15 research outputs found
Estudio descriptivo de una cohorte de pacientes con tuberculosis y análisis de los factores que influyen en el tiempo de crecimiento de mycobacterium tuberculosis complex en cultivo, en la conversión del cultivo tras el inicio del tratamiento y en la concentración plasmática de colesterol.
La tuberculosis constituye un problema de salud importante en todo el mundo. Este trabajo se centró en tres áreas de la enfermedad sobre las que todavía se desconocen muchos aspectos: (i) los factores que influyen en el tiempo transcurrido desde la siembra de las muestras hasta la detección de
M.tuberculosis complex en el cultivo (TTD), (ii) los factores que influyen en el tiempo transcurrido desde el inicio del tratameinto hasta la “negativización” de los cultivos (TTN) y (iii) la presencia de bajos niveles de colesterol plasmático total (CPT) en pacientes con tuberculosis activa (TB). Los dos primeros ítems hacen referencia a intervalos de tiempo relacionados con el cultivo de tuberculosis complex, la piedra angular sobre la que recae el diagnóstico y el seguimiento de los pacientes con TB; el último, hace referencia a un hallazgo analítico descrito desde hace años y del que todavía se desconoce la fisiopatología exacta y sus implicaciones
EUropean prospective cohort study on Enterobacteriaceae showing REsistance to CArbapenems (EURECA): a protocol of a European multicentre observational study
Introduction: The rapid worldwide spread of
carbapenem-resistant Enterobacteriaceae (CRE)
constitutes a major challenge. The aim of the EUropean
prospective cohort study on Enterobacteriaceae
showing REsistance to CArbapenems (EURECA), which
is part of the Innovative Medicines Initiative Joint
Undertaking (IMI JU) funded COMBACTE-CARE project,
is to investigate risk factors for and outcome
determinants of CRE infections to inform randomised
clinical trial designs and to provide a historical cohort
that could eventually be used for future comparisons
with new drugs targeting CRE.
Methods: A multicentre (50 sites), multinational
(11 European countries), analytical observational
project was designed, comprising 3 studies. The aims
of study 1 (a prospective cohort study) include
characterising the features, clinical management and
outcomes of hospitalised patients with intra-abdominal
infection, pneumonia, complicated urinary tract
infections and bloodstream infections caused by CRE
(202 patients in each group). The main outcomes will
be 30-day all-cause mortality and clinical response.
Study 2 (a nested case–control study) will identify
the risk factors for target infections caused by CRE;
248 selected patients from study 1 will be matched
with patients with carbapenem-susceptible
Enterobacteriaceae (1:1) and with hospitalised patients
(1:3) and will provide a historical cohort of patients
with CRE infections. Study 3 (a matched cohort study)
will follow patients in study 2 in order to assess
mortality, length of stay and hospital costs associated
with CRE. All patients will be followed for 30 days.
Different, up-to-date statistical methods will be applied
to come to unbiased estimates for all 3 studies.
Ethics and dissemination: Before-study sites will be
initiated, approval will be sought from appropriate
regulatory agencies and local Ethics Committees of
Research or Institutional Review Boards (IRBs) to
conduct the study in accordance with regulatory requirements. This is an observational study and
therefore no intervention in the diagnosis, management
or treatment of the patients will be required on behalf
of the investigation. Any formal presentation or
publication of data collected from this study will be
considered as a joint publication by the participating
physician(s) and will follow the recommendations of
the International Committee of Medical Journal Editors
(ICMJE) for authorship.Innovative Medicine Initiative (IMI)European Union's Seventh Framework Programme (FP7)Spanish Network for Research in Infectious Diseases [REIPI RD12/0015, RD16/2016
Fosfomycin versus meropenem in bacteraemic urinary tract infections caused by extended-spectrum β-lactamase-producing Escherichia coli (FOREST): study protocol for an investigator-driven randomised controlled trial
Introduction
Finding therapeutic alternatives to carbapenems in infections caused by extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) is imperative. Although fosfomycin was discovered more than 40 years ago, it was not investigated in accordance with current standards and so is not used in clinical practice except in desperate situations. It is one of the so-called neglected antibiotics of high potential interest for the future.
Methods and analysis
The main objective of this project is to demonstrate the clinical non-inferiority of intravenous fosfomycin with regard to meropenem for treating bacteraemic urinary tract infections (UTI) caused by ESBL-EC. This is a ‘real practice’ multicentre, open-label, phase III randomised controlled trial, designed to compare the clinical and microbiological efficacy, and safety of intravenous fosfomycin (4 g/6 h) and meropenem (1 g/8 h) as targeted therapy for this infection; a change to oral therapy is permitted after 5 days in both arms, in accordance with predetermined options. The study design follows the latest recommendations for designing trials investigating new options for multidrug-resistant bacteria. Secondary objectives include the study of fosfomycin concentrations in plasma and the impact of both drugs on intestinal colonisation by multidrug-resistant Gram-negative bacilli.
Ethics and dissemination
Ethical approval was obtained from the Andalusian Coordinating Institutional Review Board (IRB) for Biomedical Research (Referral Ethics Committee), which obtained approval from the local ethics committees at all participating sites in Spain (22 sites). Data will be presented at international conferences and published in peer-reviewed journals.
Discussion
This project is proposed as an initial step in the investigation of an orphan antimicrobial of low cost with high potential as a therapeutic alternative in common infections such as UTI in selected patients. These results may have a major impact on the use of antibiotics and the development of new projects with this drug, whether as monotherapy or combination therapy
Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections A Randomized Clinical Trial
Importance The consumption of broad-spectrum drugs has increased as a consequence of the spread of multidrug-resistant (MDR) Escherichia coli. Finding alternatives for these infections is critical, for which some neglected drugs may be an option.
Objective To determine whether fosfomycin is noninferior to ceftriaxone or meropenem in the targeted treatment of bacteremic urinary tract infections (bUTIs) due to MDR E coli.
Design, Setting, and Participants This multicenter, randomized, pragmatic, open clinical trial was conducted at 22 Spanish hospitals from June 2014 to December 2018. Eligible participants were adult patients with bacteremic urinary tract infections due to MDR E coli; 161 of 1578 screened patients were randomized and followed up for 60 days. Data were analyzed in May 2021.
Interventions Patients were randomized 1 to 1 to receive intravenous fosfomycin disodium at 4 g every 6 hours (70 participants) or a comparator (ceftriaxone or meropenem if resistant; 73 participants) with the option to switch to oral fosfomycin trometamol for the fosfomycin group or an active oral drug or parenteral ertapenem for the comparator group after 4 days.
Main Outcomes and Measures The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered.
Results Among 143 patients in the modified intention-to-treat population (median [IQR] age, 72 [62-81] years; 73 [51.0%] women), 48 of 70 patients (68.6%) treated with fosfomycin and 57 of 73 patients (78.1%) treated with comparators reached CMC (risk difference, −9.4 percentage points; 1-sided 95% CI, −21.5 to ∞ percentage points; P = .10). While clinical or microbiological failure occurred among 10 patients (14.3%) treated with fosfomycin and 14 patients (19.7%) treated with comparators (risk difference, −5.4 percentage points; 1-sided 95% CI, −∞ to 4.9; percentage points; P = .19), an increased rate of adverse event–related discontinuations occurred with fosfomycin vs comparators (6 discontinuations [8.5%] vs 0 discontinuations; P = .006). In an exploratory analysis among a subset of 38 patients who underwent rectal colonization studies, patients treated with fosfomycin acquired a new ceftriaxone-resistant or meropenem-resistant gram-negative bacteria at a decreased rate compared with patients treated with comparators (0 of 21 patients vs 4 of 17 patients [23.5%]; 1-sided P = .01).
Conclusions and Relevance This study found that fosfomycin did not demonstrate noninferiority to comparators as targeted treatment of bUTI from MDR E coli; this was due to an increased rate of adverse event–related discontinuations. This finding suggests that fosfomycin may be considered for selected patients with these infections
Risk factors for infections caused by carbapenem-resistant Enterobacterales: an international matched case-control-control study (EURECA)
© 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).[Background] Data on risk factors for carbapenem-resistant Enterobacterales (CRE) with wider applicability are needed to inform preventive measures and efficient design of randomised trials.[Methods] An international matched case-control-control study was performed in 50 hospitals with high CRE incidence from March 2016 to November 2018 to investigate different aspects of infections caused by CRE (NCT02709408). Cases were patients with complicated urinary tract infection (cUTI), complicated intraabdominal (cIAI), pneumonia or bacteraemia from other sources (BSI-OS) due to CRE; control groups were patients with infection caused by carbapenem-susceptible Enterobacterales (CSE), and by non-infected patients, respectively. Matching criteria included type of infection for CSE group, ward and duration of hospital admission. Conditional logistic regression was used to identify risk factors.[Findings] Overall, 235 CRE case patients, 235 CSE controls and 705 non-infected controls were included. The CRE infections were cUTI (133, 56.7%), pneumonia (44, 18.7%), cIAI and BSI-OS (29, 12.3% each). Carbapenemase genes were found in 228 isolates: OXA-48/like, 112 (47.6%), KPC, 84 (35.7%), and metallo-β-lactamases, 44 (18.7%); 13 produced two. The risk factors for CRE infection in both type of controls were (adjusted OR for CSE controls; 95% CI; p value) previous colonisation/infection by CRE (6.94; 2.74–15.53; <0.001), urinary catheter (1.78; 1.03–3.07; 0.038) and exposure to broad spectrum antibiotics, as categorical (2.20; 1.25–3.88; 0.006) and time-dependent (1.04 per day; 1.00–1.07; 0.014); chronic renal failure (2.81; 1.40–5.64; 0.004) and admission from home (0.44; 0.23–0.85; 0.014) were significant only for CSE controls. Subgroup analyses provided similar results.[Interpretation] The main risk factors for CRE infections in hospitals with high incidence included previous colonization, urinary catheter and exposure to broad spectrum antibiotics.The study was funded by the Innovative Medicines Initiative Joint Undertaking (https://www.imi.europa.eu/) under Grant Agreement No. 115620 (COMBACTE-CARE).Peer reviewe
Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections
IMPORTANCE The consumption of broad-spectrum drugs has increased as a consequence of the spread of multidrug-resistant (MDR) Escherichia coli. Finding alternatives for these infections is critical, for which some neglected drugs may be an option. OBJECTIVE To determine whether fosfomycin is noninferior to ceftriaxone or meropenem in the targeted treatment of bacteremic urinary tract infections (bUTIs) due to MDR E coli. DESIGN, SETTING, AND PARTICIPANTS This multicenter, randomized, pragmatic, open clinical trial was conducted at 22 Spanish hospitals from June 2014 to December 2018. Eligible participants were adult patients with bacteremic urinary tract infections due to MDR E coli; 161 of 1578 screened patients were randomized and followed up for 60 days. Data were analyzed in May 2021. INTERVENTIONS Patients were randomized 1 to 1 to receive intravenous fosfomycin disodium at 4 g every 6 hours (70 participants) or a comparator (ceftriaxone or meropenem if resistant; 73 participants) with the option to switch to oral fosfomycin trometamol for the fosfomycin group or an active oral drug or pa renteral ertapenem for the comparator group after 4 days. MAIN OUTCOMES AND MEASURES The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered. RESULTS Among 143 patients in the modified intention-to-treat population (median [IQR] age, 72 [62-81] years; 73 [51.0%] women), 48 of 70 patients (68.6%) treated with fosfomycin and 57 of 73 patients (78.1%) treated with comparators reached CMC (risk difference, -9.4 percentage points; 1-sided 95% CI, -21.5 to infinity percentage points; P = .10). While clinical or microbiological failure occurred among 10 patients (14.3%) treated with fosfomycin and 14 patients (19.7%) treated with comparators (risk difference, -5.4 percentage points; 1-sided 95% CI. -infinity to 4.9; percentage points; P = .19), an increased rate of adverse event-related discontinuations occurred with fosfomycin vs comparators (6 discontinuations [8.5%] vs 0 discontinuations; P = .006). In an exploratory analysis among a subset of 38 patients who underwent rectal colonization studies, patients treated with fosfomycin acquired a new ceftriaxone-resistant or meropenem-resistant gram-negative bacteria at a decreased rate compared with patients treated with comparators (0 of 21 patients vs 4 of 17 patients [23.5%]; 1-sided P = .01). CONCLUSIONS AND RELEVANCE This study found that fosfomycin did not demonstrate noninferiority to comparators as targeted treatment of bUTI from MDR E coli; this was due to an increased rate of adverse event-related discontinuations. This finding suggests that fosfomycin may be considered for selected patients with these infections
Risk factors for infections caused by carbapenem-resistant Enterobacterales: an international matched case-control-control study (EURECA)
Cases were patients with complicated urinary tract infection (cUTI), complicated intraabdominal (cIAI), pneumonia or bacteraemia from other sources (BSI-OS) due to CRE; control groups were patients with infection caused by carbapenem-susceptible Enterobacterales (CSE), and by non-infected patients, respectively. Matching criteria included type of infection for CSE group, ward and duration of hospital admission. Conditional logistic regression was used to identify risk factors. Findings Overall, 235 CRE case patients, 235 CSE controls and 705 non-infected controls were included. The CRE infections were cUTI (133, 56.7%), pneumonia (44, 18.7%), cIAI and BSI-OS (29, 12.3% each). Carbapenemase genes were found in 228 isolates: OXA-48/like, 112 (47.6%), KPC, 84 (35.7%), and metallo-beta-lactamases, 44 (18.7%); 13 produced two. The risk factors for CRE infection in both type of controls were (adjusted OR for CSE controls; 95% CI; p value) previous colonisation/infection by CRE (6.94; 2.74-15.53; <0.001), urinary catheter (1.78; 1.03-3.07; 0.038) and exposure to broad spectrum antibiotics, as categorical (2.20; 1.25-3.88; 0.006) and time-dependent (1.04 per day; 1.00-1.07; 0.014); chronic renal failure (2.81; 1.40-5.64; 0.004) and admission from home (0.44; 0.23-0.85; 0.014) were significant only for CSE controls. Subgroup analyses provided similar results. Interpretation The main risk factors for CRE infections in hospitals with high incidence included previous coloni-zation, urinary catheter and exposure to broad spectrum antibiotics
Effectiveness of fosfomycin for the treatment of multidrug-resistant escherichia coli bacteremic urinary tract infections: a randomized clinical trial
Importance: The consumption of broad-spectrum drugs has increased as a consequence of the spread of multidrug-resistant (MDR) Escherichia coli. Finding alternatives for these infections is critical, for which some neglected drugs may be an option. Objective: To determine whether fosfomycin is noninferior to ceftriaxone or meropenem in the targeted treatment of bacteremic urinary tract infections (bUTIs) due to MDR E coli. Design, setting, and participants: This multicenter, randomized, pragmatic, open clinical trial was conducted at 22 Spanish hospitals from June 2014 to December 2018. Eligible participants were adult patients with bacteremic urinary tract infections due to MDR E coli; 161 of 1578 screened patients were randomized and followed up for 60 days. Data were analyzed in May 2021. Interventions: Patients were randomized 1 to 1 to receive intravenous fosfomycin disodium at 4 g every 6 hours (70 participants) or a comparator (ceftriaxone or meropenem if resistant; 73 participants) with the option to switch to oral fosfomycin trometamol for the fosfomycin group or an active oral drug or parenteral ertapenem for the comparator group after 4 days. Main outcomes and measures: The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered. Results: Among 143 patients in the modified intention-to-treat population (median [IQR] age, 72 [62-81] years; 73 [51.0%] women), 48 of 70 patients (68.6%) treated with fosfomycin and 57 of 73 patients (78.1%) treated with comparators reached CMC (risk difference, -9.4 percentage points; 1-sided 95% CI, -21.5 to ∞ percentage points; P = .10). While clinical or microbiological failure occurred among 10 patients (14.3%) treated with fosfomycin and 14 patients (19.7%) treated with comparators (risk difference, -5.4 percentage points; 1-sided 95% CI, -∞ to 4.9; percentage points; P = .19), an increased rate of adverse event-related discontinuations occurred with fosfomycin vs comparators (6 discontinuations [8.5%] vs 0 discontinuations; P = .006). In an exploratory analysis among a subset of 38 patients who underwent rectal colonization studies, patients treated with fosfomycin acquired a new ceftriaxone-resistant or meropenem-resistant gram-negative bacteria at a decreased rate compared with patients treated with comparators (0 of 21 patients vs 4 of 17 patients [23.5%]; 1-sided P = .01). Conclusions and relevance: This study found that fosfomycin did not demonstrate noninferiority to comparators as targeted treatment of bUTI from MDR E coli; this was due to an increased rate of adverse event-related discontinuations. This finding suggests that fosfomycin may be considered for selected patients with these infections. Trial registration: ClinicalTrials.gov Identifier: NCT02142751
The role of tigecycline in the management of Clostridium difficile infection: a retrospective cohort study
[Objective] We aimed to compare the outcomes of patients with C.difficile infection (CDI) treated either with tigecycline associated with vancomycin, or with vancomycin alone.[Methods] This single-centre retrospective cohort study included all adults hospitalized from September 2014 through August 2015 for symptomatic, incident CDI confirmed by polymerase chain reaction for C. difficile toxin in stools. The primary outcome was the rate of favourable outcome, defined as a composite of clinical response (resolution of symptoms without need for additional CDI therapy) and achieving discharge without CDI-related surgery or intensive care; a secondary outcome was CDI recurrence. We constructed a non-parsimonious logistic regression model to calculate a propensity score (PS) for those receiving tigecycline.[Results] In all, 266 patients were included: 62 patients received both vancomycin and tigecycline, and 204 patients received vancomycin alone. The patients from the two groups were similar regarding demographics and comorbidities but patients in the tigecycline group had a more severe CDI. A favourable outcome in the tigecycline group versus the vancomycin group was found in 50/62 (81%) versus 193/204 (95%). We matched patients receiving tigecycline or not according to the PS and 86 patients (43 pairs) could be matched. The OR for favourable outcome with tigecycline in the matched analysis was 0.92 (95% CI 0.60–1.44; p 0.74). The rate of CDI recurrences was 8/62 (13%) in the tigecycline group versus 39/204 (19%) in the vancomycin group (p 0.2).[Conclusion] Adding tigecycline to CDI standard therapy did not increase the clinical cure nor reduce the rate of CDI recurrences.JRB received funding for research from Ministerio de Economía y Competitividad, Instituto de Salud Carlos III - co-financed by European Development Regional Fund “A way to achieve Europe” ERDF, Spanish Network for the Research in Infectious Diseases (REIPI RD16/0016)