Effect of proton pump inhibitors on in vitro activity of tigecycline against several common clinical pathogens.

In this study, we evaluated the effect of proton pump inhibitors (PPIs) on in vitro antimicrobial activity of tigecycline against several species of clinical pathogens. Clinical non-duplicate isolates of Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecalis and three species of Enterobacteriaceae (Escherichia coli, Klebsiella pneumonia and Enterobacter cloacae) were collected from a tertiary hospital and their MICs of tigecycline alone and in combination with PPIs (omeprazole, lansoprazole and pantoprazole) were determined. With one randomly selected isolate of each bacterial species, an in vitro time-kill study was performed for the confirmation of the effect of PPIs on tigecycline activity. The MIC changes after PPIs addition correlated with the PPIs concentrations in the test media. Compared with tigecycline alone, the addition of 5 mg/L PPIs could increase the MICs of tigecycline by 0 to 2-fold and the addition of 50 mg/L PPIs could increase the MICs of tigecycline by 4 to >128-fold. The time-kill study confirmed that the addition of PPIs could affect the in vitro activity of tigecycline. Even at low concentration (5 mg/L) of omeprazole and pantoprazole, antagonistic effect could be observed in E. cloacae and E. faecalis strains. We conclude that In vitro activity of tigecycline can be influenced by the presence of PPIs in a concentration-dependent manner

Prophylactic use of macrolide antibiotics for the prevention of chronic obstructive pulmonary disease exacerbation: a meta-analysis.

BACKGROUND:Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) can lead to high frequencies and rates of hospitalization and mortality. Macrolides are a class of antibiotics that possess both antimicrobial and anti-inflammatory properties. Since the occurrence of AECOPDs is associated with aggravation of airway inflammation and bacterial infections, prophylactic macrolide treatment may be an effective approach towards the prevention of AECOPDs. METHODS:We systemically searched the PubMed, Embase and Cochrane Library databases to identify randomized controlled trials (RCTs) that evaluated the effect of prophylactic macrolide therapy on the prevention of AECOPDs. The primary outcomes were the total number of patients with one or more exacerbations as well as the rate of exacerbations per patient per year. RESULTS:Nine RCTs comprising 1666 patients met the inclusion criteria. Pooled evidence showed macrolides could reduce the frequency of exacerbations in patients with COPD by both unweighted (RR = 0.70; 95% CI: 0.56-0.87; P < 0.01) and weighted approaches (RR = 0.58, 95% CI: 0.43-0.78, P < 0.01). Subgroup analysis showed only 6-12 months of erythromycin or azithromycin therapy could be effective. Moreover, among studies with 6-12 months of azithromycin therapy, both the daily dosing regimen and the intermittent regimen significantly reduced exacerbation rates. The overall number of hospitalizations and the all-cause rate of death were not significantly different between the treatment and control groups. A tendency for more adverse events was found in the treatment groups (OR = 1.55, 95%CI: 1.003-2.39, P = 0.049). CONCLUSIONS:Our results suggest 6-12 months erythromycin or azithromycin therapy could effectively reduce the frequency of exacerbations in patients with COPD. However, Long-term treatment may bring increased adverse events and the emergence of macrolide-resistance. A recommendation for the prophylactic use of macrolide therapy should weigh both the advantages and disadvantages

Efficacy of polymyxins in the treatment of carbapenem-resistant Enterobacteriaceae infections: a systematic review and meta-analysis

In recent years, carbapenem-resistant Enterobacteriaceae has become endemic in many countries. Because of limited treatment options, the abandoned “old antibiotics”, polymyxins, have been reintroduced to the clinic. To evaluate the clinical efficacy of polymyxins in the treatment of infections caused by carbapenem-resistant Enterobacteriaceae, we systemically searched the PubMed, Embase, and Cochrane Library databases and analyzed the available evidence. The Preferred Reporting Items for Systematic reviews and Meta-Analysis statement were followed, and the I2 method was used for heterogeneity. Nineteen controlled and six single-arm cohort studies comprising 1086 patients met the inclusion criteria. For controlled studies, no significant difference was noted for overall mortality (OR, 0.79; 95% CI, 0.58–1.08; p = 0.15), clinical response rate (OR, 1.24; 95% CI, 0.61–2.54; p = 0.55), or microbiological response rate (OR, 0.59; 95% CI, 0.26–1.36; p = 0.22) between polymyxin-treated groups and the control groups. Subgroup analyses showed that 28-day or 30-day mortality was lower in patients who received polymyxin combination therapy than in those who received monotherapy (OR, 0.36; 95% CI, 0.19–0.68; p < 0.01) and the control groups (OR, 0.49; 95% CI, 0.31–0.75; p < 0.01). The results of the six single-arm studies were in accordance with the findings of controlled studies. One controlled and two single-arm studies that evaluated the occurrence of nephrotoxicity reported a pooled incidence rate of 19.2%. Our results suggest that polymyxins may be as efficacious as other antimicrobial therapies for the treatment of carbapenem-resistant Enterobacteriaceae infection. Compared to polymyxin monotherapy, combination regimens may achieve lower 28-day or 30-day mortality. Future large-volume, well-designed randomized control trials are required to determine the role of polymyxins in treating carbapenem-resistant Enterobacteriaceae infections. Keywords: Polymyxin, Enterobacteriaceae, Carbapenem-resistant, Carbapenemase-producin

Multinucleated giant cells induced by a silk fibroin construct express proinflammatory agents: an immunohistological study

Multinucleated giant cells (MNGCs) are frequently observed in the implantation areas of different biomaterials. The main aim of the present study was to analyze the long-term polarization pattern of the pro- and anti-inflammatory phenotypes of macrophages and MNGCs for 180 days to better understand their role in the success or failure of biomaterials. For this purpose, silk fibroin (SF) was implanted in a subcutaneous implantation model of Wistar rats as a model for biomaterial-induced MNGCs. A sham operation was used as a control for physiological wound healing. The expression of different inflammatory markers (proinflammatory M1: CCR-7, iNos; anti-inflammatory M2: CD-206, CD-163) and tartrate-resistant acid phosphatase (TRAP) and CD-68 were identified using immunohistochemical staining. The results showed significantly higher numbers of macrophages and MNGCs within the implantation bed of SF-expressed M1 markers, compared to M2 markers. Interestingly, the expression of proinflammatory markers was sustained over the long observation period of 180 days. By contrast, the control group showed a peak of M1 macrophages only on day 3. Thereafter, the inflammatory pattern shifted to M2 macrophages. No MNGCs were observed in the control group. To the best of our knowledge, this is study is the first to outline the persistence of pro-inflammatory MNGCs within the implantation bed of SF and to describe their long-term kinetics over 180 days. Clinically, these results are highly relevant to understand the role of biomaterial-induced MNGCs in the long term. These findings suggest that tailored physicochemical properties may be a key to avoiding extensive inflammatory reactions and achieving clinical success. Therefore, further research is needed to elucidate the correlation between proinflammatory MNGCs and the physicochemical characteristics of the implanted biomaterial

Time–kill curves showing effects of proton pump inhibitors (PPIs) on the activity of tigecycline.

<p>MIC_T, MIC for tigecycline alone; MIC_L5 and MIC_L50, MIC for tigecycline in combination with 5 mg/L and 50 mg/L lansoprazole; MIC_A5 and MIC_A50, MIC for tigecycline in combination with 5 mg/L and 50 mg/L omeprazole; MIC_P5 and MIC_P50, MIC for tigecycline in combination with 5 mg/L and 50 mg/L pantoprazole. •, Control; ▴, 50 mg/L lansoprazole; ▾, 50 mg/L omeprazole; ▪, 50 mg/L pantoprazole; Δ, 5 mg/L lansoprazole; ▽, 5 mg/L omeprazole; □, 5 mg/L pantoprazole; ○, tigecycline alone. The <i>in vitro</i> time-kill experiments were duplicated; mean values are plotted. In all duplicate experiments, similar time-kill results were obtained.</p

Effect of the proton pump inhibitors (PPIs) lansoprazole, omeprazole and pantoprazole at three different concentrations on the MICs of tigecycline in clinical isolates of 6 species of pathogens.

a<p>The number of strains of each species tested in the study.</p><p>Increased MICs in >50% of isolates are indicated in boldface.</p

Forest plot of risk ratios for total number of patients with one or more exacerbations treated with macrolides compared with the control.

<p>Forest plot of risk ratios for total number of patients with one or more exacerbations treated with macrolides compared with the control.</p

Forest plot of risk ratios for exacerbations per patient per year treated with macrolides compared with the control.

<p>Forest plot of risk ratios for exacerbations per patient per year treated with macrolides compared with the control.</p

Forest plot of odds ratios for drug adverse effects in COPD patients treated with macrolides compared with the control.

<p>Forest plot of odds ratios for drug adverse effects in COPD patients treated with macrolides compared with the control.</p