Carbapenems are beta-lactam antibiotics with a very broad spectrum of activity and act by disrupting the synthesis of bacterial cell walls. Others in the family of beta-lactam antibiotics are cephalosporins, which include cefepime and ceftazidime. In contrast, beta-lactamase inhibitors have little antibacterial activity alone. They include tazobactam and clavulanate. When used with beta-lactams however, the combination therapy provides enhanced and extended spectrum of activity against bacteria containing plasmid-mediated and chromosomal beta-lactamases. In the literature, the terminology “combination therapy” varies. For instance, the combination product piperacillin-tazobactam is often referred to as monotherapy unless combined with other agents such as amikacin or tobramycin.
The growing problem of multi-drug resistance (MDR) worldwide has led to efforts in restricting the use of carbapenems. MDR and gram-negative bacterial infections are especially predominant in febrile neutropenia (FN), where over 50% of patients have an established or occult infection, and over 20% have bacteremia. If FN patients are not treated immediately, bacterial infections become rapidly fatal. In such patient populations, there are questions of how carbapenems fit in the context of care given the availability of alternative therapies such as beta-lactam/ beta-lactamase inhibitor combinations, and the different strategies of implementation such as escalation and de-escalation. Escalation begins with monotherapy and escalates to a regimen with a broader spectrum. De-escalation begins with a broad regimen and de-escalates to a regimen with a narrower spectrum after laboratory confirmation of the pathogen.
The purpose of this report is to review evidence-based guidelines on the appropriate indications or circumstances for the use of carbapenems and other empiric therapies in the context of MDR infections and FN.
Disclaimer: The Rapid Response Service is an information service for those involved in planning and providing health care in Canada. Rapid responses are based on a limited literature search and are not comprehensive, systematic reviews. The intent is to provide a list of sources of the best evidence on the topic that the Canadian Agency for Drugs and Technologies in Health (CADTH) could identify using all reasonable efforts within the time allowed. Rapid responses should be considered along with other types of information and health care considerations. The information included in this response is not intended to replace professional medical advice, nor should it be construed as a recommendation for or against the use of a particular health technology. Readers are also cautioned that a lack of good quality evidence does not necessarily mean a lack of effectiveness particularly in the case of new and emerging health technologies, for which little information can be found, but which may in future prove to be effective. While CADTH has taken care in the preparation of the report to ensure that its contents are accurate, complete and up to date, CADTH does not make any guarantee to that effect. CADTH is not liable for any loss or damages resulting from use of the information in the report.
