Broad-spectrum Antibiotics Ciprofloxacin Research Articles

Adsorption of antibiotics on montmorillonite and site energy distribution analysis

The migration and transformation of antibiotics requires further study in geochemical settings. In this study, the removal effect of montmorillonite (Mt) on antibiotics was investigated, using the broad-spectrum antibiotics ciprofloxacin (CIP) and erythromycin (ERY) as subjects. The results of adsorption kinetics and adsorption isotherm experiments showed that the generalized Langmuir model describe the adsorption process well, and the adsorption capacity of CIP was higher. The intercalation and adsorption behaviors of CIP and ERY on Mt surface were analyzed by FT-IR, SEM, TEM, XRD and Molecular simulation. In order to analyze the different adsorption capacity of these antibiotics on Mt, the theory of site energy distribution was employed. By fitting the experimental data with the Generalized-Langmuir model, the site energy distribution and average site energy were calculated, which revealed the competitive adsorption mechanism of CIP and ERY on Mt. Moreover, the adsorption of antibiotics on Mt under different pH conditions was studied, and the competitive adsorption results were also demonstrated by the potential energy distribution.

Lectin-Fortified Cationic Copper Sulfide Nanoparticles Gain Dual Targeting Capabilities to Treat Carbapenem-Resistant Acinetobacter baumannii Infection.

Targeted drug delivery maximizes the chance to combat infection caused by drug-resistant pathogens. Herein, lectin-fortified cationic copper sulfide (cCuS) nanoparticles were suggested for targeted adhesion to bacterial membranes and to enforce bacterial death. Jacalin, a lectin from jackfruit seed, was conjugated to fluorescein isothiocyanate (FITC), and its ability to recognize bacterial cell surface glycans was demonstrated. Jacalin formed a noncovalent complex with cCuS, which was investigated by fluorescence quenching measurements. The data revealed that jacalin-cCuS (JcCuS) had a good affinity with an association constant K a of 2.27 (± 0.28) × 104 M-1. The resultant JcCuS complex displayed excellent anti-infective activity against carbapenem-resistant Acinetobacter baumannii (CRAB). The minimum inhibitory concentration (MIC) of cCuS was 62.5 μM, which was 2-fold lower than that of the broad-spectrum antibiotic ciprofloxacin. Interestingly, the MIC of JcCuS was reduced to 15.63 μM, which was attributed to jacalin fortification. The mechanistic study unveiled that JcCuS affected the membrane integrity, depolarized the inner membrane, and produced excess reactive oxygen species to combat CRAB at a lower concentration compared to cCuS. A. baumannii formed a biofilm more readily, which played a critical role in pathogenesis and resistance in clinical settings. JcCuS (3.91 μM) displayed stronger antibiofilm activity without affecting the metabolic viability of CRAB. Microscopy analyses confirmed the inhibition of biofilm formation and disruption of the mature biofilm upon treatment with JcCuS. Furthermore, JcCuS hindered pellicle formation and inhibited the biofilm-associated virulence factor of CRAB such as exopolysaccharide, cell surface hydrophobicity, swarming, and twitching mobility. The anti-infective potential of JcCuS was demonstrated by rescuing CRAB-infected zebrafish. The reduction in pathogen proliferation in muscle tissues was observed in the treated group, and the fish recovered from the infection and was restored to normal life within 12 h. The findings illustrate that lectin fortification offers a unique advantage in enhancing the therapeutic potential of antimicrobials against human pathogens of critical priority worldwide.

Ternary nanoparticle complex of ciprofloxacin exhibiting sustained release at gastric pH prepared by co-complexation with polyanions and an ionic amphiphile

Poor bioavailability of the broad spectrum antibiotic ciprofloxacin (CIP) is caused by its narrow absorption window in the stomach. With the aim of prolonging the gastric residence time of CIP, we prepared a ternary nanoparticle complex (nanoplex) of CIP by co-complexation with polyanions (sodium dextran sulfate (DXT)) and an anionic amphiphile (sodium dodecyl sulfate (SDS)). We investigated the effect of the charge ratio of DXT to SDS on the size, zeta potential, CIP payload, and CIP utilization rate of the CIP-DXT-SDS nanoplex and its dissolution characteristics in simulated gastrointestinal fluids. Fourier transform infrared spectroscopy, powder X-ray diffraction, and differential scanning calorimetry analyses showed that the ternary nanoplex was made up of amorphous CIP-DXT and crystalline CIP-SDS complexes. The size of the CIP-DXT-SDS nanoplex prepared at a >90% CIP utilization rate was 110–290nm and it had a zeta potential of −16–39mV, and CIP payload of 47–62%, depending on the charge ratio. At gastric pH, the CIP-DXT-SDS nanoplex prepared with a DXT:SDS charge ratio lower than 80:20 exhibited prolonged CIP release (60% dissolution after 8h) compared with native CIP (100% dissolution after 1h) and a binary CIP-DXT nanoplex (80% dissolution after 5h), which was attributed to its lower solubility. The sustained release characteristics of the CIP-DXT-SDS nanoplex were comparable to those of existing CIP gastroretentive formulations.

Ciprofloxacin: from infection therapy to molecular imaging.

Diagnosis of deep-seated bacterial infection remains a serious medical challenge. The situation is becoming more severe with the increasing prevalence of bacteria that are resistant to multiple antibiotic classes. Early efforts to develop imaging agents for infection, such as technetium-99m (99mTc) labeled leukocytes, were encouraging, but they failed to differentiate between bacterial infection and sterile inflammation. Other diagnostic techniques, such as ultrasonography, magnetic resonance imaging, and computed tomography, also fail to distinguish between bacterial infection and sterile inflammation. In an attempt to bypass these problems, the potent, broad-spectrum antibiotic ciprofloxacin was labeled with 99mTc to image bacterial infection. Initial results were encouraging, but excitement declined when controversial results were reported. Subsequent radiolabeling of ciprofloxacin with 99mTc using tricarbonyl and nitrido core, fluorine and rhenium couldn't produce robust infection imaging agent and remained in discussion. The issue of developing a robust probe can be approached by reviewing the broad-spectrum activity of ciprofloxacin, labeling strategies, potential for imaging infection, and structure-activity (specificity) relationships. In this review we discuss ways to accelerate efforts to improve the specificity of ciprofloxacin-based imaging.

Corruption and Medicine Quality in Latin America: A Pilot Study

Abstract Fake and substandard medicines are a significant problem in developing nations, and a growing problem in developed ones too. There have been assessments of basic medicine quality from many countries and regions across the world but almost none in Central and South America. Over the past decade, as part of our research, we have collected over ten thousand samples of medicines from 22 cities in emerging markets, but the only one from the Latin region was Sao Paolo in Brazil. We have now rectified this gap, at least for one critical medicine, the broad spectrum antibiotic ciprofloxacin. Using original, self-collected data from ten countries in Latin America, we test whether the 687 Ciprofloxacin treatments pass the Global Pharma Health Fund e.V. Minilab® protocol to identify substandard or counterfeit medicines. In terms of quality, 93 percent of drugs were good quality. Within the drugs that failed the quality test, the majority were substandard rather than fake. About 26 % of the poor quality drugs were fake, with zero active pharmaceutical ingredient (API), while the rest were substandard, with less than 80 % API. In line with results from our earlier studies, we find that products that were locally registered, as well as those with SRA or WHO pre-qualification, were more likely to pass the test. A new finding in this paper is that corruption is a key predictor of poor quality drugs. Less corrupt countries had higher levels of passing drugs.

A simple way for targeted delivery of an antibiotic: In vitro evaluation of a nanoclay-based composite.

The sodium-modified form of fluorohectorite nanoclay (NaFh) is introduced as a potential drug carrier, demonstrating its ability for the controlled release of the broad-spectrum antibiotic Ciprofloxacin through in vitro tests. The new clay-drug composite is designed to target the local infections in the large intestine, where it delivers most of the incorporated drug thanks to its pH-sensitive behavior. The composite has been conceived to avoid the use of coating technology and to decrease the side-effects commonly associated to the burst-release of the ciprofloxacin at the stomach level. NaFh was obtained from lithium-fluorohectorite by ion exchange, and its lack of toxicity was demonstrated by in vivo studies. Ciprofloxacin hydrochloride (Cipro) was encapsulated into the clay at different values of the pH, drug initial concentration, temperature and time. Systematic studies by X-ray diffraction (XRD), infrared and visible spectrophotometry (FT-IR and UV-vis), and thermal analysis (TGA) indicated that the NaFh host exhibits a high encapsulation efficiency for Cipro, which reaches a 90% of the initial Cipro in solution at 65 oC, with initial concentration of drug in solution of 1.36 x 10−2 mol L-1 at acid pH. XRD revealed that a true intercalation of Cipro takes place between clay layers. TG showed an increased thermal stability of the drug when intercalated into the clay, as compared to the “free” Cipro. IR suggested a strong clay-Cipro interaction via ketone group, as well as the establishment of hydrogen bonds between the two materials. In vitro drug release tests revealed that NaFh is a potentially efficient carrier to deliver Cipro in the large intestine, where the release process is mediated by more than just one mechanism.

Abstract 2681: Oral micro biome enhances stemness in oral cancer cells by activating Toll like receptor signaling

Abstract Background: The resistance and progression of cancers after chemotherapy to invasive and metastatic stages accounts for the overwhelming majority of cancer deaths. Recent studies suggest, microbiomes can induce a cascade of host events to either support or inhibit tumor growth. Specially, in oral cancer, chemotherapy treatment may alter the oral microbial flora, which may favor or inhibit tumor growth. Hence, it is importantl to develop novel experimental approaches to study the role of oral microbial flora in oral cancer stemness (self-renewal and undifferntiated state of cancer stem cells). Importantly, patients in developing area, including Assam, where KaviKrishna laboratory is located, may have distinct oral microbial flora that could favor oral cancer growth. Hence, it is important to include patients from developing countries for such studies. Our previous research showed that chemotherapy ehances stemenss in many cancer cell types, including oral squamous cell carcinoma cell line SSC-25. The stemness switch is characterized by enhanced expression of stemness associated genes including Nanog, Lin28A/B, Oct-4, MYC, HIF-2alpha and inflammation associated genes including Toll like receptor (TLR) 2/4. Here we investigated the role of oral microbiomes in the TLR mediated stemness switch of oral cancer cells. Methods: SCC-25 oral cancer cell line was treated with bacterial product lipopoly saccharide (LPS), and the stemness switch evaluated by isolation of ABCG2+ cells and expression of stemness associated genes by these cells. Capacity of interaction of tumor stromal cells with mesenchymal stem cells was also evaluated. Additionally, we obtained sputum from oral cancer subjects undergoing chemotherapy. The patients were from the Kamrup district of Assam, where KaviKrishna laboratory is located. The sputum was processed and then added to the culture medium of SCC-25 cells. These post-sputum treated SCC-25 cells were subjected to phenotypic stemness switch analysis. Results: We found, LPS and sputum treatment led to the enhanced stemness of ABCG2+ cells, including the high expression of TLR2/4, MYC, Nanog, Sox-2, and HIF-2alpha. Importantly, sputum derived from oral cancer subjects under remission showed inhibitory activity on ABCG2+ cell self-renewal. In contrast, sputum obtained from oral cancer subjects with relapse showed enhanced stemness of ABCG2+ cells, and also increased tumorigenic potential. The post-sputum treated ABCG2+ cells exhibited high expression of TLR2/4 and associated increase of HIF-2alpha and MYC transcriptional activity. The sputum treated with broad spectrum antibiotic ciprofloxacin did not enhance the stemness and TLR2/4 signaling of SCC-25 cells. Conclusion: These results indicate that oral microbiomes may differentially influence the stemness of oral cancer cells. We also conclude that live bacteria present in the sputum may be required to enhance stemness in a TLR2/4 dependent manner. Note: This abstract was not presented at the meeting. Citation Format: Joyeeta Talukdar, Rashmi Bhuyan, Bidisha Pal, Sorra Sandhya, Hong Li, Seema Bhuyan, Sukanya Garhyan, Debabrat Baishya, Anupam Sarma, Jyotirmoy Phukan, Amal Kataki, Bikul Das. Oral micro biome enhances stemness in oral cancer cells by activating Toll like receptor signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2681. doi:10.1158/1538-7445.AM2017-2681

Synthesis, biological evaluation and molecular modeling study of new (1,2,4-triazole or 1,3,4-thiadiazole)-methylthio-derivatives of quinazolin-4(3H)-one as DHFR inhibitors

A new series of 2-mercapto-quinazolin-4-one analogues was designed, synthesized and evaluated for their in vitro DHFR inhibition, antitumor and antimicrobial activity. Compound 17 proved to be the most active DHFR inhibitor with IC50 value of 0.01μM, eight fold more active than methotrexate (MTX). Compounds 16 and 24 showed antitumor activity against human Caco2 colon and MCF-7 breast tumor cell lines with IC50 values of 25.4 and 9.5μg/ml, respectively. Compounds 15, 20, 21 and 30 showed considerable activity against the Gram-positive bacteria Staphylococcus aureus while 24 and 30 proved active against Bacillus subtilis with a magnitude of potency comparable to the broad spectrum antibiotic Ciprofloxacin. Strong activity was observed for 13, 14, 19, 20 and 24 against Candida albicans and Aspergillus flavus. Compound 17 shared a similar molecular docking mode with MTX and made a critical hydrogen bond and arene-arene interactions via Ala9 and Phe34 amino acid residues, respectively.

Antibiotic Treatment Selects for Cooperative Virulence of Salmonella Typhimurium

Antibiotics are powerful therapeutics but are not equally effective against all cells in bacterial populations. Bacteria that express an antibiotic-tolerant phenotype ("persisters") can evade treatment [1]. Persisters can cause relapses of the infection after the end of the therapy [2]. It is still poorly understood whether persistence affects the evolution of bacterial virulence. During infections, persisters have been found preferentially at particular sites within the host [3, 4]. If bacterial virulence factors are required to reach such sites, treatment with antibiotics could impose selection on the expression of virulence genes, in addition to their well-established effects on bacterial resistance. Here, we report that treatment with antibiotics selects for virulence and fosters transmissibility of Salmonella Typhimurium. In a mouse model for Salmonella diarrhea, treatment with the broad-spectrum antibiotic ciprofloxacin reverses the outcome of competition between wild-type bacteria and avirulent mutants that can spontaneously arise during within-host evolution [5]. While avirulent mutants take over the gut lumen and abolish disease transmission in untreated mice, ciprofloxacin tilts the balance in favor of virulent, wild-type bacteria. This is explained by the need for virulence factors to invade gut tissues and form a persistent reservoir. Avirulent mutants remain in the gut lumen and are eradicated. Upon cessation of antibiotic treatment, tissue-lodged wild-type pathogens reseed the gut lumen and thereby facilitate disease transmissibility to new hosts. Our results suggest a general principle by which antibiotic treatment can promote cooperative virulence during within-host evolution, increase duration of transmissibility, and thereby enhance the spread of an infectious disease.

Cerium oxide and iron oxide nanoparticles abolish the antibacterial activity of ciprofloxacin against gram positive and gram negative biofilm bacteria

Metal oxide nanoparticles have been suggested as good candidates for the development of antibacterial agents. Cerium oxide (CeO2) and iron oxide (Fe2O3) nanoparticles have been utilized in a number of biomedical applications. Here, the antibacterial activity of CeO2 and Fe2O3 nanoparticles were evaluated on a panel of gram positive and gram negative bacteria in both the planktonic and biofilm cultures. Additionally, the effect of combining CeO2 and Fe2O3 nanoparticles with the broad spectrum antibiotic ciprofloxacin on tested bacteria was investigated. Thus, minimum inhibitory concentrations (MICs) of CeO2 and Fe2O3 nanoparticles that are required to inhibit bacterial planktonic growth and bacterial biofilm, were evaluated, and were compared to the MICs of the broad spectrum antibiotic ciprofloxacin alone or in the presence of CeO2 and Fe2O3 nanoparticles. Results of this study show that both CeO2 and Fe2O3 nanoparticles fail to inhibit bacterial growth and biofilm biomass for all the bacterial strains tested. Moreover, adding CeO2 or Fe2O3 nanoparticles to the broad spectrum antibiotic ciprofloxacin almost abolished its antibacterial activity. Results of this study suggest that CeO2 and Fe2O3 nanoparticles are not good candidates as antibacterial agents, and they could interfere with the activity of important antibiotics.

Effect of ciprofloxacin incorporation in PVA and PVA bioactive glass composite scaffolds

Scaffolds are implants used to deliver cells, drugs, and genes into the body in a local controlled release pattern which offers many advantages over systematic drug delivery. Composite scaffolds of polyvinyl alcohol (PVA) and quaternary bioactive glass (46S6 system) with different ratios of glass contents were prepared by the lyophilisation technique. The broad spectrum antibiotic ciprofloxacin (Cip) was impregnated to the scaffold during the fabrication in a concentration of 5, 10 and 20%. Biodegradation rate and in-vitro mineralization of the prepared scaffolds were performed by soaking the scaffolds in simulated body fluid (SBF). Phase identification, microstructure, porosity, bioactivity, mechanical properties and drug release pattern in PBS were characterized by XRD, SEM coupled with EDS, Hg-porosimeter, inductively coupled plasma-optical emission spectroscopy (ICP-OES), universal testing machine, fourier transform infrared (FTIR) and UV-spectrophotometer, respectively. A porous scaffold has been obtained with porosity up to 85%. By increasing the glass contents in the prepared scaffold the porosity and the degradation rate decrease however, the compressive strength was enhanced. A sustained drug release pattern was observed with a quasi-Fickian diffusion mechanism. The formulated ciprofloxacin loaded porous polyvinyl alcohol scaffold gave an acceptable physicochemical properties and was able to deliver the drug in a prolonged release pattern which offers a distinguish treatment for osteomylitis as well as local antibacterial effect.

Antibacterial Derivatives of Ciprofloxacin to Inhibit Growth of Necrotizing Fasciitis Associated Penicillin Resistant Escherichia coli.

Escherichia coli (E. coli) is associated with necrotizing fasciitis (type I) and can induce enough damage to tissue causing hypoxia. Three ester derivatives of the broad-spectrum antibiotic ciprofloxacin were placed into bacteria culture simultaneously with the parent ciprofloxacin (drug 1) to ascertain the level of antibacterial activity. The n-propyl (drug 2), n-pentyl (drug 3), and n-octyl (drug 4) esters of ciprofloxacin were synthesized under mixed phase conditions and by microwave excitation. The formation of ester derivatives of ciprofloxacin modified important molecular properties such as Log P and polar surface area which improves tissue penetration, yet preserved strong antibacterial activity. The Log P values for drugs 1, 2, 3, and 4 became −0.701, 0.437, 1.50, and 3.02, respectively. The polar surface areas for drugs 1, 2, 3, and 4 were determined to be 74.6 Angstroms2, 63.6 Angstroms2, 63.6 Angstroms2, and 63.6 Angstroms2, respectively. These values of Log P and polar surface area improved tissue penetration, as indicated by the determination of dermal permeability coefficient (K p) and subsequently into the superficial fascial layer. All drugs induced greater than 60% bacterial cell death at concentrations less than 1.0 micrograms/milliliter. The ester derivatives of ciprofloxacin showed strong antibacterial activity toward penicillin resistant E. coli.

The search for new antibiotic substances from filamentous fungi

In an environment contaminated with high concentrations of antibiotic pharmaceuticals, bacteria develop multi-resistance more easily. Is it possible that these resistant bacteria would also accelerate the evolutionary response of the surrounding micro-flora that has to combat them for survival? And in that case, can we exploit that response to discover new antibiotics that have developed in that micro-environment? We have explored the antibacterial activity and chemistry of micro fungi from a river situated close to a wastewater treatment plant in the Indian city of Patancheru, where extreme concentrations of several pharmaceuticals, such as the broad spectrum antibiotic ciprofloxacin (28–31mg/mL) and other fluoroquinolones (up to 780µg/L) occur; 1From the Indian river sediment, 61 filamentous fungi were isolated, cultivated and extracted. Several strains of the genus Aspergillus showed antimicrobial activity against susceptible and multi-resistant bacteria, such as meticillin-resistant Staphylococcus aureus, ESBL-producing E. coli and vancomycin-resistant Enterococcus. The highest activity was observed for Aspergillus fumigatus, whose extract contained the secondary metabolite gliotoxin; 2The production of gliotoxin was triggered by the addition of lipopolysaccharides, indicating a direct correlation between bacterial structural elements and the production of antibiotic compounds; 1D.G. Larsson et al., J Hazard Mater, 2007; 2K.S. Svahn et al., Infect Ecol Epid, 2012 in press.

Bacteria resistant to ciprofloxacin, chloramphenicol and tetracycline isolated from western Kansas feedlots

Abstract In the United States thousands of tons of antibiotics are annually administered in low doses to livestock, both as prophylactics and growth promoters. Mounting evidence has shown that the overuse of antibiotics in livestock might render them, or their structural analogs, less effective when needed in veterinary as well as human medicine. To examine antibiotic resistance trends in feedlot soil, we collected soil samples from pens at ten beef cattle feedlots across western Kansas. Soil samples were screened for bacteria resistant to the human broad spectrum antibiotics ciprofloxacin, chloramphenicol, and tetracycline, by plating on them on Mueller-Hinton agar containing antibiotic concentrations of 100 μg mL−1. Resistant organisms were subcultured until axenic cultures were obtained. Bacteria were subsequently identified by submitting them to a commercial laboratory that utilizes 16S rRNA sequencing. We further assayed the organisms for resistance to more than one antibiotic. Some resistant isolate...

The Pharmacokinetics of The Biliary Excretion of Ciprofloxacin

The pharmacokinetics of ciprofloxacin excretion have been studied in 54 patients undergoing biliary and pancreatic operations with and without obstruction of the common bile duct. High concentrations were achieved in common duct bile within 20 minutes of intravenous injection and persisted for over 3 hours after 100 mg and for over 8 hours after 200 mg. The concentration of ciprofloxacin in the bile of functioning gall bladders was much greater than that in the common duct bile. Remarkably, it was identified in therapeutic concentrations in the bile of obstructed ducts. This and the rapid fall from initially high venous concentrations probably reflect diffusion from the circulation as a result of the exceptional tissue penetration. A unique feature of this study was the finding of clinically significant concentrations in the bile of obstructed ducts. Two patients developed wound infection and no side effects were observed. The broad spectrum antibiotic ciprofloxacin has potential as a useful agent for prophylaxis in biliary surgery maintaining biliary and venous concentrations in excess of the MIC90 for most biliary pathogens for more than 8 hours.