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Management and outcome of sepsis in term and late preterm neonates

Management and outcome of sepsis in term and late preterm neonates
Authors:
Joseph B Cantey, MD, MPH
Morven S Edwards, MD
Section Editors:
Sheldon L Kaplan, MD
Joseph A Garcia-Prats, MD
Deputy Editor:
Carrie Armsby, MD, MPH
Literature review current through: Dec 2022. | This topic last updated: Oct 24, 2022.

INTRODUCTION — Sepsis is an important cause of morbidity and mortality among newborn infants. Although the incidence of sepsis in term and late preterm neonates is low, the potential for serious adverse outcomes, including death, is of such great consequence that caregivers should have a low threshold for evaluation and treatment for possible sepsis in neonates. The approach discussed below is generally consistent with guidelines published by the American Academy of Pediatrics and the Centers for Disease Control and Prevention [1,2].

The treatment and outcome of sepsis in term and late preterm neonates will be reviewed here. The epidemiology, clinical features, diagnosis, and evaluation of sepsis in term and late preterm neonates are discussed separately. (See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates".)

Other related topics include:

Sepsis in preterm neonates (see "Clinical features and diagnosis of bacterial sepsis in preterm infants <34 weeks gestation" and "Treatment and prevention of bacterial sepsis in preterm infants <34 weeks gestation")

Group B streptococcal (GBS) infection in neonates and infants, including management of well-appearing newborns at risk for GBS (see "Group B streptococcal infection in neonates and young infants" and "Management of neonates at risk for early-onset group B streptococcal infection")

Outpatient evaluation and management of febrile neonates (see "The febrile neonate (28 days of age or younger): Outpatient evaluation and initial management")

Evaluation and management of ill-appearing infants (see "Approach to the ill-appearing infant (younger than 90 days of age)")

TERMINOLOGY — The following terms will be used throughout this discussion on neonatal sepsis:

Term neonates are those born at a gestational age of 37 weeks or greater.

Late preterm neonates (also called near-term neonates) are those born from 34 through 36 completed weeks of gestation [3]. (See "Late preterm infants".)

Neonatal sepsis is a clinical syndrome in an infant 28 days of life or younger, manifested by systemic signs of infection and isolation of a bacterial pathogen from the bloodstream. A consensus definition for neonatal sepsis is lacking [4]. (See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates", section on 'Diagnosis'.)

Sepsis is classified according to the neonate's age at the onset of symptoms.

Early-onset sepsis is defined as the onset of symptoms before 72 hours of age [1,5,6], although some experts extend the definition to infections occurring within the first seven days after birth.

Late-onset sepsis is generally defined as the onset of symptoms at ≥72 hours of age [5]. Similar to early-onset sepsis, there is variability in its definition, ranging from an onset at >72 hours of life to ≥7 days of age.

Newborn infants with early-onset sepsis typically present with symptoms during their birth hospitalization. Term neonates with late-onset sepsis generally present to the outpatient setting or emergency department unless comorbid conditions have prolonged the birth hospitalization. The approach to the evaluation and initial management of febrile neonates in the outpatient setting is discussed separately. (See "The febrile neonate (28 days of age or younger): Outpatient evaluation and initial management", section on 'Neonates 8 to 21 days old'.)

SUPPORTIVE CARE — Symptomatic neonates should be treated in a care setting with full cardiopulmonary monitoring and support because the clinical course of these neonates can deteriorate rapidly. Although there are no data demonstrating the importance of supportive care measures in neonates with sepsis, it is generally accepted that the following supportive measures are critical components of management:

Maintaining adequate oxygenation and perfusion (see "Respiratory support, oxygen delivery, and oxygen monitoring in the newborn" and "Neonatal shock: Management")

Prevention of hypoglycemia and metabolic acidosis (see "Management and outcome of neonatal hypoglycemia")

Maintenance of normal fluid and electrolyte status (see "Fluid and electrolyte therapy in newborns")

Severely ill patients may require ventilatory, volume, and/or vasopressor support to maintain adequate oxygenation and perfusion. (See "Overview of mechanical ventilation in neonates" and "Neonatal shock: Etiology, clinical manifestations, and evaluation".)

ONGOING DIAGNOSTIC EVALUATION

Other diagnostic considerations – In neonates with suspected sepsis, additional testing for other conditions may be warranted based on clinical signs and symptoms. Signs and symptoms of neonatal sepsis are often nonspecific, as summarized in the table (table 1). It may be difficult to differentiate neonatal sepsis from other diseases; however, given the morbidity and mortality of neonatal sepsis, empiric antibiotic therapy should be provided (after cultures are obtained) to neonates with suspected sepsis, pending definitive culture-based diagnosis. Alternative diagnoses should be entertained when a neonate with suspected sepsis has negative cultures. The differential diagnosis is summarized in the table (table 1) and discussed in greater detail separately. (See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates", section on 'Differential diagnosis'.)

Lumbar puncture – If not done during the initial evaluation, a lumbar puncture should be performed in neonates with culture-proven or culture-negative clinical sepsis, whenever possible. Clinical signs suggesting meningitis can be lacking. (See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates", section on 'Lumbar puncture'.)

ANTIBIOTIC THERAPY

Whom to treat — The decision to start antibiotic therapy is based on assessment of risk factors, clinical evaluation, and laboratory tests. Indications for empiric antibiotic therapy include (see "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates", section on 'Evaluation and initial management'):

Ill appearance (see "Approach to the ill-appearing infant (younger than 90 days of age)")

Concerning symptoms, including temperature instability or respiratory, cardiocirculatory, or neurologic symptoms (see "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates", section on 'Clinical manifestations')

High estimated sepsis risk based on a validated risk calculator (see "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates", section on 'Early-onset sepsis calculator')

Cerebrospinal fluid (CSF) pleocytosis (white blood cell count of >20 to 30 cells/microL) (table 2) (see "Bacterial meningitis in the neonate: Clinical features and diagnosis", section on 'Interpretation of cerebrospinal fluid')

Positive blood, urine, or CSF culture (see "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates", section on 'Blood culture')

Initial empiric therapy — The initial choice of parenteral antimicrobials for suspected sepsis depend on the neonate's age, likely pathogens, susceptibility patterns of organisms in a particular nursery, and presence of an apparent source of infection (eg, skin, joint, or bone involvement) (table 3).

Early-onset sepsis

Preferred empiric regimen – Our suggested empiric regimen for suspected early-onset sepsis (ie, age <72 hours) consists of ampicillin plus gentamicin.

Dosing – For term and late preterm newborns <72 hours old, dosing for these agents is as follows [5,7-9]:

Ampicillin 100 mg/kg/dose intravenously (IV) every eight hours

Gentamicin 4 mg/kg/dose IV every 24 hours

Monitoring – We generally obtain baseline renal function tests (ie, blood urea nitrogen [BUN] and creatinine levels) at the initiation of treatment with gentamicin. Serum gentamicin levels are not required if a treatment course of ≤48 hours is anticipated and renal function is normal; however, levels should be obtained in neonates receiving a full course of gentamycin therapy [7,10].

Rationale and supporting evidence – The combination of ampicillin and gentamicin is effective in treating most common pathogens that cause early-onset sepsis, including group B Streptococcus (GBS), Listeria, Enterococcus, and most isolates of Escherichia coli (table 4) [1,11].

In the available studies from the contemporary era, >90 percent of isolates from culture-proven, early-onset neonatal sepsis were susceptible to ampicillin, gentamicin, or both [12-14].

Ampicillin and gentamicin are preferred over ampicillin and a third-generation cephalosporin (eg, cefotaxime or ceftriaxone), based upon the following:

The regimen of ampicillin and a third-generation cephalosporin is not more effective than the combination of ampicillin and gentamicin [15].

The emergence of cephalosporin-resistant gram-negative organisms (eg, Enterobacter cloacae, Klebsiella, and Serratia species) can occur when cephalosporins are used routinely [16].

Ampicillin and gentamicin are synergistic in treating infections caused by GBS and Listeria monocytogenes. Cephalosporins are not active against L. monocytogenes.

In a large cohort study, neonates who received ampicillin plus cefotaxime had a 1.5-fold increase in mortality compared with those treated with ampicillin plus gentamicin (4.2 versus 1.9 percent; adjusted odds ratio 1.5, 95% CI 1.4-1.7) [15].

Ceftriaxone is highly bound to albumin and appears to displace bilirubin [17,18]. Although displacement of free bilirubin by ceftriaxone has not been reported, it is advisable to avoid ceftriaxone in neonates at risk for acute bilirubin encephalopathy.

Role of expanded-spectrum cephalosporins – An expanded-spectrum cephalosporin (eg, cefotaxime [where available], ceftazidime, or cefepime) should be added to the regimen for neonates with any of the following:

Critical illness

Risk factors associated with ampicillin resistance (ie, maternal colonization with multidrug-resistant organisms and/or prolonged antenatal maternal ampicillin treatment)

Suspected meningitis (see 'Coverage for focal sources of infection' below)

Late-onset sepsis — The choice of empiric therapy for late-onset sepsis (age ≥72 hours) depends upon whether the neonate is admitted from the community and thus is at lower risk for infection caused by a multidrug-resistant pathogen or is hospitalized since birth and thus at a higher risk.

Admitted from the community — Neonates admitted from the community are at lower risk for infection caused by a multidrug-resistant pathogen compared with those who remain hospitalized since birth.

Empiric regimen – Acceptable empiric regimens for late-onset sepsis without an apparent focus of infection in this setting include (table 3) [5]:

Ampicillin plus gentamicin, or

Ampicillin plus an expanded-spectrum cephalosporin (eg, cefotaxime [if available], ceftazidime, or cefepime)

The preferred regimen is generally ampicillin plus gentamicin; however, local antibiotic resistance patterns must be considered.

Dosing – Dosing depends on postnatal age:

For newborns 3 to ≤7 days old [5,7-9]:

-Ampicillin 100 mg/kg/dose IV every eight hours

-Gentamicin 4 mg/kg/dose IV every 24 hours

For newborns >7 days old [5,7-9]:

-Ampicillin 75 mg/kg/dose IV every six hours

-Gentamicin 5 mg/kg/dose IV every 24 hours

Monitoring – We generally obtain baseline BUN and creatinine levels at the initiation of treatment with gentamicin. Serum gentamicin levels are not required if a treatment course of ≤48 hours is anticipated and renal function is normal; however, levels should be obtained in neonates receiving a full course of gentamycin therapy [7,10].

Supporting evidence – In a national surveillance study (2006 to 2008), 96 percent of isolates from late-onset bacteremia were susceptible to the combination of amoxicillin and gentamicin [12].

Role of expanded-spectrum cephalosporins – The addition of an expanded-spectrum cephalosporin (eg, cefotaxime [where available], ceftazidime, or cefepime) to an ampicillin and gentamicin regimen is warranted for critically ill neonates and those with suspected meningitis. (See 'Coverage for focal sources of infection' below.)

Hospitalized since birth — Neonates who continue to be hospitalized since birth are at higher risk for resistant organisms.

Empiric regimen – Our suggested empiric regimen for suspected hospital-acquired late-onset sepsis (ie, age ≥72 hours) consists of vancomycin plus gentamicin (table 3).

In centers that routinely screen for methicillin-resistant Staphylococcus aureus (MRSA) colonization, a semisynthetic penicillin (eg, oxacillin or nafcillin) can be substituted for vancomycin if the neonate is not critically ill and the MRSA screen is negative. Oxacillin and nafcillin are superior to vancomycin for the treatment of methicillin-susceptible S. aureus (MSSA) [19]. Vancomycin should be included in the empiric regimen for neonates who are MRSA-colonized and/or critically ill at presentation [20].

Vancomycin dosing – The initial IV loading dose of vancomycin is 20 mg/kg; subsequent dosing depends on serum creatinine (Scr) [9]:

Scr <0.7 mg/dL – 15 mg/kg/dose IV every 12 hours

Scr 0.7 to 0.9 mg/dL – 20 mg/kg/dose IV every 24 hours

Scr 1 to 1.2 mg/dL – 15 mg/kg/dose IV every 24 hours

Scr 1.3 to 1.6 mg/dL – 10 mg/kg/dose IV every 24 hours

Scr >1.6 mg/dL – 15 mg/kg/dose IV every 48 hours

Alternative neonatal dosing recommendations for vancomycin based on weight and gestational age are available (refer to Lexicomp pediatric drug information) [8]. Continuous infusion dosing regimens have also been described, but further clinical trials are needed before this method can be employed routinely. Continuous infusion may be associated with earlier attainment of target concentrations and lower total daily dose compared with intermittent dosing [21,22]; however, it is unclear whether this results in more rapid clearance of infection compared with standard dosing. Most studies on continuous vancomycin infusion have focused on MRSA infections. The importance of achieving a particular vancomycin exposure for successful treatment of coagulase-negative staphylococci infections is not well established.

Gentamicin dosing Gentamicin is given at a dose of 4 mg/kg/dose (for newborns ≤7 days old) or 5 mg/kg/dose (for newborns ≤7 days old) IV every 24 hours [5,7-9].

Serum gentamicin levels are not required if a treatment course of ≤48 hours is anticipated and renal function is normal; however, levels should be obtained in neonates receiving a full course of gentamycin therapy [7,10].

Coverage for focal sources of infection — For neonates with an apparent focal source of infection, the empiric antibiotic regimen is modified as follows (table 3):

Suspected meningitis – In neonates with late-onset sepsis in whom the lumbar puncture suggests meningitis (eg, CSF pleocytosis), an expanded-spectrum cephalosporin (eg, cefotaxime [where available], ceftazidime, or cefepime) should be included in the regimen. Adding an expanded-spectrum cephalosporin to the regimen of ampicillin and gentamicin broadens empiric coverage for gram-negative organisms and provides optimal activity in the CSF against pneumococci. If there is concern for meningitis caused by a multidrug-resistant, gram-negative organism, a carbapenem (eg, meropenem) is the preferred agent for empiric therapy [23]. Treatment of bacterial meningitis in neonates is discussed in detail separately. (See "Bacterial meningitis in the neonate: Treatment and outcome", section on 'Empiric therapy'.)

Suspected pneumonia – Empiric regimens for the treatment of neonates with a pulmonary focus of infection include ampicillin and gentamicin, ampicillin and an extended-spectrum cephalosporin, vancomycin and an extended-spectrum cephalosporin, or vancomycin and gentamicin. Empiric therapy for neonatal pneumonia is discussed in detail separately. (See "Neonatal pneumonia", section on 'Initial empiric therapy'.)

Skin, soft tissue, bone, and joint infections – If there is a focus of infection involving the skin, umbilicus, soft tissues, bone, or joints (in which case, S. aureus is a likely pathogen), oxacillin, nafcillin, or vancomycin should be substituted for ampicillin [24]. In a toxic-appearing neonate, a semisynthetic penicillin (eg, oxacillin/nafcillin) can be used in combination with vancomycin. (See "Suspected Staphylococcus aureus and streptococcal skin and soft tissue infections in neonates: Evaluation and management", section on 'Antimicrobial therapy'.)

Catheter-related infection – If intravascular catheter-related infection is a concern, treatment should be initiated with vancomycin and gentamicin to provide empiric coverage for coagulase-negative staphylococci, S. aureus, and gram-negative bacteria. (See "Intravascular non-hemodialysis catheter-related infection: Treatment", section on 'Empiric antibiotic therapy'.)

Suspected intestinal source – If infection is thought to arise from the gastrointestinal tract, the empiric regimen should include coverage for anaerobic bacteria (eg, with piperacillin/tazobactam, metronidazole, or clindamycin). (See "Neonatal necrotizing enterocolitis: Management", section on 'Choice and duration of antibiotic regimen'.)

Culture-proven sepsis — In neonates with culture-proven sepsis, the usual course of therapy is 10 days [10,25]. Longer treatment courses may be warranted if a specific focus of infection is identified (eg, meningitis, osteomyelitis, or septic arthritis). Antimicrobial therapy should be altered based upon the susceptibility profile of the pathogen isolated.

Pathogen-specific therapy — For the most common causative organisms of neonatal sepsis, antimicrobial therapy is as follows (table 3):

Group B Streptococcus — The drug of choice for GBS is penicillin. Thus, when GBS is identified and resolution of bacteremia is documented by a repeat blood culture and, in neonates with meningitis, the CSF is sterile, we recommend discontinuing gentamicin and continuing therapy with penicillin G alone (table 5). (See "Group B streptococcal infection in neonates and young infants", section on 'Definitive therapy'.)

Escherichia coli — In patients with ampicillin-sensitive E. coli sepsis who have improved clinically and in whom meningitis has been excluded, ampicillin monotherapy is administered for a 10-day course.

For patients with ampicillin-resistant E. coli, the choice of definitive therapy is based upon the susceptibility profile. An expanded-spectrum cephalosporin (eg, cefotaxime [where available], ceftazidime, or cefepime) is often employed if the isolate is susceptible.

Other gram-negative bacilli — Antimicrobial treatment of infections caused by Klebsiella, Proteus, Enterobacter, Serratia, Pseudomonas, Salmonella, or Shigella should be selected based upon the susceptibility profile of the organism. Single-agent therapy is sufficient in most cases.

Infections caused by multidrug-resistant, gram-negative bacilli, including those caused by extended-spectrum beta-lactamase-producing organisms or those with hyperproduction of beta-lactamases, should be treated with meropenem.

Listeria monocytogenes — The combination of ampicillin and gentamicin is used for initial therapy. Treatment with both agents is more effective than ampicillin alone in vitro and in animal models of Listeria infection. Cephalosporins are not active against L. monocytogenes. Duration of therapy usually is 10 days. (See "Treatment and prevention of Listeria monocytogenes infection", section on 'Antibiotic therapy'.)

Staphylococcus species — Directed therapy for infection caused by staphylococci is determined by the sensitivity of the isolate to specific antibiotic agents:

S. aureusVancomycin or, in a toxic-appearing neonate, vancomycin plus nafcillin, should be employed for S. aureus infection until the susceptibility profile is available. The regimen then should be adjusted according to the susceptibility profile:

MSSA – Treatment of MSSA infection should be completed with oxacillin or nafcillin. Cefazolin is an alternative for treatment of most MSSA infections outside of the central nervous system and not involving endocarditis. (See "Staphylococcus aureus bacteremia in children: Management and outcome".)

MRSA – Treatment should be completed with vancomycin. (See "Staphylococcus aureus in children: Overview of treatment of invasive infections", section on 'Treatment of neonates'.)

Coagulase-negative staphylococci – Coagulase-negative staphylococcal infections require treatment with vancomycin.

Probable but unproven sepsis — In neonates with a negative blood culture but a clinical status that remains concerning for a systemic infection (eg, ongoing temperature instability; ongoing respiratory, cardiocirculatory, or neurologic symptoms not explained by other conditions; or laboratory abnormalities suggestive of sepsis), antibiotic therapy can be extended for as long as a total of 5 to 10 days.

After 36 to 48 hours, the empiric regimen is altered based upon whether meningitis has been excluded:

If meningitis has been excluded, the ampicillin dosing regimen can be reduced to 100 mg/kg/dose IV every 12 hours in neonates <7 days old or 50 mg/kg/dose IV every six hours in neonates ≥7 days old [8].

If a lumbar puncture has not been performed, ampicillin should be continued at a meningitic dose.

Management of neonates with CSF pleocytosis and/or positive CSF culture is discussed separately. (See "Bacterial meningitis in the neonate: Treatment and outcome".)

Alternative diagnoses should also be entertained when a neonate with suspected sepsis has negative cultures (table 1). Antibiotics should be discontinued if another diagnosis is established. (See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates", section on 'Differential diagnosis'.)

Infection unlikely — Empiric antibiotics are initiated in many neonates with maternal risk factors, abnormal laboratory values, and/or mild to moderate symptoms that subsequently resolve. Sepsis is unlikely in these neonates if they remain well and the blood culture is sterile at 36 to 48 hours. Empiric antibiotic therapy should be discontinued after 36 to 48 hours in these neonates unless there is evidence of site-specific infection [1,26].

Response to therapy — In most cases, symptomatic neonates with proven sepsis improve clinically within 24 to 48 hours.

In neonates with bacteremia, a repeat blood culture should be obtained after 24 to 48 hours of therapy to document sterility. Failure to sterilize the bloodstream suggests that the antimicrobial(s) chosen are not active against the infecting pathogen or that there is an unrecognized focus of infection. Consultation with a pediatric infectious disease specialist may be warranted.

ADJUNCTIVE THERAPIES — The following adjunctive immunotherapeutic interventions have been studied in neonatal sepsis but should not be routinely administered, because they have not been shown to conclusively improve outcomes [27-29]:

Intravenous immune globulin (IVIG) infusions [30,31]

Granulocyte transfusions [32]

Granulocyte and granulocyte-macrophage colony-stimulating factor (G-CSF and GM-CSF) [33,34]

Pentoxifylline [35]

Most of the studies investigating these therapies involved preterm neonates. These data are discussed in greater detail separately. (See "Treatment and prevention of bacterial sepsis in preterm infants <34 weeks gestation", section on 'Adjunct therapy to antibiotics'.)

PREVENTION — The primary intervention to prevent neonatal sepsis is the use of intrapartum antibiotic prophylaxis (IAP) in mothers with group B streptococcal (GBS) colonization and other risk factors. Although IAP has resulted in a decrease in the incidence of early-onset GBS invasive neonatal infection, it has not had a similar impact on the rate of late-onset GBS disease. (See "Prevention of early-onset group B streptococcal disease in neonates" and "Group B streptococcal infection in neonates and young infants", section on 'Epidemiology'.)

Other modifiable risk factors for late-onset sepsis include:

Indwelling catheters and other devices (eg, central venous catheters, endotracheal tubes, bladder catheters)

Gastric acid-blocking agents

Postnatal glucocorticoids

Use of these devices and pharmacologic agents should be reassessed often to determine if they can be safely discontinued.

Comprehensive prevention of neonatal sepsis will require a multi-interventional program including effective maternal vaccination, reduction in preterm delivery, limited exposure of term neonates to potential pathogens, antimicrobial stewardship, and enhanced infection control and prevention techniques. (See "Vaccines for the prevention of group B streptococcal disease".)

Probiotics and lactoferrin have been investigated as potential preventative interventions in preterm neonates [36,37]; however, neither approach has been conclusively proven to reduce the risk of sepsis, and these interventions are not routinely used in clinical practice. These data are discussed in greater detail separately. (See "Treatment and prevention of bacterial sepsis in preterm infants <34 weeks gestation", section on 'Potential prophylactic therapy'.)

OUTCOME — Overall mortality in term and late preterm neonates with neonatal sepsis is approximately 2 to 3 percent [15,38]. Mortality estimates vary depending on the gestational age (lower gestational age is associated with higher mortality), pathogen (gram-negative and fungal pathogens are associated with higher mortality than gram-positive infections), and sepsis definition (lower mortality rates tend to be reported if neonates with culture-negative clinical sepsis are included compared with cases of culture-proven sepsis only).

Mortality rates for group B streptococcal (GBS) sepsis in term neonates after the introduction of intrapartum antibiotic prophylaxis (IAP) and routine use of empirical antibiotic therapy range from 2 to 3 percent for early-onset disease and 1 to 2 percent for late-onset disease. The risk of mortality is higher in neonates with birth weight <2500 g, absolute neutrophil count <1500 cells/microL, hypotension, apnea, and pleural effusion [39]. (See "Group B streptococcal infection in neonates and young infants", section on 'Outcome'.)

The risk of mortality is particularly high in neonates with early-onset sepsis caused by E. coli. Estimated mortality rates for term neonates with E. coli sepsis are 6 to 10 percent [11,40,41].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Sepsis in neonates" and "Society guideline links: Group B streptococcal infection in pregnant women and neonates".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Sepsis in newborn babies (The Basics)")

SUMMARY AND RECOMMENDATIONS

Importance – Although the incidence of sepsis in term and late preterm neonates is low, the potential for serious adverse outcomes, including death, is of such great consequence that care providers should have a low threshold for evaluation and treatment for possible sepsis. (See 'Introduction' above.)

Supportive care – Symptomatic neonates should be treated in a care setting with full cardiopulmonary monitoring and support because neonates with sepsis can deteriorate rapidly. Supportive care includes (see 'Supportive care' above):

Maintaining adequate oxygenation and perfusion (see "Respiratory support, oxygen delivery, and oxygen monitoring in the newborn" and "Neonatal shock: Management")

Prevention of hypoglycemia and metabolic acidosis (see "Management and outcome of neonatal hypoglycemia")

Maintenance of normal fluid and electrolyte status (see "Fluid and electrolyte therapy in newborns")

Empiric antibiotic therapy

Indications – Indications for empiric antibiotic therapy include any of the following:

-Ill appearance (see "Approach to the ill-appearing infant (younger than 90 days of age)")

-Concerning symptoms (eg, temperature instability or respiratory, cardiocirculatory, or neurologic symptoms) and/or high estimated sepsis risk based on a validated risk calculator (see "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates", section on 'Clinical manifestations' and "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates", section on 'Early-onset sepsis calculator')

-Cerebrospinal fluid (CSF) pleocytosis (white blood cell count of >20 to 30 cells/microL) (table 2) (see "Bacterial meningitis in the neonate: Clinical features and diagnosis", section on 'Interpretation of cerebrospinal fluid')

-Positive blood, urine, or CSF culture (see "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates", section on 'Blood culture')

Empiric regimen – Empiric antibiotic therapy for neonates with suspected sepsis should provide broad coverage for the most likely pathogens (group B Streptococcus [GBS] and gram-negative enteric organisms, including Escherichia coli) (table 4). Our suggested approach is as follows (table 3):

-For neonates with early-onset sepsis (ie, within first 72 hours after birth) without an apparent focus, we suggest initial empiric therapy with ampicillin plus gentamicin rather than other agents (Grade 2C). (See 'Early-onset sepsis' above.)

-For neonates with late-onset sepsis (ie, at ≥72 hours after birth) without an apparent focus who are admitted from the community, we suggest ampicillin plus gentamicin rather than other agents (Grade 2C). (See 'Late-onset sepsis' above.)

-For neonates with late-onset sepsis without an apparent focus who continue to be hospitalized from birth, we suggest vancomycin plus gentamicin rather than other agents (Grade 2C). A regimen of oxacillin or nafcillin plus gentamicin is a reasonable alternative if the neonate has a recent negative methicillin-resistant Staphylococcus aureus (MRSA) screening test. (See 'Late-onset sepsis' above.)

Focal infections – For neonates with an apparent focal source of infection, the empiric antibiotic regimen is modified as summarized in the table (table 3) and discussed separately (see 'Coverage for focal sources of infection' above):

-Meningitis (see "Bacterial meningitis in the neonate: Treatment and outcome", section on 'Empiric therapy')

-Pneumonia (see "Neonatal pneumonia", section on 'Initial empiric therapy')

-Infection involving the skin, soft tissues, bone, or joints (ie, suspected S. aureus infection) (see "Suspected Staphylococcus aureus and streptococcal skin and soft tissue infections in neonates: Evaluation and management", section on 'Choice of initial therapy')

-Intravascular catheter-related infection (see "Intravascular non-hemodialysis catheter-related infection: Treatment", section on 'Empiric antibiotic therapy')

-Intestinal source (see "Neonatal necrotizing enterocolitis: Management", section on 'Choice and duration of antibiotic regimen')

Definitive therapy – Antibiotic therapy is altered based upon isolation of the causative agent and its antimicrobial susceptibility pattern. (See 'Pathogen-specific therapy' above.)

Response to therapy – Most neonates with culture-proven sepsis improve clinically within 24 to 48 hours after starting appropriate antibiotic treatment. The response to antibiotic therapy is assessed by a repeat blood culture 24 to 48 hours after initiation of antibiotic therapy. Failure to sterilize the bloodstream suggests either that the antimicrobial(s) chosen are not active against the infecting pathogen or that there is an unrecognized focus of infection. (See 'Response to therapy' above.)

Duration of therapy – In neonates with culture-proven sepsis, the usual course of therapy is 10 days. Longer treatment is warranted if a specific focus of infection is identified (eg, meningitis, osteomyelitis, or septic arthritis). (See 'Culture-proven sepsis' above.)

In well-appearing neonates with negative cultures after 36 to 48 hours, empiric antibiotic therapy should be discontinued since sepsis is unlikely in these neonates. (See 'Infection unlikely' above.)

Outcome – The mortality associated with neonatal sepsis in term neonates is <5 percent. The risk varies depending on gestational age (lower gestational age is associated with higher mortality) and pathogen (gram-negative and fungal pathogens are associated with higher mortality than gram-positive infections). (See 'Outcome' above.)

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Topic 5046 Version 41.0

References

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