Antibiotic Nitrofurantoin Research Articles

The structures of E. coli NfsA bound to the antibiotic nitrofurantoin; to 1,4-benzoquinone and to FMN.

NfsA is a dimeric flavoprotein that catalyses the reduction in nitroaromatics and quinones by NADPH. This reduction is required for the activity of nitrofuran antibiotics. The crystal structure of free Escherichia coli NfsA and several homologues have been determined previously, but there is no structure of the enzyme with ligands. We present here crystal structures of oxidised E. coli NfsA in the presence of several ligands, including the antibiotic nitrofurantoin. Nitrofurantoin binds with the furan ring, rather than the nitro group that is reduced, near the N5 of the FMN. Molecular dynamics simulations show that this orientation is only favourable in the oxidised enzyme, while potentiometry suggests that little semiquinone is formed in the free protein. This suggests that the reduction occurs by direct hydride transfer from FMNH− to nitrofurantoin bound in the reverse orientation to that in the crystal structure. We present a model of nitrofurantoin bound to reduced NfsA in a viable hydride transfer orientation. The substrate 1,4-benzoquinone and the product hydroquinone are positioned close to the FMN N5 in the respective crystal structures with NfsA, suitable for reaction, but are mobile within the active site. The structure with a second FMN, bound as a ligand, shows that a mobile loop in the free protein forms a phosphate-binding pocket. NfsA is specific for NADPH and a similar conformational change, forming a phosphate-binding pocket, is likely to also occur with the natural cofactor.

Tailored Helicobacter pylori therapy is more effective than conventional therapy

Background and aims Tailored (culture and sensitivity) therapy has gained attention over recent years as an effective option for eradication of Helicobacter pylori infection. The authors aimed to assess the efficacy of antibiotics sensitivity-guided therapy versus clarithromycin or levofloxacin triple therapies as the first-line therapy for H. pylori. Patients and methods Dyspeptic patients who underwent esophagogastroduodenoscopy were prospectively enrolled. Patients with positive H. pylori results by the rapid urease test were randomized to receive either antibiotics sensitivity-guided therapy or empirical clarithromycin or levofloxacin-based triple therapy for 14 days. Antimicrobial sensitivity tests for seven antibiotics (clarithromycin, amoxicillin, metronidazole, levofloxacin, tetracycline, nitrofurantoin, and rifampicin) were performed using the disk-diffusion method. Group A received antibiotics sensitivity-guided therapies that included esomeprazole plus two antibiotics for which the isolates were sensitive and group B received conventional therapies that included esomeprazole, amoxicillin plus clarithromycin or levofloxacin for 2 weeks. Eradication of H. pylori was checked using stool antigen 4 weeks after therapy. Results A total of 25 patients completed the study in each group. Both studied groups were matched for baseline characteristics. The most commonly used regimen in the antimicrobial sensitivity-based therapy was clarithromycin-based triple therapy (46.5%), followed by levofloxacin-based triple therapy and levofloxacin and nitrofurantoin plus esomeprazole. The association analysis demonstrated that, in the intention-to-treat populations, the H. pylori eradication rate was significantly higher in the antibiotic sensitivity-guided therapy group [85.7% (24/28) vs. 53.3% (16/30) in the conventional therapy group (P=0.035). In the per-protocol populations, the eradication rate was 96% for the sensitivity-guided therapy group and 64% for the conventional therapy group (P=0.005). The rates of adverse events were similar in both sensitivity-guided and conventional therapies, with no significant differences (P=0.527). Conclusions Culture-based eradication therapy demonstrated superior eradication rates than empirical therapy as a first-line therapy for H. pylori in a region with high rates of antimicrobial resistance.

Solvothermal Preparation of a Lanthanide Metal-Organic Framework for Highly Sensitive Discrimination of Nitrofurantoin and l-Tyrosine.

Metal-organic frameworks (MOFs) have been rapidly developed for their broad applications in many different chemistry and materials fields. In this work, a multi-dentate building block 5-(4-(tetrazol-5-yl)phenyl)-isophthalic acid (H3L) containing tetrazole and carbolxylate moieties was employed for the synthesis of a two-dimensional (2D) lanthanide MOF [La(HL)(DMF)2(NO3)] (DMF = N,N-dimethylformamide) (1) under solvothermal condition. The fluorescent sensing application of 1 was investigated. 1 exhibits high sensitivity recognition for antibiotic nitrofurantoin (Ksv: 3.0 × 103 M−1 and detection limit: 17.0 μM) and amino acid l-tyrosine (Ksv: 1.4 × 104 M−1 and detection limit: 3.6 μM). This work provides a feasible detection platform of 2D MOFs for highly sensitive discrimination of antibiotics and amino acids.

Antibiogram Profiles of Bacteria Isolated from Different Body Site Infections Among Patients Admitted to GAMBY Teaching General Hospital, Northwest Ethiopia.

BackgroundInfections with multi-drug resistant (MDR) bacteria are serious threats to many low-income countries associated with overuse and misuse of antibiotics. This study determined the antibiogram profiles of bacteria isolated from different body site infections among patients admitted to GAMBY Teaching General Hospital, Bahir Dar, Northwest Ethiopia.MethodsA hospital-based cross-sectional study was done between November 2015 and May 2018. Various clinical specimens were sampled from patients and analyzed for aerobic bacterial isolation and Kirby–Bauer disk diffusion susceptibility testing. Chi-square test was calculated to see association among variables, and P-value <0.05 was taken as a cutoff value for statistical significance.ResultsFrom the 716 clinical specimens processed, 134 (18.7%) were culture-positive for aerobic bacterial pathogens. Culture-confirmed positivity was higher in ear discharge (27.3%) and urine (26.3%) samples. The prevalence of infection was significantly highest among females (P = 0.001). Escherichia coli 63 (47.4%) and 10 (7.4%) of Klebsiella spp. from Gram-negative bacteria were the predominant bacterial isolates, while Staphylococcus saprophyticus 17 (12.6%) and S. aureus 14 (10.4%) were from Gram-positive bacteria. Overall, 61.8% of the isolates were found to be MDR. The proportion of MDR among Klebsiella spp., S. aureus and E. coli isolates was 90.9%, 60.9% and 50%, respectively. Gram-positive bacteria demonstrated 20%, 48.6% and 100% of resistance against norfloxacin, ciprofloxacin and clindamycin, respectively. Gram-negative bacteria also revealed from 20% resistance for the antibiotic nitrofurantoin and 100% of resistance for ampicillin and penicillin.ConclusionInfections with bacterial isolates resistant to the majority of antibiotics are a major issue in the study area. Most of the identified bacteria were resistant to the routinely used antibiotics, and MDR isolates are alarmingly high. Therefore, clinicians should practice rational choice of antibiotics and treatment should be guided by antimicrobial susceptibility testing.

Stimulation of de novo glutathione synthesis by nitrofurantoin for enhanced resilience of hepatocytes

Toxicity is not only a function of damage mechanisms, but is also determined by cellular resilience factors. Glutathione has been reported as essential element to counteract negative influences. The present work hence pursued the question how intracellular glutathione can be elevated transiently to render cells more resistant toward harmful conditions. The antibiotic nitrofurantoin (NFT) was identified to stimulate de novo synthesis of glutathione in the human hepatoma cell line, HepG2, and in primary human hepatocytes. In intact cells, activation of NFT yielded a radical anion, which subsequently initiated nuclear-factor-erythroid 2-related-factor-2 (Nrf2)-dependent induction of glutamate cysteine ligase (GCL). Application of siRNA-based intervention approaches confirmed the involvement of the Nrf2-GCL axis in the observed elevation of intracellular glutathione levels. Quantitative activation of Nrf2 by NFT, and the subsequent rise in glutathione, were similar as observed with the potent experimental Nrf2 activator diethyl maleate. The elevation of glutathione levels, observed even 48 h after withdrawal of NFT, rendered cells resistant to different stressors such as the mitochondrial inhibitor rotenone, the redox cycler paraquat, the proteasome inhibitors MG-132 or bortezomib, or high concentrations of NFT. Repurpose of the antibiotic NFT as activator of Nrf2 could thus be a promising strategy for a transient and targeted activation of the endogenous antioxidant machinery.Graphical abstract

Frequency of fimH, papC, and aer in E. coli Strains Isolated from Patients with Urinary Tract Infection, and their Antibiotic Resistance Pattern

Introduction: E. coli is the predominant causes of urinary tract infection. Several virulence factors for bacterial infections in the urinary tract are required. In this study, we have considered several virulence factors in strains isolated from the patients with UTI in Yazd. Methods: In this cross-sectional study in 1394-1395, 146 strains isolated were collected from the patients with urinary tract infection. After confirmation by phenotypic and genotype methods, frequency of gene fimH, pap C, aer was evaluated using specific primers by PCR method. The pattern of antibiotic resistance of isolates was determined by disk diffusion method. Results: In the present study, the prevalence of virulence genes was fimH (87%), aer (85.6%) and papC (9.6%). Among 146 E. coli isolates, resistance rate for various antibiotics were as follows: 57.2% to Cotrimoxazole, 54.8% to Nalidixic acid, 45.9% to Cefazolin, 40.4% to Cefixime, 42.5% to Cefalotin, 41.8% to Cefalexin, 31.5% to Norfloxacin, 30.1% to Ofloxacin, 28.3% to Ciprofloxacin, 24% to Gentamicin, 19.9% to Amikacin, 1.4% to Nitrofurantoin, and 1.4% to phosphomycin. The results showed that the most and less frequent resistant was seen in Cotrimoxazole and Nitrofurantoin, phosphomycin, respectively. Conclusion: In this study, the frequency of fimH gene was higher than other genes. In addition, according to the pattern of antibiotic resistance nitrofurantoin and phosphomycin are suitable medicines for the treatment of patients in our region.

Urinary tract infection pocket card effect on preferred antimicrobial prescribing for cystitis among patients discharged from the emergency department

DisclaimerIn an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.PurposeTo evaluate the impact of a urinary tract infection (UTI) pocket card on preferred antibiotic prescribing for patients discharged from the emergency department (ED) with a diagnosis of cystitis.MethodsA multicenter, retrospective, pre-post study was conducted to compare outcomes following the introduction of a UTI pocket card. The primary outcome was prescribing rates for institutional first-line preferred antibiotics (cephalexin and nitrofurantoin) versus other antimicrobials for cystitis. Secondary outcomes included prescriber adherence to recommended therapy in regards to discharge dose, frequency, duration, and healthcare utilization rates.ResultsThe study included 915 patients in total, 407 in the preintervention group and 508 in the postintervention group. The frequency of preferred antibiotic prescribing was significantly increased after the introduction of a UTI pocket card compared to prior to its introduction (81.7% vs 72.0%, P = 0.001). Significant increases in prescribing of an appropriate antibiotic dose (78.0% vs 66.8%, P < 0.0001) and frequency (64.2% vs 47.4%, P < 0.0001) were also found post intervention. No significant differences were seen between the pre- and postintervention groups with regards to healthcare utilization rates.ConclusionA UTI pocket card increased preferred antibiotic prescribing for cystitis in the ED. This study provides data on a successful antimicrobial stewardship intervention in the ED setting.

Bacterial Profile and Antibiotic Resistance among Cancer Patients with Urinary Tract Infection in a National Tertiary Cancer Hospital of Nepal.

Cancer patients are at high risk of antibiotic resistant bacterial urinary tract infections (UTIs). In this study, we assessed the bacterial profile and antibiotic resistance among cancer patients suspected of UTI in B.P. Koirala Memorial Cancer Hospital in Nepal through a cross-sectional study with routinely collected data. All cancer patients who had a recorded urine culture between July 2018–June 2019 were included in the study. Out of 308 patients who had undergone culture, 73 (24%) of samples had bacterial growth. The most common organisms isolated were E. coli (58%), Staphylococcus (11%) and Klebsiella (10%). These bacteria had undergone susceptibility testing to 27 different antibiotics in various proportions. Of the limited antibiotic testing levels, nitrofurantoin (54/66, 82%) and amikacin (30/51, 59%) were the most common. Among those tested, there were high levels of resistance to antibiotics in the “Access” and “Watch” groups of antibiotics (2019 WHO classification). In the “Reserve” group, both antibiotics showed resistance (polymyxin 15%, tigecycline 8%). Multidrug resistance was seen among 89% of the positive culture samples. This calls for urgent measures to optimize the use of antibiotics in UTI care at policy and health facility levels through stewardship to prevent further augmentation of antibiotic resistance among cancer patients.

Molecular Identification and Antimicrobial Sensitivity Profile of Bacteria Isolated from Food Handlers in Akure Nigeria

Hand washing and hand swab samples culminating to a total of 477 samples were collected from different food vending locations in Akure. Bacteria were isolated and identified, after which the sensitivity patterns of the isolates to standard antibiotics and plant extracts were determined using disc diffusion agar and well diffusion methods, respectively. The bacterial isolates include Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Micrococcus luteus, Proteus mirabilis, Proteusvulgaris, Pseudomonas aeruginosa, Salmonella enteritica, Salmonella typhi, Serratia marcescens, Shigella sonnei, Staphylococcus epidermidis, Staphylococcus aureus and, Streptococcus pyogenes. Staphylococcus aureus was observed to be the most prominent bacteria harboured by the food handlers. The isolated bacteria were subjected to 16s rRNA polymerase chain reaction, DNA gene extraction and sequence blasting using the amplified length of 1500 base pair. The sequence obtained was blasted in National Centre for Biotechnology Information (NCBI) database. Based on the 16s rRNA sequences, the following bacteria were confirmed; Escherichia coli str. K12 substr. DH10B, Klebsiella pneumoniae strain J1, Proteus mirabilis strain HI4320, Pseudomonas fluorescens SBW25, Salmonella enterica subsp.enterica serovar Typhi str. CT18, Salmonella enterica subsp. enterica serovar Infantis, Shigella flexneri 2a str. 2457T and Staphylococcus cohnii subsp. cohnii strain 532 Contig16. Phylogeny was employed in the phylogenetic tree construction due to its robustness, reliability and less-laboriousness. The result of the sequence was aligned and the phylogenetic tree constructed shows the evolutionary relationship between eight bacterial species. Two clusters were generated; Salmonella enterica subsp. enterica serovar Typhi, Salmoenella typhi LN854584.1 Staphylococcus cohnii, and Staphylococcus aureus are in cluster 1, Proteusmirabilis NC0100554.1, Bacillus thuringiensis KY652120.1 and Bacillus subtilis MG231261.1 is incluster 2. However, bacteria in the same cluster were observed to have different phenotypic characteristics. The antibacterial efficacy of the selected medicinal plant extracts (Ocimum gratissimum and Annona muricata) were copared to that of standard antibiotics (Ciprofloxacin, Nitrofurantoin, Ampliclox, and Chloramphenicol) using three different solvents (methanol, water and petroleum ether) at 50 mg/ml, 100 mg/ml, 200mg/ml and 300mg/ml, concentrations. Bioactive characterization of the selected plants revealed the presence ofvarious active components such as Thymol, Eugenol, Caryophyllene, Gamma-terpinene, 8-methyl-4-vanillyl-7-nonenamide, N-4-Hydroxy-3-methoxybenyl 8methyldec 6 enamide, DL-6, 8-tio acidamide and N-4-Hydroxy-3-methoxyphenyl methyl nonanamide. Phytochemical analysis of the plants affirmed the presence of Tannins, Alkaloids, Flavonoids, Anthraquinone and Saponins in O. gratissimum and A. muricata. It can be deduced from this study that food handlers play a major role in the transfer of bacterial contaminants to the edible food. Also, the metabolites present in O. gratissimum and A. muricata render these plants cost effective alternative source of therapy to food borne illnesses.

Ultrathin films to investigate the interaction of nitrofurantoin with phospholipids

The molecular properties of the antibiotic nitrofurantoin at liquid interfaces were correlated with effects observed in cellular membrane models, represented by 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine Langmuir monolayers. Nitrofurantoin adsorbs at the films, keeps their compressibility, and stabilizes them, as characterized by tensiometry. Brewster Angle Microscopy and infrared spectroscopy showed that nitrofurantoin induces the formation of aggregates and affects the lipid hydrophilic and hydrophobic chemical environments. Consequently, nitrofurantoin disturbs the cell membrane models, affecting some of their physicochemical properties, including thermodynamic, rheological, morphological, and structural. These results can help understand at the molecular level interactions between the drug and lipidic biological surfaces.

The Inhibitory Effect of the Aqueous Extract of Ceratophyllum demersum on Vibrio cholarae that Isolated from Cyprinus carpio

The current study was conducted to determine the inhibitory effect of the aqueous extract of hornwort Ceratophyllum demersum on Vibrio cholerae bacteria that affects the common carp Cyprinus carpio L. in fish farms. The inhibitory effect of the aqueous extract was determined in petri dishes. The inhibition effects of the extract and six common antibiotics (Nalidixic acid, Nitrofurantoin, Gentamicin, Streptomycin, Tetracycline, and Amoxicillin) were compared; the results showed that the inhibition effect of the aqueous extract of hornwort was higher than the inhibitory effects of the six antibiotics. The stock solution 100% of the aqueous extract showed an inhibition effect reached 35.3 mm compared with 25 mm, 15 mm, 7 mm, 10 mm, 23 mm and 11 mm of Nalidixic acid, Nitrofurantoin, Gentamicin, Streptomycin, Tetracycline, and Amoxicillin antibiotics respectively. A positive correlation was recorded between concentration of aqueous extract and its inhibitory effect. The average of inhibition diameter was 23.3 mm, 27.6 mm, 28.6 mm, and 35.3 mm for the concentrations 25%, 50%, 75% and 100% of the stock solution, respectively.

Current trends of Silver doped Zinc oxide nanowires photocatalytic degradation for energy and environmental application

A simple phyto-assisted synthesis of zinc oxide nanowires (ZnO NWs) employing urinary tract infection (UTI) controlling traditional medicinal plant Pedalium murex L. mucilage, their silver (Ag) doping by co-precipitation method has been reported. The synthesized Ag-doped ZnO NWs photocatalytic action on the UTI antibiotic nitrofurantoin (NFT) and the dye methylene blue (MB) has been reported. The synthesized NPs optical, biocomponents, structural and chemical properties were determined by UV-vis spectroscopy, FTIR, XRD, SEM, TEM, EDAX, particle size analyzer. Photocatalytic activity of the phyto-assisted synthetic Ag-doped ZnO NWs was investigated on the degradation of the antibiotic NFT and the dye MB. The percentage of degradation, as well as dye removal efficiency was calculated. The UV-vis absorption spectrum showed a surface plasmon resonance (SPR) band at 370 nm - 400 nm with blue and redshift. The vast bandgap energy (3.37 eV - 2.75 eV) reduction indicated the inclination of noble metal Ag on the surface of ZnO NWs. XRD diffractogram revealed the crystalline hexagonal wurtzite structure and c-axis oriented growth of the synthesized ZnO nanowires. FTIR spectra functional groups exposed the possible contribution of plant phytochemicals in the formation of nanowires. TEM micrographs showed the agglomerations of zinc cite crystal structure nanowire with silver inclination on their surface. EDX and SAED confirmed the elemental composition and purity of the synthesized Ag/ZnO nanowires. The synthesized Ag-doped ZnO nanowires achieved photocatalytic degradation of about 78.51% of the antibiotic NFT and 92.43% of MB dye in 150 min under UV irradiation. The present study establishes the likelihood of photocatalytic degenerative potency of the antibiotic nitrofurantoin and methylene blue employing photosynthesized phytosynthesized zinc oxide nanowires.

Simultaneous electrochemical determination of nitrofurantoin and nifedipine with assistance of needle-shaped perovskite structure: barium stannate fabricated glassy carbon electrode.

A needle-shaped perovskite, barium stannate (BaSnO3), was synthesized via a co-precipitation technique for the simultaneous electrochemical determination of antibiotic drug nitrofurantoin (NFTO) and pericardial drug nifedipine (NFP). The spectroscopic and microscopic result confirms that as-prepared BaSnO3 particles formed with desired crystalline nature, functional group, pore size, pore diameter, and fine needle-like morphology. The simultaneous electrochemical detection of thetwo pharmaceutical compounds was examined via cyclic voltammetry (CV) and differential pulse voltammetry (DPV) technique using BaSnO3-modified glassy carbon electrode (BaSnO3/GCE) at a potential range from +0.4 to - 1.2V. The discrete and simultaneous detection of NFTO and NFP at the BaSnO3 sensor exhibits higher catalytic activity in terms of cathodic current and cathodic potential compared to bare GCE. DPV results of theBaSnO3 sensor provide improvedlinear ranges and limits of detection for NFTO (0.01-42.65µM; 42.65-557.65μM, 0.062μM, respectively) and NFP (0.01-697.65μM, 0.0168μM, respectively). Besides, the BaSnO3-fabricated sensor exhibits goodsensitivity, reproducibility, and repeatability. Themodified electrode shows excellent recoveries of NFTO (97.0-100.7%) and NFP (98.7-101.3%) in plasma, urine, and milk samples with an acceptable relative standard deviation (RSD) of 1.6-4.8%. Graphical abstract Needle-shaped BaSnO3 perovskite material for simultaneous electrochemical sensing of pharmaceutical drugs.

Prevalence and antibiotic susceptibility pattern of uropathogenic Escherichia Coli strains in sonipat region of Haryana in India

Background: To study the prevalence and antibiotic susceptibility pattern of uropathogenic Escherichia coli strains in Sonipat region of Haryana in India. Urinary tract infections (UTIs) are among the most widespread infections, caused most frequently by Escherichia coli. The past few years have witnessed a rapid rise in the spread of high antibiotic-resistant forms of these uropathogenic E. coli (UPECs). Methods: In the current study, a total of 53 UPEC isolates from patients of all age groups were collected from Sonipat and its adjoining areas from September 2017 to April 2018. All the uropathogens were subjected to antibiotic susceptibility profiling using a set of 23 antibiotics and confirmed using standard microbiological procedures. The isolates which exhibited high degree of multidrug resistance (MDR) were characterized at molecular level using 16S rRNA sequencing. Results: The evaluation of age- and gender-wise prevalence of UTI revealed that women (77.3%) were more susceptible to infection as compared to men (22.6%). It was observed that 83% of the collected UPEC isolates exhibited MDR pattern. The isolates exhibited maximum resistance to cephalosporins and fluoroquinolones; and the highest susceptibility (100%) was shown toward tigecycline, followed by 96.2% to colistin, 90.5% to amikacin, 86.7% to fosfomycin, and 84.9% to nitrofurantoin. Conclusion: The study concludes that the prevalence of MDR pathogens is high in studied region. For empirical antibiotic therapy, amikacin, fosfomycin, and nitrofurantoin should be preferred; and for MDR uropathogens, colistin, and tigecycline should be recommended.

Ultrafine rhenium–ruthenium nanoparticles decorated on functionalized carbon nanotubes for the simultaneous determination of antibiotic (nitrofurantoin) and anti-testosterone (flutamide) drugs

In this work, Re–Ru@f-MWCNT nanocomposite used as a new electrode platform for simultaneous electrochemical detection of nitrofurantoin (NFT) and flutamide (FLT) drugs.

Profil kuman pada infeksi saluran kemih di Rumah Sakit Umum Pusat Sanglah Bali tahun 2019-2020

Background: As many as 150 million people worldwide have experienced urinary tract infections. Bacteria and fungi are agents that cause urinary tract infections that can be found in the urine of a person who is indicated to have a urinary tract infection. Objective: To determine the pattern of germs as well as the sensitivity and resistance of antibiotics to bacteria that cause urinary tract infections in Sanglah Hospital, Denpasar. Methods: This research is a descriptive study. The research subjects were obtained from the profile of the patient's urine culture supporting examination data at Sanglah General Hospital Denpasar Bali, December 2019 - June 2020. Results: A total of 327 samples were tested, 207 (63.3%) women and 120 men (36.7%). the mean age of the samples was 55.04 SD. The bacteria in urine culture with a colony count of 105 that most commonly caused urinary tract infections were E. coli as much as 130 (39.76%), Klebsiella pneumoniae ssp. pneumoniae as much as 36 (11.01%), Acinetobacter baumannii as much as 22 (6.73%), Proteus mirabilis as much as 15 (4.59%), Klebsiella oxytoca as much as 15 (4.59%). Conclusion: Several considerations of antibiotics as a therapeutic option in microorganisms are as follows. E. coli with the antibiotic nitrofurantoin, Klebsiella pneumoniae ssp. Pneumoniae with the antibiotic meropenem, Acinetobacter baumannii with trimethoprin/sulfamethoxazole antibiotics, Proteus mirabilis with the antibiotic ceftriaxone, and Klebsiella oxytoca with the antibiotic gentamicin.

The Amino Acid Changes T55A, A273P and R277C in the Beta-Lactamase CTX-M-14 Render E. coli Resistant to the Antibiotic Nitrofurantoin, a First-Line Treatment of Urinary Tract Infections.

The antibiotic nitrofurantoin is a furan flanked by a nitro group and a hydantoin ring. It is used to treat lower urinary tract infections (UTIs) that have a lifetime incidence of 50−60% in adult women. UTIs are typically caused by uropathogenic Escherichia coli (UPEC), which are increasingly expressing extended-spectrum beta-lactamases (ESBL), rendering them multi-drug resistant. Nitrofurantoin is a first-line treatment for gram-negative ESBL-positive UTI patients, given that resistance to it is still rare (0% to 4.4%). Multiplex PCR of β-lactamase genes of the blaCTX-M groups 1, 2, 9 and 8/25 from ESBL-positive UTI patients treated at three referral hospitals in North Wales (UK) revealed the presence of a novel CTX-M-14-like gene harbouring the missense mutations T55A, A273P and R277C. While R277 is close to the active site, T55 and A273 are both located in external loops. Recombinant expression of CTX-M-14 and the mutated CTX-M-14 in the periplasm of E. coli revealed a significant increase in the Minimum Inhibitory Concentration (MIC) for nitrofurantoin from ≥6 μg/mL (CTX-M-14) to ≥512 μg/mL (mutated CTX-M-14). Consistent with this finding, the mutated CTX-M protein hydrolysed nitrofurantoin in a cell-free assay. Detection of a novel nitrofurantoin resistance gene indicates an emerging clinical problem in the treatment of gram-negative ESBL-positive UTI patients.

An ultra-stable Cadmium(II) Coordination Framework Constructed From the new Bi-Functional Ligand and Application as Fluorescent Probe for Acetylacetone and Antibiotics

In the last thirty years, light-emitting metal organic frameworks (MOFs) sensors have attracted immense interest by scientists because these functional coordination materials possess good framework stability and high surface areas, and excellent stability in adsorption, separation, catalysis, etc. These MOFs-based sensors have the broad applications in the national security, surrounding protection and mankind's health. In this work, a new bi-functional ligand H3L (H3L = 4'-(1H-tetrazole-5)-biphenyl-2,3-dicarboxylic acid) simultaneously containing tetrazole and carboxylate groups can be synthesized. Further, the ultra-stable tetrazolium Cadmium (II) MOFs {[Cd2 (μ7-L) (μ3-OH) (H2O)2]·1.3H2O}n (1) has been successfully prepared under the solvo-thermal conditions. In 1, neighboring tetranuclear cadmium (II) building blocks are inter-linked through the bridging tetrazole moieties and aromatic bi-phenyl backbones forming the 3D micro-porous framework. It is interesting that 1 exhibits excellent chemical stability, the coordination framework of 1 can be kept not only in various different solvents but also the water environment with pH varying from 2 to 12 for 24 h. Powder X-ray diffraction (PXRD) patterns have been investigated demonstrating these bulky as-synthesized samples 1 are pure phases. Compared with other coordination polymers, 1 has some other advantages such that 1 possesses good water dispersibility, excellent photo-luminescence emissions and fluorescence stability, which has the potential to be utilized as the excellent chemical sensor. Fluorescent characterization reveals that 1 also can behave highly sensitive and real-time discrimination of acetylacetone (Hacac) with good reusability (high quenching efficiency Ksv for Hacac: 2.5 × 105 M−1) and extremely low detection limit values (For Hacac: 35 μM). On the other hand, 1 can behave highly sensitivity, recyclability and real-time chemical sensing for antibiotics nitrofurazone (NFZ) and nitrofurantoin (NFT) (Ksv for NFZ: 5.9 × 106 M−1 and NFT: 9.0 × 106 M−1) and extremely low detection limit values (For NFZ: 2.2 μM and NFT: 1.4 μM).

Biofilm formation in uropathogenic Escherichia coli strains; Relationship with virulence factors and antimicrobial resistance

Background: Urinary tract infection (UTI) is a clinical condition with characteristic symptoms, colonization and multiplication of bacteria in significant numbers. At this juncture, antimicrobial resistance in uropathogens has become one of the major concerns globally. Therefore, the present study aimed to demonstrate the biofilm formation in uropathogenic Escherichia coli strains; characterize the phenotypic & genotypic virulence factors and their relationship with antimicrobial resistance. Methods and materials: In this study, 1000 suspected UTI cases were included. Urine samples were processed for culture and antimicrobial drug susceptibility testing. Only Escherichia coli isolates were further studied for production of biofilm, ESBL and haemolysin enzymes by phenotypic methods. Virulence genes, papEF, traT & PAI were detected by multiplex PCR. Molecular confirmation & characterization of virulence genes was done by Sanger sequencing. Results: From the 1000 urine samples, 395 E. coli were isolated. Higher resistance was observed with antibiotics - ampicillin (82.53%), cefuroxime (72.41%), amoxicillin-clavulanic acid (71.90%), ceftriaxone (66.58%), ciprofloxacin (65.82%) and cefepime (57.47%). In-vitro biofilm was formed by 71.39% isolates. Biofilm-forming strains developed higher resistance towards ampicillin, cefuroxime, amoxicillin-clavulanic acid, ciprofloxacin, cefepime and ceftriaxone. Phenotypic methods detected 62.3% isolates as ESBL producers and 40.2% were β-haemolytic. Virulence gene characterization revealed presence of traT in 73.2% strains, PAI & papEF among 62.9% and 33.5% strains. ESBL & Hemolysin producing UPEC exhibited higher resistant to ampicillin, amoxicillin-clavulanic acid, aztreonam, cefriaxone, cefuroxime, cefepime, ciprofloxacin, chloramphenicol & gentamicin. Statistically proved association was seen with gene RPAI and traT with antibiotics nitrofurantoin and amikacin. All the isolates were sensitive to nitrofurantoin, piperacillin-tazobactam, and imipenem. Strains showed 99% sequence identity and no mutations were detected. Conclusion: Increase in trend of resistance was observed with antibiotics which were routinely used to treat UTI. Results indicated significant correlation between phenotypic and genotypic virulence factors and antibiotic resistance. Antibiotics nitrofurantoin, piperacillin - tazobactam, and imipenem can be effective for severe UTIs. This study concludes that expression of virulence factors by UPEC strains is responsible for increased antibiotic resistance. Hence, characterizing the UPEC strains help clinicians to reach a better therapeutic outcomes and treatment regimens in this region.

Investigation of the bacterial cell envelope nanomechanical properties after long-term exposure to nitrofurans

Antibiotic residues in the environment may negatively affect biological communities in the natural ecosystems. However, their influence on environmental bacterial strains has not been thoroughly investigated. In this study, two representatives of 5-nitrofuran antibiotics (nitrofurantoin and furaltadone) were investigated in terms of their long-term influence on the cell envelopes of newly isolated environmental bacterial strains (Sphingobacterium caeni FTD2, Achromobacter xylosoxidans NFZ2 and Pseudomonas hibiscicola FZD2). A 12-month exposure of bacterial cells to nitrofurans at a concentration of 20 mg L−1 induced changes in the cell structure and texture (bacteria under stress conditions showed a loss of their original shape and seemed to be vastly inflated, the cells increased average surface roughness after exposure to NFT and FTD, respectively). AFM observations allowed the calculation of the bacterial cell nanomechanical properties. Significant increase in adhesion energy of bacteria after prolonged contact with nitrofurantoin was demonstrated. Changes in the permeability of bacterial membrane, fatty acids’ composition and bacterial cell surface hydrophobicity were determined. Despite visible bacterial adaptation to nitrofurans, prolonged presence of pharmaceuticals in the environment has led to significant alterations in the cells’ structures which was particularly visible in P. hibiscicola.