Varicella-Zoster Virus-Induced Neurologic Disease After COVID-19 Vaccination: A Multicenter Observational Cohort Study.

Background: Early reports described an increased risk of herpes zoster following receipt of mRNA-based COVID-19 vaccines. The objective was to assess whether COVID-19 vaccine is associated with varicella-zoster virus-induced neurologic disease (VZV-ND). Methods: This multicenter retrospective case-control study with a test-negative design was conducted at 12 hospitals in Israel. We included all patients admitted with VZV-ND between January 2020 and December 2021 and matched controls with a negative polymerase chain reaction result for VZV in cerebrospinal fluid. Results: We identified 188 patients meeting the case definition of VZV-ND who were admitted during the study period. Cases were matched with 376 controls. There was no significant variation in the incidence of VZV-ND between 1 year preceding and 1 year following the deployment of BNT162b2 in Israel. Analysis of persons who had received at least 1 dose of COVID-19 vaccine (n = 259) showed similar proportions of VZV-ND and non-VZV-ND in 4 intervals (30, 42, 50, 60 days) following the last vaccine dose. The median time from the last vaccine dose to hospitalization with a neurologic syndrome was 53 days (IQR, 25-128) and 82 days (IQR, 36-132) for VZV-ND and non-VZV-ND, respectively, not reaching statistical significance (P = .056). The rate of VZV-ND in vaccinated patients was no different from the rate in the unvaccinated group (30.9% vs 35.4%, P = .2). Conclusions: We did not find an association between COVID-19 vaccine and VZV-ND. Since COVID-19 vaccine is now recommended yearly, every fall and winter, establishing the safety of the vaccine is of great importance.

Third-generation cephalosporin resistant Enterobacteriaceae in neonates and young infants: impact and outcome.

OBJECTIVE: Third-generation cephalosporins resistant Enterobacteriaceae (3GCR-EB) are a major threat in severely ill neonates hospitalized in Neonatal Intensive Care Units. Still, the particular impact of 3GCR-EB on outcomes in the wide neonatal population is not well-appreciated. We aimed to study the impact of 3GCR-EB on the length of hospital stay and mortality of a general population of neonates and young infants. STUDY DESIGN: This was a retrospective cohort study of neonates and young infants born in eight Israeli hospitals between 2009 and 2013, with a culture taken within three months after birth that tested positive for Enterobacteriaceae (EB). Data for this study were taken from centralized electronic health records included inpatient, outpatient, socio-demographic, administrative and laboratory information. The main outcomes were length of stay and mortality. The main explanatory variable was an isolation of 3GCR-EB in any bacterial culture taken from a neonate or young infant. RESULTS: Cultures were taken for 31,921 neonates and young infants; 2647 (8.3%) tested positive for EB and 290 (11%) tested positive for 3GCR-EB. Length of stay for those who tested positive was 2.8 times longer (95%CI: 2.70-2.91, p ˂ .001) than patients who tested positive for 3GC-susceptible EB. 3GCR-EB were also associated with increased mortality (OR: 12.06, 95%CI: 4.92-32.29). CONCLUSIONS: Neonates with third-generation cephalosporins resistant Enterobacteriaceae had extended hospitalization and increased mortality, which was mostly significant in normal gestational weight newborns.

Perform hand hygiene and the doors will open - the effectiveness of new system implementation on paediatric intensive care unit visitors' handwashing compliance.

Hand hygiene (HH) performance on entering intensive care units (ICUs) is commonly accepted but often inadequately performed. We developed a simple, inexpensive module that connects touchless dispensers of alcohol sanitiser (TDAS) to the automatic doors of a paediatric ICU, and assessed the impact of this intervention on HH compliance of hospital staff and visitors. A prospective observational study was conducted over a 3-week period prior to the intervention, followed by a 4-week period post intervention. HH performance was monitored by a research assistant whose office location enabled direct and video-assisted observation of the ICU entrance. A total of 609 entries to the ICU was recorded. Overall HH performance was 46.9% (92/196) before and 98.5% (406/413) after the intervention. Our findings suggest that HH performance on entering an ICU can be improved via a mechanism that makes operation of an automatic door dependent on use of a TDAS system, and thus contribute to infection control.

Risk factors for third-generation cephalosporin resistant Enterobacteriaceae in gestational urine cultures: A retrospective cohort study based on centralized electronic health records.

Third-generation-cephalosporin resistant Enterobacteriaceae (3GCR-EB) carriage in pregnant women poses challenges for infection control and therapeutic decisions. The factors associated with multidrug resistant Enterobacteriaceae carriage in the gestational period are not well documented. The aim of our study was to identify risk factors associated with 3GCR-EB isolation in gestational urine cultures. The study was designed as retrospective cohort based on centralized electronic health records database. Women delivered in Clalit Health Services hospitals in Israel in 2009-2013 and provided urine culture(s) during pregnancy were included. Multivariable analysis using the Generalized Estimating Equations model was used to assess risk factors for 3GCR-EB isolation in gestational urine cultures. The study included 15,282 pregnant women with urine cultures yielding Enterobacteriaceae (EB). The proportion of 3GCR-EB in EB isolates was 3.9% (n = 603). The following risk factors were associated with 3GCR-EB isolation: multiple hospital admissions during the year before delivery (OR,1.47;95% CI,1.21-1.79), assisted fertilization procedure (OR,1.53; 95% CI,1.12-2.10), Arab ethnicity (OR,1.22; 95% CI,1.03-1.45), multiple antibiotic courses (OR,1.76; 95% CI,1.29-2.40), specifically, cephalosporins (OR,1.56; 95% CI,1.26-1.95), fluoroquinolones (OR,1.34; 95% CI,1.04-1.74), or nitrofurantoin (OR,1.29; 95% CI,1.02-1.64). The risk factors identified by this study for 3GCR-EB in gestation, can be easily generalized for pregnant women in the Israeli population. Moreover, these risk factors, other than ethnicity, are applicable to pregnant women worldwide. The information of previous antibiotic treatments, hospitalization in the last year and assisted fertilization procedure can be easily accessed and used for appropriate infection control practices and antimicrobial therapy.

Use of antibiotics among end-of-life hospitalized patients with advanced directives: Status examination and association with infectious disease consultation and physician burnout.

BACKGROUND: Overuse of antibiotics in end-of-life patients with advanced directives increases bacterial resistance and causes morbidity and mortality. Consultations with infectious disease (ID) physicians and burnout, which can affect antibiotic days of therapy (DOT) prescribed by physicians, have not been examined so far. OBJECTIVES: To assess antibiotic use by physicians in end-of-life (EOL) patients with advanced directives and to investigate the association between ID consultations, physician burnout, and antibiotic DOT in those patients. DESIGN: A descriptive correlational study. SETTING: Acute-care and post-acute-care hospitals. PARTICIPANTS: The study included 213 physicians and 932 their hospitalized patients in the last 2 weeks of life. METHODS: We distributed questionnaires and analyzed the data collected regarding ID consultation, EOL antibiotics prescription with and without an advanced directive, and physician burnout to 278 physicians, and 213 were completed (response rate 76%). RESULTS: Of the 932 deaths, 435 of 664 (>50%) were EOL patients with advanced directives. Of these patients, 74% received antibiotics, 29.9% had bacterial resistance cultures, and antibiotics were discontinued in only 5%. Half of the physicians lacked knowledge concerning antibiotics use issues and had significantly fewer consultations with ID physicians in EOL patients with advanced directives (mean rate, 0.27) than those without advanced directives (mean rate, 0.47). ID physicians reported significantly higher emotional exhaustion levels (mean rate, 29) than other medical specialties (mean rate, 19.2). Antibiotic DOT was significantly higher when patients had ID consultations (mean rate, 21.6) than in patients who did not (mean rate, 16.2). In post-acute-care hospitals and/or geriatric wards, antibiotic DOT was significantly higher than in other types of hospitals and/or wards. Depersonalization level was negatively related to antibiotic DOT (P < .05). CONCLUSIONS: Antibiotics are overused in EOL patients with advanced directives. ID physician burnout and impact of ID consultation should be further assessed.

Reduction of hospital-acquired infections in the neonatal intensive care unit: A long-term commitment.

We instituted quality improvement program. We compare the infection rate before (2011-2012) and after (2013-2015). Central line associated blood stream infection episodes decreased from 15.2 to 2.29 episodes per 1000 catheter days (P = .004). We found two major changes, 1. Hand hygiene increased mainly "before aseptic task", from 69.9% to 89.9% and 2. A significant decrease in the length of the catheter use from 5.4 ±â€¯4.5 before to 4.4 ±â€¯2.5 days after the intervention (P = .001).

Predictors of Persistent Carbapenem-Resistant Enterobacteriaceae Carriage upon Readmission and Score Development.

BACKGROUND: Carriers of carbapenem-resistant Enterobacteriaceae (CRE) are often readmitted, exposing patients to CRE cross-transmission. OBJECTIVE To identify predictors of persistent CRE carriage upon readmission, directing a risk prediction score. DESIGN: Retrospective cohort study. SETTING: University-affiliated general hospital. PATIENTS: A cohort of 168 CRE carriers with 474 readmissions. METHODS: The primary and secondary outcomes were CRE carriage status at readmission and length of CRE carriage. Predictors of persistent CRE carriage upon readmission were analyzed using a generalized estimating equations (GEE) multivariable model. Readmissions were randomly divided into derivation and validation sets. A CRE readmission score was derived to predict persistent CRE carriage in 3 risk groups: high, intermediate, and low. The discriminatory ability of the model and the score were expressed as C statistics. RESULTS: CRE carrier status persisted for 1 year in 33% of CRE carriers. Positive CRE status was detected in 202 of 474 readmissions (42.6%). The following 4 variables were associated with persistent CRE carriage at readmission: readmission within 1 month (odds ratio [OR], 6.95; 95% confidence interval [CI], 2.79-17.30), positive CRE status on preceding admission (OR, 5.46; 95% CI, 3.06-9.75), low Norton score (OR, 3.07; 95% CI, 1.26-7.47), and diabetes mellitus (OR, 1.84; 95% CI, 0.98-3.44). The C statistics were 0.791 and 0.789 for the derivation set (n=322) model and score, respectively, and the C statistic was 0.861 for the validation set of the score (n=152). The rates of CRE carriage at readmissions (validation set) for the groups with low, intermediate, and high scores were 8.6%, 38.9%, and 77.6%, respectively. CONCLUSIONS: CRE carrier state commonly persists upon readmission, and this risk can be estimated to guide screening policy and infection control measures.

Real-time PCR for Strongyloides stercoralis-associated meningitis.

Four immunocompromised patients, immigrants from Ethiopia, presented with diverse clinical manifestations of meningitis associated with Strongyloides stercoralis dissemination as determined by identification of intestinal larvae. The cerebrospinal fluid of 3 patients was tested by a validated (for stool) real-time PCR for S. stercoralis and was found positive, establishing this association.

Intradural Extension of a Pyogenic Epidural Abscess: A Case Report.

CASE: Few cases of spinal epidural abscess involving an extradural abscess with an intradural extension have been reported. A unique complication with extension of pus from the epidural space through multiple perforations into the dura is described. Due to a proximal meningeal inflammatory reaction, which served as a proximal plug, no cerebrospinal fluid leak was encountered. CONCLUSION: Intradural extension of pus through multiple dural perforations is a rare complication of spinal epidural abscess and a treatment challenge. Early diagnosis enabling prompt surgical decompression, along with subsequent aggressive debridements and prolonged intravenous antibiotic treatment, can lead to a favorable outcome.

An effective intervention to limit the spread of an epidemic carbapenem-resistant Klebsiella pneumoniae strain in an acute care setting: from theory to practice.

BACKGROUND: The highly transmissible and virulent carbapenem-resistant Klebsiella pneumoniae (CRKP) KPC-3 strain has been spreading in our medical center and in other centers in Israel since 2006. An intervention that aimed to diminish its prevalence was constructed and applied in our institute. METHODS: We analyzed the efficacy of the intervention during the years 2006-2010 using quasi-experimental methodology. The intervention included guidelines for patient isolation, cohorting, and environment cleaning; education of staff; and a computerized notification system that flags CRKP carriers and provides instructions. The efficacy of the program was evaluated through 3 quantifiable parameters: incidence of CRKP isolates from clinical samples, rate of cross-infections, and rate of screening for CRKP carriage in patients at risk identified by rectal samples. RESULTS: The incidence of CRKP decreased by 16-fold (P < .001), and this decrease was sustained for 30 months. The rate of cross-infection decreased from 6% during 2007-2008 to 2.7% in 2009-2010 (P < .05). This period saw an increased rate of active surveillance for carriers, from 20% to 89%. CONCLUSIONS: A comprehensive infection control program can contain an outbreak of the CRKP KPC-3 strain in acute care hospitals during a nationwide outbreak of this strain.

Laryngeal syphilis: a case report.

Syphilis is a sexually transmitted disease caused by the spirochete Treponema pallidum. The complexity of the disease gained it the moniker "the great imitator"; it was William Osler who said, "He who knows syphilis, knows medicine." In 1866, Patrick Watson of Edinburgh, Scotland, reported a case of a 36-year-old man in whom syphilis destroyed the larynx.(1) The diagnosis was made postmortem. It was once believed that this was the first reported total laryngectomy, but the credit should actually be given to Christian Albert Theodor Billroth who performed this surgery on a patient with laryngeal carcinoma in 1873.

National multicenter study of predictors and outcomes of bacteremia upon hospital admission caused by Enterobacteriaceae producing extended-spectrum beta-lactamases.

Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae are pathogens that may lead to a spectrum of clinical syndromes. We aimed to identify predictors and outcomes of ESBL bacteremia upon hospital admission (UHA) in a nationwide prospective study. Thus, a multicenter prospective study was conducted in 10 Israeli hospitals. Adult patients with bacteremia due to Enterobacteriaceae diagnosed within 72 h of hospitalization were included. Patients with ESBL producers (cases) were compared to those with non-ESBL producers (controls), and a 1:1 ratio was attempted in each center. A case-control study to identify predictors and a cohort study to identify outcomes were conducted. Bivariate and multivariate logistic regressions were used for analyses. Overall, 447 patients with bacteremia due to Enterobacteriaceae were recruited: 205 cases and 242 controls. Independent predictors of ESBL were increased age, multiple comorbid conditions, poor functional status, recent contact with health care settings, invasive procedures, and prior receipt of antimicrobial therapy. In addition, patients presenting with septic shock and/or multiorgan failure were more likely to have ESBL infections. Patients with ESBL producers suffered more frequently from a delay in appropriate antimicrobial therapy (odds ratio [OR], 4.7; P, <0.001) and had a higher mortality rate (OR, 3.5; P, <0.001). After controlling for confounding variables, both ESBL production (OR, 2.3; P, 9.1) and a delay in adequate therapy (OR, 0.05; P, 0.001) were significant predictors for mortality and other adverse outcomes. We conclude that among patients with bacteremia due to Enterobacteriaceae UHA, those with ESBL producers tend to be older and chronically ill and to have a delay in effective therapy and severe adverse outcomes. Efforts should be directed to improving the detection of patients with ESBL bacteremia UHA and to providing immediate appropriate therapy.

The effects of doxorubicin on apoptosis and adhesion molecules of normal peripheral blood leukocytes-an ex vivo study.

This ex vivo study was designed to evaluate the effect of doxorubicin (Dox) on normal peripheral blood leukocytes (PBL) in terms of apoptosis and membranal expression levels of adhesion molecules. Blood was drawn immediately prior to and after Dox administration from 21 breast cancer patients, and incubated at room temperature for 24 h. Flow cytometry was employed in analysis of apoptosis with Annexin-V and protein membranal expression levels with monoclonal antibodies to CD49d, CD18, CD11a-c and CD63. Dox induced statistically significant apoptosis in all three major PBL subpopulations (p<0.01). Between 70 and 90% of samples underwent apoptosis in all PBL subgroups. No significant change was observed in the membranal level of CD63, CD49d and CD11a-c after chemotherapy in any PBL subpopulation. However, a significant reduction in the membranal level of CD18 was demonstrated in polymorphonuclear cells after Dox (p<0.005) both in apoptotic and non-apoptotic cells (p<0.05), suggesting a direct effect of Dox rather than an apoptosis-associated phenomenon. We observed the expected leukopenia 10 days after Dox administration with no correlation to apoptosis, suggesting that leukopenia by Dox is largely attributed to toxicity of blood progenitors.

Initial exposed phosphatidylserine levels correlate with cellular response to cytotoxic drugs.

Phosphatidylserine's (PS) membranal distribution is associated with an expanding variety of biological processes. We studied the relevance of preliminarily exposed membranal PS levels to cellular effects of cytotoxic agents. PBL of normal controls (n = 18) and patients with doxorubicin-treated breast carcinoma (n = 27) or 5'-fluorouracil-treated colorectal cancer (n = 32) were assayed before and after drug infusion. Membranal expression levels of PS, adhesion molecules (CD18, CD11a-c, CD63) and Fas-R of leukocyte subtypes were assessed by flow cytometer. Statistical analysis was implemented. Our results demonstrate external expression of PS on all leukocyte subpopulations despite non-apoptotic light scatter characteristics. Several distinct features were observed of which the more prominent were: leukocyte subtypes each display characteristic PS levels; cancer patients' PBL display higher preliminary PS levels than normal controls in all cell groups; and existence of negative correlations between initial membranal PS levels and drug-induced changes in its expression. Our findings underscore the complex involvement of PS in PBL apoptosis and possibly drug resistance.