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.

Ureteral Stent Colonization and Urinary Tract Infection in Children Undergoing Minimally Invasive Pyeloplasty.

INTRODUCTION: Minimally invasive pyeloplasty (MIP), namely, laparoscopic and robot-assisted interventions, has gained popularity in recent years. Double-J ureteral stents are frequently inserted during surgery. Foreign bodies in the urinary tract are considered as risk factor for developing urinary tract infection (UTI). This study aimed to specify the bacteria cultured from urine and stents responsible for UTI in children with indwelling ureteral stents undergoing MIP. PATIENTS AND METHODS: We retrospectively reviewed medical records of 30 children (22 boys and 8 girls) who had undergone MIP between 2014 and 2017. Median age at surgery was 2.7 years (interquartile range [IQR]: 0.5-7.9). Urine cultures were obtained before surgery, before stent removal, 1 month after stent removal, and if UTI was suspected. Stents were removed 4 to 8 weeks after surgery and cultured. Patients' demographics, types of stents, and surgical details were recorded. RESULTS: Median stent indwelling time was 5.09 weeks (IQR: 4-6). Postoperative febrile UTI developed in 4/30 (13%) patients. Afebrile UTI occurred in another 4/30 (13%) patients. Stent cultures were positive in 19/30 (63%) patients. Stent and urinary cultures were identical in only one patient. Three of four patients with preoperative asymptomatic bacteriuria developed postoperative UTI. There was no association between UTI, gender, stent diameter, and duration of indwelling catheter. CONCLUSION: After MIP, febrile UTI and afebrile UTI occurred in about one quarter of patients. Pathogens isolated postsurgically from urinary cultures were unrelated to those colonizing the stents. Therefore, routine stent culturing is of low clinical significance. Moreover, small-caliber stents and longer indwelling periods were not risk factors for UTI. Optimizing antibiotic treatment for children with preoperative UTI may potentially prevent morbidity after surgery.

Short- and long-term mortality in patients with urosepsis caused by Escherichia coli susceptible and resistant to 3rd generation cephalosporins.

BACKGROUND: The aim of this study was to compare short- and long-term mortality among patients with urosepsis caused by Escherichia coli susceptibile (EC-SC) and resistant (EC-RC) to 3rd generation cephalosporins. METHODS: A retrospective cohort study that included all patients with E. coli urosepsis admitted to a 700-bed hospital from January 2014 until December 2019. Mortality up to 30 days, 6 months and 1 year was assessed using logistic multivariate regression analysis and Cox regression analysis. RESULTS: A total of 313 adult were included, 195 with EC-SC and 118 patients with EC-RC. 205 were females (74%), mean age was 79 (SD 12) years. Mean Charlson score was 4.93 (SD 2.18) in the EC-SC group and 5.74 (SD 1.92) in the EC-RC group. Appropriate empiric antibiotic therapy was initiated in 245 (78.3%) patients, 100% in the EC-SC group but only 42.5% in the EC-RC group. 30-day mortality occurred in 12 (6.3%) of EC-SC group and 15 (12.7%) in the EC-RC group. Factors independently associated with 30-day mortality were Charlson score, Pitt bacteremia score, fever upon admission and infection with a EC-RC. Appropriate antibiotic therapy was not independently associated with 30-day mortality. Differences in mortality between groups remained significant one year after the infection and were significantly associated with the Charlson co-morbidity score. CONCLUSIONS: Mortality in patients with urosepsis due to E. coli is highly affected by age and comorbidities. Although mortality was higher in the EC-RC group, we could not demonstrate an association with inappropriate empirical antibiotic treatment. Mortality remained higher at 6 months and 1 year long after the infection resolved but was associated mainly with co-morbidity.

Aminoglycoside versus carbapenem or piperacillin/tazobactam treatment for bloodstream infections of urinary source caused by Gram-negative ESBL-producing Enterobacteriaceae.

OBJECTIVES: We studied the performance of aminoglycosides in treating bloodstream infections (BSIs) of urinary source caused by ESBL-producing Enterobacteriaceae (ESBL-EB). METHODS: In a retrospective study of 193 patients with a clinical diagnosis of urinary tract infection, pyelonephritis or urosepsis and blood and urine cultures positive for ESBL-EB, patients were grouped according to whether they were treated with an aminoglycoside, a carbapenem or piperacillin/tazobactam. Multivariate analysis was used to define risk factors for mortality with inverse probability of treatment weighting used to minimize confounding. The primary efficacy outcome was 30 day mortality. The primary safety outcome was acute kidney injury (AKI) at 14 days. RESULTS: Mean age was 79.3 years. Dementia, chronic kidney disease and the presence of a urinary catheter were common. Thirty-two (16.6%) patients died and risk factors for mortality included age, high Charlson score, presentation with severe sepsis/septic shock and infection with bacteria other than Escherichia coli. Aminoglycosides were non-inferior compared with other antibiotics regarding 30 day mortality [13.0% versus 21.2%, respectively; adjusted risk difference=10.29% (-0.82% to 21.41%)], but did not reach non-inferiority for bacteriuria recurrence [48.9% versus 44.7%, respectively; adjusted risk difference=-8.72% (-30.87% to 13.43%)]. AKI developed at a similar rate in both treatment groups: 12.0% versus 10.6%, respectively [OR=1.14 (0.46-2.81)]. Aminoglycosides were more efficacious in E. coli infections compared with other ESBL-EB. CONCLUSIONS: We demonstrated the efficacy and safety of aminoglycosides in treating BSI of urinary source caused by ESBL-EB. This carbapenem-sparing approach can assist in avoiding excessive carbapenem use without compromising outcomes.

Prevalence of Mycoplasma genitalium in men with urethritis and in high risk asymptomatic males in Tel Aviv: a prospective study.

We sought to investigate the prevalence of Mycoplasma genitalium, Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis in men presenting to a sexually transmitted infection (STI) clinic, with special attention to M. genitalium, its occurrence in Israeli patients, coinfections, and risk factors. In a cross-sectional study, 259 men were successively enrolled in the Tel Aviv Levinsky Clinic for STIs between November 2008 and November 2010. There were 118 men with urethritis and 141 high-risk men without symptoms. M. genitalium, C. trachomatis, N. gonorrhoeae, and T. vaginalis were detected using nucleic acid amplification tests. Demographic characteristics and risk factors were documented. The overall prevalence of infection with M. genitalium, C. trachomatis, N. gonorrhoeae, and T. vaginalis, were 6.6%, 12.7%, 23.1%, and 0%, respectively. Prevalences in men with urethritis were 11.9%, 22%, and 49%, for M. genitalium, C. trachomatis, and N. gonorrhoeae, respectively. Prevalences in men without symptoms were 2.1%, 5.0%, and 1.4%, for M. genitalium, C. trachomatis, and N. gonorrhoeae, respectively. Co-infections were found only in symptomatic individuals, in whom 5.9% were infected concomitantly with C. trachomatis and N. gonorrhoeae, and 2.5% had dual infection with M. genitalium and N. gonorrhoeae. N. gonorrhoeae, C. trachomatis, and M. genitalium were significantly more prevalent in patients with urethritis. M. genitalium was significantly more prevalent in the heterosexual population than in homosexual males. To conclude, we have found that M. genitalium infection is associated with urethritis in Israeli men, and more so in the heterosexual population. Testing men for M. genitalium as a cause of non-gonococcal urethritis is warranted, particularly because of its poor response to doxycycline and possible failure of azithromycin.

Escherichia coli isolates from patients with bacteremic urinary tract infection are genetically distinct from those derived from sepsis following prostate transrectal biopsy.

BACKGROUND: Transrectal ultrasound-guided (TRUS) prostate biopsy is a very common procedure that is generally considered relatively safe. However, severe sepsis can occur after TRUS prostate biopsies, with Escherichia coli being the predominant causative agent. A common perception is that the bacteria that cause post-TRUS prostate biopsy infections originate in the urinary tract, but this view has not been adequately tested. Yet other authors believe on the basis of indirect evidence that the pathogens are introduced into the bloodstream by the biopsy needle after passage through the rectal mucosa. METHODS: We compared E. coli isolates from male patients with bacteremic urinary tract infection (B-UTI) to isolates of patients with post prostate biopsy sepsis (PPBS), in terms of their sequence types, determined by multi-locus sequence typing (MLST) and their virulence markers. RESULTS: B-UTI isolates were much richer in virulence genes than were PPBS isolates, supporting the hypothesis that E. coli causing PPBS derive directly from the rectum. Sequence type 131 (ST131) strains and related strain from the ST131 were common (>30%) among the E. coli isolates from PPBS patients as well as from B-UTI patients and all these strains expressed extended spectrum beta-lactamases. CONCLUSIONS: Our finding supports the hypothesis that E. coli causing PPBS derive directly from the rectum, bypassing the urinary tract, and therefore do not require many of the virulence capabilities necessary for an E. coli strain that must persist in the urinary tract. In light of the increasing prevalence of highly resistant E. coli strains, a new approach for prevention of PPBS is urgently required.

Active surveillance cultures in critically ill patients: pathogens, patterns, and correlation with eventual bloodstream infections.

BACKGROUND: The role of routine active surveillance cultures (ASCs) in predicting consequent bloodstream infections is unclear. OBJECTIVES: To determine prospectively whether routine screening ASCs obtained on admission to the intensive care unit (ICU) can predict the causative agent of subsequent bloodstream infections. METHODS: We prospectively studied a cohort of 100 mechanically ventilated patients admitted consecutively to a 16-bed ICU. On admission, ASCs were obtained from four sites: skin cultures (swabs) from the axillary region, rectal swabs, nasal swabs, and deep tracheal aspirates. Thereafter, cultures were obtained from all four sites daily for the next 5 days of the ICU stay. RESULTS: Of the 100 recruited patients 31 (31%) had culture-proven bacteremia; the median time to development of bacteremia was 5 days (range 1-18). Patients with bacteremia had a longer median ICU stay than patients without bacteremia: 14 days (range 2-45) vs. 5 days (1-41) (P < 0.001). ICU and 28 day mortality were similar in patients with and without bacteremia. Most ASCs grew multiple organisms. However, there was no association between pathogens growing on ASCs and eventual development of bacteremia. CONCLUSIONS: ASCs obtained on ICU admission did not identify the causative agents of most subsequent bacteremia events. Therefore, bloodstream infections could not be related to ASCs.

The accuracy of Gram stain of respiratory specimens in excluding Staphylococcus aureus in ventilator-associated pneumonia.

OBJECTIVE: To evaluate the Gram stain of deep tracheal aspirate as a tool to direct empiric antibiotic therapy, and more specifically as a tool to exclude the need for empiric antibiotic coverage against Staphylococcus aureus in ventilator-associated pneumonia (VAP). DESIGN: A prospective, single-center, observational, cohort study. SETTING: All wards at a community hospital. PATIENTS: Adult patients requiring mechanical ventilation, identified as having VAP in a 54-month prospective surveillance database. INTERVENTIONS: Sampling of lower airway secretions by deep endotracheal aspiration was taken from each patient who developed VAP. Samples were sent immediately for Gram stain and qualitative bacterial cultures. Demographic and relevant clinical data were collected; Gram stain, culture, and antibiotic susceptibility results were documented; and outcome was followed prospectively. MEASUREMENTS AND MAIN RESULTS: The analysis included 114 consecutive patients with 115 episodes of VAP from June 2007 to January 2012. Sensitivity of Gram stain compared with culture was 90.47% for gram-positive cocci, 69.6% for gram-negative rods, and 50% for sterile cultures. Specificity was 82.5%, 77.8%, and 79%, respectively. Negative predictive value was high for gram-positive cocci (97%) and sterile cultures (96%) but low for gram-negative rods (20%). Acinetobacter baumanii (45%) and Pseudomonas aeruginosa (38 %) were the prevailing isolates. S aureus was found in 18.3% of the patients. Most isolates were multiresistant. CONCLUSIONS: Absence of gram-positive bacteria on Gram stain had a high negative predictive value. These data can be used to narrow the initial empiric antibiotic regimen and to avoid unnecessary exposure of patients to vancomycin and other antistaphyloccocal agents.

A cost-saving algorithm for rapid diagnosis of Staphylococcus aureus and susceptibility to oxacillin directly from positive blood culture bottles by combined testing with BinaxNOW® S. aureus and Xpert MRSA/SA Assay.

We studied an algorithm combining 2 rapid methods to detect Staphylococcus aureus and its susceptibility to oxacillin directly from positive blood cultures; our goal was to reduce the cost of the procedure, while maintaining accuracy and a short turnaround time. A total of 581 blood cultures containing gram-positive cocci in clusters were tested by BinaxNOW® Staphylococcus aureus Test. Positive samples were further assessed by the Xpert MRSA/SA BC Assay. Phenotypic methods have identified coagulase-negative staphylococci in 505 samples and S. aureus in 76 samples, of which 51 were oxacillin sensitive and 25 were oxacillin resistant. Sensitivity and specificity of the BinaxNOW® Test were 92% and 99%, respectively, compared to the phenotypic method. The Xpert MRSA/SA BC Assay showed complete concordance with phenotypic identification and antimicrobial susceptibility results. The combined rapid assays produced results within 2 hours and reduced the cost by 75% compared with the Xpert MRSA/SA BC Assay if used alone on all blood bottles.

Penile herpes simplex virus type 1 infection presenting two and a half years after Jewish ritual circumcision of an infant.

The association between Jewish ritual circumcision and genital herpes simplex virus type 1 infection has been well described. We report a case of genital herpes that first presented at the age of 2½ years. We believe that the infection was acquired asymptomatically through direct orogenital suction performed during circumcision in the newborn period.

Neonatal herpes simplex virus infections in Israel.

BACKGROUND: The incidence and the clinical characteristics of neonatal herpes simplex virus (NHSV) infection in Israel are unknown. METHODS: We reviewed the medical records of NHSV cases who were born between January 2001 and December 2007 in 5 medical centers located in central Israel. Cases were identified using International Classification of Diseases, 9th revision codes. In addition, parents of survivors were interviewed by telephone. RESULTS: In the 8-year study period, 22 cases of NHSV were identified (an incidence rate of 8.4 per 100,000 live births). Most patients (77.2%, 17 cases) manifested as skin, eye and/or mouth infection, 13.6% (3 cases) as localized central nervous system disease and 9.1% (2 cases) as disseminated disease. Most (76.4%) herpes viruses typed in our series were HSV-1. None of the mothers had documented intrapartum visible genital HSV lesions or a previous history of genital herpes. Ritual circumcision was the source of HSV-1 transmission in 7 infants (31.8% of cases). CONCLUSIONS: The incidence of NHSV infection in Israel was found to be similar to the lower part of the scale reported in the United States, however higher than the incidence reported in Canada or in Europe. Similar to more recent reports, our series demonstrates the shift toward the predominance of HSV-1 in NHSV infection. In addition, none of the mothers in our series had a previous history of genital herpes. This study emphasizes the need for awareness of HSV infection in Israeli neonates.

Cytomegalovirus-associated cerebral sinus vein thrombosis.

Cytomegalovirus (CMV)-associated thrombosis has been reported many times in the medical literature, and most patients had deep vein thrombosis and/or pulmonary embolism. CMV-associated cerebral sinus vein thrombosis has been reported only twice. We present an immunocompetent patient with CMV-associated cerebral sinus vein thrombosis and no other thrombosis risk factors. This is another example of the pro-thrombotic features of CMV. Physicians should be alert for symptoms and signs of acute CMV infection in patients with thrombosis.

[Hinman syndrome--an uncommon cause of recurrent urinary tract infections since childhood].

A 20-year-old female presented with a history of recurrent urinary tract infections, diurnal incontinence, nocturnal enuresis, and voiding difficulty. Imaging studies revealed a thick trabeculated bladder and high post-void residual urine volumes. Urodynamic evaluation demonstrated involuntary bladder contractions and no evidence of bladder outlet obstruction. A full neurological and urological workup were both unremarkable. A thorough history revealed her symptoms were initiated after prolonged and stressful potty training with multiple failed attempts. She developed a dysfunctional voiding pattern consistent with a non-neurogenic neurogenic bladder, also known as the "Hinman syndrome". Successful therapy relies primarily on behavior modification maneuvers combined with medical therapy to reduce unstable bladder contractions and alleviate bladder outlet obstruction.

[Tuberculosis in the 21st century].

Tuberculosis remains a significant global problem, principally affecting the developing countries, which are also heavily afflicted by HIV. In the industrialized countries, tuberculosis concerns mostly the immigrant, the immuno-compromised, and the elderly. More recently, TNF-alpha antagonists are being recognized as an important risk factor for tuberculosis, and guidelines for improved screening and control have been issued. Diagnosis of tuberculosis remains cumbersome, and the newer nucleic acid-based techniques are insufficiently sensitive. New immunologic methods to improve the diagnosis of latent tuberculosis are being studied. Isoniazid and rifampicin remain the mainstay of the treatment of active disease, but several new drugs are being evaluated. The existence of immune reconstitution inflammatory reactions in HIV patients is also becoming more widely appreciated. Treatment of latent tuberculosis still relies mainly on the use of isoniazid, and efforts continue to improve patient compliance.

Phialemonium curvatum arthritis of the knee following intra-articular injection of a corticosteroid.

Phialemonium curvatum arthritis of the knee developed in a diabetic man following intra-articular injection of a corticosteroid. Cure was achieved with a 6-week course of intravenous amphotericin B deoxycholate. P.curvatum is commonly found in the environment and is often considered a contaminant; yet, its pathogenic potential should be seriously considered in selected patients.

Epidemiology and clinical aspects of enteric fever in Israel.

Enteric fever decreased in Israel in the last 50 years, but its current epidemiology is unknown. In a nationwide study, we evaluated all cases of enteric fever from 1995 to 2003. On hundred thirty-six cases met the case definition. During the period studied, the incidence of enteric fever decreased from 0.42 to 0.23/100,000. A total of 57.4% of the cases were acquired abroad. The incidence of endemic enteric fever was 2.7 times higher in Arabs than in Jews. In Arabs, Salmonella Typhi was the causative agent in all cases, and almost all cases were endemic. In Jews, most cases were imported, with a decrease in imported S. typhi, cases and an increase in imported S. Paratyphi A cases. Salmonella Paratyphi B was endemic, and restricted to the Jewish population. The reasons for the difference in causative agents along ethnic lines need further evaluation. A more efficient vaccine for travelers that includes S. Paratyphi A is needed.

Opisthorchiasis from imported raw fish.

Liver fluke infection caused by Opisthorchiidae is a major public health problem in many parts of the Far East, Southeast Asia, and eastern Europe. However, with the growing volume of international travel and population migration, the infection is increasingly diagnosed in countries where the disease is not endemic, particularly in North America. We report an outbreak of acute opisthorchiasis in a family that was infected in a non-disease-endemic area after eating raw carp illegally imported from a highly disease-endemic area in Siberia. With the growing numbers of former Soviet Union citizens immigrating to other countries, western physicians need to be alert regarding Opisthorchis-associated pathology in this population. The epidemiology and biology of Opisthorchiidae in the former Soviet Union are reviewed.

BRCA1 and BRCA2 germline mutations in lymphoma patients.

Mutations in the BRCA1 and BRCA2 tumor suppressor genes are associated with an increased risk for breast and ovarian cancers as well as other types of malignancies. The observation of a germline BRCA1 mutation in an index case with a lymphoid neoplasm in the setting of a family history of breast cancer prompted us to explore the role of BRCA germline mutations as lymphoma susceptibility alleles. A panel of 286 DNA samples from Jewish lymphoma patients was analyzed for the three most frequent BRCA1 and BRCA2 germline mutations in those of Ashkenazi Jewish heritage, and compared to a cohort of 5010 DNA samples from healthy controls. Of the 286 cases, 2 patients carried a germline BRCA mutation; both were diagnosed at an early age with an intermediate grade non-Hodgkin's lymphoma. This data indicate that germline BRCA mutations are not associated with an increased risk for lymphoid malignancies.