Sepsis and Septic Shock

Organ dysfunction resulting from a dysregulated systemic host response to infection separates sepsis from uncomplicated infection. The etiology is mainly bacterial and pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia is the most common known source. Patients commonly present with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, tachycardia, tachypnea, hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension, and/or altered mentation. Septic shock is diagnosed during treatment when vasopressors are necessary to control hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension. Sepsis and septic shock are medical emergencies and antibiotics are given within an hour of diagnosis.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Overview

Definitions

  • Sepsis: a potentially life-threatening organ dysfunction caused by a dysregulated host response to infection
  • Septic shock: sepsis with a substantial increase in mortality risk due to circulatory and cellular/metabolic abnormalities

Epidemiology

  • Mortality ranges from 20%50% (higher in septic shock)
  • More common in survivors: 
    • Hospital readmission (about 40% within 3 months)
    • Early death
    • Physical and neurocognitive dysfunction
    • Mood disorders
    • Low quality of life
  • Leading cause of death in hospitalized patients
  • Nearly 20% of all global deaths
  • Higher incidence in extremes of age, male sex, and Black patients 
  • Septic shock follows in 30% of sepsis cases.

Risk factors

  • Chronic diseases (e.g., chronic obstructive pulmonary disease Chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD), HIV infection HIV infection Human immunodeficiency virus (HIV), a single-stranded RNA virus belonging to the Retroviridae family, is the etiologic agent of acquired immunodeficiency syndrome (AIDS). The human immunodeficiency virus is a sexually transmitted or blood-borne infection that attacks CD4+ T lymphocyte cells, macrophages, and dendritic cells, leading to eventual immunodeficiency. HIV Infection and AIDS, and cancer)
  • Immunosuppression 
  • Prior organ dysfunction
  • Delay in diagnosis and treatment

Etiology and Pathophysiology

Etiology

  • May be community- or hospital-acquired
  • Source of infection:
    • Identified in ⅓ of patients 
    • Most commonly pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia, followed by intra-abdominal and genitourinary infections
  • Cultures:
    • Blood cultures: positive in ⅓ of patients
    • Negative cultures from all sites are common
  • Most common gram-positive pathogens:
    • Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus aureus
    • Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
  • Most common gram-negative pathogens:
    • Escherichia coli Escherichia coli The gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. Escherichia coli
    • Klebsiella Klebsiella Klebsiella are encapsulated gram-negative, lactose-fermenting bacilli. They form pink colonies on MacConkey agar due to lactose fermentation. The main virulence factor is a polysaccharide capsule. Klebsiella pneumoniae is the most important pathogenic species. Klebsiella spp.
    • Pseudomonas Pseudomonas Pseudomonas is a non-lactose-fermenting, gram-negative bacillus that produces pyocyanin, which gives it a characteristic blue-green color. Pseudomonas is found ubiquitously in the environment, as well as in moist reservoirs, such as hospital sinks and respiratory equipment. Pseudomonas aeruginosa
  • Fungi: reported in about 20% of cases
  • Viruses: reported in only 1% of cases

Pathophysiology

Pathogen load and virulence + host genetic composition and comorbidities result in a complex, exaggerated, and prolonged host response to infection that evolves over time.

  1. Recognition of pathogen-associated molecular patterns (PAMPs) by pathogen recognition receptors on innate immune cells → inflammatory response (e.g., release of tumor necrosis factor Tumor necrosis factor Tumor necrosis factor (TNF) is a major cytokine, released primarily by macrophages in response to stimuli. The presence of microbial products and dead cells and injury are among the stimulating factors. This protein belongs to the TNF superfamily, a group of ligands and receptors performing functions in inflammatory response, morphogenesis, and cell proliferation. Tumor Necrosis Factor (TNF)) →  tissue damage and necrotic cell death Cell death Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects. Cell Injury and Death → release of damage-associated molecular patterns (DAMPs) → further activation of leukocytes → microvascular changes: endothelial cell dysfunction + coagulation and complement activation
  2. Macrovascular changes: vasodilation and hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension 
  3. Microvascular changes + macrovascular changes → vascular leak, edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema, intravascular volume depletion Volume depletion Volume status is a balance between water and solutes, the majority of which is Na. Volume depletion refers to a loss of both water and Na, whereas dehydration refers only to a loss of water. Volume depletion can be caused by GI losses, renal losses, bleeding, poor oral Na intake, or third spacing of fluids. Volume Depletion and Dehydration → impaired tissue oxygenation, cellular alterations such as greater glycolysis Glycolysis Glycolysis is a central metabolic pathway responsible for the breakdown of glucose and plays a vital role in generating free energy for the cell and metabolites for further oxidative degradation. Glucose primarily becomes available in the blood as a result of glycogen breakdown or from its synthesis from noncarbohydrate precursors (gluconeogenesis) and is imported into cells by specific transport proteins. Glycolysis (lactate production), mitochondrial injury, and release of oxygen species → increasing organ damage
Pathogenesis of sepsis

Pathogenesis of sepsis

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Clinical Presentation

  • Skin and peripheral pulses:
    • Early septic shock with low volume status: cold extremities and narrow pulse pressure reflecting increased systemic vascular resistance Vascular Resistance Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Vascular resistance is directly related to the diameter of the vessel (smaller vessels have higher resistance). Vascular Resistance, Flow, and Mean Arterial Pressure (SVR) and reduced cardiac output (CO)
    • With progression of shock: relatively warm extremities and widening of pulse pressure reflecting reduced SVR and increased CO
  • Respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure:
    • Symptoms of acute respiratory distress syndrome Acute Respiratory Distress Syndrome Acute respiratory distress syndrome is characterized by the sudden onset of hypoxemia and bilateral pulmonary edema without cardiac failure. Sepsis is the most common cause of ARDS. The underlying mechanism and histologic correlate is diffuse alveolar damage (DAD). Acute Respiratory Distress Syndrome ( ARDS ARDS Acute respiratory distress syndrome is characterized by the sudden onset of hypoxemia and bilateral pulmonary edema without cardiac failure. Sepsis is the most common cause of ARDS. The underlying mechanism and histologic correlate is diffuse alveolar damage (DAD). Acute Respiratory Distress Syndrome) including tachypnea, shallow breathing, use of accessory muscles, fatigue with paradoxical abdominal movement, bilateral rales (crackles), hypoxia, and bilateral pulmonary infiltrates not explained by heart failure 
  • Cardiac failure:
    • Hypotension
    • Tachycardia
    • Tachypnea
    • Rales subsequent to pulmonary edema Pulmonary edema Pulmonary edema is a condition caused by excess fluid within the lung parenchyma and alveoli as a consequence of a disease process. Based on etiology, pulmonary edema is classified as cardiogenic or noncardiogenic. Patients may present with progressive dyspnea, orthopnea, cough, or respiratory failure. Pulmonary Edema
  • Acute kidney injury Acute Kidney Injury Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury ( AKI AKI Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury) with decreased urinary output and azotemia/uremia
  • Neurologic presentation and complications: 
    • Altered mental status including delirium Delirium Delirium is a medical condition characterized by acute disturbances in attention and awareness. Symptoms may fluctuate during the course of a day and involve memory deficits and disorientation. Delirium and coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma
    • No focal lesions on imaging and global encephalopathy on electroencephalography
    • Critical-illness polyneuropathy Polyneuropathy Polyneuropathy is any disease process affecting the function of or causing damage to multiple nerves of the peripheral nervous system. There are numerous etiologies of polyneuropathy, most of which are systemic and the most common of which is diabetic neuropathy. Polyneuropathy and myopathy if especially prolonged intensive care unit (ICU) stay
    • Chronic moderate-to-severe cognitive impairment
  • Other clinical/laboratory features and complications: ileus, elevated liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes, disseminated intravascular coagulation Disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation, adrenal failure, sick euthyroid syndrome

Diagnosis

General approach

  1. Suspect sepsis in a patient presenting with any of the following:
    • Infection without apparent organ dysfunction 
    • New-onset and unexplained organ dysfunction without apparent infection
    • Abnormal vital signs such as fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, tachypnea, tachycardia, or low blood pressure
    • Altered mental status
  2. Check quick sequential organ failure assessment (qSOFA) score: With a positive qSOFA (≥ 2 criteria) or suspicion of sepsis despite a negative qSOFA (< 2 criteria), check SOFA (step 3).
  3. Check SOFA: With an increase of ≥ 2 SOFA points from baseline (baseline is considered zero without a prior history of organ dysfunction), initiate hour-1 bundle (step 4). 
  4. Initiate hour-1 bundle (see “Management”): Closely monitor for response to interventions and criteria of septic shock.

Diagnostic criteria

  • Criteria for sepsis: 
    • Suspected (or documented) infection
    • Increase in ≥ 2 SOFA points 
  • Criteria for septic shock:
    • Suspected (or documented) infection
    • Vasopressor therapy necessary to maintain mean arterial pressure Mean Arterial Pressure Mean arterial pressure (MAP) is the average systemic arterial pressure and is directly related to cardiac output (CO) and systemic vascular resistance (SVR). The SVR and MAP are affected by the vascular anatomy as well as a number of local and neurohumoral factors. Vascular Resistance, Flow, and Mean Arterial Pressure (MAP) ≥ 65 mm Hg despite adequate IV crystalloid administration
    • Serum lactate > 2.0 mmol/L despite adequate IV crystalloid administration
  • qSOFA: 
    • A simple bedside tool for use outside the ICU and in the preclinical setting:
      • In patients with suspected infection: having ≥ 2 of the following 3 criteria indicates poor outcomes (prolonged ICU course and death) and triggers further investigation, frequent monitoring, escalation of treatment, and ICU admission, as appropriate
      • In patients without previous suspicion of infection: triggers consideration of infection
    • Criteria:
      • Systolic blood pressure < 100 mm Hg 
      • Respiratory rate ≥ 22/min
      • Altered mentation 
  • Systemic inflammatory response syndrome (SIRS): no longer used for the diagnosis of sepsis
Table 1: The sequential organ failure assessment (SOFA) score
Organ/system SOFA score Indication
Respiratory system: PaO2/FiO2 (mm Hg) 0 ≥ 400
+ 1 300–399
+ 2 200–299
+ 3 100–199 + mechanically ventilated
+ 4 < 100 + mechanically ventilated
Nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the Nervous System: Glascow coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma scale 0 15
+ 1 13–14
+ 2 10–12
+3 6–9
+ 4 < 6
Cardiovascular system: mean arterial pressure Mean Arterial Pressure Mean arterial pressure (MAP) is the average systemic arterial pressure and is directly related to cardiac output (CO) and systemic vascular resistance (SVR). The SVR and MAP are affected by the vascular anatomy as well as a number of local and neurohumoral factors. Vascular Resistance, Flow, and Mean Arterial Pressure (MAP) OR need for vasopressors 0 MAP ≥ 70 mm Hg
+ 1 MAP < 70 mm Hg
+ 2 Dopamine ≤ 5 μg/kg/min or dobutamine (any dose)
+ 3 Dopamine > 5 μg/kg/min OR epinephrine ≤ 0.1 μg/kg/min OR norepinephrine ≤ 0.1 μg/kg/min
+ 4 Dopamine > 15 μg/kg/min OR epinephrine > 0.1 μg/kg/min OR norepinephrine > 0.1 μg/kg/min
Liver: bilirubin (mg/dL) 0 < 1.2
+ 1 1.2–1.9
+ 2 2–5.9
+ 3 6–11.9
+ 4 ≥ 12
Coagulation: platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets × 1000/μL 0 ≥ 150
+ 1 100–149
+ 2 50–99
+ 3 20–49
+ 4 < 20
Kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: creatinine (mg/dL) or urine output 0 < 1.2
+ 1 1.2–1.9
+ 2 2–3.4
+ 3 3.4–4.9 or < 500 mL/day
+ 4 > 5.0 or < 200 mL/day
The SOFA score quantifies the number and severity of organ failure. It assesses 6 organ systems. Each organ system is given 0–4 points based on severity of involvement. The overall SOFA score ranges from 0 (no organ failure) to 24 (most severe) points.

Management

Sepsis and septic shock are medical emergencies!

Respiratory support

  • Indications for endotracheal intubation and mechanical ventilatory support: 
    • Significant hypoxemia (PaO2 < 60 mm Hg or oxygen saturation < 90%)
    • Hypoventilation (rising PCO2
    • Significantly altered level of consciousness 
    • Inability to protect airways with risk of aspiration 
    • Persistent metabolic acidosis Metabolic acidosis The renal system is responsible for eliminating the daily load of non-volatile acids, which is approximately 70 millimoles per day. Metabolic acidosis occurs when there is an increase in the levels of new non-volatile acids (e.g., lactic acid), renal loss of HCO3-, or ingestion of toxic alcohols. Metabolic Acidosis with pH < 7.20
  • Goal: arterial oxygen saturation of 92%95%

Hour-1 bundle

The hour-1 bundle encourages physicians to act as quickly as possible. Ideally, the following steps should begin within the 1st hour after the diagnosis of sepsis. 

  1. Monitor serum lactate level (remeasure  if > 2 mmol/L).
  2. Obtain blood cultures (positive in only 30% of patients with presumed sepsis) before initiating antibiotics.
  3. Initiate broad-spectrum antibiotics.
  4. Intravenous (IV) crystalloids: Rapidly administer (30 mL/kg) if hypotensive ( mean arterial pressure Mean Arterial Pressure Mean arterial pressure (MAP) is the average systemic arterial pressure and is directly related to cardiac output (CO) and systemic vascular resistance (SVR). The SVR and MAP are affected by the vascular anatomy as well as a number of local and neurohumoral factors. Vascular Resistance, Flow, and Mean Arterial Pressure < 65 mm Hg) and/or lactate ≥ 4 mmol/L.
  5. Vasopressors: 
    • Administer if hypotensive during or after resuscitation with IV crystalloids.
    • 1st choice: norepinephrine, plus vasopressin to increase mean arterial pressure Mean Arterial Pressure Mean arterial pressure (MAP) is the average systemic arterial pressure and is directly related to cardiac output (CO) and systemic vascular resistance (SVR). The SVR and MAP are affected by the vascular anatomy as well as a number of local and neurohumoral factors. Vascular Resistance, Flow, and Mean Arterial Pressure and reduce norepinephrine use

Monitoring

  • Arterial pulse contour analysis
  • Focused echocardiography (cardiac output, beat-to-beat stroke volume, and pulse pressure variation)
  • Passive leg Leg The lower leg, or just "leg" in anatomical terms, is the part of the lower limb between the knee and the ankle joint. The bony structure is composed of the tibia and fibula bones, and the muscles of the leg are grouped into the anterior, lateral, and posterior compartments by extensions of fascia. Leg-raise maneuver
  • Inferior vena cava Inferior vena cava The venous trunk which receives blood from the lower extremities and from the pelvic and abdominal organs. Mediastinum and Great Vessels collapsibility on ultrasound

Glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids

  • Should not be used routinely
  • Dexamethasone has been shown to reduce mortality in patients with coronavirus disease 2019 Coronavirus disease 2019 Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly affects the respiratory system but can also cause damage to other body systems (cardiovascular, gastrointestinal, renal, and central nervous systems). ( COVID-19 COVID-19 Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly affects the respiratory system but can also cause damage to other body systems (cardiovascular, gastrointestinal, renal, and central nervous systems). ) who are receiving respiratory support.
  • Weak recommendation: Initiate IV hydrocortisone if septic shock does not respond to fluids and vasopressors. 
  • Wean steroids if vasopressors are no longer needed.

Additional measures

  • Red blood cell transfusion: only recommended if hemoglobin is < 7 g/dL
  • Insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin therapy: A blood glucose target of 140–180 mg/dL (7.7 to 10 mmol/L) is recommended. 
  • Prophylaxis for deep venous thrombosis: low-dose unfractionated heparin or low-molecular-weight heparin (LMWH) if no contraindications exist, such as active bleeding or significant thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia 
  • Close monitoring and treatment of electrolyte abnormalities
  • Nutritional support: Enteral route is preferred.
  • Effectively communicate sepsis status during hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand-offs.
Table: Choice of empirical antibiotic therapy in adult patients with sepsis (all antibiotics administered intravenously)
Patient’s immune status Choice of antibiotic
Immunocompetent Any of the following:
  • Piperacillin-tazobactam
  • Cefepime
  • Meropenem or imipenem-cilastatin
  • Aztreonam Aztreonam The carbapenems and aztreonam are both members of the bactericidal beta-lactam family of antibiotics (similar to penicillins). They work by preventing bacteria from producing their cell wall, ultimately leading to bacterial cell death. Carbapenems and Aztreonam, ciprofloxacin, or levofloxacin if allergic to beta-lactam antibiotics
PLUS:
Vancomycin (or linezolid) if risk of MRSA is high or if in septic shock
Neutropenic (< 500 neutrophils/μL) Any of the following:
  • Piperacillin-tazobactam
  • Cefepime
  • Meropenem or imipenem-cilastatin
PLUS:
Vancomycin (or linezolid), tobramycin, and caspofungin
Splenectomy Any of the following:
  • Ceftriaxone
  • Levofloxacin or moxifloxacin if allergic to beta-lactams
PLUS:
Vancomycin (or linezolid)
Associated with pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia Refer to the treatment of community- and ventilator-acquired pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia.
Associated with severe intra-abdominal infections Any of the following:
  • Piperacillin-tazobactam
  • Cefepime or ceftazidime
  • Meropenem or imipenem-cilastatin
  • Ciprofloxacin or levofloxacin
PLUS:
Metronidazole

References

  1. Singer M, Deutschman CS, Seymour CW, et al. (2016). The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801–810. doi:10.1001/jama.2016.0287. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4968574/
  2. Kasper DL, Fausi AS, Hauser SL, Longo DL, Lameson JL, Loscalzo J. (2018). Harrison’s Principles of Internal Medicine. New York, NY: McGraw-Hill Education.
  3. Weiss SL, Peters MJ, Alhazzani W, et al. (2020). Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children, Pediatric Critical Care Medicine. https://journals.lww.com/pccmjournal/FullText/2020/02000/Surviving_Sepsis_Campaign_International_Guidelines.20.aspx
  4. Surviving Sepsis Campaign. 1-Hour Bundle. https://www.sccm.org/getattachment/SurvivingSepsisCampaign/Guidelines/Adult-Patients/Surviving-Sepsis-Campaign-Hour-1-Bundle.pdf?lang=en-US
  5. Kalil Andre. Septic Shock. New York, NY. WebMD. Retrieved Oct 5, 2020, from https://emedicine.medscape.com/article/168402-overview

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