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ABSTRACT Introduction: The treatment of acute lymphoblastic leukemia (ALL) has evolved in recent decades, reaching an overall survival rate close to 90%. Currently, approximately 4% of patients with ALL die from secondary complications of chemotherapy. Among these complications, the most frequent is febrile neutropenia (FN). The treatment of acute myeloid leukemias (AMLs) is even more aggressive, being consequently related to a considerable amount of treatment-related toxicity with a high risk of severe infection and death. Method: In order to reduce the infection-related risks in these groups of patients, systemic antibacterial prophylaxis has emerged as a possible approach. Results: Antibiotic prophylaxis during neutropenia periods in those undergoing chemotherapy have .already been proven in adults with acute leukemias (ALs). Among the possible available therapeutic options for bacterial prophylaxis in children with cancer, fluoroquinolones emerged with the most amount of evidence. Within this class, levofloxacin became the best choice. Conclusion: Therefore, the use of levofloxacin seems to be indicated in very specific situations: in children who are known to be neutropenic for a long time, secondary to intensive chemotherapy; in children with AL undergoing chemotherapy to induce remission; or in children undergoing hematopoietic stem cell transplantation (HSCT). This article aims to describe recent evidence focusing on antibiotic prophylaxis in children with ALs.

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In this research work, the photocatalytic capacity shown by the nanoparticles of the CaTiO3 system was evaluated to degrade two pollutants of emerging concern, namely methyl orange (MO)-considered an organic contaminating substance of the textile industry that is non-biodegradable when dissolved in water-and levofloxacin (LVF), an antibiotic widely used in the treatment of infectious diseases that is released mostly to the environment in its original chemical form. The synthesis process used to obtain these powders was the polymeric precursor method (Pechini), at a temperature of 700 °C for 6 h. The characterization of the obtained oxide nanoparticles of interest revealed the presence of a majority perovskite-type phase with an orthorhombic Pbnm structure and a minority rutile-type TiO2 phase, with a P42/mnm structure and a primary particle size <100nm. The adsorption-desorption isotherms of the synthesized solids had H3-type hysteresis loops, characteristic of mesoporous solids, with a BET surface area of 10.01m2/g. The Raman and FTIR spectroscopy results made it possible to identify the characteristic vibrations of the synthesized system and the characteristic deformations of the perovskite structure, reiterating the results obtained from the XRD analysis. Furthermore, a bandgap energy of ~3.4eV and characteristic emissions in the violet (437 nm/2.8 eV) and orange (611 nm/2.03 eV) were determined for excitation lengths of 250 nm and 325 nm, respectively, showing that these systems have a strong emission in the visible light region and allowing their use in photocatalytic activity to be potentialized. The powders obtained were studied for their photocatalytic capacity to degrade methyl orange (MO) and levofloxacin (LVF), dissolved in water. To quantify the coloring concentration, UV-visible spectroscopy was used considering the variation in the intensity of the characteristic of the greatest absorption, which correlated with the change in the concentration of the contaminant in the solution. The results showed that after irradiation with ultraviolet light, the degradation of the contaminants MO and LVF was 79.4% and 98.1% with concentrations of 5 g/L and 10 g/L, respectively.

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The issue of drug resistance of Helicobacter pylori is becoming increasingly serious. To analyze the correlation between the cagA and vacA genotypes of H. pylori strains and their resistance to metronidazole, levofloxacin, and clarithromycin in patients in Xi'an, we studied 117 H. pylori strains isolated from patients in Xi'an. Antibiotic susceptibility testing of H. pylori was performed. The cagA and vacA genotypes were investigated using PCR. Among 117 strains of H. pylori, the rate of detection of cagA was 91.45% (107/117), among which the detection rate of East Asian-type cagA was 85.05% (91/107) and that of Western-type cagA was 14.95% (16/107). There were only two genotypes of vacA: s1m1 and s1m2. The detection rate of vacAs1m1 was 47.01% (55/117) and that of vacAs1m2 was 52.99% (62/117). The dominant strains in Xi'an were cagA + vacAs1m2 strains. The metronidazole resistance rate of vacAs1m2 H. pylori strains was significantly higher than that of vacAs1m1 H. pylori strains (91.94% vs. 69.09%, P = 0.002). The levofloxacin resistance rate of Western-type cagA strains was significantly higher than that of East Asian-type cagA strains (56.25% vs. 20.88%, P = 0.004). The metronidazole resistance rate of cagA + vacAs1m2 H. pylori strains was significantly higher than that of cagA + vacAs1m1 H. pylori strains (91.23% vs. 66.00%, P = 0.001). Our results showed that Western-type cagA strains were more likely to develop levofloxacin resistance than East Asian-type cagA strains. VacAs1m2 strains were more prone to metronidazole resistance than vacAs1m1 strains.

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BACKGROUND: Fluoroquinolones (FQNs) are related to several central nervous system side effects. This review aims to evaluate the clinical-epidemiological profile, pathophysiological mechanisms, and management of FQNs-associated movement disorders (MDs). METHODS: Two reviewers identified and assessed relevant reports in six databases without language restriction between 1988 and 2022. RESULTS: A total of 45 reports containing 51 cases who developed MDs secondary to FQNs were reported. The MDs included 25 myoclonus, 13 dyskinesias, 7 dystonias, 2 cerebellar syndromes, 1 ataxia, 1 tic, and 2 undefined cases. The FQNs reported were ciprofloxacin, ofloxacin, gatifloxacin, moxifloxacin, levofloxacin, gemifloxacin, and pefloxacin. The mean and median age were 64.54 (SD: 15.45) and 67 years (range: 25-87 years). The predominant sex was male (54.16%). The mean and median time of MD onset were 6.02 (SD: 10.87) and 3 days (range: 1-68 days). The mean and median recovery time after MD treatment was 5.71 (SD: 9.01) and 3 days (range: 1-56 days). A complete recovery was achieved within one week of drug withdrawal in 80.95% of the patients. Overall, 95.83% of the individuals fully recovered after management. CONCLUSIONS: Future cases need to describe the long-term follow-up of the individuals. Additionally, FQN-induced myoclonus should include electrodiagnostic studies.

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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.

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INTRODUCTION: The treatment of acute lymphoblastic leukemia (ALL) has evolved in recent decades, reaching an overall survival rate close to 90%. Currently, approximately 4% of patients with ALL die from secondary complications of chemotherapy. Among these complications, the most frequent is febrile neutropenia (FN). The treatment of acute myeloid leukemias (AMLs) is even more aggressive, being consequently related to a considerable amount of treatment-related toxicity with a high risk of severe infection and death. METHOD: In order to reduce the infection-related risks in these groups of patients, systemic antibacterial prophylaxis has emerged as a possible approach. RESULTS: Antibiotic prophylaxis during neutropenia periods in those undergoing chemotherapy have .already been proven in adults with acute leukemias (ALs). Among the possible available therapeutic options for bacterial prophylaxis in children with cancer, fluoroquinolones emerged with the most amount of evidence. Within this class, levofloxacin became the best choice. CONCLUSION: Therefore, the use of levofloxacin seems to be indicated in very specific situations: in children who are known to be neutropenic for a long time, secondary to intensive chemotherapy; in children with AL undergoing chemotherapy to induce remission; or in children undergoing hematopoietic stem cell transplantation (HSCT). This article aims to describe recent evidence focusing on antibiotic prophylaxis in children with ALs.

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ABSTRACT 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.

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Bacterial persisters represent a small subpopulation that tolerates high antibiotic concentrations without acquiring heritable resistance, and it may be generated by environmental factors. Here, we report the first antibiotic persistence mechanism in Streptococcus pneumoniae, which is induced by oxidative stress conditions and allows the pneumococcus to survive in the presence of fluoroquinolones. We demonstrated that fluoroquinolone persistence is prompted by both the impact of growth arrest and the oxidative stress response induced by H2O2 in bacterial cells. This process protected pneumococci against the deleterious effects of high ROS levels induced by fluoroquinolones. Importantly, S. pneumoniae develops persistence during infection, and is dependent on the oxidative stress status of the host cells, indicating that its transient intracellular life contributes to this mechanism. Furthermore, our findings suggest persistence may influence the outcome of antibiotic therapy and be part of a multistep mechanism in the evolution of fluoroquinolone resistance. IMPORTANCE In S. pneumoniae, different mechanisms that counteract antibiotic effects have been described, such as vancomycin tolerance, heteroresistance to penicillin and fluoroquinolone resistance, which critically affect the therapeutic efficacy. Antibiotic persistence is a type of antibiotic tolerance that allows a bacterial subpopulation to survive lethal antimicrobial concentrations. In this work, we used a host-cell infection model to reveal fluoroquinolone persistence in S. pneumoniae. This mechanism is induced by oxidative stress that the pneumococcus must overcome to survive in host cells. Many fluoroquinolones, such as levofloxacin and moxifloxacin, have a broad spectrum of activity against bacterial pathogens of community-acquired pneumonia, and they are used to treat pneumococcal diseases. However, the emergence of fluoroquinolone-resistant strains complicates antibiotic treatment of invasive infections. Consequently, antibiotic persistence in S. pneumoniae is clinically relevant due to prolonged exposure to fluoroquinolones likely favors the acquisition of mutations that generate antibiotic resistance in persisters. In addition, this work contributes to the knowledge of antibiotic persistence mechanisms in bacteria.

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Due to the abuse of antibiotics, the prevalence of antibiotic resistant Helicobacter pylori strains continues to increase. Therefore, antibiotic resistance assessment is now essential in addition to general H. pylori diagnosis in medical institutions to fulfill clinicians administering effective antibiotic regimens. However, the conventional antibiotic resistance assessment methods, such as in vitro antibiotic susceptibility test and E-test, are skilled-staff dependent and time-consuming. The aim of this study was to establish an easy-operating TaqMan-MGB probe multiplex real-time PCR system for one-step detection of levofloxacin and clarithromycin resistance mutations with concurrent H. pylori infection diagnosis. Through the optimization of primers, probes and reaction buffers, this proposed system could accurately distinguish the recombinant plasmids with different mutation markers. More importantly, the diagnosis results of this detection system exhibited excellent consistence with the gold standard of gastric biopsy and Sanger sequencing on the detection of H. pylori infection and relevant antibiotic resistant strains, the Kappa values of which all exceeded 0.90. In addition, the results of this detection system could also be applied for the prevalence statistics of antibiotic resistance patterns for patients by age, gender and geographical location. This simple and rapid system should be beneficial for clinicians issuing personalized treatments according to the patient's H. pylori strains and avoid the abuse of antibiotics.

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Abstract The objective of the present investigation was to design, optimize and characterize the gastro retentive floating levofloxacin tablets and perform in-vivo evaluation using radiographic imaging. The floating tablets were prepared by using polymers i.e hydroxy propyl methyl cellulose (HPMC-K4M) and carbopol-940 individually and in combination by nonaquous granulation method. All the Formulations were evaluated for swelling index (S.I), floating behavior and in-vitro drug release kinetics. The compatibility study of levofloxacin with other polymers was investigated by FTIR, DSC, TGA and XRD. Results from FTIR and DSC revealed no chemical interaction amongst the formulation components. The optimized formulation (F11) showed floating lag time (FLT), total floating time (TFT) swelling index (S.I) of 60 sec, >16h and approximately 75 %, respectively. Moreover, F11 showed zero order levofloxacin release in simulated gastric fluid over the period of 6 h. X-ray studies showed that total buoyancy time was able to delay the gastric emptying of levofloxacin floating tablets in rabbits for more than 4 hours. In conclusion the optimized formulation (F11) can be used for the sustained delivery of levofloxacin for the treatment of peptic ulcer.

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