Initial empirical antibiotic therapy in kidney transplant recipients with pyelonephritis: A global survey of current practice and opinions across 19 countries on six continents.

BACKGROUND: Despite the burden of pyelonephritis after kidney transplantation, there is no consensus on initial empirical antibiotic management. METHODS: We surveyed clinicians throughout the world on their practice and opinions about the initial empirical therapy of post-transplant pyelonephritis, using clinical vignettes. A panel of experts from 19 countries on six continents designed this survey, and invited 2145 clinicians to participate. RESULTS: A total of 721 clinicians completed the survey (response rate: 34%). In the hypothetical case of a kidney transplant recipient admitted with pyelonephritis but not requiring intensive care, most respondents reported initiating either a 3rd-generation cephalosporin (37%) or piperacillin-tazobactam (21%) monotherapy. Several patient-level factors dictated the selection of broader-spectrum antibiotics, including having a recent urine culture showing growth of a resistant organism (85% for extended-spectrum ß-lactamase-producing organisms, 90% for carbapenemase-producing organisms, and 94% for Pseudomonas aeruginosa). Respondents attributed high importance to the appropriateness of empirical therapy, which 87% judged important to prevent mortality. Significant practice and opinion variations were observed between and within countries. CONCLUSION: High-quality studies are needed to guide the empirical management of post-transplant pyelonephritis. In particular, whether prior urine culture results should systematically be reviewed and considered remains to be determined. Studies are also needed to clarify the relationship between the appropriateness of initial empirical therapy and outcomes of post-transplant pyelonephritis.

Scientific misconduct in infectious diseases-European Society of Clinical Microbiology and Infectious Diseases survey.

OBJECTIVES: We aimed to evaluate the prevalence and perception of scientific misconduct in infectious diseases (ID) and clinical microbiology (CM), as reported by the ID/CM community. METHODS: An anonymous online European Society of Clinical Microbiology and Infectious Diseases survey circulated among society members from October 2023 to June 2024; the questionnaire included data on participants' views on their own and their colleagues' scientific misconduct in the last 5 years. RESULTS: The survey received 220 responses. Responders were 73% ID physicians, 52% men, 56% aged 35-54 years, and represented 48 countries, mainly European (126 participants). The vast majority of participants (78%) reported that they did not personally commit scientific misconduct, whereas 54% reported witnessing misconduct by colleagues in their field. The most commonly committed misconduct by both responders and their colleagues was misconduct of authorship rules, 14% and 41%, respectively. Overall, 18% reported witnessing misleading reporting and 14% reported witnessing nonaccurate reporting of conflict of interest. Nevertheless, the majority (>60%) of responders reported high confidence in the integrity of published work in the field of ID/CM. Approximately one-third of responders were not aware of the European Society of Clinical Microbiology and Infectious Diseases ethics advisory committee as an authority to which members can report misconduct. DISCUSSION: Scientific misconduct, mostly related to violation of authorship rules, seems to be common in ID/CM. Efforts to improve scientific integrity should be made to keep trust in the scientific process.

Varicella-Zoster Virus-Induced Neurologic Disease After COVID-19 Vaccination: A Multicenter Observational Cohort Study.

Background: Early reports described an increased risk of herpes zoster following receipt of mRNA-based COVID-19 vaccines. The objective was to assess whether COVID-19 vaccine is associated with varicella-zoster virus-induced neurologic disease (VZV-ND). Methods: This multicenter retrospective case-control study with a test-negative design was conducted at 12 hospitals in Israel. We included all patients admitted with VZV-ND between January 2020 and December 2021 and matched controls with a negative polymerase chain reaction result for VZV in cerebrospinal fluid. Results: We identified 188 patients meeting the case definition of VZV-ND who were admitted during the study period. Cases were matched with 376 controls. There was no significant variation in the incidence of VZV-ND between 1 year preceding and 1 year following the deployment of BNT162b2 in Israel. Analysis of persons who had received at least 1 dose of COVID-19 vaccine (n = 259) showed similar proportions of VZV-ND and non-VZV-ND in 4 intervals (30, 42, 50, 60 days) following the last vaccine dose. The median time from the last vaccine dose to hospitalization with a neurologic syndrome was 53 days (IQR, 25-128) and 82 days (IQR, 36-132) for VZV-ND and non-VZV-ND, respectively, not reaching statistical significance (P = .056). The rate of VZV-ND in vaccinated patients was no different from the rate in the unvaccinated group (30.9% vs 35.4%, P = .2). Conclusions: We did not find an association between COVID-19 vaccine and VZV-ND. Since COVID-19 vaccine is now recommended yearly, every fall and winter, establishing the safety of the vaccine is of great importance.

Clinical impact of active screening cultures for carbapenem-resistant Acinetobacter baumannii: A systematic review and meta-analysis.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as a significant health care-associated infection carrying substantial mortality. We assessed the clinical impact of active screening cultures for CRAB. METHODS: A systematic review and meta-analysis, aiming to answer 2 questions: (1) Does screening versus no screening improve clinical outcomes? (2) Does positive screening ("CRAB carrier") predict CRAB infections? We searched the literature until January 2024 for comparative studies reporting clinical outcomes (mortality, invasive CRAB infections). RESULTS: Of 5,407 screened publications, 9 studies (10,865 individuals) were included. Invasive CRAB infection rate was significantly higher among CRAB carriers (OR 11.14, 95% CI 4.95-25.05, with substantial heterogeneity stemming from size rather than direction of the effect). Negative predictive value of noncarriage for invasive infection was 97%. CRAB bloodstream infection rate was significantly higher among carriers (odds ratio 16.23, 95% confidence interval 2.9-110.08). No difference was demonstrated between the groups for CRAB ventilator-associated pneumonia, length of stay, and mortality. Only 1 study reported outcomes for study question #1. CONCLUSIONS: Data to support active CRAB screening are scarce regarding its clinical benefit for patients. Positively screened patients are at significantly higher risk for invasive CRAB infections, with high negative predictive value for noncarriage. This did not translate to reduced mortality.

Women's Representation in RCTs Evaluating FDA-Supervised Medical Devices: A Systematic Review.

This systematic review evaluates the representation of women in randomized clinical trials (RCTs) of US Food and Drug Administration (FDA)­supervised medical devices.

Presentation, management, and outcomes of older compared to younger adults with hospital-acquired bloodstream infections in the intensive care unit: a multicenter cohort study.

PURPOSE: Older adults admitted to the intensive care unit (ICU) usually have fair baseline functional capacity, yet their age and frailty may compromise their management. We compared the characteristics and management of older (≥ 75 years) versus younger adults hospitalized in ICU with hospital-acquired bloodstream infection (HA-BSI). METHODS: Nested cohort study within the EUROBACT-2 database, a multinational prospective cohort study including adults (≥ 18 years) hospitalized in the ICU during 2019-2021. We compared older versus younger adults in terms of infection characteristics (clinical signs and symptoms, source, and microbiological data), management (imaging, source control, antimicrobial therapy), and outcomes (28-day mortality and hospital discharge). RESULTS: Among 2111 individuals hospitalized in 219 ICUs with HA-BSI, 563 (27%) were ≥ 75 years old. Compared to younger patients, these individuals had higher comorbidity score and lower functional capacity; presented more often with a pulmonary, urinary, or unknown HA-BSI source; and had lower heart rate, blood pressure and temperature at presentation. Pathogens and resistance rates were similar in both groups. Differences in management included mainly lower rates of effective source control achievement among aged individuals. Older adults also had significantly higher day-28 mortality (50% versus 34%, p < 0.001), and lower rates of discharge from hospital (12% versus 20%, p < 0.001) by this time. CONCLUSIONS: Older adults with HA-BSI hospitalized in ICU have different baseline characteristics and source of infection compared to younger patients. Management of older adults differs mainly by lower probability to achieve source control. This should be targeted to improve outcomes among older ICU patients.

Impact of Open Access status on journal metrics in infectious diseases and clinical microbiology - A cross-sectional study.

INTRODUCTION: While Open Access (OA) journals provide free access to articles, they entail high article processing charges (APC), limiting opportunities for young researchers and those from low-middle income countries to publish OA. METHODS: Cross-sectional study, evaluating APC and academic impact of full OA (FOA) journals in infectious diseases (ID) and clinical microbiology (CM) compared to hybrid journals. Data were collected from Journal Citation Reports and journals' websites. RESULTS: Among 255 journals, median APC was 2850 (interquartile range [IQR] 1325-3654$). Median APC for 120 FOA journals was significantly lower than for 119 hybrid journals (2000, IQR 648-2767$ versus 3550, IQR 2948-4120$, p < 0.001). FOA journals had lower citation numbers and impact metrics compared to hybrid journals. CONCLUSION: While FOA ID/CM journals have lower APCs, they also lower academic impact compared to hybrid journals. These findings highlight the need for reforms in the publication process in view of achieving equitable data dissemination.

Pseudomonas aeruginosa ventricular assist device infections: findings from ineffective phage therapies in five cases.

Left ventricular assist devices (LVAD) are increasingly used for management of heart failure; infection remains a frequent complication. Phage therapy has been successful in a variety of antibiotic refractory infections and is of interest in treating LVAD infections. We performed a retrospective review of four patients that underwent five separate courses of intravenous (IV) phage therapy with concomitant antibiotic for treatment of endovascular Pseudomonas aeruginosa LVAD infection. We assessed phage susceptibility, bacterial strain sequencing, serum neutralization, biofilm activity, and shelf-life of phage preparations. Five treatments of one to four wild-type virulent phage(s) were administered for 14-51 days after informed consent and regulatory approval. There was no successful outcome. Breakthrough bacteremia occurred in four of five treatments. Two patients died from the underlying infection. We noted a variable decline in phage susceptibility following three of five treatments, four of four tested developed serum neutralization, and prophage presence was confirmed in isolates of two tested patients. Two phage preparations showed an initial titer drop. Phage biofilm activity was confirmed in two. Phage susceptibility alone was not predictive of clinical efficacy in P. aeruginosa endovascular LVAD infection. IV phage was associated with serum neutralization in most cases though lack of clinical effect may be multifactorial including presence of multiple bacterial isolates with varying phage susceptibility, presence of prophages, decline in phage titers, and possible lack of biofilm activity. Breakthrough bacteremia occurred frequently (while the organism remained susceptible to administered phage) and is an important safety consideration.

Utility of echocardiogram in neutropenic patients with gram positive bacteremia - a retrospective study.

INTRODUCTION: Hemato-oncology patients are vulnerable to bloodstream infections due to immunocompromised state and use of intravascular catheters. Data regarding risk of infective endocarditis (IE) among those with gram positive bacteremia is limited. We aimed to evaluate the incidence of IE among neutropenic hemato-oncology patients, and to explore the yield of echocardiogram in this population. METHODS: we conducted a single retrospective study of all hospitalized hemato-oncology neutropenic patients with gram positive blood cultures between 2007 and 2021. Data regarding Patients' characteristics, blood cultures and echocardiogram was collected. RESULTS: Study included 241 patients, with 283 isolates. Coagulase negative staphylococcus (CONS) were the most commonly isolates found, followed by streptococcus viridans. Trans thoracic echocardiography (TTE) was performed in 45% of patients overall, of which 5.8% had additional Trans esophageal echocardiogram (TEE). Only a single case of IE was identified; 47 y/o multiple myeloma patient with neutropenic fever, streptococcus viridans bacteremia, and stroke caused by septic emboli. TTE and TEE failed to demonstrate valvular pathology consistent with IE. Conclusion In our experience, the yield of echocardiogram in hemato-oncological neutropenic patients with bacteremia is extremely low, owing to reduced probability of IE in this population, and thus could be avoided in most cases.

One-year follow-up of COVID-19 recoverees with impaired pulmonary function: A prospective cohort study.

Decreased diffusion capacity for carbon monoxide (DLCO) is the most prevalent pulmonary testing abnormality among COVID-19 recoverees. We prospectively followed 51 individuals with impaired DLCO at an average of ∼3 months following COVID-19 and re-examined them at one year. At follow-up, mean DLCO increased from 68.0 % to 72.6 % (p = 0.002); while 33 % of the cohort experienced a clinically significant rise (>10 points) in DLCO, only 29 % normalized their values. While DLCO change did not correlate with symptoms, lack of improvement was more prevalent among individuals with obesity. Regardless of COVID-19 severity, a substantial proportion continued to exhibit DLCO impairment at 1-year.

Challenges of antimicrobial stewardship among older adults.

Older adults hospitalized in internal medicine wards or long-term care facilities (LTCF) are progressively increasing. Older adults with multimorbidity are more susceptible to infections, as well as to more vulnerable to adverse effects (and interactions) of antibiotics, resulting in a need for effective and safer strategies for antimicrobial stewardship (ASM), both in hospitalization wards and long-term care facilities. Studies on antimicrobial stewardship in older patients are scarce and guidelines are required. Given the peculiarities of the optimization of antimicrobial prescription in individual older adults for common infections, tactics to overcome barriers need an update. The use of rapid diagnosis tests, biomarkers, de-escalation and switching from intravenous to oral/subcutaneous therapy strategies are examples of successful AMS interventions. AMS interventions are associated with reduced side effects, lower mortality, shorter hospital stays, and reduced costs. The proposed AMS framework in LTCF should focus on five domains: strategic vision, team, interventions, patient-centred care and awareness. Internists can partner with geriatrists, pharmacists and infectious disease specialists to address barriers and to improve patient care.

Fluoroquinolone Prophylaxis during Conventional Chemotherapy or Hematopoietic Stem Cell Transplantation for Acute Leukemia - Pros and Cons.

BACKGROUND: Prophylaxis with fluoroquinolones (FQ) is commonly used in patients with acute leukemia (AL) during neutropenia. This practice is supported by an older meta-analysis reporting reduced mortality using FQ prophylaxis. Later meta-analyses have failed to reproduce this finding, presumably due to higher background FQ resistance rates limiting their effectiveness. SUMMARY: This article reviews the pros and cons of FQ prophylaxis mainly in patients with AL. Most current guidelines do not support universal prophylaxis but rather recommend a selective approach, weighing the benefits against the risks. This recommendation is based on the lack of mortality benefit reported in more recent meta-analyses. FQ prophylaxis was demonstrated to reduce bacteremia and febrile neutropenia episodes, although mostly in trials performed in low-resistance settings (<20%), whereas current FQ resistance rates may reach 30-60%. Other disadvantages of FQ include potential adverse events, antibiotic resistance development, cost, increase in Gram-positive infections and resistant Gram-negative infections following prophylaxis, Clostridioides difficile infection, and an effect on gut microbiota. KEY MESSAGES: Taking the above into consideration, alternative approaches other than universal FQ prophylaxis should be considered. Centers with high FQ resistance rates may consider either withholding prophylaxis or providing selective prophylaxis for high-risk patients screened negative for FQ-resistant bacteria.

Prevention of Oncogenic Gammaherpesvirinae (EBV and HHV8) Associated Disease in Solid Organ Transplant Recipients.

Long-term risk for malignancy is higher among solid organ transplant (SOT) recipients compared to the general population. Four non-hepatitis viruses have been recognized as oncogenic in SOT recipients-EBV, cause of EBV-associated lymphoproliferative diseases; human herpes virus 8 (HHV8), cause of Kaposi sarcoma, primary effusion lymphoma and multicentric Castleman disease; human papilloma virus, cause of squamous cell skin cancers, and Merkel cell polyomavirus, cause of Merkel cell carcinoma. Two of these viruses (EBV and HHV8) belong to the human herpes virus family. In this review, we will discuss key aspects regarding the clinical presentation, diagnosis, treatment, and prevention of diseases in SOT recipients associated with the two herpesviruses.

Early oral antibiotic switch in Staphylococcus aureus bacteraemia: The Staphylococcus aureus Network Adaptive Platform (SNAP) Trial Early Oral Switch Protocol.

BACKGROUND: Staphylococcus aureus bloodstream infection (bacteraemia) is traditionally treated with at least two weeks of IV antibiotics in adults, 3-7 days in children, and often longer for those with complicated disease. The current practice of treating S. aureus bacteraemia (SAB) with prolonged IV antibiotics (rather than oral antibiotics) is based on historical observational research and expert opinion. Prolonged IV antibiotic therapy has significant disadvantages for patients and healthcare systems, and there is growing interest in whether a switch to oral antibiotics following an initial period of IV therapy is a safe alternative for clinically stable patients. PROTOCOL: The early oral switch (EOS) domain of the S. aureus Network Adaptive Platform (SNAP) trial will assess early switch to oral antibiotics compared with continued IV treatment in clinically stable patients with SAB. The primary endpoint is 90-day all-cause mortality. Hospitalised SAB patients are assessed at platform day 7 +/- 2 (uncomplicated SAB) and day 14 +/-2 (complicated SAB) to determine their eligibility for randomisation to EOS (intervention) or continued IV treatment (current standard of care). DISCUSSION: Recruitment is occurring to the EOS domain of the SNAP trial. As of August 2023, 21% of all SNAP participants had been randomised to the EOS domain, a total of 264 participants across 77 centres, with an aim to recruit at least 1000 participants. We describe challenges and facilitators to enrolment in this domain to aid those planning similar trials.

Utilizing Ceftazidime/Avibactam Therapeutic Drug Monitoring in the Treatment of Neurosurgical Meningitis Caused by Difficult-to-Treat Resistant Pseudomonas aeruginosa and KPC-Producing Enterobacterales.

Background: Central nervous system (CNS) infections caused by Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales and difficult-to-treat resistant (DTR) Pseudomonas aeruginosa represent a formidable clinical challenge. Antimicrobial regimens that efficiently penetrate the cerebrospinal fluid (CSF) and achieve sufficient concentrations associated with microbiologic and clinical cure are limited. We evaluated therapy with ceftazidime-avibactam (CAZ-AVI) in order to guide precise dosing in the treatment of CNS infections. Methods: Therapeutic drug monitoring (TDM) was performed in 3 patients with health care-associated ventriculitis and meningitis (HAVM) using CAZ-AVI 2.5 g infused intravenously every 8 hours as standard and extended infusion. Simultaneous CSF and plasma samples were obtained throughout the dosing interval in each patient. Concentrations of CAZ and AVI were determined by liquid chromatography/mass spectrometry. Results: Bacterial identification revealed KPC-producing Klebsiella pneumoniae (KPC-Kp), DTR Pseudomonas aeruginosa, and KPC-producing Enterobacter cloacae (KPC-Ent.c). All isolates were resistant to carbapenems. The minimum inhibitory concentrations (MICs) of CAZ-AVI were 0.25/4, 4/4, and 0.25/4 µg/mL, respectively. CAZ and AVI concentrations were determined in CSF samples ranging from 29.0 to 15.0 µg/mL (CAZ component) and 4.20 to 0.92 µg/mL (AVI component), respectively. AVI achieved concentrations ≥1 µg/mL in 11 out of 12 CSF samples collected throughout the dosing interval. Clinical and microbiologic cure were attained in all patients. Conclusions: Postinfusion concentrations of CAZ-AVI were measured in plasma and CSF samples obtained from 3 patients with complicated CNS infections caused by antimicrobial-resistant isolates. The measured concentrations revealed that standard CAZ and AVI exposures sufficiently attained values correlating to 50% fT > MIC, which are associated with efficient bacterial killing.

Early Systemic Anti-neoplastic Treatment Post SARS-CoV-2 Infection in Patients with Breast Cancer.

INTRODUCTION: It is unclear how soon after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection it is safe to resume systemic anti-neoplastic treatment in patients with cancer. We assessed the risk of admissions or postponed treatment cycle in vaccinated patients with breast cancer receiving early systemic anti-neoplastic treatment following SARS-CoV-2 infection. METHODS: This was a retrospective cohort study conducted during Omicron SARS-CoV-2 outbreak in Israel, January-July 2022. SARS-CoV-2 cohort included 30 vaccinated patients with breast cancer with SARS-CoV-2 infection 7-14 days prior to systemic treatment. All patients had resolved symptoms and a negative antigen detection test on the day of treatment. The pre-coronavirus disease 2019 (COVID-19) pandemic cohort consisted of 49 matched patients with breast cancer treated with systemic anti-neoplastic agents during 2019. RESULTS: In 30 vaccinated patients with breast cancer who received systemic anti-neoplastic treatment 7-14 days following SARS-CoV-2 infection, compared with 49 matched patients treated in 2019, the rates of emergency department (ED) visits (13% versus 6%, respectively), hospitalizations (3% versus 4%), next cycle of treatment given per protocol (90% versus 88%), and death (0% versus 0%) were similar. CONCLUSION: In a cohort of vaccinated patients with breast cancer who received systemic anti-neoplastic treatment 7-14 days after SARS-CoV-2 infection, we did not observe substantially higher rates of ED visits, hospitalizations, or deaths compared with a similar cohort of pre-COVID-19 patients with breast cancer. Most patients received the next planned cycle on time. Early resumption of systemic anti-neoplastic treatment following SARS-CoV-2 infection in vaccinated patients with breast cancer with a negative antigen test at the day of treatment appeared to be safe. Additional data on larger cohorts and other malignancies are needed to support clinical guidelines.

Screening for Asymptomatic Clostridioides difficile Carriage Among Hospitalized Patients: A Narrative Review.

Clostridioides difficile infection (CDI) has become the most common healthcare-associated infection in the United States, with considerable morbidity, mortality, and healthcare costs. Assessing new preventive strategies is vital. We present a literature review of studies evaluating a strategy of screening and isolation of asymptomatic carriers in hospital settings. Asymptomatic detection of C. difficile is reported in ~ 10-20% of admitted patients. Risk factors for carriage include recent hospitalization, previous antibiotics, older age, lower functional capacity, immunosuppression, and others. Asymptomatic C. difficile carriers of toxigenic strains are at higher risk for progression to CDI. They are also shedders of C. difficile spores and may contribute to the persistence and transmission of this bacterium. Screening for asymptomatic carriers at hospital admission can theoretically reduce CDI by isolating carriers to reduce transmission, and implementing antibiotic stewardship measures targeting carriers to prevent progression to clinical illness. Several observational studies, summarized in this review, have reported implementing screening and isolation strategies, and found a reduction in CDI rates. Nevertheless, the data are still limited to a few observational studies, and this strategy is not commonly practiced. Studies supporting screening were performed in North America, coinciding with the period of dominance of the 027/BI/NAP1 strain. Additional studies evaluating screening, followed by infection control and antibiotic stewardship measures, are needed.

Immunogenicity and Safety of Modified Vaccinia Ankara (MVA) Vaccine-A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Prevention of mpox has become an important public health interest. We aimed to evaluate the safety and immunogenicity of the Modified Vaccinia Ankara (MVA) vaccine. We conducted a systematic review and meta-analysis of randomized-controlled trials (RCTs) comparing MVA versus no intervention, placebo, or another vaccine. Outcomes included safety and immunogenicity outcomes. We also performed a systematic review of RCTs evaluating various MVA regimens. Fifteen publications were included in the quantitative meta-analysis. All but one (ACAM2000) compared MVA with placebo. We found that cardiovascular adverse events following two MVA doses were significantly more common compared to placebo (relative risk [RR] 4.07, 95% confidence interval [CI] 1.10-15.10), though serious adverse events (SAEs) were not significantly different. Following a single MVA dose, no difference was demonstrated in any adverse event outcomes. Seroconversion rates were significantly higher compared with placebo after a single or two doses. None of the RCTs evaluated clinical effectiveness in preventing mpox. This meta-analysis provides reassuring results concerning the immunogenicity and safety of MVA. Further studies are needed to confirm the immunogenicity of a single dose and its clinical effectiveness. A single vaccine dose may be considered according to vaccine availability, with preference for two doses.