Monobactams are drugs with a monocyclic β-lactam ring (Figure 43–1). Their spectrum of activity is limited to aerobic Gram-negative organisms (including P aeruginosa). Unlike other β-lactam antibiotics, they have no activity against Gram-positive bacteria or anaerobes. Aztreonam is the only monobactam available in the USA. It has structural similarities to ceftazidime, and its Gram-negative spectrum is similar to that of the third-generation cephalosporins. It is stable to many β-lactamases with notable exceptions being AmpC β-lactamases and extended-spectrum β-lactamases. It penetrates well into the cerebrospinal fluid. Aztreonam is given intravenously every 8 hours in a dose of 1–2 g, providing peak serum levels of 100 mcg/mL. The half-life is 1–2 hours and is greatly prolonged in renal failure.
Penicillin-allergic patients tolerate aztreonam without reaction. Notably, because of its structural similarity to ceftazidime, there is potential for cross-reactivity; aztreonam should be used with caution in the case of documented severe allergies to ceftazidime. Occasional skin rashes and elevations of serum aminotransferases occur during administration of aztreonam, but major toxicity is uncommon. In patients with a history of penicillin anaphylaxis, aztreonam may be used to treat serious infections such as pneumonia, meningitis, and sepsis caused by susceptible Gram-negative pathogens.
BETA-LACTAMASE INHIBITORS (CLAVULANIC ACID, SULBACTAM, TAZOBACTAM, & AVIBACTAM)
Traditional β-lactamase inhibitors (clavulanic acid, sulbactam, and tazobactam) resemble β-lactam molecules (Figure 43–7), but they have very weak antibacterial action. They are potent inhibitors of many but not all bacterial β-lactamases and can protect hydrolyzable penicillins from inactivation by these enzymes. The traditional β-lactamase inhibitors are most active against Ambler class A β-lactamases (plasmid-encoded transposable element [TEM] β-lactamases in particular), such as those produced by
FIGURE 43–7 Beta-lactamase inhibitors.
staphylococci, H influenzae, N gonorrhoeae, Salmonella, Shigella, E coli, and K pneumoniae. They are not good inhibitors of class C β-lactamases, which typically are chromosomally encoded and inducible, produced by Enterobacter sp, Citrobacter sp, S marcescens, and P aeruginosa, but they do inhibit chromosomal β-lactamases of B fragilis and M catarrhalis. The novel non-βlactam β-lactamase inhibitor avibactam is active against Ambler class A β-lactamases but also active against Ambler class C and some Ambler class D β-lactamases.