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Clinical Practice Guidelines

Neonatal antimicrobial guidelines

  • See also

    Antimicrobial guidelines (Victorian)

    Key points

    1. This guideline directs antimicrobial therapy for neonatal early-onset sepsis and late-onset sepsis 
    2. Antibiotics should be administered within 1 hour of the decision to treat
    3. Early onset sepsis (EOS <48 hours) is commonly caused by Group B streptococci (GBS) or Escherichia coli
    4. Late onset sepsis (LOS >48 hours) in the community has different causative pathogens to hospital acquired infection
    5. Listeria monocytogenes is a rare but serious infection in the neonatal period
    6. Herpes simplex virus should be considered in all septic neonates

    Background

    • Sepsis in the neonatal period causes significant morbidity with a mortality rate of up to 20% in high-income countries. Mortality is inversely related to gestational age
    • Neonatal sepsis is divided into EOS ( <48 hours) and LOS (>48 hours). EOS is typically caused by organisms from the maternal genital tract, with GBS and E. coli being the most common. GBS is more common in term infants, and E. coli in preterm infants
    • LOS is usually acquired from the community or hospital environment. Both EOS and LOS are more common in preterm and very low birthweight (VLBW) infants
    • It is important to consider HSV as a causative pathogen in neonatal sepsis, with a very low threshold for commencing empiric Aciclovir. Although less common, Listeria monocytogenes and Candida species are important to consider in specific patient groups
    • Unnecessary, broad-spectrum, and prolonged antibiotic use in the neonatal period can have detrimental outcomes on neonatal morbidity and mortality and contribute to the burden of antimicrobial resistance. This guideline aims to minimise these harms with careful guidance on choice and duration of antimicrobial therapy

    Management

    Investigations

    • FBE, CRP or procalcitonin
    • Blood culture - peripheral and from all central venous access lumens. Minimum volume = 0.5 mL but preferably 1 mL ( <1.5 kg) or 1.5 mL (1.5 – 5 kg). Minimise contamination
    • Lumbar puncture  - particularly in LOS.  Meningitis is less common in suspected EOS (1–2%) and LP should be performed if there is a high level of clinical suspicion e.g. maternal chorioamnionitis or PPROM, neurological signs in the infant, or if blood cultures are positive. Refer to CSF interpretation
    • Chest X-ray if respiratory tract infection is suspected unless clinical features are clearly consistent with bronchiolitis

    Treatment

    • Antibiotic therapy should be commenced within 1 hour of the decision to treat and should not be unduly delayed for investigations
    • Information on antimicrobial dosing and administration can be accessed within the RCH EMR NICU medical ordering panel. For pre-term neonates refer to the relevant NICU Department Guidelines and recommended medication references (including Neonatal Formulary, Lexicomp or BNFC). If you are using this guideline at another healthcare service, please refer to your local guidelines
    • For additional information on administration refer to the Paediatric Injectable Guidelines
    • Strongly consider central line removal in infants with sepsis. For infants with fulminant sepsis, urgent ID consultation to advise on broadening treatment is recommended
    • Empiric regimens are recommended for initial treatment. Tailor ongoing antibiotic use to microbiological results

    SEPSIS

    Infection

    Likely organisms

    Initial intravenous antibiotics

    Duration of treatment and
    other comments

    Early-onset sepsis
    (<48 hours)

    Meningitis NOT suspected
    or
    Normal CSF

     

     

    Group B streptococci
    E.coli
    L. monocytogenes

     

     

    Benzylpenicillin and
    Gentamicin

    Cease after 36 hours if no growth on cultures and patient well. If culture positive, treat as per Source differentiated below

    Add Aciclovir if presentation suggests possibility of HSV2

    Choose antibiotics that cover maternal and infant colonising organisms (e.g. MRSA3, ESBL4)

    Meningitis suspected
    or
    Abnormal CSF

    Benzylpenicillin and
    3rd gen cephalosporin1

    Late-onset sepsis
    (>48 hours)

    Meningitis NOT suspected
    or
    Normal CSF

     

    As above plus
    other Gram-negatives
    H. influenzae spp.
    S. pneumoniae
    N. meningitidis
    S. aureus
    Group A streptococci

     

     

    Cefazolin and
    Gentamicin

    Cease antibiotics after 36 hours if no growth on cultures. Earlier cessation possible if alternative cause identified (e.g. enterovirus)

    Add Benzylpenicillin if Listeria6  suspected

    If culture positive, treat as per Source differentiated below

    Use Vancomycin instead of Cefazolin if MRSA3 risk factors

    Add vancomycin for meningitis cover if MRSA3 risk factors

    Choose antibiotics that cover maternal and infant colonising organisms (e.g. ESBL4)

    Add Aciclovir if presentation suggests possibility of HSV2

    Add Liposomal Amphotericin if fungal infection suspected5

    Continue empiric antifungals for 72 hours pending blood culture

     

    Meningitis suspected
    or
    Abnormal CSF

    Benzylpenicillin and
    3rd gen cephalosporin1

    SOURCE DIFFERENTIATED

    Infection

    Organism

    Directed intravenous antibiotics

    Duration of treatment and
    other comments

    BLOOD

    Bacteraemia

    Group B streptococci

     

    E. coli

     

     

    Coagulase-negative Staphylococcus

    Benzylpenicillin

     

    3rd gen cephalosporin1

     

     

    Vancomycin

     

    7 days

     

    10 days
    A narrower spectrum antibiotic, e.g. amoxicillin, may be more appropriate based on laboratory susceptibility testing

     

    5 days OR
    48 hours post CVC removal

    CNS

    Meningitis (uncomplicated7)

     

     

     

     

     

     

     

    Encephalitis

    Group B streptococci

     

    E. coli

     

    L. monocytogenes

     

     

    Culture negative, abnormal CSF

     

    HSV2

    Benzylpenicillin

     

    3rd gen cephalosporin1

     

    Amoxicillin

     

     

    3rd gen cephalosporin1

     

    Aciclovir

    14 days

     

    21 days

     

    21 days
    ID referral recommended for L. monocytogenes

     

    14 days

    Consider HITH referral for completion of treatment course at home

     

    21 days
    Long-term HSV prophylaxis and follow up required

    ID referral recommended

    GASTROINTESTINAL

    Intra-abdominal infection (e.g. Necrotising enterocolitis)

    Gram-negative coliforms
    Anaerobes Enterococcus spp

    Amoxicillin and
    Gentamicin and
    Metronidazole

     

    7 – 10 days

    Change to Amoxicillin-clavulanic acid at 72 hours if infant clinically improving

    If no improvement at 72 hours, switch to Piperacillin-tazobactam
    Choose antibiotics that cover maternal and infant colonising organisms (e.g. ESBL4)

    GENITOURINARY

    Urinary tract infection

    E. coli
    P. mirabilis
    K. oxytoca
    Other Gram-negatives
    Enterococcus spp.

    Benzylpenicillin and Gentamicin

    Uncomplicated UTI8: 3 days IV then 4 days oral

    Bacteraemic UTI: 7 days IV then 3 days oral
    Narrow antibiotics based on culture result

    Request early renal ultrasound

    RESPIRATORY

    Pneumonia

     

    Ventilator-associated pneumonia

     

     

     

     

    Atypical pneumonia

    S. pneumoniae
    H. influenzae spp.

    As above plus
    S. aureus
    Group A streptococci
    Gram-negatives

     

    Ureaplasma
    Chlamydia trachomatis

    3rd gen cephalosporin1

     

    Cefazolin and
    Gentamicin

     

     

    Azithromycin

    7 days

     

    Pre-antibiotic bronchoalveolar lavage recommended

    Use empiric Vancomycin instead of cefazolin in the critically unwell infant

    ID referral to optimise antibiotic selection


    3 days

    SKIN/SOFT TISSUE

    Cellulitis,
    Post-operative wound infection

    Group A streptococci
    S. aureus

    Cefazolin

    5 – 7 days
    (IV to oral switch at 3 days if improved)


    1. Third-generation cephalosporins

    Cefotaxime/ceftriaxone: Where possible, ceftriaxone should be avoided in neonates <41 weeks gestation, particularly if jaundiced or receiving calcium containing solutions, including TPN

    2. Herpes Simplex Virus (HSV) risk factors

    • Maternal HSV
    • Recent HSV exposure (incubation period up to 12 days)
    • Abnormal neurological status or seizures
    • Vesicular rash
    • Corneal ulcer/keratitis
    • Hepatitis

    3. Methicillin-resistant Staphylococcus aureus (MRSA)

    • Fulminant infection (e.g. inotrope requirement)
      • Known infant or maternal colonisation
      • Aboriginal and Torres Strait Islander or Pacific Islander child

    4. Extended spectrum beta lactamase (ESBL)

    • Known infant or maternal colonisation (check maternal microbiology around time of delivery) 

    5. Fungal infection risk factors

    • Fulminant infection (e.g. inotrope requirement)
    • <1500 g and deteriorates while on antibiotics
    • ≥7 days antibiotics with deterioration
    • On TPN or systemic steroids
    • Thrombocytopenia

    6. Listeria risk factors

    • Disseminated abscesses, granulomas
    • Pustular skin rash
    • Maternal listeriosis

    7. Uncomplicated meningitis

    • Absence of ventriculitis, cerebritis, hydrocephalus, brain abscess, cerebral infarction, cerebral venous thrombosis, arterial stroke, or subdural effusion or empyema

    8. Uncomplicated urinary tract infection

      • Fever, but no vomiting or urological abnormalities

    MEDICAL ANTIBIOTIC PROPHYLAXIS

    Fungal

    All infants
    <1500 g

    Nystatin

    Cease when weight ≥1500 g
    Older infants with multiple risk factors for invasive fungal infection may also benefit from prophylaxis, e.g. prolonged broad-spectrum antibiotics5

    Urinary tract infection

     

    Trimethoprim
    If nil by mouth, cease prophylaxis

    Discuss with Nephrology or Urology teams to determine need for UTI prophylaxis on a case-by-case basis

    SURGICAL ANTIBIOTIC PROPHYLAXIS

    Most procedures

    Within 1 hour prior to start of surgery

    Cefazolin

    Prophylactic post-operative antibiotics
    usually not required
    (maximum 24 hours)

    If infective complications persist, consult Surgical and ID teams

    Refer to the relevant surgical antibiotic prophylaxis guideline

    If intra-abdominal, pelvic, deep wound debridement,
    ischaemic limb, risk of bowel lumen entry, open fracture

    Cefazolin and
    Metronidazole

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