Efficacy Of Ciprofloxacin Research Articles

Efficacy of Ciprofloxacin in Treating Gram-Negative Infections: Does Obesity Matter?

Obesity is considered a health issue associated with increased morbidity and a risk factor for multiple conditions, such as type 2 diabetes, cardiovascular diseases and infections. It may affect the pharmacokinetics and pharmacodynamics of many drugs, including antimicrobials like ciprofloxacin. Regrettably, data on ciprofloxacin's efficacy in obese patients remain scarce. This study aims to evaluate the impact of obesity on the efficacy of ciprofloxacin in treating Gram-negative bacterial infections. A retrospective multicenter cohort study was conducted in two tertiary hospitals in Saudi Arabia. Adult patients (≥18 years) treated with ciprofloxacin for confirmed Gram-negative infection between January 2017 and April 2023 were included. Patients were excluded if they received ciprofloxacin empirically, had inadequate source control within 72 h, or had missing weight and height information at ciprofloxacin initiation. The primary outcome was clinical cure, defined as the resolution of the clinical infection manifestations without additional therapeutic management by the end of treatment. Other secondary and safety outcomes were also assessed. A total of 99 patients were included, divided into obese (n = 42) and non-obese (n = 57) groups. The obese group had a significantly lower median age (50 years) compared to the non-obese group (64 years) (p = 0.002). The obese group had fewer male patients (38.10% vs. 68.42%; p = 0.004), higher body weight (90 (81-97) vs. 63 (55-70) days; p < 0.001), and lower height (158 (155-165) vs. 165 (158-172) days; p = 0.008) compared to non-obese. Urinary tract infection was the most common type, with Escherichia coli being the most common isolate. The median hospital length of stay was shorter in the obese group than in the non-obese group (1 vs. 3 days, p = 0.007). There were no significant differences in clinical cure rates between obese (85.71%) and non-obese (85.96%) patients (p = 1). No significant differences were observed in terms of in-hospital mortality, 30-day mortality, or 60-day infection recurrence rates between the two groups. Microbiological eradication was not achieved in the obese group, whereas a 10.53% eradication rate was observed in the non-obese group (p = 0.037). However, the majority of the patients had indeterminate eradication. The incidence of adverse drug reactions (ADRs) was lower in the obese group (4.76%) compared to the non-obese group (17.54%, p = 0.066). Treatment with ciprofloxacin in obese patients has similar efficacy and safety outcomes compared to non-obese patients with infections due to Gram-negative pathogens.

Assessing the Influence of Urine pH on the Efficacy of Ciprofloxacin and Fosfomycin in Immunocompetent and Immunocompromised Murine Models of Escherichia coli and Klebsiella pneumoniae Infection in the Lower Urinary Tract.

In vitro studies have suggested that acidic pH may reduce and increase the efficacy of ciprofloxacin and fosfomycin, respectively, when used to treat Escherichia coli and Klebsiella pneumoniae infections. We assessed the effects of acidic, neutral, and alkaline urine pH on the efficacy of optimized ciprofloxacin and fosfomycin dosages in UTI murine model of E. coli and K. pneumoniae. Immunocompetent and immunocompromised mice with adjusted urine pH were inoculated with E. coli and K. pneumoniae strains, and the efficacy was assessed based on the bacterial concentrations in tissues and fluids at 72 h, with respect to untreated controls. At acidic urine pH, both antimicrobials were effective, achieving similar reductions in E. coli concentrations in the kidneys in immunocompetent and immunocompromised mice and in K. pneumoniae in immunocompetent mice. At a neutral urine pH, both therapies reduced the presence of E. coli in the kidneys of immunocompetent mice. However, in immunocompromised mice, antimicrobials were ineffective at treating E. coli infection in the kidneys at a neutral urine pH and showed reduced efficacy against K. pneumoniae at both acidic and neutral urine pH. The results showed no correlation between urine pH and antimicrobial efficacy, suggesting that the reduced effectiveness is associated with the animals' immunocompetence status.

Murepavadin Enhances the Killing Efficacy of Ciprofloxacin against Pseudomonas aeruginosa by Inhibiting Drug Efflux.

Pseudomonas aeruginosa is a multidrug-resistant Gram-negative pathogen and one of the leading causes of ventilator-associated pneumonia and infections in patients with chronic obstructive pulmonary disease and cystic fibrosis. Murepavadin is a peptidomimetic that specifically targets outer-membrane lipopolysaccharide transport protein LptD of P. aeruginosa. In this study, we find that murepavadin enhances the bactericidal efficacy of ciprofloxacin. We further demonstrate that murepavadin increases intracellular accumulation of ciprofloxacin by suppressing drug efflux. In addition, the murepavadin-ciprofloxacin combination exhibits a synergistic bactericidal effect in an acute murine pneumonia model. In conclusion, our results identify an effective drug combination for the treatment of P. aeruginosa infections.

Investigation of the role of Cremophor RH 40 and Cremophor EL in the inhibition of efflux pump of Pseudomonas aeruginosa

BackgroundThere is increasing emphasis on restoring the efficacy of existing antibiotics instead of developing new ones. ObjectivesThis study aimed to determine the role of Cremophor EL and Cremophor RH40 in the inhibition of efflux pumps in MDR Pseudomonas aeruginosa strains. MethodsEfflux pump-active MDR strains of P. aeruginosa were identified and confirmed by flow cytometry. The identified efflux-active strains were further subjected to determination of the MIC of ciprofloxacin and the synergistic role of non-ionic surfactants (Cremophor EL and Cremophor RH40) along with ciprofloxacin. ResultsOut of 30 samples, 6 strains displayed high efflux pump activity. Both Cremophor EL and Cremophor RH40 showed efflux pump inhibitory roles. A 4-fold reduction in the MIC values of ciprofloxacin was observed when Cremophor EL was used along with ciprofloxacin, while a 6-fold reduction was observed when Cremophor RH40 was used along with ciprofloxacin. Both compounds showed synergistic effects with ciprofloxacin, ticarcillin and meropenem when used in a 24-well plate efflux pump inhibitory assay. ConclusionThe inhibition of the efflux pump of MDR Pseudomonas aeruginosa by non-ionic surfactants, namely, Cremophor RH40 and Cremophor EL, provided the best strategy to restore the efficacy of ciprofloxacin.

Enhanced Efficacy of Ciprofloxacin and Tobramycin against Staphylococcus aureus When Combined with Corydalis Tuber and Berberine through Efflux Pump Inhibition.

One way that bacteria develop antibiotic resistance is by reducing intracellular antibiotic concentrations through efflux pumps. Therefore, enhancing the efficacy of antibiotics using efflux pump inhibitors provides a way to overcome this type of resistance. Notably, an increasing number of pathogenic Staphylococcus aureus strains have efflux pump genes. In this study, the extract from Corydalis ternata Nakai tuber (Corydalis Tuber) at 512 mg/L was demonstrated to have an antibiotic synergistic effect with ciprofloxacin at 2 mg/L and tobramycin at 1024 mg/L against methicillin-resistant S. aureus (MRSA). Berberine, an isoquinoline alkaloid identified in Corydalis Tuber, was identified as contributing to this effect. Ethidium bromide efflux pump activity assays showed that Corydalis Tuber extract and berberine inhibited efflux, suggesting that they are efflux pump inhibitors. Molecular docking simulations suggested that berberine binds to S. aureus efflux pump proteins MepA, NorA, NorB, and SdrM. Additionally, berberine and Corydalis Tuber extract inhibit biofilm formation, which can confer antibiotic resistance. This study's findings suggest that Corydalis Tuber, a traditional herbal medicine, and berberine, a medicinal supplement, act as S. aureus efflux pump inhibitors, synergistically increasing the efficacy of ciprofloxacin and tobramycin and showing promise as a treatment for antibiotic-resistant S. aureus infections, including MRSA.

Comparison of Efficacy of Ciprofloxacin and Co-Trimoxazole in Escherichia Coli Urinary Tract Infection

Objective: To compare the efficacy of ciprofloxacin and co-trimoxazole in urinary tract infection due to Escherichia Coli.Study Design: A cross- sectional study. Place and Duration of Study: This study was conducted at the Department of Medicine, Muhammad TeachingHospital (MTH), Peshawar, Pakistan from 1 July 2022 to 31 December 2022.Methods: Patients were randomly and consecutively assigned to either group by using lottery method (double blind). A total of 194 patients diagnosed with urinary tract infection due to E coli were randomly divided into two groups, 97 patients in each group, using 54% efficacy of ciprofloxacin, 74% efficacy of Co-Trimoxazole, 95% confidence level, and 90% power of test, using WHO software. “Group-A' for Ciprofloxacin 500mg BD and th 'Group-B' for Co-Trimoxazole 960mg BD. All the recruited patients were followed up after the 48 hour of their treatment and results were recorded. The chi-Square test was applied to compare the efficacy results of both drugs where a PValue &lt; 0.05 was considered as significant value.Results: The mean age of group A participants were 48.4 + 11.1 years, whereas, in group B it was 48.2 + 11.5 years. There were 69.1% males and 30.9% females in group A compared to 80.4% males and 19.6% females ingroup B. After the 48 hour of end treatment, efficacy was 79.3% and 50.5%, in groups A and B respectively (p-value = 0.000).Conclusion: As compared to Cotrimoxazole, Ciprofloxacin is more effective in treating E. coli-caused urinary tract infections. How to cite this: Ayaz M, Kausar SAZ, Alamgir M, Muhammad S, Khan FM, Ullah S. Comparison of Efficacy of Ciprofloxacin and CoTrimoxazole in Escherichia Coli Urinary Tract Infection. Life and Science. 2024; 5(2): 151-159. doi: http://doi.org/10.37185/LnS.1.1.595

Doxycycline, levofloxacin, and moxifloxacin are superior to ciprofloxacin in treating anthrax meningitis in rabbits and NHP.

Efficient treatment of anthrax-related meningitis in patients poses a significant therapeutic challenge. Previously, we demonstrated in our anthrax meningitis rabbit model that ciprofloxacin treatment is ineffective with most of the treated animals succumbing to the infection. Herein we tested the efficacy of doxycycline in our rabbit model and found it highly effective. Since all of our findings are based on a rabbit model, we test the efficacy of ciprofloxacin or doxycycline in a specific central nervous system (CNS) model developed in non-human primates (NHPs). Similar to rabbits, ciprofloxacin treatment was ineffective, while doxycycline protected the infected rhesus macaques (n = 2) from the lethal CNS Bacillus anthracis infection. To test whether the low efficacy of Ciprofloxacin is an example of low efficacy of all fluoroquinolones or only this substance, we treated rabbits that were inoculated intracisterna magna (ICM) with levofloxacin or moxifloxacin. We found that in contrast to ciprofloxacin, levofloxacin and moxifloxacin were highly efficacious in treating lethal anthrax-related meningitis in rabbits and NHP (levofloxacin). We demonstrated (in naïve rabbits) that this difference probably results from variances in blood-brain-barrier penetration of the different fluoroquinolones. The combined treatment of doxycycline and any one of the tested fluoroquinolones was highly effective in the rabbit CNS infection model. The combined treatment of doxycycline and levofloxacin was effective in an inhalation rabbit model, as good as the doxycycline mono-therapy. These findings imply that while ciprofloxacin is highly effective as a post-exposure prophylactic drug, using this drug to treat symptomatic patients should be reconsidered.

Synergistic effect of spermidine and ciprofloxacin against Alzheimer's disease in male rat via ferroptosis modulation

Alzheimer's disease (AD) is a prevalent form of neurodegenerative disease with a complex pathophysiology that remains not fully understood, and the exact mechanism of neurodegeneration is uncertain. Ferroptosis has been linked to the progression of degenerative diseases observed in AD models. The present study is designed to investigate the protective effects of spermidine, a potent antioxidant and iron chelator, and its synergistic interactions with ciprofloxacin, another iron chelator, in modulating ferroptosis and mitigating AD progression in rats. This study investigated AD-related biomarkers like neurotoxic amyloid beta (Aβ), arginase I, and serotonin. Spermidine demonstrated an anti-ferroptotic effect in the AD model, evident from the modulation of ferroptosis parameters such as hippocampus iron levels, reduced protein expression of transferrin receptor 1 (TFR1), and arachidonate 15-lipoxygenase (ALOX15). Additionally, the administration of spermidine led to a significant increase in protein expression of phosphorylated nuclear factor erythroid 2-related factor 2 (p-Nrf2) and upregulation of Cystine/glutamate transporter (SLC7A11) gene expression. Moreover, spermidine notably decreased p53 protein levels, acrolein, and gene expression of spermidine/spermine N1-acetyltransferase 1 (SAT1). Overall, our findings suggest that spermidine and/or ciprofloxacin may offer potential benefits against AD by modulating ferroptosis. Furthermore, spermidine enhanced the antioxidant efficacy of ciprofloxacin and reduced its toxic effects.

Lactoferrin/pectin nanocomplex encapsulating ciprofloxacin and naringin as a lung targeting antibacterial nanoplatform with oxidative stress alleviating effect

Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium with adaptive metabolic abilities. It can cause hospital-acquired infections with significant mortality rates, particularly in people with already existing medical conditions. Its ability to develop resistance to common antibiotics makes managing this type of infections very challenging. Furthermore, oxidative stress is a common consequence of bacterial infection and antibiotic therapy, due to formation of reactive oxygen species (ROS) during their mode of action. In this study we aimed to alleviate oxidative stress and enhance the antibacterial efficacy of ciprofloxacin (CPR) antibiotic by its co-encapsulation with naringin (NAR) within a polyelectrolyte complex (PEX). The PEX comprised of polycationic lactoferrin (LF) and polyanionic pectin (PEC). CPR/NAR-loaded PEX exhibited spherical shape with particle size of 237 ± 3.5 nm, negatively charged zeta potential (−23 ± 2.2 mV) and EE% of 61.2 ± 4.9 for CPR and 76.2 ± 3.4 % for NAR. The LF/PEC complex showed prolonged sequential release profile of CPR to limit bacterial expansion, followed by slow liberation of NAR, which mitigates excess ROS produced by CPR's mechanism of action without affecting its efficacy. Interestingly, this PEX demonstrated good hemocompatibility with no significant in vivo toxicity regarding hepatic and renal functions. In addition, infected mice administrated this nanoplatform intravenously exhibited significant CFU reduction in the lungs and kidneys, along with reduced immunoreactivity against myeloperoxidase. Moreover, this PEX was found to reduce the lungs´ oxidative stress via increasing both glutathione (GSH) and catalase (CAT) levels while lowering malondialdehyde (MDA). In conclusion, CPR/NAR-loaded PEX can offer a promising targeted lung delivery strategy while enhancing the therapeutic outcomes of CPR with reduced oxidative stress.

Evaluation of the Efficacy of Ciprofloxacin as Topical Adjunctive Therapy in Non-Surgical Treatment of Stage I and II Grade A Periodontitis (Clinical and Biochemical Study)

Evaluation of the Efficacy of Ciprofloxacin as Topical Adjunctive Therapy in Non-Surgical Treatment of Stage I and II Grade A Periodontitis (Clinical and Biochemical Study)

Stability-Indicating Quantification of Ciprofloxacin in the Presence of Its Main Photo-Degradation Product by CZE and UPLC: A Comparative Study

Active pharmaceutical ingredients (APIs) can be assured to be safe and effective with the help of stability-indicating procedures. An accurate comparison comprising the utilization of capillary zone electrophoresis (CZE) and ultra-performance liquid chromatography (UPLC) for the sensitive and accurate measurement of ciprofloxacin (CPF) in the presence of its major photo-degradation product was conducted. The CZE and UPLC working conditions were optimized to obtain the best pattern of separation for CPF and its photo-degradant. The linearity range of the cited techniques was confirmed to be 0.5 to 50 µg/mL. A thorough validation scheme according to the ICH-Q2B criteria was performed, including linearity, accuracy, precision, robustness, detection, and quantification limits. Selective quantification of CPF in the presence of up to 90% of its main photo-degradant was carried out using the proposed methods. For the analysis of CPF in tablet and intravenous (I.V.) solution forms, the CZE and UPLC procedures were applied. The suggested methods can be applied to keep an eye on the safety and efficacy of CPF in either bulk or dosage forms.

Repurposing the tyrosine kinase inhibitor nilotinib for use against intracellular multidrug-resistant Salmonella Typhimurium.

The increasing incidence of infections caused by multidrug-resistant Salmonella enterica has become a serious threat to global public health. Here, we found that the tyrosine kinase inhibitor nilotinib exhibits antibacterial activity against intracellular S. enterica serovar Typhimurium in RAW264.7 macrophages. Thus, we aimed to pharmacologically exploit the anti-intracellular Salmonella activity of nilotinib and to elucidate its mechanism of action. The antibacterial activity of the compounds was assessed by high-content analysis (HCA) and intracellular CFU, minimum inhibitory concentration (MIC), and bacterial growth assays. The cytotoxicity of the compounds was evaluated by HCA and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) cell viability assays. The levels of cellular AMPK, phospho-AMPK, Atg7 and β-actin were determined by immunoblotting. The screen identified two small molecule compounds (SCT1101 and SCT1104) with potent activity against intracellular S. Typhimurium. Moreover, SCT1101 and SCT1104 enhanced the efficacy of ciprofloxacin and cefixime against intracellular S. Typhimurium. However, only SCT1101 exhibited activity against intracellular MDR and fluoroquinolone-resistant S. Typhimurium isolates. Subsequent mechanistic studies showed that neither of these nilotinib derivatives increased the phospho-AMPK level in RAW264.7cells. Neither the AMPK inhibitor compound C nor SBI-0206965 reversed the inhibitory effects of SCT1101 and SCT1104 on intracellular Salmonella. Furthermore, neither blockade of autophagy by 3-MA nor shRNA-mediated knockdown of Atg7 protein expression in RAW264.7cells affected the antibacterial activity of SCT1101 and SCT1104. The structure of nilotinib could be used to develop novel therapeutics for controlling MDR S. Typhimurium infections.

Surfaces modified with small molecules that interfere with nucleotide signaling reduce Staphylococcus epidermidis biofilm and increase the efficacy of ciprofloxacin

Staphylococcus epidermidis are common bacteria associated with biofilm related infections on implanted medical devices. Antibiotics are often used in combating such infections, but they may lose their efficacy in the presence of biofilms. Bacterial intracellular nucleotide second messenger signaling plays an important role in biofilm formation, and interference with the nucleotide signaling pathways provides a possible way to control biofilm formation and to increase biofilm susceptibility to antibiotic therapy. This study synthesized small molecule derivates of 4-arylazo-3,5-diamino-1 H-pyrazole (named as SP02 and SP03) and found these molecules inhibited S. epidermidis biofilm formation and induced biofilm dispersal. Analysis of bacterial nucleotide signaling molecules showed that both SP02 and SP03 significantly reduced cyclic dimeric adenosine monophosphate (c-di-AMP) levels in S. epidermidis at doses as low as 25 µM while having significant effects on multiple nucleotides signaling including cyclic dimeric guanosine monophosphate (c-di-GMP), c-di-AMP, and cyclic adenosine monophosphate (cAMP) at high doses (100 µM or greater). We then tethered these small molecules to polyurethane (PU) biomaterial surfaces and investigated biofilm formation on the modified surfaces. Results showed that the modified surfaces significantly inhibited biofilm formation during 24 h and 7-day incubations. The antibiotic ciprofloxacin was used to treat these biofilms and the efficacy of the antibiotic (2 µg/mL) was found to increase from 94.8% on unmodified PU surfaces to > 99.9% on both SP02 and SP03 modified surfaces (>3 log units). Results demonstrated the feasibility of tethering small molecules that interfere with nucleotide signaling onto polymeric biomaterial surfaces and in a way that interrupts biofilm formation and increases antibiotic efficacy for S. epidermidis infections.

Bacteriophages: The promising therapeutic approach for enhancing ciprofloxacin efficacy against bacterial infection.

The emergence of ciprofloxacin-resistant bacteria is a serious challenge worldwide, bringing the need to find new approaches to manage this bacterium. Bacteriophages (phages) have been shown inhibitory effects against ciprofloxacin-resistance bacteria; thus, ciprofloxacin resistance or tolerance may not affect the phage's infection ability. Additionally, researchers used phage-ciprofloxacin combination therapy for the inhibition of multidrug-resistant bacteria. The sublethal concentrations of ciprofloxacin could lead to an increase in progeny production. Antibiotic treatments could enhance the release of progeny phages by shortening the lytic cycle and latent period. Thus, sublethal concentrations of antibiotics combined with phages can be used for the management of bacterial infections with high antibiotic resistance. In addition, combination therapy exerts various selection pressures that can mutually decrease phage and antibiotic resistance. Moreover, phage ciprofloxacin could significantly reduce bacterial counts in the biofilm community. Immediate usage of phages after the attachment of bacteria to the surface of the flow cells, before the development of micro-colonies, could lead to the best effect of phage therapy against bacterial biofilm. Noteworthy, phage should be used before antibiotics usage because this condition may have allowed phage replication to occur first before ciprofloxacin interrupted the bacterial DNA replication process, thereby interfering with the activity of the phages. Furthermore, the phage-ciprofloxacin combination showed a promising result for the management of Pseudomonas aeruginosa infections in mouse models. Nevertheless, low data are existing about the interaction between phages and ciprofloxacin in combination therapies, especially regarding the emergence of phage-resistant mutants. Additionally, there is a challenging and important question of how the combined ciprofloxacin with phages can increase antibacterial functions. Therefore, more examinations are required to support the clinical usage of phage-ciprofloxacin combination therapy.

Efficacy of Ciprofloxacin in Prevention of Sepsis Among the Patients with Chemotherapy-Induced Neutropenia: A Randomized Double-Blind Clinical Trial in a University Hospital in Tehran, Iran

Background: Neutropenia is a common side effect of chemotherapy and one of the most common causes of severe infection and mortality in patients with hematological malignancies. Some studies showed that antimicrobial prophylaxis resulted in lower febrile neutropenia (FN) episodes and mortality rates. Objectives: We aimed to determine the efficacy of prophylaxis with ciprofloxacin in patients with hematological malignancies. Methods: In a randomized double-blinded clinical trial from 1 March to 1 September 2016, we assigned patients with chemotherapy-induced neutropenia into two groups. We used the random permuted blocks method for randomization. The first group received oral ciprofloxacin at a dose of 500 milligrams daily until the neutrophil count reached 1000 cells per microliter or fever occurrence, defined as the primary outcome. The second group received a placebo in the same shape and size. We compared FN episodes and the mortality rate in these two groups by SPSS-22 software, using chi-square, Fischer's exact tests, and student t-test at P-value &lt; 0.05. Results: Seventy-three males (60.8%) and 47 females (39.2%) entered our study. The mean age of the patients was 47 ± 14.6 years. Acute leukemia was the most common underlying malignancy in 81 out of 120 subjects (67.5%). Fever (P = 0.005) was significantly lower in the ciprofloxacin group, but the mortality rate (P = 0.783) did not differ between the two groups. Conclusions: We found that the prophylaxis with ciprofloxacin decreased FN in our patients but did not influence the mortality rate. We believe that antimicrobial prophylaxis may be helpful in neutropenic patients, especially in decreasing FN and its related comorbidity.

Biological synthesis of Fe 3 O 4 @Ag using Scenedesmus obliquus and evaluation of its effect on the expression of MexA‐B efflux pump genes in ciprofloxacin‐resistant Pseudomonas aeruginosa strains

This study was conducted to biosynthesize [email protected] nanocomposite with Scenedesmus obliquus extract, and to evaluate its antibacterial potential against Pseudomonas aeruginosa. In addition, the effect of the synthesized nanocomposite on the expression of MexA-B efflux pump genes was investigated. The Fe3O4@Ag nanocomposite was characterized using X-ray diffraction spectroscopy (EDX), Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), Dynamic light scattering (DLS) as well as Zeta potential analyses. Minimum inhibitory concentration (MIC) of the nanocomposite alone and in combination with ciprofloxacin against P. aeruginosa strains was determined. Finally, the expression of MexA-B efflux pump genes among the bacteria treated with the nanocomposite was evaluated using quantitative real-time PCR. Based on the results, the proper synthesis of the nanocomposite with the diameter of 40 to 70 nm and acceptable stability was confirmed. The synthesized nanocomposite had lower MIC value (8–64 μg/mL) than ciprofloxacin (64–512 μg/mL) which shows stronger antibacterial potential of the nanocomposite. In addition, treating bacteria with the nanocomposite and ciprofloxacin caused a significant reduction of MexA-B genes compared to the cells treated with ciprofloxacin or nanocomposite alone. Thus, Fe3O4@Ag nanocomposite can improve the efficacy of ciprofloxacin against P. aeruginosa by reducing the expression of MexA-B efflux pump genes.

Effect of Ciprofloxacin on Planktonic Pseudomonas aeruginosa

Pseudomonas aeruginosa is an opportunistic human pathogen that causes nosocomial, acute, and chronic infections in patients with conditions such as cystic fibrosis, severe burns, and cancer. P. aeruginosa is known for its persistence in infections due largely to its numerous means of antimicrobic resistance, one of which is its ability to form biofilms. This organism has been placed on the World Health Organization list of Priority Pathogens for Research and Development of New Antibiotics at the critical level for many reasons, that includes its high mortality, healthcare burden, prevalence of resistance, and treatability. P. aeruginosa is resistant to many antibiotics; however, &gt;70% of P. aeruginosa are susceptible to ciprofloxacin. For these reasons, the purpose of the current study was to establish antimicrobic levels of ciprofloxacin effective against P. aeruginosa. To accomplish this purpose, antimicrobic levels of bacteria in biofilms and those not associated with a biofilm (planktonic) need separate methods of testing. For planktonic bacteria, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) are performed, whereas other methods are used for biofilm‐associated bacteria. To initiate inhibition studies, a model system was identified of ciprofloxacin effect on standardized strains of P. aeruginosa (ATCC strains 10145, 27853, 1744, CRM‐9027, 9721). These strains were used to establish ciprofloxacin effect, in terms of MIC and MBC levels, on planktonic bacteria. Results indicate that MIC and MBC levels of these strains are in the same range as reported values of P. aeruginosa. These results establish ciprofloxacin efficacy of growth inhibition for each ATCC strain of planktonic P. aeruginosa and will serve as baseline results for future studies, such as effect on biofilm‐associated bacteria and combination antimicrobic treatments.

The effect of ketoprofen on the plasma concentration and pharmacokinetic parameters of ciprofloxacin in chickens

Ciprofloxacin (CFX) and ketoprofen (KPN) are used widely in combination in veterinary interventions for bacterial infections, so in this study the effect of KPN was studied on the efficacy of CFX, by measuring its plasma concentration and pharmacokinetic parameters in 7-10 day-old chickens. The analgesic median effective dose (ED50) of KPN was determined to be 1.62 mg/kg, IM, in the chickens. The preferable analgesic dose of KPN to be used with CFX was 4 mg/kg, IM, which differs significantly from KPN 2 mg/kg, IM,. The CFX plasma concentrations alone (8 mg/kg, IM) measured at different times (0.5, 1, 2, 4 and 24 hours) were 3.31, 3.60, 3.21, 2.70 and 0.17 μg/mL while its concentration was elevated by 53, 54, 90, 107 and 418 % when coadministered with KPN (4 mg/kg, IM) to 5.05, 5.53, 6.10, 5.59 and 0.88 μg/mL in the chickens, respectively. CFX pharmacokinetic parameters, such as the area under the curve (AUC), the area under the moment curve (AUMC), mean residence time (MRT), half-life (t1/2β), Tmax, and Cmax increased when KPN was coadministered with CFX by 129, 289, 70, 49, 100 and 69 %, whereas the elimination rate constant (Kel), the volume of distribution at steady state (Vss) and clearance (Cl) decreased by 36, 34 and 58 %, respectively. It was concluded that coadministration of KPN alters the plasma concentration and the pharmacokinetic parameters of CFX, suggesting that the CFX dose can be reduced when used with KPN to achieve the desired concentration of CFX in the plasma, as an antibacterial for treatment of infected animals.

Phytolectin-cationic lipid complex revive ciprofloxacin efficacy against multi-drug resistant uropathogenic Escherichia coli

The rising threat to antibiotic armamentarium demand innovative methods to use standard antibiotics against multidrug-resistant (MDR) pathogens. Herein, we demonstrated phytolectin-cationic lipid complex have the ability to renew the ciprofloxacin (CIP) activity against MDR uropathogenic Escherichia coli (R4UPEC). The minimum inhibitory concentrations (MIC) obtained for CIP against R4UPEC studied were very high (MIC = 1000 µM) which may not be suitable for clinical testing. Strikingly, CIP in combination with Butea monosperma seed lectin (BMSL) and cationic lipid, 2-((N-(2-hydroxyethyl)palmitamido)methyl)− 1-methylpyridin-1-ium iodide (cN16E) showed 64-fold lower MIC (15.63 µM). Checkerboard assay revealed that the BMSL-cN16E (BcN16E) complex and CIP work synergistically against R4UPEC. The complex, BcN16E-CIP exerts antimicrobial activity through outer membrane permeabilization, inner membrane disruption, proton motive force dissipation and enhancing the generation of reactive oxygen species. The therapeutic efficacy evaluated in a zebrafish, intramuscular infection model using R4UPEC, the BcN16E-CIP reduce the bacterial load and decrease neutrophil infiltration in muscles and low down the liver cell necrosis. The results demonstrate significantly lower MIC for CIP when complex with BcN16E and showed exceptional in vivo efficacy against infectious MDR bacteria.

Urea-Based Ligand as an Efflux Pump Inhibitor: Warhead to Counter Ciprofloxacin Resistance and Inhibit Collagen Adhesion by MRSA

Methicillin-resistant Staphylococcus aureus (MRSA) is a frontline human pathogen in which efflux pump activity confers high levels of antibiotic-resistance and poses a therapeutic challenge in the clinics. The present study illustrates the potential of urea-based ligand as an efflux pump inhibitor (EPI) in order to restore the efficacy of ciprofloxacin (CPX) against MRSA. Among eight structurally varying urea-based ligands, the ligand C8 could significantly inhibit efflux pump activity in the clinical MRSA strain S. aureus 4s and was superior to the known EPI reserpine. In combinatorial treatment, C8 enhanced cellular accumulation of CPX, rendered a 16× decrease in the MIC of CPX, and restored the susceptibility of S. aureus 4s to CPX. Notably, C8 downregulated the expression of norA gene coding for the efflux pump in MRSA and treatment with 10 μM C8 and 2.0 μM CPX prevented emergence of the CPX resistance trait and suppressed MRSA cell growth till 120 generations. For potential anti-MRSA therapy, C8-loaded poly(d,l-lactide-co-glycolide) nanocarrier (C8-PNC) was generated, which facilitated facile release of C8 in physiologically relevant fluid. C8-PNC (loaded with 50 μM C8) rendered efflux pump inhibition and eliminated MRSA in combination with only 2.0 μM CPX. Treatment with the non-toxic C8-PNC (loaded with 50 μM C8) and CPX (2.0 μM) also hindered MRSA adhesion on collagen manifold higher as compared to cells treated with 32 μM CPX and significantly downregulated norA gene expression in non-adhered MRSA cells. The urea-based ligand presented herein is a promising biocompatible therapeutic material for effective mitigation of MRSA infections.