Abstract
Background
Fosfomycin is a potentially attractive option as step-down therapy for bacteraemic urinary tract infections (BUTI), but available data are scarce. Our objective was to compare the ...effectiveness and safety of fosfomycin trometamol and other oral drugs as step-down therapy in patients with BUTI due to MDR Escherichia coli (MDR-Ec).
Methods
Participants in the FOREST trial (comparing IV fosfomycin with ceftriaxone or meropenem for BUTI caused by MDR-Ec in 22 Spanish hospitals from June 2014 to December 2018) who were stepped-down to oral fosfomycin (3 g q48h) or other drugs were included. The primary endpoint was clinical and microbiological cure (CMC) 5–7 days after finalization of treatment. A multivariate analysis was performed using logistic regression to estimate the association of oral step-down with fosfomycin with CMC adjusted for confounders.
Results
Overall, 61 patients switched to oral fosfomycin trometamol and 47 to other drugs (cefuroxime axetil, 28; amoxicillin/clavulanic acid and trimethoprim/sulfamethoxazole, 7 each; ciprofloxacin, 5) were included. CMC was reached by 48/61 patients (78.7%) treated with fosfomycin trometamol and 38/47 (80.9%) with other drugs (difference, −2.2; 95% CI: −17.5 to 13.1; P = 0.38). Subgroup analyses provided similar results. Relapses occurred in 9/61 (15.0%) and 2/47 (4.3%) of patients, respectively (P = 0.03). The adjusted OR for CMC was 1.11 (95% CI: 0.42–3.29, P = 0.75). No relevant differences in adverse events were seen.
Conclusions
Fosfomycin trometamol might be a reasonable option as step-down therapy in patients with BUTI due to MDR-Ec but the higher rate of relapses would need further assessment.
The objective of this study was to assess the prevalence and molecular epidemiology of ESBL-producing Escherichia coli causing healthcare-associated (HCA) and community-associated (CA) bacteraemia of ...urinary origin (BUO) in Spain.
An observational cohort study was conducted at eight hospitals from different Spanish geographical areas (2010-11). BUO episodes (n = 425) were classified as HCA (n = 215) and CA (n = 210), and one blood isolate per episode was collected. Susceptibility testing was performed, ESBLs were screened by double-disc diffusion test and ESBL and OXA-1 genes were characterized (PCR and sequencing). Population structure (phylogenetic groups, XbaI-PFGE and MLST) and ST131 subtyping (PCR) were determined. Virulence genes were detected by PCR and virulence score, profiles and extraintestinal pathogenic E. coli (ExPEC) status calculated.
ESBL-producing E. coli prevalence was 9.2% (39/425). ESBL-producing E. coli episodes were significantly associated with HCA-BUO episodes 14% (30/215) versus 4.3% (9/210); P = 0.001. The highest non-susceptibility proportions corresponded to ciprofloxacin (97.4%), amoxicillin/clavulanate (74.4%), co-trimoxazole (69.2%) and tobramycin (61.5%). Of the 39 ESBL-producing E. coli isolates, 34 produced CTX-M enzymes (21 CTX-M-15, 11 CTX-M-14 and 2 CTX-M-1). Fifteen STs were identified, the B2-ST131 clone being the most prevalent (54%; 21/39). All ST131 isolates were ExPEC and had the highest virulence scores, but they showed less diversity in virulence profiles than other STs. The H30Rx subclone accounted for most ST131 isolates (20/21), co-produced CTX-M-15 (20/20) and OXA-1 (19/20) enzymes and was associated with HCA episodes (16/20).
The CTX-M-15-ST131-H30Rx subclone is a relevant MDR pathogen causing BUO, mainly HCA episodes. The dominance of this subclone with comparatively less diversity of virulence profiles reflects the spread of a successful and MDR ESBL ST131 lineage in Spain.
We investigated whether the addition of fosfomycin or cloxacillin to daptomycin provides better outcomes in the treatment of methicillin-resistant
(MRSA) experimental aortic endocarditis in rabbits. ...Five MRSA strains were used to perform
time-kill studies using standard (10
) and high (10
) inocula. Combined therapy was compared to daptomycin monotherapy treatment in the MRSA experimental endocarditis model. A human-like pharmacokinetics model was applied, and the equivalents of cloxacillin at 2 g/4 h, fosfomycin at 2 g/6 h, and daptomycin at 6 to 10 mg/kg/day were administered intravenously. A combination of daptomycin and either fosfomycin or cloxacillin was synergistic in the five strains tested at both inocula. A bactericidal effect was detected in four of five strains tested with both combinations. The MRSA-277 strain (vancomycin MIC, 2 μg/ml) was used for the experimental endocarditis model. Daptomycin plus fosfomycin significantly improved the efficacy of daptomycin monotherapy at 6 mg/kg/day in terms of both the proportion of sterile vegetations (100% versus 72%,
= 0.046) and the decrease in the density of bacteria within the vegetations (
= 0.025). Daptomycin plus fosfomycin was as effective as daptomycin monotherapy at 10 mg/kg/day (100% versus 93%,
= 1.00) and had activity similar to that of daptomycin plus cloxacillin when daptomycin was administered at 6 mg/kg/day (100% versus 88%,
= 0.48). Daptomycin nonsusceptibility was not detected in any of the isolates recovered from vegetations. In conclusion, for the treatment of MRSA experimental endocarditis, the combination of daptomycin plus fosfomycin showed synergistic and bactericidal activity.
Complicated urinary tract infection (cUTI) is a frequent cause of morbidity. In this multinational retrospective cohort study, we aimed to demonstrate risk factors for enterococcal UTI. Univariate ...and multivariate analyses of risk factors for enterococcal infection were performed. Among 791 hospitalized patients with cUTI, enterococci accounted for approximately 10% of cases (78/791). Risk factors for enterococcal UTI in multivariable analysis were male gender, age range of 55–75 years, catheter-associated UTI, and urinary retention. This information may assist treating physicians in their decision-making on prescribing empiric anti-enterococcus treatment to hospitalized patients presenting with cUTI and thus improve clinical outcomes.
The objective of this study was to analyse whether there is an association between reduced susceptibility to biocides in Acinetobacter baumannii and (i) antimicrobial resistance (co-resistance), (ii) ...prevalent (epidemic) clones, (iii) changes in the fitness or (iv) expression of genes related to efflux pumps and porins.
Susceptibility to biocides and antimicrobials was determined in 49 clonally unrelated isolates of A. baumannii. Biological cost, in terms of mean generation time, was determined by spectrophotometry. Quantitative real-time RT-PCR was used to determine the relative expression of genes encoding several efflux pumps and porins.
Reduced susceptibility to chlorhexidine digluconate, benzalkonium chloride and Irgasan(®) was associated with resistance to aminoglycosides, tetracycline and ciprofloxacin (P < 0.05). The MICs of carbapenems, aminoglycosides, doxycycline and ciprofloxacin for isolate Ab70 (epidemic clone) exposed to these biocides increased by ≥2 dilutions. Reduced susceptibility to Orsan(®) was more frequent among prevalent clones than non-prevalent clones (P < 0.05). Mean generation times for Ab70 before and after exposure to benzalkonium chloride were 57.8 and 78.1 min, respectively (P = 0.02). Relative expression of abeS and adeB was increased in Ab46 and Ab70 after exposure to chlorhexidine digluconate, but was decreased for ompA and carO after exposure to Irgasan(®).
Reduced susceptibility to biocides is associated with co-resistance to carbapenems, aminoglycosides, tetracycline and ciprofloxacin. Reduced susceptibility to Orsan(®) may be a marker of prevalent clones. Acquisition of reduced susceptibility to benzalkonium chloride has a biological cost. Exposure to biocides affects the relative expression of genes related to some efflux pump genes (increased expression) or porins (reduced expression).
Healthcare-associated infections caused by Pseudomonas aeruginosa are associated with poor outcomes. However, the role of P. aeruginosa in surgical site infections after colorectal surgery has not ...been evaluated. The aim of this study was to determine the predictive factors and outcomes of surgical site infections caused by P. aeruginosa after colorectal surgery, with special emphasis on the role of preoperative oral antibiotic prophylaxis.
We conducted an observational, multicenter, prospective cohort study of all patients undergoing elective colorectal surgery at 10 Spanish hospitals (2011-2014). A logistic regression model was used to identify predictive factors for P. aeruginosa surgical site infections.
Out of 3701 patients, 669 (18.1%) developed surgical site infections, and 62 (9.3%) of these were due to P. aeruginosa. The following factors were found to differentiate between P. aeruginosa surgical site infections and those caused by other microorganisms: American Society of Anesthesiologists' score III-IV (67.7% vs 45.5%, p = 0.001, odds ratio (OR) 2.5, 95% confidence interval (95% CI) 1.44-4.39), National Nosocomial Infections Surveillance risk index 1-2 (74.2% vs 44.2%, p < 0.001, OR 3.6, 95% CI 2.01-6.56), duration of surgery ≥75thpercentile (61.3% vs 41.4%, p = 0.003, OR 2.2, 95% CI 1.31-3.83) and oral antibiotic prophylaxis (17.7% vs 33.6%, p = 0.01, OR 0.4, 95% CI 0.21-0.83). Patients with P. aeruginosa surgical site infections were administered antibiotic treatment for a longer duration (median 17 days interquartile range (IQR) 10-24 vs 13d IQR 8-20, p = 0.015, OR 1.1, 95% CI 1.00-1.12), had a higher treatment failure rate (30.6% vs 20.8%, p = 0.07, OR 1.7, 95% CI 0.96-2.99), and longer hospitalization (median 22 days IQR 15-42 vs 19d IQR 12-28, p = 0.02, OR 1.1, 95% CI 1.00-1.17) than those with surgical site infections due to other microorganisms. Independent predictive factors associated with P. aeruginosa surgical site infections were the National Nosocomial Infections Surveillance risk index 1-2 (OR 2.3, 95% CI 1.03-5.40) and the use of oral antibiotic prophylaxis (OR 0.4, 95% CI 0.23-0.90).
We observed that surgical site infections due to P. aeruginosa are associated with a higher National Nosocomial Infections Surveillance risk index, poor outcomes, and lack of preoperative oral antibiotic prophylaxis. These findings can aid in establishing specific preventive measures and appropriate empirical antibiotic treatment.
•Based on data from a large cohort of patients, a clinical tool for prediction of recurrent CDI has been developed.•The tool makes it possible to identify a subgroup of patients with a high ...probability of recurrence.•The tool enables clinicians to select patients for new and expensive therapies that reduce the risk of recurrence.
Recurrence of Clostridium difficile infection (CDI) has major consequences for both patients and the health system. The ability to predict which patients are at increased risk of recurrent CDI makes it possible to select candidates for treatment with new drugs and therapies (including fecal microbiota transplantation) that have proven to reduce the incidence of recurrence of CDI. Our objective was to develop a clinical prediction tool, the GEIH-CDI score, to determine the risk of recurrence of CDI. Predictors of recurrence of CDI were investigated using logistic regression in a prospective cohort of 274 patients diagnosed with CDI. The model was calibrated using the Hosmer-Lemeshow test. The tool comprises four factors: age (70–79 years and ≥80 years), history of CDI during the previous year, direct detection of toxin in stool, and persistence of diarrhea on the fifth day of treatment. The functioning of the GEIH-CDI score was validated in a prospective cohort of 183 patients. The area under the ROC curve was 0.72 (0.65–0.79). Application of the tool makes it possible to select patients at high risk (>50%) of recurrence and patients at low risk (<10%) of recurrence. GEIH-CDI score may be useful for clinicians treating patients with CDI.
The purpose of this study was to examine the psychometric properties of the "Autism Program Environment Rating Scale" ("APERS"), an instrument designed to assess quality of program environments for ...students with autism spectrum disorder. Data sets from two samples of public school programs that provided services to children and youth with autism spectrum disorder were utilized. Cronbach alpha analyses indicated high coefficients of internal consistency for the total "APERS" and moderate levels for item domains for the first data set, which was replicated with the second data set. A factor analysis of the first data set indicated that all domain scores loaded on one main factor, in alignment with the conceptual model, with this finding being replicated in the second data set. Also, the "APERS" was sensitive to changes resulting from a professional development program designed to promote program quality.
ObjectiveComplicated 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).DesignThis 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.SettingThe 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).ParticipantsData were obtained from 644 episodes of patients hospitalised due to cUTI.ResultsThe 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.ConclusionsThe 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.
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