Introduction: Urinary tract infection (UTI) is one of the most common infectious diseases in clinical practice. The choice of antibiotics for the treatment of UTI is limited by the rising rates of antibiotic resistance. There is an urgent need to discover new effective treatment solutions. Fosfomycin may be an interesting alternative to the currently used treatments of UTIs. Materials and Methods: The study was conducted over 6 months period (January to June 2013) in Department of Microbiology, JNMCH, AMU, Aligarh. A total of 1840 urine samples were submitted. Culture and sensitivity was done as per standard microbiological procedures. Methicillin-resistant Staphylococcus aureus (MRSA), high-level aminoglycoside resistance (HLAR), extended spectrum beta-lactamases (ESBL), AmpC and metallo-beta-lactamases (MBL) production was detected. Results: Culture was positive in 504 (27.4%) cases. Gram-negative etiology was identified in 390 (73%) cases. ESBL production was detected in 154 (37.1%) while 82 (21.6%) were Amp C. No, MBL was detected. Among Gram-positive bacteria, 68 (51.5%) were MRSA, while 4 (13.3%) were vancomycin resistant enterococci (VRE). HLAR was seen in 53.3% of enterococci. Fosfomycin was effective in 100% of MRSA, VRE, ESBL, HLAR, and overall, susceptibility to fosfomycin in AmpC producers was extremely high (99%). Norfloxacin and cotrimoxazole were not proved effective as only three isolates were sensitive to norfloxacin, while all Gram-negative isolates were resistant to cotrimoxazole. Pseudomonas species showed 65% and 75% susceptibility to colistin and polymixin B, respectively. Conclusion: Fosfomycin has emerged as a promising option, especially in cases involving multi-drug-resistant pathogens in which previous antibiotics have failed to cure the infection.

The rapid rise of antimicrobial resistance (AMR) has emerged as a critical global health crisis, driven by the widespread emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) pathogens. This growing threat, coupled with the stagnation in the development of novel antibiotics, necessitates the investigation of alternative antimicrobial strategies. Plant-derived essential oils (EOs) have emerged as promising candidates due to their broad-spectrum antibacterial activity, multi-targeted mechanisms, and capacity to enhance the efficacy of existing antibiotics. Recent studies have underscored the potential of EOs in disrupting biofilms, inhibiting quorum sensing, modulating efflux pumps, and reversing resistance in a variety of bacterial pathogens, including those listed as priorities by the World Health Organization. Notably, many of these effects have been demonstrated against resistant strains isolated directly from clinical samples, thereby enhancing the translational significance of EOs. In addition to their antimicrobial properties, advances in analytical, omics-based, and microfluidic technologies have further elucidated the mechanisms of EOs and may accelerate their therapeutic development. Nevertheless, challenges such as variability in composition, lack of standardized testing protocols, and limited in vivo data continue to impede clinical application. Therefore, the aim of this scoping review is to critically examine the advances over the past decade in the antibacterial activity of plant EOs against clinical isolates, with a particular focus on their efficacy against resistant bacterial pathogens and their potential role in combating AMR.

Background: During the second wave of the COVID-19 pandemic, outbreaks of Zika were reported from Kerala, Uttar Pradesh, and Maharashtra, India in 2021. The Dengue and Chikungunya negative samples were retrospectively screened to determine the presence of the Zika virus from different geographical regions of India.Methods: During May to October 2021, the clinical samples of 1475 patients, across 13 states and a union territory of India were screened and re-tested for Dengue, Chikungunya and Zika by CDC Trioplex Real time RT-PCR. The Zika rRTPCR positive samples were further screened with anti-Zika IgM and Plaque Reduction Neutralization Test. Next generation sequencing was used for further molecular characterization.Results: The positivity was observed for Zika (67), Dengue (121), and Chikungunya (10) amongst screened cases. The co-infections of Dengue/Chikungunya, Dengue/Zika, and Dengue/Chikungunya/Zika were also observed. All Zika cases were symptomatic with fever (84%) and rash (78%) as major presenting symptoms. Of them, four patients had respiratory distress, one presented with seizures, and one with suspected microcephaly at birth. The Asian Lineage of Zika and all four serotypes of Dengue were found in circulation.Conclusion: Our study indicates the spread of the Zika virus to several states of India and an urgent need to strengthen its surveillance.

Human serum albumin (HSA) is the most prevalent protein in the blood plasma which binds an array of exogenous compounds. Drug binding to HSA is an important consideration when developing new therapeutic molecules, and it also aids in understanding the underlying mechanisms that govern their pharmacological effects. This study aims to investigate the molecular binding of coronavirus disease 2019 (COVID-19) therapeutic candidate molecules to HSA and to identify their putative binding sites. Binding energies and interacting residues were used to evaluate the molecular interaction. Four drug candidate molecules (β-D-N4-hydroxycytidine, Chloroquine, Disulfiram, and Carmofur) demonstrate weak binding to HSA, with binding energies ranging from −5 to −6.7 kcal/mol. Ivermectin, Hydroxychloroquine, Remdesivir, Arbidol, and other twenty drug molecules with binding energies ranging from −6.9 to −9.5 kcal/mol demonstrated moderate binding to HSA. The strong HSA binding drug candidates consist of fourteen molecules (Saquinavir, Ritonavir, Dihydroergotamine, Daclatasvir, Paritaprevir etc.) with binding energies ranging from −9.7 to −12.1 kcal/mol. All these molecules bind to different HSA subdomains (IA, IB, IIA, IIB, IIIA, and IIIB) through molecular forces such as hydrogen bonds and hydrophobic interactions. Various pharmacokinetic properties (gastrointestinal absorption, blood-brain barrier permeation, P-glycoprotein substrate, and cytochrome P450 inhibitor) of each molecule were determined using SwissADME program. Further, the stability of the HSA-ligand complexes was analyzed through 100 ns molecular dynamics simulations considering various geometric properties. The binding free energy between free HSA and compounds were calculated using Molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) and molecular mechanics generalized Born surface area (MM/GBSA) approach. The findings of this study might be useful in understanding the mechanism of COVID-19 drug candidates binding to serum albumin protein, as well as their pharmacodynamics and pharmacokinetics.

Introduction: Urinary tract infection (UTI) continues to be the most common infection diagnosed in outpatients as well as in hospitalized patients. Citrobacter spp. is an emerging urinary pathogen. The present study assessed the prevalence and antibiotic sensitivity pattern of Citrobacter spp. in patients admitted to or attending outpatient departments with Complain of UTI in a tertiary care hospital. Materials and Methods: A total of 36,250 urine samples were included in the study. UTI was confirmed in 7099 samples. Of these 246 (3.46%) had UTI due to Citrobacter spp. Identification was by conventional biochemical methods. Antimicrobial susceptibility testing was performed using Kirby-Bauer disc diffusion method as recommended by Clinical and Laboratory Standards Institute M2-A9. Multidrug-resistant (MDR) was defined as resistance to more than two groups of drugs. Extended spectrum beta-lactamase (ESBL), AmpC, and metallo beta-lactamase (MBL) were detected by phenotypic methods. Results: Females predominated in the study 193 (78.4%) with 53 (21.5%) males. Most of the isolates were in the age group 21-30 and 31-40. 49 (19.9%) patients were inpatients, and 197 (80.08%) were outpatients. Aminoglycosides had a better spectrum of antimicrobial sensitivity (70.2%) with 85.2% isolates sensitive to amikacin. Fluoroquinolones had a poor activity against Citrobacter (46% sensitive). Ureidopenicillins had poor efficacy (15.4%). Out of the 246 strains, 129 (52.4%) were MDR, 61 (24.7%) of which were ESBL producers and 65 (26.4%) were AmpC producers. Most of the ESBL producing strains were isolated from inpatients. No MBL were identified in this study. Conclusion: Citrobacter though not uncommon isolate is posing a problem due to its MDR character. Infection control practices should be observed strictly, and any type of unnecessary instrumentation should be avoided.

Fosfomycin has emerged as a very useful antimicrobial in management of extremely drug resistant (XDR) and pan drug resistant (PDR) Klebsiella pneumoniae. In this study, we assessed in-vitro synergy of colistin sparing combinations of fosfomycin (FOS) with meropenem (MEM), tigecycline (TGC) and amikacin (AK) against XDR and PDR Klebsiella pneumoniae. Method: Non-replicate fully characterised 18 clinical isolates of K. pneumoniae (15 XDR and 3 PDR strains) were subjected to in-vitro synergy testing by checkerboard and time kill assay. Combinations tested were FOS-MEM, FOS-TGC and FOS-AK with glucose-6-phosphate being incorporated in all runs.WGS was carried out on the Illumina next-generation sequencing platform. Results: FOS-MEM and FOS-AK both demonstrated excellent synergy against all PDRs and all but one XDR. Synergy led to lowering of MICs to susceptible breakpoints. FOS-TGC demonstrated antagonism. MLST-231 K. pneumoniae predominated (14), followed by ST-395 (3) and ST147 (1). Majority harboured OXA-232 (n = 15), while n = 2 carried NDM-1 type and n = 1 co-carried NDM-5 + OXA-232. Mortality was high in both ST-231 (57.1%) and ST-395 (66.6%). Synergy was observed despite widespread presence of resistance markers against aminoglycosides [aph(3′)-Ic, aacA4, and rmtf], beta-lactams [blaSHV-11, blaTEM-1b, blaCTX-M-15, and blaOXA-232], fosfomycin [fosA6 and fosA5] and presence of porin proteins OmpK37, OmpA and K. pneumoniae antibiotic efflux pumps Kpn F, H, G, and E. Conclusion: FOS + MEM and FOS + AK are excellent colistin sparing combinations against ST 231, ST-395 and ST-147 XDR and PDR K. pneumoniae. FOS with fewer side effects than colistin, excellent tissue distribution and minimal side effects may be recommended in combination with meropenem.