Efficacy and safety of a structured de-escalation from antipseudomonal ß-lactams in bloodstream infections due to Enterobacterales (SIMPLIFY): an open-label, multicentre, randomised trial.

BACKGROUND: De-escalation from broad-spectrum to narrow-spectrum antibiotics is considered an important measure to reduce the selective pressure of antibiotics, but a scarcity of adequate evidence is a barrier to its implementation. We aimed to determine whether de-escalation from an antipseudomonal ß-lactam to a narrower-spectrum drug was non-inferior to continuing the antipseudomonal drug in patients with Enterobacterales bacteraemia. METHODS: An open-label, pragmatic, randomised trial was performed in 21 Spanish hospitals. Patients with bacteraemia caused by Enterobacterales susceptible to one of the de-escalation options and treated empirically with an antipseudomonal ß-lactam were eligible. Patients were randomly assigned (1:1; stratified by urinary source) to de-escalate to ampicillin, trimethoprim-sulfamethoxazole (urinary tract infections only), cefuroxime, cefotaxime or ceftriaxone, amoxicillin-clavulanic acid, ciprofloxacin, or ertapenem in that order according to susceptibility (de-escalation group), or to continue with the empiric antipseudomonal ß-lactam (control group). Oral switching was allowed in both groups. The primary outcome was clinical cure 3-5 days after end of treatment in the modified intention-to-treat (mITT) population, formed of patients who received at least one dose of study drug. Safety was assessed in all participants. Non-inferiority was declared when the lower bound of the 95% CI of the absolute difference in cure rate was above the -10% non-inferiority margin. This trial is registered with EudraCT (2015-004219-19) and ClinicalTrials.gov (NCT02795949) and is complete. FINDINGS: 2030 patients were screened between Oct 5, 2016, and Jan 23, 2020, of whom 171 were randomly assigned to the de-escalation group and 173 to the control group. 164 (50%) patients in the de-escalation group and 167 (50%) in the control group were included in the mITT population. 148 (90%) patients in the de-escalation group and 148 (89%) in the control group had clinical cure (risk difference 1·6 percentage points, 95% CI -5·0 to 8·2). The number of adverse events reported was 219 in the de-escalation group and 175 in the control group, of these, 53 (24%) in the de-escalation group and 56 (32%) in the control group were considered severe. Seven (5%) of 164 patients in the de-escalation group and nine (6%) of 167 patients in the control group died during the 60-day follow-up. There were no treatment-related deaths. INTERPRETATION: De-escalation from an antipseudomonal ß-lactam in Enterobacterales bacteraemia following a predefined rule was non-inferior to continuing the empiric antipseudomonal drug. These results support de-escalation in this setting. FUNDING: Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases; Spanish Clinical Research and Clinical Trials Platform, co-financed by the EU; European Development Regional Fund "A way to achieve Europe", Operative Program Intelligence Growth 2014-2020.

The prognostic value of toxin B and binary toxin in Clostridioides difficile infection.

To study the association between detection of the Clostridioides difficile gene encoding the binary toxin (CDT) and direct detection of toxinB (TcdB) from feces with the appearance of serious disease, complications, or recurrence in a prospective series of cases. A total of 220 confirmed cases were included, using a two-step algorithm: an initial study to detect the enzyme, glutamate dehydrogenase (GDH), followed, in cases of positivity, by detection of the tcdB. tcdB-positive patients were investigated for the presence of CDT and TcdB. Outcome variables were severe disease, the modified Illinois C. difficile infection (CDI) prognostic risk index (ZAR score), the appearance of complications (need for colectomy, CDI-related death, or toxic megacolon) and recurrence. Patients who tested positive for the presence of TcdB in feces were found to have greater disease severity than those who tested negative, with a ZAR score of 35.4% vs. 23% (p = .048), a higher recurrence rate (14.6% vs. 5.9%, p = .032), and a tendency for higher number of complications (20.7% vs. 11.5%), although without reaching statistical significance (p = .053). When presence of CDT was analyzed, higher frequencies of severe disease (39.2% vs. 21.2%, p = .005), complications and recurrence (21.6% vs. 10.9%, p = .037 and 14.9% vs. 5.8%, p = .029; respectively) were observed in patients where CDT was detected. TcdB and CDT act as prognostic markers of the appearance of serious disease, complications or recurrence in cases of CDI. Simultaneous detection of both markers, TcdB and CDT, had a greater impact on the prognosis than when they were detected separately.

Spondylodiscitis due to Aerococcus urinae infection in an elderly immunocompetent patient / Espondilodiscitis debida a Aerococcus urinae en paciente anciano inmunocompetente

No disponible

Oral decontamination with aminoglycosides is associated with lower risk of mortality and infections in high-risk patients colonized with colistin-resistant, KPC-producing Klebsiella pneumoniae.

OBJECTIVES: Invasive infections caused by KPC-producing Klebsiella pneumoniae (KPCKP) are associated with very high mortality. Because infection is usually preceded by rectal colonization, we investigated if decolonization therapy (DT) with aminoglycosides had a protective effect in selected patients. METHODS: Patients with rectal colonization by colistin-resistant KPCKP who were at high risk of developing infection (because of neutropenia, surgery, previous recurrent KPCKP infections or multiple comorbidities) were followed for 180 days. Cox regression analysis including a propensity score was used to investigate the impact of the use of two intestinal decolonization regimens with oral aminoglycosides (gentamicin and neomycin/streptomycin) on mortality, risk of KPCKP infections and microbiological success. The study was registered with ClinicalTrials.gov (NCT02604849). RESULTS: The study sample comprised 77 colonized patients, of which 44 (57.1%) received DT. At 180 days of follow-up, decolonization was associated with a lower risk of mortality in multivariate analyses (HR 0.18; 95% CI 0.06-0.55) and a lower risk of KPCKP infections (HR 0.14; 95% CI 0.02-0.83) and increased microbiological success (HR 4.06; 95% CI 1.06-15.6). Specifically, gentamicin oral therapy was associated with a lower risk of crude mortality (HR 0.15; 95% CI 0.04-0.54), a lower risk of KPCKP infections (HR 0.86; 95% CI 0.008-0.94) and increased microbiological response at 180 days of follow-up (HR 5.67; 95% CI 1.33-24.1). Neomycin/streptomycin therapy was only associated with a lower risk of crude mortality (HR 0.22; 95% CI 0.06-0.9). CONCLUSIONS: Intestinal decolonization with aminoglycosides is associated with a reduction in crude mortality and KPCKP infections at 180 days after initiating treatment.

Predictors of early mortality in very elderly patients with bacteremia: a prospective multicenter cohort.

OBJECTIVES: The proportion of very elderly people in the population is increasing, and infectious diseases in this patient group may present with specific characteristics. The objective of this study was to investigate the outcome predictors of bacteremia among the very elderly. METHODS: This was a multicenter prospective cohort study of bloodstream infections (BSI) in patients ≥ 80 years old in 15 hospitals in Spain. The outcome variables were 14-day and 30-day mortality. Multivariate analysis was performed. RESULTS: One hundred and twenty episodes were included. Mortality was 22% (n = 26) on day 14 and 28% (n = 34) on day 30. In the univariate analysis, the variables associated with mortality were neutropenia, recent surgery, Pitt score ≥ 2, intensive care unit (ICU) admission, severe sepsis or shock, and abdominal, unknown, and respiratory tract sources. In the multivariate analysis, variables associated with mortality on day 14 were high-risk source (abdominal, unknown, and respiratory tract sources; odds ratio (OR) 7.9, 95% confidence interval (CI) 1.8-33.9), Pitt score ≥ 2 (OR 5.6, 95% CI 1.3-23.3), inadequate empirical treatment (OR 11.24, 95% CI 1.6-80.2), and severe sepsis or shock at presentation (OR 5.3, 95% CI 1.4-20.7); the interaction between empiric treatment and high-risk source was significant. On day 30, mortality was independently related to a high-risk source (OR 2.92, 95% CI 1.1-7.5) and presentation with severe sepsis or shock (OR 3.81, 95% CI 1.2-12.4). CONCLUSIONS: Presentation with severe sepsis or shock and a high-risk source of BSI were independent predictors of 14-day and 30-day mortality. Inadequate empirical treatment was also a predictor of early mortality in patients with a high-risk source.

Infección de partes blandas por Stenotrophomonas maltophilia de adquisición comunitaria en paciente previamente sano / Community acquired Stenotrophomonas maltophilia soft-tissue infection in a previously healthy patient

No disponible

Hepatitis C virus and human immunodeficiency virus coinfection in Spain.

OBJECTIVE AND METHODS: In a cross-sectional study, based on a cohort composed of HIV-infected patients of fifteen tertiary level institutions of Spain, the main data of the entire cohort are described, characteristics of patients with or without hepatitis C coinfection are compared, and the possible association of hepatitis C virus coinfection with socioeconomic, HIV-related, and hepatitis B-related variables is assessed. RESULTS: A total of 4,709 patients are studied. Median of age is 37 years, 78.3% are male. HIV risk behaviours are: parenteral drug use in 63.8% of patients, heterosexual in 22.3%, and homosexual in 10.8%. Serology of hepatitis C is positive in 69.2% of participants. The following variables are associated with increased prevalence of hepatitis C coinfection, both in univariate and in multivariate analysis: HIV risk behaviour, positive anti-HBs, longer time elapsed since HIV infection diagnosis, younger age, lower social status, lower CD4 cell count increase between nadir and last available result, and lower educational level (all P<0.001). Patients with heterosexual behaviour are more frequently coinfected than patients with homosexual behaviour (P<0.001). CONCLUSION: This study highlights that, in Spain, more than two thirds of patients with HIV infection are coinfected with hepatitis C virus.