Sepsis in adults

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

presumed or confirmed sepsis

1st line – broad-spectrum empiric intravenous antibiotics

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1st line –

broad-spectrum empiric intravenous antibiotics

Broad-spectrum empiric intravenous antibiotics should be given before a pathogen is identified.[3][129][130] They should be commenced as soon as sepsis is suspected, preferably after cultures have been taken.[3][10] The timely delivery of appropriate antibiotics is of critical importance in maximizing chances of survival.[69][132][133][134][135][136][137][138]

Antibiotics should be targeted to the presumed site of infection. If there is no clinical evidence to suggest a specific site of infection and sepsis is still suspected, empiric broad-spectrum antibiotics should still be given.

Once culture and sensitivity results are known, antibiotics should be narrowed if it is possible to do so.[3][141]

When choosing empiric therapy, the suspected source of infection or causative organism, local resistance patterns, and the patient's immune status need to be considered.[60][129]

One systematic review found that prolonged infusion of antipseudomonal beta-lactam antibiotics over at least 3 hours (rather than a bolus or within 60 minutes) reduced mortality by up to 30% in patients with sepsis in the intensive care.[139]

Cultures should be repeated (e.g., at 6-hour to 8-hour intervals) if there are persistent or repeated fever spikes, or there is the identification of a new site of infection.

See below for specific choice of antibiotic regimens based on source of infection.

Plus – fluid resuscitation

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Plus –

fluid resuscitation

Treatment recommended for ALL patients in selected patient group

Early fluid resuscitation in sepsis-induced hypoperfusion is needed and admission to the high dependency unit or intensive care setting should be considered.[65][166] At least 30 mL/kg body weight of crystalloid should be given within the first 3 hours, commenced within 1 hour of sepsis being suspected.[3][127] However, optimal targets for fluid resuscitation should be individualized in certain patients, such as those with heart failure or chronic kidney disease, due to the risk of volume overload.[150][151][152] Additional fluid may be required, but this should be guided by thorough clinical assessment of the patient's hemodynamic status.[3] Repeated fluid boluses of crystalloid (typical volume 500 mL) given over 5-30 minutes may be effective in correcting hypotension secondary to hypovolemia. Boluses of a colloid solution (typical volume 250-300 mL) may be used as an alternative, but no evidence supports the use of colloids over other fluids such as crystalloids or albumin solution.[153][154][155][156][157] [ ]

Resuscitation with crystalloids requires more volume than colloids. Crystalloids and albumin should be given according to local protocols. Current evidence suggests that resuscitation using albumin-containing solutions is safe, but evidence of its efficacy is insufficient to recommend its use over crystalloids.[157][158][159] Balanced crystalloids may be preferable to normal saline in critically sick patients in intensive care.[161]

The Surviving Sepsis Campaign advises against the use of solutions containing hydroxyethyl starch (HES) for patients with sepsis and septic shock.[3] In July 2021, the US Food and Drug Administration (FDA) issued safety labeling changes for solutions containing HES stating that these products should not be used unless adequate alternative treatment is unavailable.[162] HES products are associated with adverse outcomes including kidney injury and death, particularly in critically ill patients and those with sepsis.[155][163] In view of the serious risks posed to these patient populations, the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency in February 2022 recommended suspending HES solutions for infusion in Europe.[164]

Red cell or plasma transfusion may be considered to target specific deficiencies but should not be used for volume augmentation. Aggressive red cell transfusion has not been shown to improve outcomes.[165]

Patients should be monitored closely for signs of fluid overload (e.g., pulmonary or systemic edema).[166][204]

Consider – oxygen

Consider – standard supportive intensive care setting (ICU) care

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Consider –

standard supportive intensive care setting (ICU) care

Treatment recommended for SOME patients in selected patient group

All patients with sepsis should be considered for admission to the high dependency unit or ICU.[65][166]

General intensive care measures include stress ulcer prophylaxis with H2 antagonists or proton-pump inhibitors (in patients at risk of gastrointestinal bleeding), deep venous thrombosis prophylaxis (with heparin and compression stockings), enteral or parenteral nutrition, and glycemic control.[3][182][183][184] The American Diabetes Association recommends a general glucose goal of 140-180 mg/dL in critically ill diabetic patients, preferably with use of an insulin infusion protocol.[170] The Surviving Sepsis Campaign recommends the use of validated insulin infusion protocols targeting a blood glucose level of <180 mg/dL.[3]

Transfusion of packed cells may be required; a restrictive transfusion strategy using a target hemoglobin concentration of 7 g/dL is recommended.[3][165][185][186] A higher hemoglobin level may be necessary in certain circumstances (myocardial ischemia, severe hypoxemia, or acute hemorrhage).[3][186] In the initial resuscitative phase a higher hematocrit of ≥30% may be appropriate.[65]

Patients requiring prolonged ventilatory support should receive lung protective ventilation using minimal peak inspiratory pressures (<30 cmH₂O) to specifically limit pulmonary compromise.[187] FiO₂ should be titrated to lowest effective levels to prevent oxygen toxicity and maintain central venous oxygen tension. One systematic review of acutely sick adult patients, including patients with sepsis, reported increased mortality among those who received liberal oxygen supplementation compared with those who received conservative oxygen supplementation. A target SpO₂ range of 94% to 96% was suggested for all patients with critical sickness.[128]

Bathing patients with chlorhexidine washes may reduce the risk of hospital-acquired infection.[180] Intravenous acetylcysteine as an adjuvant therapy in systemic inflammatory response syndrome (SIRS) and sepsis has been found to be ineffective, and its use is not recommended.[181]

For critically ill patients with fever, routine use of antipyretic medications should be avoided for the specific purpose of reducing the temperature.[82] However, where reduction of fever is required for the comfort of the patient, using antipyretics over nonpharmacologic methods to reduce body temperature is recommended.[82]

Tracheal intubation: animated demonstration

How to insert a tracheal tube in an adult using a laryngoscope.

Bag-valve-mask ventilation: animated demonstration

How to use bag-valve-mask apparatus to deliver ventilatory support to adults. Video demonstrates the two-person technique.

Central venous catheter insertion: animated demonstration

Ultrasound-guided insertion of a non-tunnelled central venous catheter (CVC) into the right internal jugular vein using the Seldinger insertion technique.

Consider – vasopressors

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Consider –

vasopressors

Treatment recommended for SOME patients in selected patient group

Patients unresponsive to fluid resuscitation may be treated with vasopressors.

Patients requiring vasoactive support (those with septic shock) are identified by a mean arterial pressure (MAP) <65 mmHg, persisting after adequate fluid resuscitation.[3][70]

The Surviving Sepsis Campaign recommends aiming for a MAP of 65 mmHg in patients with septic shock.[3]

Norepinephrine administered via a central venous catheter is the drug of choice as it increases MAP.[3][171][172] Vasopressin can be added to norepinephrine to achieve the target MAP.[3][70]

Vasopressors may be started via a peripheral venous line if there is a delay in securing central venous access.[3][70]

Primary options

norepinephrine: 0.02 to 0.5 micrograms/kg/minute intravenously initially, titrate to effect

Secondary options

norepinephrine: 0.02 to 0.5 micrograms/kg/minute intravenously initially, titrate to effect

and

vasopressin: 0.01 to 0.03 units/minute intravenously initially, titrate to effect

Consider – inotropes

Consider – corticosteroids

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Consider –

corticosteroids

Treatment recommended for SOME patients in selected patient group

Evidence for giving corticosteroids to patients with sepsis or septic shock is mixed and guideline recommendations vary.[3][70][174][175][176][177] [ ] [Evidence A]

One clinical practice guideline, informed by meta-analysis, reported that corticosteroids may reduce mortality (by approximately 2%) and increase the risk of neuromuscular weakness, but evidence is not definitive.[178][179] This effect was seen in sepsis, with and without shock, although the greatest benefit from corticosteroids was among those with septic shock. The clinical practice guideline concluded that both corticosteroid and non-corticosteroid management approaches are appropriate and suggested that the patient's values and preferences may guide the decision.[178] Patients who prioritize living over quality of life would likely choose to have corticosteroid treatment, whereas those who place more value on avoiding functional deterioration and maximizing quality of life than on avoiding death may be more likely to choose not to have corticosteroids.[178][179] The 2021 Surviving Sepsis Campaign guideline includes a weak recommendation to administer intravenous corticosteroids in adults with septic shock and an ongoing requirement for vasopressor therapy.[3]

Primary options

hydrocortisone sodium succinate: 50 mg intravenously every 6 hours

likely source of infection: pneumonia

Plus – broad-spectrum respiratory pathogen cover to include atypicals

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Plus –

broad-spectrum respiratory pathogen cover to include atypicals

Treatment recommended for ALL patients in selected patient group

When choosing empiric therapy, the suspected source of infection or causative organism, local resistance patterns, and the patient's immune status need to be considered.[60] Antibiotics listed are suggested as guidance only.

American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines recommend that combination therapy for patients admitted to the hospital should include a beta-lactam such as cefotaxime, ceftriaxone, ceftaroline, or ampicillin/sulbactam, with a macrolide such as azithromycin.[143] Although ATS/IDSA recommend clarithromycin in these patients, it is only available as an oral formulation in the US so is unlikely to be useful in this setting. A beta-lactam and a fluoroquinolone (e.g., moxifloxacin, levofloxacin) combination may be given to patients with severe community-acquired pneumonia. There is stronger evidence for the beta-lactam plus macrolide combination.

Fluoroquinolone antibiotics should be avoided when effective and appropriate alternatives are available and can be given promptly. Systemic fluoroquinolone antibiotics may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behavior.[142] Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics that are commonly recommended for the infection are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug information source for more information on suitability, contraindications, and precautions.

Antibiotic therapy should be given for a minimum of 5 days.[143]

Primary options

ampicillin/sulbactam: 1.5 to 3 g intravenously every 6 hours

cefotaxime: 1-2 g intravenously every 8 hours

ceftriaxone: 1-2 g intravenously every 24 hours

ceftaroline fosamil: 600 mg intravenously every 12 hours

-- AND --

azithromycin: 500 mg intravenously every 24 hours

Secondary options

ampicillin/sulbactam: 1.5 to 3 g intravenously every 6 hours

cefotaxime: 1-2 g intravenously every 8 hours

ceftriaxone: 1-2 g intravenously every 24 hours

ceftaroline fosamil: 600 mg intravenously every 12 hours

-- AND --

levofloxacin: 750 mg intravenously every 24 hours

moxifloxacin: 400 mg intravenously every 24 hours

Consider – Pseudomonas aeruginosa antibiotic cover (if needed)

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Consider –

Pseudomonas aeruginosa antibiotic cover (if needed)

Treatment recommended for SOME patients in selected patient group

Additional empiric antibiotic cover is required in patients with risk factors for Pseudomonas aeruginosa if locally validated risk factors are present. These include hospitalization, prior respiratory isolation of Pseudomonas, or systemic antibiotic use within the previous 90 days.[143]

Patients who are at risk of Pseudomonas infection and who have severe pneumonia, or who have prior respiratory isolation of P aeruginosa, should be treated with piperacillin/tazobactam, cefepime, ceftazidime, imipenem/cilastatin, meropenem, or aztreonam addition to an empiric beta-lactam combination regimen.[143]

American Thoracic Society/Infectious Diseases Society of America guidelines advise that most multidrug-resistant organisms that cause community-acquired pneumonia are effectively covered by antibiotic regimens for Pseudomonas.[143]

Primary options

piperacillin/tazobactam: 4.5 g intravenously every 6 hours

cefepime: 2 g intravenously every 8 hours

ceftazidime sodium: 2 g intravenously every 8 hours

imipenem/cilastatin: 500 mg intravenously every 6 hours

meropenem: 1 g intravenously every 8 hours

aztreonam: 2 g intravenously every 8 hours

Consider – MRSA antibiotic cover (if needed)

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Consider –

MRSA antibiotic cover (if needed)

Treatment recommended for SOME patients in selected patient group

Additional empiric antibiotic cover is required in patients with risk factors for MRSA if locally validated risk factors are present. These include hospitalization, prior respiratory isolation of MRSA, or systemic antibiotic use within the previous 90 days.[143]

In patients at risk of MRSA who have severe pneumonia, or who have prior respiratory isolation of MRSA, vancomycin or linezolid should be added to an empiric beta-lactam combination.[143]

Primary options

vancomycin: 15-20 mg/kg intravenously every 8-12 hours

linezolid: 600 mg intravenously every 12 hours

Consider – Enterobacteriaceae antibiotic cover (if needed)

likely source of infection: urinary tract infection

Plus – broad-spectrum cover for predominant gram-negative coliforms and Pseudomonas

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Plus –

broad-spectrum cover for predominant gram-negative coliforms and Pseudomonas

Treatment recommended for ALL patients in selected patient group

If urinary stasis is present, drainage is of immediate importance.

A fluoroquinolone (e.g., ciprofloxacin) may be used in patients with penicillin allergy if local sensitivity patterns are taken into account. Fluoroquinolone antibiotics should be avoided when effective and appropriate alternatives are available and can be given promptly. Systemic fluoroquinolone antibiotics may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behavior.[142] Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics that are commonly recommended for the infection are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug information source for more information on suitability, contraindications, and precautions.

Primary options

No penicillin allergy

ampicillin: 1-2 g intravenously every 6 hours

ceftriaxone: 1 g intravenously every 24 hours

cefotaxime: 1-2 g intravenously every 8 hours

-- AND --

gentamicin: 5 mg/kg intravenously every 24 hours

Penicillin allergy

ciprofloxacin: 400 mg intravenously every 12 hours

likely source of infection: intra-abdominal

Plus – broad-spectrum cover for gram-positive and gram-negative organisms including anaerobes

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Plus –

broad-spectrum cover for gram-positive and gram-negative organisms including anaerobes

Treatment recommended for ALL patients in selected patient group

Control and drainage of an intra-abdominal source of infection is of immediate importance.

A fluoroquinolone (e.g., ciprofloxacin, levofloxacin) may be used in patients with penicillin allergy if local sensitivity patterns are taken into account. Fluoroquinolone antibiotics should be avoided when effective and appropriate alternatives are available and can be given promptly. Systemic fluoroquinolone antibiotics may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behavior.[142] Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug information source for more information on suitability, contraindications, and precautions.

Primary options

No penicillin allergy

ceftazidime sodium: 2 g intravenously every 8 hours

cefepime: 2 g intravenously every 8-12 hours

-- AND --

metronidazole: 500 mg intravenously every 8 hours

No penicillin allergy

piperacillin/tazobactam: 3.375 to 4.5 g intravenously every 6 hours

Penicillin allergy

ciprofloxacin: 400 mg intravenously every 12 hours

levofloxacin: 750 mg intravenously every 24 hours

-- AND --

metronidazole: 500 mg intravenously every 8 hours

Consider – azole or echinocandin antifungal

likely source of infection: soft-tissue or joint infection (not necrotizing fasciitis), MRSA not suspected

Plus – broad-spectrum gram-positive and gram-negative cover including anaerobes

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Plus –

broad-spectrum gram-positive and gram-negative cover including anaerobes

Treatment recommended for ALL patients in selected patient group

Primary options

No penicillin allergy

nafcillin: 1-2 g intravenously every 4-6 hours

and

metronidazole: 500 mg intravenously every 8 hours

Secondary options

Penicillin allergy

clindamycin: 600-900 mg intravenously every 8 hours

Penicillin allergy

tigecycline: 100 mg intravenously initially, followed by 50 mg every 12 hours

and

metronidazole: 500 mg intravenously every 8 hours

likely source of infection: soft-tissue or joint infection (not necrotizing fasciitis), MRSA suspected

Plus – broad-spectrum cover to include MRSA

likely source of infection: necrotizing fasciitis suspected

Plus – broad-spectrum cover to include group A Streptococci and gram-negative organisms

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Plus –

broad-spectrum cover to include group A Streptococci and gram-negative organisms

Treatment recommended for ALL patients in selected patient group

If necrotizing fasciitis is suspected, surgical control and debridement is of immediate importance.

Once culture and sensitivity results are known, antibiotics should be adjusted if required; 90% of cases are polymicrobial.

Primary options

No penicillin allergy

vancomycin: 15-20 mg/kg intravenously every 8-12 hours

and

piperacillin/tazobactam: 3.375 g intravenously every 6 hours, or 4.5 g intravenously every 6-8 hours

and

clindamycin: 600-900 mg intravenously every 8 hours

Secondary options

No penicillin allergy

nafcillin: 1-2 g intravenously every 6 hours

and

clindamycin: 600-900 mg intravenously every 8 hours

Penicillin allergy

vancomycin: 15-20 mg/kg intravenously every 8-12 hours

-- AND --

meropenem: 1 g intravenously every 8 hours

ertapenem: 1 g intravenously every 24 hours

-- AND --

clindamycin: 600-900 mg intravenously every 8 hours

likely source of infection: central nervous system

Plus – broad-spectrum cover to include Neisseria meningitidis, Streptococcus pneumoniae, and other common gram-positive causative agents

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Plus –

broad-spectrum cover to include Neisseria meningitidis, Streptococcus pneumoniae, and other common gram-positive causative agents

Treatment recommended for ALL patients in selected patient group

Suspected meningitis or meningococcal septicemia should be treated immediately using a third-generation cephalosporin (e.g., ceftriaxone, cefotaxime) in combination with vancomycin.[147][148] For patients with penicillin allergy, vancomycin with chloramphenicol is a suitable alternative. Some suggest the addition of rifampin to either regimen to aid penetration.

Primary options

No penicillin allergy

ceftriaxone: 2 g intravenously every 12 hours

cefotaxime: 2 g intravenously every 4-6 hours

-- AND --

vancomycin: 15-20 mg/kg intravenously every 8-12 hours

Penicillin allergy

vancomycin: 15-20 mg/kg intravenously every 8-12 hours

and

chloramphenicol: 1 g intravenously every 6 hours

Consider – rifampin

Consider – antibiotic cover for Listeria

Consider – antiviral cover for herpes simplex virus (HSV)

sepsis of unknown source or where source is unclear, MRSA not suspected

Plus – broad-spectrum gram-positive and gram-negative cover

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Plus –

broad-spectrum gram-positive and gram-negative cover

Treatment recommended for ALL patients in selected patient group

Intensive efforts, including imaging, should be undertaken to attempt to evaluate the source of infection. Urgent broad-spectrum coverage to include all common pathogens should be administered.

Primary options

imipenem/cilastatin: 1 g intravenously every 8 hours

meropenem: 1 g intravenously every 8 hours

piperacillin/tazobactam: 4.5 g intravenously every 8 hours

and

gentamicin: 5 mg/kg intravenously every 24 hours

sepsis of unknown source or where source is unclear, MRSA suspected

Plus – broad-spectrum cover to include MRSA

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Sepsis in adults

Treatment algorithm

presumed or confirmed sepsis

broad-spectrum empiric intravenous antibiotics

fluid resuscitation

oxygen

standard supportive intensive care setting (ICU) care

vasopressors

Primary options

Secondary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Secondary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

Secondary options

inotropes

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

corticosteroids

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

likely source of infection: pneumonia

broad-spectrum respiratory pathogen cover to include atypicals

Primary options

Secondary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Secondary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

Secondary options

Pseudomonas aeruginosa antibiotic cover (if needed)

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

MRSA antibiotic cover (if needed)

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

Enterobacteriaceae antibiotic cover (if needed)

likely source of infection: urinary tract infection

broad-spectrum cover for predominant gram-negative coliforms and Pseudomonas

Primary options

No penicillin allergy

Secondary options

Penicillin allergy

These drug options and doses relate to a patient with no comorbidities.

Primary options

No penicillin allergy

Secondary options

Penicillin allergy

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

No penicillin allergy

Secondary options

Penicillin allergy

likely source of infection: intra-abdominal

broad-spectrum cover for gram-positive and gram-negative organisms including anaerobes

Primary options

No penicillin allergy

No penicillin allergy

Secondary options

Penicillin allergy

These drug options and doses relate to a patient with no comorbidities.

Primary options

No penicillin allergy

No penicillin allergy

Secondary options

Penicillin allergy