The Waning of BNT162b2 Vaccine Effectiveness for SARS-CoV-2 Infection Prevention over Time: A Test-Negative Study in Health Care Professionals of a Health Department from January 2021 to December 2021

The duration of protection of vaccines against SARS-CoV-2 infection has been evaluated in previous studies, but uncertainty remains about the persistence of effectiveness over time and the ideal timing for booster doses. Therefore, the aim of this study was to evaluate BNT162b2 vaccine effectiveness against SARS-CoV-2 infection in health care workers (HCWs) at a tertiary hospital depending on time elapsed since the completion of a two-dose vaccination regimen. We conducted a case–control with negative test study between 25 January and 12 December 2021 that included 1,404 HCWs who underwent an active infection diagnostic test (AIDT) to rule out SARS-CoV-2 infection due to COVID-19 suspicion or prior close contact with patients diagnosed with COVID-19. The adjusted vaccine effectiveness (aVE) for the prevention of SARS-CoV-2 infection 12 to 120 days after completing the full two-dose vaccination regimen was 91.9%. Then, aVE decreased to 63.7% between 121 to 240 days after completing the full two-dose regimen and to 37.2% after 241 days since the second dose. Vaccination against SARS-CoV-2 infection in HCWs remains highly effective after 12 to 120 days have elapsed since the administration of two doses of the BNT162b2 vaccine; however, effectiveness decreases as time elapses since its administration

Plasma ACE2 species are differentially altered in COVID-19 patients

Studies are needed to identify useful biomarkers to assess the severity and prognosis of COVID-19 disease, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) virus. Here, we examine the levels of various plasma species of the SARS-CoV-2 host receptor, the angiotensin-converting enzyme 2 (ACE2), in patients at different phases of the infection. Human plasma ACE2 species were characterized by immunoprecipitation and western blotting employing antibodies against the ectodomain and the C-terminal domain, using a recombinant human ACE2 protein as control. In addition, changes in the cleaved and full-length ACE2 species were also examined in serum samples derived from humanized K18-hACE2 mice challenged with a lethal dose of SARS-CoV-2. ACE2 immunoreactivity was present in human plasma as several molecular mass species that probably comprise truncated (70 and 75 kDa) and full-length forms (95, 100, 130, and 170 kDa). COVID-19 patients in the acute phase of infection (n = 46) had significantly decreased levels of ACE2 full-length species, while a truncated 70-kDa form was marginally higher compared with non-disease controls (n = 26). Levels of ACE2 full-length species were in the normal range in patients after a recovery period with an interval of 58-70 days (n = 29), while the 70-kDa species decreased. Levels of the truncated ACE2 species served to discriminate between individuals infected by SARS-CoV-2 and those infected with influenza A virus (n = 17). In conclusion, specific plasma ACE2 species are altered in patients with COVID-19 and these changes normalize during the recovery phase. Alterations in ACE2 species following SARS-CoV-2 infection warrant further investigation regarding their potential usefulness as biomarkers for the disease process and to asses efficacy during vaccination

Real-world experience with bezlotoxumab for prevention of recurrence of Clostridioides difficile infection

Bezlotoxumab is marketed for the prevention of recurrent Clostridioides difficile infection (rCDI). Its high cost could be determining its prescription to a different population than that represented in clinical trials. The objective of the study was to verify the effectiveness and safety of bezlotoxumab in preventing rCDI and to investigate factors related to bezlotoxumab failure in the real world. A retrospective, multicentre cohort study of patients treated with bezlotoxumab in Spain was conducted. We compared the characteristics of cohort patients with those of patients treated with bezlotoxumab in the pivotal MODIFY trials. We assessed recurrence rates 12 weeks after completion of treatment against C. difficile, and we analysed the factors associated with bezlotoxumab failure. Ninety-one patients were included in the study. The cohort presented with more risk factors for rCDI than the patients included in the MODIFY trials. Thirteen (14.2%) developed rCDI at 12 weeks of follow-up, and rCDI rates were numerically higher in patients with two or more previous episodes (25%) than in those who had fewer than two previous episodes of C. difficile infection (CDI) (10.4%); p = 0.09. There were no adverse effects attributable to bezlotoxumab. Despite being used in a more compromised population than that represented in clinical trials, we confirm the effectiveness of bezlotoxumab for the prevention of rCDI

Revisiting the epidemiology of bloodstream infections and healthcare-associated episodes: results from a multicentre prospective cohort in Spain (PRO-BAC Study)

PROBAC REIPI/GEIH-SEIMC/SAEI Group.The epidemiology of bloodstream infections (BSIs) is dynamic as it depends on microbiological, host and healthcare system factors. The aim of this study was to update the information regarding the epidemiology of BSIs in Spain considering the type of acquisition. An observational, prospective cohort study in 26 Spanish hospitals from October 2016 through March 2017 including all episodes of BSI in adults was performed. Bivariate analyses stratified by type of acquisition were performed. Multivariate analyses were performed by logistic regression. Overall, 6345 BSI episodes were included; 2510 (39.8%) were community-acquired (CA), 1661 (26.3%) were healthcare-associated (HCA) and 2056 (32.6%) hospital-acquired (HA). The 30-day mortality rates were 11.6%, 19.5% and 22.0%, respectively. The median age of patients was 71 years (interquartile range 60–81 years) and 3656 (58.3%; 95% confidence interval 57.1–59.6%) occurred in males. The proportions according to patient sex varied according to age strata. Escherichia coli (43.8%), Klebsiella spp. (8.9%), Staphylococcus aureus (8.9%) and coagulase-negative staphylococci (7.4%) were the most frequent pathogens. Multivariate analyses confirmed important differences between CA and HCA episodes, but also between HCA and HA episodes, in demographics, underlying conditions and aetiology. In conclusion, we have updated the epidemiological information regarding patients’ profiles, underlying conditions, frequency of acquisition types and aetiological agents of BSI in Spain. HCA is confirmed as a distinct type of acquisition.This work was financed by grants from Plan Nacional de I+D+i 2013–2016, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades [PI16/01432] and the Spanish Network for Research in Infectious Diseases (REIPI) [RD16/0016/0001; RD16/0016/0008], co‐financed by the European Development Regional Fund ‘A way to achieve Europe’, Operative program Intelligent Growth 2014–2020

Risk Factors and Predictive Score for Bacteremic Biliary Tract Infections Due to Enterococcus faecalis and Enterococcus faecium: a Multicenter Cohort Study from the PROBAC Project

Biliary-tract bloodstream infections (BT-BSI) caused by Enterococcus faecalis and E. faecium are associated with inappropriate empirical treatment and worse outcomes compared to other etiologies. The objective of this study was to investigate the risk factors for enterococcal BT-BSI. Patients with BT-BSI from the PROBAC cohort, including consecutive patients with BSI in 26 Spanish hospitals between October 2016 and March 2017, were selected; episodes caused by E. faecalis or E. faecium and other causes were compared. Independent predictors for enterococci were identified by logistic regression, and a predictive score was developed. Eight hundred fifty episodes of BT-BSI were included; 73 (8.5%) were due to target Enterococcus spp. (48 [66%] were E. faecium and 25 [34%] E. faecalis). By multivariate analysis, the variables independently associated with Enterococcus spp. were (OR; 95% confidence interval): cholangiocarcinoma (4.48;1.32 to 15.25), hospital acquisition (3.58;2.11 to 6.07), use of carbapenems in the previous month (3.35;1.45 to 7.78), biliary prosthesis (2.19;1.24 to 3.90), and moderate or severe chronic kidney disease (1.55;1.07 to 2.26). The AUC of the model was 0.74 [95% CI0.67 to 0.80]. A score was developed, with 7, 6, 5, 4, and 2 points for these variables, respectively, with a negative predictive value of 95% for a score # 6. A model, including cholangiocarcinoma, biliary prosthesis, hospital acquisition, previous carbapenems, and chronic kidney disease showed moderate prediction ability for enterococcal BT-BSI. Although the score will need to be validated, this information may be useful for deciding empirical therapy in biliary tract infections when bacteremia is suspected. IMPORTANCE Biliary tract infections are frequent, and a significant cause of morbidity and mortality. Bacteremia is common in these infections, particularly in the elderly and patients with cancer. Inappropriate empirical treatment has been associated with increased risk of mortality in bacteremic cholangitis, and the probability of receiving inactive empirical treatment is higher in episodes caused by enterococci. This is because many of the antimicrobial agents recommended in guidelines for biliary tract infections lack activity against these organisms. To the best of our knowledge, this is the first study analyzing the predictive factors for enterococcal BT-BSI and deriving a predictive score.8 página

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

Effectiveness of BNT162b2 vaccine to preventing COVID-19 in healthcare personnel

Objetivo: Conocer la efectividad de la vacuna BNT162b2 en personal sanitario de un departamento de salud. Método: Estudio de casos y controles con prueba negativa. Se incluyó personal sanitario con sospecha de COVID-19 y personal sanitario que fue contacto estrecho de casos de COVID-19 entre el 25 de enero y el 6 de junio de 2021. Se les realizó prueba de reacción en cadena de la polimerasa (PCR) para SARS-CoV-2; aquellos con PCR positiva fueron considerados casos y aquellos con PCR negativa fueron considerados controles. Se calculó la efectividad vacunal ajustada (EVa) para prevenir casos de COVID-19 y su intervalo de confianza del 95% (IC95%), mediante la fórmula EV = (1 − odds ratio) × 100. Resultados: Se incluyeron 624 profesionales sanitarios; de ellos, 43 (6,9%) casos y 581 (93,1%) controles. La EVa de la pauta completa fue del 96,3% (IC95%: 82,5-99,2) y la de la pauta incompleta del 68,0% (IC95%: 30,0-85,4). Conclusiones: La administración de la pauta completa de vacuna es efectiva para la prevención de casos de COVID-19 en el personal sanitario.Objective: To assess the effectiveness of the vaccine against SARS-CoV-2 (BNT162b2) in healthcare personnel of a health department. Method: Test-negative case̶control study. Healthcare personnel with suspected COVID-19 and healthcare personnel close contacts of COVID-19 cases were included between January 27th and June 6 th, 2021. They were PCR tested for SARS-CoV-2; those with positive PCR were considered cases and those with negative PCR were considered controls. The adjusted vaccine effectiveness (aVE) to prevent COVID-19 cases and their 95% confidence interval (95%CI) were calculated using the formula VE = (1 − odds ratio) × 100. Results: 624 healthcare personnel were included, of which 43 (6.9%) were considered cases and 581 (93.8%) controls. The aVE of the complete regimen was 96.3% (95%CI: 82.5̶99.2). The aVE of the incomplete pattern was 68.0% (95%CI: 30.0̶85.4). Conclusions: The administration of the complete pattern of BNT162b2 vaccine against SARS-CoV-2 is effective for the prevention of cases of COVID-19 in healthcare personnel

The Waning of BNT162b2 Vaccine Effectiveness for SARS-CoV-2 Infection Prevention over Time: A Test-Negative Study in Health Care Professionals of a Health Department from January 2021 to December 2021

The duration of protection of vaccines against SARS-CoV-2 infection has been evaluated in previous studies, but uncertainty remains about the persistence of effectiveness over time and the ideal timing for booster doses. Therefore, the aim of this study was to evaluate BNT162b2 vaccine effectiveness against SARS-CoV-2 infection in health care workers (HCWs) at a tertiary hospital depending on time elapsed since the completion of a two-dose vaccination regimen. We conducted a case–control with negative test study between 25 January and 12 December 2021 that included 1404 HCWs who underwent an active infection diagnostic test (AIDT) to rule out SARS-CoV-2 infection due to COVID-19 suspicion or prior close contact with patients diagnosed with COVID-19. The adjusted vaccine effectiveness (aVE) for the prevention of SARS-CoV-2 infection 12 to 120 days after completing the full two-dose vaccination regimen was 91.9%. Then, aVE decreased to 63.7% between 121 to 240 days after completing the full two-dose regimen and to 37.2% after 241 days since the second dose. Vaccination against SARS-CoV-2 infection in HCWs remains highly effective after 12 to 120 days have elapsed since the administration of two doses of the BNT162b2 vaccine; however, effectiveness decreases as time elapses since its administration

Effectiveness of the systematic use of antimicrobial filters in the water taps of critical care units for the prevention of healthcare-associated infections with Pseudomonas aeruginosa

Background: Pseudomonas aeruginosa (PA) is the third leading aetiological agent in healthcare-associated infections (HAIs) and the one most frequently found in patients with pneumonia associated with mechanical ventilation. In intensive care units (ICU), its appearance is associated with higher mortality, an increase in the days spent on ventilation, and hospital stay length and costs. Thus, evaluating strategies for preventing these infections is essential for their control. Therefore, our objective was to evaluate the effectiveness of the systematic use of antimicrobial filters in preventing PA infections in critical care units. Methods: This was an open experimental crossover study. A total of 2,156 patients admitted for more than 24 hours in critical care units were included, 1,129 of them in units with filters, and 1,027 in units without filters. The study groups were followed-up for 24 months and HAIs were checked for the presence of PA. Chi-squared test were used to compare the rate of HAIs between groups and we calculated 95% confidence intervals adjusted by Poisson regression for the rate ratio (RR) of the association magnitude. Results: Both groups were homogeneous in terms of intrinsic and extrinsic patient factors. The incidence of PA infections in the units with filters was 5.5 cases/1,000 hospitalized days and 5.4/1,000 hospitalized days for the units without water filters (RR = 1.09 [0.67-1.79]). Conclusions: Routine placing antimicrobial filters in the water taps in critical care units was not an effective means of preventing the emergence of HAIs caused by PA.This study has been funded by: Instituto de Salud Carlos III (Carlos III Health Institute) through Fund for Health Research (FIS), Ministry of Health, Spanish Government. Project # PI15/01344; Generalitat Valenciana (Valencian Regional Government) Grants for Support to a Research or Technology Transfer Project. Project # APOTIP/2016/A/011; Alicante Institute for Health and Biomedical Research through Grants to supplement the development of active research projects under the State Plan for Scientific and Technical Research and Innovation. Project # 180192 and Project # 190181