Introduction
Treatment options for carbapenem-resistant Enterobacteriaceae (CRE) infections are limited and CRE infections remain associated with high clinical failure and mortality rates, ...particularly in vulnerable patient populations. A Phase 3, multinational, open-label, randomized controlled trial (TANGO II) was conducted from 2014 to 2017 to evaluate the efficacy/safety of meropenem–vaborbactam monotherapy versus best available therapy (BAT) for CRE.
Methods
A total of 77 patients with confirmed/suspected CRE infection (bacteremia, hospital-acquired/ventilator-associated bacterial pneumonia, complicated intra-abdominal infection, complicated urinary tract infection/acute pyelonephritis) were randomized, and 47 with confirmed CRE infection formed the primary analysis population (microbiologic-CRE-modified intent-to-treat, mCRE-MITT). Eligible patients were randomized 2:1 to meropenem–vaborbactam (2 g/2 g over 3 h, q8h for 7–14 days) or BAT (mono/combination therapy with polymyxins, carbapenems, aminoglycosides, tigecycline; or ceftazidime-avibactam alone). Efficacy endpoints included clinical cure, Day-28 all-cause mortality, microbiologic cure, and overall success (clinical cure + microbiologic eradication). Safety endpoints included adverse events (AEs) and laboratory findings.
Results
Within the mCRE-MITT population, cure rates were 65.6% (21/32) and 33.3% (5/15) 95% confidence interval (CI) of difference, 3.3% to 61.3%;
P
= 0.03) at End of Treatment and 59.4% (19/32) and 26.7% (4/15) (95% CI of difference, 4.6% to 60.8%;
P
= 0.02) at Test of Cure;.Day-28 all-cause mortality was 15.6% (5/32) and 33.3% (5/15) (95% CI of difference, − 44.7% to 9.3%) for meropenem–vaborbactam versus BAT, respectively. Treatment-related AEs and renal-related AEs were 24.0% (12/50) and 4.0% (2/50) for meropenem–vaborbactam versus 44.0% (11/25) and 24.0% (6/25) for BAT. Exploratory risk–benefit analyses of composite clinical failure or nephrotoxicity favored meropenem–vaborbactam versus BAT (31.3% 10/32 versus 80.0% 12/15; 95% CI of difference, − 74.6% to − 22.9%;
P
< 0.001).
Conclusions
Monotherapy with meropenem–vaborbactam for CRE infection was associated with increased clinical cure, decreased mortality, and reduced nephrotoxicity compared with BAT.
Clinical Trials Registration
NCT02168946.
Funding
The Medicines Company.
To determine the efficacy of stress urinary incontinence treatments adding pelvic floor muscle training to vaginal electrical stimulation.
Forty-eight women with stress urinary incontinence were ...randomized into 2 groups: 24 underwent isolated vaginal electrical stimulation, and 24 vaginal electrical stimulation plus pelvic floor muscle training. History, physical examination, voiding diary, perineum strength test, and urodynamic study were assessed. Comparisons were made for adherence to treatment, muscle strength improvement, urinary symptoms, and degree of satisfaction immediately, 12 and 96 months after treatment.
Patients' degree of satisfaction on vaginal electrical stimulation, and on vaginal electrical stimulation plus pelvic floor muscle training immediately, 12 and 96 months post treatment, were, respectively: 88.2% versus 88.9% 64.7% versus 61.1% and 42.9% versus 28.6% (p>0.05).
Vaginal electrical stimulation associated to pelvic floor muscle training did not show better results than vaginal electrical stimulation alone.
Summary
Survival in cancer is continuously improving due to evolving oncological treatment. Therefore, cardiovascular short-term and long-term side effects gain crucial importance for overall ...outcome. Cardiotoxicity not only presents as heart failure, but also as treatment-resistant hypertension, acute coronary ischemia with plaque rupture or vasospasm, thromboembolism, arrhythmia, pulmonary hypertension, diastolic dysfunction, acute myocarditis and others. Recent recommendations have proposed baseline cardiac risk assessment and surveillance strategies. Major challenges are the availability of monitoring and imaging resources, including echocardiography with speckle tracking longitudinal strain (GLS), serum biomarkers such as natriuretic peptides (NT-proBNP) and highly sensitive cardiac troponins. This Austrian consensus encompasses cardiotoxicity occurrence in frequent antiproliferative cancer drugs, radiotherapy, immune checkpoint inhibitors and cardiac follow-up considerations in cancer survivors in the context of the Austrian healthcare setting. It is important to optimize cardiovascular risk factors and pre-existing cardiac diseases without delaying oncological treatment. If left ventricular ejection fraction (LVEF) deteriorates during cancer treatment (from >10% to <50%), or myocardial strain decreases (>15% change in GLS), early initiation of cardioprotective therapies (angiotensin-converting enzyme inhibitors, angiotensin or beta receptor blockers) is recommended, and LVEF should be reassessed before discontinuation. Lower LVEF cut-offs were recently shown to be feasible in breast cancer patients to enable optimal anticancer treatment. Interdisciplinary cardio-oncology cooperation is pivotal for optimal management of cancer patients.
Prostate cancer is the most common invasive cancer in men. Radical prostatectomy (RP) is a definitive treatment option, but biochemical recurrence can reach 40%. Salvage lymphadenectomy is a ...relatively recent approach to oligometasis and has been rapidly diffused primarily due to improvement in imaging diagnosis and results showing possibly promising therapy. A systematic literature review was performed in March 2020, according to the PRISMA statement. We excluded studies with patients with suspicion or confirmation of visceral and / or bone metastases. A total of 27 articles were included in the study. All studies evaluated were single arm, and there were no randomized studies in the literature. A total of 1,714 patients received salvage lymphadenectomy after previous treatment for localized prostate cancer. RP was the most used initial therapeutic approach, and relapses were based on PET / CT diagnosis, with Coline-11C being the most widely used radiopharmaceutical. Biochemical response rates ranged from 0% to 80%. The 5 years - Free Survival Biochemical recurrence was analyzed in 16 studies with rates of 0% up to 56.1%. The articles do not present high levels of evidence to draw strong conclusions. However, even if significant rates of biochemical recurrence are not evident in all studies, therapy directed to lymph node metastases may present good oncological results and postpone the onset of systemic therapy. The long-term impact in overall survival and quality of life, as well as the best strategies for case selection remains to be determined.
The impact of surgery for stress urinary incontinence (SUI) on female sexual function has received attention in the medical literature, but not in a structured manner.
To assess the most recent ...evidence on the impact of surgical management for female SUI on female sexual function.
The review and meta-analysis of available articles published in Medline, Cochrane, LILACS, SCOPUS, Web of Science, CINHAL, and EMBASE included prospective randomized and non-randomized studies that assessed patients who underwent surgical treatment for UI through 2 validated questionnaires: the Pelvic Organ Prolapse Urinary Incontinence Sexual Questionnaire (PISQ-12) and the Female Sexual Function Index (FSFI).
The following terms were searched: (urinary incontinence OR female OR woman OR women) AND (suburethral slings OR transobturator tape* OR transobturator suburethral tape OR trans-obturator tape* OR urethral sling* OR midurethral sling* OR mid-urethral sling* OR “standard midurethral slings” OR tensionless vaginal tape* OR mini sling* OR Burch* OR “Burch colposuspension” OR “urologic surgical procedures” OR “tension-free vaginal tape” OR pubovaginal sling) AND (sexual behavior OR “Female Sexual Function Index” OR FSFI OR sexual function OR “Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire” OR PISQ-12).
1,043 articles were retrieved; 9 studies were included for qualitative analysis and 4 were included for meta-analysis. 25 articles were excluded because they used questionnaires other than the FSFI and PISQ-12. Meta-analysis of 2 studies composed of 411 women who underwent to retropubic and transobturator sling intervention and completed the PISQ-12 questionnaire showed an increase in sexual function of 2.40 points after transobturator compared with retropubic sling intervention (95% CI = −2.48 to −2.32; I2 = 35%, P < .00001). However, 2 other studies composed of 183 women comparing the same techniques, but using the FSFI, did not show a statistically significant difference (95% CI = −1.77 to 3.78; I2 = 0%, P = .48).
The impact of UI surgery on sexual function is uncertain because of the imprecision of the effect and inconsistency among studies. Only limited evidence on the impact of the transobturator vs the retropubic sling was found.
Bicudo-Fürst MC, Borba Leite PH, Araújo Glina FP, et al. Female Sexual Function Following Surgical Treatment of Stress Urinary Incontinence: Systematic Review and Meta-Analysis. Sex Med Rev 2018;6:224–233.
Summary
This study was conducted to investigate the age dependent epidemiology of pneumonia and risk factors for mortality.
The data were derived from the Austrian Pneumonia Network (APNET), ...comprising nine Departments for Internal Medicine with a total of 1,011 hospital beds. All inpatients diagnosed with pneumonia during 2011 were followed until discharge. Identification of microorganisms was performed according to local standard methods. Data of patients < 65 years and ≥ 65 years were compared by Mann–Whitney and the Chi-square tests. Risk factors for hospital mortality were evaluated by univariate and multivariate analyses.
Overall, 1,956 patients were included. The hospital mortality was 10.4 %, and was higher in patients ≥ 65 (12.7 %) than in patients < 65 years of age (5.0 %;
p
< 0.001).
Streptococcus (S.)
pneumoniae
was the most important pathogen.
Enterobacteriacaeae
were revealed significantly more often in patients ≥ 65 years. Age ≥ 65 years, chronic heart failure (CHF) and neurological disease increased the risk of hospital mortality 1.96 (95 % CI 1.19–3.20), 1.59 (95 % CI 1.10–2.29), and 1.7 (95 % CI 1.19–2.41)-fold, respectively.
In conclusion, pneumonia patients with CHF, neurological disease and age ≥ 65 years could benefit from intensified care due to increased risk of in-hospital death.
Upper respiratory tract infections are the most common source of antibiotic prescriptions. Acute pharyngitis is caused mainly by viruses, viral cases can be distinguished from acute streptococcal ...pharyngitis using Centor clinical epidemiological criteria, by rapid antigen tests or throat culture. Treatment of choice for streptococcal infection is penicillin V given in two daily doses. In children, acute otitis media (AOM) is the infection for which antibiotics are most often prescribed. Predominant causative pathogens include Streptococcus pneumoniae, Haemophilus influenzae non-type b and Moraxella catarrhalis. Diagnosis is based on history, physical examination and otoscopic exam. Antibiotic treatment should be initiated promptly in all children<2 years of age, and in older children presenting bilateral AOM, otorrhoea, co-morbidities or severe illness. In Argentina, amoxicillin is the drug of choice given the low penicillin resistance rates for S. pneumoniae. In children who fail amoxicillin therapy, amoxicillin/clavulanate provides better coverage against beta-lactamase producing H. influenzae and M. catarrhalis. Rhinosinusitis is caused mainly by viruses, secondary bacterial complication occurs in less than 5% of cases. Diagnosis is based on physical examination and additional studies are not usually required. Acute bacterial sinusitis is caused by the same pathogens that cause AOM and amoxicillin is the drug of choice.
The Argentine Society for Infectious Diseases and other national societies issued updated practical guidelines for the management of acute bronchitis (AB) and reactivations of chronic obstructive ...pulmonary disease (COPD) with the aim of promoting rational use of diagnostic and therapeutic resources. AB is a condition characterized by inflammation of the bronchial airways which affects adults and children without underlying pulmonary disease. It is usually caused by a virus. The diagnosis is based on clinical findings after community acquired pneumonia has been ruled out. Treatment of AB is mainly symptomatic. Antibiotics should be used in immune-compromised hosts, patients with chronic respiratory or cardiac diseases and in the elderly with co-morbidities. Reactivation of COPD is defined as an acute change in the patient's baseline clinical situation beyond normal day to day variations, with an increase in dyspnea, sputum production and/or sputum purulence, warranting a change in medication. An increase in one symptom is considered a mild exacerbation, two as moderate, and the presence of three symptoms is considered a severe exacerbation. An infectious agent can be isolated in sputum in 50 to 75% of COPD reactivations. Moderate and severe episodes must be treated with antibiotics, amoxicillin/ beta-lactamase inhibitor, macrolides and fluoroquinolones are first choice drugs.
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is now the most common cause of skin and skin structure infections (SSSI) in several world regions. In Argentina ...prospective, multicenter clinical studies have only been conducted in pediatric populations.
PRIMARY: describe the prevalence, clinical and demographic characteristics of adult patients with community acquired SSSI due to MRSA; secondary: molecular evaluation of CA-MRSA strains. Patients with MRSA were compared to those without MRSA.
Prospective, observational, multicenter, epidemiologic study, with molecular analysis, conducted at 19 sites in Argentina (18 in Buenos Aires) between March 2010 and October 2011. Patients were included if they were ≥ 14 years, were diagnosed with SSSI, a culture was obtained, and there had no significant healthcare contact identified. A logistic regression model was used to identify factors associated with CA-MRSA. Pulse field types, SCCmec, and PVL status were also determined.
A total of 311 patients were included. CA-MRSA was isolated in 70% (218/311) of patients. Clinical variables independently associated with CA-MRSA were: presence of purulent lesion (OR 3.29; 95%CI 1.67, 6.49) and age <50 years (OR 2.39; 95%CI 1.22, 4.70). The vast majority of CA-MRSA strains causing SSSI carried PVL genes (95%) and were SCCmec type IV. The sequence type CA-MRSA ST30 spa t019 was the predominant clone.
CA-MRSA is now the most common cause of SSSI in our adult patients without healthcare contact. ST30, SCCmec IV, PVL+, spa t019 is the predominant clone in Buenos Aires, Argentina.
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