Know your Microbe Foes: The Role of Surveillance in Combatting Antimicrobial Resistance.

Antibiotic-resistant organisms (AROs) are difficult and costly to treat, associated with high mortality rates, and are on the rise. In the United States, there is limited tracking of AROs, which can contribute to transmission and inhibit infection prevention interventions. Surveillance is limited by a lack of standardized methods for colonization screening and limited communication regarding patient ARO-status between healthcare settings. Some regional surveillance and reporting efforts are in place for extensively-resistant AROs such as carbapenem-resistant Enterobacterales (CRE), but need to be further expanded nationwide and to include other AROs such as extended-spectrum ß-lactamase (ESBL) producing organisms. Increased surveillance of ARO infections and colonization will inform future targeted intervention and infection prevention strategies.

Gut Microbiota Features on Nursing Home Admission Are Associated With Subsequent Acquisition of Antibiotic-resistant Organism Colonization.

Nursing home (NH) patients often acquire colonization with antibiotic-resistant organisms (AROs). We show that patients exposed to broad-spectrum antibiotics during previous hospitalizations have elevated enterococcal relative abundances on NH admission and higher risk of subsequent ARO acquisition. Our findings suggest that interventions preventing ARO spread should extend beyond NH doors.

Application of Combined Genomic and Transfer Analyses to Identify Factors Mediating Regional Spread of Antibiotic-resistant Bacterial Lineages.

BACKGROUND: Patients entering nursing facilities (NFs) are frequently colonized with antibiotic-resistant organisms (AROs). To understand the determinants of ARO colonization on NF admission, we applied whole-genome sequencing to track the spread of 4 ARO species across regional NFs and evaluated patient-level characteristics and transfer acute care hospitals (ACHs) as risk factors for colonization. METHODS: Patients from 6 NFs (n = 584) were surveyed for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecalis/faecium (VREfc/VREfm), and ciprofloxacin-resistant Escherichia coli (CipREc) colonization. Genomic analysis was performed to quantify ARO spread between NFs and compared to patient-transfer networks. The association between admission colonization and patient-level variables and recent ACH exposures was examined. RESULTS: The majority of ARO isolates belonged to major healthcare-associated lineages: MRSA (sequence type [ST] 5); VREfc (ST6); CipREc (ST131), and VREfm (clade A). While the genomic similarity of strains between NF pairs was positively associated with overlap in their feeder ACHs (P < .05 for MRSA, VREfc, and CipREc), limited phylogenetic clustering by either ACH or NF supported regional endemicity. Significant predictors for ARO colonization on NF admission included lower functional status and recent exposure to glycopeptides (adjusted odds ratio [aOR], > 2 for MRSA and VREfc/VREfm) or third-/fourth-generation cephalosporins (aOR, > 2 for MRSA and VREfm). Transfer from specific ACHs was an independent risk factor for only 1 ARO/ACH pair (VREfm/ACH19: aOR, 2.48). CONCLUSIONS: In this region, healthcare-associated ARO lineages are endemic among connected NFs and ACHs, making patient characteristics more informative of NF admission colonization risk than exposure to specific ACHs.

Using Genetic Distance from Archived Samples for the Prediction of Antibiotic Resistance in Escherichia coli.

The rising rates of antibiotic resistance increasingly compromise empirical treatment. Knowing the antibiotic susceptibility of a pathogen's close genetic relative(s) may improve empirical antibiotic selection. Using genomic and phenotypic data for Escherichia coli isolates from three separate clinically derived databases, we evaluated multiple genomic methods and statistical models for predicting antibiotic susceptibility, focusing on potentially rapidly available information, such as lineage or genetic distance from archived isolates. We applied these methods to derive and validate the prediction of antibiotic susceptibility to common antibiotics. We evaluated 968 separate episodes of suspected and confirmed infection with Escherichia coli from three geographically and temporally separated databases in Ontario, Canada, from 2010 to 2018. Across all approaches, model performance (area under the curve [AUC]) ranges for predicting antibiotic susceptibility were the greatest for ciprofloxacin (AUC, 0.76 to 0.97) and the lowest for trimethoprim-sulfamethoxazole (AUC, 0.51 to 0.80). When a model predicted that an isolate was susceptible, the resulting (posttest) probabilities of susceptibility were sufficient to warrant empirical therapy for most antibiotics (mean, 92%). An approach combining multiple models could permit the use of narrower-spectrum oral agents in 2 out of every 3 patients while maintaining high treatment adequacy (∼90%). Methods based on genetic relatedness to archived samples of E. coli could be used to predict antibiotic resistance and improve antibiotic selection.

Recommendations for change in infection prevention programs and practice.

Fifty years of evolution in infection prevention and control programs have involved significant accomplishments related to clinical practices, methodologies, and technology. However, regulatory mandates, and resource and research limitations, coupled with emerging infection threats such as the COVID-19 pandemic, present considerable challenges for infection preventionists. This article provides guidance and recommendations in 14 key areas. These interventions should be considered for implementation by United States health care facilities in the near future.

Osteomyelitis infection caused by Arcanobacterium haemolyticum in a diabetic patient: A first case report.

Arcanobacterium haemolyticum can cause deep infections, including osteomyelitis. In this study, an automated system misidentified this causal agent as Cellulomonas species but 16 s rRNA sequencing correctly identified it as A. haemolyticum. Recognizing the capability of A. haemolyticum to establish the disease is of great importance to enable accurate diagnosis and begin the suitable antibiotic therapy. Here we present the first case of successfully treated A. haemolyticum infective osteomyelitis in a 64-year-old Saudi patient with diabetes mellitus type 2 and review the characteristics of this seldom pathogenic agent.

Impact of investigational microbiota therapeutic RBX2660 on the gut microbiome and resistome revealed by a placebo-controlled clinical trial.

BACKGROUND: Intestinal microbiota restoration can be achieved by complementing a subject's perturbed microbiota with that of a healthy donor. Recurrent Clostridioides difficile infection (rCDI) is one key application of such treatment. Another emerging application of interest is reducing antibiotic-resistant genes (ARGs) and organisms (AROs). In this study, we investigated fecal specimens from a multicenter, randomized, double-blind, placebo-controlled phase 2b study of microbiota-based investigational drug RBX2660. Patients were administered either placebo, 1 dose of RBX2660 and 1 placebo, or 2 doses of RBX2660 via enema and longitudinally tracked for changes in their microbiome and antibiotic resistome. RESULTS: All patients exhibited significant recovery of gut microbiome diversity and a decrease of ARG relative abundance during the first 7 days post-treatment. However, the microbiome and resistome shifts toward average configurations from unperturbed individuals were more significant and longer-lasting in RBX2660 recipients compared to placebo. We quantified microbiome and resistome modification by RBX2660 using a novel "transplantation index" metric. We identified taxonomic and metabolic features distinguishing the baseline microbiome of non-transplanted patients and taxa specifically enriched during the process of transplantation. We elucidated the correlation between resistome and taxonomic transplantations and post-treatment dynamics of patient-specific and RBX2660-specific ARGs. Whole genome sequencing of AROs cultured from RBX2660 product and patient samples indicate ARO eradication in patients via RBX2660 administration, but also, to a lesser extent, introduction of RBX2660-derived AROs. CONCLUSIONS: Through shotgun metagenomic sequencing, we elucidated the effects of RBX2660 in the microbiome and resistome. Antibiotic discontinuation alone resulted in significant recovery of gut microbial diversity and reduced ARG relative abundance, but RBX2660 administration more rapidly and completely changed the composition of patients' microbiome, resistome, and ARO colonization by transplanting RBX2660 microbiota into the recipients. Although ARGs and AROs were transmitted through RBX2660, the resistome post-RBX2660 more closely resembled that of the administered product-a proxy for the donor-than an antibiotic perturbed state. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02299570 . Registered 19 November 2014 Video Abstract.

Infections in patients with burn injuries receiving extracorporeal membrane oxygenation.

INTRODUCTION: Extracorporeal Membrane Oxygenation (ECMO) has only recently been described in patients with burn injuries. We report the incidence and type of infections in critically ill burn and non-burn patients receiving ECMO. METHODS: A retrospective chart review was performed on all patients at Brooke Army Medical Center who received ECMO between September 2012 and May 2018. RESULTS: 78 patients underwent ECMO. Approximately half were men with a median age of 34 years with a median time on ECMO of 237 h (IQR 121-391). Compared to patients without burns (n = 58), patients with burns (n = 20) had no difference in time on ECMO, but had more overall infections (86 vs. 31 per 1000 days, p = 0.0002), respiratory infections (40 vs. 15 per 1000 days, p = 0.01), skin and soft tissue infections (21 vs. 5 per 1000 days, p = 0.02) and fungal infections (35% vs 10%, p = 0.02). Twenty percent of bacterial burn infections were due to drug resistant organisms. CONCLUSION: This is the first study to describe the incidence of infection in burn injury patients who are undergoing ECMO. We observed an increase in infections in burn patients on ECMO compared to non-burn patients. ECMO remains a viable option for critically ill patients with burn injuries.

Utility of prior cultures in predicting antibiotic resistance of bloodstream infections due to Gram-negative pathogens: a multicentre observational cohort study.

OBJECTIVES: Appropriate empiric antibiotic therapy in patients with bloodstream infections due to Gram-negative pathogens can improve outcomes. We evaluated the utility of prior microbiologic results for guiding empiric treatment in Gram-negative bloodstream infections. METHODS: We conducted a multicentre observational cohort study in two large health systems in Canada and the United States, including 1832 hospitalized patients with Gram-negative bloodstream infection (community, hospital and intensive care unit acquired) from April 2010 to March 2015. RESULTS: Among 1832 patients with Gram-negative bloodstream infection, 28% (n = 504) of patients had a documented prior Gram-negative organism from a nonscreening culture within the previous 12 months. A most recent prior Gram-negative organism resistant to a given antibiotic was strongly predictive of the current organism's resistance to the same antibiotic. The overall specificity was 0.92 (95% confidence interval (CI) 0.91-0.93), and positive predictive value was 0.66 (95% CI 0.61-0.70) for predicting antibiotic resistance. Specificities and positive predictive values ranged from 0.77 to 0.98 and 0.43 to 0.78, respectively, across different antibiotics, organisms and patient subgroups. Increasing time between cultures was associated with a decrease in positive predictive value but not specificity. An heuristic based on a prior resistant Gram-negative pathogen could have been applied to one in four patients and in these patients would have changed therapy in one in five. CONCLUSIONS: In patients with a bloodstream infection with a Gram-negative organism, identification of a most recent prior Gram-negative organism resistant to a drug of interest (within the last 12 months) is highly specific for resistance and should preclude use of that antibiotic.

Universal contact precautions do not change the prevalence of antibiotic resistant organisms in a tertiary burn unit.

OBJECTIVE: The prevalence of antibiotic-resistant organisms (ARO) in burn units is increasing worldwide and contributes significantly to morbidity and mortality. Study aims are to describe the burden of AROs in burn patients admitted to a tertiary burn unit, to evaluate the impact of contact precautions implemented after an outbreak of antibiotic-resistant Acinetobacter baumannii, and to identify possible predictors of ARO acquisition. METHODS: Data of burn inpatients between 2006 and 2010 were retrospectively reviewed. The antibiotic susceptibility profiles of ARO colonization/infection at or after admission were reviewed in detail. Organisms of interest included: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), extended-spectrum beta-lactamase-producing Escherichia coli, and carbapenem-resistant Pseudomonas and Acinetobacter. Univariate and multivariate logistic regression analysis was employed with the p-value set at 0.05. RESULTS: Complete data analysis was available for 340 patients. The mean age was 41.8 years with male predominance. Among the AROs, the most prevalent was MRSA from clinical specimens. Prior to contact precaution implementation, the prevalence of all AROs was 27.9%, compared to 27.6% afterwards. There was an increase in Pseudomonas and VRE isolates and a disappearance of Acinetobacter. The most common isolate sites were the burn wounds. ICU stay, burns >20% TBSA, and surgical management were significant predictors of ARO acquisition. CONCLUSION: This study describes the ARO profile of burn patients admitted to a tertiary burn unit. The results suggest that implementation of unit-wide contact precautions may not significantly reduce the frequency of AROs among burn patients. Contact precautions for patients transferred from the ICU, undergoing surgery, and large burns may be of benefit.