Generic Name

Ampicillin

Mechanism

• Inhibits bacterial cell‑wall synthesis by binding to and inactivating *penicillin‑binding proteins* (PBPs) that catalyze the final cross‑linking step of peptidoglycan assembly.
• This action compromises cell integrity, leading to osmotic lysis.
• Ampicillin’s β‑lactam ring is partially protected from β‑lactamase hydrolysis, granting activity against many *E. coli*, *H. influenzae*, *B. pertussis*, and *S. pneumoniae* strains.

Pharmacokinetics

Indications

• Bacterial pharyngitis (group A β‑hemolytic streptococci)
• Otitis media, sinusitis, and pneumonia
• Serious gram‑negative infections (e.g., *E. coli*, *K. pneumoniae*, *P. mirabilis*)
• Empiric therapy for febrile neutropenia (in combination)
• Prophylaxis:
• Patients undergoing invasive dental or urologic procedures with penicillin‑sensitive *S. viridans*.
• Pre‑operative coverage for certain abdominal surgeries (if β‑lactamase‑producing flora expected).
• Pediatric use: e.g., prophylaxis for *Streptococcus*, *Enterococcus* infections in congenital heart disease.

Contraindications

• Hypersensitivity to penicillins, cephalosporins (cross‑reactivity).
• Severe renal impairment (e.g., CrCl < 15 ml/min) → significant accumulation.
• Pregnancy: category B; generally safe, though aspirin‑like reactions have been reported in the perinatal period.
• Liver disease: minimal hepatic clearance; monitor if severe dysfunction.
• Risk of Clostridioides difficile infection: avoid unnecessarily prolonged therapy.

Dosing

• *Note*: For severe sepsis or meningitis, use higher doses (2 g IV q6h) until source controlled.
• *Prophylactic* dosing in dental work: 2 g IV (or 500 mg oral) 30 min before procedure.

Adverse Effects

Common (≤ 5 %)
• Diarrhea, nausea, abdominal discomfort
• Rash, urticaria, mild oral/dermal itching
• Superficial candidiasis (especially in prolonged therapy)

Serious (≤ 1 %)
• Severe allergic reactions: anaphylaxis, angioedema
• Neurotoxicity (rare): seizures, myoclonus (especially in renal failure or CNS disease)
• Severe cutaneous adverse reactions: Stevens–Johnson syndrome / toxic epidermal necrolysis
• Non‑serious but significant: Clostridioides difficile colitis, hemolytic anemia (Coombs‑positive)
• Ototoxicity: rare, often with concomitant aminoglycosides

Monitoring

• Renal function: Serum creatinine, CrCl before initiation and every 2–3 days (or more frequently in renal impairment).
• Adverse reaction: Watch for rash, fever, GI upset; discontinue if severe.
• Drug‑level: Not routinely measured, but therapeutic drug monitoring may be considered in critical care or renal dysfunction.
• Synergy: For combination therapy (e.g., β‑lactam + aminoglycoside), monitor counts and renal function closely.

Clinical Pearls

• β‑lactamase protection: Ampicillin’s thiazolidine ring (akin to amoxicillin) reduces susceptibility to β‑lactamases, but it is still threatened by extended‑spectrum β‑lactamases (ESBLs). Use ampicillin‑sulbactam or carbapenem if ESBLs are suspected.
• Oral absorption lag: Caution in severely ill patients; IV preferred until return of adequate GI function.
• Prophylaxis dosing: A single pre‑operative dose suffices for dental and urologic procedures; prolonged course only if infection suspected.
• Renal adjustment: The elimination half‑life without adjustment can exceed 6 h in CrCl < 30 ml/min—extend interval to q12h or reduce dose by 50 %.
• Combination therapy: In febrile neutropenia, ampicillin can be combined with an aminoglycoside for synergistic coverage against *Enterococcus* spp., but monitor neuro‑toxicity.
• Pediatric dosing: Weight‑based dosing ensures adequate peak concentrations; aim for serum levels 16–32 µg/mL for enteric pathogens.

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• Keywords: Ampicillin, penicillin V, β‑lactam antibiotics, mechanism of action, pharmacokinetics, dosing guidelines, clinical indications, contraindications, renal adjustment, monitoring, antimicrobial stewardship, pediatric antibacterial therapy.