Significant increase of CTX-M-15-ST131 and emergence of CTX-M-27-ST131 Escherichia coli high-risk clones causing healthcare-associated bacteraemia of urinary origin in Spain (ITUBRAS-2 project).

OBJECTIVES: To assess the microbiological characteristics of Escherichia coli causing healthcare-associated bacteraemia of urinary origin (HCA-BUO) in Spain (ITUBRAS-2 project), with particular focus on ESBL producers and isolates belonging to ST131 high-risk clone (HiRC). Clinical characteristics and outcomes associated with ST131 infection were investigated. METHODS: A total of 222 E. coli blood isolates were prospectively collected from patients with HCA-BUO from 12 tertiary-care hospitals in Spain (2017-19). Antimicrobial susceptibility and ESBL/carbapenemase production were determined. ST131 subtyping was performed. A subset of 115 isolates were selected for WGS to determine population structure, resistome and virulome. Clinical charts were reviewed. RESULTS: ESBL-producing E. coli prevalence was 30.6% (68/222). ST131 represented 29.7% (66/222) of E. coli isolates and accounted for the majority of ESBL producers (46/68, 67.6%). The C2/H30-Rx subclone accounted for most ST131 isolates (44/66) and was associated with CTX-M-15 (37/44) and OXA-1 enzymes (27/44). Cluster C1-M27 was identified in 4/10 isolates belonging to subclade C1/H30-R1 and associated with CTX-M-27. Additionally, ST131 isolates showed a high content of other acquired resistance genes, and clade C/ST131 isolates carried characteristic QRDR mutations. They were categorized as uropathogenic E. coli and had higher aggregate virulence scores. ST131 infection was associated with more complex patients, prior use of cephalosporins and inadequate empirical treatment but was not associated with worse clinical outcomes. CONCLUSIONS: ST131 HiRC is the main driver of ESBL-producing E. coli causing HCA-BUO in Spain, mainly associated with the expansion of subclade CTX-M-15-C2/H30-Rx and the emergence of CTX-M-27-C1/H30-R1 (Cluster C1-M27).

Applicability of Outpatient Quality Indicators for Appropriate Antibiotic Use in a Primary Health Care Area: a Point Prevalence Survey.

The ability to measure the quality of antibiotic prescriptions is a critical element in all antimicrobial stewardship programs. The aims of the present study were to evaluate the clinimetric properties of 32 recently developed outpatient quality indicators (OQIs) and to identify potential room for improvement in antibiotic use in a primary health care (PHC) area. The study was performed in a PHC area in Barcelona, Spain with 260,657 inhabitants, nine PHC centers, and a 400-bed acute-care teaching hospital. We selected 9 of the 32 OQIs that were applicable to our PHC area and evaluated them for measurability, adherence, and room for improvement. Nonmeasurable OQIs, OQIs without room for improvement, and OQIs beyond the scope of the PHC antimicrobial stewardship program were excluded. Data from 260,561 registered patients were assessed. Measurability was high for all OQIs except those that required manual recording of the clinical diagnosis (OQIs on group A streptococcal diagnostic testing). Adherence to guidelines was poor for most OQIs, but particularly for the indicator on the avoidance of antibiotics for viral or self-limiting bacterial infections, where we observed more than 60% room for improvement for both acute tonsillitis and sinusitis. The QIs evaluated were applicable to clinical practice and proved useful for identifying areas with room for improvement in our setting and for guiding the design of future interventions with specific objectives.

Assessment of Quality Indicators for Appropriate Antibiotic Use.

One of the critical elements of antimicrobial stewardship programs is the ability to measure the quality of antibiotic prescriptions. The aims of the present study were to evaluate the performance properties of a set of previously developed quality indicators (QIs) and to identify the potential room for improvement in antibiotic use in our setting. A monthly cross-sectional point prevalence survey was conducted in a 400-bed acute care teaching hospital, from June to November 2015. All adult patients treated for ≥24 hours with antibiotic therapy for a suspected hospital- or community-acquired bacterial infection were included. Performance scores (adherence, room for improvement, interobserver reliability, and applicability) were calculated for 8 QIs. A total of 362 patients were evaluated. Adherence to the whole set of QIs was accomplished for 14.1% of evaluable patients. The QIs with greater room for improvement were adequate request for blood cultures (60.6%), therapeutic drug monitoring (TDM) (59.1%), sequential antibiotic therapy within 72 hours (48.2%), and empirical antibiotic therapy according to local guidelines (30.4%). The percentage of patients receiving unnecessary antibiotic treatment in the absence of clinical or microbiological evidence of infection after 5 days was 12.2%. All indicators scored kappa values of ≥0.6, suggesting good interobserver reliability. Low applicability (6.1% of reviewed patients) was found only for the TDM QI. The QIs analyzed were found to be applicable, showed good interobserver reliability, and were useful tools to identify areas with potential room for improvement in antibiotic use.

Epidemiology and risk factors for infections due to AmpC ß-lactamase-producing Escherichia coli.

OBJECTIVES: To describe the prevalence and risk factors for infection due to AmpC ß-lactamase-producing Escherichia coli (AmpC-EC). METHODS: For the prevalence study, all clinical isolates of E. coli with reduced susceptibility to third-generation cephalosporins were prospectively included from June 2010 to November 2011. For risk factor analysis, a case-control study was conducted. Cases were patients with an infection due to AmpC-EC. Controls were patients infected with cephalosporin-susceptible E. coli, matched 1 : 2. Detection of blaAmpC genes was done with a multiplex AmpC-PCR, and hyperproduction of E. coli chromosomal blaAmpC by quantitative RT-PCR. Alteration of the blaAmpC promoter was studied by PCR and sequencing. RESULTS: We identified 243 (1.1%) AmpC-EC strains out of 21 563 clinical isolates. Three cases with strains carrying ESBLs, 18 strains that were considered due to colonization and 8 cases lost to clinical follow-up were excluded. Finally, 214 cases were included in the analysis. Ninety-one cases (42.5%) and 269 (62.8%) controls were strictly community acquired (P < 0.001). Thirty-five (16.3%) cases and 186 controls (43.5%) did not have any identifiable risk factor (P < 0.001). Among cases, 158 (73.8%) were found to harbour an acquired AmpC (73.4% CMY-2). Previous use of fluoroquinolones [OR 2.6 (95% CI 1.12-3.36); P = 0.008] was independently associated with AmpC-EC in the multivariate analysis. CONCLUSIONS: Prevalence of AmpC in E. coli remains low in our area. Plasmid acquisition (CMY type) represents the main mechanism of AmpC production. A high proportion of community-acquired isolates and patients with no identifiable risk factors were found. Previous use of fluoroquinolones was identified as a risk factor.

K-Means Clustering Identifies Diverse Clinical Phenotypes in COVID-19 Patients: Implications for Mortality Risks and Remdesivir Impact.

INTRODUCTION: The impact of remdesivir on mortality in patients with COVID-19 is still controversial. We aimed to identify clinical phenotype clusters of COVID-19 hospitalized patients with highest benefit from remdesivir use and validate these findings in an external cohort. METHODS: We included consecutive patients hospitalized between February 2020 and February 2021 for COVID-19. The derivation cohort comprised subjects admitted to Hospital Clinic of Barcelona. The validation cohort included patients from Hospital Universitari Mutua de Terrassa (Terrassa) and Hospital Universitari La Fe (Valencia), all tertiary centers in Spain. We employed K-means clustering to group patients according to reverse transcription polymerase chain reaction (rRT-PCR) cycle threshold (Ct) values and lymphocyte counts at diagnosis, and pre-test symptom duration. The impact of remdesivir on 60-day mortality in each cluster was assessed. RESULTS: A total of 1160 patients (median age 66, interquartile range (IQR) 55-78) were included. We identified five clusters, with mortality rates ranging from 0 to 36.7%. Highest mortality rate was observed in the cluster including patients with shorter pre-test symptom duration, lower lymphocyte counts, and lower Ct values at diagnosis. The absence of remdesivir administration was associated with worse outcome in the high-mortality cluster (10.5% vs. 36.7%; p < 0.001), comprising subjects with higher viral loads. These results were validated in an external multicenter cohort of 981 patients. CONCLUSIONS: Patients with COVID-19 exhibit varying mortality rates across different clinical phenotypes. K-means clustering aids in identifying patients who derive the greatest mortality benefit from remdesivir use.

Risk factors and clinical impact of multidrug resistance in healthcare-associated bacteremic urinary tract infections: a post-hoc analysis of a multicenter prospective cohort in Spain.

INTRODUCTION: The global burden associated with antimicrobial resistance is of increasing concern. The aim of this study was to evaluate risk factors associated with multidrug-resistant (MDR) infection and its clinical impact in a cohort of patients with healthcare-associated (HCA) bacteremic urinary tract infections (BUTI). METHODS: This is a post-hoc analysis a prospective multicenter study of patients with HCA-BUTI (ITUBRAS-2). The primary outcome was MDR profile. Secondary outcomes were clinical response (at 48-72h and at hospital discharge) and length of hospital stay from onset of BUTI. Logistic regression was used to evaluate variables associated with MDR profile and clinical response. Length of hospital stay was evaluated using multivariate median regression. RESULTS: 443 episodes were included, of which 271 (61.17%) were classified as expressing an MDR profile. In univariate analysis, MDR profile was associated with E. coli episodes (OR 3.13, 95% CI 2.11-4.69, p<0.001) and the extensively drug-resistant (XDR) pattern with P. aeruginosa etiology (OR 7.84, 95% CI 2.37-25.95; p=0.001). MDR was independently associated with prior use of fluoroquinolones (aOR 2.43; 95% CI 1.25-4.69), cephalosporins (aOR 2.14; 95% CI 1.35-3.41) and imipenem or meropenem (aOR 2.08; 95% CI 1.03-4.20) but not with prior ertapenem. In terms of outcomes, MDR profile was not associated with lower frequency of clinical cure, but with longer hospital stay. CONCLUSIONS: MDR profile was independently associated with prior use of fluoroquinolones, cephalosporins, imipenem and meropenem, but not with prior ertapenem. MDR-BUTI episodes were not associated with worse clinical cure, although was independently associated with longer duration of hospital stay.

Host genetic variants associated with susceptibility and severity of pneumococcal pneumonia in adult patients.

BACKGROUND: Pneumococcal community-acquired pneumonia (P-CAP) is a major cause of morbidity and hospitalization. Several host genetics factors influencing risk of pneumococcal disease have been identified, with less information about its association with P-CAP. The aim of the study was to assess the influence of single nucleotide polymorphisms (SNP) within key genes involved in the innate immune response on the susceptibility to P-CAP and to study whether these polymorphic variants were associated with the severity and outcome of the episodes in a cohort of adult Caucasian patients. METHODS: Seventeen SNPs from 7 genes (IL-R1, IL-4, IL-10, IL-12B, NFKBIA, NFKBIE, NFKBIZ) were analyzed. For susceptibility, a case-control study including a cohort of 57 adult with P-CAP, and 280 ethnically matched controls was performed. Genetic influence on clinical severity and outcome was evaluated in a prospective observational study including all consecutive adult P-CAP patients from November 2015 to May 2017. RESULTS: The NFKBIA polymorphism rs696 and a haplotype combination were associated with susceptibility to P-CAP (OR = 0.62, p = 0.005 and OR = 0.63, p = 0.008, respectively). The SNP IL4 rs2227284 was associated with severe P-CAP (OR = 2.17, p = 0.04). IL-R1 (rs3917267) and IL-10 (rs3024509) variants were related with respiratory failure (OR = 3.31, p = 0.001 and OR = 0.18, p = 0.003, respectively) as well as several haplotype combinations in NFKBIA, NFKBIZ, IL-R1 and IL-10 (p = 0,02, p = 0,01, p = 0,001, p = 0,03, respectively). CURB-65 values were associated with the IL-10 rs3024509 variant (beta = - 0.4, p = 0.04), and with haplotype combinations of NFKBIZ and IL-10 (p = 0.05, p = 0.04, respectively). Genetic variants in IL-10 (rs3024509) and in IL-12B (rs730691) were associated with PSI values (beta = - 0.54, p = 0.01, and beta = - 0.28, p = 0.04, respectively), as were allelic combinations in IL-R1 (p = 0.02) and IL-10 (p = 0.01). Finally, several polymorphisms in the IL-R1 gene (rs13020778, rs2160227, & rs3917267) were associated with the time elapsed until clinical stability (beta = - 0.83, p = 0.03; beta = - 1, p = 0.02 and beta = 1.07, p = 0.008, respectively). CONCLUSIONS: A genetic variant in NFKBIA was associated with susceptibility to P-CAP in adult Caucasian patients and genetic variants from key cytokines of the innate immune response (Il-4, IL-10, IL-R1 and IL-12B) and NF-κB inhibitors were associated with different phenotypes of severe P-CAP. If validated, these SNPs may help to identify people at risk of P-CAP or severe P-CAP on which preventive measures could be applied.

Risk factors associated with inappropriate empirical antimicrobial treatment in bloodstream infections. A cohort study.

Introduction: Bloodstream infections (BSI) are a major cause of mortality all over the world. Inappropriate empirical antimicrobial treatment (i-EAT) impact on mortality has been largely reported. However, information on related factors for the election of i-EAT in the treatment of BSI in adults is lacking. The aim of the study was the identification of risk-factors associated with the use of i-EAT in BSI. Methods: A retrospective, observational cohort study, from a prospective database was conducted in a 400-bed acute-care teaching hospital including all BSI episodes in adult patients between January and December 2018. The main outcome variable was EAT appropriation. Multivariate analysis using logistic regression was performed. Results: 599 BSI episodes were included, 146 (24%) received i-EAT. Male gender, nosocomial and healthcare-associated acquisition of infection, a high Charlson Comorbidity Index (CCI) score and the isolation of multidrug resistant (MDR) microorganisms were more frequent in the i-EAT group. Adequation to local guidelines' recommendations on EAT resulted in 91% of appropriate empirical antimicrobial treatment (a-EAT). Patients receiving i-EAT presented higher mortality rates at day 14 and 30 when compared to patients with a-EAT (14% vs. 6%, p = 0.002 and 22% vs. 9%, p < 0.001 respectively). In the multivariate analysis, a CCI score ≥3 (OR 1.90 (95% CI 1.16-3.12) p = 0.01) and the isolation of a multidrug resistant (MDR) microorganism (OR 3.79 (95% CI 2.28-6.30), p < 0.001) were found as independent risk factors for i-EAT. In contrast, female gender (OR 0.59 (95% CI 0.35-0.98), p = 0.04), a correct identification of clinical syndrome prior to antibiotics administration (OR 0.26 (95% CI 0.16-0.44), p < 0.001) and adherence to local guidelines (OR 0.22 (95% CI 0.13-0.38), p < 0.001) were identified as protective factors against i-EAT. Conclusion: One quarter of BSI episodes received i-EAT. Some of the i-EAT related factors were unmodifiable (male gender, CCI score ≥3 and isolation of a MDR microorganism) but others (incorrect identification of clinical syndrome before starting EAT or the use of local guidelines for EAT) could be addressed to optimize the use of antimicrobials.

Improvement of pneumococcal pneumonia diagnosis using quantitative real-time PCR targeting lytA in adult patients: a prospective cohort study.

OBJECTIVES: The aim of the study was to assess the performance of real-time PCR targeting the lytA gene (rtPCR-lytA) in plasma, urine and nasopharyngeal (NP) samples for the diagnosis of pneumococcal community-acquired pneumonia (P-CAP). METHODS: Prospective observational study including all consecutive adults with CAP from November 2015 to May 2017. P-CAP was defined if pneumococcus was identified using conventional methods (CM) and/or a positive rtPCR-lytA was detected in blood, urine or NP samples (NP cut-off ≥8000 copies/mL). Diagnostic performance of each test was calculated. RESULTS: A total of 133 individuals with CAP were included. Of these, P-CAP was diagnosed in 62 (46.6%). The proportion of P-CAP diagnosed by rtPCR-lytA methods was significantly higher than that diagnosed by CM (87.1% versus 59.7%, p 0.005). The rtPCR-lytA identified Streptococcus pneumoniae in 25 patients (40.3% of all individuals with P-CAP) whose diagnosis would have been missed by CM. NP-rtPCR-lytA allowed diagnosis of 62.3% of P-CAP. A nasopharyngeal colonization density ≥2351 copies/mL predicted P-CAP diagnosis (area under the curve = 0.82, sensitivity 83.3%, specificity 80.9%). There was a positive correlation between increasing bacterial load in blood and CURB-65 score (Spearman correlation coefficient r = 0.4, p 0.001), pneumonia severity index (r = 0.3, p 0.02) and time to clinical stability (r = 0.33, p 0.01). Median bacterial load in blood was higher in P-CAP patients with bacteraemia (0.65 × 103 versus 0 × 103 copies/mL, p 0.002), intensive care unit admission (0.68 × 103 versus 0 × 103 copies/mL, p 0.04) or mechanical ventilation (7.45 × 103 versus 0 × 103 copies/mL, p 0.04). CONCLUSIONS: The use of rtPCR-lytA methods significantly increased the diagnosis of P-CAP compared with CM. Nasopharyngeal swabs rtPCR-lytA detection, with an accurate cut-off value, was the most promising among molecular methods for the diagnosis of P-CAP.

Risk of cardiac device-related infection in patients with late-onset bloodstream infection. Analysis on a National Cohort.

OBJECTIVES: To determine the incidence of cardiac device-related infection (CDRI) among patients with cardiac device (CD) during late-onset bloodstream infection (BSI) and to identify the risk factors associated with CDRI. METHODS: Patients with a CD (cardiac implantable electronic devices -CIED- and/or prosthetic heart valve -PHV-) and late-onset-BSI (>1 year after the CD implantation/last manipulation) were selected from the PROBAC project, a prospective, observational cohort study including adult patients with bacteraemia consecutively admitted to 26 Spanish hospitals from October 2016 to March 2017. Multivariate analyses using logistic regression were performed to identify the risk factors associated with CDRI. RESULTS: 317 BSI from patients carrying a CD were registered, 187 (56.2%) were late-onset-BSI. A total of 40 (21.4%) CDRI were identified during late-onset-BSI. The CDRI cumulative incidence in Gram-positive-BSI was 41.8% (38/91), with S. aureus, Enterococcus spp. and viridans streptococci showing the greatest percentages: 40% (12/30), 42% (11/26) and 75% (6/8), respectively. Independent predictors of CDRI were an unknown source of infection (OR: 2.88 [CI 95%:1.18-7.06], p = 0.02), Gram-positive-aetiology (23.1 [5.23-102.1], p < 0.001) and persistent bacteraemia (4.81 [1.21-19], p = 0.03). In an exploratory analysis, S. aureus (3.99 [1.37-11.65], p = 0.011), Enterococcus spp. (5.21 [1.76-15.4], p = 0.003) and viridans streptococci (28.7 [4.71-173.5], p < 0.001) aetiology were also found to be risk factors for CDRI. CONCLUSIONS: CDRI during late-onset-BSI is a frequent phenomenon. Risk of CDRI differs among species, happening in almost half of the Gram-positive-BSI. An unknown source of the primary infection, Gram-positive-aetiology -especially S. aureus, Enterococcus spp. and viridans streptococci-, and persistent bacteraemia were identified as risk factors for CDRI.

Short versus long course therapy in the treatment of febrile urinary tract infections in men based on serum PSA values.

BACKGROUND: Febrile urinary tract infections (fUTI) in men are frequently complicated with subclinical prostatic involvement, measured by a transient increase in serum prostate-specific-antigen (sPSA). The aim of this study was to evaluate recurrence rates in a 6-month follow-up period of 2-week versus 4-week antibiotic treatment in men with fUTI, based on prostatic involvement. Clinical and microbiological cure rates at the end-of-therapy (EoT) were also assessed. METHODS: Open label, not-controlled, prospective study. Consecutive men diagnosed of fUTI were included. Duration of therapy was 2 weeks for patients with a sPSA level <5mg/L (short duration therapy, SDT) or 4 weeks for PSA >5 mg/L (long duration therapy, LDT). RESULTS: Ninety-one patients were included; 19 (20%) received SDT. Median age was 56.9 years (range 23-88). Bacteremia was present in 9.8% of patients (Escherichia coli was isolated in 91%). Both groups had similar demographic, clinical characteristics and laboratory findings. Median PSA levels were 2.3 mg/L in the SDT group vs 23.4 mg/L in the LDT group. In the 6-month visit, 26% of patients had achieved complete follow-up. Nonsignificant differences between groups were found neither in recurrence rates after 6 months (9% in SDT vs 10% in LDT) nor in clinical or microbiological cure rates at EoT (100% in SDT vs 95% in LDT and 95% in SDT vs 93% in LDT respectively). CONCLUSIONS: One fifth of men with fUTI did not present apparent prostatic involvement. A 2-week regimen seems adequate in terms of clinical, microbiological cure and recurrence rates for those patients without PSA elevation.

Foodborne nosocomial outbreak of SHV1 and CTX-M-15-producing Klebsiella pneumoniae: epidemiology and control.

BACKGROUND: We describe a foodborne nosocomial outbreak due to extended-spectrum ß-lactamase (ESBL)-producing Klebsiella pneumoniae. METHODS: An outbreak of ESBL K. pneumoniae was detected in March 2008. Initial control measures included contact isolation and a protocol for routine detection and reinforcement in hand hygiene practices. ESBL producers were screened for the bla(TEM), bla(SHV), and bla(CTX-M) genes. Pulsed-field gel electrophoresis analysis was performed using XbaI as a restriction endonuclease. RESULTS: One hundred fifty-six colonized and/or infected patients were identified, 35 (22.4%) of whom had infection. The outbreak affected all hospital wards. Fecal carriage was up to 38% of patients in some wards. Of note, investigation revealed a very short delay between admission and colonization. None of the health care workers or environmental surfaces in the wards was found to be colonized. This prompted an epidemiological investigation of a possible foodborne transmission. We found that up to 35% of the hospital kitchen-screened surfaces or foodstuff were colonized and that 6 (14%) of 44 food handlers were found to be fecal carriers. Phenotypic and genotypic analysis of all clinical, environmental, and fecal carrier isolates showed the dissemination of a single strain of SHV-1 and CTX-M-15-producing K. pneumoniae. At that time, structural and functional reforms in the kitchen were performed. These were followed by a progressive reduction in colonization and infection rates among inpatients until complete control was obtained in December 2008. No restrictions in the use of antibiotics were needed. CONCLUSIONS: To our knowledge, this is the first reported hospital outbreak that provides evidence that food can be a transmission vector for ESBL K. pneumoniae.

High clonal diversity of ESBL-producing Klebsiella pneumoniae isolates from clinical samples in a non-outbreak situation. A cohort study.

Background: Klebsiella pneumoniae has been responsible for a large number of clonal hospital outbreaks. However, some epidemiological changes have been observed since the emergence of CTX-M enzymes in K. pneumoniae. Aim: To analyse the transmission dynamics of Extended Spectrum ß-Lactamase-producing Klebsiella pneumoniae (ESBL-Kp) in an acute care hospital. Methods: In 2015 a prospective cohort study was conducted. All new consecutive adult patients with ESBL-Kp isolates in all clinical samples were included. Patients with a previous known infection/colonization by ESBL-Kp and patients in high risk areas (e.g., intensive care units) were excluded. Cross-transmission was defined as the carriage of a clonally-related ESBL-Kp between newly diagnosed patients who shared the same ward for ≥48 h with another case, within a maximum time window of 4 weeks. ESBL-production was confirmed using the double-disk diffusion method and PCR. Clonal relationships were investigated by rep-PCR and multilocus sequence typing (MLST). Results: Sixty ESBL-Kp isolates from 60 patients were included and analysed. Infections and colonizations were classified as hospital-acquired (52%), healthcare-related (40%) or community-acquired (8%).High genetic diversity was detected. When epidemiological clinical data were combined with the rep-PCR, the patterns identified did not show any cases of cross-transmission. ESBL-Kp were detected in 12.5% of environmental samples. No clonal relationship could be established between environmental reservoirs and patients. The genetic mechanism detected in all strains was associated with blaCTX-M genes, and 97% were CTX-M-15. Conclusions: The dynamics of ESBL-K. pneumoniae isolated in our setting could not be explained by clonal transmission from an index patient. A polyclonal spread of ESBL-Kp was identified.

Impact of a Multifaceted Antimicrobial Stewardship Intervention in a Primary Health Care Area: A Quasi-Experimental Study.

The aim of the study was to evaluate the impact of a multifaceted antimicrobial stewardship intervention on antibiotic consumption in a primary health care (PHC) area in Spain. Quasi-experimental study conducted in a PHC area with nine PHC centers, a 400-bed acute care teaching hospital, and 18 nursing homes serving a population of 260,561. The intervention was based on the 2016 CDC Core Elements of Outpatient Antibiotic Stewardship publication and targeted 130 PHC physicians, 41 PHC pediatricians, 19 emergency physicians, and 18 nursing home physicians. The components were commitment, actions for improving antibiotic prescribing, tracking and feedback, and education and experience. The primary outcome was overall antibiotic consumption. Secondary outcomes were consumption of antibiotics to treat pharyngotonsillitis, acute otitis media, acute sinusitis, acute bronchitis, and urinary tract infection (UTI), percentage of patients treated with specific antibiotics, and dispensing costs. Consumption was measured in defined daily doses per 1,000 inhabitants per day (DID) and compared pre- and postintervention (2016 vs. 2018). Overall antibiotic consumption decreased from 16.01 to 13.31 DID (-16.85%). Consumption of amoxicillin/clavulanic acid and quinolones decreased from 6.04 to 4.72 DID (-21.88%) and 1.64 to 1.23 DID (-25.06%), respectively. The percentage of patients treated with antibiotics decreased from 26.99 to 22.41%. The intervention resulted in cost savings of €72,673. Use of antibiotics to treat pharyngotonsillitis, UTI, and acute otitis media, sinusitis, and bronchitis decreased significantly. Our antimicrobial stewardship program led to a decrease in antibiotic consumption and significantly improved the use of antibiotics for the most prevalent PHC infections.

Delayed Cerebral Vasculopathy in Pneumococcal Meningitis: Epidemiology and Clinical Outcome. A Cohort Study.

BACKGROUND: To describe the prevalence, clinical characteristics, impact of systemic steroids exposure and outcomes of delayed cerebral vasculopathy (DCV) in a cohort of adult patients with pneumococcal meningitis (PM). METHODS: Observational retrospective multicenter study including all episodes of PM from January 2002 to December 2015. DCV was defined as proven/probable/possible based upon clinical criteria and pathological-radiological findings. DCV-patients and non-DCV-patients were compared by univariate analysis. RESULTS: 162 PM episodes were included. Seventeen (10.5%) DCV-patients were identified (15 possible, 2 probable). At admission, DCV-patients had a longer duration of symptoms (>2 days in 58% vs. 25.5% (p 0.04)), more coma (52.9% vs. 21.4% (p 0.03)), lower median CSF WBC-count (243 cells/uL vs. 2673 cells/uL (p 0.001)) and a higher proportion of positive CSF Gram stain (94.1% vs. 71% (p 0.07)). Median length of stay was 49 vs. 15 days (p 0.001), ICU admission was 85.7% vs. 49.5% (p 0.01) and unfavorable outcome was found in 70.6% vs. 23.8% (p 0.001). DCV appeared 1-8 days after having completed adjunctive dexamethasone treatment (median 2,5, IQR=1.5-5). CONCLUSIONS: One tenth of the PM developed DCV. DCV-patients had a longer duration of illness, were more severely ill, had a higher bacterial load at admission and had a more complicated course. Less than one third of cases recovered without disabilities. The role of corticosteroids in DCV remains to be established.

Polymerase Chain Reaction Versus Blood Culture to Detect Candida Species in High-Risk Patients with Suspected Invasive Candidiasis: The MICAFEM Study.

INTRODUCTION: We evaluated the diagnostic reliability of serum polymerase chain reaction (PCR) versus blood culture, abdominal fluid or both (composite measure) in patients receiving empirical antifungal treatment for suspected invasive candidiasis. METHODS: This observational, prospective, non-interventional, multicentre study in Spain enrolled 176 critically ill patients admitted to the intensive care unit. Separate blood samples for culture and serum PCR were taken before the start of antifungal therapy. Patient assessment was performed according to each site's usual clinical practice. The primary end point was concordance between serum PCR and blood culture. Secondary end points were concordance between serum PCR and a positive abdominal fluid sample or the composite measure. Quality indices included sensitivity, specificity, positive/negative predictive values (PPV/NPV) and kappa indices. RESULTS: Among 175 evaluable patients, rates of Candida detection were similar for serum PCR (n = 16/175, 9.1%) versus blood culture (n = 14/175, 8.0%). Quality indices for serum PCR relative to blood culture were: sensitivity 21.4%; specificity 91.9%; PPV 18.8%; NPV 93.1%; kappa index 0.125. Thirty-two abdominal fluid samples were positive. Quality indices for serum PCR versus abdominal fluid were: sensitivity 31.3%; specificity 83.0%; PPV 15.6%; NPV 92.3%; kappa index 0.100. Quality indices for serum PCR versus the composite measure were: sensitivity 15.8%; specificity 92.7%; PPV 37.5%; NPV 79.9%; kappa index 0.107. CONCLUSION: The sensitivity of serum PCR for Candida detection was low and the rate of concordance was low between serum PCR and the other diagnostic techniques used to identify Candida infections. Hospital-based diagnostic tests need optimising to improve outcomes in patients with suspected invasive candidiasis. FUNDING: Astellas Pharma Inc.

Relationship Between Biofilm Formation and Antimicrobial Resistance in Gram-Negative Bacteria.

Gram-negative microorganisms are a significant cause of infection in both community and nosocomial settings. The increase, emergence, and spread of antimicrobial resistance among bacteria are the most important health problems worldwide. One of the mechanisms of resistance used by bacteria is biofilm formation, which is also a mechanism of virulence. This study analyzed the possible relationship between antimicrobial resistance and biofilm formation among isolates of three Gram-negative bacteria species. Several relationships were found between the ability to form biofilm and antimicrobial resistance, being different for each species. Indeed, gentamicin and ceftazidime resistance was related to biofilm formation in Escherichia coli, piperacillin/tazobactam, and colistin in Klebsiella pneumoniae, and ciprofloxacin in Pseudomonas aeruginosa. However, no relationship was observed between global resistance or multidrug-resistance and biofilm formation. In addition, compared with other reported data, the isolates in the present study showed higher rates of antimicrobial resistance. In conclusion, the acquisition of specific antimicrobial resistance can compromise or enhance biofilm formation in several species of Gram-negative bacteria. However, multidrug-resistant isolates do not show a trend to being greater biofilm producers than non-multiresistant isolates.

Serotype, virulence profile, antimicrobial resistance and macrolide-resistance determinants in Streptococcus agalactiae isolates in pregnant women and neonates in Catalonia, Spain.

INTRODUCTION: Streptococcus agalactiae, or group B streptococci (GBS), is the main aetiological agent of early neonatal sepsis in developed countries. This microorganism belongs to the gastrointestinal tract microbiota wherefrom it can colonize the vagina and be vertically transmitted to the child either before or at birth, and subsequently cause infection in the newborn. Approximately, 50% of newborns born to women with GBS become colonized, with 1-2% developing early neonatal infection if no preventive intervention is performed. The aim of this study was to characterize and compare serotypes, virulence factors and antimicrobial resistance of GBS isolates collected from pregnant women and newborns in several hospitals in Catalonia. METHODS: 242 GBS strains were analyzed including 95 colonizers and 68 pathogenic strains isolated from pregnant women, and 79 strains isolated from neonates with sepsis in order to determine serotype, virulence and antimicrobial resistance. RESULTS: Serotype distribution was different among the three groups, with serotypes Ia and II being significantly more frequent among colonizing strains (p=0.001 and 0.012, respectively). Virulence factors bca and scpB were significantly more frequent among neonatal strains than pathogenic or colonizing strains (p=0.0001 and 0.002, respectively). Pathogenic strains were significantly more resistant to erythromycin, clindamycin and azithromycin than their non-pathogenic counterparts. CONCLUSIONS: Taking into account that neonatal sepsis represents a significant problem on a global scale, epidemiological surveillance, antimicrobial resistance and GBS virulence at the local level could provide important knowledge about these microorganisms as well as help to improve treatment and prevent invasive infection caused by this microorganism.

Emerging extended-spectrum ß-lactamase-producing Klebsiella pneumoniae causing community-onset urinary tract infections: a case-control-control study.

The aim of this study was to determine the epidemiology and risk factors associated with community-onset urinary tract infections (CO-UTIs) due to extended-spectrum ß-lactamase-producing Klebsiella pneumoniae (ESBL-Kp). A cohort study including all consecutive patients with K. pneumoniae CO-UTI identified from January 2010 to December 2014 was conducted. Patients with CO-UTI due to ESBL-Kp were then included as cases in a retrospective case-control-control study; controls were outpatients with CO-UTI caused by non-ESBL-producing Escherichia coli and K. pneumoniae (non-ESBL-Ec and non-ESBL-Kp, respectively). Each control was matched in a 2:1 ratio according to patient age, sex and year of isolation. Genotyping confirming ESBL was performed by multiplex PCR and sequencing. The prevalence of ESBL-Kp CO-UTIs, calculated among all K. pneumoniae CO-UTIs, increased from 2.4% in 2010 to 10.3% in 2014 (P = 0.01). Among cases, 63.8% were truly community-acquired, and CTX-M-15 was the predominant ß-lactamase enzyme type (79.3%). A total of 83 cases and 319 controls were studied. Being a nursing home resident [odds ratio (OR) = 8.8, 95% confidence interval (CI) 2.6-29.4] and previous cephalosporin use (OR = 4.01, 95% CI 1.8-9.2) were risk factors independently associated with CO-UTI due to ESBL-Kp. In conclusion, the prevalence of CO-UTIs due to ESBL-Kp is increasing. In most cases, ESBL-Kp CO-UTIs are community-acquired and produce CTX-M-15 ß-lactamase. Exposure to cephalosporins and being a nursing home resident were risk factors associated with ESBL-Kp CO-UTIs. CTX-M-15-producing K. pneumoniae isolates are emerging in the community.