scholarly journals Single-Dose Oral Amoxicillin or Linezolid for Prophylaxis of Experimental Endocarditis Due to Vancomycin-Susceptible and Vancomycin-Resistant Enterococcus faecalis

2007 ◽  
Vol 51 (5) ◽  
pp. 1661-1665 ◽  
Author(s):  
Philippe Moreillon ◽  
Walter R. Wilson ◽  
Roland Leclercq ◽  
José M. Entenza

ABSTRACT Endocarditis prophylaxis following genitourinary or gastrointestinal procedures targets Enterococcus faecalis. Prophylaxis recommendations advocate oral amoxicillin (2 g in the United States and 3 g in the United Kingdom) in moderate-risk patients and intravenous amoxicillin (2 g) or vancomycin (1 g) plus gentamicin in high-risk patients. While ampicillin-resistant (or amoxicillin-resistant) E. faecalis is still rare, there is a concern that these regimens might fail against vancomycin-resistant and/or aminoglycoside-resistant isolates. The present study tested oral linezolid as an alternative. Rats with catheter-induced aortic vegetations were given prophylaxis simulating human pharmacokinetics of oral amoxicillin (2- to 3-g single dose), oral linezolid (600 mg, single or multiple oral doses every 12 h), or intravenous vancomycin (1-g single dose). Rats were then inoculated with the minimum inoculum infecting 90% of the animals (90% infective dose [ID90]) or with 10 times the ID90 of the vancomycin-susceptible E. faecalis strain JH2-2 or the vancomycin-resistant (VanA phenotype) E. faecalis strain UCN41. Amoxicillin was also tested with two additional vancomycin-susceptible E. faecalis strains, 309 and 1209. Animals were sacrificed 3 days later. All the tested bacteria were susceptible to amoxicillin and gentamicin. Single-dose amoxicillin provided 100% protection against all four isolates at both the ID90 and 10 times the ID90. In contrast, linezolid required up to four consecutive doses to provide full protection against the vancomycin-resistant isolate. Vancomycin protected only against the vancomycin-susceptible strain. The high efficacy of single-dose oral amoxicillin suggests that this regimen could be used for prophylaxis in both moderate-risk and high-risk patients without additional aminoglycosides. Linezolid appears to be less reliable, at least against the vancomycin-resistant strain.

2020 ◽  
Vol 11 ◽  
pp. 215145932094602
Author(s):  
Sanjit R. Konda ◽  
Joseph R. Johnson ◽  
Erin A. Kelly ◽  
Jeffrey Chan ◽  
Thomas Lyon ◽  
...  

Introduction: This study sought to investigate whether a validated trauma triage risk assessment tool can predict time to surgery and delay to surgery. Materials and Methods: Patients aged 55 and older who were admitted for operative repair or arthroplasty of a hip fracture over a 3-year period at a single academic institution were included. Risk quartiles were constructed using Score for Trauma Triage in the Geriatric and Middle-Aged (STTGMA) calculations. Negative binomial and multivariable logistic regression were used to evaluate time to surgery and delay to surgery, respectively. Pairwise comparisons were performed to evaluate 30-day mortality rates and demonstrate the effectiveness of the STTGMA tool in triaging mortality risk. Results: Six hundred eleven patients met inclusion criteria with mean age 81.1 ± 10.5 years. Injuries occurred mainly secondary to low-energy mechanisms (97.9%). Median time to surgery (31.9 hours overall) was significantly associated with STTGMA stratification ( P = .002). Moderate-risk patients had 33% longer ( P = .019) and high-risk patients had 28% longer time to surgery ( P = .041) compared to minimal risk patients. Delay to surgery (26.4% overall) was significantly associated with STTGMA stratification ( P = .015). Low-risk patients had 2.14× higher odds ( P = .009), moderate-risk patients had 2.70× higher odds ( P = .001), and high-risk patients had 2.18× higher odds of delay to surgery ( P = .009) compared to minimal risk patients. High-risk patients experienced higher 30-day mortality compared to minimal ( P < .001), low ( P = .046), and moderate-risk patients ( P = .046). Discussion: Patients in higher STTGMA quartiles encountered longer time to surgery, greater operative delays, and higher 30-day mortality. Conclusion: Score for Trauma Triage in the Geriatric and Middle-Aged can quickly identify hip fracture patients at risk for a delay to surgery and may allow treatment teams to optimize surgical timing by proactively targeting these patients. Level of Evidence: Prognostic Level III.


2003 ◽  
Vol 47 (8) ◽  
pp. 2492-2498 ◽  
Author(s):  
Alexander A. Padiglione ◽  
Rory Wolfe ◽  
Elizabeth A. Grabsch ◽  
Di Olden ◽  
Stephen Pearson ◽  
...  

ABSTRACT Accurate assessment of the risk factors for colonization with vancomycin-resistant enterococci (VRE) among high-risk patients is often confounded by nosocomial VRE transmission. We undertook a 15-month prospective cohort study of adults admitted to high-risk units (hematology, renal, transplant, and intensive care) in three teaching hospitals that used identical strict infection control and isolation procedures for VRE to minimize nosocomial spread. Rectal swab specimens for culture were regularly obtained, and the results were compared with patient demographic factors and antibiotic exposure data. Compliance with screening was defined as “optimal” (100% compliance) or “acceptable” (minor protocol violations were allowed, but a negative rectal swab specimen culture was required within 1 week of becoming colonized with VRE). Colonization with VRE was detected in 1.56% (66 of 4,215) of admissions (0.45% at admission and 0.83% after admission; the acquisition time was uncertain for 0.28%), representing 1.91% of patients. No patients developed infection with VRE. The subsequent rate of new acquisition of VRE was 1.4/1,000 patient days. Renal units had the highest rate (3.23/1,000 patient days; 95% confidence interval [CI], 1.54 to 6.77/1,000 patient days). vanB Enterococcus faecium was the most common species (71%), but other species included vanB Enterococcus faecalis (21%), vanA E. faecium (6%), and vanA E. faecalis (2%). The majority of isolates were nonclonal by pulsed-field gel electrophoresis analysis. Multivariate analysis of risk factors in patients with an acceptable screening suggested that being managed by a renal unit (hazard ratio [HR] compared to the results for patients managed in an intensive care unit, 4.6; 95% CI, 1.2 to 17.0 [P = 0.02]) and recent administration of either ticarcillin-clavulanic acid (HR, 3.6; 95% CI, 1.1 to 11.6 [P = 0.03]) or carbapenems (HR, 2.8; 95% CI, 1.0, 8.0 [P = 0.05]), but not vancomycin or broad-spectrum cephalosporins, were associated with acquisition of VRE. The relatively low rates of colonization with VRE, the polyclonal nature of most isolates, and the possible association with the use of broad-spectrum antibiotics are consistent with either the endogenous emergence of VRE or the amplification of previously undetectable colonization with VRE among high-risk patients managed under conditions in which the risk of nosocomial acquisition was minimized.


2018 ◽  
Vol 17 (3) ◽  
pp. 4-10
Author(s):  
A. Yu. Efanov ◽  
Yu. A. Vyalkina ◽  
Yu. A. Petrova ◽  
Z. M. Safiullina ◽  
O. V. Abaturova ◽  
...  

Aim. To assess the specifics of antihypertension therapy (AHT) in hypertensives of various cardiovascular risk, in the registry of chronic non-communicable diseases in Tyumenskaya oblast.Material and methods. A random sample studied, of 1704 patients with hypertension, inhabitants of Tyumenskaya oblast (region), ascribed to dispensary follow-up. Mean age 62±7,5 y.o. Of those 31,5% (n=537) males. The prevalence and efficacy of AHT assessed according to cardiovascular risk level. The significance was evaluated with the criteria χ2.Results. AHT was characterized by the growth of the frequency of treatment approaches with cardiovascular risk consideration. Regular treatment took 33,9% patients of low and moderate risk vs 41,3% of high and very high (p<0,01). In the male group such tendency also took place. Gender specifics of AHT was characterized by that in the groups of high and very high risk females took medications significantly more commonly than males — 46,6% vs 29,1% in high risk group (p<0,01) and 47,5% vs 30% in very high risk group (p<0,01). With the increase of the risk level, there was decline of treatment efficacy — from 95% in low risk group to 32,5% in very high risk group; 53,1% of the participants were taking monotherapy, 32,9% — two drugs, 14,0% — ≥3 drugs. With the increase of risk grade there is tendency to increase of combinational AHT, however with no significant increase of efficacy. Treatment efficacy in high and very high risk patients comparing to patients with low and moderate risk was significantly lower — 33,1% vs 69,7% (p<0,01), respectively. Statins intake among the high and very high risk patients was 10,6-11,0% males and 7,8% females (p<0,05).Conclusion. AHT in hypertensives in Tymenskaya oblast, under dispensary follow-up, is characterized by insufficient usage of combinational drugs. With the raise of cardiovascular risk there is tendency to higher rate of combinational AHT. However there is no significant increase in efficacy of treatment with the increase of medications number. A very low rate of statins intake is noted. The obtained specifics witness for the necessity to optimize AHT among the high and very high risk patients — inhabitants of Tyumenskya oblast.


2020 ◽  
Author(s):  
Adnan I Qureshi

Background and Purpose There is increasing recognition of a relatively high burden of pre-existing cardiovascular disease in Corona Virus Disease 2019 (COVID 19) infected patients. We determined the burden of pre-existing cardiovascular disease in persons residing in United States (US) who are at risk for severe COVID-19 infection. Methods Age (60 years or greater), presence of chronic obstructive pulmonary disease, diabetes, mellitus, hypertension, and/or malignancy were used to identify persons at risk for admission to intensive care unit, or invasive ventilation, or death with COVID-19 infection. Persons were classified as low risk (no risk factors), moderate risk (1 risk factor), and high risk (two or more risk factors present) using nationally representative sample of US adults from National Health and Nutrition Examination Survey 2017 and 2018 survey. Results Among a total of 5856 participants, 2386 (40.7%) were considered low risk, 1325 (22.6%) moderate risk, and 2145 persons (36.6%) as high risk for severe COVID-19 infection. The proportion of patients who had pre-existing stroke increased from 0.6% to 10.5% in low risk patients to high risk patients (odds ratio [OR]19.9, 95% confidence interval [CI]11.6-34.3). The proportion of who had pre-existing myocardial infection (MI) increased from 0.4% to 10.4% in low risk patients to high risk patients (OR 30.6, 95% CI 15.7-59.8). Conclusions A large proportion of persons in US who are at risk for developing severe COVID 19 infection are expected to have pre-existing cardiovascular disease. Further studies need to identify whether targeted strategies towards cardiovascular diseases can reduce the mortality in COVID-19 infected patients.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1996-1996 ◽  
Author(s):  
Michael Steurer ◽  
Marco Montillo ◽  
Lydia Scarfò ◽  
Francesca Romana Mauro ◽  
Johannes Andel ◽  
...  

Abstract Background Olaptesed pegol (NOX-A12) is a novel, potent, L-stereoisomer RNA aptamer that binds and neutralizes CXCL12/SDF-1, a chemokine which attracts and activates immune- and non-immune cells via interaction with the receptors CXCR4 and CXCR7. Signaling of CXCL12 is pivotal to the interactions of leukemic cells with bone marrow microenvironment. The therapeutic concept of olaptesed is to inhibit such tumor-supporting pathways and thereby mobilizing and sensitizing CLL cells to therapy. Here we aim to assess the activity and safety of olaptesed in combination with bendamustine and rituximab (BR) in patients with relapsed / refractory CLL. Methods Twenty-eight relapsed or refractory CLL patients were enrolled and treated in this open-label, single-arm Phase IIa study. To investigate PK/PD, a pilot dose of 1 to 4 mg/kg olaptesed alone was administered to 3 patients per dose group (plus one additional replacement pt) before start of the regular treatment regimen (pilot group). Patients were treated using a dose titration design with intravenous (IV) olaptesed at doses increasing from 1 mg/kg to 2 mg/kg and 4 mg/kg at cycles 1, 2 and 3, respectively, at 1 hour before rituximab treatment. During cycles 4 to 6, olaptesed was dosed at the highest individually titrated dose. Rituximab was administered IV at doses of 375 mg/m² on day 1 of the 1st28-day cycle and 500 mg/m² on day 1 of subsequent cycles. Bendamustine (70 - 100 mg/m²) was given IV on days 2-3 (cycle 1) or days 1-2 (cycles 2-6) of each 28-day cycle following administration of rituximab. Clinical response was assessed according to NCI-WG Guidelines (Hallek M et al. Blood 111; 2008: 5446-56). Results To date, 24 patients completed treatment (12 women, 12 men) with a median age of 68.5 years (range 52 to 79). At screening 5, 9 and 10 patients presented with Binet stage A, B and C, respectively. The median number of prior treatment lines was 1 (range 1-2). Seven high-risk patients presented an unfavorable disease state being relapsed within 24 months after fludarabine/bendamustine treatment (5 pts) and/or presenting a deletion/mutation of the TP53 gene (3 pts). Most patients (19 of 24) were previously treated with fludarabine or bendamustine. A flow cytometric analysis of CD19+/CD5+CLL cells showed a rapid mobilization into the peripheral blood by a single dose of olaptesed which lasted throughout the observational time of 72h. Interestingly, CXCR4 expression levels increased on CLL cell surface in the periphery after olaptesed treatment. This increase, which peaked at 24h, likely reflects the extended circulation of CLL cells in the periphery due to the sustained blockade of CXCL12 by olaptesed. Reduction of lymphadenopathy by ≥ 50% was achieved in 14 out of 21 evaluable patients with reported enlarged lymph nodes by the end of treatment. Concomitantly, rapid reduction of lymphocytosis in peripheral blood with normalization by treatment cycle 2 – 3 was observed and the CLL to leukocyte ratio significantly improved. Efficacy was assessed at the end of cycles 3 and 6. In the full-analysis-set, which excludes two non-evaluable patients (drop-out after the 1st cycle due to adverse events), the overall response rate was 96%: Three patients (14%) achieved a complete response at end of cycle 6 (2 confirmed, 1 investigator reported) and eighteen patients (82%) achieved a partial response (fifteen at end of cycle 6 and three at end of cycle 3). Notably, all seven high-risk patients (defined as relapsed within 24 months after fludarabine/bendamustine treatment and/or presenting a deletion/mutation of the TP53 gene) responded to treatment with olaptesed + BR with a partial response. One patient had a progressive disease. Olaptesed at 1, 2 and 4 mg/kg at a single dose and in combination with BR was safe and well tolerated. The observed adverse reactions were qualitatively and quantitatively as expected for patients treated with BR. Conclusion Olaptesed in combination with BR was safe and well tolerated. Compared with historical data, olaptesed showed superiority over baseline therapy with regards to overall response rate and increasing rates of complete remission, warranting further development of this Spiegelmer in CLL. Disclosures Montillo: Janssen: Honoraria. Kruschinski:NOXXON Pharma AG: Employment. Dümmler:NOXXON Pharma AG: Employment. Riecke:NOXXON Pharma AG: Employment.


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