Intestinal Dysbiosis Secondary to Proton-Pump Inhibitor Use.

BACKGROUND: Gut dysbiosis associated with the use of proton-pump inhibitors (PPIs) has been found to lead to the occurrence of infectious and inflammatory adverse events. A longitudinal observational cohort study has demonstrated the heightened risk of death associated with PPI use. SUMMARY: We evaluated meta-analyses to determine the association between PPI use and infectious and inflammatory diseases. Meta-analyses showed that PPI use is a potential risk for the development of enteric infections caused by Clostridium difficile, as well as small intestinal bacterial overgrowth, spontaneous bacterial peritonitis, community-acquired pneumonia, hepatic encephalopathy, and adverse outcomes in inflammatory bowel disease. We also examined changes in the composition and function of the gut microbiota with the use of PPIs. PPI use significantly increased the presence of Streptococcaceae and Enterococcaceae, which are risk factors for C. difficile infection, and decreased that of Faecalibacterium, a commensal anti-inflammatory microorganism. Key Message: High-throughput, microbial 16S rRNA gene sequencing has allowed us to investigate the association between the gut microbiome and PPI use. Future prospective comparison studies are necessary to confirm this association, and to develop new strategies to prevent complications of PPI use.

Partial rpoB Gene Sequencing Identification and Probiotic Potential of Floricoccus penangensis ML061-4 Isolated from Assam Tea (Camellia sinensis var. assamica).

Assam tea or Miang is a local name of Camellia sinensis var. assamica in northern Thailand. By the local wisdom, Assam tea leaves are used as the raw material in tea fermentation to produce "Fermented Miang" consumed by people in northern Thailand and the countries nearby. In this study, twenty-eight bacterial isolates were obtained from Assam tea leaf samples collected from Nan province, Thailand. Bacterial isolates were identified within 6 genera including Bacillus, Floricoccus, Kocuria, Lysinibacillus, Micrococcus and Staphylococcus. Among these, the strain ML061-4 shared 100.0 and 99.4% similarity of 16S rRNA and rpoB gene sequence with F. penangensis JCM 31735T, respectively. This is the first discovery of F. penangensis in Thailand. F. penangensis ML061-4 exhibited probiotic characteristics including lactic acid production (9.19 ± 0.10 mg/ml), antibacterial activities (Escherichia coli ATCC 25922 and E. coli O157:H7 DMST 12743), acid and bile salt tolerance (71.1 and 54.9%, respectively), autoaggregation (97.0%), coaggregation (66.0% with E. coli O157:H7), cell surface hydrophobicity (90.0%), bacterial adhesion (82.9% with Lactobacillus plantarum FM03-1), competitive inhibition (17.8% with E. coli O157:H7) and competitive exclusion (34.9% with E. coli O157:H7). Overall, the data suggested that F. penangensis ML061-4 had a great potential to be a probiotic.

Comparative bactericidal activities of daptomycin, glycopeptides, linezolid and tigecycline against blood isolates of Gram-positive bacteria in Taiwan.

In-vitro MICs and minimum bactericidal concentrations (MBCs) of daptomycin, linezolid, tigecycline, vancomycin and teicoplanin against Gram-positive bacteria were determined using the broth microdilution method for ten blood isolates each of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), including two vancomycin-intermediate S. aureus (VISA), vancomycin-resistant Enterococcus faecium and Enterococcus faecalis. One strain of VISA was tested in a time-kill synergism assay of daptomycin combined with oxacillin, imipenem, rifampicin and isepamicin. Daptomycin showed excellent in-vitro bactericidal activity against all the isolates tested, with no tolerance or synergism effects when combined with other agents, except with rifampicin against VISA. Vancomycin had better bactericidal activity against MRSA and MSSA than did teicoplanin. Linezolid had the poorest bactericidal activity against the isolates tested, with 100% tolerance by the MSSA and VRE isolates, and 80% tolerance by the MRSA isolates. Tolerance towards tigecycline was exhibited by 40% of the MRSA isolates, 100% of the MSSA and vancomycin-resistant E. faecalis isolates, and 90% of the vancomycin-resistant E. faecium isolates.

A quantitative approach to the effectiveness of ozone against microbiota organisms colonizing toothbrushes.

OBJECTIVES: Toothbrushes are rapidly contaminated with different microorganisms, which colonize the oral cavity and interdental spaces. This can represent a possible cause of infection or reinfection. In this study, the ozone experimental effect upon toothbrushes microflora was estimated microbiologically before and after saturation with ozone gas. METHODS: Fifty used toothbrushes coming from children and adults were entered our study. Microorganisms were enumerated and identified. Bristles from each brush were soaked in ozone saturated PBS solution for 5, 10, 15, 20 and 30 min and the total microbial population was reassessed. RESULTS: Counts of microorganisms isolated per brush varied between 10(2) and 10(7) CFU. Candida albicans was present in used toothbrushes. No obligate anaerobes were isolated. Members of Streptococcaceae family were regularly found (65.2%) belonging to the following species: Streptococcus pyogenes, S. mutans, S. mitis, S. oralis, S. sobrinus, S. viridans, S. salivarius, S. sanguis, Aerococcus viridans. A. viridans and S. mutans were more frequently isolated on children toothbrushes while Staphylococcus aureus and S. epidermidis were found on adults brushes. Escherichia coli, Pseudomonas sp. and Enterococcus sp., were also recovered. We found that the ozone treatment decreased gradually the microbial load. However, a bacterial re-growth was effective following short ozonation period. Decontamination was complete after an extended exposure to ozone for 30 min. CONCLUSIONS: Ozone application was found to remove the toothbrushes bristles microbiota following conventional brushing. Maximum decontamination efficacy of ozone treatment was observed after 30 min while exposure for short time periods seems to be inefficient which probably reflect the low dose of ozone used in this study.

Curcumin-mediated antimicrobial photodynamic therapy reduces the viability and vitality of infected dentin caries microcosms.

BACKGROUND: To our knowledge, there is a lack of evidence on the effect of Antimicrobial Photodynamic Therapy (aPDT) by the application of curcumin against complex biofilms of dental caries lesions. This study aimed to evaluate the viability, vitality, and acid metabolism of infected dentin caries microcosms treated with curcumin-mediated aPDT. METHODS: After microcosm biofilms growing anaerobically on bovine dentin disks immersed in McBain medium with 1% sucrose at 37 °C for 5 days, the biofilms were treated by the association of DMSO water solution or 600 µmol L-1 curcumin with 0, 37.5 or 75 J cm-2 blue LED (455 nm). Then, the colony-forming units (CFU) counts of total microorganisms, total streptococci, mutans streptococci, and total lactobacilli were determined by plating. The lactic acid concentration was analyzed by enzymatic spectrophotometry method, while the vitality of intact biofilms was evaluated by confocal laser scanning microscope (CLSM). Statistical analysis was performed by Kruskal Wallis and post-hoc Dunn's tests (P < 0.05). RESULTS: Curcumin alone did not affect the viability of microorganisms and the vitality of intact biofilms. However, 75 J cm-2 LED alone decreased the total microorganisms and total lactobacilli counts. The combination of curcumin and LED reduced significantly the counts of all microorganism groups and the vitality of intact biofilms. Differences were not observed between the lactic acid concentrations of distinct groups. CONCLUSIONS: Therefore, curcumin-mediated aPDT was effective in reducing the viability and the vitality of infected dentin caries microcosms, without interfering in their acidogenicity.

Immunogen-dependent quantitative and qualitative differences in phagocytic responses of the circulating hemocytes of the lobster Homarus americanus.

Phagocytic responses in circulating hemocytes of the lobster Homarus americanus were measured before and after treatment of lobsters with 2 different immunogens: (1) lipolysaccharide (LPS) or endotoxin from a non-pathogenic Pseudomonas perolens, and (2) a vancomycin/live Gram-positive pathogen (Aerococcus viridans [var.] homari) combination, essentially attenuated cells, shown previously to induce a high degree of resistance to this pathogen. The responses elicited by each of the immunogens were markedly different. Hemocytes drawn from LPS-treated lobsters showed significant, largely non-specific, increases in phagocytic responses over baseline values against sheep red blood cells and an array of test bacteria, with the notable exception of the pathogen. In marked contrast, induction with the vancomycin/live pathogen combination resulted in highly significant and specific increases in phagocytic responses to the pathogen and to the related, (but avirulent) strains of the pathogen, as well as inducing in the lobsters the usual high degree of resistance to the pathogen. These results suggest that quantitative and qualitative variations in phagocytic and resistance levels induced in at least 1 crustacean genus are determined largely by the particular characteristics of the immunogen.

Association of minimum inhibitory concentration cluster patterns with dairy management practices for environmental bacteria isolated from bulk tank milk.

Environmental bacteria have emerged over the past few years to become significant causes of mastitis. Bacteria in this group are often reported by practicing veterinarians to be increasingly resistant to intramammary therapy and responsible for elevated bulk tank somatic cell counts. The purpose of this study was to determine the extent of association of the minimum inhibitory concentrations for selected antimicrobial agents with environmental bacteria isolated from bulk tank milk on California dairies and their housing facilities, husbandry practices, and antimicrobic-use strategies. Bulk tank milk samples were collected from 2 dairy cooperatives that had their milk cultured at the Milk Quality Laboratory, University of California Davis, Veterinary Medicine Teaching and Research Center in Tulare, CA. Samples were collected from July 2001 through March 2002 on 88 d; and 404 environmental bacteria isolated from 93 dairies were found. Minimum inhibitory concentrations were determined on 337 of the isolates for 10 antimicrobial agents. Cluster analysis was performed on the minimum inhibitory concentration values for each organism, and 4 antimicrobial clusters with varying degrees of resistance were found.A 69-question survey questionnaire was completed on-farm for 49 of the 73 dairies that had at least 3 environmental bacterial isolates. The questionnaire sought information on housing facilities, milking management, mastitis prevention, antimicrobial usage strategies, and owner/veterinary involvement in disease control and prevention. Multinomial logistic regression analysis found significant associations between the antimicrobial agent-resistance cluster groups and some of the housing and bedding practices, failure to dry udders before milking, and antimicrobial treatment of nonmastitis conditions. No association was noted for antimicrobial agent treatment of mastitis and the resistance cluster patterns.

Antimicrobial susceptibility of Abiotrophia adiacens and Abiotrophia defectiva.

The susceptibilities of 27 Abiotrophia adiacens (proposed reclassification Granulicatella adiacens comb.nov., Collins & Lawson, 2000) and 12 Abiotrophia defectiva isolates were tested by microdilution in pyridoxal hydrochloride and lysed horse blood supplemented Mueller-Hinton broth. According to NCCLS interpretative criteria for Streptococcus spp. not Streptococcus pneumoniae, the susceptibilities of A. adiacens and A. defectiva were, respectively: penicillin, 55% and 8%; amoxicillin, 81% and 92%; ceftriaxone, 63% and 83%; meropenem, 96% and 100%; and 100% for both species with clindamycin, rifampin, levofloxacin, ofloxacin, quinupristin/dalfopristin, and vancomycin.

Synergism with aminoglycosides of penicillin, ampicillin and vancomycin against non-enterococcal group-D streptococci and viridans streptococci.

The antibiotic susceptibility of 10 strains of non-enterococcal group-D streptococci was compared with that of 20 strains of viridans streptococci. The minimal inhibitory concentrations of penicillin, ampicillin, oxacillin, nafcillin, cephalothin, vancomycin, erythromycin and clindamycin for the two groups of streptococci were very similar in range and median values. Both groups of streptococci were resistant to the aminoglycosides. The effect of the combination of penicillin, ampicillin or vancomycin with streptomycin, kanamycin, gentamicin or tobramycin on the in-vitro killing of the two groups of streptococci was compared. For all the antibiotic combinations tested, synergism was demonstrated against all strains of non-enterococcal group-D streptococci after one or more of the time-intervals 6, 24 and 48 h. Some or all of the antibiotic combinations were synergistic against all strains of viridans streptococci after one or more of the same time-intervals. The other aminoglycosides (kanamycin, gentamicin and tobramycin) offered no advantage over streptomycin in synergism with penicillin, ampicillin or vancomycin against nonenterococcal group-D streptococci or viridans streptococci. These results suggest that non-enterococcal group-D streptococcal endocarditis may be treated by the same regimen as endocarditis caused by the viridans streptococci.

Current antimicrobial susceptibility of cutaneous bacteria to first line antibiotics.

Antimicrobial susceptibility of common bacterial species occurring on human skin appears to be falling. Data for the antimicrobial susceptibility of major groups of bacteria isolated from human skin during routine cultures were complied and analysed over a period of 9 months. Routine diagnostics of specimens from skin lesions and normal human skin were analysed for the presence of specified groups of bacteria. The species were identified using standard methods. Anti-microbial susceptibility was determined using a broth microdilution system giving breakpoints, the Sensititre system. Of the 333 Staphylococcus aureus, 129 Streptococcaceae, 180 Enterobacteriaceae and 120 Pseudomonadaceae strains investigated more than 5% of Staphylococcus aureus strains were resistant to flucloxacillin and thus methicillin (MRSA). More than 25% of Staphylococcus aureus strains were resistant to tetracycline and erythromycin. Many MRSA strains were found multi-resistant. Gentamicin was active against a large majority of Enterobacteriaceae strains but many Pseudomonadaceae strains were resistant. Compared with previous corresponding surveys methicillin-resistant Staphylococcus aureus strains are clearly on the increase. To prevent a further increase of resistant strains a defined strategy for antibiotic use is needed in dermatology.

Multi-resistance to antimicrobial agents for the ten most frequently isolated bacterial pathogens.

Cross-resistance and multi-resistance to selected antibiotics was determined for Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. Amikacin-resistant Enterobacteriaceae often showed cross-resistance to ss-lactam antibiotics. Only 1% of the Escherichia coli isolates showed resistance to more than four antibiotics from a set of seven. This rate was higher for other Enterobacteriaceae and there were high levels of cross-resistance for P. aeruginosa. The cross-resistance of oxacillin with other antibiotics is well known in staphylococci. Penicillin-resistant pneumococcal isolates were cross-resistant to macrolides. Cross-resistance was only a minor problem in H. influenzae and M. catarrhalis. Cross- and multi-resistance are important problems for Gram-negative and Gram-positive bacteria but not for fastidious bacteria with the exception of penicillin-resistant S. pneumoniae.

Thermal resistances and lactate and diacetate sensitivities of bacteria causing bologna discolouration.

This report describes the effects of heat, sodium lactate, and sodium diacetate on the viabilities of Weissella viridescens ATCC 12706, Aerococcus viridans MPL-1 and MPL-B, and Carnobacterium viridans ATCC BAA 336. The latter three organisms were isolated from commercial product and have previously been shown to produce green discolourations in cooked cured bologna. W. viridescens was heat resistant in beef bologna (D(60 degrees C)=14.7 min) but not in APT broth. A. viridans and C. viridans were much more sensitive to heat (D(60 degrees C) in beef bologna < or =1.3 min), indicating that these organisms were probably post-pasteurization contaminants. Sodium lactate (3.0%) alone or in combination with 0.3% sodium diacetate slowed the growth rate and reduced the final cell numbers of A. viridans and C. viridans in inoculated bologna. W. viridescens was only slightly affected by the combined antimicrobials. The combination of sodium lactate and sodium diacetate prevented A. viridans and C. viridans from affecting the colour of beef bologna. However, lactate and diacetate themselves reduced red colour, as measured by HunterLab colourimetry. HunterLab a values for fresh beef bologna were 13.4 (no antimicrobial added), 9.6 (3.0% sodium lactate), 8.0 (0.3% sodium diacetate), and 7.9 (3.0% sodium lactate + 0.3% sodium diacetate).

Comparison of the target sites and mechanisms of action of glycopeptide and lipoglycodepsipeptide antibiotics.

In this brief review of glycopeptides (teicoplanin and vancomycin) and lipoglycodepsipeptides (ramoplanin), comparison is made of their structure, general mode of action, specific target site and the mechanism by which inhibition of the sensitive enzyme is achieved. Although these two groups of antibiotics are chemically very different, they both inhibit late stages in the biosynthesis of bacterial cell wall peptidoglycan and cause the accumulation of the identical cell wall precursor, UDP-MurNAc-pentapeptide, in the cytoplasm. The specific target site is at the level of the membrane-bound enzymes which catalyse the attachment of wall precursors to a lipid carrier and subsequent polymerisation: ramoplanin inhibits transfer of one of the two precursors, whereas the glycopeptides block polymerisation. As different targets are involved, cross-resistance between glycopeptides and ramoplanin is unlikely and has not yet been reported. The actual mechanisms of action are totally different: glycopeptides inhibit the sensitive reaction by binding firmly, as a result of substantial hydrogen bonding, to acyl-D-Ala-D-Ala termini of the nascent peptidoglycan chains or lipid-linked wall subunits. The substrate is sequestered in a cleft of the antibiotic molecule and cannot interact with the polymerase enzyme. The precise mechanism of action of ramoplanin has not been elucidated, but its action is not dependent on the presence of the acyl-D-Ala-D-Ala group in the substrate and its binding characteristics are different from those of the glycopeptides. It therefore has a different mechanism of action as well as a different site, compared with the glycopeptides.

A new class of acyclic nucleoside phosphonates: synthesis and biological activity of 9-[[(phosphonomethyl)aziridin-1-yl]methyl]guanine (PMAMG) and analogues.

A new class of acyclic nucleoside phosphonates PMAMG, PMAMA, PMAMC, and PMAMT (compounds 1, 2, 3 and 4) have been synthesized and tested in vitro against a wide variety of viruses, fungi and bacteria. PMAMG (1) was synthesized by the alkylation reaction of acetylguanine with the phosphonate side-chain, diisopropyl [[2-(bromomethyl)aziridin-1-yl]]methylphosphonate (9), followed by deesterification reaction in the presence of TMSBr. In similar way, PMAMA, PMAMC, and PMAMT were prepared.

Effects of formalin, chloramine-T, and low salinity dip on the behavior and hemolymph biochemistry of the American lobster.

The purpose of this research was to investigate the salinity and formalin sensitivity of a ciliate parasite (Anophryoides haemophila) of the American lobster (Homarus americanus), and to examine the target-animal (lobster) safety of chemical-bath treatments involving low salinity, formalin, or chloramine-T that could be used to control this parasite in lobster pounds. "Bumper car" disease, caused by An. haemophila, is an important concern to lobster pound operators in eastern North America, because of the implicated lobster mortality rate and the general lack of preventive and therapeutic intervention regimes. We determined, using an in vitro method, that formalin at 50 mg/L, or low salinity at 8.0 parts per thousand (ppt) for 1 hour killed 100% of the parasites. When healthy lobsters were exposed to formalin at 200 mg/L, there were no negative behavioral responses and no significant differences in a panel of hemolymph biochemical indices. Similar results occurred when lobsters were exposed to chloramine-T, a common finfish therapeutic agent for topical bacteria and protozoa, at 10 mg/L for 1 hour. The low salinity treatment (8.0 ppt) resulted in significant adverse changes in lobster behavior and biochemical indices; however, these changes did not persist for more than 1 week after treatment ended. Although these treatments are unlikely to kill parasites that have already invaded the lobster carapace, they should be effective in reducing parasite loads on the gill and carapace surface of the lobster and in the environment of the impoundment housing.

[Antibacterial effect of cefixime]. / Comportement antibactérien du céfixime.

Cefixime (CFM) is a new hemi-synthetic orally active cephalosporin which exhibits a particular affinity for PBPs 3, 1a, 1bs. Its penetration through the Gram negative bacilli outer membrane is similar to that of third generation cephalosporins. The MICs were assessed by the agar dilution method against 2,489 bacterial strains collected in 10 hospitals. Against Enterobacteriaceae, MICs50 and 90 are respectively (mg/l): naturally non beta-lactamase-producing species: E. coli and Shigella: 0.25-0.5, Salmonella: 0.06 - 0.25, P. mirabilis: 0.008 - 0.0.32; chromosomal penicillinase producing species: Klebsiella: 0.06 - 2; chromosomal cephalosporinase producing species: E. cloacae and C. freundii: 1 - greater than 128, S. marcescens: 0.25 - 16, Proteus indole: + 0.06 - 4, P. stuartii: 0.032 - 0.5. CFM activity is not altered in strains producing an acquired penicillinase. On the other hand, CFM appears to be inactive against cephalosporinase hyperproducing mutants and its activity is variably decreased against expanded spectrum beta-lactamase producing strains. CFM is inactive against P. aeruginosa (MIC50 and 90: 64 - 128) and against A. baumannii (16 - 128). Haemophilus and gonococci, beta-lactamase producing or not, as well as meningococci, are highly susceptible to CFM (MIC 0.008 - 0.12). B. catarrhalis is usually inhibited by 0.03 to 0.5. CFM is moderately active against meticillin-sensitive staphylococci (MIC50 and 90: 1-64), and inactive against meticillin-resistant strains. Enterococci are usually resistant, whereas streptococci and pneumococci are inhibited by low concentrations: 0.08 to 1. CFM is a bactericidal antibiotic, as shown by MBC and killing curves determination. These antibacterial properties relate CFM to the third generation cephalosporins and position the compound in an excellent place among the orally active cephalosporins.

In vitro antibacterial activity of ceftobiprole against clinical isolates from French teaching hospitals: proposition of zone diameter breakpoints.

The aims of this study were to determine the in vitro activity profile of ceftobiprole, a pyrrolidinone cephalosporin, against a large number of bacterial pathogens and to propose zone diameter breakpoints for clinical categorisation according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) minimum inhibitory concentration (MIC) breakpoints. MICs of ceftobiprole were determined by broth microdilution against 1548 clinical isolates collected in eight French hospitals. Disk diffusion testing was performed using 30 µg disks according to the method of the Comité de l'Antibiogramme de la Société Française de Microbiologie (CA-SFM). The in vitro activity of ceftobiprole, expressed by MIC(50/90) (MICs for 50% and 90% of the organisms, respectively) (mg/L), was as follows: meticillin-susceptible Staphylococcus aureus, 0.25/0.5; meticillin-resistant S. aureus (MRSA), 1/2; meticillin-susceptible coagulase-negative staphylococci (CoNS), 0.12/0.5; meticillin-resistant CoNS, 1/2; penicillin-susceptible Streptococcus pneumoniae, ≤ 0.008/0.03; penicillin-resistant S. pneumoniae, 0.12/0.5; viridans group streptococci, 0.03/0.12; ß-haemolytic streptococci, ≤ 0.008/0.016; Enterococcus faecalis, 0.25/1; Enterococcus faecium, 64/128; Enterobacteriaceae, 0.06/32; Pseudomonas aeruginosa, 4/16; Acinetobacter baumannii, 0.5/64; Haemophilus influenzae, 0.03/0.12; and Moraxella catarrhalis, 0.25/0.5. According to the regression curve, zone diameter breakpoints could be 28, 26, 24 and 22 mm for MICs of 0.5, 1, 2 and 4 mg/L respectively. In conclusion, this study confirms the potent in vitro activity of ceftobiprole against many Gram-positive bacteria, including MRSA but not E. faecium, whilst maintaining a Gram-negative spectrum similar to the advanced-generation cephalosporins such as cefepime. Thus ceftobiprole appears to be well suited for the empirical treatment of a variety of healthcare-associated infections.