Abstract Most urinary tract infections (UTI) are uncomplicated infections occurring in young women. An extensive evaluation is not required in the majority of cases, and they can be safely managed as ...outpatients with oral antibiotics. Escherichia coli is by far the most common uropathogen, accounting for >80% of all cases. Other major clinical problems associated with UTI include asymptomatic bacteriuria, and patients with complicated UTI. Complicated UTIs are a heterogeneous group associated with conditions that increase the risk of acquiring infection or treatment failure. Distinguishing between complicated and uncomplicated UTI is important, as it influences the initial evaluation, choice, and duration of antimicrobial therapy. Diagnosis is especially challenging in the elderly and in patients with in-dwelling catheters. The increasing prevalence of resistant uropathogens, including extended-spectrum β-lactamases and carbapenemase-producing Enterobacteriaceae, and other multidrug-resistant Gram-negative organisms further compromises treatment of both complicated and uncomplicated UTIs. The aim of these Clinical Guidelines is to provide a set of recommendations for improving the diagnosis and treatment of UTI.
•High variability was found between national UTI treatment guidelines in Europe.•The observed differences may in part be due to unavailability of antibiotics.•A more systematic approach to resistance ...surveillance should be promoted.
Appropriate antibiotic use for urinary tract infections (UTIs) is important in order to provide effective and safe treatment while minimising the risk of antimicrobial resistance development. This survey was carried out to compare existing national guidelines for UTIs in Europe. Experts in 37 European countries were asked to participate. An electronic questionnaire was used to obtain information on treatment recommendations, factors considered important when setting guidelines, acceptable resistance rates for empirical therapy, evidence grading, and existing resistance surveillance for uropathogens. Treatment guidelines and antimicrobial susceptibility data were collected. In total, 22 experts (59%) responded to the survey. National guidelines were missing in four countries and data were incomplete in three cases. Fifteen national guidelines published between 2004 and 2017 were included in the analysis. Great variability was found between guidelines in the selection of antibiotics, dosing regimens and treatment duration. For example, 10 different antibiotics were recommended as first-line therapy for uncomplicated cystitis. National surveillance data on antimicrobial susceptibility of uropathogens were available in 13 of 15 countries. Resistance epidemiology could not explain the observed differences between guidelines, and comparison of resistance rates was hampered by variations in methods. This study revealed major differences in treatment guidelines for UTIs within Europe, indicating that there are opportunities for improvement. More clinical research and a more systematic and stratified approach to resistance surveillance, including also antibiotics that are currently not available in all countries, is needed.
Background. Staphylococcus aureus bacteremia (SAB) is associated with significant morbidity and mortality. Several aspects of clinical management have been shown to have significant impact on ...prognosis. The objective of the study was to identify evidence-based quality-of-care indicators (QCIs) for the management of SAB, and to evaluate the impact of a QCI-based bundle on the management and prognosis of SAB. Methods. A systematic review of the literature to identify QCIs in the management of SAB was performed. Then, the impact of a bundle including selected QCIs was evaluated in a quasi-experimental study in 12 tertiary Spanish hospitals. The main and secondary outcome variables were adherence to QCIs and mortality. Specific structured individualized written recommendations on 6 selected evidence-based QCIs for the management of SAB were provided. Results. A total of 287 and 221 patients were included in the preintervention and intervention periods, respectively. After controlling for potential confounders, the intervention was independently associated with improved adherence to follow-up blood cultures (odds ratio OR, 2.83; 95% confidence interval CI, 1.78–4.49), early source control (OR, 4.56; 95% CI, 2.12–9.79), early intravenous cloxacillin for methicillin-susceptible isolates (OR, 1.79; 95% CI, 1.15–2.78), and appropriate duration of therapy (OR, 2.13; 95% CI, 1.24–3.64). The intervention was independently associated with a decrease in 14-day and 30-day mortality (OR, 0.47; 95% CI, .26–.85 and OR, 0.56; 95% CI, .34–.93, respectively). Conclusions. A bundle orientated to improving adherence to evidence-based QCIs improved the management of patients with SAB and was associated with reduced mortality.
To evaluate the appropriateness of antimicrobial treatment and the risk factors for mortality in patients with negative blood cultures (BC), in order to evaluate whether this population would be a ...suitable target for antimicrobial stewardship (AMS) interventions.
A multicentre prospective cohort study of patients with negative BC in three Spanish hospitals between October 2018 and July 2019 was performed. The main endpoints were the appropriateness of antimicrobial treatment (evaluated by two investigators according to local guidelines) and 30-day mortality. Cox-regression was performed to estimate the association between variables and 30-day mortality.
Of 1011 patients in whom BC was obtained, these were negative in 803 (79%) and were included; 30-day mortality was 9% (70 patients); antibiotic treatment was considered inappropriate in 299 (40%) of 747 patients evaluated at day 2, and in 266 (46%) of 573 at day 5–7. The variables independently associated with increased risk of 30-day mortality were higher age (HR 1.05; 95% CI 1.03–1.07), neoplasia (HR 2.73; 95% CI 1.64–4.56), antibiotic treatment in the 48 h prior to BC extraction (HR 2.06; 95% CI 1.23–3.43) and insufficient antibiotic coverage at day 2 after BC obtainment (HR 2.35; 95% CI 1.39–4.00). Urinary, catheter and biliary sources of infection were associated with lower risk (HR 0.40; 95% CI 0.20–0.81).
Antimicrobial treatment is frequently inappropriate among patients with negative BC; insufficient antibiotic coverage at day 2 was associated with mortality. These results suggest that patients with negative BC are a suitable population for AS interventions.
Antimicrobial treatment in patients with negative blood culture was frequently inappropriate, and inappropriate coverage at day 2 was associated with increased risk of death. These data support the consideration of this population as a potential target for antimicrobial stewardship interventions.
•Patients with negative blood culture represent 80% of patients from whom a blood culture is obtained.•Antimicrobial treatment is frequently inappropriate among patients with negative blood culture.•Insufficient antibiotic coverage at day 2 was associated with mortality in patients with negative blood culture.•Patients with negative blood culture are a suitable population for antimicrobial stewardship interventions.
Staphylococcus aureus bloodstream infection is treated with at least 14 days of intravenous antimicrobials. We assessed the efficacy and safety of an early switch to oral therapy in patients at low ...risk for complications related to S aureus bloodstream infection.
In this international, open-label, randomised, controlled, non-inferiority trial done in 31 tertiary care hospitals in Germany, France, the Netherlands, and Spain, adult patients with low-risk S aureus bloodstream infection were randomly assigned after 5–7 days of intravenous antimicrobial therapy to oral antimicrobial therapy or to continue intravenous standard therapy. Randomisation was done via a central web-based system, using permuted blocks of varying length, and stratified by study centre. The main exclusion criteria were signs and symptoms of complicated S aureus bloodstream infection, non-removable foreign devices, and severe comorbidity. The composite primary endpoint was the occurrence of any complication related to S aureus bloodstream infection (relapsing S aureus bloodstream infection, deep-seated infection, and mortality attributable to infection) within 90 days, assessed in the intention-to-treat population by clinical assessors who were masked to treatment assignment. Adverse events were assessed in all participants who received at least one dose of study medication (safety population). Due to slow recruitment, the scientific advisory committee decided on Jan 15, 2018, to stop the trial after 215 participants were randomly assigned (planned sample size was 430 participants) and to convert the planned interim analysis into the final analysis. The decision was taken without knowledge of outcome data, at a time when 126 participants were enrolled. The new sample size accommodated a non-inferiority margin of 10%; to claim non-inferiority, the upper bound of the 95% CI for the treatment difference (stratified by centre) had to be below 10 percentage points. The trial is closed to recruitment and is registered with ClinicalTrials.gov (NCT01792804), the German Clinical trials register (DRKS00004741), and EudraCT (2013–000577–77).
Of 5063 patients with S aureus bloodstream infection assessed for eligibility, 213 were randomly assigned to switch to oral therapy (n=108) or to continue intravenous therapy (n=105). Mean age was 63·5 (SD 17·2) years and 148 (69%) participants were male and 65 (31%) were female. In the oral switch group, 14 (13%) participants met the primary endpoint versus 13 (12%) in the intravenous group, with a treatment difference of 0·7 percentage points (95% CI –7·8 to 9·1; p=0·013). In the oral switch group, 36 (34%) of 107 participants in the safety population had at least one serious adverse event compared with 27 (26%) of 103 participants in the intravenous group (p=0·29).
Oral switch antimicrobial therapy was non-inferior to intravenous standard therapy in participants with low-risk S aureus bloodstream infection. However, it is necessary to carefully assess patients for signs and symptoms of complicated S aureus bloodstream infection at the time of presentation and thereafter before considering early oral switch therapy.
Deutsche Forschungsgemeinschaft.
For the German, Spanish, French and Dutch translations of the abstract see Supplementary Materials section.
To develop a score to predict mortality in patients with bloodstream infections (BSIs) due to carbapenemase-producing Enterobacteriaceae (CPE).
A multinational retrospective cohort study (INCREMENT ...project) was performed from January 1, 2004, through December 31, 2013. Patients with clinically relevant monomicrobial BSIs due to CPE were included and randomly assigned to either a derivation cohort (DC) or a validation cohort (VC). The variables were assessed on the day the susceptibility results were available, and the predictive score was developed using hierarchical logistic regression. The main outcome variable was 14-day all-cause mortality. The predictive ability of the model and scores were measured by calculating the area under the receiver operating characteristic curve. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for different cutoffs of the score.
The DC and VC included 314 and 154 patients, respectively. The final logistic regression model of the DC included the following variables: severe sepsis or shock at presentation (5 points); Pitt score of 6 or more (4 points); Charlson comorbidity index of 2 or more (3 points); source of BSI other than urinary or biliary tract (3 points); inappropriate empirical therapy and inappropriate early targeted therapy (2 points). The score exhibited an area under the receiver operating characteristic curve of 0.80 (95% CI, 0.74-0.85) in the DC and 0.80 (95% CI, 0.73-0.88) in the VC. The results for 30-day all-cause mortality were similar.
A validated score predictive of early mortality in patients with BSIs due to CPE was developed.
clinicaltrials.gov Identifier: NCT01 764490.
We analyzed the impact of continuous/extended infusion (C/EI) vs intermittent infusion of piperacillin-tazobactam (TZP) and carbapenems on 30-day mortality of patients with liver cirrhosis and ...bloodstream infection (BSI).
The BICRHOME study was a prospective, multicenter study that enrolled 312 cirrhotic patients with BSI. In this secondary analysis, we selected patients receiving TZP or carbapenems as adequate empirical treatment. The 30-day mortality of patients receiving C/EI or intermittent infusion of TZP or carbapenems was assessed with Kaplan-Meier curves, Cox-regression model, and estimation of the average treatment effect (ATE) using propensity score matching.
Overall, 119 patients received TZP or carbapenems as empirical treatment. Patients who received C/EI had a significantly lower mortality rate (16% vs 36%, P = .047). In a Cox-regression model, the administration of C/EI was associated with a significantly lower mortality (hazard ratio HR, 0.41; 95% confidence interval CI, 0.11-0.936; P = .04) when adjusted for severity of illness and an ATE of 25.6% reduction in 30-day mortality risk (95% CI, 18.9-32.3; P < .0001) estimated with propensity score matching. A significant reduction in 30-day mortality was also observed in the subgroups of patients with sepsis (HR, 0.21; 95% CI, 0.06-0.74), acute-on-chronic liver failure (HR, 0.29; 95% CI, 0.03-0.99), and a model for end-stage liver disease score ≥25 (HR, 0.26; 95% CI, 0.08-0.92). At competing risk analysis, C/EI of beta-lactams was associated with significantly higher rates of hospital discharge (subdistribution hazard 95% CI, 1.62 1.06-2.47).
C/EI of beta-lactams in cirrhotic patients with BSI may improve outcomes and facilitate earlier discharge.
Abstract Background and Aims Infections are a leading cause of morbidity and mortality in hemodialysis patients. Tunneled catheters (TC) have been associated with increased risk of infection and ...death, but mortality rates are not widely reported. Our study aimed to analyse catheter infection-free survival and mortality of patients with this vascular access. Method This is a retrospective study of all TC inserted during the period of 1 January 2005 to 31 December 2019. The TC were inserted by nephrologists, following a preimplantation protocol agreed with the Infectious Diseases Service. Patients were followed up from the tunneled catheter insertion until the study end date (December 31, 2020), TC related bacteremia or died. Results In the 14-year period under study, 406 TC were implanted in 325 patients. A total of 85 tunneled catheter related bacteremia were diagnosed, resulting in an incidence of 0.40 per 1000 catheter days (81.1% after 6 months of implantation). The predominant microorganisms isolated were Gram-positive organisms: Staphylococcus epidermidis (48.4%); Staphylococcus aureus (28.0%). During the study, a total of 145 patients had the TC removed or exchanged due different causes. The main reasons for catheter removal were the adequate development and use of the arteriovenous fistula (48, 33.1%) and discharge from hemodialysis due to recovery of renal function, transfer to peritoneal dialysis or renal transplantation (47, 32.4%). Only in 26 (17.9%) patients, the TC was removed due to bacteremia at a median of 4.8 (1.0-8.0) days from the bacteremia. The median time to catheter removal for non-infection-related reasons was 448 (185-910) days, without significant differences with the TC related bacteremia group 430 (116-695) (p=0.83). The 30-day mortality rate from the first TC related bacteremia was 8.7%. During the study period, a total of 168 (51.7%) patients died for different causes. Conclusion The incidence of bacteremia in our study was low and did not seem to have a relevant impact on catheter survival. The global mortality rate was similar to that reported in European registries for patients on renal replacement therapy. An implantation and management protocol, strict in prophylactic measures, could reduce the incidence of bacteremia and reduce its morbidity and mortality.
Bloodstream infections (BSIs) due to ESBL-producing Enterobacteriaceae (ESBL-E) are frequent yet outcome prediction rules for clinical use have not been developed. The objective was to define and ...validate a predictive risk score for 30 day mortality.
A multinational retrospective cohort study including consecutive episodes of BSI due to ESBL-E was performed; cases were randomly assigned to a derivation cohort (DC) or a validation cohort (VC). The main outcome variable was all-cause 30 day mortality. A predictive score was developed using logistic regression coefficients for the DC, then tested in the VC.
The DC and VC included 622 and 328 episodes, respectively. The final multivariate logistic regression model for mortality in the DC included age >50 years (OR = 2.63; 95% CI: 1.18-5.85; 3 points), infection due to Klebsiella spp. (OR = 2.08; 95% CI: 1.21-3.58; 2 points), source other than urinary tract (OR = 3.6; 95% CI: 2.02-6.44; 3 points), fatal underlying disease (OR = 3.91; 95% CI: 2.24-6.80; 4 points), Pitt score >3 (OR = 3.04; 95 CI: 1.69-5.47; 3 points), severe sepsis or septic shock at presentation (OR = 4.8; 95% CI: 2.72-8.46; 4 points) and inappropriate early targeted therapy (OR = 2.47; 95% CI: 1.58-4.63; 2 points). The score showed an area under the receiver operating curve (AUROC) of 0.85 in the DC and 0.82 in the VC. Mortality rates for patients with scores of < 11 and ≥11 were 5.6% and 45.9%, respectively, in the DC, and 5.4% and 34.8% in the VC.
We developed and validated an easy-to-collect predictive scoring model for all-cause 30 day mortality useful for identifying patients at high and low risk of mortality.
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