Administration Of Levofloxacin Research Articles

WITHDRAWN: A successful management of concurrent infection with cranial Nocardia gipuzkoensis and pulmonary Klebsiella pneumoniae: A case report

BackgroundSuccessful management of concurrent infection with cranial N. gipuzkoensis and pulmonary Klebsiella pneumoniae has never been described. Case presentationA 71-year-old female was given referral to our hospital due to intracal space occupying lesion for over 20 days. Initial chief complaints implied cranial and pulmonary inflammation. Subsequently, drainage of brain lesion was obtained and identified as Nocardia gipuzkoensis infection through microbial culture and metagenomic next-generation sequencing (mNGS). Sputum culture determined as Klebsiella pneumoniae infection. Combined with results of antimicrobial susceptibility tests and allergic history, the patient was improved after being treated with two-week Meropenem (2g/8h iv) combined Vancomycin (1g/12h iv), and reached neurological recovery followed with oral administration of Linezolid (0.6g/12h po) and Levofloxacin (0.5g/24h po) for over 6 weeks. ConclusionA successful administration of concurrent infections was reported. It might provide supporting evidence for shortening the intravenous administration of nocardiosis.

A case of Legionella pneumonia after robot‐assisted radical prostatectomy

IntroductionPostoperative Legionella pneumonia is very rare.Case presentationA 71‐year‐old male patient with prostate cancer (cT2bN0M0) underwent a robotic‐assisted radical prostatectomy. On the 5th postoperative day, the patient developed chills and a fever of 39.2°C. Chest radiography revealed decreased permeability in the right middle lung field, leading to the diagnosis of postoperative pneumonia. Antimicrobial therapy was initiated immediately. Blood tests on postoperative day 10 revealed mild liver function abnormalities, electrolyte abnormalities, and a markedly elevated inflammatory response. Legionella pneumonia was suspected based on blood sample results and systemic symptoms, such as diarrhea and nausea. Furthermore, Legionella antigens were detected in the patient's urine, prompting further administration of levofloxacin. The patient's subsequent clinical course was favorable.ConclusionWhen bacterial pneumonia fails to respond to antimicrobial therapy and systemic symptoms develop, atypical pneumonia, caused by pathogens such as Legionella pneumophila, should be considered even in cases of postoperative pneumonia.

Fabrication of levofloxacin-loaded porcine acellular dermal matrix hydrogel and functional assessment in urinary tract infection

Bacterial cystitis, a commonly occurring urinary tract infection (UTI), is renowned for its extensive prevalence and tendency to recur. Despite the extensive utilization of levofloxacin as a conventional therapeutic approach for bacterial cystitis, its effectiveness is impeded by adverse toxic effects, drug resistance concerns, and its influence on the gut microbiota. This study introduces Lev@PADM, a hydrogel with antibacterial properties that demonstrates efficacy in the treatment of bacterial cystitis. Lev@PADM is produced by combining levofloxacin with decellularized porcine acellular dermal matrix hydrogel and exhibits remarkable biocompatibility. Lev@PADM demonstrates excellent stability as a hydrogel at body temperature, enabling direct administration to the site of infection through intravesical injection. This localized delivery route circumvents the systemic circulation of levofloxacin, resulting in a swift and substantial elevation of the antimicrobial agent’s concentration specifically at the site of infection. The in vivo experimental findings provide evidence that Lev@PADM effectively prolongs the duration of levofloxacin’s action, impedes the retention and invasion of E.coli in the urinary tract, diminishes the infiltration of innate immune cells into infected tissues, and simultaneously preserves the composition of the intestinal microbiota. These results indicate that, in comparison to the exclusive administration of levofloxacin, Lev@PADM offers notable benefits in terms of preserving the integrity of the bladder epithelial barrier and suppressing the recurrence of urinary tract infections.Graphical

Evaluation of Levofloxacin Prescription Pattern Based on International Standards in a Tertiary Hospital in Iran

Background: The emergence of antibiotic-resistant bacteria poses a significant global concern. The improper use of antibiotics, identified as a leading contributor to this problem, is a widespread issue in medical centers worldwide. Objectives: This study aimed to investigate the utilization pattern of levofloxacin, a commonly prescribed antibiotic. Methods: We conducted a retrospective descriptive study in Ahvaz, Iran, focusing on patients who had received levofloxacin over a 6-month period. Data collection involved a questionnaire comprising patient demographic details, diagnosis information, details concerning levofloxacin administration, and outcomes, all extracted from the patients' medical records. During the assessment, we considered factors such as the correct dosage, frequency of administration, potential drug interactions, and adverse effects. Data analysis was performed using SPSS v. 20. Results: A total of 35 patients, with a mean age of 55.17 ± 20.36 years, received levofloxacin during the study period, and 48.6% of them were women. On average, each patient received 3.20 ± 2.85 grams of levofloxacin, with a minimum dose of 0.500 grams and a maximum of 11.50 grams. The average treatment duration was 3.813 ± 4.26 days. In only 8.6% of cases, the prescribed dosage was deemed inappropriate, while in 40% of cases, the duration of antibiotic use was found to be inadequate. Conclusions: The utilization of levofloxacin was deemed irrational in 40% of cases. Although the prescribed dosage for the respective diagnoses was generally accurate, the treatment duration was often incorrect, potentially contributing to antibiotic resistance.

Spontaneous Gram-negative Bacterial Meningitis Following Steroid Therapy for Severe COVID-19

Abstract This case demonstrates an unusual case of spontaneous Gram-negative bacillary meningitis (GNBM) due to Serratia following COVID-19 and steroid exposure. A 52-year-old male presented with clinical features of acute meningitis following a prolonged hospitalization for severe COVID-19 pneumonia, during which he was administered corticosteroids. Neuroimaging was normal. Cerebrospinal fluid (CSF) analysis revealed high protein, hypoglycorrhachia, and neutrophilic pleocytosis. The Gram stain showed plenty of neutrophils but no bacteria. CSF culture demonstrated convex 1–2 mm colonies, slightly umbonate with entire margins, and opaque. On VITEK2, this was identified as Serratia marcescens and was susceptible to all tested antibiotics. Clinical improvement was noted after 48 h with the administration of meropenem (2 g q8 h) and levofloxacin (750 mg once daily). After a week of treatment, repeat CSF analysis showed a decrease in the CSF protein and total white blood cells, lymphocytic pleocytosis, and an increase in the CSF glucose. The patient made a complete recovery following 3 weeks of antibiotic therapy. This case report highlights that steroids should be used cautiously and judiciously in the COVID-19 setting. Serratia is a rare cause of spontaneous GNBM.

Fibroblast inhibition by tocilizumab enabled gemcitabine/nab-paclitaxel rechallenge for pancreatic cancer.

Interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway inhibition may overcome chemoresistance of metastatic pancreatic cancer (MPC). We sought to determine the safety and recommended dose of tocilizumab (TCZ), an IL-6 receptor monoclonal antibody, and biological correlates of tumor shrinkage in patients with gemcitabine (GEM)/nanoparticle albumin-bound paclitaxel (nab-PTX)-refractory MPC. This phase 1 study enrolled 10 patients with MPC who had progressed after GEM/nab-PTX. Patients initially received TCZ 8 mg/kg on Day 1 and nab-PTX 100 mg/m2 + GEM 750 mg/m2 on Days 2, 9, and 16. Before and at the end of Cycle 1, biopsy of liver metastases was performed 3-5 h after levofloxacin (LVFX) administration to measure LVFX infiltration into tumor tissue. No dose-limited toxicities occurred, and the recommended dosage of TCZ was determined to be 8 mg/kg. Treatment-emergent adverse events occurred in 80% of patients, of which decreased neutrophil count was the most common. Tumor reduction during Cycle 1 was observed in four patients, who were defined as responders. In paired-biopsy samples, responder-related biological activities were an increase of cleaved PARP expression of tumor nuclei (p = 0.01), a decrease of proliferative cancer-associated fibroblasts (CAFs) (p = 0.08), and an increase of LVFX infiltration in the tumor (p = 0.04). A decrease of phosphorylated STAT3 expression (p = 0.02) favored an increase in LVFX infiltration. In conclusion, TCZ + GEM/nab-PTX-rechallenge had a manageable safety profile and showed preliminary activity via inhibition of CAF and improved intratumoral drug infiltration in MPC.

Retrospective analysis of risk factors for levofloxacin-induced liver injury

Levofloxacin is used as a first-line drug for the treatment of Legionella pneumonia. However, the relatively high incidence of drug-induced liver injury (DILI) remains a clinical problem. Based on the available patient data, this study aimed to identify the risk factors for DILI before levofloxacin administration. Multiple logistic regression analyses suggested that male sex (odds ratio [OR], 6.975; 95% confidence interval [CI], 1.737–28.000; p = 0.006), elevated C-reactive protein level (OR, 1.182; 95% CI, 1.089–1.283; p = 0.0006), and high haemoglobin level (OR, 1.640; 95% CI, 1.226–2.195; p = 0.001) before administration of levofloxacin were risk factors for DILI. Possible treatment with alternative drugs should be considered in male patients with elevated C-reactive protein and haemoglobin levels. Moreover, close monitoring of liver function tests when levofloxacin is administered may prevent the development and severity of DILI.

The effect of different doses of levofloxacin on leukocyte dynamics in chicken blood

The article deals with research into the effect of different doses of levofloxacin (fluoroquinolone class drug) on chicken blood parameters. Male Hisex Brown chickens were divided into 3 groups, one of them was control, the other two were experimental, the latter received the drug at concentrations 600 mg/L and 200 mg/L. The fluoroquinolone was administered via drinking water 5 consecutive days. We evaluated the following hematological parameters of chickens: leukocyte count (direct count in Goryaev's chamber) and leukogram (count in stained blood smears). The results of our research state that the administration of levofloxacin at concentration 600 mg/L causes transitory leukocytosis, lymphopenia and pseudoeosinophilia, but that does not imply a heavy toxic effect on chicken organism as by the end of the research the parameters were already within the normal range. The administration of levofloxacin at concentration 200 mg/L similarly caused a brief increase in pseudoeosinophil number and a decrease in lymphocyte number in chicken blood but they were not generally marked which would prove the negative effect of levofloxacin.

PHARMACOKINETICS OF RECTALLY AND ORALLY ADMINISTERED LEVOFLOXACIN IN ASIAN ELEPHANTS (ELEPHAS MAXIMUS).

Appropriate and effective antibiotic use is a critical component of veterinary medicine, but there are variations across species regarding dosage and administration of these drugs. Oral or rectal routes of administration are typically used in elephants, but not all medications can achieve adequate concentrations rectally. The fluoroquinolone antimicrobials are used in elephants because of their favorable antimicrobial spectrum and pharmacokinetics compared with other oral agents. They are commonly used as part of multiple antibiotic regimens for the treatment of tuberculosis (Mycobacterium tuberculosis). The objective of this study was to determine the pharmacokinetic profile of levofloxacin after oral and rectal administration in Asian elephants (Elephas maximus). Dosages of 5 mg/kg orally and 15 mg/kg rectally were evaluated in 13 Asian elephants. Blood was collected at various time points from 0 to 72 h for pharmacokinetic analysis. Pharmacokinetic parameters were determined and reached concentrations above minimum inhibitory concentrations of various bacterial organisms via both routes. A pharmacokinetic-pharmacodynamic assessment was used to estimate appropriate minimal inhibitory concentrations for bacteria that could be potentially treated with this antimicrobial. Based on these findings, levofloxacin may be a consideration for administration orally (5 mg/kg) and rectally (15 mg/kg) in Asian elephants. Antimicrobial stewardship principles, culture and susceptibility of suspected pathogens, and blood level monitoring should be used to tailor administration of levofloxacin in this species.

Clinical Efficacy and Safety Analysis of Levofloxacin for the Prevention of Infection after Traumatic Osteoarthrosis and Internal Fixation: Systematic Review and Meta-Analysis.

Objective Levofloxacin has been widely used in clinical anti-infection treatment; however, its adverse reactions to levofloxacin were also obvious in patients. Herein we aimed to systematically evaluate the clinical efficacy and safety of systemic administration of levofloxacin in the prevention of postoperative infection after traumatic osteoarthrosis and internal fixation. Methods PubMed, Cochrane Library, OVID, EBSCO, CNKI, VIP database, and Wanfang Database were searched from December 1993 to December 2021. Meanwhile, China ADR Information Bulletin and WHO Pharmaceutical were searched manually. Newsletter and FDA Drug Safety Newsletter, also to retrieve the Websites of Chinese, Chinese, and drug regulatory authorities; To obtain data on adverse events in children with systemic administration of levofloxacin. The literature was screened according to inclusion and exclusion criteria. The risk of bias was evaluated for the included RCT literature. Results There was a statistical difference in the comparison of the incidence of fever between the experimental group and the control group (OR = 2.29, 95% CI (1.75,2.98),P < 0.00001, I2 = 0%, Z = 6.11); elevated white blood cell count (OR = 1.82, 95% CI (1.31,2.52),P=0.0003, I2 = 0%, Z = 3.60); incidence of wound infection (OR = 2.11, 95% CI (1.54,2.90),P < 0.00001, I2 = 0%, Z = 4.64); adverse drug reaction (OR = 1.82, 95% CI (1.21,2.74),P=0.004, I2 = 0%, Z = 2.86). Conclusion In the clinical use of levofloxacin, adverse drug reactions including fever, elevated white blood cell count, and wound infection should be concerned.

Diagnosis and treatment of left ureteral injury as a rare complication of oblique lumbar interbody fusion surgery: a case report and literature review

BackgroundOblique lumbar interbody fusion (OLIF) surgery has been performed as a minimally invasive lateral lumbar fusion technique in recent years. Reports of operative complications of OLIF are limited, and there are fewer reports of ureteral injuries.Case presentationA 62-year-old Chinese woman diagnosed with "lumbar spondylolisthesis (L4 forward slip, I degree)" underwent OLIF treatment. The surgical decompression process was smooth, and the cage was successfully placed. After the expansion sleeve of OLIF was removed, clear liquid continuous outflow from the peritoneum was found. The patient was diagnosed with a ureteral injury. The urological surgeon expanded the original incision, and left ureteral injury anastomosis and ureteral stent implantation were performed. The patient was changed to the prone position and a percutaneous pedicle screw was placed in the corresponding vertebral body. The patient was indwelled with a catheter for 2 weeks, and regular oral administration of levofloxacin to prevent urinary tract infection. After 2 months, the double J tube was removed using a cystoscope. One year after surgery, the symptoms of lumbar back were significantly improved, and there were no urinary system symptoms. However, the patient needed an annual left ureter and kidney B-ultrasound.ConclusionUreteral injury is a rare complication and is easily missed in OLIF surgery. If the diagnosis is missed, the consequences can be serious. Patients should undergo catheterization before the operation and hematuria should be observed during the operation. We emphasize the careful use of surgical instruments to prevent intraoperative complications. In addition, after withdrawing the leaf in the operation, it is necessary to carefully observe whether a clear liquid continues to leak. If ureteral injury is found, one-stage ureteral injury repair operation should be performed to prevent ureteral stricture.

Assessment of moringa oleifera seeds extract effect on the adverse effects of levofloxacin drug induced liver injury

The current study aimed to know the protective role of the cold aqueous extract of Moringa seeds against the toxic damages caused by levofloxin in male albino rats by studying biochemical parameters. 24 male white rats were randomly divided into four groups, comprising (6 animals per group). The first group (G1) as a control group was dosed orally and daily with physiological solution for 30 days, the second group (G2)) was dosed with levofloxacin at a concentration of 10 mg / kg of body weight, the third group (G3) was dosed with aqueous extract of Moringa oleifera seeds at a concentration of 350 mg / kg The fourth group (G4) was dosed with aqueous extract of Moringa oleifera seeds 350 mg/kg 4 hours before the administration of levofloxacin at a concentration of 10 mg/kg body weight. Male rats in all study groups were administered orally via the dosing tube, with one dose per day for 30 days. . Blood samples were collected in the four groups after one month of dosing to measure the level of Malona dialdehyde and glutathione, as well as the levels of liver enzymes aspartate transaminase (AST), alanine transaminase (ALT) and alkalinephosphatase (ALP).

Evaluation of therapeutic and prophylactic effectiveness of levofloxacin in experimental colibacillosis of chickens with regard to infecting dose

The goal of the present research was to investigate therapeutic and prophylactic effectiveness of levofloxacin following experimental challenge of chickens with varying doses of Escherichia сoli namely 1 minimum lethal dose (DLM) and 4 minimum lethal doses (DLM). We conducted two experiments on two-day-old Hisex Brown chickens. For the first experiment we used 6 groups of chicks (n = 25, in each group). The drug was administered via drinking water (with free access) 24 hours before the challenge. Chicks of Groups 1 to 4 received levofloxacin via drinking water at concentrations 50 mg/L, 100 mg/L, 200 mg/L and 300 mg/L for 5 days. Group 5 was control, Group 6 was intact. The chicks were challenged with 1.5 х 108 E. сoli bacterial cells per 0.5 mL (1 minimum lethal dose (DLM)) intraperitoneally. The second experiment was conducted similarly but the infecting dose was increased by 4 times (4 minimum lethal doses (DLM)).Administration of levofloxacin at concentration 300 mg/L both in the first experiment, when the infecting dose was 1 minimum lethal dose, and in the second experiment, when the infecting dose was 4 minimum lethal doses, proved that the drug has the same high therapeutic and prophylactic effectiveness of 96 %. Administration of the drug at concentration 200 mg/L showed 100 % effectiveness in the first experiment. But in the second experiment levofloxacin at the same concentration ensured survival of only 88 % of the challenged chicks. When the drug was administered at concentration 100 mg/L we observed reliable change in indices. Accordingly in the first experiment 88 % of the chicks survived. In the second experiment, when the infecting dose increased to 4 minimum lethal doses, only 52 % of the chicks survived. Administration of levofloxacin at concentration 50 mg/L did not show significant therapeutic effect.

Black Seed Oil Protects Against Levofloxacin Hepatotoxicity: Analyses of the Biochemical and Histopathological Effects

Background: Long-term use of levofloxacin can cause alterations in the liver function. This study aimed to determine the protective effect of black seed oil (BSO) against liver injury due to levofloxacin administration in rats. Methods: The chemical composition of BSO was analyzed with gas chromatography and mass spectrophotometry (GC-MS). Rats (n=30) were treated daily with levofloxacin and BSO at three doses (1, 2 or 4 mL/kg) orally for 28 days. The presence of liver injury was determined based on serum biomarkers and liver malondialdehyde (MDA) levels, and histopathological examinations. Results: The GC-MS analyses showed that BSO contained 25 chemical compounds, including thymoquinone (10.14%). The levofloxacin administration significantly increased the liver enzymes and MDA levels, and induced a marked alteration in the liver histological structures. Treatments of rats with one or two mL/kg BSO significantly decreased the liver enzymes, and MDA levels compared to those that received levofloxacin alone (P&lt;0.05). However, the highest dose (4 mL/kg) BSO failed to improve liver MDA levels. The recovery of liver histological damages was also observed in rats treated with BSO. Conclusion: It was concluded that the BSO administration reduced the liver dysfunction due to levofloxacin at doses of 1 or 2 mL/kg, but not at 4 mL/kg. Further research is warranted to explore if the protective effect of BSO is associated with its antioxidant properties.

Effect of Levofloxacin on the Efficacy and Adverse Events in Intravesical Bacillus Calmette-Guerin Treatment for Bladder Cancer: Results of a Randomized, Prospective, Multicenter Study

BackgroundAlthough bacillus Calmette-Guerin (BCG) is a standard treatment for high-risk non–muscle-invasive bladder cancer (NMIBC), a high rate of adverse events with a variety of grades remains a difficulty. ObjectiveIn this randomized, prospective, multicenter study, we examined whether levofloxacin, given after each intravesical instillation of BCG, could improve its tolerance in patients with intermediate- to high-risk urothelial carcinoma of the bladder without compromising its efficacy. Design, setting, and participantsOverall, 106 Japanese patients (85 men and 21 women; age: median, 69.5 yr) with primary or recurrent NMIBC were randomized after transurethral resection to induce treatment with intravesical BCG plus levofloxacin (group 1) or BCG alone (group 2). InterventionPatients who underwent intravesical instillation of BCG were randomized with or without levofloxacin administration. Outcome measurements and statistical analysisAdverse events were assessed using the National Cancer Institute-Common Toxicity Criteria version 3.0. Cumulative incidence functions and Kaplan-Meier methods were applied to estimate survival outcomes. Results and limitationsThere was no significant difference in baseline characteristics between the groups. The completion rate of group 1 (85.5%) was not significantly lower than that of group 2 (76.5%; p = 0.321). There was no significant difference in the completion rate of patients with pollakisuria, painful micturition, gross hematuria, fever elevation, and others between the groups. The incidence of adverse events in patients with high-grade pollakisuria (7.3% vs 25.4%, p = 0.041) and fever (0% vs 9.1%, p = 0.034) was significantly lower in group 1. The 5-yr progression-free and cancer-specific survival rates were significantly better in group 1. ConclusionsProphylactic levofloxacin administration may reduce the severity of adverse events and contribute to better outcomes from BCG intravesical therapy in patients with NMIBC. Patient summaryLevofloxacin administration seems to be a safe and effective therapy for non–muscle-invasive bladder cancer patients treated with bacillus Calmette-Guerin intravesical therapy.

Abstract CT565: Clinical and translational results of a phase I study, tocilizumab plus gemcitabine/nab-paclitaxel in patient with gemcitabine/nab-paclitaxel-refractory metastatic pancreatic cancer

Abstract Background: Interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway inhibition may overcome chemoresistance of metastatic pancreatic cancer (MPC) refractory to gemcitabine + nab-paclitaxel (GN) due to suppression of cancer associated fibroblast (CAF) and increase of drug infiltration in tumor. We sought to determine the safety, recommended dose of tocilizumab (TCZ), an IL-6 receptor monoclonal antibody, and biological correlates of tumor shrinkage in patients with GN-refractory MPC. Methods: This phase 1, dose finding trial was conducted following preclinical study of IL-6 signaling blockade in genetically engineered mouse model of pancreatic cancer (pGEMM) and patients-derived CAF, enrolled 10 patients with MPC that had progressed after GN. During the dose-finding part to determine dose-limiting toxicity (DLT), patients initially received TCZ 8 mg/kg on Day 1 and nab-paclitaxel 100 mg/m2 + gemcitabine 750 mg/m2 on Days 2, 9, and 16. The subsequent dose-expansion part used the TCZ dose identified in the dose-finding study. Before Cycle 1 and at the end of Cycle 1, biopsy of liver metastasis was performed 3 to 5 hours after levofloxacin (LVXF) administration to measure LVFX infiltration in tumor using matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI). Results: In pGEMM tumor, mouse IL-6 receptor antibody plus GN led pathological response. The growth of CAFs from patients with pancreatic cancer was inhibited by TCZ. In this phase I study, no DLTs occurred and the recommended dosage of TCZ was determined to be 8 mg/kg. Treatment-emergent adverse events (TEAEs) occurred in 80% of patients (Grade ≥3 in 60%) with decreased neutrophil count (n=5, 7 events) being the most common TEAE. Disease control rate was 80·0% (95%CI: 44·4-97·5) and tumor reduction during cycle 1 was observed in 4 patients who were defined as responder. In paired-biopsied samples, decrease of phosphorylated (p) STAT3 expression in tumor was observed in 7 of 8 patients (88%). Responder-related biological activities were increase of cleaved PARP expression of tumor nuclei (P = 0.01), decrease of proliferative CAF (P = 0.08), and increase of LVFX infiltration in tumor (P = 0.04). Decrease of pSTAT3 expression (P = 0.02) was favor to increase of LVFX infiltration against increase of gamma-H2AX, an index of gemcitabine exposure (P = 0.20). Conclusion: TCZ+GN-rechallenge had a manageable safety profile and showed preliminary activity via inhibition of CAF and gain of intratumoral drug infiltration in MPC. Citation Format: Shuichi Mitsunaga, Masafumi Ikeda, Kazunori Aoki, Kyoko Yamaguchi, Noriaki Sawada, Etsuko Fujii, Masanobu Nishidate, Takashi Fujitomo, Hideaki Mizuno, Yoko Kayukawa, Atsuhiko Kato, Mayu Makikawa, Hiroshi Imaoka, Mitsuhito Sasaki, Kazuo Watanabe, Hiroyuki Tsunoda, Kimio Terao, Atsushi Ochiai. Clinical and translational results of a phase I study, tocilizumab plus gemcitabine/nab-paclitaxel in patient with gemcitabine/nab-paclitaxel-refractory metastatic pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT565.

PLGA Carriers for Controlled Release of Levofloxacin in Anti-Tuberculosis Therapy

Levofloxacin (LFX) is a highly effective anti-tuberculosis drug with a pronounced bactericidal activity against Mycobacterium tuberculosis (Mtb). In this work, an “organic solvent-free” approach has been used for the development of polylactic-co-glycolic acid (PLGA) microparticles and scaffolds containing LFX at a therapeutically significant concentration, providing for its sustained release. To achieve the target, both nonpolar supercritical carbon dioxide and polar supercritical trifluoromethane have been used. By changing the composition, surface morphology, size, and internal structure of the polymer carriers, one can control the kinetics of the LFX release into phosphate buffered saline solutions and physiological media, providing for its acceptable burst and desirable concentration in the prolonged phase. The biocompatibility and bactericidal efficacy of PLGA/LFX carriers assessed both in vitro (against Mtb phagocytosed by macrophages) and in vivo (against inbred BALB/c mice aerogenically infected with Mtb) demonstrated their anti-tuberculosis activity comparable with that of the standard daily intragastric levofloxacin administration. These results make it possible to consider the developed compositions as a promising candidate for anti-tuberculosis control release formulations providing for the further evaluation of their activity against Mtb and their metabolism in vivo over long periods of tuberculosis infection.

Comparative effects of systemic administration of levofloxacin and cephalexin on fracture healing in rats.

ObjectivesThis study aimed to compare the effects of systemic administration of levofloxacin or cephalexin on fracture healing in rats.Materials and MethodsIn this animal study, tibial fractures not requiring fixation were artificially induced in 30 male Wistar albino rats using a 1.1 mm surgical bur. The rats were randomly divided into 6 groups (n=5). Groups 1 and 2 received daily subcutaneous saline injections. Groups 3 and 4 received subcutaneous injections of 25 mg/kg levofloxacin twice daily. Groups 5 and 6 received daily subcutaneous injections of 20 mg/kg cephalexin. The rats in Groups 1, 3, and 5 were sacrificed after 1 week, while the rats in Groups 2, 4, and 6 were sacrificed after 4 weeks. The score of fracture healing was determined through histological assessment of sections from the fracture site according to Perry and colleagues. Data were analyzed by Kruskal–Wallis and Mann–Whitney tests.ResultsThe mean score of fracture healing at 4 weeks was significantly higher than that at 1 week in the saline, levofloxacin, and cephalexin groups (P<0.001). At 1 week, no significant difference was noted among the three groups of saline, levofloxacin, and cephalexin in the mean score of fracture healing (P=0.360). However, this difference was significant at 4 weeks (P=0.018), and the mean score in the saline group was significantly higher compared to that in the levofloxacin group (P=0.015).ConclusionIt is recommended not to prescribe levofloxacin for more than 1 week after surgical management of bone fractures due to its possible adverse effects on fracture healing.

Ocular surface flora and prophylactic antibiotics for cataract surgery in the age of antimicrobial resistance.

According to the World Health Organization alert about the antimicrobial resistance crisis released in 2015, clinicians should strongly reconsider the prolonged use of antimicrobials. In this review, we focus on the ocular surface flora with respect to the trend of fluoroquinolone resistance, and its upset and restoration after topical administration of antimicrobials and preservatives. Even 3weeks of topical administration of levofloxacin (LVFX) yields a selection of fluoroquinolone-resistant isolates bearing genetic changes in the ocular surface flora. One month of topical prophylactic administration of LVFX after cataract surgery induces the loss of diversity with LVFX-resistance of the ocular surface flora. Restoration of LVFX-sensitive flora occurs 6 to 9months after the final topical administration of LVFX. The ocular surface flora recovers earlier in patients given LVFX for 1week after the surgical procedure. These findings suggest that shorter periods of postoperative topical antibiotics are less frequently associated with persistent antimicrobial-resistant bacteria in the ocular flora. In addition, microbiologic analysis of ocular surfaces treated with a long period of eye drops containing benzalkonium chloride (BAC) showed a higher incidence of isolates resistant to methicillin and fluoroquinolones than did ocular surfaces treated with eye drops not containing BAC. To avoid the emergence of antimicrobial-resistant bacteria on the ocular surface, an urgent discussion must be held about the appropriate use of antibiotics and preservatives in the ophthalmology field.

The Nephroprotective Effect of Clove Oil (Oleum Caryophylli) Against Levofloxacin Toxicity in Rats

Background: Levofloxacin is a fluoroquinolone antibiotic that has broad-spectrum antimicrobial activity, but it may induce kidney dysfunction. Clove oil (Oleum caryophylli) has antioxidant properties that may alleviate levofloxacin toxicity. This study aimed to examine the protective effect of clove oil on levofloxacin-induced nephrotoxicity in rat animal models. Methods: A total of 24 male rats were divided into 6 groups. One group did not receive levofloxacin to serve as the control. The treatment groups received a single daily administration of levofloxacin (93 mg/kg) with either placebo or clove oil (10 mg/kg, 25 mg/kg, or 50 mg/kg per body weight) pre-treatment. Another group received Curcuma extract pre-treatment as a comparison. Blood samples were withdrawn after 28 days of treatment to measure serum biomarkers (urea and creatinine), and the kidneys were removed to measure renal Malondialdehyde (MDA) and histopathological analysis. Results: The results showed that clove oil pre-treatment at a dose of 10 mg/kg was able to reduce renal MDA and serum biomarker levels (P&lt;0.05). The effect was similar to that found in Curcuma-treated rats. In addition, clove oil (10 mg/kg) was also found to ameliorate renal histopathological damage due to levofloxacin. Conclusion: Based on biomarker and histopathological analysis, clove oil pre-treatment in rats provides a nephroprotective effect against levofloxacin toxicity.