Dalbavancin as consolidation therapy for infective endocarditis in patients with comorbidity. A real world experience.

OBJECTIVE: Infective endocarditis (IE) is a potentially life-threatening infection, the incidence of which has in creased in recent decades, particularly among elderly patients with comorbidity. The primary objective of this study was to evaluate the effectiveness of dalbavancin in the consolidation therapy of IE in patients with comorbidity six months after the end of treatment (EOT). METHODS: An observational and retrospective study was conducted on patients with a Charlson Comorbidity Index (CCI) ≥ 3 who were diagnosed with IE and received consolidation therapy with dalbavancin. RESULTS: Forty-eight patients were included, 58.3% were male, mean age of 76.2 years (IQR: 66-88), and a mean age adjusted CCI of 6.5 (IQR: 5-7.5). Definite IE was diagnosed in 77% of cases. The most frequently isolated microorganisms were Staphylococcus aureus (45.8%) followed by Enterococcus spp. (31.3%). Complications of IE were observed in 67.7% of cases, and cardiac surgery was performed in 27% of patients. The primary reason for using dalbavancin was outpatient parenteral antibiotic therapy in 85.4% of cases. The effectiveness at EOT was 93.8%. At six months, six IE-related deaths, four unrelated deaths, and two IE relapses were observed. The effectiveness was 77%. Adverse effects related to DBV were reported in 4.2% of cases, of which 2% were considered serious. CONCLUSIONS: Dalbavancin has proven to be an effective alternative as consolidation antibiotherapy for IE in elderly patients with comorbidity. Moreover, a very favorable safety profile with few associated adverse effects has been observed in this population.

Tourniquet application in time-critical aquatic emergencies on a moving rescue water craft (RWC): Can speed and precision coexist?

Lifeguards are the first responders to any type of aquatic incident, including rapid rescue situations such as boating and sporting accidents, animal bites/attacks, and cases involving massive bleeding. In their line of work, rescue boats such as Rescue Water Craft (RWC) are commonly utilized the aim of this study is to evaluate the time and technique of placing a tourniquet on the sled of an RWC navigating at full speed. METHODS: A randomized crossover study design was used with a sample of 44 lifeguards. The inclusion criteria required that participants be certified lifeguards with experience in RWC operations and possess knowledge of responding to massive bleeding. Two CAT tourniquet placement tests were performed. In the 1) Beach-Tourniquet (B-TQ) test: it was performed on land and in the 2) Rescue Water Craft-tourniquet (RWC-TQ) test, sailing at a cruising speed of 20 knots. The evaluation was recorded in a checklist on the steps and timing of the correct application TQ by direct observation by an expert instructor. RESULTS: The tourniquet placement on RWC was an average of 11 s slower than when placed on the beach (BT-TQ 35.7 ± 8.0 vs. 46.1 ± 10.9 s, p > 0.001). In the percentage analysis of the results on correct execution of the skills, higher values are obtained for the B-TQ test than in RWC-TQ in Distance to the wound (into 5-7 cm), band adjustment, checking the radial pulse and reporting the time of tourniquet placement (p > 0.005). CONCLUSION: The placement of a tourniquet on a RWC navigating at 20 knots is feasible, relatively quick, and technically well executed.

Incidence and risk factors for mortality in patients treated with combined ceftaroline for Gram-positive infective endocarditis.

BACKGROUND: Ceftaroline is a fifth-generation cephalosporin and represents an alternative in the treatment of infective endocarditis (IE). The main objective of this study was to describe the incidence of in-hospital and 42-day mortality in patients with IE treated with ceftaroline. METHODS: An observational retrospective study included adult patients with IE admitted during a 3.5-year period (January 2018-June 2021) and treated with ceftaroline in a single center. All cases were definite or possible IE according to the modified Duke criteria. RESULTS: Seventy cases were analyzed. The mean age was 67.35 ± 16.62 (16-89) and 39 (55.7%) were males. The mean number of days of treatment with ceftaroline was 21.26 ± 16.17 (1-75). Overall mortality at 42 days was 30%, 20.7% in the first line, and 36.6% in rescue therapy. Predictors of 42 days-mortality were increased Charlson comorbidity index (CCI) (OR of 1.7 per 1 point increment, 95% CI 1.2-2.4, P 0.001), presence of methicillin-resistance (OR 6.8, 95% CI 1.3-36.8, P 0.026) and evidence of septic shock (OR 8.6 95% CI 1.7-44.2, P 0.01). Predictors of 42 days of therapeutic failure were the increase in the CCI (OR of 1.6 per 1 point increment, 95% CI 1.3-2.1, P 0.000) and septic shock (OR 4.5 95% CI 1.1-18 P 0.036). Adverse effects were described in 6/70 (8.6%) of the patients, precipitating in 4/70 (5.7%) the definitive withdrawal of the antibiotic. CONCLUSIONS: The incidence of in-hospital and 42 day-mortality of IE patients treated with ceftaroline remains similar to literature data. Increased CCI, septic shock, and methicillin resistance are associated with poor prognosis.

The use of ertapenem for the treatment of community-acquired pneumonia in routine hospital practice: a matched cohort study.

OBJECTIVE: The clinical response to ertapenem in community-acquired pneumonia (CAP) at the setting of routine hospital practice has been scarcely evaluated. METHODS: We retrospectively compared CAP cases treated with ertapenem or with other standard antimicrobials (controls) at a tertiary 1,434-bed center from 2005 to 2014. RESULTS: Out of 6,145 patients hospitalized with CAP, 64 (1%) ertapenem-treated and 128 controls were studied (PSI IV-V 72%, mean age 73 years.). A significant higher proportion of bedridden patients (41% vs. 21%), residence in nursing homes (19% vs. 7%), previous use of antibiotics (39% vs. 29%) and necrotizing (13% vs. 1%) or complicated (36% vs. 19%) pneumonia, was observed in the ertapenem vs. non-ertapenem patients. Initial treatment with ertapenem was independently associated with an earlier resolution of signs of infection. In patients aged 65 or older the independent risks factors for mortality were: PSI score (7.0, 95%CI 1.8-27.7), bedridden status (4.6, 95%CI 1.1-20.9) and Health Care Associated Pneumonia (HCAP) (4.6, 95%CI 1.3-16.5). First-line treatment with ertapenem was an independent protector factor in this subgroup of patients (0.1, 95%CI 0.1-0.7). CONCLUSIONS: Ertapenem showed a superior clinical response in frail elderly patients with complicated community-acquired pneumonia, and it may be considered as a first-line therapeutic regimen in this setting.

[Daptomycin dosing greater than 6 mg/kg/day depending on pharmacokinetic and pharmacodynamic parameters infections by Staphylococcus aureus]. / Dosis superior a 6 mg/kg/día de daptomicina según parámetros farmacocinéticos/farmacodinámicos en infecciones por Staphylococcus aureus.

Daptomycin is a cyclic lipopeptide antibiotic whose approved dose is 4 to 6 mg/kg/day. Today it is a matter of controversy the use of higher doses of daptomycin in a range of 8-12 mg/kg/ day, for the treatment of Staphylococcus aureus infections, justified by its concentration-dependent action and its tolerability and safety profile, but the available studies are inconclusive. Stratification is performed by groups of patients, on the recommendation of using doses above 6 mg/kg/day based on the PK/PD parameters predictive of efficacy and safety. We conclude that doses of 8-12 mg/kg/day may be beneficial in patients with severe sepsis, patients with hypoalbuminemia and infections involving potentially high bacterial load or where there is a bacterial kidnapping. However it is not suitable exceed the dose of 6 mg/kg/day in patients with obesity and/or creatinine clearance less than 50 ml/min.

Daptomicina es un antibiótico lipopéptido cíclico cuya dosis autorizada es de 4 a 6 mg/Kg/día. Actualmente se debate la utilización de dosis mayores de daptomicina, en un rango de 8 a 12 mg/Kg/día, para el tratamiento de infecciones producidas por Staphylococcus aureus, justificado por su acción concentración dependiente y su perfil de tolerancia y seguridad, pero los estudios disponibles no son concluyentes. Se realiza una estratificación, por grupos de pacientes, de la recomendación de utilizar dosis superiores a 6 mg/Kg/día en función de los parámetros pk/pd predictores de eficacia y seguridad. Se concluye que dosis de 8 a 12 mg/Kg/día pueden ser beneficiosas en pacientes con sepsis grave, pacientes con hipoalbuminemia y en infecciones que conlleven una carga bacteriana potencialmente elevada o en las que se produzca un secuestro bacteriano. Sin embargo no es adecuado sobrepasar la dosis de 6 mg/Kg/día en pacientes con obesidad y/o con aclaramiento de creatinina inferior a 50 ml/min.

Effects of treatment with pentoxifylline on the cardiovascular manifestations of group B streptococcal sepsis in the piglet.

Pentoxifylline (PTXF) is a methylxanthine derivative which modifies leukocyte function and inhibits tumor necrosis factor (TNF)-alpha release. As TNF-alpha is considered a proximal mediator in the cascade leading to septic shock, we evaluated the ability of PTXF to attenuate the cardiovascular manifestations of sepsis secondary to an infusion of group B beta-hemolytic streptococci (GBS). Fifteen anesthetized, mechanically ventilated piglets (weight, 2815 +/- 552 g) were randomly assigned to a treatment group which received a continuous infusion of PTXF (5 mg/kg/h) beginning 30 min after GBS (7.5 x 10(8) colony-forming units/kg/min) administration was started or to a control group which received GBS plus saline as placebo. Comparison of the hemodynamic measurements and arterial blood gases over the first 120 min of bacterial infusion for treatment and control groups revealed the following statistically significant differences (120-min values presented): cardiac output was significantly higher in the PTXF group (0.159 +/- 0.035 versus 0.09 +/- 0.026 L/kg/min; p < 0.05) as was stroke volume (0.54 +/- 0.11 versus 0.27 +/- 0.126 mL/kg/beat; p < 0.01). Pulmonary and systemic vascular resistances remained lower in the PTXF-treated animals (167 +/- 45 versus 233 +/- 69 mm Hg/L/kg/min; p < 0.03) and (427 +/- 162 versus 828 +/- 426 mm Hg/L/kg/min; p < 0.03, respectively). Median survival time was significantly longer in the PTXF group (180 versus 120 min; p < 0.05). In an additional group of animals, PTXF administration before GBS infusion revealed no attenuation in the rise of TNF-alpha, accompanying sepsis. These data demonstrate that treatment with PTXF may ameliorate some of the deleterious hemodynamic manifestations of GBS sepsis and result in improved survival in a young animal model without significantly modifying plasma TNF-alpha levels.

An MRI tissue equivalent lesion phantom using a novel polysaccharide material.

A new polysaccharide material, TX-150, and method is described which will potentially allow formation of stable, multi-compartment MRI phantoms constructed without intervening septa. TX-150 can be made into water based gels which are nominally tissue equivalent. Although contiguous regions of different water content are not possible, as water diffusion will occur until equilibrium is reached, TX-150 gel T1 and T2 values can be adjusted independently, while maintaining a constant water composition, by appropriate additives. Unlike paramagnetic ions and chelates, metal phthalocyanines have been found to bind tightly to TX-150, thus, permitting formation of stable contiguous regions of differing T1 relaxation properties. Phantom T2 values can be effectively modified with 2-2-diphenyl-1 picrylhydrazyl, which has little affect on gel T1 values, to form septumless lesion phantoms of varying T1 and T2.

Retrospective analysis of hyperthermia for use in the palliative treatment of cancer: a multi-modality evaluation.

Forty-two patients with local or superficial metastatic or recurrent malignant tumors were treated in a non-randomized Phase I/II study to assess the tumoricidal effects of heat combined with radiation and/or chemotherapy. Radiation doses administered averaged 3130 +/- 350 cGy; chemotherapeutic agents employed included bleomycin, mitomycin-C, adriamycin, and cis-platin, heat was induced by radiative or interstitial microwave applicators operating at frequencies ranging from 95 to 900 MHz. Forty-one of the forty-two patients were evaluated for initial therapeutic effects yielding the following response distributions: local hyperthermia with radiation--42% complete response (CR), 44% partial response (PR), and 15% no response (NR); local hyperthermia with chemotherapy--0% CR, 50% PR and 50% NR. Long-term response duration was evaluated for local hyperthermia with radiation, yielding mean time to recurrence of 9.4 months for CR's and mean time to progression of 3.4 months for PR's. In retrospective analysis, we examined the correlations of previously established response-predictor variables of tumor volume and minimum thermal dose with both initial and long-term response rates. Initial complete response rates were correlated directly with non-site-specific minimum thermal dose, varied inversely with tumor volume and exhibited a positive correlation for a limited histologic type/treatment site combination. Surprisingly, long-term response did not correlate either with tumor volume or thermal dose. The frequency of thermally induced complications, which did not correlate with any measured thermal parameters, was found to be 42%, expressed on a per-patient basis.