Oral Administration Of Vancomycin Research Articles

Oral teicoplanin administration suppresses recurrence of Clostridioides difficile infection: Proof of concept

ObjectivesTeicoplanin is a potential antimicrobial candidate for Clostridioides difficile infection (CDI) treatment. However, the therapeutic potential of teicoplanin against severe CDI has not been clinically proven. In the present study, we investigated the efficacy of oral teicoplanin administration against severe CDI and the recurrence of severe CDI after teicoplanin treatment in a mouse model. MethodsA lethal CDI mouse model was established by colonizing the mice with C. difficile ATCC® 43255; they were orally administered teicoplanin (128 mg/kg/d) or vancomycin (160 mg/kg/d) for 10 d, 24 h after C. difficile spore challenge, and physiological and biological responses were monitored for 20 d after the initial antibiotic treatment. We also performed the in vitro time-kill assay and determined minimum inhibitory concentration (MIC), post-antibiotic effect, and toxin production with antibiotic exposure. ResultsThe therapeutic response (survival rates, body weight change, clinical sickness score grading, C. difficile load, and toxin titer in feces) of oral teicoplanin administration was comparable to that of oral vancomycin administration in the lethal CDI mouse model. Moreover, teicoplanin treatment suppressed the re-onset of diarrhea and re-increase in toxin titer 10 d after treatment compared with that by vancomycin treatment. In in vitro experiments, teicoplanin exhibited time-dependent antibacterial activity and possessed lower MIC and longer post-antibiotic effect than vancomycin against C. difficile. C. difficile toxin production was numerically lower with teicoplanin exposure than with vancomycin exposure. ConclusionsThe results obtained from the present basic experiments could suggest that teicoplanin is a potential antibiotic for the treatment of severe CDI with recurrence-prevention activity.

Intestinal microbiota controls graft-versus-host disease independent of donor-host genetic disparity

Acute graft-versus-host disease (aGVHD) remains a major limitation of allogeneic stem cell transplantation (SCT), and severe intestinal manifestation is the major cause of early mortality. Intestinal microbiota control MHC class II (MHC-II) expression by ileal intestinal epithelial cells (IECs) that promote GVHD. Here, we demonstrated that genetically identical mice of differing vendor origins had markedly different intestinal microbiota and ileal MHC-II expression, resulting in discordant GVHD severity. We utilized cohousing and antibiotic treatment to characterize the bacterial taxa positively and negatively associated with MHC-II expression. A large proportion of bacterial MHC-II inducers were vancomycin sensitive, and peri-transplant oral vancomycin administration attenuated CD4+ Tcell-mediated GVHD. We identified a similar relationship between pre-transplant microbes, HLA class II expression, and both GVHD and mortality in a large clinical SCT cohort. These data highlight therapeutically tractable mechanisms by which pre-transplant microbial taxa contribute to GVHD independently of genetic disparity.

Oral administration of vancomycin alleviates heart failure triggered by chronic kidney disease

Chronic kidney disease (CKD) induces an imbalance in the intestinal microbiota, affecting various physiological functions and leading to cardiovascular inflammation and fibrosis. However, the cardiotoxic impact of intestinal microbiota-derived uremic substances in advanced renal dysfunction remains unexplored. Therefore, we developed a 5/6 nephrectomy (5/6Nx) mouse model to investigate the intestinal microbiota and the effects of administering vancomycin (VCM) on the microbiota and the cardiac pathology associated with CKD. Despite VCM administration after the development of irreversible glomerulosclerosis and tubulointerstitial fibrosis, blood indoxyl sulfate and phenyl sulfate levels, which are intestinal bacteria-derived uremic substances, brain natriuretic peptide levels, and the fibrotic area in the heart were decreased. Moreover, VCM administration prevented 5/6Nx-induced weight loss and prolonged survival time. Our findings suggest that VCM-induced changes in the intestinal microbiota composition ameliorate heart failure and improve survival rates by reducing intestinal microbiota-derived cardiotoxic substances despite advanced renal dysfunction. This highlights the potential of using the intestinal microbiota as a target to prevent and treat cardiovascular conditions associated with CKD.

Evaluation of microbial and vancomycin treatments in ulcerative colitis in murine models.

Despite the number of available therapies for ulcerative colitis (UC), severe side effects and high cost has limited their clinical application. Thus, finding new alternative strategies with minimal side effects is inevitable. Therefore, this study aimed to compare the effectiveness of different therapeutic approaches in DSS-induced colitis. Firstly, we designed oral bio-therapeutic products, Live Bacterial Products (LBP), which include a mixture of fecal bacteria strains isolated from healthy mice and prepared by microencapsulation and freeze-dried techniques. Then we investigated the efficiency of 7 days of freeze-dried FMT, LBP, and vancomycin treatments in DSS-induced colitis. Secondly, we compared the effect of 15 days of microbial therapies (freeze-dried powder of FMT and LBP microcapsules) and seven days of oral vancomycin on the severity of colitis in mice. Furthermore, the levels of IL-1β and TNF-α were measured in serum by ELISA, and the fecal microbiota diversity was analyzed by high-throughput sequencing for all mice groups. After seven days of treatments, our results indicated that oral vancomycin reduced the severity of DSS-induced colitis in mice, where weight gain and a decrease in IL-1 β and TNF-α levels were observed in the vancomycin group compared with other treatment groups. While after two weeks of treatment, the LBP microcapsules were able to reduce the severity of colitis. And at the end of the treatment period, weight gain and a decrease in the DAI scores and the levels of IL-1β and TNF-α were noted in the LBP treatment group compared to other treatment groups. By high-throughput sequencing of the 16S rRNA gene, our results showed that while the microcapsules LBP treatment increased the fecal microbial diversity, after vancomycin therapy, most of the fecal microbiota genera and operational taxonomic units (OTUs) were depleted. Our results concluded that treatment duration and preparation methods affect the microbial therapies' efficiency in UC. Furthermore, this study highlighted the negative consequences of oral vancomycin administration on gut health that should be known before using this medication.

Vancomycin Flushing Syndrome Following Oral Administration of Vancomycin.

Vancomycin Flushing Syndrome Following Oral Administration of Vancomycin.

391. Evaluation of oral vancomycin treatment for hospital-acquired Clostridioides difficile infection prophylaxis in a community hospital: A retrospective cohort study

Abstract Background Hospital-acquired (HA) Clostridioides difficile infection (CDI) is among the most common hospital-acquired infections and is a leading cause of morbidity and mortality among hospitalized older adults. Oral vancomycin prophylaxis (OVP) has been demonstrated in recent studies to reduce the incidence of HA CDI. This study aims to evaluate the effectiveness of OVP in the prevention of HA CDI in a community hospital setting. Methods We developed a protocol to administer prophylactic oral vancomycin based on patients’ risk factors and implemented it at our community hospital in Evanston, Illinois, in September 2020. The intervention group consists of patients admitted to our hospital between October 1, 2020, to March 31, 2021, who received OVP. Patients admitted between October 1, 2019, to March 31, 2020, who had at least one risk factor of CDI and met the inclusion criteria of OVP protocol were selected as the control group. Electronic medical records were retrospectively collected and analyzed. Propensity score matching was performed for a one-to-one match between two groups. Logistic regression models were used to study the relationship between HA CDI and independent variables, including OVP, risk factors of CDI, and demographic characteristics. Table 1.Sample characteristics of the control and intervention groups A Student t-test was performed for continuous parameters. A Chi-square test was performed for categorical parameters. Non PPx = control group; OVP PPx = oral vancomycin prophylaxis group; SNF = skilled nursing facility; LOS = length of stay; PPI = proton pump inhibitor; H2RA = histamine 2 receptor antagonist. Results A total of 446 patients (267 in the intervention group and 179 in the control group) were included. The sample characteristics are summarized in Table 1. 4/175 (2.2%) patients in the control group developed HA CDI, compared with 12/255 (4.5%) in the intervention group. Before matching, patients who received OVP (OR=7.62, p=0.010) and had a longer length of stay (LOS, OR=1.11, p=0.002) were found to have increased odds ratios (OR) of development of HA CDI (Table 2). After propensity score matching, 4/176 (2.3%) patients in the control group developed HA CDI, compared with 5/176 (2.8%) (Figure 1). Patients from skilled nursing facilities (SNF, OR=15.41, p=0.021) and with longer LOS (OR 1.15, p=0.005) were found to be associated with higher OR of HA CDI (Table 3). Table 2.The odds ratio of development of hospital-acquired C.diff infection among control and intervention groups. A binary logistic regression model was used for this study. CI = 95% confidence interval. R2 Tujur = coefficients of determination (D); AIC = Akaike’s Information Criteria. OVP PPx = oral vancomycin prophylaxis group; SNF = skilled nursing facility; LOS = length of stay; PPI = proton pump inhibitor; H2RA = histamine 2 receptor antagonist. Figure 1.Propensity score matching of control and intervention groups. (A) Distribution of propensity scores between unmatched and matched control and intervention groups. (B) Distribution balance of propensity score before and after matching. Treatment o = control group; Treatment 1 = OVP intervention group. (C) The distribution balance of covariates used for propensity score calculation before and after matching. (D) Summary of propensity score matching results. HA CDI = hospital-acquired C.diff infection (after propensity score matching). Table 3.The odds ratio of development of hospital-acquired C.diff infection among control and intervention groups after propensity score matching. A binary logistic regression model was used for this study. CI = 95% confidence interval. R2 Tujur = coefficients of determination (D); AIC = Akaike’s Information Criteria. OVP PPx = oral vancomycin prophylaxis group; SNF = skilled nursing facility; LOS = length of stay; PPI = proton pump inhibitor; H2RA = histamine 2 receptor antagonist. Conclusion Prophylactic administration of oral vancomycin to patients with selected risk factors has no statistical significance in reducing or preventing HA CDI. A longer length of hospital stay may be associated with higher risk for developing HA CDI. Disclosures All Authors: No reported disclosures.

Assessment of Oral Vancomycin-Induced Alterations in Gut Bacterial Microbiota and Metabolome of Healthy Men.

Several classes of antibiotics have reduced the mortality caused by infectious diseases; however, orally administered antibiotics alter the composition of gut microbiota, leading to dysbiosis-related disease. Therefore, in this study, we used 16S rRNA gene sequencing- and metabolomics-based approaches to investigate the effects of oral vancomycin on gut bacterial microbiota and the metabolome in biospecimens collected from healthy men. Samples collected from 11 healthy men were analyzed using 16S rRNA gene sequencing and metabolomics. 16S rRNA gene sequencing was performed to analyze the gut bacterial microbiota, and GC-TOFMS-based untargeted metabolomics was performed to analyze fecal, urine, and plasma metabolomics. Spearman’s rank correlation was utilized to explore the associations between gut bacterial microbiota and metabolome. Fecal 16S rRNA gene sequencing analysis showed decreased relative abundance of genera belonging to the phyla Bacteroidetes and Firmicutes, and increased relative abundance of genera of the phyla Proteobacteria and Fusobacteria. Fecal metabolomics analysis showed that levels of uracil, L-aspartic acid, lithocholic acid, and deoxycholic acid were significantly higher at baseline, whereas that of dihydrouracil was significantly higher after vancomycin administration. No significant metabolic markers were selected from urine and plasma metabolomics analysis. This study demonstrates that oral vancomycin administration induces alterations in gut bacterial microbiota and metabolome. Correlation analysis between our two datasets shows that alteration of the gut bacterial microbiota, induced by oral vancomycin, potentially affected the systemic activity of dihydropyrimidine dehydrogenase. This correlation should be further examined in future studies to define the effects of gut bacterial microbiota on drug-metabolizing enzymes, thereby contributing to the development of personalized therapy.

Antibiotic-Induced Changes in Microbiome-Related Metabolites and Bile Acids in Rat Plasma.

Various environmental factors can alter the gut microbiome’s composition and functionality, and modulate host health. In this study, the effects of oral and parenteral administration of two poorly bioavailable antibiotics (i.e., vancomycin and streptomycin) on male Wistar Crl/Wi(Han) rats for 28 days were compared to distinguish between microbiome-derived or -associated and systemic changes in the plasma metabolome. The resulting changes in the plasma metabolome were compared to the effects of a third reference compound, roxithromycin, which is readily bioavailable. A community analysis revealed that the oral administration of vancomycin and roxithromycin in particular leads to an altered microbial population. Antibiotic-induced changes depending on the administration routes were observed in plasma metabolite levels. Indole-3-acetic acid (IAA) and hippuric acid (HA) were identified as key metabolites of microbiome modulation, with HA being the most sensitive. Even though large variations in the plasma bile acid pool between and within rats were observed, the change in microbiome community was observed to alter the composition of the bile acid pool, especially by an accumulation of taurine-conjugated primary bile acids. In-depth investigation of the relationship between microbiome variability and their functionality, with emphasis on the bile acid pool, will be necessary to better assess the potential adverseness of environmentally induced microbiome changes.

Clostridioides difficile Infection in Chronic Kidney Disease/End-Stage Renal Disease.

Clostridioides difficile infection (CDI) is a major health-care burden and increasingly seen in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Increased antibiotic use, alteration in host defenses, and gastric acid suppression are some of the etiologies for increased risk of CDI in these populations. Patients with CKD/ESRD have a higher risk of initial episode, recurrence, and development of severe CDI than those without CKD or ESRD. Diagnosis and management of CDI in patients with CKD/ESRD are similar to that in the general population. The mortality, length of stay, and health-care costs are higher in patients with CDI and CKD/ESRD. Antimicrobial stewardship with reduction in antibiotic use along with infection-control measures such as contact isolation and hand hygiene with soap and water is essential in the control and prevention of CDI in patients with CKD/ESRD.

Oral administration of vancomycin to neonatal mice could alter their immunity and allergic sensibility late in adulthood.

The prevalence of allergy has increased over the past decades, and this may be attributed in part to the intestinal microbiota dysfunction caused by antibiotics during early life. In this study, we evaluated how vancomycin could impair the intestinal microbiota during early life and then, consequently, alter susceptibilities to allergic diseases and related immunity in late adulthood. BALB/c (n=54) neonatal mice were used in this study. Mice in the vancomycin group were orally administered vancomycin for 21 days, while those in the allergy and control groups were perfused with the same volume of saline solution. Then, mice in the allergy and vancomycin groups were immunized with intraperitoneal ovalbumin with alum. At postnatal day 21, vancomycin significantly alter the fecal microbiota, with lower Bacteroidetes and Firmicutes counts and higher Proteobacteria counts. At postnatal day 56, the Bacteroidetes count was still significantly lower in vancomycin-treated mice. The serum IgE level in the control group was significantly lower than that in the vancomycin and allergy groups. The serum interleukin (IL)-6 level and the IL-4/interferon (IFN)-γ values were significantly higher in the vancomycin-treated mice, but the serum IL-17A level was lower than that in the control group. These results indicate that modifications of the intestinal microbiota composition during early life may be, at least in part, the key mechanism underlying the effect of vancomycin that influences the immune function of host animals in the adult stages.

Development and in vitro evaluation of a self-emulsifying drug delivery system (SEDDS) for oral vancomycin administration

The aim of this study was to develop a self-emulsifying drug delivery system (SEDDS) containing the glycopeptide antibiotic vancomycin (VAN) with improved intestinal mucosa permeating properties in order to increase oral drug absorption. VAN was effectively incorporated into SEDDS increasing the lipophilicity of the drug via hydrophobic ion pairing (HIP) with cetyltrimethylammonium bromid (CTAB). Newly developed SEDDS formulations containing VAN/CTAB complex were characterized with respect to droplet size, polydispersity index and zeta potential. Furthermore, permeating properties were investigated in porcine intestinal mucus using Transwell setup and on freshly excised porcine intestinal mucosa utilizing Ussing-type chamber. In addition, minimum inhibitory concentration (MIC) of VAN/CTAB-SEDDS against Staphylococcus aureus was evaluated. The developed formulations F1 (25% Capmul 808G EP/NF, 37.5% Cremophor RH 40, 37.5%), F2 (26.5% Capmul 808G EP/NF, 33.2% Cremophor RH 40, 13.8% Transcutol, 26.5% DMSO) and F3 (28.8% Captex 8000, 35% Cremophor EL, 20% Transcutol, 16.2% DMSO) with a mean droplet size of 14 nm, 15 nm and 153 nm, respectively, exhibited improved ability to permeate porcine intestinal mucosal barrier. F1-VAN/CTAB showed 219-fold, F2-VAN/CTAB 46-fold and F3-VAN/CTAB 63-fold higher permeation of VAN through the mucus layer after 4 h in comparison to free VAN. Moreover, all formulations demonstrated a 4–8-fold improvement in permeation of intestinal mucosa compared to free VAN solution. Additionally, F2-VAN/CTAB with a MIC of 0.313 mg/L showed higher effectivity against S. aureus (ATCC® 29213) compared to free VAN. According to these results, HIP combined with SEDDS should be taken into consideration as promising tool for oral antibiotic delivery.

Evidence‐based consensus on opportunistic infections in inflammatory bowel disease

Evidence‐based consensus on opportunistic infections in inflammatory bowel disease

Carbon quantum dot tailored calcium alginate hydrogel for pH responsive controlled delivery of vancomycin

Herein, we demonstrate the preparation of highly luminescent carbon quantum dots (CQDs) from Aloe vera leaf gel; in just 2h at 250°C through carbonization pathway. The prepared CQDs are structurally characterized with high resolution transmission electron microscopy (HRTEM), hydrodynamic diameter, surface polarity, Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), Raman, UV–visible absorption spectrophotometry and fluorescence spectroscopy. The functional carbon nanoparticles are observed as non-cytotoxic materials. The biocompatibility, less cytotoxicity and high aqueous dispersibility of as-synthesized CQDs are motivated to design carbon quantum dot (CQD) tailored calcium alginate (CA) hydrogel films with an aim to controlled delivery of glycopeptides antibiotic vancomycin in the gastrointestinal tract (GI). With CQD, the drug loading capacity of CA/CQD film is increased to 89% from 38% (CA film), whereas; with β-cyclodextrin (β-CD) the vancomycin uptake capacity is increased more, 96%. The release of vancomycin through CA/CQD film is more pronounced at pH1.5, close to the pH of the stomach and it is found that in pH1.5 with β-CD, the release rate of vancomycin is lowered, 56% in 120h. The high drug uptake capacity (96%) and lower release rate (56% in 120h) of CA/CQD hydrogel film in pH1.5 with β-CD can be used for its applicability as drug delivery vehicle for controlled release of vancomycin into the stomach region and therefore it can offer a potential option for oral administration of vancomycin.

Selective Induction of Homeostatic Th17 Cells in the Murine Intestine by Cholera Toxin Interacting with the Microbiota.

Th17 cells play a role as an inflammation mediator in a variety of autoimmune disorders, including inflammatory bowel disease, and thus are widely considered to be pathogenic. However, Th17 cells are present in the normal intestine and show a homeostatic phenotype; that is, they participate in the maintenance of intestinal homeostasis rather than inducing inflammation. We observed an enlarged Th17 population in the small intestine of C57BL/6.IgA-/- mice compared with wild-type mice, which was further amplified with cholera toxin (CT) immunization without causing intestinal inflammation. The increased Th17 induction and the correspondingly 10-fold higher CT B subunit-specific serum IgG response in IgA-/- mice after CT immunization was microbiota dependent and was associated with increased segmented filamentous bacteria in the small intestine of IgA-/- mice. Oral administration of vancomycin greatly dampened both CT immunogenicity and adjuvanticity, and the differential CT responses in IgA-/- and wild-type mice disappeared after intestinal microbiota equalization. Using gnotobiotic mouse models, we found that CT induction of homeostatic intestinal Th17 responses was supported not only by segmented filamentous bacteria, but also by other commensal bacteria. Furthermore, transcriptome analysis using IL-17AhCD2 reporter mice revealed a similar gene expression profile in CT-induced intestinal Th17 cells and endogenous intestinal Th17 cells at homeostasis, with upregulated expression of a panel of immune-regulatory genes, which was distinctly different from the gene expression profile of pathogenic Th17 cells. Taken together, we identified a nonpathogenic signature of intestinal homeostatic Th17 cells, which are actively regulated by the commensal microbiota and can be selectively stimulated by CT.

Hypersensitivity Reaction Following Administration of Low-Dose Oral Vancomycin for the Treatment of Clostridium difficile in a Patient With Normal Renal Function

Systemic absorption of oral vancomycin for the treatment of Clostridium difficile is thought to be trivial in patients without risk factors for increased systemic absorption and is often overlooked in clinical practice. A 51-year-old male elicits a suspected immunoglobulin E-mediated hypersensitivity following administration of low-dose oral vancomycin for the treatment of severe C difficile. The patient had normal renal function and was administered low doses of the medication, however, had a medical history significant for diverticulitis. Applying the Naranjo adverse drug reaction probability scale, a score of 5 was obtained, indicating a probable association between the administration of oral vancomycin and the hypersensitivity reaction. This case demonstrates that hypersensitivity reactions following low-dose oral vancomycin administration in patients with severe C difficile are possible, despite having normal renal function. Other risk factors for systemic absorption of oral vancomycin need to be evaluated in the literature, including severity of disease and underlying gastrointestinal processes.

A Prospective Pilot Study on the Systemic Absorption of Oral Vancomycin in Children With Colitis.

BACKGROUND: Oral vancomycin is used to treat refractory colitis due to Clostridium dificile infection. Traditionally, oral vancomycin was thought to not be absorbed systemically, but recent adult studies have demonstrated detectable serum levels in over half of patients with severe colitis. This has not been studied in children. OBJECTIVE: To determine the absorption of oral vancomycin and the renal safety profile of oral vancomycin in children hospitalized with colitis. METHODS: We performed a prospective, observational, pilot proof of principle study at the North Carolina Children's Hospital in patients 2 years to 18 years of age receiving oral vancomycin for the treatment of C dificile colitis. Severity of disease was determined using a validated scoring system. Serial serum vancomycin levels and renal function tests were performed during the administration of oral vancomycin. RESULTS: All patients enrolled (n = 8) had mild to moderate C dificile colitis and varying severity of underlying systemic diseases; 7 with inflammatory bowel disease and 1 with acute kidney injury following renal transplantation. No enrolled patients had detectable levels of serum vancomycin. Additionally, no adverse renal outcomes were attributed to oral vancomycin, and no cases of "Red Man" syndrome were observed. CONCLUSIONS: Unlike studies in adult patients, oral vancomycin is likely not absorbed in children with mild to moderate colitis. Further study is needed to determine the pharmacokinetics in severe colitis and those with severe illness in a critical care setting.

Risk factors for systemic vancomycin exposure following administration of oral vancomycin for the treatment of Clostridium difficile infection.

To identify risk factors for systemic exposure to vancomycin (VAN) following administration of oral vancomycin (POV) for the treatment of Clostridium difficile infection (CDI). Prospective, observational, single-center case series. Academic medical center. Hospitalized patients with suspected or confirmed CDI who received POV for at least 5days. Random VAN serum levels were obtained on days 5, 10, and weekly thereafter in patients treated for ≥5days with POV without concomitant intravenous VAN. Of 117 random VAN serum levels from 85 patients, 58 patients (68.2%) had one or more detectable (≥0.05μg/ml) levels and 15 (17.6%) of 85 patients had one or more levels >2.5μg/ml. Risk factors for detectable VAN exposure following administration of POV included POV dosages >500mg/day (odds ratio [OR] 35.83, 95% confidence interval [CI] 7.56-169.8), the presence of severe CDI (OR 4.11, 95% CI 2.76-10.83, p=0.028), intensive care unit (ICU) admission (OR 3.80, 95% CI 1.02-14.21, p=0.032), and the administration of POV ≥10days (OR 6.71, 95% CI 1.81-24.83, p=0.0025). Risk factors for exposure to serum VAN concentrations >2.5μg/ml included the presence of gastrointestinal (GI) pathology (OR 5.22, 95% CI 3.45-18.3, p=0.031), ICU admission (OR 3.21, 95% CI 1.40-10.28, p=0.022), the use of VAN retention enemas (OR 4.73, 95% CI 2.42-20.39, p=0.036), and having a creatinine clearance ≤50ml/minute or undergoing hemodialysis or continuous renal replacement therapy (OR 4.03, 95% CI 1.26-12.84, p=0.039). Serum VAN levels were detected in 58 (68.2%) of 85 patients receiving POV for CDI. Risk factors for systemic exposure to VAN following administration of POV included ICU admission; VAN dosages >500mg/day; administration ≥10days or as retention enemas; and the presence of severe CDI, renal dysfunction, or inflammatory conditions of the GI tract. Unique to our study, we identified ICU admission and the concomitant use of VAN retention enemas to be significant risk factors for systemic exposure to VAN.

Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity

Obesity has been associated with changes in the composition and function of the intestinal microbiota. Modulation of the microbiota by antibiotics also alters bile acid and glucose metabolism in mice. Hence, we hypothesized that short term administration of oral antibiotics in humans would affect fecal microbiota composition and subsequently bile acid and glucose metabolism. In this single blinded randomized controlled trial, 20 male obese subjects with metabolic syndrome were randomized to 7 days of amoxicillin 500 mg t.i.d. or 7 days of vancomycin 500 mg t.i.d. At baseline and after 1 week of therapy, fecal microbiota composition (Human Intestinal Tract Chip phylogenetic microarray), fecal and plasma bile acid concentrations as well as insulin sensitivity (hyperinsulinemic euglycemic clamp using [6,6-(2)H2]-glucose tracer) were measured. Vancomycin reduced fecal microbial diversity with a decrease of gram-positive bacteria (mainly Firmicutes) and a compensatory increase in gram-negative bacteria (mainly Proteobacteria). Concomitantly, vancomycin decreased fecal secondary bile acids with a simultaneous postprandial increase in primary bile acids in plasma (p<0.05). Moreover, changes in fecal bile acid concentrations were predominantly associated with altered Firmicutes. Finally, administration of vancomycin decreased peripheral insulin sensitivity (p<0.05). Amoxicillin did not affect any of these parameters. Oral administration of vancomycin significantly impacts host physiology by decreasing intestinal microbiota diversity, bile acid dehydroxylation and peripheral insulin sensitivity in subjects with metabolic syndrome. These data show that intestinal microbiota, particularly of the Firmicutes phylum contributes to bile acid and glucose metabolism in humans. This trial is registered at the Dutch Trial Register (NTR2566).

Circulatory collapse after topical application of vancomycin powder during spine surgery

A hypersensitivity reaction, either anaphylactic or anaphylactoid, is a well-known adverse effect following intravenous and oral administration of vancomycin. The authors report a case of circulatory collapse and its management after the topical application of vancomycin powder during spinal instrumentation surgery. A 52-year-old woman with breast cancer and metastasis to her spine underwent a vertebrectomy of the T-10 vertebra with instrumented reconstruction from T-8 to T-12. The patient was hemodynamically stable during most of the procedure despite a 2-L blood loss requiring administration of crystalloids, colloids, packed red blood cells, and fresh-frozen plasma. During closure of the subcutaneous layer, there was a sudden drop in blood pressure from 120/60 to 30/15 mm Hg and an increase in heart rate from 95 to 105 bpm. No skin erythema or rash was visible, and there was no bronchospasm or increase in airway pressure. The patient was treated with fluids, boluses of ephedrine, phenylephrine, and adrenaline. The operation was completed and the patient woke up neurologically intact but did require blood pressure support with a norepinephrine infusion for the next 4 hours. She was discharged from hospital in a good clinical state on the 4th postoperative day. It was speculated that the rapid absorption of vancomycin powder applied on the surgical wound caused an anaphylactoid reaction and the circulatory collapse. With an increase in the use of topical vancomycin in surgical wounds, communication and awareness among all intraoperative team members is important for rapid diagnosis of an adverse reaction and for appropriate management.

DGI-012 Antibiotics Monitoring: The Experience of Liguria Region, Italy

Background The Health Department of Regione Liguria has introduced the obligation, for every hospital department to motivate the request to obtain certain kinds of antibiotics, because their use is restricted...