Antibiotic prophylaxis in acute childhood leukemia: What is known so far?

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.

Analysis of clinical treatment outcomes of ocular lesions in 28 cases of severe ocular rosacea / 中华皮肤科杂志

Objective:To investigate clinical treatment regimens for ocular lesions in patients with severe ocular rosacea.Methods:A total of 28 patients (34 eyes) with severe rosacea complicated by blepharokeratoconjunctivitis were collected from outpatient department of the Affiliated Eye Hospital of Nanjing Medical University from December 1, 2019 to May 30, 2021. They were randomly divided into two groups: group A (13 cases, 16 eyes) topically treated with sodium hyaluronate 0.3% eye drops and levofloxacin 0.5% eye drops, and group B (15 cases, 18 eyes) topically treated with sodium hyaluronate 0.3% eye drops alone. Patients in both groups also received oral minocycline hydrochloride 100 mg every day for the first 2 weeks, and then 50 mg every day for the next 6 weeks. Meanwhile, all patients received same physical therapies such as meibomian gland massage, eyelid hot compresses and eyelid margin cleaning. LogMAR visual acuity, tear break-up time (BUT) , ocular surface disease index (OSDI) score, and meibomian gland function grading examination results in the two groups were recorded before and 8 weeks after treatment. Paired t test was used to compare within-group differences in the parameters before and after treatment, and two-independent-sample t test to compare intergroup differences after treatment. Results:After 8-week treatment, both group A and group B showed significantly increased LogMAR visual acuity ( t = 3.10, 2.15, P = 0.007, 0.046, respectively) , improved BUT ( t = 3.44, 2.85, P = 0.003, 0.011, respectively) , but significantly decreased OSDI scores ( t = 7.12, 9.33, respectively, both P < 0.001) and meibomian gland function scores ( t = 13.73, 16.82, respectively, both P < 0.001) compared with those before treatment. After treatment, no significant differences were observed in the LogMAR visual acuity ( P = 0.721) , BUT ( P = 0.189) , OSDI scores ( P = 0.808) and meibomian gland function scores ( P = 0.191) between the two groups. No adverse drug reactions occurred during the treatment. During the follow-up period (8 months or shorter) , no recurrence of ocular lesions was observed. Conclusion:Without topical antibiotics, oral minocycline hydrochloride combined with topical sodium hyaluronate eye drops is still effective for the treatment and prevention of recurrence of ocular lesions in patients with severe ocular rosacea.

Inhibitory and clearance effect of azithromycin combined with levofloxacin on biofilm of different ST types of Klebsiella pneumoniae / 中国临床药理学与治疗学

AIM: Given the biofilm formation abili- ty of different ST-type Klebsiella pneumoniae, our study was aimed at exploring the inhibitory and clearance of azithromycin combined with levofloxacin on the biofilm of Klebsiella pneumoniae of different ST-types and providing a new strategy for the prevention of biofilm formation in the treatment of post-infectious Klebsiella pneumoniae. METHODS: 9 strains of Klebsiella pneumoniae from all susceptibility groups, 19 strains of Klebsiella pneumoniae producing extended-spectrum β - lactamases (ESBLs), and 37 strains of Carbapenem-resistant Klebsiella pneumoniae (CRKP) were randomly collected from the samples of patients hospitalized in the First Affiliated Hospital of Wannan Medical College from August 2019 to November 2021. The isolates were identified using VITEK MS IVD KB V3.2 and VITEK 2-Compact 60. Multilocus sequence typing (MLST) was performed to analyze the homology of each strain; crystal violet staining was used for semi -quantitative detection of biofilm to compare the differences in biofilm formation ability between different ST-type Klebsiella pneumoniae. Different ST-type strains were selected, and the partial inhibitory concentration index (FICI) was calculated by micro broth dilution method to judge the combination effect and select the optimal combination concentration; crystalline violet staining method was used to investigate the inhibition and clearance effect of azithromycin combined with levofloxacin on the biofilm of different ST-type Klebsiella pneumoniae; laser scanning confocal fluorescence microscopy was used to observe the structural changes of the biofilm of Klebsiella pneumoniae before and after the effect of the antibacterial drugs. RESULTS: MLST typing results showed that the sensitive group of Klebsiella pneumoniae strains had 8 sequences such as ST86, ST727, etc., the ESBLs group strains belonged to 14 sequence types such as ST15, ST37, ST11, etc., of which ST15 accounted for 26.32% (5 / 19). The CRKP group strains belonged to 9 sequence types such as ST11, ST15, ST656, etc., of which ST11 accounted for 48.65% (18/37), ST15 accounted for 27.03% (10/37); ST15 (ESBLs), ST11 (CRKP), ST15 (CRKP) type Klebsiella pneumoniae biofilms all reached maturity on the 5th day, the ST15 (ESBLs) group had a stronger ability to produce material to be membranous than the ST15 (CRKP) group. The ST11 (CRKP) group had a stronger ability to produce material to be membranous than the ST15 (CRKP) group (Pazithromycin>levofloxacin, and the highest clearance rate was 44.79%. CONCLUSION: There are differences in biofilm formation ability between different ST-type Klebsiella pneumoniae, and azithromycin combined with levofloxacin has a better inhibitory effect on different ST-type Klebsiella pneumoniae biofilm, conbined application can be used in the treatment of biofilm infections early stage.

In vitro bacteriostatic and serum pharmacological tests of Qiguiyin decoction combined with levofloxacin against pseudomonas aeruginosa / 中国药理学通报

Aim To investigate the antibacterial activity and anti-resistant mutation ability of Qiguiyin decoction (a traditional Chinese herbal formula) combined with levofloxacin against pseudomonas aeruginosa byantibacterial experiment in vitro and serum pharmacology. Methods The minimal inhibitory concentrations (MICs) of levofloxacin and Qiguiyin decoction were detected respectively by the broth dilution technique.The MIC of the combination of two drugs was determined by the micro chessboard dilution method. The effects of combined drugs on enhancing the antibacterial activity of different strains were evaluated respectively by calculating the fractional inhibitory concentration index (FICI). The drug-containing serum of levofloxa-cin group, Qiguiyin decoction group, Qiguiyin decoction combined with levofloxacin group and control group was prepared. The antibacterial rate, MIC and MBC of 10% ~ 90% serum against the two strains were determined. Results Combined with Qiguiyin decoction, MIC of levofloxacin against pseudomonas aeruginosa (standard/resistant) decreased significantly, 0. 5 < FICI

Effect of thymopentin combined with levofloxacin for retreatment smear positive pulmonary tuberculosis / 中国热带医学

@#Abstract: Objective　To analyze the effect of adjuvant to levofloxacin in the treatment of retreatment smear positive pulmonary tuberculosis, as well as its effect on respiratory function, immune function and inflammatory factors. Methods　One hundred cases of retreatment smear positive pulmonary tuberculosis patients admitted to Rudong County People's Hospital in Nantong city in Jiangsu province from 2017 to 2021 were randomly divided into a control group (n=50) and an observation group (n=50) according to random number table method. Both groups received conventional treatment (3 months of isoniazid, rifampicin, ethambutol, pyrazinamide / 6 months of isoniazid, rifampicin, ethambutol), with levofloxacin added to the control group, and thymopentin added to the observation group for the first three months in addition to routine treatment. The treatment effect of the two groups were compared. Results　The sputum smear conversion rate of the observation group was significantly higher than that of the control group after 3 months and 5 months of treatment (χ2=7.142, P<0.05; χ2=6.250, P<0.05). The cavity absorption time and lesion absorption time in the observation group were significantly lower than those in the control group (t=4.006, P<0.05; t=5.165, P<0.05). The turning time of bacteriological culture in the observation group was significantly lower than that in the control group (t=4.220,P<0.05). After 3 months of treatment, CD4+, CD3+, CD4+/CD8+ of the observation group were higher than those of the control group, the differences were statistically significant (t=8.885, P<0.05; t=6.274, P<0.05; t=4.357, P<0.05). After 3 months of treatment, the IFN-γ (interferon-γ) of the observation group was higher than that of the control group (t=8.892, P<0.05), whereas the , IL-10 (interleukin-10) was significantly lower than that in the control group (t=5.986, P<0.05). After 3 months of treatment, forced vital capacity (FVC), forced expiratory volume in one second (forced expiratory volume in one second, FEV 1) and the one-second rate (forced expiratory volume in one second / forced vital capacity, FEV1/FVC) in the observation group were significantly higher than those in the control group (t=11.223, P<0.05; t=10.128, P<0.05; t=4.464, P<0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (χ2=0.378, P>0.05). Conclusions　Thymopentin combined with levofloxacin had a significant application effect in the treatment of retreatment smear positive pulmonary tuberculosis, s, which led to improved inflammatory reaction, respiratory function and immune function. Additionally, it can increase sputum smear conversion rate and accelerate patient recovery, improving overall treatment efficacy, with a relatively high clinical application value.

Levofloxacin combined with cellulase can eradicate bacille Calmette-Guerin biofilm infection / 南方医科大学学报

OBJECTIVE@#To investigate the inhibitory effects of levofloxacin (LEV) combined with cellulase against bacille CalmetteGuerin (BCG) biofilms in vitro.@*METHODS@#The mature growth cycle of BCG biofilms was determined using the XTT method and crystal violet staining. BCG planktonic bacteria and BCG biofilms were treated with different concentrations of LEV and cellulose alone or jointly, and the changes in biofilm biomass were quantified with crystal violet staining. The mature BCG biofilm was then treated with cellulase alone for 24 h, and after staining with SYTO 9 and Calcofluor White Stain, the number of viable bacteria and the change in cellulose content in the biofilm were observed with confocal laser scanning microscopy. The structural changes of the treated biofilm were observed under scanning electron microscopy.@*RESULTS@#The MIC, MBC and MBEC values of LEV determined by broth microdilution method were 4 μg/mL, 8 μg/mL and 1024 μg/mL, respectively. The combined treatment with 1/4×MIC LEV and 2.56, 5.12 or 10.24 U/mL cellulase resulted in a significant reduction in biofilm biomass (P < 0.001). Cellulase treatments at the concentrations of 10.24, 5.12 and 2.56 U/mL all produced significant dispersion effects on mature BCG biofilms (P < 0.001).@*CONCLUSION@#LEV combined with cellulose can effectively eradicate BCG biofilm infections, suggesting the potential of glycoside hydrolase therapy for improving the efficacy of antibiotics against biofilmassociated infections caused by Mycobacterium tuberculosis.

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

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.

Pharmaceutical care for one case of levofloxacin-induced hypersensitivity reaction by the participation of clinical pharmacists and literature analysis / 中国药房

OBJECTIVE To analyze the characteristics of levofloxacin-induced hypersensitivity reaction. METHODS Clinical pharmacists participated in the treatment for a case of levofloxacin-induced hypersensitivity reaction， and adjudged the relationship of levofloxacin with hypersensitivity reaction according to relative standards. Retrieved from CNKI， VIP， Wanfang database， PubMed and Embase， relevant literature about levofloxacin-induced hypersensitivity reaction was collected and analyzed. RESULTS Clinical pharmacists suggested checking the patient’s previous medication and allergy history based on symptoms such as fever and systemic rash， and determined that the drug hypersensitivity was “likely” or “highly likely” to be associated with levofloxacin. Clinicians provided symptomatic treatment to the patient based on the judgment of clinical pharmacists， and the patient improved after treatment. Results of the literature analysis showed that among 31 involved patients， there were 23 males and 8 females； 18 patients aged 50 and above； the incubation period of 24 patients was within 4 days after medication. The main adverse drug reactions were drug hypersensitivity syndrome， fixed drug eruption， erythema multiforme， etc. Most patients were improved after withdrawal and symptomatic treatment. CONCLUSIONS Hypersensitivity reaction is the rare adverse drug reaction of levofloxacin， mostly occurring within 2.5 h to 4 days after administration， and it is more likely to occur in middle-aged and elderly patients. Before clinical use， patients should be asked about their drug allergy history in detail； when patients experience fever or rash without obvious causes， medication should be stopped promptly and symptomatic treatment should be taken to ensure the safety and effectiveness of the patients’ medication.

Meta-analysis of the efficacy and safety of Gatifloxacin and Levofloxacin in the acute bacterial conjunctivitis / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To compare the clinical efficacy and safety of gatifloxacin eye drops and levofloxacin eye drops in the treatment of acute bacterial conjunctivitis using Meta-analysis.<p>METHODS: According to the Cochrane systematic evaluation method, “gatifloxacin” “levofloxacin” and “acute bacterial conjunctivitis” were used as keywords for literature search in Embase, Cochrane library, Pubmed, Medline, CNKI, Wanfang, VIP and CBMdisc from the establishment of the database to March 1, 2021. Randomized controlled trials(RCTs)gatifloxacin eye drops and levofloxacin eye drops in the treatment of acute bacterial conjunctivitis were included. Cochrane bias risk assessment tool was used to evaluate the quality of the included studies. RevMan5.3 software was used for combined analysis. Egger's test in Stata12 was used to assess publication bias, and the level of evidence was evaluated according to the GRADE system.<p>RESULTS: A total of 10 RCTs were included in this study with 1 149 patients. The control group was treated with levofloxacin and the experimental group was treated with gatifloxacin. The results of Meta-analysis showed that the clinical effective rate of acute bacterial conjunctivitis in gatifloxacin group was higher than that in levofloxacin group(<i>OR</i>=3.75, 95%<i>CI</i>: 2.52-5.58, <i>P</i><0.00001). Egger's test suggested there was publication bias among studies. And GRADE rating results indicated, the level of evidence was VERY LOW. The incidence of adverse drug reactions in the gatifloxacin group was lower than that in levofloxacin group(<i>OR</i>=0.37, 95%<i>CI</i>: 0.19-0.71, <i>P</i>=0.003). No publication bias was observed in Egger's test and GRADE showed the level of evidence was LOW.<p>CONCLUSION: Gatifloxacin eye drops is more effective than levofloxacin eye drops in the treatment of acute bacterial conjunctivitis, and has lower adverse effect rates. And due to the low levels of evidence included, more multicenter, randomized double-blind clinical trials are needed to improve the strength of evidence for the clinical efficacy of gatifloxacin eye drops in the treatment of acute bacterial conjunctivitis.

Study on the susceptibility genes that mediate the resistance of Helicobacter pylori to clarithromycin and levofloxacin based on comprehensive antibiotic research database comparison / 中华消化杂志

Objective:Taking clinical strains of Helicobacter pylori ( H. pylori) with different antimicrobial resistance as the research object, to explore the new genes related to the resistance of H. pylori to clarithromycin (CLA) and levofloxacin (LVX) based on whole-genome sequencing. Methods:From September 1st, 2016 to August 31st, 2019, 1 749 patients with upper gastrointestinal symptoms and positive 13C urea breath test who visited the Department of Gastroenterology and Hepatology, the University of Hong Kong-Shenzhen Hospital were enrolled. After gastric mucosal biopsy, H. pylori was isolated and cultured from gastric mucosa. Ninety H. pylori strains were successfully preserved. According to the results of in vitro drug sensitivity test, a total of 40 strains including 10 strains with single-drug resistance to CLA (CLA group), 10 strains with single-drug resistance to LVX (LVX group), 10 strains with dual-resistance to CLA and LVX (dual resistance group) and 10 strains sensitive to CLA, LVX, amoxicillin, furazolidone, tetracycline and metronidazole (all sensitive group) were screened out. By whole-genome sequencing and comparison to the comprehensive antibiotic research database (CARD), single nucleotide variations (SNV) and indels were analyzed, genes related to H. pylori resistance to CLA and LVX were screened out and the differences of new genes among 4 groups were analyzed. Independent sample t test, one-way analysis of variance, least significant difference method and chi-square test were used for statistical analysis. Results:Among the 4 groups there were no statistically significant differences in the number of SNV (74 952.00±8 755.21, 77 128.10±3 191.35, 78 639.90±601.23 and 77 474.60±2 421.05) and Indels (2 582.20±265.45, 2 653.60±108.37, 2 667.10±43.82 and 2 641.10±80.25) (all P>0.05). Compared to CARD, a total of 223 drug resistance-related genes were detected, of which 19 genes related to CLA mono-resistance in CLA group, 24 genes related to LVX mono-resistance in LVX group, 16 genes related to CLA mono-resistance, 14 genes related to LVX mono-resistance, and 12 dual resistance-related genes in dual resistance group, and 11 genes related to CLA mono-resistance, 17 genes related to LVX mono-resistance, and 13 dual resistance-related genes in all sensitive group. Among the genes related to CLA mono-resistance, the detection rates of erythromycin esterase gene ( ere)B in CLA group, LVX group, dual resistance group and all sensitive group were 0/10, 0/10, 3/10, 0/10, respectively, and the difference was statistically significant( χ2=5.79, P=0.049). The detection rate of erythromycin ribosomal methylase gene ( erm) family in CLA group and dual resistance group was higher than that in LVX group and all sensitive group (45.0%, 9/20 vs. 10.0%, 2/20), and the difference was statistically significant ( χ2=6.14, P=0.013). The detection rates of free methionine-(R)-sulfoxide reductase gene ( msrC) in CLA group, LVX group, dual resistance group and all sensitive group were 10/10, 7/10, 6/10, 4/10, respectively, and the difference was statistically significant ( χ2=8.97, P=0.030). Among the genes related to LVX mono-resistance, the detection rate of quinolone resistance pentapeptide repeat protein gene ( qnr) family in LVX group and dual resistance group was higher than that in CLA group and all sensitive group (60.0%, 12/20 vs. 25.0%, 5/20), and the difference was statistically significant ( χ2=5.01, P=0.025). The detection rates of qnrB4 in CLA group, LVX group, dual resistance group and all sensitive group were 1/10, 3/10, 7/10, 1/10, respectively, and the difference was statistically significant ( χ2=10.17, P=0.010). The number of efflux transporter genes related to CLA mono-resistance in 4 groups were less than those of LVX mono-resistance and dual drug resistance (11 vs. 29 and 11 vs. 23), and the differences were statistically significant ( χ2=11.87, 5.80; P=0.001, 0.016). The detected numbers of LVX resistance-related efflux transport genes in CLA group, LVX group, dual resistance group and all sensitive group were 28, 40, 24 and 27, respectively, and the difference was statistically significant ( χ2=10.26, P=0.016). Conclusions:Erm family and msrC may be important genes that mediate the resistance of H. pylori to CLA, and qnr family is related to mediating the resistance of H. pylori to LVX. Efflux transport genes may play a synergistic role in the process of drug efflux, and are more likely to mediate H. pylori resistance to LVX.

Formulation, Optimization, in vitro and in-vivo evaluation of levofloxacin hemihydrate Floating Tablets

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.

Analysis of main clinical features and pathogenic bacteria of lacrimal tracheitis / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To investigate the main clinical features, pathogen distribution and drug sensitivity of lacrimal angiitis, and to provide evidence for clinical diagnosis and treatment.<p>METHODS:Retrospective study. A total of 45 patients(45 eyes)diagnosed with lacrimal angiitis in Hebei Eye Hospital from December 2016 to October 2020 were selected to analyze the general information, clinical manifestations and previous treatment history, bacterial culture results, and drug sensitivity test results.<p>RESULTS:All 45 patients had monocular disease, including 21 eyes with tears, increased secretion, conjunctival congestion in inner canthus, 14 eyes with red and swollen inner canthus, 6 eyes similar to eyelid cyst, and 4 eyes were found and diagnosed during routine preoperative examination. 27 eyes were previously diagnosed with other eye diseases, and the misdiagnosis rate was 60.0%. The positive rate of bacterial culture was 80.0%(36/45), Staphylococcus epidermidis was the most common, followed by Streptococcus; 52.8%(19/36)of the patients were infected with multidrug-resistant bacteria. The sensitivity rate of bacteria to fluoroquinolones(82.9%, 97/117)was higher than that of aminoglycosides(70.1%, 68/97)and cephalosporins(68.1%, 111/163). Except vancomycin, rifampicin, levofloxacin and chloramphenicol were highly sensitive to Gram-positive bacteria.<p>CONCLUSION: Staphylococcus epidermidis is the most common pathogen of dacryocystitis, followed by Streptococcus. Levofloxacin and rifampicin can be the first choice antibiotics for local anti-infection. Rational drug use can reduce the formation of multidrug-resistant bacteria. The cure rate can be improved by complete removal of stones by incision and plasty of lacrimal canaliculus.

Levofloxacin-induced acute hemolytic anemia: A clinical case report / 中国输血杂志

【Objective】 To study the clinical characteristics and treatment of patients with acute hemolytic anemia crisis induced by levofloxacin. 【Methods】 The levofloxacin antibody was detected by the microcolumn gel method and scored by the Naranjo Adverse Drug Reaction Probability Scale(APS). Patients suffered from acute hemolysis anemia induced by levofloxacin was rescued by whole blood exchange(WBE) and therapeutic plasma exchange(TPE). 【Results】 The patient was diagnosed as acute hemolysis induced by levofloxacin as levofloxacin antibody was yielded, and 7 points scored by the Naranjo APS. After WBE and TPE treatment, the patient′s clinical symptoms and signs improved rapidly. Supplemented with immunoglobulin and hormone therapy, the patient was discharged on d 10 after treatment. 【Conclusion】 Levofloxacin can induce acute hemolytic anemia crisis, and WBE and TPR are effective rescue methods.

Antofloxacin-based Bismuth Quadruple Therapy for Helicobacter pylori Eradication / 胃肠病学

Background: Resistance to antibiotics is the major cause for failure of Helicobacter pylori (Hp) eradication therapy. Therefore, exploring new eradication regimen has become a hotspot of research. Aims: To investigate the efficacy, safety and optimal dose of antofloxacin-based bismuth quadruple therapy for first-line Hp eradication. Methods: Four hundred patients with Hp infection and naive to eradication therapy were prospectively recruited from January 2019 to December 2019 at the 900th Hospital of Joint Logistics Support Force, PLA and were randomly divided into four groups: low-, normal-, and high-dose antofloxacin groups and control group, 100 cases in each group. Patients in low-, normal-, and high-dose antofloxacin groups received antofloxacin 100 mg, 200 mg, and 300 mg qd, respectively, pantoprazole 40 mg bid, bismuth potassium citrate 220 mg bid, and amoxicillin 1 000 mg bid for 14 days; patients in control group received levofloxacin 500 mg qd and the other three drugs with same dose and frequency for 14 days. Adverse events during treatment were recorded. Hp eradication was confirmed by

Inhibitory and scavenging ability of ambroxol combined with levofloxacin on the bacterial biofilm of Klebsiella pneumoniae / 中国临床药理学与治疗学

AIM: To study the inhibitory and scavenging effects of ambroxol combined with levofloxacin on the bacterial biofilm of Klebsiella pneumoniae, and to provide a new strategy to treat and antagonize the formation of the biofilm. METHODS: We collected Klebsiella pneumoniae of different resistance and divided them into sensitive group (wild bacteria group), ESBLs group and CRKP group with 15 strains in each group and performed biological semi-quantitative detection of its biofilm by crystalline violet staining method. After selecting 3 strains with similar membrane yields from each group, we determined the minimum inhibitory concentration (MIC) of ambroxol and levofloxacin against Klebsiella pneumoniae by micro broth dilution method.In addition, we determined the effects of ambroxol in different concentrations on the MIC of levfloxacin by the micrdilution checkerboard techniques and calculated the partial inhibitory concentration index (FIC) to determine the joint effect and select the best synergistic concentration. Finally, the effects of ambroxol and levofloxacin in different concentrations on the inhibition formation test and removal test of Klebsiella pneumoniae biofilm were observed by crystal violet method combined with confocal laser scanning microscopy. RESULTS: We found that all three groups of bacterial biofilms became mature on the 5th day, and the sensitive group was easier to form and produce biofilm more than the ESBLs and CRKP groups (F=3.725, P=0.032). It was showed that the geometric average of levofloxacin MIC value in the three groups decreased significantly. And the selected strains all showed a synergistic effect on the two-drug combination.In the biofilm test, as the concentration of ambroxol increased, its inhibition rate reached more than 75%, but its biofilm removal rate did not reach 70%. CONCLUSION: Our study support that ambroxol combined with levofloxacin can inhibit the bacterial biofilm of Klebsiella pneumoniae early, and its optimal synergistic concentration is 0.49 mg/mL (ambroxol) + 4 μg/mL (levofloxacin).

Trend analysis of Helicobacter pylori resistance to clarithromycin and levofloxacin in Wenling area from 2014 to 2018 / 上海预防医学

Objective:To understand the trend of Helicobacter pylori （Hp） resistance to clarithromycin and levofloxacin and to provide guidance for Hp eradication therapy. Methods:From January 2014 to December 2018， a total of 66 515 patients with gastrointestinal symptoms were enrolled in the First People's Hospital of Wenling. The patients were divided into the following groups： childhood （0 to 6 years old）； juvenile （7 to 17 years old）； youth （18 to 40 years old），middle age （41 to 65 years old），and old age （≥66 years old）. All patients received gastroscopy， gastric mucosal biopsy， Hp culture and drug sensitivity test of clarithromycin and levofloxacin. Results:The Hp positive rate showed a significant downward trend in 2016， 2017 and 2018 （χ2=14.317， 47.079， 88.054， all P<0.05）. The average resistance rate of Hp to clarithromycin from 2014 to 2018 was 22.72% （4 732/20 831） showing an increasing trend， but the increase was slower after 2017. The average resistance rate to levofloxacin was 30.55% （6 364/20 831）， and the overall trend showed a sharp rise from 2015 to 2017 （χ2=38.383， 49.569， both P<0.05）， and a significant decline was detected after 2017 （χ2=18.841， P<0.05）. The resistance rate of Hp to levofloxacin in patients increased with age. The clarithromycin resistance rate first decreased and then increased with age， and the resistance rate in old age （32.52%， 763/2 346） was higher than that in youth （22.09%， 1 086/4 916） and middle age patients （21.21%， 2 854/13 458）， and the differences were significant （χ2=991.071， 144.968， both P<0.05）. The resistance rate of Hp rose from 12.73% （14/110） in juvenile to 43.31% （1 016/2 346） in old age （χ2=228.867， P<0.05）. Conclusion:In recent years， the positive rate of Hp infection in Wenling area has a decreasing trend. Although the resistance rate of Hp to clarithromycin and levofloxacin has been rising slowly or decreasing， it is still at a high level. In the selection of Hp eradication program， the differences between patients in different age groups should be considered with particular attention on the minors.

Ciprofloxacin and levofloxacin adversely affect male infertility indicated by pharmacological, andrological and pathological evidence

Background: Drug-induced reproductive organs toxicities is an important aetiology in investigation of male infertility. The aim is to study levofloxacin effect on male reproductive system in comparison to ciprofloxacin.Methods: Twenty-five male wister rats weighted 230±20 gm and aged 8 weeks were randomly divided into five groups of five. The first group received ciprofloxacin with dose 78.23 mg/kg/day in 2 doses (therapeutic dose). The second group received the double dose of the first group ciprofloxacin. The third group received levofloxacin with dose 39.11 mg/kg/day once daily (OD) (therapeutic dose). The Fourth group received the double dose of the third group levofloxacin. However, the fifth group served as a control and received normal saline with carboxymethylcellulose OD. All treatments were administered orally for 14 days. On the 15th day, blood samples and reproductive organs were obtained from all rats. Testicular tissues were prepared for genetic testing and chemical and microscopical examination.Results: Ciprofloxacin and levofloxacin negatively altered reproductive organ weights, sperm parameters and serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) level (p<0.05). Additionally, serum testosterone level was significantly deceased in ciprofloxacin-treated group (the double dose) (p<0.05) relative to control. The difference between ciprofloxacin and levofloxacin was significant in seminal vesicle weight and serum LH and FSH level (p<0.05). Testicular histopathological changes were also found with the two drugs with different degrees. Effects of levofloxacin and ciprofloxacin were dose-dependent.Conclusions: Both ciprofloxacin and levofloxacin adversely affect andrological function that should be monitored and controlled during application of these drugs.

Therapeutic effect of Xueniaoan Capsule combined with levofloxacin on chronic bacterial prostatitis / 中草药

Objective: To investigate the clinical efficacy of Xueniaoan Capsule combined with levofloxacin in the treatment of chronic bacterial prostatitis. Methods: A total of 126 patients with chronic bacterial prostatitis were randomly divided into control group (n = 60) and observation group (n = 66). The control group was treated with levofloxacin hydrochloride tablets (0.6 g/d, po) and the observation group was treated with Xueniaoan Capsule (4.2 g/d, po) combined with levofloxacin hydrochloride tablets (0.6 g/d, po). Both groups were continuously treated for eight weeks. The clinical efficacy of the two groups was evaluated through the NIH-CPSI score, prostatic fluid bacterial culture negative conversion rate, and serological parameters. Results: After treatment, the clinical efficacy in the control and treatment groups were 66.67% and 89.39%, respectively, and there were statistical differences between two groups (P < 0.05); Statistical analysis showed that the pain symptom score (5.45 ± 1.12), urination symptom score (3.31 ± 0.70) and quality of life score (3.08 ± 0.55) of NIH-CPSI scale in the observation group were significantly lower than those of the control group (P < 0.05); The negative conversion rate of prostatic fluid bacterial culture was 71.67% in the control group and 92.42% in the observation group, and the difference between the two groups had statistical significance (P < 0.05); The serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and high-sensitivity C-reactive protein (hs-CRP) in the two groups were significantly lower than those before treatment (P < 0.05), while the levels of inflammatory factors in the observation group were significantly lower than those in the control group (P < 0.05). Conclusion: Xueniaoan Capsule combined with levofloxacin is effective in the treatment of chronic bacterial prostatitis, and can effectively relieve the clinical symptoms, improve the rate of prostatic fluid bacterial clearance, and reduce the level of serum inflammatory factors, which has a certain clinical application value.

Evaluation of intraocular penetration of levofloxacin by high performance liquid chromatography / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To evaluate the levofloxacin eye drop into human eye penetration, levofloxacin eye drop concentrations in human ocular aqueous of 33 patients undergoing cataract surgery were measured by high performance liquid chromatography(HPLC).<p>METHODS:Totally 33 volunteer patients who scheduled for phacoemulsification surgery received one drop of levofloxacin every 6h for 3d before and on the day of surgery, administration of drug was stopped 1h before surgery. Levofloxacin concentration in aqueous humor was measured by HPLC method with fluorescence detector. <p>RESULTS:A simple, effective and sensitive HPLC method for determination of levofloxacin in human ocular aqueous was validated. Linearity was shown for levofloxacin concentration over a wide range of 1.95×10-3-1.50 μg/mL. The mean aqueous level of levofloxacin was 0.3399±0.03405 μg/mL. <p>CONCLUSION:Results from the present study demonstrate that topical administration of levofloxacin 0.5% before cataract surgery with routine dose(one drop every 6h)unable to reach MIC90 for most common microorganism causing acute bacterial endophthalmitis.

Simultaneously Quantifying IsoniazidPyrazinamide and Levofloxacin in Human Sputum by HPLC-MS/MS / 中国药学杂志

OBJECTIVE: To develop an UPLC-MS/MS method for simultaneous determination of 3 anti-tuberculosis drugs [isoniazid (INH) pyrazinamide (PZA) and levofloxacin(LFX)] in sputum by HPLC-MS/MS. METHODS The drugs(INH,PZAand LFX)were extracted by methanol/acetonitrile (V-V=1∶1). All of them separated on ACQUITY UPLC HSS T3 1.8 μm column (2.1 mm×100 mm,Waters Corporation) with the mobile phase of aqueous solution (containing 0.1% formic acid)-acetonitrile (containing 0.1% formic acid) at a flow rate of 0.35 mL•min-1. Multiple reaction monitoring (MRM) mode was performed combined with electrospray ionization source operating in the positive ionization mode. Furthermore, it was blindly collected 7 sputum samples, and analyzed the drug concentration by the built method in this work. RESULTS: The liner calibration curves of INHPZALFX were obtained in the concentration range of 48-6 000 ng•mL-1(r=0.998 8)480-60 000 ng•mL-1(r=0.999 3)120-15 000 ng•mL-1(r=0.999 5), respectively. The CV of intra- and inter-day precision was less than 15% and the absolute recovery was 97.21%-107.80%. In the 7 clinical samples, the concentration of INH is 44.74, 120.1, 301.5, 481, 595.5, 1 220 and 1 570 ng•mL-1, 104.2, 6 273.34 and 3 185 ng•mL-1 for PZA, and 199.86 for LFX, respectively. CONCLUSION: In this work, it is built a LC-MS method to simultaneously quantify INH, PZA and LFX, which is simple, sensitive and accurate. This method is successfully applied to analyze the clinical samples.