Rethinking urinary antibiotic breakpoints: analysis of urinary antibiotic concentrations to treat multidrug resistant organisms.
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ABSTRACT:
SUBMITTER: Chastain DB
PROVIDER: S-EPMC6053836 | biostudies-other | 2018 Jul
REPOSITORIES: biostudies-other
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Project description:Analysis of Antibiotic Resistant Organisms recovered from Clinical and Environmental Sources in Manitoba, Canada Genome sequencing and assembly
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Project description:The emergence and spread of multidrug-resistant organisms (MDROs) across global healthcare networks poses a serious threat to hospitalized individuals. Strategies to limit the emergence and spread of MDROs include oversight to decrease selective pressure for MDROs by promoting appropriate antibiotic use via antibiotic stewardship programs. However, restricting the use of one antibiotic often requires a compensatory increase in the use of other antibiotics, which in turn selects for the emergence of different MDRO species. Further, the downstream effects of antibiotic treatment decisions may also be influenced by functional interactions among different MDRO species, with the potential clinical implications of such interactions remaining largely unexplored. Here, we attempt to decipher the influence network between antibiotic treatment, MDRO colonization, and infection by leveraging active surveillance and antibiotic treatment data for 234 nursing home residents. Our analysis revealed a complex network of interactions: antibiotic use was a risk factor for primary MDRO colonization, which in turn increased the likelihood of colonization and infection by other MDROs. When we focused on the risk of catheter-associated urinary tract infections (CAUTI) caused by Escherichia coli, Enterococcus, and Staphylococcus aureus we observed that cocolonization with specific pairs of MDROs increased the risk of CAUTI, signifying the involvement of microbial interactions in CAUTI pathogenesis. In summary, our work demonstrates the existence of an underappreciated healthcare-associated ecosystem and strongly suggests that effective control of overall MDRO burden will require stewardship interventions that take into account both primary and secondary impacts of antibiotic treatments.
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Project description:OBJECTIVES:This study aims to assess the association between patient contact and intestinal carriage of multidrug-resistant organisms (MDRO) by sampling healthcare personnel (HCP) and staff without patient contact. METHODS:For this observational study, we recruited 400 HCP who worked in our 200-bed research hospital and 400 individuals without patient contact between November 2013 and February 2015. Participants submitted two self-collected perirectal swabs and a questionnaire. Swabs were processed for multidrug-resistant Gram-negative bacteria and vancomycin-resistant enterococci (VRE). Questionnaires explored occupational and personal risk factors for MDRO carriage. RESULTS:Among 800 participants, 94.4% (755/800) submitted at least one swab, and 91.4% (731/800) also submitted questionnaires. Extended spectrum ?-lactamase-producing organisms were recovered from 3.4% (26/755) of participants, and only one carbapenemase-producing organism was recovered. No VRE were detected. The potential exposure of 68.9% (250/363) of HCP who reported caring for MDRO-colonized patients did not result in a rate of MDRO carriage among HCP (4.0%; 15/379) significantly higher than that of staff without patient contact (3.2%; 12/376; p 0.55). CONCLUSIONS:This is the largest US study of HCP intestinal MDRO carriage. The low colonization rate is probably reflective of local community background rates, suggesting that HCP intestinal colonization plays a minor role in nosocomial spread of MDROs in a non-outbreak setting. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT01952158.
| S-EPMC5682231 | biostudies-literature
Project description:The spread of natural or weaponized drug-resistant plague among humans is a credible high consequence threat to public health that demands the prompt introduction of alternatives to antibiotics such as bacteriophage. Early attempts to treat plague with phages in the 1920s-1930s were sometimes promising but mostly failed, purportedly due to insufficient knowledge of phage biology and poor experimental design. We recently reported the striking stability of plague diagnostic bacteriophages, their safety for animal use, propagation in vivo and partial protection of mice from deadly plague after a single injection of phage. In this addendum we reflect on that article, other recent publications and our unpublished data, and discuss the prospects of phage therapy against plague.
| S-EPMC3530528 | biostudies-literature
Project description:OBJECTIVE To characterize the microbial disruption indices of hospitalized patients to predict colonization with multidrug-resistant organisms (MDROs). DESIGN A cross-sectional survey of the fecal microbiome was conducted in a tertiary referral, acute-care hospital in Boston, Massachusetts. PARTICIPANTS The study population consisted of adult patients hospitalized in general medical/surgical wards. METHODS Rectal swabs were obtained from patients within 48 hours of hospital admission and screened for MDRO colonization using conventional culture techniques. The V4 region of the 16S rRNA gene was sequenced to assess the fecal microbiome. Microbial diversity and composition, as well as the functional potential of the microbial communities present in fecal samples, were compared between patients with and without MDRO colonization. RESULTS A total of 44 patients were included in the study, of whom 11 (25%) were colonized with at least 1 MDRO. Reduced microbial diversity and high abundance of metabolic pathways associated with multidrug-resistance mechanisms characterized the fecal microbiome of patients colonized with MDRO at hospital admission. CONCLUSIONS Our data suggest that microbial disruption indices may be key to predicting MDRO colonization and could provide novel infection control approaches. Infect Control Hosp Epidemiol 2017;38:1312-1318.
| S-EPMC6262892 | biostudies-literature
Project description:Donor infection or colonization with a multidrug-resistant organism (MDRO) affects organ utilization and recipient antibiotic management. Approaches to identifying donors at risk of carrying MDROs are unknown. We sought to determine the risk factors for MDROs among transplant donors. A multicenter retrospective cohort study was conducted at four transplant centers between 2015 and 2016. All deceased donors who donated at least one organ were included. Cultures obtained during the donor's terminal hospitalization and organ procurement were evaluated. The primary outcome was isolation of an MDRO on culture. Multivariable Cox regression was used to determine risk factors associated with time to donor MDRO. Of 440 total donors, 64 (15%) donors grew an MDRO on culture. Predictors of an MDRO on donor culture included hepatitis C viremia (hazard ratio [HR] 4.09, 95% confidence interval [CI] 1.71-9.78, P = .002), need for dialysis (HR 4.59, 95% CI 1.09-19.21, P = .037), prior hematopoietic cell transplant (HR 7.57, 95% CI 1.03-55.75, P = .047), and exposure to antibiotics with a narrow gram-negative spectrum (HR 1.13, 95% CI 1.00-1.27, P = .045). This is the first study to determine risk factors for MDROs among deceased donors and will be important for risk stratifying potential donors and informing transplant recipient prophylaxis.
| S-EPMC6711782 | biostudies-literature
Project description:Antibiotic resistance is a major global health threat. High prevalences of colonization and infection with multi-drug resistance organisms (MDROs) have been reported in patients undergoing dialysis. It is unknown if this finding extends to patients with mild and moderate/severe kidney disease. An observational study included all adult incident patients hospitalized with a discharge diagnosis of infection in four hospitals from Guangzhou, China.Inclusion criteriaSerum creatinine measurement at admission together with microbial culture confirmed infections. Exclusion criterion: Undergoing renal replacement therapy. Four categories of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (eGFR) were compared: eGFR???105, 60-104 (reference), 30-59, and <30?ml/min/1.73?m2. The odds ratio of MDROs, defined as specific pathogens (Staphylococcus aureus, Enterococcus spp., Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp.) resistant to three or more antibiotic classes, were calculated using a multivariable logistic regression model across eGFR strata. Of 94,445 total microbial culture records, 7,288 first positive cultures matched to infection diagnosis were selected. Among them, 5,028 (68.9%) were potential MDROs. The odds of infections by MDROs was 19% and 41% higher in those with eGFR between 30-59?ml/min/1.73?m2 (Adjusted odds ratio, AOR): 1.19, 95% CI:1.02-1.38, P?=?0.022) and eGFR?<?30?ml/min/1.73?m2 (AOR: 1.41, 95% CI:1.12-1.78, P?=?0.004), respectively. Patients with impaired renal function have a higher risk of infections by MDROs. Kidney dysfunction at admission may be an indicator for need of closer attention to microbial culture results requiring subsequent change of antibiotics.
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Project description:IntroductionGuidelines for treatment of multidrug-resistant (MDR) bacteria rely on newly approved antibiotics, with limited evidence of their effectiveness for treating these infections. Data regarding cost of such an approach are lacking. We aimed to evaluate estimated cost of using newly approved antibiotic drugs compared to older antibiotics for the treatment of difficult-to-treat pathogens.MethodsMDR bacteria of interest included those defined by the World Health Organization as critical or of high priority for research. Old and newly approved antibiotics for these bacteria, defined as approved before or after January 2010, respectively, were evaluated for treatment cost and for 14-day treatment course. Estimated annual costs were calculated based on the Centers for Disease Control and Prevention's' report on MDR bacteria prevalence in US hospitalized patients. Old and new drugs costs were compared.ResultsThe cost of a 14-day treatment course for methicillin-resistant Staphylococcus aureus bacteremia with a newly approved drug was found to be 6 to 60 times higher than that of older drugs. Similarly, the cost of a 14-day course for carbapenem-resistant Enterobacterales or MDR Pseudomonas aeruginosa was doubled with new drugs; and for carbapenem-resistant Acinetobacter baumannii, ~ 20 times higher with newer drugs. Annual incremental costs of treating difficult-to-treat Gram-negative bacteria with new drugs ranged from 30 million to over 500 million USD.ConclusionsUsing newly approved antibiotic drugs for MDR infections carries a large incremental cost. Additional data to support survival benefit of these drugs are required to justify the price differences. Subgroups of patients who would benefit most from treatment should be defined.
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Project description:Nanotechnology using nanoscale materials is increasingly being utilized for clinical applications, especially as a new paradigm for infectious diseases. Infections caused by multidrug-resistant organisms (MDROs) are emerging as causes of morbidity and mortality worldwide. Antibiotic options for infections caused by MDROs are often limited. These clinical challenges highlight the critical demand for alternative and effective antimicrobial strategies. Nanoparticles (NPs) can penetrate the cell membrane of pathogenic microorganisms and interfere with important molecular pathways, formulating unique antimicrobial mechanisms. In combination with optimal antibiotics, NPs have demonstrated synergy and may aid in limiting the global crisis of emerging bacterial resistance. In this review, we summarized current research on the broad classification of the NPs that have shown in vitro antimicrobial activity against MDROs, including the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). The pharmacokinetics and pharmacodynamic characteristics of NPs and bacteria-resistant mechanisms to NPs were also discussed.
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