The effects of inulin on gut microbial composition: a systematic review of evidence from human studies.

BACKGROUND: Inulin, consisting of repetitive fructosyl units linked by ß(2,1) bonds, is a readily fermentable fiber by intestinal bacteria that generates large quantities of short-chain fatty acids (SCFA). In individuals with constipation, it was reported that inulin ingestion was associated with a significant increase in stool frequency, suggesting a potential impact of inulin on human gut microbiota composition. Progress in high-throughput technologies allow assessment of human-associated microbiomes in terms of diversity and taxonomic or functional composition, and can identify changes in response to a specific supplementation. Hence, to understand the effects of inulin on the human gut microbiome is pivotal to gain insight into their mechanisms of action. METHODS: Here, we conducted a systematic review of human studies in adult individuals showing the effects of inulin on the gut microbiome. We searched in MEDLINE, EMBASE, Web of Science, and Scopus databases for articles in English published in peer-reviewed journals and indexed up until March 2019. We used multiple search terms capturing gut microbiome, gut microflora, intestinal microbiota, intestinal flora, gut microbiota, gut flora, microbial gut community, gut microbial composition, and inulin. RESULTS: Overall, nine original articles reported the effects of inulin on microbiome composition in adult humans, most of them being randomized, double-blind, placebo-controlled trials (n = 7). Studies varied significantly in design (3 studies associated inulin and oligofructose), supplementation protocols (from 5 to 20 gr per day of inulin consumed) and in microbiome assessment methods (16S sequencing, n = 7). The most consistent change was an increase in Bifidobacterium. Other concordant results included an increase in relative abundance of Anaerostipes, Faecalibacterium, and Lactobacillus, and a decrease in relative abundance of Bacteroides after inulin supplementation. CONCLUSIONS: Our systematic review assessed the evidence for the effects of inulin supplementation on the human gut microbiome. However, these in vivo studies did not confirm in vitro experiments as the taxonomic alterations were not associated with increase in short-chain fatty acids levels.

Trends and prediction of antimicrobial susceptibility in urinary bacteria isolated in European emergency departments: the EuroUTI 2010-2016 Study.

OBJECTIVES: To assess recent trends in susceptibility to antibiotics among urinary isolates isolated in European emergency departments (EDs) and to identify isolates with a high (90% or more) predicted probability of susceptibility to fluoroquinolones or third-generation cephalosporins (3GCs). METHODS: In this cross-sectional study, we included urine cultures obtained from adult patients between 2010 and 2016 in 24 European EDs. Temporal trends were assessed using time-series analysis and multivariate logistic models. Multivariate logistic models were also used to predict susceptibility to fluoroquinolones or 3GCs from patient age and sex, year, month and ED. RESULTS: We included 88242 isolates. Time-series analysis found a significant increase in susceptibility to fluoroquinolones and no significant trend for susceptibility to 3GCs. Adjusting for patient age and sex, ED and organism, multivariate models showed that susceptibility to 3GCs decreased from 2014 to 2016, while susceptibility to fluoroquinolones increased in 2015 and 2016. Among isolates from 2016, multivariate models predicted high probability of susceptibility to fluoroquinolones in 11% of isolates (positive predictive value 91%) and a high probability of susceptibility to 3GCs in 35% of isolates (positive predictive value 94%). CONCLUSIONS: Susceptibility of ED urinary isolates to fluoroquinolones increased from 2014, while susceptibility to 3GCs decreased from 2015. Predictive models identified isolates with a high probability of susceptibility to fluoroquinolones or 3GCs. The ability of such models to guide the empirical treatment of pyelonephritis in the ED remains to be determined.

Is There an Association Between Use of Amoxicillin-Clavulanate and Resistance to Third-Generation Cephalosporins in Klebsiella pneumoniae and Escherichia coli at the Hospital Level?

AIMS: Amoxicillin-clavulanate is extensively used in European hospitals. Whether the hospital use of amoxicillin-clavulanate is associated with nonsusceptibility to third-generation cephalosporins (3GC) in Klebsiella pneumoniae is unknown. Our aim was to assess the relationship between the hospital use of amoxicillin-clavulanate and 3GC nonsusceptibility in K. pneumoniae and Escherichia coli. METHODS: Yearly data of antibiotic use and 3GC nonsusceptibility in K. pneumoniae and E. coli were obtained from 33 French hospitals between 2011 and 2016. Decreased susceptibility to 3GC and Extended-Spectrum Beta-Lactamase (ESBL) production were modelled from antibiotic use with linear mixed models on years 2011 to 2015, and validated on year 2016. RESULTS: Nonsusceptibility to 3GC increased in K. pneumoniae and E. coli. In a multivariable model that included year and use of 3GC and fluoroquinolones as explanatory variables, amoxicillin-clavulanate use was protective against 3GC nonsusceptibility in K. pneumoniae (incidence rate ratio [IRR], 0.992 [0.988-0.997]), and with ESBL production in K. pneumoniae (IRR, 0.989 [0.985-0.992]). The correlation coefficient between observed and predicted numbers of 3GC-nonsusceptible K. pneumoniae in 2016 was 0.95 (95% confidence interval, 0.89-0.98). There was no significant association between amoxicillin-clavulanate use and 3GC nonsusceptibility in E. coli. CONCLUSION: Amoxicillin-clavulanate hospital use was protective against nonsusceptibility to 3GC in K. pneumoniae. Conversely, it was not associated with susceptibility to 3GC in E. coli. To decrease the hospital use of 3GC and fluoroquinolones, and 3GC nonsusceptibility in K. pneumoniae, it may be acceptable to increase the hospital use of amoxicillin-clavulanate. Interventional studies are necessary to confirm this hypothesis.

Rapid detection of amoxicillin-susceptible Escherichia coli in fresh uncultured urine: a new tool to limit the use of broad-spectrum empirical therapy of community-acquired pyelonephritis.

Because of the high prevalence of amoxicillin resistance among uropathogens, amoxicillin is not recommended as an empirical treatment of urinary tract infections (UTIs). Quick detection of an amoxicillin-susceptible Escherichia coli (ASEC) would allow prescribing amoxicillin without preliminary broad-spectrum empirical treatment in uncomplicated pyelonephritis. To quickly diagnose UTIs due to ASEC, we developed a real-time PCR that detects in fresh uncultured urine the E. coli-specific gene yccT as well as the blaTEM and blaCTX-M genes. The ASEC rapid test was considered positive if the PCR was positive for the yccT gene but negative for blaTEM and blaCTX-M. The test was compared with culture and susceptibility testing. Among 200 patients with a suspected community-acquired UTI, 61 (30.5%) had a monobacterial UTI due to ASEC. The ASEC rapid test result was obtained in 3 h 13 [95% confidence interval (CI) 3 h 12-3 h 15] and was positive for 43 patients (21.5%). Specificity and sensitivity were 97.8% (95% CI 95.8-99.8%) and 65.6% (95% CI 59.0-72.1%), respectively. Positive and negative predictive values were 93.0% (95% CI 89.5-96.5%) and 86.6% (95% CI 81.9-91.3%), respectively. Owing to its high specificity and positive predictive value, the ASEC rapid test allows the diagnosis of UTI due to ASEC only 3 h after urine sampling. A positive ASEC rapid test may be used to treat uncomplicated pyelonephritis with amoxicillin from the start, without preliminary broad-spectrum empirical treatment. The ASEC rapid test is a promising tool to spare fluoroquinolones and third-generation cephalosporins in UTIs.

In vivo activity of a novel anti-methicillin-resistant Staphylococcus aureus cephalosporin, ceftaroline, against vancomycin-susceptible and -resistant Enterococcus faecalis strains in a rabbit endocarditis model: a comparative study with linezolid and vancomycin.

We assessed the in vitro and in vivo efficacy of the novel parenteral broad-spectrum cephalosporin ceftaroline against Enterococcus faecalis in time-kill experiments and in a rabbit endocarditis model with simulated human dosing. Ceftaroline was more active than either vancomycin or linezolid against vancomycin-sensitive and -resistant isolates of E. faecalis.

Activity of glycopeptides against Staphylococcus aureus infection in a rabbit endocarditis model: MICs do not predict in vivo efficacy.

The in vivo efficacy of vancomycin and teicoplanin against five Staphylococcus aureus strains with different susceptibilities to them and methicillin was studied. Rabbits were allocated at random to groups for endocarditis induction with one of these five strains and then treated for 2 days with vancomycin or teicoplanin. Each treated group was compared with a control group infected with the same strain. Vancomycin and teicoplanin showed similar activities. Low MICs did not predict better in vivo results.

In vivo efficacy of linezolid in combination with gentamicin for the treatment of experimental endocarditis due to methicillin-resistant Staphylococcus aureus.

Indifference or even antagonism has mainly been reported with combinations including linezolid. The presence of in vitro antagonism is not always correlated with in vivo failure. The purpose of this study was to evaluate the in vivo activity of linezolid combined with gentamicin using a methicillin-resistant Staphylococcus aureus (MRSA) endocarditis experimental model. A human-like pharmacokinetic simulation was used for linezolid and gentamicin to improve the extrapolation of the results to human therapy. Contrary to the antagonism previously described in vitro, linezolid combined with gentamicin exhibited bactericidal activity on the two strains with a decrease of at least 4 log(10)cfu/g of vegetation compared with controls. These data suggest that linezolid plus gentamicin could be an appropriate combination for the treatment of severe MRSA infections.

Combination of quinupristin-dalfopristin and gentamicin against methicillin-resistant Staphylococcus aureus: experimental rabbit endocarditis study.

The combination of quinupristin-dalfopristin (Q-D) and gentamicin was tested against two strains of gentamicin- and dalfopristin-susceptible methicillin-resistant Staphylococcus aureus (MRSA). One strain was susceptible to macrolides, lincosamides, and streptogramin B type antibiotics (MLS(B)), and the other was constitutively resistant to these antibiotics by virtue of the ermA gene. The checkerboard method and time-kill curves showed that the combination of Q-D and gentamicin was indifferent. A rabbit endocarditis model simulated the pharmacokinetics achieved in humans receiving intravenous injections of Q-D (7.5 mg/kg of body weight three times a day) and gentamicin (3 mg/kg once daily). For the MLS(B)-susceptible strain, a 4-day regimen reduced mean bacterial titers (MBT) in vegetations from 8.5 +/- 0.8 log CFU/g (control group) to 4.1 +/- 2.6 (gentamicin), 3.0 +/- 0.9 (Q-D), and 2.6 +/- 0.5 log CFU/g (Q-D plus gentamicin). For the strain constitutively resistant to MLS(B), a 4-day regimen reduced MBT in vegetations from 8.7 +/- 0.9 log CFU/g (control group) to 5.0 +/- 2.2 (gentamicin), 5.2 +/- 2.2 (Q-D), and 5.1 +/- 2.4 log CFU/g (Q-D plus gentamicin). The differences between control and treatment groups were significant for both strains (P < 0.0001), although there was no significant difference between treatment groups. No resistant variant was isolated from vegetations, and no significant difference in MBT in vegetations of treatment groups after 1-day regimens was observed. This experimental study found no additive benefit in combining Q-D and gentamicin against dalfopristin- and gentamicin-susceptible MRSA.