Based on IDSA Guidelines | Evidence-Based Medicine | Oncology/ID Pharmacotherapy Focus
| Organism / Infection | Drug of Choice (DOC) | Alternative(s) | Clinical Pearls | ⚠ Pharmacist Watchouts |
| GRAM-POSITIVE ORGANISMS | ||||
| MSSA (Methicillin-Susceptible S. aureus) | Nafcillin or Oxacillin 2 g IV q4h (bacteremia/endocarditis) | Cefazolin 2 g IV q8h Vancomycin (inferior – avoid if alternatives exist) Ceftriaxone (SSTI/mild) | • Cefazolin NON-INFERIOR to anti-staph PCN for bacteremia (NEJM 2019) • Vancomycin is 3× inferior for MSSA — ALWAYS de-escalate from vanco to cefazolin when MSSA confirmed • ID consult recommended for all S. aureus bacteremia | • NEVER leave patient on vancomycin when MSSA confirmed — outcomes worse • Cefazolin preferred over nafcillin in oncology (less hepatotoxicity) • Watch for neutropenia with nafcillin (rare) |
| MRSA (Methicillin-Resistant S. aureus) | Vancomycin Target AUC/MIC 400–600 (Bayesian PK preferred) OR Daptomycin 6–10 mg/kg IV q24h (bacteremia/endocarditis) | Linezolid 600 mg PO/IV q12h (SSTI/pneumonia) Ceftaroline 600 mg IV q8h TMP-SMX (SSTI, susceptible) Telavancin (skin) | • IDSA 2011: Vanco AUC/MIC >400–600 — trough-based monitoring ABANDONED • Daptomycin CONTRAINDICATED in pneumonia (inactivated by surfactant) • Linezolid — no cross-resistance with glycopeptides • Ceftaroline: only beta-lactam with MRSA activity | • Vancomycin: use Bayesian AUC monitoring (not trough alone) per 2020 consensus • Daptomycin: check CPK weekly — myopathy risk; hold statins • Linezolid: MAO-I properties — serotonin syndrome risk with SSRIs/fentanyl • Thrombocytopenia with linezolid >10–14 days — critical in onc |
| VRE (Vancomycin-Resistant Enterococcus) | Linezolid 600 mg PO/IV q12h (E. faecium) Daptomycin 6 mg/kg IV q24h (E. faecium bacteremia) | Quinupristin/dalfopristin (Q/D; E. faecium only) Telavancin Tigecycline (poor bacteremia data) | • VRE most common in onc/BMT patients with prior vanco or prolonged hospitalization • Daptomycin dose escalation to 8–12 mg/kg used in refractory cases (off-label) • Combo daptomycin + ampicillin: synergy (E. faecalis) | • Linezolid myelosuppression — weekly CBC mandatory in oncology patients on chemo • Daptomycin + HMG-CoA reductase inhibitors → increased myopathy risk • Q/D: NOT active vs E. faecalis |
| Streptococcus pneumoniae | Penicillin G (PCN-susceptible MIC ≤0.06) Ceftriaxone 2 g IV q12h (meningitis/severe) | Ceftriaxone/Cefotaxime Moxifloxacin/Levofloxacin Vancomycin + ceftriaxone (meningitis, PCN-R) Linezolid (PCN/ceph resistant) | • For meningitis: PCN MIC ≥0.12 → ceftriaxone; MIC ≥1 → vanco + ceftriaxone ± rifampin • PCN allergy with low cross-reactivity to cephalosporins (<1%) • PCV20/PCV15 + PPSV23 recommended in immunocompromised per ACIP | • Ensure adequate rifampin dose for meningitis adjunct (600 mg q24h) • Dexamethasone 0.15 mg/kg q6h × 4 days as adjunct in meningitis (give BEFORE or WITH first abx dose) |
| Streptococcus viridans group (including S. mitis — common in neutropenic/BMT) | PCN G 12–18 MU/day IV (susceptible) Ceftriaxone 2 g IV q24h | Vancomycin (PCN-allergic) Add aminoglycoside synergy for endocarditis (AHA 2015) | • S. mitis most virulent viridans — shock, ARDS in neutropenic patients • Increasing PCN resistance in S. mitis — send susceptibilities • FQ prophylaxis (levofloxacin) selects for resistant viridans strep | • Avoid aminoglycoside synergy in renal impairment — very common in oncology • Viridans bacteremia in neutropenic fever: empiric vanco until susceptibilities available |
| Organism | Drug of Choice (DOC) | Alternative(s) | Clinical Pearls | ⚠ Pharmacist Watchouts |
| GRAM-NEGATIVE ORGANISMS | ||||
| Pseudomonas aeruginosa | Piperacillin-tazobactam 4.5 g IV q6h (EI over 4h) OR Cefepime 2 g IV q8h OR Meropenem 2 g IV q8h (EI over 3h) for severe/MDR | Imipenem 500 mg IV q6h Aztreonam (PCN/ceph allergy) Ceftolozane-tazo (MDR) Ceftazidime-avibactam (MDR) Ciprofloxacin (step-down, susceptible) Colistin/Polymyxin B (XDR) | • DOUBLE COVERAGE debated — IDSA does NOT recommend routine dual coverage for definitive Rx • Extended infusion (EI) β-lactams increase pharmacodynamic target attainment (PD target: fT>MIC ≥50%) • Pip-tazo + imipenem can false-positive induce AmpC — prefer cefepime for AmpC-producers • De-escalate to monotx once clinical improvement | • EI pip-tazo: must use in real-time within 12h of reconstitution at room temp • Check MIC — pip-tazo MIC >16 → do NOT use even if susceptible by disk • Imipenem has seizure potential — caution in CNS lesions, adjust in renal impairment • Colistin: TDM critical, nephrotoxic — load 9 MU then 4.5 MU q12h (for GFR>80) |
| ESBL-producing E. coli / K. pneumoniae | Meropenem 1 g IV q8h Ertapenem 1 g IV q24h (for step-down/OPAT in stable patients) | Pip-tazo AVOID (inoculum effect; MERINO trial data suggests inferiority) Temocillin (not available in US) Fosfomycin (UTI only — oral) Nitrofurantoin (uncomplicated UTI) | • MERINO Trial (NEJM 2018): pip-tazo INFERIOR to meropenem for ESBL bacteremia — 30-day mortality 12.3% vs 3.7% • Ertapenem preferred for OPAT — once-daily, narrower spectrum (no Pseudomonas activity) • Ceftriaxone disk may appear susceptible — but ESBL test mandatory to catch ESBL phenotype | • NEVER use pip-tazo for definitive ESBL bacteremia treatment (MERINO trial) • Carbapenem sparing: temocillin/oral fosfomycin not widely available in US — do not assume • Ertapenem: NO Pseudomonas coverage — confirm no Pseudomonas co-infection |
| CRE/KPC-producing Klebsiella pneumoniae | Ceftazidime-avibactam 2.5 g IV q8h (EI) + Aztreonam (for NDM) Meropenem-vaborbactam 4 g IV q8h | Imipenem-cilastatin-relebactam Cefiderocol (NDM/MBL) Polymyxin B ± carbapenem (last resort) Fosfomycin (combination) | • KPC vs MBL (NDM, VIM, IMP) — avibactam covers KPC but NOT MBL; NDM needs cefiderocol or ceftaz-avi + aztreonam • Mero-vabo: covers KPC but NOT MBL or OXA-48 • Cefiderocol: broadest coverage including MBL/OXA-48 — reserve for truly pan-drug resistant | • Always get molecular resistance testing (genotype) — carbapenemase type determines beta-lactam/inhibitor combo • Ceftaz-avi + aztreonam: mix carefully — separate infusions; aztreonam dose 2 g IV q6–8h (EI) • Polymyxin B: dose by TOTAL body weight (not adjusted); fixed-dose nephrotoxicity regardless of renal function |
| Acinetobacter baumannii (MDR/CRAB) | Ampicillin-sulbactam 9 g IV q8h (EI) (sulbactam has intrinsic Acb activity) Meropenem 2 g IV q8h EI (carbapenem-susceptible) | Polymyxin B / Colistin (last resort) Cefiderocol (CRAB) Minocycline Tigecycline (combination) | • IDSA 2022 guidance: Sulbactam-based regimen preferred even in CRAB (intrinsic OMP activity) • Cefiderocol showed non-inferiority in CREDIBLE-CR trial vs BAT (best available therapy) • Tigecycline monotherapy NOT recommended for bacteremia (low serum levels) | • Amp-sulbactam high dose (3 g amp + 6 g sulbactam = 9 g q8h) — renal dose adjustment critical • Polymyxin nephrotoxicity + colistin-induced neurotoxicity — monitor daily BUN/Cr and neurological exam • Cefiderocol: siderophore cephalosporin — check iron availability; may have reduced activity in iron-replete media |
| Haemophilus influenzae | Ceftriaxone 2 g IV q24h (severe/meningitis) Amoxicillin-clavulanate (non-beta-lactamase) | Cefuroxime Azithromycin TMP-SMX Levofloxacin | • ~30-40% beta-lactamase producers —send suscept • For meningitis: ceftriaxone; add dexamethasone • Hib vaccine prevents type b — unvaccinated asplenic/hyposplenic patients at high risk | • Oncology patients with asplenia post-splenectomy: ensure Hib vaccine prior to therapy • Azithromycin: QTc monitoring essential — common in oncology with multiple QTc-prolonging agents |
| Neisseria meningitidis | Penicillin G 4 MU IV q4h Ceftriaxone 2 g IV q12h | Chloramphenicol (PCN allergy) Meropenem (beta-lactam allergy) | • Prophylaxis contacts: rifampin 600 mg PO q12h × 2 days OR ciprofloxacin 500 mg PO × 1 • Eculizumab (complement inhibition): lifelong risk of meningococcal dx — mandatory MenACWY + MenB vaccine + penicillin ppx | • Eculizumab/ravulizumab (used in PNH, aHUS, MG): strict meningococcal prophylaxis protocol — do NOT skip penicillin VK 250 mg BID even when vaccinated |
| Organism | Drug of Choice (DOC) | Alternative(s) | Clinical Pearls | ⚠ Pharmacist Watchouts |
| ANAEROBES | ||||
| Bacteroides fragilis (& Bacteroides group) | Metronidazole 500 mg PO/IV q8h Pip-tazo 3.375 g IV q6h (intra-abdominal infections) | Imipenem/Meropenem Ampicillin-sulbactam (check local resistance) Moxifloxacin (B. fragilis resistance rising — NOT preferred) | • B. fragilis: most resistant anaerobe; intrinsic beta-lactamase • Metronidazole preferred for CDiff and intra-abdominal anaerobes • Resistance to clindamycin and FQs increasing — do not rely on empirically | • Metronidazole: disulfiram-like reaction with alcohol — counsel patients explicitly • IV metronidazole contains propylene glycol — toxicity with prolonged infusion (>1–2 weeks) • Metronidazole + warfarin: major DDI — INR monitoring or dose reduction |
| Clostridium perfringens (gas gangrene/myonecrosis) | Penicillin G 24 MU/day IV + Clindamycin 900 mg IV q8h (clindamycin inhibits toxin production) | Meropenem Metronidazole | • Clindamycin added to suppress exotoxin synthesis (EF-2 ribosomal binding) • Surgical debridement is mainstay — antibiotics adjunctive only • Hyperbaric oxygen: controversial, not standard of care per IDSA | • Clindamycin: Clostridioides difficile risk — always document prior clindamycin exposure • PCN + clindamycin: distinct mechanisms — not redundant |
| ATYPICAL ORGANISMS | ||||
| Legionella pneumophila | Levofloxacin 750 mg IV/PO q24h × 5–7d (mild) or 10–14d (immunocomp) Azithromycin 500 mg IV/PO q24h × 3–5d | Doxycycline 100 mg IV/PO q12h Rifampin (add to FQ in immunocomp — controversial) | • Urinary antigen test (UAT) only detects serogroup 1 (~80% of cases) • Immunocompromised patients: longer course (14–21d); consider FQ preferred over azithromycin (better PK/tissue penetration) • Beta-lactams: intrinsically resistant (no cell wall target accessible) | • Levofloxacin: QTc prolongation — baseline ECG mandatory in onc patients on 5-HT3 antagonists, azoles, etc. • Azithromycin: CYP3A4 inhibitor — check interaction with venetoclax, ibrutinib |
| Mycoplasma pneumoniae | Azithromycin 500 mg PO × 1, then 250 mg q24h × 4d Doxycycline 100 mg PO q12h × 5d | Levofloxacin 500 mg q24h × 5d Moxifloxacin | • No cell wall — beta-lactams INACTIVE • Self-limiting in most; treat if moderate-severe • Cold agglutinins can cause hemolytic anemia — important in oncology patients | • Cold agglutinin hemolytic anemia from Mycoplasma can mimic disease progression in CLL/lymphoma patients — distinguish carefully |
| Chlamydophila pneumoniae | Doxycycline 100 mg PO q12h × 5–7d | Azithromycin × 5d Levofloxacin × 5d | • No cell wall — beta-lactams INACTIVE • Serology often negative early — clinical diagnosis | • Doxycycline + food (except dairy/antacids): take with food to reduce GI SE, but avoid calcium-rich foods within 2h |
| Pneumocystis jirovecii (PCP) | TMP-SMX (Bactrim) 15–20 mg/kg/day IV/PO ÷ q6–8h × 21 days + Prednisone 40 mg PO BID × 5d → taper (if PaO2 <70 or A-a gradient >35) | Pentamidine 4 mg/kg IV q24h × 21d Atovaquone 750 mg PO BID × 21d (mild-moderate) Primaquine 30 mg/day + Clindamycin 600 mg IV q8h | • Steroids mandatory if A-a gradient ≥35 or PaO2 ≤70 mmHg on room air (IDSA) • High-dose TMP-SMX: major myelosuppressive in oncology — weekly CBC • G6PD deficiency screen before primaquine • Prophylaxis: TMP-SMX SS q24h (1st choice); dapsone 100 mg/day (2nd line); atovaquone 1500 mg/day; pentamidine 300 mg inhaled monthly | • TMP-SMX + methotrexate: severe bone marrow suppression — critical DDI in onc • TMP-SMX raises SCr via tubular secretion inhibition of creatinine — not true AKI • Dapsone: hemolytic anemia in G6PD deficiency — test before use • Pentamidine: hypoglycemia (acute), hyperglycemia (long-term), torsades — monitor glucose and QTc |
| Organism | Drug of Choice (DOC) | Alternative(s) | Clinical Pearls | ⚠ Pharmacist Watchouts |
| FUNGAL INFECTIONS | ||||
| Candida spp. — Candidemia (IDSA 2016) | Echinocandin Caspofungin 70 mg load → 50 mg IV q24h Micafungin 100 mg IV q24h Anidulafungin 200 mg load → 100 mg IV q24h | Fluconazole (stable, non-immunocomp, susceptible spp.) Voriconazole (step-down) Liposomal AmB (azole/echinocandin-resistant) | • IDSA 2016: echinocandin is 1st-line for all candidemia — step down to fluconazole when stable + susceptible + blood cx negative × 5d • C. krusei: intrinsically FLC-resistant → use echinocandin or voriconazole • C. glabrata: FLC resistance up to 30% — echinocandin preferred • C. auris: MDR — often resistant to FLC and amphotericin; echinocandin preferred • Remove central line if possible — MANDATORY per IDSA for non-neutropenic patients | • Ophthalmology exam mandatory for ALL candidemia (endophthalmitis risk) within 1 week • Echo within 1 week if bacteremia >72h or high-risk for endocarditis • Echinocandin DDIs minimal — safest in onc poly-pharmacy • Caspofungin: dose adjustment needed if severe hepatic impairment • Duration: 14 days from FIRST negative blood culture + resolution of symptoms |
| Aspergillus spp. — Invasive Aspergillosis (IPA) (IDSA 2016) | Voriconazole 6 mg/kg IV q12h × 2 doses → 4 mg/kg IV q12h → 200–300 mg PO q12h (step-down) OR Isavuconazole 372 mg IV/PO q8h × 6 doses → 372 mg q24h | Liposomal AmB 3–5 mg/kg IV q24h Posaconazole (prophylaxis → treatment for localized) Micafungin (combination, not monotherapy) Caspofungin (salvage) | • Voriconazole: MAJOR DDI with many chemo agents — TDM target trough 1–5.5 mg/L • Isavuconazole: fewer DDIs vs voriconazole, no QTc prolongation, linear PK — preferred if DDI concern • GM (galactomannan) serum + BAL for diagnosis — serum GM less sensitive in non-heme patients • CT chest: halo sign (early), air-crescent sign (recovery) classic findings • Prophylaxis: posaconazole 300 mg PO q24h (AML induction/HSCT GVHD) — IDSA grade A-I | • Voriconazole CYP2C19 polymorphism: poor metabolizers → toxic levels; ultra-rapid → subtherapeutic; check pharmacogenomics • Voriconazole visual disturbances (photopsia) — transient, common, counsel patients • Voriconazole + TKIs (ibrutinib, venetoclax): major DDI — dose reduce per label • Isavuconazole: QTc shortening (not prolongation) — avoid in familial short QT syndrome |
| Cryptococcus neoformans (meningitis — IDSA 2010) | Induction (2 weeks): LAmB 3–4 mg/kg/day + Flucytosine 25 mg/kg PO q6h Consolidation (8 weeks): Fluconazole 400 mg/d PO q24h Maintenance: Fluconazole 200 mg PO q24h × ≥1 year | AmB deoxycholate + 5-FC (resource-limited) FLC 800–1200 mg/day (if intolerant to LAmB) Isavuconazole (limited data) | • 5-FC is CRITICAL — do not skip; synergistic with AmB, reduces relapse • Lumbar puncture pressure management (LP q24h until <20 cmH2O) as important as antifungal Rx • Immune reconstitution syndrome (IRIS) after starting ART in HIV — do NOT start ART immediately at diagnosis | • Flucytosine: monitor levels (goal 25–100 mcg/mL) — myelosuppressive; do NOT use monotherapy (resistance emerges) • LAmB vs conventional AmB: LAmB preferred for lower nephrotoxicity • Fluconazole: QTc, drug interactions |
| Mucormycosis (Rhizopus, Mucor, Rhizomucor) | Liposomal AmB 5–10 mg/kg IV q24h (high dose — IDSA/ESCMID) | Isavuconazole 372 mg IV/PO q24h (after load) Posaconazole (step-down/prophylaxis) Combination LAmB + echinocandin (refractory) | • Mucormycosis: voriconazole has NO activity — a patient on vori prophylaxis developing mold infection → assume mucor until proven otherwise • Surgical debridement is MANDATORY — antifungals alone insufficient • Reversal of immunosuppression critical (reduce steroids, control DM) • Posaconazole step-down once stabilized | • Do NOT use voriconazole for mucor — this is a classic life-threatening error in practice • LAmB high dose nephrotoxicity — aggressive prehydration with NS 500–1000 mL before each dose; monitor K/Mg daily • Isavuconazole: preferred alternative to posaconazole as fewer GI SEs; better tolerability |
| VIRAL & OTHER INFECTIONS (Oncology/ID Focus) | ||||
| Herpes Simplex Virus (HSV) — Mucocutaneous/Encephalitis | Acyclovir 5 mg/kg IV q8h (mucocutaneous, immunocomp) Acyclovir 10 mg/kg IV q8h (encephalitis) × 14–21d Valacyclovir 1 g PO q12h (mild/oral) | Famciclovir 500 mg PO q8h Foscarnet (acyclovir-resistant HSV) | • Acyclovir-resistant HSV (TK-deficient): occurs in immunocompromised — send for susceptibility if poor response • Prophylaxis in HSCT: acyclovir/valacyclovir until engraftment and CD4 recovery • Encephalitis: treat empirically — do not wait for PCR result | • Acyclovir nephrotoxicity: crystal nephropathy — hydrate aggressively (≥125 mL/hr); slow infusion over 1 hour • Foscarnet: extreme nephrotoxicity + hypocalcemia/hypoMg — requires intensive electrolyte monitoring • Valacyclovir TTP/HUS: rare but reported in HSCT patients at high dose |
| CMV — Tissue-Invasive Disease (post-HSCT / SOT) | Ganciclovir 5 mg/kg IV q12h × 14–21d (induction) → Valganciclovir 900 mg PO q12h (step-down) | Foscarnet 90 mg/kg IV q12h (GCV-resistant) Cidofovir 5 mg/kg IV weekly × 2 → q2wk (salvage) Letermovir (prophylaxis only — CMV D+/R+ HSCT) Maribavir 400 mg PO BID (refractory CMV) | • Letermovir FDA 2017: prophylaxis in CMV-seropositive allo-HSCT — reduces CMV through week 24 • Maribavir FDA 2021: refractory/resistant CMV in HSCT/SOT — NOT for prophylaxis or first-line • GCV-resistance: UL97 mutations (most common), UL54 (cross-resistance to cidofovir) • Pre-emptive therapy: treat at CMV viral load threshold before end-organ disease | • Ganciclovir: profound myelosuppression — AVOID concurrent myelotoxic chemo if possible; CBC 2–3×/week • Letermovir + cyclosporine: letermovir dose reduce to 240 mg; monitor cyclosporine levels • Cidofovir: nephrotoxicity — probenecid + IV saline prehydration mandatory • Maribavir: inhibits ganciclovir phosphorylation — do NOT combine with ganciclovir (antagonism) |
| VZV — Varicella/Zoster | Acyclovir 10 mg/kg IV q8h × 7d (disseminated/immunocomp) Valacyclovir 1 g PO TID × 7d (localized zoster, immunocomp) | Famciclovir 500 mg PO TID × 7d Foscarnet (acyclovir-resistant) | • Immunocompromised: IV acyclovir for ALL zoster until healing, then step-down to PO • VZV IGIV (VariZIG) for post-exposure prophylaxis within 10 days • Shingrix (RZV) preferred vaccine in immunocompromised cancer patients (not live) — even in post-HSCT | • Acyclovir renal dosing critical — dose adjustments in AKI very common in onc patients • Pain management for PHN: do NOT delay antivirals — start within 72h of rash onset for best outcomes |
| Clostridioides difficile Infection (CDI) (IDSA/SHEA 2021) | Non-severe CDI: Vancomycin 125 mg PO q6h × 10d OR Fidaxomicin 200 mg PO q12h × 10d Severe CDI: Vancomycin 125 mg PO q6h × 10d Fulminant CDI: Vancomycin 500 mg PO/NG q6h + Metronidazole 500 mg IV q8h | Metronidazole 500 mg PO q8h × 10d (non-severe ONLY if first recurrence + supply issues) Bezlotoxumab 10 mg/kg IV × 1 (monoclonal; reduce recurrence in high-risk) Fecal microbiota transplant (recurrent ≥3 episodes) | • IDSA 2021: metronidazole NO LONGER preferred 1st-line for any CDI — vancomycin/fidaxomicin preferred • Fidaxomicin: LOWER recurrence rate vs vancomycin (PRECEDENT trial) — preferred in high-risk for recurrence (age >65, prior CDI, ongoing immunosuppression) • Bezlotoxumab: adjunct only (not standalone treatment); reduces recurrence by ~40% in high-risk • Test of cure NOT recommended — PCR stays positive weeks after resolution | • Oral vancomycin: NOT systemically absorbed — IV vanco has NO activity vs CDI • Oncology patients: highest CDI risk (antibiotics, proton pump inhibitors, chemo-induced mucositis) • Proton pump inhibitors: independent risk factor for CDI — review need at every visit • Fidaxomicin preferred in patients receiving concomitant antibiotics for other infections (narrower disruption of microbiome) |
Last Updated: May 2026 | For Educational Purposes — Verify against current institutional protocols