Antibiotics efficacy in clinical and microbiological cure of uncomplicated urinary tract infection: a systematic review and network meta-analysis.

PURPOSE: Fosfomycin has been used more frequently in managing uncomplicated urinary tract infections (UTIs) due to decreased compliance and increased multidrug-resistant bacteria. The aim of this network meta-analysis was to assess the efficacy of Fosfomycin compared to Nitrofurantoin, Trimethoprim-Sulfamethoxazole (TMP-SMX), and Ciprofloxacin in terms of clinical and microbiological cure alongside with other measurements. MATERIALS AND METHODS: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL). We included randomized control trials (RCTs) with uncomplicated UTI patients who received Fosfomycin, Nitrofurantoin, TMP-SMX, or Ciprofloxacin and reported the clinical or microbiological cure. We used Cochrane Risk of Bias Assessment Tool to assess the included studies' quality. R-software was used for all statistical analysis. We ranked all antibiotics using the netrank function which yielded P scores. Frequentist network meta-analysis was used to assess the efficacy of all outcomes. RESULTS: We included 13 RCTs with a total number of 3856 patients that showed Fosfomycin ranked the highest among the other antibiotics with respect to clinical cure (P-score = 0.99) and microbiological cure (P-score = 0.99) while Ciprofloxacin ranked the lowest (P-score = 0.11 and 0.02, respectively). Moreover, Ciprofloxacin yielded the highest relapse rate (P-score = 1), whereas TMP-SMX had the lowest relapse rate (P-score = 0.07). As for the adverse events, Ciprofloxacin demonstrated the highest adverse events as opposed to Fosfomycin (P-score = 0.98 and 0.05, respectively). CONCLUSION: The network meta-analysis demonstrated that Fosfomycin is the most effective antibiotic in treating uncomplicated UTIs with respect to clinical cure, microbiological cure, and adverse events profile.

In vitro antitrypanosomal activity of synthesized nitrofurantoin-triazole hybrids against Trypanosoma species causing animal African trypanosomosis.

Animal African trypanosomosis (AAT) is a disease caused by Trypanosoma brucei brucei, T. vivax, T. evansi and T. congolense which are mainly transmitted by tsetse flies (maybe the family/genus scientific name for the tsetse flies here?). Synthetic trypanocidal drugs are used to control AAT but have reduced efficacy due to emergence of drug resistant trypanosomes. Therefore, there is a need for the continued development of new safe and effective drugs. The aim of this study was to evaluate the in vitro anti-trypanosomal activity of novel nitrofurantoin compounds against trypanosomes (Trypanosoma brucei brucei, T. evansi and T. congolense) causing AAT. This study assessed previously synthesized nineteen nitrofurantoin-triazole (NFT-TZ) hybrids against animal trypanosomes and evaluated their cytotoxicity using Madin-Darby bovine kidney cells. The n-alkyl sub-series hybrids, 8 (IC50 0.09 ± 0.02 µM; SI 686.45) and 9 (IC50 0.07 ± 0.04 µM; SI 849.31) had the highest anti-trypanosomal activity against T. b. brucei. On the contrary, the nonyl 6 (IC50 0.12 ± 0.06 µM; SI 504.57) and nitrobenzyl 18 (IC50 0.11 ± 0.03 µM; SI 211.07) displayed the highest trypanocidal activity against T. evansi. The nonyl hybrid 6 (IC50 0.02 ± 0.01 µM; SI 6328.76) was also detected alongside the undecyl 8 (IC50 0.02 ± 0.01 µM; SI 3454.36) and 3-bromobenzyl 19 (IC50 0.02 ± 0.01 µM; SI 2360.41) as the most potent hybrids against T. congolense. These hybrids had weak toxicity effects on the mammalian cells and highly selective submicromolar antiparasitic action efficacy directed towards the trypanosomes, hence they can be regarded as potential trypanocidal leads for further in vivo investigation.

Trends in and Risk Factors for Recurrent Clostridioides difficile Infection, New Haven County, Connecticut, USA, 2015-2020.

Recurrent Clostridioides difficile infection (RCDI) causes an increased burden on the healthcare system. We calculated RCDI incidence and identified factors associated with RCDI cases in New Haven County, Connecticut, USA, during 2015-2020 by using data from population-based laboratory surveillance. A subset of C. difficile cases had complete chart reviews conducted for RCDI and potentially associated variables. RCDI was defined as a positive C. difficile specimen occurring 2-8 weeks after incident C. difficile infection. We compared cases with and without RCDI by using multiple regression. RCDI occurred in 12.0% of 4,301 chart-reviewed C. difficile cases, showing a U-shaped time trend with a sharp increase in 2020, mostly because of an increase in hospital-onset cases. Malignancy (odds ratio 1.51 [95% CI 1.11-2.07]) and antecedent nitrofurantoin use (odds ratio 2.37 [95% CI 1.23-4.58]) were medical risk factors for RCDI. The 2020 increase may reflect the impact of the COVID-19 pandemic.

Antibacterial effect of vitamin C against uropathogenic E. coli in vitro and in vivo.

BACKGROUND: Resistance to antibiotics has increased steadily over time, thus there is a pressing need for safer alternatives to antibiotics. Current study aims to evaluate the influence of vitamin C as an antibacterial and anti-biofilm agent against uropathogenic E. coli (UPEC) strains. The expression of beta-lactamases and biofilm encoding genes among E. coli isolates before and after treating the isolates with sub MIC of vitamin C was analyzed by Real-time PCR. The in vivo assessment of the antibacterial and anti-biofilm effects of vitamin C against uropathogenic E. coli strains was done using a urinary tract infection (UTI) rat model. RESULTS: The effective concentration of vitamin C that could inhibit the growth of most study isolates (70%) was 1.25 mg/ml. Vitamin C showed a synergistic effect with most of the studied antibiotics; no antagonistic effect was detected at all. Vitamin C showed an excellent anti-biofilm effect against studied isolates, where 43 biofilm-producing isolates were converted to non-biofilm at a concentration of 0.312 mg/ml. The expression levels of most studied genes were down-regulated after treatment of E. coli isolates with vitamin C. In vivo assessment of vitamin C in treating UTIs showed that vitamin C has a rapid curative effect as the comparable antibiotic. Administration of both vitamin C and nitrofurantoin at a lower dose for treatment of UTI in rats had a better effect. CONCLUSION: Vitamin C as an antibacterial and anti-biofilm agent either alone or in combination with antibiotics could markedly improve UTI in experimental rats.

Mechanistic Insight of Polymer Effects on the Kinetic of Solution-Mediated Phase Transformation of Nitrofurantoin Anhydrate to Monohydrate.

PURPOSE: Nitrofurantoin is an effective antibacterial drug for the treatment of lower urinary tract infection. However, the anhydrate form can easily transform to the less soluble hydrate form (monohydrate) during dissolution, resulting in a reduction of dissolution rate and oral bioavailability. Therefore, inhibition of phase transformation is vital to stabilize the quality of drugs. METHODS: In this work, the potential of polyethylene glycol (PEG 8000), polyvinyl pyrrolidone (PVP K30), poloxamer 188 and hydroxypropyl methylcellulose (HPMC) to inhibit the hydration of nitrofurantoin during dissolution was investigated by experimental and simulation approaches. RESULTS: The rates of phase transformation were decreased in the presence of PEG 8000 and poloxamer 188, and PVP K30 and HPMC completely inhibited the phase transformation of anhydrate. The abundant hydrogen bond donor and acceptor groups of PVP and HPMC may easily establish intermolecular interactions with nitrofurantoin molecules, accounting for stronger inhibition of nucleation. Besides, the molecular dynamic simulation further indicated the formation of more extensive interactions between PVP K30 (or HPMC) and the (111) face of monohydrate, suggesting that the strong absorption of polymers on the surface and thus block the sites for incorporation of new growth. CONCLUSION: This study provides a mechanistic insight into the inhibition of nitrofurantoin hydration by polymeric additives, which helps design formulations and improve the physical stability of anhydrate.

Nitrofurantoin for the treatment of uncomplicated urinary tract infection in female patients: the impact of dosing regimen, age, and renal function on drug exposure.

PURPOSE: The aim of this study is to determine nitrofurantoin exposure in female patients with different age and renal function with complaints of an uncomplicated UTI. Also the nitrofurantoin exposure in relation to the dosage regimen will be studied. METHODS: Eight general practitioners (GP) participated in the study and included 38 patients with symptoms of an uncomplicated UTI, treated either with a dose of 50 mg q6h or 100 mg q12h, upon the discretion of the GP. Nitrofurantoin exposure was quantified in the patient's 24-h urine samples by UHPLC-UV and the area under the curve was calculated. RESULTS: The 38 patients provided a range of 2-17 urine samples. The urine nitrofurantoin exposure was 1028 mg h/L for the patients receiving 50 mg q6h and 1036 mg h/L for those treated with 100 mg q12h (p = 0.97) and was not affected by age and eGFR (p = 0.64 and p = 0.34, respectively). CONCLUSION: The data obtained do not support the discouragement of nitrofurantoin use in the elderly and in patients with impaired renal function. Since only a small number of patients were included, a larger study with more patients is warranted to evaluate nitrofurantoin exposure and adverse effects.

Bimetallic Cu5Zn8 alloy-embedded hollow porous carbon nanocubes derived from 3D-Cu/ZIF-8 as efficient electrocatalysts for environmental pollutant detection in water bodies.

Excessive use of nitrofurantoin (NFT) and its residues can be harmful to the ecosystem, and to mitigate this, rapid and cost-effective detection of NFT in water bodies is needed. In this regard, we prepared a three-dimensional (3D) copper-zeolitic imidazole framework (Cu/ZIF-8)-derived bimetallic Cu5Zn8 alloy-embedded hollow porous carbon nanocubes (Cu5Zn8/HPCNC) for electrochemical detection of NFT. The resultant material is characterized using suitable spectrophotometry and voltammetry methods. Cu5Zn8/HPCNC is an effective electrocatalyst with high electrical conductivity and a fast electron transfer rate. It also has more catalytic active sites for improved electrochemical reduction of NFT. Fabricated Cu5Zn8/HPCNC-modified screen-printed electrode (SPE) for NFT reduction have a wide linear range with a low detection limit, and high sensitivity (15.343 µA µÐœ-1 cm-2), appreciable anti-interference ability with related nitro compounds, storage stability, reproducibility, and repeatability. Also, the practicability of Cu5Zn8/HPCNC/SPE can be successfully employed in NFT monitoring in water bodies (drinking water, pond water, river water, and tap water) with satisfactory recoveries.

Nitrofurantoin-induced liver injury: long-term follow-up in two prospective DILI registries.

Nitrofurantoin is a synthetic antibiotic that is recommended as first-choice treatment for uncomplicated urinary tract infections. The prescription of this drug has increased dramatically, especially in Latin American countries. We described the demographics, clinical characteristics, biochemical features, and outcome of nitrofurantoin-induced liver injury. We analyzed 23 cases from the Latin American DILI Network (LATINDILI) and the Spanish DILI Registry. Causality was assessed with the RUCAM and RECAM scale. Of the 23 DILI cases included in our series, 96% patients were women, and the mean age of the whole cohort was 61 years. The median time of drug exposure was 175 days (interquartile range [IQR] 96-760), with 11 patients who were prescribed nitrofurantoin for more than six months. Hepatocellular damage was the most frequent pattern of liver injury (83%), and nearly half of the patients had an asymptomatic presentation (52%). Neither death nor liver transplantation was documented in this series. Overall, 65% of the patients (n = 15) presented with positive autoantibody titres. The median time to resolution was 81 days (IQR 57-141), and 15 patients (83%) recovered within six months. Five patients (22%) developed nitrofurantoin-induced autoimmune-like hepatitis (NI-AILH), of whom two were characterized by a persistent increase in transaminases that required immunosuppressive treatment to achieve normalization of liver enzymes. Clinicians who prescribe nitrofurantoin should be aware that patients who had taken nitrofurantoin for a long term may be at risk of developing nitrofurantoin-induced autoimmune-like hepatitis.

Application of high throughput in vitro metabolomics for hepatotoxicity mode of action characterization and mechanistic-anchored point of departure derivation: a case study with nitrofurantoin.

Omics techniques have been increasingly recognized as promising tools for Next Generation Risk Assessment. Targeted metabolomics offer the advantage of providing readily interpretable mechanistic information about perturbed biological pathways. In this study, a high-throughput LC-MS/MS-based broad targeted metabolomics system was applied to study nitrofurantoin metabolic dynamics over time and concentration and to provide a mechanistic-anchored approach for point of departure (PoD) derivation. Upon nitrofurantoin exposure at five concentrations (7.5 µM, 15 µM, 20 µM, 30 µM and 120 µM) and four time points (3, 6, 24 and 48 h), the intracellular metabolome of HepG2 cells was evaluated. In total, 256 uniquely identified metabolites were measured, annotated, and allocated in 13 different metabolite classes. Principal component analysis (PCA) and univariate statistical analysis showed clear metabolome-based time and concentration effects. Mechanistic information evidenced the differential activation of cellular pathways indicative of early adaptive and hepatotoxic response. At low concentrations, effects were seen mainly in the energy and lipid metabolism, in the mid concentration range, the activation of the antioxidant cellular response was evidenced by increased levels of glutathione (GSH) and metabolites from the de novo GSH synthesis pathway. At the highest concentrations, the depletion of GSH, together with alternations reflective of mitochondrial impairments, were indicative of a hepatotoxic response. Finally, a metabolomics-based PoD was derived by multivariate PCA using the whole set of measured metabolites. This approach allows using the entire dataset and derive PoD that can be mechanistically anchored to established key events. Our results show the suitability of high throughput targeted metabolomics to investigate mechanisms of hepatoxicity and derive point of departures that can be linked to existing adverse outcome pathways and contribute to the development of new ones.

Susceptibility to Fosfomycin and Nitrofurantoin of ESBL-Positive Escherichia coli and Klebsiella pneumoniae Isolated From Urine of Pediatric Patients.

BACKGROUND: Pediatric urinary tract infection (UTI) caused by extended-spectrum ß-lactamase (ESBL)-positive gram-negative bacilli (GNB) has limited options for oral antibiotic treatment. The purpose of this study was to investigate the susceptibility of ESBL-positive Escherichia coli and Klebsiella pneumoniae isolates from pediatric urine samples to two oral antibiotics (fosfomycin and nitrofurantoin). METHODS: From November 2020 to April 2022, ESBL-positive E. coli and K. pneumoniae isolates from urine samples were collected at Samsung Medical Center, Seoul, Korea. Patients over 18 years of age or with malignancy were excluded. For repeated isolates from the same patient, only the first isolate was tested. Minimum inhibitory concentrations (MICs) were measured using agar (fosfomycin) or broth (nitrofurantoin) dilution methods. MIC50 and MIC90 were measured for fosfomycin and nitrofurantoin in both E. coli and K. pneumoniae. RESULTS: There were 117 isolates from 117 patients, with a median age of 7 months (range, 0.0-18.5 years). Among 117 isolates, 92.3% (108/117) were E. coli and 7.7% (9/117) were K. pneumoniae. Isolates from the pediatric intensive care unit (PICU) and general ward (GW) was 11.1% (13/117) and 88.9% (104/117), respectively. Among 108 E. coli isolates, MIC50 and MIC90 for fosfomycin were 0.5 µg/mL and 2 µg/mL, respectively. Fosfomycin susceptibility rate was 97.2% (105/108) with a breakpoint of 128 µg/mL. Fosfomycin susceptibility rate was significantly lower in PICU isolates than in GW isolates (81.8% vs. 99.0%, P = 0.027). For nitrofurantoin, both the MIC50 and MIC90 were 16 µg/mL. Nitrofurantoin susceptibility rate was 96.3% (104/108) with a breakpoint of 64 µg/mL based on Clinical and Laboratory Standards Institute guidelines. Among the nine K. pneumoniae isolates, the MIC50 and MIC90 for fosfomycin was 2 µg/mL and 32 µg/mL, respectively. MIC50 and MIC90 for nitrofurantoin were 64 µg/mL and 128 µg/mL, respectively. CONCLUSION: For uncomplicated UTI caused by ESBL-positive GNB in Korean children, treatment with fosfomycin and nitrofurantoin for E. coli infections can be considered as an effective oral therapy option.

Selective detection of nitrofurantoin by histidine-capped silver nanoclusters with blue luminescence.

In view of the significance of nitrofurantoin, there is an urgent need for efficient analytical methods for accurate detection of nitrofurantoin. Considering their superior fluorescence performance and rarity of reports regarding nitrofurantoin detection by fluorescent silver nanoclusters (Ag NCs), Ag NCs with good stability and uniform size were synthesized through a simple method by protection of histidine (His) and reduction of ascorbic acid (AA). Based on the quenching by nitrofurantoin, Ag NCs were applied successfully in the detection of nitrofurantoin with high sensitivity. In the range of 0.5-150 µM, a linear relationship was found between ln(F0 /F) and nitrofurantoin amounts. Static quenching and inner filter effect were proved to be the main quenching mechanisms. Significantly superior selectivity and satisfactory recovery results in bovine serum indicate that Ag NCs provide a better choice for nitrofurantoin detection.

Insight into the mechanism and toxicology of nitrofurantoin: a metabolomics approach.

Safety and effectiveness are the two ends of the balance in drug development that needs to be evaluated. The biotransformation of drugs within a living organism could potentiate biochemical insults in the tissue and compromise the safety of drugs. Nitrofurantoin (NFT) is a cheap clinical antibiotic with a wide array of activities against gram-positive and gram-negative organisms. The NFT scaffold has been utilized to develop other derivates or analogues in the quest to repurpose drugs against other infectious diseases. Several techniques were developed over the years to study the mechanism of NFT metabolism and toxicity, such as voltammetry, chromatographic analysis, protein precipitation, liquid-liquid extraction, etc. Due to limitations in these methods, the mechanism of NFT biotransformation in the cell is poorly understood. Metabolomics has been adopted in drug metabolism to understand the mechanism of drug toxicity and could provide a solution to overcome the limitations of current techniques to determine mechanisms of toxicity. Unfortunately, little or no information regarding the metabolomics approach in NFT metabolism and toxicity is available. Hence, this review highlights the metabolomic techniques that can be adopted in NFT metabolism and toxicological studies to encourage the research community to widely adopt and utilize metabolomics in understanding NFT's metabolism and toxicity.

Exploration of ethylene glycol linked nitrofurantoin derivatives against Leishmania: Synthesis and in vitro activity.

Leishmaniasis is a neglected tropical disease that is caused by the Leishmania parasite. It is estimated that there are more than 350 million people at risk of infection annually. Current treatments that are in clinical use are expensive, have toxic side effects, and are facing parasitic resistance. Therefore, new drugs are urgently required. In the quest for new, safe, and cost-effective drugs, a series of novel ethylene glycol derivatives of nitrofurantoin was synthesised and the in vitro antileishmanial efficacy of the compounds tested against Leishmania donovani and Leishmania major strains. Arylated ethylene glycol derivatives were found to be the most potent, with submicromolar activity up to 294-fold greater than the parent compound nitrofurantoin. Analogues 2j and 2k had the best antipromastigote activities with submicromolar IC50 values against L. major IR-173 and antimonial-resistant L. donovani 9515 strains.

A Ni(II) Coordination Polymer as a Multifunctional Luminescent Sensor for Detection of UO22+, Cr2O72-, CrO42- and Nitrofurantoin.

A new Ni coordination polymer [Ni(MIP)(BMIOPE)]n (1) was constructed (BMIOPE = 4,4'-bis(2-methylimidazol-1-yl)diphenyl ether, and H2MIP = 5-methylisophthalic acid), possessing two-dimensional (2D) twofold parallel interwoven net structure with a 44∙62 point symbol. Complex 1 has been successfully obtained based on mixed-ligand strategy. The fluorescence titration experiments revealed that complex 1 could act as multifunctional luminescent sensor to simultaneously detect UO22+, Cr2O72- and CrO42-, and NFT (nitrofurantoin). The limit of detection (LOD) values for complex 1 are 2.86 × 10-5, 4.09 × 10-5, 3.79 × 10-5 and 9.32 × 10-5 M for UO22+, Cr2O72-, CrO42- and NFT. The Ksv values are 6.18 × 103, 1.44 × 104, 1.27 × 104 and 1.51 × 104 M-1 for NFT, CrO42-, Cr2O72- and UO22+. Finally, the mechanism of its luminescence sensing is studied in detail. These results manifest that complex 1 is a multifunctional sensor for sensitive fluorescent UO22+, Cr2O72-, CrO42- and NFT detection.

Frequency Of Uropathogens Showing Resistance To Nitrofurantoin.

Urinary tract infection (UTI) caused by bacteria is the commonest infection accountable for the unforeseen healthcare cost throughout the globe. Nitrofurantoin is being studied as a solution to the perpetually increasing threat of antimicrobial resistance. The objectives of this study were to determine the frequency of urinary isolates causing UTI and their susceptibility pattern against Nitrofurantoin. Data of all isolates reported as uropathogens from April 1, to December 31, 2021, was collected through Electronic Medical Record system of Shalamar Hospital, Lahore. Results of Nitrofurantoin susceptibility were recorded to find the resistance pattern of bacterial isolates. Out of a total of 3,221 samples, 672 (20.9%) were positive with significant bacteriuria. Of the positive samples, 418 (62.2%) were collected from females and 254 (37.8%) from males, with female to male ratio of 1.65:1. The number of female patients was higher in adult age. Of the positive samples, E. coli was the commonest isolate seen in 390 (58%) of samples, followed by Enterococcus spp. 92 (13.7%), Klebsiella spp. 86 (12.8%), Pseudomonas spp. 35 (5.2%), Staphylococcus saprophyticus 24 (3.6%), Proteus spp. 21 (3.1%), Citrobacter spp. 15 (2.2%), and Acinetobacter spp. 9 (1.3%). Overall, 587 (87.4%) isolates were sensitive to Nitrofurantoin. However, it showed increased resistance to 28 (32.6%) isolates of Klebsiella spp. E. coli remains the commonest uropathogen. In conclusion, Nitrofurantoin can be used to treat UTI caused by common bacterial pathogens except Klebsiella spp.

Eeyarestatin 24 impairs SecYEG-dependent protein trafficking and inhibits growth of clinically relevant pathogens.

Eeyarestatin 1 (ES1) is an inhibitor of endoplasmic reticulum (ER) associated protein degradation, Sec61-dependent Ca2+ homeostasis and protein translocation into the ER. Recently, evidence was presented showing that a smaller analog of ES1, ES24, targets the Sec61-translocon, and captures it in an open conformation that is translocation-incompetent. We now show that ES24 impairs protein secretion and membrane protein insertion in Escherichia coli via the homologous SecYEG-translocon. Transcriptomic analysis suggested that ES24 has a complex mode of action, probably involving multiple targets. Interestingly, ES24 shows antibacterial activity toward clinically relevant strains. Furthermore, the antibacterial activity of ES24 is equivalent to or better than that of nitrofurantoin, a known antibiotic that, although structurally similar to ES24, does not interfere with SecYEG-dependent protein trafficking. Like nitrofurantoin, we find that ES24 requires activation by the NfsA and NfsB nitroreductases, suggesting that the formation of highly reactive nitroso intermediates is essential for target inactivation in vivo.

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.

Smart prototype for an electronic color sensor device for visual simultaneous detection of macrofuran based on a coated paper strip.

Nowadays, in the clinical, pharmaceutical, and environmental sectors, the development of facile and sensitive analytical methods and/or innovative devices for the follow-up and detection of antibiotics and pharmaceutical formulations, in general, are urgently needed and still challenging. This work declared three vital applications for broad-spectrum nitrofurantoin (macrofuran) antibiotic detection and quantification: A colorimetric method, a coated paper strip-based nano-lanthanum complex prototype and fabrication of smart electronic color sensor device-based coated paper strips. The colorimetric method showed a significant response upon increasing the concentration of the nitrofurantoin in a range between (1.0-100.0 ng/mL) via a visual color change from orange-yellow to red colors degree with detection and quantification limits of 0.175 and 0.53 ng/mL, respectively, whereas the nano-lanthanum complex coated paper strip prototype showed qualitative on-site sensing for nitrofurantoin via naked eye color changes which can be detected anywhere. Moreover, a smart prototype for detecting macrofuran in the means of paper color change in the RGB color component extraction algorithm and the grayscale projection value processing algorithm was fabricated. The change in RGB color on the coated paper strip was detected using an electronic color sensor device. The developed colorimetric method, coated paper strip, and the electronic color sensor device prototype exhibited fast, simple, costless, and selective towards macrofuran over the competing analyzed. As well as, showed good applicability in the different real samples spiked with different concentrations of macrofuran.

In vitro assessment of the antibacterial effects of the combinations of fosfomycin, colistin, trimethoprim and nitrofurantoin against multi-drug-resistant Escherichia coli.

MDR UPEC has become a global health challenge. Our study investigates the pairwise interactions among FOS, COL, NIT and TRI against 29 UPEC strains using the checkerboard method. The synergistic combinations are further evaluated for their bactericidal effects against the most resistant strain (MRS) using the time-kill method. The results showed that 100% of these strains were resistant to TRI and NIT, whereas 75·86% of them were susceptible to FOS and COL. Among all tested strains, only seven strains were highly resistant to all used antibiotics. Remarkably, FOS/COL, COL/NIT and COL/TRI combinations represent the most effective synergistic (fractional inhibitory concentration index <1) combinations against the seven strains at MICs lower than the susceptible breakpoint ranges, followed by FOS/NIT and FOS/TRI, which achieved synergistic interactions against 1/7 and 2/7 of these strains. Importantly, the bactericidal effects (reduction ≥3·0 log10 CFU per ml) were only observed with FOS/COL, COL/NIT and COL/TRI combinations against MRS after 24 h of post-treatment. Our data suggested that FOS/COL, COL/NIT and COL/TRI combinations could be a promising option against MDR UPEC infections. Additionally, FOS/NIT and FOS/TRI probably represent a good option for MDR UPEC with lower MICs.

Highly sensitive SERS detection of residual nitrofurantoin and 1-amino-hydantoin in aquatic products and feeds.

Nitrofurantoin (NFT), a typical highly effective nitrofuran antibiotic drug, has been prohibited but still widely found in animal food products. It can be metabolized in animals to form 1-amino-hydantoin (AHD) that can then form stable and toxic metabolite-protein adducts. Hence, the detection of NFT and AHD in aquatic products and feeds is very important. However, there are limited reports concerning NFT detection and none about AHD by using surface-enhanced Raman spectroscopy (SERS) method. Herein, potassium bromide (KBr) decorated silver (Ag) nanoparticles (Ag-BrNPs)-based SERS approach was proposed for NFT and AHD detection. The limit of detection (LOD) for NFT was 1 µg/L. The detection of NFT residues in sea cucumber and fish feeds was also realized with the LOD of 1 and 50 ng/g, respectively. More importantly, the sensing of AHD was easily realized with the SERS approach for the first time. After the derivatization with 2-nitrobenzaldehyde (2-NBA), Ag-BrNPs were also successfully utilized for AHD detection in sea cucumber with the LOD of 5 ng/g.