Effects Of Broad-spectrum Antibiotics Research Articles

Antibiotics administration alleviates the high fat diet-induced obesity through altering the lipid metabolism in young mice.

Currently, there is a global trend of rapid increase in obesity, especially among adolescents. The antibiotics cocktails (ABX) therapy is commonly used as an adjunctive treatment for gut microbiota related diseases, including obesity. However, the effects of broad-spectrum antibiotics alone on young obese hosts have rarely been reported. In the present study, the 3-week-old C57BL/6J male mice fed a high-fat diet (HFD) were intragastric administration with ampicillin, vancomycin, metronidazole or neomycin for 30 days. The lipid metabolites in plasma were assessed by biochemical assay kits, and genes related to lipid metabolite in the white adipose were assessed by qPCR. To further analyze the underlying mechanisms, the expression of genes related to lipid metabolism, inflammatory reactions and oxidative stress in the liver were determined by qPCR assay. In addition, the expression of oxidative damage-associated proteins in the liver were detected by western blot. The results showed that oral antibiotics exposure could reduce body weight and fat index in HFD-fed mice, concurrent with the increase of white adipose lipolysis genes and the decrease of hepatic lipogenic genes. Furthermore, antibiotics treatment could clearly reverse the HFD-induced elevation of oxidative damage-related proteins in the liver. Together, these findings will provide valuable clues into the effects of antibiotics on obesity.

The Response of the Rodent Gut Microbiome to Broad-Spectrum Antibiotics Is Different in Males and Females.

Gut microbiome composition is different in males and females, but sex is rarely considered when prescribing antibiotics, and sex-based differences in gut microbiome recovery following antibiotic treatment are poorly understood. Here, we compared the effects of broad-spectrum antibiotics on both the stool and small bowel microbiomes in male and female rats. Adult male and female Sprague Dawley rats were exposed to a multi-drug antibiotic cocktail for 8 days, or remained unexposed as controls. Following cessation of antibiotics, rats were monitored for an additional 13-day recovery period prior to euthanasia. Baseline stool microbiome composition was similar in males and females. By antibiotic exposure day 8 (AbxD8), exposed male rats exhibited greater loss of stool microbial diversity compared to exposed females, and the relative abundance (RA) of numerous taxa were significantly different in exposed males vs. exposed females. Specifically, RA of phylum Proteobacteria and genera Lactobacillus, Sutterella, Akkermansia, and Serratia were higher in exposed males vs. exposed females, whereas RA of phyla Firmicutes and Actinobacteria and genera Turicibacter and Enterococcus were lower. By 13 days post antibiotics cessation (PAbxD13), the stool RA of these and other taxa remained significantly different from baseline, and also remained significantly different between exposed males and exposed females. RA of phyla Firmicutes and Actinobacteria and genus Enterococcus remained lower in exposed males vs. exposed females, and genus Sutterella remained higher. However, RA of phylum Proteobacteria and genus Akkermansia were now also lower in exposed males vs. females, whereas RA of phylum Bacteroidetes and genus Turicibacter were now higher in exposed males. Further, the small bowel microbiome of exposed rats on PAbxD13 was also significantly different from unexposed controls, with higher RA of Firmicutes, Turicibacter and Parabacteroides in exposed males vs. females, and lower RA of Bacteroidetes, Proteobacteria, Actinobacteria, Oscillospira, Sutterella, and Akkermansia in exposed males vs. females. These findings indicate that broad-spectrum antibiotics have significant and sex-specific effects on gut microbial populations in both stool and the small bowel, and that the recovery of gut microbial populations following exposure to broad-spectrum antibiotics also differs between sexes. These findings may have clinical implications for the way antibiotics are prescribed.

The genetic basis for medium‐dependent bacteriophage infection

While broad spectrum antibiotics have served a major role in combatting bacterial pathogens over the past decades, we are currently witnessing the rise of antibiotic‐resistant pathogenic strains. Moreover, the harmful effects of broad spectrum antibiotics on the natural human microbiome have been demonstrated in numerous cases. For these reasons, bacteriophages have been recently gaining attention as promising candidates for treatment of bacterial‐related diseases. Bacteriophages are natural viruses that infect and often kill specific bacterial strains; it is the phages’ high accuracy and specificity, alongside their natural origin, that highlights their value as an alternative treatment for diseases with bacterial involvement.However, a major challenge in screening for bacteriophages relevant for treatment of human diseases is the phages’ medium‐dependent infection trait. Several factors have been suggested to take a role in explaining this discrepancy, including the mechanism of infection, the spatial structure of the phage capsid, the biochemical characteristics of the bacterial cell wall, and other phage life‐cycle features. However, a comprehensive model for characterizing the media‐range for phage infection is still missing. This uncertainty often translates into multiple laborious screening rounds, since common practice in vitro assays are typically based on either liquid or solid medium infection, whereas the state of matter relevant for in vivo application is often hard to determine; thus, one must screen the same phages using multiple assays.In attempt to lay the groundwork for such a model, in this work we set out to determine the genetic‐basis for medium‐dependent infection of pathogenic Klebsiella pneumoniae phages. To this end we obtained 285 K. pneumonia strains, that span across the entire domain of known K. pneumonia genotypes. Subsequently we obtained 50 phages that were able to propagate on at least some of these hosts. For each phage‐host pair we determined whether infection occurs in two different assays: in liquid culture, and on solid agar plates. As expected, the results show that liquid medium enables more phage infections compared to solid; this is traditionally associated with the higher mobility enabled by the liquid. However, cases where a phage was able to infect its host in solid, but not in liquid, were observed as well. Finally, by analyzing genomic differences between the phages in the experiment we were able to discern several genetic features that correlate with the observed phenotype. Further exploration of these genetic features are the basis for a constructing a model for characterizing the media‐range for phage infection.

Microbiota and Graft-versus Host disease: a double-edged sword.

Microbiota and Graft-versus Host disease: a double-edged sword.

The comparative study of the bactericidal properties of laser and photodiode radiation in the violet region of the spectrum (405 nm) on the bacteria of the mouth cavity

The ever increasing number of the patients presenting with postoperative wound infections and abscess is attributed by the majority of the authors to the significant changes in microflora, the impairment of therapeutic effectiveness of broad-spectrum antibiotics, and the reduction of the immune responsiveness. The present study has demonstrated that the microorganisms present in the mouth cavity show high in vitro sensitivity to laser radiation in the violet range of the spectrum. Specifically, irradiation at a distance of 3 cm from the treated surface and the time of exposure 5 minutes (at the power density 70 mW/cm2) produced a well apparent bacteriostatic effect whereas irradiation of a surface positioned 1 cm from the emitting source at the power density of 150 mW/cm2 caused complete eradication of the microorganisms.

Treatment as diagnosis and diagnosis as treatment: empirical management of presumptive tuberculosis in India.

Mismanagement of TB is a concern in the Indian private sector, and empirical management might be a key contributor. To understand factors associated with empirical diagnosis and treatment of presumed TB in India's private sector and examine their effects on TB care. In this ethnographic study, 110 private practitioners of varying qualification who interacted with TB patients (90 in Mumbai and 20 in Patna) were interviewed, and a subset was observed while providing clinical care. Interviews and observations were analysed for indicators of empirical diagnosis and treatment. All non-specialist practitioners began antibiotic treatment, especially quinolones, for persistent cough before prescribing a test. Several factors contribute to empirical management. These include a common practice use of medications as diagnostic tools, a desire to provide rapid symptom relief to patients, a desire to manage illness costs effectively, uncertainty about the presentation of TB, the effects of broad spectrum antibiotics on TB symptomology, and uncertainty about the accuracy of available TB tests. Empiricism in general and in TB care is widespread in the urban private sector in India. Ethnography might offer useful insights for addressing this in public-private mix models.

Helicobacter pylori Eradication Causes Perturbation of the Human Gut Microbiome in Young Adults

BackgroundAccumulating evidence shows that Helicobacter pylori protects against some metabolic and immunological diseases in which the development of these diseases coincide with temporal or permanent dysbiosis. The aim of this study was to assess the effect of H. pylori eradication on the human gut microbiome.MethodsAs part of the currently on-going ESSAY (Eradication Study in Stable Adults/Youths) study, we collected stool samples from 17 H. pylori-positive young adult (18–30 years-old) volunteers. The same cohort was followed up 6, 12 and 18 months-post H. pylori eradication. The impact of H. pylori on the human gut microbiome pre- and post-eradication was investigated using high throughput 16S rRNA gene (V3-V4 region) sequencing using the Illumina Miseq followed by data analysis using Qiime pipeline.ResultsWe compared the composition and diversity of bacterial communities in the fecal microbiome of the H. pylori-positive volunteers, before and after H. pylori eradication therapy. The 16S rRNA gene was sequenced at an average of 150,000–170,000 reads/sample. The microbial diversity were similar pre- and post-H. pylori eradication with no significant differences in richness and evenness of bacterial species. Despite that the general profile of the gut microbiome was similar pre- and post-eradication, some changes in the bacterial communities at the phylum and genus levels were notable, particularly the decrease in relative abundance of Bacterioidetes and corresponding increase in Firmicutes after H. pylori eradication. The significant increase of short-chain fatty acids (SCFA)-producing bacteria genera could also be associated with increased risk of metabolic disorders.ConclusionsOur preliminary stool metagenomics study shows that eradication of H. pylori caused perturbation of the gut microbiome and may indirectly affect the health of human. Clinicians should be aware of the effect of broad spectrum antibiotics used in H. pylori eradication regimen and be cautious in the clinical management of H. pylori infection, particularly in immunocompromised patients.

Effects of broad-spectrum antibiotics on the metabolism and pharmacokinetics of ginsenoside Rb1: A study on rats׳ gut microflora influenced by lincomycin

Ginsenoside Rb1 is a biologically active compound that is abundant in ginseng (Panax ginseng). It has been reported that ginsenosides could be metabolized by enzymes and bacteria in the large intestine. In this study, the effects of intestinal bacteria on the metabolism and pharmacokinetics of ginsenoside Rb1 were investigated using lincomycin-treated rat models (4.8g/kg and 0.12g/kg). Specifically, ginsenoside Rb1 was incubated anaerobically with rat fecal suspensions obtained from the control and two model groups at 0, 6, 12, 24, and 48h. Ginsenoside Rb1 and its metabolites were determined by HPLC analysis. Compared with the normal rats case where Rd and compound K were detected in the incubation mixture, ginsenoside Rd and F2 were found in the 0.12g/kg group, but only Rd was found in the 4.8g/kg group. Moreover, fecal β-glucosidase activity was significantly lower in lincomycin-treated (0.12g/kg and 4.8g/kg) model rats. After administration of Rb1 to rats, ginsenoside Rb1 and its metabolites Rd, Rg3, and Rh2 were detectable in normal rat urine, whereas none was detected in the two model groups. The plasma concentration-time Rb1 were compared between model groups and normal rats. The systemic exposure as evidenced by the AUC and T1/2 values was significantly higher in model groups than in normal rats. Our findings demonstrated that consumption of lincomycin could lead to the formation of specific metabolites and pharmacokinetic changes of ginsenoside Rb1 in the gut, attributed to alterations in metabolic activities of intestinal bacteria. Our results also suggested that patients who want to use intestinal bacteria-metabolized drugs such as ginseng (Panax ginseng) should pay attention to the profile of intestinal bacteria or potential drug interactions to ensure therapeutic efficacy.

Short-term effect of antibiotics on human gut microbiota.

From birth onwards, the human gut microbiota rapidly increases in diversity and reaches an adult-like stage at three years of age. After this age, the composition may fluctuate in response to external factors such as antibiotics. Previous studies have shown that resilience is not complete months after cessation of the antibiotic intake. However, little is known about the short-term effects of antibiotic intake on the gut microbial community. Here we examined the load and composition of the fecal microbiota immediately after treatment in 21 patients, who received broad-spectrum antibiotics such as fluoroquinolones and β-lactams. A fecal sample was collected from all participants before treatment and one week after for microbial load and community composition analyses by quantitative PCR and pyrosequencing of the 16S rRNA gene, respectively. Fluoroquinolones and β-lactams significantly decreased microbial diversity by 25% and reduced the core phylogenetic microbiota from 29 to 12 taxa. However, at the phylum level, these antibiotics increased the Bacteroidetes/Firmicutes ratio (p = 0.0007, FDR = 0.002). At the species level, our findings unexpectedly revealed that both antibiotic types increased the proportion of several unknown taxa belonging to the Bacteroides genus, a Gram-negative group of bacteria (p = 0.0003, FDR<0.016). Furthermore, the average microbial load was affected by the treatment. Indeed, the β-lactams increased it significantly by two-fold (p = 0.04). The maintenance of or possible increase detected in microbial load and the selection of Gram-negative over Gram-positive bacteria breaks the idea generally held about the effect of broad-spectrum antibiotics on gut microbiota.

Fidaxomicin: A new fight against clostridium difficile-associated diarrhea

Clostridium difficile-associated diarrhea (CDAD) occurs commonly as a side effect of broad-spectrum antibiotics. Drugs approved for CDAD are only two of them, metronidazole and vancomycin. Most promising drug for treatment of CDAD is vancomycin, but due to emergence of hypervirulent strains, outcomes have become poor. Fidaxomicin has being approved lately for treatment of CDAD, which has shown good results as compared to vancomycin. Fidaxomicin inhibits protein synthesis by inhibiting transcription carried out by sigma subunit of RNA polymerase. Fidaxomicin has been seen to be a well tolerated, with minimal adverse effects. Clinical trials has showed that fidaxomicin has similar results to vancomycin in showing clinical response, whereas it was superior to vancomycin in having sustained clinical effect, in CDAD.

Antibiotics Can Interfere with Priming of Neutrophils by Gut Microbiota

Administering broad-spectrum antibiotics to infected patients can also knock out benign intestinal bacteria, which play a key role in overall immunity by priming neutrophils in bone marrow, say researchers at the University of Pennsylvania (Penn) School of Medicine in Philadelphia. Because such losses of gut flora can disrupt host-immune responses, heavy-duty antibiotic treatments thus raise the risk for such patients of developing severe secondary infections, particularly while in hospital settings. On the plus side, replacing the bacterial signals that routinely prime neutrophils may someday provide a valuable means for offsetting these disruptive effects of broad-spectrum antibiotics, suggests Jeffrey Weiser, a professor of microbiology and pediatrics at Penn, and his collaborators.

An in vitro assessment of the effects of broad-spectrum antibiotics on the human gut microflora and concomitant isolation of a Lactobacillus plantarum with anti-Candida activities

An in vitro assessment of the effects of broad-spectrum antibiotics on the human gut microflora and concomitant isolation of a Lactobacillus plantarum with anti-Candida activities

Stimulation of mucosal inflammatory activity by the normal fecal flora in a rat model of colitis

: Bacteria and their products stimulate inflammatory responses and may play a role in the pathogenesis of inflammatory bowel diseases. We investigated interactions between fecal flora and injured colonic mucosa using the trinitrobenzenesulfonic acid model of colitis in the rat. First, we tested the effects of broad-spectrum antibiotics administered at different times after induction of colitis. Second, in rats pretreated with antibiotics, we studied the effects of reintroduction of fecal flora on the release of inflammatory mediators and on the morphology of colonic lesions. Antibiotics reduced colonic lesion scores when started on day 1 after induction of colitis, but had no significant effect when started on day 7. In antibiotic-treated rats, intracolonic administration of a suspension of fecal contents 6 h after induction of colitis enhanced mucosal inflammatory activity and aggravated lesion scores. This effect was not observed when the suspension was administered 3 days after induction. Sonication of the suspension inhibited bacterial growth in aerobic and anaerobic cultures, and abolished its effect on colonic inflammation. In this model, bacteria of the common flora stimulate inflammatory activity and play a role in the induction of colonic mucosal lesions.

Effects of broad-spectrum antibiotics on colonization of gastrointestinal tracts of mice by Candida albicans.

Three-month-old, male, Crl:CD1 (ICR) BR mice were fed chow containing Candida albicans or regular chow. Subsequently, both groups were given either antibiotics or normal saline for 10 days. Stool cultures were performed immediately before administration, at the end of antibiotic administration, and 1 week after the discontinuation of antibiotics, to determine the effect on the concentration of C. albicans in the stools. The stools of mice fed C. albicans and given antibiotics had substantially higher Candida counts than those of control mice fed C. albicans and given saline. Significantly higher candidal concentrations were observed in the stools of mice given chloramphenicol compared with those of mice given ciprofloxacin, sulfamethoxazole-trimethoprim, and ampicillin. No mice developed histopathological evidence of local gastrointestinal invasion or disseminated candidiasis. In this mouse model, Candida colonization increases substantially after the administration of antimicrobial agents with broad spectra and anaerobic activities.

Effect ob broad-spectrum antibiotics on in vitro synthesis of DNA in the rabbit colon.

Rabbit colonic mucosa was cultured in vitro in the presence of broad-spectrum antibiotics. DNA synthesis, as determined by [3H]thymidine incorporation into DNA, was inhibited by clindamycin (32%) and tetracycline (28%). Penicillin G, ampicillin, and metronidazole had no effect. When bile acids were added to the incubation at a concentration of 10 mM, the more lipophilic drug, lincomycin, inhibited DNA synthesis by 38% (cholic acid) and by 23% (chenic acid). Bile acids alone did not alter thymidine incorporation. Inhibition by clindamycin demonstrated a gradual dose-response curve, with inhibition first noted at about 20 microgram of antibiotic/ml and maximal inhibition at 1,000 microgram/ml. The more biologically active metabolite of clindamycin, N-demethylclindamycin, inhibited DNA synthesis at concentrations of as low as 10 microgram/ml. The inhibition was reversible, and the drugs did not affect thymidine uptake, thymidine pool concentrations, or protein or mucopolysaccharide synthesis at concentrations of up to 300 microgram/ml. These data demonstrate a direct but reversible toxic action on mammalian colonic mucosa by certain antibiotics implicated in the production of pseudomembranous colitis and are consistent with the hypothesis that such a toxic action may be one factor in the pathogenesis of antibiotic-associated colitis.

Studies on the Influence of Terephthalic Acid and Broad Spectrum Antibiotics on Egg Production and Egg Shell Coloration in Caged Layers

TEREPHTHALIC ACID has been shown to increase the effectiveness of broad spectrum antibiotics in the domestic fowl. Terephthalic acid has increased the activity of the tetracycline antibiotics (oxytetracycline and chlortetracycline) in combatting certain diseases in poultry (Peterson, 1958, 1960; Peterson et al., 1959; Shelton and Olson, 1958). Reports by Peterson et al. (1959), Price et al. (1959) and Pensack et al. (1960) have shown that terephthalic acid fed with the tetracycline antibiotics (chlortetracycline and oxytetracycline) will increase the blood serum antibiotic level. The above studies mainly concern short term effects of terephthalic acid on antibiotic potentiation with little evidence of other physiological effects of terephthalic acid in the laying bird. In preliminary studies in this laboratory, a yellowish coloration was observed in egg shells from hens fed high levels of chlortetracycline. A review of previous work with antibiotics and terephthalic acid does not reveal any reported effect of the drugs …

Use of Nystatin (Mycostatin) to Retard Yeast Growth on Chlortetracycline-treated Chicken Meat

ABSTRACT THE effectiveness of broad spectrum antibiotics for the control of red meat spoilage has been reported in a series of papers by Cahill et al. (1952), Lepovetsky et al. (1953), Goldberg et al. (1953), and Weiser et al. (1953 (1954). Tarr et al. (1952 (1954), and Tarr (1954) reported that antibiotics can be used to prolong the shelf life of fish as well as red meat. The use of antibiotics for the control of poultry meat spoilage was reported by Kohler et al. (1955) and Ziegler and Stadelman (1955). In studies using chicken halves dipped in chlortetracycline solutions, Ziegler and Stadelman (1955) found that the organisms predominant on the chlortetracycline-treated halves were yeasts having the shape and budding characteristics of the family Saccharomycetacae. Tarr et al. (1952) also reported noticeable yeast growth on meats and fish treated with broad spectrum antibiotics. The purpose of the work reported herein was to . . .