Twenty-five years of sentinel laboratory-based surveillance of shigellosis in a high-income country endemic for the disease, Israel, 1998 to 2022.

BackgroundShigella is a leading cause of moderate-to-severe diarrhoea worldwide and diarrhoeal deaths in children in low- and-middle-income countries.AimWe investigated trends and characteristics of shigellosis and antimicrobial resistance of Shigella sonnei in Israel.MethodsWe analysed data generated by the Sentinel Laboratory-Based Surveillance Network for Enteric Pathogens that systematically collects data on detection of Shigella at sentinel laboratories, along with the characterisation of the isolates at the Shigella National Reference Laboratory. Trends in the shigellosis incidence were assessed using Joinpoint regression and interrupted time-series analyses.ResultsThe average incidence of culture-confirmed shigellosis in Israel declined from 114 per 100,000 population (95% confidence interval (CI): 112-115) 1998-2004 to 80 per 100,000 population (95% CI: 79-82) 2005-2011. This rate remained stable 2012-2019, being 18-32 times higher than that reported from the United States or European high-income countries. After decreasing to its lowest values during the COVID-19 pandemic years (19/100,000 in 2020 and 5/100,000 in 2021), the incidence of culture-confirmed shigellosis increased to 39 per 100,000 population in 2022. Shigella sonnei is the most common serogroup, responsible for a cyclic occurrence of propagated epidemics, and the proportion of Shigella flexneri has decreased. Simultaneous resistance of S. sonnei to ceftriaxone, ampicillin and sulphamethoxazole-trimethoprim increased from 8.5% (34/402) in 2020 to 92.0% (801/876) in 2022.ConclusionsThese findings reinforce the need for continuous laboratory-based surveillance and inform the primary and secondary prevention strategies for shigellosis in Israel and other endemic high-income countries or communities.

Group A Streptococcus Carriage in Adults in Southern Israel: A Prospective Study.

BACKGROUND: The prevalence of Group A streptococcus (GAS) carriage among adults is studied less than in children. The variability of reported carriage rates is considerably large and differs among diverse geographic areas and populations. OBJECTIVES: To evaluate the prevalence of GAS carriage among adults in Israel. METHODS: In this prospective study, conducted in a large healthcare maintenance organization in Israel, we obtained pharyngeal cultures from adults attending the clinic without upper respiratory tract complaints or fever. Patient data included sex, age, number of children, and religious sectors. RESULTS: From May to December 2022, eight family physicians collected a total of 172 throat swabs (86% response rate). The median age was 37 years (range 18-65); 72.7% were females, 22.7% were ultra-Orthodox Jewish, and 69.2% had children. The prevalence of GAS carriage was 6.98%, 95% confidence interval (95%CI) 3.7%-11.9%. GAS carriers were younger (31.7 vs. 39.3 years, P = 0.046), and the majority were ultra-Orthodox Jews (58.3% vs. 20%, P = 0.006). All GAS carriers were from lower socioeconomic status. When assessing risk factors for GAS carriage using multivariate analysis, only being an ultra-Orthodox Jew was positively related to GAS carriage (adjusted odds ratio 5.6, 95%CI 1.67-18.8). CONCLUSIONS: Being an ultra-Orthodox Jew was the single variable associated with a GAS carriage, which may be related to having many children at home and living in overcrowded areas. Primary care physicians in Israel should recognize this situation when examining patients with sore throats, mainly ultra-Orthodox Jews.

Oral cavity swabbing for diagnosis of group a Streptococcus: a prospective study.

BACKGROUND: Throat pain is a common complaint in the ambulatory setting. Diagnosis of group A Streptococcus is made with a culture, molecular test or a rapid antigen detection test from the tonsils or the posterior pharyngeal wall, while other areas of the oral cavity are considered unacceptable. The purpose of the study is to compare cultures from the tonsils or posterior pharyngeal wall (throat) with cultures from the oral cavity (mouth). METHODS: A prospective study conducted in ambulatory care. Eleven family physicians collected 2 swabs (throat and mouth) from 200 consecutive patients who complaint about throat pain. Inclusion criteria were throat pain and Centor Criteria > 2. Exclusion criteria were tonsillectomy and age (< 3 or > 65 years old). Participants were later divided into two groups - pediatrics (3-18 years old) and adults (19-65 year old). Sensitivity and specificity of mouth culture were calculated, with throat culture considered the reference gold standard. RESULTS: Between November 2017 and March 2019, 200 swabs were collected (101 adults and 99 children). In the adult group sensitivity of mouth culture was 72.1% (95% Confidence Interval [CI] 59.9-82.3%) and specificity was 100% (95% CI 92.7-89.4%-100%). In the pediatric group sensitivity of mouth culture was 78.3% (95% CI 65.8-87.9%) and specificity was 100% (95% CI 92.5-100%). CONCLUSION: Our study demonstrated higher sensitivity of mouth culture for GAS than previously published. This finding suggests that areas of the oral cavity that were considered as unacceptable sites for culture of GAS pharyngitis may be considered as acceptable swabbing sites. TRIAL REGISTRATION: Trial registration: ClinicalTrials.gov, ID NCT03137823. Registered 3 May 2017.

Minimizing treatment-induced emergence of antibiotic resistance in bacterial infections.

Treatment of bacterial infections currently focuses on choosing an antibiotic that matches a pathogen's susceptibility, with less attention paid to the risk that even susceptibility-matched treatments can fail as a result of resistance emerging in response to treatment. Combining whole-genome sequencing of 1113 pre- and posttreatment bacterial isolates with machine-learning analysis of 140,349 urinary tract infections and 7365 wound infections, we found that treatment-induced emergence of resistance could be predicted and minimized at the individual-patient level. Emergence of resistance was common and driven not by de novo resistance evolution but by rapid reinfection with a different strain resistant to the prescribed antibiotic. As most infections are seeded from a patient's own microbiota, these resistance-gaining recurrences can be predicted using the patient's past infection history and minimized by machine learning-personalized antibiotic recommendations, offering a means to reduce the emergence and spread of resistant pathogens.

Personal clinical history predicts antibiotic resistance of urinary tract infections.

Antibiotic resistance is prevalent among the bacterial pathogens causing urinary tract infections. However, antimicrobial treatment is often prescribed 'empirically', in the absence of antibiotic susceptibility testing, risking mismatched and therefore ineffective treatment. Here, linking a 10-year longitudinal data set of over 700,000 community-acquired urinary tract infections with over 5,000,000 individually resolved records of antibiotic purchases, we identify strong associations of antibiotic resistance with the demographics, records of past urine cultures and history of drug purchases of the patients. When combined together, these associations allow for machine-learning-based personalized drug-specific predictions of antibiotic resistance, thereby enabling drug-prescribing algorithms that match an antibiotic treatment recommendation to the expected resistance of each sample. Applying these algorithms retrospectively, over a 1-year test period, we find that they greatly reduce the risk of mismatched treatment compared with the current standard of care. The clinical application of such algorithms may help improve the effectiveness of antimicrobial treatments.

Distinctiveness and Similarities Between Extended-Spectrum ß-Lactamase-Producing Escherichia coli Isolated from Cattle and the Community in Israel.

The goal of this study was to compare the molecular features of bovine- and human community-acquired extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli in Israel. Bovine ESBL-producing E. coli were isolated during a point-prevalence study from the main farming locations throughout Israel. Human ESBL-producing E. coli isolates were collected from community-acquired urinary tract infection cases. Molecular typing was done initially by repetitive extragenic palindromic-PCR. Representative isolates were subjected to next-generation sequencing (NGS) and analyzed for multilocus sequence typing (MLST), core genome MLST (cgMLST), blaCTX-M gene allele, and mobile genetic elements (MGEs) surrounding it. Out of the 287 bovine- and 104 community-derived ESBL-producing E. coli isolates, 44 and 26 isolates were subjected to NGS, respectively. Both populations exhibited a diverse but distinct clonal structure with predominance of several sequence types (STs); two clones, ST-10/167 (n = 13) and ST-38 (n = 8), were present. cgMLST analysis of these clones revealed that the majority of isolates exhibited phylogenetic distance (PD) of >178 gene difference from their closest isolate, with the exception of five isolates that exhibited PD of <24 gene difference, including two bovine- to three community-derived isolates. Hence, clonal transmission of ESBL-producing E. coli between cattle and the community, although uncommon, is likely to have occurred. The blaCTX-M-15 gene was identified in 52/70 (74%) isolates from both cattle and the community and was surrounded by MGEs that were composed mostly of either the Tn3 or IS1380 families. Thus, MGEs are likely to play an important role in the exchange of resistance genes.

A national survey of the molecular epidemiology of Clostridium difficile in Israel: the dissemination of the ribotype 027 strain with reduced susceptibility to vancomycin and metronidazole.

Our goals were to study the molecular epidemiology and antimicrobial susceptibilities of C. difficile strains in Israel. Microbiology laboratories serving 6 general hospitals (GH) and 10 long-term care facilities (LTCF) were asked to submit all stool samples in January-February 2014 that tested positive for C. difficile. Toxigenic C. difficile isolates were recovered in 208 out of 217 samples (95.8%), of which 50 (23.6%) were from LTCFs. Ribotype 027 was the most common type overall, identified in 65 samples (31.8%), and was the predominant strain in the 3 GHs with the highest incidence of C. difficile infections. Other common strains were slpA types cr-02 (n = 45) and hr-02 (n = 18). The proportions of vancomycin and metronidazole MIC values >2mg/L were high in ribotype 027 (87.7% and 44.6%, respectively) and slpA-cr-02 strains (88.8% and 17.8%, respectively). This study demonstrates that the ribotype 027 strain has disseminated across Israel and is now the most common strain.

Positive deamidated gliadin peptide antibodies and negative tissue transglutaminase IgA antibodies in a pediatric population: to biopsy or not to biopsy.

Reports from our clinical laboratory database show that 75% of children <2 years old tested for celiac serology who were found positive for deamidated gliadin peptide (DGP) antibodies had negative results for tissue transglutaminase IgA. DGP levels were shown to decline and disappear without a gluten-free diet. This observation questions DGP's specificity for diagnosis of celiac disease.

Performance of serology assays for diagnosing celiac disease in a clinical setting.

Diagnosis of celiac disease frequently depends upon serology assays. We set out to prospectively assess the diagnostic value of five serology tests: an enzyme-linked immunosorbent assay (ELISA) for tissue transglutaminase (tTG)-immunoglobulin A (IgA) and tTG-IgG, a chemiluminescence assay for tTG-IgA, an ELISA for deamidated gliadin peptide (DGP) IgG and IgA screening, and detection of endomysial antibodies (Abs) by indirect immunofluorescence. One hundred sixteen children at high risk for developing celiac disease were evaluated clinically and underwent small bowel biopsies and blood serology tests. We examined differences between younger and older children in terms of clinical presentation, test performance, and the ability of high Ab levels to correctly predict diagnosis of celiac disease. Celiac disease was diagnosed for 85 (73%) children. No significant clinical differences were observed between the biopsy-positive and biopsy-negative groups. Children < or = 3 years of age revealed higher concentrations of tTG-IgA and DGP Abs than children >3 years old (P = 0.017 and 0.007, respectively). High Ab concentrations were predictive of villous atrophies, with sensitivities ranging from 92.8% to 97.9%, depending on the assay and the cutoff points applied. Sensitivities, specificities, positive predictive values, and negative predictive values varied among assays and improved after correction for best cutoff points. Assay specificities obtained in the clinical setting were lower than expected. The new tTG-IgA chemiluminescence assay demonstrated high throughput but low specificity (74.2%). The tTG-IgA ELISA exhibited the highest test efficiency, and the tTG-IgA chemiluminescence assay was suitable for large-scale screening, with reduced specificity. High concentrations of celiac disease-specific Abs bring into question the need for performance of biopsies on children at high risk.