Duration of Treatment for Pseudomonas aeruginosa Bacteremia: a Retrospective Study

Introduction: There is no consensus regarding optimal duration of antibiotic therapy for Pseudomonas aeruginosa bacteremia. We aimed to evaluate the impact of short antibiotic course. Methods: We present a retrospective multicen ter study including patients with P. aeruginosa bacteremia during 2009–2015. We evaluated outcomes of patients treated with short (6–- 10 days) versus long (11–15 days) antibiotic courses. The primary outcome was a composite of 30-day mortality or bacteremia recurrence and/or persistence. Univariate and inverse probability treatment-weighted (IPTW) adjusted multivariate analysis for the primary outcome was performed. To avoid immortal time bias, the landmark method was used. Results: We included 657 patients; 273 received a short antibiotic course and 384 a long course. There was no significant difference in baseline characteristics of patients. The com posite primary outcome occurred in 61/384 patients in the long-treatment group (16%) versus 32/273 in the short-treatment group (12%) (p = 0.131). Mortality accounted for 41/384 (11%) versus 25/273 (9%) of cases, respectively. Length of hospital stay was signif icantly shorter in the short group [median 13 days, interquartile range (IQR) 9–21 days, versus median 15 days, IQR 11–26 days, p = 0.002]. Ten patients in the long group dis continued antibiotic therapy owing to adverse events, compared with none in the short group. On univariate and multivariate analyses, dura tion of therapy was not associated with the primary outcome. Conclusions: In this retrospective study, 6–- 10 days of antibiotic course for P. aeruginosa bacteremia were as effective as longer courses in terms of survival and recurrence. Shorter ther apy was associated with reduced length of stay and less drug discontinuation

Risk factors for hospital readmission following complicated urinary tract infection

Hospital readmissions following severe infections are a major economic burden on the health care system and have a negative influence on patients' quality of life. Understanding the risk factors for readmission, particularly the extent to which they could be prevented, is of a great importance. In this study we evaluated potentially preventable risk factors for 60-day readmission in patients surviving hospitalization for complicated urinary tract infection (cUTI). This was a multinational, multicentre retrospective cohort study conducted in Europe and the Middle East. Our cohort included survivors of hospitalization due to cUTI during the years 2013-2014. The primary outcome was 60-day readmission following index hospitalization. Patient characteristics that could have influenced readmission: demographics, infection presentation and management, microbiological and clinical data; were collected via computerized medical records from infection onset up to 60 days after hospital discharge. Overall, 742 patients were included. The cohort median age was 68 years (interquartile range, (IQR) 55-80) and 43.3% (321/742) of patients were males. The all-cause 60-day readmission rate was 20.1% (149/742) and more than half were readmitted for infection [57.1%, (80/140)]. Recurrent cUTI was the most frequent cause for readmission [46.4% (65/140)]. Statistically significant risk factors associated with 60-day readmission in multivariable analysis were: older age (odds ratio (OR) 1.02 for an one-year increment, confidence interval (CI) 1.005-1.03), diabetes mellitus (OR 1.63, 95% CI 1.04-2.55), cancer (OR 1.7, 95% CI 1.05-2.77), previous urinary tract infection (UTI) in the last year (OR 1.8, 95% CI: 1.14-2.83), insertion of an indwelling bladder catheter (OR 1.62, 95% CI 1.07-2.45) and insertion of percutaneous nephrostomy (OR 3.68, 95% CI 1.67-8.13). In conclusion, patients surviving hospitalization for cUTI are frequently re-hospitalized, mostly for recurrent urinary infections associated with a medical condition that necessitated urinary interventions. Interventions to avoid re-admissions should target these patients

Cost of hospitalised patients due to complicated urinary tract infections: a retrospective observational study in countries with high prevalence of multidrug-resistant Gram-negative bacteria: the COMBACTE-MAGNET, RESCUING study

Objective: Complicated urinary tract infections (cUTIs) impose a high burden on healthcare systems and are a frequent cause of hospitalisation. The aims of this paper are to estimate the cost per episode of patients hospitalised due to cUTI and to explore the factors associated with cUTI-related healthcare costs in eight countries with high prevalence of multidrug resistance (MDR). Design: This is a multinational observational, retrospective study. The mean cost per episode was computed by multiplying the volume of healthcare use for each patient by the unit cost of each item of care and summing across all components. Costs were measured from the hospital perspective. Patient-level regression analyses were used to identify the factors explaining variation in cUTI-related costs. Setting: The study was conducted in 20 hospitals in eight countries with high prevalence of multidrug resistant Gram-negative bacteria (Bulgaria, Greece, Hungary, Israel, Italy, Romania, Spain and Turkey). Participants: Data were obtained from 644 episodes of patients hospitalised due to cUTI. Results: The mean cost per case was 5700, with considerable variation between countries (largest value 7740 in Turkey; lowest value 4028 in Israel), mainly due to differences in length of hospital stay. Factors associated with higher costs per patient were: type of admission, infection source, infection severity, the Charlson comorbidity index and presence of MDR. Conclusions: The mean cost per hospitalised case of cUTI was substantial and varied significantly between countries. A better knowledge of the reasons for variations in length of stays could facilitate a better standardised quality of care for patients with cUTI and allow a more efficient allocation of healthcare resources. Urgent admissions, infections due to an indwelling urinary catheterisation, resulting in septic shock or severe sepsis, in patients with comorbidities and presenting MDR were related to a higher cost

Using external data to assess the external validity of a randomised controlled trial

Background: Few studies have addressed external validity of randomized controlled trials in infectious diseases. We aimed to assess the external validity of an investigator-initiated trial on treatment for uncomplicated urinary tract infection.Methods: In the original study, women (n = 513) with urinary tract infection were randomized to nitrofurantoin or fosfomycin treatment in three countries between 2013 and 2017. In the present study we compared women who were screened for enrolment but excluded to women who participated in the trial, both groups in Israel. The primary outcome was the rate of emergency department index visits resulting in hospitalization within 28 days.Results: We compared 127 included to 110 excluded patients. The most common reasons for exclusion were logistic difficulties in recruitment and antibiotic use in the preceding month. Included patients tended to be older [39 (IQR 29-59) vs. 35.5 (IQR 24-56.25 years)], more likely to have history of recurrent infection and had more urinary symptoms. Among excluded patients, 13.6% (15/110) had initial visits resulting in hospitalization compared to 3.1% (4/127) of included participants (p = .003). The rate of emergency department visits within 28 days was similar in both groups. Clinical and microbiological failures were significantly more common in included patients [26% (33/127) vs. 1.8% (2/110), p Conclusions: While differences were observed between included and excluded patients, the excluded group did not represent a more 'complicated' population. The present study shows the importance of collecting data on patients excluded from randomized controlled trials.</p

Risk factors for treatment failure in women with uncomplicated lower urinary tract infection

Given rising antibiotic resistance and increasing use of delayed prescription for uncomplicated lower urinary tract infections (UTI), patients at risk for treatment failure should be identified early. We assessed risk factors for clinical and microbiological failure in women with lower UTI. This case-control study nested within a randomized clinical trial included all women in the per-protocol population (PPP), those in the PPP with microbiologically confirmed UTI, and those in the PPP with UTI due to Escherichia coli. Cases were women who experienced clinical and/or microbiologic failure; controls were those who did not. Risk factors for failure were assessed using multivariate logistic regression. In the PPP, there were 152 clinical cases for 307 controls. Among 340 women with microbiologically confirmed UTI, 126 and 102 cases with clinical and microbiological failure were considered with, respectively, 214 and 220 controls. Age ≥52 years was independently associated with clinical (adjusted OR 3.01; 95%CI 1.84–4.98) and microbiologic failure (aOR 2.55; 95%CI 1.54–4.25); treatment with fosfomycin was associated with clinical failure (aOR 2.35; 95%CI 1.47–3.80). The association with age persisted among all women, and women with E. coli-related UTI. Diabetes was not an independent risk factor, nor were other comorbidities. Postmenopausal age emerged as an independent risk factor for both clinical and microbiological treatment failure in women with lower UTI and should be considered to define women at-risk for non-spontaneous remission, and thus for delayed antibiotic therapy; diabetes mellitus was not associated with failure

Effect of 5-Day Nitrofurantoin vs Single-Dose Fosfomycin on Clinical Resolution of Uncomplicated Lower Urinary Tract Infection in Women: A Randomized Clinical Trial

The use of nitrofurantoin and fosfomycin has increased since guidelines began recommending them as first-line therapy for lower urinary tract infection (UTI)

Risk factors for functional decline among survivors of Gram-negative bloodstream infection: A prospective cohort study

To identify risk factors for functional decline after hospitalization for Gram-negative bacteremia

Seven versus fourteen Days of Antibiotic Therapy for uncomplicated Gram-negative Bacteremia: a Non-inferiority Randomized Controlled Trial

Gram-negative bacteremia is a major cause of morbidity and mortality in hospitalized patients. Data to guide the duration of antibiotic therapy are limited

Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria: An open-label, randomised controlled trial

Background: Colistin-carbapenem combinations are synergistic in vitro against carbapenem-resistant Gram-negative bacteria. We aimed to test whether combination therapy improves clinical outcomes for adults with infections caused by carbapenem-resistant or carbapenemase-producing Gram-negative bacteria. Methods: A randomised controlled superiority trial was done in six hospitals in Israel, Greece, and Italy. We included adults with bacteraemia, ventilator-associated pneumonia, hospital-acquired pneumonia, or urosepsis caused by carbapenem-non-susceptible Gram-negative bacteria. Patients were randomly assigned (1:1) centrally, by computer-generated permuted blocks stratified by centre, to intravenous colistin (9-million unit loading dose, followed by 4·5 million units twice per day) or colistin with meropenem (2-g prolonged infusion three times per day). The trial was open-label, with blinded outcome assessment. Treatment success was defined as survival, haemodynamic stability, improved or stable Sequential Organ Failure Assessment score, stable or improved ratio of partial pressure of arterial oxygen to fraction of expired oxygen for patients with pneumonia, and microbiological cure for patients with bacteraemia. The primary outcome was clinical failure, defined as not meeting all success criteria by intention-to-treat analysis, at 14 days after randomisation. This trial is registered at ClinicalTrials.gov, number NCT01732250, and is closed to accrual. Findings: Between Oct 1, 2013, and Dec 31, 2016, we randomly assigned 406 patients to the two treatment groups. Most patients had pneumonia or bacteraemia (355/406, 87%), and most infections were caused by Acinetobacter baumannii (312/406, 77%). No significant difference between colistin monotherapy (156/198, 79%) and combination therapy (152/208, 73%) was observed for clinical failure at 14 days after randomisation (risk difference -5·7%, 95% CI -13·9 to 2·4; risk ratio [RR] 0·93, 95% CI 0·83-1·03). Results were similar among patients with A baumannii infections (RR 0·97, 95% CI 0·87-1·09). Combination therapy increased the incidence of diarrhoea (56 [27%] vs 32 [16%] patients) and decreased the incidence of mild renal failure (37 [30%] of 124 vs 25 [20%] of 125 patients at risk of or with kidney injury). Interpretation: Combination therapy was not superior to monotherapy. The addition of meropenem to colistin did not improve clinical failure in severe A baumannii infections. The trial was unpowered to specifically address other bacteria. Funding: EU AIDA grant Health-F3-2011-278348

External Validity of a Randomized Controlled Trial on Duration of Antibiotics for the Treatment of Gram-Negative Bacteremia

Introduction: Reports regarding the external validity of randomized controlled trials (RCTs) are scarce. We aimed to assess the population external validity of an investigator-initiated RCT on the duration of antibiotics for the treatment of Gram-negative bacteremia by comparing patients included in the RCT to patients that were not included in the trial. Methods: Hospitalized patients with Gram-negative bacteremia were recruited into an RCT and randomized to receive 7 or 14 days of covering antibiotic therapy in Israel and Italy from 2013 to 2017. In a concomitant observational study, RCT participants were compared with patients who fulfilled the inclusion criteria but were not included in the trial due to participation in other trials, discharge before approached by researchers, refusal to participate, or unwillingness of the treating physician to allow participants' recruitment. Results: Six hundred and four RCT patients were compared with 613 nonincluded patients. Almost 50% of nonincluded patients (288/613) were dependent on others for activities of daily living at baseline compared to 37.7% of RCT participants (228/604). Dementia was nearly 2-fold more frequent in nonincluded patients than those included (5.9% [36/613] versus 3.6% [22/604], p = 0.07). Patients who were not included in the RCT were more likely to acquire their infection in the hospital (53.3% [327/613] versus 29.1% [176/604], p &lt; 0.001). The primary composite outcome of mortality, clinical failure, readmissions, or extended hospitalization at 90 days occurred in 353 of 613 nonincluded patients (57.6%) compared to 299 of 604 RCT participants (49.6%), p = 0.005. However, on multivariate analysis noninclusion in the RCT was not an independent risk factor for clinical failure and mortality. Conclusions: RCTs, even with broad eligibility criteria, do not represent the whole spectrum of patients and leave out a population with more severe illness for whom the evidence is lacking