Avi Peretz

Role of antibiotics for treatment of inflammatory bowel disease.

Inflammatory bowel disease is thought to be caused by an aberrant immune response to gut bacteria in a genetically susceptible host. The gut microbiota plays an important role in the pathogenesis and complications of the two main inflammatory bowel diseases: Crohns disease (CD) and ulcerative colitis. Alterations in gut microbiota, and specifically reduced intestinal microbial diversity, have been found to be associated with chronic gut inflammation in these disorders. Specific bacterial pathogens, such as virulent Escherichia coli strains, Bacteroides spp, and Mycobacterium avium subspecies paratuberculosis, have been linked to the pathogenesis of inflammatory bowel disease. Antibiotics may influence the course of these diseases by decreasing concentrations of bacteria in the gut lumen and altering the composition of intestinal microbiota. Different antibiotics, including ciprofloxacin, metronidazole, the combination of both, rifaximin, and anti-tuberculous regimens have been evaluated in clinical trials for the treatment of inflammatory bowel disease. For the treatment of active luminal CD, antibiotics may have a modest effect in decreasing disease activity and achieving remission, and are more effective in patients with disease involving the colon. Rifamixin, a non absorbable rifamycin has shown promising results. Treatment of suppurative complications of CD such as abscesses and fistulas, includes drainage and antibiotic therapy, most often ciprofloxacin, metronidazole, or a combination of both. Antibiotics might also play a role in maintenance of remission and prevention of post operative recurrence of CD. Data is more sparse for ulcerative colitis, and mostly consists of small trials evaluating ciprofloxacin, metronidazole and rifaximin. Most trials did not show a benefit for the treatment of active ulcerative colitis with antibiotics, though 2 meta-analyses concluded that antibiotic therapy is associated with a modest improvement in clinical symptoms. Antibiotics show a clinical benefit when used for the treatment of pouchitis. The downsides of antibiotic treatment, especially with recurrent or prolonged courses such as used in inflammatory bowel disease, are significant side effects that often cause intolerance to treatment, Clostridium dificile infection, and increasing antibiotic resistance. More studies are needed to define the exact role of antibiotics in inflammatory bowel diseases.

Detection and characterization of carbapenemase-producing Enterobacteriaceae in wounded Syrian patients admitted to hospitals in northern Israel.

Since 2013, four hospitals in northern Israel have been providing care for Syrian nationals, primarily those wounded in the ongoing civil war. We analyzed carbapenemase-producing Enterobacteriaceae (CPE) isolates obtained from these patients. Isolate identification was performed using the VITEK 2 system. Polymerase chain reaction (PCR) was performed for the presence of blaKPC, blaNDM, and blaOXA-48. Susceptibility testing and genotyping were performed on selected isolates. During the study period, 595 Syrian patients were hospitalized, most of them young men. Thirty-two confirmed CPE isolates were grown from cultures taken from 30 patients. All but five isolates were identified as Klebsiella pneumoniae and Escherichia coli. Nineteen isolates produced NDM and 13 produced OXA-48. Among a further 29 isolates tested, multilocus sequence typing (MLST) showed that ST278 and ST38 were the major sequence types among the NDM-producing K. pneumoniae and OXA-48-producing E. coli isolates, respectively. Most were resistant to all three carbapenems in use in Israel and to gentamicin, but susceptible to colistin and fosfomycin. The source for bacterial acquisition could not be determined; however, some patients admitted to different medical centers were found to carry the same sequence type. CPE containing blaNDM and blaOXA-48 were prevalent among Syrian wounded hospitalized patients in northern Israel. The finding of the same sequence type among patients at different medical centers implies a common, prehospital source for these patients. These findings have implications for public health throughout the region.

Resistance of Helicobacter pylori to tetracycline, amoxicillin, clarithromycin and metronidazole in Israeli children and adults.

The aim of this study was to examine Helicobacter pylori-resistance rate to different antibiotics: tetracycline, amoxicillin, clarithromycin and metronidazole, and to compare eradication rates in adults and children in Israel. The study was based on the hypothesis of high-resistance rates to clarithromycin and metronidazole especially in adults and overall low-resistance rates to tetracycline and amoxicillin. One seventy six biopsies from patients with dyspeptic symptoms were cultured of which 100 were from adults (19–79 years) and 76 from children (7–17 years). All positive cultures were examined by Epsilometer test for MIC determination against tetracycline, amoxicillin, clarithromycin and metronidazole. 48.3% (85 out of 176) were H. pylori positive, of which 44% were from adults and 54% from children. Antibiotic resistance was seen in 31 out of 44 (70.5%) for metronidazole, 1 out of 44 (2.3%) for amoxicillin, 10 out of 44 (22.3%) for clarithromycin and 1 out of 44 (2.3%) for tetracycline among adults. Antibiotic resistance was seen in 10 out of 41 (24.4%) for metronidazole, 5 out of 41 (12.2%) for amoxicillin, 10 out of 41 (24.4%) for clarithromycin and 1 out of 41 (2.4%) for tetracycline among children. High rates of H. pylori resistance to metronidazole and clarithromycin was found especially among adults. Therefore, to increase the success rate of anti-H. pylori treatment, other classes of antibiotics need to be considered.

A rare bacteremia caused by Cedecea davisae in patient with chronic renal disease

Patient: Female, 77 Final Diagnosis: Bacteremia Symptoms: Chills • diarrhea • fever • nausea Medication: — Clinical Procedure: X-Ray • CBC • urine and blood cultur Specialty: Infectious diseases Objective: Rare disease Background: Cedecea davisae is a gram negative, oxidase negative bacilli that include 5 species. In the medical literature there are very few reports that describe infections caused by different species of the Cedecea genus. Case Report: In this paper we report a fourth case of bacteremia in a 77 year-old patient with a chronic renal disease that was successfully treated with ceftazidim and ciprofloxacin. Additionally, we present a review of all the reported infections that were caused by C. davisae. Conclusions: Five cases (not including our report) of Cedecea bacteremia were reported so far. Cedecea infections and particularly C. davisae infections can be difficult to treat due to the antibiotic resistance of the bacterium. Therefore we propose to consider treating C. davisae bacteremia with a combined antibiotic treatment until getting laboratory results for antibiotic-sensitivity tests.

Association of Streptococcus bovis presence in colonic content with advanced colonic lesion

AIM To prospectively examine the association between presence of Streptococcus bovis (S. bovis) in colonic suction fluid and the endoscopic findings on colonoscopy. METHODS From May 2012 to March 2013, 203 consecutive patients who underwent colonoscopy for any reason were enrolled in the study. Exclusion criteria included: antibiotic use in the previous month, age younger than 18 years, and inadequate preparation for colonoscopy. The colonoscopy was performed for the total length of the colon or to the occluding tumor. The endoscopic findings were registered. Samples were obtained proximal to the colonoscopic part of the suction tube from each patient and sent to the clinical microbiology laboratory for isolation and identification of S. bovis. Samples were incubated in enrichment media with addition of antibiotic disks for inhibition of growth of Gram-negative rods. The samples were seeded on differential growth media; suspected positive colonies were isolated and identified with Gram staining, catalase, and pyrrolidonyl arylamidase tests, and further identified using a VITEK2 system. Statistical analyses were performed using the Students t and χ(2) tests. RESULTS Of the 203 patients recruited, 49 (24%) patients were found to be S. bovis carriers; of them, the endoscopic findings included: 17 (34.7%) cases with malignant tumors, 11 (22.4%) with large polyps, 5 (10.2%) with medium-sized polyps, 6 (12.2%) with small polyps, 4 (8.1%) with colitis, and 6 (12.2%) normal colonoscopies. Of 154 patients found negative for S. bovis, the endoscopic findings included: none with malignant tumors, 9 (5.8%) cases with large polyps, 11 (7.1%) with medium-sized polyps, 26 (16.9%) with small polyps, 7 (4.5%) with colitis, and 101 (65.6%) normal colonoscopies. S. bovis (Gram-positive coccus) is considered part of the normal intestinal flora. There is an association between S. bovis bacteremia and colonic neoplasia. It is not well understood whether the bacterium has a pathogenetic role in the development of neoplasia or constitutes an epiphenomenon of colorectal neoplasms. There was a clear relationship between positivity for S. bovis in colonic suction fluid and findings of malignant tumors and large polyps in the colon. CONCLUSION There is an association between S. bovis bacteremia and malignant colonic lesions; this should prompt for development of a reliable screening method for advanced colonic lesions.

Do wheelchairs spread pathogenic bacteria within hospital walls

Transmission of nosocomial pathogens has been linked to transient colonization of health care workers, medical devices and other constituents of patients’ environment. In this paper we present our findings concerning the presence of pathogenic bacteria on wheelchairs, and the possibility that wheelchairs constitute a reservoir of these bacteria and a means of spreading them. In this work we examined four wheelchairs, each from a different location: the internal medicine ward, the emergency department, the general surgery ward and wheelchair stockpile of the transportation unit of the hospital. The samples were collected and cultured on different media. Bacterial identification and antimicrobial sensitivity testing were carried out using accepted practices in the microbiology laboratory. We found that wheelchairs are contaminated with several pathogenic bacteria, among them antibiotic-resistant strains such as MRSA, Pseudomonas aeruginosa, Acinetobacter baumanni etc. Since there is no specific guideline protocol that deals with disinfection and cleaning frequency of wheelchairs in hospitals, we suggest each hospital to write one.

Temperature-dependent growth modeling of environmental and clinical Legionella pneumophila MLVA-genotypes.

Legionella pneumophila cause waterborne infections resulting in severe pneumonia. High resolution genotyping of L. pneumophila isolates can be achieved by Multiple-Locus Variable number of tandem repeat Analysis (MLVA). Recently, we found that different MLVA genotypes of L. pneumophila , dominated different sites in a small drinking-water network, with a genotype-related temperature and abundance regime. The current study focuses on understanding the temperature-dependent growth kinetics of the genotypes that dominated the water network. Our aim was to model mathematically the influence of temperature on the growth kinetics of different environmental and clinical L. pneumophila genotypes and compare it with their ecological niches. Environmental strains showed a distinct temperature preference with significant differences among the growth kinetics of the three studied genotypes (Gt4, Gt6 and Gt15). Gt4 strains exhibited superior growth at lower temperatures (25-30 °C) while Gt15 strains appeared to be best adapted to relatively higher temperatures (42-45 °C). The temperature-dependent growth traits of the environmental genotypes were consistent with their distribution and temperature preferences in the water network. Clinical isolates exhibited significantly higher growth rates and reached higher maximal cell densities at 37°C and 42°C than the environmental strains. Further research on the growth preferences of L. pneumophila clinical and environmental genotypes will result in better understanding of their ecological niches in drinking water systems as well as in the human body. Importance: Legionella pneumophila is a waterborne pathogen that threatens humans in developed countries. The bacteria inhabit natural and man-made freshwater environments. Here we demonstrate that different environmental L. pneumophila genotypes have different temperature-dependent growth kinetics. Moreover, Legionella strains that belong to the same species but were isolated from environmental and clinical sources possess adaptations for growth at different temperatures. These growth preferences may influence the bacterial colonization at specific ecological niches within the drinking-water network. Adaptations for growth at the human body temperatures may facilitate some L. pneumophila strains abilities to infect and cause illness in humans. Our findings may be used as a tool to improve Legionella monitoring in drinking-water networks. Risk assessment models for predicting the risk of legionellosis should take into account not only Legionella concentrations but also the isolates temperature-dependent growth kinetics.ABSTRACT Legionella pneumophila causes waterborne infections resulting in severe pneumonia. High-resolution genotyping of L. pneumophila isolates can be achieved by multiple-locus variable-number tandem-repeat analysis (MLVA). Recently, we found that different MLVA genotypes of L. pneumophila dominated different sites in a small drinking-water network, with a genotype-related temperature and abundance regime. The present study focuses on understanding the temperature-dependent growth kinetics of the genotypes that dominated the water network. Our aim was to model mathematically the influence of temperature on the growth kinetics of different environmental and clinical L. pneumophila genotypes and to compare it with the influence of their ecological niches. Environmental strains showed a distinct temperature preference, with significant differences among the growth kinetics of the three studied genotypes (Gt4, Gt6, and Gt15). Gt4 strains exhibited superior growth at lower temperatures (25 and 30°C), while Gt15 strains appeared to be best adapted to relatively higher temperatures (42 and 45°C). The temperature-dependent growth traits of the environmental genotypes were consistent with their distribution and temperature preferences in the water network. Clinical isolates exhibited significantly higher growth rates and reached higher maximal cell densities at 37°C and 42°C than the environmental strains. Further research on the growth preferences of L. pneumophila clinical and environmental genotypes will result in a better understanding of their ecological niches in drinking-water systems as well as in the human body. IMPORTANCE Legionella pneumophila is a waterborne pathogen that threatens humans in developed countries. The bacteria inhabit natural and man-made freshwater environments. Here we demonstrate that different environmental L. pneumophila genotypes have different temperature-dependent growth kinetics. Moreover, Legionella strains that belong to the same species but were isolated from environmental and clinical sources possess adaptations for growth at different temperatures. These growth preferences may influence the bacterial colonization at specific ecological niches within the drinking-water network. Adaptations for growth at human body temperatures may facilitate the abilities of some L. pneumophila strains to infect and cause illness in humans. Our findings may be used as a tool to improve Legionella monitoring in drinking-water networks. Risk assessment models for predicting the risk of legionellosis should take into account not only Legionella concentrations but also the temperature-dependent growth kinetics of the isolates.

The antimicrobial susceptibility of Helicobacter pylori in strains isolated from children in Israel

OBJECTIVES Helicobacter pylori is a bacterial pathogen causing inflammation of the gastric mucosa that may lead to peptic ulcer, perforation or malignancy. Children are at risk of contracting H. pylori and developing subsequent morbidity. Diagnosis and management in children are difficult and merit a different approach compared with adults. This study aimed to describe the antimicrobial resistance rates of H. pylori to amoxicillin, tetracycline, clarithromycin, metronidazole, levofloxacin and rifampicin. METHODS Biopsies (n=154) collected during endoscopic examinations were cultivated for 10days using a growth medium selective for H. pylori, of which 89 were H. pylori-positive. Antimicrobial resistance of the strains was assessed by Etest to establish minimum inhibitory concentrations (MICs) according to British Society for Antimicrobial Chemotherapy guidelines. RESULTS Resistance rates were most notable for amoxicillin and clarithromycin at 12% and 35% with MICs of 0.74μg/mL and 2.51μg/mL, respectively. Resistance rates to tetracycline and levofloxacin were 8% and 2% with MICs of 2.57μg/mL and 2.0μg/mL, respectively. Resistance rates to rifampicin and metronidazole were 3% and 8% with MICs of 2.0μg/mL and 9.71μg/mL, respectively. CONCLUSION Current rising antibiotic resistance rates for H. pylori are of concern. Performance of culture enables determination of the susceptibility profile, which may lead to a better choice of, and perhaps narrower spectrum, antibiotic agent. In light of these findings, we suggest that optimising the choice of antibiotic agent in children with H. pylori infection remains a challenge for clinicians and thus requires further investigation in randomised clinical trials.

Peripartum maternal transmission of extended-spectrum β-lactamase organism to newborn infants

The aim of this study was to determine whether the route of extended-spectrum β-lactamase (ESBL) transmission to hospitalized newborns was from their mothers during delivery. Neonatal intensive care unit (NICU) hospitalized newborns were sampled for ESBL presence by stool cultures on the first and fourth days of life. Mothers of ESBL-positive newborns were sampled for possible correlation detection. Bacteria isolates were molecularly identified and susceptibility tests for antibiotic agents were performed. Of the 225 newborns, 14 (6.2%) were ESBL positive, 10 (4.4%) were Escherichia coli positive, and 4 (1.7%) were Klebsiella pneumoniae positive. Among the 14 mothers of positive newborns, 13 (92.8%) were found ESBL positive and one mother of a newborn with E. coli carriage was found ESBL negative. Genes encoding for ESBL resistance were identified. Antibiotic sensitivity and resistance were tested. This study demonstrated that ESBL bacteria carrier neonates hospitalized in NICU may be a result of transmission from mother to baby during delivery.

Antimicrobial susceptibility of Clostridium difficile isolates in Israel

OBJECTIVES An increase of Clostridium difficile isolates with reduced susceptibility to various antimicrobial agents has been observed, including isolates that are non-susceptible to antibiotics that are routinely used for treatment of C. difficile, such as vancomycin and metronidazole. We determined the susceptibility rates of C. difficile isolates from hospitals in northern Israel to various antibiotics including tigecycline, which was not previously reported from Israel. METHODS A total of 81 stool samples were collected from three hospitals in northern Israel from patients with C. difficile infection. Specimens were screened for BI/NAP1/027 ribotype, cultured, and sensitivity tests were performed for vancomycin, metronidazole, moxifloxacin, and tigecycline. Statistical tests were applied for analysing the differences in distribution of resistance between the different antibiotics and between BI/NAP1/027 and resistance of antibiotics. RESULTS Reduced susceptibility was found among 6/81 isolates for vancomycin, 4/81 for metronidazole, and 17/81 for moxifloxacin. Only 1 isolate had reduced susceptibility to tigecycline, with a mean MIC of 0.05μg/mL. Reduced susceptibility to moxifloxacin was significantly associated with reduced susceptibility to vancomycin (p=0.016) and to metronidazole (p=0.0276), and reduced susceptibility to metronidazole was associated with reduced susceptibility to vancomycin (p=0.0259). Eight of 81 isolates (9.9%) were positive for BI/NAP1/027 ribotype and had significantly higher non-susceptibility rates to moxifloxacin and vancomycin compared with BI/NAP1/027 negative isolates (p<0.0001 and p=0.0113, respectively). CONCLUSIONS We found higher non-susceptibility rates to vancomycin and metronidazole than most previous studies, while tigecycline resistance rates are very low in northern Israel, rendering it a potential agent for treating CDI.