Abstract
Purpose (i) To compare infections caused by carbapenem-susceptible (CS) and carbapenemase producing carbapenem-resistant Enterobacteriaceae (CP-CRE); (ii) to evaluate the clinical effectiveness of the double-carbapenem (DC) regimen in comparison with the best available treatment (BAT) in infections caused by CP-CRE; and (iii) to determine the exact minimal inhibitory concentrations (MICs) of meropenem/ertapenem (MEM/ETP) and the degree of in vitro ETP+MEM synergism in subjects receiving the DC. Methodology Over a 3-year period (2014-2017), patients with infections due to Enterobacteriaceae were included in a single-center, retrospective, observational study. According to the susceptibility to carbapenems, subjects were divided into CSE and CP-CRE groups. CP-CRE group was further divided into subjects receiving the DC regimen and those treated with other regimens (BAT group). Clinical characteristics and the presence of 5th-day response and 60-day outcome were evaluated for DC and BAT groups. The determination of MEM and ETP actual MICs and the MEM+ETP synergistic activity were performed on strains obtained from subjects receiving the DC regimen. Results A total of 128 patients were included in the study: 55/128 (43%) with infections due to CP-CRE and 73/128 (57%) with infections due to CSE. Among CP-CRE (n=55), 21 subjects (39%) were treated with the DC regimen whereas 34 (61%) received BAT. No differences in terms of severity of infection, presence/absence of concomitant bacteremia, type of infection, and resolution of infection were found; in contrast, DC group tended to have a higher rate of sepsis or septic shock at the onset of infection and a higher rate of 5th-day response. MICs 50/90 were 256/512 and 256/256 μg/mL for MEM and ETP, respectively. Overall, complete in vitro synergism was found in 6/20 strains (30%). Conclusion The DC regimen is a valid and effective therapeutic option in patients with infections due to KPC producing CRE, including those with bacteremic infection and more severe clinical conditions. The clinical effectiveness is maintained even in the presence of extremely high MEM MICs.
Highlights
The rapid spread of multidrug-resistant bacteria has become a public health concern, especially in some countries where the spread of carbapenem-resistant microorganisms is endemic [1]
A total of 128 patients were included in the study: 55/128 (43%) with infections due to carbapenem-resistant Enterobacteriaceae (CP-CRE) and 73/128 (57%) with infections due to Carbapenem-susceptible Enterobacteriaceae (CSE) (Table 1)
Length of hospitalization before the onset of infection was higher in CP-CRE than in CSE
Summary
The rapid spread of multidrug-resistant bacteria has become a public health concern, especially in some countries where the spread of carbapenem-resistant microorganisms is endemic [1]. Infections caused by CP-CRE are associated with a high treatment failure and consequent high mortality, given the limited therapeutic options and the lack of worldwide availability of new drugs such as ceftazidime/avibactam [2]. The combination therapy is preferred over monotherapy, the optimal management of CP-CRE systemic infections remains a real challenge, which seems even more complicated given the emergence of resistance to ceftazidime/avibactam [4] and the rising diffusion of strains harbouring enzymes other than carbapenemases [1]. Subjects hospitalized at Department of Public Health and Infectious Diseases (2014-2017) N=1291. Subjects with infections caused by Enterobacteriaceae N=140. Subjects with Enterobacteriaceae isolates not receiving therapy N=12
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