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Background: Admission and discharge screening of patients for asymptomatic gut colonization with multidrug-resistant organisms (MDROs) is a common approach to active surveillance, but its sensitivity for detecting colonization is uncertain., Methods: Daily rectal or fecal swab samples and associated clinical data were collected over 12 months from patients in one 25-bed medical intensive care unit (ICU) in Chicago, IL and tested for the following MDROs: vancomycin-resistant enterococci; third-generation cephalosporin-resistant Enterobacterales, including extended-spectrum β-lactamase-producing Enterobacterales; and carbapenem-resistant Enterobacterales. MDRO detection by (1) admission and discharge surveillance cultures or (2) clinical cultures were compared to daily surveillance cultures. Samples underwent 16S rRNA gene sequencing to measure the relative abundance of operational taxonomic units (OTUs) corresponding to each MDRO., Results: Compared with daily surveillance cultures, admission/discharge cultures detected 91% of prevalent MDRO colonization and 63% of MDRO acquisitions among medical ICU patients. Few (7%) MDRO carriers were identified by clinical cultures alone. Higher relative abundance of MDRO-associated OTUs and specific antibiotic exposures were independently associated with higher probability of MDRO detection by culture., Conclusions: Admission and discharge surveillance cultures underestimated MDRO acquisitions in an ICU. These limitations should be considered when designing sampling strategies for epidemiologic studies that use culture-based surveillance., Competing Interests: Potential conflicts of interest. M. K. H. reported conducting studies for which participating healthcare facilities received contributed antiseptic and cleaning products from Stryker (formerly Sage), Molnlycke, and Clorox outside of the submitted work. M. Y. L. reported conducting studies for which participating healthcare facilities received laboratory testing at no charge from OpGen and contributed antiseptic products from Stryker (formerly Sage) outside of the submitted work. V. B. Y. serves as a consultant to Vedanta Biosciences and Debiopharm; and has received an honorarium from Aimmune. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: To characterize the relationship between chlorhexidine gluconate (CHG) skin concentration and skin microbial colonization., Design: Serial cross-sectional study., Setting/participants: Adult patients in medical intensive care units (ICUs) from 7 hospitals; from 1 hospital, additional patients colonized with carbapenemase-producing Enterobacterales (CPE) from both ICU and non-ICU settings. All hospitals performed routine CHG bathing in the ICU., Methods: Skin swab samples were collected from adjacent areas of the neck, axilla, and inguinal region for microbial culture and CHG skin concentration measurement using a semiquantitative colorimetric assay. We used linear mixed effects multilevel models to analyze the relationship between CHG concentration and microbial detection. We explored threshold effects using additional models., Results: We collected samples from 736 of 759 (97%) eligible ICU patients and 68 patients colonized with CPE. On skin, gram-positive bacteria were cultured most frequently (93% of patients), followed by Candida species (26%) and gram-negative bacteria (20%). The adjusted odds of microbial recovery for every twofold increase in CHG skin concentration were 0.84 (95% CI, 0.80-0.87; P < .001) for gram-positive bacteria, 0.93 (95% CI, 0.89-0.98; P = .008) for Candida species, 0.96 (95% CI, 0.91-1.02; P = .17) for gram-negative bacteria, and 0.94 (95% CI, 0.84-1.06; P = .33) for CPE. A threshold CHG skin concentration for reduced microbial detection was not observed., Conclusions: On a cross-sectional basis, higher CHG skin concentrations were associated with less detection of gram-positive bacteria and Candida species on the skin, but not gram-negative bacteria, including CPE. For infection prevention, targeting higher CHG skin concentrations may improve control of certain pathogens.

Plasmids are extrachromosomal genetic elements that often encode fitness-enhancing features. However, many bacteria carry "cryptic" plasmids that do not confer clear beneficial functions. We identified one such cryptic plasmid, pBI143, which is ubiquitous across industrialized gut microbiomes and is 14 times as numerous as crAssphage, currently established as the most abundant extrachromosomal genetic element in the human gut. The majority of mutations in pBI143 accumulate in specific positions across thousands of metagenomes, indicating strong purifying selection. pBI143 is monoclonal in most individuals, likely due to the priority effect of the version first acquired, often from one's mother. pBI143 can transfer between Bacteroidales, and although it does not appear to impact bacterial host fitness in vivo, it can transiently acquire additional genetic content. We identified important practical applications of pBI143, including its use in identifying human fecal contamination and its potential as an alternative approach to track human colonic inflammatory states., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Importance: Universal nasal mupirocin plus chlorhexidine gluconate (CHG) bathing in intensive care units (ICUs) prevents methicillin-resistant Staphylococcus aureus (MRSA) infections and all-cause bloodstream infections. Antibiotic resistance to mupirocin has raised questions about whether an antiseptic could be advantageous for ICU decolonization., Objective: To compare the effectiveness of iodophor vs mupirocin for universal ICU nasal decolonization in combination with CHG bathing., Design, Setting, and Participants: Two-group noninferiority, pragmatic, cluster-randomized trial conducted in US community hospitals, all of which used mupirocin-CHG for universal decolonization in ICUs at baseline. Adult ICU patients in 137 randomized hospitals during baseline (May 1, 2015-April 30, 2017) and intervention (November 1, 2017-April 30, 2019) were included., Intervention: Universal decolonization involving switching to iodophor-CHG (intervention) or continuing mupirocin-CHG (baseline)., Main Outcomes and Measures: ICU-attributable S aureus clinical cultures (primary outcome), MRSA clinical cultures, and all-cause bloodstream infections were evaluated using proportional hazard models to assess differences from baseline to intervention periods between the strategies. Results were also compared with a 2009-2011 trial of mupirocin-CHG vs no decolonization in the same hospital network. The prespecified noninferiority margin for the primary outcome was 10%., Results: Among the 801 668 admissions in 233 ICUs, the participants' mean (SD) age was 63.4 (17.2) years, 46.3% were female, and the mean (SD) ICU length of stay was 4.8 (4.7) days. Hazard ratios (HRs) for S aureus clinical isolates in the intervention vs baseline periods were 1.17 for iodophor-CHG (raw rate: 5.0 vs 4.3/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 4.1 vs 4.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 18.4% [95% CI, 10.7%-26.6%] for mupirocin-CHG, P < .001). For MRSA clinical cultures, HRs were 1.13 for iodophor-CHG (raw rate: 2.3 vs 2.1/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 2.0 vs 2.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 14.1% [95% CI, 3.7%-25.5%] for mupirocin-CHG, P = .007). For all-pathogen bloodstream infections, HRs were 1.00 (2.7 vs 2.7/1000) for iodophor-CHG and 1.01 (2.6 vs 2.6/1000) for mupirocin-CHG (nonsignificant HR difference in differences, -0.9% [95% CI, -9.0% to 8.0%]; P = .84). Compared with the 2009-2011 trial, the 30-day relative reduction in hazards in the mupirocin-CHG group relative to no decolonization (2009-2011 trial) were as follows: S aureus clinical cultures (current trial: 48.1% [95% CI, 35.6%-60.1%]; 2009-2011 trial: 58.8% [95% CI, 47.5%-70.7%]) and bloodstream infection rates (current trial: 70.4% [95% CI, 62.9%-77.8%]; 2009-2011 trial: 60.1% [95% CI, 49.1%-70.7%])., Conclusions and Relevance: Nasal iodophor antiseptic did not meet criteria to be considered noninferior to nasal mupirocin antibiotic for the outcome of S aureus clinical cultures in adult ICU patients in the context of daily CHG bathing. In addition, the results were consistent with nasal iodophor being inferior to nasal mupirocin., Trial Registration: ClinicalTrials.gov Identifier: NCT03140423.

Objective: To assess whether measurement and feedback of chlorhexidine gluconate (CHG) skin concentrations can improve CHG bathing practice across multiple intensive care units (ICUs)., Design: A before-and-after quality improvement study measuring patient CHG skin concentrations during 6 point-prevalence surveys (3 surveys each during baseline and intervention periods)., Setting: The study was conducted across 7 geographically diverse ICUs with routine CHG bathing., Participants: Adult patients in the medical ICU., Methods: CHG skin concentrations were measured at the neck, axilla, and inguinal region using a semiquantitative colorimetric assay. Aggregate unit-level CHG skin concentration measurements from the baseline period and each intervention period survey were reported back to ICU leadership, which then used routine education and quality improvement activities to improve CHG bathing practice. We used multilevel linear models to assess the impact of intervention on CHG skin concentrations., Results: We enrolled 681 (93%) of 736 eligible patients; 92% received a CHG bath prior to survey. At baseline, CHG skin concentrations were lowest on the neck, compared to axillary or inguinal regions ( P < .001). CHG was not detected on 33% of necks, 19% of axillae, and 18% of inguinal regions ( P < .001 for differences in body sites). During the intervention period, ICUs that used CHG-impregnated cloths had a 3-fold increase in patient CHG skin concentrations as compared to baseline ( P < .001)., Conclusions: Routine CHG bathing performance in the ICU varied across multiple hospitals. Measurement and feedback of CHG skin concentrations can be an important tool to improve CHG bathing practice.

To understand how a bacterium ultimately succeeds or fails in adapting to a new host, it is essential to assess the temporal dynamics of its fitness over the course of colonization. Here, we introduce a human-derived commensal organism, Bacteroides thetaiotaomicron (Bt), into the guts of germ-free mice to determine whether and how the genetic requirements for colonization shift over time. Combining a high-throughput functional genetics assay and transcriptomics, we find that gene usage changes drastically during the first days of colonization, shifting from high expression of amino acid biosynthesis genes to broad upregulation of diverse polysaccharide utilization loci. Within the first week, metabolism becomes centered around utilization of a predominant dietary oligosaccharide, and these changes are largely sustained through 6 weeks of colonization. Spontaneous mutations in wild-type Bt also evolve around this locus. These findings highlight the importance of considering temporal colonization dynamics in developing more effective microbiome-based therapies., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Changes in microbial community composition as a function of human health and disease states have sparked remarkable interest in the human gut microbiome. However, establishing reproducible insights into the determinants of microbial succession in disease has been a formidable challenge., Results: Here we use fecal microbiota transplantation (FMT) as an in natura experimental model to investigate the association between metabolic independence and resilience in stressed gut environments. Our genome-resolved metagenomics survey suggests that FMT serves as an environmental filter that favors populations with higher metabolic independence, the genomes of which encode complete metabolic modules to synthesize critical metabolites, including amino acids, nucleotides, and vitamins. Interestingly, we observe higher completion of the same biosynthetic pathways in microbes enriched in IBD patients., Conclusions: These observations suggest a general mechanism that underlies changes in diversity in perturbed gut environments and reveal taxon-independent markers of "dysbiosis" that may explain why widespread yet typically low-abundance members of healthy gut microbiomes can dominate under inflammatory conditions without any causal association with disease., (© 2023. The Author(s).)

Emerging and re-emerging respiratory viruses can spread rapidly and cause pandemics as demonstrated by the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The early human immune responses to respiratory viruses are in the nasal cavity and nasopharyngeal regions. Defining biomarkers of disease trajectory at the time of a positive diagnostic test would be an important tool to facilitate decisions such as initiation of antiviral treatment. We hypothesize that nasopharyngeal tRNA profiles could be used to predict Coronavirus Disease 19 (COVID-19) severity. We carried out multiplex small RNA sequencing (MSR-seq) on residual nasopharyngeal swabs to measure simultaneously full-length tRNA abundance, tRNA modifications, and tRNA fragmentation for the human tRNA response to SARS-CoV-2 infection. We identified distinct tRNA signatures associated with mild symptoms versus severe COVID-19 manifestations requiring hospitalization. These results highlight the utility of host tRNA properties as biomarkers for the clinical outcome of SARS-CoV-2., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Katanski, Alshammary, Watkins, Huang, Gonzales-Reiche, Sordillo, van Bakel, Mount Sinai PSP study group, Lolans, Simon and Pan.)

Background: A crucial barrier to the routine application of whole-genome sequencing (WGS) for infection prevention is the insufficient criteria for determining whether a genomic linkage is consistent with transmission within the facility. We evaluated the use of single-nucleotide variant (SNV) thresholds, as well as a novel threshold-free approach, for inferring transmission linkages in a high-transmission setting., Methods: We did a retrospective genomic epidemiology analysis of samples previously collected in the context of an intervention study at a long-term acute care hospital in the USA. We performed WGS on 435 isolates of Klebsiella pneumoniae harbouring the bla KPC carbapenemase (KPC-Kp) collected from 256 patients through admission and surveillance culturing (once every 2 weeks) of almost every patient who was admitted to hospital over a 1-year period., Findings: Our analysis showed that the standard approach of using an SNV threshold to define transmission would lead to false-positive and false-negative inferences. False-positive inferences were driven by the frequent importation of closely related strains, which were presumably linked via transmission at connected health-care facilities. False-negative inferences stemmed from the diversity of colonising populations that were spread among patients, with multiple examples of hypermutator strain emergence within patients and, as a result, putative transmission links separated by large genetic distances. Motivated by limitations of an SNV threshold, we implemented a novel threshold-free transmission cluster inference approach, in which each of the acquired KPC-Kp isolates were linked back to the imported KPC-Kp isolate with which it shared the most variants. This approach yielded clusters that varied in levels of genetic diversity but where 105 (81%) of 129 unique strain acquisition events were associated with epidemiological links in the hospital. Of 100 patients who acquired KPC-Kp isolates that were included in a cluster, 47 could be linked to a single patient who was positive for KPC-Kp at admission, compared with 31 and 25 using 10 SNV and 20 SNV thresholds, respectively. Holistic examination of clusters highlighted extensive variation in the magnitude of onward transmission stemming from more than 100 importation events and revealed patterns in cluster propagation that could inform improvements to infection prevention strategies., Interpretation: Our results show how the integration of culture surveillance data into genomic analyses can overcome limitations of cluster detection based on SNV-thresholds and improve the ability to track pathways of pathogen transmission in health-care settings., Funding: US Center for Disease Control and Prevention and University of Michigan., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

By offering extremely long contiguous characterization of individual DNA molecules, rapidly emerging long-read sequencing strategies offer comprehensive insights into the organization of genetic information in genomes and metagenomes. However, successful long-read sequencing experiments demand high concentrations of highly purified DNA of high molecular weight (HMW), which limits the utility of established DNA extraction kits designed for short-read sequencing. The challenges associated with input DNA quality intensify further when working with complex environmental samples of low microbial biomass, which requires new protocols that are tailored to study metagenomes with long-read sequencing. Here, we use human tongue scrapings to benchmark six HMW DNA extraction strategies that are based on commercially available kits, phenol-chloroform (PC) extraction and agarose encasement followed by agarase digestion. A typical end goal of HMW DNA extractions is to obtain the longest possible reads during sequencing, which is often achieved by PC extractions, as demonstrated in sequencing of cultured cells. Yet our analyses that consider overall read-size distribution, assembly performance and the number of circularized elements found in sequencing results suggest that column-based kits with enzyme supplementation, rather than PC methods, may be more appropriate for long-read sequencing of metagenomes., (© 2022 The Authors. Molecular Ecology Resources published by John Wiley & Sons Ltd.)

Pseudouridine (Ψ) is an abundant mRNA modification in mammalian transcriptome, but its functions have remained elusive due to the difficulty of transcriptome-wide mapping. We develop a nanopore native RNA sequencing method for quantitative Ψ prediction (NanoPsu) that utilizes native content training, machine learning modeling, and single-read linkage analysis. Biologically, we find interferon inducible Ψ modifications in interferon-stimulated gene transcripts which are consistent with a role of Ψ in enabling efficacy of mRNA vaccines., (© 2021. The Author(s).)

Introduction: Microbial residents of the human oral cavity have long been a major focus of microbiology due to their influence on host health and intriguing patterns of site specificity amidst the lack of dispersal limitation. However, the determinants of niche partitioning in this habitat are yet to be fully understood, especially among taxa that belong to recently discovered branches of microbial life., Results: Here, we assemble metagenomes from tongue and dental plaque samples from multiple individuals and reconstruct 790 non-redundant genomes, 43 of which resolve to TM7, a member of the Candidate Phyla Radiation, forming six monophyletic clades that distinctly associate with either plaque or tongue. Both pangenomic and phylogenomic analyses group tongue-specific clades with other host-associated TM7 genomes. In contrast, plaque-specific TM7 group with environmental TM7 genomes. Besides offering deeper insights into the ecology, evolution, and mobilome of cryptic members of the oral microbiome, our study reveals an intriguing resemblance between dental plaque and non-host environments indicated by the TM7 evolution, suggesting that plaque may have served as a stepping stone for environmental microbes to adapt to host environments for some clades of microbes. Additionally, we report that prophages are widespread among oral-associated TM7, while absent from environmental TM7, suggesting that prophages may have played a role in adaptation of TM7 to the host environment., Conclusions: Our data illuminate niche partitioning of enigmatic members of the oral cavity, including TM7, SR1, and GN02, and provide genomes for poorly characterized yet prevalent members of this biome, such as uncultivated Flavobacteriaceae.

Objective: Cohorting patients who are colonized or infected with multidrug-resistant organisms (MDROs) protects uncolonized patients from acquiring MDROs in healthcare settings. The potential for cross transmission within the cohort and the possibility of colonized patients acquiring secondary isolates with additional antibiotic resistance traits is often neglected. We searched for evidence of cross transmission of KPC+ Klebsiella pneumoniae (KPC-Kp) colonization among cohorted patients in a long-term acute-care hospital (LTACH), and we evaluated the impact of secondary acquisitions on resistance potential., Design: Genomic epidemiological investigation., Setting: A high-prevalence LTACH during a bundled intervention that included cohorting KPC-Kp-positive patients., Methods: Whole-genome sequencing (WGS) and location data were analyzed to identify potential cases of cross transmission between cohorted patients., Results: Secondary KPC-Kp isolates from 19 of 28 admission-positive patients were more closely related to another patient's isolate than to their own admission isolate. Of these 19 cases, 14 showed strong genomic evidence for cross transmission (<10 single nucleotide variants or SNVs), and most of these patients occupied shared cohort floors (12 patients) or rooms (4 patients) at the same time. Of the 14 patients with strong genomic evidence of acquisition, 12 acquired antibiotic resistance genes not found in their primary isolates., Conclusions: Acquisition of secondary KPC-Kp isolates carrying distinct antibiotic resistance genes was detected in nearly half of cohorted patients. These results highlight the importance of healthcare provider adherence to infection prevention protocols within cohort locations, and they indicate the need for future studies to assess whether multiple-strain acquisition increases risk of adverse patient outcomes.

Background: An association between increased relative abundance of specific bacterial taxa in the intestinal microbiota and bacteremia has been reported in some high-risk patient populations., Methods: We collected weekly rectal swab samples from patients at 1 long-term acute care hospital (LTACH) in Chicago from May 2015 to May 2016. Samples positive for Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) by polymerase chain reaction and culture underwent 16S rRNA gene sequence analysis; relative abundance of the operational taxonomic unit containing KPC-Kp was determined. Receiver operator characteristic (ROC) curves were constructed using results from the sample with highest relative abundance of KPC-Kp from each patient admission, excluding samples collected after KPC-Kp bacteremia. Cox regression analysis was performed to evaluate risk factors associated with time to achieve KPC-Kp relative abundance thresholds calculated by ROC curve analysis., Results: We collected 2319 samples from 562 admissions (506 patients); KPC-Kp colonization was detected in 255 (45.4%) admissions and KPC-Kp bacteremia in 11 (4.3%). A relative abundance cutoff of 22% predicted KPC-Kp bacteremia with sensitivity 73%, specificity 72%, and relative risk 4.2 (P = .01). In a multivariable Cox regression model adjusted for age, Charlson comorbidity index, and medical devices, carbapenem receipt was associated with achieving the 22% relative abundance threshold (P = .044)., Conclusion: Carbapenem receipt was associated with increased hazard for high relative abundance of KPC-Kp in the gut microbiota. Increased relative abundance of KPC-Kp was associated with KPC-Kp bacteremia. Whether bacteremia arose directly from bacterial translocation or indirectly from skin contamination followed by bloodstream invasion remains to be determined., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective: We assessed the impact of personal protective equipment (PPE) doffing errors on healthcare worker (HCW) contamination with multidrug-resistant organisms (MDROs)., Design: Prospective, observational study., Setting: The study was conducted at 4 adult ICUs at 1 tertiary-care teaching hospital., Participants: HCWs who cared for patients on contact precautions for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci, or multidrug-resistant gram-negative bacilli were enrolled. Samples were collected from standardized areas of patient body, garb sites, and high-touch environmental surfaces in patient rooms. HCW hands, gloves, PPE, and equipment were sampled before and after patient interaction. Research personnel observed PPE doffing and coded errors based on CDC guidelines., Results: We enrolled 125 HCWs; most were nurses (66.4%) or physicians (19.2%). During the study, 95 patients were on contact precautions for MRSA. Among 5,093 cultured sites (HCW, patient, environment), 652 (14.7%) yielded the target MDRO. Moreover, 45 HCWs (36%) were contaminated with the target MDRO after patient interactions, including 4 (3.2%) on hands and 38 (30.4%) on PPE. Overall, 49 HCWs (39.2%) made multiple doffing errors and were more likely to have contaminated clothes following a patient interaction (risk ratio [RR], 4.69; P = .04). All 4 HCWs with hand contamination made doffing errors. The risk of hand contamination was higher when gloves were removed before gowns during PPE doffing (RR, 11.76; P = .025)., Conclusion: When caring for patients on CP for MDROs, HCWs appear to have differential risk for hand contamination based on their method of doffing PPE. An intervention as simple as reinforcing the preferred order of doffing may reduce HCW contamination with MDROs.

Wolbachia is a genus of obligate intracellular bacteria found in nematodes and arthropods worldwide, including insect vectors that transmit dengue, West Nile, and Zika viruses. Wolbachia's unique ability to alter host reproductive behavior through its temperate bacteriophage WO has enabled the development of new vector control strategies. However, our understanding of Wolbachia's mobilome beyond its bacteriophages is incomplete. Here, we reconstruct near-complete Wolbachia genomes from individual ovary metagenomes of four wild Culex pipiens mosquitoes captured in France. In addition to viral genes missing from the Wolbachia reference genome, we identify a putative plasmid (pWCP), consisting of a 9.23-kbp circular element with 14 genes. We validate its presence in additional Culex pipiens mosquitoes using PCR, long-read sequencing, and screening of existing metagenomes. The discovery of this previously unrecognized extrachromosomal element opens additional possibilities for genetic manipulation of Wolbachia.

Competing Interests: All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. Michael Lin reports receiving research support in the form of contributed product from OpGen and Sage Products, and an investigator-initiated grant from CareFusion Foundation (now part of BD). Mary Hayden reports receiving support in the form of contributed product from Sage (now Stryker) and from Molnlycke. Deb Burdsall and Mary Alice Lavin report receiving personal fees from APIC Consulting Services. No other potential conflicts of interest were disclosed.

Background: Identification of gut microbiota features associated with antibiotic-resistant bacterial colonization may reveal new infection prevention targets., Methods: We conducted a matched, case-control study of long-term acute care hospital (LTACH) patients to identify gut microbiota and clinical features associated with colonization by Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp), an urgent antibiotic resistance threat. Fecal or rectal swab specimens were collected and tested for KPC-Kp; 16S rRNA gene-based sequencing was performed. Comparisons were made between cases and controls in calibration and validation subsamples using microbiota similarity indices, logistic regression, and unit-weighted predictive models., Results: Case (n = 32) and control (n = 99) patients had distinct fecal microbiota communities, but neither microbiota diversity nor inherent clustering into community types distinguished case and control specimens. Comparison of differentially abundant operational taxonomic units (OTUs) revealed 1 OTU associated with case status in both calibration (n = 51) and validation (n = 80) subsamples that matched the canonical KPC-Kp strain ST258. Permutation analysis using the presence or absence of OTUs and hierarchical logistic regression identified 2 OTUs (belonging to genus Desulfovibrio and family Ruminococcaceae ) associated with KPC-Kp colonization. Among clinical variables, the presence of a decubitus ulcer alone was independently and consistently associated with case status. Combining the presence of the OTUs Desulfovibrio and Ruminococcaceae with decubitus ulcer increased the likelihood of KPC-Kp colonization to >38% in a unit-weighted predictive model., Conclusions: We identified microbiota and clinical features that distinguished KPC-Kp gut colonization in LTACH patients, a population particularly susceptible to KPC-Kp infection. These features may warrant further investigation as markers of risk for KPC-Kp colonization.

Background: In 2007, Illinois became the first state in the United States to mandate active surveillance of methicillin-resistant Staphylococcus aureus (MRSA). The Illinois law applies to intensive care unit (ICU) patients; contact precautions are required for patients found to be MRSA colonized. However, the effectiveness of a legislated "search and isolate" approach to reduce MRSA burden among critically ill patients is uncertain. We evaluated whether the prevalence of MRSA colonization declined in the 5 years after the start of mandatory active surveillance., Methods: All hospitals with an ICU having ≥10 beds in Chicago, Illinois, were eligible to participate in single-day serial point prevalence surveys. We assessed MRSA colonization among adult ICU patients present at time of survey using nasal and inguinal swab cultures. The primary outcome was region-wide MRSA colonization prevalence over time., Results: All 25 eligible hospitals (51 ICUs) participated in serial point prevalence surveys over 8 survey periods (2008-2013). A total of 3909 adult ICU patients participated in the point prevalence surveys, with 432 (11.1%) found to be colonized with MRSA (95% confidence interval [CI], 10.1%-12.0%). The MRSA colonization prevalence among patients was unchanged during the study period; year-over-year relative risk for MRSA colonization was 0.97 (95% CI, .89-1.05; P = .48)., Conclusions: MRSA colonization prevalence among critically ill adult patients did not decline during the time period following legislatively mandated MRSA active surveillance. Our findings highlight the limits of legislated MRSA active surveillance as a strategy to reduce MRSA colonization burden among ICU patients.

BACKGROUND Bathing intensive care unit (ICU) patients with 2% chlorhexidine gluconate (CHG)-impregnated cloths decreases the risk of healthcare-associated bacteremia and multidrug-resistant organism transmission. Hospitals employ different methods of CHG bathing, and few studies have evaluated whether those methods yield comparable results. OBJECTIVE To determine whether 3 different CHG skin cleansing methods yield similar residual CHG concentrations and bacterial densities on skin. DESIGN Prospective, randomized 2-center study with blinded assessment. PARTICIPANTS AND SETTING Healthcare personnel in surgical ICUs at 2 tertiary-care teaching hospitals in Chicago, Illinois, and Boston, Massachusetts, from July 2015 to January 2016. INTERVENTION Cleansing skin of one forearm with no-rinse 2% CHG-impregnated polyester cloth (method A) versus 4% CHG liquid cleansing with rinsing on the contralateral arm, applied with either non-antiseptic-impregnated cellulose/polyester cloth (method B) or cotton washcloth dampened with sterile water (method C). RESULTS In total, 63 participants (126 forearms) received method A on 1 forearm (n=63). On the contralateral forearm, 33 participants received method B and 30 participants received method C. Immediately and 6 hours after cleansing, method A yielded the highest residual CHG concentrations (2500 µg/mL and 1250 µg/mL, respectively) and lowest bacterial densities compared to methods B or C (P<.001). CONCLUSION In healthy volunteers, cleansing with 2% CHG-impregnated cloths yielded higher residual CHG concentrations and lower bacterial densities than cleansing with 4% CHG liquid applied with either of 2 different cloth types and followed by rinsing. The relevance of these differences to clinical outcomes remains to be determined. Infect Control Hosp Epidemiol 2018;39:405-411.

Development of effective strategies to limit the proliferation of multidrug-resistant organisms requires a thorough understanding of how such organisms spread among health care facilities. We sought to uncover the chains of transmission underlying a 2008 U.S. regional outbreak of carbapenem-resistant Klebsiella pneumoniae by performing an integrated analysis of genomic and interfacility patient-transfer data. Genomic analysis yielded a high-resolution transmission network that assigned directionality to regional transmission events and discriminated between intra- and interfacility transmission when epidemiologic data were ambiguous or misleading. Examining the genomic transmission network in the context of interfacility patient transfers (patient-sharing networks) supported the role of patient transfers in driving the outbreak, with genomic analysis revealing that a small subset of patient-transfer events was sufficient to explain regional spread. Further integration of the genomic and patient-sharing networks identified one nursing home as an important bridge facility early in the outbreak-a role that was not apparent from analysis of genomic or patient-transfer data alone. Last, we found that when simulating a real-time regional outbreak, our methodology was able to accurately infer the facility at which patients acquired their infections. This approach has the potential to identify facilities with high rates of intra- or interfacility transmission, data that will be useful for triggering targeted interventions to prevent further spread of multidrug-resistant organisms., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

OBJECTIVE To identify modifiable risk factors for acquisition of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae (KPC) colonization among long-term acute-care hospital (LTACH) patients. DESIGN Multicenter, matched case-control study. SETTING Four LTACHs in Chicago, Illinois. PARTICIPANTS Each case patient included in this study had a KPC-negative rectal surveillance culture on admission followed by a KPC-positive surveillance culture later in the hospital stay. Each matched control patient had a KPC-negative rectal surveillance culture on admission and no KPC isolated during the hospital stay. RESULTS From June 2012 to June 2013, 2,575 patients were admitted to 4 LTACHs; 217 of 2,144 KPC-negative patients (10.1%) acquired KPC. In total, 100 of these patients were selected at random and matched to 100 controls by LTACH facility, admission date, and censored length of stay. Acquisitions occurred a median of 16.5 days after admission. On multivariate analysis, we found that exposure to higher colonization pressure (OR, 1.02; 95% CI, 1.01-1.04; P=.002), exposure to a carbapenem (OR, 2.25; 95% CI, 1.06-4.77; P=.04), and higher Charlson comorbidity index (OR, 1.14; 95% CI, 1.01-1.29; P=.04) were independent risk factors for KPC acquisition; the odds of KPC acquisition increased by 2% for each 1% increase in colonization pressure. CONCLUSIONS Higher colonization pressure, exposure to carbapenems, and a higher Charlson comorbidity index independently increased the odds of KPC acquisition among LTACH patients. Reducing colonization pressure (through separation of KPC-positive patients from KPC-negative patients using strict cohorts or private rooms) and reducing carbapenem exposure may prevent KPC cross transmission in this high-risk patient population. Infect Control Hosp Epidemiol 2017;38:670-677.

Background: Sample collection for gut microbiota analysis from in-patients can be challenging. Collection method and storage conditions are potential sources of variability. In this study, we compared the bacterial microbiota from stool stored under different conditions, as well as stool and swab samples, to assess differences due to sample storage conditions and collection method., Methods: Using bacterial 16S rRNA gene sequence analysis, we compared the microbiota profiles of stool samples stored and collected under various conditions. Stool samples (2 liquid, 1 formed) from three different patients at two hospitals were each evaluated under the following conditions: immediately frozen at -80°C, stored at 4°C for 12-48 hours before freezing at -80°C and stored at -20°C with 1-2 thaw cycles before storage at -80°C. Additionally, 8 stool and 30 rectal swab samples were collected from 8 in-patients at one hospital. Microbiota differences were assessed using the Yue and Clayton dissimilarity index (θ YC distance) and analysis of molecular variance (AMOVA)., Results: Regardless of the storage conditions, the bacterial communities of aliquots from the same stool samples were very similar based on θ YC distances (median intra-sample θ YC distance: 0.035, IQR: 0.015-0.061) compared to aliquots from different stool samples (median inter-sample θ YC distance: 0.93, IQR: 0.85-0.97) (Wilcoxon test p-value: <0.0001). For the stool and rectal swab comparison, samples from different patients, regardless of sample collection method, were significantly different (AMOVA p-values: <0.001-0.029) compared to no significant difference between all stool and swab samples (AMOVA p-value: 0.976). The θ YC dissimilarity index between swab and stool samples was significantly lower within individuals (median 0.17, IQR: 0.10-0.27) than between individuals (median 0.93, IQR: 0.85-0.97) (Wilcoxon test p-value: <0.0001), indicating minimal differences between stool and swab samples collected from the same individual over the sampling period., Conclusion: For gastrointestinal microbiota studies based on bacterial 16S rRNA gene sequence analysis, interim stool sample storage at 4 °C or -20 °C, rather than immediate storage at -80 °C, does not significantly alter results. Additionally, stool and rectal swab microbiotas from the same subject were highly similar, indicating that these sampling methods could be used interchangeably to assess the community structure of the distal GI tract.

Background: In theory, active surveillance of methicillin-resistant Staphylococcus aureus (MRSA) reduces MRSA spread by identifying all MRSA-colonized patients and placing them under contact precautions. In October 2007, Illinois mandated active MRSA surveillance in all intensive care units, including neonatal intensive care units (NICUs) and pediatric intensive care units (PICUs). We evaluated MRSA trends in a large metropolitan region in the wake of this law., Methods: Chicago hospitals with a NICU or PICU were recruited for 8 single-day point prevalence surveys that occurred twice-yearly between June 2008 and July 2011 and then yearly in 2012 to 2013. Samples from all patients were cultured for MRSA (nose and umbilicus for neonates, nose and groin for pediatric patients). Hospital-reported admission MRSA-screening results also were obtained. Point prevalence cultures were screened for MRSA by using broth enrichment, chromogenic agar, and standard confirmatory methods., Results: All eligible hospitals (N = 10) participated (10 NICUs, 6 PICUs). Hospital-reported adherence to state-mandated MRSA screening at admission was high (95% for NICUs, 94% for PICUs). From serial point prevalence surveys, overall MRSA prevalences in the NICUs and PICUs were 4.2% (89 of 2101) and 5.7% (36 of 632), respectively. MRSA colonization prevalences were unchanged in the NICUs (year-over-year risk ratio [RR], 0.93 [95% confidence interval (CI), 0.78-1.12]; P = .45) and trended toward an increase in the PICUs (RR, 1.25 [95% CI, 0.72-2.12]; P = .053). We estimated that 81% and 40% of MRSA-positive patients in the NICUs and PICUs, respectively, had newly acquired MRSA., Conclusions: In a region with mandated active MRSA surveillance, we found ongoing unchanged rates of MRSA colonization and acquisition among NICU and PICU patients., (© The Author 2015. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Whether targeted or universal decolonization strategies for the control of methicillin-resistant Staphylococcus aureus (MRSA) select for resistance to decolonizing agents is unresolved. The REDUCE-MRSA trial (ClinicalTrials registration no. NCT00980980) provided an opportunity to investigate this question. REDUCE-MRSA was a 3-arm, cluster-randomized trial of either screening and isolation without decolonization, targeted decolonization with chlorhexidine and mupirocin, or universal decolonization without screening to prevent MRSA infection in intensive-care unit (ICU) patients. Isolates from the baseline and intervention periods were collected and tested for susceptibility to chlorhexidine gluconate (CHG) by microtiter dilution; mupirocin susceptibility was tested by Etest. The presence of the qacA or qacB gene was determined by PCR and DNA sequence analysis. A total of 3,173 isolates were analyzed; 2 were nonsusceptible to CHG (MICs, 8 μg/ml), and 5/814 (0.6%) carried qacA or qacB At baseline, 7.1% of MRSA isolates expressed low-level mupirocin resistance, and 7.5% expressed high-level mupirocin resistance. In a mixed-effects generalized logistic regression model, the odds of mupirocin resistance among clinical MRSA isolates or MRSA isolates acquired in an ICU in intervention versus baseline periods did not differ across arms, although estimates were imprecise due to small numbers. Reduced susceptibility to chlorhexidine and carriage of qacA or qacB were rare among MRSA isolates in the REDUCE-MRSA trial. The odds of mupirocin resistance were no different in the intervention versus baseline periods across arms, but the confidence limits were broad, and the results should be interpreted with caution., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Background.  High prevalence of Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae has been reported in long-term acute care hospitals (LTACHs), in part because of frequent readmissions of colonized patients. Knowledge of the duration of colonization with KPC is essential to identify patients at risk of KPC colonization upon readmission and to make predictions on the effects of transmission control measures. Methods.  We analyzed data on surveillance isolates that were collected at 4 LTACHs in the Chicago region during a period of bundled interventions, to simultaneously estimate the duration of colonization during an LTACH admission and between LTACH (re)admissions. A maximum-likelihood method was used, taking interval-censoring into account. Results.  Eighty-three percent of patients remained colonized for at least 4 weeks, which was the median duration of LTACH stay. Between LTACH admissions, the median duration of colonization was 270 days (95% confidence interval, 91-∞). Conclusions.  Only 17% of LTACH patients lost colonization with KPC within 4 weeks. Approximately half of the KPC-positive patients were still carriers when readmitted after 9 months. Infection control practices should take prolonged carriage into account to limit transmission of KPCs in LTACHs.

There has been an increasing interest in the use of probiotic products for the prevention of Clostridium difficile infection (CDI). Bio-K+(®) is a commercial probiotic product comprising three strains of lactobacilli--Lactobacillus acidophilus CL1285(®), Lact. casei LBC80R(®) and Lact. rhamnosus CLR2(®)--that have been applied to prevent CDI. Generally considered as safe, lactobacilli have potential to cause bacteremia, endocarditis and other infections. The source of Lactobacillus bacteremia can be normal human flora or lactobacilli-containing probiotic. The aim of this study was to assess whether probiotic lactobacilli caused bacteremia and to show the value of molecular identification and typing techniques to determine probiotic and patient strain relatedness. We report an episode of Lactobacillus bacteremia in a 69-year-old man admitted to a hospital with severe congestive heart failure. During his hospitalization, he required long-term antibiotic therapy. Additionally, the patient received Bio-K+(®) probiotic as part of a quality improvement project to prevent CDI. Subsequently, Lactobacillus bacteremia occurred. Two independent blinded laboratory evaluations, using pulse field gel electrophoresis, 16S rRNA gene sequencing and DNA fingerprint analysis (rep-PCR), were performed to determine whether the recovered Lact. acidophilus originated from the probiotic product. Ultimately, the patient strain was identified as Lact. casei and both laboratories found no genetic relation between the patient's strain and any of the probiotic lactobacilli. This clinical case of lactobacillus bacteremia in the setting of probiotic exposure demonstrates the value of using discriminatory molecular methods to clearly determine whether there were a link between the patient's isolate and the probiotic strains.

Objective: Prevalence of bla KPC-encoding Enterobacteriaceae (KPC) in Chicago long-term acute care hospitals (LTACHs) rose rapidly after the first recognition in 2007. We studied the epidemiology and transmission capacity of KPC in LTACHs and the effect of patient cohorting., Methods: Data were available from 4 Chicago LTACHs from June 2012 to June 2013 during a period of bundled interventions. These consisted of screening for KPC rectal carriage, daily chlorhexidine bathing, medical staff education, and 3 cohort strategies: a pure cohort (all KPC-positive patients on 1 floor), single rooms for KPC-positive patients, and a mixed cohort (all KPC-positive patients on 1 floor, supplemented with KPC-negative patients). A data-augmented Markov chain Monte Carlo (MCMC) method was used to model the transmission process., Results: Average prevalence of KPC colonization was 29.3%. On admission, 18% of patients were colonized; the sensitivity of the screening process was 81%. The per admission reproduction number was 0.40. The number of acquisitions per 1,000 patient days was lowest in LTACHs with a pure cohort ward or single rooms for colonized patients compared with mixed-cohort wards, but 95% credible intervals overlapped., Conclusions: Prevalence of KPC in LTACHs is high, primarily due to high admission prevalence and the resultant impact of high colonization pressure on cross transmission. In this setting, with an intervention in place, patient-to-patient transmission is insufficient to maintain endemicity. Inclusion of a pure cohort or single rooms for KPC-positive patients in an intervention bundle seemed to limit transmission compared to use of a mixed cohort.

Background: Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae (hereafter "KPC") are an increasing threat to healthcare institutions. Long-term acute-care hospitals (LTACHs) have especially high prevalence of KPC., Methods: Using a stepped-wedge design, we tested whether a bundled intervention (screening patients for KPC rectal colonization upon admission and every other week; contact isolation and geographic separation of KPC-positive patients in ward cohorts or single rooms; bathing all patients daily with chlorhexidine gluconate; and healthcare-worker education and adherence monitoring) would reduce colonization and infection due to KPC in 4 LTACHs with high endemic KPC prevalence. The study was conducted between 1 February 2010 and 30 June 2013; 3894 patients were enrolled during the preintervention period (lasting from 16 to 29 months), and 2951 patients were enrolled during the intervention period (lasting from 12 to 19 months)., Results: KPC colonization prevalence was stable during preintervention (average, 45.8%; 95% confidence interval [CI], 42.1%-49.5%), declined early during intervention, then reached a plateau (34.3%; 95% CI, 32.4%-36.2%; P<.001 for exponential decline). During intervention, KPC admission prevalence remained high (average, 20.6%, 95% CI, 19.1%-22.3%). The incidence rate of KPC colonization fell during intervention, from 4 to 2 acquisitions per 100 patient-weeks (P=.004 for linear decline). Compared to preintervention, average rates of clinical outcomes declined during intervention: KPC in any clinical culture (3.7 to 2.5/1000 patient-days; P=.001), KPC bacteremia (0.9 to 0.4/1000 patient-days; P=.008), all-cause bacteremia (11.2 to 7.6/1000 patient-days; P=.006) and blood culture contamination (4.9 to 2.3/1000 patient-days; P=.03)., Conclusions: A bundled intervention was associated with clinically important and statistically significant reductions in KPC colonization, KPC infection, all-cause bacteremia, and blood culture contamination in a high-risk LTACH population., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

We evaluated the effectiveness of daily chlorhexidine gluconate (CHG) bathing in decreasing skin carriage of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae (KPC) among long-term acute care hospital patients. CHG bathing reduced KPC skin colonization, particularly when CHG skin concentrations greater than or equal to 128 μg/mL were achieved.

In a comparison of 3 agar plate methods, we found that a novel chromogenic medium, Remel Spectra™ CRE, had the best overall sensitivity (97.8%) when compared to the CHROMagar™ KPC (76.6%) and a direct ertapenem disk method (83.0%) for the detection of blaKPC-positive Enterobacteriaceae from perirectal swabs., (© 2014.)

Background: In the United States, Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae are increasingly detected in clinical infections; however, the colonization burden of these organisms among short-stay and long-term acute care hospitals is unknown., Methods: Short-stay acute care hospitals with adult intensive care units (ICUs) in the city of Chicago were recruited for 2 cross-sectional single-day point prevalence surveys (survey 1, July 2010-January 2011; survey 2, January-July 2011). In addition, all long-term acute care hospitals (LTACHs) in the Chicago region (Cook County) were recruited for a single-day point prevalence survey during January-May 2011. Swab specimens were collected from rectal, inguinal, or urine sites and tested for Enterobacteriaceae carrying blaKPC., Results: We surveyed 24 of 25 eligible short-stay acute care hospitals and 7 of 7 eligible LTACHs. Among LTACHs, 30.4% (119 of 391) of patients were colonized with KPC-producing Enterobacteriaceae, compared to 3.3% (30 of 910) of short-stay hospital ICU patients (prevalence ratio, 9.2; 95% confidence interval, 6.3-13.5). All surveyed LTACHs had patients harboring KPC (prevalence range, 10%-54%), versus 15 of 24 short-stay hospitals (prevalence range, 0%-29%). Several patient-level covariates present at the time of survey-LTACH facility type, mechanical ventilation, and length of stay-were independent risk factors for KPC-producing Enterobacteriaceae colonization., Conclusions: We identified high colonization prevalence of KPC-producing Enterobacteriaceae among patients in LTACHs. Patients with chronic medical care needs in long-term care facilities may play an important role in the spread of these extremely drug-resistant pathogens.

We assessed the performance of a duplex real-time PCR assay for bla(KPC) and bla(NDM) performed directly (D-PCR) on perianal and perirectal swabs and stool. Spiked specimens and 126 clinical surveillance swabs (comprising a sensitivity panel of 46 perirectal double swabs previously determined to be culture positive for bla(KPC)-PCR-positive Enterobacteriaceae and a specificity panel of 80 perianal swabs from patients at risk of carbapenemase-producing Enterobacteriaceae [CPE] colonization) were studied. For the surveillance swabs, D-PCR was compared to PCR after broth enrichment (BE-PCR) and two culture-based methods: the HardyCHROM ESBL agar (HC-A) and the CDC screening (CDC-A) methods. PCR was performed on morphologically distinct colonies that were isolated by culture. All of the initial PCR testing was done without extraction using a simple lysis procedure. The analytical sensitivities of D-PCR for bla(KPC) were 9 CFU/μl (for swabs) and 90 CFU/μl (for stool), and for bla(NDM), it was 1.9 CFU/μl (for both swabs and stool). In the clinical sensitivity panel, D-PCR and BE-PCR were initially positive for bla(KPC) in 41/46 (89.1%) and 43/46 (93.5%) swabs, respectively. The swabs that were initially negative by D-PCR (n = 5) and BE-PCR (n = 3) were visibly stool soiled; all swabs were bla(KPC) positive upon repeat testing after lysate extraction. The CDC-A and HC-A yielded bla(KPC)-positive Enterobacteriaceae from 36/46 (78.3%) and 35/46 (76.1%) swabs, respectively (sensitivities of D-PCR/BE-PCR postextraction of soiled specimens versus HC-A, P = 0.0009, and versus CDC-A, P = 0.0016). All swabs in the specificity panel were negative for CPE by all four methods. D-PCR allows for the timely detection of bla(KPC) and bla(NDM) carriage with excellent sensitivity when specimens visibly soiled with stool undergo preparatory extraction.

We compared carbapenemase detection among 271 Gram-negative bacilli (of which 131 were carbapenemase producers) using a novel chromogenic rapid test--the Carba NP test (CNP)--and the modified Hodge test (MHT). Sensitivities were comparable (CNP, 100%, versus MHT, 98%; P = 0.08), but CNP was more specific (100% versus 80%; P < 0.0001) and faster.

Background: Both targeted decolonization and universal decolonization of patients in intensive care units (ICUs) are candidate strategies to prevent health care-associated infections, particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA)., Methods: We conducted a pragmatic, cluster-randomized trial. Hospitals were randomly assigned to one of three strategies, with all adult ICUs in a given hospital assigned to the same strategy. Group 1 implemented MRSA screening and isolation; group 2, targeted decolonization (i.e., screening, isolation, and decolonization of MRSA carriers); and group 3, universal decolonization (i.e., no screening, and decolonization of all patients). Proportional-hazards models were used to assess differences in infection reductions across the study groups, with clustering according to hospital., Results: A total of 43 hospitals (including 74 ICUs and 74,256 patients during the intervention period) underwent randomization. In the intervention period versus the baseline period, modeled hazard ratios for MRSA clinical isolates were 0.92 for screening and isolation (crude rate, 3.2 vs. 3.4 isolates per 1000 days), 0.75 for targeted decolonization (3.2 vs. 4.3 isolates per 1000 days), and 0.63 for universal decolonization (2.1 vs. 3.4 isolates per 1000 days) (P=0.01 for test of all groups being equal). In the intervention versus baseline periods, hazard ratios for bloodstream infection with any pathogen in the three groups were 0.99 (crude rate, 4.1 vs. 4.2 infections per 1000 days), 0.78 (3.7 vs. 4.8 infections per 1000 days), and 0.56 (3.6 vs. 6.1 infections per 1000 days), respectively (P<0.001 for test of all groups being equal). Universal decolonization resulted in a significantly greater reduction in the rate of all bloodstream infections than either targeted decolonization or screening and isolation. One bloodstream infection was prevented per 54 patients who underwent decolonization. The reductions in rates of MRSA bloodstream infection were similar to those of all bloodstream infections, but the difference was not significant. Adverse events, which occurred in 7 patients, were mild and related to chlorhexidine., Conclusions: In routine ICU practice, universal decolonization was more effective than targeted decolonization or screening and isolation in reducing rates of MRSA clinical isolates and bloodstream infection from any pathogen. (Funded by the Agency for Healthcare Research and the Centers for Disease Control and Prevention; REDUCE MRSA ClinicalTrials.gov number, NCT00980980).

Objective: To determine anatomic sites of colonization in patients and to assess environmental contamination with Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae., Design, Setting, and Patients: We conducted a cross-sectional microbiologic survey of 33 patients and their environments at 6 long-term acute care hospitals (LTACHs) in metropolitan Chicago. Swab samples of anatomic sites and inanimate surfaces in patients' rooms and common areas were cultured. bla(KPC) was verified by polymerase chain reaction. Patient charts were reviewed for covariates known to be associated with colonization and environmental contamination., Results: Mean age was 66 years. Median length of stay prior to surveillance was 50 days. Thirty (91%) patients were mechanically ventilated, 32 (97%) were bedbound, and 27 (82%) had fecal incontinence. Of the 24 patients with KPC-producing Enterobacteriaceae recovered from 1 or more anatomic sites, 23 (96%) had KPC-producing Enterobacteriaceae detected at 1 or more skin sites. Skin colonization was more common in patients with positive rectal/stool swab cultures or positive clinical cultures ([Formula: see text]). Rectal/stool swab was the single most sensitive specimen for detecting KPC-producing Enterobacteriaceae colonization (sensitivity, 88%; 95% confidence interval [CI], 68%-97%); addition of inguinal skin swab culture resulted in detection of all colonized patients (sensitivity, 100%; 95% CI, 86%-100%). Only 2 (0.5%) of 371 environmental specimens grew KPC-producing Enterobacteriaceae., Conclusions: Culture of more than 1 anatomic site was required to detect all KPC-producing Enterobacteriaceae-colonized patients. Skin colonization was common, but environmental contamination was rare. These results can guide development of multimodal interventions for control of KPC-producing Enterobacteriaceae in LTACHs.