Sepsis and Septic Shock
Clinical Snapshot
Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection — an acute rise in the Sequential (Sepsis-related) Organ Failure Assessment (SOFA) score of 2 points or more, attributable to the infection.[1] Septic shock is the subset of sepsis in which circulatory, cellular, and metabolic abnormalities are profound enough to substantially increase mortality — clinically identified by a vasopressor requirement to maintain mean arterial pressure (MAP) at or above 65 mmHg and a serum lactate above 2 mmol/L (18 mg/dL) despite adequate fluid resuscitation.[1] These are Sepsis-3 consensus definitions, not simply "severe infection" — a patient can be profoundly septic with a completely normal blood pressure, and a patient can look hemodynamically stable while already meeting organ-dysfunction criteria.
This is a genuine pharmacotherapy emergency: each hour that effective antimicrobial therapy is delayed after the onset of hypotension in septic shock measurably increases mortality, with an average absolute survival decrease of roughly 7.6% per hour of delay in the landmark multicentre cohort that established this relationship.[2] The Surviving Sepsis Campaign (SSC) — a joint initiative of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine — packages the first hour of care into the Hour-1 Bundle: measure lactate, obtain blood cultures before antimicrobials, give broad-spectrum empiric antibiotics, begin rapid crystalloid resuscitation, and apply vasopressors for persistent hypotension.[3] The most current SSC guideline (2026) is used throughout this chapter; its 69-person international panel is co-vice-chaired by a Canadian intensivist and includes several further Canadian panelists, and the prior (2021) SSC guideline documents formal endorsement by the Canadian Critical Care Society among its sponsoring professional societies.[4]
Recognize the Condition
Presentation is defined by organ dysfunction, not just infection severity
Sepsis can present with the expected picture — fever, tachycardia, tachypnea, and a clear infectious source — but the organ-dysfunction pattern is what actually defines it, and it can dominate the picture even when infectious symptoms are subtle. Look specifically for: altered mentation or new confusion; hypotension or a widened pulse pressure; tachypnea or new oxygen requirement; oliguria or a rising creatinine; mottled or cool, poorly perfused skin with delayed capillary refill; jaundice or coagulopathy; and a rising lactate.
Atypical presentation
Older adults, neutropenic or otherwise immunosuppressed patients, and patients on beta-blockers or with chronic autonomic dysfunction frequently do not mount a fever or tachycardia even with severe sepsis — a normal temperature and heart rate never excludes the diagnosis in these groups, and a low threshold for reassessment is essential. Early sepsis, before hypotension develops, is easy to miss; the whole point of routine screening (see Assessment & Diagnosis) is to catch it before shock develops.
Common sources and their focal clues
Pulmonary
Cough, dyspnea, new hypoxemia, a focal infiltrate on chest imaging.
Intra-abdominal
Abdominal pain, distension, peritoneal signs, vomiting — think a perforated viscus, cholangitis, or an abscess.
Urinary
Dysuria, flank pain, costovertebral angle tenderness — particularly with an indwelling catheter or known obstruction.
Skin/soft tissue
Erythema, warmth, pain out of proportion to exam findings (a red flag for necrotizing infection), a wound, or a diabetic foot ulcer.
Catheter/device-related
Erythema or purulence at an insertion site, or unexplained bacteremia in a patient with a central line, dialysis catheter, or other indwelling device.
CNS
Headache, neck stiffness, altered mentation out of proportion to hemodynamics — see the Bacterial Meningitis chapter for the dedicated CNS-source pathway.
Risk Factors
- Extremes of age — infants and adults over 65.
- Immunosuppression: chemotherapy-induced neutropenia, solid organ or stem cell transplantation, chronic high-dose corticosteroids, biologic/immunomodulatory therapy, HIV infection, and functional or anatomic asplenia.
- Diabetes mellitus, chronic kidney disease, cirrhosis, chronic obstructive pulmonary disease, and heart failure.
- An indwelling intravascular catheter, urinary catheter, or other implanted device.
- Recent surgery, trauma, or another invasive procedure.
- Injection drug use.
- Recent hospitalization, residence in a long-term care facility, or known colonization with a multidrug-resistant (MDR) organism.
- Malnutrition and frailty.
- Pregnancy and the immediate postpartum period.
- A prior episode of sepsis or septic shock.
Red Flags & Refer
Suspected sepsis with any of the following is itself the red flag — activate the institution's sepsis protocol and begin the Hour-1 Bundle immediately; do not wait for a complete workup or ICU bed before starting treatment.
- Any two of: respiratory rate ≥22/min, altered mentation, systolic blood pressure ≤100 mmHg (the qSOFA criteria) in a patient with suspected infection warrants urgent reassessment for sepsis, even outside a monitored setting.
- Hypotension unresponsive to an initial fluid bolus, or an ongoing vasopressor requirement to maintain MAP ≥65 mmHg — this is septic shock until proven otherwise.
- Lactate above 4 mmol/L.
- New or worsening organ dysfunction: altered mentation, new oxygen requirement or respiratory failure, oliguria/anuria, a rapidly rising creatinine, new coagulopathy, or new jaundice.
- Mottled skin, cool extremities, or markedly delayed capillary refill — clinical signs of poor peripheral perfusion.
- Pain out of proportion to exam findings over a wound or soft-tissue site — evaluate emergently for necrotizing soft tissue infection, which needs immediate surgical involvement in addition to antibiotics.
- Neutropenic fever — treat as a sepsis emergency regardless of how well the patient looks; do not wait for the absolute neutrophil count to result before giving antibiotics if the clinical picture and history support it.
Assessment & Diagnosis
Sepsis-3 definitions
Sepsis = suspected or confirmed infection + an acute SOFA score increase of ≥2 points attributable to the infection. Septic shock = sepsis + vasopressor requirement to maintain MAP ≥65 mmHg + serum lactate >2 mmol/L (18 mg/dL) despite adequate fluid resuscitation.[1] Septic shock carries a substantially higher mortality than sepsis without shock, which is why recognizing it specifically — not just "the patient has an infection" — drives the urgency of the Hour-1 Bundle.
qSOFA — a quick bedside prompt, not a diagnostic or rule-out test
Quick SOFA (qSOFA) was designed as a fast bedside prompt to raise suspicion for sepsis outside the ICU, using 3 criteria — 1 point each, 2 or more suggests a higher-risk patient who needs further evaluation.
| Criterion | Threshold |
|---|---|
| Respiratory rate | ≥22 breaths/min |
| Mentation | Altered (any deviation from the patient's baseline) |
| Systolic blood pressure | ≤100 mmHg |
A qSOFA score under 2 does not rule out sepsis — it has limited sensitivity, especially early in the illness. The current (2026) SSC guideline specifically recommends that hospitals use a validated track-and-trigger tool such as NEWS, NEWS2, MEWS, or even simple SIRS criteria over qSOFA alone as the single hospital screening tool, given qSOFA's documented sensitivity limitations in this setting — qSOFA remains a reasonable quick prompt, particularly prehospital or where a fuller screening tool isn't in use, but should not be treated as a definitive gate.[3]
SOFA score — the Sepsis-3 diagnostic criterion
An acute SOFA increase of ≥2 points is the actual organ-dysfunction criterion that defines sepsis under Sepsis-3. It scores 6 organ systems from 0 (normal) to 4 (most severe) using values already available from routine labs, vitals, and the ventilator/vasopressor record.
| System | Parameter | Worsens toward |
|---|---|---|
| Respiratory | PaO2/FiO2 ratio (with or without ventilatory support) | Lower ratio, especially with mechanical ventilation |
| Coagulation | Platelet count | Lower count (<20 x109/L scores highest) |
| Hepatic | Bilirubin | Higher bilirubin (>204 μmol/L / 12 mg/dL scores highest) |
| Cardiovascular | MAP, or vasopressor type/dose required | MAP <70 mmHg through escalating vasopressor doses |
| CNS | Glasgow Coma Scale | Lower GCS (<6 scores highest) |
| Renal | Creatinine, or urine output | Higher creatinine or lower urine output (anuria scores highest) |
A live calculator is intentionally not provided for either qSOFA or SOFA here — SOFA in particular depends on the specific vasopressor agent and dose band in use, which is easy to encode incorrectly in a simplified checkbox tool, and clinical judgment plus the teaching tables above should drive practice rather than a point-sum alone.
Investigations
- Blood cultures — at least 2 sets from separate sites, obtained as soon as possible and ideally before the first antimicrobial dose, but never at the cost of delaying antibiotics beyond the target window.[3]
- Lactate — obtain immediately; an elevated initial lactate should be followed by serial measurements to guide resuscitation via lactate decrement (a clear downward trend), rather than continuing fluids and vasopressors chasing full lactate normalization.[3]
- CBC and differential, electrolytes, creatinine/urea, liver function tests, coagulation studies, and venous or arterial blood gas.
- Source-directed investigations based on the focal clues above — chest imaging, urinalysis and urine culture, abdominal imaging, wound/soft-tissue assessment, and any relevant line/catheter cultures.
- Procalcitonin is not required to decide whether to start antimicrobials, but has a defined, narrower role later in guiding duration of therapy in ambiguous cases (see Monitoring & Follow-Up).[3]
Treatment Targets
- Recognize sepsis and septic shock as early as possible — before, not after, irreversible organ injury develops.
- Complete the Hour-1 Bundle: lactate, blood cultures, broad-spectrum empiric antibiotics, rapid fluid resuscitation, and vasopressors for persistent hypotension.
- Achieve and maintain a MAP of at least 65 mmHg (60-65 mmHg is a reasonable target in patients 65 years and older).
- Achieve a clear downward lactate trend, not necessarily full normalization.
- Identify and control any anatomic source needing drainage, debridement, or device removal, ideally within 6 hours.
- De-escalate or narrow antimicrobial therapy as soon as culture and susceptibility data allow, and use the shortest effective duration once source control is adequate.
- Avoid the harms of over-treatment — unnecessary fluid volume, unnecessarily broad or prolonged antimicrobials, and unnecessary invasive monitoring.
- Support a safe transition of care, including comprehensive medication reconciliation, at every handoff.
Choose Initial Treatment
The Hour-1 Bundle
Complete the following within 1 hour of recognizing possible, probable, or definite sepsis or septic shock:
- Measure lactate; remeasure if the initial value is elevated to track the trend.
- Obtain blood cultures (at least 2 sets) before giving antimicrobials, without letting this delay antibiotics past the target window.
- Give broad-spectrum empiric antimicrobial therapy — possible, probable, or definite septic shock and probable or definite sepsis without shock both warrant antimicrobials immediately, ideally within 1 hour of recognition. Possible sepsis without shock a brief, time-limited course of rapid investigation is reasonable, with antimicrobials given within 3 hours if concern for infection persists.[3]
- Begin rapid IV fluid resuscitation for hypoperfusion or septic shock — at least 30 mL/kg of balanced crystalloid within the first 3 hours, individualized to the patient (heart failure, end-stage renal disease, and BMI over 30 kg/m² all warrant a more cautious, weight-adjusted approach).[3]
- Apply vasopressors during or immediately after fluid resuscitation if hypotension persists, or immediately and concurrently with fluids in a patient who already shows unstable shock physiology (severely low blood pressure, mottled skin, cyanosis, or altered mentation) — do not wait for a fixed fluid volume to run in first.[3]
Empiric antibiotic selection by suspected source
Cover the most likely pathogens for the suspected source immediately; narrow once culture and susceptibility data return (see De-escalation below). Add coverage for multidrug-resistant (MDR) organisms only with a specific risk factor — recent broad-spectrum antibiotic exposure, known MDR colonization, or prolonged hospitalization in a unit with high MDR prevalence — not routinely.[3]
Source unknown / undifferentiated
Piperacillin-tazobactam 4.5 g IV, or meropenem 1 g IV if MDR risk factors are present; add vancomycin if there is a specific risk for MRSA (hemodialysis, known MRSA colonization, injection drug use, or recent hospitalization).
Pulmonary
Ceftriaxone 2 g IV daily + azithromycin 500 mg IV daily for atypical coverage. If critically ill, structurally lung-diseased, or at risk for Pseudomonas, use piperacillin-tazobactam or cefepime instead of ceftriaxone; add vancomycin or linezolid for MRSA risk (post-influenza, cavitary infiltrate, injection drug use).
Intra-abdominal
Piperacillin-tazobactam or meropenem (both cover anaerobes); if using a backbone without anaerobic activity, add metronidazole 500 mg IV Q8H. Empiric antifungal coverage is not routine — reserve it for a specific risk factor such as recent GI surgery, recurrent GI perforation, or significant immunosuppression, decided case by case.[3]
Urinary
Ceftriaxone 2 g IV daily if no MDR risk factors; piperacillin-tazobactam or meropenem if MDR risk factors are present.
Skin/soft tissue
Vancomycin (MRSA risk) or cefazolin/cloxacillin (MSSA-focused) for cellulitis; add piperacillin-tazobactam for a diabetic foot or otherwise broader-risk wound source. For necrotizing soft tissue infection, add clindamycin 900 mg IV Q8H for antitoxin effect against toxin-producing streptococci/staphylococci, alongside vancomycin or linezolid plus piperacillin-tazobactam or meropenem — and obtain emergency surgical debridement, since source control is just as critical as the antibiotic regimen here.
Catheter/line-associated
Vancomycin plus an antipseudomonal beta-lactam (cefepime or piperacillin-tazobactam); remove or exchange the catheter as source control.
Neutropenic fever
Cefepime, piperacillin-tazobactam, or meropenem as immediate monotherapy — do not delay for the absolute neutrophil count to result. Add vancomycin only for a specific indication (hemodynamic instability, a skin/soft-tissue or line-source suspicion, known MRSA colonization), not routinely.
Fluid resuscitation
1st line balanced crystalloid (e.g., lactated Ringer's or a similar balanced solution) over 0.9% saline for initial resuscitation — exception use 0.9% saline in patients with concomitant traumatic brain injury.[3] Avoid starches and gelatin for resuscitation in sepsis/septic shock — both are associated with worse outcomes.[3] After the initial 30 mL/kg bolus, individualize further fluid administration using dynamic measures (passive leg raise response, stroke volume or pulse pressure variation) rather than a fixed volume target or continuing fluids until lactate fully normalizes.[3]
Vasopressor ladder
Start vasopressors peripherally rather than delaying initiation until central venous access is secured.[3] 1st line norepinephrine, titrated to a MAP target of 65 mmHg (60-65 mmHg is a reasonable alternative target in patients 65 years and older) — preferred over dopamine, epinephrine, selepressin, vasopressin, or angiotensin II as the initial agent, an approach also supported by the SOAP II trial showing more arrhythmias with dopamine and no survival advantage over norepinephrine.[3][5] Escalating norepinephrine doses add fixed-dose vasopressin rather than continuing to escalate norepinephrine alone.[3] MAP still inadequate on norepinephrine + vasopressin add epinephrine.[3] Persistent hypoperfusion with cardiac dysfunction despite adequate fluids and MAP, consider adding an inotrope (dobutamine or epinephrine).[3]
Adjunctive corticosteroid: add IV hydrocortisone for septic shock with an ongoing vasopressor requirement despite adequate fluid resuscitation and MAP support.[3]
Source control
Rapidly evaluate every patient with sepsis or septic shock for a specific anatomic diagnosis or infection source requiring emergent source control (drainage of an abscess, debridement of necrotic tissue, removal of an infected device, or relief of an obstruction), and complete it as early as medically and logistically possible, ideally within 6 hours.[3]
De-escalation
Confirmed microbiologic diagnosis and susceptibility available de-escalate antimicrobial therapy — this is now a strong recommendation, not merely a suggestion.[3] No pathogen identified on final culture results de-escalation is still suggested over continuing the fixed broad regimen without reassessment.[3] Use prolonged/extended-infusion beta-lactam dosing for maintenance doses (after a full loading dose) over conventional bolus administration.[3] With adequate source control, favour a shorter over a longer duration of therapy; where the optimal duration is genuinely unclear, use procalcitonin together with clinical evaluation — not procalcitonin alone — to help decide when to stop.[3]
Non-Pharmacologic Treatment
- Manage septic shock, and any sepsis with red-flag features, in an ICU or equivalent critical care setting with continuous monitoring.
- Source control — drainage of an abscess or empyema, debridement of necrotic or infected tissue, removal or exchange of an infected catheter/device, or relief of a urinary/biliary obstruction — is not adjunctive, it is core therapy; antibiotics alone will not resolve an uncontrolled source.
- For hypoxemic respiratory failure, use high-flow nasal cannula (HFNC) as the initial device over conventional oxygen therapy, and over non-invasive positive pressure ventilation as the first choice where HFNC is available; a trial of awake proning is reasonable in a non-intubated, cooperative patient.[3]
- For sepsis-associated ARDS, use a low tidal volume strategy (6 mL/kg ideal body weight), limit plateau pressure to 30 cm H2O or less, and use higher PEEP over lower PEEP for moderate-severe ARDS — but avoid an incremental PEEP titration strategy.[3]
- Establish a hospital-level sepsis performance-improvement program — standardized screening for acutely ill, high-risk patients; standard operating procedures for treatment; and a "code sepsis"-style multidisciplinary huddle protocol activated on a positive screen.[3]
- Start early enteral nutrition, generally within 72 hours, once hemodynamically stabilized.[3]
- Apply a restrictive red blood cell transfusion strategy rather than a liberal one.[3]
- Give pharmacologic VTE prophylaxis (low molecular weight heparin preferred over unfractionated heparin) unless contraindicated.[3]
- Give stress ulcer prophylaxis with a proton pump inhibitor in patients with GI bleeding risk factors.[3]
- Do not use antipyretic therapy (pharmacologic or surface cooling) for the specific purpose of improving sepsis outcomes — this does not apply to treating fever for the patient's own comfort or for other indications (e.g., neurocritical care, post-cardiac-arrest temperature management).[3]
- Discuss goals of care and prognosis with the patient and/or family early — within 72 hours rather than later — as part of routine sepsis care, not only when the trajectory looks poor.[3]
Special Populations
Pregnancy
Normal pregnancy physiology (higher resting heart rate, lower baseline blood pressure, physiologic leukocytosis) can mask or mimic early sepsis, so maintain a lower threshold for suspicion. Obstetric sources — chorioamnionitis, septic abortion, and postpartum endometritis — need prompt source-specific antibiotics and source control (delivery or uterine evacuation) without delay. Beta-lactams (penicillins, cephalosporins, carbapenems) are generally safe throughout pregnancy and remain first-line empiric choices. Avoid tetracyclines; fluoroquinolones are generally avoided but may be used if no adequate alternative exists and the maternal benefit clearly outweighs the risk in life-threatening sepsis. Norepinephrine and the same vasopressor ladder apply; use left lateral positioning/uterine displacement to relieve aortocaval compression during resuscitation.
Breastfeeding
Piperacillin-tazobactam, meropenem, vancomycin, clindamycin, and metronidazole are all considered compatible with breastfeeding at standard treatment doses; confirm specifics against each drug's own Drug Database entry.
Renal impairment
Do not reduce loading doses of piperacillin-tazobactam, meropenem, or vancomycin for renal impairment in a hemodynamically unstable patient — underdosing the first dose to "protect the kidneys" is a real and avoidable cause of treatment failure. Reduce only the maintenance dose or extend the interval, and monitor vancomycin levels and renal function closely thereafter.
Hepatic impairment / cirrhosis
Supplemental albumin for fluid resuscitation may specifically be considered in patients with cirrhosis, or in those who have already received large volumes of crystalloid — this is a case-by-case addition, not routine first-line fluid therapy.[3]
Obesity
Use actual body weight for beta-lactam and vancomycin loading doses. Weight-based fluid volume calculations should use actual or adjusted/ideal body weight in patients with a BMI over 30 kg/m² to avoid substantial over-resuscitation.[3]
Older adults (65 and older)
May not mount fever or tachycardia even with severe infection — maintain suspicion despite reassuring vital signs. A MAP target of 60-65 mmHg (rather than 65 mmHg) is a reasonable alternative in this group given the trial evidence informing this specific age-based recommendation.[3] Polypharmacy and age-related changes in renal function make careful dose review essential, and this group is also more susceptible to hydrocortisone- and insulin-related adverse effects — monitor glucose and mental status closely.
Immunocompromised and neutropenic patients
Give broad empiric coverage immediately on suspicion — do not wait for neutrophil recovery or a confirmed source. Empiric antifungal coverage is still not routine even in this group; reserve it for a specific risk factor and involve infectious diseases early.
Monitoring & Follow-Up
Reassess frequently in the first hours: repeat lactate to confirm a clear downward trend (not necessarily full normalization), hemodynamics guided by dynamic measures, urine output, and mental status.[3] Reassess daily — earlier if new culture data return — for an opportunity to de-escalate or narrow antimicrobial therapy once susceptibility results are available; where the ideal duration is genuinely unclear despite adequate source control, use procalcitonin together with clinical evaluation to help decide when to stop, rather than defaulting to a fixed long course.[3] Monitor vancomycin and aminoglycoside levels and renal function throughout therapy. Once insulin therapy is started for a glucose ≥180 mg/dL (10 mmol/L), monitor glucose per institutional protocol, avoiding both severe hyperglycemia and hypoglycemia.[3] Review VTE and stress ulcer prophylaxis daily, and confirm the restrictive transfusion threshold is being followed rather than a liberal one.[3]
Medication reconciliation is a specific, named recommendation at every transition of care — ICU to ward, and hospital to home — ideally using a pharmacist-based approach; this is one of the highest-yield, most concrete points where a pharmacist directly improves sepsis outcomes, since antimicrobial duration, dose adjustments made during acute illness, and medications paused on admission are all easy to lose at a handoff.[3] A pharmacist embedded in the sepsis response — in the emergency department or as part of a rapid-response/sepsis team — is independently associated with faster time to first antibiotic dose across multiple studies, in addition to this discharge/transition role.[6]
Before discharge, screen for economic and social support needs relevant to recovery (housing, nutritional, financial, spiritual), address goals of care and prognosis early (within 72 hours of presentation, not only late in a poor trajectory), and give the patient and family written and verbal education on the sepsis diagnosis, treatment received, and common post-ICU/post-sepsis impairments before discharge and again at follow-up.[3] Arrange follow-up for any new physical, cognitive, or psychological impairment identified at discharge (post-intensive care syndrome).[3]
Common Errors to Avoid
- Delaying empiric antibiotics to complete imaging, await culture results, or secure an ICU bed — give antibiotics within 1 hour of recognizing probable or definite sepsis/septic shock regardless of what else hasn't happened yet.
- Reducing the loading dose of a beta-lactam or vancomycin for renal impairment in a hemodynamically unstable patient — adjust the maintenance dose or interval instead, never the first dose.
- Continuing broad-spectrum empiric antibiotics for the full course by default rather than de-escalating once culture and susceptibility data support narrowing — this is now a strong recommendation, not an optional step.
- Adding empiric antifungal coverage or extended MDR coverage without an actual risk factor — unnecessary broad coverage carries real costs (C. difficile, resistance, cost) that current guidance specifically recommends against absent a genuine risk factor.
- Continuing aggressive fluid resuscitation past the initial 30 mL/kg bolus toward a fixed volume target instead of reassessing with dynamic measures — over-resuscitation causes real harm (pulmonary edema, worse oxygenation).
- Escalating norepinephrine indefinitely instead of adding vasopressin once doses are climbing.
- Forgetting source control — antibiotics alone will not resolve an undrained abscess, necrotic tissue, or an infected device that needs to come out.
- Treating a qSOFA score under 2 as if it excludes sepsis — it does not, and current SSC guidance favours a fuller track-and-trigger tool (e.g., NEWS2) over qSOFA alone for hospital screening.
- Missing atypical presentation (no fever, no tachycardia) in older, immunosuppressed, or neutropenic patients.
- Skipping medication reconciliation at ICU or hospital-discharge transitions — a common point where antimicrobial duration, dose adjustments made during acute illness, or paused home medications get lost.
Clinical Decision Algorithm
Drug Tables
How to use this table: Doses are adult doses and require patient-specific confirmation (renal/hepatic function, weight, allergy history). Pediatric dosing is weight-based per the current product monograph unless stated. Drug pricing is intentionally omitted. Select any drug name to open its complete Pharmasist Drug Database page.
Empiric Antibiotic Regimens by Suspected Source
Narrow every regimen below once culture and susceptibility data are available — see Choose Initial Treatment for the de-escalation principle.
| Suspected source | Typical first-line regimen | MDR-risk or resistant-organism alternative | Notes |
|---|---|---|---|
| Unknown/undifferentiated | Piperacillin-tazobactam 4.5 g IV Q6-8H | Meropenem 1 g IV Q8H ± vancomycin | Add vancomycin for a specific MRSA risk factor (dialysis, known colonization, IVDU, recent hospitalization). |
| Pulmonary | Ceftriaxone 2 g IV daily + azithromycin 500 mg IV daily | Piperacillin-tazobactam or cefepime + azithromycin ± vancomycin/linezolid | Use the antipseudomonal option for structural lung disease or recent hospitalization/broad-antibiotic exposure. |
| Intra-abdominal | Piperacillin-tazobactam or meropenem (both anaerobe-active) | Ceftriaxone + metronidazole 500 mg IV Q8H if a non-anaerobic backbone is used | Empiric antifungal only with a specific risk factor (recent GI surgery, recurrent perforation, significant immunosuppression) — not routine. |
| Urinary | Ceftriaxone 2 g IV daily | Piperacillin-tazobactam or meropenem if MDR risk factors present | Confirm any prior urine culture/resistance history before selecting the backbone agent. |
| Skin/soft tissue (non-necrotizing) | Cefazolin/cloxacillin (MSSA) or vancomycin (MRSA risk) | Add piperacillin-tazobactam for a diabetic foot or broader-risk wound | Reassess for a necrotizing process at every exam if pain is out of proportion to findings. |
| Necrotizing soft tissue infection | Vancomycin or linezolid + piperacillin-tazobactam or meropenem + clindamycin 900 mg IV Q8H | Emergency surgical debridement is mandatory, not optional | Clindamycin's antitoxin effect targets toxin-producing streptococci/staphylococci — always combined, never monotherapy. |
| Catheter/line-associated | Vancomycin + cefepime or piperacillin-tazobactam | Adjust once organism/susceptibility known | Remove or exchange the catheter as source control alongside antibiotics. |
| Neutropenic fever | Cefepime, piperacillin-tazobactam, or meropenem monotherapy | Add vancomycin only for a specific indication (instability, skin/line source, known MRSA) | Give immediately — do not wait for the absolute neutrophil count to result. |
Broad-Spectrum Beta-Lactams
Give a full, unreduced loading dose regardless of renal function in a hemodynamically unstable patient; adjust only the maintenance dose/interval for renal impairment.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Piperacillin-tazobactam | Loading dose: 4.5 g IV Maintenance: 4.5 g IV Q6-8H, extended infusion, renally adjusted | GI upset, rash, interstitial nephritis, electrolyte disturbance (sodium load) | May increase methotrexate levels; false-positive galactomannan assay | Extended/prolonged infusion (over ~4 hours) for maintenance doses is preferred over conventional bolus dosing once the loading dose is given. |
| Cefepime | Adults: 2 g IV Q8H, renally adjusted | Neurotoxicity/encephalopathy at high doses with renal impairment, GI upset | None significant at standard doses | Antipseudomonal cephalosporin alternative to piperacillin-tazobactam for pulmonary or line-associated sources. |
| Ceftriaxone | Adults: 2 g IV once daily | Hypersensitivity, biliary sludging, transient LFT elevation | Do not co-administer with calcium-containing IV solutions | Reasonable backbone for pulmonary or urinary sources without MDR risk factors — does not cover Pseudomonas. |
| Meropenem | Standard: 1 g IV Q8H, extended infusion, renally adjusted CNS source/higher-MIC pathogen: 2 g IV Q8H | GI upset, hypersensitivity, seizure at high doses with renal impairment | Can decrease valproic acid levels | Reserve for confirmed or strongly suspected MDR risk, severe non-anaphylactic penicillin allergy, or a CNS source — extended infusion preferred for maintenance dosing. |
Anti-MRSA / Gram-Positive Agents
Add for a specific MRSA risk factor rather than routinely to every regimen.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Vancomycin | Loading dose: 25-30 mg/kg IV, actual body weight Maintenance: Dosed to AUC/trough per pharmacy protocol, renally adjusted | Nephrotoxicity, vancomycin infusion reaction (flushing, hypotension with rapid infusion), ototoxicity | Enhanced nephro/ototoxicity with other nephrotoxins/ototoxins | Never reduce or delay the loading dose for renal impairment — adjust maintenance dosing/interval to levels instead. |
| Linezolid | Adults: 600 mg IV Q12H | Thrombocytopenia and myelosuppression with prolonged use, serotonin syndrome with serotonergic drugs, optic/peripheral neuropathy with prolonged use | Avoid with serotonergic drugs (SSRIs, SNRIs, MAOIs) given serotonin syndrome risk | No renal dose adjustment needed. Reasonable alternative when vancomycin levels are hard to manage, or as part of toxin-suppression therapy. |
| Cefazolin | Adults: 2 g IV Q8H, renally adjusted | Rash, hypersensitivity, drug fever | Possible increased INR with warfarin | MSSA-focused option for skin/soft tissue or line sources once staphylococcal susceptibility is confirmed. |
Anaerobic and Toxin-Suppression Adjuncts
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Metronidazole | Adults: 500 mg IV Q8H | GI upset, metallic taste, peripheral neuropathy with prolonged use | Disulfiram-like reaction with alcohol | Add only when the antibiotic backbone lacks anaerobic activity (e.g., ceftriaxone) — not needed with piperacillin-tazobactam or meropenem. |
| Clindamycin | Adults: 900 mg IV Q8H | Clostridioides difficile-associated diarrhea, GI upset | None significant at standard doses | Adjunct for antitoxin/toxin-suppression effect in necrotizing or toxin-mediated soft tissue infection — always combined with a bactericidal backbone plus surgical source control, never monotherapy. |
Vasopressors and Inotropes
Start peripherally rather than delaying for central access; titrate to a MAP target of 65 mmHg (60-65 mmHg if age 65 or older).
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Norepinephrine | Adults: Start ~0.05 mcg/kg/min IV, titrate to MAP target (typical range 0.01-1 mcg/kg/min) | Arrhythmia, peripheral/digital ischemia at high doses, bradycardia (reflex) | Enhanced pressor effect with MAOIs; caution with tricyclic antidepressants | First-line vasopressor, preferred over dopamine, epinephrine, selepressin, vasopressin, or angiotensin II as the initial agent. |
| Vasopressin | Adults: 0.03 units/min IV, fixed | Digital and mesenteric ischemia, hyponatremia | None significant at fixed low dose | Add-on for escalating norepinephrine requirements — a fixed dose, not titrated up or down for effect. |
| Epinephrine | Adults: 0.01-0.5 mcg/kg/min IV, titrated | Tachyarrhythmia, hyperglycemia, lactate elevation (can confound lactate-trend monitoring) | Enhanced arrhythmia risk with other sympathomimetics | Added when MAP remains inadequate on norepinephrine plus vasopressin, or used as norepinephrine's alternative first agent if vasopressin is unavailable. |
| Dobutamine | Adults: Per current institutional inotrope dosing protocol, titrated | Tachyarrhythmia, hypotension (vasodilatory effect), myocardial oxygen demand increase | Enhanced arrhythmia risk with other sympathomimetics | Reserved for persistent hypoperfusion with cardiac dysfunction despite adequate fluid status and MAP on vasopressors — added to, not substituted for, the vasopressor regimen. |
Resuscitation Fluids
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Balanced crystalloid (e.g., lactated Ringer's) | Initial bolus: At least 30 mL/kg IV over the first 3 hours Ongoing: Individualize using dynamic measures (passive leg raise, stroke volume/pulse pressure variation) | Fluid overload/pulmonary edema with over-resuscitation, hyperkalemia (lactated Ringer's) in severe renal failure | None significant | Preferred first-line resuscitation fluid over 0.9% saline. Weight-based dosing should use actual or adjusted/ideal body weight in patients with BMI over 30 kg/m². |
| 0.9% sodium chloride | Dosing: As for balanced crystalloid, per the same volume/reassessment approach | Hyperchloremic metabolic acidosis with large volumes, fluid overload | None significant | Reserve for the specific exception of concomitant traumatic brain injury, where balanced crystalloids are not preferred. |
Adjunctive Corticosteroid
Add once vasopressor requirement persists despite adequate fluids and MAP support — not first-line for every septic shock patient.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Hydrocortisone | Adults: 200 mg/day IV — 50 mg IV Q6H, or by continuous infusion | Hyperglycemia, GI upset/bleeding risk, delayed wound healing with prolonged use | May reduce antibody response if a live-virus vaccine is given concurrently |
References
- The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) — JAMA (Singer M, Deutschman CS, Seymour CW, et al.). JAMA 2016;315(8):801-810
- Duration of Hypotension Before Initiation of Effective Antimicrobial Therapy Is the Critical Determinant of Survival in Human Septic Shock — Critical Care Medicine (Kumar A, Roberts D, Wood KE, et al.). Crit Care Med 2006;34(6):1589-1596
- Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2026 — Critical Care Medicine, Society of Critical Care Medicine/European Society of Intensive Care Medicine (Prescott HC, Antonelli M, Alhazzani W, et al.). Crit Care Med 2026;54(4):725-812
- Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021 — Critical Care Medicine, Society of Critical Care Medicine/European Society of Intensive Care Medicine, endorsed by sponsoring professional societies including the Canadian Critical Care Society (Evans L, Rhodes A, Alhazzani W, et al.). Crit Care Med 2021;49(11):e1063-e1143
- Comparison of Dopamine and Norepinephrine in the Treatment of Shock — New England Journal of Medicine (De Backer D, Biston P, Devriendt J, et al.). N Engl J Med 2010;362(9):779-789
- Pharmacist Involvement in Sepsis Response and Time to Antibiotics: A Systematic Review — Journal of the American College of Clinical Pharmacy (Atkins PE, Thompson Bastin ML, Morgan RJ, Laine ME, Flannery AH). J Am Coll Clin Pharm 2023;6(8):942-953
Professional reference only. Apply clinical judgment and verify patient-specific decisions against current authoritative guidance and product information.