Beta-lactams are a group of antibiotics that contain a beta-lactam ring in their structure that is essential for the antibacterial activity of antibiotics like penicillins and cephalosporins. However, over time, due to their widespread use, some bacteria have acquired resistance by developing enzymes called beta-lactamases. For this reason, some beta-lactam antibiotics are often combined with a class of medications known as beta-lactamase inhibitors in order to treat infections caused by beta-lactam-resistant bacteria like Haemophilus influenzae, methicillin-sensitive Staphylococcus aureus, Bacteroides fragilis, Proteus spp., Escherichia coli, Klebsiella spp., and Acinetobacter spp. Additionally, cephalosporin-containing combinations are effective against Pseudomonas aeruginosa.
Now, beta-lactam/beta-lactamase inhibitor combinations typically contain either a penicillin or a cephalosporin combined with a beta-lactamase inhibitor. Commonly used penicillin beta-lactamase inhibitor combinations include amoxicillin-clavulanate, which is given orally; ampicillin-sulbactam, which is given intramuscularly and intravenously; and piperacillin-tazobactam, which is given intravenously. Commonly used cephalosporin beta-lactamase inhibitor combinations include ceftazidime-avibactam, which is given intravenously; and ceftolozane-tazobactam, which is given orally.
Once administered, beta-lactam antibiotics act by inhibiting bacterial cell wall synthesis, which kills the bacteria. However, in resistant bacteria, the beta-lactamase enzyme binds to the beta-lactam ring within the antibiotic and breaks it down, thus inactivating the antibiotic. This is where the beta-lactamase inhibitors come into play, by binding to the beta-lactamase enzymes in the bacteria. As a result, beta-lactamase inhibitors prevent the beta-lactamase enzyme from inactivating the beta-lactam antibiotic. As a result, the antibiotics are left free to go about their job of killing the bacteria.
The beta-lactam/beta-lactamase inhibitor combinations are generally well tolerated, and the few side effects they produce are usually the results of the antibiotic, or beta-lactam, counterpart. Allergy to beta-lactams is quite common, and clients typically present with urticaria, pruritus, and some can even progress to anaphylaxis. Other common side effects include headaches and gastrointestinal disturbances, such as nausea, vomiting, and diarrhea.
Beta-lactams can also affect the healthy bacterial flora, making clients more susceptible to superinfections by more resistant pathogens, including vaginitis, candidiasis, and more rarely, Clostridioides difficile infection or CDI for short. In particular, clavulanate increases the gastrointestinal side effects of amoxicillin, causing antibiotic-associated diarrhea, which can range from frequent loose stools to more severe colitis. Additionally, clients on amoxicillin-clavulanate can also develop cholestatic hepatitis.
Now, beta-lactam/beta-lactamase inhibitor combinations are contraindicated in clients allergic to any beta-lactam antibiotics due to the risk of cross-reactivity between the different classes. They should also be used with caution in clients with hepatic or renal disease, as well as during pregnancy and breastfeeding. With respect to drug interactions, the beta-lactam/beta-lactamase inhibitor combinations should not be given along with aminoglycoside antibiotics, since this combination can result in reduced antibacterial effects of both medications. Finally, penicillins increase the effects of methotrexate and warfarin and decrease the effects of oral contraceptives.
Okay, when caring for a pediatric client with otitis media who has been prescribed a beta-lactam/beta-lactamase inhibitor combination like amoxicillin-clavulanate, first perform a baseline assessment by asking the parents or caregivers about current signs of infection, such as unusual fussiness, decreased appetite, as well as rubbing or tugging on the ear. Then, assess weight, vital signs, especially temperature; and the ear canal, making note of the presence of any drainage. Lastly, review recent laboratory test results including renal and liver function tests, as well as CBC.
