Sink-traps are a major source for carbapenemase-producing Enterobacteriaceae transmission.

OBJECTIVE: We studied the extent of carbapenemase-producing Enterobacteriaceae (CPE) sink contamination and transmission to patients in a nonoutbreak setting. METHODS: During 2017-2019, 592 patient-room sinks were sampled in 34 departments. Patient weekly rectal swab CPE surveillance was universally performed. Repeated sink sampling was conducted in 9 departments. Isolates from patients and sinks were characterized using pulsed-field gel electrophoresis (PFGE), and pairs of high resemblance were sequenced by Oxford Nanopore and Illumina. Hybrid assembly was used to fully assemble plasmids, which are shared between paired isolates. RESULTS: In total, 144 (24%) of 592 CPE-contaminated sinks were detected in 25 of 34 departments. Repeated sampling (n = 7,123) revealed that 52%-100% were contaminated at least once during the sampling period. Persistent contamination for >1 year by a dominant strain was common. During the study period, 318 patients acquired CPE. The most common species were Klebsiella pneumoniae, Escherichia coli, and Enterobacter spp. In 127 (40%) patients, a contaminated sink was the suspected source of CPE acquisition. For 20 cases with an identical sink-patient strain, temporal relation suggested sink-to-patient transmission. Hybrid assembly of specific sink-patient isolates revealed that shared plasmids were structurally identical, and SNP differences between shared pairs, along with signatures for potential recombination events, suggests recent sharing of the plasmids. CONCLUSIONS: CPE-contaminated sinks are an important source of transmission to patients. Although traditionally person-to-person transmission has been considered the main route of CPE transmission, these data suggest a change in paradigm that may influence strategies of preventing CPE dissemination.

The Use of Rapid COVID-19 Antigen Test in the Emergency Department as a Decision-Support Tool.

The emergency department (ED) is the initial point of contact between hospital staff and patients potentially infected with SARS-CoV-2, thus, prevention of inadvertent exposure to other patients is a top priority. We aimed to assess whether the introduction of antigen-detecting rapid diagnostic tests (Ag-RDTs) to the ED affected the likelihood of unwanted SARS-CoV-2 exposures. In this retrospective single-center study, we compared the rate of unwarranted exposure of uninfected adult ED patients to SARS-CoV-2 during two separate research periods; one before Ag-RDTs were introduced, and one with Ag-RDT used as a decision-support tool. The introduction of Ag-RDTs to the ED significantly decreased the relative risk of SARS-CoV-2-negative patients being incorrectly assigned to the COVID-19 designated site ("red ED"), by 97%. There was no increase in the risk of SARS-CoV-2-positive patients incorrectly assigned to the COVID-19-free site ("green ED"). In addition, duration of ED admission was reduced in both the red and the green ED. Therefore, implementing the Ag-RDT-based triage protocol proved beneficial in preventing potential COVID-19 nosocomial transmission.

Rapid Antigen Tests For Safe School Opening in the COVID-19 Pandemic Era.

BACKGROUND: Since the beginning of the Sever Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, school closure as a mitigating measure was at the center of a public and professional debate. While the negative effects of school closure cannot be ignored, accumulating data suggested that it is necessary for reducing community transmission. Our study presents an optional strategy for safe school opening during a pandemic, implemented in selected Israeli high schools by a special task force constructed by the Sheba Medical Center (SMC). METHODS: The study took place between November 2020 and April 2021. Three schools from different areas of Israel were enrolled. The participants were asked to undergo bi-weekly SARS-CoV-2 rapid diagnostic antigen tests (Ag-RDT). Those who tested positive were requested to self-isolate, whereas their school contacts were tested daily by Ag-RDT. Participants with a previously documented SARS-CoV-2 infection or who were found to be SARS-CoV-2 seropositive upon enrollment were exempted from screening. RESULTS: Of a total of 361 participants who enrolled in the study, 12.3% were found to be seropositive. Fourteen SARS-CoV-2 cases were detected (3.5%), 12 of them in one single school located in an endemic area for SARS-CoV-2. The 14 cases resulted in 84 days of COVID-19-related absence from school, comparing with 1775 potential days of COVID-19-related absence under a strategy implementing self-isolation instead of testing. CONCLUSIONS: Safe continuation of academic routine during the pandemic is possible when using rapid Ag-RDT as a screening tool, while allowing swab collection by trained students and teachers.

Coronavirus disease 2019 (COVID-19) vaccination uptake among healthcare workers.

OBJECTIVE: To assess reasons for noncompliance with COVID-19 vaccination among healthcare workers (HCWs). DESIGN: Cohort observational and surveillance study. SETTING: Sheba Medical Center, a 1,600-bed tertiary-care medical center in Israel. PARTICIPANTS: The study included 10,888 HCWs including all employees, students, and volunteers. INTERVENTION: The BNT162b2 mRNA COVID-19 vaccine was offered to all HCWs of the hospital. Noncompliance was assessed, and pre-rollout and post-rollout surveys were conducted. Data regarding uptake of the vaccine as well as demographic data and compliance with prior influenza vaccination were collected, and 2 surveys were distributed. The survey before the rollout pertained to the intention to receive the vaccine, and the survey after the rollout pertained to all unvaccinated HCWs regarding causes of hesitancy. RESULTS: In the pre-rollout survey, 1,673 (47%) of 3,563 HCWs declared their intent to receive the vaccine. Overall, 8,108 (79%) HCWs received the COVID-19 vaccine within 40 days of rollout. In a multivariate logistic regression model, the factors that were significant predictors of vaccine uptake were male sex, age 40-59 years, occupation (paramedical professionals and doctors), high socioeconomic level, and compliance with flu vaccine. Among 425 unvaccinated HCWs who answered the second survey, the most common cause for hesitancy was the risk during pregnancy (31%). CONCLUSIONS: Although vaccine uptake among HCWs was higher than expected, relatively low uptake was observed among young women and those from lower socioeconomic levels and educational backgrounds. Concerns regarding vaccine safety during pregnancy were common and more data about vaccine safety, especially during pregnancy, might improve compliance.

First reported nosocomial SARS-CoV-2 outbreak in a hospital-based laundry facility.

Nosocomial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks among health care workers have been scarcely reported so far. This report presents the results of an epidemiologic and molecular investigation of a SARS-CoV-2 outbreak among laundromat facility workers in a large tertiary centre in Israel. Following the first three reported cases of SARS-CoV-2 among laundromat workers, all 49 laundromat personnel were screened by qRT-PCR tests using naso- and oropharingeal swabs. Epidemiologic investigations included questionnaires, interviews and observations of the laundromat facility. Eleven viral RNA samples were then sequenced, and a phylogenetic analysis was performed using MEGAX.The integrated investigation defined three genetic clusters and helped identify the index cases and the assumed routes of transmission. It was then deduced that shared commute and public showers played a role in SARS-CoV-2 transmission in this outbreak, in addition to improper PPE use and social gatherings (such as social eating and drinking). In this study, we present an integrated epidemiologic and molecular investigation may help detect the routes of SARS-CoV-2 transmission, emphasising such routes that are less frequently discussed. Our work reinforces the notion that person-to-person transmission is more likely to cause infections than environmental contamination (e.g. from handling dirty laundry).

Covid-19 Breakthrough Infections in Vaccinated Health Care Workers.

BACKGROUND: Despite the high efficacy of the BNT162b2 messenger RNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rare breakthrough infections have been reported, including infections among health care workers. Data are needed to characterize these infections and define correlates of breakthrough and infectivity. METHODS: At the largest medical center in Israel, we identified breakthrough infections by performing extensive evaluations of health care workers who were symptomatic (including mild symptoms) or had known infection exposure. These evaluations included epidemiologic investigations, repeat reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays, antigen-detecting rapid diagnostic testing (Ag-RDT), serologic assays, and genomic sequencing. Correlates of breakthrough infection were assessed in a case-control analysis. We matched patients with breakthrough infection who had antibody titers obtained within a week before SARS-CoV-2 detection (peri-infection period) with four to five uninfected controls and used generalized estimating equations to predict the geometric mean titers among cases and controls and the ratio between the titers in the two groups. We also assessed the correlation between neutralizing antibody titers and N gene cycle threshold (Ct) values with respect to infectivity. RESULTS: Among 1497 fully vaccinated health care workers for whom RT-PCR data were available, 39 SARS-CoV-2 breakthrough infections were documented. Neutralizing antibody titers in case patients during the peri-infection period were lower than those in matched uninfected controls (case-to-control ratio, 0.361; 95% confidence interval, 0.165 to 0.787). Higher peri-infection neutralizing antibody titers were associated with lower infectivity (higher Ct values). Most breakthrough cases were mild or asymptomatic, although 19% had persistent symptoms (>6 weeks). The B.1.1.7 (alpha) variant was found in 85% of samples tested. A total of 74% of case patients had a high viral load (Ct value, <30) at some point during their infection; however, of these patients, only 17 (59%) had a positive result on concurrent Ag-RDT. No secondary infections were documented. CONCLUSIONS: Among fully vaccinated health care workers, the occurrence of breakthrough infections with SARS-CoV-2 was correlated with neutralizing antibody titers during the peri-infection period. Most breakthrough infections were mild or asymptomatic, although persistent symptoms did occur.

Sink traps as the source of transmission of OXA-48-producing Serratia marcescens in an intensive care unit.

BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) outbreaks are mostly attributed to patient-to-patient transmission via healthcare workers. OBJECTIVE: We describe successful containment of a prolonged OXA-48-producing S. marcescens outbreak after recognizing the sink traps as the source of transmission. METHODS: The Sheba Medical Center intensive care unit (ICU), contains 16 single-bed, semi-closed rooms. Active CPE surveillance includes twice-weekly rectal screening of all patients. A case was defined as a patient detected with OXA-48 CPE >72 hours after admission. A root-cause analysis was used to investigate the outbreak. All samples were inoculated on chrom-agar CRE, and carbapenemase genes were detected using commercial molecular Xpert-Carba-R. Environmental and patient S. marcescens isolates were characterized using PFGE. RESULTS: From January 2016 to May 2017, 32 OXA-48 CPE cases were detected, and 81% of these were S. marcescens. A single clone was the cause of all but the first 2 cases. The common factor in all cases was the use of relatively large amounts of tap water. The outbreak clone was detected in 2 sink outlets and 16 sink traps. In addition to routine strict infection control measures, measures taken to contain the outbreak included (1) various sink decontamination efforts, which eliminated the bacteria from the sink drains only temporarily and (2) educational intervention that engaged the ICU team and lead to high adherence to 'sink-contamination prevention guidelines.' No additional cases were detected for 12 months. CONCLUSIONS: Despite persistence of the outbreak clones in the environmental reservoir for 1 year, the outbreak was rapidly and successfully contained. Addressing sink traps as hidden reservoirs played a major role in the intervention.

Genetic divergence of Influenza A(H3N2) amino acid substitutions mark the beginning of the 2016-2017 winter season in Israel.

BACKGROUND: Influenza vaccine composition is reevaluated each year due to the frequency and accumulation of genetic changes that influenza viruses undergo. The beginning of the 2016-2017 influenza surveillance period in Israel has been marked by the dominance of influenza A(H3N2). OBJECTIVES: To evaluate the type, subtype, genetic evolution and amino acid substitutions of influenza A(H3N2) viruses detected among community patients with influenza-like illness (ILI) and hospitalized patients with respiratory illness in the first weeks of the 2016-2017 influenza season. STUDY DESIGN: Respiratory samples from community patients with influenza-like illness and from hospitalized patients underwent identification, subtyping and molecular characterization. Hemagglutinin sequences were compared to the vaccine strain, phylogenetic tree was created, and amino acid substitutions were determined. RESULTS: Influenza A(H3N2) predominated during the early stages of the 2016-2017 influenza season. Noticeably, approximately 20% of community patients and 36% of hospitalized patients, positive for influenza3), received the 2016-2017 influenza vaccine. The influenza A(H3N2) viruses demonstrated genetic divergence from the vaccine strain into three separate subgroups within the 3C.2a clade. One resembled the new 3C.2a1 subclade, one resembled the recently proposed 3C.2a2 subclade and the other was not previously described. Diversity was observed within each subgroup, in terms of additional amino acid substitutions. CONCLUSIONS: Characterization of the 2016-2017 A(H3N2) influenza viruses is imperative for determining the future influenza vaccine composition.

Rapid detection of blaKPC carbapenemase genes by internally controlled real-time PCR assay using bactec blood culture bottles.

Rapid detection of drug-resistant bacteria in clinical samples plays an instrumental role in patients' infection management and in implementing effective infection control policies. In the study described in this report, we validated a multiplex TaqMan real-time quantitative PCR (qPCR) assay for the detection of bla(KPC) genes and the human RNase P gene in Bactec blood culture bottles. The MagNA Pure LC (version 2.0) instrument was utilized to extract nucleic acids from the inoculated broth, while bovine serum albumin (BSA) was utilized as the PCR inhibitor reliever. The multiplex assay, which was specific for the detection of bla(KPC) genes, had a limit of detection of 19 CFU per reaction mixture with human blood-spiked Bactec bottles. Of the 323 Bactec blood culture sets evaluated, the same 55 (17%) blood cultures positive for carbapenem-resistant bacteria by culture were also positive by the validated qPCR assay. Thus, the sensitivity, specificity, positive predictive value, and negative predictive value of the qPCR assay compared to the results of culture were all 100%. bla(KPC) genes were also detected from the same Bactec bottle broth after manual extraction with a QIAamp DNA minikit; however, there was an average 3-threshold-cycle delay in the qPCR readings. With the limited therapeutic options available, the accurate and rapid detection of bla(KPC)-possessing bacteria by the described bla(KPC)/RNase P assay will be a crucial first step in ensuring optimal clinical outcomes and infection control.

Potential role of active surveillance in the control of a hospital-wide outbreak of carbapenem-resistant Klebsiella pneumoniae infection.

BACKGROUND: The recent emergence of carbapenem resistance among Enterobacteriaceae is a major threat for hospitalized patients, and effective strategies are needed. OBJECTIVE: To assess the effect of an intensified intervention, which included active surveillance, on the incidence of infection with carbapenem-resistant Klebsiella pneumoniae. SETTING: Sheba Medical Center, a 1,600-bed tertiary care teaching hospital in Tel Hashomer, Israel. DESIGN: Quasi-experimental study. METHODS: The medical records of all the patients who acquired a carbapenem-resistant K. pneumoniae infection during 2006 were reviewed. An intensified intervention was initiated in May 2007. In addition to contact precautions, active surveillance was initiated in high-risk units. The incidence of clinical carbapenem-resistant K. pneumoniae infection over time was measured, and interrupted time-series analysis was performed. RESULTS: The incidence of clinical carbapenem-resistant K. pneumoniae infection increased 6.42-fold from the first quarter of 2006 up to the initiation of the intervention. In 2006, of the 120 patients whose clinical microbiologic culture results were positive for carbapenem-resistant K. pneumoniae, 67 (56%) developed a nosocomial infection. During the intervention period, the rate of carbapenem-resistant K. pneumoniae rectal colonization was 9%. Of the 390 patients with carbapenem-resistant K. pneumoniae colonization or infection, 204 (52%) were identified by screening cultures. There were a total of 12,391 days of contact precautions, and of these, 4,713 (38%) were added as a result of active surveillance. After initiation of infection control measures, we observed a significant decrease in the incidence of carbapenem-resistant K. pneumoniae infection. CONCLUSIONS: The use of active surveillance and contact precautions, as part of a multifactorial intervention, may be an effective strategy to decrease rates of nosocomial transmission of carbapenem-resistant K. pneumoniae colonization or infection.

Rapid detection of blaKPC carbapenemase genes by real-time PCR.

Carbapenem resistance among Enterobacteriaceae is an emerging problem worldwide. Klebsiella pneumoniae carbapenemase (bla(KPC)) enzymes are among the most common beta-lactamases described. In this study, we report the development and validation of a real-time PCR (q-PCR) assay for the detection of bla(KPC) genes using TaqMan chemistry. The q-PCR amplification of bla(KPC) DNA was linear over 7 log dilutions (r(2) = 0.999; slope, 3.54), and the amplification efficiency was 91.6%. The q-PCR detection limit was 1 CFU, and there was no cross-reaction with DNA extracted from several multidrug-resistant bacteria. Perianal/rectal swabs (n = 187) collected in duplicate from 128 patients admitted to Sheba Medical Center surgical intensive care units were evaluated for the presence of carbapenem-resistant bacteria by culturing on MacConkey agar-plus-carbapenem disks and for bla(KPC) genes by q-PCR. Carbapenem-resistant organisms, all K. pneumoniae, were isolated from 47 (25.1%) of the 187 samples collected, while bla(KPC) genes were detected in 54 (28.9%) of the patient samples extracted by the NucliSENS easyMAG system. Of these, seven samples were positive for bla(KPC) genes by q-PCR but negative for carbapenem resistance by culture, while all samples in which no carbapenem-resistant bacteria were detected by culture also tested negative by q-PCR. Thus, the sensitivity and specificity of the q-PCR assay after extraction by the NucliSENS easyMAG system were 100% and 95%, respectively. Similar values were obtained after DNA extraction by the Roche MagNA Pure LC instrument: 97.9% sensitivity and 96.4% specificity. Overall, the bla(KPC) q-PCR assay appears to be highly sensitive and specific. The utilization of q-PCR will shorten the time to bla(KPC) detection from 24 h to 4 h and will help in rapidly isolating colonized or infected patients and assigning them to cohorts.

Serum prolactin levels in unmedicated first-episode and recurrent schizophrenia patients: a possible marker for the disease's subtypes.

Various studies indicate that we must consider schizophrenia not as a single disease but as several distinct etiological processes that give rise to characteristic symptoms. In the current study, we aimed to examine prolactin serum levels in unmedicated first-episode and recurrent schizophrenic patients. The prolactin levels were compared among the different schizophrenia subtypes, i.e. paranoid, schizoaffective and disorganized. Prolactin serum samples were assessed on the morning after the admission in 48 first-episode and 38 recurrent unmedicated hospitalized schizophrenia patients. Two psychiatrists made the diagnosis without knowledge of laboratory results and completed the rating scales. Despite all prolactin levels being within or close to the normal range, we found significant differences in prolactin serum levels among schizophrenia subtype patients: the lowest values were for the paranoid type, intermediate for the schizoaffective and the highest for the disorganized patients. The results seem to indicate a pronounced hyperdopaminergic activity in paranoid schizophrenia, suggesting differences in dopaminergic tone between the schizophrenia subtypes, and support the clinical and the neuropsychological individuality of disease subtypes. There were no significant differences in prolactin serum levels of the schizophrenia subtypes between the first-episode and the recurrent patients. It appears that there are constant patterns of dopamine bioactivity in acutely psychotic unmedicated schizophrenia patients, whether the patients are first admitted or recurrent.