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At the end of 2022 and in the following months, an increase in the incidence of Streptococcus pyogenes infections was observed in many European countries that was simultaneously accompanying to enhance of invasive infections (iGAS). We have showed a risen trend of S. pyogenes infections among preschoolers after the pandemic event. A thorough epidemiological investigation of both paediatric and adult samples positive for S. pyogenes indicate a more complex scenario leading to need of important improvement in surveillance programs. [ABSTRACT FROM AUTHOR]

Background: Respiratory viral infections (RVIs) exhibit seasonal patterns influenced by biological, ecological, and climatic factors. Weather variables such as temperature, humidity, and wind impact the transmission of droplet-borne viruses, potentially affecting disease severity. However, the role of climate in predicting complications in pediatric RVIs remains unclear, particularly in the context of climate-change-driven extreme weather events. Methods: This retrospective cohort study analyzed 1610 hospitalization records of children (0–18 years) with lower respiratory tract infections in Rome, Italy, between 2018 and 2023. Viral pathogens were identified using nasopharyngeal molecular testing, and weather data from the week preceding hospitalization were collected. Several machine learning models were tested, including logistic regression and random forest, comparing the baseline (demographic and clinical) models with those including climate variables. Results: Logistic regression showed a slight improvement in predicting severe RVIs with the inclusion of weather variables, with accuracy increasing from 0.785 to 0.793. Average temperature, dew point, and humidity emerged as significant contributors. Other algorithms did not demonstrate similar improvements. Conclusions: Climate variables can enhance logistic regression models' ability to predict RVI severity, but their inconsistent impact across algorithms highlights challenges in integrating environmental data into clinical predictions. Further research is needed to refine these models for use in reliable healthcare applications. [ABSTRACT FROM AUTHOR]

We developed a flow cytometry (FC) assay enabling the rapid and accurate identification of bacterial and viral infections using whole blood samples. The streamlined flow cytometry assay is designed to be user-friendly, making it accessible even for operators with limited experience in FC techniques. The key components of the assay focus on the expression levels of specific surface markers—CD64 on polymorphonuclear neutrophils (PMN) as a marker for bacterial infection, and CD169 on monocytes (MO) for viral infection. The strong performance indicated by an area under the receiver operating characteristic (ROC) curve of 0.94 for both PMN CD64 positive predictive value (PPV) 97.96% and negative predictive value (NPV) 76.67%, and MO CD169 PPV 82.6% and NPV 86.9%, highlight the assay's robustness in differentiating between bacterial and viral infections accurately. The FC assay includes the assessment of immune system status through HLA-DR and IL-1R2 modulation in MO, providing a useful insight into the patients' immune response. The significant increase in the frequency of MO exhibiting reduced HLA-DR expression and elevated IL-1R2 levels in infected patients (compared to healthy controls) underscores the potential of these markers as indicators of infection severity. Although the overall correlation between HLA-DR and IL-1R2 expression levels was not significant across all patients, there was a trend in patients with more severe disease suggesting that these markers may have the potential to assist in stratifying patient risk. The present FC assay has the potential to become routine in the clinical microbiology laboratory community and to be helpful in guiding clinical decision making. [ABSTRACT FROM AUTHOR]

Patients with hematological malignancies (HMs) are at high risk of respiratory viral infections due to the intrinsic deterioration of the immune system and chemotherapy treatments. In the recent past, SARS-CoV-2 respiratory viral infection has been responsible for most infectious complications in HMs. We analyzed 2950 samples from 505 patients admitted to the Hematology department from 2019 to 2023. The aim of this study was to determine the epidemiological trend of respiratory viruses in the SARS-CoV-2 era, the characteristics of the patients involved and their outcomes. In our analysis, we found a reduction in non-SARS-CoV-2 respiratory viral (NSRV) positivity during the pandemic period, although these data did not show statistical significance. Most of the HMs involved were Multiple Myeloma and Acute Myeloid Leukemia. Overall mortality rate was very low and characterized by the progression of the HMs as well as the worsening of respiratory failure. In conclusion, a reduction in non-COVID viral infections was highlighted, probably also thanks to the increase in prevention measures and environmental modifications of the viral background. [ABSTRACT FROM AUTHOR]

The pandemic marked the beginning of an era of dynamic and rapid changes in the diagnosis of respiratory infections. Herein we describe Legionnaires' disease trend in the years 2016–2023 in a large Italian hospital showing how improvements in diagnostic algorithms impact on its detection. [ABSTRACT FROM AUTHOR]

This retrospective analysis at a major Italian university hospital (January 2018–September 2022) assessed the prognostic significance of fever in patients with bloodstream infections (BSIs). Of the 1299 patients with positive blood cultures, a comparison between febrile and afebrile patients at emergency department admission was conducted. This study particularly focused on the mortality rates associated with these two groups. Notably, afebrile patients exhibited a higher mortality rate. The odds ratio for mortality in afebrile patients was significantly higher compared to febrile patients. This suggests that the absence of fever might be an indicator of increased mortality risk, highlighting the complexity of diagnosing bloodstream infections based on fever presence. This study contributes to the understanding of fever as a diagnostic marker in emergency settings. [ABSTRACT FROM AUTHOR]

We performed this study to evaluate factors associated with antibiotic prescriptions in children with adenovirus infection, since no studies have attempted to address this aspect in the pediatric population. Retrospective study of children younger than 18 years of age tested positive for adenovirus on a syndromic nasopharyngeal test from 2018 to 2023. We compared the need of pediatric intensive care unit (PICU), invasive ventilation, and other respiratory support, viral etiologies, clinical presentations, imaging, and laboratory results in the precovid (2018–2019) and covid (2020–2022) period. The use of antibiotics was studied with multivariable logistic regression including demographic as well as clinical data as covariates. Two hundred fifty-eight patients were enrolled. One hundred fifty-eight patients received an antibiotic (mean duration 6.2 (±2.7) days (median 4; IQR: 4–7)). Presence of seizures and C-reactive protein values as predictors for antibiotic prescription (OR for seizures: 12.17; 95% CI: 1.42–103.91; p = 0.022; OR for CrP: 1.03; 95% CI: 1.01–1.04; p = 0.001). Seventy-four patients received intravenous antibiotics (74/156, 47.4%). Risk factors for intravenous antibiotic were the presence of decay (OR: 3.74; 95% CI: 1.25–11.71; p = 0.018), CrP values (OR: 1.02; 95% CI: 1.00–1.03; p = 0.001), and presence of seizures (OR: 16.34; 95% CI: 2.65–100.83; p = 0.003). Duration of intravenous antibiotics correlated with the presence of seizures (Coeff: 1.6; 95% CI: 0.41–2.89; p = 0.009) even when adjusted for CrP values. Conclusion: The clinical presentation of adenovirus infection in children is non-specific, leading to frequent antibiotic prescription despite bacterial co-infections was rare. Higher CrP values and presenting with seizures are significantly associated with a higher risk of receiving antibiotics. Rapid microbiological tests and newer biomarkers can help clinicians to improve antibiotic prescription in this cohort of children. What is Known: •Adenovirus infection is a common cause of fever and respiratory tract infections in children. •Children with adenovirus infections frequently receive antibiotics, but determinants of this practice are poorly established. What is New: • Higher C-reactive protein values and presenting with seizures are significantly associated with antibiotic prescription. • Since the beginning of COVID-19 and implementation of rapid diagnostics, less children with adenovirus infection received antibiotics. [ABSTRACT FROM AUTHOR]

The aim of the study was to build a machine learning-based predictive model to discriminate between hospitalized patients at low risk and high risk of bloodstream infection (BSI). A Data Mart including all patients hospitalized between January 2016 and December 2019 with suspected BSI was built. Multivariate logistic regression was applied to develop a clinically interpretable machine learning predictive model. The model was trained on 2016–2018 data and tested on 2019 data. A feature selection based on a univariate logistic regression first selected candidate predictors of BSI. A multivariate logistic regression with stepwise feature selection in five-fold cross-validation was applied to express the risk of BSI. A total of 5660 hospitalizations (4026 and 1634 in the training and the validation subsets, respectively) were included. Eleven predictors of BSI were identified. The performance of the model in terms of AUROC was 0.74. Based on the interquartile predicted risk score, 508 (31.1%) patients were defined as being at low risk, 776 (47.5%) at medium risk, and 350 (21.4%) at high risk of BSI. Of them, 14.2% (72/508), 30.8% (239/776), and 64% (224/350) had a BSI, respectively. The performance of the predictive model of BSI is promising. Computational infrastructure and machine learning models can help clinicians identify people at low risk for BSI, ultimately supporting an antibiotic stewardship approach. [ABSTRACT FROM AUTHOR]

Objectives To assess the impact of piperacillin/tazobactam MICs on in-hospital 30 day mortality in patients with third-generation cephalosporin-resistant Escherichia coli bloodstream infection treated with piperacillin/tazobactam, compared with those treated with carbapenems. Methods A multicentre retrospective cohort study was conducted in three large academic hospitals in Italy between 2018 and 2022. The study population comprised patients with monomicrobial third-generation cephalosporin-resistant E. coli bloodstream infection, who received either piperacillin/tazobactam or carbapenem therapy within 48 h of blood culture collection. The primary outcome was in-hospital 30 day all-cause mortality. A propensity score was used to estimate the likelihood of receiving empirical piperacillin/tazobactam treatment. Cox regression models were performed to ascertain risk factors independently associated with in-hospital 30 day mortality. Results Of the 412 consecutive patients included in the study, 51% received empirical therapy with piperacillin/tazobactam, while 49% received carbapenem therapy. In the propensity-adjusted multiple Cox model, the Pitt bacteraemia score [HR 1.38 (95% CI, 0.85–2.16)] and piperacillin/tazobactam MICs of 8 mg/L [HR 2.35 (95% CI, 1.35–3.95)] and ≥16 mg/L [HR 3.69 (95% CI, 1.86–6.91)] were significantly associated with increased in-hospital 30 day mortality, while the empirical use of piperacillin/tazobactam was not found to predict in-hospital 30 day mortality [HR 1.38 (95% CI, 0.85–2.16)]. Conclusions Piperacillin/tazobactam use might not be associated with increased mortality in treating third-generation cephalosporin-resistant E. coli bloodstream infections when the MIC is <8 mg/L. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial resistance (AMR) remains a significant public health concern, closely linked to antibiotic overuse. During the COVID-19 pandemic, broad-spectrum antibiotics were frequently administered, potentially exacerbating AMR. This study aimed to assess AMR patterns in our urology department before and after the pandemic. Methods: The study encompassed patients admitted to our urology department from January 2016 to December 2022, with confirmed urinary tract infection, bloodstream infection, or wound infection based on positive culture results. Descriptive statistics, including mean, frequency, and percentage, summarized the data. Trends were analyzed using the Joinpoint Regression program. Results: A total of 506 patients were included. Escherichia coli and Klebsiella pneumoniae displayed resistance rates of 65% and 62% to ciprofloxacin, respectively. K. pneumoniae showed resistance rates of 41% to piperacillin tazobactam and 3rd generation cephalosporins (3GC). Carbapenem resistance was observed in 38% of K. pneumoniae isolates. Additionally, 26% of E. coli, 26% of K. pneumoniae, and 59% of Proteus mirabilis isolates were ESBL-positive. Among gram+, 72% of Staphylococcus aureus isolates were MRSA, and 23% of Enterococcus faecium isolates were VRE. Trends in antimicrobial susceptibility patterns over the 7-year study period revealed a statistically significant decrease in E. coli resistance to amoxicillin-clavulanic acid (APC: −5.85; C.I. 95% p < 0.05) and a statistically significant increase in K. pneumoniae resistance to 3GC (APC: 9.93; CI (−19.9–14.4 95% p < 0.05). There were no statistically significant differences in AMR incidence pre- and post-COVID-19. Conclusion: The COVID-19 pandemic did not appear to influence the AMR incidence in our urology department. However, the overall prevalence of AMR and MDROs in our department remains high compared to European AMR. [ABSTRACT FROM AUTHOR]

COVID-19 pandemic has changed in-hospital care and was linked to superimposed infections. Here, we described epidemiology and risk factors for hospital-acquired bloodstream infections (HA-BSIs), before and during COVID-19 pandemic. This retrospective, observational, single-center real-life study included 14,884 patients admitted to hospital wards and intensive care units (ICUs) with at least one blood culture, drawn 48 h after admission, either before (pre-COVID, N = 7382) or during pandemic (N = 7502, 1203 COVID-19+ and 6299 COVID-19–). Two thousand two hundred and forty-five HA-BSI were microbiologically confirmed in 14,884 patients (15.1%), significantly higher among COVID-19+ (22.9%; ptrend <.001). COVID-19+ disclosed a significantly higher mortality rate (33.8%; p <.001) and more ICU admissions (29.7%; p <.001). Independent HAI-BSI predictors were: COVID-19 (OR: 1.43, 95%CI: 1.21–1.69; p <.001), hospitalization length (OR: 1.04, 95%CI: 1.03–1.04; p <.001), ICU admission (OR: 1.38, 95%CI: 1.19–1.60; p <.001), neoplasms (OR:1.48, 95%CI: 1.34–1.65; p <.001) and kidney failure (OR: 1.81, 95%CI: 1.61–2.04; p <.001). Of note, HA-BSI IRs for Acinetobacter spp. (0.16 × 100 patient-days) and Staphylococcus aureus (0.24 × 100 patient-days) peaked during the interval between first and second pandemic waves in our National context. Patients with HA-BSI admitted before and during pandemic substantially differed. COVID-19 represented a risk factor for HA-BSI, though not confirmed in the sole pandemic period. Some etiologies emerged between pandemic waves, suggesting potential COVID-19 long-term effect on HA-BSIs. [ABSTRACT FROM AUTHOR]

The growing phenomenon of antibiotic resistance and the presence of limited data concerning the pediatric area prompted us to focus on Staphylococcus aureus infection in this study, its antibiotic resistance profile, and the therapeutic management of affected children. We conducted a retrospective study by collecting clinical data on infants and children with antibiogram-associated S. aureus infection. We enrolled 1210 patients with a mean age of 0.9 years. We analyzed the resistance patterns and found 61.5% resistance to oxacillin, 58.4% resistance to cephalosporins, 41.6% resistance to aminoglycosides, and 38.3% resistance to fluoroquinolones. Importantly, we found no resistance to glycopeptides, a key antibiotic for MRSA infections whose resistance is increasing worldwide. We also found that the main risk factors associated with antibiotic resistance are being aged between 0 and 28 days, the presence of devices, and comorbidities. Antibiotic resistance is a growing concern; knowing the resistance profiles makes it possible to better target the therapy; however, it is important to use antibiotics according to the principles of antibiotic stewardship to limit their spread. [ABSTRACT FROM AUTHOR]

Purpose: SARS-COV-2 pandemic led to antibiotic overprescription and unprecedented stress on healthcare systems worldwide. Knowing the comparative incident risk of bloodstream infection due to multidrug-resistant pathogens in COVID ordinary wards and intensive care-units may give insights into the impact of COVID-19 on antimicrobial resistance. Methods: Single-center observational data extracted from a computerized dataset were used to identify all patients who underwent blood cultures from January 1, 2018 to May 15, 2021. Pathogen-specific incidence rates were compared according to the time of admission, patient's COVID status and ward type. Results: Among 14,884 patients for whom at least one blood culture was obtained, a total of 2534 were diagnosed with HA-BSI. Compared to both pre-pandemic and COVID-negative wards, HA-BSI due to S. aureus and Acinetobacter spp. (respectively 0.3 [95% CI 0.21–0.32] and 0.11 [0.08–0.16] new infections per 100 patient-days) showed significantly higher incidence rates, peaking in the COVID-ICU setting. Conversely, E. coli incident risk was 48% lower in COVID-positive vs COVID-negative settings (IRR 0.53 [0.34–0.77]). Among COVID + patients, 48% (n = 38/79) of S. aureus isolates were resistant to methicillin and 40% (n = 10/25) of K. pneumoniae isolates were resistant to carbapenems. Conclusions: The data presented here indicate that the spectrum of pathogens causing BSI in ordinary wards and intensive care units varied during the pandemic, with the greatest shift experienced by COVID-ICUs. Antimicrobial resistance of selected high-priority bacteria was high in COVID positive settings. [ABSTRACT FROM AUTHOR]

Aim: We examined the prevalence of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in children during the autumn and winter season from 1 September 2021 to 30 January 2022 and compared it with the same period in 2020–2021. Methods: This study was carried out int the paediatric emergency department (PED) of a tertiary Italian hospital. We compared the clinical and demographical features of all children who presented during the two study periods and tested positive for SARS‐CoV‐2. Results: During the 2021–2022 autumn and winter season 5813 children presented to the PED, 19.0% were tested for SARS‐CoV‐2 and 133 (12.0%) of those tested positive. In 2020–2021, 2914 presented to the PED, 12.3% were tested, and 30 (8.3%) of those tested positive. There were no statistically significant differences in clinical severity during the two study periods, despite a higher percentage of neurological symptoms in 2020–2021. Of the SARS‐CoV‐2‐positive cases, 29/133 (21.8%) were hospitalised during the 2021–2022 season and 10/30 (33.3%) during the previous one. Only 3/163 children required intensive care. Conclusion: The greater spread of SARS‐CoV‐2 was probably due to the greater transmissibility of the Omicron variant, but the symptoms were mild and only 3 children required intensive care. [ABSTRACT FROM AUTHOR]

This study aimed to assess the comparability of in vitro susceptibility testing methods to ceftazidime-avibactam (CZA) and ceftolozane-tazobactam (C/T). Meropenem-resistant and/or carbapenemase-producing clinical isolates of Enterobacterales (Enterobacteriaceae) and Pseudomonas aeruginosa were tested by both bioMérieux ETEST and VITEK-2 AST-N397 card and compared with a Micronaut AST-system broth microdilution (BMD) method. CZA and C/T MICs were interpreted using EUCAST breakpoints. Of the 153 Enterobacteriaceae isolates, 55.6% and 0.0% (VITEK 2) and 56.9% and 0.0% (ETEST and BMD) were susceptible to CZA and C/T, respectively. Of 52 P. aeruginosa isolates, 50.0% and 40.4% (VITEK 2, ETEST, and BMD) were susceptible to CZA and C/T, respectively. The essential agreement (EA) was 96.1% (197/205; VITEK 2 versus BMD) and 95.6% (196/205; ETEST versus BMD) for CZA testing, whereas EA was 98.0% (201/205; VITEK 2 versus BMD) and 96.6% (198/205; ETEST versus BMD) for C/T testing. The categorical agreement (CA) was 98.0% (201/205; VITEK 2 versus BMD) and 100% (ETEST versus BMD) for CZA testing, whereas CA was 100% (VITEK 2 versus BMD) and 100% (ETEST versus BMD) for C/T testing. Categorical errors regarded four Enterobacteriaceae isolates. VITEK 2 and ETEST yielded equivalent CZA and C/T susceptibility testing results, compared to the BMD method, in such a clinical context. [ABSTRACT FROM AUTHOR]

Introduction: Antibody response plays a fundamental role in the natural history of infectious disease. A better understanding of the immune response in patients with SARS-CoV-2 infection could be important for identifying patients at greater risk of developing a more severe form of disease and with a worse prognosis. Methods: We performed a cross-sectional analysis to determine the presence and the levels of both anti-SARS-CoV-2 IgG and IgA in a cohort of hospitalized patients with confirmed infection at different times in the natural history of the disease. Patients enrolled when admitted at the emergency department were prospectively followed up during hospital stay. Results: Overall, 131 patients were considered with a total of 237 samples processed. Cross-sectional analysis showed that seroconversion for IgA seems to occur between days 6 and 15, while IgG response seems to occur slightly later, peaking at day 20 after symptoms onset. Both IgA and IgG were maintained beyond 2 months. Severe patients showed a higher IgA response compared with mild patients when analyzing optical density (8.3 versus 5.6, p < 0.001). Prospective analysis conducted on 55 patients confirmed that IgA appear slightly earlier than IgG. After stratifying for the severity of disease, both the IgA and IgG responses were more vigorous in severe cases. Moreover, while IgG tended to stabilize, there was a relevant decline after the first month of IgA levels in mild cases. Conclusion: IgA and IgG antibody response is closely related, although seroconversion for IgA occurs earlier. Both IgA and IgG are maintained beyond 2 months. Severe patients showed a more vigorous IgA and IgG response. IgA levels seem to decline after 1 month since the onset of symptoms in mild cases. Our results should be interpreted with cautions due to several limitations in our study, mainly the small number of cases, lack of data on viral load and clinical setting. [ABSTRACT FROM AUTHOR]

Background/Objectives: We investigated whether behavioral precautions adopted during Coronavirus disease (COVID‐19) pandemic also influenced the spreading and multidrug resistance (MDR) of ESKAPEEc (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii [AB], Pseudomonas aeruginosa, Enterobacter spp and Escherichia Coli, [EC]) among Intensive Care Unit (ICU) patients. Subjects/Methods: We performed a single‐center retrospective study in adult patients admitted to our COVID‐19‐free surgical ICU. Only patients staying in ICU for more than 48 hours were included. The ESKAPEEc infections recorded during the COVID‐19 period (June 1, 2020 ‐ February 28, 2021) and in the corresponding pre‐pandemic period (June 1, 2019 ‐ February 28, 2020) were compared. An interrupted time series analysis was performed to rule out possible confounders. Results: Overall, 173 patients in the COVID‐19 period and 132 in the pre‐COVID‐19 period were investigated. The ESKAPEEc infections were documented in 23 (13.3%) and 35 (26.5%) patients in the pandemic and the pre‐pandemic periods, respectively (p = 0.005). Demographics, diagnosis, comorbidities, type of surgery, Simplified Acute Physiology Score II, length of mechanical ventilation, hospital and ICU length of stay, ICU death rate, and 28‐day hospital mortality were similar in the two groups. In comparison with the pre‐pandemic period, no AB was recorded during COVID‐19 period, (p = 0.017), while extended‐spectrum beta‐lactamase‐producing EC infections significantly decreased (p = 0.017). Overall, the ESKAPEEc isolates during pandemic less frequently exhibited multidrug‐resistant (p = 0.014). Conclusions: These findings suggest that a robust adherence to hygiene measures together with human contact restrictions in a COVID‐19 free ICU might also restrain the transmission of ESKAPEEc pathogens. [ABSTRACT FROM AUTHOR]

We aimed to report a 32-month laboratory experience with the eazyplex® CSF direct panel assay for the rapid diagnosis of meningitis due to six most common bacterial species (Escherichia coli, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis, Streptococcus agalactiae, and Streptococcus pneumoniae). We included all cerebrospinal fluid (CSF) samples from patients admitted with a clinical suspicion of meningitis/encephalitis between May 2016 and December 2018 at our hospital. In addition to the eazyplex® assay, both Gram stain microscopy and culture were performed, and results were confirmed with 16S rRNA PCR/sequencing. Patients' demographics and relevant clinical information were collected. Of 135 studied patients, 44 (32.6%) had a microbiologically documented diagnosis of meningitis. Overall, we identified 21 S. pneumoniae, 10 N. meningitidis, 6 L. monocytogenes, 3 E. coli, 2 Streptococcus pyogenes, 1 S. agalactiae, and 1 Citrobacter koseri as aetiological agents. The eazyplex® assay allowed identification in 40 (90.9%) cases, with four not identified cases due to microorganisms not included in the panel at the time of testing. Thirty-two (72.7%) cases had positive culture results, whereas 28 (63.6%) cases had positive Gram stain results. Notably, combining Gram stain and eazyplex® assay allowed identification in 100% of cases. After notification of rapid results, physicians modified the empiric antibiotic therapy, which became appropriate in three patients (all with L. monocytogenes meningitis). The eazyplex® CSF panel assay worked better than culture in detecting the most common agents of bacterial meningitis and accelerated the diagnosis leading to timely initiation or continuation of appropriate antibiotic therapy. [ABSTRACT FROM AUTHOR]

Blood culture (BC) is still the standard for diagnosing bloodstream infections (BSIs), especially those caused by bacteria and fungi. Infection-complicating sepsis or septic shock often occurs at BSI onset, making necessary to improve the diagnostic yield of positive BCs. Among the BC systems currently available, the BACT/ALERT® VIRTUO® (VIRTUO) system has been developed to shorten time to detection (TTD) of positive BCs. In this study, we assessed TTD for 330 clinically relevant species including 14 Gram-positive, 14 Gram-negative, and 5 yeast isolates in spiked human blood samples that were tested in parallel with VIRTUO BACT/ALERT® 3D (BTA3D) and BACTEC™ FX (BACTEC) systems. We inoculated 30 colony-forming unit (CFU) from each microbial suspension into BACT/ALERT® Plus or BACTEC™ Plus (aerobic/anaerobic or pediatric) BC bottles, and we used two different blood volumes to simulate, respectively, the BCs collected from adult and pediatric patients. Of 2,610 bottles tested, 2,600 (99.6%) signaled positive in the three systems. Only the BACTEC system did not detect Staphylococcus lugdunensis isolates in anaerobic bottles. Among adult simulated cultures, the median TTD was significantly shorter for aerobic/anaerobic bottles incubated in VIRTUO (11.6 h and 10.1 h) compared to bottles incubated in either BTA3D (13.3 and 12.3 h) or BACTEC (13.5 and 12.2 h) system. Among pediatric simulated cultures, the median TTD was significantly shorter for bottles incubated in VIRTUO (11.2 h) compared to bottles incubated in either the BTA3D (13.0 h) or BACTEC (12.5 h) system. Compared to BTA3D and/or BACTEC systems, VIRTUO allowed faster growth detection for most of the 33 microbial species tested. Notable examples were Salmonella spp. (7.4 h by VIRTUO vs. 10.1 h and 9.2 h by either BTA3D or BACTEC) and Streptococcus agalactiae (8.1 h by VIRTUO vs. 10.3 and 9.4 h by either BTA3D or BACTEC). The few notable exceptions included Stenotrophomonas maltophilia and some Candida species. Together, these findings confirm that VIRTUO has greater potential of improving the laboratory detection of bacteremia and fungemia than the progenitor BTA3D or the competitor BACTEC system. [ABSTRACT FROM AUTHOR]

We herein report on EUCAST RAST results for BCs consecutively collected between June 2019 and December 2019 that contained E. coli (n" 134) or K. pneumoniae (n" 66) isolates (Table S1, available as Supplementary data at JAC Online), of which 75 (37.5%) were phenotypically resistant to third-generation cephalosporins and/or carbapenems. In conclusion, we showed that the EUCAST RAST method affords an accurate and relatively easy means of testing antimicrobial susceptibility of E. coli and K. pneumoniae isolates directly in positive BC samples. Note that we tested only BC samples containing E. coli or K. pneumoniae, which are two species for which all DD plates could be read at the three timepoints. [Extracted from the article]

The proportion of antimicrobial resistance (AMR) among the ESKAPE and Escherichia coli (ESKAPEEc) pathogens causing bloodstream infection (BSI) increased worldwide. We described longitudinal trends in ESKAPEEc BSI and AMR over 9 years (2007-2015) at a large teaching hospital in Italy. Of 9720 unique BSI episodes, 6002 (61.7%) were caused by ESKAPEEc pathogens. The majority of these episodes (4374; 72.9%) were hospital-onset infections. The most frequent pathogen was E. coli (32.8%), followed by Staphylococcus aureus (20.6%), Klebsiella pneumoniae (16.1%), and Pseudomonas aeruginosa (11.6%). There was a significant increase of hospital-onset K. pneumoniae (from 2.3 to 5.0 per 10,000 patient-days; P = 0.001) and community-onset E. coli (from 3.3 to 9. 1 per 10,000 emergency admissions; P = 0.04) BSIs. Among hospital-onset BSIs, increases of extended-spectrum β-lactamase (ESBL)-producing E. coli (from 25.4 to 35.2%, P = 0.006), carbapenemase-producing K. pneumoniae (from 4.2 to 51.6%, P < 0.001), and methicillin-resistant S. aureus (from 33.9 to 44.4%, P < 0.001) BSIs were observed between the 2007-2009 and 2010-2012 study periods. In contrast, a decrease of BSIs caused by P. aeruginosa resistant to ceftazidime (from 45.5 to 28.2%, P < 0.001), ciprofloxacin (from 46 to 36.3%, P = 0.05), and meropenem (from 55 to 39.9%, P = 0.03) was observed through all 9 years of the study period. Among community-onset BSIs, increases of BSIs caused by ESBL-producing E. coli (from 28.6 to 42.2%, P = 0.002) and carbapenemase-producing K. pneumoniae (from 0 to 17.6%) were observed between the 2007-2009 and 2010-2012 study periods. Our findings show increased rates of BSI and relative AMR for specific pathogen-health care setting combinations, and call for continued active surveillance and infection control policies. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the potential synergism of colistin in combination with N-acetylcysteine against Acinetobacter baumannii strains grown in planktonic phase or as biofilms.Methods: Sixteen strains were investigated, including nine colistin-susceptible (MIC range 0.5-1 mg/L) and seven colistin-resistant (MIC range 16-256 mg/L) strains. Synergism of colistin in combination with N-acetylcysteine was investigated by chequerboard assays. The activity of colistin/N-acetylcysteine combinations was further evaluated by time-kill assays with planktonic cultures (three colistin-resistant strains and one colistin-susceptible strain) and by in vitro biofilm models (three colistin-resistant and three colistin-susceptible strains).Results: Chequerboard assays revealed a relevant synergism of colistin/N-acetylcysteine combinations with all colistin-resistant strains, whereas no synergism was observed with colistin-susceptible strains. Time-kill assays showed a concentration-dependent potentiation of colistin activity by N-acetylcysteine against colistin-resistant strains, with eradication of the culture by combinations of N-acetylcysteine at 8000 mg/L plus colistin at 2 or 8 mg/L. A static effect during the first 8 h of incubation was demonstrated with the colistin-susceptible strain exposed to 0.25 × MIC colistin plus 8000 mg/L N-acetylcysteine. A remarkable antibiofilm synergistic activity of 8 mg/L colistin plus 8000 mg/L N-acetylcysteine was demonstrated with all colistin-resistant and colistin-susceptible strains. The effects were greater with colistin-resistant strains (marked reduction of viable biofilm cells was observed at sub-MIC colistin concentrations).Conclusions: N-acetylcysteine, at concentrations achievable by topical administration, was shown to revert the colistin-resistant phenotype in A. baumannii, and to exert a relevant activity against biofilms of colistin-susceptible and colistin-resistant A. baumannii strains. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study was to evaluate the efficacy and tolerability of trimethoprim-sulfamethoxazole (also known as co-trimoxazole, TMPS) to treat Klebsiella pneumoniae (Kp)- K. pneumoniae carbapenemase (KPC) infections. Methods: Clinical data of patients with a TMPS-susceptible Kp-KPC infection were collected as a case series. Results: We report clinical outcomes and tolerability for 14 patients infected by Kp-KPC strains susceptible to TMPS, including three bloodstream infections. In ten cases (71.4%), TMPS was administered as monotherapy. In all but one case, Kp-KPC infection was cured. In the remaining patient, therapy was discontinued because of an adverse event. Conclusions: The use of TMPS to treat TMPS-susceptible Kp-KPC infections seems promising. [ABSTRACT FROM AUTHOR]

Background: Very few data exist on risk factors for developing biofilm-forming Candida bloodstream infection (CBSI) or on variables associated with the outcome of patients treated for this infection. Methods and Findings: We identified 207 patients with CBSI, from whom 84 biofilm-forming and 123 non biofilm-forming Candida isolates were recovered. A case-case-control study to identify risk factors and a cohort study to analyze outcomes were conducted. In addition, two sub-groups of case patients were analyzed after matching for age, sex, APACHE III score, and receipt of adequate antifungal therapy. Independent predictors of biofilm-forming CBSI were presence of central venous catheter (odds ratio [OR], 6.44; 95% confidence interval [95% CI], 3.21-12.92) or urinary catheter (OR, 2.40; 95% CI, 1.18-4.91), use of total parenteral nutrition (OR, 5.21; 95% CI, 2.59-10.48), and diabetes mellitus (OR, 4.47; 95% CI, 2.03-9.83). Hospital mortality, post-CBSI hospital length of stay (LOS) (calculated only among survivors), and costs of antifungal therapy were significantly greater among patients infected by biofilm-forming isolates than those infected by non-biofilm-forming isolates. Among biofilm-forming CBSI patients receiving adequate antifungal therapy, those treated with highly active antibiofilm (HAAB) agents (e.g., caspofungin) had significantly shorter post-CBSI hospital LOS than those treated with non-HAAB antifungal agents (e.g., fluconazole); this difference was confirmed when this analysis was conducted only among survivors. After matching, all the outcomes were still favorable for patients with non-biofilm-forming CBSI. Furthermore, the biofilmforming CBSI was significantly associated with a matched excess risk for hospital death of 1.77 compared to non-biofilmforming CBSI. Conclusions: Our data show that biofilm growth by Candida has an adverse impact on clinical and economic outcomes of CBSI. Of note, better outcomes were seen for those CBSI patients who received HAAB antifungal therapy. [ABSTRACT FROM AUTHOR]

Background: Pseudomonas aeruginosa represents, among the nosocomial pathogens, one of the most serious threats, both for the severity of its clinical manifestations and its ability to develop complex profiles of resistance; Methods: we retrospectively collected the data of 21 patients admitted to a tertiary-care University Hospital of Rome with infections due to XDR-P. aeruginosa isolates during the second half of 2020; Results: in our institution, the percentage of XDR-P. aeruginosa isolates is 3.1%. None of the patients was admitted to the intensive care unit at the moment of the infection's onset. Susceptibility to colistin was preserved in all the tested isolates. Rates of resistance to ceftolozane/tazobactam and ceftazidime/avibactam in these XDR strains were consistent; Conclusions: XDR-P. aeruginosa can be a threatening problem even outside the ICUs, especially in frail patients in wards with features of long-term acute care hospitals. In such a setting, ceftolozane/tazobactam and ceftazidime/avibactam should be administered with caution taking into account the microbiological susceptibility results. Colistin, even with its known safety and efficacy limits, could represent the only available therapeutic option due to its highly preserved susceptibility against XDR isolates of P. aeruginosa. [ABSTRACT FROM AUTHOR]

The aim of this study was to characterize COVID-19 (SARS-CoV-2-infected) patients who develop bloodstream infection (BSI) and to assess risk factors associated with in-hospital mortality. We conducted a retrospective observational study of adult patients admitted for ≥48 h to a large Central Italy hospital for COVID-19 (1 March to 31 May 2020) who had or had not survived at discharge. We included only patients having blood cultures drawn or other inclusion criteria satisfied. Kaplan–Meier survival or Cox regression analyses were performed of 293 COVID-19 patients studied, 46 patients (15.7%) had a hospital-acquired clinically relevant BSI secondary to SARS-CoV-2 infection, accounting for 58 episodes (49 monomicrobial and 9 polymicrobial) in total. Twelve episodes (20.7%) occurred at day 3 of hospital admission. Sixty-nine species were isolated, including Staphylococcus aureus (32.8%), Enterobacterales (20.7%), Enterococcus faecalis (17.2%), Candida (13.8%) and Pseudomonas aeruginosa (10.3%). Of 69 isolates, 27 (39.1%) were multidrug-resistant organisms. Twelve (54.5%) of 22 patients for whom empirical antimicrobial therapy was inappropriate were infected by a multidrug-resistant organism. Of 46 patients, 26 (56.5%) survived and 20 (43.5%) died. Exploring variables for association with in-hospital mortality identified > 75-year age (HR 2.97, 95% CI 1.15–7.68, p = 0.02), septic shock (HR 6.55, 95% CI 2.36–18.23, p < 0.001) and BSI onset ≤ 3 days (HR 4.68, 95% CI 1.40–15.63, p = 0.01) as risk factors independently associated with death. In our hospital, mortality among COVID-19 patients with BSI was high. While continued vigilance against these infections is essential, identification of risk factors for mortality may help to reduce fatal outcomes in patients with COVID-19. [ABSTRACT FROM AUTHOR]

(1) Background: Empirical antibiotics for suspected neonatal early-onset sepsis are often prolonged administered, even in the absence of clinical signs of infection, while awaiting the blood cultures results. The C-reactive protein is widely used to guide antibiotic therapy, although its increase in the first hours of life is not always evidence of infection. The aim of this study was to evaluate the time to positivity (TTP) of blood cultures (BC) that develop pathogens in our population of neonates and determine whether TTP could safely inform the decisions on empirical antibiotic discontinuation in neonatal early-onset sepsis and reduce the use of unnecessary antibiotics. (2) Methods: We retrospectively collected data of all newborns ≥ 34 weeks admitted to the Neonatal Intermediate-Care Unit at Policlinico "A. Gemelli" University Hospital (Rome, Italy) from 2014 to 2018, with suspected early-onset sepsis (EOS). The TTP was the time in hours from the first BC inoculation to the bacterial growth. We defined as positive BC only those with a pathogenic organism. (3) Results: In total, 103 out of 20,528 infants born in the five-year study period were admitted to our Neonatal Intermediate-Care Unit because of a suspected EOS and enrolled into the study. The mean TTP of pathogenic organisms was 17.7 ± 12.5 h versus 80.5 ± 55.8 h of contaminants (p = 0.003). We found ten positive BCs. The TTP of BC was lower than 12, 36, and 48 h in 80%, 90%, and 100% of cases, respectively. CRP levels on admission were similar in infants with a positive and negative BC (p = 0.067). The discontinuation of therapy in asymptomatic infants 48 h after initiation would have resulted in a saving of 217 days of antibiotics (31.1% of total days administered). (4) Conclusion: From our data, the TTP of blood cultures that develop pathogens is less than 48 h in 100% of cases. Therefore, in late preterm and full-term infants with suspected EOS, stopping empiric antibiotics 48 h after initiation may be a safe practice to reduce unnecessary antibiotic use, when blood cultures are negative and infants asymptomatic. [ABSTRACT FROM AUTHOR]

Corrigendum: In vitro Evaluation of BACT/ALERT® VIRTUO®, BACT/ALERT 3D®, and BACTEC™ FX Automated Blood Culture Systems for Detection of Microbial Pathogens Using Simulated Human Blood Samples Keywords: blood culture; automated system; microbial species; spiked human blood sample; diagnostic accuracy Blood culture, automated system, microbial species, spiked human blood sample, diagnostic accuracy. [Extracted from the article]

A letter to the editor is presented in response to the article "High-dose daptomycin for cardiac implantable electronic device-related infectiveendocarditis," in the November 28, 2011 issue of the journal.