Monobactams Monobactams have a monocyclic β-lactam ring and are resistant to β-lactamases. They are active against Gram negative rods primarily through binding to PBP3 but not against Gram-positive bacteria or anaerobes. The first such drug to become available was aztreonam, which resembles aminoglycosides in activity and is given intravenously or intramuscularly every 8 or 12 hours. Patients with IgE-mediated penicillin allergy can tolerate it without reaction, and apart from skin rashes and minor aminotransferase disturbances, no major toxicity has been reported. Superinfections with staphylococci and enterococci can occur.

Carbapenems These drugs are structurally related to the β-lactam antibiotics. Imipenem, the first drug of this type, has good activity against many Gram-negative rods, Gram-positive organisms, and anaerobes. It is resistant to β-lactamases but is inactivated by dehydropeptidases in renal tubules. Consequently, it is administered together with a peptidase inhibitor, cilastatin.

Imipenem penetrates body tissues and fluids well, including CSF. The drug is given intravenously every 6–8 hours and in reduced dosage in renal insufficiency. Imipenem may be indicated for infections caused by organisms resistant to other drugs. Compared to the other carbapenems, imipenem may have better Gram-positive coverage. Meropenem and doripenem have better Gram-negative coverage.

Adverse effects of imipenem include vomiting, diarrhea, skin rashes, and reactions at infusion sites. Excessive levels in patients with renal failure may lead to seizures. Patients who are allergic to penicillins may be allergic to imipenem as well.

Meropenem is similar to imipenem in pharmacology and antimicrobial spectrum of activity. However, it is not inactivated by dipeptidases and is less likely to cause seizures than imipenem.

Ertapenem has a long half-life suitable for once-daily administration. It is useful for treatment of complicated infections not involving hospital pathogens. It has poor activity against Enterococcus species and P. aeruginosa and other glucose-nonfermenting Gram-negative rods.

Doripenem is the most recent carbapenem to be approved for use in the United States. The sulfamoylamimoethyl pyrrolidinylthio group in its side chain at position 2 enhances its activity against glucose-nonfermenting Gram-negative rods. This drug has been reported to have strong affinity for PBPs that are species specific. For example, doripenem has affinity for PBP3 in P. aeruginosa. It is reported that doripenem is more active against P. aeruginosa than imipenem but equal in activity to meropenem. None of the carbapenems have activity against Stenotrophomonas maltophilia.

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