Fluoroquinolones tackling antimicrobial resistance: Rational design, mechanistic insights and comparative analysis of norfloxacin vs ciprofloxacin derivatives.

Antimicrobial resistance poses a global health concern and develops a need to discover novel antimicrobial agents or targets to tackle this problem. Fluoroquinolone (FN), a DNA gyrase and topoisomerase IV inhibitor, has helped to conquer antimicrobial resistance as it provides flexibility to researchers to rationally modify its structure to increase potency and efficacy. This review provides insights into the rational modification of FNs, the causes of resistance to FNs, and the mechanism of action of FNs. Herein, we have explored the latest advancements in antimicrobial activities of FN analogues and the effect of various substitutions with a focus on utilizing the FN nucleus to search for novel potential antimicrobial candidates. Moreover, this review also provides a comparative analysis of two widely prescribed FNs that are ciprofloxacin and norfloxacin, explaining their rationale for their design, structure-activity relationships (SAR), causes of resistance, and mechanistic studies. These insights will prove advantageous for new researchers by aiding them in designing novel and effective FN-based compounds to combat antimicrobial resistance.

Delafloxacin, an alternative treatment for levofloxacin-resistant staphylococci in osteoarticular infections: To use or not to use?

Susceptibility of delafloxacin on 199 osteoarticular levofloxacin-resistant staphylococci strains was reported in 49% and 1% using SSTI S. aureus breakpoint (0.25 mg/L) and general S. aureus breakpoint (0.016 mg/L) respectively. Fifty percents levofloxacin-resistant staphylococci showed resistance to delafloxacin using CA-SFM/EUCAST recommendations. Microbiological societies should define new breakpoints especially for CoNS.

Diagnosis and treatment challenges in a rare Clostridium infection: A case report.

The Clostridium genus includes >180 species of Gram-positive, anaerobic, sporulating bacteria. Under certain conditions, these can cause a wide range of invasive infections in humans. Clostridium paraputrificum occurs in the commensal intestinal flora and related bacteremia typically occurs secondary to an injury to the intestinal mucosa and in the presence of predisposing conditions, such as gastrointestinal disorders, malignancies, diabetes, HIV infection or neutropenia. The current study presents the case of a 70-year-old male patient, a rural resident living in poverty, with a history of alchohol consumption and cardiovascular pathology. Several initial and subsequent diagnoses were ruled out by successive investigations (e.g., stroke, meningitis, localized tetanus). Blood cultures were eventually found positive for Clostridium paraputrificum and the patient developed septic shock despite treatment with metronidazole and penicillin G. Once switched to carbapenem, the patient progressed favorably, suggesting that carbapenem could work as a first-line antibiotic treatment for Clostridium paraputrificum infections.

Evaluation of the efficiency of various methods to load fluoroquinolones into Escherichia coli outer membrane vesicles as a novel antibiotic delivery platform.

The development of novel antibacterial agents that are effective against Gram-negative bacteria is limited primarily by transport issues. This class of bacteria maintains a complex cell envelope consisting of two membrane bilayers, preventing the passage of most antibiotics. These drugs must therefore pass through protein channels called porins; however, many antibiotics are too large to pass through porins, and a common mechanism of acquired resistance is down-regulation of porins. To overcome this transport limitation, we have proposed the use of outer membrane vesicles (OMVs), released by Gram-negative bacteria, which deliver cargo to other bacterial cells in a porin-independent manner. In this work, we systematically studied the ability to load fluoroquinolones into purified Escherichia coli OMVs using in vivo and in vitro passive loading methods, and active loading methods such as electroporation and sonication. We observed limited loading of all of the antibiotics using passive loading techniques; sonication and electroporation significantly increased the loading, with electroporation at low voltages (200 and 400V) resulting in the greatest encapsulation efficiencies. We also demonstrated that imipenem, a carbapenem antibiotic, can be readily loaded into OMVs, and its administration via OMVs increases the effectiveness of the drug against E. coli. Our results demonstrate that small molecule antibiotics can be readily incorporated into OMVs to create novel delivery vehicles to improve antibiotic activity.

Fate of emerging antibiotics in soil-plant systems: A case on fluoroquinolones.

Fluoroquinolones (FQs), a class of broad-spectrum antibiotics widely used to treat human and animal diseases globally, have limited adsorption and are often excreted unchanged or as metabolites. These compounds enter the soil environment through feces, urban wastewater, or discharge of biological solids. The fluorine atoms in FQs impart high electronegativity, chemical stability, and resistance to microbial degradation, allowing them to potentially enter food chains. The persistence of FQs in soils raises questions about their impacts on plant growth, an aspect not yet conclusively determined. We reviewed whether, like other organic compounds, FQs are actively absorbed by plants, resulting in bioaccumulation and posing threats to human health. The influx of FQs has led to antibiotic resistance in soil microbes by exerting selective pressure and contributing to multidrug-resistant bacteria. Therefore, the environmental risks of FQs warrant further attention. This work provides a comprehensive review of the fate and behavior of FQs at the plant-environment interface, their migration and transport from the environment into plants, and associated toxicity. Current limitations in research are discussed and prospects for future investigations outlined. Thus, understanding antibiotic behavior in plants and translocation within tissues is not only crucial for ecosystem health (plant health), but also assessing potential human health risks. In addition, it can offer insights into the fate of emerging soil pollutants in plant-soil systems.

High performance enrichment and analysis of fluoroquinolones residues in environmental water using cobalt ion mediated paper-based molecularly imprinted polymer chips.

BACKGROUND: Fluoroquinolones (FQs) are widely used for their excellent antimicrobial properties, yet their release into aquatic environments pose risks to ecosystems and public health. The accurate monitoring and analysis of FQs present challenges due to their low concentrations and the complex matrices found in actual environmental samples. To address the need for auto-pretreatment and on-line instrumental analysis, developing new microextraction materials and protocols is crucial. Such advancements will provide better analytical assurance for the effective extraction and determination of FQs at trace levels, which is of great significance to environmental protection and human health. RESULTS: In this work, we presented a Co2+ mediated paper-based molecularly imprinted polymer chip (CMC@Co-MIP), combined with UPLC analysis, to develop an effective analytical method for identifying and quantifying trace amounts of ciprofloxacin (CIP) and enrofloxacin (ENR) in water samples. Notably, the addition of Co2+ in CMC@Co-MIP helped to capture the template molecule CIP through coordination before imprinting, which significantly improved the ordering of the imprinted cavities. CMC@Co-MIP exhibited a maximum adsorption capacity up to 500.20 mg g-1 with an imprinting factor of 4.12, surpassing previous reports by a significant margin. Furthermore, the enrichment mechanism was extensively analyzed by various characterization techniques. The developed method showed excellent repeatability and reproducibility (RSD < 13.0 %) with detection limits ranging from 0.15 to 0.21 µg L-1 and recoveries ranging from 64.9 % to 102.3 % in real spiked water samples. SIGNIFICANCE: We developed a novel microextraction paper-based chip based on Co2+ mediation, which effectively improved the selectivity and convenience of extracting FQs. This breakthrough allowed the chip to have a high enrichment efficiency as well as provide a robust on-line instrumental program. It also confirms that the imprinting scheme based on metal ion coordination is a high-performance strategy.

Alkaline metal tungstate anchored on functionalized-MWCNT: A co-active electrocatalyst for the detection of levofloxacin.

The widespread usage of levofloxacin (LVF) intake is executed for several urinary and respiratory systems infections in human. But, its over intake leads to severe damage to humans and the environment by its exposure. Hence the detection of LVF is concerned and we herein developed an electrocatalyst, strontium tungsten oxide nanospheres and later decorated onto the functionalized multiwall carbon nanotubes (SrWO4/f-MWCNT) to perform effective electrochemical recognition of LVF in aquatic and biological samples. Binary metal oxide with carbon composite SrWO4/f-MWCNT was developed due to its specific features as nanostructures. Various methods of investigation have been examined to identify the physiochemical characteristics like X-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and morphological characteristics including field emission scanning electron microscopy, and transmission electron microscopy. The synthesized SrWO4/f-MWCNT sample crystalline size was around 32.9 nm. The SrWO4/f-MWCNT modified glassy carbon electrode (GCE) has been subjected to electrochemical investigation with a wide linear range of 0.049 µM-574.73 µM with good sensitivity 2.86 µA µM-1 cm2, the limit of detection at 14.9 nM for LVF sensing. Furthermore, the designed LVF detection exhibited excellent anti-interference, stability, reproducibility, and repeatability. The as-developed sensor's electrochemical outcomes indicate the superior performance inherent in the developed composite.

Recent Development of Fluoroquinolone Derivatives as Anticancer Agents.

Cancer is the second leading cause of death in the world following cardiovascular disease. Its treatment, including radiation therapy and surgical removal of the tumour, is based on pharmacotherapy, which prompts a constant search for new and more effective drugs. There are high costs associated with designing, synthesising, and marketing new substances. Drug repositioning is an attractive solution. Fluoroquinolones make up a group of synthetic antibiotics with a broad spectrum of activity in bacterial diseases. Moreover, those compounds are of particular interest to researchers as a result of reports of their antiproliferative effects on the cells of the most lethal cancers. This article presents the current progress in the development of new fluoroquinolone derivatives with potential anticancer and cytotoxic activity, as well as structure-activity relationships, along with possible directions for further development.

Green Approach for Simultaneous Quantitative Analysis of Fluoroquinolones in the Environment using Three-Dimensional Fluorescence Coupled with Second-Order Calibration Method.

In this study, a straightforward and quick analytical technique based on the self-weighted alternating trilinear decomposition (SWATLD) algorithm in conjunction with excitation-emission matrix (EEM) fluorescence for the simultaneous determination of the antibiotics levofloxacin (LVFX) and ciprofloxacin (CIP) in environmental waters and sediments was developed. This approach completely utilizes the "second-order advantage" and inherits the great sensitivity of classic fluorescence. It replaces or improves the conventional "physical/chemical separation" with "mathematical separation", enabling direct and quick quantification of the target analytes even in the presence of unknown interferences, greatly streamlining sample preparation procedures, consuming less solvent, and speeding up analysis time, and allows successful and environmentally friendly solution of overlapping fluorescence spectra of multiple components in complicated environmental matrices without cumbersome pretreatment steps and complex and expensive instrumentation. The limits of detection varied between 0.34 and 0.67 ng mL- 1, and the average spiking recoveries of LVFX and CIP in water and sediment ranged from 97.6 to 107.7% with relative standard deviations lower than 6.6%. The developed method shows the reliability of the technology and the ability to quickly detect trace antibiotics in lake water even in the presence of unidentified interferents.

Development of Magnetic Porous Polymer Composite for Magnetic Solid Phase Extraction of Three Fluoroquinolones in Milk.

In this study, a magnetic porous polymer composite with both hydrophilic and hydrophobic groups was synthesized for magnetic solid phase extraction (MSPE) of milk substrates. Optimization was conducted on various parameters, including adsorption dose, solution pH, adsorption time, and some elution conditions. Coupled with a high-performance liquid chromatography fluorescence detector, a novel MSPE method for determination of norfloxacin (NFX), ciprofloxacin (CIP), and enrofloxacin (ENR) in milk was developed based on magnetic metal organic framework polystyrene polymer (Fe3O4@MOF@PLS) as adsorbent. The Fe3O4@MOF@PLS exhibited significantly improved adsorption performance compared to MOF and PLS. Under optimized experimental conditions, the method exhibited good linearity for the three fluoroquinolones (FQs) in the range of 0.5-1000 µg/kg, with limit of detections (LODs) ranging from 0.21 to 1.33 µg/kg, and limit of quantitations (LOQs) from 0.71 to 4.42 µg/kg. The relative standard deviation (RSD) for the three FQs were 3.4-8.8%. The recoveries of three FQs in milk samples ranged from 84.2% to 106.2%. This method was successfully applied to the detection of three FQs in 20 types of milk, demonstrating its simplicity, speed, and effectiveness in analyte enrichment and separation. The method presented advantages in adsorbent dosage, adsorption time, LODs, and LOQs, making it valuable for the analysis and detection of FQs in milk.

Green adsorbents for pharmaceutics removal from urine: Analysis of isotherms, kinetics, adsorption interactions, cost estimation, and environmental impact.

Husks of rice (RH), coffee (CH), and cholupa (CLH) were used to produce natural adsorbents. The natural adsorbents were used to remove pharmaceuticals such as diclofenac, ciprofloxacin, and acetaminophen in a mixture of distilled water. However, CH stood out for its efficiency in removing ciprofloxacin (74%) due to the higher concentration of acidic groups, as indicated by the Boehm method. In addition, CH removed 86% of ciprofloxacin individually. Therefore, CH was selected and used to remove other fluoroquinolones, such as levofloxacin and Norfloxacin. Although electrostatic interactions favored removals, better removal was observed for ciprofloxacin due to its smaller molecular volume. Then, ciprofloxacin was selected, and the effect of pH, matrix, and adsorbent doses were evaluated. In this way, using a pH of 6.2 in urine with a dose of 1.5 g L-1, it is possible to adsorb CIP concentrations in the range (0.0050-0.42 mmol L-1). Subsequently, the high R2 values and low percentages of APE and Δq indicated better fits for pseudo-second-order kinetics, suggesting a two-stage adsorption. At the same time, the Langmuir isotherm recommends a monolayer adsorption with a Qm of 25.2 mg g-1. In addition, a cost of 0.373 USD/g CIP was estimated for the process, where the material can be reused up to 4 times with a CIP removal in the urine of 51%. Consequently, thermodynamics analysis showed an exothermic and spontaneous process with high disorder. Furthermore, changes in FTIR analysis after adsorption suggest that CH in removing CIP in urine involves electrostatic attractions, hydrogen bonds and π-π interactions. In addition, the life cycle analysis presents, for the 11 categories evaluated, a lower environmental impact of the CIP removal in urine with CH than for the preparation of adsorbent, confirming that the adsorption process is more environmentally friendly than materials synthesis or other alternatives of treatments. Furthermore, future directions of the study based on real applications were proposed.

A triple-channel sensor array utilizing fluorescent carbon dots for simultaneous discrimination and detection of multiple fluoroquinolones.

The presence of fluoroquinolones (FQs) residues in food and the environment has prompted concerns regarding food safety and public health. Consequently, it is of great significance to analyze the types and levels of FQs present. However, the majority of studies have concentrated on the specific detection of individual FQs, with a notable absence of high-throughput and rapid analysis methods for the simultaneous detection of multiple FQs that may coexist in food and the environment. Hereon, a triple-channel sensor array was successfully constructed utilizing fluorescent carbon dots (TA-CDs), with the assistance of Cu2+ and Fe3+, for the qualitative discrimination and quantitative detection of eight types of FQs. The sensor array can distinguish between different concentrations of FQs and various mixtures of FQs, as well as 100 % accuracy in the discrimination of unknown samples. Impressively, the sensor platform can quantitatively detect FQs in animal-derived foods, such as honey, milk, eggs, and pork, as well as in water samples. This research has the potential to be extended to other analytes with similar chemical structures or properties.

Fluorescence array sensor based on lanthanide complex for pattern recognition detection of fluoroquinolone antibiotics.

Fluoroquinolone antibiotics, a class of animal and human useful antibiotics, are widely utilized in numerous fields including biomedical science, animal husbandry, and aquatic finfish farming. Its high demand and wide application have directly or indirectly led to substantial consumption and discharge of antibiotics, affecting not only the environment but also endangering human health through bioaccumulation. Hence, rapid and precise detection of trace antibiotics in water, food, and biological samples is critically important. This research synthesized Tb3+/Eu3+ complexes with dual emission centers, and a fluorescence sensor array was constructed with the fluorescence intensity ratio F1/F2 of the two emission centers as a signal. Different sensitization effect of fluoroquinolone antibiotics towards lanthanide complexes aided in differentiating five fluoroquinolone antibiotics from two others. Additionally, the sensor array can effectively detect fluoroquinolone antibiotics in real samples, suggesting its reliability and practicality of complex sample analysis. The excellent qualitative and quantitative analysis ability of this strategy for fluoroquinolone antibiotics offers a novel perspective for antibiotic residue detection, showcasing a new opportunity for lanthanide complex application in sensor arrays.

A ratiometric fluorescence sensor with different responsive modes based on carbon dots-embedded Tb-MOFs for the determination of norfloxacin and levofloxacin.

Norfloxacin (NOR) and levofloxacin (LEV) are the two most frequently used fluoroquinolones (FQs) in clinic. Their residues seriously endanger the ecosystem and human health. Due to their similarity in structure and properties, it is urgent to develop an efficient and sensitive strategy for detection and differentiation. Herein, we synthesized a novel ratiometric fluorescent sensor for the first time by combining N, S co-doped carbon dots (CDs) and the precursors of Tb-MOFs through a facile one-pot method. The introduction of CDs effectively facilitated the energy transfer between Tb3+ and FQs, overcoming the limitation that single Tb-MOFs could not identify similar antibiotics. Specifically, the presence of NOR resulted in reverse signal response through the inner filter effect and antenna effect. The synergistic effect of these two mechanisms contributed to achieving signal amplification accompanied by a distinguishable color transition. The limit of detection (LOD) was 0.036 µM. Different from NOR, the addition of LEV reduced the electron density of the system, weakened the coordination ability of Tb3+ with LEV, and induced a single signal response with Tb3+ fluorescence intensity as a reference signal (LOD = 0.383 µM). Furthermore, the method proved to be rapid and visual, allowing for the straightforward analysis of FQs residues in water, food matrices, and biological samples with satisfactory precision. By integrating N, S-CDs@Tb-MOFs with flexible substrates, the paper-based sensor facilitated the visual quantitative determination of FQs by reading RGB values. The developed sensor presents a promising strategy for the identification and real-time monitoring of antibiotics.

Levofloxacin-Induced Arthralgia in Multidrug-Resistant Tuberculosis Patients: A Case Series Spanning Three Age Groups.

Multidrug-resistant TB (MDR-TB) is a form of tubercular disease caused by a strain of Mycobacterium tuberculosis complex that is resistant to rifampicin and isoniazid. Microbiologically diagnosed patients are started on an all-oral longer regimen or shorter regimen based on the Guidelines on Programmatic Management of Drug Resistant TB (PMDT) in India. Fluoroquinolones (FQs), being the cornerstone in the treatment of MDR-TB, are categorized as class A drugs. Levofloxacin (Lfx) administered at a dose of 11-14 mg/kg/day holds a strong bactericidal activity against Mycobacterium tuberculosis. FQs are associated with a wide range of adverse drug reactions, such as nausea, bloating, headache, dizziness, and insomnia. Tendon rupture, arthralgia though rare, can also occur due to Lfx. Even though arthralgia is commonly seen in patients on Lfx-associated treatment, only a few cases have been reported in India to date. We present a case series involving three cases of Lfx-induced arthralgia in patients of different age groups who are started on an all-oral longer regimen after they were diagnosed with MDR-TB. Based on the treatment protocol, patients were rechallenged or switched to other drugs in the replacement sequence as per the weight band.

Comparison of Mutant Prevention Concentrations of Fluoroquinolones Against ESBL-Positive and ESBL-Negative Klebsiella pneumoniae Isolates from Orthopedic Patients.

The majority of Klebsiella pneumonia isolates possess the extended-spectrum beta-lactamase (ESBL) enzymes. Therefore, K. pneumoniae can easily develop drug resistance. How to effectively overcome the problem of drug resistance in K. pneumoniae is still a research hotspot. This study aimed to compare the mutant prevention concentration (MPC) of ESBL-positive and ESBL-negative K. pneumoniae isolated from orthopedic patients, which may provide a basis for the effective use of drugs to control the enrichment of resistance mutants of K. pneumoniae. The MPC90 values of 55 isolates of ESBL-positive K. pneumoniae against 4 fluoroquinolones were 32 µg/mL for levofloxacin and gatifloxacin, 16 µg/mL for ciprofloxacin, and 4 µg/mL for gemifloxacin. The selection index value was 8 for levofloxacin and ciprofloxacin and 2 for gemifloxacin and gatifloxacin, respectively. For ESBL-negative K. pneumoniae isolates, the MPC90 values were 16 µg/mL for levofloxacin and ciprofloxacin, 4 µg/mL for gemifloxacin, and 32 µg/mL for gatifloxacin. The selection index value was 8 for levofloxacin and ciprofloxacin, 2 for gemifloxacin, and 4 for gatifloxacin. For the ESBL-positive K. pneumoniae, the %T>MIC90 order was gemifloxacin > levofloxacin > ciprofloxacin > gatifloxacin. For the ESBL-negative K. pneumoniae, the %T>MIC90 order was levofloxacin > gemifloxacin > ciprofloxacin > gatifloxacin. The mutant-preventing ability of gatifloxacin and gemifloxacin was the strongest among the 4 fluoroquinolones. So gemifloxacin may be the first choice of drug to treat K. pneumoniae infection.

Pattern and characteristics of mutations conferring resistance to second line drugs in Mycobacterium tuberculosis isolates of pulmonary and extrapulmonary TB samples.

BACKGROUND & OBJECTIVES: The purpose of present study is to analyse the distribution and pattern of genetic mutations in PRE-XDR-TB and extensive drug resistant Mycobacterium tuberculosis (XDR-TB) using second-line line probe assay and to compare them with different parameters. METHOD: Sputum, Lymph node aspirate and cold accesses from patients with rifampicin resistant Tuberculosis were subjected to first line and second line Probe Assay (Genotype MTBDRsl by Hain Life Science, Germany) to assess additional drug resistance to fluroquinolones (Levofloxacin & Moxifloxacin) and Aminoglycosides (Amikacin, Ofloxacin and Kanamycin). The genetic mutation pattern was analysed and compared with demographic, clinical and other parameters. RESULTS: The final study population included 123 fluoroquinolone resistant isolates including 14 isolates with additional second line aminoglycosides drug resistance. The most frequent mutation observed among Gyr A drug resistance mutation was D94G (Gyr A MUT3C, 50/123,40%) corresponding to high level resistance to levofloxacin and moxifloxacin. The most frequent wild type mutant among Gyr A gene locus was WT 3 (85/123,69%). The most common mutation among second line aminoglycoside resistant isolates was at eis WT2 (7/14,50%) followed by rrs MUT 2 (4/14,29%). CONCLUSIONS: GyrA MUT3C (Asp94Gly) was the most common mutation in Gyr A gene locus in M. tuberculosis causing high level levofloxacin and moxifloxacin resistance. Patients with Asp94Gly mutation was significantly associated with underweight body mass index (p = 0.026). This study also observed that history of anti-tuberculosis therapy is a risk factor for FQ drug resistance mutations (p < 0.001).

Silver nanoparticle with potential antimicrobial and antibiofilm efficiency against multiple drug resistant, extensive drug resistant Pseudomonas aeruginosa clinical isolates.

BACKGROUND: The study aims to investigate the effect of combining silver nanoparticles (AGNPs) with different antibiotics on multi-drug resistant (MDR) and extensively drug resistant (XDR) isolates of Pseudomonas aeruginosa (P. aeruginosa) and to investigate the mechanism of action of AGNPs. METHODS: AGNPs were prepared by reduction of silver nitrate using trisodium citrate and were characterized by transmission electron microscope (TEM) in addition to an assessment of cytotoxicity. Clinical isolates of P. aeruginosa were collected, and antimicrobial susceptibility was conducted. Multiple Antibiotic Resistance (MAR) index was calculated, and bacteria were categorized as MDR or XDR. Minimum inhibitory concentration (MIC) of gentamicin, ciprofloxacin, ceftazidime, and AGNPs were determined. The mechanism of action of AGNPs was researched by evaluating their effect on biofilm formation, swarming motility, protease, gelatinase, and pyocyanin production. Real-time PCR was performed to investigate the effect on the expression of genes encoding various virulence factors. RESULTS: TEM revealed the spherical shape of AGNPs with an average particle size of 10.84 ± 4.64 nm. AGNPS were safe, as indicated by IC50 (42.5 µg /ml). The greatest incidence of resistance was shown against ciprofloxacin which accounted for 43% of the bacterial isolates. Heterogonous resistance patterns were shown in 63 isolates out of the tested 107. The MAR indices ranged from 0.077 to 0.84. Out of 63 P. aeruginosa isolates, 12 and 13 were MDR and XDR, respectively. The MIC values of AGNPs ranged from 2.65 to 21.25 µg /ml. Combination of AGNPs with antibiotics reduced their MIC by 5-9, 2-9, and 3-10Fold in the case of gentamicin, ceftazidime, and ciprofloxacin, respectively, with synergism being evident. AGNPs produced significant inhibition of biofilm formation and decreased swarming motility, protease, gelatinase and pyocyanin production. PCR confirmed the finding, as shown by decreased expression of genes encoding various virulence factors. CONCLUSION: AGNPs augment gentamicin, ceftazidime, and ciprofloxacin against MDR and XDR Pseudomonas isolates. The efficacy of AGNPs can be attributed to their effect on the virulence factors of P. aeruginosa. The combination of AGNPs with antibiotics is a promising strategy to attack resistant isolates of P. aeruginosa.