Toxicity Of Ciprofloxacin Research Articles

Microbial community response to ciprofloxacin toxicity in sponge membrane bioreactor

This study aims to offer insights into how ciprofloxacin (CIP) impact bacterial community structures in the Sponge-MBR process when CIP is spiked into hospital wastewater. We found that the CIP toxicity decreased richness critical phylotypes such as phylum class ẟ-, β-, ɣ-proteobacteria, and Flavobacteria that co-respond to suppress denitrification and cake fouling to 37% and 28% respectively. Cluster analysis shows that the different community structures were formed under the influence of CIP toxicity. CIP decreased attached growth biomass by 2.3 times while increasing the concentration of permeate nitrate by 3.8 times, greatly affecting TN removal by up to 26%. Ammonia removal was kept stable by inflating the ammonia removal rate (p < 0.003), with the wealthy Nitrospira genus guaranteeing the nitrification activity. In addition, we observed an increasing richness of Chloroflexi and Planctomycetes, which may play a role in fouling reduction in the Sponge-MBR. Therefore, if the amount of antibiotics in hospital wastewater continues to increase, it is so important to extend biomass retention for denitrification recovery.

Chemical speciation of ciprofloxacin in aqueous solution regulates its phytotoxicity and uptake by rice (Oryza sativa L.)

Ciprofloxacin (CIP), a widely used fluoroquinolone antibiotic, is frequently detected in aqueous environments, and could be assimilated by vegetable plants to possess potential threats to human and animal health through food chains. However, plant uptake of CIP in different chemical speciation has still far from clear now. Thus, the toxicity and uptake of CIP by rice plants were investigated under different solution pH, owing to its contribution to different chemical speciation of CIP. Results display that high pH-driven changes of CIP from cation (CIP+) to anion (CIP−) decreased its adsorption and uptake by excised roots and intact plants, respectively. However, CIP concentrations in roots, stems and leaves all exhibited no significant differences with increasing solution pH. Moreover, six intermediates of CIP were detected and two possible transformation pathways were proposed in rice plants, including firstly oxidation and following consecutive cleavage of piperazine ring. After accumulated in plant tissues, CIP significantly inhibited the plant growth, decreased the photosynthetic pigments contents and enhanced the antioxidant enzyme activities in a concentration-dependent manner. Besides, high pH exacerbated the growth inhibition and changed the oxidative damage responses of rice plants to CIP. These findings indicate that the uptake and toxicity of CIP in rice plants were influenced by solution pH-driven changes of its chemical speciation.

Ciprofloxacin and Graphene Oxide Combination-New Face of a Known Drug.

Drug modification with nanomaterials is a new trend in pharmaceutical studies and shows promising results, especially considering carbon-based solutions. Graphene and its derivatives have attracted much research interest for their potential applications in biomedical areas as drug modifiers. The following work is a comprehensive study regarding the toxicity of ciprofloxacin (CIP) modified by graphene oxide (GO). The influence on the morphology, viability, cell death pathway and proliferation of T24 and 786-0 cells was studied. The results show that ciprofloxacin modified with graphene oxide (CGO) shows the highest increase in cytotoxic potential, especially in the case of T24 cells. We discovered a clear connection between CIP modification with GO and the increase in its apoptotic potential. Our results show that drug modification with carbon-based nanomaterials might be a promising strategy to improve the qualities of existing drugs. Nevertheless, it is important to remember that cytotoxicity effects are highly dependent on dose and nanomaterial size. It is necessary to conduct further research to determine the optimal dose of GO for drug modification.

Multi-parametric analysis of ciprofloxacin toxicity at ecologically relevant levels: Short- and long-term effects on Daphnia magna

The increased presence of emergent compounds, such as pharmaceuticals drugs, in the aquatic compartment has been acknowledged as an evolving environmental issue whose consequences are not yet fully characterized. Specific classes of pharmaceutical drugs, such as fluoroquinolone antibiotics, can exert toxic effects to non-target species with ecological significance, since these compounds are environmentally stable and persistent, and may interact with some of the key physiologic processes of organisms. Despite such characteristics, knowledge about the effects of these drugs is still scarce, especially to non-target organisms. The present study aimed to evaluate the effects of chronic and acute exposures of the cladoceran Daphnia magna to the fluoroquinolone antibiotic ciprofloxacin. Putative toxic effects were assessed, following acute and chronic exposures to ecologically relevant concentrations of ciprofloxacin, through enzymatic (cholinesterase – ChEs, catalase – CAT, glutathione S-transferases – GSTs) and non-enzymatic (thiobarbituric acid reactive substances – TBARS, glycogen – Gly) biomarkers. In addition, we also determined behavioural (swimming distance – SD) and morphological (body length of the first brood – BL1B) endpoints in animals exposed to this drug. Ciprofloxacin acute exposure resulted in increased CAT and ChEs activities, and inhibited GSTs activity. After chronic exposure, ChEs activity was significantly inhibited, while GSTs activity was significantly enhanced. TBARS levels were only increased at higher concentrations of ciprofloxacin. CAT activity and Gly content did not evidence a clear and significant pattern of variation. SD was slightly inhibited during dark cycles. BL1B presented a significant decrease for animals subjected to an intermediate concentration. Results showed that even ecologically relevant concentrations of ciprofloxacin may cause oxidative stress in individuals of D. magna. The present study showed important data that corroborate the occurrence of significant biochemical alterations in key features of an aquatic organism when exposed to relevant levels of a widely used antibiotic, establishing essential links between environmental exposure to this specific drug and putative toxic challenges that may result in irreversible changes and damages, especially at the individual level. However, changes in the size of neonates suggest that population alterations are likely to occur under real scenarios of chronic contamination by this drug.

Stress-responses of activated sludge and anaerobic sulfate-reducing bacteria sludge under long-term ciprofloxacin exposure

The activated sludge (AS) and sulfate-reducing bacteria (SRB) sludge systems were continuously operated for 200 days in laboratory to investigate the stress-responses of these two sludge systems under ciprofloxacin (CIP) exposure. It was found that CIP was effectively removed by SRB sludge via adsorption and biodegradation, but little biodegradation in AS system. The CIP biodegradation by SRB sludge made the SRB sludge system more sustainable and tolerant to long-term CIP exposure than AS system with significant (p < 0.05) CIP desorption and decrease of CIP removal. CIP shaped the microbial communities in AS and SRB sludge, and significantly (p < 0.05) inhibited the family Nitrosomonadaceae (ammonia-oxidizing bacteria (AOB)) and genus Nitrospira (nitrite-oxidizing bacteria (NOB)/complete ammonia oxidizer(comammox)) and the nitrogen removal in AS system. Moreover, CIP posed the increase of genus Zoogloea-like organisms and the non-filamentous bulking of AS, e.g. 313 ± 12 mL/g of sludge volume index (SVI) at phase V (influent CIP = 5000 μg/L). The genus Desulfobacter was enriched in SRB sludge system under long-term CIP exposure, and stimulated chemical oxygen demand (COD) removal and sulfate reduction. The increase of genera Zoogloea, Acinetobacter and Flavobacterium in AS, and Zoogloea and Acinetobacter in SRB sludge systems under CIP exposure promoted extracellular polymeric substances (EPS) production and CIP adsorption for self-protection of microbes against CIP toxicity. The functional groups of N–H, O–H, C–O–C and C=O in EPS of AS and SRB sludge provided adsorption sites for CIP and impeded CIP impact on microbial cells. The findings of this study provide an insight into the stress-responses of AS and SRB sludge under long-term CIP exposure, and exhibit the great potential of treating CIP-laden wastewater by SRB sludge system.

Continuous degradation of ciprofloxacin in a manganese redox cycling system driven by Pseudomonas putida MnB-1

Ciprofloxacin (CIP), as an extensively used antibiotic, has been widely detected at a high level in the environment and has raised environmental pollution concerns. Thus, efficient and cost-effective methods for CIP degradation are highly desired. Biologically produced manganese oxides (BioMnOx) offer a promising perspective for CIP degradation because of their catalytic reactivity and cost-effectiveness. However, the release of Mn(II) from BioMnOx prevents the further oxidation of pollutants. As a consequence, continuous CIP degradation by BioMnOx is not feasible. In this work, a manganese redox cycling system driven by Pseudomonas putida MnB-1 was constructed for continuous degradation of CIP. In such a system CIP was oxidized continuously and rapidly by re-oxidizing the formed Mn(II) to regenerate reactive BioMnOx, which also protected the strain from CIP toxicity. CIP was degraded through N-dealkylation passway. No significant loss of BioMnOx reactivity was observed in three-cycle CIP degradation process, suggesting the stability of this system. An overlooked intracellular BioMnOx, which was involved in CIP degradation, was discovered in P. putida MnB-1. Moreover, the important role of Mn(III) in facilitating CIP removal in this system was also identified. This work provides useful information to better understand the degradation of antibiotic compounds mediated by microbes in environments.

Electrochemical oxidation of fluoroquinolone antibiotics: Mechanism, residual antibacterial activity and toxicity change

In this paper, we studied the electrochemical oxidation mechanisms of three typical fluoroquinolone antibiotics (FQs), and investigated residual antibacterial activity and toxicity changes after oxidation processes. Electrochemistry coupled to mass spectrometry (EC-MS) was used to study the oxidation processes of ciprofloxacin (CIP), norfloxacin (NOR) and ofloxacin (OFL). Eight oxidation products for each parent compound were identified and their chemical structures were elucidated. The transformation trend of each product, with the continuous increase of voltage from 0 to 3000 mV, was recorded by online EC-MS. The oxidation pathways were proposed based on the structural information and transformation trends of oxidation products. We found the oxidation mechanisms of FQs consisted of the hydroxylation and cleavage of piperazinyl ring via reactions with hydroxyl radicals, while the fluoroquinolone core remained intact. The antibacterial activity of the parent compounds and their oxidation mixtures was estimated using zone inhibition tests for gram-negative bacteria Salmonella typhimurium. It was found that the oxidation mixtures of CIP and NOR retained the antibacterial properties with lower activity compared to their parent compounds, while the antibacterial activity of OFL was almost eliminated after oxidation. Furthermore, the toxicity of the three FQs and their oxidation mixtures were evaluated using algal growth inhibition test (Desmodesmus subspicatus). The median effective concentration (EC50) values for the algal inhibition tests were calculated for the end point of growth rate. The toxicity of CIP and NOR to green algae after electrochemical oxidation, remained unchanged, while that of OFL significantly increased. The results presented in this paper contribute to an understanding of the electrochemical oxidation mechanisms of FQs, and highlight the potential environmental risks of FQs after electrochemical oxidation processes.

Ciprofloxacin toxicity and its co-metabolic removal by a freshwater microalga Chlamydomonas mexicana

This study evaluated the toxicity and cellular stresses of ciprofloxacin (CIP) and its co-metabolic removal in a freshwater microalga Chlamydomonas mexicana. The toxicological effects of CIP on C. mexicana were assessed by studying the growth and biochemical characteristics of the microalga including total chlorophyll, carotenoid content, malondialdehyde (MDA) and superoxide dismutase (SOD) activity. The calculated effective concentration (EC50) of CIP on C. mexicana was 65±4mgL−1 at 96h. The growth of C. mexicana was significantly inhibited at increased concentrations of CIP, showing 36±1, 75±3. and 88±3% inhibition at 40, 60 and 100mgL−1 CIP, respectively, compared to the control after 11days of cultivation. The total chlorophyll, carotenoid, MDA and SOD activity were significantly increased as a result of relatively high concentrations of CIP stress. C. mexicana showed 13±1% removal of CIP (2mgL−1) after 11days of cultivation; however, the addition of an electron donor (sodium acetate, 4gL−1) highly enhanced the removal of CIP (2mgL−1) by>3-fold after 11days. Kinetic studies showed that removal of CIP followed a first-order model (R2 0.94–0.97) with the apparent rate constants (k) ranging from 0.0121 to 0.079 d−1.

The degradation of two fluoroquinolone based antimicrobials by SilA, an alkaline laccase from Streptomyces ipomoeae.

The presence of fluoroquinolone based antimicrobials in natural waters represents a significant emerging environmental problem. In this study the suitability of a novel alkaline bacterial laccase, SilA, from Streptomyces ipomoeae to degrade two key antimicrobials, Ciprofloxacin and Norfloxacin under alkaline conditions in the presence of natural mediators was assessed. Results showed that only the selected SilA-acetosyringone system was able to degrade more than 90% of both fluoroquinolones. HPLC analysis of the degradation products obtained after enzyme treatment confirmed the disappearance of the antimicrobials and the mediator after 24 h. The time course of the degradation showed that during the first 4 h a 75% of degradation of fluoroquinolones was detected while the mediator remained stable. A concomitant appearance of new chromatographic peaks derived from the fluoroquinolones and/or the mediator was detected. Moreover, toxicity assays demonstrated that the SilA-acetosyringone system was able to reduce the toxicity of Ciprofloxacin and Norfloxacin by 90 and 70%, respectively. In conclusion, these findings support the suitability of a low cost and environmentally friendly strategy based on the SilA-acetosyringone system for a primary treatment of contaminated alkaline wastewaters with this type of emerging pollutants.

Ciprofloxacin wastewater treated by UVA photocatalysis: contribution of irradiated TiO2and ZnO nanoparticles on the final toxicity as assessed by Vibrio fischeri

Photocatalysis has become an attractive process to treat wastewater since it allows a rapid and efficient degradation of micropollutants in water. A solution of ciprofloxacin (CIP) was photocatalytically treated by ultraviolet A light (UVA) and titanium dioxide (TiO2) or zinc oxide (ZnO) nanoparticles. Toxicity of CIP and of the treated CIP solutions, as well as the toxicity of TiO2 and ZnO irradiated nanoparticles, was evaluated towards Vibrio fischeri. The lowest concentration of CIP tested, 10 μg L−1, leads to 50% of luminescence inhibition. Regarding irradiated nanoparticles, ZnO presented higher bacteria luminescence inhibition than TiO2, 97 and 38%, respectively. Due to high toxicity of ZnO, it was only possible to evaluate the CIP solution treated by UVA/TiO2. Initially, the toxicity decreased with the time of the process, but after 15 min the toxicity increased significantly (55%) and after 45 min of treatment, was 70%. High-performance liquid chromatography (HPLC) and Fourier transform infrared spectroscopy (FTIR) analysis proved that the initial decrease of toxicity was caused by CIP adsorption on catalyst surface, which latter increased due to the generation of by-products and toxicity contribution of soluble nanoparticles. Ten by-products were identified by liquid chromatography-mass spectrometry (LC-MS) and the mechanism of CIP photocatalytic degradation was proposed.

Toxicity of ciprofloxacin and sulfamethoxazole to marine periphytic algae and bacteria

Ciprofloxacin and sulfamethoxazole are two antibiotics commonly detected in the aquatic environment, but information on their toxicity towards natural microbial communities is largely absent. In particular no data are available for marine microorganisms. The aim of the current study was therefore to evaluate the chronic toxicity of ciprofloxacin and sulfamethoxazole to natural marine biofilms (periphyton), a complex ecological community comprising a variety of bacterial and algal species. The biofilms were sampled along the Swedish west coast and subsequently exposed over 4 days in a semi-static system to a concentration series of each antibiotic.Effects on the bacterial part of the periphyton community were assessed using Biolog Ecoplates, reflecting total respiration and functional diversity of the bacterial community. Exposure to either antibiotic resulted in a clear concentration–response relationship with EC10 and EC50 values for the inhibition of total carbon source utilization of 46.1nmol/L and 490.7nmol/L for ciprofloxacin, and 56nmol/L and 1073nmol/L for sulfamethoxazole. The NOEC for ciprofloxacin was 26nmol/L, with a minimum significant difference of 19.24%, for sulfamethoxazole it was 140nmol/L with a minimum significant difference of 14%. Multivariate data exploration of the whole carbon source utilization pattern confirmed these results. The data indicate that sulfamethoxazole leads to a general decrease in carbon source utilization, while ciprofloxacin exposure leads to a re-arrangement of the carbon-utilization pattern in the region of 20– 50% effect. This corresponds with the higher specificity of ciprofloxacin for certain bacterial species.Effects on the algal part of the communities were evaluated by analyzing the amount and composition of photosynthetic pigments, and neither ciprofloxacin nor sulfamethoxazole caused any inhibitory effects up to the maximum tested concentration of 9000nmol/L. However, sulfamethoxazole exposure did lead to a significant stimulation (75% above control level) of the total pigment content of the biofilm already at the lowest tested concentration of 5nmol/L. The stimulation then decreased with increasing concentrations to finally return to control level at 3000nmol/L. No shifts in the relative pigment composition were observed, indicating a generally increased algal biomass without major shifts in community composition.

Toxic effects of erythromycin, ciprofloxacin and sulfamethoxazole exposure to the antioxidant system in Pseudokirchneriella subcapitata

We tested antioxidant responses of the green microalga Pseudokirchneriella subcapitata exposed to different concentrations of the three antibiotics erythromycin (ETM), ciprofloxacin (CPF) and sulfamethoxazole (SMZ). Measurements included the level of lipid peroxidation, the total antioxidative capacity and three major antioxidant mechanisms: the ascorbate–glutathione cycle, the xanthophyll cycle and the enzyme activities of catalase (CAT), superoxide dismutase (SOD), guaiacol glutathione peroxidase (GPX) and glutathione-S-transferase (GST). Three antibiotics significantly affect the antioxidant system of P. subcapitata, but in different ways the alga was more tolerant to CPF and SMZ exposures than to ETM exposure. ETM caused reductions in AsA and GSH biosynthesis, ascorbate–glutathione cycle, xanthophylls cycle and antioxidant enzyme activities. The toxicity of CPF seems to be mainly overcome via induction of the ascorbate–glutathione cycle and CAT, SOD and GPX activities, while the toxicity of SMZ on the photosynthetic apparatus is predominantly reduced by the xanthophyll cycle and GST activity.

Evaluation of cardiac subacute toxicity of ciprofloxacin in rats using serum biochemical parameters.

Cardiac subacute toxicity induced by ciprofloxacin (1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid, CAS 86393-32-0) a relatively new quinolone carboxylic acid derivative with an extensive antibacterial spectrum was investigated in healthy rats using serum biochemical parameters. Toxicological evaluation was performed in serum samples following the administration of the therapeutic dose regimens of the compound. Cardiac subacute toxicity was evaluated by measuring serum enzyme activity of creatine kinase, creatine kinase isoenzyme-MB (muscular-brain), lactate dehydrogenase and aspartate aminotransferase. The serum biochemical parameters indicated that the cardiac subactue toxicity of ciprofloxacin was: Cipro 1.2 (250 mg) = Cipro 2.4 (500 mg) < Cipro 4.3 (750 mg).

Epithelial Profiling of Antibiotic Controlled Release Respiratory Formulations

Release profiles of two ciprofloxacin hydrochloride formulations for the treatment of respiratory infection were evaluated using different in vitro methodologies and characterised for aerosol performance and toxicity. Spray-dried ciprofloxacin and ciprofloxacin spray-dried with polyvinyl alcohol as a controlled release (CR) agent at a 50:50 w/w ratio were formulated and physico-chemically characterised. Aerosol performances were assessed in vitro using a liquid impinger. Drug release was performed using a modified Franz cell and a validated air interface Calu-3-modified twin stage impinger (TSI). Ciprofloxacin toxicity was also established in vitro. Both formulations had a similar size distribution, while CR ciprofloxacin had superior aerosol performance and stability. The release profiles showed the CR formulation to have a higher transport rate compared to ciprofloxacin alone in the cell model. Contrary results were observed using the diffusion cell. Results suggest that the air interface cell model provides a more physiologically relevant model than the modified Franz cell. Toxicity analysis showed that the lung epithelial cells could tolerate a wide range of ciprofloxacin concentrations. This study establishes that the in vitro modified TSI air interface Calu-3 model is capable of evaluating the fate of inhaled powder formulations.

A rare case of supraspinatus tendon rupture

Dear Editor, A 66-year-old man was treated for acute myelomonocytic leukemia with mitoxantrone, cytarabine, and etoposide. As it is our practice, we gave him 500 mg ciprofloxacin every 12 h per os for antibacterial prophylaxis. Two weeks later, he complained of pain in both shoulders which worsened until he could no longer raise his arms. He also had pain in his hips and knees, but the Achilles tendons were not involved. There were no signs of inflammation, but palpation of the insertion point of the supraspinatus tendon proved painful. Ultrasound examination showed a bilateral partial rupture of the supraspinatus tendon and subscapularis tendinopathy (Fig. 1). We suspected ciprofloxacin toxicity so we stopped the drug and he was given analgesics and physiotherapy. The pain resolved completely within a few days; however, full functional recovery took several months. We did not re-challenge with ciprofloxacin as the side effects had been so severe. Fig. 1 Ultrasound of the left supraspinatus tendon. The ultrasound shows a partial longitudinal rupture of the supraspinatus tendon (white arrows) Antibiotic prophylaxis reduces infections and enhances survival when given to high-risk patients receiving chemotherapy for acute leukemia or stem cell transplant. Current guidelines recommend prophylaxis be given from the start of chemotherapy until bone marrow recovery when the expected duration of neutropenia is more than 7 days [1, 2]. Fluoroquinolones, which provide a broad antimicrobial spectrum, are generally well tolerated and have a good safety profile. However, they can cause tendinitis and other forms of tendon damage in 10–15 per 100,000 prescriptions, a rate that increases with older age, renal dysfunction, and corticosteroid use. The onset of symptoms is typically within 2 weeks after starting treatment, but symptoms can occur within 2 h after the first dose until 6 months after cessation of treatment. The Achilles tendon is affected in 90% cases, almost half involving both ankles and the tendon ruptures in approximately 50% of the cases. Other sites of tendon injury have been reported but are rare. Recovery usually takes 1–2 months requiring rest and immobilization and surgery is seldom needed [3, 4]. How fluoroquinolones induce tendon injury is not understood. Our patient's age appears to have been the only risk factor as he had not used corticosteroids and did not have renal dysfunction. In July 2008, the FDA added a black box warning to alert doctors and patients of the raised risk of tendinitis and tendon rupture associated with fluoroquinolones [5]. As clinicians will be treating an increasing number of elderly patients for hematological malignancies, it is very important for them to recognize these symptoms and switch to an alternative treatment before tendon rupture occurs.

Study of ocular drug delivery system using drug-loaded liposomes

Background:This project aims to formulate and characterize a drug-eluting contact lens to provide controlled release of drug for a longer period of time, using liposomes as drug delivery system.Materials and Methods:Drug delivering contact lenses were created by coating disposable soft contact lenses with ciprofloxacin entrapped in the liposomes. Reverse phase evaporation and lipid film hydration methods were used for the preparation of ciprofloxacin trapping reverse phase evaporation vesicles, that is, unilamellar vesicles (REVs) and multilamellar vesicles (MLVs), respectively. Soya lecithin and cholesterol (CH) were used in the molar ratios of 7:4 and 7:2. The spherical structure of the liposomes, the mean diameter, and their purity were determined by photomicroscopic, transmission electron microscope, and chromatographic analysis, respectively. The prepared liposomes were evaluated for their entrapment efficiency, in vitro drug release, stability, and toxicity.Results:MLVs were larger than REVs with their mean diameter 338.32 nm and also entrapped greater amount of ciprofloxacin. Drug loading and its release from the liposomal vesicles was dependent on CH content. Ciprofloxacin released from the liposomes coated on the contact lenses not only inhibited both Staphylococcus aureus and Pseudomonas aeruginosa on an agar plate but also showed an enhanced antibacterial effect as determined by minimal inhibitory concentrations. Approximately 40% of ciprofloxacin was retained up to a period of 3 months at 4°C. Furthermore, the formulation was found to be nontoxic and also a reduction in toxicity of ciprofloxacin was observed after entrapment when assessed by lymphocyte toxicity assay and chick embryo inoculation.Conclusions:An innovative drug delivery system consisting of drug-loaded liposomes coated onto the surface of contact lenses has been developed. This system is highly specific in terms of localized and sustained application of the drug.

Toxic effect of ciprofloxacin on some biochemical variables in chicks

The aim of the present study was to examine the acute and sub acute toxicity of ciprofloxacin on lipids metabolism of chicks which included determination of cholesterol, triglyceride, high density lipoprotein, low density lipoprotein, and albumin levels in serum of chicks. The biochemical changes induced by giving ciprofloxacin as a single dose (200 and 400 mg/kg. body weight intraperitoneally) included significant increases of cholesterol, triglyceride and low density lipoprotein levels in serum, whereas albumin level significantly decreased, and there was no significant changes in high density lipoprotein levels as compared with control group. Repeated treatment with ciprofloxacin (100 mg/kg. body weight intra peritoneal) for 14 days caused significant increase in cholesterol level, albumin level significantly decreased as compared with control group, whereas it did not change significantly high density lipoprotein and triglyceride levels, repeated treatment of ciprofloxacin also showed significant decrease of the body weights of the chicks as compared with control group. The results suggest that there are toxic effects of ciprofloxacin on lipids metabolism as seen through changes in cholesterol, triglyceride, albumin and low density lipoprotein level.

Pharmacokinetics and toxicity of ciprofloxacin in adult horses

Using a randomized, cross-over study design, ciprofloxacin was administered i.g. to eight adult mares at a dose of 20 mg/kg, and to seven of the eight horses at a dose of 5 mg/kg by bolus i.v. injection. The mean C(0) was 20.5 μg/mL (±8.8) immediately after i.v. administration. The C(max) was 0.6 μg/mL (±0.36) at T(max) 1.46 (±0.66) h after the administration of oral ciprofloxacin. The mean elimination half-life after i.v. administration was 5.8 (±1.6) h, and after oral administration the terminal half-life was 3.6 (±1.7) h. The overall mean systemic availability of the oral dose was 10.5 (±2.8)%. Transient adverse effects of mild to moderate severity included agitation, excitement and muscle fasciculation, followed by lethargy, cutaneous edema and loss of appetite developed in all seven horses after i.v. administration. All seven horses developed mild transient diarrhea at 36-48 after i.v. dosing. All eight horses dosed intragastrically experienced adverse events attributable to ciprofloxacin administration. Adverse events included mild transient diarrhea to severe colitis, endotoxemia and laminitis necessitating euthanasia of three horses on humane grounds. The high incidences of adverse events preclude oral and rapid i.v. push administration of ciprofloxacin.

PBP3 inhibition elicits adaptive responses in Pseudomonas aeruginosa

Adaptive evolution depends on both the genetic variability in a population of organisms and the selection of the better adapted genotypes. However, for the fittest variants to be selected they must survive over a sufficient period under the new conditions. Bacteria are often exposed to different types of stress in nature, including antibiotics. We analysed the global expression profiles of the opportunistic pathogen Pseudomonas aeruginosa in response to ceftazidime, a PBP3 inhibitor, at different concentrations and times. PBP3 inhibition exerts a global impact on the transcription of a large number of genes. From an adaptive perspective, it is noteworthy the induction of several SOS genes, as well as adaptation, protection and antibiotic resistance genes. Intriguingly, transcription of pyocin genes, previously described as SOS-regulated, was repressed upon PBP3 inhibition. Ciprofloxacin, an SOS inducer, produced transcriptional induction of pyocins. Our results indicate that: (i) the SOS responses resulting from treatments with these two antibiotics cause only partially overlapping transcription profiles; (ii) PBP3 and DNA-gyrase inhibition produce opposite effects on transcription of pyocin genes. Consequently, ceftazidime decreases ciprofloxacin toxicity; (iii) error-prone DNA-polymerase DinB is induced by PBP3 inhibition but not by DNA-gyrase inhibition; (iv) PBP3 inhibition causes induced mutagenesis; (v) ceftazidime upregulates several antibiotic-resistance and adaptation genes; and (vi) ceftazidime concentrations thought previously to be lethal are not, as most cells treated with ceftazidime remain alive and recover their capacity to form colonies. Thus, transcriptional changes demonstrated in this work are likely to be adaptively relevant to cells that survive.

Ciprofloxacin vs an Aminoglycoside in Combination With a β-Lactam for the Treatment of Febrile Neutropenia: A Meta-analysis of Randomized Controlled Trials

To compare the effectiveness and toxicity of ciprofloxacin vs an aminoglycoside, both in combination with a beta-lactam, for the treatment of febrile neutropenia in the inpatient setting. For this meta-analysis of randomized controlled trials (RCTs) that compared the ciprofloxacin/beta-lactam combination vs an aminoglycoside/beta-lactam combination for the treatment of febrile neutropenia and reported data on effectiveness, mortality, and/or toxicity, we searched PubMed (1950-2004), Current Contents, Cochrane Central Register of Controlled Trials, and reference lists of retrieved articles, including review articles, as well as abstracts presented at international conferences. Data for 3 primary and 2 secondary outcomes were extracted by 2 investigators. Eight RCTs were included in the analysis. Comparable or better outcomes were observed with the ciprofloxacin/beta-lactam combination vs an aminoglycoside/beta-lactam combination: clinical cure without modification of the initial regimen (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.00-1.74; P=.05), clinical cure in the subset of patients with documented Infections (OR, 1.56; 95% CI, 1.05-2.31; P=.03), all-cause mortality (OR, 0.85; 95% CI, 0.54-1.35; P=.49), withdrawal of the study drugs due to toxicity (OR, 0.87; 95% CI, 0.57-1.32; P-.51), and nephrotoxicity (OR, 0.30; 95% CI, 0.16-0.59; P<.001). The ciprofloxacin/beta-lactam combination was also associated with better clinical cure compared to the aminoglycoside/beta-actam combination in the subset of RCTs with non-low-risk patients (OR, 1.38; 95% CI, 1.01-1.88; P=-.04), as well as in the subset of studies that included the same beta-lactam in both treatment arms (OR, 1.47; 95% CI, 1.06-2.05; P=.02). The combination of ciprofloxacin with a beta-actam antibiotic should be considered an important therapeutic option in hospitalized febrile neutropenic patients who have not received a quinolone for prevention of infections and in settings in which quinolone resistance is not common.