Repurposing Loperamide as an Anti-Infection Drug for the Treatment of Intracellular Bacterial Pathogens

Infections caused by intracellular bacterial pathogens are difficult to treat since most antibiotics have low cell permeability and undergo rapid degradation within cells.The rapid development and dissemination of antimicrobial–resistant strains have exacerbated this dilemma.With the increasing knowledge of host–pathogen interactions,especially bacterial strategies for survival and proliferation within host cells,host-directed therapy(HDT)has attracted increased interest and has emerged as a promising antiinfection method for treating intracellular infection.Herein,we applied a cell-based screening approach to a US Food and Drug Administration(FDA)-approved drug library to identify compounds that can inhibit the intracellular replication of Salmonella Typhimurium(S.Typhimurium).This screening allowed us to identify the antidiarrheal agent loperamide(LPD)as a potent inhibitor of S.Typhimurium intracellular proliferation.LPD treatment of infected cells markedly promoted the host autophagic response and lysosomal activity.A mechanistic study revealed that the increase in host autophagy and elimination of intracellular bacteria were dependent on the high expression of glycoprotein nonmetastatic melanoma protein B(GPNMB)induced by LPD.In addition,LPD treatment effectively protected against S.Typhimurium infection in Galleria mellonella and mouse models.Thus,our study suggested that LPD may be useful for the treatment of diseases caused by intracellular bacterial pathogens.Moreover,LPD may serve as a promising lead compound for the development of anti-infection drugs based on the HDT strategy.

Research Progress of Radical Treatment of Helicobacter Pylori Based on Drug Sensitivity Test as First-Line Treatment

Helicobacter pylori (HP) infection is a global problem that affects about half of the world’s population and requires sufficient attention in clinical and scientific work. Due to differences in economic and medical conditions among countries around the world, there is currently no unified treatment plan for anti-HP. In China, empirical quadruple therapy is mainly used. With the abuse of antibiotics, many patients face the problem of secondary eradication after failure, and the resistance rate of HP is gradually increasing. After eradication failure, drug sensitivity cultivation is carried out to choose sensitive antibiotics for treatment. A new strategy is currently needed to address how to improve the eradication rate of HP during the first eradication. This article aims to discuss the first-line treatment plans and research progress for eradicating HP based on drug sensitivity testing before eradication. Compared with traditional empirical therapies, treatment based on drug sensitivity results can effectively improve the eradication rate of HP, and reduce drug resistance rates, and adverse reactions, among other benefits. .

Threefold Increase in the Number of Drug Resistant TB Cases after Introduction of Universal Drug Susceptibility Testing: Experiences from Two South India Districts

Background: In India, tuberculosis (TB) is a major public health problem, and the advent of drug resistance TB (DR-TB) has worsened the situation. The Revised National TB Control Programme (RNTCP) has introduced universal drug susceptibility testing (UDST) for all diagnosed TB cases in 2018. We conducted this study to know the advantage of implementing UDST when compared to selective testing existent in 2017 on key diagnostic cascade parameters and to identify the challenges in the implementation of UDST. Methods: The study was conducted in two districts of Karnataka, India during January 2017-December 2018. The quantitative part consisted of before-and-after design and the qualitative part consisted of descriptive design. Results: In 2017 (during selective testing/“before” period) out of the 2440 TB patients, 80 (3%) were diagnosed with Isoniazid and Rifampicin resistance patients;in contrast in 2018 (during UDST/“after” period) of the 5129 TB patients 258 (5%) were diagnosed with Isoniazid and Rifampicin resistance. However, the proportion of eligible patients tested for rifampicin resistance during the “after” period was 60% when compared to 100% during the “before” period and median turnaround time for testing was also longer during the “after” period when compared to the “before” period (32.5 days vs 27.5 days). Major reasons for these two gaps were found to be difficulties in collecting sputum specimens and transportation. Conclusion: The rollout of UDST has led to a three-fold increase in a number of DR-TB cases detected in the region. There is a need for the programme to increase the proportion tested for DST by increasing the laboratory capacity and address the challenges in sputum collection and transportation.

Diagnostic Validity of Cica Beta Test 1 for the Detection of Extended Spectrum Beta-Lactamase (ESBL) Producing Gram Negative Bacteria by Comparing with Phenotypic Method

Background: Detection of extended spectrum beta lactamase producing bacteria is an important issue in the clinical settings. Objective: The purpose of the present study was to validate the Cica Beta Test 1 for detection of extended spectrum beta-lactamase (ESBL) producing bacteria. Method: This analytical type of cross-sectional study was carried out in the Department of Microbiology and Immunology at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka from January 2006 to December 2006 for a period of one (01) year. All the patients presented with the clinical features of urinary tract infection and surgical as well as burn wound infection at any age with both sexes were selected as study population. All bacteria were isolated and identified by their colony morphology, staining characters, pigment production, motility and other relevant biochemical tests. Phenotypic confirmation of ESBLs producing isolates were done by inhibitor potentiated disc diffusion test according to CLSI recommendation. The Cica Beta Test 1 was performed according to the manufacturer’s instructions. Result: A total number of 288 Gram negative bacteria were isolated. Among these isolates Cica Beta test 1 was positive in 97 strains and phenotypic confirmatory test was positive in 89 strains. The test sensitivity of Cica Beta Test 1 was 100% (95% CI 95.9% to 100.0%). Specificity of the test was 96.0% (95% CI 92.2% to 98.2%). The positive predictive value (PPV) and negative predictive value (NPV) were 92.7% (95% CI 84.5% to 95.7%) and 100.0% (95% CI 98.0% to 100.0%) respectively. The accuracy of the test was 97.2% (95% CI 95.1% to 99.1%). Area under ROC curve = 0.980 (95% CI 0.964 to 0.996);p value 0.0001. Conclusion: In conclusion, Cica Beta Test 1 is very high sensitivity and specificity for the detection of ESBL from Gram negative bacteria.

Selection of Test Samples for Monitoring Veterinary Drug Residue in Bred Animals

[Objective] This study aimed to compare the residue situation of cimaterol,a kind of forbidden veterinary drug in hair, urine and flesh of pig, so as to provide theoretical basis for monitoring veterinary drug residue in bred animals. [Method]Total three different concentrations of cimaterol were administered to pigs, and the residue amounts of cimaterol in pig hair, urine and flesh were monitored at different raising stage. [Result] During the administration period, the residue amount of cimaterol was highest in urine, so urine is the suitable sample for rapid detection of cimaterol in manufacturing enterprises. Cimaterol could be accumulated in pig hair,where cimaterol was metabolized slowly. Thus, pig hair can be used as the test sample for tracing illegal use of veterinary drugs and for vivo detection. Flesh can be used as test sample for direct judgment whether cimaterol residue exceeds the relevant standard. [Conclusion] This study will provide certain theoretical basis for drug monitor in animal husbandry.

Distribution of pathogenic bacteria and antimicrobial sensitivity of eye infections in Suzhou

AIM:To investigate the types of bacteria in patients with eye infections in Suzhou and their drug resistance to commonly used antibacterial drugs.METHODS:The clinical data of 155 patients were retrospectively collected in this study,and the pathogenic bacteria species and drug resistance of each pathogenic bacteria were analyzed.RESULTS:Among the 155 patients(age from 12 to 87 years old,with an average age of 57,99 males and 56 females)with eye infections(160 eyes:74 in the left eye,76 in the right eye and 5 in both eyes,all of which were exogenous),71(45.81%)strains were gram-positive bacteria,23(14.84%)strains were gram-negative bacteria and 61(39.35%)strains were fungi.Gram-positive bacteria were highly resistant to penicillin and erythromycin(78.87%and 46.48%respectively),but least resistant to vancomycin at 0.Gram-negative bacteria were highly resistant to cefoxitin and compound sulfamethoxazole(100%and 95.65%respectively),but least resistant to meropenem at 0.Comparison of the resistance of gram-positive and gram-negative bacteria to some drugs revealed statistically significant differences(P<0.05)in the resistance of both to cefoxitin,cotrimoxazole,levofloxacin,cefuroxime,ceftriaxone and ceftazidime,and both had higher rates of resistance to gram-negative bacteria than to gram-positive bacteria.The distribution of bacterial infection strains showed that Staphylococcus epidermidis was the most common strain in the conjunctiva,cornea,aqueous humor or vitreous body and other eye parts.Besides,Fusarium and Pseudomonas aeruginosa were also among the most common strains of conjunctival and corneal infections.CONCLUSION:Gram-positive bacteria are the dominant bacteria in eye infections,followed by gram-negative bacteria and fungi.Considering the resistance of gramnegative bacteria to multiple drugs,monitoring of bacteria should be strengthened in eye bacterial infections for effective prevention and control to reduce complications caused by eye infections.

Epidemiologic Profile Urinary Tract Infections: Experience of the Microbiology Laboratory of the University Hospital Mohamed VI in Tangier

Urinary tract infection is one of the most common bacterial infections in humans. The urine cytobacteriological examination is the key test for its diagnosis. This work aims to Evaluate the prevalence of urinary tract infection at the Microbiology Laboratory of the University Hospital Mohamed VI in Tangier and to highlight its epidemiological and bacteriological characteristics. It was a descriptive study with retrospective data collection which took place from January 2021 to June 2022, at the Microbiology Laboratory of the university hospital Mohamed VI in Tangier. It covered all urine cytobacteriological examinations (ECBU) during the study period. We identified 77 cases of urinary tract infections out of 300 requests for (ECBU), that is a positivity rate of 25 %. The mean age was 55 years. The male gender was predominant. The epidemiological profile of the isolated strains was dominated by Enterobacteriaceae 81 %, followed by Gram-positive cocci 11 % and non-fermenting gram-negative bacteria 8 %. The main bacteria responsible for urinary tract infections in order of frequency: Escherichia coli 42 %, Klebsiella pneumoniae 20 %, Enterobacter cloacae 9 %, Staphylococcus aureus 6 %, Pseudomonas aeruginosa 5 % and Acinetobacter baumannii 3%. Most of the analyzed organisms showed resistance, especially to the beta-lactam antibiotic;the enterobacteria strains isolated had revealed resistance to amoxicillin: 74%, to amoxicillin-clavulanic acid in 40% of cases, and to third-generation cephalosporins in 24%. In terms of resistance mechanisms, 11 % of the Enterobacteriaceae were extended-spectrum β-lactamase producers and 9 % of the specimens were identified as carbapenemase producers. Of the Staphylococcus aureus strains isolated, 75% were resistant to meticillin. The Glycopeptides and linezolid were the most active molecules on these isolated strains. 15% of Enterococcus species isolated in our laboratory were resistant to glycopeptides (vancomycin and teicoplanin).

Distribution and drug resistance of pathogenic bacteria in emergency patients

BACKGROUND Antibiotic resistance has become a global threat for human health,calling for rational use of antibiotics.AIM To analyze the distribution and drug resistance of the bacteria,providing the prerequisite for use of antibiotics in emergency patients.METHODS A total of 2048 emergency patients from 2013 to 2017 were enrolled.Their clinical examination specimens were collected,followed by isolation of bacteria.The bacterial identification and drug susceptibility testing were carried out.RESULTS A total of 3387 pathogens were isolated.The top six pathogens were Acinetobacter baumannii(660 strains),Staphylococcus aureus(436 strains),Klebsiella pneumoniae(347 strains),Pseudomonas aeruginosa(338 strains),Escherichia coli(237 strains),and Candida albicans(207 strains).The isolation rates of these pathogens decreased year by year except Klebsiella pneumoniae,which increased from 7.1%to 12.1%.Acinetobacter baumannii is a widely-resistant strain,with multiple resistances to imipenem,ciprofloxacin,minocycline and tigecycline.The Staphylococcus aureus had high resistance rates to levofloxacin,penicillin G,and tetracycline.But the susceptibility of it to vancomycin and tigecycline were 100%.Klebsiella pneumoniae had high resistance rates to imipenem,cefoperazone/sulbactam,amikacin,and ciprofloxacin,with the lowest resistance rate to tigecycline.The resistance rates of Pseudomonas aeruginosa to cefoperazone/sulbactam and imipenem were higher,with the resistance rate to amikacin below 10%.Besides,Escherichia coli had high resistance rates to ciprofloxacin and cefoperazone/sulbactam and low resistance rates to imipenem,amikacin,and tigecycline.CONCLUSION The pathogenic bacteria isolated from the emergency patients were mainly Acinetobacter baumannii,Staphylococcus aureus,Klebsiella pneumoniae,Pseudomonas aeruginosa,Escherichia coli,and Candida albicans.The detection rates of drugresistant bacteria were high,with different bacteria having multiple drug resistances to commonly used antimicrobial agents,guiding the rational use of drugs and reducing the production of multidrug-resistant bacteria.

Identification and Antibacterial Activity Study of a Terrestrial Strain of Brevibacterium aureus 431

This study isolated and purified strain 431 from an animal probiotic product.Through staining and microscopic examination,colony morphology analysis,biochemical reaction tests,and 16S rDNA sequence alignment,the strain was identified and named Brevibacterium aureus 431.The study focused on the production of biosurfactants by strain 431,and antibacterial activity tests were conducted on the strain and its secondary metabolites.The results showed that strain 431 exhibited no resistance to 10 commonly used drugs,and its concentrated secondary metabolites were highly sensitive to the indicator bacterium Escherichia coli.Oral administration of strain 431 to BALB/c mice resulted in normal mental state,diet,and bowel movements,with no signs of illness or death,indicating that strain 431 is highly safe and non-pathogenic to mice.The study suggests that Brevibacterium aureus 431 has significant research value as a new source of actinomycetes and that its secondary metabolites have potential application value in the development of antibacterial drugs.

Comparison of Antibacterial Activities of Six Bacillus amyloliquefaciens Strains

In this study, six bacterial strains were isolated from the sediment, probiotic fermentation products, and lake sediments, they were identified as Bacillus amyloliquefaciens using genetic evolution analysis, which were named B3, B4, B5, XD3, YF6, and YF8. The comparison of the antibacterial activity, hemolytic activity, and antibiotic sensitivity of six Bacillus amyloliquefaciens strains laid a foundation for the development and application of antimicrobial peptide products. A surface activity assay was used to determine the production of biosurfactants in six Bacillus amyloliquefaciens strains. With Staphylococcus aureus and Escherichia coli as indicator bacteria, their antibacterial activity was determined using the agar diffusion method;the same diffusion method was used to determine the antibiotic susceptibility of Bacillus amyloliquefaciens. The results showed that the six Bacillus amyloliquefaciens strains had obvious biosurface activity, and the bacteria inhibited Staphylococcus aureus and Escherichia coli, from strong to weak: YF8, XD3, B3, B4, YF6, and B5. Strain YF8 had the best broad-spectrum bacteriostatic effect, followed by strain XD3. All Bacillus amyloliquefaciens strains were susceptible to 16 common drugs, except for Bacillus amyloliquefaciens strain YF8, which was intermediate to neomycin. The study shows that Bacillus amyloliquefaciens and secondary metabolites have the ability to produce a variety of active peptides, exert a certain inhibitory effect on common pathogens, and have the potential to develop as animal probiotics.

Predisposing factors for positive D-Xylose breath test for evaluation of small intestinal bacterial overgrowth:A retrospective study of 932 patients

AIM: To investigate, in the largest cohort to date, patient characteristics and associated risk factors for developing small intestinal bacterial overgrowth(SIBO) using the D-Xylose breath test(XBT).METHODS: We performed a retrospective crosssectional study to analyze patient characteristics who underwent the XBT for evaluation of SIBO. Diagnostic testing with the XBT was performed based on a clinical suspicion for SIBO in patients with symptoms of bloating, abdominal pain, abdominal distension, weight loss, diarrhea, and/or constipation. Consecutive electronicmedical records of 932 patients who completed the XBT at the University of Florida between 2005 and 2009 were reviewed. A two-way Analysis of Variance(ANOVA) was used to test for several associations including age, gender, and body mass index(BMI) with a +XBT. A two-way ANOVA was also performed to control for the differences and interaction with age and between genders. A similar analysis was repeated for BMI. Associations between medical conditions and prior surgical histories were conducted using the Mantel-Haenszel method for 2 by 2 contingency tables, stratified for gender. Reported odds ratio estimates reflect the odds of the prevalence of a condition within the +XBT group to that of the-XBT group. P values of less than 0.05(two-sided) were considered statistically significant.RESULTS: In the 932 consecutive eligible subjects studied, 513 had a positive XBT. A positive association was found between female gender and a positive XBT(P = 0.0025), and females with a positive test were, on average, greater than 5 years older than those with a negative test(P = 0.024). The mean BMI of positive XBT subjects was normal(24.5) and significantly lower than the subjects with a negative XBT(29.5)(P = 0.0050). A positive XBT was associated with gastroesophageal reflux disease(GERD)(OR = 1.35; 95%CI: 1.02-1.80, P = 0.04), peptic ulcer disease(PUD)(OR = 2.61; 95%CI: 1.48-4.59, P < 0.01), gastroparesis(GP)(OR = 2.04; 95%CI: 1.21-3.41, P < 0.01) and steroid use(OR = 1.35; 95%CI: 1.02-1.80, P = 0.01). Irritable bowel syndrome, independent protonpump inhibitor(PPI) usage, or previous abdominal surgery was not significantly associated with a positive XBT. No single subdivision by gender or PPI use was associated with a significant difference in the odds ratios between any of the subsets. CONCLUSION: Female gender, lower BMI, steroid use, PUD, GERD(independent of PPI use), and GP were more prevalent in patients with SIBO, determined by a positive XBT. Increasing age was associated with SIBO in females, but not in males.

The promises and challenges of patient-derived tumor organoids in drug development and precision oncology

In the era of precision medicine,cancer researchers and oncologists are eagerly searching for more realistic,cost effective,and timely tumor models to aid drug development and precision oncology.Tumor models that can faithfully recapitulate the histological and molecular characteristics of various human tumors will be extremely valuable in increasing the successful rate of oncology drug development and discovering the most efficacious treatment regimen for cancer patients.Two‐dimensional(2D)cultured cancer cell lines,genetically engineered mouse tumor(GEMT)models,and patient‐derived tumor xenograft(PDTX)models have been widely used to investigate the biology of various types of cancers and test the efficacy of oncology drug candidates.However,due to either the failure to faithfully recapitulate the complexity of patient tumors in the case of 2D cultured cancer cells,or high cost and untimely for drug screening and testing in the case of GEMT and PDTX,new tumor models are urgently needed.The recently developed patient‐derived tumor organoids(PDTO)offer great potentials in uncovering novel biology of cancer development,accelerating the discovery of oncology drugs,and individualizing the treatment of cancers.In this review,we will summarize the recent progress in utilizing PDTO for oncology drug discovery.In addition,we will discuss the potentials and limitations of the current PDTO tumor models.

Distribution and drug resistance of pathogenic bacteria isolated from cancer hospital in 2013

Objective： To understand distribution and drug resistance of pathogenic bacteria from a specialized cancer hospital in 2013 in order to provide a basis for rational clinical antimicrobial agents. Methods： Pathogenic bacteria identification and drug sensitivity tests were performed with a VITEK 2 compact automatic identification system and data were analyzed using WHONET5.6 software.Results： Of the 1,378 strains tested, 980 were Gram-negative bacilli, accounting for 71.1%, in which Klebsiella pneumonia, Escherichia coli and Pseudomonas aeruginosa were the dominant strains. We found 328 Gram-positive coccus, accounting for 23.8%, in which the amount of Staphylococcus aureus was the highest. We identified 46 fungi, accounting for 4.1%. According to the departmental distribution within the hospital, the surgical departments isolated the major strains, accounting for 49.7%. According to disease types, lung cancer, intestinal cancer and esophagus cancer were the top three, accounting for 20.9%, 17.3% and 14.2%, respectively. No strains were resistant to imipenem, ertapenem or vancomycin.Conclusions： Pathogenic bacteria isolated from the specialized cancer hospital have different resistance rates compared to commonly used antimicrobial agents; therefore antimicrobial agents to reduce the morbidity and mortality of infections should be used.

Monitoring the hydrolyzation of aspirin during the dissolution testing for aspirin delayed-release tablets with a fiber-optic dissolution system

The purpose of this study was to investigate the hydrolyzation of aspirin during the process of dissolution testing for aspirin delayed-release tablets. Hydrolysis product of salicylic acid can result in adverse effects and affect the determination of dissolution rate assaying. In this study, the technique of differential spectra was employed, which made it possible to monitor the dissolution testing in situ. The results showed that the hydrolyzation of aspirin made the percentage of salicylic acid exceed the limit of free salicylic acid （4.0）, and the hydrolyzation may affect the quality detection of aspirin delayed-release tablets.

Causative Microorganisms Isolated from Patients with Intra-Abdominal Infections and Their Drug Resistance Profiles:An 11-Year(2011–2021)Single-Center Retrospective Study

Objective To investigate the distribution and antimicrobial susceptibility of causative microorganisms recovered from patients with intra-abdominal infections(IAIs).Methods A total of 2,926 bacterial and fungal strains were identified in samples collected from 1,679 patients with IAIs at the Peking Union Medical College Hospital between 2011 and 2021.Pathogenic bacteria and fungi were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.Antimicrobial susceptibility testing(AST)was performed using the VITEK 2 compact system and the Kirby–Bauer method.AST results were interpreted based on the M100-Ed31 clinical breakpoints of the Clinical and Laboratory Standards Institute.Results Of the 2,926 strains identified,49.2%,40.8%,and 9.5%were gram-negative bacteria,gram-positive bacteria,and fungi,respectively.Escherichia coli was the most prevalent pathogen in intensive care unit(ICU)and non-ICU patients;however,a significant decrease was observed in the isolation of E.coli between 2011 and 2021.Specifically,significant decreases were observed between 2011 and 2021 in the levels of extended-spectrumβ-lactamase(ESBL)-producing E.coli(from 76.9%to 14.3%)and Klebsiella pneumoniae(from 45.8%to 4.8%).Polymicrobial infections,particularly those involving co-infection with gram-positive and gram-negative bacteria,were commonly observed in IAI patients.Moreover,Candida albicans was more commonly isolated from hospital-associated IAI samples,while Staphylococcus epidermidis had a higher ratio in community-associated IAIs.Additionally,AST results revealed that most antimicrobial agents performed better in non-ESBL-producers than in ESBL-producers,while the overall resistance rates(56.9%–76.8%)of Acinetobacter baumanmii were higher against all antimicrobial agents than those of other common gram-negative bacteria.Indeed,Enterococcus faecium,Enterococcus faecalis,S.epidermidis,and S.aureus were consistently found to be susceptible to vancomycin,teicoplanin,and linezolid.Similarly,C.albicans exhibited high susceptibility to all the tested antifungal drugs.Conclusion The distribution and antimicrobial susceptibility of the causative microorganisms from patients with IAls were altered between 2011 and 2021.This finding is valuable for the implementation of evidence-based antimicrobial therapy and provides guidance for the control of hospital infections.

Patch testing and cross sensitivity study of adverse cutaneous drug reactions due to anticonvulsants: A preliminary report

AIM To evaluate the utility of patch test and cross-sensitivity patterns in patients with adverse cutaneous drug reactions(ACDR) from common anticonvulsants. METHODS Twenty-four(M:F = 13:11) patients aged 18-75 years with ACDR from anticonvulsants were patch tested 3-27 mo after complete recovery using carbamazepine, phenytoin, phenobarbitone, lamotrigine, and sodium valproate in 10%, 20% and 30% conc. in pet. after informed consent. Positive reactions persisting on D3 and D4 were considered significant. RESULTS Clinical patterns were exanthematous drug rash with or without systemic involvement(DRESS) in 18(75%), Stevens-Johnsons syndrome/toxic epidermal necrolysis(SJS/TEN) overlap and TEN in 2(8.3%) patients each, SJS and lichenoid drug eruption in 1(4.2%) patient each, respectively. The implicated drugs were phenytoin in 14(58.3%), carbamazepine in 9(37.5%), phenobarbitone in 2(8.3%), and lamotrigine in 1(4.7%) patients,respectively. Twelve(50%) patients elicited positive reactions to implicated drugs; carbamazepine in 6(50%), phenytoin alone in 4(33.3%), phenobarbitone alone in 1(8.3%), and both phenytoin and phenobarbitone in 1(8.33%) patients, respectively. Cross-reactions occurred in 11(92%) patients. Six patients with carbamazepine positive patch test reaction showed cross sensitivity with phenobarbitone, sodium valproate and/or lamotrigine. Three(75%) patients among positive phenytoin patch test reactions had cross reactions with phenobarbitone, lamotrigine, and/or valproate. CONCLUSION Carbamazepine remains the commonest anticonvulsant causing ACDRs and cross-reactions with other anticonvulsants are possible. Drug patch testing appears useful in DRESS for drug imputability and cross-reactions established clinically.

Ability of lactulose breath test results to accurately identify colorectal polyps through the measurement of small intestine bacterial overgrowth

BACKGROUND While colorectal polyps are not cancerous,some types of polyps,known as adenomas,can develop into colorectal cancer over time.Polyps can often be found and removed by colonoscopy;however,this is an invasive and expensive test.Thus,there is a need for new methods of screening patients at high risk of developing polyps.AIM To identify a potential association between colorectal polyps and small intestine bacteria overgrowth(SIBO)or other relevant factors in a patient cohort with lactulose breath test(LBT)results.METHODS A total of 382 patients who had received an LBT were classified into polyp and non-polyp groups that were confirmed by colonoscopy and pathology.SIBO was diagnosed by measuring LBTderived hydrogen(H)and methane(M)levels according to 2017 North American Consensus recommendations.Logistic regression was used to assess the ability of LBT to predict colorectal polyps.Intestinal barrier function damage(IBFD)was determined by blood assays.RESULTS H and M levels revealed that the prevalence of SIBO was significantly higher in the polyp group than in the non-polyp group(41%vs 23%,P<0.01;71%vs 59%,P<0.05,respectively).Within 90 min of lactulose ingestion,the peak H values in the adenomatous and inflammatory/hyperplastic polyp patients were significantly higher than those in the non-polyp group(P<0.01,and P=0.03,respectively).In 227 patients with SIBO defined by combining H and M values,the rate of IBFD determined by blood lipopolysaccharide levels was significantly higher among patients with polyps than those without(15%vs 5%,P<0.05).In regression analysis with age and gender adjustment,colorectal polyps were most accurately predicted with models using M peak values or combined H and M values limited by North American Consensus recommendations for SIBO.These models had a sensitivity of≥0.67,a specificity of≥0.64,and an accuracy of≥0.66.CONCLUSION The current study made key associations among colorectal polyps,SIBO,and IBFD and demonstrated that LBT has moderate potential as an alternative noninvasive screening tool for colorectal polyps.

<i>In Vitro</i>Antibacterial Activity of Flavonoid Extracts of Two Selected Libyan Algae against Multi-Drug Resistant Bacteria Isolated from Food Products

This study aimed to evaluate the antibacterial activity of flavonoids extracted from two Libyan brown algae namely Cystoseira compressa and Padina pavonica using microwave-assisted extraction method against pathogenic bacteria isolated from meat, meat products, milk and dairy products (Staphylococcus aureus subsp. aureus (5 isolates), Bacillus cereus (3 isolates), Bacillus pumilus (1 isolate), Salmonella enterica subsp. enteric (4 isolates) and Enterohaemor-rhagic Escherichia coli O157 (EHEC O157) (4 isolates)). All of these isolates were muti-drug resistant with high MAR index. The results showed that C. compressa extract exhibited better and stronger antibacterial activities against the seventeen tested isolates with inhibition zones diameter ranged from 14 - 22 mm compared to P. pavonica extract which showed positive effect against 9 isolates with low inhibition zone ranged from 11 - 16.5 mm. Flavonoids extracted from C. compressa also displayed the best spectrum of bactericidal effect with a ratio MBC/MIC ≤ 4 obtained on all susceptible tested bacterial strains. Flavonoids and proanthocyanidins significantly contributed to the antibacterial properties. The mode of action of these active extracts is under investigation.

Current concepts and future strategies in the antimicrobial therapy of emerging Gram-positive spontaneous bacterial peritonitis

Spontaneous bacterial peritonitis(SBP) is the most common infection in end-stage liver disease patients.SBP is defined as an ascitic fluid infection with a polymorphonuclear leucocyte count ≥ 250/mm^3 without an evident intra-abdominal surgically treatable source.Several mechanisms contribute to SBP occurrence,including translocation of gut bacteria and their products,reduced intestinal motility provoking bacterial overgrowth,alteration of the gut's barrier function and local immune responses.Historically,Gram-negative enteric bacteria have been the main causative agents of SBP,thereby guiding the empirical therapeutic choice.However,over the last decade,a worryingly increasing prevalence of Gram-positive and multi-drug resistant(MDR) SBP has been seen.Recently,the microbiological spectrum of SBP seems to have changed in Europe due to a high prevalence of Gram-positive bacteria(48%-62%).The overall proportion of MDR bacteria is up to 22%-73% of cases.Consequently,empirical therapy based on thirdgeneration cephalosporins or amoxicillin/clavulanic acid,can no longer be considered the standard of care,as these drugs are associated with poor outcomes.Theaim of this review is to describe,with an epidemiological focus,the evidence behind this rise in Gram-positive and MDR SBP from 2000 to present,and illustrate potential targeted therapeutic strategies.An appropriate treatment protocol should include daptomycin plus ceftaroline and meropenem,with prompt stepdown to a narrower spectrum when cultures and sensitivity data are available in order to reduce both cost and potential antibiotic resistance development.