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Dose & administration
The dose depends on gestational age (GA) and postnatal age (PNA):

  • ≤ 34 weeks GA and ≤ 7 days PNA: 50 mg/kg/dose, every 12 hours (q12h).
  • ≤ 34 weeks GA and 8 - 28 days PNA: 75 mg/kg/dose, every 12 hours (q12h).
  • ≥ 35 weeks GA and 0-28 days PNA: 50 mg/kg/dose, every 8 hours (q8h).

In the case of meningitis or severe septicemia the doses may be increased twofold. Maximal dose: 400 mg/kg/day

IV administration is preferable, as an IV push over 3-5 min. Intraosseous injection may be used if venous access is not available, but intramuscular injection is not recommended.

Early onset neonatal infection (sepsis), proved or strongly suspected caused by sensitive bacterias, such as Group B streptococcus, enterococcus, E coli,and  Listeria monocytogenes.

Contraindications and special considerations
Hypersensitivity to penicillin derivatives is a contraindication.
Dosage adjustment may be necessary in patients with renal impairment

Known Y-site incompatibilities are amikacin, amiodarone, dopamine, epinephrine, erythromycin, fluconazole, gentamicin, hydralazine, metoclopramide, midazolam, nicardipine, sodium bicarbonate, tobramycin.

Adverse effects
Most common adverse events are:

  • Oral or gluteal/perineal candidiasis
  • Vomiting, diarrhea
  • Hepatic impairment with long term use
  • Hypersensitivity reaction - maculopapular rash, urticarial rash,  hemolytic anemia, thrombocytopenia, pancytopenia or fever (hypersensitivity reactions are not commonly seen in the neonatal period, although one have to be aware about the possibility of anaphylaxis reaction)
  • Pseudomembranous enterocolitis
  • Some risk of convulsions exists if high serum concentration of ampicillin (>140mg/ml) is achieved

Pharmacological  aspects
Ampicillin is a wide spectrum antibiotic, semi-synthetic penicillin with bactericidal action, acting by inhibiting synthesis of the bacterial cell wall . It may effective against a wide range of Gramm-positive and Gramm-negative bacteria, for example hemolytic and nonhemolytic streptococci, nonpenicillinase-producing staphylococci, Clostridium spp., Listeria monocytogenes, many strains of enterococci, H. influenzae, N. Gonorrhoeae, N. Meningitidis,and E. coli.

Ampicillin is prone to destruction by penicillinasae activity and therefore is inefficient against penicillinasae producing bacteria. Furthermore, resistance to ampicillin may develop and an increasing numbers of Haemophilus influenza are becoming resistant.

However, most of the bacteria causing early onset neonatal infection are sensitive still to ampicillin and/or its combination with gentamicin. Positive bacterial cultures should always be combined with antimicrobial sensitivity testing.

Clearance is ensured predominantly by kidneys in infants with a gestational age >37 weeks. Half-life (T1/2)  ranged from 2.2 to 3.9 h in term infants whereas in preterm infants T1/2 was 4.0 h. T1/2 decrease with increasing postnatal age.

There is lack of data available relative to clearance and volume of distribution in neonates. 

Reconstitution with sterile water for injection is recommended. Maximum concentration for the IV infusion is 100 mg/ml. Reconstituted solution should be used within 1 hour.
Solution compatibility: 5% glucose (loss of stability after 1 hour), Sodium chloride 0.95%, Mixture of 5% Glucose (Dextrose) and Sodium chloride 0.45%, Ringer’s Lactate solution
Solution incompatibility: solutions for  parenteral nutrition


  • Gian Maria Pacifici. Clinical Pharmacokinetics of Penicillins, Cephalosporins and Aminoglycosides in the Neonate: A Review. Pharmaceuticals (Basel). 2010 Aug; 3(8): 2568–2591; doi:10.3390/ph3082568; http://www.mdpi.com/1424-8247/3/8/2568/htm
  • Leslie C. Pineda and Kevin M. Watt. New Antibiotic Dosing. Clin Perinatol. 2015 March ; 42(1): 167–176. doi:10.1016/j.clp.2014.10.009. PMID:25678003
  • Adriana Tremoulet, Jennifer Le, Brenda Poindexter, Janice E. Sullivan et al. Characterization of the Population Pharmacokinetics of Ampicillin in Neonates Using an Opportunistic Study Design. Antimicrobial Agents and Chemotherapy.  2014 Volume 58 Number 6p. 3013–3020 . URL http://aac.asm.org/content/58/6/3013.full?sid=48f1a07e-4438-48ac-8eb4-d4ee6836b7e1 
  • J. Jacobs, Dina Kletter, E. Superstine et al. Intravenous infusions of heparin and penicillins. J Clin Pathol. 1973 Oct; 26(10): 742–746. PMID:4750455
  • Hanne Colding and Gunnar Eg Andersen. Stability of Antibiotics and Amino Acids in Two Synthetic Amino Acid Solutions Commonly Used for Total Parenteral Nutrition in Children. Antimicrobial Agents and Chemotherapy, Apr. 1978, p. 555-558 PMID:27137
  • R A Johnson. Adverse reactions in ten years' general practice, computer analysed. Journal of the Royal Society of Medicine Volume 79 March 1986, 145-148. PMID:3486291
  • P. Brodlie, C. Henney, A. J. J. Wood. Problems of Administering Drugs by Continuous Infusion. British Medical Journal 2 March 1974,383-385 PMID:4819177
  • E. D. Hodby, J. Hirsh, and C. Adeniyi-Jones. The influence of drugs upon the anticoagulant activity of heparin. Can Med Assoc J., v.106(5); 1972 Mar 4, 562-564. PMID:5027639

Document version history
Created 2016-07-04 / Yuriy Korzhynskyy

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Neonate (IM/IV):

<7 days:

<2 kg:  50–100 mg/kg/24 hr ÷ Q12 hr ≥2 kg:  75–150 mg/kg/24 hr ÷ Q8 hr Group B streptococcal meningitis:  200–300 mg/kg/24 hr ÷ Q8 hr


≥7 days:

<1.2 kg:  50–100 mg/kg/24 hr ÷ Q12 hr

1.2–2 kg:  75–150 mg/kg/24 hr ÷ Q8 hr

>2 kg:  100–200 mg/kg/24 hr ÷ Q6 hr Group B streptococcal meningitis:  300 mg/kg/24 hr ÷ Q4–6 hr

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