Definitions

💠 Sepsis :
● is a life-threatening organ dysfunction caused by a dysregulated host response to an
infection.
● organ dysfunction should be defined using SOFA or qSOFA
● is suspected or documented infection with qSOFA score 2 or more
● qSOFA score includes a respiratory rate of 22 breaths/minute or more, systolic blood
pressure of 100 mm Hg or less, and altered level of consciousness
● In pregnant women use modified qSOFA (SOMANZ score) . The SOMANZ score
includes systolic blood pressure 90 mmHg, respiratory rate >25 per minute, and
altered mental status.

💠 Multiple organ dysfunction syndrome (MODS) is characterized by progressive organ

dysfunction in a severely ill patient, with failure to maintain homeostasis without intervention.
It is the end stage in infectious conditions (sepsis, septic shock) and noninfectious conditions
(eg, SIRS due to pancreatitis). following parameters are used to assess individual organ
dysfunction :
● Respiratory system: Partial pressure of arterial oxygen (PaO2)/fraction of inspired
oxygen (FiO2) ratio
● Hematology: Platelet count, coagulation panel (prothrombin time and partial
thromboplastin time)
● Liver: Serum bilirubin
● Renal: Serum creatinine (or urine output)
● Brain: Glasgow coma score
● Cardiovascular: Hypotension and vasopressor requirement
💠 Septic shock : defined as sepsis with hypotension requiring vasopressor therapy to
maintain a mean blood pressure of more than 65 mm Hg and a serum lactate level

💠
exceeding 2 mmol/L (18 mg/dL) after adequate fluid resuscitation.
Pseudosepsis : defined as fever, leukocytosis, and hypotension due to causes other
than sepsis. Examples might include the clinical picture seen with salicylate intoxication,

💠
methamphetamine overdose, or bilateral adrenal hemorrhage.
patient at risk (but not in sepsis) : infection in the presence of two or more SIRS criteria
may identify patients without organ dysfunction who are no longer defined as having sepsis
but are an ‘at risk’ population. SIRS criteria are (1) temperature above 38.3 or below 36.0°C,
(2) heart rate above 90/min, (3) respiratory rate above 20/min, (4) new
confusion/drowsiness, (5) white blood cells (WBCs) greater than 12.0 or less than 4.0 × 109
/L and (6) blood glucose above 7.7 mmol/L (in the absence of diabetes).

Risk factors
💠 age >65 years , particularly high risk in people aged >75 years
💠 Age younger than 1 year
💠 immunocompromised :
● treatment (e.g., chemotherapy, corticosteroids, or other immunosuppressants)
● underlying disease (e.g., diabetes, sickle cell)

💠
● surgery (e.g., splenectomy).

💠
indwelling lines or catheters
surgery or other invasive procedures in the past 6 weeks , particularly high risk following

💠
oesophageal, pancreatic, or elective gastric surgery.

💠
haemodialysis

💠
diabetes mellitus

💠
intravenous drug misuse

💠
alcohol dependency
Pregnancy (and the 6 weeks after delivery/termination/miscarriage) , risk is higher if they
have :
1. Obesity
2. impaired immunity
3. Anaemia
4. gestational diabetes, diabetes (or other comorbid condition)
5. needed invasive procedures during pregnancy (e.g., Amniocentesis , caesarean
section, forceps delivery, removal of retained products of conception)
6. Cervical cerclage
7. had prolonged rupture of membranes during pregnancy
8. History of pelvic infection
9. History of group B streptococcal infection
10. have or have been in close contact with people with group A streptococcal infection
(e.g., scarlet fever)
11. Wound haematoma
12. Vaginal trauma

💠
13. have continued vaginal bleeding or an abnormal vaginal discharge with odour.

💠
breached skin integrity (e.g., cuts, burns, blisters, skin infection).

💠
lung disease
male
💠 urban residence
💠 winter season
history and physical examination

💠 NEWS2 score
💠 In a patient with a known or likely infection, a NEWS2 score of 5 or more is likely to
indicate sepsis.
💠 General signs and symptoms of sepsis may include the following :
💠 Fever, with or without shaking chills (temperature >38.3ºC or < 36ºC)
● rise in temperature can be a physiological response (eg: after surgery or trauma).
● Never rule out sepsis on the basis of a normal temperature reading.

💠
● some patients are apyrexial or have hypothermia (poorer prognosis than fever) .
groups may not develop a raised temperature with sepsis include :
1. older (>75 years) or very frail (regardless of age)
2. Infants or children
3. People with cancer receiving treatment

💠
4. Severely ill patients.
Impaired mental status (in the setting of fever or hypoperfusion) :
● identify any change from the patient’s normal behaviour or cognitive state. Relative
might describe the patient as ‘not themselves’.
● In people with dementia, change in mental state may present as irritability or
aggression, but equally could present with hypoactive delirium (e.g., with lethargy,

💠
apathy).
sepsis may be signalled by a deterioration in functional ability (e.g., a patient newly

💠
unable to stand from sitting).

💠
malaise/lethargy

💠
nausea/vomiting/diarrhoea
purpura fulminans :
● late sign of possible organ dysfunction; may be seen on presentation.
● classically associated with meningococcal sepsis but can occur with pneumococcal

💠
sepsis
Low oxygen saturation
● often seen in people with sepsis
● Difficulty obtaining peripheral oxygen saturations may be a red flag for possible
shock. You should have a high index of suspicion for shock if you are unable to

💠
measure oxygen saturations.

💠
Increased breathing rate (>20 breaths/min) resulting in respiratory alkalosis
Warm or cold skin, depending on the adequacy of organ perfusion and dilation of the

💠
superficial skin vessels
Hypotension requiring pressor agents to maintain systolic blood pressure above 65

💠
mmHg
Elderly individuals, persons with diabetes, and patients on beta-blockers may not exhibit

💠
an appropriate tachycardia as blood pressure falls.
Patients with chronic hypertension may develop critical hypoperfusion at a blood

💠
pressure that is higher than in healthy patients (ie, relative hypotension).
Younger patients develop a severe and prolonged tachycardia without hypotension until

💠
acute decompensation occurs.

💠
Systemic signs and symptoms :
sites of infection :
● Lungs: 64%
● Abdomen: 20%
● Bloodstream: 15%

💠
● Renal or genitourinary tract: 14%.

💠
In people over 65, the most common site is the genitourinary tract.
definite source of infection cannot be found in 20% to 30% of people with sepsis.
💠 Respiratory infection : Cough, chest pain , dyspnea may suggest pneumonia or
💠 Gastrointestinal (GI) or genitourinary (GU) infection :
empyema , also seen in pulmonary embolism , pleural effusion.

● jaundice (biliary sepsis)

● Patients with an intra-abdominal or pelvic source of infection usually have a history of
antecedent conditions that predispose to perforation or abscess (eg, chronic or
retrocecal subacute appendicitis, diverticulitis, Crohn disease, previous abdominal
surgery, or cholecystitis).
● Diffuse abdominal pain may suggest pancreatitis or generalized peritonitis , Elderly
patients may present with peritonitis and may not experience rebound tenderness of
the abdomen
● right upper abdominal quadrant (RUQ) tenderness may suggest a biliary tract
etiology (eg, cholecystitis, cholangitis)
● tenderness in the right lower abdominal quadrant (RLQ) suggests appendicitis or
Crohn disease.
● Discrete tenderness over the left lower abdominal quadrant suggests diverticulitis,
particularly in elderly patients.
● rectal examination may reveal exquisite tenderness caused by a prostatic abscess
or, more commonly, an enlarged noninflamed prostate suggestive of prostatitis.
● urinary tract source is suggested by an antecedent history of pyelonephritis, stone
disease, congenital abnormal collecting system, prostatic hypertrophy, or previous
operations or procedures involving the prostate or kidneys.
● Costovertebral angle tenderness with a fever suggests acute pyelonephritis.
Subacute or chronic pyelonephritis may manifest as only mild tenderness.

💠
● The most common cause of sepsis in pregnancy is urosepsis.
Intravenous line infection :
● Evidence of infection at a central IV line site , many patients with central IV line
infections do not have superficial evidence of infection at the insertion site.
● Always suspect IV line infections, especially when other sources of sepsis are
eliminated.
● Central IV lines are the lines most commonly associated with bacteremia or sepsis.
● Peripheral venous lines and arterial lines are rarely associated with bacteremia.

💠
Thrombophlebitis may be noted at the peripheral IV line site.
Surgical wound infection : Pain, purulent exudate, or crepitus in a surgical wound may

💠
suggest wound infection, cellulitis, or abscess.

💠
Signs of end-organ hypoperfusion :
Warm, flushed skin may be present in the early phases of sepsis. The skin may become
cool and clammy with progression to shock due to redirection of blood flow to core organs.

💠
Decreased capillary refill, purpura cyanosis, or mottling may be seen.

💠
Altered mental status, obtundation, restlessness
Oliguria or anuria due to hypoperfusion
● low urine output may suggest intravascular volume depletion and/or acute kidney
injury and is therefore a marker of sepsis severity.
● categorises any patient who has not passed urine in the previous 18 hours (or for
catheterised patients passed less than 0.5 mL/kg of urine per hour) as being at high

💠
risk of severe illness or death from sepsis.
Ileus or absent bowel sounds
Differential Diagnosis
💠 Diagnostic studies should be sent within the first 3 hours of suspected sepsis, and
antibiotics should be initiated within the first 45 minutes after appropriate cultures are

💠
collected
It is essential to reach a preliminary diagnosis within the first 12 hours of presentation to

💠
decrease the likelihood of adverse clinical outcomes.
If the blood pressure remains less than 65 mm Hg despite initial fluid resuscitation of 30
mL/kg or if the initial lactate level is 4 mmol/L (36 mg/dl) or higher within 6 hours, further

💠
hemodynamic assessments should be performed to ensure adequate organ perfusion.
Sepsis is often associated with or preceded by other conditions
💠 Pseudosepsis
💠 Pseudosepsis is a common cause of misdiagnosis in hospitalised patients ,
pseudosepsis produce pulmonary artery catheter readings that are compatible with sepsis

💠
(ie, increased cardiac output and decreased peripheral resistance)
before embarking on a workup for sepsis or beginning empiric antibiotic therapy, it is vital
to rule out the treatable causes of pseudosepsis early in the disease process.

💠 Most causes of pseudosepsis are readily treatable if recognized and managed early. they
💠 The most common causes of pseudosepsis include gastrointestinal (GI) hemorrhage,
require supportive, rather than antimicrobial, therapy.

pulmonary embolism, acute myocardial infarction (MI), acute pancreatitis (edematous or

hemorrhagic), diuretic-induced hypovolemia, and relative adrenal insufficiency.

💠 Otherwise healthy hosts with community-acquired pneumonia virtually never present with
hypotension or sepsis , If an otherwise healthy patient with community-acquired pneumonia
presents with shock and all of the other causes of pseudosepsis are ruled out, then it must

💠
be assumed that the patient is a compromised host with impaired or absent splenic function.
Non-infectious causes of systemic inflammatory response syndrome (SIRS) : can result
from
1. post-operative recovery
2. trauma
3. burns
4. transplant rejection
5. hyperthyroidism
 6. Addisonian crisis
7. blood product transfusion reactions
8. serum sickness
9. immunisations

💠
10. central nervous system infarction or haemorrhages.
MI : low-grade fever and raised C-reactive protein may also be present.

Workup

💠 admission to hospital if
💠 at risk of neutropenic sepsis and presents with symptoms and signs of infection
💠 Meets one or more of the
(NICE) high-risk criteria (red flags) :
1. Objective evidence of new altered mental state (e.g., new deterioration in Glasgow
Coma Scale score/AVPU ['Alert, responds to Voice, responds to Pain, Unresponsive']
scale)
2. Respiratory rate: ≥25 breaths per minute OR new need for oxygen (40% or more
fraction of inspired oxygen [FiO 2]) to maintain saturation >92% (or >88% in known
chronic obstructive pulmonary disease)
3. Heart rate: >130 beats per minute
4. Systolic blood pressure ≤90 mmHg or more than 40 mmHg below normal
5. Not passed urine in previous 18 hours, or for catheterised patients passed <0.5
mL/kg of urine per hour
 6. Mottled or ashen appearance
7. Cyanosis of skin, lips, or tongue

💠
8. Non-blanching rash of skin
Importantly, the identification of a pathogenic organism, although preferred, is not always

💠
feasible since the responsible organism may be unidentified in many patients.

💠
blood cultures
Take bloods immediately, before antibiotics are started (although sampling should not

💠
delay the administration of antibiotics)
Ideally, take peripheral blood cultures (aerobic and anaerobic) from at least two different

💠
sites

💠
If you suspect a line infection, remove the line and culture the tip.

💠
serum lactate

💠
Take blood cultures and measure serum lactate at the same time.
Lactate measured using
1. blood gas analyser

💠
2. laboratory analysis
Measure serum lactate, on a blood gas, to :
1. determine the severity of the sepsis

💠
2. monitor response to treatment.

💠
Lactate is a marker of stress , hypoperfusion.
Do not be falsely reassured by a normal lactate (<2 mmol/L [<18 mg/dL]). Calculate

💠
NEWS2 score.

💠
Lactate may normalise quickly after fluid resuscitation
Persistent raised lactate should incite efforts to identify other hidden causes including

💠
thiamine deficiency, adrenaline or other drugs, and liver failure.

💠
urine output

💠
CBC
Thrombocytopenia :
1. Thrombocytopenia of non-haemorrhagic origin may occur in patients who are
severely ill with sepsis.

💠
2. Persistent thrombocytopenia is associated with an increased risk of mortality.

💠
Lymphocytopenia (useful sign in a patient with sepsis.)

💠
WBC count is neither sensitive nor specific for sepsis , used in ild criteria but not now
Non-infectious (e.g., crush) injury, surgery, cancer, and immunosuppressive agents can

💠
also lead to either increased or decreased WBC counts.

💠
urea and electrolytes
use to :
1. Evaluate the patient for renal dysfunction
2. Determine whether the patient would benefit from haemofiltration or intermittent
haemodialysis

💠
3. Identify sodium, potassium, calcium, magnesium, and chloride abnormalities.

💠
serum glucose

💠
elevated or low (rare)
elevation due to :
1. stress response

💠
2. Drug therapy (e.g., with corticosteroids and catecholamines)

💠
Persisting hypoglycaemia may suggest acute liver failure.
CRP :elevated (sensitive, but not specific)
💠 serum procalcitonin :
💠 elevated
💠 using procalcitonin alongside clinical evaluation to decide when to discontinue
💠 clotting screen
antimicrobials.

💠 elevated PT; elevated PTT; elevated D-dimer; elevated fibrinogen

💠 associated with a worse prognosis.
💠 liver function tests
💠 elevated bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline
💠 blood gas
phosphatase, and gamma glutamyl transpeptidase

💠 VBG is increasingly being used in preference to ABG in the emergency department

💠 ABG will be used instead of VBG if the patient is escalated to critical care as an arterial
💠 PaCO₂ <4.3 kPa (32 mmHg) is one of the diagnostic criteria for systemic inflammatory
line is usually inserted for ease of access.

💠 Be aware that venous PCO 2 may be artificially high if taken from a tourniqueted limb.
response syndrome; may be hypoxaemia, hypercapnia

💠 ECG
💠 Request a baseline ECG for any patient with suspected sepsis to :
1. Rule out differential diagnoses: for example, myocardial infarction, pericarditis, or
myocarditis
2. Detect arrhythmias (e.g., atrial fibrillation); commonly seen in older people with

💠
sepsis.
urine analysis :
1. show evidence of infection (nitrates; leucocytes; blood/protein)
2. this does not definitively confirm a urinary source, particularly as urine analysis has a

💠
low specificity.

💠
chest x-ray
show evidence of infection, such as consolidation or pleural effusion, cardiac

💠
abnormalities, or a pneumothorax
lumbar puncture : if you suspect meningitis or encephalitis, provided there is no
suspicion of raised intracranial pressure (a computed tomography scan should be performed

💠
prior to lumbar puncture if you suspect raised intracranial pressure)

💠
CT scan
findings may include: a hidden collection (e.g., a visceral abscess or effusion); free air

💠
(perforation)

💠
ultrasound
identify :
1. abscess; free fluid (peritonitis)
2. common bile duct dilatation (cholangitis)
3. areas of infarction secondary to emboli (e.g., infective endocarditis)

💠
4. hydronephrosis (pyelonephritis)

💠
Ultrasound has a reasonable false negative rate
viral swabs : PCR in people with suspected respiratory aetiology.
💠 HIV screen
💠 Consider screen for HIV infection in patients presenting with :
1. recurrent infections
2. atypical infections

💠
3. in high-risk groups.
risk factors for contracting HIV infection include :
1. intravenous drug use

💠
2. unprotected sexual intercourse (heterosexual and homosexual).

💠
Echocardiogram
Use echo to assess :
1. left or right ventricular dysfunction, which may be caused by sepsis
2. detect vegetations (endocarditis) .
3. assess inferior vena cava collapsibility, which is a marker of hypovolaemia, and to
guide fluid resuscitation.

Management
💠 Check the hands of the septic patient; if warm and well-perfused, then early septic shock
is likely. If the hands are cold and clammy, then septic shock is late, under resuscitated, or

💠
involves severe cardiac depression.

💠
broad-spectrum intravenous antibiotics
Where there is evidence of a bacterial infection give antibiotic :
● Within 1 hour of initial severity assessment for patients with a NEWS2 score of 7 or
more (or with a score of 5 or 6 if there are additional clinical or carer concerns,
continuing deterioration, neutropenia, or blood gas/laboratory evidence of organ
dysfunction), or

💠
● Within 3 hours for patients with a NEWS2 score of 5 or 6.
empirical combination therapy (using at least two antibiotics of different antimicrobial
classes covering gram-negative bacilli) for patients at high risk of infection from multidrug

💠
resistant (MDR) organisms, particularly in those with septic shock.

💠
Single agents are recommended for patients with a low risk for MDR organisms

💠
give empirical therapy until pathogen has been identified
If a patient has a mild allergy (e.g., rash) to an unknown antibiotic, you should still give
empirical broad-spectrum antibiotics if indicated to prevent delay in the treatment of sepsis,

💠
which is likely to worsen outcome.
repeat cultures indicated :
1. if there are persistent or repeated fever spikes

💠
2. if you identify a potential new site of infection.

💠
switching from intravenous to oral antibiotics as soon as possible.
using procalcitonin alongside clinical evaluation to decide when to discontinue
antimicrobials.
💠 reassess and monitor
💠 continuous monitoring, or a minimum of once every 30 minutes :
1. Oxygen saturation
2. Respiratory rate
3. Heart rate
4. Blood pressure
5. Temperature
6. Hourly fluid balance (including urine output)

💠
7. Lactate level.
if NEWS2 score of less than 5 , look for indicators that suggest the possibility of
underlying infection and sepsis :
1. single NEWS parameter of 3 or more
2. Non-blanching rash/mottled/ashen/cyanotic skin
3. Responds only to voice or pain, or unresponsive
4. Not passed urine in last 18 hours or urine output <0.5 mL/kg/hour

💠
5. Lactate ≥2 mmol/L (≥18 mg/dL).
Ensure urgent review by a senior clinician of any patient with a (NEWS2) score of 5 or
more :
● Within 30 minutes of initial severity assessment for any patient with an aggregate
NEWS2 score of 7 or more; or with a NEWS2 score of 5 or 6 if there is clinical or
carer concern, continuing deterioration, surgically remediable sepsis, neutropenia, or
blood gas/laboratory evidence of organ dysfunction (including elevated serum lactate
● Within 1 hour of initial severity assessment for any patient with an aggregate NEWS2

💠
score of 5 or 6.
discuss with a consultant if Does not respond to initial therapy (antibiotics/fluid
resuscitation/oxygen) within the first hour. Failure to respond to treatment is defined as:
● Systolic blood pressure remains less than 90 mmHg
● Persistent reduced level of consciousness
● Respiratory rate more than 25 breaths per minute or the new need for mechanical
ventilation
● Lactate has not reduced by more than 20%

💠 fluid resuscitation
💠 Give 500 mL of crystalloid fluid over less than 15 minutes to patients who need fluid
💠 Monitor for signs of fluid overload such as pulmonary or systemic oedema before and
resuscitation (if there is any sign of circulatory insufficiency) , Reassess after the first bolus

💠 In patients with sepsis-induced hypoperfusion (as indicated by a systolic blood pressure

after each additional fluid bolus.

<90 mmHg, a raised lactate level, or signs of organ dysfunction), guideline recommends a

💠
total of at least 30 mL/kg of intravenous crystalloid over the first 3 hours.
If the patient’s initial lactate level is raised, the guideline recommends serial lactate
measurements to guide the need for further intravenous fluids (with the goal of normalising
lactate levels).

💠 oxygen
💠 standard intensive care unit supportive care
💠 Stress ulcer prophylaxis
💠 Deep venous thrombosis prophylaxis : With heparin and compression stockings
💠 Enteral or parenteral nutrition
💠 Glycaemic control :
● targeting a blood glucose level <10.0 mmol/L (<180 mg/dL) , not less than 110
mg/dL (risk of hypoglycemia)
● Strict glucose control 80-110 mg/dL associated with decreased mortality more but

💠
more risk of hypoglycemia

💠
Blood products
Transfusion of packed cells : threshold of 70 g/L (7 g/dL) , giving transfusions at a higher
haemoglobin level in some patients (e.g., people with myocardial ischaemia, severe

💠
hypoxaemia, intracerebral pathology or acute haemorrhage).
Do not use FFp to correct laboratory clotting abnormalities, unless there is bleeding or

💠
planned invasive procedures.
Administer platelets when platelet counts are <20 × 109/L and there is significant

💠
bleeding risk.

💠
Vasopressors
vasopressors should be started within the first hour if blood pressure is not restored after

💠
initial fluid resuscitation.
sign of septic shock : Vasopressors are used in a critical care setting to maintain a mean

💠
arterial pressure (MAP) ≥65 mmHg if the patient is unresponsive to fluid resuscitation.
Patients with previously uncontrolled hypertension may require a mean arterial pressure

💠
of 75 mm Hg or even higher.
Do not use MAP as indicator of overall efficacy of therapeutic intervention alone , but
must be correlated with other indicators of adequate perfusion, such as mental status and

💠
urine output.

💠
Noradrenaline (norepinephrine) is the vasopressor of choice

💠
add vasopressin to noradrenaline If further vasopressor therapy is required

💠
Inotropes
considered for patients with low cardiac output despite adequate fluid resuscitation and

💠
vasopressor therapy.
Suspect low cardiac output if the clinical examination reveals
1. prolonged capillary refill times
2. low urine output

💠
3. poor peripheral perfusion
guideline recommends either adding dobutamine to noradrenaline or using adrenaline

💠
(epinephrine) alone
When using inotropes, keep the patient’s heart rate at less than 100 beats per minute to

💠
minimise myocardial ischaemia.

💠
corticosteroids
intravenous hydrocortisone for patients with an ongoing requirement for vasopressor

💠
therapy. Steroid therapy should be continued as long as vasopressor therapy is required.

💠
hydrocortisone : 50 mg intravenously every 6 hours
Intravenous hydrocortisone is preferred to dexamethasone (because of the
mineralocorticoid effects of hydrocortisone), and the dose should not exceed 300 mg daily
(to limit the risk of infection).

  TABLE 151-2    Empiric Antibiotic Selection in Severe Sepsis and Septic Shock (Continued)
Host
Adults (nonneutropenic) without an
obvious source of infection
Adults (nonneutropenic), suspected
biliary source
Adults (nonneutropenic), suspected
pneumonia
Adults (nonneutropenic), suspected
illicit use of IV drugs
Adults with petechial rash
Adults (nonneutropenic), suspected
intra-abdominal source
Adults (nonneutropenic), suspected
urinary source (hospitalized with
pyelonephritis)
Tintinalli_Sec13_p0997-1100.indd 1003
Likely Pathogens
Staphylococcus aureus, streptococci,
gram-negative bacilli, others
Aerobic gram-negative bacilli, enterococci
Streptococcus pneumoniae,
methicillin-resistant S. aureus,
gram-negative bacilli, Legionella
S. aureus
Neisseria meningitidis, RMSF
Mixture of aerobic and anaerobic
gram-negative bacilli
Aerobic gram-negative bacilli, enterococci
1003 
CHAPTER 151: Sepsis   
Initial Antibiotic Selection
Imipenem, 500 milligrams every 6 h to 1 gram IV every 8 h
or
Meropenem, 1 gram IV every 8 h
or
Doripenem, 500 milligrams IV every 8 h
or
Ertapenem*, 1 gram IV every 24 h
plus
Vancomycin†, 15 milligrams/kg loading dose
Ampicillin/sulbactam, 3 grams IV every 6 h
or
Piperacillin/tazobactam, 4.5 grams IV every 6 h
or
Ticarcillin/clavulanate, 3.1 grams IV every 4 h
plus
Metronidazole, 15 milligrams/kg IV load then 7.5 milligrams/kg every 8 h
Ceftriaxone, 1–2 grams IV every 12 h
plus
Azithromycin, 500 milligrams IV, then 250 milligrams IV every 24 h
plus
Levofloxacin, 750 milligrams IV every 24 h or moxifloxacin, 400 milligrams IV every 24 h
plus
Vancomycin†, 15 milligrams/kg loading dose
Vancomycin†, 15 milligrams/kg loading dose
Ceftriaxone, 2 grams IV every 12 h
or
Cefotaxime, 2 grams IV every 4–6 h
Consider
Addition of doxycycline 100 milligrams IV every 12 h for possible RMSF
Imipenem, 500 milligrams IV every 6 h to 1 gram IV every 8 h
or
Meropenem, 1 gram IV every 8 h
or
Doripenem, 500 milligrams IV every 8 h
or
Ertapenem, 1 gram IV every 24 h
or
Ampicillin/sulbactam, 3 grams IV every 6 h
or
Piperacillin/tazobactam, 4.5 grams IV every 6 h
plus
Metronidazole, 15 milligrams/kg IV load then 7.5 milligrams/kg every 8 h#
Levofloxacin, 750 milligrams IV every 24 h
or
Moxifloxacin, 400 milligrams IV every 24 h
or
Piperacillin/tazobactam, 4.5 grams IV every 6 h
or
Ceftriaxone, 1–2 grams IV every 12–24 h
or
Ampicillin, 1–2 grams IV every 4–6 h
plus
Gentamicin, 1.0–1.5 milligrams/kg every 8 h‡
(Continued)
8/2/19 8:11 PM
 1004   SECTION 13: Infectious Diseases

  TABLE 151-2    Empiric Antibiotic Selection in Severe Sepsis and Septic Shock (Continued)
Host Likely Pathogens Initial Antibiotic Selection
Adults (nonneutropenic), suspected Enterobacteriaceae, Pseudomonas aeruginosa, Piperacillin/tazobactam, 4.5 grams IV every 6 h
urinary source (complicated urinary tract enterococci, rarely S. aureus or
infection/urinary catheter) Imipenem, 500 milligrams every 6 h to 1 gram IV every 8 h
or
Meropenem, 1 gram IV every 8 h
or
Doripenem, 500 milligrams IV every 8 h
or
Ampicillin, 1–2 grams IV every 4–6 h
plus
Gentamicin, 1.0–1.5 milligrams/kg every 8 h‡
Neutropenic adults Aerobic gram-negative bacilli, especially Ceftazidime, 2 grams IV every 8 h
P. aeruginosa, S. aureus or
Cefepime, 2 grams IV every 8 h
or
Imipenem, 500 milligrams IV every 6 h to 1 gram IV every 8 h
or
Meropenem, 1 gram IV every 8 h
or
Piperacillin/tazobactam, 4.5 grams IV every 6 h
plus
Levofloxacin, 750 milligrams IV every 24 h or moxifloxacin, 400 milligrams IV every 24 h
plus
Vancomycin†, 15 milligrams/kg loading dose
and consider
Fluconazole, 400 milligrams IV every 24 h or micafungin, 100 milligrams every 24 h
Patients with suspected anaerobic Anaerobic bacteria plus gram-negative bacilli Metronidazole, 15 milligrams/kg IV load, then 7.5 milligrams/kg every 8 h#
source: intra-abdominal, biliary, female (also see suspected biliary or intra-abdominal or
genital tract infection; necrotizing cellu- source, above) Clindamycin, 600–900 milligrams IV every 8 h
litis; odontogenic infection; or anaerobic
soft tissue infection
Patients with indwelling vascular Coagulase-negative Staphylococcus, Vancomycin†, 15 milligrams/kg loading dose
devices methicillin-resistant S. aureus
Patients with potential for Legionella   Azithromycin, 500 milligrams IV, then 250 milligrams IV every 24 h
species infection or
Erythromycin, 800 milligrams IV every 6 h should be added to the regimen
Asplenic patients S. pneumoniae, N. meningitidis, Haemophilus Ceftriaxone, 1 gram IV every 24 h up to 2 grams IV every 12 h if meningitis
influenzae, Capnocytophaga
Abbreviation: RMSF = Rocky Mountain spotted fever.
*
Ertapenem has no antipseudomonal coverage and is not recommended in many intensive care units due to concerns of potentiating pseudomonal antimicrobial resistance.
†
Methicillin-resistant S. aureus colonization is extremely high, and consideration should be given to including vancomycin in addition to the antibiotic recommendations. Vancomycin dosage is typically suggested
at 15 milligrams/kg but can delay effective antimicrobial activity; initial dosages of 25 to 30 milligrams/kg have been recommended by some authorities. If the patient has an allergy to vancomycin, linezolid 600
milligrams IV can be substituted.
‡
Multiple daily dosing: 2 milligrams/kg load then 1.7 milligrams/kg every 8 h.
#
Metronidazole is often prepackaged as 500-milligram bags. Dosing at 500 milligrams IV every 6 or 8 h to approximate the milligram per kilogram dosing may speed time to antibiotic administration.

rapid and dramatic progression of their disease process, manage asplenic
patients quickly. Although not relevant at the time of initial sepsis care,
these patients should have appropriate bacterial immunization following
a splenectomy.
 NEUTROPENIC FEVER
Due to an impaired immune system, neutropenic patients are at
increased risk for developing sepsis and worse outcomes. Any fever in
a neutropenic patient is suspicious for infection, and all patients should
have source organ and blood cultures drawn followed by empiric antibi-
otics. After conferring with an oncologist, some patients may be treated
at home with oral broad-spectrum agents (often including a quinolone)
if they look well and are closely followed; the rest are admitted.
REFERENCES
The complete reference list is available online at www.TintinalliEM.com.

Tintinalli_Sec13_p0997-1100.indd 1004 8/2/19 8:11 PM

Adult Sepsis Antibiotic Administration Table
Adapted with permission from the Australian Injectable Drugs Handbook, 8 th Edition

General information

• Appropriate recognition and timely management of patients with severe infection and sepsis is a significant problem in NSW hospitals. Delayed treatment
is associated with high mortality rates, significant morbidity and high costs to the health care system.
• From a microbiological perspective and to ensure compliance with the Medication Handling in NSW Public Health Facilities policy directive, injectable
medication must be prepared for only one patient at a time, immediately prior to their intended use. Aseptic technique must be maintained during
preparation.
• Displacement volume is the volume that the powder component of a drug takes up upon reconstitution. It needs to be added to the diluent volume to
ensure accuracy in calculating doses that are less than a full vial. Thus, the diluent volume recommended in the Product Information (PI) may sometimes
differ from the volume recommended in this guideline. If part doses are required, refer to the Australian Injectable Drugs Handbook.

Volume of diluent to reconstitute a vial + displacement volume of drug powder = Final volume of vial

• Where possible use separate dedicated lines for resuscitation fluid and for medications. When injecting antibiotics directly into an IV injection
port which has resuscitation fluid running:
• clamp the infusion fluid line and flush with 20 mL sterile sodium chloride 0.9% solution
• administer antibiotic over the required time
• flush the line with 20 mL sterile sodium chloride 0.9% solution and recommence resuscitation fluid.

July 2020
Adult Sepsis Antibiotic Administration Table – Adapted with permission from the Australian Injectable Drugs Handbook, 8th Edition

Reconstitution
Medication Presentation Administration Notes
fluid/volume

amikacin Vial: Reconstitution not IV Injection: For doses less than 500 mg • Dose obese patients (BMI >30) using ADJUSTED
500 mg/2 mL required inject over 3 to 5 minutes BODYWEIGHT
• Gentamicin is inactivated by penicillin and
Intermittent IV Infusion: Dilute dose in a cephalosporin antibiotics. Do not mix in the same
injection or infusion solution. Administer at separate
suitable volume of sodium chloride 0.9%
sites if possible.
and infuse over 15 to 30 minutes
• Therapeutic drug monitoring may be required for use
beyond 48 hours
• Potential for ototoxicity and nephrotoxicity, adjustment
required in renal impairment

amoxicillin Vial: Add 20 mL water IV Injection: Inject slowly over at least 3 • Contraindicated in patients with immediate
1g for injection to 4 minutes (preferably over 10 to 15 hypersensitivity to penicillins, carbapenems and
minutes) cephalosporin antibiotics
• Rapid IV administration may cause seizures
Intermittent IV Infusion: Dilute the dose
in 50–100 mL sodium chloride 0.9% and
infuse over 30 to 60 minutes

amoxicillin + Vial: 600 mg vial: Add IV Injection: Inject over 3 to 4 minutes • Contraindicated in patients with immediate
clavulanic acid 600 mg 10 mL water for hypersensitivity to penicillins, carbapenems and
1.2 g injection Intermittent IV Infusion: Dilute 600 mg cephalosporin antibiotics
2.2 g dose in 50 mL or larger doses in 100 mL • Rapid IV administration may cause seizures
1.2 g, 2.2 g vial: of sodium chloride 0.9% and infuse over
Add 20 mL water 30 to 40 minutes
for injection

ampicillin Vial: Add 10 - 20 mL IV Injection: • Contraindicated in patients with immediate

500 mg water for injection Doses < 1 g inject over 3 to 5 minutes hypersensitivity to penicillins, carbapenems and
1g Doses of 1 – 2 g inject over 10 to 15 cephalosporin antibiotics
minutes • Rapid IV administration may cause seizures

July 2020
Adult Sepsis Antibiotic Administration Table – Adapted with permission from the Australian Injectable Drugs Handbook, 8th Edition

Reconstitution
Medication Presentation Administration Notes
fluid/volume

azithromycin Vial: Add 4.8 mL water Intermittent IV Infusion: Dilute the dose • IV injection not recommended
500 mg for injection in 250 mL sodium chloride 0.9% and • Local infusion-site reactions may occur
infuse over 60 minutes
• Severe allergic reactions may occur

benzylpenicillin Vial: 600 mg vial: IV Injection (doses ≤ 1.2 g): Inject slowly • Contraindicated in patients with immediate
600 mg Add 10 mL water over 5 to 10 minutes. hypersensitivity to penicillins, carbapenems and
1.2 g for injection cephalosporin antibiotics
Intermittent IV Infusion (doses > 1.2 g): • Rapid IV administration may cause seizures
1.2 g vial: Add Dilute the dose in 100 mL of sodium
20 mL water for chloride 0.9 % and infuse over 30 to 60
injection minutes

cefepime Vial: Add 10-20 mL IV Injection: Inject slowly over 3 to 5 • Contraindicated in patients with immediate
1g sodium minutes hypersensitivity to penicillins, carbapenems and
2g chloride 0.9% cephalosporin antibiotics
Intermittent IV Infusion: Dilute the dose in
50–100 mL of sodium chloride 0.9% and
infuse over 30 minutes

ceftazidime Vial: Add 10-20 mL IV Injection: Inject slowly over 3 to 5 • Contraindicated in patients with immediate
1g water for minutes to avoid vein irritation hypersensitivity to penicillins, carbapenems
2g injection and cephalosporin antibiotics
Intermittent IV Infusion: Dilute the dose to • Shake vial after reconstitution to dissolve. Solution will
a suitable volume with sodium chloride fizz and become clear in 1 to 2 minutes
0.9% and infuse over 15 to 30 minutes.
Maximum concentration is 40 mg/mL

July 2020
Adult Sepsis Antibiotic Administration Table – Adapted with permission from the Australian Injectable Drugs Handbook, 8th Edition

Reconstitution
Medication Presentation Administration Notes
fluid/volume

ceftriaxone Vial: 500 mg vial: IV Injection (for doses up to 1 g): Inject • Contraindicated in patients with immediate
500 mg Add 5 mL of over 2 to 4 minutes hypersensitivity to penicillins, carbapenems and
1g water for cephalosporin antibiotics
2g injection • Ceftriaxone must not be administered at the same time
Intermittent IV Infusion (2 g doses):
Dilute dose with 40 mL of sodium chloride as IV calcium-containing products due to risk of
1 g vial: Add 0.9% and infuse reconstituted solution over precipitation. Sequential administration should occur
10 mL of water at least 30 minutes after thorough flushing of the infusion line with a
for injection compatible fluid.

2 g vial: Add
40 mL of
sodium
chloride 0.9%
cefazolin Vial: Add 10 mL of IV Injection: Inject slowly over 3 to 5 • Contraindicated in patients with immediate
500 mg water for injection minutes. Dose of 2 g can be given over at hypersensitivity to penicillins, carbapenems and
1g least 5 minutes cephalosporin antibiotics
2g
Intermittent IV Infusion: Dilute the dose in
50–100 mL of sodium chloride 0.9% and
infuse over 10 to 60 minutes
ciprofloxacin Vial or infusion Reconstitution Intermittent IV Infusion: Infuse into a • Contraindicated in patients with known hypersensitivity
bag: not required large vein over at least 60 minutes reactions to ciprofloxacin and other quinolones
100 mg/50 mL
200 mg/100 mL
400 mg/200 mL

July 2020
Adult Sepsis Antibiotic Administration Table – Adapted with permission from the Australian Injectable Drugs Handbook, 8th Edition

Reconstitution
Medication Presentation Administration Notes
fluid/volume

clindamycin Ampoule: Reconstitution Intermittent IV Infusion: Dilute doses up • Dalacin-C ampoules must be kept in the refrigerator
300 mg/2 mL not required to 600 mg in 50 mL sodium chloride 0.9% (between 2-8oC) prior to administration whilst the Mylan
600 mg/4 mL and infuse over at least 20 minutes. brand can be kept at ambient temperature (< 25oC).
• Do not give by IV injection, rapid IV administration may
cause hypotension and cardiac arrest
Dilute doses up to 1200 mg in 100 mL
sodium chloride 0.9% and infuse over at
least 30 to 40 minutes.

Maximum rate is 30 mg/minute.

dexamethasone Ampoule or vial: Reconstitution IV Injection: Inject slowly over 3 to 5
4 mg/1 mL not required minutes (may be diluted with 10 mL of
8 mg/2 mL sodium chloride 0.9 % to facilitate slow
injection)

Intermittent IV Infusion: Dilute the dose in

50-100 mL of sodium chloride 0.9 % and
infuse over 15 minutes
flucloxacillin Vial: 500 mg vial: Add IV Injection: Inject slowly over 3 to 4 • Contraindicated in patients with immediate
500 mg 10 mL water for minutes. A dose of 2 g can be injected hypersensitivity to penicillins, carbapenems and
1g injection over 6 to 8 minutes however infusion cephalosporin antibiotics
2g preferred • Pain and phlebitis are common and can be severe –
1 g vial: Add 15- central venous access may be required for prolonged
20 mL water for Intermittent IV Infusion (preferred for therapy
injection 2 g doses): Dilute the dose in a suitable
volume of sodium chloride 0.9% and infuse
2 g vial: Add over 20 to 30 minutes
40 mL of water for
injection

July 2020
Adult Sepsis Antibiotic Administration Table – Adapted with permission from the Australian Injectable Drugs Handbook, 8th Edition

Reconstitution
Medication Presentation Administration Notes
fluid/volume

gentamicin Ampoule: Reconstitution not IV Injection: Inject undiluted over 3 to 5 • Dose obese patients (BMI > 30) using ADJUSTED
10 mg/1 mL required minutes (may be diluted to 20 mL with BODYWEIGHT
80 mg/2 mL sodium chloride 0.9 % to aid slow • Gentamicin is inactivated by penicillin and
injection) cephalosporin antibiotics. Do not mix in the same
injection or infusion solution. Administer at separate
sites if possible.
Intermittent IV Infusion: Dilute the dose
• Therapeutic drug monitoring may be required for use
in 50-100 mL of sodium chloride 0.9% and
beyond 48 hours
infuse over 30 minutes
• Potential for ototoxicity and nephrotoxicity, adjustment
required in renal impairment
meropenem Vial: 500 mg vial: Add IV Injection: Inject over 5 minutes • Contraindicated in patients with immediate
500 mg 10 mL water for hypersensitivity to penicillins, carbapenems and
1g injection cephalosporin antibiotics
Intermittent IV Infusion: Dilute the dose
in 50–200 mL of sodium chloride 0.9 %
1 g vial: Add and infuse over 15 to 30 minutes
20 mL water for
injection
metronidazole Infusion bag: Reconstitution not Intermittent IV Infusion: Infuse 500 mg
500 mg/100 mL required undiluted over 20 minutes (rate of
25 mg/minute)
moxifloxacin Infusion bag or Reconstitution not Intermittent IV Infusion: Infuse undiluted
bottle: required over 60 minutes
400 mg/250 mL
piperacillin + Vial: Add 20 mL water Intermittent IV Infusion: Dilute the dose • Contraindicated in patients with immediate
tazobactam 4.5 g for injection in 50 mL sodium chloride 0.9%. Infuse hypersensitivity to penicillins, carbapenems and
over 20 to 30 minutes cephalosporin antibiotics
• Reconstituted solution may take 5 to 10 minutes of
constant shaking to dissolve

July 2020
Adult Sepsis Antibiotic Administration Table – Adapted with permission from the Australian Injectable Drugs Handbook, 8th Edition

Reconstitution
Medication Presentation Administration Notes
fluid/volume

tobramycin Ampoule: Reconstitution not Intermittent IV Infusion: Dilute the dose • Dose obese patients (BMI > 30) using ADJUSTED
80 mg/2 mL required in 50-100 mL of sodium chloride 0.9% and BODYWEIGHT
infuse over 20 to 30 minutes • Tobramycin is inactivated by penicillin and
cephalosporin antibiotics. Do not mix in the same
injection or infusion solution. Administer at separate
sites if possible
• Therapeutic drug monitoring may be required for use
beyond 48 hours
• Potential for ototoxicity and nephrotoxicity, adjustment
required in renal impairment
trimethoprim + Ampoule: Dilute each Intermittent IV Infusion: Infuse over 60 to • Dilute 1 ampoule (5 mL) in 125 mL sodium chloride
sulfamethoxazole 80 mg + ampoule in at 90 minutes 0.9%
400 mg least 125 mL of • Dilute 2 ampoules (10 mL) in 250 mL sodium chloride
/5 mL sodium chloride 0.9%
0.9% (see • Dilute 3 ampoules (15 mL) in 500 mL sodium chloride
notes) 0.9% and so forth
• In critical care settings may be given undiluted through
a central venous catheter
vancomycin Vial: 500 mg vial: Add Intermittent IV Infusion: Dilute the dose to • Infusion related effects (for example pain at the
500 mg 10 mL water for 5 mg/mL with sodium chloride. For injection site and Red man syndrome) are common. If
1g injection example, dilute a 500 mg dose with 100 mL these occur, decrease infusion rate and monitor closely
and 1 g dose with 200 mL sodium chloride • A maximum rate of infusion of 10 mg/minute is
0.9% and infuse over at least 60 minutes. recommended to minimise the risk of Red-man
1 g vial: Add syndrome.
20 mL water for For doses over 1 g, increase the infusion
time by 30 minutes for each additional • Red-man syndrome presents as tingling, flushing or
injection
500 mg i.e. 1.5 g over 1.5 hours and 2 g rash of the face, neck and upper body, muscle spasm
over 2 hours of the chest and back, and rarely hypotension and
shock-like symptoms. If symptoms of Red-man
For fluid-restricted patients, maximum
syndrome occur, slow the rate of the infusion
concentration is 10 mg/mL

July 2020