Nephroprotective effect of vitamin D Against Levofloxacin-induced renal injury: an observational study.

The pathogenesis of kidney damage involves complicated interactions between vascular endothelial and tubular cell destruction. Evidence has shown that vitamin D may have anti-inflammatory effects in several models of kidney damage. In this study, we evaluated the effects of synthetic vitamin D on levofloxacin-induced renal injury in rats. Forty-two white Albino rats were divided into six groups, with each group comprising seven rats. Group I served as the control (negative control) and received intraperitoneal injections of normal saline (0.5 ml) once daily for twenty-one days. Group II and Group III were treated with a single intraperitoneal dose of Levofloxacin (50 mg/kg/day) and (100 mg/kg/day), respectively, for 14 days (positive control groups). Group IV served as an additional negative control and received oral administration of vitamin D3 (500 IU/rat/day) for twenty-one days. In Group V, rats were orally administered vitamin D3 (500 IU/rat/day) for twenty-one days, and intraperitoneal injections of Levofloxacin (50 mg/kg/day) were administered on day 8 for 14 days. Group VI received oral vitamin D3 supplementation (500 IU/rat/day) for twenty-one days, followed by intraperitoneal injections of Levofloxacin (100 mg/kg/day) on day 8 for fourteen days. Blood samples were collected to measure creatinine, urea, malondialdehyde, glutathione reductase, and superoxide dismutase levels. Compared to the positive control group, vitamin D supplementation lowered creatinine, urea, and malondialdehyde levels, while increasing glutathione reductase and superoxide dismutase levels. Urea, creatinine, and malondialdehyde levels were significantly (p<0.05) higher in rats administered LFX 50mg and 100mg compared to rats given (LFX + vitamin D). The main findings of this study show that vitamin D reduces renal dysfunction, suggesting that vitamin D has antioxidant properties and may be used to prevent renal injury.

Safety of levofloxacin as an antibiotic prophylaxis in the induction phase of children newly diagnosed with acute lymphoblastic leukemia: an interim analysis of a randomized, open-label trial in Brazil.

BACKGROUND: Despite high cure rates, treatment-related mortality in children with acute lymphoblastic leukemia (ALL) remains significant. About 4% of patients die during remission induction therapy and approximately two-thirds of treatment-related deaths are due to infectious complications. METHODS: From May 2021 to June 2022, children aged one through 18 years, with a recent diagnosis of ALL, admitted to three pediatric oncology centers in Brazil, were enrolled in this multicenter, open-label, randomized, phase 3 clinical trial. Eligible patients were randomly divided into two groups, based on a 1:1 allocation ratio, to receive, or not, levofloxacin as a prophylactic agent during the induction phase. All patients were treated according to the IC-BFM 2009 chemotherapy protocol. Primary endpoints were carbapenemase-producing Enterobacteriaceae (CPE) colonization, Clostridioides difficile diarrhea, and other adverse events related to the use of levofloxacin. The secondary endpoint was febrile neutropenia during induction. The median follow-up was 289 days. RESULTS: Twenty patients were included in this trial, 10 in each group (control and levofloxacin). Mild adverse reactions related to levofloxacin were observed in three patients (30%). Three patients had Clostridioides difficile diarrhea, two in the levofloxacin group and one in the control group (p > 0.99). Only one patient presented colonization by CPE. This patient belonged to the levofloxacin group (p > 0.99). Nine patients presented febrile neutropenia, five in the control group and four in the levofloxacin intervention group (p > 0.99), one patient died due to febrile neutropenia. CONCLUSION: The use of levofloxacin was shown to be safe in the induction phase in children with de novo ALL. The use of this medication did not increase the rate of colonization by CPE nor the rate of diarrhea by C. difficile. All adverse reactions were mild and remitted either spontaneously or after switching medicine administration from oral to intravenous route.

QTc prolongation during levofloxacin and triazole combination chemoprophylaxis: Prevalence and predisposing risk factors in a cohort of hematopoietic cell transplantation recipients.

BACKGROUND: QTc interval prolongation has been reported when combining fluoroquinolones and triazoles for chemoprophylaxis in cancer patients. Herein, we aimed to identify the prevalence and contributing factors to QTc prolongation in hematopoietic cell transplantation (HCT) recipients who received these agents during the neutropenic phase. METHODS: This is a retrospective medical chart review conducted at a university hospital in Lebanon from 2017 to 2020. It included all adult HCT inpatients on antimicrobial prophylaxis with fluoroquinolones and triazoles and whose baseline ECG monitoring done prior to chemoprophylaxis administration, then on day-3 and day-6 of therapy, were available. RESULTS: Overall, 68 HCT recipients met our inclusion criteria, of which 22% developed QTc prolongation. Based on bivariate analysis, female gender contributed to QTc prolongation (P = 0.001). There was a trend to QTc prolongation in patients with predisposing thyroid disease (P = 0.12), grade 2 vomiting and diarrhea (P = 0.16, P = 0.46, respectively), baseline hypokalemia (P = 0.18) and hypocalcemia (P = 0.3), hypomagnesemia on day-3 (P = 0.21) and day-6 hyponatremia (P = 0.36). Patients receiving two or more drugs with a known or probable risk of QTc prolongation (other than the fluoroquinolone/ triazole combination) were more prone to experience a prolonged QTc interval (P = 0.09). None of the patients that had QTc prolongation died or developed serious arrhythmias. CONCLUSION: The prevalence of QTc prolongation was 22% among HCT recipients on fluoroquinolone and triazole prophylaxis, yet we did not identify any independent risk factors for this issue. None of the patients that had QTc interval prolongation died or developed serious arrhythmias.

Levofloxacin-Associated Bullous Pemphigoid in a Hemodialysis Patient After Kidney Transplant Failure.

BACKGROUND Patients with end-stage renal disease (ESRD) who require dialysis can develop a variety of skin conditions, such as pruritus, xerosis, skin infections, and autoimmune reactions. Bullous pemphigoid (BP) is an autoimmune bullous disorder with an increasing incidence. It can be caused by over 90 medications, but levofloxacin-induced BP in hemodialysis patients has not yet been reported. This report is of a 27-year-old woman with ESRD on hemodialysis who developed BP after levofloxacin treatment. CASE REPORT A 27-year-old woman with hemodialysis after kidney transplantation failure was started with levofloxacin for suspected urinary tract infection 1.5 months prior to admission. Her urinary tract infection symptoms were improved after 3 weeks of levofloxacin treatment, but a serious rash developed, presenting with progressive bullous throughout the body and facial involvement. A thorough workup showed a remarkably elevated hemidesmosomal antigen, BP180 (116 RU/mL), and cutaneous indirect immunofluorescence on human salt-split skin substrate was positive for serum basement membrane zone IgG with an epidermal pattern. Skin biopsy direct immunofluorescence staining showed continuous linear C3 deposition along the basement membrane zone. Prednisone 60 mg daily was started with a taper schedule. She no longer had new skin rash during a follow-up of over 3 months. CONCLUSIONS To the best of our knowledge, this is the first case of levofloxacin-induced BP in a patient undergoing hemodialysis. This report highlights the importance of recognizing skin reactions associated with ESRD in dialysis patients, the correct diagnosis by biopsy and histopathology, and the correct and timely management.

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.

Drug-Induced Histiocytoid Sweet Syndrome: Two Cases With Levofloxacin and Amoxicillin-Clavulanate.

ABSTRACT: Histiocytoid Sweet syndrome (HSS) is an uncommon histologic variant of Sweet syndrome (SS). HSS can be distinguished from the classic SS with an infiltrate of histiocyte-like immature myeloid cells rather than dense neutrophilic infiltration, although the clinical features are similar. Previous studies have shown that the risk of hematologic malignancy is significantly higher in HSS compared with classic SS. To lesser extent, HSS is also associated with infections, inflammatory diseases, and drugs, particularly with antineoplastic agents as well. Here, we report a case of 2 patients with an abrupt onset of erythematous, tender plaques accompanied by fever, with that revealed similar histopathologic and immunohistochemical features, whom had a history of antibiotic use. Clinicopathologic correlation led to diagnosis of drug-induced HSS, associated with the use of levofloxacin and amoxicillin-clavulanate, respectively. Both patients were then successfully treated with systemic corticosteroid therapy, and neither of them had recurrence during the period of 24-month follow-up.

Dermatomyositis Developed After Exposure to Epstein-Barr Virus Infection and Antibiotics Use.

Dermatomyositis is an inflammatory disorder involving muscle and skin. Similar to many other autoimmune diseases, environmental factors appear to trigger the onset of disease in some cases. Many drugs have been reported to be associated with dermatomyositis, and rarely infections have been described as potential triggering agents. Here we are describing a case of dermatomyositis that developed after doxycycline and levofloxacin use, who also had recent Epstein-Barr virus infection. Dermatomyositis associated with doxycycline or levofloxacin use has not yet been described in the literature, while reports of dermatomyositis after Epstein-Barr virus infection have been rare and limited to juvenile dermatomyositis or in association with cancer. It is important for clinicians to be aware of this rare association so that the diagnosis and treatment can be exercised promptly.

A comparison of different antibiotic regimens for the treatment of infective endocarditis.

BACKGROUND: Infective endocarditis is a microbial infection of the endocardial surface of the heart. Antibiotics are the cornerstone of treatment, but due to the differences in presentation, populations affected, and the wide variety of micro-organisms that can be responsible, their use is not standardised. This is an update of a review previously published in 2016. OBJECTIVES: To assess the existing evidence about the clinical benefits and harms of different antibiotics regimens used to treat people with infective endocarditis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase Classic and Embase, LILACS, CINAHL, and the Conference Proceedings Citation Index - Science on 6 January 2020. We also searched three trials registers and handsearched the reference lists of included papers. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) assessing the effects of antibiotic regimens for treating definitive infective endocarditis diagnosed according to modified Duke's criteria. We considered all-cause mortality, cure rates, and adverse events as the primary outcomes. We excluded people with possible infective endocarditis and pregnant women. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, 'Risk of bias' assessment, and data extraction in duplicate. We constructed 'Summary of findings' tables and used GRADE methodology to assess the quality of the evidence. We described the included studies narratively. MAIN RESULTS: Six small RCTs involving 1143 allocated/632 analysed participants met the inclusion criteria of this first update. The included trials had a high risk of bias. Three trials were sponsored by drug companies. Due to heterogeneity in outcome definitions and different antibiotics used data could not be pooled. The included trials compared miscellaneous antibiotic schedules having uncertain effects for all of the prespecified outcomes in this review. Evidence was either low or very low quality due to high risk of bias and very low number of events and small sample size. The results for all-cause mortality were as follows: one trial compared quinolone (levofloxacin) plus standard treatment (antistaphylococcal penicillin (cloxacillin or dicloxacillin), aminoglycoside (tobramycin or netilmicin), and rifampicin) versus standard treatment alone and reported 8/31 (26%) with levofloxacin plus standard treatment versus 9/39 (23%) with standard treatment alone; risk ratio (RR) 1.12, 95% confidence interval (CI) 0.49 to 2.56. One trial compared fosfomycin plus imipenem 3/4 (75%) versus vancomycin 0/4 (0%) (RR 7.00, 95% CI 0.47 to 103.27), and one trial compared partial oral treatment 7/201 (3.5%) versus conventional intravenous treatment 13/199 (6.53%) (RR 0.53, 95% CI 0.22 to 1.31). The results for rates of cure with or without surgery were as follows: one trial compared daptomycin versus low-dose gentamicin plus an antistaphylococcal penicillin (nafcillin, oxacillin, or flucloxacillin) or vancomycin and reported 9/28 (32.1%) with daptomycin versus 9/25 (36%) with low-dose gentamicin plus antistaphylococcal penicillin or vancomycin; RR 0.89, 95% CI 0.42 to 1.89. One trial compared glycopeptide (vancomycin or teicoplanin) plus gentamicin with cloxacillin plus gentamicin (13/23 (56%) versus 11/11 (100%); RR 0.59, 95% CI 0.40 to 0.85). One trial compared ceftriaxone plus gentamicin versus ceftriaxone alone (15/34 (44%) versus 21/33 (64%); RR 0.69, 95% CI 0.44 to 1.10), and one trial compared fosfomycin plus imipenem versus vancomycin (1/4 (25%) versus 2/4 (50%); RR 0.50, 95% CI 0.07 to 3.55). The included trials reported adverse events, the need for cardiac surgical interventions, and rates of uncontrolled infection, congestive heart failure, relapse of endocarditis, and septic emboli, and found no conclusive differences between groups (very low-quality evidence). No trials assessed quality of life. AUTHORS' CONCLUSIONS: This first update confirms the findings of the original version of the review. Limited and low to very low-quality evidence suggests that the comparative effects of different antibiotic regimens in terms of cure rates or other relevant clinical outcomes are uncertain. The conclusions of this updated Cochrane Review were based on few RCTs with a high risk of bias. Accordingly, current evidence does not support or reject any regimen of antibiotic therapy for the treatment of infective endocarditis.

A case of bilateral leg edema associated with levofloxacin: A case report.

RATIONALE: A number of medicines are associated with edema. However, only 2 cases of edema of both lower legs, associated with levofloxacin, have been reported. PATIENT: We report the case of levofloxacin-associated bilateral leg edema in an 81-year-old male. The patient was referred to the Division of Nephrology due to edema limited to both lower legs, which had developed 1 day before. He had undergone supraglottic laryngectomy due to supraglottic cancer in our institution 6 months ago. He had been admitted to the Department of Otolaryngology due to persistent aspiration and general weakness 5 days ago. DIAGNOSIS: The patient had no underlying diseases that could result in edema. No abnormalities were detected in several diagnostic tests. He strongly denied using other medications including herbal or traditional remedies, recreational drugs, or drugs of abuse. The patient had been intravenously administered levofloxacin at 750 mg per day 5 days earlier; on this basis levofloxacin-induced edema was suspected. INTERVENTIONS AND OUTCOMES: Levofloxacin was immediately withdrawn and conservative management (salt restriction and withdrawal of intravenous fluid) was initiated. His edema was completely restored within 3 weeks after withdrawal of levofloxacin. OUTCOMES: The patient stopped taking levofloxacin and he did not have any recurrent edema until his death due to uncontrolled pneumonia. LESSONS: Levofloxacin should be added to the list of drugs associated with the development of bilateral leg edema. This might obviate the need for time-consuming studies for diagnostic purposes and application of ineffective or harmful treatments.

Levofloxacin-associated Encephalopathy with Severe Hyperventilation.

A 64-year-old woman with no previous mental illness took a single 500 mg tablet of levofloxacin for cystitis. Two hours later, she developed psychosis with involuntary movement and severe hyperventilation with respiratory alkalosis. Cranial magnetic resonance imaging findings were unremarkable, and an electroencephalogram revealed no epileptiform discharge. Her symptoms improved on the third day after levofloxacin was discontinued. Levofloxacin-associated encephalopathy with psychotic features is a rare adverse event. Disturbance of gamma-aminobutyric acid-ergic (GABAergic) interneurons by levofloxacin may lead to hyperventilation via dysfunction of the brainstem respiratory network. Physicians should be aware of hyperventilation as an additional serious symptom of levofloxacin-associated encephalopathy in acute settings.

Concomitant use of levofloxacin and fluconazole leading to possible torsades de pointes.

Prolongation of the corrected QT interval can lead to the deadly arrhythmia torsades de pointes. There are many risk factors for corrected QT prolongation, one being medication. The goal of this case report is to add to the limited literature surrounding the possibility of torsades de pointes when levofloxacin and fluconazole are used concomitantly. Additionally, provide guidance for patient factors that need to be assessed when prescribing the two drugs.

Efficacy of standard triple therapy versus Levofloxacin based alternate therapy against Helicobacter pylori infection.

OBJECTIVE: To assess the effectiveness of clarithromycin based standard triple therapy verses levofloxacin based first line therapy against Helicobacter pylori infection. METHODS: This prospective observational study was performed at Akhter Saeed Trust Teaching Hospital, Lahore, from May 2016 to 31st May 2017 and comprised of all patients with positive H. pylori, confirmed by gastroscopic biopsy; fulfill the inclusion criteria of this study. Patients were divided into two groups (Group A and Group B). Group A received clarithromycin 500mg, amoxicillin 1g and omeprazole 20mg twice a day for two weeks. In group B levofloxacin 250mg was replaced by clarithromycin whereas rests of medicines remain the same. Patients were followed up at end of first week, second week and at end of treatment to record any adverse effects and cure rate. Data was analyzed by using SPSS version 24.0 and MINITAB V.16.. RESULTS: Out of 300 enrolled patients (150 patients in each group), 123 (87.85%) patients cured in group A whereas 134 (92.4%) patients cured in group B. Both treatment regimens were almost equally effective in our population with no statistically significant difference in outcome. Significantly less adverse effects were observed in patients having levofloxacin as compared to standard triple therapy. CONCLUSIONS: Effectiveness of both standard triple therapy and alternate triple therapy were found satisfactory to be used for treatment in our region. Levofloxacin based alternate therapy is safer to the patients. It can be used in conditions where adverse effects caused by standard therapy are unbearable.

Helicobacter pylori Eradication With Levofloxacin or Clarithromycin in Dialysis Versus Nonuremic Patients.

INTRODUCTION: Various medication regimens have been used to eradicate Helicobacter pylori in dialysis patients; however, optimal response to treatment is still a challenge. This study aimed to compare response to H pylori eradication in dialysis and nonuremic patients. MATERIALS AND METHODS: In a randomized controlled trial, dialysis patients with dyspepsia and confirmed positive endoscopic biopsy for H pylori were compared to nonuremic patients. Participants were randomly assigned to receive clarithromycin or levofloxacin. H pylori eradication was assessed using stool antigen test 4 weeks later. RESULTS: Forty-four dialysis and 44 nonuremic patients participated in the study. Four dialysis patients and 2 nonuremic patients did not respond to levofloxacin (P = .35). Six dialysis patients and 4 nonuremic patients did not respond to clarithromycin (P = .47). CONCLUSIONS: Response rate to H pylori eradication by clarithromycin and levofloxacin was slightly lower in dialysis patients compare to nonuremic patients. In dialysis patients, response rate to levofloxacin was slightly higher than clarithromycin, but the results were not significantly different.

Comparison of 10-day levofloxacin bismuth-based quadruple therapy and levofloxacin-based triple therapy for Helicobacter pylori.

OBJECTIVE: This was a prospective study aiming to investigate whether levofloxacin plus bismuth-based quadruple therapy was more effective than levofloxacin-based triple therapy after failed first-line eradication therapies for Helicobacter pylori (H. pylori) infection. METHODS: Sixty-seven patients infected with H. pylori were randomly assigned to two groups; the levofloxacin plus bismuth-based quadruple therapy group (RBAL [n = 33]; rabeprazole 20 mg twice daily, bismuth subcitrate 120 mg four times daily, amoxicillin 1 g twice daily and levofloxacin 500 mg once daily, for 10 days) and the levofloxacin-based triple therapy group (RAL [n = 34]; rabeprazole 20 mg twice daily, amoxicillin 1 g twice daily and levofloxacin 500 mg once daily, for 10 days). Endoscopy was performed 4-8 weeks after H. pylori eradication to assess treatment response. We followed up patient response and compliance and checked their resistance to antibiotics. RESULTS: Intention-to-treat analysis revealed that both groups had similar eradication rates (RBAL vs RAL: 84.8% [95% confidence interval {CI} 72.6-97.1%] vs 67.6% [95% CI 51.9-83.4%], P = 0.0987). No significant differences in compliance or adverse events were found (P = 0.9829 and 0.0720). Epsilometer test showed that most eradication failure cases were levofloxacin-resistant. CONCLUSIONS: Adding bismuth subcitrate to levofloxacin-based triple therapy was not more effective than not doing so, but no further side effects were noted. Both eradication therapies were equally safe and patients had the same tolerance to both regimens. Resistance rate to levofloxacin may be important when choosing second-line therapy.

Comparison of levofloxacin and garenoxacin for antibacterial prophylaxis during neutropenia.

Levofloxacin (LVFX) is widely used for antibacterial prophylaxis during neutropenia. Garenoxacin (GRNX), which has been investigated in Japan, has stronger antibacterial activity than LVFX against gram-positive bacteria; however, no studies have compared the effectiveness of LVFX and GRNX. We retrospectively analyzed 42 patients with acute leukemia and 32 patients who underwent hematopoietic cell transplantation. Thirty-one patients before September 2009 received GRNX, and subsequent 43 patients received LVFX. We compared the cumulative incidences of positive blood and stool cultures. There was no significant difference in the incidence of bacteremia between the GRNX and LVFX groups. However, while gram-negative bacteria were detected in 80% of the patients with bacteremia in the GRNX group, they were detected in only 33% of the patients with bacteremia in the LVFX group. Patients in the GRNX group more frequently experienced positive stool cultures than those in the LVFX group, and this was confirmed by a multivariate analysis. Gram-negative bacteria accounted for 100 and 67% of the stool culture results in the GRNX and LVFX groups, respectively. While both fluoroquinolones may be appropriate antibacterial prophylactic agents for neutropenia patients with hematological malignancies, vigilance for gram-negative bacterial infections should be exercised when GRNX is used as prophylaxis.

Levofloxacin Induced Toxic Epidermal Necrolysis: Successful Therapy with Omalizumab (Anti-IgE) and Pulse Prednisolone.

BACKGROUND Toxic epidermal necrolysis (TEN) is characterized by widespread erythematous and bullous lesions on the skin. Nowadays, considerable progress has been made in the understanding of its pathogenesis. Immunologically it is similar to graft-versus-host disease. Therefore, we may propose that TEN is a disorder of cell-mediated immunity. CASE REPORT Our patient was a 74-year-old white female who had pneumonia and was positive for hepatitis C virus (HCV), and who had been on levofloxacin therapy. After the first levofloxacin dose, erythematous dusky red macules occurred on her extremities and trunk, and on the following day, confluent purpuric lesions tended to run together over 85% of her body. Her biopsy results indicated TEN. Laboratory testing for serum ECP (eosinophil cationic peptide) and serum immunoglobulin (Ig) levels were performed, and blister fluid was investigated. The patient responded positively to omalizumab treatment and after treatment laboratory tests revealed decreased high sensitive CRP, ECP, IgG1, IgG2, IgG3, IgG4, IgA, and IgM levels. CONCLUSIONS To the best of our knowledge, this is the first case of a patient with HCV who developed cutaneous adverse drug reaction on levofloxacin medication and recovered with omalizumab treatment. This is the first documentation of omalizumab treatment of a TEN patient.