Multidrug-resistant Bacterial Pathogens Research Articles

Extended Spectrum β-Lactamase (ESBL) Producing Multidrug Resistant Gram-Negative Bacteria from Various Clinical Specimens of Patients Visiting a Tertiary Care Hospital

Objectives: The purpose of this study was to assess multidrug resistance and Extended Spectrum β-Lactamase (ESBL) production in Gram negative bacterial pathogens.Methods: The study included clinical specimens sent for routine culture and antibiotic susceptibility testing. A total of 469 different clinical specimens were processed according to the standard methodology. The isolates were identified by standard microbiological procedures and subjected to antimicrobial susceptibility testing by modified Kirby-Bauer disk diffusion method. Production of ESBL was determined by combined disk method.Results: Of the total sample processed, 80 (17.0%) Gram negative bacteria were isolated and 82.5% of them were multidrug resistant (MDR). From the total MDR isolates, 47% were ESBL positive. The higher rate of growth among Intensive Care Units (ICUs) patients was found statistically significant. Higher prevalence of MDR isolates was observed in blood and pus specimens. The majority of the ESBL producers were Escherichia coli (38.7%). Higher rate of ESBL producers was detected from blood (55.6%). Polymyxin B, imipenem and amikacin were the most effective antibiotics against Acinetobacter spp. and Pseudomonas aeruginosa whereas imipenem, amikacin, meropenem were the most effective antibiotics against Enterobacteriaceae.Conclusion: Higher prevalence of ESBL producing MDR Gram negative pathogens in hospitalized patients indicates these bacteria are important health care associated pathogens and requires proper infection control measures that check the transfer of MDR and β-lactamase producing bacterial pathogens among the hospitalized patients.

Isolation and characterization of cyclic lipopeptides with broad-spectrum antimicrobial activity from Bacillus siamensis JFL15.

In this research, the antimicrobial substance anti-JFL15 was partially purified using a simple two-step extraction process from the cell-free supernatants of Bacillus siamensis JFL15. Anti-JFL15 exhibited a strong antibacterial activity against various multidrug-resistant aquatic bacterial pathogens, including Escherichia coli, Edwardsiella tarda, Pseudomonas aeruginosa, Aeromonas hydrophila, and Vibrio. Liquid chromatography-mass spectrometry revealed that anti-JFL15 contained eight cyclic lipopeptides belonging to two families: bacillomycin F (m/z 1056.56-1084.59) and surfactin (m/z 1007.65-1049.70) analogs. PCR analysis showed the presence of genes (i.e., sfp gene, surfactin synthetase D, fengycin synthetase B, iturin synthetase A, iturin synthetase C and bacillomycin synthetase D) involved in the biosynthesis of cyclic lipopeptides. This study is the first to identify cyclic lipopeptides from B. siamensis and use them to suppress the growth of various multidrug-resistant aquatic bacterial pathogens. Results indicated that B. siamensis JFL15 is a promising biocontrol agent for the effective and environmentally friendly control of various multidrug-resistant aquatic bacterial pathogens.

Population wide assessment of antimicrobial use in dogs and cats using a novel data source – A cohort study using pet insurance data

Antimicrobial use in veterinary practice is under increasing scrutiny as a contributor to the rising risk of multidrug resistant bacterial pathogens. Surveillance of antimicrobial use in food animals is extensive globally, but population level data is lacking for companion animals. Lack of census data means cohorts are usually restricted to those attending veterinary practices, which precludes aggregating data from large cohorts of animals, independent of their need for veterinary intervention. The objective of this study was to investigate the exposure of dogs and cats to antimicrobials at a population level. A retrospective cohort study was performed using a novel data source; a pet insurance database. The rate of antimicrobial prescribing, and the rate of prescribing of critically important antimicrobials, was measured in a large population of dogs (813,172 dog-years) and cats (129,232 cat-years) from 2013 - 2017. The incidence rate of antimicrobial prescribing was 5.8 prescriptions per 10 dog years (95% CI 5.8–5.9 per 10 dog years) and 3.1 prescriptions per 10 cat years (95% CI 3.1–3.2 per 10 cat years). Critically important antimicrobials accounted for 8% of all the antimicrobials prescribed over the 4-year study. Cats were 4.8-fold more likely than dogs to be prescribed 3rd-generation cephalosporins. The level of antimicrobial exposure in dogs and cats was less than half that for the coincident human community. Data such as this provides a unique opportunity to monitor antimicrobial prescribing in veterinary medicine, which is a critical component of optimal antimicrobial stewardship.

Multidrug Resistant Bacterial Pathogens in the Indoor Air and Floors of Surgical Wards in a University Hospital

Objective: The hospital environment is a major source of
 nosocomial pathogens. These pathogens could contaminate and colonize surgical
 wounds leading to infections. This study evaluated the bacteriological quality
 of air and floors of surgical wards of a University Teaching Hospital in Abuja,
 Nigeria.
 
 Methods: Bacteriological
 quality of air and floor of surgical wards of the hospital was evaluated using
 passive air sampling and swabbing methods respectively. The isolates were
 characterized using rapid test kits and antibiotic susceptibility was
 determined by the modified Kirby-Bauer disc diffusion method. 
 
 Results: A
 total of 121 bacterial isolates comprising eleven species were isolated. In the
 air and floor of all the surgical wards, Staphylococcus
 spp. (>42%) was the most prevalent Gram-positive bacterium followed by
 Bacillus subtilis (20.4%). Among the Gram-negative bacterial isolates, Pseudomonas aeruginosa (13.0%) and Proteus mirabilis (9.0%) were the most
 prevalent in the air and floor, with occasional detection of Acinetobacter baumannii and other
 members of the Enterobacteriaceae
 family. The bacterial isolates exhibited diverse degrees of susceptibility to
 the commonly prescribed antibiotics. The isolated bacteria were mostly
 sensitive to fluoroquinolones.
 
 Conclusion: This study documented the diverse environmental
 microbiota of the surgical wards of the hospital. The high resistance of the
 isolated bacteria to the commonly prescribed antibiotics in the hospital
 highlighted the need for improved infection control and patient safety
 protocols in the hospital so as to mitigate the spread of nosocomial infections
 in the surgical wards of the hospital. J
 Microbiol Infect Dis 2018; 8(3):108-113

Inactivation of multidrug-resistant pathogens and Yersinia enterocolitica with cold atmospheric-pressure plasma on stainless-steel surfaces

The objective of this study was to investigate the impact of cold atmospheric-pressure plasma (CAP) produced by a surface micro-discharge plasma source as a new strategy to combat the transmission of five multidrug-resistant (MDR) pathogens and Yersinia enterocolitica on typical hospital- and food-producing surfaces, e.g. stainless-steel. Approximately 106 CFU/cm2 of vancomycin-resistant Enterococcus faecium, methicillin-resistant Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Y. enterocolitica were inoculated on a 3.14-cm2 stainless-steel surface. Bovine serum albumin (BSA) (3%) was used as a disruptive factor simulating natural organic material. The inoculated surfaces were subsequently exposed to CAP, generated by a peak-to-peak voltage of 10 kV with sinusoidal waveform and a frequency of 2 kHz, for 5, 10 and 20 min, respectively. Fluorescent staining with propidium iodide and SYTOTM 9 was used to demonstrate the manner of bacterial cell damage. Significant (P < 0.05) inactivation of 1.68 ± 0.17 up to 2.80 ± 0.17 log steps was achieved after 5 min of CAP treatment. However, bacterial reduction could be increased to 3.35 ± 0.1 up to 5.17 ± 0.67 log steps after 20 min of CAP treatment. Bacterial cells covered with BSA were statistically significantly less inactivated by CAP. Fluorescent staining showed a predominant level of orange-stained, sublethally damaged bacterial cells after 10 min of CAP treatment. In conclusion, CAP has the ability to inactivate MDR bacterial pathogens on stainless-steel surfaces. Further research is required to investigate the clinical features of CAP.

Potential bactericidal activity of S. nux-vomica–ZnO nanocomposite against multidrug-resistant bacterial pathogens and wound-healing properties

Multidrug resistance in bacterial strains has become the greatest challenge for healthcare professionals for treating non-healing ulcers such as diabetic foot infections (DFI). Plant-mediated synthesis of S. nux-vomica–ZnO nanocomposite appears as a potential new alternative therapeutic agent that might be capable of tackling antibiotic-resistant bacterial pathogens and for treating a non-healing ulcer. The aim of the study was to investigate the antibacterial potential of S. nux-vomica–ZnO nanocomposite biosynthesised from Strychnos nux-vomica against multidrug-resistant organisms (MDROs) from DFU, wound-healing properties, and cytotoxic effects. The antibacterial potential was assessed by minimum inhibitory concentration (MIC)/ minimum bactericidal concentration (MBC) assays, time-kill kinetics, protein-leakage, and flow cytometric analysis. The wound-healing properties were assessed by scratch assay on mouse L929 fibroblastic cell line to quantify cell migration towards the injured area. Cytotoxicity was assessed using 3-[4,5-dimethyl-2-thiazol-yl]-2,5-diphenyl- 2H-tetrazolium bromide (MTT) cellular viability assay on the L929 cell line and human embryonic kidney epithelial (HEK-293) cell line. Strychnos nux-vomica–ZnO nanocomposite at a size range of 10–12 nm exhibited significant bactericidal potency at a concentration of 100–200 μg/ml against MDR–Methicillin-resistant Staphylococcus aureus, MDR–Escherichia coli, MDR–Pseudomonas aeruginosa, MDR–Acinetobacter baumannii, and also against standard bacterial strains S. aureus ATCC 29213, E. coli ATCC 25922, P. aeruginosa ATCC 27853, E. faecalis ATCC 29212. S. nux-vomica–ZnO nanocomposite also exhibited wound-healing and reduced cytotoxic properties at the antimicrobially active concentrations. Our findings thus suggested remarkable bactericidal properties of S. nux-vomica–ZnO nanocomposite and can be further exploited towards for the development of an antibacterial agent against the threatening superbugs

Identification of a Novel Polyamine Scaffold With Potent Efflux Pump Inhibition Activity Toward Multi-Drug Resistant Bacterial Pathogens.

We have previously reported the use of combinatorial chemistry to identify broad-spectrum antibacterial agents. Herein, we extend our analysis of this technology toward the discovery of anti-resistance molecules, focusing on efflux pump inhibitors. Using high-throughput screening against multi-drug resistant Pseudomonas aeruginosa, we identified a polyamine scaffold that demonstrated strong efflux pump inhibition without possessing antibacterial effects. We determined that these molecules were most effective with an amine functionality at R1 and benzene functionalities at R2 and R3. From a library of 188 compounds, we studied the properties of 5 lead agents in detail, observing a fivefold to eightfold decrease in the 90% effective concentration of tetracycline, chloramphenicol, and aztreonam toward P. aeruginosa isolates. Additionally, we determined that our molecules were not only active toward P. aeruginosa, but toward Acinetobacter baumannii and Staphylococcus aureus as well. The specificity of our molecules to efflux pump inhibition was confirmed using ethidium bromide accumulation assays, and in studies with strains that displayed varying abilities in their efflux potential. When assessing off target effects we observed no disruption of bacterial membrane polarity, no general toxicity toward mammalian cells, and no inhibition of calcium channel activity in human kidney cells. Finally, combination treatment with our lead agents engendered a marked increase in the bactericidal capacity of tetracycline, and significantly decreased viability within P. aeruginosa biofilms. As such, we report a unique polyamine scaffold that has strong potential for the future development of novel and broadly active efflux pump inhibitors targeting multi-drug resistant bacterial infections.

New fluorescent rosamine chelator showing promising antibacterial activity against Gram-positive bacteria

The restricted number of antibiotics to treat infections caused by common multidrug resistant bacterial pathogens in the clinical setting demands a continuous search for new molecules with antibacterial properties. Bacterial iron deprivation represents a promising alternative, being iron chelators an attractive class for drug design in which particular compounds seem to have antibacterial effect.In this work, we report the synthesis and characterization of a new fluorescent 3-hydroxy-4-pyridinone (3,4-HPO) iron chelator functionalized with a carboxyrosamine fluorophore (MRB20). The antibacterial activity of MRB20 was assessed against representative strains from clinically relevant Gram-positive and Gram-negative bacterial species and further compared with the inhibitory effect of a set of structurally related iron chelators including Deferiprone (1,2-dimethyl-3-hydroxy-4-pyridinone). Compounds exhibiting a promising minimal inhibitory concentration (MIC < 10 mg/L) were further tested against a wider range of bacterial genera and species (Staphylococcus spp. Enterococcus spp. Listeria monocytogenes, Bacillus spp.), including multidrug resistant bacteria.With the exception of the novel compound (MRB20), all chelators inhibited the strains assayed at very high concentrations [minimum inhibitory concentrations (MIC) ranging from 70 mg/L to >180 mg/L]. MRB20 revealed a good antibacterial activity (6.7–13.2 mg/L) against Gram-positive strains from different genera and species, including clinically relevant species (Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecium, Enterococcus faecalis), which might be eventually compatible with a therapeutic application or as adjuvant.

English

There is little information about the diversity of bacterial pathogens present in the rumen and feces of healthy cow and the subsequent effects on the performance of the host animal. The objectives of the present study were to genetically characterize the enteric bacterial pathogens found in the rumen fluid and cow feces and to identify the resistant genes responsible for antimicrobial resistance in the detected pathogens. The cow feces and rumen fluid samples (6 rumen fluid and 42 feces) were collected from lactating dairy cows. Using next generation sequencing, the enteric bacterial pathogens detected were screened for antimicrobial resistance genes using ResFinder-2.1 database in the center of Abricate. The characterized enteric bacterial pathogens include Escherichia coli, Salmonella enterica, Streptococcus agalactiae, Streptococcus pyogenes, Campylobacter coli, and Campylobacter fetus among others. Those enteric bacterial pathogens were also drug resistant bacteria except Campylobacter coli. The Campylobacter fetus fetus was identified as the only multidrug resistant bacterial pathogen detected in the cow feces. However, the abundant resistant genes detected confer resistance to tetracycline (17 genes from 209 contigs), beta-lactam (21 genes from 67 contigs), streptomycin (6 genes from 153 contigs), and sulfamethoxazole (2 genes from 72 contigs). This is the first study to identify the diversity of enteric bacterial pathogens from the station based and smallholder dairy cows in Kenya and Tanzania, respectively. Key words: Antimicrobial resistant genes, enteric bacterial pathogens, dairy cows, next generation sequencing.

Glycyrrhiza glabra HPLC fractions: identification of Aldehydo Isoophiopogonone and Liquirtigenin having activity against multidrug resistant bacteria

BackgroundMedicinal plants have been founded as traditional herbal medicine worldwide. Most of the plant’s therapeutic properties are due to the presence of secondary metabolites such as alkaloids, glycosides, tannins and volatile oil.MethodsThe present investigation analyzed the High-Pressure Liquid Chromatography (HPLC) fractions of Glycyrrhiza glabra (Aqueous, Chloroform, Ethanol and Hexane) against multidrug resistant human bacterial pathogens (Escherichia coli, Acinetobacter baumannii, Staphylococcus aureus and Pseudomonas aeruginosa). All the fractions showed antibacterial activity, were subjected to LC MS/MS analysis for identification of bioactive compounds.ResultsAmong total HPLC fractions of G. glabra (n = 20), three HPLC fractions showed potential activity against multidrug resistant (MDR) bacterial isolates. Fraction 1 (F1) of aqueous extracts, showed activity against A. baumannii (15 ± 0.5 mm). F4 from hexane extract of G. glabra showed activity against S. aureus (10 ± 0.2 mm). However, F2 from ethanol extract exhibited activity against S. aureus (10 ± 0.3 mm). These active fractions were further processed by LC MS/MS analysis for the identification of compounds. Ellagic acid was identified in the F1 of aqueous extract while 6-aldehydo-isoophiopogonone was present in F4 of hexane extract. Similarly, Liquirtigenin was identified in F2 of ethanol.ConclusionsGlycyrrhiza glabra extracts HPLC fractions showed anti-MDR activity. Three bioactive compounds were identified in the study. 6-aldehydo-isoophiopogonone and Liquirtigenin were for the first time reported in G. glabra. Further characterization of the identified compounds will be helpful for possible therapeutic uses against infectious diseases caused by multidrug resistant bacteria.

Alkoxyphenylthiazoles with broad-spectrum activity against multidrug-resistant gram-positive bacterial pathogens

With the continued rise of antibiotic resistance and reduced susceptibility to almost all front-line antibiotics, multidrug-resistant Gram-positive bacterial infections represent an incessant threat to healthcare providers. This study presents a new series of phenylthiazole compounds where two active moieties were combined into one scaffold. The antibacterial activity of the hybrid structures extended to include several clinically-relevant multi-drug resistant pathogens including methicillin-resistant and vancomycin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, vancomycin-resistant enterococci, cephalosporin-resistant and methicillin-resistant Streptococcus pneumoniae, and Listeria monocytogenes. In addition, the most potent compounds, 16a and 17a, exhibited a fast bactericidal mode of action in vitro with low susceptibility to induce bacterial resistance. In addition to its potent spectrum of activity against Gram-positive bacterial pathogens, compound 17a was found to be metabolically stable in rats, with a half-life of 4 h.

New analogs of temporin-LK1 as inhibitors of multidrug-resistant (MDR) bacterial pathogens

ABSTRACTThe peptide temporin-LK1 (1) was obtained from the skin secretion of frog Limnonectes kuhlii (Ranidae). It is a unique antimicrobial peptide with 17 residues, including four L-phenylalanines and single glycine. Mass spectrometry and Edmand degradation were used for the determination of sequence of amino acids in temporin-LK 1 (1), and confirmed by cDNA cloning. We report here the synthesis and structural studies of temporin-LK1 (1) and its analogs 2–4. Peptides 2–4 were prepared by substitution of achiral glycine residue of temporin-LK1 (1) with D-alanine, L-phenylglycine, and L-naphthylalanine, respectively. Peptides 1–4 were evaluated against multidrug-resistant (MDR) strains of Staphylococcus aureus and Pseudomonas aeruginosa. Analog 2 was found active against all MDR strains of S. aureus and P. aeruginosa at a much lower dose than the clinically used antibiotics.

Phenylthiazoles with tert-Butyl side chain: Metabolically stable with anti-biofilm activity

A new series of phenylthiazoles with t-butyl lipophilic component was synthesized and their antibacterial activity against a panel of multidrug-resistant bacterial pathogens was evaluated. Five compounds demonstrated promising antibacterial activity against methicillin-resistant staphylococcal strains and several vancomycin-resistant staphylococcal and enterococcal species. Additionally, three derivatives 19, 23 and 26 exhibited rapid bactericidal activity, and remarkable ability to disrupt mature biofilm produced by MRSA USA300. More importantly, a resistant mutant to 19 couldn't be isolated after subjecting MRSA to sub-lethal doses for 14 days. Lastly, this new series of phenylthiazoles possesses an advantageous attribute over the first-generation compounds in their stability to hepatic metabolism, with a biological half-life of more than 9 h.

Alkynyl-containing phenylthiazoles: Systemically active antibacterial agents effective against methicillin-resistant Staphylococcus aureus (MRSA)

The promising activity of phenylthiazoles against multidrug-resistant bacterial pathogens, in particular MRSA, has been hampered by their limited systemic applicability, due to their rapid metabolism by hepatic microsomal enzymes, resulting in short half-lives. Here, we investigated a series of phenylthiazoles with alkynyl side-chains that were synthesized with the objective of improving stability to hepatic metabolism, extending the utility of phenylthiazoles from topical applications to treatment of a more invasive, systemic MRSA infections. The most promising compounds inhibited the growth of clinically-relevant isolates of MRSA in vitro at concentrations as low as 0.5 μg/mL, and exerted their antibacterial effect by interfering with bacterial cell wall synthesis via inhibition of undecaprenyl diphosphate synthase and undecaprenyl diphosphate phosphatase. We also identified two phenylthiazoles that successfully eradicated MRSA inside infected macrophages. In vivo PK analysis of compound 9 revealed promising stability to hepatic metabolism with a biological half-life of ∼4.5 h. In mice, compound 9 demonstrated comparable potency to vancomycin, and at a lower dose (20 mg/kg versus 50 mg/kg), in reducing the burden of MRSA in a systemic, deep-tissue infection, using the neutropenic mouse thigh-infection model. Compound 9 thus represents a new phenylthiazole lead for the treatment of MRSA infections that warrants further development.

Metals Enhance the Killing of Bacteria by Bacteriophage in Human Blood

Multidrug-resistant bacterial pathogens are a major medical concern. E. coli, particularly the pathotype extraintestinal pathogenic E. coli (ExPEC), is a leading cause of bloodstream infections. As natural parasites of bacteria, bacteriophages are considered a possible solution to treat patients infected with antibiotic resistant strains of bacteria. However, the development of phage as an anti-infective therapeutic is hampered by limited knowledge of the physiologic factors that influence their properties in complex mammalian environments such as blood. To address this barrier, we tested the ability of phage to kill ExPEC in human blood. Phages are effective at killing ExPEC in conventional media but are substantially restricted in this ability in blood. This phage killing effect is dependent on the levels of free metals and is inhibited by the anticoagulant EDTA. The EDTA-dependent inhibition of ExPEC killing is overcome by exogenous iron, magnesium, and calcium. Metal-enhanced killing of ExPEC by phage was observed for several strains of ExPEC, suggesting a common mechanism. The addition of metals to a murine host infected with ExPEC stimulated a phage-dependent reduction in ExPEC levels. This work defines a role for circulating metals as a major factor that is essential for the phage-based killing of bacteria in blood.

Simultaneous emergence and rapid spread of three OXA-23 producing Acinetobacter baumannii ST208 strains in intensive care units confirmed by whole genome sequencing

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a common nosocomial bacterial pathogen with limited treatment options. CRAB outbreaks are disastrous for critically ill patients. This study investigated carbapenemase-produced A. baumannii outbreaks in a tertiary hospital. Although multiple outbreaks were suggested by pulse-field gel electrophoresis, the genetic lineages and evolution between these isolates were not clear. To investigate the genomic epidemiology of these outbreaks and to reveal possible transmission routes, whole genome sequences (WGS) were compared and analyzed. From the WGS data, thirty isolates had the same sequence type (ST208); acquired resistance genes and chromosome resistant genes were detected and were responsible for multidrug resistance. A phylogenetic tree of single-nucleotide polymorphisms (SNPs) compared to the earliest index isolate found that three outbreaks had emerged and disseminated simultaneously. Of these, <10 SNPs were detected within the cluster, whereas at least 600 SNPs were found between the clusters. The probable transmission routes of outbreaks were generated combined with the genetic distance of isolates and patient epidemiological data. In conclusion, WGS was a convenient and accurate monitoring method for genomic epidemiologic investigation of outbreaks, and the genomic surveillance of multidrug-resistant bacterial pathogens would be a powerful warning system for the surveillance and prevention of outbreaks.

Plazomicin for the treatment of patients with complicated urinary tract infection

In June 2018, the United States Food and Drug Administration (FDA) approved plazomicin, a novel neoglycoside, for the treatment of adults with complicated urinary tract infections who have limited or no alternative treatment options. This approval was based on substantial preclinical and clinical work, and marks an important advance in the treatment of multidrug-resistant bacterial pathogens. This manuscript reviews the in vivo and in vitro work that led to the approval of plazomicin and examines how the drug may be used in the years ahead to treat patients with aggressive and life-threatening infections.

Multidrug-Resistant Bacterial Pathogens Assessment in Canine Ophthalmic Infections

The objective of this study was to identify the main microorganisms associated with ophthalmic infections and determine the resistance profile of these isolates against antimicrobial drugs. 26 bacterial isolates from 18 canine ophthalmic infections were submited to the phenotypic resistance profile for 36 drugs of 12 classes of antimicrobials, research of multidrug-resistant strains with importance in public health and detection of Staphylococcus mecA gene by PCR. The bacterial isolates were identified as Staphylococcus spp. (n = 18), Enterococcus spp. (n = 1), enterobacteria (n = 6) and Pseudomonas spp. (n = 1). The percentage of resistance and intermediate resistance were 42.48% (n = 325). Considering separate antimicrobials drugs, 18 isolates were characterized by multidrug resistant, while by the assesment of resistance to class, 20 isolates were multiresistant. In the phenotypic detection, 61.11% (11/18) of Staphylococcus spp. were predicted by Methicillin-Resistant Staphyloccus (MRS), whereas the genotypic detection, 38.89% (7/18) were carriers of the mecA gene. Two enterobacterias were considered producers of expectro Extended of Betalactamase (ESBL). EUCAST was more reliable for detecting MRS strains than the CLSI. The present study detected multiresistant isolates of great importance and are involved in cases of public health, such as MRS, MRSMLSb, ESBL, very important to be readily identified and controled so as to prevent the spread of this type of resistance.

Enhanced antibacterial effects of green synthesized ZnO NPs using Aristolochia indica against Multi-drug resistant bacterial pathogens from Diabetic Foot Ulcer.

Increased incidence of Multi-drug resistance in microorganisms has become the greatest challenge in the treatment of Diabetic Foot Ulcer (DFU) and urges the need of a new antimicrobial agent. In this study, we determined the bactericidal effects of ZnO nanoparticles (ZnO NPs) green synthesized from Aristolochia indica against Multi-drug Resistant Organisms (MDROs) isolated from pus samples of DFU patients attending in a tertiary care hospital in South India. ZnO NPs were characterized by UV-vis-DRS spectroscopy, Atomic Force Microscopy (AFM), Transmission Electron Microscopy (TEM) and for its zeta potential value. MIC/MBC assays were performed to determine bactericidal or bacteriostatic effects. Time-kill assays, Protein leakage and Flow cytometric analysis evaluated bacterial cell death at 1x MIC and 2x MIC concentrations of ZnO NPs. ZnO NPs of size 22.5nm with a zeta potential of -21.9±1mV exhibited remarkable bactericidal activity with MIC/MBC ranging from 25 to 400μg/ml with a significant reduction in viable count from 2h onwards. Protein leakage and Flow cytometric analysis confirmed bacterial cell death due to ZnO NPs. This study concluded that green synthesis protocol offers reliable, eco-friendly approach towards the development of antimicrobial ZnO NPs to combat antibiotic drug resistance.

Multidrug-resistant Enterobacteriaceae, Pseudomonas aeruginosa, and vancomycin-resistant Enterococcus: Three major threats to hematopoietic stem cell transplant recipients.

Hematopoietic stem cell transplant (HSCT) recipients are uniquely threatened by the emergence of multidrug-resistant (MDR) bacteria because these patients rely on immediate active antimicrobial therapy to combat bacterial infections. This review describes the epidemiology and treatment considerations for three challenging MDR bacterial pathogens in HSCT recipients: MDR Enterobacteriaceae, including extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant Enterobacteriaceae (CRE), Pseudomonas aeruginosa, and vancomycin-resistant Enterococcus (VRE). These bacteria are common causes of infection in this population and bacteremias caused by these organisms are associated with high mortality rates. Carbapenems remain the treatments of choice for serious infections due to ESBL-producing Enterobacteriaceae in HSCT recipients. Administration of β-lactam agents as an extended infusion is associated with improved outcomes in patients with severe infections caused by P.aeruginosa. Older agents used for the treatment of CRE and MDR P.aeruginosa infections, such as polymyxins and aminoglycosides, have major limitations. Newer agents, such as ceftazidime-avibactam and ceftolozane-tazobactam have great potential for the treatment of Klebsiella pneumoniae carbapemenase-producing CRE and MDR P.aeruginosa, respectively, but more pre-clinical and clinical data are needed to better evaluate their efficacy. Daptomycin dosages ≥8mg/kg/day are recommended to treat VRE infections in this population, particularly in the setting of increasing daptomycin resistance. Strategies to prevent these infections include strict adherence to recommended infection control practices and multidisciplinary antimicrobial stewardship. Last, gastrointestinal screening to guide empirical therapy and the use of polymerase chain reaction-based rapid diagnostics may decrease the time to administration of appropriate therapy for these infections, thereby leading to improved outcomes.