Assessment of Long-Term Macrolide Exposure on the Oropharyngeal Microbiome and Macrolide Resistance in Healthy Adults and Consequences for Onward Transmission of Resistance.

While the use of long-term macrolide therapy to prevent exacerbations in chronic respiratory diseases is widespread, its impact on the oropharyngeal microbiota and macrolide resistance, and the potential for onward transmission of resistance to close contacts are poorly understood. We determined the effects of long-term exposure to azithromycin or erythromycin on phenotypic and genotypic macrolide resistance within the oropharyngeal microbiome of healthy adults and their close contacts in a randomized, single-blinded, parallel-group trial of 4 weeks of twice-daily oral 400 mg erythromycin ethylsuccinate or twice-daily oral 125 mg azithromycin. Using oropharyngeal swabs collected from 20 index healthy adults and 20 paired close contacts, the oropharyngeal microbial composition and macrolide resistance in streptococci were assessed by 16S rRNA sequencing and antibiotic susceptibility testing of oropharyngeal cultures, respectively, at baseline and weeks 4 and 8 (washout). Targeted quantitative PCR of antibiotic resistance genes was performed to evaluate paired changes in resistance gene levels in index patients and close contacts and to relate the potential transmission of antibiotic resistance. Neither azithromycin nor erythromycin altered oropharyngeal microbiota characteristics significantly. Proportional macrolide resistance in oropharyngeal streptococci increased with both erythromycin and azithromycin, remaining above baseline levels for the azithromycin group at washout. Levels of resistance genes increased significantly with azithromycin[erm(B) and mef] and erythromycin (mef), returning to baseline levels at washout only for the erythromycin group. We found no evidence of onward transmission of resistance to close contacts, as indicated by the lack of concomitant changes in resistance gene levels detected in close contacts. (This study has been registered with the Australian and New Zealand Clinical Trials Registry under identifier ACTRN12617000278336.).

Large-scale characterization of the macrolide resistome reveals high diversity and several new pathogen-associated genes.

Macrolides are broad-spectrum antibiotics used to treat a range of infections. Resistance to macrolides is often conferred by mobile resistance genes encoding Erm methyltransferases or Mph phosphotransferases. New erm and mph genes keep being discovered in clinical settings but their origins remain unknown, as is the type of macrolide resistance genes that will appear in the future. In this study, we used optimized hidden Markov models to characterize the macrolide resistome. Over 16 terabases of genomic and metagenomic data, representing a large taxonomic diversity (11 030 species) and diverse environments (1944 metagenomic samples), were searched for the presence of erm and mph genes. From this data, we predicted 28 340 macrolide resistance genes encoding 2892 unique protein sequences, which were clustered into 663 gene families (<70 % amino acid identity), of which 619 (94 %) were previously uncharacterized. This included six new resistance gene families, which were located on mobile genetic elements in pathogens. The function of ten predicted new resistance genes were experimentally validated in Escherichia coli using a growth assay. Among the ten tested genes, seven conferred increased resistance to erythromycin, with five genes additionally conferring increased resistance to azithromycin, showing that our models can be used to predict new functional resistance genes. Our analysis also showed that macrolide resistance genes have diverse origins and have transferred horizontally over large phylogenetic distances into human pathogens. This study expands the known macrolide resistome more than ten-fold, provides insights into its evolution, and demonstrates how computational screening can identify new resistance genes before they become a significant clinical problem.

Rapid and real-time monitoring of bacterial growth against antibiotics in solid growth medium using a contactless planar microwave resonator sensor.

Infection diagnosis and antibiotic susceptibility testing (AST) are pertinent clinical microbiology practices that are in dire need of improvement, due to the inadequacy of current standards in early detection of bacterial response to antibiotics and affordability of contemporarily used methods. This paper presents a novel way to conduct AST which hybridizes disk diffusion AST with microwave resonators for rapid, contactless, and non-invasive sensing and monitoring. In this research, the effect of antibiotic (erythromycin) concentrations on test bacterium, Escherichia coli (E. coli) cultured on solid agar medium (MH agar) are monitored through employing a microwave split-ring resonator. A one-port microwave resonator operating at a 1.76 GHz resonant frequency, featuring a 5 mm2 sensitive sensing region, was designed and optimized to perform this. Upon introducing uninhibited growth of the bacteria, the sensor measured 0.005 dB/hr, with a maximum change of 0.07 dB over the course of 15 hours. The amplitude change decreased to negligible values to signify inhibited growth of the bacteria at higher concentrations of antibiotics, such as a change of 0.005 dB in resonant amplitude variation while using 45 µg of antibiotic. Moreover, this sensor demonstrated decisive results of antibiotic susceptibility in under 6 hours and shows great promise to expand automation to the intricate AST workflow in clinical settings, while providing rapid, sensitive, and non-invasive detection capabilities.

Pneumococcal disease in Thailand.

This review examines the epidemiology of pneumococcal disease, serotype prevalence, antibiotic resistance, and national vaccination recommendations in Thailand. The incidence of invasive pneumococcal disease (IPD) and annualized hospitalization rates for pneumococcal bacteremia in Thailand were highest in children aged <5years and the elderly. The most prevalent serotype is serotype 6B, which is included in both the 10- and 13-valent pneumococcal conjugate vaccines (PCV10 [also known as PHiD-CV] and PCV13, respectively) registered in Thailand. Other common serotypes are 14, 18C, 19F, and 23F (included in both PCVs) and 6A and 19A (only included in PCV13). PCV10/PHiD-CV and PCV13 should cover 48.8%-74% and 73.2%-92% of isolates among children aged ≤5 years, respectively, and 40.0%-47.9% and 58.3%-60.9% of isolates among adults aged ≥65 years. Only PCV13 is licensed for adults in Thailand. Pneumococcal isolates were most commonly resistant to erythromycin, cefuroxime, and penicillin. Despite their demonstrated cost effectiveness and efficacy in reducing nasopharyngeal carriage and IPD, PCVs are not included in the Thai national immunization program. The serotype-specific IPD incidence in Thailand suggests that PCVs will reduce the disease burden in all age groups, but particularly in children and older adults.

Ultrasonographic assessment of the effect of metoclopramide, erythromycin, and exenatide on solid-phase gastric emptying in healthy cats.

BACKGROUND: Available data on the effect of gastrointestinal motility-modifying drugs in cats are limited. Most recommendations for drug usage and dosage are based on collective clinical experience. OBJECTIVES: To assess the effects of metoclopramide, erythromycin, and exenatide on gastric emptying (GE) and gastric motility in comparison to placebo. We hypothesized that metoclopramide and erythromycin would have prokinetic gastric effects, whereas exenatide would prolong GE times and decrease the motility index (MI) of antral contractions. ANIMALS: Eight healthy domestic shorthair cats. METHODS: Each cat had 4 separate ultrasonographic assessments. In a prospective, randomized, double-blind, 4-way crossover design, cats received placebo, metoclopramide, erythromycin, or exenatide for 2 days followed by a minimum 5-day washout period. Ultrasonographic GE times and MI were compared to placebo. RESULTS: When compared to placebo, the rate of GE was significantly faster after administration of metoclopramide and erythromycin. Significant differences were found at all fractions of GE after administration of erythromycin and all but 1 fraction after metoclopramide when compared to placebo. The rate of GE in the first half of the GE curve was significantly slower after exenatide administration. The total area under the Ml curve was significantly larger after administration of metoclopramide and erythromycin than after placebo. CONCLUSIONS AND CLINICAL IMPORTANCE: Metoclopramide and erythromycin shorten GE times and increase the MI of antral contractions, thus having a prokinetic effect in the stomach of healthy cats, whereas exenatide causes an initial delay in GE.

The molecular characters and antibiotic resistance of Clostridioides difficile from economic animals in China.

BACKGROUND: It has been performed worldwidely to explore the potential of animals that might be a reservoir for community associated human infections of Clostridioides difficile. Several genetically undistinguished PCR ribotypes of C. difficile from animals and human have been reported, illustrating potential transmission of C. difficile between them. Pig and calf were considered as the main origins of C. difficile with predominant RT078 and RT033, respectively. As more investigations involved, great diversity of molecular types from pig and calf were reported in Europe, North American and Australia. However, there were quite limited research on C. difficile isolates from meat animals in China, leading to non-comprehensive understanding of molecular epidemiology of C. difficile in China. RESULTS: A total of 55 C. difficile were isolated from 953 animal stool samples, within which 51 strains were from newborn dairy calf less than 7 days in Shandong Province. These isolates were divided into 3 STs and 6 RTs, of which ST11/RT126 was predominant type, and responsible for majority antibiotic resistance isolates. All the isolates were resistant to at least one tested antibiotics, however, only two multidrug resistant (MDR) isolates were identified. Furthermore, erythromycin (ERY) and clindamycin (CLI) were the two main resistant antibiotics. None of the isolates were resistant to vancomycin (VAN), metronidazole (MTZ), tetracycline (TET), and rifampin (RIF). CONCLUSIONS: In this study, we analyzed the prevalence, molecular characters and antibiotic resistance of C. difficile from calf, sheep, chicken, and pig in China. Some unique features were found here: first, RT126 not RT078 were the dominant type from baby calf, and none isolates were got from pig; second, on the whole, isolates from animals display relative lower resistant rate to these 11 tested antibiotics, compared with isolates from human in China in our previous report. Our study helps to deep understanding the situation of C. difficile from economic animals in China, and to further study the potential transmission of C. difficile between meat animals and human.

Assessment of the correlation among antibiotic resistance, adherence to abiotic and biotic surfaces, invasion and cytotoxicity of Pseudomonas aeruginosa isolated from diseased gilthead sea bream.

Improper uses of antibiotics to treat fish disease pose an increase of multidrug resistance in Pseudomonas aeruginosa. In order to escape host antimicrobial agents and induce cytotoxicity, different virulence properties are needed by these bacteria such as, biofilm formation, adhesion and invasion ability. This study was conducted to isolate Pseudomonas aeruginosa from diseased cultured gilthead sea bream. Seventeen isolates of Pseudomonas aeruginosa were identified by PCR. All of the isolates tested were susceptible to Gentamicin and Ciprofloxacin. Highest level of resistance was observed against Erythromycin, Ampicillin and Tetracycline. Among the 17 isolates, 11 showed multi-drug resistance. The isolates were screened for biofilm formation in abiotic surfaces, adherence, invasion and cytotoxicity against Hep-2 cells. We found that some strains were able to adhere to abiotic and biotic surface and to enter inside Hep-2 cells. Using cytochalasin D inhibitor, we observed a significant decrease in invasion of epithelial cells. The 17 washed bacterial cells induce variable degree of cytotoxicity. However, no cytotoxic effects on Hep-2 cells were obtained among the totality of cell free filtrate of Pseudomonas strains. By studying the relationship between different virulence properties, a significant positive correlation was obtained between both biofilm formation and adherence, and between adherence and invasion to epithelial cells. Subsequently, we found that the mean values of adhesion and invasion in the MDR group were significantly higher than those observed in the non-MDR group. Likewise, a significant positive correlation was found among adhesive and invasive capacities of Pseudomonas strains and their antibiotic resistance phenotypes.

Assessment of phenotypic and genotypic antibiotic susceptibility of vaginal Lactobacillus sp.

AIM: To assess antibiotic susceptibility of vaginal lactobacilli strains and provide the data required for assessing the potential of antibiotic resistance risk of new strains selected as probiotic. METHODS AND RESULTS: Potential probiotic vaginal lactobacilli used in the study included 31 vaginal strains of Lactobacillus crispatus (n = 27), Lactobacillus gasseri (n = 3) and Lactobacillus jensenii (n = 1) obtained from the collection of Competence Centre on Health Technologies. Two commercial probiotic strains were used as controls (Lactobacillus rhamnosus GR-1 and Lactobacillus fermentum RC-14). The phenotypic and genotypic antibiotic resistances of the strains were determined by E-test and PCR methods. The location (chromosomal DNA or plasmid) of antibiotic resistance genes was also detected. All lactobacilli strains expressed high level of resistance to kanamycin, metronidazole, norfloxacin and trimethoprim/sulphamethoxazole. Some of the strains also expressed resistance to other antibiotics (chloramphenicol, vancomycin) indicating acquired resistance. I class integrons were found in 20% (6/31) of the strains. The RPP (ribosomal protection protein) gene was found to be positive in 30% (9/31) of the strains. Only one L. jensenii strain was determined with tet(M) gene. The tet(K) gene was positive in 26·7% (8/31) and erm(B) gene in 43·3% (13/31) of strains. Three RPP and both four tet(K) and erm(B) genes were located in plasmids. CONCLUSIONS: High antibiotic resistance to clinically important antibiotics was demonstrated, including metronidazole, sulphonamides, aminoglycoside and quinolones. In addition, acquired tetracycline and erythromycin resistance genes were detected in either plasmid or chromosomal DNA of certain isolates, in some of the cases for the first time in the literature. It appears that antibiotic resistance genes erm(B) and tet(K) are widely spread in vaginal lactobacilli. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides new data about antimicrobial resistance and genotypic diversity of vaginal Lactobacillus isolates. In addition, it provides data assessing the potential of antibiotic resistance risk of new strains selected as probiotic.

Antibacterial resistance in Streptococcus pyogenes (GAS) from healthy carriers and tonsillitis patients and association with antibacterial sale in the Faroe Islands.

The aim of this study was to investigate the antibacterial resistance of Streptococcus pyogenes (GAS), and correlate the findings with the sales of erythromycin and tetracycline. General practitioners in the Faroe Islands were recruited to send oropharyngeal swabs. From an ongoing pneumococcal study, nasopharyngeal swabs were sampled from healthy children 0-7 years of age. Erythromycin susceptibility data from Iceland were obtained from the reference laboratory at the Landspitali University Hospital. Susceptibility testing in the Faroe Islands and Iceland was performed according to CLSI methods and criteria. The resistance rate to erythromycin and tetracycline found in patients in the Faroe Islands in 2009/2010 was 6% and 30% respectively. Tetracycline resistance in patients declined significantly from 2009 to 2010 (37-10%, p-value = 0.006 < 0.05) and differed significantly between age groups (p-value = 0.03 < 0.05). In Iceland, there was a peak in erythromycin resistance in 2008 (44%) and a substantial decrease in 2009 (5%). Although the prevalence of erythromycin and tetracycline resistance in the Faroe Islands and Iceland may be associated with antimicrobial use, sudden changes can occur with the introduction of new resistant clones.

Assessment of anaerobic bacterial diversity and its effects on anaerobic system stability and the occurrence of antibiotic resistance genes.

This study evaluated the link between anaerobic bacterial diversity and, the biodegradation of antibiotic combinations and assessed how amending antibiotic combination and increasing concentration of antibiotics in a stepwise fashion influences the development of resistance genes in anaerobic reactors. The biodegradation, sorption and occurrence of the known antibiotic resistance genes (ARGs) of erythromycin and tetracycline were investigated using the processes of UV-HPLC and qPCR analysis respectively. Ion Torrent sequencing was used to detect microbial community changes in response to the addition of antibiotics. The overall results indicated that changes in the structure of a microbial community lead to changes in biodegradation capacity, sorption of antibiotics combinations and occurrence of ARGs. The enhanced biodegradation efficiency appeared to generate variations in the structure of the bacterial community. The results suggested that controlling the ultimate Gram-negative bacterial community, especially Acinetobacter-related populations, may promote the successful biodegradation of antibiotic combinations and reduce the occurrence of ARGs.

Prevalence and resistance patterns of commensal S. aureus in community-dwelling GP patients and socio-demographic associations. A cross-sectional study in the framework of the APRES-project in Austria.

BACKGROUND: The aim of the present study was to assess the prevalence and resistance of commensal S. aureus in the nasal microbiota of community-dwelling persons in Austria, as well as to identify possible associations with socio-demographic factors. Multi-drug resistance in this population was additionally studied. METHOD: This cross-sectional study was conducted within the context of the European APRES project. In nine European countries, nasal swabs were collected from 32,206 general practice patients who received care for non-infectious reasons. In Austria, 20 GPs attempted to recruit 200 consecutive patients without infectious diseases, with each patient completing demographic questionnaires as well as providing a nose swab sample. Isolation, identification, and resistance testing of S. aureus were performed. Statistical analyses included subgroup analyses and logistic regression models. RESULTS: 3309 nose swabs and corresponding questionnaires from Austrian subjects were analyzed. S. aureus was identified in 16.6 % (n = 549) of nose swabs, of which 70.1 % were resistant against one or more antibiotics, mainly penicillin. S. aureus carrier status was significantly associated with male sex (OR 1.6; 1.3-2.0), younger age (OR 1.3; 1.0-1.8), living in a rural area (OR 1.4; 1.1-1.7) and working in the healthcare sector (OR 1.5; 1.0-2.1). Multi-drug resistances were identified in 13.7 % (n = 75) of the S. aureus carriers and 1.5 % (n = 8) tested positive for MRSA. The highest resistance rate was observed against penicillin (64.8 %), followed by azithromycin (13.5 %) and erythromycin with 13.3 %. CONCLUSION: This study describes the prevalence and resistance patterns of commensal S. aureus in community-dwelling persons in Austria and shows that differences exist between socio-demographic groups. Demographic associations have been found for S. aureus carriers but not for carriers of resistant S. aureus strains. Only two thirds of S. aureus strains were found to be resistant against small spectrum penicillin. As it is recognized that one of the corner stones for the containment of antibiotic resistance is the appropriate prescription of antibiotics in the outpatient sector, this finding lends support to the avoidance of prescription of broad-spectrum antibiotics to treat S. aureus infections in the community.

[Inhibition of methanogenium by erythromycin and its domestation].

Erythromycin is a kind of antibiotic drugs with certain biological toxicity. In order to investigate the inhibitory effect of erythromycin on methanogens and its acclimation capacity, Anaerobic Toxicity Assay (ATA) and continuous experiment were conducted in anaerobic bottles and the Up-flow Anaerobic Sludge Blanket Reactor (UASB), respectively, to determine the accumulated methane production, ratio of methane production rate, COD removal efficiency, and methane content. The results showed that the methane production ratio was reduced to 56.1% in the presence of 150 mg x L(-1) of erythromycin and it was reduced by 99% when the erythromycin reached 250 mg x L(-1), indicating that the activity was completely inhibited. Keeping the erythromycin at an concentration of 20 mg x L(-1) in the process of continuous operation for 60d, the COD removal efficiency and methane content reached up to 81.4% and 64.2%, respectively. The results suggested that erythromycin had an inhibitory effect on methane bacteria, and the half inhibitory concentration was 150 mg x L(-1) (IC50:150 mg x L(-1)). The COD removal efficiency and methane content were increased by 15.13% and 22.05%, respectively, after domestication for 60 d.

Sub-inhibitory concentrations of antibiotics and wastewater influencing biofilm formation and gene expression of multi-resistant Pseudomonas aeruginosa wastewater isolates.

Sub-inhibitory concentrations of antibiotics, which are found in environmental water systems and sewage plants due to an increased use in therapeutical and preventive fields, influence bacterial behavior in biofilms. The application of sulfamethoxazole, erythromycin, and roxithromycin induced changes in biofilm dynamics regarding biomass formation, spatial structure and specific gene expression in different Pseudomonas aeruginosa isolates. Exposing multi-resistant environmental isolated strains for 17 h to environmental concentrations of antibiotics or wastewater, directly, an increase in biofilm biomass and thickness could be observed for each strain. Additionally, multi-resistant strains responded to the applied growth conditions with changes in transcriptional activity. Here, sub-inhibitory concentrations of macrolides specifically upregulated expression of quorum sensing genes (rhlR, lasI), whereas sulfonamides and municipal wastewater, instead upregulated expression of specific resistant genes (sul1) and efflux pumps (mexD). Antibiotic sensitive isolates demonstrated an overall higher transcriptionally activity, but did not show a specific gene response to the applied exogenous stimuli. Furthermore, the presence of low concentrated antibiotics induced also phenotypical change in the biofilm architecture observed by 3D-imaging.

Assessment of tetracycline and erythromycin resistance transfer during sausage fermentation by culture-dependent and -independent methods.

The food chain is considered one of the main routes of antibiotic resistance diffusion between animal and human population. The resistance to antimicrobial agents among enterococci could be related to the efficient exchange of transferable genetic elements. In this study a sausage model was used to evaluate the persistence of antibiotic resistant enterococci during meat fermentation and to assess horizontal gene transfer among bacteria involved in meat fermentation. Enterococcus faecalis OG1rf harbouring either pCF10 or pAMß1 plasmid was used as donor strain. The analysis of population dynamics during fermentation confirmed that the human isolate E. faecalis OG1rf was able to colonize the meat ecosystem with similar growth kinetics to that of food origin enterococci and to transfer the mobile genetic elements coding for tetracycline and erythromycin resistances. Transconjugant strains were detected after only two days of fermentation and increased their numbers during ripening even in the absence of selective antibiotic pressure. By means of culture-dependent and -independent molecular techniques, transconjugant strains carrying both tetracycline and erythromycin resistance genes were identified in enterococci, pediococci, lactobacilli and staphylococci groups. Our results suggest that the sausage model provides a suitable environment for horizontal transfer of conjugative plasmids and antibiotic resistance genes among food microbiota.

Determination of time-dependent inactivation of CYP3A4 in cryopreserved human hepatocytes and assessment of human drug-drug interactions.

Assessment of time-dependent inhibition (TDI), especially CYP3A4, is an important parameter for preclinical and clinical development. The use of human liver microsomes (HLM) is the most common in vitro matrix to assess TDI, but this often leads to an overprediction of an actual effect observed clinically. Recently, the use of human hepatocytes has been hypothesized as a more relevant and possibly predictive matrix for the assessment of CYP3A4 TDI. Our work evaluates and optimizes three different human hepatocyte assays for the assessment of CYP3A4 TDI using pooled cryopreserved human hepatocytes. Using two of the optimized methods, the time-dependent inhibition kinetic parameters (K(I) and k(inact)) for four known CYP3A4 TDI (diltiazem, erythromycin, verapamil, and troleandomycin) were determined. When comparing TDI in HLM, the K(I) values from hepatocytes were in general 4- to 13-fold higher than that in HLM, whereas the k(inact) values in human hepatocytes were similar or slightly higher or lower depending on the inhibitor. The inactivation potency (k(inact)/K(I)) for four tested CYP3A4 inactivators in human hepatocytes was generally lower than that in HLM due to either lower affinity (K(I)) or lower inactivation rate (k(inact)) or both. When drug interactions were simulated with Simcyp using either HLM or human hepatocyte data, the predictions using the kinetic parameters from human hepatocytes resulted in a much better simulated change in pharmacokinetics compared with observed clinical data.

Rapid assessment of antibacterial activity against Mycobacterium ulcerans by using recombinant luminescent strains.

Mycobacterium ulcerans causes Buruli ulcer, an emerging infectious disease for which antimicrobial therapy has only recently proven to be beneficial. The discovery and development of new drugs against M. ulcerans are severely impeded by its very slow growth. Recombinant bioluminescent strains have proven useful in drug development for other mycobacterial infections, but the ability of such strains to discriminate bacteriostatic from bactericidal activity has not been well demonstrated. We engineered recombinant M. ulcerans strains to express luxAB from Vibrio harveyi. In drug susceptibility tests employing a wide range of antimicrobial agents and concentrations, the relative light unit (RLU) count measured in real time was a reliable surrogate marker for CFU counts available 3 months later, indicating utility for the rapid determination of drug susceptibility and discrimination of bacteriostatic and bactericidal effects. A second important finding of this study is that the addition of subinhibitory concentrations of the ATP-binding cassette transporter inhibitor reserpine increases the susceptibility of M. ulcerans to tetracycline and erythromycin, indicating that drug efflux may explain at least part of the intrinsic resistance of M. ulcerans to these agents.

Sub-antibiotic doses of erythromycin as a prokinetic in abdominal surgeries: reviving the old.

All patients undergoing major abdominal procedures have some degree of gastricatony in the immediate postoperative period, presenting mainly with vomiting. Many prokinetic agents have been used in the past, but none is a universal remedy. Studies showed that subantibiotic doses of erythromycin, a macrolide antibiotic and motilin agonist, accelerates gastric emptying. This study investigated whether preoperative subantibiotic dose oral erythromycin (250 mg), altered residual gastric volume and postoperative adverse effects in patients scheduled for abdominal surgeries. Erythromycin was compared with the commonly used prokinetic metoclopramide and antiemetic ondansetron, in terms of prokinetic efficacy, cost and adverse effects. In a double-blind study, eighty patients (20 each) were allocated randomly to receive orally, either erythromycin 250 mg (E250) or erythromycin 500 mg (E500), or 10 mg metoclopramide (M), or 4 mg ondansetron (Z), an hour pre-induction of anesthesia. Preoperative oral erythromycin in subantibiotic dose 250 mg elicited a significntly lower residual gastric volume (P < 0.001) and a lower VAS for vomiting, compared with ondansetron. As for metoclopramide and erythromycin 500, residual gastric volume was comparable, but E 250 had a lower VAS for vomiting than both groups. Rescue remedy for vomiting was required for groups E500, M and Z (100, 10 and 10%) compared to 0% in group E250. Ultimately, subantibiotic oral dose of erythromycin (250 mg), given 1 hr preoperatively, is an inexpensive prokinetic alternative with a promising post-operative profile which may be superior to the inexpensive prokinetic metoclopramide with known adverse effects, and the expensive antiemetic ondansetron.

Assessment of antimicrobial resistance transfer between lactic acid bacteria and potential foodborne pathogens using in vitro methods and mating in a food matrix.

The transferability of antimicrobial resistance from lactic acid bacteria (LAB) to potential pathogenic strains was studied using in vitro methods and mating in a food matrix. Five LAB donors containing either erythromycin or tetracycline resistance markers on transferable elements were conjugally mated with LAB (Enterococcus faecalis, Lactococcus lactis) and pathogenic strains (Listeria spp., Salmonella ssp., Staphylococcus aureus, and Escherichia coli). In vitro transfer experiments were carried out with the donors and recipients using both the filter and plate mating methods. The food matrix consisted of fermented whole milk (fermented with the LAB donors) with the pathogenic recipients added as contaminants during the production process. All transconjugants were confirmed by phenotypic and molecular methods. Erythromycin resistance transfer from LAB strains to Listeria spp. was observed using both in vitro mating methods at high transfer frequencies of up to 5.1 x 10(-4) transconjugants per recipient. Also, high frequency transfer (ranging from 2.7 x 10(-8) up to 1.1 x 10(-3) transconjugants per recipient) of both erythromycin and tetracycline-resistance was observed between LAB species using in vitro methods. No resistance transfer was observed to Salmonella spp., Staphylococcus aureus, and E. coli. The only conjugal transfer observed in the fermented milk matrix was for tetracycline resistance between two LAB strains (at a transfer frequency of 2.6 x 10(-7) transconjugants per recipients). This study demonstrates the transfer of antimicrobial resistance from LAB to Listeria spp. using in vitro methods and also the transfer of resistance between LAB species in a food matrix. It highlights the involvement of LAB as a potential source of resistance determinants that may be disseminated between LAB and pathogenic strains including Listeria spp. Furthermore, it indicates that food matrices such as fermented milks may provide a suitable environment to support gene exchange.

23S rRNA mutation A2074C conferring high-level macrolide resistance and fitness cost in Campylobacter jejuni.

To examine the development of macrolide resistance in Campylobacter jejuni and assess the fitness of the macrolide-resistant mutants, two macrolide-susceptible C. jejuni strains, American Type Culture Collection (ATCC) 33291 and H1, from different geographic areas were exposed to tylosin in vitro. Multiple mutant strains were obtained from the selection. Most of the high-level macrolide-resistant strains derived from the selection exhibited the A2074C transversion in all three copies of 23S rRNA and displayed strong stability in the absence of antibiotic selection pressure. The competition experiments demonstrated that the strains containing the A2074C transversion imposed a fitness cost in competition mixtures. In addition, the fitness cost of the mutation was not ameliorated after approximately 500 generations of evolution under laboratory conditions. These findings indicate that the A2074C transversion in C. jejuni is not only correlated with stable and high-level macrolide resistance but also associated with a fitness cost.

Use of multichannel electrointestinography for noninvasive assessment of myoelectrical activity in the cecum and large colon of horses.

OBJECTIVE: To evaluate whether changes in myoelectrical activity in the cecum and large colon of horses can be detected via multichannel electrointestinography (EIG). ANIMALS: 6 healthy mature horses. PROCEDURES: Each horse underwent 3 EIG procedures. Intestinal myoelectrical activity (cecum and large colon) was recorded during a 20-minute period following i.v. administration of physiologic saline (0.9% NaCl) solution (20 mL; baseline), erythromycin lactobionate (0.5 mg/kg), or detomidine (0.015 mg/kg); intestinal contractions were concurrently viewed via B-mode ultrasonography. By use of computer software, 8-channel EIG recordings were analyzed and the mean of the dominant frequency (a measure of the rhythmicity of gastric electrical activity) expressed in cycles per minute (cpm) was obtained. Total power (muV(2)) was calculated, and treatment effect was expressed as the power ratio (ie, treatment-associated power divided by the baseline power). RESULTS: The dominant frequency cpm values were not stable, and no significant differences between treatments were detected. Compared with the effects of saline solution treatment, detomidine significantly reduced the mean cecal and colonic power ratios. Erythromycin significantly reduced the cecal power ratio and increased the colonic power ratio, although the increase was significant in only 1 channel. Ultrasonographic findings and total power (predominantly from the long-distance electrode pairs) were significantly correlated. CONCLUSIONS AND CLINICAL RELEVANCE: In horses, EIG was useful for assessment of changes in myoelectrical activity in the cecum and large colon. Multiple electrodes should be used to cover a larger area of the intestine, and agreement between multiple channels is needed to make the analysis meaningful.