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Introduction: Diarrhea is a frequent complication after kidney transplantation, however the etiology is often not identified. Multiplex PCR assays may increase the detection of diarrheal pathogens among kidney transplant recipients (KTRs), leading to improved management. Methods: This was a retrospective before–after study, conducted in a high-volume transplant center. In September 2017, multiplex PCR assay was introduced. We reviewed all hospitalized KTRs with diarrhea during 1/2015–8/2017 (pre-GI PCR, n= 111) and 9/2017–12/2021 (GI PCR, n= 159) and followed them for 3 years. We performed univariate and multivariate analysis for predictors of pathogen identification, introducing the study period as an independent variable. Results: Among 270 hospitalized KTRs with diarrhea, 64 (24%) had an identified diarrheal pathogen. The proportion of KTRs with an identified pathogen increased from 20% (13/64) in the pre-GI PCR to 80% (51/64) post GI PCR (p< 0.01). Of 51 KTRs with an identified pathogen in the post GI PCR, 44 (86%) were diagnosed using GI PCR. GI PCR was more likely used in younger KTRs with more recent transplantation and higher creatinine level at admission. The most common non-C. difficilediarrheal pathogens in the post-GI PCR cohort were enteropathogenicEscherichia coli(n= 23, 58%), norovirus (n= 11, 28%), andCampylobacter(n= 11, 28%). Implementing GI PCR significantly increased the detection and identification of GI pathogens (odds ratio [OR] = 21, CI 95% 10–44; p< 0.001). Conclusions: Infectious etiologies of diarrhea were identified in a higher proportion of KTRs after the implementation of GI PCR. This emphasizes the importance of integrating this diagnostic tool into diarrhea workup in KTRs.

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.

Introduction: Microbiological diagnosis is central for adequate treatment of bone and joint infections. Culture-based methods have a limited diagnostic sensitivity and a long turnaround time (TAT). The objective of this study was to compare the diagnostic performance of BioFire Joint Infection Panel Investigational Use Only version (hereafter BioFire)—a sample-to-result multiplex PCR panel—with culture-based methods and 16S ribosomal RNA (rRNA) PCR and sequencing, when available. Methods: This study presents a retrospective analysis of a prospective validation study of the BioFire panel. Specimens were obtained from consecutive patients evaluated for suspected bone and joint infections and processed using culture, BioFire, and 16S rRNA PCR and sequencing. Final clinical diagnosis was used as the reference for definition of infection. Results: Samples, including synovial fluid, bone and periarticular tissue, were obtained from 57 patients, 39 of whom were finally diagnosed with a bone or joint infection. Cultures were positive in 27/39 infected patients and in 3/18 uninfected patients (sensitivity 69%, specificity 83%). BioFire was positive in 22/39 infected patients and in none of the uninfected patients (sensitivity 56%, specificity 100%). Sensitivity for PCR panel organisms was 92% (22/24) and sensitivity for organisms identified by any microbiological modality was 69% (22/32). Gram stain results were positive in 13/39 infected patients and in none of the uninfected patients (sensitivity 33%, specificity 100%). 16S rRNA was positive in 20/28 infected patients and in 0/12 uninfected patients (sensitivity 71%, specificity 100%). Net machine time for BioFire—1 h—was shorter than the mean TAT for Gram stain results, which was 4 h. Conclusion: BioFire offered equivalent diagnostic performance with superior TAT for bone and joint infections, compared with conventional methods.

Clostridioides difficileinfection (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. difficileis 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. difficilecarriers of toxigenic strains are at higher risk for progression to CDI. They are also shedders of C. difficilespores 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.

Background: Older adults and immunocompromised individulas are often excluded from vaccine trials. Aim: We hypothesised that during the coronavirus disease 2019 (COVID-19) pandemic, the proportion of trials excluding these patients decreased. Methods: Using the US Food and Drug Administration and and European Medicines Agency search engines, we identified all vaccines approved against pneumococcal disease, influenza (quadrivalent vaccines), and COVID-19 from 2011 to 2021. Study protocols were screened for direct and indirect age exclusion criteria and exclusion of immunocompromised individuals. In addition, we reviewed the studies with no explicit exclusion criteria and investigated the actual inclusion of those individuals. Results: We identified 2024 trial records; 1702 were excluded (e.g., use of other vaccine or risk group); and 322 studies were eligible for our review. Among the pneumococcal and influenza vaccine trials (n= 193), 81 (42%) had an explicit direct age exclusion, and 150 (78%) had an indirect age-related exclusion. In total, 163 trials (84%) trials were likely to exclude older adults. Among the COVID-19 vaccine trials (n= 129), 33 (26%) had direct age exclusion and 82 (64%) had indirect age exclusion; in total, 85 (66%) trials were likely to exclude older adults. Therefore was a 18% decrease in the proportion of trials with age-related exclusion between 2011 and 2021 (only influenza and pneumococcal vaccine trials) and 2020–2021 (only COVID-19 vaccine trials) (p= 0.014). In a sub-analysis assessing observational and randomised trials, the decrease was 25% and 9%, respectively. Immunocompromised individuals were included in 87 (45%) of the pneumococcal and influenza vaccine trials compared with 54 (42%) of the COVID-19 vaccine trials (p = 0.058). Conclusions: During the COVID-19 pandemic, we found a decrease in the exclusion of older adults from vaccine trials but no significant change in the inclusion of immunocompromised individulas.

Introduction: There is no consensus regarding optimal duration of antibiotic therapy for Pseudomonas aeruginosabacteremia. We aimed to evaluate the impact of short antibiotic course. Methods: We present a retrospective multicenter study including patients with P. aeruginosabacteremia during 2009–2015. We evaluated outcomes of patients treated with short (6–10 days) versus long (11–15 days) antibiotic courses. The primary outcome was a composite of 30-day mortality or bacteremia recurrence and/or persistence. Univariate and inverse probability treatment-weighted (IPTW) adjusted multivariate analysis for the primary outcome was performed. To avoid immortal time bias, the landmark method was used. Results: We included 657 patients; 273 received a short antibiotic course and 384 a long course. There was no significant difference in baseline characteristics of patients. The composite primary outcome occurred in 61/384 patients in the long-treatment group (16%) versus 32/273 in the short-treatment group (12%) (p= 0.131). Mortality accounted for 41/384 (11%) versus 25/273 (9%) of cases, respectively. Length of hospital stay was significantly shorter in the short group [median 13 days, interquartile range (IQR) 9–21 days, versus median 15 days, IQR 11–26 days, p= 0.002]. Ten patients in the long group discontinued antibiotic therapy owing to adverse events, compared with none in the short group. On univariate and multivariate analyses, duration of therapy was not associated with the primary outcome. Conclusions: In this retrospective study, 6–10 days of antibiotic course for P. aeruginosabacteremia were as effective as longer courses in terms of survival and recurrence. Shorter therapy was associated with reduced length of stay and less drug discontinuation.

Introduction: 18-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is a well-established tool for managing metastatic infections. Nocardiosis, a primarily pulmonary infection, disseminates at high rates. Routine imaging includes chest CT and brain imaging. We examined the use of FDG-PET/CT in nocardiosis and assessed its contribution to diagnosis and management. Methods: A retrospective study in two tertiary medical centers during 2011–2020. Individuals with nocardiosis for whom FDG-PET/CT was implemented for any reason were included and their medical records were reviewed. A board-certified nuclear medicine physician independently reviewed all scans. Additionally, a systematic review was conducted according to the PRISMA guidelines, to extract data from publications reporting FDG-PET/CT use for the management of nocardiosis. Results: FDG-PET/CT contributed to the management of all seven patients who met inclusion criteria. It assisted in ruling out an underlying malignancy (29%, 2/7); establishing a wide infection extent (57%, 4/7); and affecting decisions regarding treatment (57%, 4/7), including drug regimen, oral step-down, and duration of therapy. We identified 20 published case reports on this topic. In 80% (16/20), FDG-PET/CT contributed to the management of nocardiosis similar to our study. In addition, in most of the literature cases, FDG-PET/CT guided the diagnostic biopsy. Conclusion: FDG-PET/CT is valuable in the diagnosis and management of individuals with nocardiosis. The contribution of incorporating FDG-PET/CT to the management of individuals with nocardiosis and its role in monitoring treatment response and shortening treatment duration should be evaluated in prospective studies.

IMPORTANCE: Patients with cancer undergoing treatment are at high risk of COVID-19 following SARS-CoV-2 infection; however, their ability to produce an adequate antibody response to messenger RNA SARS-CoV-2 vaccines is unclear. OBJECTIVE: To evaluate rates of antispike (anti-S) antibody response to a BNT162b2 vaccine in patients with cancer who are undergoing systemic treatment vs healthy controls. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study included 102 adult patients with solid tumors undergoing active intravenous anticancer treatment and 78 controls who received the second dose of the BNT162b2 vaccine at least 12 days before enrollment. The controls were taken from a convenience sample of the patients’ family/caregivers who accompanied them to treatment. The study was conducted between February 22, 2021, and March 15, 2021 at Davidoff Cancer Center at Beilinson Hospital (Petah Tikva, Israel). INTERVENTIONS: Blood samples were drawn from the study participants. Serum samples were analyzed and the titers of the IgG antibodies against SARS-CoV-2 spike receptor–binding domain were determined using a commercially available immunoassay. Seropositivity was defined as 50 or greater AU/mL. MAIN OUTCOMES AND MEASURES: The primary outcome was the rate of seropositivity. Secondary outcomes included comparisons of IgG titers and identifying factors that were associated with seropositivity using univariate/multivariable analyses. RESULTS: The analysis included 180 participants, which comprised 102 patients with cancer (median [interquartile range (IQR)] age, 66 [56-72] years; 58 men [57%]) and 78 healthy controls (median [IQR] age, 62 [49-70] years; 25 men [32%]). The most common tumor type was gastrointestinal (29 [28%]). In the patient group, 92 (90%) were seropositive for SARS-CoV 2 antispike IgG antibodies after the second vaccine dose, whereas in the control group, all were seropositive. The median IgG titer in the patients with cancer was significantly lower than that in the controls (1931 [IQR, 509-4386] AU/mL vs 7160 [IQR, 3129-11 241] AU/mL; P < .001). In a multivariable analysis, the only variable that was significantly associated with lower IgG titers was treatment with chemotherapy plus immunotherapy (β, −3.5; 95% CI, −5.6 to −1.5). CONCLUSIONS AND RELEVANCE: In this cohort study of patients with cancer who were receiving active systemic therapy, 90% of patients exhibited adequate antibody response to the BNT162b2 vaccine, although their antibody titers were significantly lower than those of healthy controls. Further research into the clinical relevance of lower titers and their durability is required. Nonetheless, the data support vaccinating patients with cancer as a high priority, even during therapy.

ABSTRACTVaccines have changed modern medicine, and are a mainstay in reducing morbidity and mortality from infections. Our research group recently published a study in which we found that vaccines approved by the US Food and Drugs Administration were safe with few clinically important post-approval adverse effects. The current COVID-19 pandemic presents regulators with the unprecedented challenge of balancing a public demand for the rapid development and approval of a safe and effective SARS-CoV-2 vaccine without compromising the strict pre-marketing requirements used for previous vaccines. Here, we review the approval process and safety profiles of FDA approved vaccines and discuss some of the challenges currently facing the FDA regarding the SARS-CoV-2 vaccine approval.

•Respiratory symptoms and decreased DLCO are common among COVID-19 recoverees.•We prospectively followed 51 COVID-19 recoverees with impaired DLCO at 3 months and found that only one-third normalized their DLCO at one year.•Respiratory symptoms did not correlate with DLCO at one year follow-up.

Bloodstream infections (BSI) represent a serious bacterial infection with substantial morbidity and mortality. Population-based studies demonstrate an increased incidence, especially among elderly patients. Controversy exists regarding whether presentation of BSI are different in older patients compared to younger patients; our narrative review of the literature suggests that BSI in elderly patients would probably include one or more of the traditional symptoms/signs of fever, severe sepsis or septic shock, acute kidney injury, and/or leukocytosis. Sources of BSI in older adults are most commonly the urinary tract (more so than in younger adults) and the respiratory tract. Gram-negative bacteria are the most common isolates in the old (~ 40–60% of BSI); isolates from the elderly patient population show higher antibiotic resistance rates, with long-term care facilities serving as reservoirs for multidrug-resistant bacteria. BSI entail significantly higher rates of mortality in older age, both short and long term. Some of the risk factors for mortality are modifiable, such as the appropriateness of empirical antibiotic therapy and nosocomial acquisition of infection. Health-related quality of life issues regarding the elderly patient with BSI are not well addressed in the literature. Utilization of comprehensive geriatric assessment and comprehensive geriatric discharge planning need to be investigated further in this setting and might serve as key for improved results in this population. In this review, we address all these aspects of BSI in old patients with emphasis on future goals for management and research.

Introduction: Guidelines for treatment of multidrug-resistant (MDR) bacteria rely on newly approved antibiotics, with limited evidence of their effectiveness for treating these infections. Data regarding cost of such an approach are lacking. We aimed to evaluate estimated cost of using newly approved antibiotic drugs compared to older antibiotics for the treatment of difficult-to-treat pathogens. Methods: MDR bacteria of interest included those defined by the World Health Organization as critical or of high priority for research. Old and newly approved antibiotics for these bacteria, defined as approved before or after January 2010, respectively, were evaluated for treatment cost and for 14-day treatment course. Estimated annual costs were calculated based on the Centers for Disease Control and Prevention’s' report on MDR bacteria prevalence in US hospitalized patients. Old and new drugs costs were compared. Results: The cost of a 14-day treatment course for methicillin-resistant Staphylococcus aureusbacteremia with a newly approved drug was found to be 6 to 60 times higher than that of older drugs. Similarly, the cost of a 14-day course for carbapenem-resistant Enterobacterales or MDR Pseudomonas aeruginosawas doubled with new drugs; and for carbapenem-resistant Acinetobacter baumannii, ~ 20 times higher with newer drugs. Annual incremental costs of treating difficult-to-treat Gram-negative bacteria with new drugs ranged from 30 million to over 500 million USD. Conclusions: Using newly approved antibiotic drugs for MDR infections carries a large incremental cost. Additional data to support survival benefit of these drugs are required to justify the price differences. Subgroups of patients who would benefit most from treatment should be defined.

Background: Advanced age is an important factor affecting Clostridioides difficileinfection (CDI) risk and outcome. While fever and leukocytosis are prominent findings in young individuals with CDI, they are usually blunted in the elderly. Furthermore, chronic kidney disease often exists among this population prior to the CDI episode onset. Aim: We aimed to examine whether the accepted definition of severe CDI (leukocytosis ≥ 15,000 cells/μl or serum creatinine > 1.5 mg/dl) predicts poor outcomes in the elderly. Methods: All CDI hospitalized individuals between January-2013 and May-2020 were included. The study population was dichotomized into older group (≥ 65 years) and younger group (< 65 years). Primary composite outcome was 30-day mortality, colectomy due to severe colitis, or intensive care unit admission. The older group was divided according to the primary outcome to evaluate the effect of CDI severity criteria. Results: The study included 853 patients. Of them, 571 were in the older group and 282 in the younger one. The primary outcome was significantly more common in the older group (93/571, 16% vs. 31/282, 11%; p= 0.04). Ninety days mortality was significantly higher in the older group [116/571, 20% vs. 30/282, 11%; p< 0.01]. In multivariate analysis, accepted CDI severity criteria were not significantly associated with poor outcomes (odds ratio [OR] = 1.2, 95% confidence interval [CI] 0.7–2.2, p= 0.5). Advanced dementia and low serum albumin were significant predictors of poor outcomes (OR = 3, 95%CI 1.5–6, p= 0.002 and OR = 3.1, 95%CI 1.7–5.8, p< 0.01). Conclusion: The accepted definition of CDI severity was not useful in predicting CDI poor outcomes in older adults. In this population, we suggest advanced dementia and low albumin among others as CDI severity markers.

Introduction: Diarrhea affects a significant proportion of patients undergoing hematopoietic cell transplantation (HCT). We explored the diagnostic yield of stool cultures for enteric pathogens among patients undergoing HCT. Methods: This is a single-center, retrospective study. Between 5/2007 and 4/2020, consecutive patients who underwent HCT were included if inpatient bacterial stool cultures were collected. Patient characteristics, results, and timing of stool cultures obtained during hospitalization were collected. Results: A total of 1072 individuals underwent autologous (n= 603) and allogeneic (n= 469) HCT. Overall, 947 stool culture samples were obtained from 561 (52%) patients with diarrheal illness during hospitalization for HCT. Most (99%) samples were obtained beyond 3 days of admission, mainly (77%) during neutropenia. Overall, only four (0.42%) (autologous, n= 3; allogeneic, n= 1) patients had a positive stool culture and in all cases Campylobacter spp. were the pathogens identified. The number of stool cultures needed-to-test to diagnose one case of bacterial infection was 237. The cost of diagnosing one case of bacterial diarrhea was US $8770. Patients with a positive stool culture did not have discerning characteristics. Conclusions: In our experience, the yield of stool cultures for enteropathogens in patients undergoing HCT is extremely low and thus should be avoided in most cases.

Objectives: Intranasal septal splints are often used in nasal septal surgeries. Routine use of postoperative antibiotics is an accepted practice, although data regarding its efficacy in preventing postsurgical complications are limited. This study aimed to examine bacterial colonization on septal splints following prophylactic antibiotic therapy and the association with postoperative infections.Methods: Fifty-five patients underwent septoplasty by a single surgeon between March 2015 and April 2016. All had intranasal septal splints and were given antibiotic prophylaxis for 7 days until removal of splints. Nasal cultures were taken before surgery, and septal splints were examined for bacterial colonization following their removal.Results: Thirty-six patients (65%) had positive nasal culture prior to surgery. The most common isolates were Staphylococcus aureus(30%) and Enterobacteriaceaespecies (66%). All these patients had postoperative bacterial colonization on septal splints. In 15 patients with negative preoperative cultures, bacteria were isolated postoperatively. An increased resistance profile was documented postoperatively in 9 patients (16%), including two with multidrug resistance. In two of these patients preoperative wild-type strains acquired antibiotic resistance postoperatively. No adverse drug reactions to antibiotics were reported.Conclusions: Increased bacterial growth and emergence of resistant strains were observed on intranasal septal splints despite prophylactic antibiotic treatment. Nonetheless, this did not translate into clinical infection. Thus, considering antibiotics overuse and increasing bacterial resistance, further research is needed to determine the role of antibiotic prophylaxis in the setting of intranasal splints.

•Physiological changes that occur with ageing can affect antibiotic pharmacokinetics.•Renal clearance is the most important factor affecting antibiotic levels in the elderly.•Few studies on antibiotic pharmacokinetics are available in elderly patients.•Inadequate drug dosages may favour drug-related adverse events in the elderly.•Therapeutic drug monitoring can guide antibiotic therapy in elderly patients.

•No data are currently available on open access (OA) publication cost and academic impact in the field of infectious diseases (ID).•Following evaluation of 255 ID journals, the median cost of full OA journals was lower than that of hybrid journals (2000$ vs 3550$).•Full OA journals had lower citation numbers, immediacy index, influence score, and Eigenfactor.•In ID, considerable costs are required for OA publication, limiting the ability of researchers to share their data.•Trying to lower the cost by choosing full OA journal is associated with measures entailing lower quality.

Introduction: Hemato-oncology patients are vulnerable to bloodstream infections (BSI) due to their immunocompromised and neutropenic state, and the common use of intravascular catheters. The risk of infective endocarditis (IE) among non-neutropenic patients with gram positive bacteremia is substantial, however the risk is considered to be lower among neutropenic patients, though data is limited. We aimed to evaluate the incidence of IE among neutropenic hemato-oncology patients' cohort, and to explore the yield of echocardiogram in this specific population.

The incidence of Staphylococcus aureusbacteremia (SAB) increases with advancing age with higher mortality reported in older adults. We aimed to describe the clinical presentation, management and outcomes of older patients with SAB. We analyzed data from a retrospectively collected database including 1692 patients with SAB, and compared 1158 older patients (≥65 years) with 534 younger patients (<65 years) in terms of clinical features, management of infection, and outcomes. Older patients were significantly less likely to be febrile on presentation, with 37.5 % (415/1106) of older patients presenting with normal body temperature [versus 29.2 % (152/520) of younger patients]. Older patients were however, more likely to have leukocytosis, septic shock, lower heart rate and lower diastolic blood pressure compared with younger patients. Management of older patients included significantly less imaging studies, performance of transesophageal echocardiogram (TEE) and infectious diseases consultation. TEE was performed less in older patients [124/726 (17.1 %) versus 72/285 (25.3 %)]. Mortality was significantly higher in older patients [550/1158 (47.5 %) versus 124/534 (23.2 %)], with predictors for mortality for the entire cohort in multivariate analysis including older age, higher Charlson comorbidity index, female sex, impaired functional capacity, pneumonia or primary bacteremia, and non-performance of TEE. Mortality rates in older patients with SAB are higher compared with younger patients. Several diagnostic and therapeutic procedures in the management of SAB were less likely to be performed in older patients in our cohort. These may have implications on outcome and should not be dismissed on the basis of age alone.

ABSTRACTBloodstream infections (BSIs) are both common and fatal in older patients. We describe data from studies evaluating older patients hospitalized with BSIs. Most older patients with BSIs present “typically” with either fever or leukocytosis. The most common source of BSI in older patients is the urinary tract, and accordingly, Gram-negative organisms predominate. A significant part of these BSIs may thus be preventable by removal of unnecessary urinary catheters. Increased long term mortality is reported following BSIs in older patients, however, data on other long-term outcomes, including functional capacity, cognitive decline and others are lacking. Management of BSIs may include less invasive procedures due to the fragility of older patients. This approach may delay the diagnosis and treatment in some cases. Older patients are probably under-represented in clinical trials assessing treatment of bacteremia. Physicians treating older patients should consider the relevance of these studies' outcomes.

Diarrhea affects a significant proportion of patients undergoing hematopoietic cell transplantation (HCT). In this single center retrospective study, we explored the diagnostic yield of stool cultures for enteric pathogens among patients undergoing HCT. Between May 2007 and April 2020, a total of 1072 individuals underwent autologous (n=603) and allogeneic (n=469) HCT. Overall, 947 stool culture samples were obtained from 561 (52%) patients with diarrheal illness during hospitalization for HCT. Most (99%) samples were obtained beyond 3 days of admission and mainly (77%) during neutropenia. Overall, only four (autologous HCT, n=3; allogeneic HCT, n=1) patients were diagnosed with positive stool culture (0.42%) and in all cases, Campylobacter spp. was the pathogen identified. All isolates grew from the first stool culture obtained. The number of stool cultures needed-to-test to diagnose one case of bacterial infection was 237. The cost of diagnosing one case of bacterial infectious diarrhea was 8,770 US dollars. The median time from admission to positive stool culture sample was 12 (range, 7 to 13) days. Patients with a positive stool culture did not have discerning clinical or laboratory characteristics. In conclusion, according to our experience, the yield of stool cultures for enteropathogens in patients undergoing HCT is extremely low and thus should be avoided in most cases.

Wolach: Amgen: Other: Fees for lectures and Consultancy; Janssen: Other: Fees for lectures and Consultancy; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: Fees for lectures and Consultancy; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Fees for lectures and Consultancy, Research Funding; Astellas: Consultancy, Honoraria, Other: Fees for lectures and Consultancy.

ABSTRACTPCR in bronchoalveolar lavage (BAL) fluid has not been accepted as a diagnostic criterion for invasive pulmonary aspergillosis (IPA). We conducted a systematic review assessing the diagnostic accuracy of PCR in BAL fluid with a direct comparison versus galactomannan (GM) in BAL fluid. We included prospective and retrospective cohort and case-control studies. Studies were included if they used the EORTC/MSG consensus definition criteria of IPA and assessed =80% of patients at risk for IPA. Two reviewers abstracted data independently. Risk of bias was assessed using QUADAS-2. Summary sensitivity and specificity values were estimated using a bivariate model and reported with a 95% confidence interval (CI). Nineteen studies published between 1993 and 2012 were included. The summary sensitivity and specificity values (CIs) for diagnosis of proven or probable IPA were 90.2% (77.2 to 96.1%) and 96.4% (93.3 to 98.1%), respectively. In nine cohort studies strictly adherent to the 2002 or 2008 EORTC/MSG criteria for reference standard definitions, the summary sensitivity and specificity values (CIs) were 77.2% (62 to 87.6%) and 93.5% (90.6 to 95.6%), respectively. Antifungal treatment before bronchoscopy significantly reduced sensitivity. The diagnostic performance of PCR was similar to that of GM in BAL fluid using an optical density index cutoff of 0.5. If either PCR or GM in BAL fluid defined a positive result, the pooled sensitivity was higher than that of GM alone, with similar specificity. We conclude that the diagnostic performance of PCR in BAL fluid is good and comparable to that of GM in BAL fluid. Performing both tests results in optimal sensitivity with no loss of specificity. Results are dependent on the reference standard definitions.

To determine the prevalence, characteristics, and risk factors for nosocomial infections (NIs) in children postcardiac surgery and hospitalized in a pediatric intensive care unit (PICU).

Objectives:Compared with the general population, patients after allogeneic hematopoietic cell transplantation (HCT) are at higher risk to develop severe disease or die from COVID-19. Immunosuppressive therapy and graft-vs-host disease (GVHD) may abrogate the ability of transplanted patients to mount an adequate immune response to vaccines. We assessed the immune response of patients after allogeneic HCT to the BNT162b2 vaccine (Pfizer-BioNTech) and identified patient and treatment-related factors that predict humoral response in this population.

Yeshurun: Astellas: Consultancy; Jannsen: Consultancy. Wolach: Janssen: Consultancy; Abbvie: Consultancy, Honoraria, Research Funding; Astellas: Consultancy; Amgen: Research Funding; Novartis: Consultancy; Neopharm: Consultancy.

OBJECTIVE:s To determine and quantify differences in efficacy between treatment regimens for brucellosis. Design Systematic review and meta-analysis of randomised controlled trials assessing different antibiotic regimens and durations of treatment for human brucellosis. DATA SOURCES: PubMed, CENTRAL, Lilacs, conference proceedings, and bibliographies with no restrictions on language, study year, or publication status. Review methods Search, application of inclusion and exclusion criteria, data extraction, and assessment of methodological quality independently performed in duplicate. Primary outcomes were relapse and overall failure resulting from primary failure or relapse. Relative risks with 95% confidence intervals were calculated and pooled with a fixed effect model. RESULTS: 30 trials and 77 treatment arms were included. Overall failure was significantly higher with doxycycline-rifampicin compared to doxycycline-streptomycin, mainly due to a higher rate of relapse (relative risk 2.80, 95% confidence interval 1.81 to 4.36; 13 trials, without heterogeneity). Results were consistent among patients with bacteraemia and complicated brucellosis. Doxycycline-streptomycin resulted in a significantly higher rate of failure than doxycycline-rifampicin-aminoglycoside (triple drug regimen) (2.50, 1.26 to 5.00; two trials). Gentamicin was not inferior to streptomycin (1.45, 0.52 to 4.00 for failure; two trials). Quinolones combined with rifampicin were significantly less effective than doxycycline combined with rifampicin or streptomycin (1.83, 1.11 to 3.02, for failure; five trials). Monotherapy was associated with a higher risk of failure than combined treatment when administered for a similar duration (2.56, 1.55 to 4.23; five trials). Treatment for six weeks or more offered an advantage over shorter treatment durations. CONCLUSIONS: There are significant differences in effectiveness between currently recommended treatment regimens for brucellosis. The preferred treatment should be with dual or triple regimens including an aminoglycoside.

Objectives: Early, empirical broad-spectrum antibiotic treatment is the established practice for febrile neutropenia. Several β-lactams are accepted for monotherapy. We asked whether patients' outcomes are influenced by the chosen β-lactam.Methods: Systematic review and meta-analysis of randomized controlled trials comparing anti-pseudomonal β-lactams administered as empirical monotherapy for febrile neutropenia, with or without vancomycin. The search included The Cochrane Library, PubMed, Embase, Lilacs databases, bibliography, conference proceedings, trial registries and FDA new drug approvals. Two reviewers independently applied selection criteria, performed quality assessment and extracted the data. Trials assessing the same β-lactam were pooled using the fixed effect model. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated. The primary outcome assessed was all-cause mortality.Results: Thirty-three trials fulfilled inclusion criteria. Cefepime was associated with higher all-cause mortality at 30 days than other β-lactams (RR 1.44, 95% CI 1.06–1.94, 3123 participants). Carbapenems were associated with fewer treatment modifications, including addition of glycopeptides, than ceftazidime or other comparators. Adverse events were significantly more frequent with carbapenems, specifically pseudomembranous colitis (RR 1.94, 95% CI 1.24–3.04, 2025 participants). All-cause mortality was unaltered. Piperacillin/tazobactam was compared only with cefepime and carbapenems, in six trials. No significant differences were demonstrated with paucity of data for all-cause mortality.Conclusions: The use of cefepime for febrile neutropenia is associated with increased mortality and should be carefully considered pending further analysis. Empirical use of carbapenems entails fewer treatment modifications, but an increased rate of pseudomembranous colitis. Ceftazidime, piperacillin/tazobactam, imipenem/cilastatin and meropenem appear to be suitable agents for monotherapy.

The limited armamentarium against drug-resistant Gram-negative bacilli has led to the development of several novel ß-lactam–ß-lactamase inhibitor combinations (BLBLIs). In this review, we summarize their spectrum of in vitroactivities, mechanisms of resistance, and pharmacokinetic-pharmacodynamic (PK-PD) characteristics. A summary of available clinical data is provided per drug. Four approved BLBLIs are discussed in detail. All are options for treating multidrug-resistant (MDR) Enterobacteralesand Pseudomonas aeruginosa.

(Abstracted from JAMA2018;319:1781–1789)Guidelines for the treatment of uncomplicated lower urinary tract infections (UTIs) were modified in 2010 because of increasing antimicrobial resistance. The new guidelines recommend nitrofurantoin and fosfomycin as first-line agents.