scholarly journals Tapering Courses of Oral Vancomycin Induce Persistent Disruption of the Microbiota That Provide Colonization Resistance to Clostridium difficile and Vancomycin-Resistant Enterococci in Mice

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Myreen E. Tomas ◽  
Thriveen S. C. Mana ◽  
Brigid M. Wilson ◽  
Michelle M. Nerandzic ◽  
Samira Joussef-Piña ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Anaerobic Bacteria ◽  
Multiple Time ◽  
Colonization Resistance ◽  
Content Type ◽  
Vancomycin Resistant Enterococci ◽  
Indigenous Microbiota ◽  
Vancomycin Resistant ◽  
Multiple Time Points ◽  
The Impact

ABSTRACT Vancomycin taper regimens are commonly used for the treatment of recurrent Clostridium difficile infections. One rationale for tapering and pulsing of the dose at the end of therapy is to reduce the selective pressure of vancomycin on the indigenous intestinal microbiota. Here, we used a mouse model to test the hypothesis that the indigenous microbiota that provide colonization resistance against C. difficile and vancomycin-resistant enterococci (VRE) is repopulated during tapering courses of vancomycin. Mice were treated orally with vancomycin daily for 10 days, vancomycin in a tapering dose for 42 days, fidaxomicin for 10 days, or saline. To assess colonization resistance, subsets of mice were challenged with 10 4 CFU of C. difficile or VRE at multiple time points during and after completion of treatment. The impact of the treatments on the microbiome was measured by cultures, real-time PCR for selected anaerobic bacteria, and deep sequencing. Vancomycin taper-treated mice developed alterations of the microbiota and disruption of colonization resistance that was persistent 18 days after treatment. In contrast, mice treated with a 10-day course of vancomycin exhibited recovery of the microbiota and of colonization resistance by 15 days after treatment, and fidaxomicin-treated mice maintained intact colonization resistance. These findings demonstrate that alteration of the indigenous microbiota responsible for colonization resistance to C. difficile and VRE persist during and after completion of tapering courses of vancomycin.

scholarly journals A Phenotypically Silent vanB2 Operon Carried on a Tn1549-Like Element in Clostridium difficile

mSphere ◽  
2016 ◽  
Vol 1 (4) ◽  
Author(s):  
Daniel R. Knight ◽  
Grace O. Androga ◽  
Susan A. Ballard ◽  
Benjamin P. Howden ◽  
Thomas V. Riley
Keyword(s):  
Health Care ◽  
Clostridium Difficile ◽  
Resistance Genes ◽  
Vancomycin Resistance ◽  
Content Type ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant ◽  
Emergence Of Resistance ◽  
First Time

ABSTRACT In an era when the development of new antimicrobial drugs is slow, vancomycin remains the preferred antimicrobial therapy for Clostridium difficile infection (CDI), the most important health care-related infection in the world today. The emergence of resistance to vancomycin would have significant consequences in relation to treating patients with CDI. In this paper, we describe for the first time a complete set of vancomycin resistance genes in C. difficile. The genes were very similar to genes found in vancomycin-resistant enterococci (VRE) that were associated with the emergence and global dissemination of this organism. Fortunately, the C. difficile strain did not show any reduced susceptibility to vancomycin in vitro (MIC, 1 mg/liter), possibly because of a small difference in one gene. However, this observation signals that we may be very close to seeing a fully vancomycin-resistant strain of C. difficile. In the last decade, Clostridium difficile infection (CDI) has reached an epidemic state with increasing incidence and severity in both health care and community settings. Vancomycin is an important first-line therapy for CDI, and the emergence of resistance would have significant clinical consequences. In this study, we describe for the first time a vanB2 vancomycin resistance operon in C. difficile, isolated from an Australian veal calf at slaughter. The operon was carried on an ~42-kb element showing significant homology and synteny to Tn1549, a conjugative transposon linked with the emergence and global dissemination of vancomycin-resistant enterococci (VRE). Notably, the C. difficile strain did not show any reduced susceptibility to vancomycin in vitro (MIC, 1 mg/liter), possibly as a result of an aberrant vanRB gene. As observed for other anaerobic species of the animal gut microbiota, C. difficile may be a reservoir of clinically important vancomycin resistance genes. IMPORTANCE In an era when the development of new antimicrobial drugs is slow, vancomycin remains the preferred antimicrobial therapy for Clostridium difficile infection (CDI), the most important health care-related infection in the world today. The emergence of resistance to vancomycin would have significant consequences in relation to treating patients with CDI. In this paper, we describe for the first time a complete set of vancomycin resistance genes in C. difficile. The genes were very similar to genes found in vancomycin-resistant enterococci (VRE) that were associated with the emergence and global dissemination of this organism. Fortunately, the C. difficile strain did not show any reduced susceptibility to vancomycin in vitro (MIC, 1 mg/liter), possibly because of a small difference in one gene. However, this observation signals that we may be very close to seeing a fully vancomycin-resistant strain of C. difficile.

scholarly journals Effect of Surotomycin, a Novel Cyclic Lipopeptide Antibiotic, on Intestinal Colonization with Vancomycin-Resistant Enterococci and Klebsiella pneumoniae in Mice

2016 ◽  
Vol 60 (6) ◽  
pp. 3333-3339 ◽  
Author(s):  
Abhishek Deshpande ◽  
Kelly Hurless ◽  
Jennifer L. Cadnum ◽  
Laurent Chesnel ◽  
Lihong Gao ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Oral Vancomycin ◽  
Gram Negative ◽  
Content Type ◽  
Orogastric Tube ◽  
Cyclic Lipopeptide ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant ◽  
Lipopeptide Antibiotic ◽  
The Impact

Surotomycin (formerly called CB-183,315) is a novel, orally administered cyclic lipopeptide antibacterial in development for the treatment ofClostridium difficileinfection (CDI) that has potent activity against vancomycin-resistant enterococci (VRE) but limited activity against Gram-negative bacilli, includingBacteroidesspp. We used a mouse model to investigate the impact of surotomycin exposure on the microbiome, and to test the consequences of the disruption on colonization by vancomycin-resistant enterococci (VRE) and extended-spectrum β-lactamase-producingKlebsiella pneumoniae(ESBL-KP), in comparison with the effects of oral vancomycin and metronidazole. Mice (8 per group) received saline, vancomycin, metronidazole, or surotomycin through an orogastric tube daily for 5 days and were challenged with 105CFU of VRE or ESBL-KP administered through an orogastric tube on day 2 of treatment. The concentrations of the pathogens in stool were determined during and after treatment by plating on selective media. A second experiment was conducted to determine if the antibiotics would inhibit established VRE colonization. In comparison to controls, oral vancomycin promoted VRE and ESBL-KP overgrowth in stool (8 log10to 10 log10CFU/g;P< 0.001), whereas metronidazole did not (<4 log10CFU/g;P> 0.5). Surotomycin promoted ESBL-KP overgrowth (>8 log10CFU/g;P, <0.001 for comparison with saline controls) but not VRE overgrowth. Surotomycin suppressed preexisting VRE colonization, whereas metronidazole and vancomycin did not. These results suggest that treatment of CDI with surotomycin could reduce levels of VRE acquisition and overgrowth from those with agents such as vancomycin and metronidazole. However, surotomycin and vancomycin may promote colonization by antibiotic-resistant Gram-negative bacilli.

scholarly journals Cadazolid Does Not Promote Intestinal Colonization of Vancomycin-Resistant Enterococci in Mice

2015 ◽  
Vol 60 (1) ◽  
pp. 628-631 ◽  
Author(s):  
Peter Seiler ◽  
Michel Enderlin-Paput ◽  
Philippe Pfaff ◽  
Maria Weiss ◽  
Daniel Ritz ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Gut Microbiota ◽  
Side Effect ◽  
Clinical Development ◽  
Intestinal Colonization ◽  
Potential Side Effect ◽  
Content Type ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant

ABSTRACTThe promotion of colonization with vancomycin-resistant enterococci (VRE) is one potential side effect during treatment ofClostridium difficile-associated diarrhea (CDAD), resulting from disturbances in gut microbiota. Cadazolid (CDZ) is an investigational antibiotic with potentin vitroactivity againstC. difficileand against VRE and is currently in clinical development for the treatment of CDAD. We report that CDZ treatment did not lead to intestinal VRE overgrowth in mice.

scholarly journals Effect of Fidaxomicin versus Vancomycin on Susceptibility to Intestinal Colonization with Vancomycin-Resistant Enterococci and Klebsiella pneumoniae in Mice

2016 ◽  
Vol 60 (7) ◽  
pp. 3988-3993 ◽  
Author(s):  
Abhishek Deshpande ◽  
Kelly Hurless ◽  
Jennifer L. Cadnum ◽  
Laurent Chesnel ◽  
Lihong Gao ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Intestinal Microbiota ◽  
Deep Sequencing ◽  
Sequencing Analysis ◽  
Oral Vancomycin ◽  
Content Type ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant ◽  
The Impact ◽  
Vancomycin Treatment

ABSTRACTThe use of oral vancomycin or metronidazole for treatment ofClostridium difficileinfection (CDI) may promote colonization by health care-associated pathogens due to disruption of the intestinal microbiota. Because the macrocyclic antibiotic fidaxomicin causes less alteration of the intestinal microbiota than vancomycin, we hypothesized that it would not lead to a loss of colonization resistance to vancomycin-resistant enterococci (VRE) and extended-spectrum-β-lactamase-producingKlebsiella pneumoniae(ESBL-Kp). Mice (8 per group) received orogastric saline, vancomycin, or fidaxomicin daily for 5 days at doses resulting in stool concentrations in mice similar to those measured in humans. The mice were challenged with 105CFU of orogastric VRE or ESBL-Kp on day 2 of treatment and concentrations of the pathogens in stool were monitored. The impact of drug exposure on the microbiome was measured by cultures, real-time PCR for selected anaerobic bacteria, and deep sequencing. In comparison to saline controls, oral vancomycin promoted establishment of high-density colonization by VRE and ESBL-Kp in stool (8 to 10 log10CFU/g;P< 0.001), whereas fidaxomicin did not (<4 log10CFU;P> 0.5). Vancomycin treatment resulted in significant reductions in enterococci,Bacteroidesspp., andClostridium leptum, whereas the population of aerobic and facultative Gram-negative bacilli increased; deep-sequencing analysis demonstrated suppression ofFirmicutesand expansion ofProteobacteriaduring vancomycin treatment. Fidaxomicin did not cause significant alteration of the microbiota. In summary, in contrast to vancomycin, fidaxomicin treatment caused minimal disruption of the intestinal microbiota and did not render the microbiota susceptible to VRE and ESBL-Kp colonization.

scholarly journals Impact of Different Antimicrobial Therapies on Clinical and Fiscal Outcomes of Patients with Bacteremia Due to Vancomycin-Resistant Enterococci

2014 ◽  
Vol 58 (7) ◽  
pp. 3968-3975 ◽  
Author(s):  
Kayoko Hayakawa ◽  
Emily T. Martin ◽  
Uma Mahesh Gudur ◽  
Dror Marchaim ◽  
Dalia Dalle ◽  
...  
Keyword(s):  
Propensity Score ◽  
Medical Center ◽  
Bloodstream Infections ◽  
Multivariate Models ◽  
Median Dose ◽  
Content Type ◽  
Treatment Groups ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant ◽  
The Impact

ABSTRACTVancomycin-resistant enterococci (VRE) are a growing health problem, and uncertainties exist regarding the optimal therapy for bloodstream infection due to VRE. We conducted systematic comparative evaluations of the impact of different antimicrobial therapies on the outcomes of patients with bloodstream infections due to VRE. A retrospective study from January 2008 to October 2010 was conducted at Detroit Medical Center. Unique patients with blood cultures due to VRE were included and reviewed. Three major therapeutic classes were analyzed: daptomycin, linezolid, and β-lactams. Three multivariate models were conducted for each outcome, matching for a propensity score predicting the likelihood of receipt of one of the therapeutic classes. A total of 225 cases of bacteremia due to VRE were included, including 86 (38.2%) cases of VREnterococcus faecalisand 139 (61.8%) of VREnterococcus faecium. Bacteremia due to VRE. faecaliswas more frequent among subjects treated with β-lactams than among those treated with daptomycin or linezolid. The median dose of daptomycin was 6 mg/kg of body weight (range, 6 to 12 mg/kg). After controlling for propensity score and bacteremia due to VRE. faecalis, differences in mortality were nonsignificant among the treatment groups. Therapy with daptomycin was associated with higher median variable direct cost per day than that for linezolid. This large study revealed the three therapeutic classes (daptomycin, linezolid, and β-lactams) are similarly efficacious in the treatment of bacteremia due to susceptible strains of VRE.

Fourier-Transform Infrared (FTIR) Spectrophotometry: An Ecofriendly Method for the Analysis of Injectable Daptomycin

2017 ◽  
Vol 100 (5) ◽  
pp. 1569-1576 ◽  
Author(s):  
Eliane Gandolpho Tótoli ◽  
Hérida Regina Nunes Salgado
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Sustainable Consumption ◽  
Toxic Waste ◽  
Vancomycin Resistant Enterococci ◽  
Ir Spectrophotometry ◽  
Vancomycin Resistant ◽  
Ftir Spectrophotometry ◽  
The Impact

Abstract Daptomycin (DPT) is an important antimicrobial agent used in clinical practice because it is very active against several types of medicinally challengingGram-positive bacteria, such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci. In addition to concerns about the quality of the analytical methods used in the QC of drugs, there is also concern about the impact of these methods on the environment. The trend toward sustainable consumption is increasingly evident and has forced the pharmaceutical industry to reduce the generation of toxic waste. Inthis context, IR spectrophotometry stands out because it does not use organic solvents and, although it is formally accepted for the identification of individual compounds, also allows the quantification of substances. Therefore, the aim of this work was to develop and validate a green analytical method for theanalysis of DPT in a lyophilized powder for injection by FTIR spectrophotometry. The method involved absorbance measurements in the spectral region of 1700–1600 cm−1. The method was properly validated and found to be linear, precise, accurate, selective, and robust for the concentrationrange between 0.2 and 0.6 mg/150 mg. The validated method was able to quantify DPT powder for injection and can be used as an environmentally friendly alternative for routine analysis in QC.

Control of Vancomycin-Resistant Enterococci at a Community Hospital: Efficacy of Patient and Staff Cohorting

1999 ◽  
Vol 20 (2) ◽  
pp. 106-109 ◽  
Author(s):  
Elise M. Jochimsen ◽  
Laurie Fish ◽  
Kelly Manning ◽  
Sally Young ◽  
Daniel A. Singer ◽  
...  
Keyword(s):  
Community Hospital ◽  
Point Prevalence ◽  
Control Measures ◽  
Prevalence Survey ◽  
Infection Control Measures ◽  
Contact Isolation ◽  
Point Prevalence Survey ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant ◽  
The Impact

AbstractObjective:To evaluate the efficacy of patient and staff cohorting to control vancomycin-resistant enterococci (VRE) at an Indianapolis community hospital.Design:To interrupt transmission of VRE, a VRE point-prevalence survey of hospital inpatients was conducted, and VRE-infected or -colonized patients were cohorted on a single ward with dedicated nursing staff and patient-care equipment. To assess the impact of the intervention, staff compliance with contact isolation procedures was observed, and the VRE point-prevalence survey was repeated 2 months after the cohort ward was established.Results:Following the establishment of the cohort ward, VRE prevalence among all hospitalized inpatients decreased from 8.1% to 4.7% (25 positive cultures among 310 patients compared to 13 positive cultures among 276 patients,P=.14); VRE prevalence among patients whose VRE status was unknown before cultures were obtained decreased from 5.9% to 0.8% (18 positive cultures among 303 patients compared to 2 positive cultures among 262 patients,P=.002); and observed staff-patient interactions compliant with published isolation recommendations increased (5 [22%] of 23 interactions compared to 36 [88%] of 41 interactions,P<.0001).Conclusions:Our data suggest that, in hospitals with endemic VRE or continued VRE transmission despite implementation of contact isolation measures, establishing a VRE cohort ward may be a practical and effective method to improve compliance with infection control measures and thereby to control epidemic or endemic VRE transmission.

scholarly journals Streptomycin-Induced Inflammation Enhances Escherichia coli Gut Colonization Through Nitrate Respiration

mBio ◽  
2013 ◽  
Vol 4 (4) ◽  
Author(s):  
Alanna M. Spees ◽  
Tamding Wangdi ◽  
Christopher A. Lopez ◽  
Dawn D. Kingsbury ◽  
Mariana N. Xavier ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Microbial Community ◽  
Intestinal Inflammation ◽  
Anaerobic Bacteria ◽  
Nitrate Respiration ◽  
Colonization Resistance ◽  
Content Type ◽  
E Coli ◽  
Gut Colonization ◽  
Facultative Anaerobic Bacteria

ABSTRACTTreatment with streptomycin enhances the growth of human commensalEscherichia coliisolates in the mouse intestine, suggesting that the resident microbial community (microbiota) can inhibit the growth of invading microbes, a phenomenon known as “colonization resistance.” However, the precise mechanisms by which streptomycin treatment lowers colonization resistance remain obscure. Here we show that streptomycin treatment rendered mice more susceptible to the development of chemically induced colitis, raising the possibility that the antibiotic might lower colonization resistance by changing mucosal immune responses rather than by preventing microbe-microbe interactions. Investigation of the underlying mechanism revealed a mild inflammatory infiltrate in the cecal mucosa of streptomycin-treated mice, which was accompanied by elevated expression ofNos2, the gene that encodes inducible nitric oxide synthase. In turn, this inflammatory response enhanced the luminal growth ofE. coliby nitrate respiration in aNos2-dependent fashion. These data identify low-level intestinal inflammation as one of the factors responsible for the loss of resistance toE. colicolonization after streptomycin treatment.IMPORTANCEOur intestine is host to a complex microbial community that confers benefits by educating the immune system and providing niche protection. Perturbation of intestinal communities by streptomycin treatment lowers “colonization resistance” through unknown mechanisms. Here we show that streptomycin increases the inflammatory tone of the intestinal mucosa, thereby making the bowel more susceptible to dextran sulfate sodium treatment and boosting theNos2-dependent growth of commensalEscherichia coliby nitrate respiration. These data point to the generation of alternative electron acceptors as a by-product of the inflammatory host response as an important factor responsible for lowering resistance to colonization by facultative anaerobic bacteria such asE. coli.

scholarly journals Ceftolozane-Tazobactam Activity against Phylogenetically Diverse Clostridium difficile Strains

2015 ◽  
Vol 59 (11) ◽  
pp. 7084-7085 ◽  
Author(s):  
Mark D. Gonzalez ◽  
Meghan A. Wallace ◽  
Tiffany Hink ◽  
Erik R. Dubberke ◽  
Carey-Ann D. Burnham
Keyword(s):  
Urinary Tract ◽  
Clostridium Difficile ◽  
Urinary Tract Infections ◽  
Anaerobic Bacteria ◽  
Content Type ◽  
Tract Infections ◽  
High Mics

ABSTRACTCeftolozane-tazobactam (C/T) is approved for the treatment of complicated intra-abdominal and urinary tract infections and has varied activity against anaerobic bacteria. Here, we evaluate the activity of C/T against a phylogenetically diverse collection ofClostridium difficileisolates and report uniformly high MICs (≥256 μg/ml) to C/T.

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