Bacterial resistance to existent antibiotherapy is a perpetual internationally-recognized problem. Year after year, there is a continuous need for novel antibacterial drugs and this research and development efforts recently resulted in few new drugs or combination of drugs proposed for the use into the clinic. This review focuses on the novel US FDA approved antibacterial agents in the last two years (2018-2019). Plazomicin, eravacycline, sarecycline, omadacycline, rifamycin (2018) and imipenem, cilastatin and relebactam combination, pretomanid, lefamulin, cefiderocol (2019) are new therapeutic options. Plazomicin aminoglycoside antibiotic targets Enterobacteriaceae infections, being mainly used for the complicated urinary tract infections. The fully synthetic fluorocycline eravacycline gained approval for the complicated intra-abdominal infections. The tetracycline-derived antibiotic sarecycline might be a useful strategy for the management of non-nodular moderate to severe acne, while the other tetracycline-derived antibiotic approved, omadacycline, may be used for the patients with acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. The already-known RNA-synthesis suppressor rifamycin is now also approved for noninvasive Escherichia Coli-caused travelers' diarrhea. Two combinatorial strategies were approved for complicated urinary tract infections, complicated intra-abdominal infections (imipenem, cilastatin and relebactam) and lung tuberculosis (pretomanid in combination with bedaquiline and linezolid). Lefamulin is a semisynthetic pleuromutilin antibiotic for community-acquired bacterial pneumonia, while cefiderocol, a cephalosporin antibiotic is the last antibacterial drug approved in 2019, for the use in complicated urinary tract infections. Despite of these new developments, there is an ongoing need and urgency to develop novel antibiotic strategies and drugs to overrun the bacterial resistance to antibiotics.

Background: The importance of assessing venous congestion in ICU patients is widely acknowledged, but its study is hampered by the lack of a practical evaluation tool. The Venous Excess Ultrasound Grading System (VExUS), based on a semi-quantitative combined ultrasound assessment, has been associated with acute kidney injury (AKI) in cardiac ICU patients. The objectives of this study were to assess the prevalence of congestion using VExUS in general ICU patients, and to evaluate the association between VExUS, AKI and death. Methods: This prospective, observational study included adult patients within 24 h of ICU admission. VExUS and hemodynamic parameters were measured four times during the ICU stay: within 24 h of ICU admission, after day 1 (between 24 and 48 h), after day 2 (between 48 and 72 h), and last day of ICU stay. The prevalence of AKI during the first week in ICU and 28-day mortality were assessed. Results: Among the 145 patients included, the percentage of patients with a VExUS score of 2 (moderate congestion) and 3 (severe congestion) was 16% and 6%, respectively. The prevalence did not change over the study period. There was no significant association between admission VExUS scores and AKI (p = 0.136) or 28-day mortality (p = 0.594). Admission VExUS ≥ 2 was not associated with AKI (OR 0.499, CI_95% 0.21–1.17, p = 0.109) nor 28-day mortality (OR 0.75, CI_95% 0.2–2.8, p = 0.669). The results were similar for VExUS scores measured at day 1 and day 2. Conclusions: In general ICU cohort the prevalence of moderate to severe venous congestion was low. Early assessment of systemic venous congestion using VExUS scores was not associated with the development of AKI or with 28-day mortality.

Background: Fluid overload and venous congestion are associated with morbi-mortality in the ICU (intensive care unit). Administration of diuretics to correct the fluid balance is common, although there is no strong relationship between the consequent fluid loss and clinical improvement. The aim of the study was to evaluate the ability of the portal pulsatility index, the renal venous impedance index, and the VEXUS score (venous ultrasound congestion score) to predict appropriate diuretic-induced fluid depletion. Methods: The study had a prospective, observational, single-center observational design and was conducted in a university-affiliated medico-surgical ICU. Adult patients for whom the clinician decided to introduce loop diuretic treatment were included. Hemodynamic and ultrasound measurements (including the portal pulsatility index, renal venous impedance index and VEXUS score) were performed at inclusion and 2 hours after the initiation of the diuretics. The patients’ characteristics were noted at inclusion, 24 h later, and at ICU discharge. The appropriate diuretic-induced fluid depletion was defined by a congestive score lower than 3 after diuretic fluid depletion. The congestive score included clinical and biological parameters of congestion. Results: Eighty-one patients were included, and 43 (53%) patients presented with clinically significant congestion score at inclusion. Thirty-four patients (42%) had an appropriate response to diuretic-induced fluid depletion. None of the left- and right-sided echocardiographic parameters differed between the two groups. The baseline portal pulsatility index was the best predictor of appropriate response to diuretic-induced fluid depletion (AUC = 0.80, CI_95%:0.70–0.92, p = 0.001), followed by the renal venous impedance index (AUC = 0.72, CI_95% 0.61–0.84, p = 0.001). The baseline VEXUS score (AUC of 0.66 CI_95% 0.53–0.79, p = 0.012) was poorly predictive of appropriate response to diuretic-induced fluid depletion. Conclusion: The portal pulsatility index and the renal venous impedance index were predictive of the appropriate response to diuretic-induced fluid depletion in ICU patients. The portal pulsatility index should be evaluated in future randomized studies.

Increasing bacterial resistance to antibiotics is a worldwide ongoing issue. Urgent need for new antibacterial agents has resulted in significant research efforts, with new molecules proposed for use in clinical practice. However, as highlighted by many groups this process does not have an optimal rhythm and efficacy, to fully combat highly adaptive germs, particularly in the intensive care units. This review focuses on the last three years of novel FDA approved antibacterial agents (2015-2017): ceftazidime/avibactam, obiltoxaximab, bezlotoxu-mab, delafloxacin, meropenem/vaborbactam, ozenoxacin. Ceftazidime/avibactam and meropenem/ vaborbactam are new players in the field of resistant bacteria treatment. Ceftazidime/avibactam is validated in selected patients with complicated urinary or intra-abdominal infections, hospital and ventilator-associated pneumonia. Meropenem/ vaborbactam gained approval for the cases of complicated urinary tract infections. Other potential indications are under investigation, widened and validated by future studies. Obiltoxaximab is a monoclonal antibody that can be used in the prevention and treatment of inhalational anthrax. Bezlotoxumab monoclonal antibody is an useful and specific tool for the management of recurrent Clostridium difficile infection. Delafloxacin is approved for patients with acute skin or skin structure infections. Despite recent progress, it is imperative to continue the development of new antibiotic drugs and new strategies to counteract resistance to antibiotics.

As an extension of the traditional heart-centred pressure-flow model, the ventriculo-arterial coupling concept is based on the pressure–volume relationship of the left ventricle and the vascular system. Even though ventriculo-arterial coupling has been studied in cardiology for more than 30 years, its value in clinical practice in anaesthesia and ICU remains poorly known and used. The clinical interest in ventriculo-arterial coupling is derived from its strong connection with cardiac energetics and efficiency. An alteration of ventriculo-arterial coupling is a marker of disease severity and is associated with outcome. The main categories of cardio-circulatory failures observed in ICU patients commonly exhibit alterations in ventriculo-arterial coupling with typical patterns. Furthermore, the effectiveness of usual haemodynamic treatments and interventions correlates with ventriculo-arterial coupling improvements in ICU patients. Consequently, treatment and management bundles may be proposed to specifically target the correction of ventriculo-arterial uncoupling to optimise the patients’ haemodynamic status and outcome. Restoring ventriculo-arterial coupling with treatments improves outcomes in subgroups of ICU patients. Even though ventriculo-arterial coupling evaluation cannot be considered as a part of the basic core curriculum of anaesthesiologists and ICU residents, anaesthesia and ICU practitioners must be familiarised with the clinical significance of ventriculo-arterial (un)coupling and availability of its bedside noninvasive evaluation. The understanding of ventriculo-arterial coupling may be particularly important in complex haemodynamic clinical situations.

Introduction: The determination of ventriculo-arterial coupling is gaining an increasing role in cardiovascular and sport medicine. However, its relevance in critically ill patients is still under investigation. In this study we measured the association between ventriculo-arterial coupling and oxygen consumption (VO₂) response after hemodynamic interventions in cardiac surgery patients with acute circulatory instability.Material and Methods: Sixty-one cardio-thoracic ICU patients (67 ± 12 years, 80% men) who received hemodynamic therapeutic interventions (fluid challenge or norepinephrine infusion) were included. Arterial pressure, cardiac output, heart rate, arterial (E_A), and ventricular elastances (E_V), total indexed peripheral resistances were assessed before and after hemodynamic interventions. VO₂ responsiveness was defined as VO₂ increase >15% following the hemodynamic intervention. Ventriculo-arterial coupling was assessed measuring the E_A/E_V ratio by echocardiography. The left ventricle stroke work to pressure volume area ratio (SW/PVA) was also calculated.Results: In the overall cohort, 24 patients (39%) were VO₂ responders, and 48 patients had high ventriculo-arterial (E_A/E_V) coupling ratio with a median value of 1.9 (1.6–2.4). Most of those patients were classified as VO₂ responders (28 of 31 patients, p = 0.031). Changes in VO₂ were correlated with those of indexed total peripheral resistances, E_A, E_A/E_V and cardiac output. E_A/E_V ratio predicted VO₂ increase with an AUC of 0.76 [95% CI: 0.62–0.87]; p = 0.001. In principal component analyses, E_A/E_V and SW/PVA ratios were independently associated (p < 0.05) with VO₂ response following interventions.Conclusions: VO₂ responders were characterized by baseline high ventriculo-arterial coupling ratio due to high E_A and low E_V. Baseline E_A/E_V and SW/PVA ratios were associated with VO₂ changes independently of the hemodynamic intervention used. These results underline the pathophysiological significance of measuring ventriculo-arterial coupling in patients with hemodynamic instability, as a potential therapeutic target.