Antibiotic Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae: Systematic Evaluation of the Available Evidence

Abstract

We sought to evaluate the effectiveness of the antibiotic treatment administered for infections caused by carbapenemase-producing Enterobacteriaceae. The PubMed and Scopus databases were systematically searched. Articles reporting the clinical outcomes of patients infected with carbapenemase-producing Enterobacteriaceae according to the antibiotic treatment administered were eligible. Twenty nonrandomized studies comprising 692 patients who received definitive treatment were included. Almost all studies reported on Klebsiella spp. In 8 studies, the majority of infections were bacteremia, while pneumonia and urinary tract infections were the most common infections in 12 studies. In 10 studies, the majority of patients were critically ill. There are methodological issues, including clinical heterogeneity, that preclude the synthesis of the available evidence using statistical analyses, including meta-analysis. From the descriptive point of view, among patients who received combination treatment, mortality was up to 50% for the tigecycline-gentamicin combination, up to 64% for tigecycline-colistin, and up to 67% for carbapenem-colistin. Among the monotherapy-treated patients, mortality was up to 57% for colistin and up to 80% for tigecycline. Certain regimens were administered to a small number of patients in certain studies. Three studies reporting on 194 critically ill patients with bacteremia showed individually significantly lower mortality in the combination arm than in the monotherapy arm. In the other studies, no significant difference in mortality was recorded between the compared groups. Combination antibiotic treatment may be considered the optimal option for severely ill patients with severe infections. However, well-designed randomized studies of specific patient populations are needed to further clarify this issue.

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

“…A number of other recent observational studies and some small, prospective trials also support initial combination therapy for selected patients with specific pathogens (e.g., severe pneumococcal infection, multidrug-resistant gram-negative pathogens) [172,[176][177][178][179][180][181][182]. Unfortunately, in most cases and pending the development of rapid bedside pathogen detection techniques, the offending pathogen is not known at the time of presentation.…”

Clinical and laboratory considerations for the rapid detection of carbapenem-resistant Enterobacteriaceae

“…48,[52][53][54] This remains controversial as not all studies found a survival advantage among patients with CRE infections who received combination therapy vs. monotherapy and results of ongoing randomized studies are not yet available. 55 There is some evidence that non-colistin based regimens had worse outcomes than colistin-based regimens. 56 Antibiotics that are active against CRE depend on carbapenemase type, but include polymyxins B and E (colistin), tigecycline, fosfomycin, aminoglycosides, aztreonam, carbapenems (often administered at high doses using prolonged infusion), and the newly approved agent ceftazidime/avibactam.…”

Risk Factors for Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae (CP-CRE) Acquisition Among Contacts of Newly Diagnosed CP-CRE Patients

“…Strains of K. pneumoniae and other Enterobacteriaceae harboring bla KPC are often extremely drug resistant and pose a significant therapeutic challenge. 1,2 Infections by these strains have also been associated with poor clinical outcomes. [3][4][5] Since they were originally reported in nosocomial outbreaks in the northeastern United States more than a decade ago, these strains have disseminated rapidly to become endemic pathogens in North America, and they are also widespread in Europe, Latin America, and Asia.…”