A prospective study of treatment of carbapenem-resistant Enterobacteriaceae infections and risk factors associated with outcome

Abstract

BackgroundTo describe the clinical and microbiological data of carbapenem-resistant Enterobacteriaceae (CRE) infections, the treatment used, hospital- and infection-related mortality, and risk factors for death.MethodsA prospective cohort conducted from March 2011 to December 2012. Clinical, demographic, and microbiological data such as in vitro sensitivity, clonality, carbapenemase gene mortality related to infection, and overall mortality were evaluated. Data were analyzed using Epi Info version 7.0 (CDC, Atlanta, GA, USA) and SPSS (Chicago, IL, USA).ResultsOne hundred and twenty-seven patients were evaluated. Pneumonia, 52 (42 %), and urinary tract infections (UTI), 51 (40.2 %), were the most frequent sites of infection. The isolates were polyclonal; the Bla KPC gene was found in 75.6 % of isolates, and 27 % of isolates were resistant to colistin. Mortality related to infection was 34.6 %, and was higher among patients with pneumonia (61.4 %). Combination therapy was used in 98 (77.2 %), and monotherapy in 22.8 %; 96.5 % of them were UTI patients. Shock, age, and dialysis were independent risk factors for death. There was no difference in infection-related death comparing colistin-susceptible and colistin-resistant infections (p = 0.46); neither in survival rate comparing the use of combination therapy with two drugs or more than two drugs (p = 0.32).ConclusionsCRE infection mortality was higher among patients with pneumonia. Infections caused by colistin-resistant isolates did not increase mortality. The use of more than two drugs on combination therapy did not show a protective effect on outcome. The isolates were polyclonal, and the bla KPC gene was the only carbapenemase found. Shock, dialysis, and age over 60 years were independent risk factors for death.

How Should We Treat HAP/VAP Caused by Carbapenemase-Producing Enterobacteriaceae?

“…In this cohort, pneumonia was the most common site of infection (52 cases, 42%) and was associated with a significantly higher infection-related mortality compared with other site CRE infections (61 vs. 34.6%). 21 The same results have been confirmed by other studies reporting high mortality rates in CRE respiratory tract infections. Wang et al collected 94 cases of CRE infections from October 2010 to November 2014 in two large teaching hospitals in China.…”

“…19,20 Giacobbe et al in a multicenter, retrospective study including 729 cases of bloodstream infections (BSIs) due to KPC-producing K. pneumoniae (KPC-Kp), found that colistin-resistant KPC-Kp were more often associated with lower respiratory tract infections and inadequate empirical antibiotic treatment than colistin-susceptible strains, leading to a higher percentage of initial treatment failure and 30-day crude mortality (51 vs. 39.4%). 21 The global epidemiology of CRE and colistin-resistant K. pneumoniae is described in ►Table 2.…”

Exploring colistin pharmacodynamics against Klebsiella pneumoniae: a need to revise current susceptibility breakpoints

“…Furthermore, using the 2 mg/L breakpoint, no difference was found in mortality between carbapenem-resistant Enterobacteriaceae infections by colistinsusceptible and colistin-resistant isolates. 32 More important is the finding that the clinical outcomes of colistin therapy in patients infected with susceptible (MIC 2 mg/L) A. baumannii isolates but high colistin MICs (1-2 mg/L) were poorer than in patients infected with isolates with lower (,1 mg/L) MICs (7 day outcome 38% versus 20.2%, P " 0.025). 33 Finally, it was suggested that current maintenance doses may not be effective against isolates with an MIC .0.5 mg/l.…”

Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and Carbapenemase-Producing Enterobacteriaceae

“…Observational studies comparing the outcomes for patients treated with monotherapy or combination therapy were reviewed, and control for confounders was taken into account. Most studies focused on or supplied data for BSI (212)(213)(214)(215)(216)(217)(218)(219)(220)(221)(222)(223)(224)(225)(226)(227)(228)(229) (Table 4), while others included other types of infection (213,215,227,(230)(231)(232)(233)(234)(235)(236) (Table 5). Systematic reviews published in 2014 found major limitations in the studies analyzed and therefore could not draw strong conclusions (47,237).…”