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.

Translating a theory-based positive deviance approach into an applied tool: Mitigating barriers among health professionals (HPs) regarding infection prevention and control (IPC) guidelines.

BACKGROUND: Although a wide range of intervention programs and methods have been implemented to increase health professionals' (HPs) adherence with infection prevention and control (IPC) guidelines and decrease the incidence of healthcare associated infections (HAIs), a significant discrepancy remains between the guidelines and their implementation in practice. OBJECTIVES: This study proposes an applied tool based on the integrated theoretical framework of the positive deviance (PD) approach for developing more effective interventions to mitigate this discrepancy. METHODS: A qualitative study guided by the PD approach based on data from two sources: (1) in-depth archival analysis of systematic review articles, and (2) integration and synthesis of findings based on an extensive empirical study we conducted, involving 250 HPs (nurses, physicians, support staff and cleaning staff) from three governmental hospitals in Israel, over 35 months (January 2017 to November 2020). RESULTS: The barriers faced by HPs were classified into four main categories: (1) individual-motivational, (2) social-cultural, (3) organizational, and (4) work environment and resource-centered. For each barrier, we constructed a set of questions based on the PD approach. For each question, we adapted and applied methodological tools (e.g., in-depth interviews, focus groups, social network maps, video clips and simulations) to help solve the problem. CONCLUSION: Translating a theory-based approach into an applied tool that offers step-by-step actions can help researchers and practitioners adopt and implement the approach within intervention programs to mitigate barriers.

Therapeutic Potential of Injectable Nano-Mupirocin Liposomes for Infections Involving Multidrug-Resistant Bacteria.

Antibiotic resistance is a global health threat. There are a few antibiotics under development, and even fewer with new modes of action and no cross-resistance to established antibiotics. Accordingly, reformulation of old antibiotics to overcome resistance is attractive. Nano-mupirocin is a PEGylated nano-liposomal formulation of mupirocin, potentially enabling parenteral use in deep infections, as previously demonstrated in several animal models. Here, we describe extensive in vitro profiling of mupirocin and Nano-mupirocin and correlate the resulting MIC data with the pharmacokinetic profiles seen for Nano-mupirocin in a rat model. Nano-mupirocin showed no cross-resistance with other antibiotics and retained full activity against vancomycin-, daptomycin-, linezolid- and methicillin- resistant Staphylococcus aureus, against vancomycin-resistant Enterococcus faecium, and cephalosporin-resistant Neisseria gonorrhoeae. Following Nano-mupirocin injection to rats, plasma levels greatly exceeded relevant MICs for >24 h, and a biodistribution study in mice showed that mupirocin concentrations in vaginal secretions greatly exceeded the MIC90 for N. gonorrhoeae (0.03 µg/mL) for >24 h. In summary, Nano-mupirocin has excellent potential for treatment of several infection types involving multiresistant bacteria. It has the concomitant benefits from utilizing an established antibiotic and liposomes of the same size and lipid composition as Doxil®, an anticancer drug product now used for the treatment of over 700,000 patients globally.

Utilization of the Public Health Ordinance to prevent nosocomial spread in a case of acute measles-associated psychosis.

Measles is a highly contagious disease. A 24 years old patient, recently exposed to measles (unvaccinated), presented in the emergency department with severe agitation, compatible with an acute psychotic episode, during the measles epidemic which spread in Israel in 2018-2019. Upon hospital admission, strict isolation was instructed, yet, without compliance, probably due to the patient's status. Measles diagnosis was promptly confirmed. As measles transmission was eminent, public health measures were employed through immediate implementation of the section 15 of the Public Health Ordinance, allowing for compulsory short-term isolation. The patient's condition improved within a few days and the measures were no longer necessary. This measles case occurred in the pre-Coronavirus disease 2019 (COVID-19) epidemic when use of a Public Health Ordinance was considered an extreme measure. This is in contrast to the current global use of Public Health laws to enforce strict quarantine and isolation on persons infected or potentially exposed to COVID-19. Nevertheless, minimizing infectious diseases transmission is a core function of public health law. Utilizing legal enforcement in circumstances of immediate public health hazard, such as nosocomial measles transmission, necessitates careful consideration. The integrative clinical and public health approach and prompt measures employed in this exceptional case, led to prevention of further infection spread.

Is it financially beneficial for hospitals to prevent nosocomial infections?

BACKGROUND: Financial incentives represent a potential mechanism to encourage infection prevention by hospitals. In order to characterize the place of financial incentives, we investigated resource utilization and cost associated with hospital-acquired infections (HAI) and assessed the relative financial burden for hospital and insurer according to reimbursement policies. METHODS: We conducted a prospective matched case-control study over 18 months in a tertiary university medical center. Patients with central-line associated blood-stream infections (CLABSI), Clostridium difficile infection (CDI) or surgical site infections (SSI) were each matched to three control patients. Resource utilization, costs and reimbursement (per diem for CLABSI and CDI, diagnosis related group (DRG) reimbursement for SSI) were compared between patients and controls, from both the hospital and insurer perspective. RESULTS: HAIs were associated with increased resource consumption (more blood tests, imaging, antibiotic days, hospital days etc.). Direct costs were higher for cases vs. controls (CLABSI: $6400 vs. $2376 (p < 0.001), CDI: $1357 vs $733 (p = 0.047) and SSI: $6761 vs. $5860 (p < 0.001)). However as admissions were longer following CLABSI and CDI, costs per-day were non-significantly different (USD/day, cases vs. controls: CLABSI, 601 vs. 719, (p = 0.63); CDI, 101 vs. 93 (p = 0.5)). For CLABSI and CDI, reimbursement was per-diem and thus the financial burden ($14,608 and $5430 respectively) rested on the insurer, not the hospital. For SSI, as reimbursement was per procedure, costs rested primarily on the hospital rather than the insurer. CONCLUSION: Nosocomial infections are associated with both increased resource utilization and increased length of stay. Reimbursement strategy (per diem vs DRG) is the principal parameter affecting financial incentives to prevent hospital acquired infections and depends on the payer perspective. In the Israeli health care system, financial incentives are unlikely to represent a significant consideration in the prevention of CLABSI and CDI.

Vaginal microbiome transplantation in women with intractable bacterial vaginosis.

We report the results of a first exploratory study testing the use of vaginal microbiome transplantation (VMT) from healthy donors as a therapeutic alternative for patients suffering from symptomatic, intractable and recurrent bacterial vaginosis (ClinicalTrials.gov NCT02236429 ). In our case series, five patients were treated, and in four of them VMT was associated with full long-term remission until the end of follow-up at 5-21 months after VMT, defined as marked improvement of symptoms, Amsel criteria, microscopic vaginal fluid appearance and reconstitution of a Lactobacillus-dominated vaginal microbiome. One patient presented with incomplete remission in clinical and laboratory features. No adverse effects were observed in any of the five women. Notably, remission in three patients necessitated repeated VMT, including a donor change in one patient, to elicit a long-standing clinical response. The therapeutic efficacy of VMT in women with intractable and recurrent bacterial vaginosis should be further determined in randomized, placebo-controlled clinical trials.

Deconstruction of central line insertion guidelines based on the positive deviance approach-Reducing gaps between guidelines and implementation: A qualitative ethnographic research.

BACKGROUND: Despite a proven association between the implementation of prevention guidelines for central line associated blood stream infections (CLABSI) and reduction in CLABSI rates, in practice there is poor adherence. Furthermore, current guidelines fail to address the multiple process on the care continuum. This research is based on the bottom-up "Positive Deviance" (PD) approach, through which multiple creative and safer solutions for central line (CL) insertion were identified that were not previously described in the guidelines. The aim of the study was to deconstruct CLABSI prevention guidelines ("during insertion" process only) through the PD approach, working with physicians to identify additional actions that, in practice, help maintain a sterile environment and contribute to patient safety. METHODS AND FINDINGS: Our study included a qualitative ethnographic study involving 76 physicians, working in a division of internal medicine and two intensive care units (ICUs). We triangulated findings from a combination of data-collection methods: semi-structured interviews, focused observations, video documentation, Discovery & Action Dialogue (DAD), and simulations. Deconstruction analysis was performed. A total of 23 creative extensions and variations of CL insertion practices were identified. CONCLUSIONS: The PD approach enables the identification of vital nuggets of hidden wisdom missing from the formal explicit CLABSI guidelines, and therefore helps bridge the gap between theory and praxis. During the guideline's deconstruction process, through collaborative staff learning, the written procedure is transformed into a living, breathing and cooperative one. It can reduce hospital stays and save lives, and therefore needs careful attention of healthcare scholars and practitioners.

Access-related infections in two haemodialysis units: results of a nine-year intervention and surveillance program.

Background: Access-related infections are a major cause of morbidity and mortality in haemodialysis patients. Our goal was to decrease the rate of these infections by implementing an intervention and surveillance program. Methods: This intervention took place in two haemodialysis units (Units A and B) and was a joint effort by the haemodialysis staff and the unit for infection prevention and control. It included reviewing the work methods and work space, observations on compliance with standard precautions and handling of the vascular access, creating a checklist and a designated kit for handling the vascular access and prospective surveillance of access-related infections. Results: During a nine-year period, the haemodialysis units A and B treated 4471 and 7547 patients (mean number of patients per year: 497 (range 435-556) and 839 (range 777-1055), respectively). For most patients, the procedure was done through an arteriovenous fistula (66.7%, range 50.3-81.5%). The access-related infection rate decreased significantly in both haemodialysis units: from 3 to 0.9% (trend: p < 0.05, linear regression: p < 0.001) in Unit A and from 0.9 to 0.2% (trend: p < 0.05, linear regression: p = 0.01) in Unit B. Conclusions: An intervention which included introduction of a checklist and designated kit, together with ongoing surveillance and feedback, resulted in a significant decrease in the access-related infection rates in both haemodialysis units.

The Clinical Presentation of Pediatric Mycoplasma pneumoniae Infections-A Single Center Cohort.

BACKGROUND: Mycoplasma pneumoniae (MP) is a major cause of community-acquired upper and lower respiratory infections in school-age children; however, there is increasing recognition that younger children are also affected. Clinical manifestations vary from asymptomatic, to severe complicated pneumonia sometimes with extrapulmonary manifestations. METHODS: We reviewed the medical records of all MP positive pediatric patients admitted to the Hadassah-Hebrew University Medical Center. MP positive case was defined if MP polymerase chain reaction was positive from an oropharyngeal swab sent from 2007 to 2017. RESULTS: During the study period, we identified 353 MP positive pediatric cases, of which 51.3% (181 of 353) were younger than 6 years old. Full clinical data were available for 332 of 353 (94%). The median age was 5.7 years (range, 3 weeks to 18 years). Disease presentation differed between younger and older children. Children older than 6 years were more likely to have chest radiograph confirmed pneumonia (66% vs. 52%; P = 0.009), while younger children were more likely to have other respiratory manifestations (37% vs. 25%; P = 0.017). The duration of hospitalization and pediatric intensive care unit admission rate, however, did not differ between age groups. The rate of extrapulmonary manifestations were also similar. CONCLUSIONS: MP-associated infection is a significant cause of hospitalization in the pediatric population including younger children (<6 years old). However, the clinical presentation in younger age is less typical than is thought. These findings should prompt clinicians to consider MP infections also in children younger than 6 admitted with fever even without pneumonia.

Successful Treatment of Antibiotic-resistant, Poly-microbial Bone Infection With Bacteriophages and Antibiotics Combination.

A patient with a trauma-related left tibial infection associated with extensively drug-resistant Acinetobacter baumannii and multidrug-resistant Klebsiella pneumoniae was treated with bacteriophages and antibiotics. There was rapid tissue healing and positive culture eradication. As a result, the patient's leg did not have to be amputated and he is undergoing rehabilitation.

Obstacles to the successful introduction of an electronic hand hygiene monitoring system, a cohort observational study.

Background: Hand hygiene (HH) compliance remains low in many intensive care units (ICU). Technology has been suggested to improve HH compliance.We describe the introduction of an electronic HH surveillance and intervention system into the general ICU of a tertiary care teaching hospital, the obstacles to success and reasons for the system's ultimate failure and removal. Methods: The system was based on radiofrequency transmitters in patient areas, on HH dispensers, and individual personal bracelets. The transmitters were connected to a central computer. The system was designed to detect entry and exit from patient areas and provide real time alerts of missed HH performance.A staff satisfaction questionnaire was administered followed by validation of system accuracy. Electronic data were compared to human observer data collected during defined observation periods. Results: Data from 41 questionnaires revealed low satisfaction rate (21/41, 51%). Low system accuracy (31/41, 76%) and inconvenience (18/41, 44%) being the most frequent reasons.During 44 one hour observation periods the observer recorded more HH opportunities and performances than the electronic system (mean number of HH opportunities/hour 10.9 ± 7.6 vs 6.8 ± 6.9, p < 0.001, correlation r = 0.75, p < 0.001, and performances/hour 8.7 ± 3.9 vs 6.0 ± 3.1, p < 0.001, correlation r = 0.60, p < 0.001, respectively). Correlation between observer and HH electronic system was very low (correlation coefficient r = 0.03, p = 0.91). Conclusions: The electronic HH system was not accepted by ICU staff principally due to inaccuracy and inconvenience. Inaccuracies were verified by direct observations. In order for an electronic HH system to succeed we suggest it must be highly accurate and comfortable to use.

Early onset, non-rheumatic, group A streptococcal-associated myocarditis.

OBJECTIVES: Group A streptococcal (GAS) tonsillitis is reported as an uncommon cause of acute non-rheumatic fever (non-RF) myocarditis. The aim of this research was to study the occurrence, diagnosis, management and prognosis of this condition. METHODS: We conducted a retrospective computerised search through medical records of patients admitted to our tertiary medical center between 1998-2016 with the diagnosis of either acute rheumatic fever or non-RF streptococcal myocarditis based on criteria we developed and review the relevant literature from 1973-2016. RESULTS: We identified 283 cases diagnosed with acute myocarditis. Eight patients with non-RF GAS-myocarditis were identified, 7 of whom were men. Average age was 28.5 (22-35) years, and average latency period between onset of sore throat and chest pain 4.8 (3-10) days. Most patients presented with ST-segment elevations on the ECG and 2 underwent coronary catheterisation with presumed diagnosis of myocardial infarction. Three patients had heart failure, as documented by echocardiogram. All patients were treated with antibiotics and 6 patients received non-steroidal anti-inflammatory drugs (NSAIDs). All patients recovered with no evidence of heart failure a few months after the initial infection. One patient had a recurrent episode. CONCLUSIONS: Non-RF GAS myocarditis typically affects healthy young males and represents about 3% of all hospitalised patients with myocarditis. These patients may be mistakenly diagnosed with an acute rheumatic fever or myocardial infarction. The prognosis in generally good following treatment with antibiotics and possibly NSAIDs.

The Effect of Repeated Versus Initial Procalcitonin Measurements on Diagnosis of Infection in the Intensive Care Setting: A Prospective Observational Study.

Procalcitonin (PCT) measurement has been proposed to direct antibiotic use. We examined whether repeated PCT measurements (0, 6, and/or 12 hours) versus the initial measurement only (time 0) increased the sensitivity and specificity of PCT for diagnosing infection in intensive care unit patients. Infection was identified in 67/176 (38%) patients. The sensitivity of repeated versus the initial PCT measurement (with a cutoff value 0.5 ng/mL) was 52/67 (77%; 95% confidence interval [CI], 66%-87%) vs 46/67 (69%; 95% CI, 56%-79%; P = .04) and specificity 60/109 (55%; 95% CI, 45%-65%) vs 59/109 (54%; 95% CI, 44%-64%; P = 1.0). Repeat PCT evaluations over 12 hours did not provide a clinically significant improvement in diagnostic accuracy when compared to the initial single test.

Staphylococcus aureus Bacteremia in Children: Antibiotic Resistance and Mortality.

BACKGROUND: Staphylococcus aureus (SA) is a major cause of bacteremia in children. Methicillin-resistant SA (MRSA) is considered a public health threat; however, the differences in the prognosis of children with methicillin-susceptible SA (MSSA) versus MRSA bacteremia are not well defined. METHODS: Data from all SA bacteremia events in children (0-16 years) from 2002 to 2016 in a single Israeli tertiary center were collected. Positive cultures within 48 hours of hospitalization were considered community associated (CA). Those obtained afterward or from children hospitalized within the previous year were considered health-care associated (HA). RESULTS: We recorded 427 events, 284 (66%) were HA, 64 (15%) were MRSA and 9 (2%) were CA-MRSA. There was no increase in MRSA during the study period. In-hospital, 30-day and 1-year mortality were 3% (12 cases), 3.5% (16 cases), and 12% (50 cases), respectively. A multivariable analysis controlling for demographics, admitting department and prior morbidity showed an increased 1-year mortality in children with HA bacteremia (hazard ratio [HR] 4.1; 95% confidence interval [CI]: 1.3-12) and prior chronic disease (HR 3.4; 95% CI 1.2 to 9.0). MRSA was not independently associated with increased one-year mortality compared with MSSA: HR (95% CI: 1.4 [0.6-3.1]). CONCLUSIONS: Short-term pediatric mortality after SA bacteremia is low. HA-SA bacteremia has an increased long-term risk for mortality, particularly in children with chronic diseases. Our data suggest mortality was not increased for MRSA compared with MSSA bacteremia. The very low rate of CA-MRSA bacteremia justifies the current practice not to include glycopeptides in the empiric treatment of CA bacteremia in Israel.

Carriage of multi-drug resistant bacteria among foreigners seeking medical care.

Medical tourism has a potential of spreading multi-drug resistant bacteria (MDR). The Hadassah Medical Center serves as a referral center for global medical tourists and for Palestinian Authority residents. In order to assess whether patients of these groups are more likely to harbor MDR bacteria than local residents, we reviewed data from all patients admitted to our institution between 2009 and 2014. We compared MDR rates between countries of residency, controlling for gender, age, previous hospitalization and time from admission to MDR detection. Overall, among 111,577 patients with at least one microbiological specimen taken during hospitalization, there were 3,985 (3.5%) patients with at least one MDR-positive culture. Compared to Israeli patients, tourists and patients from the Palestinian Authority had increased rates of MDR positivity (OR, 95%CI): 2.3 (1.6 to 2.3) and 8.0 (6.3 to 10.1), respectively. Our data show that foreign patients seeking advanced medical care are more likely to carry MDR bacteria than the resident population. Strategies to minimize MDR spread, such as pre-admission screening or pre-emptive isolation should be considered in this population.

Empiric antibiotic protocols for cancer patients with neutropenia: a single-center study of treatment efficacy and mortality in patients with bacteremia.

BACKGROUND: There are several empiric antibiotic treatment options for febrile neutropenia, yet there is no universally-accepted initial protocol. We aimed to assess the performance of a protocol (piperacillin, gentamicin and cefazolin) introduced over 40 years ago and compare its coverage against bacteria isolated from blood of neutropenic patients with that of various commonly used antibiotic treatment protocols. METHODS: Adults with neutropenia admitted between 2003 and 2012 to the hemato-oncologic departments and in whom blood cultures were taken on admission were included. Appropriateness of several common antibiotic protocols was assessed based on the susceptibility of the blood isolates. Crude mortality rates were computed by the susceptibility of bacteria isolated from patients' blood to the actual treatment given. RESULTS: In total, 180 admissions of neutropenic patients (95 in patients who had fever above 38 °C) with positive blood cultures were analyzed. The actual antibiotic regimen prescribed was deemed appropriate in 82% of bacteremia episodes. The recommended institutional protocol was used in 62% of bacteremia episodes in neutropenic patients. This protocol would have been appropriate in 85% of all neutropenic bacteremia episodes and 89% of episodes in febrile neutropenia patients compared with piperacillin/tazobactam (79%, P = 0.13 and 76%, P = 0.002, respectively) and imipenem (93%, P = 0.004 and 92%, P = 0.74, respectively). Isolation of bacteria resistant to the actual antibiotic treatment given was associated with higher mortality at one week and at 30 days. CONCLUSION: Common current antibiotic regimens provide similar coverage among febrile neutropenic patients, whereas broad spectrum antibiotic combinations maximize coverage among neutropenic patients.

Multi-center evaluation of one commercial and 12 in-house real-time PCR assays for detection of Mycoplasma pneumoniae.

Detection of Mycoplasma pneumoniae by real-time PCR is not yet standardized across laboratories. We have implemented a standardization protocol to compare the performance of thirteen commercial and in-house approaches. Despite differences on threshold values of samples, all assays were able to detect at least 20M. pneumoniae genomes per reaction.

Analysis of Influenza and RSV dynamics in the community using a 'Local Transmission Zone' approach.

Understanding the dynamics of pathogen spread within urban areas is critical for the effective prevention and containment of communicable diseases. At these relatively small geographic scales, short-distance interactions and tightly knit sub-networks dominate the dynamics of pathogen transmission; yet, the effective boundaries of these micro-scale groups are generally not known and often ignored. Using clinical test results from hospital admitted patients we analyze the spatio-temporal distribution of Influenza Like Illness (ILI) in the city of Jerusalem over a period of three winter seasons. We demonstrate that this urban area is not a single, perfectly mixed ecology, but is in fact comprised of a set of more basic, relatively independent pathogen transmission units, which we term here Local Transmission Zones, LTZs. By identifying these LTZs, and using the dynamic pathogen-content information contained within them, we are able to differentiate between disease-causes at the individual patient level often with near-perfect predictive accuracy.