Septic shock: antibiotics within 1 hour, after blood cultures if that causes no delay
Two sets of blood cultures plus a culture from the suspected source first
Choose by the local antibiogram and the patient's prior cultures and resistance risks (recent antibiotics, hospitalization, MDR colonization)
Dose for the kidneys: Cockcroft-Gault creatinine clearance; CRRT clears most beta-lactams and vancomycin
Vancomycin: load 20–35 mg/kg, then dose to an AUC of 400–600 per pharmacy (2020 consensus; trough-only targets of 15–20 are no longer advised)
Aminoglycosides: once-daily extended-interval dosing where possible; monitor levels and creatinine
Penicillin allergy: most patients tolerate cephalosporins; clarify the reaction before choosing a worse drug
Reassess at 48–72 hours: narrow to culture results and set a stop date
Sepsis, source unknown
Broad coverage until the source declares itself
Community onset, no MDR risk
Piperacillin-tazobactam or ceftriaxone, plus vancomycin if MRSA risk
Hospital onset or MDR risk
Cefepime, piperacillin-tazobactam or meropenem, plus vancomycin
Severe beta-lactam allergy
Aztreonam plus vancomycin, plus metronidazole if anaerobes matter
Septic shock with MDR risk
Consider adding a second gram-negative agent (aminoglycoside) until cultures return
Add antifungal cover (echinocandin) for candidemia risk: TPN, prolonged broad antibiotics, abdominal surgery, central lines, immunosuppression.
Pneumonia
CAP, HAP and VAP
CAP, ward
Ceftriaxone plus azithromycin (or doxycycline), or a respiratory fluoroquinolone
CAP, ICU
Ceftriaxone (or ampicillin-sulbactam) plus azithromycin; add vancomycin or linezolid for MRSA risk; antipseudomonal beta-lactam for Pseudomonas risk
HAP/VAP
Antipseudomonal beta-lactam (piperacillin-tazobactam, cefepime, meropenem); add vancomycin or linezolid for MRSA risk; two antipseudomonal agents if septic shock or high MDR rates
Aspiration
Ampicillin-sulbactam or ceftriaxone; anaerobic cover only for empyema or abscess
Influenza
Oseltamivir for any hospitalized patient, regardless of symptom duration
MRSA risks: prior MRSA, IV antibiotics in the past 90 days, nasal swab positive. A negative nasal MRSA swab supports stopping vancomycin. Usual course 7 days.
Meningitis and CNS
Do not wait for the LP
Bacterial meningitis, adult
Ceftriaxone 2 g every 12 h plus vancomycin; dexamethasone 10 mg every 6 h for 4 days, first dose before or with antibiotics
Over 50, immunocompromised, pregnant
Add ampicillin 2 g every 4 h for Listeria
Post-neurosurgery or shunt
Vancomycin plus cefepime or meropenem
Encephalitis (HSV)
Acyclovir 10 mg/kg every 8 h, hydrate (crystals); stop only when HSV is excluded (an early negative PCR may need a repeat LP); proven HSV 14–21 days
Abdomen and urine
Intra-abdominal infection, C. difficile, pyelonephritis
Intra-abdominal, community
Ceftriaxone plus metronidazole, or piperacillin-tazobactam; source control is the treatment
Intra-abdominal, hospital or severe
Piperacillin-tazobactam or meropenem; add vancomycin for Enterococcus risk, echinocandin for Candida
Spontaneous bacterial peritonitis
Ceftriaxone or cefotaxime; albumin 1.5 g/kg day 1 and 1 g/kg day 3
C. difficile
Fidaxomicin 200 mg twice daily (or vancomycin 125 mg PO four times daily) for 10 days; fulminant: vancomycin 500 mg PO/NG four times daily plus IV metronidazole, rectal vancomycin for ileus
Complicated UTI or pyelonephritis
Ceftriaxone, or piperacillin-tazobactam/carbapenem for MDR risk; avoid fluoroquinolones empirically where resistance is high
Catheter-associated UTI
Remove or replace the catheter, then culture and treat
Cefazolin or ceftriaxone; oral cephalexin when mild
Purulent abscess
Drain; vancomycin, or doxycycline/TMP-SMX orally
Necrotizing soft-tissue infection
Surgery now; vancomycin plus piperacillin-tazobactam (or meropenem) plus clindamycin for toxin suppression
Central line infection (CLABSI)
Vancomycin plus cefepime or piperacillin-tazobactam; remove the line for S. aureus, Pseudomonas, Candida, sepsis or tunnel infection, and a short-term line also for any gram-negative rod or enterococcus (IDSA 2009)
Native valve endocarditis, empiric
Vancomycin plus ceftriaxone; blood cultures first, three sets
Prosthetic valve endocarditis, empiric
Within 12 months of surgery or health care–associated: vancomycin, gentamicin and rifampin (ESC 2023); later: as for a native valve
Diabetic foot, severe
Vancomycin plus piperacillin-tazobactam; imaging for osteomyelitis
Neutropenic fever
ANC under 500, or expected below 500 within 48 h, with 38.3 °C once or 38.0 °C for an hour
Add vancomycin for hypotension, pneumonia, skin or line infection, MRSA colonization, or severe mucositis after fluoroquinolone prophylaxis when ceftazidime is the empiric drug (IDSA 2010)
Fever after 4–7 days with neutropenia expected to last over 7 days: add antifungal cover (echinocandin or voriconazole)
Avoid rectal temperatures and exams, enemas and suppositories
Penicillin and β-lactam allergy
Who can safely get a β-lactam (2022 AAAAI/ACAAI parameter)
The label
How often it is wrong
About 10% report it; 90% or more tolerate penicillin when evaluated; under 5% of unverified labels are true allergy (2022 parameter)
Why it matters
Vancomycin, fluoroquinolones or clindamycin instead: more C. difficile, MRSA, VRE; 50% higher odds of surgical site infection (Blumenthal 2018)
Allergy fades
About 80% of people with true IgE-mediated penicillin allergy lose it within 10 years (CDC)
Sort the history (2022 parameter)
History to take
Drug, reaction, when, treatment needed, any β-lactam tolerated since; IDSA/SHEA 2016 asks stewardship to promote this
Not allergy
Headache, nausea, diarrhea or family history only: remove the label without testing; one amoxicillin dose if the patient wants proof
Low risk
Benign rash or hives, no systemic features, over 5 years ago (any time in children): direct amoxicillin challenge, no skin test
High risk
Anaphylaxis, or a recent reaction that sounds IgE-mediated: penicillin skin testing, then a challenge if negative
Do not challenge
SJS/TEN, DRESS, AGEP, hemolytic anemia, drug liver injury or interstitial nephritis: avoid the drug; allergist decides
PEN-FAST
Reaction 5 years ago or less 2; anaphylaxis, angioedema or severe skin reaction 2; treatment needed 1. Under 3 is low risk (Trubiano 2020)
Cross-reactivity
Cephalosporins overall
About 2% in proven penicillin allergy, not 10% (pre-1980 drugs held penicillin); driven by the R1 side chain, not the ring
Shared side chains
Amoxicillin and ampicillin share R1 with cephalexin, cefadroxil, cefaclor, cefprozil: about 16% in proven aminopenicillin allergy
Cefazolin
Unique side chains, about 1% cross-reactivity: OK even after penicillin anaphylaxis (CBS 12); SHEA/IDSA/APIC 2022 backs it for surgery
Other cephalosporins
Any cephalosporin after a non-anaphylactic label (CBS 13); after anaphylaxis, a dissimilar R1 such as ceftriaxone or cefepime
Carbapenems
Under 1% (0.87%): give without testing or extra precautions, even after anaphylaxis (CBS 17); not after SCAR or organ injury
Aztreonam
No cross-reactivity with penicillins or other cephalosporins; avoid only after ceftazidime allergy (shared R1; cefiderocol is similar)
Challenge (2022 parameter)
1-step (direct) challenge
One full treatment dose (oral amoxicillin to clear a penicillin label), then watch 30–60 min; no multi-day challenges (CBS 7)
2-step challenge (test dose)
One-tenth of the dose, then the rest 30 min later if no reaction; watch 30–60 min. Consider it for a more severe or recent history
Positive challenge
Hives, angioedema, wheeze, hypoxia or hypotension: stop, treat (IM epinephrine for anaphylaxis), keep the label and refer
After a pass
Remove the label in the chart, pharmacy and other systems and tell the patient in writing; labels often come back
For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow your local protocols and medical direction.