Ampicillin
Aminopenicillin as a standard in hospital therapy
Ampicillin is a bactericidal broad spectrum aminopenicillin, introduced to the market by Beecham in 1961 and still a standard antibiotic in hospital medicine today. Parenteral forms (intravenous and intramuscular) and combination preparations with sulbactam (Unacid parenteral, sultamicillin oral) are approved. Oral monotherapy with ampicillin has largely been replaced in Germany by amoxicillin, which has substantially better bioavailability and thereby better tissue penetration.
In the hospital ampicillin continues to be an integral part of empirical therapy in listeriosis, in enterococcal infections, in neonatal sepsis and in endocarditis therapy in combination with aminoglycosides. Intravenous use in sepsis therapy and in obstetric infections is also well established. Despite increasing β lactamase resistance ampicillin retains a clear niche within its specific spectrum of activity.
Mechanism of Action
Ampicillin binds to penicillin binding proteins (PBPs) in the bacterial cell wall and inhibits the transpeptidase that catalyses peptidoglycan cross linking. The cell wall loses its stability and osmotic pressure causes lysis of the bacteria. The effect is bactericidal and is preferentially exerted during the proliferation phase of the organisms.
The spectrum covers Gram positive cocci (streptococci, enterococci, some staphylococci), Gram positive rods (Listeria monocytogenes), Gram negative rods (Escherichia coli without β lactamase, Proteus mirabilis, salmonellae, shigellae, Haemophilus influenzae without β lactamase) and some anaerobes. Resistant organisms include penicillinase producing staphylococci, Enterobacter, Klebsiella, Pseudomonas, Bacteroides fragilis, MRSA, ESBL producers and intracellular pathogens (chlamydiae, mycoplasmas, legionellae).
The half life is about one hour and elimination is predominantly renal and unchanged. In severe renal impairment the half life is considerably prolonged. Tissue concentrations in lung, bile, cerebrospinal fluid (in meningitis) and prostate are sufficiently high at therapeutic doses. Ampicillin crosses the placenta and reaches the fetus, which is clinically desirable in the treatment of obstetric infections.
Indications
- Listeriosis including listerial meningitis and neonatal listeriosis, in combination with an aminoglycoside
- Enterococcal endocarditis in combination with gentamicin or ceftriaxone (high dose ampicillin ceftriaxone regimen)
- Neonatal sepsis empirically in combination with an aminoglycoside
- Group B streptococcal prophylaxis during labour in colonised or at risk pregnant women
- Meningitis empirically in the neonatal period and in elderly patients (to cover Listeria)
- Cholangitis and peritonitis in combination with an aminoglycoside or metronidazole
- Urinary tract infections caused by enterococci or Proteus mirabilis with documented susceptibility
- Typhoid fever and Salmonella enteritis in susceptible strains, today largely replaced by fluoroquinolones or azithromycin
Dosage and Administration
Intravenous in adults: 4 to 12 g per day, divided into 4 to 6 single doses. In endocarditis 12 g per day, in listerial meningitis 12 to 18 g per day. Single doses are given as a short infusion over 15 to 30 minutes.
Neonates: 50 to 100 mg per kg per day in 2 to 4 single doses, up to 300 mg per kg per day in meningitis. Infants and children: 50 to 100 mg per kg per day in 3 to 4 single doses. Paediatric doses depend on age, weight and site of infection.
Renal impairment: dose adjustment according to creatinine clearance. Creatinine clearance 30 to 50 ml/min no adjustment, 10 to 30 ml/min prolong the dose interval to 8 to 12 hours, below 10 ml/min to 12 to 24 hours. In haemodialysis an additional dose is given after dialysis. Hepatic impairment: no formal dose adjustment.
Reconstitution of the dry substance uses water for injection or isotonic saline, and the solution must be administered within one hour. Intramuscular injection is painful and is uncommon today. The intravenous bolus should be given over at least three minutes to avoid cardiovascular reactions and pain.
Side Effects
Common: diarrhoea, nausea, vomiting, abdominal pain, rash, vaginal candidiasis, headache, phlebitis at the infusion site.
Uncommon: immediate type allergic reactions (urticaria, angioedema, anaphylaxis), pseudomembranous colitis due to Clostridioides difficile, interstitial nephritis, blood count changes (eosinophilia, thrombocytosis, reversible leukopenia).
Rare: anaphylactic shock, Stevens Johnson syndrome, toxic epidermal necrolysis, haemolytic anaemia, acute hepatitis, seizures at high doses with severe renal impairment.
Epstein Barr virus infection: in patients with infectious mononucleosis a maculopapular rash appears under ampicillin in almost all cases. This is not a true penicillin allergy but should be documented. The recommendation is not to give ampicillin in unclear pharyngitis with lymphadenitis until an EBV infection has been excluded.
Interactions
- Allopurinol: increased risk of rash when used concomitantly
- Methotrexate: reduced renal elimination of methotrexate, risk of toxicity rises
- Oral anticoagulants: fluctuations in INR possible, close monitoring
- Probenecid: reduces renal elimination, elevated ampicillin plasma concentrations
- Aminoglycosides: combination in the same infusion line is not recommended (inactivation), administer separately
- Bacteriostatic antibiotics (tetracyclines, macrolides, sulphonamides): may attenuate the bactericidal effect
- Oral contraceptives: the theoretical reduction of efficacy is clinically disputed; during diarrhoea on antibiotic therapy an additional barrier method should be used
Special Notes
Penicillin allergy: a known type I allergy to penicillins is a contraindication, and cross allergy to cephalosporins is possible in severe immediate type reactions. A thorough history must be taken before use, and in suspected anaphylactic reactions allergological evaluation is required.
Mononucleosis: if infectious mononucleosis is suspected, avoid ampicillin and wait for EBV serology, since the specific rash appears in over 70 percent of patients and is wrongly interpreted as an allergy.
Sodium content: ampicillin is administered as the sodium salt. A daily dose of 12 g contains about 36 mmol of sodium, which is relevant in patients with heart failure, hypertension or severe renal impairment.
Pregnancy: ampicillin has been well studied in pregnancy and is a standard option, for example in obstetrics for group B streptococcal colonisation or chorioamnionitis. Breastfeeding: small passage into breast milk, breastfeeding during therapy is possible; the infant may develop diarrhoea or candidiasis.
Monitoring: with prolonged intravenous therapy monitor renal retention values, liver values, full blood count and electrolytes. In at risk patients daily review and reassessment of treatment duration. Early switch to oral therapy (sequential therapy) with amoxicillin or sultamicillin where possible.
You might also be interested in
- Amoxicillin, an oral aminopenicillin with better bioavailability
- Sultamicillin, an oral ampicillin sulbactam prodrug
- Clavulanic acid, a β lactamase inhibitor in combination with amoxicillin
- Cefpodoxime, an oral third generation cephalosporin
- Clarithromycin, a macrolide for penicillin allergy
Frequently Asked Questions
Why is ampicillin rarely given orally today?
Oral bioavailability is only about 40 percent and depends on food. Amoxicillin has substantially better absorption at around 80 percent, with higher plasma concentrations and more convenient dosing. Amoxicillin is therefore the predominant choice in ambulatory infections, while ampicillin remains the intravenous standard option in the hospital.
Where is ampicillin indispensable?
In listeriosis, enterococcal endocarditis and neonatal sepsis ampicillin remains the essential component of empirical therapy. The intrinsic resistance of many cephalosporins against enterococci and Listeria leaves no real alternative. For these indications no better option is available.
Why the rash risk in EBV infection?
In infectious mononucleosis a specific interaction between the viral immune response and ampicillin leads to a maculopapular rash in over 70 percent of patients. This is not a true immediate type allergy, but the rash should be classified correctly. If the clinical picture of pharyngitis is unclear, serology before antibiotic administration is advisable.
How does ampicillin differ from amoxicillin?
Both are aminopenicillins with almost identical spectrum of activity. Amoxicillin is the better oral form, ampicillin the stronger intravenous form. When given intravenously both reach comparable tissue concentrations; in everyday hospital use ampicillin is preferred because of the better availability of dry ampoules and lower costs.
Sources
- EMA, European Medicines Agency
- AWMF, S3 Guideline on Endocarditis and Meningitis
- Gelbe Liste, Ampicillin active substance profile
- Paul Ehrlich Society for Chemotherapy
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