A Randomized, Double-blind, Multicenter Trial Comparing Efficacy and Safety of Imipenem/Cilastatin/Relebactam Versus Piperacillin/Tazobactam in Adults With Hospital-acquired or Ventilator-associated Bacterial Pneumonia (RESTORE-IMI 2 Study).

BACKGROUND: Imipenem combined with the ß-lactamase inhibitor relebactam has broad antibacterial activity, including against carbapenem-resistant gram-negative pathogens. We evaluated efficacy and safety of imipenem/cilastatin/relebactam in treating hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP). METHODS: This was a randomized, controlled, double-blind phase 3 trial. Adults with HABP/VABP were randomized 1:1 to imipenem/cilastatin/relebactam 500 mg/500 mg/250 mg or piperacillin/tazobactam 4 g/500 mg, intravenously every 6 hours for 7-14 days. The primary endpoint was day 28 all-cause mortality in the modified intent-to-treat (MITT) population (patients who received study therapy, excluding those with only gram-positive cocci at baseline). The key secondary endpoint was clinical response 7-14 days after completing therapy in the MITT population. RESULTS: Of 537 randomized patients (from 113 hospitals in 27 countries), the MITT population comprised 264 imipenem/cilastatin/relebactam and 267 piperacillin/tazobactam patients; 48.6% had ventilated HABP/VABP, 47.5% APACHE II score ≥15, 24.7% moderate/severe renal impairment, 42.9% were ≥65 years old, and 66.1% were in the intensive care unit. The most common baseline pathogens were Klebsiella pneumoniae (25.6%) and Pseudomonas aeruginosa (18.9%). Imipenem/cilastatin/relebactam was noninferior (P < .001) to piperacillin/tazobactam for both endpoints: day 28 all-cause mortality was 15.9% with imipenem/cilastatin/relebactam and 21.3% with piperacillin/tazobactam (difference, -5.3% [95% confidence interval {CI}, -11.9% to 1.2%]), and favorable clinical response at early follow-up was 61.0% and 55.8%, respectively (difference, 5.0% [95% CI, -3.2% to 13.2%]). Serious adverse events (AEs) occurred in 26.7% of imipenem/cilastatin/relebactam and 32.0% of piperacillin/tazobactam patients; AEs leading to treatment discontinuation in 5.6% and 8.2%, respectively; and drug-related AEs (none fatal) in 11.7% and 9.7%, respectively. CONCLUSIONS: Imipenem/cilastatin/relebactam is an appropriate treatment option for gram-negative HABP/VABP, including in critically ill, high-risk patients. CLINICAL TRIALS REGISTRATION: NCT02493764.

Enhanced terminal room disinfection and acquisition and infection caused by multidrug-resistant organisms and Clostridium difficile (the Benefits of Enhanced Terminal Room Disinfection study): a cluster-randomised, multicentre, crossover study.

BACKGROUND: Patients admitted to hospital can acquire multidrug-resistant organisms and Clostridium difficile from inadequately disinfected environmental surfaces. We determined the effect of three enhanced strategies for terminal room disinfection (disinfection of a room between occupying patients) on acquisition and infection due to meticillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, C difficile, and multidrug-resistant Acinetobacter. METHODS: We did a pragmatic, cluster-randomised, crossover trial at nine hospitals in the southeastern USA. Rooms from which a patient with infection or colonisation with a target organism was discharged were terminally disinfected with one of four strategies: reference (quaternary ammonium disinfectant except for C difficile, for which bleach was used); UV (quaternary ammonium disinfectant and disinfecting ultraviolet [UV-C] light except for C difficile, for which bleach and UV-C were used); bleach; and bleach and UV-C. The next patient admitted to the targeted room was considered exposed. Every strategy was used at each hospital in four consecutive 7-month periods. We randomly assigned the sequence of strategies for each hospital (1:1:1:1). The primary outcomes were the incidence of infection or colonisation with all target organisms among exposed patients and the incidence of C difficile infection among exposed patients in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01579370. FINDINGS: 31 226 patients were exposed; 21 395 (69%) met all inclusion criteria, including 4916 in the reference group, 5178 in the UV group, 5438 in the bleach group, and 5863 in the bleach and UV group. 115 patients had the primary outcome during 22 426 exposure days in the reference group (51·3 per 10 000 exposure days). The incidence of target organisms among exposed patients was significantly lower after adding UV to standard cleaning strategies (n=76; 33·9 cases per 10 000 exposure days; relative risk [RR] 0·70, 95% CI 0·50-0·98; p=0·036). The primary outcome was not statistically lower with bleach (n=101; 41·6 cases per 10 000 exposure days; RR 0·85, 95% CI 0·69-1·04; p=0·116), or bleach and UV (n=131; 45·6 cases per 10 000 exposure days; RR 0·91, 95% CI 0·76-1·09; p=0·303) among exposed patients. Similarly, the incidence of C difficile infection among exposed patients was not changed after adding UV to cleaning with bleach (n=38 vs 36; 30·4 cases vs 31·6 cases per 10 000 exposure days; RR 1·0, 95% CI 0·57-1·75; p=0·997). INTERPRETATION: A contaminated health-care environment is an important source for acquisition of pathogens; enhanced terminal room disinfection decreases this risk. FUNDING: US Centers for Disease Control and Prevention.

Two-Phase Hospital-Associated Outbreak of Mycobacterium abscessus: Investigation and Mitigation.

BACKGROUND: Nontuberculous mycobacteria (NTM) commonly colonize municipal water supplies and cause healthcare-associated outbreaks. We investigated a biphasic outbreak of Mycobacterium abscessus at a tertiary care hospital. METHODS: Case patients had recent hospital exposure and laboratory-confirmed colonization or infection with M. abscessus from January 2013 through December 2015. We conducted a multidisciplinary epidemiologic, field, and laboratory investigation. RESULTS: The incidence rate of M. abscessus increased from 0.7 cases per 10000 patient-days during the baseline period (January 2013-July 2013) to 3.0 cases per 10000 patient-days during phase 1 of the outbreak (August 2013-May 2014) (incidence rate ratio, 4.6 [95% confidence interval, 2.3-8.8]; P < .001). Thirty-six of 71 (51%) phase 1 cases were lung transplant patients with positive respiratory cultures. We eliminated tap water exposure to the aerodigestive tract among high-risk patients, and the incidence rate decreased to baseline. Twelve of 24 (50%) phase 2 (December 2014-June 2015) cases occurred in cardiac surgery patients with invasive infections. Phase 2 resolved after we implemented an intensified disinfection protocol and used sterile water for heater-cooler units of cardiopulmonary bypass machines. Molecular fingerprinting of clinical isolates identified 2 clonal strains of M. abscessus; 1 clone was isolated from water sources at a new hospital addition. We made several water engineering interventions to improve water flow and increase disinfectant levels. CONCLUSIONS: We investigated and mitigated a 2-phase clonal outbreak of M. abscessus linked to hospital tap water. Healthcare facilities with endemic NTM should consider similar tap water avoidance and engineering strategies to decrease risk of NTM infection.

Delay in diagnosis of invasive surgical site infections following knee arthroplasty versus hip arthroplasty.

BACKGROUND: The timing of diagnosis of invasive surgical site infection (SSI) following joint replacement surgery is an important criterion used to determine subsequent medical and surgical management. METHODS: We compared time to diagnosis of invasive SSI following hip vs knee arthroplasty. SSIs were included in the analysis if they occurred within 365 days following procedures performed from 1 January 2007 through 31 December 2011 at 36 community acute care hospitals and 1 ambulatory surgery center in the Duke Infection Control Outreach Network. A Cox regression model was fitted to estimate the association between procedure type and time to diagnosis of SSI, adjusted for age, pathogen virulence, American Society of Anesthesiologists' score, and hospital surgical volume. RESULTS: Six hundred sixty-one invasive SSIs were identified; 401 (61%) occurred following knee arthroplasties. The median time to diagnosis of SSI was 25 days (interquartile range [IQR], 17-48 days) following hip arthroplasty vs 42 days (IQR, 21-114 days) following knee arthroplasty (unadjusted hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.37-1.87; P < .001). Time to diagnosis of invasive SSI remained significantly shorter for hip than for knee arthroplasties after adjusting for age, pathogen virulence, and hospital surgical volume (HR, 1.51; 95% CI, 1.28-1.78; P < .001). CONCLUSIONS: The diagnosis of invasive SSI was delayed following knee arthroplasty compared with hip arthroplasty. We hypothesize that differences in symptom manifestation and disparities in access to care may contribute to the observed differential timing of diagnosis. Our findings have important implications for the management of prosthetic joint infections, because treatment strategies depend on the timing of diagnosis.

RNA populations in immunocompromised patients as reservoirs for novel norovirus variants.

UNLABELLED: Noroviruses are the leading cause of acute gastroenteritis outbreaks worldwide. The majority of norovirus outbreaks are caused by genogroup II.4 (GII.4). Novel GII.4 strains emerge every 2 to 4 years and replace older variants as the dominant norovirus. Novel variants emerge through a combination of recombination, genetic drift, and selection driven by population immunity, but the exact mechanism of how or where is not known. We detected two previously unknown novel GII.4 variants, termed GII.4 UNK1 and GII.4 UNK2, and a diverse norovirus population in fecal specimens from immunocompromised individuals with diarrhea after they had undergone bone marrow transplantation. We hypothesized that immunocompromised individuals can serve as reservoirs for novel norovirus variants. To test our hypothesis, metagenomic analysis of viral RNA populations was combined with a full-genome bioinformatic analysis of publicly available GII.4 norovirus sequences from 1974 to 2014 to identify converging sites. Variable sites were proportionally more likely to be within two amino acids (P < 0.05) of positively selected sites. Further analysis using a hypergeometric distribution indicated that polymorphic site distribution was random and its proximity to positively selected sites was dependent on the size of the norovirus genome and the number of positively selected sites.In conclusion, random mutations may have a positive impact on driving norovirus evolution, and immunocompromised individuals could serve as potential reservoirs for novel GII.4 strains. IMPORTANCE: Norovirus is the most common cause of viral gastroenteritis in the United States. Every 2 to 3 years novel norovirus variants emerge and replace dominant strains. The continual emergence of novel noroviruses is believed to be caused by a combination of genetic drift, population immunity, and recombination, but exactly how this emergence occurs remains unknown. In this study, we identified two novel GII.4 variants in immunocompromised bone marrow transplant patients. Using metagenomic and bioinformatic analysis, we showed that most genetic polymorphisms in the novel variants occur near 0 to 2 amino acids of positively selected sites, but the distribution of mutations was random; clustering of polymorphisms with positively selected sites was a result of genome size and number of mutations and positively selected sites. This study shows that immunocompromised patients can harbor infectious novel norovirus variants, and although mutations in viruses are random, they can have a positive effect on viral evolution.

Widespread dissemination of CTX-M-15 genotype extended-spectrum-ß-lactamase-producing enterobacteriaceae among patients presenting to community hospitals in the southeastern United States.

Extended-spectrum-ß-lactamase (ESBL)-producing organisms are increasingly prevalent. We determined the characteristics of 66 consecutive ESBL-producing isolates from six community hospitals in North Carolina and Virginia from 2010 to 2012. Fifty-three (80%) ESBL-producing isolates contained CTX-M enzymes; CTX-M-15 was found in 68% of Escherichia coli and 73% of Klebsiella isolates. Sequence type 131 (ST131) was the commonest type of E. coli, accounting for 48% of CTX-M-15-producing and 66% of CTX-M-14-producing isolates. In conclusion, the CTX-M genotype and ST131 E. coli were common among ESBL isolates from U.S. community hospitals.

Imipenem/cilastatin/relebactam efficacy, safety and probability of target attainment in adults with hospital-acquired or ventilator-associated bacterial pneumonia among patients with baseline renal impairment, normal renal function, and augmented renal clearance.

Objectives: To assess the relationship between renal function and efficacy/safety of imipenem/cilastatin/relebactam for the treatment of hospital-acquired/ventilator-associated pneumonia (HABP/VABP) from RESTORE-IMI 2 and determine the PTA. Methods: Adults with HABP/VABP were randomized 1:1 to IV imipenem/cilastatin/relebactam 1.25 g or piperacillin/tazobactam 4.5 g every 6 h for 7-14 days. Initial doses were selected by CLCR and adjusted thereafter, as appropriate. Outcomes included Day 28 all-cause mortality (ACM), clinical response, microbiological response and adverse events. Population pharmacokinetic modelling and Monte Carlo simulations assessed PTA. Results: The modified ITT population comprised those with normal renal function (n = 188), augmented renal clearance (ARC; n = 88), mild renal impairment (RI; n = 124), moderate RI (n = 109) and severe RI (n = 22). ACM rates were comparable between treatment arms among all baseline renal function categories. Clinical response rates were comparable between treatment arms for participants with RI and normal renal function but were higher (91.7% versus 44.4%) for imipenem/cilastatin/relebactam-treated versus piperacillin/tazobactam-treated participants with CLCR ≥250 mL/min (n = 21). Microbiologic response rates were comparable between treatment arms for participants with RI but higher among those treated with imipenem/cilastatin/relebactam in participants with CLCR ≥90 mL/min (86.6% versus 67.2%). Adverse events were comparable between treatment arms across renal function categories. Joint PTA was >98% for key pathogen MICs for susceptible pathogens (MIC ≤2 mg/L). Conclusions: Prescribing information-defined dose adjustments in participants with baseline RI and full dosing of imipenem/cilastatin/relebactam 1.25 g every 6 h for participants with normal renal function or augmented renal clearance achieved sufficiently high drug exposures and favourable safety and efficacy profiles.

Participant- and Disease-Related Factors as Independent Predictors of Treatment Outcomes in the RESTORE-IMI 2 Clinical Trial: A Multivariable Regression Analysis.

Background: In the RESTORE-IMI 2 trial, imipenem/cilastatin/relebactam (IMI/REL) was noninferior to piperacillin/tazobactam in treating hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia. This post hoc analysis was conducted to determine independent predictors of efficacy outcomes in the RESTORE-IMI 2 trial, to assist in treatment decision making. Methods: A stepwise multivariable regression analysis was conducted to identify variables that were independently associated with day 28 all-cause mortality (ACM), favorable clinical response at early follow-up (EFU), and favorable microbiologic response at end of treatment (EOT). The analysis accounted for the number of baseline infecting pathogens and in vitro susceptibility to randomized treatment. Results: Vasopressor use, renal impairment, bacteremia at baseline, and Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II scores ≥15 were associated with a greater risk of day 28 ACM. A favorable clinical response at EFU was associated with normal renal function, an APACHE II score <15, no vasopressor use, and no bacteremia at baseline. At EOT, a favorable microbiologic response was associated with IMI/REL treatment, normal renal function, no vasopressor use, nonventilated pneumonia at baseline, intensive care unit admission at randomization, monomicrobial infections at baseline, and absence of Acinetobacter calcoaceticus-baumannii complex at baseline. These factors remained significant after accounting for polymicrobial infection and in vitro susceptibility to assigned treatment. Conclusions: This analysis, which accounted for baseline pathogen susceptibility, validated well-recognized patient- and disease-related factors as independent predictors of clinical outcomes. These results lend further support to the noninferiority of IMI/REL to piperacillin/tazobactam and suggests that pathogen eradication may be more likely with IMI/REL. Clinical Trials Registration: NCT02493764.

Pharmacokinetics, Safety, and Tolerability of Imipenem/Cilastatin/Relebactam in Children with Confirmed or Suspected Gram-Negative Bacterial Infections: A Phase 1b, Open-Label, Single-Dose Clinical Trial.

Imipenem/cilastatin/relebactam is approved for the treatment of serious gram-negative bacterial infections in adults. This study assessed the pharmacokinetics (PK), safety, and tolerability of a single dose of imipenem/cilastatin/relebactam (with a fixed 2:1 ratio of imipenem/cilastatin to relebactam, and with a maximum dose of 15 mg/kg imipenem and 15 mg/kg cilastatin [≤500 mg imipenem and ≤500 mg cilastatin] and 7.5 mg/kg relebactam [≤250 mg relebactam]) in children with confirmed/suspected gram-negative bacterial infections receiving standard-of-care antibacterial therapy. In this phase 1, noncomparative study (ClinicalTrials.gov identifier, NCT03230916), PK parameters from 46 children were analyzed using both population modeling and noncompartmental analysis. The PK/pharmacodynamic (PD) target for imipenem was percent time of the dosing interval that unbound plasma concentration exceeded the minimum inhibitory concentration (%fT>MIC) of ≥30% (MIC = 2 mcg/mL). For relebactam, the PK/PD target was a free drug area under the plasma concentration-time curve (AUC) normalized to MIC (at 2 mcg/mL) of ≥8.0 (equivalent to an AUC from time zero extrapolated to infinity of ≥20.52 mcg·h/mL). Safety was assessed up to 14 days after drug infusion. For imipenem, the ranges for the geometric mean %fT>MIC and maximum concentration (Cmax ) across age cohorts were 56.5%-93.7% and 32.2-38.2 mcg/mL, respectively. For relebactam, the ranges of the geometric mean Cmax and AUC from 0 to 6 hours across age cohorts were 16.9-21.3 mcg/mL and 26.1-55.3 mcg·h/mL, respectively. In total, 8/46 (17%) children experienced ≥1 adverse events (AEs) and 2/46 (4%) children experienced nonserious AEs that were deemed drug related by the investigator. Imipenem and relebactam exceeded plasma PK/PD targets; single doses of imipenem/cilastatin/relebactam were well tolerated with no significant safety concerns identified. These results informed imipenem/cilastatin/relebactam dose selection for further pediatric clinical evaluation.

Cluster of oseltamivir-resistant 2009 pandemic influenza A (H1N1) virus infections on a hospital ward among immunocompromised patients--North Carolina, 2009.

BACKGROUND: Oseltamivir resistance among 2009 pandemic influenza A (H1N1) viruses (pH1N1) is rare. We investigated a cluster of oseltamivir-resistant pH1N1 infections in a hospital ward. METHODS: We reviewed patient records and infection control measures and interviewed health care personnel (HCP) and visitors. Oseltamivir-resistant pH1N1 infections were found with real-time reverse-transcription polymerase chain reaction and pyrosequencing for the H275Y neuraminidase (NA) mutation. We compared hemagglutinin (HA) sequences from clinical samples from the outbreak with those of other surveillance viruses. RESULTS: During the period 6-11 October 2009, 4 immunocompromised patients within a hematology-oncology ward exhibited symptoms of pH1N1 infection. The likely index patient became febrile 8 days after completing a course of oseltamivir; isolation was instituted 9 days after symptom onset. Three other case patients developed symptoms 1, 3, and 5 days after the index patient. Three case patients were located in adjacent rooms. HA and NA sequences from case patients were identical. Twelve HCP and 6 visitors reported influenza symptoms during the study period. No other pH1N1 isolates from the hospital or from throughout the state carried the H275Y mutation. CONCLUSIONS: Geographic proximity, temporal clustering, presence of H275Y mutation, and viral sequence homology confirmed nosocomial transmission of oseltamivir-resistant pH1N1. Diagnostic vigilance and prompt isolation may prevent nosocomial transmission of influenza.

Correlation of cross-sectional diameter with image quality and radiation exposure in MDCT examinations of the neck.

OBJECTIVE: The purpose of this study was to identify an optimal cross-sectional neck diameter that correlates with image quality and radiation exposure in MDCT examinations of the neck performed with automatic tube current modulation. MATERIALS AND METHODS: Ninety-six adults underwent 64-MDCT of the neck with automatic tube current modulation at the same noise setting. On frontal and lateral scout images, maximal body diameters were measured in the transverse and anteroposterior planes at two levels: just below the mandible (upper neck) and at the lung apex (lower neck). Neck diameters were correlated with image quality on a subjective 4-point scale and with radiation exposure (volume CT dose index). RESULTS: As continuous variables, both anteroposterior and transverse diameters in the lower neck were associated with image quality (p ≤ 0.0012). Diameters in the upper neck were not associated with image quality. When diameters in the lower neck were categorized into small, medium, and large, image quality grades were higher for smaller patients (p < 0.001). Images of 81% of small patients (lower neck transverse diameter < 40 cm) had a high image quality grade, compared with images of 7-20% of large patients (diameter > 48 cm). Transverse diameter in the lower neck correlated best with radiation dose measured as volume CT dose index (r = 0.78). When transverse diameter in the lower neck was used to categorize patients' size, the mean volume CT dose index for small patients was 34.1 mSv and that for large patients was 63.5 mSv. CONCLUSION: Lower neck transverse diameter on the CT scout image best correlates with image quality and radiation exposure for neck MDCT examinations performed with automatic tube current modulation. Images of patients with a lower neck transverse diameter less than 40 cm are of higher quality than those of larger patients. Individualized dose reduction techniques therefore may be appropriate for smaller patients.

Community-Acquired Methicillin-Resistant Staphylococcus aureus Skin and Soft Tissue Infections: Management and Prevention.

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was a rare phenomenon until the past decade; now CA-MRSA is endemic in many communities and is the most common cause of skin and soft tissue infections presenting to emergency rooms. CA-MRSA is distinct from its hospital-acquired counterpart, and has caused devastating infections in many healthy individuals. The epidemiology of CA-MRSA continues to evolve, and the challenge is to use the most appropriate and effective therapeutic and preventative strategies against this pathogen. This article reviews the current epidemiology of CA-MRSA, its definitions, and common clinical manifestations in the community. The article also summarizes current therapeutic options for CA-MRSA as well as strategies to reduce the transmission and the impact of CA-MRSA in both community and health care settings.

CT mucosal window settings: a novel approach to evaluating early T-stage head and neck carcinoma.

OBJECTIVE: The purpose of this study is to evaluate the CT densities of small head and neck mucosal cancers as a means of deriving a CT mucosal window display of narrower window width and higher window level to better detect and delineate head and neck carcinomas. MATERIALS AND METHODS: We retrospectively studied 19 subjects with T1-2 head and neck carcinomas. The density of tumor and adjacent normal mucosa on CT were measured. CT scans for the 19 patients with tumors and 35 subjects without mucosal tumors were anonymized and interpreted by two readers using standard soft-tissue windows and were reviewed again 1 week later with the addition of mucosal windows. RESULTS: The mean (± SD) attenuation of 17 visible tumors was 85.5 ± 18.3 Hounsfield units (HU) and that of the surrounding normal mucosa was 55.3 ± 15.2 HU (p < 0.0001). From our data, we derived guideline mucosal window settings-a window width of 120 HU and a window level of 60 HU. On blinded review, reader A detected 12 tumors with the addition of mucosal windows (sensitivity, 63%; specificity, 82%) and nine tumors on soft-tissue windows alone (sensitivity, 47%; specificity, 94%). Reader B detected nine tumors with use of mucosal windows (sensitivity, 47%; specificity, 71%) and eight tumors on soft-tissue windows alone (sensitivity, 42%; specificity, 74%). CONCLUSION: Early T-stage tumors have higher CT density than normal mucosa. Their conspicuity can be amplified using display windows with narrower window width and higher window level. The potential clinical applications are for the improved detection of unknown primary tumors and delineation of a known mucosal tumor.

Mycobacterium avium pseudo-outbreak associated with an outpatient bronchoscopy clinic: Lessons for reprocessing.

We identified a pseudo-outbreak of Mycobacterium avium in an outpatient bronchoscopy clinic following an increase in clinic procedure volume. We terminated the pseudo-outbreak by increasing the frequency of automated endoscope reprocessors (AER) filter changes from quarterly to monthly. Filter changing schedules should depend on use rather than fixed time intervals.

A prospective study of transmission of Multidrug-Resistant Organisms (MDROs) between environmental sites and hospitalized patients-the TransFER study.

OBJECTIVE: Hospital environmental surfaces are frequently contaminated by microorganisms. However, the causal mechanism of bacterial contamination of the environment as a source of transmission is still debated. This prospective study was performed to characterize the nature of multidrug-resistant organism (MDRO) transmission between the environment and patients using standard microbiological and molecular techniques. SETTING: Prospective cohort study at 2 academic medical centers. DESIGN: A prospective multicenter study to characterize the nature of bacterial transfer events between patients and environmental surfaces in rooms that previously housed patients with 1 of 4 'marker' MDROs: methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, Clostridium difficile, and MDR Acinetobacter baumannii. Environmental and patient microbiological samples were obtained on admission into a freshly disinfected inpatient room. Repeat samples from room surfaces and patients were taken on days 3 and 7 and each week the patient stayed in the same room. The bacterial identity, antibiotic susceptibility, and molecular sequences were compared between organisms found in the environment samples and patient sources. RESULTS: We enrolled 80 patient-room admissions; 9 of these patients (11.3%) were asymptomatically colonized with MDROs at study entry. Hospital room surfaces were contaminated with MDROs despite terminal disinfection in 44 cases (55%). Microbiological Bacterial Transfer events either to the patient, the environment, or both occurred in 12 patient encounters (18.5%) from the microbiologically evaluable cohort. CONCLUSIONS: Microbiological Bacterial Transfer events between patients and the environment were observed in 18.5% of patient encounters and occurred early in the admission. This study suggests that research on prevention methods beyond the standard practice of room disinfection at the end of a patient's stay is needed to better prevent acquisition of MDROs through the environment.

What's new in Rocky Mountain spotted fever?

Rocky Mountain spotted fever (RMSF) remains an important illness despite an effective therapy because it is difficult to diagnose and is capable of producing a fatal outcome. The pathogenesis of RMSF remains, in large part, an enigma. However, recent research has helped shed light on this mystery. Importantly, the diagnosis of RMSF must be considered in all febrile patients who have known or possible exposure to ticks, especially if they live in or have traveled to endemic regions during warmer months. Decisions about giving empiric therapy to such patients are difficult and require skill and careful judgement.

Enhanced disinfection leads to reduction of microbial contamination and a decrease in patient colonization and infection.

In this prospective study, we monitored 4 epidemiologically important pathogens (EIPs): methicillin-resistane Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), Clostridium difficile, and multidrug-resistant (MDR) Acinetobacter to assess the effectiveness of 3 enhanced disinfection strategies for terminal room disinfection against standard practice. Our data demonstrated that a decrease in room contamination with EIPs of 94% was associated with a 35% decrease in subsequent patient colonization and/or infection.

Implementation Lessons Learned From the Benefits of Enhanced Terminal Room (BETR) Disinfection Study: Process and Perceptions of Enhanced Disinfection with Ultraviolet Disinfection Devices.

OBJECTIVE To summarize and discuss logistic and administrative challenges we encountered during the Benefits of Enhanced Terminal Room (BETR) Disinfection Study and lessons learned that are pertinent to future utilization of ultraviolet (UV) disinfection devices in other hospitals DESIGN Multicenter cluster randomized trial SETTING AND PARTICIPANTS Nine hospitals in the southeastern United States METHODS All participating hospitals developed systems to implement 4 different strategies for terminal room disinfection. We measured compliance with disinfection strategy, barriers to implementation, and perceptions from nurse managers and environmental services (EVS) supervisors throughout the 28-month trial. RESULTS Implementation of enhanced terminal disinfection with UV disinfection devices provides unique challenges, including time pressures from bed control personnel, efficient room identification, negative perceptions from nurse managers, and discharge volume. In the course of the BETR Disinfection Study, we utilized several strategies to overcome these barriers: (1) establishing safety as the priority; (2) improving communication between EVS, bed control, and hospital administration; (3) ensuring availability of necessary resources; and (4) tracking and providing feedback on compliance. Using these strategies, we deployed ultraviolet (UV) disinfection devices in 16,220 (88%) of 18,411 eligible rooms during our trial (median per hospital, 89%; IQR, 86%-92%). CONCLUSIONS Implementation of enhanced terminal room disinfection strategies using UV devices requires recognition and mitigation of 2 key barriers: (1) timely and accurate identification of rooms that would benefit from enhanced terminal disinfection and (2) overcoming time constraints to allow EVS cleaning staff sufficient time to properly employ enhanced terminal disinfection methods. TRIAL REGISTRATION Clinical trials identifier: NCT01579370 Infect Control Hosp Epidemiol 2018;39:157-163.

Effectiveness of targeted enhanced terminal room disinfection on hospital-wide acquisition and infection with multidrug-resistant organisms and Clostridium difficile: a secondary analysis of a multicentre cluster randomised controlled trial with crossover design (BETR Disinfection).

BACKGROUND: The hospital environment is a source of pathogen transmission. The effect of enhanced disinfection strategies on the hospital-wide incidence of infection has not been investigated in a multicentre, randomised controlled trial. We aimed to assess the effectiveness of four disinfection strategies on hospital-wide incidence of multidrug-resistant organisms and Clostridium difficile in the Benefits of Enhanced Terminal Room (BETR) Disinfection study. METHODS: We did a prespecified secondary analysis of the results from the BETR Disinfection study, a pragmatic, multicentre, crossover cluster-randomised trial that assessed four different strategies for terminal room disinfection in nine hospitals in the southeastern USA. Rooms from which a patient with a specific infection or colonisation (due to the target organisms C difficile, meticillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci (VRE), or multidrug-resistant Acinetobacter spp) was discharged were terminally disinfected with one of four strategies: standard disinfection (quaternary ammonium disinfectant, except for C difficile, for which 10% hypochlorite [bleach] was used; reference); standard disinfection and disinfecting ultraviolet light (UV-C), except for C difficile, for which bleach and UV-C was used (UV strategy); 10% hypochlorite (bleach strategy); and bleach and UV-C (bleach and UV strategy). We randomly assigned the sequence of strategies for each hospital (1:1:1:1), and each strategy was used for 7 months, including a 1-month wash-in period and 6 months of data collection. The prespecified secondary outcomes were hospital-wide, hospital-acquired incidence of all target organisms (calculated as number of patients with hospital-acquired infection with a target organism per 10 000 patient days), and hospital-wide, hospital-acquired incidence of each target organism separately. BETR Disinfection is registered with ClinicalTrials.gov, number NCT01579370. FINDINGS: Between April, 2012, and July, 2014, there were 271 740 unique patients with 375 918 admissions. 314 610 admissions met all inclusion criteria (n=73 071 in the reference study period, n=81 621 in the UV study period, n=78 760 in the bleach study period, and n=81 158 in the bleach and UV study period). 2681 incidenct cases of hospital-acquired infection or colonisation occurred during the study. There was no significant difference in the hospital-wide risk of target organism acquisition between standard disinfection and the three enhanced terminal disinfection strategies for all target multidrug-resistant organisms (UV study period relative risk [RR] 0·89, 95% CI 0·79-1·00; p=0·052; bleach study period 0·92, 0·79-1·08; p=0·32; bleach and UV study period 0·99, 0·89-1·11; p=0·89). The decrease in risk in the UV study period was driven by decreases in risk of acquisition of C difficile (RR 0·89, 95% CI 0·80-0·99; p=0·031) and VRE (0·56, 0·31-0·996; p=0·048). INTERPRETATION: Enhanced terminal room disinfection with UV in a targeted subset of high-risk rooms led to a decrease in hospital-wide incidence of C difficile and VRE. Enhanced disinfection overcomes limitations of standard disinfection strategies and is a potential strategy to reduce the risk of acquisition of multidrug-resistant organisms and C difficile. FUNDING: US Centers for Disease Control and Prevention.

Real-Time Surveillance of Influenza Morbidity: Tracking Intensive Care Unit Resource Utilization.

RATIONALE: Existing real-time surveillance of influenza morbidity, based primarily on time-trended U.S. hospitalization and death data, is inadequate. These surveillance methods do not accurately predict hospital resource requirements or sufficiently capture the public health impact of the current influenza season. OBJECTIVES: To determine the feasibility and potential usefulness of tracking surrogate markers of influenza morbidity among patients hospitalized with influenza. METHODS: We performed a pilot study at three tertiary care referral hospitals and retrospectively collected and analyzed data on patients admitted with influenza during the 2013-2014 influenza season. We analyzed traditional influenza surveillance metrics, including weekly statistics on admissions and deaths, as well as weekly rates and trends of intensive care unit (ICU), mechanical ventilation, and extracorporeal membrane oxygenation (ECMO) utilization. RESULTS: In our three-hospital cohort, 431 patients were hospitalized with influenza and spent a total of 1,520 days in ICUs. Eighty-six (20%) of these patients required 1,080 days of mechanical ventilation, and 17 patients (4%) received 229 days of ECMO. Trends of ICU and mechanical ventilation use were similar but differed notably from trends of ECMO use, hospitalization, and death. In particular, at two hospitals, increases in utilization of ICU and mechanical ventilation among patients with influenza occurred several weeks after increases in hospitalization rates. Furthermore, ICU, mechanical ventilation, and ECMO utilization rates at the three-hospital network remained elevated for several weeks after the influenza-associated hospitalization rate declined. CONCLUSIONS: Surrogate markers of influenza severity were feasible to collect and revealed trends of ICU resource utilization that differed notably from trends of hospitalization and death given by traditional influenza surveillance metrics. A national network of sentinel hospitals that prospectively collects, time-trends, and reports additional influenza morbidity data would be useful to hospital administrators, hospital epidemiologists, infection preventionists, and public health officials.