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.

More than 1 year into the current tragedy in Ethiopia,1Mackintosh E Ethiopia is at war with itself. Here's what you need to know about the conflict.https://edition.cnn.com/2021/11/03/africa/ethiopia-tigray-explainer-2-intl/index.htmlDate: Nov 5, 2021Date accessed: January 7, 2022Google Scholar the situation at Ayder Comprehensive Specialised Hospital, a major teaching institution in Mekele in Tigray, is dire.2Houreld K Paravicini G Doctors say lives are lost in hospitals in Ethiopia's Tigray due to dwindling supplies, blame blockade.https://www.reuters.com/business/healthcare-pharmaceuticals/doctors-say-lives-are-lost-hospitals-ethiopias-tigray-due-dwindling-supplies-2022-01-05/Date: Jan 5, 2022Date accessed: January 7, 2022Google Scholar In wars there are always many wrongs, often on both sides, but the worst is to deny food and medical care to innocent civilians—anywhere. As such, we, along with signatories of this Correspondence, appeal to the world's medical community to demand protection of hospitals such as Ayder from attack, and furthermore we plead for assistance in ensuring the provision of food, equipment, and medications to care for the civilian population of Tigray. As staff, and as colleagues who have worked in, visited, and collaborated with staff or are familiar with Ayder Hospital, we know the lengths to which its dedicated team has gone to provide humane, high-standard care in the past 14 years. Now, the hospital has been forced to cancel basic surgeries. The availability of essential medications has, as estimated by the Ayder Hospital,2Houreld K Paravicini G Doctors say lives are lost in hospitals in Ethiopia's Tigray due to dwindling supplies, blame blockade.https://www.reuters.com/business/healthcare-pharmaceuticals/doctors-say-lives-are-lost-hospitals-ethiopias-tigray-due-dwindling-supplies-2022-01-05/Date: Jan 5, 2022Date accessed: January 7, 2022Google Scholar plummeted from almost 80% 1 year ago to less than 20%, and laboratory tests have dropped from 94% to less than 50%. Patients are dying from a simple lack of a reliable oxygen supply. Due to the blockade of Tigray, spare parts for all medical machinery are not just in short supply—they are non-existent. Neurosurgeons are operating without the benefit of imaging, depending on clinical skills only—a situation reminiscent of the 19th century. In Ayder Hospital, which only recently could boast of its achievements in providing haemodialysis to those in need,3Paltiel O Berhe E Aberha AH Tequare MH Balabanova D A public-private partnership for dialysis provision in Ethiopia: a model for high-cost care in low-resource settings.Health Policy Plan. 2020; 35: 1262-1267Google Scholar patients with renal failure are dying before the eyes of attending staff due to the lack of basic supplies. Hospital staff have gone unpaid for most of 2021; and for those who still have some savings, the banks are closed. It is becoming impossible to feed the staff and their children. In short—a medical catastrophe is unfolding, in the background of war, famine, and a humanitarian tragedy. We demand that the relevant bodies, the UN, the African Union, WHO and, above all, the Ethiopian Government stand by the health workers and the patients in Mekele. It is heartbreaking to see that those with the capacity to help do nothing, merely muttering that they are gravely concerned. We write this on Christmas Day in Ethiopia. We pray for deliverance for Mekele's sick and helpless patients. This online publication has been corrected. The corrected version first appeared at thelancet.com on Jan 27, 2022 This online publication has been corrected. The corrected version first appeared at thelancet.com on Jan 27, 2022 We declare no competing interests. Signatories are listed in the appendix. Download .pdf (.11 MB) Help with pdf files Supplementary appendix Department of ErrorClarfield AM, Gill G, Leuner CJ, Moses AE, Paltiel O. An appeal to world leaders: restore health care for Ethiopians in Tigray. Lancet 2022; 399: 433—The title of this Correspondence has been corrected as of Jan 27, 2022, and the printed version is correct. Full-Text PDF

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.

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.

AbstractDuring December 2021 the fifth COVID-19 wave started in Israel, caused mostly by the Omicron variant, affecting the unvaccinated and vaccinated population. Ninety percent of the Israeli adults, including most healthcare workers (HCWs), received three doses of the BNT162b2 vaccine until September 2021. Following the success and safety of the 3rd dose in preventing infection and severe disease, on December 30, 2021, the Israeli Ministry of Health recommended a voluntary 4th vaccine dose to adults above 60 years, immunocompromised, and HCWs. We compared breakthrough infections in HCWs, between 3 and 4-dose recipients.Hospitals collected data on personnel vaccinations and infections dates. The study cohort included all HCWs in eleven hospitals in Israel, who have been vaccinated with three doses up to September 30, 2021, and had not contracted COVID-19 before the vaccination campaign (January 2, 2022).We calculated breakthrough infection rates in 4-dose recipients (more than six days after vaccination) vs. 3-dose recipients. Rate-ratios were calculated for the entire cohort and for subgroups (hospital, sex, age-groups, and profession). Additionally, we repeated the calculations on 4-dose and 3-dose recipients who received the 3rd dose on the same date and were matched for sex, age group, profession and hospital. We generated time-dependent Cox-regression models to account for 4th dose administration timing (Supplement).There were 29,612 HCWs who received 3 vaccine doses between August and September 2021; of these, 5,331 (18.0%) received the 4th dose during January 2022 and were not infected by the first week after vaccination. Overall breakthrough infection rates in the 4-dose and 3-dose groups were 368/5331 (6.9%) and 4802/24280 (19.8%), respectively. The RR (95%CI) was 0.35 (0.32 to 0.39) for crude analysis, and 0.61 (0.54 to 0.71) in the matched analysis. The adjusted HR in the Cox-regression model was 0.56 (0.50 to 0.63). In both groups, severe disease and death were not reported.Our data shows that the 4th BNT162b2 dose resulted in reduced breakthrough infection rates among HCWs. This reduction, similar to the findings in the Israeli elderly population, is lower than that observed after the 3rd dose.Nevertheless, considering the high infectivity of the Omicron variant, which led to critical medical staff shortages, a 4th vaccine dose should be considered to mitigate the infection rate among HCWs.

Background Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection in immunocompromised patients. Clusters of PJP, especially among organ transplant recipients in clinic settings were described. Data regarding nosocomial PJP infection among inpatients are limited. Objectives To assess the magnitude and characteristics of inpatient healthcare-associated PJP infection (HCA-PJP) in HIV-negative patients. Methods A retrospective chart review of hospitalized PJP patients was performed to identify HCA-PJP. The study was performed at six medical centers in Israel from 2006 to 2016. HCA-PJP was defined as cases of hospital-onset or those with documented contact with a PJP patient. We reviewed and cross-matched temporal and spatial co-locations of patients. Clinical laboratory characteristics and outcomes were compared. Results Seventy-six cases of PJP were identified. Median age was 63.7 years; 64% men; 44% hematological malignancies; 18% inflammatory diseases; and 61% steroid usage. Thirty-two patients (42%) were defined as HCA-PJP: 18/32 (23.6%) were hospitalized at onset and 14/32 (18.4%) had a previous encounter with a PJP patient. Time from onset of symptoms to diagnosis was shorter in HCA-PJP vs. community-PJP (3.25 vs. 11.23 days, P = 0.009). In multivariate analysis, dyspnea at presentation (odds ratio [OR] 16.79, 95% confidence interval [95%CI] 1.78-157.95) and a tendency toward higher rate of ventilator support (72% vs. 52%, P = 0.07, OR 5.18, 95%CI 0.7-30.3) were independently associated with HCA-PJP, implying abrupt disease progression in HCA-PJP. Conclusions HCA-PJP was common. A high level of suspicion for PJP among selected patients with nosocomial respiratory infection is warranted. Isolation of PJP patients should be considered.

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.

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.

Past studies using the positive deviance (PD) approach in the field of infection prevention and control (IPC) have primarily focused on impacts on healthcare-associated infection rates. This research aimed to determine if health professionals who exhibit PD behaviours have distinctive socio-cognitive profiles compared to non-PD professionals, and to examine the impact of a PD intervention on healthcare professionals' (HPs) behavioural changes in maintaining IPC guidelines. In a cross-sectional study among 135 HPs, respondents first filled out a socio-cognitive characteristics questionnaire, and after 5 months were requested to complete a self-reported behavioural change questionnaire. The main findings indicate that socio-cognitive variables such as external locus of control, perceived threat and social learning were significant predictors of a person exhibiting PD behaviours. Almost 70% of HPs reported behavioural change and creating social networks as a result of the PD intervention in maintaining IPC guidelines, 16.9% of them are a 'PD boosters' (a new group of HPs who have adopted the positive practices of PDs that were originally identified, and also added additional practices of their own). Social networks can contribute to internalizing and raising personal accountability even among non-PD professionals, by creating a mind map that makes each person believe they are an important node in the network, regardless of their status and role. Health intervention programmes should purposely make visible and prominent social network connections in the hospital system.

Background Acute tonsillitis is a very common medical condition. Despite different methods of detection, all tests are based on GAS sampling using a throat swab. However, obtaining the swab can elicit vomiting and is often accompanied by fear and apprehension in children. The aim of this study was to find a non-invasive method for the detection of GAS pharyngitis. Methods A classic throat swab was obtained for culture, and a saliva sample was taken from 100 subjects recruited from Meuhedet Health Care Organization clinic. Real time PCR was performed to detect GAS dnaseB specific gene in the saliva samples. Results 56% of the throat cultures and 48% of the PCR samples were positive for GAS. The overall sensitivity and specificity of the saliva PCR method was 79% and 91% respectively; NPV and PPV were 77% and 92% respectively. When excluding patients who presented on the first day of fever, sensitivity and specificity increased to 90% and 100% respectively. No other anamnestic or clinical findings increased the yield of the test. Conclusion Saliva-based PCR amplification of GAS DNA method is effective in detection of GAS pharyngitis. Further studies are needed to achieve detection rates to replace the traditional throat swab-based approach.

Background Mycoplasma pneumoniae is a leading cause of community-acquired pneumonia, with large epidemics previously described to occur every 4 to 7 years. Aim To better understand the diagnostic methods used to detect M. pneumoniae; to better understand M. pneumoniae testing and surveillance in use; to identify epidemics; to determine detection number per age group, age demographics for positive detections, concurrence of epidemics and annual peaks across geographical areas; and to determine the effect of geographical location on the timing of epidemics. Methods A questionnaire was sent in May 2016 to Mycoplasma experts with national or regional responsibility within the ESCMID Study Group for Mycoplasma and Chlamydia Infections in 17 countries across Europe and Israel, retrospectively requesting details on M. pneumoniae-positive samples from January 2011 to April 2016. The Moving Epidemic Method was used to determine epidemic periods and effect of country latitude across the countries for the five periods under investigation. Results Representatives from 12 countries provided data on M. pneumoniae infections, accounting for 95,666 positive samples. Two laboratories initiated routine macrolide resistance testing since 2013. Between 2011 and 2016, three epidemics were identified: 2011/12, 2014/15 and 2015/16. The distribution of patient ages for M. pneumoniae-positive samples showed three patterns. During epidemic years, an association between country latitude and calendar week when epidemic periods began was noted. Conclusions An association between epidemics and latitude was observed. Differences were noted in the age distribution of positive cases and detection methods used and practice. A lack of macrolide resistance monitoring was noted.

Objective Pneumocystis jiroveciipneumonia (PJP) was reported among immunosuppressed patients with deficits in cell-mediated immunity and in patients treated with immunomodulatory drugs. The aim of this study was to identify risk-factors for PJP in noninfected HIV patients. Methods This retrospective, test negative, case-control study was conducted in six hospitals in Israel, 2006-2016. Cases were hospitalized HIV-negative patients with pneumonia diagnosed as PJP by bronchoalveolar lavage. Controls were similar patients negative for PJP. Results Seventy-six cases and 159 controls were identified. Median age was 63.7 years, 65% males, 34% had hematological malignancies, 11% inflammatory diseases, 47% used steroids and 9% received antilymphocyte monoclonal antibodies. PJP was independently associated with antilymphocyte monoclonal antibodies (OR 11.47, CI 1.50-87.74), high-dose steroid treatment (OR 4.39, CI 1.52-12.63), lymphopenia (OR 8.13, CI 2.48-26.60), low albumin (OR 0.15, CI 0.40-0.54) and low BMI (OR 0.80, CI 0.68-0.93). Conclusion In conclusion, rituximab, which is prescribed for a wide variety of malignant and inflammatory disorders, was found to be significant risk-factor for PJP. Increased awareness of possible PJP infection in this patient population is warranted.

BackgroundFinancial 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.MethodsWe conducted a prospective matched case-control study over 18months 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.ResultsHAIs 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.ConclusionNosocomial 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.

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.

Objectives: Blood culture contamination carries risks for patients, such as unnecessary antimicrobial therapy and other additional hazards and costs. One method shown to be effective in reducing contamination is initial blood specimen diversion during collection. We hypothesized that initial blood specimen diversion without a designated device or procedure would suffice for reduction in blood culture contamination rate. Methods: From 1 September 2017 through to 6 September 2018, we conducted a randomized controlled trial to assess the effect of an initial-specimen diversion technique (ISDT) on the rate of blood-culture contamination by changing the order of sampling using regular vacuum specimen tubes instead of commercially available sterile diversion devices. We included adults from whom the treating physician planned to take blood cultures and additional blood chemistry tests. Additionally, we evaluated the potential economic benefits of an ISDT. This was a researcher-initiated trial, Clinicaltrials.gov NCT03088865. Results: In all, 756 patients were enrolled. This method, compared with the standard procedure in use at our medical centre, reduced contamination by 66% (95% CI 17%-86%), from 20/400 (5%) with the standard method to 6/356 (1.6%) with the ISDT, without compromising detection of true bloodstream infection and at no additional cost. Hospital-wide implementation of ISDT was associated with a 1.1% saving in hospitalization days. Conclusions: We offer this novel approach as a simple, cost-effective measure to reduce risks to patient safety from contaminated blood cultures, without the need for using costly devices. (C) 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

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.

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.

The effectiveness of post-exposure prophylaxis (PEP), a major strategy in the battle against HIV, depends on awareness of this modality and its proper timing among high-risk groups. While general awareness of PEP is improving, recently estimated to be 36–47% among men who have sex with men (MSM), PEP implementation remains disappointingly low and may be driven by limited awareness of effective PEP timing window. The level of detailed understanding of PEP timing and effectiveness among populations at risk has not been prospectively assessed to date. We prospectively evaluated, for the first time, actionable awareness regarding effective timing of PEP among a large cohort of individuals tested for HIV following unprotected sexual intercourse. Four hundred participants were assessed between December 2014 and February 2016. Overall awareness of the option of PEP was 60% and was significantly higher among male members of the LGBTQ community (75·5% as compared to 52·6% among heterosexual males) and those undergoing past HIV testing (67·1%). However, only 24% of individuals at risk were aware as to the proper timing of effective PEP treatment, thereby leading, in the majority of cases, to missing the window of opportunity for PEP treatment. This study highlights the lack of knowledge as to the specific requirements needed for effective PEP timing. Expanded advertising, better targeting of the heterosexual population, training of family physicians in the field of gender, sexuality, and LGBTQ medicine, may improve effective PEP availability, thereby reducing HIV transmission.

Abstract Background Respiratory pathogens are a common cause of disease. Currently there is not a practical tool to predict the putative etiology of each case with an inexpensive, fast point-of-care assay. Here, we describe a decision support tool that enables the prediction of both bacterial and viral respiratory pathogen infections in a single patient, using a Machine Learning model. Methods The data were obtained from the Hadassah-Hebrew University Medical Center during a period of 10 years beginning from 2007 and contained more than 40,000 patients from a 1,000,000-population community for whom specimens were tested by either PCR or culture. The pathogens included were, H. influenzae; M. catarrhalis; S. pneumoniae; M. pneumoniae; Adenovirus; Human metapneumovirus; Influenza H1N1, A, B; parainfluenza 1,2 and 3; and RSV. We then created a Machine-Learning algorithm to simulate the spread of infection in the entire Jerusalem area. We defined transmission areas based on geographical distances of patients’ home-addresses. Then we prospectively tested the tool accuracy over a 4-month period, in addition to real-time improvement of the model. Results Initial model was created based on gender, age, home addresses and the diagnostics test results. We then reconstructed a putative spread pattern for each of the pathogens that can be correlated to potential “transmission routes.” The initial prediction tool had an AUC for most pathogens around 0.85. It ranged from 0.75 to 0.8 for the bacterial and 0.82 to 0.89 for the viral pathogens. In almost all pathogens the NPV was 0.98–0.99. We then tested the decision support tool prospectively over four consecutive months (January to April 2019—1,700 patients with respiratory complaints from whom samples were sent to the lab). While the AUC in the prospective cohort was 0.81 on average, the NPV remained high on 0.98. Conclusion The implementation of the decision support tool on respiratory pathogen diagnostics enables better prediction of patients not infected with either viral or bacterial pathogens. The use of such a tool can save more than 50% of diagnostic tests expenses as well as real-time mapping of disease spread. Improvement of the Machine Learning protocol may further promote the optimization of positive predictive values. Disclosures All authors: No reported disclosures.