- Clinical characteristics of anorectal Mycoplasma genitalium infection and microbial cure in men who have sex with men. [Journal Article]
- STSex Transm Dis 2018 Jan 18
- CONCLUSIONS: MG was almost as common as chlamydia in men presenting to a sexual health centre with symptoms of proctitis. Men with anorectal MG monoinfection were less likely to have symptoms and signs compared to those with chlamydia or gonococcus monoinfection. Cure for men with symptomatic anorectal MG by azithromycin was low. We suggest routine testing for MG in cases of proctitis, with test of cure following treatment being essential.
- Prophylactic Antibiotic Use in COPD and the Potential Anti-Inflammatory Activities of Antibiotics. [Review]
- RCRespir Care 2018 Feb 20
- Antibiotics have previously demonstrated anti-inflammatory properties, and they have been linked to therapeutic benefit in several pulmonary conditions that feature inflammation. Previous research su...
Antibiotics have previously demonstrated anti-inflammatory properties, and they have been linked to therapeutic benefit in several pulmonary conditions that feature inflammation. Previous research suggests that these anti-inflammatory properties may be beneficial in the treatment of COPD. This review assesses the potential benefit of prophylactic, long-term, and low-dose antibiotic therapy in COPD, and whether any effects seen are anti-inflammatory in nature. Randomized, controlled trials comparing antibiotic therapy with placebo in subjects with stable COPD were evaluated. Twelve trials involving 3,784 participants and a range of antibiotics were included: azithromycin (6 studies, 1,972 participants), clarithromycin (1 study, 67 participants), erythromycin (3 studies, 254 participants), roxithromycin (1 study, 191 participants), and moxifloxacin (2 studies, 1,198 participants). In vitro, in vivo, and ex vivo experimental study designs exploring the mechanisms via which antibiotics may act in subjects with stable COPD were evaluated. Azithromycin and erythromycin showed the greatest effect in subjects with COPD, with evidence suggesting improvement in exacerbation-related outcomes and health status, as measured by the St George Respiratory Questionnaire. An increase in antibiotic resistance was reported in 2 studies. The macrolide class of antibiotics exhibited convincing anti-inflammatory properties with relevance to COPD, implicating several pathways as potential mechanisms of action. In conclusion, the therapeutic benefit of macrolide antibiotics in subjects with stable COPD is consistent with anti-inflammatory properties, and macrolides should be considered as a potential therapy in COPD. Safety concerns regarding antibiotic resistance need to be addressed before widespread use in clinical practice.
- Elevated Plasma Moxifloxacin Concentrations andSLCO1B1g.-11187G>A Polymorphism in Adults with Pulmonary Tuberculosis. [Journal Article]
- AAAntimicrob Agents Chemother 2018 Feb 20
- Moxifloxacin exhibits concentration-dependent prolongation of human QTc intervals and bactericidal activity againstMycobacterium tuberculosisHowever, moxifloxacin plasma concentrations are variable b...
Moxifloxacin exhibits concentration-dependent prolongation of human QTc intervals and bactericidal activity againstMycobacterium tuberculosisHowever, moxifloxacin plasma concentrations are variable between patients. We evaluated whether human gene polymorphisms affect moxifloxacin plasma concentrations in tuberculosis patients from two geographic regions. We enrolled a convenience sample of 49 adults with drug-sensitive pulmonary tuberculosis from Africa and the United State s enrolled in two treatment trials of moxifloxacin as part of multidrug therapy. Pharmacokinetic parameters were evaluated by noncompartmental techniques. Human single-nucleotide polymorphisms of transporter genes were evaluated with analysis of covariance on moxifloxacin exposure and peak concentration (Cmax). Moxifloxacin area under the concentration-time curve from 0 to 24 h (AUC0-24) and Cmaxwere significantly increased by drug mg/kg dosage and genotype of variant g.-11187G>A in theSLCO1B1gene (rs4149015), but not by geographic region. Median moxifloxacin AUC0-24was 46% higher and Cmax30% higher in 4 (8% of) participants who had theSLCO1B1g.-11187 AG genotype compared with 45 participants who had the wild type GG genotype (median from model, AUC0-2434.4 vs. 23.6 μg*h/mL,P=.005; Cmax3.5 vs. 2.7 μg/mL,P=.009, ANCOVA). Because moxifloxacin exhibits concentration-dependent prolongation of human QTc intervals, and prolonged QTc intervals are associated with cardiac arrhythmia, further study is needed to evaluate risk associated with theSLCO1B1g.-11187G>A variant.
- Comparative activity of antimicrobials againstPseudomonas aeruginosa,Achromobacter xylosoxidansandStenotrophomonas maltophiliakeratitis isolates. [Journal Article]
- BJBr J Ophthalmol 2018 Feb 19
- CONCLUSIONS: There is a significant difference in susceptibility patterns betweenA. xylosoxidans,S. maltophiliaandP. aeruginosa. Fluoroquinolones and aminoglycosides may not be effective againstA. xylosoxidansandS. maltophilia. Antibiotics that are not commercially available as eye drops, such as beta-lactams forA. xylosoxidans, and trimethoprim/sulfamethoxazole and minocycline for bothA. xylosoxidansandS. maltophiliashould be considered.
- In vitro activity of various antibiotics against clinical strains of Legionella species isolated in Japan. [Journal Article]
- JIJ Infect Chemother 2018 Feb 17
- The activities of various antibiotics against 58 clinical isolates of Legionella species were evaluated using two methods, extracellular activity (minimum inhibitory concentration [MIC]) and intracel...
The activities of various antibiotics against 58 clinical isolates of Legionella species were evaluated using two methods, extracellular activity (minimum inhibitory concentration [MIC]) and intracellular activity. Susceptibility testing was performed using BSYEα agar. The minimum extracellular concentration inhibiting intracellular multiplication (MIEC) was determined using a human monocyte-derived cell line, THP-1. The most potent drugs in terms of MICs against clinical isolates were levofloxacin, garenoxacin, and rifampicin with MIC90values of 0.015 μg/ml. The activities of ciprofloxacin, pazufloxacin, moxifloxacin, clarithromycin, and azithromycin were slightly higher than those of levofloxacin, garenoxacin, and rifampicin with an MIC90of 0.03-0.06 μg/ml. Minocycline showed the highest activity, with an MIC90of 1 μg/ml. No resistance against the antibiotics tested was detected. No difference was detected in the MIC distributions of the antibiotics tested between L. pneumophila serogroup 1 and L. pneumophila non-serogroup 1. The MIECs of ciprofloxacin, pazufloxacin, levofloxacin, moxifloxacin, garenoxacin, clarithromycin, and azithromycin were almost the same as their MICs, with MIEC90values of 0.015-0.06 μg/ml, although the MIEC of minocycline was relatively lower and that of rifampicin was higher than their respective MICs. No difference was detected in the MIEC distributions of the antibiotics tested between L. pneumophila serogroup 1 and L. pneumophila non-serogroup 1. The ratios of MIEC:MIC for rifampicin (8) and pazufloxacin (2) were higher than those for levofloxacin (1), ciprofloxacin (1), moxifloxacin (1), garenoxacin (1), clarithromycin (1), and azithromycin (1). Our study showed that quinolones and macrolides had potent antimicrobial activity against both extracellular and intracellular Legionella species. The present data suggested the possible efficacy of these drugs in treatment of Legionella infections.
- Antimicrobial activity against Mycobacterium tuberculosis under in vitro lipid-rich dormancy conditions. [Journal Article]
- JMJ Med Microbiol 2018 Jan 15
- Although tuberculosis treatment is dependent on drug-susceptibility testing (DST) and molecular drug-resistance detection, treatment failure and relapse remain a challenge. This could be partially du...
Although tuberculosis treatment is dependent on drug-susceptibility testing (DST) and molecular drug-resistance detection, treatment failure and relapse remain a challenge. This could be partially due to the emergence of antibiotic-tolerant dormant mycobacteria, where host lipids have been shown to play an important role. This study evaluated the susceptibility of Mycobacterium tuberculosis to two antibiotic combinations - rifampicin, moxifloxacin, amikacin and metronidazole (RIF-MXF-AMK-MTZ), and rifampicin, moxifloxacin, amikacin and pretomanid (RIF-MXF-AMK-PA) - in a lipid-rich dormancy model. Although their effectiveness in in vitro cultures with dextrose as a carbon source has been proved, we observed that none of the antibiotic mixtures were bactericidal in the presence of lipids. The presence of lipids may confer tolerance to M. tuberculosis against the mixture of antibiotics tested and such tolerance could be even higher during the dormant stages. The implementation of lipids in DST on clinical isolates could potentially lead to a better treatment strategy.
- PCR ribotyping and antimicrobial susceptibility testing of isolates of Clostridium difficile cultured from toxin-positive diarrheal stools of patients receiving medical care in Canadian hospitals: the Canadian Clostridium difficile Surveillance Study (CAN-DIFF) 2013-2015. [Journal Article]
- DMDiagn Microbiol Infect Dis 2018 Jan 31
- Clostridium difficile toxin-positive diarrheal stool specimens submitted to eight Canadian hospital laboratories from 2013 to 2015 were cultured. Polymerase chain reaction ribotyping of isolates was ...
Clostridium difficile toxin-positive diarrheal stool specimens submitted to eight Canadian hospital laboratories from 2013 to 2015 were cultured. Polymerase chain reaction ribotyping of isolates was performed using an internationally standardized, high-resolution capillary gel-based electrophoresis protocol and antimicrobial susceptibility testing conducted by CLSI-defined agar dilution (M11-A8, 2012). Among the 1310 isolates of C. difficile cultured, 141 different ribotypes were identified; the most common ribotypes were 027 (24.5% of isolates), 014 (7.7%), 020 (6.6%), 106 (6.1%), and 002 (4.6%). Ribotype 027 was the commonest ribotype in all geographic regions of Canada and was more frequently isolated from patients aged ≥80 years (40.6%) than younger patients (P<0.00001). Ribotype 027 isolates were frequently moxifloxacin-resistant (92.2% of isolates) and multidrug-resistant (49.5%). Fidaxomicin demonstrated the greatest in vitro potency (lowest MIC90, 0.5 μg/mL; lowest maximum MIC, 2 μg/mL) of eight antimicrobial agents tested and was the most active agent against each of the five commonest ribotypes (MIC90, 0.25-1 μg/mL).
- Improving sustained drug delivery from ophthalmic lens materials through the control of temperature and time of loading. [Journal Article]
- EJEur J Pharm Sci 2018 Feb 14; 117:107-117
- Although the possibility of using drug-loaded ophthalmic lens to promote sustained drug release has been thoroughly pursued, there are still problems to be solved associated to the different alternat...
Although the possibility of using drug-loaded ophthalmic lens to promote sustained drug release has been thoroughly pursued, there are still problems to be solved associated to the different alternatives. In this work, we went back to the traditional method of drug loading by soaking in the drug solution and tried to optimize the release profiles by changing the temperature and the time of loading. Two materials commercially available under the names of CI26Y and Definitive 50 were chosen. CI26Y is used for intraocular lenses (IOLs) and Definitive 50 for soft contact lenses (SCLs). Three drugs were tested: an antibiotic, moxifloxacin, and two anti-inflammatories, diclofenac and ketorolac. Sustained drug release from CI26Y disks for, at least 15 days, was obtained for moxifloxacin and diclofenac increasing the loading temperature up to 60 °C or extending the loading time till two months. The sustained release of ketorolac was limited to about 8 days. In contrast, drug release from Definitive 50 disks could not be improved by changing the loading conditions. An attempt to interpret the impact of the loading conditions on the drug release behavior was done using solid-state NMR and differential scanning calorimetry. These studies suggested the establishment of reversible, endothermic interactions between CI26Y and the drugs, moxifloxacin and diclofenac. The loading temperature had a slight effect on the mechanical and optical properties of drug loaded CI26Y samples, which still kept adequate properties to be used as IOL materials. The in vivo efficacy of CI26Y samples, drug loaded at 60 °C for two weeks, was predicted using a simplified mathematical model to estimate the drug concentration in the aqueous humor. The estimated concentrations were found to comply with the therapeutic needs, at least, for moxifloxacin and diclofenac.
- In vitro activity of zoliflodacin (ETX0914) against macrolide-resistant, fluoroquinolone-resistant and antimicrobial-susceptible Mycoplasma genitalium strains. [Journal Article]
- JAJ Antimicrob Chemother 2018 Feb 12
- CONCLUSIONS: Zoliflodacin is a promising candidate for the treatment of M. genitalium and it is important to further develop and evaluate this drug.
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- In vitro activity of lascufloxacin againstStreptococcus pneumoniaewith mutations in the quinolone resistance-determining regions (QRDRs). [Journal Article]
- AAAntimicrob Agents Chemother 2018 Feb 12
- Lascufloxacin showed potent activity againstStreptococcus pneumoniaewith GyrA or ParC mutation (first-step mutants). The frequency of selecting resistant strains tended to be lower for lascufloxacin ...
Lascufloxacin showed potent activity againstStreptococcus pneumoniaewith GyrA or ParC mutation (first-step mutants). The frequency of selecting resistant strains tended to be lower for lascufloxacin than levofloxacin and garenoxacin after drug exposure in first-step mutants, but was similar in the comparison between lascufloxacin and moxifloxacin. The increase in MIC was smaller for lascufloxacin than for levofloxacin, garenoxacin, and moxifloxacin when clinical strains with only ParC mutation were exposed to the corresponding drug.