Search

Background: Parabens are synthetic preservatives present in many consumer products. Their antimicrobial and endocrine-disrupting properties have raised concerns that they might play a role in respiratory and allergic diseases; however, studies exploring these associations are scarce., Objective: We examined the cross-sectional association between parabens and asthma morbidity among 450 children with asthma and with asthma prevalence among 4023 children in the US general population participating in the National Health and Nutrition Examination Survey (2005-2014)., Methods: We conducted multivariable logistic regression to examine associations between urinary paraben biomarker concentrations (butyl paraben, ethyl paraben, methyl paraben [MP], and propyl paraben [PP]) and asthma attacks and emergency department visits among children with asthma and with a current asthma diagnosis among all children. We also examined heterogeneity of associations by sex., Results: We observed an increased prevalence odds of reporting emergency department visits for every 10-fold increase in MP and PP concentrations among boys with asthma (adjusted prevalence odds ratio, 2.61 [95% CI, 1.40-4.85] and 2.18 [95% CI, 1.22-3.89, respectively; P interaction-MP  = .002 and P interaction-PP  = .003); associations remained after adjusting for other phenolic compounds previously linked to respiratory outcomes. No other dimorphic effects of exposure by sex were observed. Among children in the general population, no overall associations with current asthma were observed, although there was a positive trend with PP and a current asthma diagnosis., Conclusion: We identified differential effects of exposure to select parabens by sex on asthma morbidity. Further studies are needed to replicate these findings and elucidate mechanisms by which parabens could affect respiratory health and elicit dimorphic effects by sex., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Rifaximin has been proposed as an alternative treatment for specific cases of Clostridium difficile infection (CDI) and intestinal decontamination. Rifaximin-resistant C. difficile has occasionally been reported. Antibiotic susceptibility testing relies on anaerobic agar dilution (reference method), which is cumbersome and not routinely used. There is no commercial test for detection of resistance to rifaximin., Objectives: To assess resistance to rifaximin by C. difficile and to evaluate the correlation between the results of the rifampicin E-test and susceptibility to rifaximin., Methods: We compared the in vitro susceptibility of clinical CDI isolates to rifaximin over a 6-month period using the agar dilution method with susceptibility to rifampicin using the E-test. All isolates were characterized using PCR-ribotyping. Clinical data were recorded prospectively., Results: We recovered 276 consecutive C. difficile isolates and found that 32.2% of episodes were caused by rifaximin-resistant strains. The MICs for rifaximin ranged from <0.0009-256 mg/L, with a geometric mean (GM) of 0.256 mg/L, an MIC 50/90 of 0.015/>256 mg/L. Rifaximin and rifampicin MICs were comparable, and all strains classed as resistant by agar dilution were correctly classified as resistant by E-test. The most common ribotypes were 001 (37.2%), 078/126 (14.3%), and 014 (12.0%). Ribotype 001 exhibited the highest MICs for rifaximin., Conclusions: Resistance to rifaximin was common; resistance rates were higher in ribotype 001 strains. Susceptibility to rifaximin determined by agar dilution correlated with susceptibility to rifampicin determined using the E-test, including rifaximin-resistant strains. Our results suggest that the rifampicin E-test is a valid method for the prediction of rifaximin-resistant C. difficile., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: Clostridium difficile infection (CDI) is the leading cause of hospital-acquired diarrhoea in developed countries. Metronidazole and vancomycin are the mainstay of treatment, although they are associated with treatment failure and recurrence. Novel agents have emerged to address these shortcomings. We investigated the in vitro activity of a novel agent, surotomycin (formerly CB-183,315), and seven other antimicrobial agents against clinical C. difficile isolates., Methods: Antimicrobial susceptibility to surotomycin, fidaxomicin, metronidazole, vancomycin, clindamycin, rifaximin, moxifloxacin and tigecycline was determined for 100 contemporary clinical isolates of C. difficile collected in 2013. MICs were determined by agar dilution according to CLSI procedures. In addition, 10 strains with reduced susceptibility to metronidazole (n = 6) and vancomycin (n = 4) were also tested. Strains were PCR ribotyped., Results: The MICs of surotomycin for the 100 isolates ranged from ≤0.06 to 2 mg/L, with a geometric mean (GM) of 0.31 mg/L and an MIC50/90 of 0.25/0.5 mg/L. The MIC range of surotomycin was 0.25-1 mg/L (GM = 0.45 mg/L) for isolates with reduced metronidazole susceptibility and 0.125-0.5 mg/L (GM = 0.25 mg/L) for isolates with reduced vancomycin susceptibility. The three most common ribotypes were 001 (31.0%), 014/020 (17.0%) and 078/126 (17.0%). Ribotype 014/020 exhibited the lowest MICs of surotomycin (GM = 0.22 mg/L); the highest MICs were for ribotype 078/126 (GM = 0.72 mg/L)., Conclusions: Surotomycin exhibited potent in vitro activity against all the isolates tested, including those with elevated metronidazole and vancomycin MICs. The potential role of this agent in the treatment of CDI requires further clinical evaluation., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

At our institution, the prevalence of clinical isolates of Clostridium difficile with resistance to metronidazole is 6.3%. We observed that initial metronidazole MICs of 16 to 64 mg/liter against toxigenic, primary fresh C. difficile isolates, as determined by agar dilution, decreased to 0.125 mg/liter after the isolates were thawed. In this study, we examined the possibility of heterogeneous or inducible resistance. Totals of 14 metronidazole-resistant and 10 metronidazole-susceptible clinical isolates of toxigenic C. difficile were studied. The isolates were investigated for the presence of nim genes by PCR. After the isolates were thawed, susceptibility testing was done by agar dilution, by disc diffusion using a 5-mug metronidazole disc, and by the Etest method. An experiment for determining the effect of prolonged exposure to metronidazole was applied to all resistant isolates and to susceptible control strains. None of the isolates presented the nim genes. All initially metronidazole-resistant C. difficile isolates became susceptible after thawing; however, they presented slow-growing subpopulations within the inhibition zones of both the disk and the Etest strip. All metronidazole-susceptible isolates remained homogeneously susceptible by both methods. After prolonged exposure in vitro to metronidazole, no zone of inhibition was found around the 5-microg disk in any of the metronidazole-resistant isolates, and the MICs as determined by the Etest method ranged from 0.125 to >256 mg/liter, with colonies growing inside the inhibition zone. Our results indicate that (i) resistance to metronidazole was not due to the presence of nim genes, (ii) resistance to metronidazole in toxigenic C. difficile isolates is heterogeneous, and (iii) prolonged exposure to metronidazole can select for in vitro resistance. We recommend routine performance of the disk diffusion method (5-microg metronidazole disk) with primary fresh C. difficile isolates in order to ensure that metronidazole-heteroresistant populations do not go undetected.

We evaluated the in vitro activities of ofloxacin, levofloxacin, grepafloxacin, trovafloxacin and ciprofloxacin against Clostridium difficile. The MIC(90) was 128 mg/L for ofloxacin and levofloxacin, 64 mg/L for ciprofloxacin, 16 mg/L for grepafloxacin and 8 mg/L for trovafloxacin. Thirty per cent of isolates were resistant to trovafloxacin, and rates of resistance to ofloxacin, levofloxacin, grepafloxacin and ciprofloxacin were considerably higher. None of the antimicrobials studied would be a reliable therapeutic option against C. difficile. Whether some of the new fluoroquinolones can induce C. difficile-associated diarrhoea remains to be answered.

Two hundred fifty isolates of Mycobacterium tuberculosis were evaluated for susceptibility to ciprofloxacin, ofloxacin, levofloxacin, grepafloxacin, trovafloxacin, and gemifloxacin (SB-265805). Levofloxacin, ciprofloxacin, and grepafloxacin showed the greatest activity (MIC for 90% of strains tested [MIC(90)] 1 microg/ml), although ofloxacin also showed good activity, with an MIC(90) of 2 microg/ml. Trovafloxacin and gemifloxacin showed lower in vitro activity, with MIC(90)s of 64 and 8 microg/ml, respectively.

The novel 8-methoxyquinolone, moxifloxacin (Bay 12-8039), was compared with ciprofloxacin and eight other antimicrobials for activity against 425 strains Gram-positive clinical isolates, including 73 methicillin-resistant staphylococci, 35 vancomycin-resistant enterococci, and 80 penicillin- or eythromycin-resistant streptococci. Overall, 82% of the strains were inhibited at < or = 2 micrograms/mL. Moxifloxacin was more active than ciprofloxacin against staphylococci (8- to 32-fold), enterococci (0- to 16-fold), pneumococci (16-fold) and other streptococci (4- to 16-fold) when MIC90 results were compared. Moxifloxacin demonstrated good activity against all Gram-positive isolates tested except for ciprofloxacin-resistant enterococci (MIC90, 32 micrograms/mL) and methicillin-resistant staphylococci (MIC90, 8 micrograms/mL). Clinical trials should be initiated to define the role of this new quinolone.