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 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 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 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 Comparison of the Superpolymyxin and ChromID Colistin R Screening Media for the Detection of Colistin-Resistant Enterobacteriaceae from Spiked Rectal Swabs

2018 ◽  
Vol 63 (1) ◽  
Author(s):  
Delphine Girlich ◽  
Thierry Naas ◽  
Laurent Dortet
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Confidence Interval ◽  
Enterobacter Cloacae ◽  
Bacterial Isolates ◽  
Colistin Resistance ◽  
Gram Negative ◽  
Content Type ◽  
Rectal Swabs ◽  
Stool Samples

ABSTRACT The dissemination of carbapenemase-producing Enterobacteriaceae (CPE) has led to the increased use of colistin, which has resulted in the emergence of colistin-resistant Enterobacteriaceae worldwide. One of the most threatening scenarios is the dissemination of colistin resistance in CPE, particularly the plasmid-encoded resistance element MCR. Thus, it has now become mandatory to possess reliable media to screen for colistin-resistant Gram-negative bacterial isolates, especially Enterobacteriaceae. In this study, we evaluated the performances of the Superpolymyxin medium (ELITechGroup) and the ChromID Colistin R medium (bioMérieux) to screen for colistin-resistant Enterobacteriaceae from spiked rectal swabs. Stool samples were spiked with a total of 94 enterobacterial isolates (Escherichia coli, Klebsiella pneumoniae, Salmonella enterica, Enterobacter cloacae), including 53 colistin-resistant isolates. ESwabs (Copan Diagnostics) were then inoculated with those spiked fecal suspensions, and culture proceeded as recommended by both manufacturers. The sensitivity of detection of colistin-resistant Enterobacteriaceae was 86.8% (95% confidence interval [95% CI] = 74.0% to 94.0%) using both the Superpolymyxin medium and the ChromID Colistin R plates. Surprisingly, the isolates that were not detected were not the same for both media. The specificities were high for both media, at 97.9% (95% CI = 87.3% to 99.9%) for the Superpolymyxin medium and 100% (95% CI = 90.4% to 100%) for the ChromID Colistin R medium. Both commercially available media, ChromID Colistin R and Superpolymyxin, provide useful tools to screen for colistin-resistant Enterobacteriaceae from patient samples (rectal swabs) regardless of the level and mechanism of colistin resistance.

scholarly journals Activities of Oxadiazole Antibacterials against Staphylococcus aureus and Other Gram-Positive Bacteria

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Sara Ceballos ◽  
Choon Kim ◽  
Derong Ding ◽  
Shahriar Mobashery ◽  
Mayland Chang ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant ◽  
Mrsa Strains

ABSTRACT The activities of four oxadiazoles were investigated with 210 methicillin-resistant Staphylococcus aureus (MRSA) strains. MIC50 and MIC90 values of 1 to 2 and 4 μg/ml, respectively, were observed. We also evaluated the activity of oxadiazole ND-421 against other staphylococci and enterococci and in the presence of oxacillin for selected MRSA strains. The MIC for ND-421 is lowered severalfold in combination with oxacillin, as they synergize. The MIC90 of ND-421 against vancomycin-resistant enterococci is ≤1 μg/ml.

scholarly journals Crystal Structures of Klebsiella pneumoniae Dihydrofolate Reductase Bound to Propargyl-Linked Antifolates Reveal Features for Potency and Selectivity

2014 ◽  
Vol 58 (12) ◽  
pp. 7484-7491 ◽  
Author(s):  
Kristen M. Lamb ◽  
Michael N. Lombardo ◽  
Jeremy Alverson ◽  
Nigel D. Priestley ◽  
Dennis L. Wright ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Crystal Structures ◽  
Dihydrofolate Reductase ◽  
Next Generation ◽  
Gram Negative ◽  
Content Type ◽  
Resistant Species ◽  
Loop Conformations ◽  
The Family ◽  
Dihydrofolate Reductases

ABSTRACTResistance to the antibacterial antifolate trimethoprim (TMP) is increasing in members of the familyEnterobacteriaceae, driving the design of next-generation antifolates effective against these Gram-negative pathogens. The propargyl-linked antifolates are potent inhibitors of dihydrofolate reductases (DHFR) from several TMP-sensitive and -resistant species, includingKlebsiella pneumoniae. Recently, we have determined that these antifolates inhibit the growth of strains ofK. pneumoniae, some with MIC values of 1 μg/ml. In order to further the design of potent and selective antifolates against members of theEnterobacteriaceae, we determined the first crystal structures ofK. pneumoniaeDHFR bound to two of the propargyl-linked antifolates. These structures highlight that interactions with Leu 28, Ile 50, Ile 94, and Leu 54 are necessary for potency; comparison with structures of human DHFR bound to the same inhibitors reveal differences in residues (N64E, P61G, F31L, and V115I) and loop conformations (residues 49 to 53) that may be exploited for selectivity.

scholarly journals Oritavancin Activity against Vancomycin-Susceptible and Vancomycin-Resistant Enterococci with Molecularly Characterized Glycopeptide Resistance Genes Recovered from Bacteremic Patients, 2009-2010

2011 ◽  
Vol 56 (3) ◽  
pp. 1639-1642 ◽  
Author(s):  
Rodrigo E. Mendes ◽  
Leah N. Woosley ◽  
David J. Farrell ◽  
Helio S. Sader ◽  
Ronald N. Jones
Keyword(s):  
Resistance Genes ◽  
Glycopeptide Resistance ◽  
Content Type ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant

ABSTRACTOritavancin exhibited potent activity against vancomycin-susceptible (MIC50and MIC90, 0.015/0.03 μg/ml) andvanB-carryingE. faecalisisolates (MIC50and MIC90, 0.015 and 0.015 μg/ml). Higher (16- to 32-fold) MIC50s and MIC90s forvanA-harboringE. faecaliswere noted (MIC50and MIC90, 0.25 and 0.5 μg/ml), although oritavancin inhibited all strains at ≤0.5 μg/ml. Vancomycin-susceptible andvanB-carryingE. faeciumstrains (MIC50and MIC90, ≤0.008 and ≤0.008 μg/ml for both) were very susceptible to oritavancin, as were VanA-producing isolates (MIC50and MIC90, 0.03 and 0.06 μg/ml). Oritavancin exhibited goodin vitropotency against this collection of organisms, including vancomycin-resistant enterococci.

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