In vitro activity of rifaximin against clinical isolates of Escherichia coli and other enteropathogenic bacteria isolated from travellers returning to the UK

Rifaximin is licensed in the EU and USA for treating travellers’ diarrhoea caused by non-invasive bacteria. Selection for resistance mechanisms of public health significance might occur if these are linked to rifamycin resistance. Rifaximin MICs were determined by agar dilution for 90 isolates each of Escherichia coli, Shigella spp., nontyphoidal Salmonella enterica, typhoidal S. enterica and Campylobacter spp., an additional 60 E. coli with CTX-M ESBLs isolated from patients with travellers’ diarrhoea, and 30 non-diarrhoeal carbapenemase-producing E. coli. Comparators were rifampicin, ciprofloxacin, azithromycin, trimethoprim/sulfamethoxazole and doxycycline. Isolates with rifaximin MICs>32 mg/L were screened for arr genes, and critical rpoB regions were sequenced. Rifaximin was active at ≤32 mg/L against 436/450 (96.9%) diverse Enterobacteriaceae, whereas 81/90 (90%) Campylobacter spp. were resistant to rifaximin at ≥128 mg/L. Rifaximin MICs were ≥128 mg/L for two Shigella and five MDR E. coli producing NDM (n = 3), OXA-48 (n = 1) or CTX-M-15 (n = 1). Two of the five MDR E. coli had plasmids harbouring arr-2 together with bla_NDM, and two (one each with bla_NDM and bla_CTX-M-15) had His526Asn substitutions in RpoB. The rifamycin resistance mechanism remained undefined in one MDR E. coli isolate (with bla_OXA-48) and the two Shigella isolates. Rifaximin showed good in vitro activity against diverse Enterobacteriaceae but was largely inactive against Campylobacter spp. Rifaximin has potential to co-select MDR E. coli in the gut flora, but much stronger associations were seen between ESBL and/or carbapenemase production and resistance to alternative treatments for travellers’ diarrhoea, notably ciprofloxacin and azithromycin.     

Review of rifaximin as treatment for SIBO and IBS

Background: Rifaximin is a broad-range, gastrointestinal-specific antibiotic that demonstrates no clinically relevant bacterial resistance. Therefore, rifaximin may be useful in the treatment of gastrointestinal disorders associated with altered bacterial flora, including irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth (SIBO). Objective: To review rifaximin for treatment of IBS and SIBO. Methods: Review of rifaximin clinical trials. Results/conclusion: Rifaximin improved global symptoms in 33 – 92% of patients and eradicated SIBO in up to 84% of patients with IBS, with results sustained up to 10 weeks post-treatment. Rifaximin caused a lower number of adverse events compared with metronidazole or levofloxacin and may have a more favorable adverse event profile than systemic antibiotics, without clinically relevant antibiotic resistance.     

Assessment of bacterial quality of honey produced in Tamale metropolis (Ghana)

The bacterial quality of honey from different production sites within Tamale metropolis, Ghana, was estimated using standard microbiological methods. Honey samples were bought from six different production sites within Tamale metropolis and labeled. Samples that were taken from location B recorded the least mean bacterial count of 6.0 × 10⁴ colony forming units/mL with samples taken from location D showing the highest, 1.1 × 10⁵ colony forming units/mL. However, samples from production sites E and F recorded no bacteria growth. Bacteria isolated included Escherichia coli, Staphylococcus spp., Shigella spp., Streptococcus spp., and Bacillus spp. The pH values of honey samples from the various locations were found to be directly correlated to the average bacteria load. The variation in bacteria load and species at the various production sites and the absence of bacteria growth in two production sites is an indication of the differences in production practices, as well as hygienic conditions at these sites. The presence of these isolates is a cause for concern as pathogenic strains of these bacteria can cause serious health related problems.     

Characterising the post-antifungal effects of micafungin against Candida albicans,Candida glabrata,Candida parapsilosis and Candida krusei isolates

In this study, we measured time–kills and post-antifungal effects (PAFEs) for micafungin against Candida albicans (n = 4), Candida glabrata (n = 3), Candida parapsilosis (n = 3) and Candida krusei (n = 2) isolates and further characterised the PAFEs. Minimum inhibitory concentrations (MICs) were 0.5–1.0 mg/L against C. parapsilosis and 0.008–0.125 mg/L against the other species. Micafungin caused kills >1 log at 1 × MIC, 4 × MIC (range 1.19–3.10 log) and 16 × MIC (2.27–3.68 log), achieving fungicidal levels (≥3 log) against nine isolates. One-hour drug exposure during PAFE experiments resulted in kills of 0.73–2.88 log and 1.72–3.55 log at 4× and 16× MIC, respectively, achieving fungicidal levels against five isolates. Isolates of each species collected 8 h after a 1-h exposure to micafungin (4× and 16× MIC) were hypersusceptible to sodium dodecyl sulphate (SDS) and Calcofluor White. Cells tested during the PAFE period demonstrated cell wall disturbances as evident on electron micrographs as well as significant reductions in adherence to epithelial cells. Phagocytosis by J774 macrophages was significantly enhanced for three PAFE isolates tested. Micafungin is fungicidal and exerts PAFEs that kill diverse Candida spp., disturb cell walls of viable organisms, reduce adherence and enhance susceptibility to phagocytosis.     

Regulatory efficacy of fermented plant extract on the intestinal microflora and lipid profile in mildly hypercholesterolemic individuals

In recent years, the use of fermented plant products to protect against various metabolic syndromes has been increasing enormously. The objective of this study was to check the regulatory efficacy of fermented plant extract (FPE) on intestinal microflora, lipid profile, and antioxidant status in mildly hypercholesterolemic volunteers. Forty-four mildly hypercholesterolemic individuals (cholesterol 180–220 mg/dL) were recruited and assigned to two groups: experimental or placebo. Volunteers were requested to drink either 60 mL of FPE or placebo for 8 weeks. Anthropometric measurements were done in the initial, 4^th, 8^th, and 10^th weeks. The anthropometric parameters such as body weight, body fat, and body mass index were markedly lowered (p < 0.05) on FPE intervention participants. Moreover, the total antioxidant capacity and total phenolics in plasma were considerably increased along with a reduction (p < 0.05) in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) after FPE supplementation. Participants who drank FPE showed a pronounced increase (p < 0.05) in the number of beneficial bacteria such as Bifidobacterium spp. and Lactobacillus spp., whereas the number of harmful bacteria such as Escherichia coli and Clostridium perfringens (p < 0.05) were concomitantly reduced. Furthermore, the lag time of LDL oxidation was substantially ameliorated in FPE-administered group, thus indicating its antioxidative and cardioprotective properties. Treatment with FPE substantially improved the intestinal microflora and thereby positively regulated various physiological functions by lowering the anthropometric parameters, TC, and LDL-c, and remarkably elevated the antioxidant capacity and lag time of LDL oxidation. Therefore, we recommended FPE beverage for combating hypercholesterolemia.     

Application of pharmacokinetic/pharmacodynamic modelling and simulation for the prediction of target attainment of ceftobiprole against meticillin-resistant Staphylococcus aureus using minimum inhibitory concentration and time–kill curve based approaches

The purpose of this report was to compare two different methods for dose optimisation of antimicrobials. The probability of target attainment (PTA) was calculated using Monte Carlo simulation to predict the PK/PD target of fT_>MIC or modelling and simulation of time–kill curve data. Ceftobiprole, the paradigm compound, activity against two MRSA strains was determined, ATCC 33591 (MIC = 2 mg/L) and a clinical isolate (MIC = 1 mg/L). A two-subpopulation model accounting for drug degradation during the experiment adequately fit the time–kill curve data (concentration range 0.25–16× MIC). The PTA was calculated for plasma, skeletal muscle and subcutaneous adipose tissue based on data from a microdialysis study in healthy volunteers. A two-compartment model with distribution factors to account for differences between free serum and tissue interstitial space fluid concentration appropriately fit the pharmacokinetic data. Pharmacodynamic endpoints of fT_>MIC of 30% or 40% and 1- or 2-log kill were used. The PTA was >90% in all tissues based on the PK/PD endpoint of fT_>MIC >40%. The PTAs based on a 1- or 2-log kill from the time–kill experiments were lower than those calculated based on fT_>MIC. The PTA of a 1-log kill was >90% for both MRSA isolates for plasma and skeletal muscle but was slightly below 90% for subcutaneous adipose tissue (both isolates ca. 88%). The results support a dosing regimen of 500 mg three times daily as a 2-h intravenous infusion. This dose should be confirmed as additional pharmacokinetic data from various patient populations become available.     

Comparison of two DNA microarrays for detection of plasmid-mediated antimicrobial resistance and virulence factor genes in clinical isolates of Enterobacteriaceae and non-Enterobacteriaceae

A DNA microarray was developed to detect plasmid-mediated antimicrobial resistance (AR) and virulence factor (VF) genes in clinical isolates of Enterobacteriaceae and non-Enterobacteriaceae. The array was validated with the following bacterial species: Escherichiacoli (n = 17); Klebsiellapneumoniae (n = 3); Enterobacter spp. (n = 6); Acinetobacter genospecies 3 (n = 1); Acinetobacterbaumannii (n = 1); Pseudomonasaeruginosa (n = 2); and Stenotrophomonasmaltophilia (n = 2). The AR gene profiles of these isolates were identified by polymerase chain reaction (PCR). The DNA microarray consisted of 155 and 133 AR and VF gene probes, respectively. Results were compared with the commercially available Identibac AMR-ve Array Tube. Hybridisation results indicated that there was excellent correlation between PCR and array results for AR and VF genes. Genes conferring resistance to each antibiotic class were identified by the DNA array. Unusual resistance genes were also identified, such as bla_SHV-5 in a bla_OXA-23-positive carbapenem-resistant A. baumannii. The phylogenetic group of each E. coli isolate was verified by the array. These data demonstrate that it is possible to screen simultaneously for all important classes of mobile AR and VF genes in Enterobacteriaceae and non-Enterobacteriaceae whilst also assigning a correct phylogenetic group to E. coli isolates. Therefore, it is feasible to test clinical Gram-negative bacteria for all known AR genes and to provide important information regarding pathogenicity simultaneously.     

Safety evaluation of Whole Algalin Protein (WAP) from Chlorella protothecoides

Microalgae such as Chlorella spp., were once consumed as traditional human foods; now they are being developed as ingredients for modern diets. Whole Algalin Protein (WAP) from dried milled Chlorella protothecoides was evaluated for dietary safety in a 13-week feeding trial in rodents with genotoxic potential evaluated using in vitro and in vivo assays and the likelihood of food allergy potential evaluated via human repeat-insult patch test (HRIPT). In the subchronic study, rats consumed feed containing 0, 25,000, 50,000 or 100,000 ppm WAP for 92–93 days. No treatment-related mortalities or effects in general condition, body weight, food consumption, ophthalmology, urinalysis, hematology, clinical chemistry, gross pathology, organ weights, and histopathology occurred. Several endpoints exhibited statistically significant effects, but none was dose-related. The no-observed-adverse-effect level (NOAEL) was based on the highest WAP concentration consumed by the rats and was equivalent to 4805 mg/kg/day in males and 5518 mg/kg/day in females. No mutagenicity occurred in Salmonella typhimurium or Escherichia coli tester strains (⩽5000 μg/plate WAP) with or without mutagenic activation. No clastogenic response occurred in bone marrow from mice administered a single oral dose (2000 mg/kg WAP). Skin sensitization was not induced by WAP via HRIPT, indicating little potential for food allergy.     

Daptomycin activity tested against 164 457 bacterial isolates from hospitalised patients: Summary of 8 years of a Worldwide Surveillance Programme (2005–2012)

We report the results of 8 years (2005–2012) of the Daptomycin Surveillance Programme Worldwide. Consecutive non-duplicate bacterial isolates (prevalence design) were collected from patients with documented infections in 410 medical centres and were susceptibility tested by reference broth microdilution methods. A total of 164 457 Gram-positive isolates were evaluated, including 97 542 Staphylococcus aureus, 21 413 coagulase-negative staphylococci (CoNS), 29 619 enterococci and 15 883 β-haemolytic streptococci. The prevalence of daptomycin-non-susceptible isolates was extremely low for all species in all geographic regions. Overall, the highest occurrence of non-susceptible isolates was observed among CoNS (0.19%), followed by Enterococcus faecium (0.18%), S. aureus (0.05%), Enterococcus faecalis (0.02%) and β-haemolytic streptococci (0.00%). Moreover, no trend towards increased daptomycin resistance (non-susceptibility) was observed for any species in any geographic region during the study interval. Against S. aureus, the daptomycin MIC_50/90 was 0.25/0.5 mg/L in all geographic regions (99.95% susceptible overall). Only 53 daptomycin-non-susceptible S. aureus isolates were observed and the vast majority (49; 92.5%) had a daptomycin MIC value only 1 log₂ dilution above the published susceptible breakpoint. Daptomycin was also active against CoNS (MIC_50/90, 0.25/0.5 mg/L; 99.81% susceptible), E. faecalis (MIC_50/90, 1/2 mg/L; 99.98% susceptible), E. faecium (MIC_50/90, 2/4 mg/L; 99.82% susceptible) including vancomycin-non-susceptible isolates (4521 isolates; MIC_50/90, 2/2 mg/L; 99.76% susceptible), and β-haemolytic streptococci (MIC_50/90, ≤0.06/0.25 mg/L; 100.0% susceptible). In conclusion, daptomycin has remained very active against indicated species worldwide, and no significant year-to-year or regional variation in daptomycin activity has been detected.     

Solid lipid nanoparticles as anti-inflammatory drug delivery system in a human inflammatory bowel disease whole-blood model

Standard treatment for inflammatory bowel diseases (IBD) necessitates frequent intake of anti-inflammatory and/or immunosuppressive drugs, leading to significant adverse events.To evaluate the role solid lipid nanoparticles (SLN) play as drug delivery system in enhancing anti-inflammatory activity for drugs such as dexamethasone and butyrate in a human inflammatory bowel diseases whole-blood model. ELISA assay and the peripheral blood mononuclear cell (PBMC) cytokine mRNA expression levels were evaluated by quantitative SYBR Green real-time RT-PCR to determine the IL-1β, TNF-α, IFN-γ and IL-10 secretion in inflammatory bowel diseases patients’ PBMC culture supernatants. There was a significant decrease in IL-1β (p < 0.01) and TNF-α (p < 0.001) secretion, whilst IL-10 (p < 0.05) secretion significantly increased after cholesteryl butyrate administration, compared to that of butyrate alone at the highest concentration tested (100 μM), at 24 h exposure. There was a significant decrease in IL-1β (p < 0.01), TNF-α (p < 0.001) and IL-10 (p < 0.001) secretion after dexamethasone loaded SLN administration, compared to dexamethasone alone at the highest concentration tested (250 nM) at 24 h exposure. No IFN-γ was detected under any conditions and no cytotoxic effects observed even at the highest concentration tested.The incorporation of butyrate and dexamethasone into SLN has a significant positive anti-inflammatory effect in the human inflammatory bowel disease whole-blood model.     

Ceftaroline activity tested against uncommonly isolated Gram-positive pathogens: report from the SENTRY Antimicrobial Surveillance Program (2008–2011)

Ceftaroline was tested against 1859 clinically significant Gram-positive organisms from uncommonly isolated species. The organisms (31 species/groups) were collected from 133 medical centres worldwide over a 4-year period (2008–2011). Coagulase-negative staphylococci were generally susceptible to ceftaroline, with MIC₅₀ values (minimum inhibitory concentration required to inhibit 50% of the isolates) of 0.06–0.5 mg/L. Ceftaroline was active against Micrococcus spp. [minimum inhibitory concentration required to inhibit 90% of the isolates (MIC₉₀) = 0.06 mg/L], but showed more limited potency versus some Corynebacterium spp. and Listeria monocytogenes isolates. Ceftaroline was active against all β-haemolytic streptococci and viridans group streptococcal species/groups listed, with MIC₅₀ and MIC₉₀ values ranging from ≤0.015 mg/L to 0.03 mg/L and from ≤0.015 mg/L to 0.5 mg/L, respectively. Based on these in vitro findings, ceftaroline may have a potential role in the treatment of infections caused by these rarer species as guided by reference MIC test results.     

Antimicrobial susceptibility of Gram-negative organisms isolated from patients hospitalised with pneumonia in US and European hospitals: Results from the SENTRY Antimicrobial Surveillance Program, 2009–2012

Here we evaluated the frequency of occurrence and antimicrobial susceptibility patterns of Gram-negative bacteria isolated from patients hospitalised with pneumonia in medical centres in the USA (n = 28) and Europe and the Mediterranean region (EMR) (n = 25) in 2009–2012. Susceptibility testing was performed by reference broth microdilution methods. Overall, 12 851 isolates were collected (6873/5978 in USA/EMR). The same top 11 organisms were observed in both geographic regions, but in different rank orders, and Gram-negative organisms represented 61.5/76.1% of strains in USA/EMR. Pseudomonas aeruginosa was the most frequently isolated Gram-negative organism in both regions (20.9/20.9% of cases in USA/EMR) and showed reduced susceptibility to most antimicrobials tested, including ceftazidime (79.6/68.7% susceptibility in USA/EMR), meropenem (76.3/65.8%) and piperacillin/tazobactam (72.9/63.9%). Klebsiella spp. was isolated from 9.7/11.6% of cases and showed extended-spectrum β-lactamase (ESBL) phenotype rates of 19.5/35.1% in USA/EMR. Meropenem and amikacin were active against 62.3/78.7% and 60.8/85.2% of ESBL phenotype Klebsiella spp. from USA/EMR, respectively. Enterobacter spp. ranked fourth in the USA (5.9%) and sixth in EMR (5.5%), whereas Escherichia coli ranked fifth in the USA (5.5%) and third in EMR (11.8%). Acinetobacter spp. and Stenotrophomonas maltophilia combined were isolated from 8.0/10.7% of cases in USA/EMR. A significant increase in P. aeruginosa susceptibility to meropenem and a significant decrease in gentamicin susceptibility among Klebsiella spp. were noted in EMR. These results confirm that very few agents remain broadly active against the most frequently isolated Gram-negative organisms from patients with pneumonia in US and EMR medical centres.     

Evaluation of dalbavancin,tigecycline, minocycline,tetracycline, teicoplanin and vancomycin against community-associated and multidrug-resistant hospital-associated meticillin-resistant Staphylococcus aureus

Dalbavancin is an investigational semisynthetic lipoglycopeptide that is structurally related to teicoplanin. We examined the activity of dalbavancin (DAL) compared with tigecycline (TIG), minocycline (MIN), tetracycline (TET), teicoplanin (TEC) and vancomycin (VAN) against community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA) and multidrug-resistant hospital-associated meticillin-resistant S. aureus (MDR HA-MRSA). Two hundred and twenty clinical isolates of CA-MRSA and MDR HA-MRSA were utilised. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined according to Clinical and Laboratory Standards Institute guidelines. Selective time–kill studies were performed against CA-MRSA and MDR HA-MRSA in triplicate. Overall, DAL exhibited low MIC values against all strains of MRSA. Time–kill studies with CA-MRSA demonstrated DAL = VAN > TIG > MIN = TEC > TET (P < 0.006), and with MDR HA-MRSA demonstrated DAL = VAN = TEC > TIG = MIN > TET (P > 0.05). DAL demonstrated potent activity against clinical strains of CA-MRSA and MDR HA-MRSA, including tetracycline-resistant S. aureus.     

Rifaximin for the treatment of irritable bowel syndrome – a drug safety evaluation

ABSTRACT

Introduction: Irritable bowel syndrome is a functional gastrointestinal disorder with a multifactorial etiology. Alterations of intestinal motility and immunity, gut-brain interactions, as well as gut microbiota dysbiosis contribute to the development of irritable bowel syndrome. Therefore, gut microbiota modulation by non-absorbable antibiotics is a therapeutic option in patients with IBS.

Areas covered: Published articles including patients with irritable bowel syndrome reporting data about rifaximin activity and safety have been searched throughout the literature and selected.

Expert opinion: The optimal antibiotic molecule should be local-acting, long-acting and safe-acting. Rifaximin is a non-absorbable antibiotic with additional anti-inflammatory and gut microbiota-modulating activity. It is effective in inducing symptoms relief in patients with IBS, even after repeated treatment courses. Rifaximin-related side effects in patients with IBS are reported to be mild and infrequent; microbial resistance is rare and transient, due to the high local concentration of the drug and to the absence of horizontal transmission. Clostridium difficile infection is not usual in patients receiving rifaximin in absence of predisposing conditions such as hospitalization and immunosuppression, which are uncommon in patients affected by irritable bowel syndrome. Nevertheless rifaximin is an antibiotic active against Clostridium difficile infection. Rifaximin has limited metabolic interactions and is not expected to interfere with drug metabolism in patients with normal hepatic function. These properties make rifaximin a safe antibiotic for gut microbiota modulation in patients with IBS.     

Worldwide dissemination of acquired carbapenem-hydrolysing class D β-lactamases in Acinetobacter spp. other than Acinetobacter baumannii

The aim of this study was to identify acquired OXA-type carbapenemases in Acinetobacter spp. other than Acinetobacter baumannii. From a total of 453 carbapenem-susceptible and -resistant Acinetobacter isolates collected worldwide, 23 were positive for bla_OXA genes by multiplex PCR. These isolates were identified as Acinetobacter pittii (n = 18), Acinetobacter nosocomialis (n = 2), Acinetobacter junii (n = 1) and Acinetobacter genomic species 14TU/13BJ (n = 2). The bla_OXA genes and associated insertion sequence (IS) elements were sequenced by primer walking. In 11 of these isolates, sequencing of the PCR products revealed that they were false-positive for bla_OXA. The remaining 12 isolates, originating from Europe, Asia, South America, North America and South Africa, harboured OXA-23 (n = 4), OXA-58 (n = 5), OXA-40-like (n = 1) and OXA-143-like (n = 1); one A. pittii isolate harboured both OXA-23 and OXA-58. IS elements were associated with bla_OXA in 10 isolates. OXA multiplex PCR showed a high degree of false-positive results (47.8%), indicating that detection of bla_OXA in non-baumannii Acinetobacter spp. should be confirmed using additional methods.     

Colistin/daptomycin: an unconventional antimicrobial combination synergistic in vitro against multidrug-resistant Acinetobacter baumannii

The in vitro activity of the combination colistin/daptomycin was evaluated against multidrug-resistant Acinetobacter baumannii clinical isolates. Clonal relationships were assessed by pulsed-field gel electrophoresis. The following synergy studies were undertaken: (i) daptomycin MICs were determined by E-test on Mueller–Hinton agar plates supplemented with a subinhibitory concentration of colistin; and (ii) time–kill methodology using tubes containing an inoculum of 5 × 10⁵ CFU/mL and subinhibitory concentrations of each antibiotic alone or in combination subcultured at 0, 5 and 24 h for colony counting. Synergy was defined as ≥2 log₁₀ CFU/mL decrease of viable colonies compared with colistin alone. Ten colistin-susceptible and four colistin-resistant A. baumannii isolates were tested. Isolates were assigned to nine different clonal types. Enhanced in vitro activity of the combination was detected only against colistin-susceptible isolates; using plates supplemented with colistin, the daptomycin MIC was reduced by 4- to 128-fold. From a total of 30 isolate–concentration combinations in time–kill studies, a synergistic interaction was detected in 16 (53.3%). The combination exhibited synergy against 8 and 12 of these combinations at 5 h and 24 h, respectively. No antagonism was detected. Colistin alone was bactericidal against two colistin-susceptible isolates at 24 h, whereas the combination was bactericidal against 9 colistin-susceptible isolates at 24 h. Against all colistin-resistant isolates, the combination exhibited a static effect and indifference in time–kill studies. Potent in vitro synergistic interactions between colistin and daptomycin provide evidence that this unorthodox combination may be beneficial in the treatment of colistin-susceptible multidrug-resistant A. baumannii.     

Rifaximin for the treatment of irritable bowel syndrome

INTRODUCTION: Few therapeutic options are available for irritable bowel syndrome (IBS). Lubiprostone is approved by the FDA for IBS with constipation, and alosetron in IBS with diarrhea (IBS-D). It has been proposed that alterations in the bowel microflora may play a role in the pathophysiology of IBS, and that modulation of the microflora holds therapeutic potential. Rifaximin is a nonsystemic antibiotic that has shown efficacy in IBS. AREAS COVERED: This narrative review covers the treatment options available for IBS-D and focuses on rifaximin. Rifaximin pharmacodynamics, clinical pharmacology and results of clinical studies from proof of concept to the latest Phase III and retreatment studies in IBS are summarized. Challenges to rifaximin use, safety issues and regulatory data are also discussed. EXPERT OPINION: The evidence supports rifaximin as an emerging treatment for IBS. Strategies for appropriate patient selection need to be further developed, and continued efficacy of rifaximin over repeated treatment courses needs to be better characterized.     

Carbapenemase-producing Enterobacteriaceae in a tertiary hospital in Madrid,Spain: high percentage of colistin resistance among VIM-1-producing Klebsiella pneumoniae ST11 isolates

Here we describe the carbapenemase genes, genetic relatedness and antimicrobial susceptibility data of 123 carbapenemase-producing Enterobacteriaceae (CPE) clinical isolates recovered from 2010 to 2012, comprising Klebsiella pneumoniae (n = 79), Klebsiella oxytoca (n = 13), Serratia marcescens (n = 14), Enterobacter cloacae (n = 12), Enterobacter asburiae (n = 4) and Enterobacter aerogenes (n = 1). VIM-1 was the most common carbapenemase (n = 101) followed by KPC-2 (n = 19), OXA-48 (n = 2) and IMP-22 (n = 1). Among the K. pneumoniae isolates, nine sequence types (STs) were identified but two clones were dominant: ST11 (54/79) containing mainly VIM-1-producing isolates; and ST101 (13/79) constituted by KPC-2-producing strains. Pulsed-field gel electrophoresis (PFGE) showed a higher genetic diversity among the remaining Enterobacteriaceae. Amikacin and fosfomycin were the most active agents with 82.9% and 80.5% susceptibility, respectively. Non-susceptibility to tigecycline was detected in 36.5% of strains. Overall, colistin resistance was 24.7% and was as high as 47% in Enterobacter spp. An increase in colistin resistance from 13.5% to 31.7% was observed among K. pneumoniae isolates during the study period. Resistance was focused on ST11 since 83.3% of colistin-resistant strains belonged to this clone. The high level of colistin resistance observed in this study is worrying with respect to the already limited therapeutic options for infections caused by multidrug-resistant Gram-negative bacteria.     

Toxicity evaluation of CdTe quantum dots with different size on Escherichia coli

Quantum dots (QDs) have a great potential for applications in nanomedicine. However, a few studies showed that they also exhibited toxicity. We used Escherichia coli (E. coli) as the model to study the effect of CdTe QDs on the cell growth by microcalorimetric technique, optical density (OD₆₀₀) and attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectra. Three size aqueous-compatible CdTe QDs with maximum emission of 543 nm (green-emitting QDs, GQDs), 579 nm (yellow-emitting QDs, YQDs) and 647 nm (red-emitting QDs, RQDs) were tested. The growth rate constants (k) and half-inhibiting concentration (IC₅₀) were calculated from the microcalorimetric data. The results indicated that CdTe QDs exhibited a dose-dependent inhibitory effect on cell growth. The order of toxicity is GQDs > YQDs > RQDs. The smaller the particle size of QDs is, the more toxicity it is. ATR-FTIR spectra indicated that the outer membrane of the cell was changed or damaged by the QDs, which may induce QDs and harmful by-products to enter into the cells. These could be one of the reasons that CdTe QDs have cytotoxic effects on E. coli.     

Isolation and screening of bioactive principle from Chaetomorpha antennina against certain bacterial strains

Microbial pathogens develop resistance to a particular antibiotic after repeated administration during the treatment of infectious diseases. Moreover, multiple drug resistance is a very common problem especially in hospital acquired infections. Therefore, it is necessary to find out alternative antibacterial drugs and the present trend is focused on seaweeds. This preliminary research work was carried out to find out the antibacterial activity of petroleum ether extract of Chaetomorpha antennina. The extracts were tested against Staphylococcus aureus MTCC 121, Bacillus cereus MTCC 492, Bacillus subtilis MTCC 441, Klebsiella pneumoniae MTCC 530, Escherichia coli MTCC 443 and Pseudomonas aeruginosa MTCC 779 by agar well diffusion technique. It was observed that petroleum ether extract showed prominent zone of inhibition against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus even at 50 μg/ml concentration. The maximum spectrum of activity was observed against Staphylococcus aureus ranged from 7.3 ± 0.8 to 18 ± 2.4 mm at the concentration 50 to 500 μg/ml, respectively. Hence the most susceptible bacterium was Staphylococcus aureus among the tested organisms. However, Escherichia coli and Pseudomonas aeruginosa are also susceptible. But the Bacillus cereus and Klebsiella pneumoniae are resistant against the tested extract.