ampicillin-sulbactam

**Class/Composition:** Ampicillin (aminopenicillin, beta-lactam) + sulbactam (beta-lactamase inhibitor). Given IV/IM (typically 3 g = 2 g ampicillin + 1 g sulbactam q6h). Oral analog: sultamicillin (not US). Related combo: amoxicillin-clavulanate (oral).

**Mechanism:** - Ampicillin: binds penicillin-binding proteins (PBPs, transpeptidases), inhibiting peptidoglycan cross-linking -> cell wall lysis (bactericidal, time-dependent killing). - Sulbactam: a "suicide" (irreversible) inhibitor of many plasmid-mediated class A beta-lactamases (e.g., TEM-1, SHV-1, staphylococcal penicillinase). It has little antibacterial activity alone, except against Acinetobacter baumannii, Neisseria, and Bacteroides (it binds PBPs of these).

**Spectrum:** - Gram-positive: Strep (including viridans), Enterococcus faecalis (ampicillin-sensitive), MSSA (because of the inhibitor). NOT MRSA. - Gram-negative: H. influenzae and Moraxella catarrhalis (beta-lactamase producing), E. coli, Klebsiella, Proteus (community strains; resistance is increasing). - Anaerobes: Bacteroides fragilis, oral anaerobes, Peptostreptococcus. - Acinetobacter baumannii: sulbactam is the active agent (high-dose sulbactam is used in multidrug-resistant strains). - Gaps: Pseudomonas aeruginosa (use piperacillin-tazobactam, cefepime, etc.), MRSA, ESBL-producing Enterobacterales (sulbactam is a weak inhibitor of ESBLs, so use a carbapenem), AmpC producers, atypicals (Mycoplasma, Chlamydia, Legionella), and Stenotrophomonas.

**Clinical uses (high yield):** - Aspiration pneumonia / lung abscess (oral anaerobes) - Polymicrobial skin and soft tissue infections: diabetic foot infections, human and animal bites (Pasteurella, Eikenella, Capnocytophaga, Staph, anaerobes) - Intra-abdominal infections (community-acquired, mild-moderate) - Pelvic inflammatory disease/gynecologic infections (often combined with doxycycline) - Acute otitis media, sinusitis, and epiglottitis (beta-lactamase-producing H. influenzae) - MDR Acinetobacter infections

**Adverse effects:** - Hypersensitivity (rash, urticaria, anaphylaxis); cross-reactivity with other penicillins - Ampicillin rash: a non-IgE-mediated maculopapular rash, classically seen in patients with EBV mononucleosis (also with allopurinol). It does not necessarily mean true penicillin allergy. - GI upset, diarrhea, C. difficile colitis - Interstitial nephritis, hemolytic anemia (Coombs-positive), and reversible transaminase elevations - Pain at the injection site - Seizures with high doses in renal failure

**Pharmacokinetics:** Renal excretion (tubular secretion, so probenecid prolongs half-life). Dose adjust in renal impairment. Both components have similar half-lives (~1 hr), so they are co-dosed. Pregnancy: generally considered safe (Category B).

**Resistance:** Beta-lactamases not inhibited by sulbactam (ESBLs, AmpC, carbapenemases), altered PBPs (MRSA, penicillin-resistant pneumococci), and decreased porin permeability. Rising E. coli resistance limits empiric use for many infections.

**Boards pearls:** - "Bite wound" -> think amoxicillin-clavulanate (oral) or ampicillin-sulbactam (IV). - "Aspiration pneumonia" -> ampicillin-sulbactam (or clindamycin/amox-clav alternatives). - Combination with a beta-lactamase inhibitor extends the spectrum of a penicillin to beta-lactamase producers. Mnemonic of inhibitors: "Clavulanic acid, Sulbactam, Tazobactam" (CST). - Penicillins are not effective against organisms lacking a cell wall (Mycoplasma) or with intracellular niches (Chlamydia, Rickettsia). - Contraindicated with a history of severe penicillin allergy (anaphylaxis, SJS/TEN).