Assessment of risk-adjusted mortality ratio (RAMR) in bloodstream infections using all-patient refined diagnosis-related groups (APR-DRGs).

OBJECTIVES: To calculate a risk-adjusted mortality ratio (RAMR) for bloodstream infections (BSIs) using all-patient refined diagnosis-related groups (APR-DRGs) and compare it with the crude mortality rate (CMR). METHODS: Retrospective observational study of prevalent BSI at our institution from January 2019 to December 2022. In-hospital mortality was adjusted with a binary logistic regression model adjusting for sex, age, admission type and mortality risk for the hospitalization episode according to the four severity levels of APR DRGs. The RAMR was calculated as the ratio of observed to expected in-hospital mortality, and the CMR was calculated as the proportion of deaths among all bacteraemia episodes. RESULTS: Of 2939 BSIs, 2541 were included: Escherichia coli (n = 1310), Klebsiella pneumoniae (n = 428), Pseudomonas aeruginosa (n = 209), Staphylococcus aureus (n = 498) and candidaemia (n = 96). A total of 436 (17.2%) patients died during hospitalization and 279 died within the first 14 days after the onset of BSI. Throughout the period, all BSI cases had a mortality rate above the expected adjusted mortality (RAMR value greater than 1), except for Escherichia coli (1.03; 95% CI 0.86-1.21). The highest overall RAMR values were observed for P. aeruginosa, Candida and S. aureus with 2.06 (95% CI 1.57-2.62), 1.99 (95% CI 1.3-2.81) and 1.8 (95% CI 1.47-2.16), respectively. The temporal evolution of CMR may differ from RAMR, especially in E. coli, where it was reversed. CONCLUSIONS: RAMR showed higher than expected mortality for all BSIs studied except E. coli and provides complementary to and more clinically comprehensive information than CMR, the currently recommended antibiotic stewardship programme mortality indicator.

Bacteremia due to Leuconostoc species: A 13-year single-center case series / Bacteriemia por Leuconostoc spp: serie de casos en un hospital de tercer nivel a lo largo de 13 años

Introduction: Leuconostoc spp. are facultatively anaerobic Gram-positive cocci involved in cases of hospital-acquired bacteremia, mainly in immunocompromised hosts. The available data is scarce due to its uncommon presentation. Methods: We describe all the episodes of Leuconostoc spp. bacteremia in a third level hospital in a 13-year period (2008–2021). Results: Four cases of clinically relevant bacteremia were detected. All cases were categorized as catheter-related. The following risk factors were found: previous glycopeptide therapy (75%), use of parenteral nutrition (100%) and cancer (75%). All isolates showed susceptibility to beta-lactams. Catheter removal was performed and wide spectrum antimicrobials were administered, with clinical response in all cases except one. Discussion: Apart from cancer and glycopeptide exposure, disruption of skin barrier and gastrointestinal conditions were identified as risk factors, as it was concordantly underlined in other case series. Susceptibility to beta-lactams is usually maintained. Catheter removal and administration of an active antibacterial therapy seem to be the best approach for Leuconostoc spp. catheter-related bacteremia.(AU)

Introducción: Los microorganismos del género Leuconostoc son cocos grampositivos anaerobios facultativos, involucrados en casos de bacteriemia en pacientes hospitalizados, especialmente con factores de inmunosupresión. La literatura disponible es escasa por su baja frecuencia. Métodos: Describimos todos los episodios de bacteriemia por Leuconostoc spp. en un hospital de tercer nivel en un periodo de 13 años (2008-2021). Resultados: Se detectaron 4 aislamientos clínicamente significativos. Todos ellos fueron categorizados como bacteriemia relacionada con catéter. Se identificaron como factores de riesgo: la exposición previa a glucopéptidos (75%), nutrición parenteral (100%) y cáncer (75%). Todos los aislamientos presentaron sensibilidad a betalactámicos. Se procedió a retirada del catéter y se administraron antimicrobianos de amplio espectro con buena respuesta clínica, salvo en un caso. Discusión: Además del cáncer y la exposición a glucopéptidos, la disrupción de la barrera cutánea y las enfermedades gastrointestinales se identificaron como factores de riesgo, al igual que en otras series. La sensibilidad a betalactámicos suele mantenerse. La retirada del catéter y el uso de terapia antibiótica activa parece ser la mejor alternativa terapéutica para la bacteriemia relacionada con catéter por Leuconostoc spp.(AU)

Bacteremia due to Leuconostoc species: A 13-year single-center case series.

INTRODUCTION: Leuconostoc spp. are facultatively anaerobic Gram-positive cocci involved in cases of hospital-acquired bacteremia, mainly in immunocompromised hosts. The available data is scarce due to its uncommon presentation. METHODS: We describe all the episodes of Leuconostoc spp. bacteremia in a third level hospital in a 13-year period (2008-2021). RESULTS: Four cases of clinically relevant bacteremia were detected. All cases were categorized as catheter-related. The following risk factors were found: previous glycopeptide therapy (75%), use of parenteral nutrition (100%) and cancer (75%). All isolates showed susceptibility to beta-lactams. Catheter removal was performed and wide spectrum antimicrobials were administered, with clinical response in all cases except one. DISCUSSION: Apart from cancer and glycopeptide exposure, disruption of skin barrier and gastrointestinal conditions were identified as risk factors, as it was concordantly underlined in other case series. Susceptibility to beta-lactams is usually maintained. Catheter removal and administration of an active antibacterial therapy seem to be the best approach for Leuconostoc spp. catheter-related bacteremia.

Predictive value of fecal calprotectin and lactoferrin levels for negative outcomes in Clostridioides difficile infection.

PURPOSE: We investigated the role of fecal calprotectin (FC) and lactoferrin (FL) as predictive biomarkers in Clostridioides difficile infection (CDI). METHODS: We assembled a prospective cohort including all patients with a laboratory-confirmed CDI diagnosis between January and December 2017. FL and FC levels were measured at diagnosis by commercial ELISA and EIA kits. We investigated the diagnostic accuracy of FC and FL to predict CDI recurrence and severity (study outcomes) and explored optimal cut-off values in addition to those proposed by the manufacturers (200 µg/g and 7.2 µg/mL, respectively). RESULTS: We included 170 CDI cases (152 first episodes and 18 recurrences). The rates of recurrence (first episodes only) and severity (entire cohort) were 9.2% (14/152) and 46.5% (79/170). Both FL and FC levels were significantly higher in patients who developed study outcomes. Optimal cut-off values for FC and FL to predict CDI recurrence were 1052 µg/g and 6.0 µg/mL. The optimal cut-off value for FC yielded higher specificity (60.9%) and positive predictive value (PPV) (16.9%) than that proposed by the manufacturer. Regarding CDI severity, the optimal cut-off value for FC (439 µg/g) also provided higher specificity (43.9%) and PPV (54.1%) than that of the manufacturer, whereas the optimal cut-off value for FL (4.6 µg/mL) resulted in an improvement of PPV (57.5%). CONCLUSION: By modifying the thresholds for assay positivity, the measurement of FC and FL at diagnosis is useful to predict recurrence and severity in CDI. Adding these biomarkers to current clinical scores may help to individualize CDI management.

Bacteremia in Patients with Solid Organ Cancer: Insights into Epidemiology and Antibiotic Consumption.

Epidemiology and risk factors associated to bacterial resistance in solid organ cancer (SOC) patients has been barely described. This retrospective monocentric study analyzed clinical variables in SOC patients who developed bacteremia between 1 January 2019 and 31 December 2022. We described rates of bacterial resistance in Gram negative bacteria (80.6%): E. coli-ESBL, K. pneumoniae-ESBL, Carbapenem-Resistant K. pneumoniae and Meropenem-Resistant P. aeruginosa, as well as antibiotic consumption, and compared these rates between the medical and oncology wards. In total, we included 314 bacteremias from 253 patients. SOC patients are frequently prescribed antibiotics (40.8%), mainly fluoroquinolones. Nosocomial bacteremia accounted for 18.2% of the cases and only 14.3% of patients were neutropenic. Hepatobiliary tract was the most frequent tumor (31.5%) and source of bacteremia (38.5%). Resistant bacteria showed a decreased rate of resistance during the years studied in the oncology ward. Both K-ESBL and K-CBP resistance rates decreased (from 45.8% to 20.0%, and from 29.2% to 20.0%, respectively), as well as MRPA, which varied from a resistance rate of 28% to 16.7%. The presence of a urinary catheter (p < 0.001) and previous antibiotic prescription (p = 0.002) were risk factors for bacterial resistance. Identifying either of these risk factors could help in guiding antibiotic prescription for SOC patients.

PACTA-Ped: programa de optimización de antimicrobianos en un hospital de tercer nivel en España / PACTA-Ped: Antimicrobial stewardship programme in a tertiary care hospital in Spain

Introducción: La lucha contra la resistencia a los antimicrobianos es actualmente prioritaria; son necesarios esfuerzos para mejorar la prescripción y reducir la propagación de infecciones en el entorno pediátrico. Métodos: Estudio longitudinal prospectivo sobre el uso de antimicrobianos realizado desde el inicio del programa de optimización del uso de antimicrobianos (PROA) en enero de 2016 hasta diciembre de 2017 (período 2; P2) en el hospital infantil. Los resultados obtenidos se han comparado retrospectivamente con el periodo anterior al inicio del PROA (2014-2015, periodo 1; P1). La población estudiada fueron niños ingresados que recibieron antimicrobianos de amplio espectro, antifúngicos o tratamiento antibiótico intravenoso durante más de 5 días.Resultados: Durante el P2 se incluyeron un total de 160 pacientes. Los antibióticos más comunes para los que se realizó una recomendación fueron: meropenem (41,6%) y cefotaxima (23,4%). En el 45% de los episodios se recomendó «no cambiar» el antimicrobiano prescrito. La tasa de aceptación de las recomendaciones por parte de los facultativos responsables fue del 89%. Se objetivó una disminución promedio del 27,8 y del 22,9% en los días de tratamiento (DOT)/1.000 días de ingreso y el número de tratamientos iniciados/1.000 ingresos, respectivamente. El uso de carbapenémicos, cefalosporinas y glucopéptidos disminuyó del P1 al P2. El coste medio anual del tratamiento antimicrobiano pasó de 150.356€/año durante en el P1 a 98.478€/año en el P2. Conclusiones: Nuestro PROA conllevó una disminución significativa en el uso de antibióticos y antifúngicos de amplio espectro. Los costes asociados con la prescripción de antimicrobianos disminuyeron desde el inicio del PROA y resultó una acción coste-efectiva durante el período de estudio.(AU)

Introduction: Fighting against antimicrobial resistance is a current priority, and further efforts need to be made to improve antimicrobial prescribing and reduce the spread of infections in paediatric care settings. Methods: We conducted a prospective longitudinal study on the use of antimicrobials from the time the antimicrobial stewardship programme (ASP) was introduced in January 2016 to December 2017 (period 2 [P2]) in our children's hospital. We compared the obtained results on antimicrobial prescribing with retrospective data from the period preceding the introduction of the ASP (2014–2015, period 1 [P1]). The sample consisted of paediatric in patients who received broad-spectrum antimicrobials, antifungals or intravenous antibiotherapy lasting more than 5 days. We compared the use of antimicrobials in P1 versus P2. Results: A total of 160 patients were included during P2. The antibiotics for which a recommendation was made most frequently were meropenem (41.6%) and cefotaxime (23.4%). In 45% of care episodes, the consultant recommended “no change” to the prescribed antimicrobial. The final rate of acceptance of received recommendations by the prescribing physicians was 89%. We found average decreases of 27.8% in the days of treatment per 1000 inpatient days and 22.9% in the number of antimicrobial starts per 1000 admissions in P2. The use of carbapenems, cephalosporins and glycopeptides decreased in P2 compared to P1. The average annual cost of antimicrobial treatment decreased from €150 356/year during P1 to €98 478/year in P2. Conclusion: Our ASP achieved a significant decrease in the use of broad-spectrum antibiotics and antifungals. The costs associated with antimicrobial prescribing decreased following the introduction of the ASP, which was a cost-effective action in this study period.(AU)

PACTA-Ped: Antimicrobial stewardship programme in a tertiary care hospital in Spain.

INTRODUCTION: Fighting against antimicrobial resistance is a current priority, and further efforts need to be made to improve antimicrobial prescribing and reduce the spread of infections in paediatric care settings. METHODS: We conducted a prospective longitudinal study on the use of antimicrobials from the time the antimicrobial stewardship programme (ASP) was introduced in January 2016 to December 2017 (period 2 [P2]) in our children's hospital. We compared the obtained results on antimicrobial prescribing with retrospective data from the period preceding the introduction of the ASP (2014-2015, period 1 [P1]). The sample consisted of paediatric inpatients who received broad-spectrum antimicrobials, antifungals or intravenous antibiotherapy lasting more than 5 days. We compared the use of antimicrobials in P1 versus P2. RESULTS: A total of 160 patients were included during P2. The antibiotics for which a recommendation was made most frequently were meropenem (41.6%) and cefotaxime (23.4%). In 45% of care episodes, the consultant recommended "no change" to the prescribed antimicrobial. The final rate of acceptance of received recommendations by the prescribing physicians was 89%. We found average decreases of 27.8% in the days of treatment per 1000 inpatient days and 22.9% in the number of antimicrobial starts per 1000 admissions in P2. The use of carbapenems, cephalosporins and glycopeptides decreased in P2 compared to P1. The average annual cost of antimicrobial treatment decreased from є150 356/year during P1 to є98 478/year in P2. CONCLUSION: Our ASP achieved a significant decrease in the use of broad-spectrum antibiotics and antifungals. The costs associated with antimicrobial prescribing decreased following the introduction of the ASP, which was a cost-effective action in this study period.

Evaluation of the effectiveness and safety of oral vancomycin versus placebo in the prevention of recurrence of Clostridioides difficile infection in patients under systemic antibiotic therapy: a phase III, randomised, double-blind clinical trial.

INTRODUCTION: Clostridioides difficile infection (CDI) is the most prevalent cause of nosocomial bacterial diarrhoea and it is strongly associated with antibiotic use. The recurrence of CDI is a growing medical problem. Data from real-life studies and one open label randomised clinical trial (RCT) suggest that secondary prophylaxis with oral vancomycin (SPV) during subsequent courses of systemic antibiotics is a promising approach for reducing the risk of CDI recurrence. Our aim is to confirm the role of SPV through a double-blind RCT. METHODS AND ANALYSIS: We will perform a phase III, multicentre, placebo-controlled RCT (PREVAN trial) in a 2:1 ratio in favour of SPV (experimental treatment), in four tertiary care hospitals in Spain. Adult patients (≥18 years) with a previous history of CDI in the previous 180 days and with requirement for hospitalisation and systemic antibiotic therapy will be randomly allocated to receive either 125 mg of oral vancomycin or placebo every 6 hours for 10 days. Patients will be followed for 60 days after the end of treatment to verify a reduction in the rate of CDI recurrence in the experimental group. We assume a recurrence rate of 5% in the experimental group versus 25% in the placebo group. Accepting an alpha risk of 0.05 and a beta risk of 0.2 in a two-sided test, 104 subjects will be required in total (68 assigned to the SPV group and 34 to the placebo group). ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Ethic Committee for Research with medicinal products of the University Hospital '12 de Octubre' (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), which is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders. TRIAL REGISTRATION NUMBER: NCT05320068.

Clinical impact of time-to-positivity of blood cultures on mortality in patients with Pseudomonas aeruginosa bacteremia.

OBJECTIVES: To investigate the impact of the time-to-positivity of blood cultures (TTP) on 30-day mortality in patients with Pseudomonas aeruginosa bacteremia. METHODS: All nonduplicated episodes of P. aeruginosa monomicrobial bacteremia in adult patients from January 2013 to February 2020 were analysed. Epidemiological and clinical data were collected. TTP of blood cultures for P. aeruginosa isolates was automatically recorded. Multivariate analysis identified factors predicting 30-day overall mortality. RESULTS: A total of 328 patients were identified. The median TTP for P. aeruginosa isolates was 15 h (interquartile range [IQR] 12-18 h). All multidrug-resistant and extensively drug-resistant (MDR/XDR) episodes were positive within the first 36 h. The 30-day mortality rate was 32.3%. The best cut-off value of the TTP for predicting mortality was 16 h (area under the receiver operating characteristic curve 0.62, 95% confidence interval [CI] 0.56-0.67, P = 0.001). The 30-day mortality rate was significantly higher in the TTP ≤16 h group (41.0% vs. 19.5%, P < 0.001). In a multivariate analysis, severe neutropenia (adjusted odds ratio [aOR] 2.67, 95% CI 1.4-5.09, P = 0.002), septic shock (aOR 3.21, 95% CI 1.57-5.89, P < 0.001), respiratory source (aOR 4.37, 95% CI 2.24-8.52, P < 0.001), nosocomial acquisition (aOR 1.99, 95% CI 1.06-3.71, P = 0.030), TTP ≤16 h (aOR 2.27, 95% CI 2.12-4.25, P = 0.010), and MDR/XDR phenotype (aOR 2.54, 95% CI 1.38-4.67, P = 0.002) were independently associated with 30-day mortality. CONCLUSIONS: A short TTP (≤16 h) was independently associated with increased 30-day mortality. After local validation, this routinely available microbiological parameter might be useful for guiding empirical antipseudomonal therapies and supporting the close monitoring of patients with P. aeruginosa bacteremia.

Genomic Analysis of Ceftazidime/Avibactam-Resistant GES-Producing Sequence Type 235 Pseudomonas aeruginosa Isolates.

The emergence of ceftazidime/avibactam (CZA) resistance among Guiana extended-spectrum ß-lactamase (GES)-producing Pseudomonas aeruginosa isolates has rarely been described. Herein, we analyze the phenotypic and genomic characterization of CZA resistance in different GES-producing P. aeruginosa isolates that emerged in our institution. A subset of nine CZA-resistant P. aeruginosa isolates was analyzed and compared with thirteen CZA-susceptible isolates by whole-genome sequencing (WGS). All CZA-resistant isolates belonged to the ST235 clone and O11 serotype. A variety of GES enzymes were detected: GES-20 (55.6%, 5/9), GES-5 (22.2%, 2/9), GES-1 (11.1%, 1/9), and GES-7 (11.1%, 1/9). WGS revealed the presence of two mutations within the blaGES-20 gene comprising two single-nucleotide substitutions, which caused aspartic acid/serine and leucine/premature stop codon amino acid changes at positions 165 (D165S) and 237 (L237X), respectively. No major differences in the mutational resistome (AmpC, OprD porin, and MexAB-OprM efflux pump-encoding genes) were found among CZA-resistant and CZA-susceptible isolates. None of the mutations that have been previously demonstrated to cause CZA resistance were observed. Different mutations within the blaGES-20 gene were documented in CZA-resistant GES-producing P. aeruginosa isolates belonging to the ST235 clone in our institution. Although further analysis should be performed, according to our results, other resistance mechanisms might be involved in CZA resistance.

Clinical and bacterial characteristics of Pseudomonas aeruginosa affecting the outcome of patients with bacteraemic pneumonia.

Few studies have assessed the clinical and bacterial characteristics of Pseudomonas aeruginosa (PA) bacteraemic pneumonia (BP) episodes. This study analysed all non-duplicate PA-BP episodes from a tertiary hospital in 2013-2017. Epidemiology, clinical data, antimicrobial therapy and outcomes were recorded. Whole-genome sequencing was performed on PA blood isolates. The impact on early and late overall mortality of host, antimicrobial treatment and pathogen factors was assessed by multivariate logistic regression analysis. Of 55 PA-BP episodes, 32 (58.2%) were caused by extensively drug-resistant (XDR) PA. ST175 (32.7%) and ST235 (25.5%) were the most frequent high-risk clones. ß-Lactamases/carbapenemases were detected in 29 isolates, including blaVIM-2 (27.2%) and blaGES type (25.5%) [blaGES-5 (20.0%), blaGES-1 (3.6%) and blaGES-20 (1.8%)]. The most prevalent O-antigen serotypes were O4 (34.5%) and O11 (30.9%). Overall, an extensive virulome was identified in all isolates. Early mortality (56.4%) was independently associated with severe neutropenia (aOR = 4.64, 95% CI 1.11-19.33; P = 0.035) and inappropriate empirical antimicrobial therapy (aOR = 5.71, 95% CI 1.41-22.98; P = 0.014). Additionally, late mortality (67.3%) was influenced by septic shock (aOR = 8.85, 95% CI 2.00-39.16; P = 0.004) and XDR phenotype (aOR = 5.46, 95% CI 1.25-23.85; P = 0.024). Moreover, specific genetic backgrounds [ST235, blaGES, gyrA (T83I), parC (S87L), exoU and O11 serotype] showed significant differences in patient outcomes. Our results confirm the high mortality associated with PA-BP. Besides relevant clinical characteristics and inappropriate empirical therapy, bacteria-specific genetics factors, such as XDR phenotype, adversely affect the outcome of PA-BP.

Eradication of Staphylococcus aureus Post-Sternotomy Mediastinitis Following the Implementation of Universal Preoperative Nasal Decontamination With Mupirocin: An Interrupted Time-Series Analysis.

BACKGROUND: Although presurgical nasal decontamination with mupirocin (NDM) has been advocated as a measure for preventing postsurgical mediastinitis (PSM) due to Staphylococcus aureus, this strategy is not universally recommended due to lack of robust supporting evidence. We aimed to evaluate the role of preoperative NDM in the annual incidence of S. aureus PSM at our institution. METHODS: An interrupted time-series analysis, with an autoregressive error model, was applied to our single-center cohort by comparing preintervention (1990-2003) and postintervention (2005-2018) periods. Logistic regression was performed to analyze risk factors for S. aureus PSM. RESULTS: 12 236 sternotomy procedures were analyzed (6370 [52.1%] and 5866 [47.9%] in the pre- and postintervention periods, respectively). The mean annual percentage adherence to NDM estimated over the postintervention period was 90.2%. Only 4 of 127 total cases of S. aureus PSM occurred during the 14-year postintervention period (0.68/1000 sternotomies vs 19.31/1000 in the preintervention period; P < .0001). Interrupted time-series analysis demonstrated a statistically significant annual reduction in S. aureus PSM of -9.85 cases per 1000 sternotomies (-13.17 to -6.5; P < .0001) in 2005, with a decreasing trend maintained over the following 5 years and an estimated relative reduction of 84.8% (95% confidence interval [CI], 89.25-74.09%). Chronic obstructive pulmonary disease was the single independent risk factor for S. aureus PSM (odds ratio, 3.7; 95% CI, 1.72-7.93) and was equally distributed in patients undergoing sternotomy during pre- or postintervention periods. CONCLUSIONS: Our experience suggests the implementation of preoperative NDM significantly reduces the incidence of S. aureus PSM.

Impact of duration of antibiotic therapy in central venous catheter-related bloodstream infection due to Gram-negative bacilli.

BACKGROUND: A progressive increase in the incidence of catheter-related bloodstream infection (CRBSI) due to Gram-negative bacilli (GNB) has been reported. Current guidelines recommend antibiotic treatment for at least 7-14 days, although the supporting evidence is limited. METHODS: We performed a retrospective single-centre study including all patients with a definite diagnosis of GNB CRBSI from January 2012 to October 2018 in which the central venous catheter (CVC) was removed. The occurrence of therapeutic failure [clinical failure (persistence of symptoms and laboratory signs of infection), microbiological failure (persistent bacteraemia or relapse) and/or all-cause 30 day mortality] was compared between episodes receiving short [≤7 days (SC)] or long courses [>7 days (LC)] of appropriate antibiotic therapy following CVC removal. RESULTS: We included 54 GNB CRBSI episodes with an overall rate of therapeutic failure of 27.8% (15/54). Episodes receiving SC therapy were more frequently due to MDR GNB [60.9% (14/23) versus 34.5% (10/29); P = 0.058] and had higher Pitt scores [median (IQR) 1 (0-4) versus 0 (0-2); P = 0.086]. There were no significant differences in the rate of therapeutic failure between episodes treated with SC or LC therapy [30.4% (7/23) versus 27.6% (8/29); OR 1.15; 95% CI 0.34-3.83; P = 0.822]. The use of SCs was not associated with increased odds of therapeutic failure in any of the exploratory models performed. CONCLUSIONS: The administration of appropriate antibiotic therapy for ≤7 days may be as safe and effective as longer courses in episodes of GNB CRBSI once the CVC has been removed.

Direct identification of pneumococcal serotypes in blood cultures by a PCR-reverse-hybridisation technique / Identificación directa de serotipos de neumococo en frascos de hemocultivo mediante una técnica de PCR seguida de hibridación reversa

INTRODUCTION: The objective of this study was to assess the performance of a technique (S. PneumoStrip test) based on PCR followed by reverse strip hybridisation for the detection of Streptococcus pneumoniae serotypes directly in blood culture vials. METHODS: One hundred and ten (110) pairs of isolated strains and their corresponding original blood cultures vials were studied in parallel. Pure isolated strains were conventionally serotyped using latex agglutination and the Quellung reaction. The S. PneumoStrip test was carried out directly in the original blood culture samples. RESULTS: In 102 cases (92.7%), results of the serotype obtained by Quellung coincided with their corresponding original blood cultures typed by S. PneumoStrip. CONCLUSIONS: S. PneumoStrip test is a good alternative technique for direct pneumococcal serotyping in blood culture clinical simples

INTRODUCCIÓN: El objetivo de este estudio fue evaluar el rendimiento de una técnica de PCR seguida de hibridación reversa (S. PneumoStrip test) para su aplicación directa en muestras de frasco de hemocultivo. MÉTODOS: Se estudiaron 110 cepas aisladas en sangre y sus correspondientes muestras de frasco de hemocultivo. Las cepas fueron serotipadas convencionalmente mediante aglutinación por látex y reacción de Quellung. El test de S. PneumoStrip se realizó directamente en las muestras originales de hemocultivo. RESULTADOS: En 102 casos (92,7%) el serotipado por Quellung coincidió con el obtenido directamente en su original frasco de hemocultivo. CONCLUSIONES: S. PneumoStrip constituye una buena alternativa para el serotipado directo en muestras de frasco de hemocultivo

Direct identification of pneumococcal serotypes in blood cultures by a PCR-reverse-hybridisation technique.

INTRODUCTION: The objective of this study was to assess the performance of a technique (S. PneumoStrip test) based on PCR followed by reverse strip hybridisation for the detection of Streptococcus pneumoniae serotypes directly in blood culture vials. METHODS: One hundred and ten (110) pairs of isolated strains and their corresponding original blood cultures vials were studied in parallel. Pure isolated strains were conventionally serotyped using latex agglutination and the Quellung reaction. The S. PneumoStrip test was carried out directly in the original blood culture samples. RESULTS: In 102 cases (92.7%), results of the serotype obtained by Quellung coincided with their corresponding original blood cultures typed by S. PneumoStrip. CONCLUSIONS: S. PneumoStrip test is a good alternative technique for direct pneumococcal serotyping in blood culture clinical samples.

Predictors of Mortality in Bloodstream Infections Caused by Pseudomonas aeruginosa and Impact of Antimicrobial Resistance and Bacterial Virulence.

Whether multidrug resistance (MDR) is associated with mortality in patients with Pseudomonas aeruginosa bloodstream infections (BSI) remains controversial. Here, we explored the prognostic factors of P. aeruginosa BSI with emphasis on antimicrobial resistance and virulence. All P. aeruginosa BSI episodes in a 5-year period were retrospectively analyzed. The impact in early (5-day) and late (30-day) crude mortality of host, antibiotic treatment, and pathogen factors was assessed by multivariate logistic regression analysis. Of 243 episodes, 93 (38.3%) were caused by MDR-PA. Crude 5-day (20%) and 30-day (33%) mortality was more frequent in patients with MDR-PA (34.4% versus 11.3%, P < 0.001 and 52.7% versus 21.3%, P < 0.001, respectively). Early mortality was associated with neutropenia (adjusted odds ratio [aOR], 9.21; 95% confidence interval [CI], 3.40 to 24.9; P < 0.001), increased Pitt score (aOR, 2.42; 95% CI, 1.34 to 4.36; P = 0.003), respiratory source (aOR, 3.23; 95% CI,2.01 to 5.16; P < 0.001), inadequate empirical therapy (aOR, 4.57; 95% CI, 1.59 to 13.1; P = 0.005), shorter time to positivity of blood culture (aOR, 0.88; 95% CI, 0.80 to 0.97; P = 0.010), an exoU-positive genotype (aOR, 3.58; 95% CI, 1.31 to 9.79; P = 0.013), and the O11 serotype (aOR, 3.64; 95% CI, 1.20 to 11.1; P = 0.022). These risk factors were similarly identified for late mortality, along with an MDR phenotype (aOR, 2.18; 95% CI, 1.04 to 4.58; P = 0.040). Moreover, the O11 serotype (15.2%, 37/243) was common among MDR (78.4%, 29/37) and exoU-positive (89.2%, 33/37) strains. Besides relevant clinical variables and inadequate empirical therapy, pathogen-related factors such as an MDR phenotype, an exoU-positive genotype, and the O11 serotype adversely affect the outcome of P. aeruginosa BSI.

Pathogenic characteristics of Pseudomonas aeruginosa bacteraemia isolates in a high-endemicity setting for ST175 and ST235 high-risk clones.

Multidrug-resistant (MDR) Pseudomonas aeruginosa represents a major clinical concern. The interplay between antimicrobial resistance and virulence of P. aeruginosa was investigated in in vitro and in vivo studies. Thirty-eight well-characterized (21 MDR and 17 non-MDR) P. aeruginosa strains from patients with bacteraemia were analysed. Resistance phenotype, carbapenemase production, clonal relatedness, type III secretion system genotype, O-antigen serotype, cytotoxicity (ability to lyse cells) on A549 cells, and virulence (lethality in nematodes) in a Caenorhabditis elegans model were investigated. MDR strains showed lower cytotoxicity (35.4 ± 21.30% vs. 45.0 ± 18.78 %; P = 0.044) and virulence (66.7% vs. 100%; P = 0.011) than non-MDR strains. However, the pathogenicity of MDR high-risk clones varied broadly, with ST235 and ST175 clones being the most and least cytotoxic (51.8 ± 10.59% vs. 11.0 ± 1.25%; P < 0.0001) and virulent ([100% vs. 73.1; P = 0.075] and [0% vs. 93.9%; P < 0.0001], respectively). The pathogenicity of the ST235 clone was similar to that of non-MDR strains, and its ability to lyse cells and high virulence were related with the exoU-positive genotype. Furthermore, the O11 serotype was more frequent among the ST235 clone and exoU-positive genotype strains and was also essential for the pathogenicity of P. aeruginosa. Our data suggest that the pathogenicity of MDR high-risk clones is the result not only of the resistance phenotype but also of the virulence genotype. These findings have implications for the clinical management of patients and infection control programmes.

A short course of antibiotic treatment is safe after catheter withdrawal in catheter-related bloodstream infections due to coagulase-negative staphylococci.

CoNS is the main cause of catheter-related bloodstream infections (CRBSI). Current guidelines recommend catheter withdrawal followed by antibiotics for at least 5 days. We aimed to assess the efficacy and safety of a shorter course of antibiotherapy in patients with CoNS CRBSI. All proven cases of CoNS CRBSI at our institution (Jan 12/Dec 17) were retrospectively analysed. Comparison of clinical characteristics and outcomes between patients receiving a short (SC ≤ 3 days) versus long antibiotic course (LC > 3 days) was performed. Cox regression models predicting the risk for complications (including propensity score [PS] for treatment assignment as covariate) were designed to adjust baseline differences among both treatment groups. A total of 79 cases were included. Most patients (75.9%) showed clinical response at day 7 after catheter removal. Complications occurred in 3.8% (three cases of septic thrombophlebitis) with no cases of endocarditis. Microbiological relapse (MR) occurred in 13 patients (16.5%). SC and LC were administered to 25 (31.6%) and 54 (68.4%) patients, respectively, with no significant differences in MR-free survival between SC and LC groups (87.8 vs 86.3%; P = 0.6). In PS-adjusted Cox regression analyses, a tunnelled catheter as the source of CRBSI was the only independent risk factor for MR (hazard ratio, 5.71; 95% confidence interval, 1.6-21) whereas the duration of therapy had no apparent impact. Shortening antibiotic therapy to ≤ 3 days is not associated with a poorer outcome or a greater risk of MR in patients with CoNS CRBI with catheter withdrawal.

Toxin B PCR Amplification Cycle Threshold Adds Little to Clinical Variables for Predicting Outcomes in Clostridium difficile Infection: a Retrospective Cohort Study.

The objective of the present study was to evaluate the value of the PCR cycle threshold (CT ) for predicting the recurrence/severity of infection compared to that of toxin detection plus clinical variables. First episodes of Clostridium difficile infection (CDI) diagnosed during 2015 at our institution were included. Samples were tested for glutamate dehydrogenase (GDH) and toxin A/B by use of a single enzyme immunoassay (EIA). The Xpert C. difficile PCR assay was performed on GDH-positive samples. Medical data were reviewed by investigators blinded to diagnostic results for comparison of patients with and without recurrence or a poor outcome (severe/severe-complicated CDI episodes and all-cause death). We generated two sets of predictive models by incorporating the presence of a positive toxin EIA ("EIA-including model") or the optimal PCR CT cutoff value ("PCR-including model") into the clinical variables. Among 227 episodes of CDI included in the study, the rates of recurrence and poor outcome were 15.8% and 30.8%, respectively. The mean PCR CT was lower for episodes with recurrence (24.00 ± 3.28 versus 26.02 ± 4.54; P = 0.002) or a poor outcome (24.9 ± 4.24 versus 26.05 ± 4.47; P = 0.07). The optimal cutoff value for recurrence was 25.65 (sensitivity, 77.8% [95% confidence interval {CI}, 60.9 to 89.9]; and specificity, 46.6% [95% CI, 39.4 to 53.9]). The area under the receiver operator characteristics curve (auROC) for the "PCR-including model" was similar to that for the "EIA-including model" (0.785 versus 0.775, respectively). The optimal PCR CT value for poor outcome was 27.55 (sensitivity, 78.6% [95% CI, 67.1 to 87.5]; and specificity, 35.7% [95% CI, 28.2 to 43.7]). The auROC of the "PCR-including model" was again similar to that of the "EIA-including model" (0.804 versus 0.801). Despite the inverse correlation between PCR CT and the risk of CDI recurrence/severity, this determination does not meaningfully increase the predictive value of clinical variables plus toxin EIA.

Bacteraemia due to extensively drug-resistant Pseudomonas aeruginosa sequence type 235 high-risk clone: Facing the perfect storm.

Predictors of mortality and the impact of multidrug resistance and virulence on patients with Pseudomonas aeruginosa (PA) bacteraemia were evaluated. Patients with PA bacteraemia in a 12-month period were retrospectively analysed. Carbapenemase production, molecular typing and identification of virulence factor ExoU were carried out. The activity of ceftolozane-tazobactam and ceftazidime-avibactam was also investigated. The primary endpoint was 30-day crude mortality. Of 64 patients with bacteraemia, 24 (37.5%) were caused by extensively drug-resistant PA (XDR-PA): 10 (41.7%) cases involved the VIM-2 carbapenemase-producing ST175 clone, 11 (45.8%) the GES-5 carbapenemase-producing ST235 clone, and 3 (12.5%) were non-carbapenemase producers. The exoU genotype was detected in all ST235 strains and in 6 (15%) of the non-XDR isolates. Ceftazidime-avibactam (58.3%) showed greater activity than ceftolozane-tazobactam (12.5%) against XDR-PA isolates, particularly in GES-5 producers (100%). The 30-day crude mortality rate in patients with XDR-PA bacteraemia was higher than in cases caused by susceptible strains (62.5% vs. 30%; P=0.02). Multivariate analysis showed that independent risk factors associated with 30-day crude mortality were Pitt score ≥2 (OR, 42.31; 95% CI, 4.88-366.7; P=0.001) and respiratory source of bacteraemia (OR, 49.13; 95% CI 3.89-620.5; P=0.003). Stratified analysis adjusting for respiratory source revealed a non-significant trend towards higher mortality in patients with bacteraemia caused by the ST235 clone and exoU-producing isolates. These data support the notion that the XDR phenotype associated with the GES-5 carbapenemase-producing ST235 clone and the exoU-positive genotype adversely affects the outcome of patients with PA bacteraemia, particularly those with respiratory tract infections and a severe clinical presentation.