Sepsis in children

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 – prompt recognition and airway management and temperature control

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1st line –

prompt recognition and airway management and temperature control

Management of sepsis in children first requires prompt recognition.

Airway and breathing should be managed as per paediatric advanced life support and resuscitation algorithms.

The patient's airway should be maintained at all times; not all patients with sepsis or septic shock require intubation and ventilation. Intubation is recommended if respiratory support is required or for patients with a reduced level of consciousness. Mechanical ventilation reduces the cardiac workload in patients with cardiovascular compromise by reducing the effort of breathing and through positive effects on left ventricular function.[102]

The clinician should be prepared for cardiovascular collapse and/or cardiac arrest on induction of anaesthesia for intubation. Concomitant fluid resuscitation and inotrope use should be considered during anaesthetic induction. Anaesthetic agents with a relatively stable cardiovascular profile are recommended (e.g., ketamine with atropine).[95] Etomidate is not currently recommended for anaesthesia in children with septic shock, due to concerns regarding adrenal suppression.[6]

Supplemental oxygen should be provided, initially at high concentration if there is evidence of cardiovascular instability or shock.[95] Supplemental oxygen is one of the interventions that should be given within one hour of recognition of suspected sepsis under the Paediatric Sepsis Six care protocol.[59] It should be delivered, preferably, via a mask with a reservoir bag or headbox in neonates. Oxygen should then be titrated according to pulse oximetry, aiming for an oxygen saturation of >94% once the patient is haemodynamically stable. Caution should be exercised in premature neonates or neonates suspected of having congenital heart disease.

There is no evidence for or against the use of antipyretics in febrile children with sepsis, though it is reasonable and recommended to provide antipyretic therapy to optimise patient comfort, reduce extreme body temperature, and reduce metabolic demand.[6][136] Both paracetamol and ibuprofen are safe and effective in reducing fever compared with placebo. Alternating or combined use of these is often used in practice; however, there is no evidence that combination therapy results in overall improvement in clinical outcomes and it may put children at increased risk due to dosing errors and adverse outcomes so these risks must be carefully considered.[136]

Primary options

ketamine: consult local protocols for guidance on dose

and

atropine: consult local protocols for guidance on dose

Plus – intravenous or intraosseous (IO) access and blood tests

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Plus –

intravenous or intraosseous (IO) access and blood tests

Treatment recommended for ALL patients in selected patient group

Intravenous or IO access should be obtained within 5 minutes of presentation.[95] A blood sample should be taken for basic blood tests, including: blood cultures, blood glucose (low blood glucose should be treated), and arterial, capillary, or venous blood gases. Full blood count, serum lactate, and C-reactive protein should also be ordered for baseline assessment.

Obtaining intravenous or IO access and ordering these blood tests is one of the interventions recommended under the Paediatric Sepsis Six care protocol.

Plus – intravenous fluids

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Plus –

intravenous fluids

Treatment recommended for ALL patients in selected patient group

Profound fluid loss from the intravascular space occurs in sepsis due to capillary leakage and may persist for several days. Fluid resuscitation aims to restore the patient’s normal heart rate, blood pressure, and capillary refill time. Considering the need for fluid resuscitation is one of the interventions that should be initiated within one hour of recognition of suspected sepsis under the Paediatric Sepsis Six protocol.[59]

Choice of fluid is a topic of debate, but is less important provided the fluid is isotonic. The paediatric Surviving Sepsis Campaign guidelines recommend using balanced/buffered crystalloid solutions (Hartmann's solution, or lactated Ringer's solution), rather than normal saline or albumin for initial resuscitation. Although high quality paediatric data are lacking, evidence from observational and adult interventional studies favours use of balanced solutions due to the chloride content in normal saline inducing hyperchloraemic metabolic acidosis when given in large amounts.[6] There is currently insufficient evidence to make a recommendation for or against the use of colloids in children.[103][104][105] [ ] [Evidence B]

Starch-containing solutions (including hydroxyethyl starch - HES) should not be used in the management of sepsis as there is evidence to show that they increase the risk of kidney dysfunction and mortality.[108][109][110]

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.[107] The Surviving Sepsis Campaign advises against the use of starches for patients with sepsis and septic shock.[111] In the US, the Food and Drug Administration (FDA) issued safety labelling changes in July 2021 for solutions containing HES stating that HES products should not be used unless adequate alternative treatment is unavailable.[106]

Guidance from the paediatric Surviving Sepsis Campaign on initial fluid resuscitation stratifies recommended fluid management according to whether or not the child is being treated at a centre with critical care availability.[6]

If a critical care facility is present, administer up to 40-60 mL/kg in bolus fluid (given as individual boluses of 10-20 mL/kg at a time) over the first hour, titrated to clinical markers of cardiac output and discontinued if signs of fluid overload develop. If a child has evidence of abnormal perfusion after 40-60 mL/kg of fluids according to the Surviving Sepsis Campaign (or 20 mL/kg according to the Sepsis 6 Toolkit), or earlier if they develop fluid overload, treatment should be escalated to include initiation of inotropes/vasopressors, which would be typically given in a critical care environment.

If there is no critical care availability and the child is normotensive, maintenance fluids should be started without administration of bolus fluids. This recommendation is based on the FEAST trial, in which rapid bolus fluid in the first hour of resuscitation given in a resource-limited setting increased mortality compared with maintenance fluids only.[112][113]

If there is no critical care availability and the child is hypotensive, up to 40 mL/kg in bolus fluid is recommended over the first hour, given as individual boluses of 10-20 mL/kg at a time and titrated according to clinical markers of cardiac output. This should be discontinued if signs of fluid overload develop (i.e., increased work of breathing, pulmonary crepitations, hepatomegaly, gallop rhythm).

Patients may require large volumes of fluid to support their circulating volume. It would not be unusual for a child in septic shock to receive >100 mL/kg of fluid resuscitation within the first 24 hours of admission, due to fluid maldistribution. However, they should always be monitored closely for signs of fluid overload. Identifying fluid overload is especially difficult in young children, in whom crackles (rales) are often absent on respiratory examination even in the context of gross pulmonary oedema. Worsening respiratory status, particularly increasing respiratory rate, radiological evidence of pulmonary oedema, or new or expanding hepatomegaly may be the only clues of evolving fluid overload.[6]

Maintenance fluid requirements vary depending on the clinical condition and should be assessed and tailored according to each child's needs. The following equation is used to calculate fluid requirements: (4 mL/kg for the first 10 kg) + (2 mL/kg for each kg between 11-20 kg) + (1 mL/kg for every kg >20) = hourly rate. For example, to calculate the hourly maintenance fluid rate for a child weighing 23 kg: (4 mL x 10 kg) + (2 mL x 10 kg) + (1 mL x 3 kg) = hourly rate; 40 mL + 20 mL + 3 mL = 63 mL/hour.

Fluid requirements assessed using this equation are often overestimated. The usual advice is to restrict fluid to 60% to 80% of the estimated value based on the equation, as children with sepsis often have water retention due to the presence of syndrome of inappropriate antidiuretic hormone. In contrast, insensible losses of water may be increased if the child has significant fever.

It is important to review fluids alongside regular formal review of hydration status, fluid balance, renal function, and serum electrolyte levels.

The National Institute for Health and Care Excellence (NICE) has published guidance on sepsis, as well as guidance on intravenous fluid administration in hospitalized children and infants.[50][114][Evidence B][Evidence C] The NICE guidelines on sepsis recommend that age, risk factor profile, and lactate measurement of a patient should guide fluid resuscitation.[50]

Plus – early administration of parenteral broad-spectrum antibiotics (stratified by age group as indicated below)

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Plus –

early administration of parenteral broad-spectrum antibiotics (stratified by age group as indicated below)

Treatment recommended for ALL patients in selected patient group

Early administration of antibiotics saves lives. Initiating antibiotics within one hour of recognition of suspected sepsis is one of the interventions under the Paediatric Sepsis Six care protocol.[59] The paediatric Surviving Sepsis Campaign guidelines strongly recommend that antibiotics should be given as soon as possible, and always within 1 hour of sepsis recognition if there are signs of septic shock.[6]

The Academy of Medical Royal Colleges (AOMRC) have recently issued a statement (May 2022; amended October 2022) recommending the assessment and management of paediatric sepsis be guided by the National Paediatric Early Warning Scoring Tool (PEWS).[117] This aims to balance the requirement for early antibiotic therapy with the emerging worldwide public health issue of antimicrobial resistance. If the child looks unwell or scores >9 they will continue to receive broad-spectrum antimicrobials within the first hour (alongside senior review and investigation to ascertain source of infection). The time frame extends to <3 hours for those scoring 5-8 and <4 hours for scoring 1-4. This is not a recommendation to delay antimicrobial administration unnecessarily, but to provide further time within protocols to investigate for potential sources of infection to guide targeted therapy and to prevent incorrect treatment of conditions that mimic sepsis. Unfortunately, many current protocols and performance metrics do not adequately differentiate between uncomplicated infection and sepsis, and allow insufficient time to distinguish sepsis from non-infective inflammatory syndromes.[123][124] This potentially promotes the unnecessary administration of broad spectrum antibiotics and contributes to antimicrobial resistance which is an emerging threat to global public health.[125]

Treatment with broad-spectrum antibiotic cover appropriate for the prevalent organisms for each age group and geographical area should be initiated (see examples of suitable empirical antibiotic regimens for specific age groups below). This should be changed to an appropriate narrow-spectrum antibiotic regimen once a causative pathogen is identified.[6]

An infectious disease specialist should be consulted if there are any unusual features to the case, or for advice on appropriate antimicrobial choice and length of treatment if the clinical condition is not improving.

Plus – early specialist consultation

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Plus –

early specialist consultation

Treatment recommended for ALL patients in selected patient group

Experienced senior clinicians or specialists should be involved and consulted early. Review by senior clinicians is one of the interventions that should take place within one hour of recognition of suspected sepsis under the Paediatric Sepsis Six care protocol.[59] A child death review in the UK has suggested that the most significant recurrent avoidable factor was a failure to recognise and/or failure to appreciate the history or clinical signs pointing to the severity of illness.[93][94] This most often occurred at the point of first contact between the sick (and often febrile) child and healthcare services. In many cases this leads to a critical delay in referral or treatment.

Consider – vasoactive support

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Consider –

vasoactive support

Additional treatment recommended for SOME patients in selected patient group

Peripheral intravenous or IO: dilute-strength vasoactive medications run through peripheral intravenous access are recommended prior to central line access in order not to delay therapy. Early use of vasoactive medications in fluid refractory shock has been shown to improve outcomes.[95][134]

Adrenaline (epinephrine) or noradrenaline (norepinephrine) are the preferred first line vasoactive agents. Dopamine may be substituted if adrenaline or noradrenaline are not readily available.[6]

Under the Paediatric Sepsis Six care protocol, consideration should be given to the need for early vasoactive support if normal physiological parameters are not restored after giving ≥20 mL/kg of fluids (or ≥10 mL/kg in neonates). Inform PICU or a regional centre at this stage urgently.[101]

If advanced haemodynamic monitoring is available, distinguishing vasoconstrictive ('cold') shock and vasodilatory ('warm') shock may be helpful to guide therapy.

Central intravenous or IO: in vasoconstrictive shock (defined as low cardiac output with high systemic vascular resistance or low cardiac output with low systemic vascular resistance), inotropes (such as milrinone, dobutamine, or levosimendan) should be given in addition to fluid titration and initial vasoactive agent (adrenaline, noradrenaline, or dopamine).

Central intravenous or IO: in vasodilatory shock (defined as a high cardiac output with low systemic vascular resistance), vasopressin-receptor agonists (vasopressin) should be given alongside fluid titration and initial vasoactive agent (adrenaline, noradrenaline, or dopamine).

Cardiac output should be monitored throughout. The use of focused echocardiography is becoming more widespread within paediatric intensive care units and may provide valuable information to differentiate vasodilatory shock from patients with a low cardiac output.[135]

If a patient becomes refractory to the vasopressor or inotrope they were initially responding to, re-evaluation is needed. An additional or substitute vasopressor or inotrope may be required.[6][95]

Primary options

adrenaline (epinephrine): 0.1 to 1 microgram/kg/min intravenous infusion initially, titrate dose according to response

noradrenaline (norepinephrine): 0.1 to 1 microgram/kg/min intravenous infusion initially, titrate dose according to response

Secondary options

dopamine: 1-5 micrograms/kg/min intravenous infusion initially, titrate dose according to response, usual dose range is 2-20 micrograms/kg/min; use caution when titrating dose in neonates

Tertiary options

dobutamine: 0.5 to 1 microgram/kg/min intravenous infusion initially, titrate dose according to response, usual dose range is 2-20 micrograms/kg/min

milrinone: consult specialist for guidance on dose

vasopressin: consult specialist for guidance on dose

levosimendan: consult specialist for guidance on dose

Consider – cardiac output monitoring

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Consider –

cardiac output monitoring

Additional treatment recommended for SOME patients in selected patient group

Subsequent intensive care support with therapy guided by advanced haemodynamic monitoring (such as cardiac output/cardiac index, systemic vascular resistance, or central venous oxygen saturation [Scvo2]) is recommended when this is available, alongside clinical assessment.[6][95]

There are no data from RCTs to support specific haemodynamic targets in children; however the Surviving Sepsis Campaign paediatric guideline panel members reported using mean arterial blood pressure (MAP) targets of either between the 5th and 50th percentile or greater than 50th percentile for age. RCTs to define optimal haemodynamic targets, including MAP, are urgently required to inform practice in paediatric sepsis.[6]

Other means of cardiac output monitoring include: central venous oxygen saturation (Scvo2), measured by blood gas analysis on a blood sample from the superior vena cava (SVC) through an indwelling central venous catheter; transoesophageal doppler ultrasound; ultrasound cardiac output monitoring; pulse index contour cardiac output monitoring.

Consider – further fluid balance maintenance

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Consider –

further fluid balance maintenance

Additional treatment recommended for SOME patients in selected patient group

In patients who cannot maintain an even fluid balance naturally following adequate fluid resuscitation, diuresis or renal replacement therapy (RRT) may be indicated.[6]

Fluid overload is common in critically ill children with haemodynamic instability and acute kidney injury, and it is important to monitor for clinical signs (e.g., pulmonary crepitations on auscultation, hepatomegaly, >10% weight increase from baseline).

Early diuretics and continuous RRT should be considered if fluid overload occurs. In the context of acute kidney injury and fluid overload, there is increasing evidence that early use of RRT and active management of fluid balance confers survival benefit.[115][116]

Venoarterial extracorporeal membrane oxygenation (ECMO) may be used as a rescue therapy in children with septic shock only if refractory to all other treatments.[6]

Consider – infection source control

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Consider –

infection source control

Additional treatment recommended for SOME patients in selected patient group

When there is the possibility of localised source of infection that is not likely to be treated by antibiotics alone, consideration should be given to instituting physical measures to remove the source of infection.

The principles of source control are the same for different age groups, although the practicalities may be different depending on the source of infection.

Examples of source control include: incision and drainage of abscess or infected fluid collections; debridement of infected soft tissue; removal of infected foreign bodies; removal of urinary catheter in cases of sepsis arising from the urinary tract; removal of percutaneous long lines or central lines in cases of central line-associated bloodstream infection; and laparotomy and resection of ischaemic bowel (or damage control surgery) in cases of necrotising enterocolitis.

Consider – blood transfusion

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Consider –

blood transfusion

Additional treatment recommended for SOME patients in selected patient group

Haemoglobin is essential for tissue oxygen delivery and important in the overall management of the septic child who is haemodynamically unstable (poor cardiac output, low mean arterial pressure) with impaired oxygen delivery. It is suggested that a haemoglobin concentration of >10 g/dL (approximate haematocrit of 0.3) should be maintained in these patients.

Once shock has resolved, a lower transfusion threshold may be appropriate. In a subgroup analysis of the TRIPICU (Transfusion Requirements in the Pediatric Intensive Care Unit) trial of children with haemodynamically stable sepsis showed no significant differences found in mortality, length of stay, or progressive organ failure between restrictive and liberal transfusion thresholds (haemoglobin <7 g/dL vs <9.5 g/dL, respectively).[141] There were, however, slightly more temporary protocol suspensions and transfusions in the restrictive group. In the TRISS (Transfusion Requirements in Septic Shock) trial, adult patients with septic shock showed no significant differences in mortality at 90 days, length of life support, and adverse events between transfusion thresholds of <7 g/dL and <9 g/dL.[142]

Information on the safety of restrictive transfusion thresholds in children with haemodynamic instability is lacking, particularly in septic shock, and transfusion to a goal of 10 g/dL to achieve signs of adequate oxygen delivery (ScvO₂ ≥70%) is currently recommended by the American College of Critical Care Medicine.[95]

Consider – corticosteroid

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Consider –

corticosteroid

Additional treatment recommended for SOME patients in selected patient group

Intravenous hydrocortisone is not recommended by the paediatric Surviving Sepsis Campaign guidelines to treat children with septic shock if fluid resuscitation and vasopressor therapy are able to restore haemodynamic stability, but can be considered in fluid-refractory and inotrope-resistant shock. No high-quality investigations currently support or refute the routine use of adjunctive corticosteroids for paediatric septic shock or sepsis-associated organ dysfunction. Evidence for their use has often been conflicting.[6][143] There is evidence for the use of hydrocortisone in fluid-refractory and inotrope-resistant shock with suspected or proven absolute adrenal insufficiency.[6][144]

early-onset neonatal sepsis (first 72 hours of life)

Plus – empirical antibiotic therapy

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Plus –

empirical antibiotic therapy

Treatment recommended for ALL patients in selected patient group

Administer within 1 hour of the identification of sepsis.[6][50][111]

Should cover group B streptococci and gram-negative bacilli.

Selection of regimen should be based on the clinical syndrome, underlying disease, drug intolerances, and local pathogen susceptibility. There is insufficient evidence to support any antibiotic regimen for early-onset neonatal sepsis being superior to another. Large randomised controlled trials are needed.[126]

An example of a suitable empirical antibiotic regimen is ampicillin plus gentamicin.[9] The National Institute for Health and Care Excellence recommends benzylpenicillin plus gentamicin.[83] This should be changed to an appropriate narrow-spectrum antibiotic regimen once a causative pathogen is identified.

It is good practice to review antibiotic therapy on a daily basis for clinical effect and de-escalate when appropriate. A 5- to 7-day course of intravenous antibiotics would suffice in most uncomplicated infections. In deep-seated or disseminated infections, or infections in immunocompromised patients, prolonged courses of antimicrobials may be required.

Primary options

ampicillin: 100-200 mg/kg/day intravenously given in divided doses every 6-12 hours (depending on age and weight); consult specialist for further guidance on dose

and

gentamicin: 4-5 mg/kg intravenously every 24-48 hours (depending on age and weight); consult specialist for further guidance on dose

benzylpenicillin sodium: 25-50 mg/kg intravenously every 12 hours (depending on age and weight); consult specialist for further guidance on dose

and

gentamicin: 4-5 mg/kg intravenously every 24-48 hours (depending on age and weight); consult specialist for further guidance on dose

Consider – antiviral therapy

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Consider –

antiviral therapy

Additional treatment recommended for SOME patients in selected patient group

Cover for herpes simplex virus (e.g., aciclovir) should be considered in sepsis or if indicated from the patient history. Herpes simplex virus type 1 (HSV-1) infection may be acquired at birth from mothers with an active infection. Congenital HSV-1 infection can be severe and devastating; therefore, treatment should be started before test results are available in these patients.

Primary options

aciclovir: 20 mg/kg intravenously every 8 hours

Consider – nystatin

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Consider –

nystatin

Additional treatment recommended for SOME patients in selected patient group

The practice of providing antifungal prophylaxis while receiving antibiotic therapy varies between institutions. However, neonates may be given oral nystatin to help prevent candidiasis.[83]

Primary options

nystatin: 100,000 units (1 mL) orally four times daily

Consider – prostaglandin

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Consider –

prostaglandin

Additional treatment recommended for SOME patients in selected patient group

Septic shock is difficult to differentiate from other forms of shock in the premature neonate and newborn infant. Any neonate less than 72 hours old presenting with signs of cardiogenic shock (e.g., poor perfusion, cyanosis, heart murmur, hepatomegaly, differential pulse volume and limb pressure between upper and lower limbs) should be started on a prostaglandin (i.e., alprostadil) infusion under expert guidance until a duct-dependent cardiac lesion can be ruled out.

Alprostadil can cause apnoea above a certain dose. Dinoprostone is used in some countries for the maintenance of ductal patency.

Primary options

alprostadil: 0.05 to 0.1 micrograms/kg/min intravenous infusion initially, titrate to response, maximum 0.4 micrograms/kg/min

Secondary options

dinoprostone: consult specialist for guidance on dose

late-onset neonatal sepsis (72 hours of life to 1 month)

Plus – empirical antibiotic therapy

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Plus –

empirical antibiotic therapy

Treatment recommended for ALL patients in selected patient group

Administer within 1 hour of the identification of sepsis.[6][50][111]

Should cover coagulase-negative staphylococci, group B streptococci, and gram-negative bacteria.

Selection of regimen should be based on the clinical syndrome, underlying disease, drug intolerances, and local pathogen susceptibility. There is insufficient evidence to support any antibiotic regimen for late-onset neonatal sepsis being superior to another. Large randomised controlled trials are needed.[151]

Examples of suitable empirical antibiotic regimens include ampicillin plus gentamicin or cefotaxime, or vancomycin plus gentamicin or cefotaxime. This should be changed to an appropriate narrow-spectrum antibiotic regimen once a causative pathogen is identified.

Ampicillin covers Listeria monocytogenes. Cefotaxime covers group B streptococci, Escherichia coli, and enterococci. Gentamicin covers gram-negative bacteria. Vancomycin covers coagulase-negative staphylococci and can replace ampicillin in hospital-acquired infections.

Primary options

ampicillin: 100-200 mg/kg/day intravenously given in divided doses every 6-12 hours (depending on age and weight); consult specialist for further guidance on dose

-- AND --

gentamicin: 4-5 mg/kg intravenously every 24-48 hours (depending on age and weight); consult specialist for further guidance on dose

cefotaxime: 100-150 mg/kg/day intravenously given in divided doses every 8-12 hours (depending on age and weight); consult specialist for further guidance on dose

vancomycin: 10-15 mg/kg intravenously every 8-24 hours (depending on age and weight); consult specialist for further guidance on dose

-- AND --

gentamicin: 4-5 mg/kg intravenously every 24-48 hours (depending on age and weight); consult specialist for further guidance on dose

cefotaxime: 100-150 mg/kg/day intravenously given in divided doses every 8-12 hours (depending on age and weight); consult specialist for further guidance on dose

Consider – antibiotic cover for Pseudomonas

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Consider –

antibiotic cover for Pseudomonas

Additional treatment recommended for SOME patients in selected patient group

Pseudomonas (usually hospital acquired) is treated with ceftazidime or piperacillin/tazobactam in addition to the empirical regimen. However, some physicians may advocate using either of these antibiotics as monotherapy as the spectrum of cover overlaps with the empirical regimen. An infectious disease specialist should be consulted.

Primary options

ceftazidime: 50 mg/kg intravenously every 8-12 hours (depending on age and weight); consult specialist for further guidance on dose

piperacillin/tazobactam: 75-100 mg/kg intravenously every 6-12 hours (depending on age and weight); consult specialist for further guidance on dose

Consider – antibiotic cover for anaerobes/necrotising enterocolitis

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Consider –

antibiotic cover for anaerobes/necrotising enterocolitis

Additional treatment recommended for SOME patients in selected patient group

Treatment of choice is metronidazole or clindamycin in addition to the empirical regimen.

Primary options

metronidazole: 7.5 mg/kg intravenously every 24-48 hours, or 15 mg/kg intravenously every 12-24 hours (depending on age and weight); consult specialist for further guidance on dose

clindamycin: 5 mg/kg intravenously every 6-12 hours (depending on age and weight); consult specialist for further guidance on dose

Consider – antifungal therapy

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Consider –

antifungal therapy

Additional treatment recommended for SOME patients in selected patient group

The practice of providing antifungal prophylaxis while receiving antibiotic therapy varies between institutions. However, neonates may be given oral nystatin to help prevent candidiasis.[83]

Patients may require prolonged treatment with intravenous fluconazole or liposomal amphotericin-B if invasive fungal infection is suspected or confirmed. Antifungal treatment should be given in addition to empirical antibiotics in very low birth weight infants (i.e., <1500 g) and immunocompromised patients with suspected sepsis.

Primary options

nystatin: 100,000 units (1 mL) orally four times daily

fluconazole: 6-12 mg/kg intravenously every 24-72 hours; consult specialist for further guidance on dose

amphotericin B liposomal: 3-5 mg/kg intravenously every 24 hours; consult specialist for further guidance on dose

Consider – antiviral therapy

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Consider –

antiviral therapy

Additional treatment recommended for SOME patients in selected patient group

Cover for herpes simplex virus (e.g., aciclovir) should be considered in sepsis or if indicated from the patient history or investigative tests.[60]

Primary options

aciclovir: 20 mg/kg intravenously every 8 hours

infants and children (>1 month)

Plus – empirical antibiotic therapy

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Plus –

empirical antibiotic therapy

Treatment recommended for ALL patients in selected patient group

Administer within 1 hour of the identification of sepsis.[6][50][111]

Should cover Staphyloccus, Streptococcus, N meningitides, and Haemophilus influenzae.

Selection of regimen should be based on the clinical syndrome, underlying disease, drug intolerances, and local pathogen susceptibility.

For community-acquired infection, a third-generation cephalosporin (e.g., cefotaxime, ceftriaxone) is a suitable first-line option. For hospital-acquired infection, an extended-spectrum penicillin (e.g., piperacillin/tazobactam) or a carbapenem (e.g., meropenem) may be used. Additional broadening of this cover (e.g., with gentamicin or vancomycin) may be considered depending on case-specific factors.[127] This can be changed to an appropriate narrow-spectrum antibiotic regimen once a causative pathogen is identified. Meropenem provides broad-spectrum cover against both gram-positive and gram-negative bacteria, including Pseudomonas. In children without immune compromise and without high risk for multidrug-resistant pathogens, routine use of multiple empiric antimicrobials directed against the same pathogen is not recommended.[6]

In neutropenic patients, piperacillin/tazobactam or meropenem are considered first-line agents. The National Institute for Health and Care Excellence supports the use of piperacillin/tazobactam as a first-line agent with escalation to a carbapenem such as meropenem if there is clinical deterioration (e.g., shock).[128]

Primary options

cefotaxime: 150-200 mg/kg/day intravenously given in divided doses every 6-8 hours

ceftriaxone: 100 mg/kg/day intravenously given in divided doses every 12-24 hours

piperacillin/tazobactam: 300-400 mg/kg/day intravenously given in divided doses every 6-8 hours

meropenem: 60 mg/kg/day intravenously given in divided doses every 8 hours

Consider – antibiotic cover for gram-negative bacteria

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Consider –

antibiotic cover for gram-negative bacteria

Additional treatment recommended for SOME patients in selected patient group

Gentamicin or ciprofloxacin are sometimes recommended in addition to the empirical regimen to provide additional cover for gram-negative bacteria if necessary;[127] however, local advice from an infectious disease specialist should be sought. Ciprofloxacin resistance is increasing in some areas, and safety issues should be considered.

Primary options

gentamicin: 2.5 mg/kg intravenously every 8 hours; or 5 to 7.5 mg/kg intravenously once daily

Secondary options

ciprofloxacin: 20-30 mg/kg/day intravenously given in divided doses every 12 hours

Consider – antibiotic cover for coagulase-negative staphylococci and/or MRSA

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Consider –

antibiotic cover for coagulase-negative staphylococci and/or MRSA

Additional treatment recommended for SOME patients in selected patient group

Vancomycin is recommended in addition to the empirical regimen to cover vascular catheter-associated coagulase-negative staphylococci and/or MRSA . It is also recommended in patients with neutropenia to treat line sepsis, although this is not usually indicated as first-line therapy unless there are signs of line-related sepsis.[128]

Teicoplanin may also be used for this indication.

Primary options

vancomycin: 15 mg/kg intravenously every 6 hours; loading dose may be considered in seriously ill children

teicoplanin: 10 mg/kg intravenously every 12 hours for 3 doses initially, followed by 10 mg/kg once daily thereafter

Consider – antibiotic cover for toxic shock

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Consider –

antibiotic cover for toxic shock

Additional treatment recommended for SOME patients in selected patient group

Clindamycin should be used in addition to the empirical regimen for toxin-induced toxic shock syndromes with refractory hypotension.[6]

Primary options

clindamycin: 30-40 mg/kg/day intravenously given in divided doses every 6-8 hours

Consider – antifungal therapy

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Consider –

antifungal therapy

Additional treatment recommended for SOME patients in selected patient group

Patients with neutropenia are at high risk of invasive fungal infection and should receive appropriate antifungal cover with intravenous fluconazole or liposomal amphotericin-B.

Primary options

fluconazole: 6-12 mg/kg intravenously every 24 hours

amphotericin B liposomal: 3-5 mg/kg intravenously every 24 hours

Consider – antiviral therapy

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Consider –

antiviral therapy

Additional treatment recommended for SOME patients in selected patient group

Cover for herpes simplex virus (e.g., aciclovir) should be considered in sepsis or if indicated from the patient history or investigative tests.[60]

For patients with sepsis complicating an influenza-like illness during the local influenza season, empirical antiviral therapy (e.g., oseltamivir) should be given while awaiting respiratory virus testing.

Primary options

aciclovir: infants <3 months of age: 20 mg/kg intravenously every 8 hours; infants ≥3 months of age: 250-500 mg/square metre of body surface area intravenously every 8 hours

oseltamivir: children <1 year of age: consult specialist for guidance on dose; children ≥1 year of age and body weight ≤15 kg: 30 mg orally twice daily for 5 days; 16-23 kg: 45 mg orally twice daily for 5 days; 24-40 kg: 60 mg orally twice daily for 5 days; >40 kg: 75 mg orally twice daily for 5 days

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Sepsis in children

Treatment algorithm

presumed or confirmed sepsis

prompt recognition and airway management and temperature control

Primary options

intravenous or intraosseous (IO) access and blood tests

intravenous fluids

early administration of parenteral broad-spectrum antibiotics (stratified by age group as indicated below)

early specialist consultation

vasoactive support

Primary options

Secondary options

Tertiary options

cardiac output monitoring

further fluid balance maintenance

infection source control

blood transfusion

corticosteroid

empirical antibiotic therapy

Primary options

antiviral therapy

Primary options

nystatin

Primary options

prostaglandin

Primary options

Secondary options

empirical antibiotic therapy

Primary options

antibiotic cover for Pseudomonas

Primary options

antibiotic cover for anaerobes/necrotising enterocolitis

Primary options

antifungal therapy

Primary options

antiviral therapy

Primary options

empirical antibiotic therapy

Primary options

antibiotic cover for gram-negative bacteria

Primary options

Secondary options

antibiotic cover for coagulase-negative staphylococci and/or MRSA

Primary options

antibiotic cover for toxic shock

Primary options

antifungal therapy

Primary options

antiviral therapy

Primary options