Combatting resistance in intensive care: the multimodal approach of the Spanish ICU "Zero Resistance" program.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2015 and co-published as a series in Critical Care. Other articles in the series can be found online at http://ccforum.com/series/annualupdate2015. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.

Predictors of mechanical ventilation and mortality in critically ill patients with COVID-19 pneumonia.

OBJECTIVE: To determine if potential predictors for invasive mechanical ventilation (IMV) are also determinants for mortality in COVID-19-associated acute respiratory distress syndrome (C-ARDS). DESIGN: Single center highly detailed longitudinal observational study. SETTING: Tertiary hospital ICU: two first COVID-19 pandemic waves, Madrid, Spain. PATIENTS OR PARTICIPANTS: 280 patients with C-ARDS, not requiring IMV on admission. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Target: endotracheal intubation and IMV, mortality. PREDICTORS: demographics, hourly evolution of oxygenation, clinical data, and laboratory results. RESULTS: The time between symptom onset and ICU admission, the APACHE II score, the ROX index, and procalcitonin levels in blood were potential predictors related to both IMV and mortality. The ROX index was the most significant predictor associated with IMV, while APACHE II, LDH, and DaysSympICU were the most with mortality. CONCLUSIONS: According to the results of the analysis, there are significant predictors linked with IMV and mortality in C-ARDS patients, including the time between symptom onset and ICU admission, the severity of the COVID-19 waves, and several clinical and laboratory measures. These findings may help clinicians to better identify patients at risk for IMV and mortality and improve their management.

Efficacy of tigecycline for the treatment of complicated skin and soft-tissue infections in real-life clinical practice from five European observational studies.

OBJECTIVES: Tigecycline is an approved treatment for complicated skin and soft-tissue infections (cSSTIs). The efficacy of tigecycline as monotherapy or in combination with other antibacterials in the treatment of cSSTI in routine practice is described. PATIENTS AND METHODS: Individual patient-level data were pooled from five European observational studies (July 2006 to October 2011). RESULTS: A total of 254 cSSTI patients who received tigecycline were included (mean age 63.2 ± 14.9 years). Of these, 34.4% were in intensive care units, 54.5% acquired their infection in hospital and 90.9% had at least one comorbidity. Infection most commonly affected the limbs (62.4%) and 43.8% of infections were classified as necrotizing. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores at the beginning of treatment were 15.0 ± 7.9 (n = 205) and 5.8 ± 3.9 (n = 32), respectively, indicating high disease severity. Staphylococcus aureus (52.7%), Escherichia coli (18.0%) and Enterococcus faecium (12.0%) were the most frequently isolated pathogens; 32.9% of infections were polymicrobial and 30.5% were due to resistant pathogens. Overall, 71.8% received tigecycline as monotherapy and 28.2% as combination therapy for a mean duration of 12 days. Clinical response rates at the end of treatment were 79.6% for all patients who received the standard dosage (183/230), 86.7% for patients who received tigecycline as monotherapy (143/165), 75.0% for patients with a nosocomial infection (96/128), 75.3% for patients with an APACHE II score >15 (61/81) and 58.3% for patients with a SOFA score ≥ 7 (7/12). CONCLUSIONS: In these real-life studies, tigecycline, alone and in combination, achieved favourable clinical response rates in patients with cSSTI with a high severity of illness.

Resistance mechanisms and epidemiology of multiresistant pathogens in Europe and efficacy of tigecycline in observational studies.

OBJECTIVES: Antimicrobial drug resistance is a growing problem in Europe and, even with differences in epidemiology, it is of great concern. The treatment of complicated skin and soft-tissue infections (cSSTIs) and complicated intra-abdominal infections (cIAIs) is hindered further by pathogens that are resistant to methicillin, carbapenems, third-generation cephalosporins and glycopeptides. PATIENTS AND METHODS: An analysis of the microbiological results from five European observational studies (July 2006 to October 2011) evaluating the efficacy of tigecycline (prescribed as monotherapy or in combination with other antibacterials) for the treatment of cSSTI and cIAI is presented. RESULTS: In total, 213 cSSTI and 623 cIAI patients were included; 34.4% and 56.6%, respectively, were critically ill in intensive care units. At baseline, at least one pathogen was isolated in 167 (78.4%) cSSTI and 464 (74.5%) cIAI patients, and 32.9% and 49.1% of infections were polymicrobial. In cSSTI, Staphylococcus aureus and Escherichia coli (52.7% and 18.0%, respectively) were the most frequently isolated pathogens, whereas in cIAI most infections were due to E. coli (41.8%), Enterococcus faecium (40.1%) and Enterococcus faecalis (21.1%). Clinical response was observed in >80% of patients with E. coli in both cIAI and cSSTI. In cSSTI patients, the clinical response rate to S. aureus was 80.8%. For cIAI, 77.4% of E. faecium and 79.5% of E. faecalis patients responded to treatment. CONCLUSIONS: Tigecycline when given alone or in combination with other antibacterials appeared to be efficacious against multiple pathogens, affirming its role in real-life clinical practice as a broad-spectrum antibacterial for the treatment of patients with cSSTI and cIAI, including the critically ill, across Europe.

Genetic Diversity and Genome-Wide Association Study for the Phenology Response of Winter Wheats of North America, Western Asia, and Europe.

Wheat is a staple food in many areas around the World. In the 20th century, breeders and scientists were able to boost wheat yield considerably. However, a yield plateau has become a concern and is threatening food security. Investments in cutting-edge technologies, including genomics and precision phenology measurements, can provide valuable tools to drive crop improvement. The objectives of this study were to (i) investigate the genetic diversity in a set of winter wheat lines, (ii) characterize their phenological response under different vernalization and photoperiod conditions, and (iii) identify effective markers associated with the phenological traits. A total of 249 adapted genotypes of different geographical origin were genotyped using the 35K Axiom® Wheat Breeder's Array. A total of 11,476 SNPs were used for genetic analysis. The set showed an average polymorphism information content of 0.37 and a genetic diversity of 0.43. A population structure analysis revealed three distinct subpopulations mainly related to their geographical origin (Europe, North America, and Western Asia). The lines of CGIAR origin showed the largest diversity and the lowest genetic distance to all other subpopulations. The phenology of the set was studied under controlled conditions using four combinations of long (19 h light) and short photoperiod (13 h light) and long vernalization (49 days at 5 °C) and no vernalization. With this, phenological traits such as earliness per se (Eps), relative response to vernalization (RRV), and relative response to photoperiod (RRP) were calculated. The phenotypic variation of growing degree days was significant in all phenology combinations. RRV ranged from 0 to 0.56, while RRP was higher with an overall average of 0.25. The GWAS analysis detected 30 marker-trait associations linked to five phenological traits. The highest significant marker was detected on chromosome 2D with a value of -log10(p) = 11.69. Only four loci known to regulate flowering exceeded the Bonferroni correction threshold of -log10(p) > 5.1. These results outline a solid foundation to address global food security and offer tremendous opportunities for advancing crop improvement strategies.

BAY41-6551 achieves bactericidal tracheal aspirate amikacin concentrations in mechanically ventilated patients with Gram-negative pneumonia.

PURPOSE: To conduct a multicenter, randomized, placebo-controlled, double-blind, phase II study of BAY41-6551 (NCT01004445), an investigational drug-device combination of amikacin, formulated for inhalation, and a proprietary Pulmonary Drug Delivery System, for the treatment of Gram-negative pneumonia in mechanically ventilated patients. METHODS: Sixty-nine mechanically ventilated patients with Gram-negative pneumonia, a clinical pulmonary infection score ≥6, at risk for multidrug-resistant organisms, were randomized to BAY41-6551 400 mg every 12 h (q12h), 400 mg every 24 h (q24h) with aerosol placebo, or placebo q12h for 7-14 days, plus standard intravenous antibiotics. The combined primary endpoint was a tracheal aspirate amikacin maximum concentration ≥6,400 µg/mL (25 × 256 µg/mL reference minimum inhibitory concentration) and a ratio of area under the aspirate concentration-time curve (0-24 h) to minimum inhibitory concentration ≥100 on day 1. RESULTS: The primary endpoint was achieved in 50% (6/12) and 16.7% (3/18) of patients in the q12h and q24h groups, respectively. Clinical cure rates, in the 48 patients getting ≥7 days of therapy, were 93.8% (15/16), 75.0% (12/16), and 87.5% (14/16) in the q12h, q24h, and placebo groups, respectively (p = 0.467). By the end of aerosol therapy, the mean number of antibiotics per patient per day was 0.9 in the q12h, 1.3 in the q24h, and 1.9 in the placebo groups, respectively (p = 0.02 for difference between groups). BAY41-6551 was well tolerated and attributed to two adverse events in one patient (mild bronchospasm). CONCLUSIONS: BAY41-6551 400 mg q12h warrants further clinical evaluation.

Comparación analgésica postquirúrgica de la infiltración corticoanestésica y la anestésica pura tras meniscectomía artroscópica de rodilla / Postoperative pain comparison between steroids anesthetic infiltration, and pure anesthetic infiltration after arthoscopic knee menisectomy

Objetivo: Evaluar la efectividad de las infiltraciones postquirúrgicas de anestésico local solo y combinado con corticoide, para el tratamiento del dolor e inflamación en el postoperatorio temprano en pacientes intervenidos de menisco artroscópicamente. Material y método: Estudio clínico prospectivo randomizado de 60 pacientes a los que se les practicó menisectomía artroscópica. Finalizada la intervención, los pacientes fueron asignados aleatoriamente a uno de los dos grupos de estudio y se infiltró en un grupo 10 ml de clorhidrato de bupivacaína al 0,5% y en el otro el mismo anestésico, asociado a triamcinolona acetónido (solución de 40 mg). La percepción del dolor fue medida objetivamente por la Escala Visual Análoga (EVA), registrándose el dolor postquirúrgico a las 2, 4 y 24 horas y a los 15 días y al mes, después de la intervención. Resultados: No se encontraron diferencias significativas entre los diferentes grupos de estudio. Conclusión: La infiltración anestésica postquirúrgica en dosis única es un procedimiento muy útil para el manejo del dolor postoperatorio en pacientes que requieren la realización de una menisectomía artroscópica (AU)

Objective: To evaluate the effectiveness of postoperative local anesthetic infiltration alone and combined with corticosteroid for the treatment of pain and inflammation in the early postoperative period in patients undergoing arthroscopic meniscal pathology. Material and method: A prospective randomized clinical study, 60 patients who underwent arthroscopic meniscectomy. After surgery, patients were randomly assigned to one of two study groups and infiltrated a group 10 ml of bupivacaine hydrochloride 0.5% and on the other the same anesthetic, associated with triamcinolone acetonide (solution of 40 mg). Pain perception was objectively measured by the Visual Analog Scale (VAS), postoperative pain recorded at 2, 4 and 24 hours and 15 days and a month after the intervention. Results: No significant differences were found between the different groups. Conclusion: Postoperative anesthetic infiltration single dose is a very useful procedure for the management of postoperative pain in patients requiring arthroscopic meniscectomy performing (AU)