Yield of Emergency Department Stool Culture Tests Among Children With Acute Gastroenteritis in Israel.

Previous studies have attempted to predict a positive stool culture in pediatric patients with acute gastroenteritis (AGE), but most of them are either from developing countries or are outdated. In all, 276 patients with AGE and 560 control patients were analyzed for differences in clinical factors including the presence of fever, highest recorded temperature, bloody diarrhea, number of bowel movements in 24 hours prior to presentation, and the presence of seizures, as well as laboratory parameters including leukocyte count and C-reactive protein (CRP). Positive stool sample rate was 13.7%. The most common bacterial pathogen was Campylobacter jejuni. Bacterial AGE was significantly associated with fever >37.9°C, bloody diarrhea, higher stool passing frequency, seizures, and CRP levels. For pediatric patients who present to the emergency department with AGE and present without bloody diarrhea, fever, frequent stool passing, or seizures, a stool culture test is of poor yield and may not be necessary.

Prevalence and Molecular Characterization of Extended-Spectrum ß-Lactamase Producing Enterobacterales in Healthy Community Dogs in Israel.

BACKGROUND: antimicrobial resistance is a global problem in human and veterinary medicine. We aimed to investigate the extended spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) gut colonization in healthy community dogs in Israel. METHODS: Rectal swabs were sampled from 145 healthy dogs, enriched, plated on selective plates, sub-cultured to obtain pure cultures, and ESBL production was confirmed. Bacterial species and antibiotic susceptibility profiles were identified. WGS was performed on all of the ESBL-PE isolates and their resistomes were identified in silico. Owners' questionnaires were collected for risk factor analysis. RESULTS: ESBL-PE gut colonization rate was 6.2% (n = 9/145, 95% CI 2.9-11.5). Overall, ten isolates were detected (one dog had two isolates); the main species was Escherichia coli (eight isolates), belonging to diverse phylogenetic groups-B1, A and C. Two isolates were identified as Citrobacter braakii, and C. portucalensis. A phylogenetic analysis indicated that all of the isolates were genetically unrelated and sporadic. The isolates possessed diverse ESBL genes and antibiotic-resistance gene content, suggesting independent ESBL spread. In a multivariable risk factor analysis, coprophagia was identified as a risk factor for ESBL-PE gut colonization (p = 0.048, aOR = 4.408, 95% CI 1.014-19.169). CONCLUSIONS: healthy community dogs may be colonized with ESBL-PE MDR strains, some of which were previously reported in humans, that carry wide and diverse resistomes and may serve as a possible source for AMR.

Managing an evolving pandemic: Cryptic circulation of the Delta variant during the Omicron rise.

SARS-CoV-2 continued circulation results in mutations and the emergence of various variants. Until now, whenever a new, dominant, variant appeared, it overpowered its predecessor after a short parallel period. The latest variant of concern, Omicron, is spreading swiftly around the world with record morbidity reports. Unlike the Delta variant, previously considered to be the main variant of concern in most countries, including Israel, the dynamics of the Omicron variant showed different characteristics. To enable quick assessment of the spread of this variant we developed an RT-qPCR primers-probe set for the direct detection of Omicron variant. Characterized as highly specific and sensitive, the new Omicron detection set was deployed on clinical and wastewater samples. In contrast to the expected dynamics whereupon the Delta variant diminishes as Omicron variant increases, representative results received from wastewater detection indicated a cryptic circulation of the Delta variant even with the increased levels of Omicron variant. Resulting wastewater data illustrated the very initial Delta-Omicron dynamics occurring in real time. Despite this, the future development and dynamics of the two variants side-by-side is still mainly unknown. Based on the initial results, a double susceptible-infected-recovered model was developed for the Delta and Omicron variants. According to the developed model, it can be expected that the Omicron levels will decrease until eliminated, while Delta variant will maintain its cryptic circulation. If this comes to pass, the mentioned cryptic circulation may result in the reemergence of a Delta morbidity wave or in the possible generation of a new threatening variant. In conclusion, the deployment of wastewater-based epidemiology is recommended as a convenient and representative tool for pandemic containment.

Microbiome Characterization of Infected Diabetic Foot Ulcers in Association With Clinical Outcomes: Traditional Cultures Versus Molecular Sequencing Methods.

Background: Infected diabetic foot ulcers (IDFU) are a major complication of diabetes mellitus. These potentially limb-threatening ulcers are challenging to treat due to impaired wound healing characterizing diabetic patients and the complex microbial environment of these ulcers. Aim: To analyze the microbiome of IDFU in association with clinical outcomes. Methods: Wound biopsies from IDFU were obtained from hospitalized patients and were analyzed using traditional microbiology cultures, 16S rRNA sequencing and metagenomic sequencing. Patients' characteristics, culture-based results and sequencing data were analyzed in association with clinical outcomes. Results: A total of 31 patients were enrolled. Gram-negative bacteria dominated the IDFU samples (79%, 59% and 54% of metagenomics, 16S rRNA and cultures results, respectively, p<0.001). 16S rRNA and metagenomic sequencing detected significantly more anaerobic bacteria, as compared to conventional cultures (59% and 76%, respectively vs. 26% in cultures, p=0.001). Culture-based results showed that Staphylococcus aureus was more prevalent among patients who were treated conservatively (p=0.048). In metagenomic analysis, the Bacteroides genus was more prevalent among patients who underwent amputation (p<0.001). Analysis of metagenomic-based functional data showed that antibiotic resistance genes and genes related to biofilm production and to bacterial virulent factors were more prevalent in IDFU that resulted in amputation (p<0.001). Conclusion: Sequencing tools uncover the complex biodiversity of IDFU and emphasize the high prevalence of anaerobes and Gram-negative bacteria in these ulcers. Furthermore, sequencing results highlight possible associations among certain genera, species, and bacterial functional genes to clinical outcomes.

Downregulation of CD45 Signaling in COVID-19 Patients Is Reversed by C24D, a Novel CD45 Targeting Peptide.

CD45, the predominant transmembrane tyrosine phosphatase in leukocytes, is required for the efficient induction of T cell receptor signaling and activation. We recently reported that the CD45-intracellular signals in peripheral blood mononuclear cells (PBMCs) of triple negative breast cancer (TNBC) patients are inhibited. We also reported that C24D, an immune modulating therapeutic peptide, binds to CD45 on immune-suppressed cells and resets the functionality of the immune system via the CD45 signaling pathway. Various studies have demonstrated that also viruses can interfere with the functions of CD45 and that patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are immune-suppressed. Given the similarity between the role of CD45 in viral immune suppression and our findings on TNBC, we hypothesized that the C24D peptide may have a similar "immune-resetting" effect on PBMCs from COVID-19 patients as it did on PBMCs from TNBC patients. We tested this hypothesis by comparing the CD45/TCR intracellular signaling in PBMCs from ten COVID-19 patients vs. PBMCs from ten healthy volunteers. Herein, we report our findings, demonstrating the immune reactivating effect of C24D via the phosphorylation of the tyrosine 505 and 394 in Lck, the tyrosine 493 in ZAP-70 and the tyrosine 172 in VAV-1 proteins in the CD45 signaling pathway. Despite the relatively small number of patients in this report, the results demonstrate that C24D rescued CD45 signaling. Given the central role played by CD45 in the immune system, we suggest CD45 as a potential therapeutic target.

Characteristics of pelvic inflammatory disease caused by sexually transmitted disease - An epidemiologic study.

INTRODUCTION: Pelvic inflammatory disease (PID) is an infection of the upper genital organs, diagnosed by clinical findings. The nucleic acid amplification test (NAAT) identify sexually transmitted (STD) pathogens from endocervical swabs, via real time PCR. This study explored the prevalence of STD detected by NAAT for women with PID. We also aimed to identify predictive characteristics for positive test. MATERIAL & METHODS: This retrospective cohort study explored the prevalence of positive NAAT for women with clinically diagnosed PID, 2016-2019, in a secondary referral center. The primary outcome was the prevalence of positive STD tests and specific pathogens. The secondary outcome was predictive clinical and laboratory parameters for positive NAAT. RESULTS: Among the 610 women in our cohort, 103 had a positive STD PCR, which accounts for 17%. Most of the patients had Urea parvum (39.4%) Mycoplasma hominis (17.2%) or Urea urealyticum (15.7%). Other pathogens with lower incidence were Chlamydia trachomatis (9.8%), Trichomonas vaginalis (3.4%), Mycoplasma genitalium (2.1%) and the lowest rate was for Neisseria gonorrhea (1.5%). CONCLUSION: In our population, we found lower prevalence of Chlamydia trachomatis and Neisseria gonorrhea compared to other large populations. This may be due to a high prevalence of married and religious women and also due to administration of a wide range of empirical antibiotic treatment, even for a low suspicion of PID. The study also gives reassurance that our empirical antibiotic protocol is adjusted to the endemic PID pathogens found in our population.

Third Generation Cephalosporin Resistant Enterobacterales Infections in Hospitalized Horses and Donkeys: A Case-Case-Control Analysis.

In human medicine, infections caused by third-generation cephalosporin-resistant Enterobacterales (3GCRE) are associated with detrimental outcomes. In veterinary medicine, controlled epidemiological analyses are lacking. A matched case-case-control investigation (1:1:1 ratio) was conducted in a large veterinary hospital (2017-2019). In total, 29 infected horses and donkeys were matched to 29 animals with third-generation cephalosporin-susceptible Enterobacterales (3GCSE) infections, and 29 uninfected controls (overall n = 87). Despite multiple significant associations per bivariable analyses, the only independent predictor for 3GCRE infection was recent exposure to antibiotics (adjusted odds ratio (aOR) = 104, p < 0.001), but this was also an independent predictor for 3GCSE infection (aOR = 22, p < 0.001), though the correlation with 3GCRE was significantly stronger (aOR = 9.3, p = 0.04). In separated multivariable outcome models, 3GCRE infections were independently associated with reduced clinical cure rates (aOR = 6.84, p = 0.003) and with 90 days mortality (aOR = 3.6, p = 0.003). Klebsiella spp. were the most common 3GCRE (36%), and blaCTX-M-1 was the major ß-lactamase (79%). Polyclonality and multiple sequence types were evident among all Enterobacterales (e.g., Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae). The study substantiates the significance of 3GCRE infections in equine medicine, and their independent detrimental impact on cure rates and mortality. Multiple Enterobacterales genera, subtypes, clones and mechanisms of resistance are prevalent among horses and donkeys with 3GCRE infections.

Transcontinental Dissemination of the L2b/D-Da Recombinant Chlamydia trachomatis Lymphogranuloma venereum (LGV) Strain: Need of Broad Multi-Country Molecular Surveillance.

Previously, we identified a Chlamydia trachomatis lymphogranuloma venereum (LGV) recombinant strain possessing a non-LGV ompA genotype. Here, culture-independent genome sequencing confirms its circulation in Europe, Middle East, and North America, and unveils emergence of antibiotic resistance. Broad surveillance is needed.

Regressing SARS-CoV-2 Sewage Measurements Onto COVID-19 Burden in the Population: A Proof-of-Concept for Quantitative Environmental Surveillance.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an RNA virus, a member of the coronavirus family of respiratory viruses that includes severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and the Middle East respiratory syndrome (MERS). It has had an acute and dramatic impact on health care systems, economies, and societies of affected countries during the past 8 months. Widespread testing and tracing efforts are being employed in many countries in attempts to contain and mitigate this pandemic. Recent data has indicated that fecal shedding of SARS-CoV-2 is common and that the virus RNA can be detected in wastewater. This indicates that wastewater monitoring may provide a potentially efficient tool for the epidemiological surveillance of SARS-CoV-2 infection in large populations at relevant scales. In particular, this provides important means of (i) estimating the extent of outbreaks and their spatial distributions, based primarily on in-sewer measurements, (ii) managing the early-warning system quantitatively and efficiently, and (iii) verifying disease elimination. Here we report different virus concentration methods using polyethylene glycol (PEG), alum, or filtration techniques as well as different RNA extraction methodologies, providing important insights regarding the detection of SARS-CoV-2 RNA in sewage. Virus RNA particles were detected in wastewater in several geographic locations in Israel. In addition, a correlation of virus RNA concentration to morbidity was detected in Bnei-Barak city during April 2020. This study presents a proof of concept for the use of direct raw sewage-associated virus data, during the pandemic in the country as a potential epidemiological tool.

Nontuberculous mycobacteria infections of peritoneal dialysis patients: A multicenter study.

OBJECTIVES: Nontuberculous mycobacteria (NTM) infections pose a diagnostic challenge in peritoneal dialysis (PD) patients. In this study, we sought to identify findings that are suggestive of NTM infection in PD adult patients. METHODS: All patients with NTM exit-site infection (ESI) with/without tunnel infection and peritonitis identified during the last decade in eight medical centers in Israel were included. Clinical, microbiological, and outcome data were collected and analyzed. RESULTS: Thirty patients were identified; 16 had ESI (53%) and 14 had peritonitis (47%). Median age was 65 years (interquartile range 52-76). Abdominal pain and cloudy PD fluid were reported in all patients with peritonitis, whereas exit-site discharge and granulation tissue were common in patients with ESI. Fourteen patients (47%) had negative cultures prior NTM diagnosis, and isolation of diphtheroids or Corynebacterium spp. was reported in 9 of 30 patients (30%). Antimicrobial treatment prior to diagnosis was documented in 13 of 30 patients (43%). Delayed diagnosis was frequent. Treatment regimens and duration of therapy varied widely. In 26 of 30 (87%) patients, catheter was removed and 19 of 30 patients (63%) required permanent transition to hemodialysis. Two patients with peritonitis (2 of 14, 14%) and seven with ESI (7 of 16, 44%) were eligible for continuation of PD. CONCLUSIONS: Culture negative peritonitis, isolation of diphtheroids or Corynebacterium spp., previous exposure to antibiotics, and/or a refractory infection should all prompt consideration of PD-related NTM infection and timely workup. Catheter removal is recommended aside prolonged antimicrobial therapy. In select patients with ESI, continuation of PD may be feasible.

Extended spectrum ß lactamase-producing Enterobacteriaceae shedding by race horses in Ontario, Canada.

BACKGROUND: We aimed to investigate the prevalence, molecular epidemiology and prevalence factors for Extended Spectrum ß-Lactamase-producing Enterobacteriaceae (ESBL-E) shedding by race horses. A cross-sectional study was performed involving fecal samples collected from 169 Thoroughbred horses that were housed at a large racing facility in Ontario, Canada. Samples were enriched, plated on selective plates, sub-cultured to obtain pure cultures and ESBL production was confirmed. Bacterial species were identified and antibiotic susceptibility profiles were assessed. E. coli sequence types (ST) and ESBL genes were determined using multilocus sequence type (MLST) and sequencing. Whole genome sequencing was performed to isolates harboring CTX-M-1 gene. Medical records were reviewed and associations were investigated. RESULTS: Adult horses (n = 169), originating from 16 different barns, were sampled. ESBL-E shedding rate was 12% (n = 21/169, 95% CI 8-18%); 22 ESBL-E isolates were molecularly studied (one horse had two isolates). The main species was E. coli (91%) and the major ESBL gene was CTX-M-1 (54.5%). Ten different E. coli STs were identified. Sixty-four percent of total isolates were defined as multi-drug resistant. ESBL-E shedding horses originated from 8/16 different barns; whereas 48% (10/21) of them originated from one specific barn. Overall, antibiotic treatment in the previous month was found as a prevalence factor for ESBL-E shedding (p = 0.016, prevalence OR = 27.72, 95% CI 1.845-416.555). CONCLUSIONS: Our findings demonstrate the potential diverse reservoir of ESBL-E in Thoroughbred race horses. Multi-drug resistant bacteria should be further investigated to improve antibiotic treatment regimens and equine welfare.

Extended-Spectrum ß-Lactamase-Producing Enterobacterales Shedding by Dogs and Cats Hospitalized in an Emergency and Critical Care Department of a Veterinary Teaching Hospital.

Extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) gut shedding in human medicine is considered as a major reservoir for ESBL-associated infections in high risk patients. In veterinary medicine, data regarding ESBL-PE gut shedding on admission to emergency and critical care department is scarce. We aimed to determine ESBL-PE shedding rates by dogs and cats in this setting and to determine the risk factors for shedding, at two separate periods, three-years apart. Rectal swabs were collected from animals, on admission and 72 h post admission, enriched and plated on Chromagar ESBL plates, followed by bacterial identification. ESBL phenotype was confirmed and antibiotic susceptibility profiles were determined (Vitek 2). Medical records were reviewed for risk factor analysis (SPSS). Overall, 248 animals were sampled, including 108 animals on period I (2015-2016) and 140 animals on period II (2019). In both periods combined, 21.4% of animals shed ESBL-PE on admission, and shedding rates increased significantly during hospitalization (53.7%, p-value < 0.001). The main ESBL-PE species were Escherichia coli and Klebsiella pneumoniae, accounting for more than 85% of the isolates. In a multivariable analysis, previous hospitalization was a risk factor for ESBL-PE gut shedding (p-value = 0.01, Odds ratio = 3.05, 95% Confidence interval 1.28-7.27). Our findings demonstrate significant ESBL-PE gut shedding among small animals in the emergency and critical care department, posing the necessity to design and implement control measures to prevent transmission and optimize antibiotic therapy in this setting.

Massive Orbital Myiasis Caused by Sarcophaga argyrostoma Complicating Eyelid Malignancy.

Purpose. To report a case of massive orbital myiasis caused by the larvae of Sarcophaga argyrostoma, complicating eyelid malignancy. Observations. A 98-year-old man first presented to our clinic noted to have a fast-growing lesion on his right upper and lower eyelids. Squamous cell carcinoma of the eyelids was highly suspected, and surgical excision was advised, but the patient refused any surgical or nonsurgical intervention. For the next eight months, the patient's family members continued to observe a high rate of tumor growth accompanied by deterioration of the general condition. During this whole period, the patient rejected admission to the hospital and was observed by nursing home staff. He was admitted to the emergency room in cachexic, unresponsive condition with fetid discharge and multiple live maggots crawling out from a large necrotic mass over the right orbit. On examination, no eyelids, eyeball, or other ocular tissue could be seen, while an extension of necrotic mass to forehead and midcheek was noted. Manual removal of larvae was performed. The patient passed away eight hours after his admission and larval removal. The maggots were identified as the third-instar larvae of Sarcophaga argyrostoma. Conclusions and Importance. This is the first reported case of home-acquired, massive orbital myiasis by S. argyrostoma. This case illustrates the crucial role of fly control as part of medical and home care in immobile patients. Moreover, it shows the importance of awareness by nursing home staff, paramedical, and medical personnel of possible myiasis, especially in bed-bound patients with skin malignancies and open wounds.

Extended-Spectrum ß-lactamase-Producing Enterobacteriaceae Shedding in Farm Horses Versus Hospitalized Horses: Prevalence and Risk Factors.

: We aimed to investigate the prevalence, molecular characteristics and risk factors of extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) shedding in horses. A prospective study included three cohorts: (i) farm horses (13 farms, n = 192); (ii) on hospital admission (n = 168) and; (iii) horses hospitalized for ≥72 h re-sampled from cohort (ii) (n = 86). Enriched rectal swabs were plated, ESBL-production was confirmed (Clinical and Laboratory Standards Institute (CLSI)) and genes were identified (polymerase chain reaction (PCR)). Identification and antibiotic susceptibility were determined (Vitek-2). Medical records and owners' questionnaires were analyzed. Shedding rates increased from 19.6% (n = 33/168) on admission to 77.9% (n = 67/86) during hospitalization (p < 0.0001, odds ratio (OR) = 12.12). Shedding rate in farms was 20.8% (n = 40/192), significantly lower compared to hospitalized horses (p < 0.0001). The main ESBL-E species (n = 192 isolates) were E. coli (59.9%, 115/192), Enterobacter sp. (17.7%, 34/192) and Klebsiella pneumoniae (13.0%, 25/192). The main gene group was CTX-M-1 (56.8%). A significant increase in resistance rates to chloramphenicol, enrofloxacin, gentamicin, nitrofurantoin, and trimethoprim-sulpha was identified during hospitalization. Risk factors for shedding in farms included breed (Arabian, OR = 3.9), sex (stallion, OR = 3.4), and antibiotic treatment (OR = 9.8). Older age was identified as a protective factor (OR = 0.88). We demonstrated an ESBL-E reservoir in equine cohorts, with a significant ESBL-E acquisition, which increases the necessity to implement active surveillance and antibiotic stewardship programs.

CTX-M-15 Producing Escherichia coli Sequence Type 361 and Sequence Type 38 Causing Bacteremia and Umbilical Infection in a Neonate Foal.

An eighteen-hour-old Tennessee walking horse foal was referred due to weakness and abdominal pain. Physical examination revealed dehydration, distended abdomen, and uveitis. Blood analysis revealed leukopenia, neutrophils' toxicity and left shift. The foal developed bloody diarrhea, gastric reflux, and was diagnosed with sepsis and enterocolitis. The foal was treated with intravenous fluids, plasma, antibiotics (ceftriaxone and metronidazole), partial parenteral nutrition (dextrose and amino acids), flunixin meglumine, and ophthalmic drops. Umbilical ultrasound revealed a fluid pocket adjacent to the umbilical vein; therefore, omphalectomy was performed. Umbilicus and blood were cultured. Results recovered two multidrug-resistant extended-spectrum ß-lactamase (ESBL) producing Escherichia coli clones, identified as ST38 (umbilicus) and ST361 (blood), harboring two different plasmids encoding blaCTX-M-15. Antibiotic treatment was replaced with imipenem and amikacin, but the foal deteriorated and was euthanized. Postmortem investigation revealed severe ulcerative enteritis, a perforation site and acute renal infarcts. Sepsis due to several different ESBL-producing E. coli strains should be considered, investigated, and treated accordingly.

Petting Zoo Animals as an Emerging Reservoir of Extended-Spectrum ß-Lactamase and AmpC-Producing Enterobacteriaceae.

Extended spectrum beta-lactamases and AmpC-producing Enterobacteriaceae (ESBL/AmpC-E) have become a great concern in both human and veterinary medicine. One setting in which this risk could be particularly prominent is petting zoos, in which humans, especially children, directly and indirectly interact with the animals. Yet, while the zoonotic transmission of various Enterobacteriaceae has been reported previously in petting zoos, reports on ESBL/AmpC-E shedding in this setting is currently lacking, despite the high potential risk. To fill this knowledge gap, we conducted a prospective cross-sectional study to explore the prevalence, molecular epidemiology, and risk for shedding of ESBL/AmpC-E in petting zoos. We performed a prospective cross-sectional study in eight petting zoos. Altogether, we collected 381 fecal and body-surface samples from 228 animals, broth-enriched them, and then plated them onto CHROMagar ESBL-plates for ESBL/AmpC-E isolation. Next, we identified the isolated species and tested their susceptibility to various antibiotics using the Vitek-2 system, determined bacterial relatedness by multilocus sequence typing (MLST), and identified ESBL/AmpC genes by using PCR and sequencing. Finally, we asked petting zoo owners and veterinarians to complete questionnaires, which we then analyzed to evaluate risk factors for ESBL/AmpC-E shedding. We found that ESBL/AmpC-E shedding is an important, currently oversighted risk in petting zoos, as the overall shedding rate was 12% (35 isolates, including 29% ESBL-producers, 34% AmpC-producers, and 37% ESBL and AmpC-producers). The isolated bacteria included Enterobacter cloacae (55%), Escherichia coli (31%), and Citrobacter freundii (14%), with diverse ESBL genes. MLST revealed diverse sequence types (STs), including the highly virulent Enterotoxigenic ST656 and the Uropathogenic ST127 E. coli strains, indicating complex epidemiology with inter-animal bacterial transmission. Shedding was associated with petting permission and antibiotic treatment in the petting zoo (OR = 7.34), which were identified as risk factors for ESBL/AmpC shedding. Our findings highlight petting zoos as a source for antibiotic-resistant ESBL/AmpC-producing bacteria, including highly virulent, disease-associated MDR E. coli strains. As this risk has not been previously described in detail, it calls for the implementation of infection control and active surveillance programs in petting zoos and raises the need for a comprehensive guideline to restrain this emerging concern.

Extended-Spectrum ß-Lactamase-Producing Enterobacteriaceae in Hospitalized Neonatal Foals: Prevalence, Risk Factors for Shedding and Association with Infection.

Extended-spectrum ß-lactamase Enterobacteriaceae (ESBL-E) have been investigated in adult horses, but not in foals. We aimed to determine shedding and infection in neonatal foals and mares. Rectal swabs were sampled from mare and foal pairs on admission and on the 3rd day of hospitalization; enriched, plated, and bacteria were verified for ESBL production. Identification and antibiotic susceptibility profiles were determined (Vitek2). Genotyping was performed by multilocus sequence typing (MLST). Genes were identified by PCR and Sanger sequencing. Medical data were analyzed for risk factors (SPSS). On admission, 55 pairs were sampled, of which 33 pairs were re-sampled. Shedding rates on admission in foals and mares were 33% (95% CI 21-47%) and 16% (95% CI 8-29%), respectively, and during hospitalization, these increased significantly to 85% (95% CI 70-94%) and 58% (95% CI 40-73%), respectively. Foal shedding was associated with umbilical infection on admission (P = 0.016) and with ampicillin treatment during hospitalization (p = 0.011), and was independent of the mare's shedding. The most common ESBL-E was Escherichia coli. During hospitalization, species diversity increased. Four foals were infected with ESBL-E strains, including umbilical infections and wounds. This study substantiates an alarming prevalence of shedding in neonatal foals, which should be further investigated in order to reduce resistance rates.

Effect of Photodynamic Antibacterial Chemotherapy Combined with Antibiotics on Gram-Positive and Gram-Negative Bacteria.

The well-known and rapidly growing phenomenon of bacterial resistance to antibiotics is caused by uncontrolled, excessive and inappropriate use of antibiotics. One of alternatives to antibiotics is Photodynamic Antibacterial Chemotherapy (PACT). In the present study, the effect of PACT using a photosensitizer Rose Bengal alone and in combination with antibiotics including methicillin and derivatives of sulfanilamide synthesized by us was tested against antibiotic-sensitive and antibiotic-resistant clinical isolates of Gram-positive S. aureus and Gram-negative P. aeruginosa. Antibiotic-sensitive and resistant strains of P. aeruginosa were eradicated by Rose Bengal under illumination and by sulfanilamide but were not inhibited by new sulfanilamide derivatives. No increase in sensitivity of P. aeruginosa cells to sulfanilamide was observed upon a combination of Rose Bengal and sulfanilamide under illumination. All tested S. aureus strains (MSSA and MRSA) were effectively inhibited by PACT. When treated with sub-MIC concentrations of Rose Bengal under illumination, the minimum inhibitory concentrations (MIC) of methicillin decreased significantly for MSSA and MRSA strains. In some cases, antibiotic sensitivity of resistant strains can be restored by combining antibiotics with PACT.

Current Trends in Antimicrobial Resistance of Escherichia coli.

Escherichia coli is the most common Gram-negative bacterial pathogen, presenting both a clinical and an epidemiological challenge. In the last decade, several successful multidrug-resistant high-risk strains, such as strain E. coli ST131 have evolved, mainly due to the growing selective pressure of antimicrobial use. These strains present enhanced fitness and pathogenicity, effective transmission and colonization abilities, global distribution due to efficient dissemination, and resistance to various antimicrobial resistances. Here, we describe the emerging trends and epidemiology of resistant E. coli, including carbapenemase-producing E. coli, E. coli ST131 and colistin resistant E. coli.

Performance of the Bladder EpiCheck™ Methylation Test for Patients Under Surveillance for Non-muscle-invasive Bladder Cancer: Results of a Multicenter, Prospective, Blinded Clinical Trial.

BACKGROUND: The highly frequent strategy of surveillance for non-muscle-invasive bladder cancer (NMIBC) involves cystoscopy and cytology. Urine assays currently available have not shown performance sufficient to replace the current gold standard for follow-up, which would require a very high negative predictive value (NPV), especially for high-grade tumors. Bladder EpiCheck (BE) is a novel urine assay that uses 15 proprietary DNA methylation biomarkers to assess the presence of bladder cancer. OBJECTIVE: To assess the performance of BE for NMIBC recurrence. DESIGN, SETTING, AND PARTICIPANTS: This was a blinded, single-arm, prospective multicenter study. The inclusion criteria were age ≥22 yr, urothelial carcinoma (UC) being monitored cystoscopically at 3-mo intervals, all UC resected within 12 mo, able to produce 10ml of urine, and able to consent. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The BE test characteristics were calculated and compared to cytology and cystoscopy results confirmed by pathology. RESULTS AND LIMITATIONS: Out of 440 patients recruited, 353 were eligible for the performance analysis. Overall sensitivity, specificity, NPV, and positive predictive value were 68.2%, 88.0%, 95.1%, and 44.8%, respectively. Excluding low-grade (LG) Ta recurrences, the sensitivity was 91.7% and NPV was 99.3%. The area under receiver operating characteristic (ROC) curves with and without LG Ta lesions was 0.82 and 0.94, respectively. CONCLUSIONS: In follow-up of NMIBC patients, the BE test showed an overall high NPV of 95.1%, and 99.3% when excluding LG Ta recurrences. With high specificity of 88.0%, the test could be incorporated in NMIBC follow-up since high-grade recurrences would be instantly detected with high confidence. Thus, the current burden of repeat cystoscopies and cytology tests could be reduced. PATIENT SUMMARY: The Bladder EpiCheck urine test has a clinically relevant and high negative predictive value. Its use in clinical routine could reduce the number of follow-up cystoscopies, and thus associated patient and financial burdens.