Intense 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. Included 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. A 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. The 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.

Our objective was to examine the evidence of in vitro synergy of polymyxin-carbapenem combination therapy against Gram-negative 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 objective of this study was to summarize available data on polymyxin-based combination therapy or monotherapy for carbapenem-resistant Gram-negative bacteria. This is a systematic review. We included observational studies and randomized controlled trials (RCTs) comparing polymyxin monotherapy versus polymyxin-based combination therapy in adult patients with infections caused by carbapenem-resistant or carbapenemase-producing Gram-negative bacteria. Only named antibiotic regimens were included. The primary outcome was 30 day mortality. Unadjusted OR (uOR) and adjusted OR where available with 95% CI were pooled in random-effects meta-analyses. Twenty-two studies including 28 comparisons were included. Polymyxin monotherapy was associated with a uOR of 1.58 (95% CI = 1.03–2.42) for mortality compared with polymyxin/carbapenem combination therapy (seven observational studies, 537 patients), without heterogeneity. Subgrouping studies to serious and critical risk of bias resulted in uORs of 0.94 (95% CI = 0.42–2.09) and 1.94 (95% CI = 1.17–3.23), respectively. Mortality was significantly higher with polymyxin monotherapy compared with combination therapy with tigecycline, aminoglycosides or fosfomycin (potentially double-coverage regimens): uOR of 1.57 (95% CI = 1.06–2.32) overall (10 observational studies and 1 RCT, 585 patients, no heterogeneity) and uOR of 2.09 (95% CI = 1.21–3.6) for Klebsiella pneumoniae bacteraemia (7 observational studies, 285 patients, no heterogeneity); very low quality evidence. Two RCTs and one observational study assessing rifampicin/colistin combination therapy for Acinetobacter baumannii infections showed no difference in mortality compared with colistin monotherapy; moderate quality evidence. 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.

Background—: Coronary artery disease (CAD) is highly prevalent in patients undergoing transcatheter aortic valve replacement. In the overall CAD population, complete revascularization or reasonable incomplete revascularization (ICR) is associated with improved outcomes; whether the same applies for the transcatheter aortic valve replacement population is still a matter of debate. Methods and Results—: We conducted a systematic review and meta-analysis of studies that examined the prognostic effect of revascularization completeness in patients undergoing transcatheter aortic valve replacement using the residual SYNTAX score (Synergy Between PCI With Taxus and Cardiac Surgery) to separate between reasonable ICR and ICR (using the individual threshold used by each study). Six studies with a total of 3107 patients were included. The duration of follow-up ranged from 0.7 to 3 years. Overall, ICR was associated with an increased risk for mortality. This was true when comparing ICR patients to those with no CAD (odds ratio, 1.85; 95% confidence interval, 1.42–2.40; P <0.01), to those with reasonable ICR (odds ratio, 1.69; 95% confidence interval, 1.26–2.28; P <0.001), or to both groups combined (odds ratio, 1.71; 95% confidence interval, 1.36–2.16; P <0.001). On the contrary, patients in the reasonable ICR category did not show an increased risk for mortality when compared with those with no CAD (odds ratio, 1.11; 95% confidence interval, 0.89–1.39; P =0.33). Conclusions—: Our results suggest that for patients with CAD undergoing transcatheter aortic valve replacement, a residual SYNTAX score–guided revascularization strategy may carry significant benefits in terms of mortality. Adequate revascularization may offer a unique and valuable opportunity to improve the prognosis of these patients.