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BackgroundBaricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19.MethodsIn this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site). Hospitalised adults (≥18 years) with COVID-19 who required supplemental oxygen administered by low-flow (≤15 L/min), high-flow (>15 L/min), or non-invasive mechanical ventilation modalities who met the study eligibility criteria (male or non-pregnant female adults ≥18 years old with laboratory-confirmed SARS-CoV-2 infection) were enrolled in the study. Patients were randomly assigned (1:1) to receive either baricitinib, remdesivir, and placebo, or dexamethasone, remdesivir, and placebo using a permuted block design. Randomisation was stratified by study site and baseline ordinal score at enrolment. All patients received remdesivir (≤10 days) and either baricitinib (or matching oral placebo) for a maximum of 14 days or dexamethasone (or matching intravenous placebo) for a maximum of 10 days. The primary outcome was the difference in mechanical ventilation-free survival by day 29 between the two treatment groups in the modified intention-to-treat population. Safety analyses were done in the as-treated population, comprising all participants who received one dose of the study drug. The trial is registered with ClinicalTrials.gov, NCT04640168.FindingsBetween Dec 1, 2020, and April 13, 2021, 1047 patients were assessed for eligibility. 1010 patients were enrolled and randomly assigned, 516 (51%) to baricitinib plus remdesivir plus placebo and 494 (49%) to dexamethasone plus remdesivir plus placebo. The mean age of the patients was 58·3 years (SD 14·0) and 590 (58%) of 1010 patients were male. 588 (58%) of 1010 patients were White, 188 (19%) were Black, 70 (7%) were Asian, and 18 (2%) were American Indian or Alaska Native. 347 (34%) of 1010 patients were Hispanic or Latino. Mechanical ventilation-free survival by day 29 was similar between the study groups (Kaplan-Meier estimates of 87·0% [95% CI 83·7 to 89·6] in the baricitinib plus remdesivir plus placebo group and 87·6% [84·2 to 90·3] in the dexamethasone plus remdesivir plus placebo group; risk difference 0·6 [95% CI -3·6 to 4·8]; p=0·91). The odds ratio for improved status in the dexamethasone plus remdesivir plus placebo group compared with the baricitinib plus remdesivir plus placebo group was 1·01 (95% CI 0·80 to 1·27). At least one adverse event occurred in 149 (30%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 179 (37%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·5% [1·6 to 13·3]; p=0·014). 21 (4%) of 503 patients in the baricitinib plus remdesivir plus placebo group had at least one treatment-related adverse event versus 49 (10%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 6·0% [2·8 to 9·3]; p=0·00041). Severe or life-threatening grade 3 or 4 adverse events occurred in 143 (28%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 174 (36%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·7% [1·8 to 13·4]; p=0·012).InterpretationIn hospitalised patients with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, baricitinib plus remdesivir and dexamethasone plus remdesivir resulted in similar mechanical ventilation-free survival by day 29, but dexamethasone was associated with significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events. A more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered.FundingNational Institute of Allergy and Infectious Diseases.

We performed a secondary analysis of the National Institutes of Health-sponsored Adaptive COVID-19 Treatment Trial (ACTT-2) randomized controlled trial and found that baricitinib was associated with a 50% reduction in secondary infections after controlling for baseline and postrandomization patient characteristics. This finding provides a novel mechanism of benefit for baricitinib and supports the safety profile of this immunomodulator for the treatment of coronavirus disease 2019.

Objectives : In multiple countries, endovascular/disseminated Mycobacterium chimaera infections have occurred in post-cardiac surgery patients in association with contaminated, widely-distributed cardiac bypass heater-cooler devices. To contribute to long-term characterization of this recently recognized infection, we describe the clinical course of 28 patients with 3-7 years of follow-up for survivors. Methods : Identified at five hospitals in the United States 2010-2016, post-cardiac surgery patients in the cohort had growth of Mycobacterium avium complex (MAC)/M. chimaera from a sterile site or surgical wound, or a clinically compatible febrile illness with granulomatous inflammation on biopsy. Case follow-up was conducted in May 2019. Results : Of 28 patients, infection appeared to be localized to the sternum in four patients. Among 18 with endovascular/disseminated infection who received combination anti-mycobacterial treatment and had sufficient follow-up, 39% appeared to have controlled infection (>12 months), 56% died, and one patient is alive with relapsed bacteremia. While the number of patients is small and interpretation is limited, four (67%) of six patients who had cardiac prosthesis removal/replacement appeared to have controlled infection compared to three (25%) of 12 with retained cardiac prosthesis (p >0.14; Fisher's exact test). Conclusions : Given poor response to treatment and potential for delayed relapses, post-cardiac surgery M. chimaera infection warrants aggressive treatment and long-term monitoring.

Background The coronavirus disease 2019 (COVID-19) pandemic of 2020 changed organ transplantation. All elective cases at our institution were postponed for approximately 3 months. Centers for Medicare and Medicaid Services considers organ transplant surgery a Tier 3b case, along with other high acuity procedures, recommending no postponement. Our transplant program collaborated with our transplant infectious disease colleagues to create a protocol that would ensure both patient and staff safety during these unprecedented times. Methods The living donor program was electively placed on hold until we had the proper protocols in place. Preoperative COVID-19 testing was required for all recipients and living donors. All patients underwent a rapid nasopharyngeal swab test. After testing negative by nasopharyngeal swab, recipients also underwent a low-radiation-dose computed tomography scan to rule out any radiographic changes suggestive of a COVID-19 infection. Results We performed 8 living donor and 9 deceased donor kidney transplants. In comparison, we performed 10 living donor and 4 deceased donor transplants during the same time period in the previous year. Our testing protocol enabled efficient use of all suitable organs offered during the viral pandemic. No recipients or living donors tested positive or developed COVID-19. Conclusions Creation of a viral testing protocol, developed in conjunction with our infectious disease team, permitted kidney transplantation to be performed safely, and the number of deceased donor transplants increased considerably without adversely affecting our outcomes.

Ultraviolet (UV) light has destructive activity against pathogenic bacteria including Clostridioides difficile spores. Portable pulsed-xenon UV disinfecting devices were implemented for terminal room cleaning in 6 units of our academic hospital with high C. difficile infection (CDI) rates. CDI rates were measured in a 9-month period before and a 9-month period after device implementation. Despite documented administration of UV disinfection for 87% of terminal room cleaning, no impact on CDI rates was detected.

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of urinary tract infections (UTI) in solid organ transplantation, focusing on kidney transplant (KT) recipients. KT recipients have unique risk factors for UTI, including indwelling stents and surgical manipulation of the genitourinary tract. KT recipients experience multi-drug antibiotic-resistant infections-UTI prevention and management strategies must consider risks of antimicrobial resistance. Non-antimicrobial prevention strategies for UTI in KT recipients are reviewed. It is important to recognize that some renal transplant recipients with UTI may primarily present with fever, malaise, leukocytosis, or a non-specific sepsis syndrome without symptoms localized to the urinary tract. However, asymptomatic bacteriuria (AB) must be distinguished from UTI because AB is not necessarily a disease state. Accumulating data indicate that there are no benefits of antibiotics for treatment of AB in KT recipients more than 2 months after post-transplant. Further research is needed on management of AB in the early (2 months) post-transplant period, prophylaxis for UTI in this era of antibiotic resistance, recurrent UTI, non-antimicrobial prevention of UTI, and uropathogens identified in donor urine and/or preservative fluid cultures.

OBJECTIVETo determine the impact of total household decolonization with intranasal mupirocin and chlorhexidine gluconate body wash on recurrent methicillin-resistant Staphylococcus aureus (MRSA) infection among subjects with MRSA skin and soft-tissue infection.DESIGNThree-arm nonmasked randomized controlled trial.SETTINGFive academic medical centers in Southeastern Pennsylvania.PARTICIPANTSAdults and children presenting to ambulatory care settings with community-onset MRSA skin and soft-tissue infection (ie, index cases) and their household members.INTERVENTIONEnrolled households were randomized to 1 of 3 intervention groups: (1) education on routine hygiene measures, (2) education plus decolonization without reminders (intranasal mupirocin ointment twice daily for 7 days and chlorhexidine gluconate on the first and last day), or (3) education plus decolonization with reminders, where subjects received daily telephone call or text message reminders.MAIN OUTCOME MEASURESOwing to small numbers of recurrent infections, this analysis focused on time to clearance of colonization in the index case.RESULTSOf 223 households, 73 were randomized to education-only, 76 to decolonization without reminders, 74 to decolonization with reminders. There was no significant difference in time to clearance of colonization between the education-only and decolonization groups (log-rank P=.768). In secondary analyses, compliance with decolonization was associated with decreased time to clearance (P=.018).CONCLUSIONSTotal household decolonization did not result in decreased time to clearance of MRSA colonization among adults and children with MRSA skin and soft-tissue infection. However, subjects who were compliant with the protocol had more rapid clearanceTrial registration. ClinicalTrials.gov identifier: NCT00966446Infect Control Hosp Epidemiol 2016;1–8

Patients with community-onset (CO) methicillin-resistant Staphylococcus aureus (MRSA) infections contribute to MRSA contamination of the home environment and may be reexposed to MRSA strains from this reservoir. This study evaluates One Health risk factors, which focus on the relationship between humans, animals, and the environment, for the increased prevalence of multiple antimicrobial-resistant MRSA isolates in the home environment. During a trial of patients with CO-MRSA infection, MRSA was isolated from the household environment at the baseline and 3 months later, following randomization of patients and household members to mupirocin-based decolonization therapy or an education control group. Up to two environmental MRSA isolates collected at each visit were tested. MRSA isolates were identified in 68% (65/95) of homes at the baseline ( n = 104 isolates) and 51% (33/65) of homes 3 months later ( n = 56 isolates). The rates of multidrug resistance (MDR) were 61% among isolates collected at the baseline and 55% among isolates collected at the visit 3 months later. At the baseline, 100% (14/14) of MRSA isolates from rural homes were MDR. While antimicrobial use by humans or pets was associated with an increased risk for the isolation of MDR MRSA from the environment, clindamycin use was not associated with an increased risk for the isolation of MDR MRSA. Incident low-level mupirocin-resistant MRSA strains were isolated at 3 months from 2 (5%) of 39 homes that were randomized to mupirocin treatment but none of the control homes. Among patients recently treated for a CO-MRSA infection, MRSA and MDR MRSA were common contaminants in the home environment. This study contributes to evidence that occupant use of antimicrobial drugs, except for clindamycin, is associated with MDR MRSA in the home environmental reservoir. (This study has been registered at ClinicalTrials.gov under registration no. NCT00966446.) IMPORTANCE MRSA is a common bacterial agent implicated in skin and soft tissue infections (SSTIs) in both community and health care settings. Patients with CO-MRSA infections contribute to environmental MRSA contamination in these settings and may be reexposed to MRSA strains from these reservoirs. People interact with natural and built environments; therefore, understanding the relationships between humans and animals as well as the characteristics of environmental reservoirs is important to advance strategies to combat antimicrobial resistance. Household interactions may influence the frequency and duration of exposure, which in turn may impact the duration of MRSA colonization or the probability for recurrent colonization and infection. Therefore, MRSA contamination of the home environment may contribute to human and animal recolonization and decolonization treatment failure. The aim of this study was to evaluate One Health risk factors that may be amenable to intervention and may influence the recovery of MDR and mupirocin resistance in CO-MRSA isolates.

SUMMARYGuidelines for the severity classification and treatment of Clostridium difficile infection (CDI) were published by Infectious Diseases Society of America (IDSA)/Society for Healthcare Epidemiology of America (SHEA) in 2010; however, compliance and efficacy of these guidelines has not been widely investigated. This present study assessed compliance with guidelines and its effect on CDI patient outcomes as compared with before these recommendations. A retrospective study included all adult inpatients with an initial episode of CDI treated in a single academic center from January 2009 to August 2014. Patients after guideline publication were compared with patients treated in 2009–2010. Demographic, clinical, and laboratory data were collected to stratify for disease severity. Outcome measures included compliance with guidelines, mortality, length of stay (LOS), and surgical intervention for CDI. A total of 1021 patients with CDI were included. Based upon the 2010 guidelines, 42 (28·8%) of 146 patients treated in 2009 would have been considered undertreated, and treatment progressively improved over time, as inadequate treatment decreased to 10·0% (15/148 patients) in 2014 (P = 0·0005). Overall, patient outcomes with guideline-adherent treatment decreased CDI attributable mortality twofold (P = 0·006) and CDI-related LOS by 1·9 days (P = 0·0009) when compared with undertreated patients. Compliance with IDSA/SHEA guidelines was associated with a decreased risk of mortality and LOS in hospitalized patients with CDI.

SUMMARYWe conducted a prospective cohort study between 1 January 2010 and 31 December 2012 at five adult and paediatric academic medical centres to identify factors associated with persistent methicillin-resistantStaphylococcus aureus(MRSA) colonisation. Adults and children presenting to ambulatory settings with a MRSA skin and soft tissue infection (i.e. index cases), along with household members, performed self-sampling for MRSA colonisation every 2 weeks for 6 months. Clearance of colonisation was defined as two consecutive negative sampling periods. Subjects without clearance by the end of the study were considered persistently colonised and compared with those who cleared colonisation. Of 243 index cases, 48 (19·8%) had persistent colonisation and 110 (45·3%) cleared colonisation without recurrence. Persistent colonisation was associated with white race (odds ratio (OR), 4·90; 95% confidence interval (CI), 1·38–17·40), prior MRSA infection (OR 3·59; 95% CI 1·05–12·35), colonisation of multiple sites (OR 32·7; 95% CI 6·7–159·3). Conversely, subjects with persistent colonisation were less likely to have been treated with clindamycin (OR 0·28; 95% CI 0·08–0·99). Colonisation at multiple sites is a risk factor for persistent colonisation and may require more targeted decolonisation efforts. The specific effect of clindamycin on MRSA colonisation needs to be elucidated.

The American Society of Transplantation Infectious Diseases (ID) Community of Practice has established an education workgroup to identify core components of a curriculum for training specialists in transplant ID. Clinical, laboratory, and research training form the triad of components on which an additional year of ID training, dedicated to the care of solid organ and hematopoietic stem cell transplant recipients, should be based. The recommended training environment would have access to adequate numbers of transplant patients, along with qualified faculty committed to teaching specialized fellows in this area. The learning objectives for both inpatient and outpatient clinical training are presented. The laboratory component requires trainees to attain expertize in utilizing and interpreting cutting-edge diagnostics used in transplant medicine. The research component may involve basic science, and translational or clinical research individualized to the trainee. Finally, suggestions for evaluation of both the fellows and the training program are provided.

Purpose. The development and implementation of an electronically based, nurse-driven pneumococcal vaccination protocol for hospitalized patients are described. Summary. A multidisciplinary team was formed to address the development, implementation, and management of an automatic pneumococcal vaccination program. Screening of patients was performed by the nursing staff on admission to the hospital; the screening process was streamlined using computer-generated assessment forms. The electronic program enabled systematic identification of patients eligible for vaccination, standardization of vaccine order instructions, documentation of vaccinations in a centralized electronic database, automatic documentation of vaccinations on patients’ discharge instructions, and collection of vaccination data for future analysis. If vaccination was indicated, an electronic order was automatically generated for the vaccine to be administered within 24 hours. The electronic order appeared on the electronic medication administration record like any other medication. Given the prominent role of nursing in the protocol, the largest training effort was in the nursing department, with education targeting 1200 nurses. Precautions were taken to minimize unintended duplicate vaccine administration. Patients were excluded from the vaccination protocol if they were younger than age 65 years, had a fever, were still in an intensive care unit, had an acute neurologic disorder, or had any condition for which there was doubt about the safety or appropriateness of the vaccination. Multidisciplinary resources are used to further reevaluate and refine the vaccine protocol. Conclusion. A multidisciplinary team successfully developed and implemented an electronically based, nurse-driven pneumococcal vaccination protocol for hospitalized patients in a teaching hospital.

We analyzed the emergence of daptomycin nonsusceptibility in a patient with persistent vancomycin-intermediate Staphylococcus aureus (VISA) bacteremia. The daptomycin-nonsusceptible VISA's cell wall demonstrated a reduction in muramic acid O -acetylation, a phenotypic parameter not previously reported for VISA; some isolates also contained a single point mutation in the mprF gene.

OBJECTIVETo identify risk factors for recurrent methicillin-resistantStaphylococcus aureus(MRSA) colonization.DESIGNProspective cohort study conducted from January 1, 2010, through December 31, 2012.SETTINGFive adult and pediatric academic medical centers.PARTICIPANTSSubjects (ie, index cases) who presented with acute community-onset MRSA skin and soft-tissue infection.METHODSIndex cases and all household members performed self-sampling for MRSA colonization every 2 weeks for 6 months. Clearance of colonization was defined as 2 consecutive sampling periods with negative surveillance cultures. Recurrent colonization was defined as any positive MRSA surveillance culture after clearance. Index cases with recurrent MRSA colonization were compared with those without recurrence on the basis of antibiotic exposure, household demographic characteristics, and presence of MRSA colonization in household members.RESULTSThe study cohort comprised 195 index cases; recurrent MRSA colonization occurred in 85 (43.6%). Median time to recurrence was 53 days (interquartile range, 36–84 days). Treatment with clindamycin was associated with lower risk of recurrence (odds ratio, 0.52; 95% CI, 0.29–0.93). Higher percentage of household members younger than 18 was associated with increased risk of recurrence (odds ratio, 1.01; 95% CI, 1.00–1.02). The association between MRSA colonization in household members and recurrent colonization in index cases did not reach statistical significance in primary analyses.CONCLUSIONA large proportion of patients initially presenting with MRSA skin and soft-tissue infection will have recurrent colonization after clearance. The reduced rate of recurrent colonization associated with clindamycin may indicate a unique role for this antibiotic in the treatment of such infection.Infect. Control Hosp. Epidemiol.2015;36(7):786–793

We report findings from our investigation of the world's second clinical isolate of vancomycin-resistant Staphylococcus aureus (VRSA). An elderly man was hospitalized with an infected chronic heel ulcer and osteomyelitis. Before hospital admission, he received multiple courses of antibiotic therapy but, notably, no vancomycin. Numerous cultures of ulcer specimens (performed on an outpatient basis) grew methicillin-resistant, vancomycin-susceptible S. aureus and vancomycin-resistant Enterococcus species. At admission, an additional culture of a specimen from the heel ulcer grew S. aureus that was identified as VRSA (minimal inhibitory concentration for vancomycin [by broth-microdilution], 32 microg/mL). Further evaluation confirmed the presence of the vanA gene mediating vancomycin resistance. To assess VRSA transmission, we performed a carriage study of 283 identified contacts and an environmental survey of the patient's home; no VRSA isolates were recovered. This case illustrates that recent exposure by patients to vancomycin is not necessary for development of vanA-containing VRSA. For clinical and public health reasons, it is essential that microbiology laboratories adequately test for vancomycin-resistance in S. aureus.

While enteroviruses have been the most commonly identified cause of aseptic meningitis in the United States, the role of the emerging, neurotropic West Nile virus (WNV) is not clear. In summer 2001, an aseptic meningitis epidemic occurring in an area of a WNV epizootic in Baltimore, Maryland, was investigated to determine the relative contributions of WNV and enteroviruses. A total of 113 aseptic meningitis cases with onsets from June 1 to September 30, 2001, were identified at six hospitals. WNV immunoglobulin M tests were negative for 69 patients with available specimens; however, 43 (61%) of 70 patients tested enterovirus-positive by viral culture or polymerase chain reaction. Most (76%) of the serotyped enteroviruses were echoviruses 13 and 18. Enteroviruses, including previously rarely detected echoviruses, likely caused most aseptic meningitis cases in this epidemic. No WNV meningitis cases were identified. Even in areas of WNV epizootics, enteroviruses continue to be important causative agents of aseptic meningitis.

We conducted a serosurvey of landscapers to determine if they were at increased risk for exposure to Francisella tularensis and to determine risk factors for infection. In Martha’s Vineyard, Massachusetts, landscapers (n=132) were tested for anti–F. tularensis antibody and completed a questionnaire. For comparison, serum samples from three groups of nonlandscaper Martha’s Vineyard residents (n=103, 99, and 108) were tested. Twelve landscapers (9.1%) were seropositive, compared with one person total from the comparison groups (prevalence ratio 9.0; 95% confidence interval 1.2 to 68.1; p=0.02). Of landscapers who used a power blower, 15% were seropositive, compared to 2% who did not use a power blower (prevalence ratio 9.2; 95% confidence interval 1.2 to 69.0; p=0.02). Seropositive landscapers worked more hours per week mowing and weed-whacking and mowed more lawns per week than their seronegative counterparts. Health-care workers in tularemia-endemic areas should consider tularemia as a diagnosis for landscapers with a febrile illness.

The 1999 New York epidemic of human West Nile virus (WN) encephalitis and meningitis was preceded by a crow die-off also caused by WN infection. As one component of the subsequently developed national surveillance system, crow mortality data were collected to detect WN activity before humans might become infected. However, predicting areas at risk for human WN disease likely requires assessment of multiple factors, including the intensity and timing of crow epizootics. To identify early season measures of WN activity in crows associated with subsequent WN disease in humans, county-level crow mortality data from seven northeastern states were analyzed. A predictive model was developed based on analysis of 2000 surveillance data and then assessed for 2001. To characterize the intensity of early season WN activity in crows, 15 variables were constructed from surveillance data of 52 counties that tested at least four crows during the early season (defined as June 17-July 28, 2000). County values for each variable were dichotomized at the 75th percentile into "high" and "low" activity. Multivariate analysis indicated that "high" early season activity of two variables-density of reported dead crow sightings (reported dead crows/area) and [(WN-infected crows/tested crows) x (human population)]--were associated with report of at least one human WN disease case (for each variable: adjusted odds ratio, 6.9; 95% confidence interval, 1.2-40.6). An assessment of this model using 2001 surveillance data from 61 counties yielded similar findings. With emphasis on early season WN activity, crow surveillance may allow timely targeting of interventions to protect the public health.

Background Combating antimicrobial resistance (AR) calls for widespread implementations of stewardship programs coupled with infrastructure for detection and response to multi-drug-resistant organisms (MDROs). Our aim was to document the use of the web by public health jurisdictions to disseminate practical information to strengthen antimicrobial stewardship and enhance surveillance for MDROs including carbapenem-resistant Enterobacteriaceae (CRE). Methods In May 2017 we collected Web-based antimicrobial stewardship and surveillance information in each of the 57 jurisdictions that submit data on nationally notifiable diseases to the Centers for Disease Control and Prevention (CDC). On each jurisdiction’s websites, we searched for practical information highlighting appropriate antibiotics use and stewardship in acute care and long-term care facilities. We also recorded presence of information on drug-resistant infections including surveillance for CRE. Results Most (84.2%) of the public health jurisdictions websites have AR information and five (8%) had highlighted it on their homepage. Information on appropriate antibiotic use across healthcare settings varied and 30% had ≥1link to guidelines for antimicrobial stewardship. Two-thirds of the jurisdictions’ sites included a link to the CDC Get Smart website while 35% promoted judicious use of antibiotics on the farm (Figure). Eight jurisdictions (14%) included requirements for reporting CRE and five of these jurisdictions had specific details on submission of isolates. Conclusion Public health jurisdictions have begun to take advantage of the web to increase general awareness about the threat of antimicrobial resistance. Limited presence of information to promote antimicrobial stewardship and enhance surveillance suggests need for improvement. The web could be leveraged as a source of practical information to support antimicrobial stewardship and surveillance for MDROs including CRE by increased communication among web designers, epidemiologists, and healthcare providers. Figure Practical information to promote antimicrobial stewardship and enhance surveillance on public health jurisdictions’ websites, United States — 2017 Disclosures All authors: No reported disclosures.

Background Strategies to interrupt household transmission of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) that target human colonization show mixed results. Our aim was to determine whether home environmental contamination and pet carriage with MRSA were associated with re-colonization or persistent colonization of index patients diagnosed with CA-MRSA skin or soft-tissue infection (SSTI). Methods Index patients from a randomized controlled trial (NCT00966446) that tested household-wide decolonization of people were eligible to participate in this substudy. Before randomization, eight environmental sites and all pets were sampled in the home. Patients were treated by their physician for the initial SSTI between diagnosis (visit 0) and the home visit (visit 1). They provided swabs every 2 weeks for 3 months (7 visits). After broth-enrichment culture, MRSA isolates were PCR-confirmed and spa-typed. Results Of 88 index patients recruited from the main trial, 64 (73%) provided swabs for ≥3 visits and were included in this analysis. At visit 1, 41 (64%) households were MRSA contaminated and 6 (9%) had MRSA-positive pet(s). All MRSA-positive pets lived in homes with MRSA environmental contamination. After visit 1, 42 (66%) index patients and their household members were block-randomized to nasal mupirocin and chlorhexidine body wash decolonization. Thirty-seven (58%) index patients had two consecutive negative swabs (de-colonized); 13 (35%) of these later were MRSA-positive (re-colonized). Patients with home contamination had higher rates of re-colonization than those without (Cox proportional hazard ratio 6.0 [95% CI: 1.2, 30.6], P Conclusion In patients with MRSA SSTI, MRSA-contaminated homes, and potentially MRSA-positive pets, are associated with re-colonization and persistent colonization. Future studies are needed to determine whether environmental decontamination can improve the success of household decolonization interventions. Disclosures All authors: No reported disclosures.

Background. The duration of colonization and factors associated with clearance of methicillin-resistant Staphylococcus aureus (MRSA) after community-onset MRSA skin and soft-tissue infection (SSTI) remain unclear. Methods. We conducted a prospective cohort study of patients with acute MRSA SSTI presenting to 5 adult and pediatric academic hospitals from 1 January 2010 through 31 December 2012. Index patients and household members performed self-sampling for MRSA colonization every 2 weeks for 6 months. Clearance of colonization was defined as negative MRSA surveillance cultures during 2 consecutive sampling periods. A Cox proportional hazards regression model was developed to identify determinants of clearance of colonization. Results. Two hundred forty-three index patients were included. The median duration of MRSA colonization after SSTI diagnosis was 21 days (95% confidence interval [CI], 19–24), and 19.8% never cleared colonization. Treatment of the SSTI with clindamycin was associated with earlier clearance (hazard ratio [HR], 1.72; 95% CI, 1.28–2.30; P < .001). Older age (HR, 0.99; 95% CI, .98–1.00; P = .01) was associated with longer duration of colonization. There was a borderline significant association between increased number of household members colonized with MRSA and later clearance of colonization in the index patient (HR, 0.85; 95% CI, .71–1.01; P = .06). Conclusions. With a systematic, regular sampling protocol, duration of MRSA colonization was noted to be shorter than previously reported, although 19.8% of patients remained colonized at 6 months. The association between clindamycin and shorter duration of colonization after MRSA SSTI suggests a possible role for the antibiotic selected for treatment of MRSA infection.

We retrospectively assessed our center's experience with a protocol of low-dose (450 mg once daily) valganciclovir administered for 3-6 months (median 5 months) in a cohort of of 55 cytomegalovirus (CMV) donor-positive (D+) and/or recipient-positive (R+) heart transplant recipients. Although no CMV disease occurred in patients while receiving low-dose valganciclovir, during the 12-month post-transplantation observation period of this study, 4 (22.2%) of the 18 D+/R- patients and 1 (2.7%) of the 37 R+ patients developed symptomatic CMV viremia. Leukopenia was frequent, including neutropenia [absolute neutrophil count (ANC)

Patients colonized with methicillin-resistant Staphylococcus aureus (MRSA) are at increased risk for invasive infection compared with noncolonized patients; however, the magnitude of risk for MRSA surgical site infection (SSI) is unclear. To aid in planning of infection prevention strategies, we sought to assess the incidence of MRSA SSI in MRSA carriers.We conducted a retrospective cohort study at our tertiary care center of inpatients who underwent MRSA polymerase chain reaction (PCR) screen of the nares within 30 days before a National Healthcare Safety Network principal procedure between April 2008 and July 2010.The rate of MRSA SSI was 1.86% in the MRSA PCR-positive group (n = 431) and 0.20% in the MRSA PCR-negative group (n = 9432). Multivariate analysis identified MRSA PCR-positive status as an independent risk factor for MRSA SSI (odds ratio, 9.20; 95% confidence interval, 3.81-20.47; P.0001); other risk factors included duration of surgery ≥137 minutes, American Society of Anesthesiologists score ≥3, and abdominal surgery.Surgical patients with a positive nasal MRSA PCR screen had a 9-fold greater odds of developing a subsequent MRSA SSI compared with patients with a negative nasal MRSA PCR screen. The incidence of MRSA SSI in PCR-positive patients was low (1.86%), however, and identifying subsets of patients at greatest risk for SSI may help target decolonization and other interventions.

Antimicrobial resistance, particularly in pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), limits treatment options and increases healthcare costs. To understand patient risk factors, including household and animal contact, potentially associated with colonization with multidrug-resistant MRSA isolates, we performed a prospective study of case patients colonized with MRSA on admission to a rural tertiary care hospital. Patients were interviewed and antimicrobial resistance patterns were tested among isolates from admitted patients colonized with MRSA in 2009-10. Prevalence of resistance was compared by case-patient risk factors and length-of-stay outcome among 88 MRSA case patients. Results were compared to NHANES 2003-04. Overall prevalence of multidrug resistance (non-susceptibility to ≥ four antimicrobial classes) in MRSA nasal isolates was high (73%) and was associated with a 1.5-day increase in subsequent length of stay (p = 0.008). History of hospitalization within the past six months, but not antimicrobial use in the same time period, was associated with resistance patterns. Within a subset of working-age case patients without recent history of hospitalization, animal contact was potentially associated with multidrug resistance. History of hospitalization, older age, and small household size were associated with multidrug resistance in NHANES data. In conclusion, recent hospitalization of case patients was predictive of antimicrobial resistance in MRSA isolates, but novel risk factors associated with the household may be emerging in CA-MRSA case patients. Understanding drivers of antimicrobial resistance in MRSA isolates is important to hospital infection control efforts, relevant to patient outcomes and to indicators of the economic burden of antimicrobial resistance.

BACKGROUND: While methicillin-resistant Staphylococcus aureus (MRSA) originally was associated with healthcare, distinct strains later emerged in patients with no prior hospital contact. The epidemiology of MRSA continues to evolve. METHODS: To characterize the current epidemiology of MRSA-colonized patients entering a hospital serving both rural and urban communities, we interviewed patients with MRSA-positive admission nasal swabs between August 2009 and March 2010. We applied hospitalization risk factor, antimicrobial resistance phenotype, and multi-locus sequence genotype (MLST) classification schemes to 94 case-patients. RESULTS: By MLST analysis, we identified 15 strains with two dominant clonal complexes (CCs)-CC5 (51 isolates), historically associated with hospitals, and CC8 (27 isolates), historically of community origin. Among patients with CC5 isolates, 43% reported no history of hospitalization within the past six months; for CC8, 67% reported the same. Classification by hospitalization risk factor did not correlate strongly with genotypic classification. Sensitivity of isolates to ciprofloxacin, clindamycin, or amikacin was associated with the CC8 genotype; however, among CC8 strains, 59% were resistant to ciprofloxacin, 15% to clindamycin, and 15% to amikacin. CONCLUSIONS: Hospitalization history was not a strong surrogate for the CC5 genotype. Conversely, patients with a history of hospitalization were identified with the CC8 genotype. Although ciprofloxacin, clindamycin, and amikacin susceptibility distinguished CC8 strains, the high prevalence of ciprofloxacin resistance limited its predictive value. As CC8 strains become established in healthcare settings and CC5 strains disseminate into the community, community-associated MRSA definitions based on case-patient hospitalization history may prove less valuable in tracking community MRSA strains.

Although much has been written about excess cost and duration of stay (DOS) associated with surgical site infections (SSIs) after cardiothoracic surgery, less has been reported after vascular and general surgery. We used data from the National Surgical Quality Improvement Program (NSQIP) to estimate the total cost and DOS associated with SSIs in patients undergoing general and vascular surgery.Using standard NSQIP practices, data were collected on patients undergoing general and vascular surgery at a single academic center between 2007 and 2009 and were merged with fully loaded operating costs obtained from the hospital accounting database. Logistic regression was used to determine which patient and preoperative variables influenced the occurrence of SSIs. After adjusting for patient characteristics, costs and DOS were fit to linear regression models to determine the effect of SSIs.Of the 2,250 general and vascular surgery patients sampled, SSIs were observed in 186 inpatients. Predisposing factors of SSIs were male sex, insulin-dependent diabetes, steroid use, wound classification, and operative time (P.05). After adjusting for those characteristics, the total excess cost and DOS attributable to SSIs were $10,497 (P.0001) and 4.3 days (P.0001), respectively.SSIs complicating general and vascular surgical procedures share many risk factors with SSIs after cardiothoracic surgery. Although the excess costs and DOS associated with SSIs after general and vascular surgery are somewhat less, they still represent substantial financial and opportunity costs to hospitals and suggest, along with the implications for patient care, a continuing need for cost-effective quality improvement and programs of infection prevention.

We investigated emergence of linezolid resistance among coagulase-negative staphylococci at our tertiary care center in 2007. All 17 cases were healthcare associated, and prior administration of linezolid was documentedor=2 months before first isolation of linezolid-resistant coagulase-negative staphylococci for all but 1 patient. Pulse-field gel electrophoresis analysis of the 14 available strains demonstrated 1 predominant clonal type, suggesting nosocomial spread. In addition to mutations in 23S rRNA and L4 previously described, we observed novel alterations in the 23S rRNA gene (G(2215)A) and in the L3 protein (substitutions L(101)V, H(146)Q/R, F(147)I, V(154)L, M(156)T). The increase in linezolid-resistant coagulase-negative staphylococci correlated with nosocomial transmission of selected mutated strains in patients who had received linezolid.

hospital in Lilongwe, Malawi, we analyzed readmission patterns in the inpatient medicine wards. We described the prevalence of early readmissions, assessed factors associated with readmissions, and explored the impact of HIV/AIDS on readmission. Methods: We investigated the prevalence of and factors associated with all-cause early readmission using regression models with a log link and binomial distribution to estimate risk ratios (RR) and 95% confidence intervals (CI). A retrospective review of the medical ward database at Kamuzu Central Hospital was conducted between February and December 2013. Findings: There were 3547 patients with an index admission and 74.4% of these survived and were eligible for readmission: 48.1% female, mean age 40.8, 38.5% HIV-infected. The prevalence of early hospital readmission was 5.5%. Persons who were HIV infected were more likely to experience an early readmission (9.2%) than those who were HIV-uninfected (3.5%) or with an unknown HIV status (3.3%). Factors associated with 30-day readmission were being HIV-positive (RR1⁄42.59; 95% CI: 1.743.83), comorbidity (RR1⁄41.52; 95% CI: 1.11-2.06), and prolonged length of stay (14 days) at the index hospitalization (RR1⁄45.01; 95% CI: 2.38, 10.53). Interpretation: Targeting HIV-infected inpatients with comorbid conditions and longer index admissions may prevent early readmission and improve quality of care. Further investigation is needed to identify quality improvement initiatives. Funding: Kashmira Chawla is supported by the Doris Duke International Clinical Research Fellowship program and this work is supported by the University of North Carolina Center for AIDS research. Abstract #: 02CD005