• Penicillins And others

  • Beta-lactamase inhibitors

    • Sulbactam

      • Sulbactam

       

      • Mechanism of Action

        • Sulbactam is a semisynthetic beta-lactamase inhibitor derived from penicillanic acid sulfone.

          • Like clavulanate, it irreversibly acylates serine beta-lactamases and permanently inactivates them.¹

            • Sulbactam’s structure is similar to a penicillin, and it covalently binds to the enzyme’s active site.

              • In addition to its enzyme-inhibiting action, sulbactam itself has weak intrinsic antibacterial activity against certain bacteria.

                • Sulbactam can bind to penicillin-binding proteins of Acinetobacter baumannii and Neisseria species, conferring some direct bactericidal effect.¹ 

                  • Carbapenem-Resistant Acinetobacter

                    "This is the medical illustration of carbapenem-resistant, Acinetobacter sp. bacteria, presented in the Centers for Disease Control and Prevention (CDC) publication entitled, Antibiotic Resistance Threats in the United States, 2019." Attribution: CDC/Antibiotic Resistance Coordination and Strategy Unit, 2019. Photo Credit: Medical Illustrators: Dan Higgins; James Archer. https://phil.cdc.gov/Details.aspx?pid=23235

                • This intrinsic activity is limited but clinically relevant against A. baumannii.

                • high-dose sulbactam can be used as a treatment option for multi-drug-resistant Acinetobacter infections where sulbactam’s own antibacterial effect is leveraged.¹

      • Pharmacokinetics

        • Sulbactam is usually given parenterally (IV/IM), most often as ampicillin-sulbactam (brand name Unasyn).

          • Sulbactam exhibits poor oral absorption unless given as the double-ester prodrug sultamicillin.

          • After IV administration, sulbactam distributes in extracellular fluid compartments; it achieves therapeutic levels in tissues like lung, pleural fluid, bile, and peritoneal fluid. Its half-life is roughly 1 hour in patients with normal renal function.² 

            • Sulbactam is ~38% protein-bound in plasma.² 

          • Sulbactam undergoes minimal metabolism; <25% of the dose may be metabolized hepatically.³  Renal excretion is the dominant elimination route, with about 70–85% of a dose excreted unchanged in the urine.^2,3

            • Because of this, dose adjustments are required in renal impairment to avoid accumulation.

        • Sulbactam’s pharmacokinetics are not significantly altered by coadministration with ampicillin – the two drugs have parallel kinetics and are often given in a fixed 2:1 ampicillin:sulbactam ratio.²

      • Therapeutic Uses

        • Sulbactam is combined with the aminopenicillin ampicillin in a 2:1 ratio.

          • Ampicillin-sulbactam exhibits of productivity, covering many ß-lactamase-producing bacteria responsible for community-acquired in some hospital-acquired infections.

          • Ampicillin-sulbactam is typically considered an empiric therapy for moderate community-acquired infections requiring hospitalization, such as intra-abdominal or pelvic infections, and remains a reliable agent in both adult and pediatric infections.¹

            Oral sultamicillin is available in some regions for step-down therapy or outpatient treatment of milder infections, providing an oral route for sulbactam use.¹

            • Intra-abdominal and gynecologic infections

              • Diverticulitis, peritonitis, cholecystitis, endometritis are examples of infection where Enterobacteriaceae and anaerobes (Bacteroides, etc.) are common. 

                • Ampicillin-sulbactam provides broad coverage of these, except Pseudomonas.¹

            • Respiratory tract infections

              • These infections include aspiration pneumonia and ventilator-associated pneumonia (if due to susceptible organisms).

                • Ampicillin-sulbactam is effective for aspiration pneumonia as it covers oral anaerobes along with typical respiratory pathogens.¹

                  • Ampicillin-sulbactam is also used in acute epiglottitis and periorbital/orbital cellulitis, where H. influenzae and mixed flora are concerns.¹

            • Skin and soft tissue infections

              • Examples of skin/soft tissue infections include  diabetic foot infections or deep soft tissue abscesses, especially polymicrobial ones, given ampicillin-sulbactam activity against staphylococci, streptococci, and anaerobes.¹

            • Obstetric infections

              •  Ampicillin-sulbactam is indicated for postpartum endometritis, pelvic inflammatory disease, or septic abortion, covering Enterobacteriaceae and anaerobes.

            • Community-acquired pneumonia

              • Ampicillin-sulbactam IV can be used for hospitalized patients with pneumonia due to beta-lactamase producing H. influenzae or Moraxella, as well as for aspiration pneumonia as noted.

            • Acinetobacter infections

              • Sulbactam is uniquely useful against carbapenem-resistant A. baumannii, as A. baumannii often has intrinsic susceptibility to sulbactam’s antibiotic action on PBP-2.

              • High-dose sulbactam (often administered as ampicillin-sulbactam or with a new enhancer durlobactam) is used off-label for difficult Acinetobacter infections when other options are limited.¹

      • Adverse Reactions

        • The addition of sulbactam does not greatly change the adverse effect profile of ampicillin; overall it is well tolerated.

          • The most common side effect is diarrhea (and related GI upset), as is typical for broad-spectrum penicillins.^1,2 

            • Ampicillin by itself frequently causes diarrhea due to incomplete absorption and high biliary excretion; sulbactam may add to this by altering gut flora.

          • Other adverse effects include nausea, rash, and injection site pain (if given IV or IM).

            • Hypersensitivity reactions can occur (any patient allergic to penicillin should not receive ampicillin-sulbactam, as cross-reactivity is expected).² 

August, 2025