Diagnosis and Risk Factors of Prediabetes and Diabetes in People Living With Human Immunodeficiency Virus: Evaluation of Clinical and Microbiome Parameters.

Diabetes mellitus (DM) is more common among people living with human immunodeficiency virus (PLWH) compared with healthy individuals. In a prospective multicenter study (N = 248), we identified normoglycemic (48.7%), prediabetic (44.4%), and diabetic (6.9%) PLWH. Glycosylated hemoglobin (HbA1c) and fasting blood glucose (FBG) sensitivity in defining dysglycemia was 96.8%, while addition of oral glucose tolerance test led to reclassification of only 4 patients. Inclusion of 93 additional PLWH with known DM enabled identification of multiple independent predictors of dysglycemia or diabetes: older age, higher body mass index, Ethiopian origin, HIV duration, lower integrase inhibitor exposure, and advanced disease at diagnosis. Shotgun metagenomic microbiome analysis revealed 4 species that were significantly expanded with hyperglycemia/hyperinsulinemia, and 2 species that were differentially more prevalent in prediabetic/diabetic PLWH. Collectively, we uncover multiple potential host and microbiome predictors of altered glycemic status in PLWH, while demonstrating that FBG and HbA1c likely suffice for diabetes screening. These potential diabetic predictors merit future prospective validation.

An international multicenter study comparing COVID-19 omicron outcomes in patients with hematological malignancies treated with obinutuzumab versus rituximab.

OBJECTIVES: Hematological malignancy (HM) patients treated with anti-CD20 monoclonal antibodies are at higher risk for severe COVID-19. A previous single-center study showed worse outcomes in patients treated with obinutuzumab compared to rituximab. We examined this hypothesis in a large international multicenter cohort. METHODS: We included HM patients from 15 centers, from five countries treated with anti-CD20, comparing those treated with obinutuzumab (O-G) to rituximab (R-G) between December 2021 and June 2022, when Omicron lineage was dominant. RESULTS: We collected data on 1048 patients. Within the R-G (n = 762, 73%), 191 (25%) contracted COVID-19 compared to 103 (36%) in the O-G. COVID-19 patients in the O-G were younger (61 ± 11.7 vs. 64 ± 14.5, p = 0.039), had more indolent HM diagnosis (aggressive lymphoma: 3.9% vs. 67.0%, p < 0.001), and most were on maintenance therapy at COVID-19 diagnosis (63.0% vs. 16.8%, p < 0.001). Severe-critical COVID-19 occurred in 31.1% of patients in the O-G and 22.5% in the R-G. In multivariable analysis, O-G had a 2.08-fold increased risk for severe-critical COVID-19 compared to R-G (95% CI 1.13-3.84), adjusted for Charlson comorbidity index, sex, and tixagevimab/cilgavimab (T-C) prophylaxis. Further analysis comparing O-G to R-G demonstrated increased hospitalizations (51.5% vs. 35.6% p = 0.008), ICU admissions (12.6% vs. 5.8%, p = 0.042), but the nonsignificant difference in COVID-19-related mortality (n = 10, 9.7% vs. n = 12, 6.3%, p = 0.293). CONCLUSIONS: Despite younger age and a more indolent HM diagnosis, patients receiving obinutuzumab had more severe COVID-19 outcomes than those receiving rituximab. Our findings underscore the need to evaluate the risk-benefit balance when considering obinutuzumab therapy for HM patients during respiratory viral outbreaks.

Evaluation of a novel surface-coating formulation with time-extended antimicrobial activity for healthcare environment disinfection.

BACKGROUND: The importance of environmental contamination in the transmission of pathogens among hospitalized patients is universally recognized, and disinfection of surfaces is a widely accepted modality for reducing healthcare-associated infections. Nevertheless, hospital disinfection is still suboptimal. In this study, we evaluated the sustained effects of the novel formulation OxiLast™ which extends the antimicrobial effects of chlorine-based disinfectants. METHODS: In an experimental lab phase, PVC surfaces were coated with OxiLast™ and then inoculated with representative Gram-positive and Gram-negative pathogenic bacteria. Cells were recovered at different contact times (5, 15, 30 min) to assess the reduction in bacterial counts compared to uncoated surfaces and also subject to various challenges to assess robustness. A similar methodology was then applied in an unoccupied hospital room to evaluate the sustained effect of OxiLast™ on high-touch surfaces. RESULTS: OxiLast™ demonstrated notable activity against the range of bacterial strains tested with ≥ 4 log10 reduction in bacterial counts observed for up to seven days following one surface application, for various strains and contact times. Similar results were observed following challenges such as simulated abrasion of coated surfaces, organic contamination or successive inoculations. The results were confirmed in a simulated patient care environment. CONCLUSIONS: The addition of OxiLast™ to common chlorine-based disinfectants has shown a substantial and sustained reduction in bacterial pathogen counts for up to 7 days following one application. The consistent results in the laboratory and hospital are promising and should be tested in a real-life clinical scenario.

Refractory Pseudomonas aeruginosa infections treated with phage PASA16: A compassionate use case series.

BACKGROUND: A growing number of compassionate phage therapy cases were reported in the last decade, with a limited number of clinical trials conducted and few unsuccessful clinical trials reported. There is only a little evidence on the role of phages in refractory infections. Our objective here was to present the largest compassionate-use single-organism/phage case series in 16 patients with non-resolving Pseudomonas aeruginosa infections. METHODS: We summarized clinical phage microbiology susceptibility data, administration protocol, clinical data, and outcomes of all cases treated with PASA16 phage. In all intravenous phage administrations, PASA16 phage was manufactured and provided pro bono by Adaptive Phage Therapeutics. PASA16 was administered intravenously, locally to infection site, or by topical use to 16 patients, with data available for 15 patients, mainly with osteoarticular and foreign-device-associated infections. FINDINGS: A few minor side effects were noted, including elevated liver function enzymes and a transient reduction in white blood cell count. Good clinical outcome was documented in 13 out of 15 patients (86.6%). Two clinical failures were reported. The minimum therapy duration was 8 days with a once- to twice-daily regimen. CONCLUSIONS: PASA16 with antibiotics was found to be relatively successful in patients for whom traditional treatment approaches have failed previously. Such pre-phase-1 cohorts can outline potential clinical protocols and facilitate the design of future trials. FUNDING: The study was funded in part by The Israeli Science Foundation IPMP (ISF_1349/20), Rosetrees Trust (A2232), United States-Israel Binational Science Foundation (2017123), and the Milgrom Family Support Program.

Real-Life Comparison of Fosfomycin to Nitrofurantoin for the Treatment of Uncomplicated Lower Urinary Tract Infection in Women.

In this study, we compared the failure rates of fosfomycin and nitrofurantoin for uncomplicated urinary tract infections. We used Meuhedet Health Services' large database to collect data on all female patients, older than 18 years, who were prescribed either antibiotic during 2013-2018. Treatment failure was a composite endpoint of hospitalization, emergency-room visit, IV antibiotic treatment, or prescription of a different antibiotic, within seven days of the initial prescription. Reinfection was considered when one of these endpoints appeared 8-30 days following the initial prescription. We found 33,759 eligible patients. Treatment failure was more common in the fosfomycin group than the nitrofurantoin group (8.16% vs. 6.87%, p-value < 0.0001). However, reinfection rates were higher among patients who received nitrofurantoin (9.21% vs. 7.76%, p-value < 0.001). Among patients younger than 40 years, patients treated with nitrofurantoin had more reinfections (8.68% vs. 7.47%, p value = 0.024). Treatment failure rates were mildly higher in patients treated with fosfomycin, despite having less reinfections. We suggest that this effect is related to a shorter duration of treatment (one vs. five days) and encourage clinicians to be more patient before declaring fosfomycin failure and prescribing another antibiotic.

Sources of primary bloodstream infections in internal medicine patients - a cohort study.

PURPOSE: To describe the sources of bloodstream infections (BSIs) in internal-medicine patients, on admission and during hospitalization, and to determine the proportion of BSIs in which no secondary cause could be defined (i.e., primary-BSI). METHODS: We analyzed all BSIs at the internal-medicine wards of the two campuses of the Hadassah Hebrew-University Medical Center, during 2017-2018. We defined the BSI source of each event (secondary, Central-line associated BSI (CLABSI) or primary non-CLABSI) and compared BSIs present on admission (POA) to hospital acquired (HA). RESULTS: There were 595 patient-unique BSI events, 316 (53.1%) POA-BSI and 279 (46.9%) HA-BSI. Overall, 309 (51.9%) were secondary, 194 (32.6%) primary non-CLABSI and 92 (15.5%) CLABSI. Primary non-CLABSI in the POA-BSI group was 20.6% vs. 46.2% in the HA-BSI group (p = 0.001). The length of hospital stay (LOS) of the HA-BSI group was longer than in the POA-BSI group (mean LOS, 19 days vs. 13.6 days, p = 0.01) and mortality rate was higher (48.7% vs. 19%, p = 0.001). Staphylococcus aureus was more common in primary non-CLABSI than in CLABSI and secondary BSI (29.5%, 12.8% and 16.2%, respectively). CONCLUSIONS: The proportion of primary non-CLABSI among HA-BSI events is very high (46.2%). The absence of any plausible source for these BSIs, and the fact that in our hospital more than 90% of patients in medicine wards have peripheral lines, suggests that these may be a possible source for primary non-CLABSIs. Measures to prevent peripheral-line associated BSI (PLABSI), like those implemented successfully for the prevention of CLABSI, should be considered.

Viral and Bacterial Respiratory Pathogens during the COVID-19 Pandemic in Israel.

BACKGROUND: previous worldwide reports indicated a substantial short-term reduction in various respiratory infections during the early phase of the SARS-CoV-2 pandemic. AIMS: exploring the long-term impact of the COVID-19 pandemic on respiratory pathogens. METHODS: retrospective analysis of bacterial and viral positivity rate in respiratory samples, between 1 January 2017-30 June 2022 in a tertiary hospital in Jerusalem, Israel. RESULTS: A decline in overall respiratory tests and positivity rate was observed in the first months of the pandemic. Respiratory isolations of Hemophilus influenza and Streptococcus pneumoniae were insignificantly affected and returned to their monthly average by November 2020, despite a parallel surge in COVID-19 activity, while Mycoplasma pneumoniae was almost eliminated from the respiratory pathogens scene. Each viral pathogen acted differently, with adenovirus affected only for few months. Human-metapneumovirus and respiratory-syncytial-virus had reduced activity for approximately a year, and influenza A virus resurged in November 2021 with the elimination of Influenza-B. CONCLUSIONS: After an immediate decline in non-SARS-CoV-2 respiratory infections, each pathogen has a different pattern during a 2-year follow-up. These patterns might be influenced by intrinsic factors of each pathogen and different risk reduction behaviors of the population. Since some of these measures will remain in the following years, we cannot predict the timing of return to pre-COVID-19 normalcy.

Are Healthcare Workers Infected with SARS-CoV-2 at Home or at Work? A Comparative Prevalence Study.

Prior to the widespread use of vaccinations, healthcare workers (HCWs) faced the double burden of caring for unprecedented numbers of critically ill COVID-19 patients while also facing the risk of becoming infected themselves either in healthcare facilities or at home. In order to assess whether SARS-CoV-2-positivity rates in HCWs reflected or differed from those in their residential areas, we compared the SARS-CoV-2-positivity rates during 2020 among HCWs in Hadassah Hebrew University Medical Centers (HHUMC), a tertiary medical center in Jerusalem, Israel, to those of the general population in Jerusalem, stratified by neighborhood. Additionally, we compared the demographic and professional parameters in every group. Four percent of the adult population (>18 years) in Jerusalem tested positive for SARS-CoV-2 during 2020 (24,529/605,426) compared to 7.1% of HHUMC HCWs (317/4470), rate ratio 1.75 (95% CI 1.57-1.95), with wide variability (range 0.38-25.0) among different neighborhoods. Of the 30 neighborhoods with more than 50 infected HCWs, 25 showed a higher positivity rate for HCWs compared to the general population. The higher risk of HCWs compared to residents representing the general population in most neighborhoods in Jerusalem may be explained by their behavior in and out of the hospital.

Characteristics of endovascular pneumococcal infections; a decade of nationwide surveillance study.

In order to characterize pneumococcal endovascular infection in the post-vaccination era, a retrospective nationwide study based on the Israeli Adult IPD database was conducted. Between 2010 and 2019, 0.6% (23 cases) of IPD cases were of endovascular type, occurring mainly in males (72.3%) with underlying medical conditions (78.2%). Additional pneumococcal source (10 patients) and concomitant infections were not uncommon. Penicillin and ceftriaxone susceptibility rates were 65.2% and 91.3%, respectively; 60.9% of the isolates were not covered by the pneumococcal conjugate vaccine. 21.7% of patients died during hospitalization. In conclusion, pneumococcal endovascular infections still carry significant morbidity and mortality.

A Rare Case of Endocarditis and Mycotic Pseudoaneurysm of the Left Ventricle Caused by Escherichia coli Following Transcatheter Aortic Valve Replacement.

Infective endocarditis caused by gram-negative enteral bacteria is very rare. Herein, we report the first case of infective endocarditis complicated by a paravalvular mycotic pseudoaneurysm of the left ventricle caused by Escherichia coli post transcatheter aortic valve replacement, highlighting the diagnostic workup, multimodality imaging, and treatment options.

Association of Receiving a Fourth Dose of the BNT162b Vaccine With SARS-CoV-2 Infection Among Health Care Workers in Israel.

Importance: Despite the high 3-dose vaccination rate among health care workers (HCWs) in Israel, a high rate of SARS-CoV-2 breakthrough infections in this group was observed during the Omicron wave. As a result, the Israeli Ministry of Health decided to recommend a fourth vaccine dose to medical staff. Objective: To evaluate the benefit of a fourth BNT162b2 vaccine dose on the breakthrough infection rate among HCWs. Design, Setting, and Participants: This multicenter cohort study was performed in January 2022, the first month of the 4-dose vaccination campaign, during a surge of the Omicron variant wave. All health care workers at 11 general hospitals in Israel who had been vaccinated with 3 doses up to September 30, 2021, and had not contracted COVID-19 before the vaccination campaign were included. Exposures: Vaccination with a fourth dose of the BNT162b2 vaccine during January 2022. Main Outcomes and Measures: Breakthrough COVID-19 infections in 4-dose recipients vs 3-dose recipients measured by a polymerase chain reaction test result positive for SARS-CoV-2. Health care workers were tested based on symptoms or exposure. Results: A total of 29 611 Israeli HCWs (19 381 [65%] female; mean [SD] age, 44 [12] years) had received 3 vaccine doses between August and September 2021; of these, 5331 (18%) received the fourth dose in January 2022 and were not infected by the first week after vaccination. Overall breakthrough infection rates were 368 of 5331 (7%) in the 4-dose group and 4802 of 24280 (20%) in the 3-dose group (relative risk, 0.35; 95% CI, 0.32-0.39). Similar reductions were found in a matched analysis by the exact day of receiving the third vaccine (relative risk, 0.61; 95% CI, 0.54-0.71) and in a time-dependent Cox proportional hazards regression model (adjusted hazard ratio, 0.56; 95% CI, 0.50-0.63). In both groups, no severe disease or death occurred. Conclusions and Relevance: In this cohort study, the fourth BNT162b2 vaccine dose resulted in a reduced breakthrough infection rate among hospital staff. This reduction was lower than that observed after the third dose; nevertheless, considering the high infectivity of the Omicron variant, which led to critical medical staff shortages, a fourth vaccine dose should be considered to mitigate the infection rate among HCWs.

A Case Report of Mycoplasma hominis Subdural Empyema Following Decompressive Craniotomy, and a Review of Central Nervous System Mycoplasma hominis Infections.

Background: Mycoplasma hominis is a small cell-wall-free organism, part of the normal microbiota of the genitourinary tract. It is rarely involved in extragenital infections, mainly joint, surgical-site, and respiratory infections. Methods: We describe a case of M. hominis subdural empyema and lower limb surgical site infections, following decompressive craniotomy, after traumatic brain and extremities injury. In addition, a literature review of 34 cases M. hominis CNS infections was done. Results: Our case depicts a 25-years old patient who developed subdural empyema and surgical site infections in his cranium and fibula. Both sites were cultured, and small pinpoint colonies grew on blood agar. MALDI-TOF MS identified M. hominis. Simultaneously 16S-rDNA PCR from CSF detected M. hominis. Antimicrobial treatment was switched to doxycycline with improvement. Literature review revealed 21 adults and 13 pediatric cases of M. hominis CNS infection. Risk factors in adults were head trauma, neurosurgery, or post-partum period. Conclusions: Based upon the literature reviewed, we postulate that adult patients with head trauma or neurosurgical procedure, rarely are infected either through direct contamination during the trauma, or by undergoing urgent, urinary catheterization, and may experience distant infection due to translocation of M. hominis into the bloodstream. In such cases diagnosis is delayed due to difficulties in growing and identifying the bacteria. Empiric antimicrobials are usually not effective against mycoplasmas. These factors contributed to the mortality in adult cases (15%). Our rare case highlights the necessity of combining classical microbiology routines with advanced molecular techniques to establish a diagnosis in complicated cases.

Native aortic valve Staphylococcus warneri endocarditis after COVID-19 infection: a case report and a review of literature.

We report a case of Staphylococcus warneri native valve endocarditis in an immunocompetent healthy adult, without known risk factors for infective endocarditis, two months following COVID-19 infection, who recovered with conservative treatment. Additionally, we reviewed previous cases of native valve endocarditis caused by Staphylococcus warneri and summarized the main clinical implications.

The effect of a third BNT162b2 vaccine on breakthrough infections in health care workers: a cohort analysis.

OBJECTIVES: In August 2021, 6 months after mass vaccination of the Israeli population with the two-dose BNT162b2 mRNA vaccine, a surge of coronavirus disease 2019 infections, mostly from the delta variant, appeared also among the vaccinated. In response, the Israeli Ministry of Health initiated a booster (third dose) vaccination program. We assessed the protective effect of the third dose among health care workers (HCWs). METHODS: Infections with severe acute respiratory syndrome coronavirus 2 are monitored systematically among HCWs at the Hadassah tertiary care medical centre in Jerusalem, Israel. In this cohort, we included breakthrough infections, defined as those occurring >180 days since the second vaccine dose. The follow-up period lasted 120 days. We compared infection rates between HCWs who received the booster dose and those who received only the two-dose regimen. RESULTS: The rate of breakthrough infections among HCWs who received only the two-dose regimen was 21.4% (85 of 398). The rate in the boosted group was 0.7% (35/4973; relative risk 30, 95% CI 20-50). Those results were seen in all age groups. DISCUSSION: The significantly lower rate of breakthrough infections in boosted HCWs indicates substantial protection by a third vaccine dose.

Impact of tozinameran (BNT162b2) mRNA vaccine on kidney transplant and chronic dialysis patients: 3-5 months follow-up.

BACKGROUND: Determining the humoral immunogenicity of tozinameran (BNT162b2) in patients requiring chronic renal replacement therapy, and its impact on COVID-19 morbidity several months after vaccination, may guide risk assessment and changes in vaccination policy. METHODS: In a prospective post-vaccination cohort study with up to 5 months follow-up we studied outpatient dialysis and kidney transplant patients and respective healthcare teams. Outcomes were anti S1/S2 antibody responses to vaccine or infection, and infection rate during follow-up. RESULTS: One hundred seventy-five dialysis patients (40% women, 65 ± 15 years), 252 kidney transplant patients (33% women, 54 ± 14 years) and 71 controls (65% women, 44 ± 14 years) were followed. Three months or longer after vaccination we detected anti S1/S2 IgG antibodies in 79% of dialysis patients, 42% of transplant recipients and 100% of controls, whereas respective rates after infection were 94%, 69% and 100%. Predictors of non-response were older age, diabetes, history of cancer, lower lymphocyte count and lower vitamin-D levels. Factors associated with lower antibody levels in dialysis patients were modality (hemodialysis vs peritoneal) and high serum ferritin levels. In transplant patients, hypertension and higher calcineurin or mTOR inhibitor drug levels were linked with lower antibody response. Vaccination was associated with fewer subsequent infections (HR 0.23, p < 0.05). Moreover, higher antibody levels (particularly above 59 AU/ml) were associated with fewer events, with a HR 0.41 for each unit increased in log10titer (p < 0.05). CONCLUSIONS: Dialysis patients, and more strikingly kidney transplant recipients, mounted reduced antibody response to COVID-19 mRNA vaccination. Lesser humoral response was associated with more infections. Measures to identify and protect non-responsive patients are required.