Less frequently reported side effects include inflammation of veins (1.2%), sometimes associated with a blood clot (3%). The most commonly reported systemic reactions are diarrhea (3%) and rash (2%). Less frequent systemic reactions to ampicillin/sulbactam include chest pain, fatigue, seizure, headache, painful urination, urinary retention, intestinal gas, nausea, vomiting, itching, hairy tongue, tightness in throat, reddening of the skin, nose bleeding, and facial swelling. These are reported to occur in less than 1% of patients. Pharmacology
Pharmacodynamics and pharmacokinetics
The addition of sulbactam to ampicillin enhances the effects of ampicillin. This increases the antimicrobial activity by 4- to 32-fold when compared to ampicillin alone. Ampicillin is a time-dependent antibiotic. Its bacterial killing is largely related to the time that drug concentrations in the body remain above the minimum inhibitory concentration (MIC). The duration of exposure will thus correspond to how much bacterial killing will occur. Various studies have shown that, for maximum bacterial killing, drug concentrations must be above the MIC for 50-60% of the time for the penicillin group of antibiotics. This means that longer durations of adequate concentrations are more likely to produce therapeutic success. However, when ampicillin is given in combination with sulbactam, regrowth of bacteria has been seen when sulbactam levels fall below certain concentrations. As with many other antibiotics, under-dosing of ampicillin/sulbactam may lead to resistance.Ampicillin/sulbactam has poor absorption when given orally. The two drugs have similar pharmacokinetic profiles that appear unchanged when given together.
Ampicillin and sulbactam are both hydrophilic antibiotics and have a volume of distribution (Vd) similar to the volume of extra-cellular body water. The volume that the drug distributes throughout in healthy patients is approximately 0.2 liters per kilogram of body weight. Patients on hemodialysis, elderly patients, and pediatric patients have shown a slightly increased volume of distribution. Using typical doses, ampicillin/sulbactam has been shown to reach desired levels to treat infections in the brain, lungs, and abdominal tissues. Both agents have moderate protein binding, reported at 38% for sulbactam and 28% for ampicillin.15,16  The half-life of ampicillin is approximately 1 hour, when used alone or in combination with sulbactam; therefore it will be eliminated from a healthy person in around 5 hours. It is eliminated primarily by the urinary system, with 75% excreted unchanged in the urine. Only small amounts of each drug were found to be excreted in the bile. Ampicillin/sulbactam should be given with caution in infants less than a week old and premature neonates. This is due to the underdeveloped urinary system in these patients, which can cause a significantly increased half-life for both drugs.16   Based on its elimination, ampicillin/sulbactam is typically given every 6 to 8 hours. Slowed clearance of both drugs has been seen in the elderly, renal disease patients, and critically ill patients on renal replacement therapy. Reduced clearance has been seen in both pediatric and post-operative patients. Adjustments in dosing frequency may be required in these patients due to these changes.