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BackgroundIntense debate exists regarding the optimal energy and protein intake for intensive care unit (ICU) patients. However, most studies use predictive equations, demonstrated to be inaccurate to target energy intake. We sought to examine the outcome of a large cohort of ICU patients in relation to the percent of administered calories divided by resting energy expenditure (% AdCal/REE) obtained by indirect calorimetry (IC) and to protein intake.MethodsIncluded patients were hospitalized from 2003 to 2015 at a 16-bed ICU at a university affiliated, tertiary care hospital, and had IC measurement to assess caloric targets. Data were drawn from a computerized system and included the % AdCal/REE and protein intake and other variables. A Cox proportional hazards model for 60-day mortality was used, with the % AdCal/REE modeled to accommodate non-linearity. Length of stay (LOS) and length of ventilation (LOV) were also assessed.ResultsA total of 1171 patients were included. The % AdCal/REE had a significant non-linear (p < 0.01) association with mortality after adjusting for other variables (p < 0.01). Increasing the percentage from zero to 70 % resulted in a hazard ratio (HR) of 0.98 (CI 0.97–0.99) pointing to reduced mortality, while increases above 70 % suggested an increase in mortality with a HR of 1.01 (CI 1.01–1.02). Increasing protein intake was also associated with decreased mortality (HR 0.99, CI 0.98–0.99, p = 0.02). An AdCal/REE >70 % was associated with an increased LOS and LOV.ConclusionsThe findings of this study suggest that both underfeeding and overfeeding appear to be harmful to critically ill patients, such that achieving an Adcal/REE of 70 % had a survival advantage. A higher caloric intake may also be associated with harm in the form of increased LOS and LOV. The optimal way to define caloric goals therefore requires an exact estimate, which is ideally performed using indirect calorimetry. These findings may provide a basis for future randomized controlled trials comparing specific nutritional regimens based on indirect calorimetry measurements.

e Our objective was to examine the evidence of in vitro synergy of polymyxin-carbapenem combination therapy against Gramnegative bacteria (GNB). A systematic review and meta-analysis were performed. All studies examining in vitro interactions of antibiotic combinations consisting of any carbapenem with colistin or polymyxin B against any GNB were used. A broad search was conducted with no language, date, or publication status restrictions. Synergy rates, defined as a fractional inhibitory concentration index of <0.5 or a >2-log reduction in CFU, were pooled separately for time-kill, checkerboard, and Etest methods in a mixed-effect meta-analysis of rates. We examined whether the synergy rate depended on the testing method, type of antibiotic, bacteria, and resistance to carbapenems. Pooled rates with 95% confidence intervals (CI) are shown. Thirty-nine published studies and 15 conference proceeding were included, reporting on 246 different tests on 1,054 bacterial isolates. In time-kill studies, combination therapy showed synergy rates of 77% (95% CI, 64 to 87%) for Acinetobacter baumannii, 44% (95% CI, 30 to 59%) for Klebsiella pneumoniae, and 50% (95% CI, 30 to 69%) for Pseudomonas aeruginosa, with low antagonism rates for all. Doripenem showed high synergy rates for all three bacteria. For A. baumannii, meropenem was more synergistic than imipenem, whereas for P. aeruginosa the opposite was true. Checkerboard and Etest studies generally reported lower synergy rates than time-kill studies. The use of combination therapy led to less resistance development in vitro. The combination of a carbapenem with a polymyxin against GNB, especially A. baumannii, is supported in vitro by high synergy rates, with low antagonism and less resistance development. These findings should be examined in clinical studies.

The significant association observed in observational studies between polymyxin monotherapy and mortality cannot be taken as proof of combination therapy effects due to the low quality of the evidence. The only three RCTs to date show no effect of rifampicin/colistin or fosfomycin/colistin on mortality for Acinetobacter infections.

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It is currently uncertain whether early administration of protein improves patient outcomes. We examined mortality rates of critically ill patients receiving early compared to late protein administration. This was a retrospective cohort study of mixed ICU patients receiving enteral or parenteral nutritional support. Patients receiving >0.7 g/kg/d protein within the first 3 days were considered the early protein group and those receiving less were considered the late protein group. The latter were subdivided into late-low group (LL) who received a low protein intake (<0.7 g/kg/d) throughout their stay and the late-high group (LH) who received higher doses (>0.7 g/kg/d) of protein following their first 3 days of admission. The outcome measure was all-cause mortality 60 days after admission. Of the 2253 patients included in the study, 371 (36%) in the early group, and 517 (43%) in the late-high group had died (p < 0.001 for difference). In multivariable Cox regression analysis, while controlling for confounders, early protein administration was associated with increased survival (HR 0.83, 95% CI 0.71–0.97, p = 0.017). Administration of protein early in the course of critical illness appears to be associated with improved survival in a mixed ICU population, even after adjusting for confounding variables.

Background We evaluated the association between mortality and colistin resistance in Acinetobacter baumannii infections and the interaction with antibiotic therapy. Methods This is a secondary analysis of a randomized controlled trial of patients with carbapenem-resistant gram-negative bacterial infections treated with colistin or colistin-meropenem combination. We evaluated patients with infection caused by carbapenem-resistant A. baumannii (CRAB) identified as colistin susceptible (CoS) at the time of treatment and compared patients in which the isolate was confirmed as CoS with those whose isolates were retrospectively identified as colistin resistant (CoR) when tested by broth microdilution (BMD). The primary outcome was 28-day mortality. Results Data were available for 266 patients (214 CoS and 52 CoR isolates). Patients with CoR isolates had higher baseline functional capacity and lower rates of mechanical ventilation than patients with CoS isolates. All-cause 28-day mortality was 42.3% (22/52) among patients with CoR strains and 52.8% (113/214) among patients with CoS isolates (P = .174). After adjusting for variables associated with mortality, the mortality rate was lower among patients with CoR isolates (odds ratio [OR], 0.285 [95% confidence interval {CI}, .118–.686]). This difference was associated with treatment arm: Mortality rates among patients with CoR isolates were higher in those randomized to colistin-meropenem combination therapy compared to colistin monotherapy (OR, 3.065 [95% CI, 1.021–9.202]). Conclusions Colistin resistance determined by BMD was associated with lower mortality among patients with severe CRAB infections. Among patients with CoR isolates, colistin monotherapy was associated with a better outcome compared to colistin-meropenem combination therapy. Clinical Trials Registration NCT01732250