title: Combination therapy for carbapenem-resistant Enterobacteriaceae: increasing evidence, unanswered questions, potential solutions.
abstract: Carbapenem-resistant Enterobacteriaceae (CRE) are associated with a high mortality rate and are an increasing problem worldwide. In this mini-review, we consider the growing number of observational studies in favour of combination therapy but highlight the absence of randomised control trials. We discuss the importance of data on minimum inhibitory concentrations (MICs), both for surveillance and for individual patient management. We examine the issues surrounding the use of carbapenems, polymyxins and tigecycline in the treatment of CRE. When and how should we be using carbapenems? Which polymyxin is best? Is tigecycline much maligned? Further studies are urgently needed to validate drug combinations, doses and ratios to maximise efficacy whilst reducing drug exposure and adverse effects.
authors.affiliation: Public Health England, London, UK. Laura.nabarro@nhs.net.|Department of Microbiology, Christian Medical College, Vellore, Tamil Nadu, India. Laura.nabarro@nhs.net.
authors.forename: L E B
authors.initials: LE
authors.lastname: Nabarro
authors.affiliation: Department of Microbiology, Christian Medical College, Vellore, Tamil Nadu, India.
authors.forename: B
authors.initials: B
authors.lastname: Veeraraghavan
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D015780:Carbapenems / Q000494:pharmacology*; D019090:Case Management; D004359:Drug Therapy, Combination / Q000379:methods; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000382:microbiology*; D062665:Epidemiological Monitoring; D006801:Humans; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives / Q000627:therapeutic use; D064887:Observational Studies as Topic; D011113:Polymyxins / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D000078304:Tigecycline; D016896:Treatment Outcome; D018440:beta-Lactam Resistance
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D011113:Polymyxins; D000078304:Tigecycline; D008911:Minocycline