Prevalence Of Resistant Strains Research Articles

Comparative Analysis of Genetic Landscape of Carbapenem-Resistant Acinetobacter baumannii in India: A Computational Whole-Genome Study

Acinetobacter baumannii is a Gram-negative, aerobic bacterium responsible for multidrug-resistant nosocomial infections, especially in Intensive Care Units. This study investigated the genetic diversity, antimicrobial genes, virulence factors, and mobile genetic elements, resistance genes in clinically relevant strains of A. baumannii circulating in the Indian population, consistent with reports from other Asian countries, including China, Southeast Asia, and Thailand. A comprehensive analysis of carbapenem-resistant A. baumannii strains was conducted using publicly available genomic data. Pan-genome fanalysis revealed an open genome structure, indicating the pathogen's potential for ongoing genetic evolution. The study identified significant resistance genes, including blaOXA-23, AdeIJK and AdeFGH type efflux pumps, and carbapenemases. Virulence factors such as OmpA, phospholipase, and Csu pili were prevalent, contributing to the bacterium's pathogenicity. Mobile genetic elements, including Tn2006 and ISAba1/blaOXA-23 gene combinations, were also identified, highlighting the mechanisms behind the rapid spread of resistance genes. Subtractive proteomics was employed to identify core proteins essential to the bacterium but non-homologous to humans, highlighting them as potential drug targets. This analysis identified 2,165 core proteins, with 550 non-homologous essential proteins located in the cytoplasm. Further evaluation of these proteins based on stability and involvement in essential pathways, we identified 15 druggable proteins as potential targets for antimicrobial agents. The findings underscore the critical need for continuous surveillance, innovative drug development, and targeted therapeutic strategies to mitigate the impact of multidrug-resistant A. baumannii in healthcare settings. Addressing antimicrobial resistance in A. baumannii remains a global health priority, especially in high-burden regions like India, where the prevalence of resistant strains is notably high. This study provides a foundation for future research and development in combating this formidable pathogen.

Antifungal Plant Defensins as an Alternative Tool to Combat Candidiasis.

Currently, the spread of fungal infections is becoming an urgent problem. Fungi of the Candida genus are opportunistic microorganisms that cause superficial and life-threatening systemic candidiasis in immunocompromised patients. The list of antifungal drugs for the treatment of candidiasis is very limited, while the prevalence of resistant strains is growing rapidly. Therefore, the search for new antimycotics, including those exhibiting immunomodulatory properties, is of great importance. Plenty of natural compounds with antifungal activities may be extremely useful in solving this problem. This review evaluates the features of natural antimicrobial peptides, namely plant defensins as possible prototypes of new anticandidal agents. Plant defensins are important components of the innate immune system, which provides the first line of defense against pathogens. The introduction presents a brief summary regarding pathogenic Candida species, the pathogenesis of candidiasis, and the mechanisms of antimycotic resistance. Then, the structural features of plant defensins, their anticandidal activities, their mechanisms of action on yeast-like fungi, their ability to prevent adhesion and biofilm formation, and their combined action with conventional antimycotics are described. The possible mechanisms of fungal resistance to plant defensins, their cytotoxic activity, and their effectiveness in in vivo experiments are also discussed. In addition, for the first time for plant defensins, knowledge about their immunomodulatory effects is also presented.

Quinolone Resistance in Gallibacterium anatis Determined by Mutations in Quinolone Resistance-Determining Region.

Control of the important pathogen, Gallibacterium anatis, which causes salpingitis and peritonitis in poultry, relies on treatment using antimicrobial compounds. Among these, quinolones and fluoroquinolones have been used extensively, leading to a rise in the prevalence of resistant strains. The molecular mechanisms leading to quinolone resistance, however, have not previously been described for G. anatis, which is the aim of this study. The present study combines phenotypic antimicrobial resistance data with genomic sequence data from a collection of G. anatis strains isolated from avian hosts between 1979 and 2020. Minimum inhibitory concentrations were determined for nalidixic acid, as well as for enrofloxacin for each included strain. In silico analyses included genome-wide queries for genes known to convey resistance towards quinolones, identification of variable positions in the primary structure of quinolone protein targets and structural prediction models. No resistance genes known to confer resistance to quinolones were identified. Yet, a total of nine positions in the quinolone target protein subunits (GyrA, GyrB, ParC and ParE) displayed substantial variation and were further analyzed. By combining variation patterns with observed resistance patterns, positions 83 and 87 in GyrA, as well as position 88 in ParC, appeared to be linked to increased resistance towards both quinolones included. As no notable differences in tertiary structure were observed between subunits of resistant and sensitive strains, the mechanism behind the observed resistance is likely due to subtle shifts in amino acid side chain properties.

Anti-virulence therapeutic strategies against bacterial infections: recent advances.

The emergence and increasing prevalence of multidrug-resistant pathogens has become a major global healthcare problem. According to the World Health Organization if these trends continue, mortality from infection in 2050 will be higher than that from cancer. Microorganisms have various resistance mechanisms against different classes of antibiotics that emphasize the need for discovery of new antimicrobial compounds to treat bacterial infections. An interesting and new strategy for disarming pathogens is antivirulence therapy by blocking bacterial virulence factors or pathogenicity. Therefore, the use of these new pathoblockers could reduce the administration of broad-spectrum antimicrobials and prevalence of resistant strains. This review provides an overview of the antivirulence strategies published studies between years 2017 and 2021. Most antivirulence strategies focused on adhesins, toxins and bacterial communication. Additionally, targeting two-component systems and ncRNA elements were also examined in some studies. These new strategies have the potential to replace traditional antimicrobial agents and can be used to treat infections, especially infections caused by resistant pathogens, by targeting virulence factors.

Evaluation of the Outcome of Antiviral Therapy among Individuals Infected HIV-1 in Suqian District of Jiangsu Province, China.

Background:To evaluate the condition of antiviral therapy (ART) for individuals infected HIV-1 in Suqian district of Jiangsu Province, China.Methods:Altogether, 561 HIV-positive patients who received antiviral therapy in Suqian district in 2019 were recruited. EDTA anticoagulated blood was collected and separated to obtain the plasma samples. Viral load (VL) were tested for evaluating the outcome of ART. Then samples with VL beyond 1000IU/mL were used to conduct the molecular test in order to master the characters of HIV-1 and the prevalence of resistance strains.Results:VL results showed that the virus in 91.1% of the patients who received continuous antiviral treatment for more than 6 months were effectively inhibited (VL ≤ 1000 IU / ml). Among the 50 patients who failed in the treatment, 46 HIV-1 pol gene sequences were obtained, and the positive rate was 92.0%. The most prevalent strain was CRF_ 07bc (32.6%), and new epidemic strains, such as 67_01B, 79_0107, 87_cpx, were popular in this district. Drug resistance test results showed that 56.5% of the patients failed in antiviral treatment due to drug resistance, mainly resistant to the national first-line antiviral drug 3TC. Drug-resistant strains were not found in 43.5% of the patients.Conclusion:ART achieved a satisfied result in Suqian district, but the main cause resulting in ART-failure was resistant, so it is very necessary to enhance the education of adherence prior to the initiation of ART.

Gut microbiota and urinary tract infections in children

Aim. To evaluate the role of intestinal dysbiosis in the development of urinary tract infections in children admitted to a multidisciplinary hospital.Materials and Methods. We performed a bacteriological analysis of 2,694 urine samples collected from ≤ 3-years-old children who have been admitted to a multidisciplinary hospital (Kemerovo, Russian Federation). Urine specimens were inoculated by the 4-sector technique. Concurrently, we quantified the intestinal microbiota and its antimicrobial resistance in 100 children with urinary tract infections.Results. Titers of pathogenic microbes significantly differed in patients from distinct units (p = 0.02). The highest number of positive samples was detected in the neonatal pathology and neonatal intensive care units (43.8% each) as well as urology unit (37.9%). The most frequent pathogens belonged to Enterobacteriaceae family, in particular Escherichia coli, Klebsiella spp., Enterobacter spp., and Proteus spp. All studied children (100/100) suffered from intestinal dysbiosis. Titers of Bifidobacterium spp. and Lactobacillus spp. were reduced to 6 (5.0; 8.0) and 5 (4.0; 6.0) lg CFU/g, respectively. In 89.2% children, Escherichia coli lac+ levels were elevated to 9-10 lg CFU/g. Of note, 18.9% children had high Escherichia coli lac- titers [8 (6.0; 9.0) lg] and 24.3% had high Escherichia coli hly+ titers [5 (4.5; 6.0) lg] in the intestine. We have also found a high frequency (44.6%) and density [8.1 (7.0; 8.5) lg] of Klebsiella spp., in the intestinal mucosa of such patients. Notably, Enterobacter spp. and Proteus spp. were abundant [7 (5.0; 8.0) CFU/g] in the intestinal microbiota of 10.8% children. The prevalence of resistance strains in the studied setting reached 63%.Conclusions. More than 75% children with urinary tract infections suffer from intestinal dysbiosis. The microbiome of these patients was predominantly composed of Enterobacteriaceae and was characterized by high titers of Escherichia coli lac+, Klebsiella spp., Enterobacte spp., and Proteus spp. Similar profile of antimicrobial resistance in urinary and intestinal isolates of enterobacteria suggests intestinal microbiome as the main source of pathogens causing urinary tract infections in children.

Coagulase-positive staphylococci in dogs and their antimicrobial resistance (systematic review)

Staphylococcus spp. a common genus of bacteria that colonizes the body of dogs. Some families of this genus are pathogenic and are involved in the development of diseases of various systems and organs, especially the skin and outer ear. One of the main signs of the most pathogenic families of this genus is the secretion of the enzyme coagulase. They are grouped into the group of coagulase-positive Staphylococcus (CoPS). S. pseudintermedius most often is isolated from a dog, about 10-60% isolates. S. aureus is identified less frequently, in 4-15% of cases, but it is associated with people who are its natural carriers. S. schleiferi subsp. coagulans is another family that can be identified in the pathological material obtained from dogs. However, coagulase is one of much different pathogenicity factors in this family. Also, microorganisms of this family can exist both in the form of a planktonic culture and in the structure of a biofilm, on which the effect of antibacterial agents is weakened. Some strain of CoPS carry genes of resistance to various antibacterial agents and may occupy a dominant position in the pathogenic process. Such strains can colonize the environment in places where animals congregate, which leads, for example, to the occurrence of clinical infections. Also resistant are strains of this family that can colonize other animals or humans. Owners and specialists working with animals are constantly at risk. To date, the issue of the emergence of resistance to beta-lactam antibiotics (methicelin-resistant strains) and the acquisition of resistance to several groups of antibacterial agents is acute. In the countries of the European Union, a fairly large number of studies are conducted aimed at studying the spread of Staphylococcus spp. analysis of virulence and pathogenicity factors, as well as mechanisms of acquiring antibacterial resistance. Programs to control the prevalence of resistant strains are also being developed there. Different authors show resistance to a large number of antibacterial agents, the profile of antibacterial resistance may differ both within different groups and between different drugs of the same pharmaceutical group. In Ukraine, there are no systematic studies of the spread of resistant strains of microorganisms among small animals. Key words: Staphylococcus spp., S. pseudintermedius, S. aureus, S. schleiferi subsp. Coagulans, CoPS, MRSP, MRSA, antibacterial resistance, dogs.

Mupirocin-resistant methicillin-resistant Staphylococcus aureus - Are these strains wrongly reported and treated?

Background: Mupirocin is an antibacterial drug and it is used for topical application either alone or along with other antiseptics, in areas where ever infections or colonization of methicillin-resistant Staphylococcus aureus (MRSA) are found. Enhanced use of mupirocin ointment these days for local application has led to the rise in data of its resistance. Many carriers and patients are treated inappropriately due to lack of sensitivity testing and improper reporting for mupirocin and development of different levels of resistance in these strains. Due to the lack of next level treatment possibilities, we need to report sensitivity accurately, record prevalence of resistant strains, and figure out the cause of resistance. Objective: We carried out this study to demonstrate levels of mupirocin resistance in MRSA strains isolated from patients samples and to check the resistance pattern of these strains to other antibacterial, in our hospital located in Delhi, North India. Materials and Methods: The study is framed as prospective type and performed on the strains of MRSA collected from the different samples from outpatient departments and inpatient departments from January 2017 to December 2017. Out of 221 Staphylococcus aureus collected from different clinical specimens, 113 isolates were confirmed as MRSA strains. Two of the suggested methods were selected to detect mupirocin resistance: Disk diffusion method by 5 μg disc and microbroth dilution method. Results: From our 113 MRSA isolates, resistance for mupirocin was noted in 16 (14.15%) isolates when subjected to disk diffusion and microbroth dilution test. These 16 strains showed varied level of resistance. High-level resistance was shown by 4 (3.5%) isolates and 12 (10.6%) isolates were found as low-level resistant (MuL). Mupirocin resistant MRSA isolates showed higher antibiotic resistance to erythromycin (81.26% vs. 78.76%), clindamycin (56.25% vs. 42.47%), linezolid (12.50% vs. 7.90%), and tigecycline (6.25% vs. 6.19%) as compared to MRSA strains. Not even single MRSA isolates were identified as vancomycin-resistant strain. Conclusion: Both high- and low-level mupirocin-resistant MRSA was found in high numbers from these patients. It is recommended that routine test must be performed to detect resistance for mupirocin subsequent to the detection of MRSA colonization among visitors, patients, and health care workers and its isolation from local sites. Treatment and decolonization of mupirocin-resistant strains are mandatory to reduce infection and spread in hospital after having done proper sensitivity testing only.

Enhanced killing of multiresistant strains of Staphylococcus aureus and Acinetobacter baumannii through a combined action of antibiotics and bacteriocins

A search for multidrug-resistant bacteria was conducted in 1,143 clinical samples in Morocco from which 244 isolates were tested against 29 different antibiotics. This showed a prevalence of resistant strains of 68.4%. The spectra of resistance ranged from 1 to 21. Ampicillin, Ticarcilin, Amoxicillin, Piperacillin and Ciproflaxin were the most frequently resisted. Eight antibiotics were tested against two selected strains, S. aureus 400037 from conjunctive mucosa and A. baumannii 280291 urine, which showed resistance to concentrations up to 240 µg.ml-1. A. baumannii 280291 also resisted the two bacteriocins nisin A and pediocin PA-1, while S. aureus 400037 showed relative sensitivity to nisin A with a MIC of 125 µg.ml-1 but was insensitive to pediocin PA-1. However, the combined use of antibiotics and bacteriocins showedpotentiating effects of bacteriocins on antibiotics or synergistic effects between the two antimicrobials. Combinations with nisin A resulted for instance in a sensitisation of S. aureus 400037 to penicillin G, amoxicillin, ampicillin, cefaclor and ciprofloxacin with MIC values as low as 0.19; 0.78; 0.31; 3.75 and 0.62 µg.ml-1 respectively. Against A. baumannii 280291, the MIC value of gentamycin decreased from 60 to 3.75 µg.ml-1, in the presence of nisin. Similar results were obtained when antibiotics were combined with pediocin PA-1 and such effects were even stronger when both bacteriocins were used along with antibiotics. The present study shows that pathogenic bacteria that developed high levels of resistance to a wide array of antibiotics can be rendered sensitive to the same antibiotics simply by combining them with bacteriocins.

Emergence of Resistance to Quinolones and β-Lactam Antibiotics in Enteroaggregative and Enterotoxigenic Escherichia coli Causing Traveler's Diarrhea.

The objective of this study was to assess the antimicrobial resistance of enteroaggregative Escherichia coli (EAEC) and enterotoxigenic E. coli (ETEC) strains causing traveler's diarrhea (TD) and to investigate the molecular characterization of antimicrobial resistance genes to third-generation cephalosporins, cephamycins, and quinolones. Overall, 39 EAEC and 43 ETEC clinical isolates were studied. The susceptibilities of EAEC and ETEC against ampicillin, amoxicillin-clavulanic acid, cefotaxime, imipenem, chloramphenicol, tetracycline, co-trimoxazole, nalidixic acid, ciprofloxacin, azithromycin, and rifaximin were determined. All genes encoding resistance determinants were detected by PCR or PCR plus DNA sequencing. The epidemiology of selected EAEC and ETEC strains was studied using multilocus sequence typing (MLST). The resistance to quinolones of EAEC and ETEC strains causing TD has significantly increased over the last decades, and high percentages have been found especially in patients traveling to India and sub-Saharan Africa. Sequence type 38 (ST38) and ST131, carrying the blaCTX-M-15 and blaCTX-M-27 genes, respectively, are highly prevalent among extended-spectrum β-lactamase (ESBL)-producing EAEC and ETEC strains. The cephamycinase ACT-20 is described in the present study for the first time in EAEC and ETEC strains causing TD in patients who had traveled to Central America. The percentages of resistance to azithromycin in EAEC and ETEC isolates from patients to Southeast Asia/India and Africa are above 25%. Meanwhile, rifaximin is still active against EAEC and ETEC, with the prevalence of resistant strains not being high. In conclusion, fluoroquinolones should no longer be considered the drugs of choice for the prevention or treatment in TD for travelers traveling to India and Africa. Azithromycin and rifaximin are still a good alternative to treat TD caused by EAEC or ETEC.

Synthesis and evaluation of polymeric micelle containing piperacillin/tazobactam for enhanced antibacterial activity

Infections caused by multidrug-resistant bacteria such as P. aeruginosa are important therapeutic complications. Piperacillin/Tazobactam is considered a safe antimicrobial agent. But we should not ignore the prevalence of resistant strains to this drug. In this work, a new polymeric micelle composed of Piperacillin/Tazobactam-loaded Poly (ethylene glycol) methyl ether-block-poly (lactide-co-glycolide) (PLGA-PEG) was developed to improve the antimicrobial performance of P/T. The SEM and TEM studies of PLGA-PEG micelle showed, semi-spherical morphology with a mean diameter of below 30 nm. Zeta potential results indicated that the surface charge of PLGA-PEG micelle was −2.98 mV, while after encapsulation of P/T, the surface charge decreases to −4.13 mV. Clinical strains of P. aeruginosa were isolated and their resistance pattern against different antibiotics was evaluated. The MIC of free and P/T -Loaded PLGA-PEG micelles was determined. Also, the effect of free or P/T micelle against minimal biofilm eradication concentration and motility inhibition was evaluated. The bacterial isolates were resistant to most common antibiotics. The MIC of the free drug form and micelle form ranged from 4 to 512 µg/ml and 2 to 256 µg/ml, respectively. Generally, micelle showed more effective antibiofilm activities, inhibition of bacterial motility and reducing the MIC than that free drug form.

Comprehensive Assessment of Antimicrobial Drug Consumption at the St. Petersburg Hospitals in 2014–2016

Aim. To measure comprehensive indicators of consumption in order to assess their correlation with the level of resistance of S. aureus, K. pneumoniae, E. coli in multidisciplinary hospitals of St. Petersburg in 2014–2016. Materials and methods. We extracted data on the public procurement of antimicrobial drugs for systemic use (ATC code J01) in multidisciplinary hospitals of St.-Petersburg in 2014–2015 from IMS Health database. Prevalence of resistant strains was assessed based on the results of bacteriological surveys, St. Petersburg Medical Information-analytical Center (MIAC). The indicators of antimicrobial drugs consumption, drug resistance, drug resistance index were calculated. Results. The structure of public procurement of antimicrobial drugs does not correlate with the the prevalence of multi-resistant infections in St. Petersburg hospitals as a result of out-dated standards for specialized medical care. Current epidemiological situation requires purchasing of the the expensive antimicrobial drugs of limited access and performing epidemiological control measures that demand additional investments. Conclusion. The existing standards for specialized medical care should be timely updated with regard to recommendations on antibacterial treatment in accordance with the current epidemiological situation.

Impact of Rapid Susceptibility Testing and Antibiotic Selection Strategy on the Emergence and Spread of Antibiotic Resistance in Gonorrhea.

Increasing antibiotic resistance limits treatment options for gonorrhea. We examined the impact of a hypothetical point-of-care (POC) test reporting antibiotic susceptibility profiles on slowing resistance spread. A mathematical model describing gonorrhea transmission incorporated resistance emergence probabilities and fitness costs associated with resistance based on characteristics of ciprofloxacin (A), azithromycin (B), and ceftriaxone (C). We evaluated time to 1% and 5% prevalence of resistant strains among all isolates with the following: (1) empiric treatment (B and C), and treatment guided by POC tests determining susceptibility to (2) A only and (3) all 3 antibiotics. Continued empiric treatment without POC testing was projected to result in >5% of isolates being resistant to both B and C within 15 years. Use of either POC test in 10% of identified cases delayed this by 5 years. The 3 antibiotic POC test delayed the time to reach 1% prevalence of triply-resistant strains by 6 years, whereas the A-only test resulted in no delay. Results were less sensitive to assumptions about fitness costs and test characteristics with increasing test uptake. Rapid diagnostics reporting antibiotic susceptibility may extend the usefulness of existing antibiotics for gonorrhea treatment, but ongoing monitoring of resistance patterns will be critical.

Multi-drug resistant <i>Staphylococcus aureus</i> isolated from emergency ward of an Iranian hospital

Purpose : To study the prevalence of resistant strains of S. aureus isolated from surfaces, beds and various equipment of an Iranian hospital emergency ward. Methods : Two hundred swab samples were collected from the surfaces, beds, trolleys, surgical equipment and diagnostic medical devices in emergency ward. Samples were cultured and those that were S. aureus -positive were confirmed using polymerase chain reaction (PCR). Antimicrobial resistance pattern was analyzed using disk diffusion method. Results : Nine of 200 samples (4.5 %) collected were positive for S. aureus . Surfaces (8.8 %), beds (5 %) and trolleys (5 %) were the most commonly contaminated. S. aureus isolates exhibited varying levels of resistance against antibiotics with the following being the highest: tetracycline (88.8 %), penicillin (88.8 %) and ampicillin (77.7 %). The prevalence of resistance against methicillin, oxacillin and azithromycin were 44.4, 33.3 and 33.3 %, respectively. There was no pattern of resistance against imipenem. Conclusion : Efficient disinfection of surfaces, beds, trolleys and surgical instruments should be performed periodically to reduce colonization of resistant strains of S. aureus in various areas of emergency health care centers. Keywords : Staphylococcus aureus , Nocosomial infection, Antibiotic resistance, Hospital equipment, Emergency ward

Evolutionary Explanations for Antibiotic Resistance in Daily Press, Online Websites and Biology Textbooks in Sweden

The present study explores the extent and precision of evolutionary explanations for antibiotic resistance in communication directed toward the Swedish public. Bacterial resistance develops through evolutionary mechanisms and knowledge of these helps to explain causes underlying the growing prevalence of resistant strains, as well as important countermeasures to address the problem. A content analysis based on key evolutionary concepts underpinning resistance development was conducted on three different data sources: print newspapers, online websites and biology textbooks. The results revealed that evolutionary mechanisms are seldom included in accounts of antibiotic resistance provided by these sources. One of the included textbooks (n = 6) but none of the newspaper articles (n = 221) or websites (n = 19) covered all six concepts considered in the analysis. A cluster of four concepts regarded as most important for understanding the evolution of resistance development was only included in one news article, one textbook and two websites. Moreover, explanations were seldom supported visually and only two accompanying illustrations were found during the analysis. The results indicated that a large proportion of the Swedish public might never encounter an explanation of antibiotic resistance in evolutionary terms. This could be problematic since increased public awareness and understanding is crucial to counter the issue of bacterial resistance.

Binding mode characterization of novel RNA polymerase inhibitors using a combined biochemical and NMR approach.

Bacterial RNA polymerase (RNAP) represents a validated target for the development of broad-spectrum antibiotics. However, the medical value of RNAP inhibitors in clinical use is limited by the prevalence of resistant strains. To overcome this problem, we focused on the exploration of alternative target sites within the RNAP. Previously, we described the discovery of a novel RNAP inhibitor class containing an ureidothiophene-2-carboxylic acid core structure. Herein, we demonstrate that these compounds are potent against a set of methicillin-resistant Staphylococcus aureus (MRSA) strains (MIC 2-16 μg mL(-1)) and rifampicin-resistant Escherichia coli TolC strains (MIC 12.5-50 μg mL(-1)). Additionally, an abortive transcription assay revealed that these compounds inhibit the bacterial transcription process during the initiation phase. Furthermore, the binding mode of the ureidothiophene-2-carboxylic acids was characterized by mutagenesis studies and ligand-based NMR spectroscopy. Competition saturation transfer difference (STD) NMR experiments with the described RNAP inhibitor myxopyronin A (Myx) suggest that the ureidothiophene-2-carboxylic acids compete with Myx for the same binding site in the RNAP switch region. INPHARMA (interligand NOE for pharmacophore mapping) experiments and molecular docking simulations provided a binding model in which the ureidothiophene-2-carboxylic acids occupy the region of the Myx western chain binding site and slightly occlude that of the eastern chain. These results demonstrate that the ureidothiophene-2-carboxylic acids are a highly attractive new class of RNAP inhibitors that can avoid the problem of resistance.

Bifidobacterium thermophilum RBL67 Inhibits Salmonella enterica Serovar Typhimurium in an In vitro Intestinal Fermentation Model

Infectious gastroenteritis caused by non-typhoidal serovars of Salmonella is usually self-limiting but life-threatening complications may require appropriate antibiotic therapies. Probiotics have evolved as potential alternatives to antibiotics in response to an increasing prevalence of resistant strains, but there are no studies comparing the effectiveness of both treatment strategies on the same intestinal microbiota. We used an in vitro intestinal fermentation system with immobilized fecal microbiota to model enteric Salmonella infection in children. The effects of antibiotics, amoxicillin/clavulanic acid at two dosages, and a probiotic candidate, Bifidobacterium thermophilum RBL67, on Salmonella counts, intestinal microbiota composition, and metabolic activity were compared. Antibiotic therapy, in agreement with current clinical reports, produced only a transient decrease of Salmonella concentrations but strongly modified bacterial population profiles and metabolic activity, confirming the suitability of the model. B. thermophilum RBL67 grew in the intestinal environment and exerted a strong inhibition on Salmonella when added before or after infection and was able to rebalance the metabolic activity of gut microbiota after antibiotic treatments. Our study revealed a high potential of B. thermophilum RBL67 for prevention and treatment of Salmonella infection. The exact mechanism has to be further elucidated.

Macrolide-resistant Mycoplasma pneumoniae in adolescents with community-acquired pneumonia.

BackgroundAlthough the prevalence of macrolide-resistant Mycoplasma pneumoniae isolates in Japanese pediatric patients has increased rapidly, there have been no reports concerning macrolide-resistant M. pneumoniae infection in adolescents aged 16 to 19 years old. The purpose of this study was to clarify the prevalence and clinical characteristics of macrolide-resistant M. pneumoniae in adolescent patients with community-acquired pneumonia.MethodsA total of 99 cases with M. pneumoniae pneumonia confirmed by polymerase chain reaction (PCR) and culture were analyzed. Forty-five cases were pediatric patients less than 16 years old, 26 cases were 16 to 19-year-old adolescent patients and 28 cases were adult patients. Primers for domain V of 23S rRNA were used and DNA sequences of the PCR products were compared with the sequence of an M. pneumoniae reference strain.ResultsThirty of 45 pediatric patients (66%), 12 of 26 adolescent patients (46%) and seven of 28 adult patients (25%) with M. pneumoniae pneumonia were found to be infected with macrolide-resistant M. pneumoniae (MR patients). Although the prevalence of resistant strains was similar in pediatric patients between 2008 and 2011, an increase in the prevalence of resistant strains was observed in adolescent patients. Among 30 pediatric MR patients, 26 had an A-to-G transition at position 2063 (A2063G) and four had an A-to-G transition at position 2064 (A2064G). In 12 adolescent MR patients, 10 showed an A2063G transition and two showed an A2064G transition, and in seven adult MR patients, six showed an A2063G transition and one showed an A2064G transition.ConclusionsThe prevalence of macrolide-resistant M. pneumoniae is high among adolescent patients as well as pediatric patients less than 16-years old. To prevent outbreaks of M. pneumoniae infection, especially macrolide-resistant M. pneumoniae, in closed populations including among families, in schools and in university students, physicians should pay close attention to macrolide-resistant M. pneumoniae.

Discovery and characterization of ß-1,6-glucan inhibitors

Importance of the field: The increasing number of patient populations at high risk of opportunistic infections has highlighted the need for the improvement in antifungal treatments. Due to the limited number of currently available antifungal drugs and the concerns for possible prevalence of resistant strains, drugs with a new mechanism of action are most desirable.Areas covered in this review: Although the cell wall is considered to be one of the ideal targets for antifungal drugs, insufficient information on the enzymes involved in its construction has restricted the discovery of new inhibitors. This review introduces the recent discovery of the inhibitors of β-1,6-glucan, one of the essential components of the yeast cell wall.What the reader will gain: The readers will gain the strategy to obtain the β-1,6-glucan synthesis inhibitors, their mechanisms of actions, and antifungal activities in vitro as well as in vivo.Take home message: The β-1,6-glucan inhibitors are considered to be promising candidates for new antifungal drugs which could give valuable options in a clinical setting, although their usage may be limited because of their fungistatic action and limited spectrum. Additionally, they can be useful tools in the study on β-1,6-glucan synthesis and the virulence of Candida species.

Antimicrobial Resistance of Listeria monocytogenes Strains Isolated from Humans in France

Susceptibility to antibiotics of 4,816 clinical L. monocytogenes strains isolated since 1926 was studied, and the temporal evolution of susceptibility to antibiotics was analyzed through several decades. The mechanisms of resistance in each resistant strain were studied. The prevalence of resistant strains was estimated at 1.27% among isolates from humans. Resistance to tetracyclines+ and fluoroquinolones was more common and has recently emerged. Although acquired resistance in clinical L. monocytogenes did not implicate clinically relevant antibiotics, the possibility of resistance gene transfers, the description of the first clinical isolate with high-level resistance to trimethoprim, and the recent increase in penicillin MICs up to 2 microg/ml reinforce the need for microbiological surveillance.