Levofloxacin reduces inflammatory cytokine levels in human bronchial epithelia cells: implications for aerosol MP-376 (levofloxacin solution for inhalation) treatment of chronic pulmonary infections

Inflammation resulting from chronic bacterial infection in the lung contributes to long-term pulmonary complications in chronic pulmonary infections such as cystic fibrosis. Aerosol administration of levofloxacin as in the form of the investigational formulation MP-376 results in higher concentrations in lung tissues that are higher than those that can be attained with oral or intravenous dosing of levofloxacin. The objective of this study was to evaluate the effect of high concentrations of levofloxacin achieved with aerosol administration of MP-376 on proinflammatory cytokine secretion by immortalized human bronchial epithelia cells in vitro. Additionally, we investigated the potential mechanisms of the immunomodulatory effect of levofloxacin. In vitro studies in human lung epithelial cell lines showed that levofloxacin led to a dose-related reduction in IL-6 and IL-8 concentrations, with 300 μg mL(-1) resulting in the reduction of levels of IL-6 by fourfold and IL-8 by twofold (P<0.05); in contrast, tobramycin increased IL-6 levels by 50%, but had no effect on IL-8. Levofloxacin treatment did not affect the cytokine mRNA level and nuclear factor-κB-dependent promoter activity. These findings suggest that high concentrations of levofloxacin obtained in pulmonary tissues following the administration of aerosol MP-376 may provide additional benefits in patients with chronic pulmonary infections that are independent of its antibacterial properties.     

树[鼠句]正常肠道细菌的培养分离鉴定及其药敏试验研究

目的了解人工饲养树[鼠句]肠道菌群感染情况及其各种细菌对药物的敏感性。方法通过肠道细菌采样、培养、分离和菌落生长特性观察,并经革兰氏染色、氧化酶试验、触酶试验、生化编码鉴定管试验和9种药敏试验分析,初步鉴定了107例人工饲养树[鼠句]肠道感染细菌的种类和这些细菌对药物的敏感程度。结果本次细菌培养共从树[鼠句]肠道中培养分离出5株细菌,其中革兰氏阳性菌2株,革兰氏阴性菌3株,以大肠杆菌和葡萄球菌最为多见。同时确定了菌株的药敏情况为：（1）大肠杆菌对头孢类药头孢哌酮最为敏感,对药物磺胺甲嚼唑／甲氧苄定、氧氟沙星、左氧氟沙星、呋喃妥因、诺氟沙星、氨苄西林高敏;（2）沙门氏菌对阿米卡星最为敏感,对药物头孢哌酮青霉素G高敏;（3）链球菌对试验药物氨苄西林、头孢哌酮、呋喃妥因显示为中敏;（4）葡萄球菌对头孢类药头孢哌酮、磺胺类磺胺甲晤唑／甲氧苄定、沙星类诺氟沙星、左氧氟沙星、氧氟沙星、呋喃妥因和氨苄西林最为敏感,对其它药物均为中敏;（5）假单胞菌对药物左氧氟沙星最为敏感,对大多数药物都显示高敏。结论大肠杆菌和葡萄球菌可能是树鼢肠道中正常寄生的主要菌群,同时其它菌群也有寄生。用药敏实验筛选出的药物可为临床用药和动物的生物净化提供指导依据。     

High Helicobacter pylori resistance to metronidazole but zero or low resistance to clarithromycin, levofloxacin, and other antibiotics in Malaysia

Objective: Bacterial resistance to antibiotics is the single most important determinant of treatment success. The objective of this study was to determine the prevalence of Helicobacter pylori resistance to clarithromycin, amoxicillin, metronidazole, tetracycline, levofloxacin, rifabutin, and furazolidone in our local bacterial strains. Methods: Samples from consecutive ninety patients were obtained for culture and sensitivity testing. Resistance to individual antibiotics were tested using the E‐test and MIC₉₀ read from the strips. Resistance to rifampicin and nitrofurantoin were used as a surrogate for rifabutin and furazolidine. Results: There was a high prevalence of resistance to metronidazole 68/90 (75.5%). No male (34/45 (75.5%) versus female (35/45 (77.7%) difference in frequency of metronidazole resistance was noted (p = 1.000). There was zero resistance ₀ to clarithromycin, levofloxacin, amoxicillin, and nitrofurantoin/furazolidone. Resistance to rifampicin/rifabutin was for breakpoints of 1 and 4 μg/mL of 14.4 and 2.2% respectively. Conclusions: Although there was high bacterial resistance to metronidazole, the absence of resistance particularly to the key antibiotics used in H. pylori eradication therapy: clarithromycin and levofloxacin is reassuring to note. Continued monitoring of antibiotic resistance should be carried out.     

Pseudomonas aeruginosa Keratitis in Mice: Effects of Topical Bacteriophage KPP12 Administration

The therapeutic effects of bacteriophage (phage) KPP12 in Pseudomonas aeruginosa keratitis were investigated in mice. Morphological analysis showed that phage KPP12 is a member of the family Myoviridae, morphotype A1, and DNA sequence analysis revealed that phage KPP12 is similar to PB1-like viruses. Analysis of the phage KPP12 genome did not identify any genes related to drug resistance, pathogenicity or lysogenicity, and so phage KPP12 may be a good candidate for therapeutic. KPP12 showed a broad host range for P. aeruginosa strains isolated from clinical ophthalmic infections. Inoculation of the scarified cornea with P. aeruginosa caused severe keratitis and eventual corneal perforation. Subsequent single-dose administration of KPP12 eye-drops significantly improved disease outcome, and preserved the structural integrity and transparency of the infected cornea. KPP12 treatment resulted in the suppression of neutrophil infiltration and greatly enhanced bacterial clearance in the infected cornea. These results indicate that bacteriophage eye-drops may be a novel adjunctive or alternative therapeutic agent for the treatment of infectious keratitis secondary to antibiotic-resistant bacteria.     

Topical flagellin protects the injured corneas from Pseudomonas aeruginosa infection

Among bacterial pathogens, Pseudomonas (P.) aeruginosa infection is the most sight threatening. The corneal innate immune responses are key mediators of the host’s defense to P. aeruginosa. Using a mouse model of Pseudomonas keratitis, we evaluated the protective effects of topical application of flagellin, a ligand for Toll-Like receptor 5 (TLR5), on the development of Pseudomonas keratitis and elucidated the underlying mechanisms. Topical application of purified flagellin 6 and 24 h prior to P. aeruginosa inoculation on injured mouse corneas significantly attenuated clinical symptoms of P. aeruginosa keratitis, decreased bacterial burden, and suppressed infection induced inflammation in the B6 mouse cornea. Topical application of flagellin on wounded cornea induced PMN infiltration and markedly upregulated cathelicidin-related antimicrobial peptide (CRAMP) expression. In PMN depleted mice, flagellin promoted bacterial clearance in the cornea compared to that of the PBS treated mice, but was unable to prevent corneal perforation and systemic bacterial dissemination and sepses. Deletion of CRAMP increased corneal susceptibility to P. aeruginosa and abolished flagellin-induced protection in B6 mice. Our findings illustrate the profound protective effect of flagellin on the cornea innate defense, a response that can be exploited for prophylactic purposes to prevent contact lens associated Pseudomonas keratitis.     

Evaluating the role of Burkholderia pseudomallei K96243 toxins BPSS0390, BPSS0395, and BPSS1584 in persistent infection

Burkholderia pseudomallei is the causative agent of melioidosis, a disease with a mortality rate of up to 40% even with treatment. Despite the ability of certain antibiotics to control initial infection, relapse occurs in treated patients. The inability of antibiotics to clear this bacterial infection is in part due to persistence, an evasion mechanism against antibiotics and the effect of host defenses. Evaluation of antibiotic efficacy against B. pseudomallei revealed that up to 48% of in vitro grown populations can survive in a persister state. Toxin–antitoxin (TA) systems have been previously implicated in modulating bacterial persistence. We generated three isogenic TA mutants and found that loss of each toxin gene did not alter antibiotic persistence or macrophage survival. In response to macrophage‐induced persistence, all three toxin mutants demonstrated increased intracellular susceptibility to levofloxacin which in part was due to the inability of the mutants to induce persistence after nitric oxide or nutrient starvation. In an inhalational model of murine melioidosis, both ΔBPSS0395 and ΔBPSS1584 strains were attenuated, and treatment with levofloxacin led to significant reduction in lung colonisation and reduced splenic colonisation by ΔBPSS0395. Based on our findings, these toxins deserve additional evaluation as putative therapeutic targets.     

Macrophages restrict Pseudomonas aeruginosa growth,regulate polymorphonuclear neutrophil influx,and balance pro- and anti-inflammatory cytokines in BALB/c mice

The role of macrophages in Pseudomonas aeruginosa corneal infection in susceptible (cornea perforates), C57BL/6 (B6) vs resistant (cornea heals), BALB/c mice was tested by depleting macrophages using subconjunctival injections of clodronate-containing liposomes before corneal infection. Both groups of inbred mice treated with clodronate-liposomes compared with PBS-liposomes (controls) exhibited more severe disease. In B6 mice, the cornea perforated and the eye became extremely shrunken, whereas in BALB/c mice, the cornea perforated rather than healed. The myeloperoxidase assay detected significantly more PMN in the cornea of both groups of mice treated with clodronate-liposomes vs PBS-liposomes. In independent experiments, ELISA analysis showed that protein levels for IL-1 beta, macrophage-inflammatory protein 2, and macrophage-inflammatory protein 1 alpha, all regulators of PMN chemotaxis, also were elevated in both groups of mice treated with clodronate-liposomes. Bacterial plate counts in B6 mice treated with clodronate-liposomes were unchanged at 3 days and were higher in control-treated mice at 5 days postinfection (p.i.), whereas in BALB/c mice, bacterial load was significantly elevated in the cornea of mice treated with clodronate-liposomes at both 3 and 5 days p.i. mRNA expression levels for pro (IFN-gamma and TNF-alpha)- and anti (IL-4 and IL-10)-inflammatory cytokines also were determined in BALB/c mice treated with clodronate-liposomes vs control-treated mice. Expression levels for IFN-gamma were significantly elevated in mice treated with clodronate-liposomes at 3 and 5 days p.i., while IL-10 levels (mRNA and protein) were reduced. These data provide evidence that macrophages control resistance to P. aeruginosa corneal infection through regulation of PMN number, bacterial killing and balancing pro- and anti-inflammatory cytokine levels.     

IL-18 contributes to host resistance against infection with Pseudomonas aeruginosa through induction of IFN-gamma production

Pseudomonas aeruginosa keratitis destroys the cornea in susceptible (B6), but not resistant (BALB/c) mice. To determine mechanisms mediating resistance, the role of IFN-gamma, IL-12, and IL-18 was tested in BALB/c mice. RT-PCR analysis detected IFN-gamma mRNA expression levels in cornea that were significantly increased at 1-7 days postinfection. IL-18 mRNA was detected constitutively in cornea and, at 1-7 days postinfection, levels were elevated significantly, while no IL-12 mRNA was similarly detected. To test whether IL-18 contributed to IFN-gamma production, mice were treated with anti-IL-18 mAb. Treatment decreased corneal IFN-gamma mRNA levels, and bacterial load and disease increased/worsened, compared with IgG-treated mice. To stringently examine the role of IFN-gamma in bacterial killing, knockout (-/-) vs wild-type (wt) mice also were tested. All corneas perforated, and bacterial load was increased significantly in -/- vs wt mice. Because disease severity was increased in IFN-gamma(-/-) vs IL-18-neutralized mice, and since IL-18 also induces production of TNF, we tested for TNF-alpha in both groups. ELISA analysis demonstrated significantly elevated corneal TNF-alpha protein levels in IFN-gamma(-/-) vs wt mice after infection. In contrast, RT-PCR analysis of IL-18-neutralized vs IgG-treated infected mice revealed decreased corneal TNF-alpha mRNA expression. Next, to resolve whether TNF was required for bacterial killing, TNF-alpha was neutralized in BALB/c mice. No difference in corneal bacterial load was detected in neutralized vs IgG-treated mice. These data provide evidence that IL-18 contributes to the resistance response by induction of IFN-gamma and that IFN-gamma is required for bacterial killing.     

Combination Therapy with Antibiotics and Anthrax Immune Globulin Intravenous (AIGIV) Is Potentially More Effective than Antibiotics Alone in Rabbit Model of Inhalational Anthrax

Background

We have evaluated the therapeutic efficacy of AIGIV when given in combination with levofloxacin and the effective window of treatment to assess the added benefit provided by AIGIV over standard antibiotic treatment alone in a New Zealand white rabbit model of inhalational anthrax.

Methods

Rabbits were exposed to lethal dose of aerosolized spores of Bacillus anthracis (Ames strain) and treated intravenously with either placebo, (normal immune globulin intravenous, IGIV) or 15 U/kg of AIGIV, along with oral levofloxacin treatment at various time points (30–96 hours) after anthrax exposure.

Results

The majority of treated animals (>88%) survived in both treatment groups when treatment was initiated within 60 hours of post-exposure. However, reduced survival of 55%, 33% and 25% was observed for placebo + levofloxacin group when the treatment was initiated at 72, 84 and 96 hours post-exposure, respectively. Conversely, a survival rate of 65%, 40% and 71% was observed in the AIGIV + levofloxacin treated groups at these time points.

Conclusions

The combination of AIGIV with antibiotics provided an improvement in survival compared to levofloxacin treatment alone when treatment was delayed up to 96 hours post-anthrax exposure. Additionally, AIGIV treatment when given as an adjunct therapy at any of the time points tested did not interfere with the efficacy of levofloxacin.     

Clinical and economic expedience of ertapenem therapy of complicated urinary tract infection

Clinical and economic investigation of various antibiotics use in the treatment of complicated urinary tract infection (CUTI) was performed under the Russian economic environment. The drugs of comparison were ertapenem, ceftriaxone and levofloxacin. Direct costs and their structure were shown, and the cost efficiency was calculated. Alternative analysis and one-side susceptibility analysis were performed. In complicated urinary tract infections when the major pathogens were Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis it was clinically and economically reasonable to start the treatment with ceftriaxone or ertapenem, while levofloxacin could be an alternative strategy. When the effects of the acquired resistance on the treatment effectiveness were evaluated (SIS model) it was shown that the pathogens susceptibility to ertapenem was preserved for a significantly longer time than that to ceftriaxone or levofloxacin (60 months). Such a parameter may serve as an additional evidence of the reasonable use of ertapenem as the starting treatment of CUTI.     

Contribution of the cornea to cytokine levels in the whole eye induced during the early phase of Pseudomonas aeruginosa challenge

Pseudomonas aeruginosa keratitis is one of the most destructive diseases of the cornea. The host response to this infection is critical to the outcome, and is regulated by cytokines produced in the ocular tissue. In this study, we assessed the relative contribution of the cytokines produced in the cornea to the inflammatory response of the whole eye to gain a better understanding of the inflammatory and regulatory processes in the ocular environment during localized corneal infection. C57BL/6 mice were challenged by topical application of P. aeruginosa to wounded corneas. Corneas and whole eyes were harvested 24 h post-challenge and bacterial numbers, myeloperoxidase levels and the levels of cytokines known to be important in keratitis were determined. The site of production of IL-6 and KC in the retina was determined by in situ hybridization. Before infection, 90% of macrophage inflammatory protein (MIP)-2 and approximately 80% of all IFN-gamma and IL-10 produced constitutively in the eye was found outside the cornea. Twenty-four hours after infection, bacterial numbers, levels of myeloperoxidase, and levels of MIP-2 and IL-1 were not different, whether measured in cornea or whole eye. However, expression of IL-6, KC, IFN-gamma and IL-10 was significantly greater in whole eyes than in the corneas of infected eyes. The cells expressing IL-6 and KC in the retina were identified by in situ hybridization. This study indicates that during corneal inflammation, the response of the whole eye as well as the cornea needs to be considered.     

Clinical applications of azithromycin microspheres in respiratory tract infections

Few adequately designed clinical trials have addressed optimal treatment duration in lower respiratory tract infections. Drugs possessing favourable pharmacokinetic and pharmacodynamic profiles may obtain early bacterial eradication allowing shorter treatment duration. This may be associated with a number of advantages including reduced resistance induction, increased compliance, lesser adverse events, and cost containment. Recently, a novel 2.0 g single dose of azithromycin microspheres has been compared with 7-day levofloxacin 500 mg or extended release clarithromycin in over 400 patients with community-acquired pneumonia. Clinical cure and bacteriological eradication rates, hospitalizations, and deaths were similar between azithromycin and comparators. Azithromycin 2.0 g microspheres proved as effective as 7 days of levofloxacin 500 mg in acute exacerbation of chronic bronchitis patients across all degrees of obstruction severity. In both settings Azithromycin microspheres obtained clinical cure in most patients harbouring macrolide-resistant Streptococcus pneumoniae strains. The drug was well tolerated in clinical studies and in healthy volunteers with modest and transitory adverse events. An undoubted advantage of single-dose azithromycin administration is the facility in ensuring that patients complete their prescribed course of therapy. A further advantage of single-dose therapy is the potential for use as directly-observed therapy, which may be useful in specific clinical conditions.     

Role of the preliminary susceptibility testing for initial and after failed therapy of Helicobacter pylori infection with levofloxacin, amoxicillin, and esomeprazole

BACKGROUND: Levofloxacin has been proposed as an alternative to classic therapy in secondary resistance to Helicobacter pylori. AIM: To evaluate primary and secondary resistance of H. pylori to levofloxacin, and to test the role of susceptibility test on the efficacy of levofloxacin-based triple therapy. METHODS: Eighty consecutive dyspeptic patients with positive (13)C-urea breath test never treated were randomly allocated into group A(1) (40 patients) and group B(1) (39 patients). Eighty-three patients already treated unsuccessfully with positive (13)C-urea breath test were divided into group A(2) (51 patients) and group B(2) (32 patients). Patients in group A(1) and group A(2) underwent upper gastrointestinal endoscopy for H. pylori susceptibility test to amoxicillin, clarithromycin, tinidazole, rifabutin, and levofloxacin. These patients were treated with levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.) and esomeprazole (20 mg b.i.d.) for 10 days if sensitive to these two antibiotics. If H. pylori was found resistant to amoxicillin and/or levofloxacin the treatment was based on the indications of the susceptibility test. Patients in group B(1) and group B(2) were treated empirically with levofloxacin, amoxicillin, and esomeprazole at the same dose and duration as group A. All patients underwent (13)C-urea breath test 2 months after the end of therapy. RESULTS: The antibiotic resistance of H. pylori strains in group A(1) and group A(2) was (%): amoxicillin: 2.4, 10; clarithromycin: 21.9, 43.1; tinidazole: 31.7, 70; rifabutin: 2.4, 4; and levofloxacin: 9.7, 12.2, respectively. In group A(1) with susceptibility test-driven therapy, eradication was 97.2%, and in group B(1) with empirical treatment, 94.1% (n.s.). In group A(2) with susceptibility test, eradication was 97.5%, whereas in group B(2) with empirical treatment 81.2% (p < .01). CONCLUSION: Primary and secondary resistance of H. pylori to levofloxacin is approximately 10% of the tested strains. The susceptibility test does not influence therapeutic outcome of triple therapy with amoxicillin and levofloxacin in patients never treated, while it is determinant for patients who were previously treated without success.     

用二次谐波成像技术研究经飞秒激光切削后角膜变化

本文用二次谐波成像技术（second harmonic generation SHG）来研究飞秒激光切削后角膜结构的变化.在生物学研究,材料科学等方面都有很广泛应用的SHG成像技术能在不破坏的角膜情况下获得高对比度的角膜层析图像,分辨率为500 nm,实验装置是利用现有的双光子显微镜.本文还根据成像结果评价了飞秒激光在角膜切削中的质量,为飞秒激光微米级的精确切削和临床应用提供了实验支持.     

Identification of causative pathogens in mouse eyes with bacterial keratitis by sequence analysis of 16S rDNA libraries

The clone library method using PCR amplification of the 16S ribosomal RNA (rRNA) gene was used to identify pathogens from corneal scrapings of C57BL/6-corneal opacity (B6-Co) mice with bacterial keratitis. All 10 samples from the eyes with bacterial keratitis showed positive PCR results. All 10 samples from the normal cornea showed negative PCR results. In all 10 PCR-positive samples, the predominant and second most predominant species accounted for 20.9 to 40.6% and 14.7 to 26.1%, respectively, of each clone library. The predominant species were Staphylococcus lentus, Pseudomonas aeruginosa, and Staphylococcus epidermidis. The microbiota analysis detected a diverse group of microbiota in the eyes of B6-Co mice with bacterial keratitis and showed that the causative pathogens could be determined based on percentages of bacterial species in the clone libraries. The bacterial species detected in this study were mostly in accordance with results of studies on clinical bacterial keratitis in human eyes. Based on the results of our previous studies and this study, the B6-Co mouse should be considered a favorable model for studying bacterial keratitis.     

Prolonged elevation of IL-1 in Pseudomonas aeruginosa ocular infection regulates macrophage-inflammatory protein-2 production, polymorphonuclear neutrophil persistence, and corneal perforation

The kinetics of IL-1 (alpha and beta) production after Pseudomonas aeruginosa corneal infection was examined in susceptible (cornea perforates) C57BL/6J (B6) and resistant (cornea heals) BALB/cByJ (BALB/c) mice. IL-1alpha and -1beta (mRNA and protein) were elevated in both mouse strains, and levels peaked at 1 day postinfection (p.i. ). Significantly greater amounts of IL-1 protein were detected in B6 vs BALB/c mice at 1 and 3 days p.i. At 5 days p.i., IL-1alpha and -1beta (mRNA and protein) remained elevated in B6, but began to decline in BALB/c mice. To test the significance of elevated IL-1 in B6 mice, a polyclonal neutralizing Ab against IL-1beta was used to treat infected B6 mice. A combination of subconjunctival and i.p. administration of IL-1beta polyclonal Ab significantly reduced corneal disease. The reduction in disease severity in infected B6 mice was accompanied by a reduction in corneal polymorphonuclear neutrophil number, bacterial load, and macrophage inflammatory protein-2 mRNA and protein levels. These data provide evidence that IL-1 is an important contributor to P. aeruginosa corneal infection. At least one mechanism by which prolonged and/or elevated IL-1 expression contributes to irreversible corneal tissue destruction appears to be by increasing macrophage inflammatory protein-2 production, resulting in a prolonged stimulation of polymorphonuclear neutrophil influx into cornea. In contrast, a timely down-regulation of IL-1 appears consistent with an inflammatory response that is sufficient to clear the bacterial infection with less corneal damage.     

Inhibition of Candida albicans virulence factors by novel levofloxacin derivatives

Candida albicans is an important opportunistic fungal pathogen, responsible for biofilm associated infections in immunocompromised patients. The aim of the present study was to investigate the antibiofilm properties of novel levofloxacin derivatives on C. albicans biofilms. The levofloxacin derivatives at their Biofilm Inhibitory Concentrations (BIC) were able to inhibit the biofilms of C. albicans, the yeast-to-hyphal transition and were also able to disrupt their mature biofilms. Furthermore, Real-time PCR analysis showed that the expression of ergosterol biosynthesis pathway gene (ERG11) and the efflux pump-encoding genes (CDR1 and MDR1) was decreased upon treatment with the levofloxacin derivatives. The total ergosterol content quantified using UV spectrophotomer showed decrease in ergosterol in the presence of levofloxacin derivatives. Overall, levofloxacin derivatives (6a, 6c and 7d) are capable of inhibiting C. albicans virulence factors. Therefore, these compounds with potential therapeutic implications can be used as new strategy to treat biofilm-related candidal infections.     

Review of the in vitro activity and potential clinical efficacy of levofloxacin in the treatment of anaerobic infections

The activity of levofloxacin against aerobic bacteria has been well documented both in vitro and clinically, but its anaerobic activity has been infrequently studied. This new fluoroquinolone exhibits good in vitro activity (MIC(S) < or =2.0 microg/mL) against many anaerobic pathogens associated with acute sinusitis, bite wounds, and other soft-tissue infections. It is less active against Bacteroides fragilis (MIC (90)=2-4 microg/mL ) and has poor inhibitory activity against non-fragilis B. fragilis group species that are associated with gastrointestinal and genitourinary tract infections. Levofloxacin does not antagonize the in vitro activity of clindamycin and metronidazole and often provides additive or synergistic activity against anaerobic bacteria with these agents. In pharmacodynamic models, levofloxacin exhibits rapid bactericidal activity at 2-4 times the MIC of anaerobic bacteria. Prolonged killing is observed when the area-under-the concentration-time-curve to MIC ratio is greater than 40. In clinical efficacy trials, levofloxacin has been effective in the treatment of patients with gynecologic, skin and skin-structure, and bone infections involving anaerobic pathogens. Both micro-biologic and pharmacodynamic studies support further evaluations of levofloxacin in the treatment of selective mixed aerobic/anaerobic infections.     

海口市流感嗜血杆菌流行病学及耐药性研究

目的:研究海口市呼吸系统疾病患儿流感嗜血杆菌流行病学及耐药性情况,为疾病的预防和治疗提供参考。方法:收集2006-2010年海口市各医院(海南医学院附属医院、海南省人民医院、海口市人民医院、海南省农垦总医院)临床送检的咽拭子、鼻咽分泌物、痰、脑脊液等标本486例,然后分离鉴定流感嗜血杆菌;采用Etest法测定对分离到的95株流感嗜血杆菌进行抗生素药敏试验检测。结果:流感嗜血杆菌总检出率19.55%,其检出情况在不同地区和不同民族之间存在差异,考虑其原因可能和社会经济条件有关,流感嗜血杆菌对常用抗生素的体外药敏结果依次为:左氧氟沙星、头孢曲松>阿莫西林/克拉维酸、阿奇霉素>氯霉素>头孢克洛>阿莫西林>氨苄西林>磺胺甲基异噁唑。结论:海口流感嗜血杆菌由于全年气温较高,其发病率无明显季节性,细菌检出率在不同地区及不同民族之间存在差别。对左氧氟沙星、头孢曲松、阿莫西林/克拉维酸、阿奇霉素、氯霉素的耐药率低,其可作为临床治疗流感嗜血杆菌感染的首选药物,而对氨苄西林和磺胺甲基异噁唑的耐药率较高,其作为临床治疗流感嗜血杆菌首选药物的传统地位受到了严重挑战。     

Levofloxacin- vs. ranitidine bismuth citrate-containing therapy after H. pylori treatment failure

AIM: Ranitidine bismuth citrate and levofloxacin-based regimen may be an alternative to quadruple therapy after Helicobacter pylori eradication failure. Our aim was to compare two 7-day triple second-line regimens containing ranitidine bismuth citrate or levofloxacin. METHODS: Patients in whom a first eradication trial with omeprazole-clarithromycin-amoxicillin had failed were randomized to receive 7-day treatment with: 1, ranitidine bismuth citrate (400 mg b.i.d.), tetracycline (500 mg q.i.d.), and metronidazole (250 mg q.i.d.), or 2, levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.), and omeprazole (20 mg b.i.d.). Cure rates were evaluated by (13)C-urea breath test. RESULTS: One-hundred patients were included: 50 received the ranitidine bismuth citrate regimen, and 50 the levofloxacin one. Groups were comparable in terms of demographic variables. Two percent of the patients (one in each group) did not return for follow up. Compliance was similar in both groups (90% took all the medications correctly). Side-effects (only mild/moderate) in the two groups were also comparable (38% with ranitidine bismuth citrate and 36% with levofloxacin). Per-protocol cure rates were 69% (95% CI = 54-80%) in the ranitidine bismuth citrate group, and 71% (57-82%) in the levofloxacin one. Intention-to-treat cure rates were, respectively, 68% (59-79%) and 68% (59-79%) (nonstatistically significant differences). CONCLUSIONS: Both 7-day ranitidine bismuth citrate- and levofloxacin-containing second-line regimens represent alternatives to quadruple therapy in patients with previous omeprazole-clarithromycin-amoxicillin failure.