Effectiveness of fosfomycin trometamol as oral step-down therapy for bacteraemic urinary tract infections due to MDR Escherichia coli: a post hoc analysis of the FOREST randomized trial.

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.

Incidence and predictors of sternal surgical wound infection in cardiac surgery: A prospective study.

Sternal surgical wound infection (SSWI) in cardiac surgery is associated with increased morbidity. We investigated the incidence of SSWI, the main germs implicated and predictors of SSWI. Prospective study including patients undergoing full median sternotomy between January 2017 and December 2019. Patients were followed-up for 3 months after hospital discharge. All sternal wound infections up to 90 days after discharge were considered SSWI. 1004 patients were included. During follow-up, 68 (6.8%) patients presented SSWI. Patients with SSWI had a higher incidence of postoperative renal failure (29.4% vs 17.1%, P = .007), a higher incidence of early postoperative reoperation for non-infectious causes (42.6% vs 9.1%, P < .001), longer ICU stay (3 [2-9] days vs 2 [2-4] days, P = .006), and longer hospital stay (24.5 [14.8-38.3] days vs 10 [7-18] days, P < .001). Gram-positive germs were presented in 49% of the cultures, and gram-negative bacteria in 35%. Early reoperation for non-infectious causes (OR 4.90, 95% CI 1.03-23.7), and a longer ICU stay (OR 1.37 95% CI 1.10-1.72) were independent predictors of SSWI. SSWI is rare but leads to more postoperative complications. The need for early reoperation because of non-infectious cause and a longer ICU stay were independently associated with SSWI.

Infected bone defects in the lower limb. Management by means of a two-stage distraction osteogenesis protocol.

INTRODUCTION: Although bone transport is generally accepted as the gold standard for the treatment of segmental septic bone defects, some aspects of its practical application are still open to debate. We present our results in this field and compare them with the series published so far. MATERIAL AND METHODS: We reviewed all our patients (2010-2018) that underwent a bone transport procedure in the lower limb due to a septic bone defect. We calculated the bone healing index (BHI), the external fixation index (EFI), the rate of complications and the clinical results. We statistically compared our results with 63 publications with a similar scope. RESULTS: Thirty-five patients (30 M/5F) with a mean age of 40 years and a mean follow-up of 45 months were included. Bone segment was 24 T/11F and mean defect was 8.4 cm (7.34 T/ 10.73F). Mean global BHI was 45.62 days/cm (48.16 T/40.09F). Mean EFI was 2.37 months/cm. Results were excellent in 9 patients, good in 23 and bad in 3. Bone graft was used in 60% of the cases. DISCUSSION: The size of our series is similar to previously published ones, although the mean age of our patients is higher and they present a larger bone defect. BHI of our series is similar to that of other series, although EFI is significantly higher. The number of complications is also in line with the existing literature. CONCLUSION: The use of a two-stage technique for managing segmental bone defects of septic origin in the lower extremity is a valid alternative. Our series shows results comparable to the current literature.

Development and validation of the INCREMENT-ESBL predictive score for mortality in patients with bloodstream infections due to extended-spectrum-ß-lactamase-producing Enterobacteriaceae.

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Pseudoaneurysm as an unusual complication in bone lengthening.

One of the risks of distraction osteogenesis-based techniques is the development of vascular complications, such as pseudoaneurysms associated with the osteotomies performed or the fixation elements of the external fixator used in the procedure. Pseudoaneurysm are formed when the tunica adventitia of the artery is injured, resulting in a gradual and persistent blood extravasation into the surrounding tissues that is encapsulated and connected to the arterial lumen. This report describes a rare case of a late-presentation pseudoaneurysm in the anterior tibial artery resulting from a tibial lengthening procedure aimed at addressing a leg length discrepancy in a 57-year-old female with severe peripheral neuropathy resulting from long-standing poorly controlled diabetes mellitus. We describe the diagnostic process, the treatment options and confirm how the shape of the bony callus can be a reliable indicator of this pathology, as has already been described in the literature.

Cutaneous leishmaniasis in a patient receiving infliximab.

Leishmaniasis is endemic in the Mediterranean region, and the prevalence of latent infection in this area is high. Treatment with tumour necrosis factor (TNF) antagonists represents a major breakthrough in the treatment of several inflammatory diseases, including psoriasis. Reports describing opportunistic leishmaniasis in European patients treated with TNF-α antagonist drugs are rapidly accumulating. We describe a case of cutaneous leishmaniasis in a patient treated with infliximab and corticosteroids.

When is coagulase-negative Staphylococcus bacteraemia clinically significant?

BACKGROUND: Coagulase-negative staphylococci (CoNS) are common contaminants in blood cultures (BC). A prospective study of patients with ≥ 2 blood culture sets and at least 1 positive CoNS BC was performed to develop an algorithm to assist in determining the clinical significance of CoNS bacteraemia. METHODS: A single reviewer examined the medical records of patients with CoNS bacteraemia (January-June 2010). The determination of clinical significance was made according to CDC/NHSN (US Centers for Disease Control and Prevention/National Healthcare Safety Network) criteria. To explore risk factors associated with clinical significance, a multivariate analysis was performed. The performances of various algorithms were then compared. An algorithm to assist in determining clinical significance was developed. RESULTS: Two hundred and sixty-nine cases were included; 97 (36%) were considered clinically significant bacteraemia (CSB). Predictors of CSB in the multivariate analysis were: time to positivity < 16 h (odds ratio (OR) 4.540, 95% confidence interval (CI) 1.734-11.884), identification of Staphylococcus epidermidis (OR 4.273, 95% CI 2.124-5.593), central venous catheter (OR 4.932, 95% CI 2.467-9.858), > 2 CoNS-positive bottles from different BC sets (OR 1.957, 95% CI 1.401-2.733), and Charlson score ≥ 3 (OR 2.102, 95% CI 1.078-4.099). The algorithm with best sensitivity (62%) and specificity (93%) for determining clinical significance of CoNS included Charlson score ≥ 3, Pitt score ≥ 1, neutropenic patients, presence of central venous catheter, identification of S. epidermidis, and time to positivity < 16 h. The positive predictive value was 83% and the negative predictive value was 81% (likelihood ratio 8.87). CONCLUSION: The use of this algorithm could potentially reduce the misclassification of nosocomial bloodstream infections and inappropriate antibiotic treatment in patients for whom a positive CoNS does not represent a CSB.

What is the impact of a rapid diagnostic E-test in the treatment of patients with Gram-negative bacteraemia?

OBJECTIVE: To evaluate the influence of a rapid diagnostic test (RDT) in antibiotic therapeutic decisions in non-paediatric patients with Gram-negative bacteraemia (GNB). PATIENTS AND METHODS: A RDT consisting of a direct antibiogram was used on blood isolates of GNB. GNB were also identified and sensitivity tests were performed according to standard criteria. Information on empirical treatment was registered (T1), as well as the antibiotic administered once the results of the RDT were available (T2). Finally, we noted the ideal antibiotic that the infectious diseases specialist (IDS) would have prescribed (T3). The decision regarding T2 was always taken by the patient's physician or the physician on duty. RESULTS: A RDT was performed for 248 patients. The most frequently isolated bacterium was Escherichia coli (13% producing extended-spectrum beta-lactamase). T1 was considered appropriate in 74% and appropriate but optimizable in 43%. T2 was considered appropriate in 95%, appropriate but optimizable in 36%, and inappropriate in 5%. The cost of the optimizable treatment (T2) was € 2210, while the cost of the ideal treatment would have been € 416; the saving in antibiotic cost of 1 day of treatment would have been € 1694. CONCLUSIONS: Treatment prescribed by a non-IDS after a RDT was inappropriate in 5% and optimizable in 36%. It is our recommendation that information provided by a RDT should be interpreted by an IDS to make the information more beneficial both economically and 'ecologically'.

Daily tenofovir disoproxil fumarate/emtricitabine and hydroxychloroquine for pre-exposure prophylaxis of COVID-19: a double-blind placebo-controlled randomized trial in healthcare workers.

OBJECTIVES: To assess the effect of hydroxychloroquine (HCQ) and Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) as pre-exposure prophylaxis on COVID-19 risk. METHODS: EPICOS is a double-blind, placebo-controlled randomized trial conducted in Spain, Bolivia, and Venezuela. Healthcare workers with negative SARS-CoV-2 IgM/IgG test were randomly assigned to the following: daily TDF/FTC plus HCQ for 12 weeks, TDF/FTC plus HCQ placebo, HCQ plus TDF/FTC placebo, and TDF/FTC placebo plus HCQ placebo. Randomization was performed in groups of four. Primary outcome was laboratory-confirmed, symptomatic COVID-19. We also studied any (symptomatic or asymptomatic) COVID-19. We compared group-specific 14-week risks via differences and ratios with 95% CIs. RESULTS: Of 1002 individuals screened, 926 (92.4%) were eligible and there were 14 cases of symptomatic COVID-19: 220 were assigned to the TDF/FTC plus HCQ group (3 cases), 231 to the TDF/FTC placebo plus HCQ group (3 cases), 233 to the TDF/FTC plus HCQ placebo group (3 cases), and 223 to the double placebo group (5 cases). Compared with the double placebo group, 14-week risk ratios (95% CI) of symptomatic COVID-19 were 0.39 (0.00-1.98) for TDF + HCQ, 0.34 (0.00-2.06) for TDF, and 0.49 (0.00-2.29) for HCQ. Corresponding risk ratios of any COVID-19 were 0.51 (0.21-1.00) for TDF + HCQ, 0.81 (0.44-1.49) for TDF, and 0.73 (0.41-1.38) for HCQ. Adverse events were generally mild. DISCUSSION: The target sample size was not met. Our findings are compatible with both benefit and harm of pre-exposure prophylaxis with TDF/FTC and HCQ, alone or in combination, compared with placebo.

Risk Factors of DAIR Failure and Validation of the KLIC Score: A Multicenter Study of Four Hundred Fifty-Five Patients.

Background: Debridement, antibiotic agents, and implant retention (DAIR) is a currently accepted approach for the treatment of early prosthetic joint infections (PJI). The success of a DAIR procedure has shown variable results throughout the published literature. Scoring systems such as the Kidney, Liver, Index surgery, Cemented prosthesis, and C-reactive protein value (KLIC) score for the selection of patients that are likely to benefit from DAIR have proved to be helpful in decision making. Our study aims to further validate the KLIC score using a large external multicentric cohort and to evaluate other risk factors for failure. Patients and Methods: A retrospective analysis of patients with an early acute PJI who were treated with DAIR and recorded in a database of eight Spanish university hospitals was performed. According to pre-operative variables of the KLIC study, patients were categorized into five groups: group A, ≤2 points; group B, 2.5-3.5 points; group C, 4-5 points; group D, 5.5-6.5 points; and group E, ≥7 points. Failure rates were compared between groups at 60 days and after 60 days of DAIR. Further variables for risk of failure were also analyzed. Results: A total of 455 patients with early acute PJI were included in the analyses. At 60 days, patients presenting with pre-operative elevated C-reactive protein serum levels, Staphylococcus aureus, and polymicrobial infections were associated with failure. Failure rates recorded were 12% for group A (n = 210), 18% for group B (n = 83), 26% for group C (n = 89), 24% for group D (n = 66), and 0% for group E (n = 7). Univariable analysis between consecutive groups of the KLIC score showed no differences for failure before 60 days of the DAIR procedure. Scheduled surgery and having the procedure performed by a specialized unit were also identified as important factors for DAIR success. Conclusions: Our results suggest the KLIC score was not useful for predicting failure in our cohort. Furthermore, our results indicate a specialized unit should conduct DAIR procedures.

Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections: A Randomized Clinical Trial.

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 parenteral 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 ∞ 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, -∞ 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. Trial Registration: ClinicalTrials.gov Identifier: NCT02142751.

[Predictive factors of ESBL versus non-ESBL Escherichia coli bacteraemia and influence of resistance on the mortality of the patients]. / Bacteriemia por Escherichia coli: factores predictivos de presencia de bacterias productoras de betalactamasas de espectro extendido e influencia de la resistencia en la mortalidad de los pacientes.

BACKGROUND AND OBJECTIVES: To analyze predictor factors of extended-spectrum betalactamasa (ESBL)-producing E. coli and its repercussion in mortality. PATIENTS AND METHODS: Observational and comparative study of a cohort of non-paediatric admitted patients with E. coli bacteraemia (EB). RESULTS: 153 EB (22% ESBL-producing strains). Risk factors associated with ESBLB: previous antibiotic treatment (OR 2.61; 95% CI 1.1-6.19), severity Winston score ≤2 (OR 9.83, 95% CI 3.42-28.26) and health-related acquired infection (OR 5.35; 95% CI 1.57-18.27). Related mortality rate was 21%, being independent risk factors: cancer (OR 4.02; 95% CI 1.08-14.82), high severity of underlying disease (McCabe) (OR 7.69; 95% CI 1.96-30.09) and critical severity of illness at onset (Winston) (OR 48.89; 95% CI 11.58-206.97). Inappropriate empirical therapy was more frequent in EBSL-producing group (67%, p<0.05). CONCLUSIONS: Previous antibiotic treatment, severity Winston score ≤2 and health-related acquisition are factors associated to ESBL EB. EBSL-producing strains or inadequate treatment were not associated to higher mortality. Factors statistically associated to mortality were cancer, severity of underlying diseases and critical severity of illness at onset.

Nosocomial candidemia at a general hospital: prognostic factors and impact of early empiric treatment on outcome (2002-2005).

OBJECTIVES: To evaluate epidemiological and clinical prognosis factors related to mortality and impact of early empiric treatment on patients with nosocomial candidemia (NC). PATIENTS AND METHODS: Observational study of a cohort of 107 adult patients with NC admitted at a tertiary hospital (2002-5). RESULTS: In bivariate analysis, risk factors significantly associated with mortality rate (49.5%) were: age >65 years, previous steroid treatment, solid organ transplant, acute severity of illness, shock, renal failure and respiratory distress at onset, delayed or inadequate antifungal treatment, non-removal of central venous catheter and associated post-surgical bacterial sepsis or respiratory infection. In multivariate analysis, risk factor associated with mortality was acute severity of illness at onset (OR 76.9; CI 12.5-500) being early and adequate treatment (OR 11.8; CI 1.7-81.2) and early (<48h) removing of central venous catheter (OR 12.2; CI 1.9-74.9) factors associated with cure; there was no statistically significant difference between fungistatic (azoles) or fungicidal (amphotericin or caspofungin) treatment. CONCLUSIONS: Acute severity of illness at onset is associated with mortality in patients with NC whereas early and adequate treatment and early removing of central venous catheter are associated with cure.

[Carbapenem and multidrug-resistant Acinetobacter baumannii colonisation/infection: epidemiology and factors associated with infection]. / Colonización/infección por Acinetobacter baumannii multirresistente y resistente a carbapenémicos: epidemiología y factores predictivos de infección.

BACKGROUND AND OBJECTIVE: To study an outbreak of nosocomial colonisation/infection due to multidrug and carbapenem resistant A. baumannii (ABMDR-C). PATIENTS AND METHODS: Prospective study of patients with ABMDR-C colonisation/infection (January 2007-June 2008). Epidemiological and clinical variables and predictors of infection versus colonization were analysed. RESULTS: 24 out of 101 cases were considered colonisations and 77 infections (27 bacteraemia); global mortality (colonisations and infections) was 42% (4 colonisations and 38 infections -18 bacteraemia). All together, the incidence was 3.2/1000 admissions/day; 29% had been previously admitted and 79% had received previous antibiotic treatment (29% carbapenem; 34% piperacillin-tazobactam; 12.5% both); 78% had an underlying condition; 81% were UCI patients; 90% had gone through invasive procedures; 65% had another microorganism isolated. In multivariate analysis, infection predictor factors were isolation of ABMDR-C in respiratory samples (OR 5.406; 95% CI 1.419-20.599); male patients (OR 8.842; 95% CI 1.988-39.325); previous hospitalization (OR 9.720; 95% CI 1.383-68.291) and initial clinical severity (OR 30.897; 95% CI 5.533-172.543). CONCLUSIONS: Our cohort of patients with ABMDR-C colonisation/infection is characterised by their underlying comorbidity, the high rate of previous invasive procedures, previous hospitalisation and previous broad-spectrum betalactam treatments (especially carbapenem). Initial severity and respiratory samples with ABMDR-C isolates were predictors of infection versus colonisation.

Nosocomial candidemia at a general hospital: the change of epidemiological and clinical characteristics. A comparative study of 2 cohorts (1993-1998 versus 2002-2005).

BACKGROUND: Nosocomial candidemia (NC) is associated with high mortality, increased hospital stay and greater economical cost. AIMS: To evaluate epidemiological and clinical aspects of 2 different cohorts of non-paediatric patients with NC. METHODS: A retrospective observational and comparative study of patients with NC. Patients were identified by review of results of blood cultures from the hospital microbiology laboratory. We analysed epidemiological, clinical, microbiological and laboratory data and changes in the 2 cohorts: 1993-1998 (P1) and from 2002 to 2005 (P2). RESULTS: Eighty patients were studied during P1 and 107 during P2; incidence was 9/10,000 in P1 and 15.8/10,000 admitted patients in P2 (p<0.05). Mean age was 52 years in P1 and 61 years in P2 (p<0.05); 66% and 49% NC were due to Candida albicans in P1 and P2, respectively (p<0.05); diabetes was present in 12% in P1 and in 25% in P2 (p<0.05). All of the patients had previously received at least one course of broad-spectrum antibiotics. A statistically significant difference (p<0.05) in predisposing conditions was identified in central intravenous line rate (100% in P1 and 91% in P2) and previous surgery (43% in P1 and 78% in P2). Acute severity of illness at onset and complications were more frequent in P2 (p<0.05). Mortality rate was similar in P1 and P2 (51% and 49.5%, respectively). CONCLUSIONS: Frequency of NC has increased and non-albicans Candida is now more frequent than C. albicans. Although acute severity of illness at onset and complications are now more frequent, mortality remains the same.

Comparison of Predictors and Mortality Between Bloodstream Infections Caused by ESBL-Producing Escherichia coli and ESBL-Producing Klebsiella pneumoniae.

OBJECTIVETo compare the epidemiology, clinical characteristics, and mortality of patients with bloodstream infections (BSI) caused by extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (ESBL-EC) versus ESBL-producing Klebsiella pneumoniae (ESBL-KP) and to examine the differences in clinical characteristics and outcome between BSIs caused by isolates with CTX-M versus other ESBL genotypesMETHODSAs part of the INCREMENT project, 33 tertiary hospitals in 12 countries retrospectively collected data on adult patients diagnosed with ESBL-EC BSI or ESBL-KP BSI between 2004 and 2013. Risk factors for ESBL-EC versus ESBL-KP BSI and for 30-day mortality were examined by bivariate analysis followed by multivariable logistic regression.RESULTSThe study included 909 patients: 687 with ESBL-EC BSI and 222 with ESBL-KP BSI. ESBL genotype by polymerase chain reaction amplification of 286 isolates was available. ESBL-KP BSI was associated with intensive care unit admission, cardiovascular and neurological comorbidities, length of stay to bacteremia >14 days from admission, and a nonurinary source. Overall, 30-day mortality was significantly higher in patients with ESBL-KP BSI than ESBL-EC BSI (33.7% vs 17.4%; odds ratio, 1.64; P=.016). CTX-M was the most prevalent ESBL subtype identified (218 of 286 polymerase chain reaction-tested isolates, 76%). No differences in clinical characteristics or in mortality between CTX-M and non-CTX-M ESBLs were detected.CONCLUSIONSClinical characteristics and risk of mortality differ significantly between ESBL-EC and ESBL-KP BSI. Therefore, all ESBL-producing Enterobacteriaceae should not be considered a homogeneous group. No differences in outcomes between genotypes were detected.CLINICAL TRIALS IDENTIFIERClinicalTrials.gov. Identifier: NCT01764490.Infect Control Hosp Epidemiol 2018;39:660-667.

Geographical variation in therapy for bloodstream infections due to multidrug-resistant Enterobacteriaceae: a post-hoc analysis of the INCREMENT study.

We describe regional differences in therapy for bloodstream infection (BSI) caused by extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). Patients (n = 1482) in 12 countries from an observational study of BSI caused by ESBL-E or CPE were included. Multivariate logistic regression was used to calculate adjusted odds ratios (aORs) for the influence of country of recruitment on empirical use of ß-lactam/ß-lactamase inhibitors (BLBLIs) or carbapenems, targeted use of BLBLIs for ESBL-E and use of targeted combination therapy for CPE. Compared with Spain, BLBLI use for empirical therapy was least likely in sites from Israel (aOR 0.34, 95% CI 0.14-0.81), Greece (aOR 0.49, 95% CI 0.26-0.94) and Canada (aOR 0.31, 95% CI 0.11-0.88) but more likely in Italy (aOR 1.58, 95% CI 1.11-2.25) and Turkey (aOR 2.09, 95% CI 1.14-3.81). Empirical carbapenem use was more likely in sites from Taiwan (aOR 1.73, 95% CI 1.03-2.92) and USA (aOR 1.89, 95% CI 1.05-3.39) and less likely in Italy (aOR 0.44, 95% CI 0.28-0.69) and Canada (aOR 0.10, 95% CI 0.01-0.74). Targeted BLBLIs for ESBL-E was more likely in Italian sites. Treatment at sites within Israel, Taiwan, Turkey and Brazil was associated with less combination therapy for CPE. Although this study does not provide precise data on the relative prevalence of ESBL-E or CPE, significant variation in therapy exists across countries even after adjustment for patient factors. Better understanding of what influences therapeutic choices for these infections will aid antimicrobial stewardship efforts.

Use of antibiotics at a University Clinic Hospital: effect of protocolized antibiotic treatment in the evolution of hospital patients with infections.

OBJECTIVES: To analyse factors associated to "failure" in patients under antibiotic (AB) treatment at a third level hospital. PATIENTS AND METHODS: All patients receiving an AB treatment along April 2012 were prospectively observed and factors associated to failure were analyzed. Failure was defined as clinical or microbiological failure, relapse or death. Statistically significance was established as p<0.05. RESULTS: 602 of 1,265 admitted patients during the study month included an AB in their medical prescriptions, being 178 considered as prophylactic AB prescriptions, 342 empirical treatments and 82 directed treatments as empiric treatments. Ceftriaxone and levofloxacin were the most used AB; choice of empirical and directed treatments were in line with protocols in 71% (242 of 342 cases) and 67% (55 of 82), respectively. Of all the patients receiving antibiotics for therapy (n=424), 402 had infection criteria (in 22 cases antibiotic treatment was deemed unnecessary since the patient showed no infectious process). Of these, 292 (72%) showed a good evolution, while the others were considered as failed therapies, either because of microbiological persistence in 49 (12.8%), relapse in 31 (7.71%) and death in en 30 (7.46%). Factors associated to "failure" were Charlson score ≥3 (OR 3.35; 95%CI 1.602-7.009); empirical and/or directed treatment not in keeping with the protocol (OR 5.68; 95%CI 2.898-11.217); and infection by ESBL and/or ciprofloxacin resistant E. coli (OR 4.43; 95%CI 1.492-13.184). CONCLUSIONS: A high rate of AB prescriptions in admitted patients correspond to empirical infection treatment, being ceftriaxone and levofloxacin the most used AB. Inadequate empirical and/or directed treatment is associated to clinical or microbiological failure and death.

Risk factors for methicillin-resistant Staphylococcus aureus and extended-spectrum Beta-lactamase-producing Enterobacterales in patients with diabetic foot infections requiring hospital admission / Factores de riesgo de infección por Staphylococcus aureus resistente a meticilina y enterobacterias productoras de betalactamasas en infecciones de pie diabético que requieren hospitalización

OBJETIVO: Staphylococcus aureus resistente a meticilina (MRSA) y las enterobacterias productoras de betalactamasas (ESBL-E) pueden complicar el tratamiento de las infecciones del pie del diabético (DFIs). El objetivo de este estudio fue determinar los factores de riesgo de las infecciones por estos microorganismos en el pie del diabético. MATERIAL Y MÉTODOS: Estudio observacional prospectivo de 167 pacientes consecutivos con infecciones del pie del diabético. El diagnóstico y gravedad de las infecciones se basó en la guía de la Infectious Disease Society of America (IDSA). Para identificar los factores de riesgo de las infecciones por MRSA y (ESBL-E) se llevó a cabo mediante un estudio multivariante. RESULTADOS: S. aureus fue el microorganismo más aislado (n= 82; 37,9 %) seguido por Escherichia coli (n= 40; 18,5%). El 57,3% de S. aureus fueron MRSA y el 70% de Klebsiella pneumoniae y el 25% de E. coli eran productores ESBL, respetivamente. Los factores de riesgo independientes de las infecciones por MRSA fueron las úlceras profundas [OR 8,563; IC 95% (1,068-4,727)], uso previo de fluoroquinolonas [OR 2,78; IC 95% (1,156-6,685)] y la vasculopatía periférica [OR 2,47; IC 95% (1.068-4.727)], mientras que para las infecciones por (ESBL-E) lo fueron osteomielitis [OR 6,351; 95% IC 95% (1,609-25,068)] y el uso previo de cefalosporinas [OR 5,824; IC 95% (1,517-22,361)]. CONCLUSIONES: MRSA y ESBL-E han adquirido una gran relevancia clínica en las DFIs. La disponibilidad de sus factores de riesgo es muy conveniente para elegir el tratamiento empírico en las formas graves

PURPOSE: Methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum Beta-lactamase-producing Enterobacterales (ESBL-E) may complicate the treatment of diabetic foot infections (DFIs). The aim of this study was to determine the risk factors for these pathogens in DFIs. MATERIAL AND METHODS: This was a prospective observational study of 167 consecutive adult patients with DFIs. The diagnosis and severity of DFIs were based on the Infectious Disease Society of America (IDSA) classification system. Multivariate analyses were performed in order to identify risk factors for MRSA and ESBL-E infections. RESULTS: S. aureus was the most isolated pathogen (n=82, 37.9 %) followed by Escherichia coli (n= 40, 18.5%). MRSA accounted for 57.3% of all S. aureus and 70% of Klebsiella pneumoniae and 25% of E. coli were ESBL producers, respectively. Deep ulcer [OR 8,563; 95% CI (1,068-4,727)], previous use of fluoroquinolones [OR 2,78; 95% CI (1,156-6,685)] and peripheral vasculopathy [OR 2,47; 95% CI (1.068-4.727)] were the independent predictors for MRSA infections; and osteomyelitis [OR 6,351; 95% CI (1,609-25,068)] and previous use of cephalosporins [OR 5,824; 95% CI (1,517-22,361)] for ESBL-E infections. CONCLUSIONS: MRSA and ESBL-E have adquired a great clinical relevance in DFIs. The availability of their risk factors is very convenient to choose the empirical treatment in severe forms

[Study of a cohort of patients with Enterococcus spp. Bacteraemia. Risk factors associated to high-level resistance to aminoglycosides]. / Estudio de una cohorte de pacientes con bacteriemias por Enterococcus spp. Factores de riesgo para resistencia de alto nivel a aminoglicósidos.

OBJECTIVES: To analyze a cohort of patients with Enterococcus sp. bacteraemia. PATIENTS AND METHODS: Retrospective and observational study of a cohort of non-pediatric in-patients with Enterococcus spp. bacteraemia (June 2007-September 2009). Data collection from clinical records was done according to a standard protocol. We analyzed epidemiological, clinical and microbiological data. Treatment with glycopeptides in non allergic patients or in case of betalactam susceptibility (ampicillin) was considered "optimizable". RESULTS: Three were 106 cases of bacteraemia (2.2/1000 admitted patients; 84% E. faecalis); 83% had an underlying condition; 88% nosocomial or health related cases. Urinary infection was present in 20% and primary bacteraemia in 47%. High level resistance to gentamicin (HLRG) was present in 60%; there was no vancomycin or linezolid resistance. Most frequent empiric treatments were penicillin-betalactamase inhibitor (25%) and glycopeptides (22%). Most frequent definitive treatment was glycopeptides (34%), being "optimized" 21% and 44% of empiric and definitive treatments, respectively. Mortality was 23% (related, 14%). In the multivariate analysis, risk factors associated with HLRG were nosocomial acquired infection (OR 6.083; 95CI% 1.428-25.915) and no-abdominal origin (OR 6.006; 95CI%1.398-25.805). In multivariate analysis, independent risk factors for mortality were: Pitt > 3 (OR 14.405; 95CI%2.236-92.808) and active empiric treatment (OR 8.849; 95CI% 1.101-71.429). Incidence in previous cohort was similar but HLRG rate has increased. CONCLUSIONS: Risk factors associated with HLRG were nosocomial acquired infection and no-abdominal origin. Risk factors for mortality were initial clinical severity and having received active empiric treatment. HLRG rate has increased.