Enterobacterales bloodstream infections in neonates and children younger than 3 months

In neonates and children younger than 3 months with a bloodstream infection caused by Enterobacterales (eg Escherichia coli, Klebsiella species, Proteus, Citrobacter, Enterobacter, Serratia species), treat according to the results of susceptibility testing for the neonate, child and, if relevant, the birthing parent (eg mother).

Enterobacterales species can exhibit multidrug resistance. The ceftriaxone and cefotaxime recommendations below provide empirical therapy for infection due to E. coli and most Klebsiella species; however, seek expert advice from a clinical microbiologist or infectious diseases physician for antibiotic choice if:

the neonate or child younger than 3 months is at increased risk of infection with multidrug-resistant gram-negative bacteria (see also Managing suspected infection with multidrug-resistant gram-negative bacteria)
Enterobacterales that are more likely to produce clinically significant amounts of AmpC beta-lactamases¹ are identified (see also AmpC and Extended-spectrum beta-lactamases).

Perform a lumbar puncture to exclude meningitis in neonates. In infants 1 month to younger than 3 months, a lumbar puncture may not be required – follow local guidelines and seek expert advice from a senior clinician.

In term neonates (gestational age 37 weeks or older) and children younger than 3 months who do not have meningitis (ie excluded by lumbar puncture), while awaiting the results of susceptibility testing, the following regimens may be used:

1ceftriaxone (child 1 month or older: 50 mg/kg) intravenously, daily. For children with septic shock or requiring intensive care support, use ceftriaxone (child 1 month or older: 50 mg/kg) intravenously, 12-hourly² ³. See advice on modification and duration of therapy ceftriaxone

1cefotaxime 50 mg/kg intravenously. See advice on modification and duration of therapy cefotaxime

neonate younger than 8 days: 8-hourly

neonate 8 days or older: 6-hourly

child 1 month to younger than 3 months: 8-hourly. For children with septic shock or requiring intensive care support, use cefotaxime 50 mg/kg intravenously, 6-hourly⁴.

In term neonates (gestational age 37 weeks or older) and children younger than 3 months with suspected or confirmed meningitis (ie not excluded by lumbar puncture), cefotaxime and ceftriaxone have been considered standard therapy for Enterobacterales, but resistance to these drugs is increasing. Where possible, select therapy based on local susceptibility data. While awaiting the results of susceptibility testing, the following regimens may be used:

1ceftriaxone (child 1 month or older): 50 mg/kg intravenously, 12-hourly³. See advice on modification and duration of therapy ceftriaxone

1cefotaxime 50 mg/kg intravenously. See advice on modification and duration of therapy cefotaxime

neonate younger than 8 days: 8-hourly

neonate 8 days or older: 6-hourly

child 1 month to younger than 3 months: 6-hourly.

In term neonates (gestational age 37 weeks or older) and children younger than 3 months who have had a nonsevere (immediate or delayed) or a severe (immediate)⁵ hypersensitivity reaction to a penicillin, use ceftriaxone or cefotaxime as above.

In neonates and children younger than 3 months who have had a severe delayed⁶ hypersensitivity reaction to a penicillin who do not have meningitis (ie excluded by lumbar puncture), while awaiting expert advice, use:

1gentamicin intravenously; see Principles of aminoglycoside use for prescribing considerations and subsequent dosing. See advice on modification and duration of therapy gentamicin

term and preterm neonate: see Initial aminoglycoside dosage for treating infection in neonates for initial dose

child 1 month to younger than 3 months: 7 mg/kg for initial dose

1tobramycin intravenously; see Principles of aminoglycoside use for prescribing considerations and subsequent dosing. See advice on modification and duration of therapy tobramycin

term and preterm neonate: see Initial aminoglycoside dosage for treating infection in neonates for initial dose

child 1 month to younger than 3 months: 7 mg/kg for initial dose.

In neonates and children younger than 3 months who have had a severe delayed⁶ hypersensitivity reaction to a penicillin and have suspected or confirmed meningitis (ie not excluded by lumbar puncture), seek expert advice.

¹ Bacteria at high risk of clinically significant AmpC beta-lactamase production, previously referred to as the ESCAPPM group, includes Hafnia alvei, Enterobacter cloacae complex, Citrobacter freundii, Klebsiella aerogenes and Yersinia enterocolitica.Return

² Pharmacokinetics may be altered in children 1 month to younger than 3 months who are critically ill (eg because of enhanced kidney clearance or changes in volume of distribution). To ensure adequate drug exposure for children 1 month to younger than 3 months with septic shock or requiring intensive care support, a modified dosage of ceftriaxone is recommended. Once the critical illness has resolved, consider switching to the standard dosage. If the isolate is not reported to have dose-dependent susceptibility to ceftriaxone (ie susceptible dose dependent [SDD] or susceptible increased exposure [I or SIE]), it may also be appropriate to switch to the standard dosage – seek expert advice.Return

³ Ceftriaxone may be a suitable alternative to cefotaxime in term neonates who are not receiving intravenous calcium solutions (eg parenteral nutrition, compound sodium lactate [Hartmann solution], lactated Ringer solution) and do not have jaundice, hypoalbuminaemia, acidosis, unconjugated hyperbilirubinaemia or impaired bilirubin binding – seek expert advice and see Practical information on using beta lactams: cephalosporins.Return

⁴ Pharmacokinetics may be altered in children younger than 3 months who are critically ill (eg because of enhanced kidney clearance or changes in volume of distribution). To ensure adequate drug exposure for children younger than 3 months with septic shock or requiring intensive care support, a modified dosage of cefotaxime is recommended. Once the critical illness has resolved, consider switching to the standard dosage. If the isolate is not reported to have dose-dependent susceptibility to cefotaxime (ie susceptible dose dependent [SDD] or susceptible increased exposure [I or SIE]), it may also be appropriate to switch to the standard dosage – seek expert advice.Return

⁵ Severe immediate hypersensitivity reactions include anaphylaxis, compromised airway, airway angioedema, hypotension and collapse.Return

⁶ Severe delayed hypersensitivity reactions include cutaneous adverse drug reactions (eg drug rash with eosinophilia and systemic symptoms [DRESS], Stevens–Johnson syndrome/toxic epidermal necrolysis [SJS/TEN], severe blistering or desquamative rash), and significant internal organ involvement (eg acute interstitial nephritis).Return