High Rates of Fosfomycin Resistance in Gram-Negative Urinary Isolates from Israel.

BACKGROUND: Increasing antimicrobial resistance is a major problem worldwide. Many urinary tract infection (UTI) isolates are resistant to all oral antimicrobial agents, necessitating intravenous treatment even for cystitis. Fosfomycin is a broad-spectrum antibiotic that achieves high and prolonged urinary drug concentration and is considered first-line treatment for uncomplicated cystitis. Our aim was to investigate fosfomycin susceptibility among urinary isolates and search for demographic or bacterial characteristics associated with fosfomycin nonsusceptibility. MATERIALS AND METHODS: This is a retrospective study of all Gram-negative urinary isolates at Padeh-Poriya Medical Center in northern Israel. A total of 1503 isolates were tested for fosfomycin susceptibility, as well as susceptibility to other antimicrobial agents, by VITEK2 system and disk diffusion testing. Demographic and clinical data were obtained from patient electronic files. RESULTS: A total of 1,503 isolates from patients' urine were included. Mean patient age was 64.6 years, 937 (62.3%) were female, 913 (60.7%) were Jews, and in 1,058 (70.4%) cases, the infection was community acquired; 28.1% were extended-spectrum beta lactamase (ESBL)-positive. A total of 1099 (73.1%) isolates were susceptible to fosfomycin. Fosfomycin nonsusceptibility was significantly correlated to year: 124 (20.7%) in 2015 versus 280 (30.9%) in 2016; patient age: 17.6% in patients ≤50 years versus 30% in patients >50 years; hospital-acquired UTI: 34.2% versus 23.8%; and presence of ESBL positivity: 31.1% in ESBL-positive versus 20.9% in ESBL-negative isolates (p for all <0.001). CONCLUSIONS: Fosfomycin nonsusceptibility among urine culture isolates is a worrisome phenomenon that is on the rise and is more often found in elderly patients, patients with nosocomial UTI, and isolates that are ESBL positive.

In Vitro Antileishmanial Activity of a Black Morel, Morchella importuna (Ascomycetes).

We studied the anti-Leishmania activity of a fractionated extract from the mushroom Morchella importuna in an in vitro system. Leishmaniasis is an important infectious disease caused by a range of Leishmania species, which are multihost protozoa parasites transmitted to humans by the sand fly and infecting macrophages. Leishmaniasis is an increasing worldwide health problem, including in the Mediterranean basin. Current chemotherapy treatments are limited by their toxic effects, the need for long-term treatment, and the increasing development of resistance by the parasite cells. Thus, alternative therapies are being considered, including herbal and mushroom products. We studied the effect of extracts from M. importuna on L. tropica promastigote cell proliferation and survival, and on their toxicity against human macrophages. The aqueous mushroom extract was compared with 3 successive extracted fractions: an 80% ethanol fraction, a water-soluble polysaccharide fraction, and a polyphenolic fraction. All 4 extracts showed anti-Leishmania activity; the aqueous extract was most active. The inhibition activity was dose dependent in killing Leishmania. No cell recovery was recorded after exposure to the mushroom extract. Microscopic observation showed morphological changes and the loss of flagella on the parasites. No cytotoxic activity was recorded against human macrophages at the same extract concentrations. The findings suggest the potential use of extracts of an edible Morchella mushroom against the Leishmania parasite in humans.

[COMPARISON OF CLINICAL AND DEMOGRAPHIC CHARACTERISTICS OF ARAB AND JEWISH CHILDREN LIVING IN THE GALILEE WHO HAVE SUFFERED FROM AN INTESTINAL INFECTION CAUSED BY CAMPYLOBACTER].

INTRODUCTION: Among all infectious agents that cause gastrointestinal infection in children, the most common is the Campylobacter bacterium. The bacterium has multiple virulence factors such as motility, adhesion and invasion of the human intestinal lining, and enzyme secretion. In recent years, there has been a worldwide increase in Campylobacter resistance to antibiotics. AIMS: To examine the frequency of Campylobacter among children who were hospitalized at the Poriya Medical Center during 2012-2014 and suffered from an intestinal infection caused by Campylobacter; to compare the demographic, clinical, and laboratory data of Jewish and Arab children; to examine the resistance rate of the bacterium to antibiotics. METHODS: The data on Campylobacter frequency in children who suffered from an intestinal infection was extracted from the medical records: age, sex, hospitalization duration, hemoglobin and leukocyte values in blood chemistry, the residential environment, and antibiotic treatment during hospitalization. In addition, antibiotic susceptibility tests were performed for Erythromycin and Ciprofloxacin for all Campylobacter cultures that were isolated from patients' stool samples and kept frozen. RESULTS: Campylobacter is the most prevalent bacterial factor among children who were hospitalized following enteritis. There are differences in the bacterium frequency among Jewish children in comparison to frequency in Arab children in the following aspects: Campylobacter is more frequent in Arab children, more common among children living in rural areas, and especially those of Arab origin. Arab children were hospitalized for longer durations than Jewish children. The mean age of Jewish children who suffered from infection caused by Campylobacter was higher compared to the mean age of Arab children. No difference was found in leukocyte values in the cell count. Hemoglobin values were lower among Jewish children compared to Arab children. There was a high percentage of children treated with antibiotics due to intestinal infection caused by Campylobacter, especially among Arab children. Resistance to Erythromycin was not found; however the rate of resistance to Ciprofloxacin was 10.7%. CONCLUSIONS: There are significant differences in intestinal infection caused by Campylobacter among Jewish and Arab children in parameters such as: mean age, hospitalization duration, and residential area. The antibiotic resistance rate that was found is low; however, presently, it still exists.

[RESISTANCE OF HELICOBACTER PYLORI TO ANTIBIOTICS IN ISRAEL: PAST VS PRESENT].

INTRODUCTION: Helicobacter Pylori (H. Pylori) is a spiral shaped Gram-negative bacterium which is known to cause chronic gastric inflammation (gastritis) that could develop into a gastric or duodenal ulcer. The standard first line therapy for H. Pylori infection is a 7-14 days period of "triple therapy" consisting of proton pump inhibitors (PPI) and the antibiotics clarithromycin and amoxicillin or metronidazole. Recently there has been an increase in H. Pylori resistance to antibiotic treatment. Throughout the years 1999, 2002, 2010, 2013 and 2014 studies have been conducted in Israel that examined H. Pylori resistance rates for commonly used antibiotics. These studies included 40-138 participants who were diagnosed with infection caused by H. Pylori. Based on information derived from these studies, there is a clear increase in H. Pylori resistance to antibiotics, particularly to tetracycline, amoxicillin and clarithromycin.

Microbiologic Data in Acute Cholecystitis: Ten Years' Experience from Bile Cultures Obtained during Percutaneous Cholecystostomy.

BACKGROUND: The aim of the study was to describe the microbiology and susceptibility patterns in acute cholecystitis by examining bile culture results from patients who underwent percutaneous cholecystostomy and examine concordance with empiric treatment. PATIENTS AND METHODS: A total of 124 patients with acute cholecystitis underwent percutaneous cholecystostomy between 2003 and 2012 at Emek Medical Center, Israel. Data on bile and blood culture results, isolate susceptibility, and clinical outcomes were retrieved from patient files. RESULTS: Bile cultures obtained from 116 patients were positive in 70 (60.3%) patients. Blood cultures obtained from 77 patients were positive in 23 (31.1%). Escherichia coli was the most common isolate in 28.6% of bile cultures and 43.5% of blood cultures. The concordance between empiric treatment coverage and culture isolate susceptibility was 67.6%. In most discordant cases, the isolates were Enterobacter spp. (40.9%) and Enterococcus spp. (31.8%). Overall, the in-hospital mortality rate was 7%: 2% in patients with concordant treatment compared with 14% in patients with discordant treatment (p = 0.09). Empiric antibiotic regimens were adequate in only two-thirds of patients. CONCLUSIONS: There might be a trend for poorer outcome in patients treated with inadequate antibiotic agents, emphasizing the importance of tailoring antibiotic treatment.

A cheap, simple high throughput method for screening native Helicobacter pylori urease inhibitors using a recombinant Escherichia coli, its validation and demonstration of Pistacia atlantica methanolic extract effectivity and specificity.

Helicobacter pylori is the most frequent and persistent bacterial infection worldwide, and a risk factor for active gastritis, peptic ulcers, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Although combined antibiotics treatment is effective cases of antibiotic resistance are reported at an alarming rate. The H. pylori urease enzyme is essential for the bacteria establishment in the gastric mucosa, resulting urease inhibitors being sought after as effective and specific anti- H. pylori treatment. To-date, screening assays are based mostly on the analog plant urease enzyme but difference in properties of the plant and bacterial enzymes hamper these efforts. We have developed a screening assay based on recombinant Escherichia coli expressing native H. pylori urease, and validated this assay using thiourea and a methanolic extract of Pistacia atlantica. The assay demonstrated the thiourea and the extract to be potent urease inhibitors, with the extract having strong bacteriostatic activity against clinical isolates of H. pylori, including such with antibiotic resistance. The extract was also found to be neutral toward common probiotic bacteria, supporting its specificity and compatibility with digestive system desired microflora and suggesting it could be a good source for anti-H. pylori compounds. The assay has proven to be cheap, simple and native alternative to the plant enzyme based assay and could allow for high throughput screening for new urease inhibitors and could expedite screening and development of novel, better H. pylori remedies helping us to combat this infection.

Reconsidering the Current Preterm Premature Rupture of Membranes Antibiotic Prophylactic Protocol.

OBJECTIVE: The purpose of our study was to determine whether the current antibiotic regimen for preterm premature rupture of membranes (PPROM) is adequate for covering the current causative agents and sensitivities of chorioamnionitis and early-onset neonatal sepsis. STUDY DESIGN: During a 3-year period, we retrieved the results from placental and amniotic membrane cultures obtained at delivery in cases of maternal fever, chorioamnionitis, and PPROM, and from blood cultures obtained from neonates with early-onset sepsis (EOS) in three participating hospitals. Sensitivity of pathogens to antimicrobial agents was performed using routine microbiologic techniques. RESULTS: There were 1,133 positive placental or amniotic cultures, 740 (65.3%) were from gram-negative Enterobacteriaceae. There were 27 neonates diagnosed with EOS with positive blood cultures. Aerobic Enterobacteriaceae accounted for 14 cases (52%) and group B streptococcus for 7 cases (26%). Of the Escherichia coli and Klebsiella sp., only 38% were sensitive to ampicillin. CONCLUSION: Local pathogens and their antibiotic sensitivity profiles should be explored every few years and an effective antibiotic protocol chosen to cover the main pathogens causing chorioamnionitis and EOS. Consideration should be made for changing ampicillin in women with PPROM to a regimen with better coverage of gram-negative Enterobacteriaceae.