Sultamicillin
Oral aminopenicillin prodrug with beta lactamase inhibitor
Sultamicillin is an orally available mutual prodrug of ampicillin and the β lactamase inhibitor sulbactam. The two substances are covalently linked through a methylene ester. After absorption in the small intestine, esterases cleave the bond, both components are released and can act synergistically. The brand name in Germany is Unacid PD, with authorisation dating from the 1980s; generics have been available for many years.
The advantage of sultamicillin lies in an oral fixed combination systemically equivalent to intravenous ampicillin plus sulbactam. In infections caused by β lactamase producing organisms such as Haemophilus influenzae, Moraxella catarrhalis or Bacteroides species, ampicillin alone would be ineffective. Sulbactam irreversibly blocks bacterial β lactamases and so protects the ampicillin molecule. Coverage gaps correspond to those of the intravenous combination.
Mechanism of Action
Ampicillin belongs to the aminopenicillin class. It binds to penicillin binding proteins (PBPs) of the bacterial cell wall and inhibits transpeptidase, which catalyses cross linking of peptidoglycans. Without a stable cell wall, bacteria lyse. The spectrum covers gram positive cocci (streptococci), gram negative rods such as Escherichia coli, Proteus mirabilis, salmonellae, shigellae, Listeria monocytogenes and some anaerobes.
Many clinically relevant organisms, however, produce β lactamases that inactivate ampicillin. Sulbactam is an irreversible inhibitor of these β lactamases and acts structurally as a suicide substrate. The β lactamase cleaves sulbactam but is itself inactivated, and ampicillin remains in active form. This combination extends the spectrum to strains of Staphylococcus aureus (except MRSA), Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae and Bacteroides fragilis.
Against ESBL producing Enterobacteriaceae, AmpC producing strains and Pseudomonas aeruginosa the combination is not adequately effective. MRSA, vancomycin resistant enterococci and certain carbapenemase producers also escape. In therapy of community acquired infections, however, sultamicillin covers a large part of the expected microbial spectrum.
Indications
- Acute otitis media after failure on amoxicillin or with β lactamase producing organisms
- Acute bacterial rhinosinusitis of moderate severity
- Tonsillitis and pharyngitis caused by β lactamase positive anaerobes
- Mild community acquired pneumonia, particularly when aspiration is suspected
- Urinary tract infections including pyelonephritis with appropriate susceptibility confirmation
- Skin and soft tissue infections, including bite and puncture wounds (carnivore flora)
- Gynaecological and gastrointestinal infections as monotherapy or in combination
- Sequential therapy after intravenous ampicillin sulbactam for oral continuation
Dosage and Administration
Adults and adolescents from 30 kg: 375 mg to 750 mg twice daily, for severe infections up to 750 mg three times daily. Children under 30 kg: 25 to 50 mg per kg per day divided into two doses, in severe infections up to 75 mg per kg per day. Suspension formulations simplify paediatric dosing.
Treatment duration depends on the indication and clinical response, typically 5 to 14 days. Taking the drug before meals slightly increases bioavailability, but in practice intake with food is more tolerable and is the recommended approach. Swallow tablets with plenty of fluid.
Renal impairment: with creatinine clearance below 30 ml/min extend the dosing interval (e.g. 750 mg once daily). Hepatic impairment: no formal adjustment required; check liver transaminases during prolonged therapy. Haemodialysis: administer additional dose after dialysis.
Side Effects
Common: diarrhoea, nausea, vomiting, abdominal pain, rash, vaginal candidiasis, headache.
Uncommon: urticaria, pruritus, elevated liver transaminases, blood count changes (eosinophilia, thrombocytosis, reversible leukopenia), pseudomembranous colitis caused by Clostridioides difficile, interstitial nephritis.
Rare: anaphylactic reactions, Stevens Johnson syndrome, toxic epidermal necrolysis, haemolytic anaemia, acute kidney injury, seizures in overdose or severe renal impairment.
Pseudoallergic rash: during Epstein Barr virus infection nearly all patients on ampicillin or sultamicillin develop a maculopapular rash, which is not equivalent to a true penicillin allergy. Sultamicillin is therefore contraindicated in infectious mononucleosis.
Interactions
- Allopurinol: increased risk of rash with concomitant use
- Methotrexate: reduced renal elimination of methotrexate, raised toxicity risk
- Oral anticoagulants (warfarin, phenprocoumon): INR may fluctuate, close monitoring required
- Probenecid: reduces renal elimination, ampicillin plasma levels rise
- Oral contraceptives: theoretical reduction of efficacy is clinically debated, an additional barrier method is advisable during diarrhoea under antibiotic therapy
- Other antibacterial agents: bacteriostatic partners (tetracyclines, macrolides, sulfonamides) may weaken the bactericidal effect of ampicillin
Special Notes
Penicillin allergy: sultamicillin is contraindicated in known type I allergy to penicillins. Take a detailed history before prescribing. Cross allergy to cephalosporins in a minority of cases; in at risk patients consider allergological evaluation before use.
Mononucleosis: contraindication because of the high rate of rashes. In unclear pharyngitis with lymphadenitis, splenomegaly and fatigue, check EBV serology first and then determine antibiotic therapy.
Pregnancy: aminopenicillins including ampicillin sulbactam combinations are well studied in pregnancy and can be used on strict indication. Breastfeeding: small amounts pass into breast milk, breastfeeding during therapy is possible; infants may develop diarrhoea or thrush.
Monitoring: during prolonged therapy check blood count, liver and renal values. Inform patients about signs of Clostridioides difficile infection; bloody mucous diarrhoea requires immediate reassessment. Complete the full course even when symptoms resolve to avoid resistance.
You might also be interested in
- Amoxicillin, widely used aminopenicillin
- Clavulanic acid, β lactamase inhibitor in amoxicillin combinations
- Ampicillin, aminopenicillin in inpatient therapy
- Cefpodoxime, oral third generation cephalosporin
- Doxycycline, tetracycline for respiratory tract infections
Frequently Asked Questions
What is the difference between sultamicillin and amoxicillin plus clavulanic acid?
Both combine an aminopenicillin with a β lactamase inhibitor and act on a comparable spectrum. Sultamicillin combines ampicillin and sulbactam in a mutual prodrug. Amoxicillin clavulanic acid contains two substances formulated separately. The choice depends on local resistance patterns, tolerability and availability; in Germany amoxicillin clavulanic acid is used more frequently.
Why not in glandular fever?
Infectious mononucleosis from Epstein Barr virus is not a bacterial disease, so antibiotics are ineffective. In addition, ampicillin triggers a pronounced maculopapular rash in 70 to 100 percent of those affected, which is misinterpreted as an allergy. Sultamicillin is therefore contraindicated in mononucleosis.
How long should therapy last?
Depending on the indication, 5 to 14 days. For uncomplicated sinusitis and tonsillitis 5 to 7 days are enough, for pyelonephritis 10 to 14 days. It is important to take the full course as prescribed, even if symptoms improve earlier.
Does the pill lose efficacy under sultamicillin?
Current evidence shows no clinically relevant loss of efficacy of oral contraceptives under most antibiotics except rifampicin. With diarrhoea or vomiting during antibiotic therapy, absorption may be impaired, so an additional barrier method is advisable. Discuss uncertain situations with your gynaecologist or pharmacist.
Sources
- EMA, European Medicines Agency
- AWMF, S3 Guidelines on Respiratory and Urinary Tract Infections
- Gelbe Liste, Sultamicillin active substance profile
- Paul Ehrlich Society for Chemotherapy
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