Otitis media is an infection of the middle ear mainly caused by bacteria, and current treatments rely heavily on antibiotics. However, the emergence of antibiotic-resistant bacterial strains seriously affects their efficacy. In our study, we found that extracellular vesicles (EVs) derived from human natural killer cells (NKs) inhibit the proliferation of both standard and levofloxacin (LVX)-resistant strains of Staphylococcus aureus in a dose-dependent manner. Moreover, compared to LVX, EVs were more effective at reducing effusion and rescuing hearing thresholds in animal models. For LVX-sensitive strains, EVs were significantly more effective in terms of curative time but not curative rate. For LVX-resistant strains, EVs were significantly more effective in terms of both curative rate and curative time when applied alone or applied jointly with LVX. In summary, we found that NK EVs are highly effective in treating otitis media, providing an alternative approach for treating this common disease.
Killer Cells, Natural/metabolism* ; Exosomes/metabolism* ; Animals ; Humans ; Otitis Media/therapy* ; Staphylococcus aureus/drug effects* ; Disease Models, Animal ; Anti-Bacterial Agents/pharmacology* ; Levofloxacin/pharmacology*

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.
Levofloxacin/pharmacology* ; Gentian Violet/pharmacology* ; BCG Vaccine/pharmacology* ; Anti-Bacterial Agents/pharmacology* ; Biofilms ; Cellulases/pharmacology* ; Microbial Sensitivity Tests

A new isobenzoisofuran(1) has been isolated from the whole plant of Cassia pumila using various chromatographic techniques, including silica gel, Sephadex, MCI-gel resin, and RP-HPLC, and its structure was determined as 9-(2-hydroxyethyl)-2,2-dimethyl-2H-furo[3,4-g]chromen-6(8H)-one. This compound was also evaluated for its antibacterial activity. The results showed that it had prominent antibacterial activity with MIC_(90) value of(45.2±4.2) μg·mL~(-1) for methicillin resistant Staphylococcus aureus(MRSA) strain. This value was closed to that of levofloxacin [with MIC_(90) value(48.5±4.3) μg·mL~(-1)].
Anti-Bacterial Agents/pharmacology* ; Benzofurans/pharmacology* ; Cassia/chemistry* ; Levofloxacin ; Methicillin-Resistant Staphylococcus aureus/drug effects* ; Microbial Sensitivity Tests ; Phytochemicals/pharmacology* ; Plants, Medicinal/chemistry*

ObjectiveTo investigate the effects of fosfomycin tromethamine (FT) on the expressions of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), and interleukin-6 (IL-6) in the prostate tissue of the rats with chronic bacterial prostatitis (CBP).

METHODSWe randomly divided 70 male SD rats into 7 groups of equal number: blank control, CBP model control, positive control, 14 d low-dose FT, 7 d low-dose FT, 14 d high-dose FT, and 7 d high-dose FT. The CBP model rats in the latter five groups were treated intragastrically with levofloxacin at 100 mg/kg/d for 30 days and FT at 200 mg/kg/d for 14 and 7 days and at 300 mg/kg/d for 14 and 7 days, respectively. Then we collected the prostate tissue from the animals for determination of the levels of TNF-α, IL-8 and IL-6 by ELISA.

RESULTSCompared with the blank controls, the CBP model rats showed significantly increased levels of TNF-α (［19.83 ± 6.1］ vs ［32.93 ± 6.21］ ng/g prot, P <0.01), IL-8 (［8.26 ± 0.52］ vs ［16.2 ± 2.84］ ng/g prot, P <0.01) and IL-6 (［1.55 ± 0.11］ vs ［2.51 ± 1.06］ ng/g prot, P <0.05) in the prostate tissue. In comparison with the CBP model controls, the levels of TNF-α and IL-8 were remarkably decreased in the groups of positive control (［20.54 ± 5.78］ ng/g prot, P <0.01; ［12.43 ± 4.02］ ng/g prot, P <0.05), 14 d low-dose FT (［21.95 ± 6.48］ ng/g prot, P <0.01; ［11.11 ± 2.86］ ng/g prot, P <0.01), 7 d low-dose FT (［23.8 ± 6.93］ ng/g prot, P <0.05; ［12.43 ± 4.02］ ng/g prot, P <0.05), 14 d high-dose FT (［19.97 ± 2.58］ ng/g prot, P <0.01; ［8.83 ± 1.32］ ng/g prot, P <0.01), and 7 d high-dose FT (［21.97 ± 3.38］ ng/g prot, P <0.01; ［12.68±1.97］ ng/g prot, P <0.05). No statistically significant differences were observed between the positive control and FT groups in the contents of TNF-α, IL-8 or IL-6 (P >0.05). The expression of IL-6 was markedly reduced in the 14 d high-dose FT group as compared with the model controls (［1.76 ± 0.46］ vs ［2.51 ± 1.06］ ng/g prot, P<0.05) but exhibited no significant difference between the CBP model control and the other groups (P >0.05).

CONCLUSIONSFosfomycin tromethamine inhibits the expressions of TNF-α, IL-8 and IL-6 in the prostate tissue, suppresses its inflammatory reaction, promotes the repair of damaged prostatic structure, and thus contributes to the treatment of chronic bacterial prostatitis in rats.

Animals ; Anti-Bacterial Agents ; pharmacology ; Bacterial Infections ; drug therapy ; microbiology ; Fosfomycin ; pharmacology ; Interleukin-6 ; metabolism ; Interleukin-8 ; metabolism ; Levofloxacin ; pharmacology ; Male ; Prostate ; drug effects ; metabolism ; Prostatitis ; drug therapy ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism

BACKGROUNDAcinetobacter baumannii has emerged as an important pathogen causing a variety of infections. Using data from the China Surveillance of Antimicrobial Resistance Program conducted biennially, we investigated the secular changes in the resistance of 2917 isolates of A. baumannii from 2004 to 2014 to differ antimicrobial agents.

METHODSPathogen samples were collected from 17 to 20 hospitals located in the eastern, central, and western regions of China. Minimum inhibitory concentrations (MICs) were determined by a 2-fold agar dilution method, and antimicrobial susceptibility was established using the 2014 Clinical Laboratory Standards Institute-approved breakpoints. Isolates not susceptible to all the tested aminoglycosides, fluoroquinolones, β-lactams, β-lactam/β-lactam inhibitors and carbapenems were defined as extensively drug resistant.

RESULTSThe rates of nonsusceptibility to common antimicrobial agents remained high (>65%) over the years with some fluctuations to certain agents. The prevalence of imipenem-resistant A. baumannii (IRAB) increased from 13.3% in 2004 to 70.5% in 2014 and that of extensively drug-resistant A. baumannii (XDRAB) increased from 11.1% in 2004 to 60.4% in 2014. The activity of tigecycline was stable with MIC90 ≤4 mg/L against A. baumannii from 2009 to 2014. Susceptibility to colistin remained high (97.0%) from 2009 to 2014. The prevalence of XDRAB increased in all the three surveillance regions over the years and was significantly higher in Intensive Care Unit (ICU) wards than non-ICU wards.

CONCLUSIONSThis longitudinal multicenter surveillance program revealed the nationwide emergence of A. baumannii in China and showed a significant increase in prevalence from 2004 to 2014. High levels of bacterial resistance were detected among samples collected from clinical settings in China, with IRAB and XDRAB being especially prevalent. This study will help to guide empirical therapy and identify at-risk groups requiring more intense interventional infection control measures, while also helping to focus surveillance efforts.

Acinetobacter baumannii ; drug effects ; Amikacin ; pharmacology ; Anti-Infective Agents ; pharmacology ; Cefoperazone ; pharmacology ; Ceftazidime ; pharmacology ; Cephalosporins ; pharmacology ; China ; Colistin ; pharmacology ; Drug Resistance, Multiple, Bacterial ; Humans ; Imipenem ; pharmacology ; Levofloxacin ; pharmacology ; Microbial Sensitivity Tests ; Minocycline ; pharmacology ; Penicillanic Acid ; analogs & derivatives ; pharmacology ; Piperacillin ; pharmacology ; Sulbactam ; pharmacology

PURPOSE: Fluoroquinolones, rapidly gaining prominence in treatment of Stenotrophomonas maltophilia (SMP), are noted for their potency and tolerability. However, SMP may rapidly acquire resistance to fluoroquinolones. We evaluated associations of clinical factors with acquisition of levofloxacin resistance (LFr) in SMP. MATERIALS AND METHODS: Our retrospective cohort study was based on patient data collected between January 2008 and June 2010. Through screening of 1275 patients, we identified 122 patients with data for SMP antibiotic susceptibility testing in > or =3 serial SMP isolates. RESULTS: We assigned the 122 patients to either the SS group (n=54) in which levofloxacin susceptibility was maintained or the SR group (n=31) in which susceptible SMP acquired resistance. In multivariate regression analysis, exposure to levofloxacin for more than 3 weeks [odds ratio (OR) 15.39, 95% confidential interval (CI) 3.08-76.93, p=0.001] and co-infection or co-colonization with Klebsiella pneumoniae resistant to levofloxacin (OR 4.85, 95% CI 1.16-20.24, p=0.030) were independently associated with LFr acquisition in SMP. CONCLUSION: Acquisition of LFr during serial sampling of SMP was related to the levofloxacin exposure.
Aged ; Anti-Bacterial Agents/*pharmacology/*therapeutic use ; Fluoroquinolones/pharmacology/therapeutic use ; Gram-Negative Bacterial Infections/drug therapy ; Humans ; Levofloxacin/*pharmacology/*therapeutic use ; Microbial Sensitivity Tests ; Middle Aged ; Retrospective Studies ; Stenotrophomonas maltophilia/drug effects/*pathogenicity

OBJECTIVETo investigate the resistance of Helicobacter pylori (H. pylori) to antimicrobial agents in adolescents.

METHODSOne hundred and eight adolescents (6-18 years old) underwent a gastroscopy examination. H. pylori strains were isolated from gastric mucosa. Antimicrobial susceptibility testing was performed by means of Kirby-Baner.

RESULTSThirty-six H. pylori strains were identified. The resistant rate of H. pylori strains to clarithromycin, fruranzolidone and amoxicillin was 8.3%, 16.7% and 33.3%, respectively. H. pylori strains showed a high resistance to metronidazole (94.4%), while no strain was resistant to gentamicin and levofloxacin.

CONCLUSIONSThe H. pylori strains from the adolescents in Zhejiang showed a high resistance to metronidazole and amoxicillin but a low resistance to clarithromycin and fruranzolidone. All of H. pylori strains were susceptive to gentamicin and levofloxacin.

Adolescent ; Amoxicillin ; pharmacology ; Anti-Infective Agents ; pharmacology ; Child ; Clarithromycin ; pharmacology ; Drug Resistance, Bacterial ; Female ; Gastroscopy ; Helicobacter pylori ; drug effects ; Humans ; Levofloxacin ; Male ; Metronidazole ; pharmacology ; Microbial Sensitivity Tests ; Ofloxacin ; pharmacology

AIMTo learn the electrophysiological interference of levofloxacin (LVFX) to heart in guinea pig.

METHODSHigh, moderate and low doses of LVFX were given to the anesthetic guinea pig via i.p., and QT interval span and corrected QT-interval span in the II leading lines of ECG were recorded and analyzed from 5 min to 360 min after the drug administration. Single ventricular myocytes were obtained and impacted by LVFX solution of different concentrations. Then delayed rectifier potassium currents (I(K)) on single cells were recorded with whole-cell patch clamp technique, and compared with control group(without impact of LVFX).

RESULTS(1) After the administration of LVFX, at the dose of 200 mg/kg. QT-interval span was significantly elongated, and the increasing rate is 19.38% +/- 3.15% (P < 0.05). While at the relatively lower doses of 50 mg/kg and 100 mg/kg, the elongation is of low/no significance (P > 0.05). (2) LVFX inhibited I(K) dose-dependently and time-dependently.

CONCLUSIONLVFX might prolong the QT-interval span by the mechanism of inhibiting I(K), which implies a potential risk in clinical application.

Animals ; Guinea Pigs ; Levofloxacin ; Membrane Potentials ; Myocytes, Cardiac ; drug effects ; physiology ; Ofloxacin ; pharmacology ; Patch-Clamp Techniques