Reducing Hospitalizations and Multidrug-Resistant Organisms via Regional Decolonization in Hospitals and Nursing Homes.

Importance: Infections due to multidrug-resistant organisms (MDROs) are associated with increased morbidity, mortality, length of hospitalization, and health care costs. Regional interventions may be advantageous in mitigating MDROs and associated infections. Objective: To evaluate whether implementation of a decolonization collaborative is associated with reduced regional MDRO prevalence, incident clinical cultures, infection-related hospitalizations, costs, and deaths. Design, Setting, and Participants: This quality improvement study was conducted from July 1, 2017, to July 31, 2019, across 35 health care facilities in Orange County, California. Exposures: Chlorhexidine bathing and nasal iodophor antisepsis for residents in long-term care and hospitalized patients in contact precautions (CP). Main Outcomes and Measures: Baseline and end of intervention MDRO point prevalence among participating facilities; incident MDRO (nonscreening) clinical cultures among participating and nonparticipating facilities; and infection-related hospitalizations and associated costs and deaths among residents in participating and nonparticipating nursing homes (NHs). Results: Thirty-five facilities (16 hospitals, 16 NHs, 3 long-term acute care hospitals [LTACHs]) adopted the intervention. Comparing decolonization with baseline periods among participating facilities, the mean (SD) MDRO prevalence decreased from 63.9% (12.2%) to 49.9% (11.3%) among NHs, from 80.0% (7.2%) to 53.3% (13.3%) among LTACHs (odds ratio [OR] for NHs and LTACHs, 0.48; 95% CI, 0.40-0.57), and from 64.1% (8.5%) to 55.4% (13.8%) (OR, 0.75; 95% CI, 0.60-0.93) among hospitalized patients in CP. When comparing decolonization with baseline among NHs, the mean (SD) monthly incident MDRO clinical cultures changed from 2.7 (1.9) to 1.7 (1.1) among participating NHs, from 1.7 (1.4) to 1.5 (1.1) among nonparticipating NHs (group × period interaction reduction, 30.4%; 95% CI, 16.4%-42.1%), from 25.5 (18.6) to 25.0 (15.9) among participating hospitals, from 12.5 (10.1) to 14.3 (10.2) among nonparticipating hospitals (group × period interaction reduction, 12.9%; 95% CI, 3.3%-21.5%), and from 14.8 (8.6) to 8.2 (6.1) among LTACHs (all facilities participating; 22.5% reduction; 95% CI, 4.4%-37.1%). For NHs, the rate of infection-related hospitalizations per 1000 resident-days changed from 2.31 during baseline to 1.94 during intervention among participating NHs, and from 1.90 to 2.03 among nonparticipating NHs (group × period interaction reduction, 26.7%; 95% CI, 19.0%-34.5%). Associated hospitalization costs per 1000 resident-days changed from $64 651 to $55 149 among participating NHs and from $55 151 to $59 327 among nonparticipating NHs (group × period interaction reduction, 26.8%; 95% CI, 26.7%-26.9%). Associated hospitalization deaths per 1000 resident-days changed from 0.29 to 0.25 among participating NHs and from 0.23 to 0.24 among nonparticipating NHs (group × period interaction reduction, 23.7%; 95% CI, 4.5%-43.0%). Conclusions and Relevance: A regional collaborative involving universal decolonization in long-term care facilities and targeted decolonization among hospital patients in CP was associated with lower MDRO carriage, infections, hospitalizations, costs, and deaths.

Chlorhexidine and Mupirocin for Clearance of Methicillin-Resistant Staphylococcus aureus Colonization After Hospital Discharge: A Secondary Analysis of the Changing Lives by Eradicating Antibiotic Resistance Trial.

BACKGROUND: The CLEAR Trial demonstrated that a multisite body decolonization regimen reduced post-discharge infection and hospitalization in methicillin-resistant Staphylococcus aureus (MRSA) carriers. Here, we describe decolonization efficacy. METHODS: We performed a large, multicenter, randomized clinical trial of MRSA decolonization among adult patients after hospital discharge with MRSA infection or colonization. Participants were randomized 1:1 to either MRSA prevention education or education plus decolonization with topical chlorhexidine, oral chlorhexidine, and nasal mupirocin. Participants were swabbed in the nares, throat, axilla/groin, and wound (if applicable) at baseline and 1, 3, 6, and 9 months after randomization. The primary outcomes of this study are follow-up colonization differences between groups. RESULTS: Among 2121 participants, 1058 were randomized to decolonization. By 1 month, MRSA colonization was lower in the decolonization group compared with the education-only group (odds ration [OR] = 0.44; 95% confidence interval [CI], .36-.54; P ≤ .001). A similar magnitude of reduction was seen in the nares (OR = 0.34; 95% CI, .27-.42; P < .001), throat (OR = 0.55; 95% CI, .42-.73; P < .001), and axilla/groin (OR = 0.57; 95% CI, .43-.75; P < .001). These differences persisted through month 9 except at the wound site, which had a relatively small sample size. Higher regimen adherence was associated with lower MRSA colonization (P ≤ .01). CONCLUSIONS: In a randomized, clinical trial, a repeated post-discharge decolonization regimen for MRSA carriers reduced MRSA colonization overall and at multiple body sites. Higher treatment adherence was associated with greater reductions in MRSA colonization.

Inter-species geographic signatures for tracing horizontal gene transfer and long-term persistence of carbapenem resistance.

BACKGROUND: Carbapenem-resistant Enterobacterales (CRE) are an urgent global health threat. Inferring the dynamics of local CRE dissemination is currently limited by our inability to confidently trace the spread of resistance determinants to unrelated bacterial hosts. Whole-genome sequence comparison is useful for identifying CRE clonal transmission and outbreaks, but high-frequency horizontal gene transfer (HGT) of carbapenem resistance genes and subsequent genome rearrangement complicate tracing the local persistence and mobilization of these genes across organisms. METHODS: To overcome this limitation, we developed a new approach to identify recent HGT of large, near-identical plasmid segments across species boundaries, which also allowed us to overcome technical challenges with genome assembly. We applied this to complete and near-complete genome assemblies to examine the local spread of CRE in a systematic, prospective collection of all CRE, as well as time- and species-matched carbapenem-susceptible Enterobacterales, isolated from patients from four US hospitals over nearly 5 years. RESULTS: Our CRE collection comprised a diverse range of species, lineages, and carbapenem resistance mechanisms, many of which were encoded on a variety of promiscuous plasmid types. We found and quantified rearrangement, persistence, and repeated transfer of plasmid segments, including those harboring carbapenemases, between organisms over multiple years. Some plasmid segments were found to be strongly associated with specific locales, thus representing geographic signatures that make it possible to trace recent and localized HGT events. Functional analysis of these signatures revealed genes commonly found in plasmids of nosocomial pathogens, such as functions required for plasmid retention and spread, as well survival against a variety of antibiotic and antiseptics common to the hospital environment. CONCLUSIONS: Collectively, the framework we developed provides a clearer, high-resolution picture of the epidemiology of antibiotic resistance importation, spread, and persistence in patients and healthcare networks.

Pediatric coccidioidal orbital granuloma.

PURPOSE: To report a case of orbital coccidiomycosis in an otherwise healthy 11-month-old male. OBSERVATIONS: An 11-month-old male presented to his pediatrician with parental complaints of swelling, erythema, and pain of the right orbit that increased over ten days in the absence of constitutional symptoms. The child's parents reported an earlier fall onto a carpeted floor. After four weeks of conservative treatment and a course of oral cephalexin, he developed a fever, increased erythema, and palpable enlargement of a mass posterior to the lower eyelid. Ultrasound revealed an encysted mass in the inferior orbit, suggestive of an abscess. Urgent ophthalmic referral led to incision and drainage via orbitotomy. Culture, histopathology, and serological testing were positive for Coccidioides spp.. Blood studies revealed mild anemia and thrombocytosis. There was complete resolution of symptoms after surgical drainage and several weeks of oral fluconazole. CONCLUSION AND IMPORTANCE: We describe a patient with orbital coccidiomycosis without apparent systemic involvement, following what was most likely an unrelated minor trauma. Despite being rare, orbital coccidiomycosis should be considered as a primary manifestation of infection when ocular inflammation is encountered, especially in endemic regions.

Double-swab 5% versus single-swab 10% iodophor for reducing methicillin-resistant Staphylococcus aureus with routine chlorhexidine bathing.

In a prospective cohort study, we compared a 2-swabs-per-nostril 5% iodophor regimen with a 1-swab-per-nostril 10% iodophor regimen on methicillin-resistant Staphylococcus aureus carriage in nursing-home residents. Compared with baseline, both single-swab and double-swab regimens resulted in an identical 40% reduction in nasal carriage and 60% reduction in any carriage, skin or nasal.

Associations of Postbaccalaureate Coursework with Underrepresented Race/Ethnicity, Academic Performance, and Primary Care Training among Matriculants at Five California Medical Schools.

Studies employing data collected over 15 years ago suggested salutary effects of postbaccalaureate (PB) premedical coursework on medical school class diversity, academic performance, and primary care training. The studies may have limited current applicability given changes in medical school admissions paradigms and population demographics. Using data from interviewees at >1 of 5 California public medical schools between 2011-2013 (N=3805), we examined associations of PB premedical coursework with underrepresented race/ethnicity; academic performance (United States Medical Licensing Examination Step 1 and Step 2 scores, clerkship Honors); and primary care residency. Adjusting for age, sex, and year, PB coursework was associated with underrepresented race/ethnicity, but not after further adjustment for self-designated disadvantage (SDA). PB coursework was not associated with academic performance or primary care residency. Holistic consideration of SDA and UIM status in admissions coupled with robust matriculant support may merit exploration as an alternative to PB coursework for increasing medical school diversity.

High Prevalence of Multidrug-Resistant Organism Colonization in 28 Nursing Homes: An "Iceberg Effect".

OBJECTIVE: Determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp. (VRE), extended-spectrum beta-lactamase producing organisms (ESBLs), and carbapenem-resistant Enterobacteriaceae (CRE) among residents and in the environment of nursing homes (NHs). DESIGN: Point prevalence sampling of residents and environmental sampling of high-touch objects in resident rooms and common areas. SETTING: Twenty-eight NHs in Southern California from 2016 to 2017. PARTICIPANTS: NH participants in Project PROTECT, a cluster-randomized trial of enhanced bathing and decolonization vs routine care. METHODS: Fifty residents were randomly sampled per NH. Twenty objects were sampled, including 5 common room objects plus 5 objects in each of 3 rooms (ambulatory, total care, and dementia care residents). RESULTS: A total of 2797 swabs were obtained from 1400 residents in 28 NHs. Median prevalence of multidrug-resistant organism (MDRO) carriage per NH was 50% (range: 24%-70%). Median prevalence of specific MDROs were as follows: MRSA, 36% (range: 20%-54%); ESBL, 16% (range: 2%-34%); VRE, 5% (range: 0%-30%); and CRE, 0% (range: 0%-8%). A median of 45% of residents (range: 24%-67%) harbored an MDRO without a known MDRO history. Environmental MDRO contamination was found in 74% of resident rooms and 93% of common areas. CONCLUSIONS AND IMPLICATIONS: In more than half of the NHs, more than 50% of residents were colonized with MDROs of clinical and public health significance, most commonly MRSA and ESBL. Additionally, the vast majority of resident rooms and common areas were MDRO contaminated. The unknown submerged portion of the iceberg of MDRO carriers in NHs may warrant changes to infection prevention and control practices, particularly high-fidelity adoption of universal strategies such as hand hygiene, environmental cleaning, and decolonization.

The Relationships among Self-Designated Disadvantage, Socioeconomic Disadvantage, and Academic Performance in Medical School: A Multi-Institutional Study.

As medical schools seek to address the growing disparity between the socioeconomic makeup of their students and the general population, it is important to understand the academic trajectory of disadvantaged students. We used a locally-developed multicomponent socioeconomic disadvantage (SED) measure and the self-designated disadvantaged (SDA) question ["yes" (+) or "no" (-)] from the American Medical College Application Service application to examine academic performance of students from three disadvantaged categories (high SED/SDA+, high SED/SDA-, and low SED/SDA+); with low SED/SDA-as the reference group across five California schools. Compared with reference, the DA+ subgroups scored lower on USMLE Step 1 and Step 2 Clinical Knowledge examinations and received fewer clerkship Honors. After adjustment for academic metrics and sociodemographic variables, high SED subgroups performed similarly to reference, but performance gaps for low SED/SDA+ students persisted. Medical schools must better understand the institutional and other drivers of academic success in disadvantaged students.

Rapid bacterial detection and antibiotic susceptibility testing in whole blood using one-step, high throughput blood digital PCR.

Sepsis due to antimicrobial resistant pathogens is a major health problem worldwide. The inability to rapidly detect and thus treat bacteria with appropriate agents in the early stages of infections leads to excess morbidity, mortality, and healthcare costs. Here we report a rapid diagnostic platform that integrates a novel one-step blood droplet digital PCR assay and a high throughput 3D particle counter system with potential to perform bacterial identification and antibiotic susceptibility profiling directly from whole blood specimens, without requiring culture and sample processing steps. Using CTX-M-9 family ESBLs as a model system, we demonstrated that our technology can simultaneously achieve unprecedented high sensitivity (10 CFU per ml) and rapid sample-to-answer assay time (one hour). In head-to-head studies, by contrast, real time PCR and BioRad ddPCR only exhibited a limit of detection of 1000 CFU per ml and 50-100 CFU per ml, respectively. In a blinded test inoculating clinical isolates into whole blood, we demonstrated 100% sensitivity and specificity in identifying pathogens carrying a particular resistance gene. We further demonstrated that our technology can be broadly applicable for targeted detection of a wide range of antibiotic resistant genes found in both Gram-positive (vanA, nuc, and mecA) and Gram-negative bacteria, including ESBLs (blaCTX-M-1 and blaCTX-M-2 families) and CREs (blaOXA-48 and blaKPC), as well as bacterial speciation (E. coli and Klebsiella spp.) and pan-bacterial detection, without requiring blood culture or sample processing. Our rapid diagnostic technology holds great potential in directing early, appropriate therapy and improved antibiotic stewardship in combating bloodstream infections and antibiotic resistance.

Autophagy Limits Inflammasome During Chlamydia pneumoniae Infection.

Autophagy can either antagonize or promote intracellular bacterial growth, depending on the pathogen. Here, we investigated the role of autophagy during a pulmonary infection with the obligate intracellular pathogen, Chlamydia pneumoniae (CP). In mouse embryonic fibroblasts (MEFs) or macrophages, deficiency of autophagy pathway components led to enhanced CP replication, suggesting that autophagy exerts a bactericidal role. However, in vivo, mice with myeloid-specific deletion of the autophagic protein ATG16L1 suffered increased mortality during CP infection, neutrophilia, and increased inflammasome activation despite no change in bacterial burden. Induction of autophagy led to reduced CP replication in vitro, but impaired survival in CP-infected mice, associated with an initial reduction in IL-1ß production, followed by enhanced neutrophil recruitment, defective CP clearance, and later inflammasome activation and IL-1ß production, which drove the resulting mortality. Taken together, our data suggest that a delicate interplay exists between autophagy and inflammasome activation in determining the outcome of CP infection, perturbation of which can result in inflammatory pathology or unrestricted bacterial growth.

The SHIELD Orange County Project: Multidrug-resistant Organism Prevalence in 21 Nursing Homes and Long-term Acute Care Facilities in Southern California.

BACKGROUND: Multidrug-resistant organisms (MDROs) spread between hospitals, nursing homes (NHs), and long-term acute care facilities (LTACs) via patient transfers. The Shared Healthcare Intervention to Eliminate Life-threatening Dissemination of MDROs in Orange County is a regional public health collaborative involving decolonization at 38 healthcare facilities selected based on their high degree of patient sharing. We report baseline MDRO prevalence in 21 NHs/LTACs. METHODS: A random sample of 50 adults for 21 NHs/LTACs (18 NHs, 3 LTACs) were screened for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp. (VRE), extended-spectrum ß-lactamase-producing organisms (ESBL), and carbapenem-resistant Enterobacteriaceae (CRE) using nares, skin (axilla/groin), and peri-rectal swabs. Facility and resident characteristics associated with MDRO carriage were assessed using multivariable models clustering by person and facility. RESULTS: Prevalence of MDROs was 65% in NHs and 80% in LTACs. The most common MDROs in NHs were MRSA (42%) and ESBL (34%); in LTACs they were VRE (55%) and ESBL (38%). CRE prevalence was higher in facilities that manage ventilated LTAC patients and NH residents (8% vs <1%, P < .001). MDRO status was known for 18% of NH residents and 49% of LTAC patients. MDRO-colonized adults commonly harbored additional MDROs (54% MDRO+ NH residents and 62% MDRO+ LTACs patients). History of MRSA (odds ratio [OR] = 1.7; confidence interval [CI]: 1.2, 2.4; P = .004), VRE (OR = 2.1; CI: 1.2, 3.8; P = .01), ESBL (OR = 1.6; CI: 1.1, 2.3; P = .03), and diabetes (OR = 1.3; CI: 1.0, 1.7; P = .03) were associated with any MDRO carriage. CONCLUSIONS: The majority of NH residents and LTAC patients harbor MDROs. MDRO status is frequently unknown to the facility. The high MDRO prevalence highlights the need for prevention efforts in NHs/LTACs as part of regional efforts to control MDRO spread.

Do Admissions Multiple Mini-Interview and Traditional Interview Scores Predict Subsequent Academic Performance? A Study of Five California Medical Schools.

PURPOSE: To compare the predictive validities of medical school admissions multiple mini-interviews (MMIs) and traditional interviews (TIs). METHOD: This longitudinal observational study of 2011-2013 matriculants to five California public medical schools examined the associations of MMI scores (two schools) and TI scores (three schools) with subsequent academic performance. Regression models adjusted for sociodemographics and undergraduate academic metrics examined associations of standardized mean MMI and TI scores with United States Medical Licensing Examination Step 1 and Step 2 Clinical Knowledge (CK) scores and, for required clerkships, with mean National Board of Medical Examiners Clinical Science subject (shelf) exam score and number of honors grades. RESULTS: Of the 1,460 medical students, 746 (51.1%) interviewed at more than one study school; 579 (39.7%) completed at least one MMI and at least one TI. Neither interview type was associated with Step 1 scores. Higher MMI scores were associated with more clerkship honors grades (adjusted incidence rate ratio [AIRR] 1.28 more [95% CI 1.18, 1.39; P < .01] per SD increase) and higher shelf exam and Step 2 CK scores (adjusted mean 0.73 points higher [95% CI 0.28, 1.18; P < .01] and 1.25 points higher [95% CI 0.09, 2.41; P = .035], respectively, per SD increase). Higher TI scores were associated only with more honors grades (AIRR 1.11 more [95% CI 1.01, 1.20; P = .03] per SD increase). CONCLUSIONS: MMI scores were more strongly associated with subsequent academic performance measures than were TI scores.

Do Multiple Mini-Interview and Traditional Interview Scores Differ in Their Associations With Acceptance Offers Within and Across Five California Medical Schools?

PURPOSE: In single-school studies, multiple mini-interview (MMI) and traditional interview (TI) scores are associated with acceptance offers. Unexamined is whether scores at one school are associated with acceptance at other schools; such analyses would mitigate single-school design biases and better estimate how well interviews capture desired applicant attributes. Using data from the 5 California Longitudinal Evaluation of Admissions Practices (CA-LEAP) medical schools, the authors examined associations of MMI and TI scores with acceptance offers within and across schools. METHOD: The analyses included applicants who interviewed at ≥1 CA-LEAP school during the 2011-2013 admissions cycles. Three CA-LEAP schools employed TIs and 2 employed MMIs. Interview scores were standardized (z scores: mean = 0, SD = 1), and associations with acceptance offers were examined within and across schools in analyses stratified by school, adjusting for applicant sociodemographics, academic metrics, year, and total number of interviews. RESULTS: Of 4,993 applicants interviewed, 428 (8.6%) interviewed at both MMI schools, 681 (13.6%) at ≥2 TI schools, and 1,327 (26.6%) at ≥1 MMI and ≥1 TI school. For each school, acceptance was associated with interview score at that school and also with interview scores at the other 4 schools. Cross-school associations of MMI versus TI scores with acceptance did not differ statistically. CONCLUSIONS: Interview score at a given school was associated with acceptance at the other 4 schools, with no significant differences in associations for MMIs versus TIs. The findings suggest both MMIs and TIs captured attributes valued by admissions teams across CA-LEAP schools.

Medical School Applicant Characteristics Associated With Performance in Multiple Mini-Interviews Versus Traditional Interviews: A Multi-Institutional Study.

PURPOSE: To examine applicant characteristics associated with multiple mini-interview (MMI) or traditional interview (TI) performance at five California medical schools. METHOD: Of the five California Longitudinal Evaluation of Admission Practices consortium schools, three used TIs and two used MMIs. Schools provided retrospective data on 2011-2013 admissions cycle interviewees: age, gender, race/ethnicity (underrepresented in medicine [UIM] or not), disadvantaged (DA) status, undergraduate GPA, Medical College Admission Test (MCAT) score, and interview score (standardized as z score; mean = 0; SD = 1). Adjusted linear regression analyses, stratified by interview type, examined associations with interview performance. RESULTS: The 4,993 applicants who completed 7,516 interviews included 931 (18.6%) UIM and 962 (19.3%) DA individuals; 3,226 (64.6%) had only 1 interview. Mean age was 24.4 (SD = 2.7); mean GPA and MCAT score were 3.72 (SD = 0.22) and 33.6 (SD = 3.7), respectively. Older age, female gender, and number of prior interviews were associated with better performance on both MMIs and TIs. Higher GPA was associated with lower MMI scores (z score, per unit GPA = -0.26; 95% CI = -0.45, -0.06) but unrelated to TI scores. DA applicants had higher TI scores (z score = 0.17; 95% CI = 0.07, 0.28) but lower MMI scores (z score = -0.18; 95% CI = -0.28, -0.08) than non-DA applicants. Neither UIM status nor MCAT score was associated with interview performance. CONCLUSIONS: These findings have potentially important workforce implications, particularly regarding MMI performance of DA applicants, and illustrate the need for other multi-institutional studies.

Reliability of Multiple Mini-Interviews and traditional interviews within and between institutions: a study of five California medical schools.

BACKGROUND: Many medical schools use admissions Multiple Mini-Interviews (MMIs) rather than traditional interviews (TIs), partly because MMIs are thought to be more reliable. Yet prior studies examined single-school samples of candidates completing either an MMI or TI (not both). Using data from five California public medical schools, the authors examined the within- and between-school reliabilities of TIs and MMIs. METHODS: The analyses included applicants interviewing at ≥1 of the five schools during 2011-2013. Three schools employed TIs (TI1, TI2, TI3) and two employed MMIs (MMI1, MMI2). Mixed linear models accounting for nesting of observations within applicants examined standardized TI and MMI scores (mean = 0, SD = 1), adjusting for applicant socio-demographics, academic metrics, year, number of interviews, and interview date. RESULTS: A total of 4993 individuals (completing 7516 interviews [TI = 4137, MMI = 3379]) interviewed at ≥1 school; 428 (14.5%) interviewed at both MMI schools and 687 (20.2%) at more than one TI school. Within schools, inter-interviewer consistency was generally qualitatively lower for TI1, TI2, and TI3 (Pearson's r 0.07, 0.13, and 0.29, and Cronbach's α, 0.40, 0.44, and 0.61, respectively) than for MMI1 and MMI 2 (Cronbach's α 0.68 and 0.60, respectively). Between schools, the adjusted intraclass correlation coefficient was 0.27 (95% CI 0.20-0.35) for TIs and 0.47 (95% CI 0.41-0.54) for MMIs. CONCLUSIONS: Within and between-school reliability was qualitatively higher for MMIs than for TIs. Nonetheless, TI reliabilities were higher than anticipated from prior literature, suggesting TIs may not need to be abandoned on reliability grounds if other factors favor their use.

Multi-institute analysis of carbapenem resistance reveals remarkable diversity, unexplained mechanisms, and limited clonal outbreaks.

Carbapenem-resistant Enterobacteriaceae (CRE) are among the most severe threats to the antibiotic era. Multiple different species can exhibit resistance due to many different mechanisms, and many different mobile elements are capable of transferring resistance between lineages. We prospectively sampled CRE from hospitalized patients from three Boston-area hospitals, together with a collection of CRE from a single California hospital, to define the frequency and characteristics of outbreaks and determine whether there is evidence for transfer of strains within and between hospitals and the frequency with which resistance is transferred between lineages or species. We found eight species exhibiting resistance, with the majority of our sample being the sequence type 258 (ST258) lineage of Klebsiella pneumoniae There was very little evidence of extensive hospital outbreaks, but a great deal of variation in resistance mechanisms and the genomic backgrounds carrying these mechanisms. Local transmission was evident in clear phylogeographic structure between the samples from the two coasts. The most common resistance mechanisms were KPC (K. pneumoniae carbapenemases) beta-lactamases encoded by blaKPC2, blaKPC3, and blaKPC4, which were transferred between strains and species by seven distinct subgroups of the Tn4401 element. We also found evidence for previously unrecognized resistance mechanisms that produced resistance when transformed into a susceptible genomic background. The extensive variation, together with evidence of transmission beyond limited clonal outbreaks, points to multiple unsampled transmission chains throughout the continuum of care, including asymptomatic carriage and transmission of CRE. This finding suggests that to control this threat, we need an aggressive approach to surveillance and isolation.

Prevalence of and Factors Associated With Multidrug Resistant Organism (MDRO) Colonization in 3 Nursing Homes.

Nursing home residents are at risk for acquiring and transmitting MDROs. A serial point-prevalence study of 605 residents in 3 facilities using random sampling found MDRO colonization in 45% of residents: methicillin-resistant Staphylococcus aureus (MRSA, 26%); extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL, 17%); vancomycin-resistant Enterococcus spp. (VRE, 16%); carbapenem-resistant Enterobacteriaceae (CRE, 1%). MDRO colonization was associated with history of MDRO, care needs, incontinence, and catheters. Infect Control Hosp Epidemiol 2016;1485-1488.

Chlamydia trachomatis Type III Secretion Proteins Regulate Transcription.

UNLABELLED: The Scc4 protein (CT663) of the pathogenic bacterium Chlamydia has been described as a type III secretion (T3S) chaperone as well as an inhibitor of RNA polymerase. To examine if these roles are connected, we first investigated physical interactions between Chlamydia trachomatis Scc4 and the T3S chaperone Scc1 and a T3S substrate, CopN. In a yeast 3-hybrid assay, Scc4, Scc1, and CopN were all required to detect an interaction, which suggests that these proteins form a trimolecular complex. We also detected interactions between any two of these three T3S proteins in a pulldown assay using only recombinant proteins. We next determined whether these interactions affected the function of Scc4 as an inhibitor of RNA transcription. Using Escherichia coli as a heterologous in vivo system, we demonstrated that expression of C. trachomatis Scc4 led to a drastic decrease in transcript levels for multiple genes. However, coexpression of Scc4 with Scc1, CopN, or both alleviated Scc4-mediated inhibition of transcription. Scc4 expression also severely impaired E. coli growth, but this growth defect was reversed by coexpression of Scc4 with Scc1, CopN, or both, suggesting that the inhibitory effect of Scc4 on transcription and growth can be antagonized by interactions between Scc4, Scc1, and CopN. These findings suggest that the dual functions of Scc4 may serve as a bridge to link T3S and the regulation of gene expression in Chlamydia. IMPORTANCE: This study investigates a novel mechanism for regulating gene expression in the pathogenic bacterium Chlamydia. The Chlamydia type III secretion (T3S) chaperone Scc4 has been shown to inhibit transcription by RNA polymerase. This study describes physical interactions between Scc4 and the T3S proteins Scc1 and CopN. Furthermore, Chlamydia Scc1 and CopN antagonized the inhibitory effects of Scc4 on transcription and growth in a heterologous Escherichia coli system. These results provide evidence that transcription in Chlamydia can be regulated by the T3S system through interactions between T3S proteins.

Differential Expression of mRNA Encoding Cytokines and Chemokines in the Reproductive Tract after Infection of Mice with Chlamydia trachomatis.

Infection with Chlamydia trachomatis targets epithelial cells within the genital tract which respond by secreting chemokines and cytokines. Persistent inflammation can lead to fibrosis, tubal infertility and/or ectopic pregnancy; many infections are asymptomatic. Most studies have investigated the inflammatory response in the initial stages of infection, less is known about the later stages of infection, especially with a low, potentially asymptomatic, bacterial load. Our objective was to determine the inflammatory mediators involved in clearance of low-grade infection and the potential involvement in chronic inflammation. Six to eight week old C3H/HeJ mice were pretreated with 2.5 mg medroxyprogesterone acetate on day -10 and -3 before infection. Mice (n=3 for 28 d, n=3 for 35 d) were infected with 5 × 102 inclusion-forming units of C. trachomatis, serovar D; vaginal cultures were obtained weekly to monitor infection. Control mice (n=3 for 28 d, n=3 for 35 d) were sham infected. Mice were killed on day 28 (experiment 1) and day 35 (experiment 2) post-infection and vaginal tissue, uterine horns and oviducts collected for analysis of mRNAs encoding inflammatory cytokines and chemokines. Total RNA was isolated and a superarray analysis performed using mouse Cytokines and Chemokines PCR arrays (Qiagen, Valencia, CA). Statistical differences in gene expression were determined using a paired Students t-test. At 28 days after infection, the expression of mRNA encoding 6, 35 and 3 inflammatory genes differed from controls in vaginal, uterine and oviductal tissues, respectively (P<0.05). At 35 days after infection, the expression of mRNA encoding 16, 38 and 14 inflammatory genes differed from controls in vaginal, uterine and oviductal tissues, respectively (P<0.05). Understanding the mechanisms involved in the inflammatory response at later stages of infection should aid in the development of treatment options that minimize the development of asymptomatic, chronic inflammation-induced infertility.