic valve) |
| large GPB | Clostridium, Bacillus | C. perfringens → look for gas gangrene/GI source |
| small GPB | Listeria (blood/CSF), Corynebacterium/Cutibacterium (usually contaminants) | ampicillin if Listeria plausible |
| branching GPB | Nocardia (weakly acid-fast), Actinomyces | ID; TMP-SMX (Nocardia), penicillin (Actinomyces) |
| GN diplococci | Neisseria, Moraxella | ceftriaxone |
| GNB | Enterobacterales (lactose fermenters: E. coli, Klebsiella, Enterobacter; non-fermenters of lactose: Proteus, Serratia), Pseudomonas, anaerobes (Bacteroides, Fusobacterium) | per source and prior isolates — ceftriaxone vs pip-tazo vs carbapenem |
| GN coccobacilli | H. influenzae, Acinetobacter, HACEK | ceftriaxone; meropenem if Acinetobacter in ICU |
| yeast | Candida | echinocandin, remove lines |
Gram-positive cocci
| organism | preferred | alternative | oral step-down | traps |
|---|---|---|---|---|
| MSSA | cefazolin 2 g IV q8h or cloxacillin 2 g IV q4h | vancomycin only if β-lactams contraindicated | cephalexin (SSTI); TMP-SMX or linezolid (low-risk SAB, ID) | vancomycin inferior for MSSA — switch; S. aureus bacteraemia |
| MRSA | vancomycin (AUC 400–600) | daptomycin (not lung); linezolid (lung, SSTI) | TMP-SMX, doxycycline, linezolid | daptomycin inactivated by surfactant |
| S. lugdunensis | treat as S. aureus | — | — | virulent CoNS — endocarditis risk |
| other CoNS (true infection) | vancomycin; cefazolin/cloxacillin if oxacillin-susceptible | daptomycin, linezolid | linezolid, TMP-SMX, doxycycline per susceptibility | line or device infection → remove/exchange |
| GAS (S. pyogenes) | penicillin G IV / penicillin V PO | cefazolin, ceftriaxone | penicillin V, amoxicillin, cephalexin | + clindamycin for necrotising infection/toxic shock |
| GBS | penicillin G or ampicillin | cefazolin | amoxicillin | diabetic foot, elderly, malignancy |
| S. pneumoniae (non-meningeal) | amoxicillin / penicillin G | ceftriaxone | amoxicillin | macrolide and clindamycin resistance common |
| S. pneumoniae (meningitis) | per penicillin and ceftriaxone MIC — see bacterial meningitis | — | — | meningeal breakpoints are lower |
| viridans streptococci / S. gallolyticus | penicillin G or ceftriaxone | vancomycin | amoxicillin (POET step-down) | S. gallolyticus → echo + colonoscopy; infective endocarditis |
| S. anginosus group | penicillin G or ceftriaxone | vancomycin | amoxicillin | abscess-forming → image for a collection |
| E. faecalis | ampicillin 2 g IV q4–6h | vancomycin | amoxicillin; nitrofurantoin (cystitis) | endocarditis: ampicillin + ceftriaxone; cephalosporins alone inactive |
| E. faecium | vancomycin | linezolid, daptomycin | linezolid | usually ampicillin-resistant |
| VRE | linezolid or daptomycin (10–12 mg/kg) | — | linezolid; nitrofurantoin/fosfomycin (cystitis) | VRE in urine without symptoms → do not treat |
Gram-positive rods and fastidious organisms
| organism | preferred | alternative | notes |
|---|---|---|---|
| Listeria | ampicillin ± gentamicin | TMP-SMX | cephalosporins inactive |
| C. perfringens / clostridial myonecrosis | penicillin G + clindamycin + surgery | — | gas gangrene → surgical emergency |
| H. influenzae | amoxicillin (β-lactamase negative); ceftriaxone or amoxicillin-clavulanate | doxycycline, FQ | β-lactamase production common — check report |
| Moraxella | amoxicillin-clavulanate | doxycycline, cefuroxime | almost all β-lactamase positive |
| N. meningitidis | penicillin G or ceftriaxone | — | contacts need prophylaxis |
| HACEK | ceftriaxone | FQ | endocarditis |
| Pasteurella | amoxicillin-clavulanate | doxycycline | cephalexin and clindamycin unreliable |
| Legionella | azithromycin or levofloxacin | doxycycline | ≥7 days |
| Mycoplasma / Chlamydophila | azithromycin | doxycycline, FQ | 3–5 days |
enteric Gram-negatives
Enterobacterales: E. coli, Klebsiella, Proteus, Enterobacter, Citrobacter, Serratia, Morganella.
| phenotype | preferred | alternative | oral step-down |
|---|---|---|---|
| susceptible (ceftriaxone-S, no AmpC risk) | narrowest active: ampicillin → cefazolin → ceftriaxone | FQ, TMP-SMX | TMP-SMX, FQ, amoxicillin, or cephalexin per susceptibility |
| ESBL — cystitis | nitrofurantoin, TMP-SMX, pivmecillinam, single-dose aminoglycoside | fosfomycin (E. coli only) | same |
| ESBL — pyelonephritis/cUTI | TMP-SMX or FQ if susceptible; else ertapenem/meropenem | aminoglycoside, pip-tazo | TMP-SMX or FQ |
| ESBL — outside urinary tract (incl. bacteraemia) | meropenem or ertapenem | — | TMP-SMX or FQ once improved, if susceptible |
| AmpC risk — E. cloacae, K. aerogenes, C. freundii, Hafnia | cefepime 2 g IV q8h (MIC ≤8) | carbapenem | TMP-SMX or FQ; ceftriaxone acceptable only after clear improvement in uncomplicated infection |
| low AmpC risk — Serratia, Morganella, Providencia | ceftriaxone if susceptible | cefepime | per susceptibility |
| CRE | ID consult — KPC: ceftazidime-avibactam or meropenem-vaborbactam; NDM: aztreonam-avibactam or cefiderocol; OXA-48: ceftazidime-avibactam | — | rarely |
- pip-tazo for ESBL bacteraemia → higher mortality than meropenem (MERINO (2018)) — even if reported susceptible
- AmpC organisms reported ceftriaxone-susceptible can derepress on therapy → failure; use cefepime for serious infection
- Proteus, Morganella, Providencia, Serratia: intrinsically resistant to nitrofurantoin and tetracyclines (Proteus/Morganella also to colistin)
non-fermenting Gram-negatives
| organism | preferred | alternative | oral step-down | traps |
|---|---|---|---|---|
| Pseudomonas aeruginosa (susceptible) | one active agent: pip-tazo, cefepime, ceftazidime, or meropenem | aminoglycoside (UTI), aztreonam | ciprofloxacin or levofloxacin | drop the second agent once susceptibilities return |
| Pseudomonas (difficult-to-treat resistance) | ceftolozane-tazobactam | cefiderocol, imipenem-relebactam | — | ID consult |
| Acinetobacter (susceptible) | per susceptibility (meropenem, ampicillin-sulbactam) | — | — | often colonisation in respiratory samples |
| carbapenem-resistant Acinetobacter | sulbactam-durlobactam + carbapenem | cefiderocol | — | ID consult |
| Stenotrophomonas | TMP-SMX (high dose) ± second agent | levofloxacin, minocycline; cefiderocol (IDSA preferred for invasive) | TMP-SMX | intrinsically carbapenem-resistant; frequent colonisation |
anaerobes
| organism | preferred | alternative | traps |
|---|---|---|---|
| B. fragilis group | metronidazole | pip-tazo, carbapenem, amoxicillin-clavulanate | clindamycin resistance high — unreliable |
| oral anaerobes (aspiration, dental) | amoxicillin-clavulanate or ceftriaxone | clindamycin | added metronidazole rarely needed |
| C. difficile | oral vancomycin or fidaxomicin | — | see C. difficile |
yeasts
Candidaemia: start echinocandin (caspofungin 70 mg → 50 mg daily, micafungin 100 mg daily, or anidulafungin 200 mg → 100 mg daily); remove CVC; dilated eye exam; repeat cultures daily until negative; 14 days after first negative culture if no metastatic focus.
| species | step-down / preferred | traps |
|---|---|---|
| C. albicans, C. tropicalis | fluconazole 400 mg daily after 5–7 days if susceptible and cleared | — |
| C. parapsilosis | fluconazole | higher echinocandin MICs; line-associated |
| C. glabrata (Nakaseomyces glabratus) | echinocandin | fluconazole only if susceptible (high dose) |
| C. krusei (Pichia kudriavzevii) | echinocandin | intrinsically fluconazole-resistant |
| C. auris | echinocandin | multidrug-resistant; contact precautions + IPAC notification |
Candida in sputum, or in urine without symptoms (non-neutropaenic, no urological procedure) → colonisation; do not treat.
coverage gaps
| agent | does not cover |
|---|---|
| ceftriaxone | Pseudomonas, Enterococcus, Listeria, MRSA, atypicals, reliable anaerobes |
| cefazolin | anaerobes, many Gram-negatives beyond susceptible E. coli/Klebsiella; no CNS use |
| piperacillin-tazobactam | MRSA, atypicals; not for ESBL bacteraemia |
| ertapenem | Pseudomonas, Acinetobacter, Enterococcus |
| meropenem | MRSA, E. faecium, Stenotrophomonas, atypicals; unreliable for E. faecalis (imipenem better) |
| vancomycin | Gram-negatives; inferior to β-lactams for MSSA |
| aztreonam | Gram-positives, anaerobes (IV via Special Access Programme only) |
| moxifloxacin | Pseudomonas; poor urinary levels |
| metronidazole | aerobes |
| nitrofurantoin | anything outside the bladder; Proteus |
| clindamycin | Gram-negatives; B. fragilis unreliable; rising S. aureus/GAS resistance |
| daptomycin | pneumonia |
| echinocandins | urine (poor levels); CNS and eye |
traps
- narrowing is not optional — a susceptible organism on ceftriaxone should move to cefazolin or ampicillin where the site allows
- repeat blood cultures for S. aureus, Candida, and endovascular infection only — not routinely for Gram-negative bacteraemia that is responding
- a urine or sputum culture reflects colonisation until symptoms say otherwise — treat the patient, not the report
- MSSA on vancomycin “because it’s working” → switch (SNAP (2026): cefazolin is as effective as cloxacillin and less nephrotoxic)