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.

Detoxified synthetic bacterial membrane vesicles as a vaccine platform against bacteria and SARS-CoV-2.

The development of vaccines based on outer membrane vesicles (OMV) that naturally bud off from bacteria is an evolving field in infectious diseases. However, the inherent inflammatory nature of OMV limits their use as human vaccines. This study employed an engineered vesicle technology to develop synthetic bacterial vesicles (SyBV) that activate the immune system without the severe immunotoxicity of OMV. SyBV were generated from bacterial membranes through treatment with detergent and ionic stress. SyBV induced less inflammatory responses in macrophages and in mice compared to natural OMV. Immunization with SyBV or OMV induced comparable antigen-specific adaptive immunity. Specifically, immunization with Pseudomonas aeruginosa-derived SyBV protected mice against bacterial challenge, and this was accompanied by significant reduction in lung cell infiltration and inflammatory cytokines. Further, immunization with Escherichia coli-derived SyBV protected mice against E. coli sepsis, comparable to OMV-immunized group. The protective activity of SyBV was driven by the stimulation of B-cell and T-cell immunity. Also, SyBV were engineered to display the SARS-CoV-2 S1 protein on their surface, and these vesicles induced specific S1 protein antibody and T-cell responses. Collectively, these results demonstrate that SyBV may be a safe and efficient vaccine platform for the prevention of bacterial and viral infections.

Prevalence of Urinary Tract Infection, Bacteremia, and Meningitis Among Febrile Infants Aged 8 to 60 Days With SARS-CoV-2.

Importance: The prevalence of urinary tract infection (UTI), bacteremia, and bacterial meningitis in febrile infants with SARS-CoV-2 is largely unknown. Knowledge of the prevalence of these bacterial infections among febrile infants with SARS-CoV-2 can inform clinical decision-making. Objective: To describe the prevalence of UTI, bacteremia, and bacterial meningitis among febrile infants aged 8 to 60 days with SARS-CoV-2 vs without SARS-CoV-2. Design, Setting, and Participants: This multicenter cross-sectional study was conducted as part of a quality improvement initiative at 106 hospitals in the US and Canada. Participants included full-term, previously healthy, well-appearing infants aged 8 to 60 days without bronchiolitis and with a temperature of at least 38 °C who underwent SARS-CoV-2 testing in the emergency department or hospital between November 1, 2020, and October 31, 2022. Statistical analysis was performed from September 2022 to March 2023. Exposures: SARS-CoV-2 positivity and, for SARS-CoV-2-positive infants, the presence of normal vs abnormal inflammatory marker (IM) levels. Main Outcomes and Measures: Outcomes were ascertained by medical record review and included the prevalence of UTI, bacteremia without meningitis, and bacterial meningitis. The proportion of infants who were SARS-CoV-2 positive vs negative was calculated for each infection type, and stratified by age group and normal vs abnormal IMs. Results: Among 14 402 febrile infants with SARS-CoV-2 testing, 8413 (58.4%) were aged 29 to 60 days; 8143 (56.5%) were male; and 3753 (26.1%) tested positive. Compared with infants who tested negative, a lower proportion of infants who tested positive for SARS-CoV-2 had UTI (0.8% [95% CI, 0.5%-1.1%]) vs 7.6% [95% CI, 7.1%-8.1%]), bacteremia without meningitis (0.2% [95% CI, 0.1%-0.3%] vs 2.1% [95% CI, 1.8%-2.4%]), and bacterial meningitis (<0.1% [95% CI, 0%-0.2%] vs 0.5% [95% CI, 0.4%-0.6%]). Among infants aged 29 to 60 days who tested positive for SARS-CoV-2, 0.4% (95% CI, 0.2%-0.7%) had UTI, less than 0.1% (95% CI, 0%-0.2%) had bacteremia, and less than 0.1% (95% CI, 0%-0.1%) had meningitis. Among SARS-CoV-2-positive infants, a lower proportion of those with normal IMs had bacteremia and/or bacterial meningitis compared with those with abnormal IMs (<0.1% [0%-0.2%] vs 1.8% [0.6%-3.1%]). Conclusions and Relevance: The prevalence of UTI, bacteremia, and bacterial meningitis was lower for febrile infants who tested positive for SARS-CoV-2, particularly infants aged 29 to 60 days and those with normal IMs. These findings may help inform management of certain febrile infants who test positive for SARS-CoV-2.

[Impact of Staphylococcus aureus bacteremia in COVID-19 patients]. / Impacto de la bacteriemia por Staphylococcus aureus en pacientes con COVID-19.

OBJECTIVE: The disease caused by SARS-CoV-2 (COVID-19) has been a challenge for healthcare professionals since its appearance. Staphylococcus aureus has been described as one of the main pathogens causing bacterial infections in viral pandemics. However, co- infection with S. aureus causing bacteremia in patients with COVID-19 has yet to be well studied. METHODS: We performed a e study of S. aureus bacteremia (SAB) at Hospital Miguel Servet (Zaragoza) from March 2020 to February 2021. The clinical characteristics, mortality and risk factors of adults hospitalized patients with BSA associated COVID-19 compared to patients without COVID-19. RESULTS: A total of 95 patients with SAB were identified. 27.3% were positive for SARS-CoV-2. SAB represented 9.9% of bacteremia, being the second agent in frequency after E. coli. Nosocomial bacteremia was more frequent in the group of COVID-19 patients. The most frequent source of BSA in these patients was the respiratory source (26.9% vs 0%; P<0.001) followed by the skin (15.5% vs 15.9%; P=1). The development of sepsis was more frequent in COVID-19 patients (61,5% vs 7,8%; P=0,336) and among them, who received dexamethasone at doses > 6 mg/day (62.5% vs. 37.5%, P<0.05). CONCLUSIONS: Our data suggest that BSA has a negative impact on the evolution of patients with COVID-19. However, further and preferably prospective studies are required to obtain solid data on the impact of BSA on coronavirus patients.

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.

Endofungal Mycetohabitans rhizoxinica Bacteremia Associated with Rhizopus microsporus Respiratory Tract Infection.

We report Mycetohabitans rhizoxinica bacteremia in a 65-year-old woman in California, USA, who was undergoing chimeric antigen receptor T-cell therapy for multiple myeloma. Acute brain infarction and pneumonia developed; Rhizopus microsporus mold was isolated from tracheal suction. Whole-genome sequencing confirmed bacteria in blood as genetically identical to endofungal bacteria inside the mold.

[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.

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.

Clearance of blood stream infections in patients receiving extracorporeal membrane oxygenation: a retrospective single-center cohort study.

BACKGROUND: There are limited data on the treatment of blood stream infections (BSIs) in patients receiving extracorporeal membrane oxygenation (ECMO). Current guidance recommends documenting clearance only in fungal and Gram-positive BSIs. This study investigates the incidence and clinical significance of blood stream infections with positive repeat cultures (BSIPRC) in ECMO as well as clinical factors that may predict positive repeat cultures. METHODS: All BSIs in patients receiving ECMO at Brooke Army Medical Center between September 2012 and October 2021 were included in this study. BSIPRC was defined as re-isolation of the same organism on repeat blood cultures following an initial positive blood culture. RESULTS: A total of 60 patients developed 87 BSI (38.5 BSI per 1000 ECMO days). Of the 80 (92%) BSIs who had repeat blood cultures drawn, patients had BSIPRC in 35 (44%) of cases. Fever, leukocytosis, and vasopressor requirement on day of repeat culture were not associated with persistent positivity. There was no difference in survival to discharge for patients with BSIPRC as compared to single day BSI (58% vs. 63%, p = 0.78). 19% of patients with Gram-negative bacteremia had BSIPRC, and gram-negative bacteremia in general was associated with an 83% morality. CONCLUSIONS: There were no clinical findings that differentiated patients with BSIPRC from those who had a single day of positivity. BSI was associated with high mortality in patients with Gram-negative bacteremia. Given high incidence of positive repeat cultures being seen in Gram-negative BSIs, repeat blood cultures have utility for all BSIs in patients receiving ECMO.

Inquilinus limosus Bacteremia in Lung Transplant Recipient after SARS-CoV-2 Infection.

Inquilinus limosus is an environmental bacterium associated with respiratory tract colonization in cystic fibrosis patients. We report a case of I. limosus bacteremia in a patient in France who received a lung transplant and experienced chronic graft dysfunction and SARS-CoV-2 infection. This case suggests I. limosus displays virulence factors associated with invasion.

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.

COVID-19 in Patients with Cancer: Insights from a Tertiary Care Intensive Care Unit (preprint)

Background & Aim: Since The emergence of the COVID-19, patients with cancer have been among the most vulnerable patients, as this infection can be severe and mostly requires intensive care therapy. Literature discussing the risk factors and the outcome of these patients in intensive care units (ICU) is accumulating. Our study aims to search for the incidence of COVID-19 infection in cancer patients and analyses their associated comorbidities, possible risk factor for infections, and their outcomes. Methods: Patients with active cancer under treatment and those recently diagnosed with cancer and had confirmed COVID-19 infection requiring ICU admission were included in our study over 8 months, from March to October 2022. Patient demographic data, comorbidities, ICU stay, duration of hospital stay, oxygenation/ventilatory requirements, treatment, secondary bacterial infection, and outcome were collected from the COVID-19 patients' registry in the ICU. Data were entered into the SPSS program version 23, and results were considered statistically significant at p ≤ 0.05. Results:  A total of 24 patients with cancer and COVID-19 infection required intensive care therapy. The most common type of malignancy in those patients was solid organ tumor (13 vs. 11 patients), and most of the study sample were males (20/ 83.3%). Seventy-five percent (18 patients) required intubation and invasive ventilation. Twenty-nine percent (7 patients) had secondary bacterial pneumonia and bacteremia. In addition, 70% had septic shock and required vasopressors. Acute kidney injury (AKI) due to rhabdomyolysis (P<0.001), secondary bacterial infection (P<0.006), bacteremia and pneumonia (P<0.02), invasive ventilation (P<0.02) and requiring muscle relaxant (P<0.02), the requirement for High flow nasal cannula and prone position (P<0.03 and 0.01) respectively, shock (P<0.004) were significantly associated with increased mortality. Patients with cancer and COVID-19 had higher severity scores (P<0.003), longer ventilation duration (P<0.002), and ICU stay (P<0.002). Overall mortality was 45%.8, there was no significant difference in mortality rate between patients with solid organ tumors and hematological malignancy with COVID-19 infection requiring intensive care therapy (P<0.68). Conclusion: Cancer patients requiring ICU were more prone to develop AKI, rhabdomyolysis, secondary infection, requiring ventilation and prone position, and septic shock. These patients had a significantly high mortality rate and were severely ill, requiring prolonged ventilation and ICU stays.

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.

COVID-19 bacteremic co-infection is a major risk factor for mortality, ICU admission, and mechanical ventilation.

BACKGROUND: Recent single-center reports have suggested that community-acquired bacteremic co-infection in the context of Coronavirus disease 2019 (COVID-19) may be an important driver of mortality; however, these reports have not been validated with a multicenter, demographically diverse, cohort study with data spanning the pandemic. METHODS: In this multicenter, retrospective cohort study, inpatient encounters were assessed for COVID-19 with community-acquired bacteremic co-infection using 48-h post-admission blood cultures and grouped by: (1) confirmed co-infection [recovery of bacterial pathogen], (2) suspected co-infection [negative culture with ≥ 2 antimicrobials administered], and (3) no evidence of co-infection [no culture]. The primary outcomes were in-hospital mortality, ICU admission, and mechanical ventilation. COVID-19 bacterial co-infection risk factors and impact on primary outcomes were determined using multivariate logistic regressions and expressed as adjusted odds ratios with 95% confidence intervals (Cohort, OR 95% CI, Wald test p value). RESULTS: The studied cohorts included 13,781 COVID-19 inpatient encounters from 2020 to 2022 in the University of Alabama at Birmingham (UAB, n = 4075) and Ochsner Louisiana State University Health-Shreveport (OLHS, n = 9706) cohorts with confirmed (2.5%), suspected (46%), or no community-acquired bacterial co-infection (51.5%) and a comparison cohort consisting of 99,170 inpatient encounters from 2010 to 2019 (UAB pre-COVID-19 pandemic cohort). Significantly increased likelihood of COVID-19 bacterial co-infection was observed in patients with elevated ≥ 15 neutrophil-to-lymphocyte ratio (UAB: 1.95 [1.21-3.07]; OLHS: 3.65 [2.66-5.05], p < 0.001 for both) within 48-h of hospital admission. Bacterial co-infection was found to confer the greatest increased risk for in-hospital mortality (UAB: 3.07 [2.42-5.46]; OLHS: 4.05 [2.29-6.97], p < 0.001 for both), ICU admission (UAB: 4.47 [2.87-7.09], OLHS: 2.65 [2.00-3.48], p < 0.001 for both), and mechanical ventilation (UAB: 3.84 [2.21-6.12]; OLHS: 2.75 [1.87-3.92], p < 0.001 for both) across both cohorts, as compared to other risk factors for severe disease. Observed mortality in COVID-19 bacterial co-infection (24%) dramatically exceeds the mortality rate associated with community-acquired bacteremia in pre-COVID-19 pandemic inpatients (5.9%) and was consistent across alpha, delta, and omicron SARS-CoV-2 variants. CONCLUSIONS: Elevated neutrophil-to-lymphocyte ratio is a prognostic indicator of COVID-19 bacterial co-infection within 48-h of admission. Community-acquired bacterial co-infection, as defined by blood culture-positive results, confers greater increased risk of in-hospital mortality, ICU admission, and mechanical ventilation than previously described risk factors (advanced age, select comorbidities, male sex) for COVID-19 mortality, and is independent of SARS-CoV-2 variant.

Staphylococcus aureus bacteremia in patients with SARS-CoV-2 infection.

OBJECTIVES: The aim was to compare the incidence of Staphylococcus aureus bacteremia in COVID-19 and non-COVID-19 adult patients during the pandemic period versus the previous two years. Also, we described the characteristics of both cohorts of patients in pandemic period to find differences. MATERIAL AND METHODS: Retrospective study in our tertiary-care centre reviewing S. aureus bacteremia episodes in COVID-19 and non-COVID-19 patients through clinical records and the Microbiology Department database. RESULTS: In 2018 and 2019, the incidence of S. aureus bacteremia episodes was 1.95 and 1.63 per 1000 admissions respectively. In the pandemic period, global incidence was 1.96 episodes per 1000 non-COVID-19 admissions and 10.59 episodes per 1000 COVID-19 admissions. A total of 241 bacteremia was registered during this pandemic period in 74 COVID-19 patients and in 167 non-COVID-19 patients. Methicillin resistance was detected in 32.4% and 13.8% of isolates from COVID-19 and non-COVID-19 patients respectively. In COVID-19 patients, mortality rates were significantly higher. CONCLUSIONS: We showed a significantly high rates of S. aureus bacteremia incidence in COVID-19 patients and higher methicillin resistance and 15-day mortality rates than in non-COVID-19 patients.

Phase I Clinical Trial. Safety of Baricitinib to prevent respiratory insufficiency in oncohematological patients affected by Coronavirus Disease-19: BARCOVID19 study (preprint)

Background Oncohematological patients, due to their secondary immunodeficiency, are at a higher risk of mortality related to COVID-19 infection. Baricitinib, a JAK2 inhibitor, has a dual effect in this context, reducing the inflammatory response to the virus and diminishing virus endocytosis. Methods This phase I safety run-in cohort study aimed to determine the dose-limiting toxicity of baricitinib in terms of the rate of serious events in oncohematological patients with COVID-19. The drug was administered on an inpatient basis at an oral dose of 4 mg daily for 5 to 7 days, associated with the institutional standard of care (SOC). Results Six patients with solid tumors or hematological malignancies were enrolled in the study. Sixty percent of the patients received active anticancer treatment at the time of inclusion. Lymphopenia and elevation of acute-phase reactants were the most frequent laboratory findings that improved during the treatment course. All patients received corticosteroids, but only 3 of them received remdesivir as the SOC. The most common adverse events were bacterial infections, including pneumonia, urinary tract infections, and bacteremia. The mortality rate due to disease progression and respiratory insufficiency is 33%. The severe adverse event rate was less than 33%, with no adverse events or mortality caused by baricitinib. Conclusions The results of the present study demonstrate that baricitinib is a safe treatment for patients with oncohematological diseases and COVID-19. However, its efficacy and superiority to standard treatment will require further testing in phases 2 and 3 trials. Trial registration: AEMPs: 20–0356 EudraCT: 2020-001789-12