Carbapenems and monobactams: Imipenem, meropenem, and aztreonam

Imipenem and meropenem, members of the carbapenem class of beta-lactam anti biotics, are among the most broadly active antibiotics available for system ic use in humans. They are active against streptococci, methicillin-sensiti ve staphylococci, Neisseria, Haemophilus, anaerobes, and the common aerobic gram-negative nosocomial pathogens including Pseudomonas. Resistance to im ipenem and meropenem may emerge during treatment of P. aeruginosa infection s, as has occurred with other beta-lactam agents; Stenotrophomonas maltophi lia is typically resistant to both imipenem and meropenem. Like the penicil lins, the carbapenems have inhibitory activity against enterococci. In gene ral, the in vitro activity of imipenem against aerobic gram-positive cocci is somewhat greater than that of meropenem, whereas the in vitro activity o f meropenem against aerobic gram-negative bacilli is somewhat greater than that of imipenem. Daily dosages may range from 0.5 to 1 g every 6 to 8 hour s in patients with normal renal function; the daily dose of meropenem, howe ver, can be safely increased to 6 g. Infusion-related nausea and vomiting, as well as seizures, which have been the main toxic effects of imipenem, oc cur no more frequently during treatment with meropenem than during treatmen t with other beta-lactam antibiotics. The carbapenems should be considered for treatment of mixed bacterial infections and aerobic gram-negative bacte ria that are not susceptible to other beta-lactam agents. Indiscriminate us e of these drugs will promote resistance to them. Aztreonam, the first mark eted monobactam, has activity against most aerobic gram-negative bacilli in cluding P. aeruginosa. The drug is not nephrotoxic, is weakly immunogenic, and has not been associated with disorders of coagulation. Aztreonam may be administered intramuscularly or intravenously; the primary route of elimin ation is urinary excretion. In patients with normal renal function, the rec ommended dosing interval is every 8 hours. Patients with renal impairment r equire dosage adjustment. Aztreonam is used primarily as an alternative to aminoglycosides and for the treatment of aerobic gram-negative infections. It is often used in combination therapy for mixed aerobic and anaerobic inf ections. Approved indications for its use include infections of the urinary tract or lower respiratory tract, intra-abdominal and gynecologic infectio ns, septicemia, and cutaneous infections caused by susceptible organisms. C oncurrent initial therapy with other antimicrobial agents is recommended be fore the causative organism has been determined in patients who are serious ly ill or at risk for gram-positive or anaerobic infection.