Impact of ciprofloxacin with autophagy on renal tubular injury.

BACKGROUNDS: Renal tubular injury caused by oxidative stress and inflammation results in acute kidney injury. Recent research reported that antibiotics may protect renal tubules from progressive deterioration, but the underlying mechanism remains unclear. Therefore, we investigated the efficacy and mechanism of action of antibiotics against renal tubular injury. METHODS: We screened ciprofloxacin, ceftizoxime, minocycline, and netilmicin and selected ciprofloxacin to examine further because of its low toxicity towards renal tubular cells. We evaluated the effect of ciprofloxacin on cell survival by analyzing apoptosis and autophagy. RESULTS: Terminal deoxynucleotidyl transferase-mediated d-UTP nick end labeling (TUNEL) assay results showed that the ciprofloxacin group had less apoptotic cells than the control group. The ratio of cleaved caspase 3 to caspase 3, the final effector in the apoptosis process, was decreased, but the ratio of B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax) to Bcl-2 located upstream of caspase 3 was not decreased in the ciprofloxacin group. Therefore, apoptosis inhibition does not occur via Bax/Bcl-2. Conversely, the levels of phosphorylated Bcl-2, and Beclin-1, an autophagy marker, were increased, and that of caspase-3 was decreased in the ciprofloxacin group. CONCLUSION: This indicates that ciprofloxacin enhances autophagy, increasing the amount of free Beclin-1 via phosphorylated Bcl-2, and inhibits caspase activity. Therefore, ciprofloxacin might protect against renal tubular injury through the activation of autophagy in the setting of acute kidney injury.

The fluoroquinolones may positively affect tendon healing after surgical repair.

OBJECTIVES: This study aimed to evaluate the biomechanical and histological effects of fluoroquinolones on surgically repaired tendon healing. MATERIALS AND METHODS: The Achilles tendons of 40 Wistar rats (mean weight: 213.5 g; range 201 to 242 g) were bilaterally surgically cut and repaired. The rats were randomly divided into four groups: the first and third groups were designated as control groups and did not receive drug therapy, whereas the second and fourth groups received 300 mg/kg ciprofloxacin for a week after the surgical procedure. The first and second groups had both tendons dissected at the end of the first week, while the third and fourth groups were dissected at the end of the third week. The left tendons were examined biomechanically, while the right tendons were examined histologically. RESULTS: Statistical analysis revealed that the mean maximum tensile forces of tendons in the first and second groups were 5.2±1.84 N (range, 2.9 to 8.5 N) and 11.1±2.65 N (range, 7.3 to 13.9 N), respectively, which was found to be statistically significant (p< 0.05). At the end of the third week, mean maximum tensile forces of the third and fourth groups were determined to be 20.7±5.0 N (range, 22.1 to 29.8 N) and 28.7±4.6 N (range, 22.1 to 36.8 N), respectively, which was also statistically significant (p< 0.05). Histologically, our results were compatible. CONCLUSION: This study demonstrated that ciprofloxacin did not exhibit the expected adverse effects on surgically repaired tendon healing in the early stages but likely contributed to healing in the short term by affecting the inflammatory phase.

A phase ib clinical trial of oral ciprofloxacin and etoposide in subjects with resistant acute myeloid leukemia.

A phase 1b study was conducted to evaluate the safety and feasibility of ciprofloxacin and etoposide combination treatment in subjects with relapsed and refractory acute myeloid leukemia. Eleven subjects were enrolled in the study. Utilizing the standard '3 + 3' design, escalating ciprofloxacin doses (750 mg, 1000 mg) twice daily on D1-D10 in combination with a fixed dose (200 mg) of etoposide on D2-D8 were administered. Maximum tolerated dose was determined to be 1000 mg of ciprofloxacin in combination with 200 mg of etoposide. Serious adverse events occurred in 54.5% (n = 6) subjects and 91% (n = 10) subjects reported ≥ grade 3 toxicities. Nine subjects completed treatment, one had a dose-limiting toxicity, and one withdrew. One subject achieved complete remission with a duration of 111 days and one subject achieved morphologic leukemia-free state after cycle 1. While the combination demonstrated safety and an acceptable toxicity profile, only modest hematologic and clinical benefits were observed.This trial was registered at www.clinicaltrials.gov as #NCT02773732.

Crystalline keratopathy secondary to the use of ciprofloxacin after cataract surgery with confirmation by histopathological study: A case report and review of the literature.

OBJECTIVE: To report the case of a 75-year-old patient who presented crystalline keratopathy secondary to the use of topical ciprofloxacin with histopathological verification, after cataract surgery without complications. METHOD: Case report with clinical and photographic follow-up, as well as slides with samples of epithelium and crystalline deposits. RESULTS: Corneal deposits resolved after drug suspension, topical lubricant change, and subsequent surgical debridement. The histopathological examination reported epithelial cells and basophilic particles compatible with drug precipitates. CONCLUSIONS: Crystalline keratopathy is a condition in which crystals of various kinds are deposited in the corneal epithelium and/or in the anterior stroma. It may have an infectious, pharmacological cause or, in rarer cases, corneal dystrophies. Certain factors such as a previous epithelial defect, systemic pathology with diabetes mellitus, ocular surgery and previous dry eye can favor the deposition of ciprofloxacin leading to the formation of a keratopathy.

Aplastic anaemia following antibiotic use for urinary tract infection.

Aplastic anaemia is often associated with recent viral illnesses to include EBV and parvovirus along with certain medications such as anticonvulsants and sulfa containing antibiotics. We describe a case report of a female patient in her 70s who presented with pancytopenia after being treated with nitrofurantoin and ciprofloxacin for suspected urinary tract infection. She underwent an extensive workup to rule out alternative aetiologies of her pancytopenia to include a broad viral, autoimmune and malignancy evaluation which were unrevealing. Given her recent exposure to ciprofloxacin and nitrofurantoin and marrow recovery following removal of these agents, it was presumed that antibiotic exposure was the underlying cause of her aplastic anaemia.

Assessing National Trends and Perceived Safety of Off-Label Ciprofloxacin-Dexamethasone Use by Pediatric Otolaryngologists.

OBJECTIVES: Off-label use of Ciprodex® (ciprofloxacin-dexamethasone: CPD), an antibiotic-steroid combination solution, in the airway has been reported by pediatric otolaryngologists with anecdotal success. We examined national trends regarding off-label CPD use including prevalence, common indications, prescriber patterns, adverse events, and accessibility. METHODS: 15-item cross-sectional survey was distributed to American Society of Pediatric Otolaryngology members from January-April 2022. Univariate analyses were performed to compare responses for users of off-label CPD versus non-users. Ease of access was compared across geographies and practice types using multivariate logistic regressions. RESULTS: Of the 163 complete responses (26.6% response rate), 156 (95.7%) reported using off-label CPD. Most common indications for off-label CPD were tracheal granulation (87.8%, n = 137) and choanal atresia (82.1%, n = 128). Ease of access was significantly increased in the Midwest (OR:18.79, 95%CI:3.63-1.24, p = 0.001) and West (OR:29.92, 95%CI:3.55-682.00, p = 0.006). Ease of access was significantly lower at tertiary referral centers (OR:0.11, 95%CI:0.01-0.64, p = 0.041) and private practices (OR:0.04, 95%CI:0.002-0.33, p = 0.009) compared to academic free-standing children's hospitals. Two-thirds of respondents reported feeling "Very Comfortable" with the safety profile of off-label CPD; 99.4% (n = 156) felt that the benefits outweighed the risks of off-label use. Seven respondents (4.5%) reported adverse events (e.g., local allergic reaction, cushingoid symptoms) from off-label use. CONCLUSIONS: Our findings (26.6% response rate) suggest that off-label CPD is commonly used by pediatric otolaryngologists, many of whom reported feeling that the benefits of off-label CPD outweigh the risks. Our results establish a baseline for future efforts to assess the efficacy and safety of off-label CPD and to improve its accessibility. LEVEL OF EVIDENCE: V Laryngoscope, 134:2922-2930, 2024.

Multivariate guard-bands and total risk assessment on multiparameter evaluations with correlated and uncorrelated measured values

Abstract The quality, efficacy, and safety of medicines are usually verified by analytical results. Measurement uncertainty is a critical aspect for the reliability of these analytical results. The pharmacopeial compendia usually adopt a simple acceptance rule that does not consider information from measurement uncertainty. In this work, we compared decision-making using simple acceptance and decision rules with the use of guard-band for multiparameter evaluation of ofloxacin ophthalmic solution and acyclovir topical cream. Ciprofloxacin ophthalmic solution and acyclovir topical cream samples were subject to pharmacopeial tests and assays. Multivariate guard-band widths were calculated by multiplying the standard uncertainty (u) by an appropriate multivariate coverage factor (k'). The multivariate coverage factor (k') was obtained by the Monte Carlo method. According to the simple acceptance rule, all the results obtained for ciprofloxacin ophthalmic solution and acyclovir topical cream are within the specification limits. However, the risk of false conformity decisions increases for ciprofloxacin tests. Decisions made using the simple acceptance rule and decision rules with the use of guard-band may differ. The simple acceptance rule may increase the risk of false conformity decisions when the measured value is close to the regulatory specification limits and/or when the measurement uncertainty value is inappropriately high. Nevertheless, the guard-band decision rule will always reduce the risk of false conformity decisions. Therefore, using information on measurement uncertainty in conformity assessment is highly recommended to ensure the proper efficacy, safety, and quality of medicines.

FOVOCIP study: a multicenter randomized trial of fosfomycin versus ciprofloxacin for febrile neutropenia in hematologic patients-efficacy and microbiologic safety.

BACKGROUND: Multidrug-resistant Gram-negative bacterial (MRGNB) infections represent a major public health threat. Cancer patients and, among them, hematological patients are most vulnerable to these infections. Gut colonization by MRGNB is a common phenomenon occurring during hospitalization and chemotherapy exposure. In the neutropenic phase that occurs after chemotherapy, MRGNB translocation occurs increasing patient's mortality. Fluoroquinolone prophylaxis with ciprofloxacin or levofloxacin efficacy is now being questioned due to the increase of incidence in MRGNB. METHODS: A phase III randomized, controlled, clinical trial, open-label parallel-group with a 1:1 ratio, aimed to demonstrate the non-inferiority of oral fosfomycin versus oral ciprofloxacin for febrile neutropenia prevention in patients with acute leukemia (AL) or hematopoietic cell transplant (HSC) receptors. Weekly surveillance cultures are planned to detect gut colonization. Changes in fecal microbiome at the beginning and end of prophylaxis will also be analyzed. DISCUSSION: This trial will provide evidence of the efficacy of an alternative drug to ciprofloxacin for febrile neutropenia prevention in high-risk hematological patients. The battery of planned microbiological studies will allow us to evaluate prospectively the microbiological safety of both pharmacological strategies in terms of the selection of MRGNB occurring in each arm. In addition, valuable information on the way in which each drug changes the fecal microbiome of the patients throughout the treatment will be generated. TRIAL REGISTRATION: Clinical trials NCT05311254, Registered on 5 April 2022, https://clinicaltrials.gov/ct2/show/NCT05311254?term=FOVOCIP&cntry=ES&draw=2&rank=1 . PROTOCOL VERSION: 3.0, dated 20 May 2022.

Comparative effectiveness and safety of antibiotic prophylaxis during induction chemotherapy in children with acute leukaemia: a systematic review and meta-analysis.

BACKGROUND: Bacterial infections are common during induction therapy in children and adolescents with acute leukaemia and may cause infection-related mortality. AIM: To determine the efficacy and safety of prophylactic antibiotics in paediatric patients with acute leukaemia receiving induction chemotherapy. METHODS: From three English databases and four Chinese databases, we searched for randomized controlled trials (RCTs) and cohort studies that compared prophylactic antibiotics to placebo, no prophylaxis, or that compared one antibiotic versus another in paediatric patients with acute leukaemia undergoing induction chemotherapy. Two reviewers independently screened the studies, extracted data, and assessed the risk of bias using Cochrane Risk of Bias 2 tool and Newcastle-Ottawa Scale, and the certainty of evidence using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). FINDINGS: Two RCTs and ten cohort studies were finally included. For children with acute lymphoblastic leukaemia, antibiotic prophylaxis, including levofloxacin, sulfamethoxazole-trimethoprim, or other antibiotics, probably reduced bacteraemia (risk ratio (RR): 0.44; 95% confidence interval (CI): 0.33-0.60; moderate certainty) without significantly increasing Clostridioides difficile infection (CDI) or invasive fungal infection. Levofloxacin reduced the CDI rate (RR: 0.08; 95% CI: 0.01-0.62; high certainty). Ciprofloxacin prophylaxis probably reduced infection-related mortality (RR: 0.12; 95% CI: 0.01-0.97; moderate certainty). In children with acute myeloid leukaemia, ciprofloxacin plus vancomycin may reduce febrile neutropenia (RR: 0.79; 95% CI: 0.66-0.94; low certainty). Individual studies indicated that prophylaxis increased antibiotic exposure but reduced non-preventive antibiotic exposure. CONCLUSION: In children with acute leukaemia undergoing induction therapy, antibiotic prophylaxis may improve the bacterial infection and mortality.

Exposure of anti-infective drugs and the dynamic changes of the gut microbiota during gastrointestinal mucositis in autologous stem cell transplant patients: a pilot study.

Gastrointestinal mucositis could potentially compromise drug absorption due to functional loss of mucosa and other pathophysiological changes in the gastrointestinal microenvironment. Little is known about this effect on commonly used anti-infectives. This study aimed to explore the association between different stages of gastrointestinal mucositis, drug exposure, and gut microbiota. A prospective, observational pilot study was performed in HSCT patients aged ≥ 18 years receiving anti-infectives orally. Left-over blood samples and fecal swabs were collected from routine clinical care until 14 days after HSCT to analyze drug and citrulline concentrations and to determine the composition of the gut microbiota. 21 patients with a median age of 58 (interquartile range 54-64) years were included with 252 citrulline, 155 ciprofloxacin, 139 fluconazole, and 76 acyclovir concentrations and 48 fecal swabs obtained. Severe gastrointestinal mucositis was observed in all patients. Due to limited data correlation analysis was not done for valacyclovir and fluconazole, however we did observe a weak correlation between ciprofloxacin and citrulline concentrations. This could suggest that underexposure of ciprofloxacin can occur during severe mucositis. A follow-up study using frequent sampling rather than the use of left-over would be required to investigate the relationship between gastrointestinal mucositis, drug exposure, and gut microbiome.

Administration of ciprofloxacin through a nasogastric tube in pediatric oncology and stem cell transplantation patients.

Pediatric oncology and hematopoietic stem cell transplantation patients are facing many gastrointestinal side effects of chemotherapy, including nausea, vomiting, mucositis, and diarrhea. International guidelines advise early enteral tube feeding as the first option of nutritional support in children undergoing myeloablative hematopoietic stem cell transplantation. When using enteral feeding tubes for nutritional purposes as well as drug administration, some pharmaceutical, nursing, and technical issues have to be taken into account. Ciprofloxacin is a fluoroquinolone, widely used because of its broad spectrum antimicrobial activity and favorable pharmacokinetic properties. However, its co-administration with polyvalent cations (as present in enteral feeding) makes the absorption of ciprofloxacin more difficult and may alter the pharmacokinetic parameters. Literature data are conflicting on how long the enteral feeding should be discontinued for patients receiving ciprofloxacin via an enteral feeding tube, ranging from 2 h before to 6 h after the administration of ciprofloxacin. Our research question was guided by challenges and concerns of nurses about the delay time between ciprofloxacin administration and restart of the enteral feeding without compromising the nutritional intake of the children. Our guideline was adapted, nurses were instructed accordingly, and patient leaflets with correct information were created.

A preventable, life-altering case of fluoroquinolone-associated tendonitis.

ABSTRACT: Fluoroquinolones, such as ciprofloxacin and levofloxacin, are broad-spectrum antibacterial agents that have historically been widely used for urinary tract infections, pneumonia, and intra-abdominal infections but are associated with several serious adverse reactions, including tendinopathy and tendon rupture, peripheral neuropathy, and aortic aneurysm. These drugs should not be used for uncomplicated infections unless no other antimicrobial treatment is feasible. This article describes a patient who experienced life-altering disability from a fluoroquinolone, reviews the adverse reactions of this drug class, and discusses recommended treatment for acute uncomplicated cystitis and asymptomatic bacteriuria.

Targeted AntiBiotics for Chronic pulmonary diseases (TARGET ABC): can targeted antibiotic therapy improve the prognosis of Pseudomonas aeruginosa-infected patients with chronic pulmonary obstructive disease, non-cystic fibrosis bronchiectasis, and asthma? A multicenter, randomized, controlled, open-label trial.

BACKGROUND: Pseudomonas aeruginosa infection is seen in chronic pulmonary disease and is associated with exacerbations and poor long-term prognosis. However, evidence-based guidelines for the management and treatment of P. aeruginosa infection in chronic, non-cystic fibrosis (CF) pulmonary disease are lacking. The aim of this study is to investigate whether targeted antibiotic treatment against P. aeruginosa can reduce exacerbations and mortality in patients with chronic obstructive pulmonary disease (COPD), non-CF bronchiectasis, and asthma. METHODS: This study is an ongoing multicenter, randomized, controlled, open-label trial. A total of 150 patients with COPD, non-CF bronchiectasis or asthma, and P. aeruginosa-positive lower respiratory tract samples will be randomly assigned with a 1:1 ratio to either no antibiotic treatment or anti-pseudomonal antibiotic treatment with intravenous beta-lactam and oral ciprofloxacin for 14 days. The primary outcome, analyzed with two co-primary endpoints, is (i) time to prednisolone and/or antibiotic requiring exacerbation or death, in the primary or secondary health sector, within days 20-365 from study allocation and (ii) days alive and without exacerbation within days 20-365 from the study allocation. DISCUSSION: This trial will determine whether targeted antibiotics can benefit future patients with chronic, non-CF pulmonary disease and P. aeruginosa infection in terms of reduced morbidity and mortality, thus optimizing therapeutic approaches in this large group of chronic patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03262142 . Registered on August 25, 2017.

Rifampicin-induced fever during treatment against staphylococcal biofilm in a patient with periprosthetic joint infection.

Periprosthetic joint infection (PJI) after total knee arthroplasty remains a challenging complication. The treatment options for PJI include different procedures; however, regardless of the strategy, antibiotics are required. The combination of different antibiotics increased the rates of PJI eradication. For almost 3 decades, rifampicin has been used as part of antibiotic therapy for PJI. Drug fever, a febrile response that coincides with the onset of drug administration and disappears after drug discontinuation in the absence of other underlying conditions that could cause fever, is frequently misdiagnosed. We present the case of a 72-year-old man with PJI 6 months after total knee arthroplasty. Two-stage revision surgery was followed by culture-directed antibiotic treatment (ciprofloxacin and rifampicin) against Staphylococcus aureus isolated from the periprosthetic tissue. On the fifth day of antibiotic treatment, the patient became febrile and, in the next 5 days, he had an intermittent fever of up to 40°C, although he showed clinical improvement. The patient was normotensive without a maculopapular rash, urticaria or clotting abnormalities. A drug fever was suspected, and rifampicin was discontinued. A re-challenge test was performed, and the fever recurred. Antibiotic treatment with ciprofloxacin was continued and, after 12 months of follow-up, the patient was doing well. Clinicians should be aware that fever could be a clinical presentation of drug fever. If it occurs during an infection, drug fever could necessitate additional diagnostic procedures for further evaluation, inadequate antibiotic therapy and prolonged hospitalisation.

Long-term Antibiotic Treatment in Pouchitis-Patterns of Use and Safety.

INTRODUCTION: Pouchitis, often developing after colectomy and ileal pouch-anal anastomosis for ulcerative colitis, is highly responsive to antibiotics. Ciprofloxacin and/or metronidazole are commonly used, often for prolonged periods. We report patterns of antibiotic use, adverse events, and resistant infections in patients with pouchitis with long-term antibiotic treatment. METHODS: In a cohort of patients following pouch surgery, a retrospective nested case-control analysis was performed between 2010 and 2017. Ultra-long-term use, defined as the top 10% of users, was compared with the remaining users. Patterns of antibiotic use, adverse events, and resistant infections were analyzed. RESULTS: The cohort included 205 patients with UC, of whom 167 (81.5%) used antibiotics for pouchitis, predominantly ciprofloxacin. The long-term antibiotic use rate was 18% and 42% at 5 and 20 years postsurgery, respectively. Mean antibiotic use of at least 1, 3, and 6 months/year was noted in 54 (26.3%), 31 (15.1%), and 14 (6.8%) patients, respectively. Twenty-two (13.2%) and 4 (2.4%) patients reported mild and severe (transient) adverse events, respectively, without mortalities, tendinopathies or arrhythmias. Adverse event rates for ciprofloxacin and metronidazole were 1per 10,000 and 6 per 10,000 use-days, respectively. Longer, but not ultra-long antibiotic use, was associated with mild adverse events. There was no association between antibiotic use and resistant infections. Thirteen (6.3%) patients required ileostomy procedures-more commonly in the ultra-long-term antibiotic users. CONCLUSIONS: Patients with pouchitis may require prolonged antibiotic treatment, reflecting clinical benefit and favorable safety profile. Few adverse events and resistant infections were observed with long-term antibiotics use. However, resistant microbial strains selection, which are potentially transmittable, warrants consideration of different therapeutic alternatives.

[Achilles tendinopathy in a hemodialysis patient complicated by rupture of the Achilles tendon due to self-medication with ciprofloxacin: about a case]. / Tendinopathie achilléenne compliquée d´une rupture du tendon d´Achille consécutives à une automédication par la ciprofloxacine chez une hémodialysée: à propos d´un cas.

This study aims to remind clinicians of fluoroquinolone-related tendinopathies. They are rare side effects, but which can result in functional disability. We report the case of a 79-year-old woman with a 11-year history of haemodialysis who had sudden left ankle pain and functional impairment in the ipsilateral member on day 5th after self-medication with ciprofloxacin. Comorbidities included chronic gonarthrosis, secondary hyperparathyroidism and ischemic heart disease. The diagnosis of bilateral Achilles tendinopathy and rupture of the left Achilles tendon was retained due to clinical features and confirmed by ultrasound of ankles. Ciprofloxacin-associated tendon rupture was evaluated using the French method of accountability for drug unexpected side effects or toxicity. Tendon rupture management was based on surgery followed by functional rehabilitation program with satisfactory outcome. The frequency of fluoroquinolone-related tendinopathies ranges from 15 to 20 accidents per 100,000 subjects treated, a third of whom are complicated by tendon rupture. Incidence is related to age, affecting mainly people > 60 years and involving tissular aging. Pefloxacin and ciprofloxacin are the most offending molecules. In our study, the delay in the onset of symptoms on day 5 after self-medication was consistent with literature. We detected some common contributing factors including chronic renal failure, hemodialysis and the assumption of statins and corticosteroids. Fluoroquinolone-related tendinopathies are characterized by common clinical features which allow diagnosis. They mostly affect Achilles tendon. They are bilateral in 40-66% of cases. Tendon rupture is the main complication. Management is based on surgery. It allows to restore anatomy and to prevent detrimental functional disability. We here report a rare but potentially serious fluoroquinolones-related side effect, exposing the patient to the risk of functional disability. Advanced age, chronic renal failure, chronic haemodialysis, concomitant use of statins and corticosteroids are common contributing factors confirmed in this study. Hemodialysis patients constitute a population at risk; hence the importance of remote monitoring after treatment with these molecules.

Atypical presentation of allergic interstitial nephritis likely induced by ciprofloxacin.

Though the prevalence of drug induced allergic interstitial nephritis (AIN) appears to be increasing, the diagnostic and treatment strategies still remain vague. We present a 56-year-old man with a history of hypertension, chronic kidney disease stage IIIa, recent exposure to ciprofloxacin who presented with acute kidney injury. Though the suspicion of AIN was high, his urinary sediment was bland, that is, no leucocytes or leucocyte casts. A renal biopsy subsequently showed features of AIN correlating with a resolving phase of inflammation. Given the resolving nature of the pathology, we chose not to complete a course of corticosteroids despite his need for temporary haemodialysis. He was able to fully recover his renal function. In this report, we emphasise the unreliable nature of the urinary sediment in the diagnosis of AIN, the utility of a renal biopsy in helping to guide treatment, and the controversial data in corticosteroid treatment.

Neuroprotective role of camphor against ciprofloxacin induced depression in rats: modulation of Nrf-2 and TLR4.

BACKGROUND: Depression affects people feeling to be anxious, worried, and restless. They also lose interest in activities, concentrating and appetite, they finally may attempt suicide. Depression is the second chronic disease, as a source of the global burden of disease, after heart disease. Its prevalence elevated seven times during the COVID-19. AIM: The current study was designed to evaluate camphor neuroprotective role against rats' ciprofloxacin-induced depression. MATERIALS AND METHODS: Depression was induced by administration of ciprofloxacin (50 mg/kg; orally) for 21 days. Wister albino male rats were divided into five groups. Group I (normal control): rats were given normal saline. Group II: rats received camphor (10 mg/kg; i.p.) for 21 days. Group III (depression control): rats received ciprofloxacin only. Groups IV and V: rats received camphor (5 and 10 mg/kg; i.p.) for 21 days concurrent with ciprofloxacin. Behavior tests as forced swimming test, activity cage, and rotarod were estimated. Oxidative stress and antioxidant biomarkers as malondialdehyde (MDA), nitric oxide (NO), catalase, and nuclear factor erythroid 2-related factor 2 (Nrf-2) besides inflammatory biomarkers as Toll-like receptor 4 (TLR4) and tumor necrosis factor alpha (TNF-α) as well as neurotransmitters were determined. Finally, histopathological examination was done. RESULTS: Camphor increased catalase and Nrf-2 activities, decreased NO, MDA, TNF-α, TLR4 serum levels, and elevating brain contents of serotonin, dopamine, gamma-amino butyric acid (GABA) and P190-RHO GTP protein with normal neuronal cells of the frontal cortex. CONCLUSION: Camphor has neuroprotective effect via modulation of Nrf-2 and TLR4 against ciprofloxacin-induced depression in rats.