Limited treatment options and multidrug-resistant (MDR) Klebsiella pneumoniae present a significant therapeutic challenge, underscoring the need for novel approaches. Drug repurposing is a promising tool for augmenting the activity of many antibiotics. This study aimed to identify novel synergistic drug combinations against K. pneumoniae based on drug repurposing. We used the clinically isolated GN 172867 MDR strain of K. pneumoniae to determine the reversal resistance activity of zidovudine (AZT). The combined effects of AZT and various antibiotics, including nitrofurantoin (NIT) and omadacycline (OMC), were examined using the checkerboard method, growth curves, and crystal violet assays to assess biofilms. An in vitro combination activity testing was carried out in 12 isolates of K. pneumoniae. In vivo murine urinary tract and lung infection models were used to evaluate the therapeutic effects of AZT + NIT and AZT + OMC, respectively. The fractional inhibitory concentration index and growth curve demonstrated that AZT synergized with NIT or OMC against K. pneumoniae strains. In addition, AZT + NIT inhibited biofilm formation and cleared mature biofilms. In vivo, compared with untreated GN 172867-infected mice, AZT + NIT and AZT + OMC treatment decreased colony counts in multiple tissues (P < 0.05) and pathological scores in the bladder and kidneys (P < 0.05) and increased the survival rate by 60% (P < 0.05). This study evaluated the combination of AZT and antibiotics to treat drug-resistant K. pneumoniae infections and found novel drug combinations for the treatment of acute urinary tract infections. These findings suggest that AZT may exert significant anti-resistance activity.

The excessive use of nitrofurantoin (NFT) represents a threat to ecosystems and food safety, making it necessary to develop efficient and accurate detection methods. Herein, the Ru/NiFe-LDH-MXene/SPCE electrode was successfully synthesized by one-step electrodeposition and employed to the NFT electrochemical sensing. Combining 2D MXenes with multifunctional 2D layered double hydroxides (LDHs) creates synergistic interactions within the MXene-LDH heterostructures, modifying the electrochemical performance. Furthermore, the incorporation of noble metal nanoparticles and nanoclusters can significantly enhance electrochemical performance by promoting favorable interactions at the metal-carrier interface and optimizing the rearrangement of electronic structure. Based on this, the developed Ru/NiFe-LDH-MXene/SPCE sensor demonstrates remarkable sensitivity (152.44 μA μM-1 cm-2) and an ultralow detection limit (2.2 nM). Notably, the sensor was employed for NFT detection in food samples with satisfactory recoveries, making it a promising electrochemical sensor for the detection of NFT.

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Polyurethane (PU) has a diverse array of customized physical, chemical, mechanical, and structural characteristics, rendering it a superb option for biomedical applications. The current study involves modifying the polyurethane surface by the process of aminolysis (aminolyzed polyurethane; PU-A), followed by covalently immobilizing Carboxymethyl cellulose (CMC) polymer utilizing Schiff base chemistry. Oxidation of CMC periodically leads to the creation of dialdehyde groups along the CMC chain. When the aldehyde groups on the OCMC contact the amine group on a modified PU surface, they form an imine bond. Scanning electron microscopy (SEM), contact angle, and X-ray photoelectron spectroscopy (XPS) techniques are employed to analyze and confirm the immobilization of OCMC on aminolyzed PU film (PU-O). The OCMC gel incorporates Nitrofurantoin (NF) and immobilizes it on the PU surface (PU-ON), creating an antibacterial PU surface. The confirmation of medication incorporation is achieved using EDX analysis. The varying doses of NF have demonstrated concentration-dependent bacteriostatic and bactericidal effects on both Gram-positive and Gram-negative bacteria, in addition to sustained release. The proposed polyurethane (PU-ON) surface exhibited excellent infection resistance in in vivo testing. The material exhibited biocompatibility and is well-suited for biomedical applications.

UNASSIGNED: Serious cutaneous adverse drug reactions (cADRs) are potentially life-threatening drug hypersensitivity reactions involving the skin and internal organs. Antibiotics are a recognized cause of these reactions, but no studies have compared relative risks across antibiotic classes.
UNASSIGNED: To explore the risk of serious cADRs associated with commonly prescribed oral antibiotics, and to characterize outcomes of patients hospitalized for them.
UNASSIGNED: Nested case-control study using population-based linked administrative datasets among adults aged 66 years or older who received at least 1 oral antibiotic between 2002 and 2022 in Ontario, Canada. Cases were those who had an emergency department (ED) visit or hospitalization for serious cADRs within 60 days of the prescription, and each case was matched with up to 4 controls who did not.
UNASSIGNED: Various classes of oral antibiotics.
UNASSIGNED: Conditional logistic regression estimate of the association between different classes of oral antibiotics and serious cADRs, using macrolides as the reference group.
UNASSIGNED: During the 20-year study period, we identified 21 758 older adults (median age, 75 years; 64.1% female) who had an ED visit or hospitalization for serious cADRs following antibiotic therapy and 87 025 matched controls who did not. In the primary analysis, sulfonamide antibiotics (adjusted odds ratio [aOR], 2.9; 95% CI, 2.7-3.1) and cephalosporins (aOR, 2.6; 95% CI, 2.5-2.8) were most strongly associated with serious cADRs relative to macrolides. Additional associations were evident with nitrofurantoin (aOR, 2.2; 95% CI, 2.1-2.4), penicillins (aOR, 1.4; 95% CI, 1.3-1.5), and fluoroquinolones (aOR, 1.3; 95% CI, 1.2-1.4). The crude rate of ED visits or hospitalization for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions; 95% CI, 4.86-4.99) and sulfonamide antibiotics (3.22 per 1000 prescriptions; 95% CI, 3.15-3.28). Among the 2852 case patients hospitalized for cADRs, the median length of stay was 6 days (IQR, 3-13 days), 9.6% required transfer to a critical care unit, and 5.3% died in the hospital.
UNASSIGNED: Commonly prescribed oral antibiotics are associated with an increased risk of serious cADRs compared with macrolides, with sulfonamides and cephalosporins carrying the highest risk. Prescribers should preferentially use lower-risk antibiotics when clinically appropriate.

BACKGROUND: Urinary tract infections (UTIs) are among the most common bacterial infections, and antibiotic resistance complicates empiric treatment. This study aimed to describe recent resistance patterns among uropathogens in a tertiary-care teaching hospital to optimize empiric UTI management.
METHODS: This retrospective observational study included 280 patients diagnosed with UTIs at the Dr. Patnam Mahender Reddy Institute of Medical Sciences, Hyderabad, over a six-month period from June 2023 to November 2023. Urine culture and antibiotic susceptibility data were collected from electronic medical records. Patient demographics, including age, sex, and comorbid diabetes, were recorded. Causative uropathogens and their resistance rates to commonly prescribed UTI antibiotics were analyzed. Empiric antibiotic treatment patterns and outcomes were talked about. These included clinical cure, recurrence, susceptibility match, and microbiologic eradication.
RESULTS:  The mean age of patients was 43.5 years, with 196 (70%) being female and 70 (25%) having diabetes. Escherichia coli caused 210 (75%) of UTIs, Klebsiella pneumoniae 42 (15%), Proteus mirabilis 14 (5%), Enterococcus faecalis 8 (3%), and Staphylococcus saprophyticus 6 (2%). E. coli resistance rates were 48% for ampicillin, 25% for ciprofloxacin, 18% for trimethoprim/sulfamethoxazole (TMP/SMX), and 5% for nitrofurantoin. K. pneumoniae resistance rates were 89% for ampicillin, 67% for ciprofloxacin, 44% for TMP/SMX, and 22% for nitrofurantoin. The most frequently prescribed antibiotic was nitrofurantoin (45%), then ciprofloxacin (35%). Clinical cure was achieved in 75% of cases. Recurrent UTIs within four weeks occurred in 25% of cases. Treatment matched urine culture susceptibility in 82% of patients.
CONCLUSIONS:  The rising fluoroquinolone resistance highlights the need for current local data to guide empiric UTI treatment. Nitrofurantoin had low resistance rates and was an effective first-line therapy. Ongoing monitoring of resistance patterns in UTIs is essential to optimize antibiotic selection.

Nitrofurantoin is the antibiotic of choice for treatment and prophylaxis of recurrent episodes of lower urinary tract infections. Although adverse effects such as anorexia, vomiting, and pulmonary hypersensitivity are commonly reported with nitrofurantoin use, studies have demonstrated that rarely nitrofurantoin can also induce diverse forms of liver injury, spanning from mild hepatitis to severe and potentially fatal fulminant liver failure. These occur especially in elderly females with preexisting liver or renal impairment. Here, we present a case of a 62-year-old female in good health who exhibited symptoms of fatigue, abdominal pain, and dark-colored urine. Through investigation, she was diagnosed with a case of drug-induced liver injury associated with the prolonged use of nitrofurantoin.
RésuméLa nitrofurantoïne est l’antibiotique de choix pour le traitement de la prophylaxie d’épisodes récurrents d’infections des voies urinaires intérieures. Bien que des effets indésirables tels que l’anorexie, des vomissements et une hypersensibilité pulmonaire soient fréquemments rapportés lors de l’utilisation de la nitrofuratoïne, des études ont demontré que dans de rares cas, la nitrofurantoïne peut également induire diverses formes de lésions hépatiques, allant d’une hépatite légère à une incapacité hépatique fulminante grave et potentiellement mortelle. Celle-ci surviennent particulièrement chez des femmes âgées ayant une insuffisance hépatique ou rénale préexistante.Nous présentons ici l’étude d’une femme de 62 ans en bonne santé qui manifestait des symptômes de fatigue, de douleurs abdominales et d’urine de couleur foncée. À travers une enquête, on lui a diagnostiquée un cas de lésion hépatique d’origine médicamenteuse associée à l’utilisation prolongée de la nitrofurantoïne.

OBJECTIVE: Nitrofurantoin is recommended as first-line therapy for the optimal treatment of uncomplicated urinary tract infections (UTIs) caused by enterococci and Escherichia coli. However, the mechanisms of nitrofurantoin resistance in enterococci have not been elucidated. This study aimed to investigate the mechanisms of nitrofurantoin resistance in E. faecium, focusing on the role of the nitroreductase NrmA.
METHODS: Enterococcus strains isolated from the urinary tract samples were collected and were tested for nitrofurantoin susceptibility. Potential genes associated with nitrofurantoin resistance were screened in the NCBI nucleotide database and by polymerase chain reaction (PCR). Complementation assays and enzyme kinetic tests were performed to assess the impact of the Q48K mutation in NrmA on nitrofurantoin resistance.
RESULTS: Of the 128 E. faecium isolates tested, 59 (46.1%) were resistant to nitrofurantoin. Analysis revealed the presence of a type IB nitroreductase, designated NrmA, in all E. faecium strains studied, shared 18.7% sequence identity with nitroreductase NfsB in E. coli. Different from NrmA in nitrofurantoin-susceptible E. faecium, nitrofurantoin-resistant strains had a single amino acid substitution, i.e., a lysine instead of a glutamine at position 48 (Q48K mutation). Complementation assays of nitrofurantoin-resistant E. faecium HS17-112 showed that the nitrofurantoin minimal inhibitory concentration of the complemented strain HS17-112: pIB166-nrmA (wild type [WT]) decreased from 128 mg/L to 4 mg/L. Compared with NrmA (WT), NrmA (Q48K) showed significantly reduced catalytic efficiency, with a kcat/Km value decreasing from 0.122 µM-1 s-1 to 0.000042 µM-1 s-1.
CONCLUSIONS: The Q48K mutation in nitroreductase NrmA is responsible for nitrofurantoin resistance in E. faecium.

1-Aminohydantoin (AHD), the residual marker of nitrofurantoin, is usually detected after derivatisation using the derivatisation reagent 2-nitrobenzaldehyde. Avoiding the antibody recognition of the derivatisation reagent is essential for the accurate detection of AHD residues. In this paper, a novel hapten called hapten D was designed, and then, a monoclonal antibody that did not recognise 2-nitrobenzaldehyde was prepared based on this novel hapten. An ultra-sensitive indirect competitive enzyme linked-immunosorbent assay (icELISA) was established under optimal conditions. The 50% inhibition concentration and limit of detection of AHD were 0.056 and 0.0060 ng/mL, respectively, which improved the sensitivity by 9-37-fold compared with the previously reported icELISA methods. The average recovery rates were 88.1%-97.3%, and the coefficient of variation was <8.6%. The accuracy and reliability of the icELISA were verified using liquid chromatography-tandem mass spectrometry. These results demonstrated that the developed icELISA is a useful and reliable tool.

UNASSIGNED: Wagenlehner F, Perry CR, Hooton TM, et al. Oral gepotidacin versus nitrofurantoin in patients with uncomplicated urinary tract infection (EAGLE-2 and EAGLE-3): two randomised, controlled, double-blind, double-dummy, phase 3, non-inferiority trials. Lancet. 2024;403:741-755. 38342126.