Epidemiology and risk factors of 28-day mortality of hospital-acquired bloodstream infection in Turkish intensive care units: a prospective observational cohort study.

OBJECTIVES: To uncover clinical epidemiology, microbiological characteristics and outcome determinants of hospital-acquired bloodstream infections (HA-BSIs) in Turkish ICU patients. METHODS: The EUROBACT II was a prospective observational multicontinental cohort study. We performed a subanalysis of patients from 24 Turkish ICUs included in this study. Risk factors for mortality were identified using multivariable Cox frailty models. RESULTS: Of 547 patients, 58.7% were male with a median [IQR] age of 68 [55-78]. Most frequent sources of HA-BSIs were intravascular catheter [182, (33.3%)] and lower respiratory tract [175, (32.0%)]. Among isolated pathogens (n = 599), 67.1% were Gram-negative, 21.5% Gram-positive and 11.2% due to fungi. Carbapenem resistance was present in 90.4% of Acinetobacter spp., 53.1% of Klebsiella spp. and 48.8% of Pseudomonas spp. In monobacterial Gram-negative HA-BSIs (n = 329), SOFA score (aHR 1.20, 95% CI 1.14-1.27), carbapenem resistance (aHR 2.46, 95% CI 1.58-3.84), previous myocardial infarction (aHR 1.86, 95% CI 1.12-3.08), COVID-19 admission diagnosis (aHR 2.95, 95% CI 1.25-6.95) and not achieving source control (aHR 2.02, 95% CI 1.15-3.54) were associated with mortality. However, availability of clinical pharmacists (aHR 0.23, 95% CI 0.06-0.90) and source control (aHR 0.46, 95% CI 0.28-0.77) were associated with survival. In monobacterial Gram-positive HA-BSIs (n = 93), SOFA score (aHR 1.29, 95% CI 1.17-1.43) and age (aHR 1.05, 95% CI 1.03-1.08) were associated with mortality, whereas source control (aHR 0.41, 95% CI 0.20-0.87) was associated with survival. CONCLUSIONS: Considering high antimicrobial resistance rate, importance of source control and availability of clinical pharmacists, a multifaceted management programme should be adopted in Turkish ICUs.

Efficacy of cefiderocol- vs colistin-containing regimen for treatment of bacteraemic ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii in patients with COVID-19.

INTRODUCTION: Ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) in patients hospitalized in intensive care units (ICUs) is an important and challenging complication, including in patients with coronavirus disease 2019 (COVID-19). Considering the poor lung penetration of most antibiotics, including intravenous colistin due to the poor pharmacokinetics/pharmacodynamics at the infection site, the choice of the best antibiotic regimen is still being debated. METHODS: This single-centre, observational study was conducted from March 2020 to August 2022, and included all patients hospitalized consecutively with VAP and concomitant bloodstream infection due to CRAB in the COVID-ICU. The main goal of the study was to evaluate risk factors associated with survival or death at 30 days from VAP onset. A propensity score for receiving therapy was added to the model. RESULTS: During the study period, 73 patients who developed VAP and concomitant positive blood cultures caused by CRAB were enrolled in the COVID-ICU. Of these patients, 67 (91.7%) developed septic shock, 42 (57.5%) had died at 14 days and 59 (80.8%) had died at 30 days. Overall, 54 (74%) patients were treated with a colistin-containing regimen and 19 (26%) were treated with a cefiderocol-containing regimen. Cox regression analysis showed that chronic obstructive pulmonary disease and age were independently associated with 30-day mortality. Conversely, cefiderocol-containing regimens and cefiderocol + fosfomycin in combination were independently associated with 30-day survival, as confirmed by propensity score analysis. CONCLUSIONS: This real-life study in patients with bacteraemic VAP caused by CRAB provides useful suggestions for clinicians, showing a possible benefit of cefiderocol and its association with fosfomycin.

Treatment and outcome of gram-positive bacteremia in patients receiving extracorporeal membrane oxygenation.

BACKGROUND: While guidance exists for management of blood stream infections with various invasive devices, there are currently limited data to guide antibiotic selection and duration for bacteremia in patients receiving extracorporeal membrane oxygenation (ECMO). OBJECTIVE: To evaluate the treatment and outcomes of thirty-six patients with Staphylococcus aureus and Enterococcus bacteremia on ECMO support. METHODS: Blood culture data was retrospectively analyzed from patients with Staphylococcus aureus bacteremia (SAB) or Enterococcus bacteremia who underwent ECMO support between March 2012 and September 2021 at Brooke Army Medical Center. RESULTS: Of the 282 patients who received ECMO during this study period, there 25 (9%) patients developed Enterococcus bacteremia and 16 (6%) developed SAB. SAB occurred earlier in ECMO as compared to Enterococcus (median day 2 IQR (1-5) vs. 22 (12-51), p = 0.01). The most common duration of antibiotics was 28 days after clearance for SAB and 14 days after clearance for Enterococcus. 2 (5%) patients underwent cannula exchange with primary bacteremia, and 7 (17%) underwent circuit exchange. 1/3 (33%) patients with SAB and 3/10 (30%) patients with Enterococcus bacteremia who remained cannulated after completion of antibiotics had a second episode of SAB or Enterococcus bacteremia. CONCLUSION: This single center case series is the first to describe the specific treatment and outcomes of patients receiving ECMO complicated by SAB and Enterococcus bacteremia. For patients who remain on ECMO after completion of antibiotics, there is a risk of a second episode of Enterococcus bacteremia or SAB.

Gram-negative ESKAPE bacteria bloodstream infections in patients during the COVID-19 pandemic.

Bloodstream infections due to bacteria are a highly consequential nosocomial occurrences and the organisms responsible for them are usually multidrug-resistant. The aims of this study were to describe the incidence of bacteremia caused by Gram-negative ESKAPE bacilli during the COVID-19 pandemic and characterize the clinical and microbiological findings including antimicrobial resistance. A total of 115 Gram-negative ESKAPE isolates were collected from patients with nosocomial bacteremia (18% of the total bacteremias) in a tertiary care center in Mexico City from February 2020 to January 2021. These isolates were more frequently derived from the Respiratory Diseases Ward (27), followed by the Neurosurgery (12), Intensive Care Unit (11), Internal Medicine (11), and Infectious Diseases Unit (7). The most frequently isolated bacteria were Acinetobacter baumannii (34%), followed by Klebsiella pneumoniae (28%), Pseudomonas aeruginosa (23%) and Enterobacter spp (16%). A. baumannii showed the highest levels of multidrug-resistance (100%), followed by K. pneumoniae (87%), Enterobacter spp (34%) and P. aeruginosa (20%). The bla CTX-M-15 and bla TEM-1 genes were identified in all beta-lactam-resistant K. pneumoniae (27), while bla TEM-1 was found in 84.6% (33/39) of A. baumannii isolates. The carbapenemase gene bla OXA-398 was predominant among carbapenem-resistant A. baumannii (74%, 29/39) and bla OXA-24was detected in four isolates. One P. aeruginosa isolate was bla VIM-2 gene carrier, while two K. pneumoniae and one Enterobacter spp were bla NDM gene carriers. Among colistin-resistant isolates mcr-1 gene was not detected. Clonal diversity was observed in K. pneumoniae, P. aeruginosa and Enterobacter spp. Two outbreaks caused by A. baumannii ST208 and ST369 were detected, both belonging to the clonal complex CC92 and IC2. A. baumannii was associated with a death rate of 72% (28/32), most of them (86%, 24/28) extensively drug-resistant or pandrug-resistant isolates, mainly in patients with COVID-19 (86%, 24/28) in the Respiratory Diseases Ward. A. baumannii isolates had a higher mortality rate (72%), which was higher in patients with COVID-19. There was no statistically significant association between the multidrug-resistant profile in Gram-negative ESKAPE bacilli and COVID-19 disease. The results point to the important role of multidrug-resistant Gram-negative ESKAPE bacteria causing bacteremia in nosocomial settings before and during the COVID-19 epidemic. Additionally, we were unable to identify a local impact of the COVID-19 pandemic on antimicrobial resistance rates, at least in the short term.

[Salmonella Bacteremia Accompanying COVID-19: The First Salmonella Co-Infection in the World Unrelated to Pakistan]. / COVID-19'a Eslik Eden Salmonella Bakteremisi: Pakistan ile Iliskisiz Dünyadaki Ilk Salmonella Ko-Enfeksiyonu.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection emerged in China at the end of 2019 and caused coronavirus disease 2019 (COVID-19). The lymphopenia seen in COVID-19 increases the incidence of susceptibility to other microorganisms and may cause co-infections. As the signs and symptoms of the diseases overlap with other infectious diseases and due to the intensity in health services, the diagnosis of co-infections becomes difficult and the treatment may be delayed. Therefore, infections accompanying COVID-19 cause an increase in morbidity and mortality.The isolation and quarantine measures taken during the COVID-19 process have reduced the number of infections transmitted from person to person. However, there was no significant decrease in diseases transmitted by food, such as salmonellosis. During the pandemic, salmonellosis continued to be a problem, especially in endemic areas such as Pakistan, and an increase in Salmonella infections associated with backyard poultry has been reported in countries such as the United States. A co-infection of COVID-19 and enteric fever associated with travel to Pakistan was reported for the first time in the literature in February 2021. In this case report, the first co-infection of COVID-19 and Salmonella in our country was presented. A 56-yearold male patient with no known systemic disease was admitted to the hospital with fever, shortness of breath, weakness and myalgia lasting for three days. SARS-CoV-2 polymerase chain reaction test was positive. The patient has been hospitalized and favipiravir, moxifloxacin, and methylprednisolone were started. Blood cultures were taken from the patient whose clinical picture worsened and fever continued despite of the medical treatment. Salmonella enterica spp. enterica was isolated and ceftriaxone treatment was started. The patient's anamnesis was deepened, but no diarrhea, abdominal pain, suspicious food consumption, travel history were determined. From the second day of the ceftriaxone treatment, the patient's fever decreased and no growth was detected in the control blood cultures. Ceftriaxone treatment was completed in 14 days and the patient was discharged on the 28th day. Approximately 87-95% of Salmonella strains isolated in our country are S.enterica spp. enterica, and S.enterica spp. enterica was also isolated in our case. Salmonella infections most commonly present as gastroenteritis, but the risk of bacteremia increases in case of immunosuppression. Although there was no additional disease in our case, it was considered that the infection in the form of bacteremia occurred due to an immunosuppression caused by COVID-19. In this context; drawing blood cultures of patients hospitalized with the diagnosis of COVID-19 is very important in terms of detecting co-infections and superinfections, and administering appropriate antibiotic therapy at appropriate treatment times. Presentation of first case of Salmonella bacteremia and simultaneous COVID-19 infection in our country was the strong side of our report. In addition, our case is also important as being the first SARS-CoV-2 and Salmonella co-infection unrelated to Pakistan in the literature. The limitation of our case was that S.enterica spp. enterica detected in the blood culture could not be subtyped and the stool culture could not be examined. However, this does not constitute a diagnostic requirement. In addition, the patient's pre-COVID-19 Salmonella carrier status was also unknown. As a result, patients become vulnerable to other infections due to the lymphopenia seen in COVID-19. Therefore, Salmonella bacteremia can be seen with SARS-CoV-2 infection without a comorbid condition. Drawing blood cultures in hospitalized patients with the diagnosis of COVID-19 is very important in terms of detecting concomitant infections in a short time. In patients whose clinical condition does not improve and fever continues despite of treatment, blood cultures should be taken, especially in the case of an advanced immunosuppresive treatment plan, and it should always be kept in mind that secondary infections and co-infections may occur.

Unresolved issues in the epidemiology and diagnosis of bacteremia: an opinion paper.

Bacteremia is an important cause of morbidity and mortality worldwide and, despite the diagnostic and therapeutic advances of the last decades, the evidence supporting many diagnostic aspects of bacteremia is scarce. Information on the epidemiological evolution of this entity is limited and many methodological aspects of blood culture collection and analysis are under discussion. Furthermore, the recommendations of the main scientific societies on many of these aspects are variable and, in many cases, have not been updated recently. In this scenario, we have arranged a series of questions on different aspects of bacteremia and reviewed the literature trying to find proper answers for them. We offer our opinion on the topics where the evidence was weak. The topics covered include epidemiological aspects of bacteremia, indications for blood culture extraction, methods for obtaining and incubating samples, or ways of transmitting results from the microbiology laboratory. We do not intend to summarize the current clinical practice guidelines, nor will we deal with the therapeutic management of this entity. The aim of this paper is to review the current perspective on the diagnosis of bacteremia with a critical approach, to point out the gaps in the literature, to offer the opinion of a team dedicated to infectious diseases and clinical microbiology, and to identify some areas of knowledge on which future studies should focus.

Antimicrobial resistance prevalence of Escherichia coli and Staphylococcus aureus amongst bacteremic patients in Africa: a systematic review.

OBJECTIVES: Antimicrobial resistance (AMR) is a global concern among infectious diseases. Bloodstream infections can potentially become life-threatening if they become untreatable with conventional antimicrobials. This review aims to provide an understanding of the AMR prevalence and trends of common bacteremic pathogens, namely Escherichia coli and Staphylococcus aureus in the World Health Organization (WHO) Africa region. METHODS: PubMed and Google Scholar were searched using relevant keywords for published human studies (excluding case reports and reviews) reporting bacteremic AMR data on the pathogens of interest between 2008 and 2019. Two reviewers independently screened the articles against a pre-defined eligibility criterion. Data extraction and analysis were achieved with different platforms: Covidence, Excel, R version 3.6.3, and QGIS v3.4.5. The pooled prevalence, 95% confidence intervals, and I2 index (a measure of heterogeneity) were calculated for the various pathogen-antibiotic combinations. RESULTS: Five hundred sixty-two papers were retrieved, with 27 papers included in the final analysis. Only 23.4% (11/47) of member states of the WHO African region had reports on AMR in bacteremia. The Clinical and Laboratory Standards Institute (CLSI) (78.5%) was the most common standard used in the region. For E. coli, the pooled resistance was: cefotaxime (42%), imipenem (4%), meropenem (0%), and colistin (0%). For S. aureus, the calculated pooled resistance was cloxacillin (34%), oxacillin (12%), and vancomycin (0%). There was a high degree of variation across studies (I2 > 90%). CONCLUSION: The pooled resistance rates indicate a concerning degree of methicillin-resistant and Extended Spectrum-ß-lactamase-producing pathogens. The paucity of AMR data also presents challenges for a comprehensive understanding of the situation in the region. Continent-wide and standardized surveillance efforts therefore need strengthening.

Diagnostic significance of secondary bacteremia in patients with COVID-19.

OBJECTIVES: We investigated the occurrence of non-respiratory bacterial and fungal secondary infections, causative organisms, impact on clinical outcomes, and association between the secondary pathogens and mortality in hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS: This was a retrospective cohort study that included data from inpatients with COVID-19 from multiple centers participating in the Japan COVID-19 Taskforce (April 2020 to May 2021). We obtained demographic, epidemiological, and microbiological data throughout the course of hospitalization and analyzed the cases of COVID-19 complicated by non-respiratory bacterial infections. RESULTS: Of the 1914 patients included, non-respiratory bacterial infections with COVID-19 were diagnosed in 81 patients (4.2%). Of these, 59 (3.1%) were secondary infections. Bacteremia was the most frequent bacterial infection, occurring in 33 cases (55.9%), followed by urinary tract infections in 16 cases (27.1%). Staphylococcus epidermidis was the most common causative organism of bacteremia. Patients with COVID-19 with non-respiratory secondary bacterial infections had significantly higher mortality, and a multivariate logistic regression analysis demonstrated that those with bacteremia (aOdds Ratio = 15.3 [5.97-39.1]) were at higher risk of death. Multivariate logistic regression analysis showed that age, male sex, use of steroids to treat COVID-19, and intensive care unit admission increased the risk for nosocomial bacteremia. CONCLUSIONS: Secondary bacteremia is an important complication that may lead to poor prognosis in cases with COVID-19. An appropriate medical management strategy must be established, especially for patients with concomitant predisposing factors.

Waterhouse-Friderichsen Syndrome with Bilateral Adrenal Hemorrhage Associated with Methicillin-Resistant Staphylococcus aureus (MRSA) Bacteremia in an Adult Patient with History of Intravenous Drug Use.

BACKGROUND Waterhouse-Friderichsen syndrome, also known as acute adrenal insufficiency due to adrenal gland hemorrhage, is an uncommon and frequently fatal condition classically presenting with fever, shock, rash, and coagulopathy. Although most often associated with Meningococcemia, many other etiologies have been implicated, including reports of Staphylococcus aureus infection on autopsy examinations. This report details an adult intravenous drug user with adrenal hemorrhage associated with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. CASE REPORT A 58-year-old man with a history of intravenous drug use presented to the hospital with weakness. Vitals were initially normal and exam findings were notable for decreased right-sided motor strength. Magnetic resonance imaging (MRI) revealed a cervical epidural abscess with spinal cord compression. Despite initiation of broad-spectrum antibiotics and intravenous fluids, the patient progressed to shock, requiring vasopressor administration, and his blood cultures later grew MRSA. Further imaging of the abdomen/pelvis was completed, revealing bilateral adrenal hemorrhage. Random cortisol at that time was 5.6 µg/dL, confirming a diagnosis of critical illness-related corticosteroid insufficiency in addition to likely septic and spinal shock. The patient was initiated on hydrocortisone with improvement in his hypotension. He was transitioned to prednisone and fludrocortisone in addition to 8 weeks of antibiotics after achieving clinical stability. CONCLUSIONS This report brings to attention the risk of adrenal hemorrhage and acute adrenal insufficiency as a sequela of the relatively common illness of Staphylococcus aureus bacteremia. As symptoms of adrenal insufficiency can overlap with septic shock related to the primary condition, this diagnosis requires a high index of suspicion in the critically ill patient.

Risk stratification for selecting empiric antibiotherapy during and after COVID-19.

PURPOSE OF REVIEW: SARS-CoV-2 deeply modified the risk of bacterial infection, bacterial resistance, and antibiotic strategies. This review summarized what we have learned. RECENT FINDINGS: During the COVID-19 pandemic, we observed an increase in healthcare-acquired infection and multidrug-resistant organism-related infection, triggered by several factors: structural factors, such as increased workload and ongoing outbreaks, underlying illnesses, invasive procedures, and treatment-induced immunosuppression. The two most frequently healthcare-acquired infections described in patients hospitalized with COVID-19 were bloodstream infection, related or not to catheters, health-acquired pneumonia (in ventilated or nonventilated patients). The most frequent species involved in bacteremia were Gram-positive cocci and Gram-negative bacilli in health-acquired pneumonia. The rate of Gram-negative bacilli is particularly high in late-onset ventilator-associated pneumonia, and the specific risk of Pseudomonas aeruginosa- related pneumonia increased when the duration of ventilation was longer than 7 days. A specificity that remains unexplained so far is the increase in enterococci bacteremia. SUMMARY: The choice of empiric antibiotimicrobials depends on several factors such as the site of the infection, time of onset and previous length of stay, previous antibiotic therapy, and known multidrug-resistant organism colonization. Pharmacokinetics of antimicrobials could be markedly altered during SARS-CoV-2 acute respiratory failure, which should encourage to perform therapeutic drug monitoring.

Omicron variant of SARS-CoV-2, an epidemiologic assessment of pediatric oncology patients in the Bronx.

BACKGROUND: Children receiving cytotoxic therapy for cancer have increased risk of infection due to drug-induced neutropenia and are therefore treated empirically for bacteremia when febrile or ill-appearing. However, viral infections, which are not frequently life-threatening, are the most common etiology of febrile episodes and there has been increased effort to differentiate patients who may have a higher risk for adverse outcomes. CASE: We performed a retrospective chart review of pediatric oncology patients diagnosed with COVID-19 between December 20, 2021 and February 22, 2022 during the Omicron (B.1.1.529) surge at The Children's Hospital at Montefiore, a tertiary care center in the Bronx. CONCLUSION: We found that no patients in our cohort developed respiratory distress, bacteremia, or serious illness after COVID-19 infection during the Omicron surge. Future studies will aid in understanding the relationship between community-acquired infections and bacteremia, and this knowledge can then be applied to develop optimal infection prevention clinical care guidelines.

Human Cell-Camouflaged Nanomagnetic Scavengers Restore Immune Homeostasis in a Rodent Model with Bacteremia.

Bloodstream infection caused by antimicrobial resistance pathogens is a global concern because it is difficult to treat with conventional therapy. Here, scavenger magnetic nanoparticles enveloped by nanovesicles derived from blood cells (MNVs) are reported, which magnetically eradicate an extreme range of pathogens in an extracorporeal circuit. It is quantitatively revealed that glycophorin A and complement receptor (CR) 1 on red blood cell (RBC)-MNVs predominantly capture human fecal bacteria, carbapenem-resistant (CR) Escherichia  coli, and extended-spectrum beta-lactamases-positive (ESBL-positive) E. coli, vancomycin-intermediate Staphylococcus aureus (VISA), endotoxins, and proinflammatory cytokines in human blood. Additionally, CR3 and CR1 on white blood cell-MNVs mainly contribute to depleting the virus envelope proteins of Zika, SARS-CoV-2, and their variants in human blood. Supplementing opsonins into the blood significantly augments the pathogen removal efficiency due to its combinatorial interactions between pathogens and CR1 and CR3 on MNVs. The extracorporeal blood cleansing enables full recovery of lethally infected rodent animals within 7 days by treating them twice in series. It is also validated that parameters reflecting immune homeostasis, such as blood cell counts, cytokine levels, and transcriptomics changes, are restored in blood of the fatally infected rats after treatment.

Update on Staphylococcus aureus bacteraemia.

PURPOSE OF REVIEW: To review recently published evidence relevant to Staphylococcus aureus bacteremia (SAB). RECENT FINDINGS: Staphylococcus aureus is the most common pathogen causing co-infections and superinfections in patients with COVID-19. Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia ratios have sharply risen during the pandemic. SAB mortality is 18% at 1 month and 27% at 3 months but has gradually decreased over the last 30 years. Recurrences and reinfections are common (9%). Standardised items to define complicated SAB, and a new cut-off defining persisting bacteremia after 2 days with positive blood cultures have been proposed. Multiple antibiotic combinations have been trialled including vancomycin or daptomycin with ß-lactams, fosfomycin, or clindamycin, without significant results. In the recently published guidelines, vancomycin remains the first line of treatment for MRSA bacteremia. For the management of methicillin-susceptible Staphylococcus aureus , cefazolin less frequently causes acute kidney injury than flucloxacillin, and when susceptibility is demonstrated, de-escalation to penicillin G is suggested. SUMMARY: Our review confirms that Staphylococcus aureus represents a special aetiology among all causes of bloodstream infections. Pending results of platform and larger trials, its distinct epidemiology and determinants mandate careful integration of clinical variables and best available evidence to optimize patient outcomes.

Decreased quality of care for Staphylococcus aureus bacteremia during the COVID-19 pandemic.

OBJECTIVES: Staphylococcus aureus bacteremia (SAB) is one of the most frequent bloodstream infections. High mortality of SAB can be significantly reduced by regular infectious disease (ID) consultations and appropriate clinical management. Because the pandemic of coronavirus disease 2019 (COVID-19) has had a negative impact on hospital ID service, it can be assumed that it has also led to decreased quality of care for SAB patients. METHODS: This study enrolled all (n = 68) patients with proven SAB who were hospitalized in Military University Hospital, Prague, in 2019 and 2020 and the quality of care indicators for SAB patients were compared. RESULTS: A total of 33 and 35 patients with SAB were hospitalized in our hospital in 2019 and 2020, respectively. The significant difference between the pandemic year 2020 and year 2019 was in ID consultations performed (74% vs. 100%; p = 0.002) and fulfilment of all quality of care indicators (66% vs. 93%; p = 0.012). Next, higher in-hospital mortality was observed in 2020 than in 2019 (6% vs. 23%; p = 0.085). There was no significant difference in the percentages of patients with performed echocardiographic examinations (66% vs. 83%; p = 0.156) and collected follow-up blood cultures (85% vs. 94%; p = 0.428). In addition, there was no difference between the two years in the adequate antibiotic therapy, sources, and bacterial origin of SAB. CONCLUSIONS: The quality of care of SAB patients significantly decreased during the COVID-19 pandemic in our institution.

Managing hospitalized patients with bacterial infections: the price-to-pay upon site of infection.

INTRODUCTION: Infections impose a significant burden on healthcare costs worldwide. We aimed to explore antibiotic- and hospital-related costs of infections needing admission in a tertiary university hospital in Greece. METHODS: We performed a prospective cohort study in the medical care unit of a tertiary university hospital in Greece, for the period May 2016 to May 2018. Patients admitted with respiratory, urinary, gastrointestinal tract, skin, soft tissue and bone infections or primary bacteremia were included in this study. Costs of hospitalization and unit cost of antibiotic regimen were retrieved from a database for Greek hospitals containing data for each International Classification of Diseases (ICD-10) code and the national formulary respectively, and manually calculated for each patient. RESULTS: Antibiotic costs represent approximately 14-40% of total hospital-related costs depending on infection studied. Skin, soft tissue and bone infections and primary bacteremia led hospital- and antibiotic-related costs, with median costs of €6370 (interquartile range (IQR) 3330.90-11 503.90), €2519.90 (IQR 431.50-8371.10), €4418.10 (IQR 2335-8281.90) and €1394.30 (IQR 519.12-6459.90), respectively. Antibiotic- and hospital-related costs significantly differs with site of infection (p<0.0001). Length of stay is strongly correlated with antibiotic- and hospital-related costs, while site of infection is moderately related to antibiotic cost (eta value 0.445), and hospital-related cost (eta value 0.387). CONCLUSION: Healthcare-related costs vary substantially depending on site of infection. Information about real-life costs can drive best decisions and help to reduce healthcare expenditures.

Bacteremia in Children with Solid Tumors: Etiology, Antimicrobial Susceptibility, Factors Associated with Multidrug Resistance, and Mortality.

This retrospective study aims to describe the etiology and resistance patterns of pathogens causing bacteremia in children with solid tumors in a tertiary pediatric hematology-oncology center in Jerusalem, Israel (2011-2019). Factors associated with multidrug-resistant (MDR) bacteremia and mortality were analyzed. A total of 228 pathogens were isolated in 126 patients; 61.0% were gram-negative rods (GNR) and 38.2% were gram-positive cocci (GPC). The most common pathogens were Klebsiella pneumoniae (19.3%), Escherichia coli (17.5%), and coagulase-negative staphylococci (16.2%). The proportion of MDR-GNR was 18.2%, while the proportion of MDR-GPC was 55.2%. In logistic regression analysis, breakthrough bacteremia on a penicillin-group antibiotic (odds ratio [OR] 5.69, [95% confidence interval 1.42-22.76], p-value = 0.014) was associated and underlying diagnosis of neuroblastoma was inversely associated (OR 0.17, [0.04-0.81], p-value = 0.026) with MDR-GNR bacteremia; while the previous hospitalizations' duration (OR 1.032/day, [1.01-1.06], p-value = 0.007) and oncologic treatment intensity (OR 2.19, [1.08-4.45, p-value = 0.03) were associated with MDR-GPC bacteremia. Shock, prolonged profound neutropenia, and pediatric intensive care unit (PICU) admission were associated with 7-day mortality; and relapsed disease, oncologic treatment intensity, prolonged profound neutropenia, and PICU admission-with 30-day mortality in the univariate analyses. Empirical antibiotic choice should be based on factors associated with MDR infections in this specific population.

A case of Bacillus subtilis var. natto bacteremia caused by ingestion of natto during COVID-19 treatment in a maintenance hemodialysis patient with multiple myeloma.

A 70-year-old woman, who started on hemodialysis 7 months before for end-stage renal disease due to diabetic nephropathy and was diagnosed with symptomatic multiple myeloma 1 month before, was admitted to our hospital with critical coronavirus disease 2019 and treated with long-term immunosuppressive therapy such as steroids and tocilizumab. During treatment, Bacillus subtilis was detected in the blood cultures. We could not exclude the association of natto (fermented soybeans) with B. subtilis var. natto, which the patient had been eating every day from 8 days after admission. She was prohibited from eating natto and treated with vancomycin. Later, B. subtilis detected in the blood culture was identified as B. subtilis var. natto, which was identical with those contained in the natto that the patient consumed daily using a next-generation sequencer. Gut dysbiosis due to old age, malignant tumor, diabetes mellitus, end-stage renal disease, and intestinal inflammation caused by severe acute respiratory syndrome coronavirus 2 increased intestinal permeability and the risk of bacterial translocation, causing B. subtilis var. natto bacteremia. Therefore, careful consideration might be given to the intake of fermented foods containing live bacteria in patients with severe immunocompromised conditions.