Pharmacodynamics and pharmacokinetics The addition of<unk>  to<unk>  enhances the effects of<unk> . This increases the antimicrobial activity by 4- to 32-fold when compared to<unk>  alone.<unk>  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<unk>  is given in combination with<unk> , regrowth of bacteria has been seen when<unk>  levels fall below certain concentrations. As with many other antibiotics, under-dosing of<unk>  may lead to resistance.<unk>  has poor absorption when given orally. The two drugs have similar pharmacokinetic profiles that appear unchanged when given together.<unk>  and<unk>  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,<unk>  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<unk>  and 28% for<unk> .15,16 The half-life of<unk>  is approximately 1 hour, when used alone or in combination with<unk> ; 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.<unk>  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,<unk>  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. Mechanism of action<unk>  is a combination of a β-lactam antibiotic and a β-lactamase inhibitor.<unk>  works by binding to penicillin-binding proteins (PBPs) to inhibit bacterial cell wall synthesis. This causes disruption of the bacterial cell wall and leads to bacterial cell death. However, resistant pathogens may produce β-lactamase enzymes that can inactivate<unk>  through hydrolysis. This is prevented by the addition of<unk> , which binds and inhibits the β-lactamase enzymes. It is also capable of binding to the PBP of Bacteroides fragilis and Acinetobacter spp., even when it is given alone. The activity of<unk>  against Acinetobacter spp. seen in in-vitro studies makes it distinctive compared to other β-lactamase inhibitors, such as tazobactam and clavulanic acid.
Ampicillin/sulbactam
Ceftazidime/avibactam
Piperacillin/tazobactam
Imipenem/cilastatin
Ceftolozane/tazobactam
Avibactam
Meropenem
Imipenem/cilastatin/relebactam