Ciprofloxacin Versus Levofloxacin Prophylaxis in Hematopoietic Stem Cell Transplantation: A Randomized Trial.

OBJECTIVES: We aimed to assess whether there is a difference between ciprofloxacin and levofloxacin as prophylaxis in hematopoietic stem cell transplant (SCT) recipients. METHODS: This is a prospective, randomized trial in patients receiving SCT at Henry Ford Health in the United States of America. We randomly assigned patients (1:1) to receive ciprofloxacin or levofloxacin. The primary outcome was incidence of bloodstream bacterial infections (BSI) up to day 60 after SCT. RESULTS: Between June 4, 2018, and May 23, 2022, we randomly assigned 308 consecutive patients to receive ciprofloxacin (154 patients) or levofloxacin (154 patients). BSI was similar in both the ciprofloxacin and levofloxacin groups (18 [11.7%] vs 18 [11.7%]). Pneumonia was more frequent in the ciprofloxacin group compared to the levofloxacin group (18 [18%] vs 7 [23%]; relative risk 2.57, 95% CI 1.11-5.98; p = 0.028). There were no differences in neutrophil engraftment, fever, Clostridium difficile infection, relapse incidence, overall survival, non-relapse mortality, length of stay post-SCT, or intensive care unit admission. CONCLUSIONS: Although both prophylaxis regimens demonstrated the same efficacy in SCT recipients, levofloxacin prophylaxis led to less pneumonia in the first 60 days post-SCT. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov, NCT03850379.

Modification of polyvinylidene fluoride membrane with ciprofloxacin to improve the bacteriostatic performance.

The common polyvinylidene fluoride (PVDF) membrane itself is susceptible to membrane fouling, especially biofouling, which is a serious threat. In this study, PVDF membrane was modified with ciprofloxacin (CIP) through co-blending to investigate the filtration properties, bacterial inhibition and fouling resistance. Modified membranes were prepared by adding 0.3 g (MC0.3), 0.6 g (MC0.6), 0.9 g (MC0.9) and 1.2 g (MC1.2) CIP per 100 g casting solution. Among these modified membranes, MC0.6 showed the best filtration performances, with the pure water flux stabilized at about 416.67 L/(m2·h) and bovine serum albumin (BSA) rejection of 92.0% at a trans-membrane pressure of 0.1 MPa. The pore size was reduced, the average roughness was reduced to 29.4 nm, the contact angle was lowered to 68.9°, and the hydrophilicity was greatly improved. The width of the inhibition circle produced by MC0.6 was 0.35-0.45 mm, and the modified membrane showed good inhibition of non-specific bacteria and algal removal during urban river water filtration. The rejection of BSA was increased by 16.32% compared to the base membrane and the adsorption rate for BSA was reduced by 68.45%. In addition, the removal of conventional pollutants in urban river water by the modified membranes for was also improved. Compared with that of the base membrane, the removal of TN, NH3-N, TP and COD by MC0.6 was increased by 10.58%, 12.45%, 15.44% and 13.53%. The results showed that CIP co-blending modified PVDF membrane could effectively improve membrane performances and has good value for water treatment.

Type I Kounis Syndrome: Allergic Myocardial Infarction Triggered by Ciprofloxacin.

Kounis syndrome (KS), known as allergic myocardial infarction (MI), is an uncommon but potentially life-threatening disease characterized by acute coronary artery disease (CAD) in the setting of allergic reactions. KS is most frequently triggered by medication, and ciprofloxacin-induced KS-I is rarely reported. Here, we present a case of KS-I triggered by ciprofloxacin in a young female with no prior CAD. A 35-year-old female presented with sudden onset chest pain, diaphoresis, and lightheadedness, accompanied by itching, confusion, and collapse, shortly after taking oral ciprofloxacin. Her electrocardiogram showed inferior wall MI with elevated cardiac troponin levels. Urgent coronary angiography was unremarkable. Her condition improved after sublingual nitroglycerine, methylprednisolone, and intramuscular injection of epinephrine. This case highlights the importance of recognizing drug-induced allergic reactions as a potential cause of acute coronary events, particularly in young patients without traditional risk factors.

Achilles tendon complications of fluoroquinolone treatment: a molecule-stratified systematic review and meta-analysis.

Purpose: The association between fluoroquinolone intake and Achilles tendinopathy (AT) or Achilles tendon rupture (ATR) is widely documented. However, it is not clear whether different molecules have the same effect on these complications. The purpose of this study was to document Achilles tendon complications for the most prescribed fluoroquinolones molecules. Methods: A literature search was performed on Pubmed, Cochrane, Embase, and Web of Science databases up to April 2023. Inclusion criteria: studies of any level of evidence, written in English, documenting the prevalence of AT/ATR after fluoroquinolone consumption and stratifying the results for each type of molecule. The Downs and Black's 'Checklist for Measuring Quality' was used to evaluate the risk of bias. Results: Twelve studies investigating 439,299 patients were included (59.7% women, 40.3% men, mean age: 53.0 ± 15.6 years). The expected risk of AT/ATR was 0.17% (95% CI: 0.15-0.19, standard error (s.e.): 0.24) for levofloxacin, 0.17% (95% CI: 0.16-0.19, s.e.: 0.20) for ciprofloxacin, 1.40% (95% CI: 0.88-2.03, s.e.: 2.51) for ofloxacin, and 0.31% (95% CI: 0.23-0.40, s.e.: 0.77) for the other molecules. The comparison between groups documented a significantly higher AT/ATR rate in the ofloxacin group (P < 0.0001 for each comparison). Levofloxacin and ciprofloxacin showed the same risk (P = n.s.). The included studies showed an overall good quality. Conclusion: Ofloxacin demonstrated a significantly higher rate of AT/ATR complications in the adult population, while levofloxacin and ciprofloxacin showed a safer profile compared to all the other molecules. More data are needed to identify other patient and treatment-related factors influencing the risk of musculoskeletal complications.

Interfacial bonding of Co3O4 and oxygen vacancies engineering on ZnO induced efficient peroxymonosulfate activation and pollutants degradation.

A heterojunction of trace Co3O4 bonded on oxygen vacancies (OVs)-rich ZnO (OVs-ZnO/Co3O4) was synthesized via defect-assisted method to promote peroxymonosulfate (PMS) activation and pollutants degradation. Experiments and theoretical calculations demonstrated that electrons could efficiently transfer from OVs-ZnO to Co3O4. OVs-ZnO and Co3O4 played different roles in activating PMS. PMS was easily adsorbed on the OVs-ZnO to form PMS* complex and mediated electron transfer to oxide ciprofloxacin (CIP), whereas, Co3O4 facilitated breakup of peroxide bond to produce radicals. The optimal OVs-ZnO/Co3O4 with Co content of 1.34% exhibited good PMS decomposition ability (94.2% in 30 min) compared to unmodified ZnO (24.2%), stability and anti-interference feature in removing CIP, 96.9% CIP (10 ppm) and 79.6% of total organic carbon were removed in 30 min. Moreover, the OVs-ZnO/Co3O4 achieved 91.2% CIP removal ratio with 1.0 mM PMS via a flow-through device in 180 min. This study proposes a new strategy to enhance PMS activation of ZnO and provides new viewpoint in PMS activation way.

Association between host defence peptide IDR-1002 and ciprofloxacin: Effects on human dental pulp cells.

To evaluate the effects of the association of host defence peptide IDR-1002 and ciprofloxacin on human dental pulp cells (hDPSCs). hDPSCs were stimulated with ciprofloxacin and IDR-1002. Cell viability (by MTT assay), migration capacity (by scratch assay), production of inflammatory and anti-inflammatory mediators by hDPSCs (RT-PCR) and osteogenic differentiation (alizarin red staining) were evaluated. Phenotypic profile of hDPSCs demonstrated 97% for positive marked mesenchymal stem cell. Increased pulp cell migration and proliferation were observed after 24 and 48 h of exposure to IDR-1002 with ciprofloxacin. Mineral matrix formation by hDPSCs was observed of the association while its reduction was observed in the presence of peptide. After 24 h, the association between ciprofloxacin and IDR-1002 significantly downregulated TNFRSF-1, IL-1ß, IL-8, IL-6 and IL-10 gene expression (p ≤ 0.0001). The association between the IDR-1002 and ciprofloxacin showed favourable immunomodulatory potential, emerging as a promising option for pulp revascularisation processes.

Chitosan-based crosslinking for controlled topical drug release in rhinosinusitis.

KEY POINTS: Chitosan is a promising drug delivery vector for therapeutics owing to its biocompatibility. Once crosslinked with chitosan, prolonged drug release was noted regardless of hydrophilicity. Hydrophilic drugs may require different strategies to obtain a sustained release profile.

A biochemical assessment of apoptosis-inducing impact of Salinomycin in combination with ciprofloxacin on human leukemia KG1-a stem-like cells in the presence and absence of insulin.

BACKGROUND: Acute Myeloid Leukemia (AML) is a fast-developing invading cancer that impacts the blood and bone marrow, marked by the rapid proliferation of abnormal white blood cells. Chemotherapeutic agents, a primary treatment for AML, encounter clinical limitations such as poor solubility and low bioavailability. Previous studies have highlighted antibiotics as effective in inducing cancer cell death and potentially preventing metastasis. Besides, insulin is known to activate the PI3K/Akt pathway, often disrupted in cancers, leading to enhanced cell survival and resistance to apoptosis. In light of the above-mentioned points, we examined the anti-cancer impact of antibiotics Ciprofloxacin (CP) and Salinomycin (SAL) and their combination on KG1-a cells in the presence and absence of insulin. METHODS: This was accomplished by exposing KG1-a cells to different doses of CP and SAL alone, in combination, and with or without insulin for 24-72 h. Cell viability was evaluated using the MTT assay. Besides, apoptotic effects were examined using Hoechst staining and Annexin-V/PI flow cytometry. The expression levels of Bax, p53, BIRC5, Akt, PTEN, and FOXO1 were analyzed through Real-Time PCR. RESULTS: CP and SAL demonstrated cytotoxic and notable pro-apoptotic impact on KG1-a cells by upregulating Bax and p53 and downregulating BIRC5, leading to G0/G1 cell cycle arrest and prevention of the PI3K-Akt signaling pathway. Our findings demonstrated that combination of CP and SAL promote apoptosis in the KG1-a cell line by down-regulating BIRC5 and Akt, as well as up-regulating Bax, p53, PTEN, and FOXO1. Additionally, the findings strongly indicated that insulin effectively mitigates apoptosis by enhancing Akt expression and reducing FOXO1 and PTEN gene expression in the cells treated with CP and SAL. CONCLUSION: Our findings showed that the combined treatment of CP and SAL exhibit a strong anti-cancer effect on leukemia KG1-a cells. Moreover, it was discovered that the PI3K-Akt signaling can be a promising target in leukemia treatment particularly in hyperinsulinemia condition.

Metal-free Carbon Material Derived from Lantana Camara for the Detection and Removal of Ciprofloxacin.

This work reports the preparation of a metal-free nitrogen and sulphur functionalized graphitic carbon sheets from a unique and less expensive precursor Lantana camara, which is a common hazardous weed in India. The synthesized material NS-CN-180 was successfully tested for the adsorption and removal of fluoroquinolone antibiotics ciprofloxacin. The surface morphology and elemental composition of NS-CN-180 were investigated through FESEM and XPS analyses. The SEM data reveals the graphitic sheets stacked onto each other with cavities in between them. The presence of various functional groups was identified through FT-IR spectroscopy and the degree of graphitization was calculated from XRD pattern. The probable mechanism of interaction for ciprofloxacin molecule with NS-CN-180 was also investigated with the help of FT-IR and zeta potential analyses. The fabricated material was found to be excellent for ciprofloxacin detection with a limit of detection value 16.08 nM. Also, the prepared material efficiently removes the 66.2% ciprofloxacin drug in 1 h. Adsorption and desorption experiments were performed to demonstrate the reusability of the material.

Ciprofloxacin is a novel anti-ferroptotic antibiotic.

Cancer patients undergoing chemotherapy are susceptible to various bacterial infections, necessitating prompt and precise antimicrobial treatment with antibiotics. Ciprofloxacin is a clinically utilized broad-spectrum antimicrobial agent known for its robust antiseptic activity. While ferroptosis, an oxidative form of cell death, has garnered attention as a promising avenue in cancer therapy, the potential impact of ciprofloxacin on the anticancer effects of ferroptosis remains unclear. This study seeks to investigate the potential influence of antibiotics on ferroptosis in human pancreatic ductal adenocarcinoma (PDAC) cells. Here, we report a previously unrecognized role of ciprofloxacin in inhibiting ferroptosis in human PDAC cells. Mechanistically, ciprofloxacin suppresses erastin-induced endoplasmic reticulum (ER) stress through the activating transcription factor 6 (ATF6) and ER to nucleus signaling 1 (ERN1) pathway. Excessive ER stress activation can trigger glutathione peroxidase 4 (GPX4) degradation through autophagic mechanisms. In contrast, ciprofloxacin enhances the protein stability of GPX4, a crucial regulator that suppresses ferroptosis by inhibiting lipid peroxidation. Thus, our study demonstrates the anti-ferroptotic role of ciprofloxacin, highlighting the importance of careful consideration when contemplating the combination of ciprofloxacin with specific ferroptosis inducers in PDAC patients.

Gut microbiota and serum metabolomic alterations in modulating the impact of fecal microbiota transplantation on ciprofloxacin-induced seizure susceptibility.

Introduction: The gut microbiota and the microbiota-gut-brain axis have gained considerable attention in recent years, emerging as key players in the mechanisms that mediate the occurrence and progression of many central nervous system-related diseases, including epilepsy. In clinical practice, one of the side effects of quinolone antibiotics is a lower seizure threshold or aggravation. However, the underlying mechanism remains unclear. Methods: We aimed to unravel the intrinsic mechanisms through 16S rRNA sequencing and serum untargeted metabolomic analysis to shed light on the effects of gut microbiota in ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models. Results: We observed that ciprofloxacin treatment increased seizure susceptibility and caused gut dysbiosis. We also found similar changes in the gut microbiota of rats with lithium pilocarpine-induced epilepsy. Notably, the levels of Akkermansia and Bacteroides significantly increased in both the ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models. However, Marvinbryantia, Oscillibacter, and Ruminococcaceae_NK4A214_group showed a coincidental reduction. Additionally, the serum untargeted metabolomic analysis revealed decreased levels of indole-3-propionic acid, a product of tryptophan-indole metabolism, after ciprofloxacin treatment, similar to those in the plasma of lithium pilocarpine-induced epilepsy in rats. Importantly, alterations in the gut microbiota, seizure susceptibility, and indole-3-propionic acid levels can be restored by fecal microbiota transplantation. Conclusion: In summary, our findings provide evidence that ciprofloxacin-induced seizure susceptibility is partially mediated by the gut microbiota and tryptophan-indole metabolism. These associations may play a role in epileptogenesis, and impacting the development progression and treatment outcomes of epilepsy.

Design, synthesis and structure-activity relationships of novel non-ketolides: 9-Oxime clarithromycin featured with seven-to thirteen-atom-length diamine linkers at 3-OH.

We report here on the structure-activity relationships of hybrids combining 3-descladinosyl clarithromycin with quinolones linked by extended diamine connectors. Several hybrids, exemplified by 23Bc, 23Be, 23Bf, 26Be, and 30Bc, not only restored potency against inducibly resistant pathogens but also exhibited significantly enhanced activities against constitutively resistant strains of Staphylococcus pneumoniae and Staphylococcus pyogenes, which express high-level resistance independent of clarithromycin or erythromycin induction. Additionally, the novel hybrids showed susceptibility against Gram-negative Haemophilus influenzae. Notably, hybrid 23Be demonstrated dual modes of action by inhibiting both protein synthesis and DNA replication in vitro and in vivo. Given these promising characteristics, 23Be emerges as a potential candidate for the treatment of community-acquired bacterial pneumonia.

Micropollutants (ciprofloxacin and norfloxacin) remediation from wastewater through laccase derived from spent mushroom waste: Fate, toxicity, and degradation.

Fluoroquinolone antibiotics frequently found in environmental matrices (wastewater treatment plants, hospital wastewater, industrial wastewater and surface wastewater) causes potential threat to the environment. Enzymatic treatment for degradation of antibiotics from environmental matrices is a green and sustainable approach. Focusing on this, this study aimed to degrade two frequently found fluroquinolone emergent pollutants, ciprofloxacin and norfloxacin from wastewater. The trinuclear cluster of copper ions present in laccase has the ability to effectively remove organic micropollutants (OMPs). The uniqueness of this study is that it utilizes laccase enzyme extracted from spent mushroom waste (SMW) of P. florida for degradation of ciprofloxacin and norfloxacin and to achieve highest degradation efficiency various parameters were tweaked such as pH (3-6), temperature (30 °C and 50 °C), and ABTS (0.05, 0.6, and 1 mM) concentration. The results showed that the most effective degradation of ciprofloxacin (86.12-75.94%) and norfloxacin (83.27-65.94%) was achieved in 3 h at pH 4.5, temperature 30 °C, and 2,2'-azino-bis 3-ethylbenzothiazoline-6-sulfonic acid (ABTS), 0.05 mM concentration. Nevertheless, achieving degradation at 50 °C for both antibiotics, indicates thermostability nature of laccase (P. florida). Further, the fate of transformed products obtained from laccase mediated degradation was confirmed by liquid chromatography (LC-MS). Both the antibiotics undergo decarboxylation, depiperylyzation, dealkylation and defluorination as a result of laccase-mediated bond breakage. Anti-microbial activity of the biodegraded products was monitored by residual anti-bacterial toxicity test (E. coli and Staphylococcus aureus). The biodegraded products were found to be non-toxic and resulted in the growth of E. coli and Staphylococcus aureus, as determined by the agar-diffusion method. Moreover, the storage stability of laccase was determined for 28-day duration at varying pH (3-10) and temperature (4-50 °C). The maximum storage stability was obtained at pH 4.5 and temperature 30 °C. Therefore, utilizing SMW for the degradation of OMPs from wastewater not only benefits in degradation but also reuses SMW agro waste, shedding light on agro waste management. Thus, SMW is a one-pot solution for both OMPs biodegradation and circularity in the economy.

Thymoquinone' potent impairment of multidrug-resistant Staphylococcus aureus NorA efflux pump activity.

The drug efflux pump is a crucial mechanism implicated in resistance to multiple antimicrobials. Thymoquinone (TQ) has evidently demonstrated multiple activities, antibacterial being the most effective. Knowledge about TQ activity against multidrug-resistant Staphylococcus aureus is very scarce. Therefore, the present study was conducted to investigate TQ resistance modulation in ciprofloxacin (CIP) and doxycycline (DO) multidrug-resistant S. aureus. Forty-seven samples were collected from different sources, and S. aureus was isolated and identified. Then, S. aureus resistance profiles to antimicrobials, N. sativa essential oil, and TQ; the correlation between TQ-MIC readings and disc diffusion; cartwheel and ethidium bromide (EtBr) accumulation assays; and norA gene expression were all described within silico molecular docking for TQ interactions with norA efflux pump protein. TQ-MICs ranged from 5-320 µg/ml. TQ down-regulated norA gene expression, resulting in a drop in efflux pump activity of 77.5-90.6% in the examined strains, comparable to that observed with verapamil. Exposure of S. aureus strains to CIP and DO raises the initial basal efflux pumping expression to 34.2 and 22.9 times, respectively. This induced efflux pumping overexpression was substantially reduced by 97.7% when TQ was combined with CIP or DO. There was a significant reduction of MICs of CIP and DO MICs by 2-15 and 2-4 folds, respectively, after treatment with 0.5XMIC-TQ in resistance modulation assays. These results refer to TQ ligand inhibitory interactions with NorA protein in molecular docking. Interpretations of inhibition zone diameters (IZDs) of disc diffusion and TQ-MICs exhibit independence of MICs from IZDs, as indicated by invalid linear regression analysis. TQ significantly reduced efflux pumping S. aureus induced by CIP and DO, but further investigations are needed to improve TQ-pharmacokinetics to restore CIP and DO activity and suppress fluoroquinolone and doxycycline-resistant S. aureus selection in clinical and animal settings.

An "in control" hyaluronic acid nanogel with light-cleavable for rational use of antibiotics.

The consequences caused by bacterial resistance are becoming more and more serious. The rate of antibiotic development is far behind the rate of bacterial resistance, so it is urgent to develop a new drug system. In this study, photoresponsive nanogels based on hyaluronic acid were prepared and loaded with ciprofloxacin as a model molecule. The results showed that the nanogels had the advantages of high stability and good cytocompatibility. The inhibition effect of drug-loaded nanogels after light irradiation on the growth of Staphylococcus aureus and Salmonella typhimurium was significantly better than that before light irradiation, and ciprofloxacin could be released on demand and in control. This strategy is of great significance to reduce the unnecessary use of antibiotics and weaken bacterial resistance.

Efficient removal of ciprofloxacin from aqueous solution using Zn-C battery derived graphene oxide enhanced by hydrogen bonding, electrostatic and π-π interaction.

In this study, graphene oxide (GO) derived from waste Zinc-Carbon (Zn-C) batteries was proposed for the efficient removal of antibiotics from the aqueous solution. Ciprofloxacin (CIP) antibiotic was selected as a typical contaminants. GO was prepared via an economical and environment-friendly route by using carbon rods from waste Zn-C batteries as the precursor. Characterization techniques were applied to determine the properties of as prepared GO. Effects of pH, contact time, and adsorbent dose on the adsorption were explored, and an optimum condition was established. Adsorption equilibrium was established in just 20 min for maximum removal of CIP (99.0%) at pH 5.7 for the adsorbent dose of 20 mg L-1 and at the initial concentration of CIP 2.0 mg L-1. The rapid and efficient removal of CIP was greatly influenced by the electrostatic attractions, pi-pi interactions and hydrogen bonding on the surface and edge of GO which was also proved by density functional theory (DFT). Langmuir model showed the best fit among the isotherm models and the calculated maximum adsorption capacity (qm) was 419.62 mg g-1 at 30°C. The kinetic studies also revealed that the adsorption process followed the pseudo-second-order model. The endothermic and spontaneous nature of adsorption was evaluated in thermodynamic studies.

Impact of a Switch From Ciprofloxacin to Ceftriaxone Prophylaxis on Infectious Complications After Transrectal Ultrasound-Guided Biopsy of the Prostate.

In a 12-year single-center quasi-experimental study, a switch from ciprofloxacin to ceftriaxone prophylaxis for transrectal ultrasound-guided prostate biopsy procedures was associated with a significant reduction in 30-day postprocedure urinary tract infection, urinary tract infection-related hospitalizations, antibiotic prescriptions, and isolation of fluoroquinolone-resistant organisms from urine or blood cultures.

Improving selectivity and antifouling properties of a PES hollow fibre membrane with a photo-enzyme for the removal of ciprofloxacin and sulfamethoxazole.

A multifunctional hollow fibre was prepared by the modification of polyethersulfone (PES) with laccase (Lac) and phosphorus-doped graphitic carbon nitride (P-gC3N4) for the removal of ciprofloxacin and sulfamethoxazole. The properties and structure elucidation of the prepared membranes were evaluated using contact angle analysis, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), correlative light electron microscopy (CLEM), atomic force microscopy (AFM), tensile strength, water-intake capacity, and pure water flux. The modified multifunctional hollow fibre membranes showed increased root mean square surface roughness from 50 nm for neat PES to 104 nm, which contributed to the significantly higher water flux of 90 L.m-2h-1 compared to 54 L.m-2h-1 for pristine PES. The hydrophilicity also improved after modification as the contact angle reduced from 72° ± 1.01° to 42° ± 2.26°. The modified hollow fibre membranes showed an enhanced removal of ciprofloxacin (77%) and sulfamethoxazole (80%). Moreover, antifouling properties towards bovine serum albumin were 89% for FRR, 7% for Rr, 9% for Rir and 17% for Rt. Regeneration studies showed that the multifunctional hollow fibre membrane obtained a high removal percentage of 79% towards sulfamethoxazole after five cycles. Hence, this work proposes a new system that can be successfully utilized in the treatment of emerging pharmaceutical pollutants in water.

How denitrifiers defense ciprofloxacin: Insights from intracellular and extracellular stress response.

Overuse of antibiotics has led to their existence in nitrogen-containing water. The impacts of antibiotics on bio-denitrification and the metabolic response of denitrifiers to antibiotics are unclear. We systematically analyzed the effect of ciprofloxacin (CIP) on bio-denitrification and found that 5 mg/L CIP greatly inhibited denitrification with a model denitrifier (Paracoccus denitrificans). Nitrate reduction decreased by 32.89 % and nitrous oxide emission increased by 75.53 %. The balance analysis of carbon and nitrogen metabolism during denitrification showed that CIP exposure blocked electron transfer and reduced the flow of substrate metabolism used for denitrification. Proteomics results showed that CIP exposure induced denitrifiers to use the pentose phosphate pathway more for substrate metabolism. This caused a substrate preference to generate NADPH to prevent cellular damage rather than NADH for denitrification. Notably, despite denitrifiers having antioxidant defenses, they could not completely prevent oxidative damage caused by CIP exposure. The effect of CIP exposure on denitrifiers after removal of extracellular polymeric substances (EPS) demonstrated that EPS around denitrifiers formed a barrier against CIP. Fluorescence and infrared spectroscopy revealed that the binding effect of proteins in EPS to CIP prevented damage. This study shows that denitrifiers resist antibiotic stress through different intracellular and extracellular defense strategies.