Nimalie D. Stone

Surveillance definitions of infections in long-term care facilities: revisiting the McGeer criteria.

(See the commentary by Moro, on pages 978-980 .) Infection surveillance definitions for long-term care facilities (ie, the McGeer Criteria) have not been updated since 1991. An expert consensus panel modified these definitions on the basis of a structured review of the literature. Significant changes were made to the criteria defining urinary tract and respiratory tract infections. New definitions were added for norovirus gastroenteritis and Clostridum difficile infections.

Multiple-Dose Escalation Study of the Safety, Pharmacokinetics, and Biologic Activity of Oral AMD070, a Selective CXCR4 Receptor Inhibitor, in Human Subjects

ABSTRACT AMD070 is an oral CXCR4 antagonist with in vitro activity against X4-tropic human immunodeficiency virus type 1. Thirty fasting healthy male volunteers received oral doses of AMD070 ranging from a single 50-mg dose to seven 400-mg doses given every 12 h (q12h). Nine subjects received a 200-mg dose during fasting and prior to a meal. Subjects were monitored for safety and pharmacokinetics. AMD070 was well tolerated, without serious adverse events. Transient headaches (13 subjects) and neurocognitive (8 subjects) and gastrointestinal (7 subjects) symptoms were the most common complaints. Seven subjects had sinus tachycardia, and two were symptomatic. AMD070 plasma concentrations peaked 1 to 2 h after patient dosing. The estimated terminal half-life ranged from 11.2 to 15.9 h among cohorts. Dose proportionality was not demonstrated. Less than 1% of the drug appeared unchanged in the urine. Food reduced the maximum concentration of drug in serum and the area under the concentration-time curve from 0 to 24 h by 70% and 56%, respectively (P ≤ 0.01). A dose-dependent elevation of white blood cells (WBC) demonstrated a maximum twofold increase over baseline (95% confidence interval, 2.0- to 2.1-fold) in an Emax model. In healthy volunteers, AMD070 was well tolerated and demonstrated mixed-order pharmacokinetics, and food reduced drug exposure. AMD070 induced a dose-related elevation of WBC which was attributed to CXCR4 blockade. Using leukocytosis as a surrogate marker for CXCR4 inhibition, this dose-response relationship suggests that the doses used in this study were active in vivo, though not maximal, throughout the dosing interval. Trough concentrations with the 400-mg dose q12h exceeded the antiviral in vitro 90% effective concentration of AMD070.

Asymptomatic bacteriuria, antibiotic use, and suspected urinary tract infections in four nursing homes

BackgroundUrinary tract infections (UTIs) are the most commonly treated infection among nursing home residents. Even in the absence of specific (e.g., dysuria) or non-specific (e.g., fever) signs or symptoms, residents frequently receive an antibiotic for a suspected infection. This research investigates factors associated with the use of antibiotics to treat asymptomatic bacteriuria (ASB) among nursing home residents.MethodsThis was a cross-sectional study involving multi-level multivariate analyses of antibiotic prescription data for residents in four nursing homes in central Texas. Participants included all nursing home residents in these homes who, over a six-month period, received an antibiotic for a suspected UTI. We investigated what factors affected the likelihood that a resident receiving an antibiotic for a suspected UTI was asymptomatic.ResultsThe most powerful predictor of antibiotic treatment for ASB was the presence of an indwelling urinary catheter. Over 80 percent of antibiotic prescriptions written for catheterized individuals were written for individuals with ASB. For those without a catheter, record reviews identified 204 antibiotic prescriptions among 151 residents treated for a suspected UTI. Almost 50% of these prescriptions were for residents with no documented UTI symptoms. Almost three-quarters of these antibiotics were ordered after laboratory results were available to clinicians. Multivariate analyses indicated that resident characteristics did not affect the likelihood that an antibiotic was prescribed for ASB. The only statistically significant factor was the identity of the nursing home in which a resident resided.ConclusionsWe confirm the findings of earlier research indicating frequent use of antibiotics for ASB in nursing homes, especially for residents with urinary catheters. In this sample of nursing home residents, half of the antibiotic prescriptions for a suspected UTI in residents without catheters occurred with no documented signs or symptoms of a UTI. Urine studies were performed in almost all suspected UTI cases in which an antibiotic was prescribed. Efforts to improve antibiotic stewardship in nursing homes must address clinical decision-making solely on the basis of diagnostic testing in the absence of signs or symptoms of a UTI.

Infections in long-term care populations in the United States.

To estimate infection prevalence and explore associated risk factors in nursing home (NH) residents, individuals receiving home health care (HHC), and individuals receiving hospice care.

Methicillin-resistant Staphylococcus aureus (MRSA) nasal carriage in residents of Veterans Affairs long-term care facilities: role of antimicrobial exposure and MRSA acquisition.

OBJECTIVE To identify risk factors associated with methicillin-resistant Staphylococcus aureus (MRSA) acquisition in long-term care facility (LTCF) residents. DESIGN Multicenter, prospective cohort followed over 6 months. SETTING Three Veterans Affairs (VA) LTCFs. PARTICIPANTS All current and new residents except those with short stay (<2 weeks). METHODS MRSA carriage was assessed by serial nares cultures and classified into 3 groups: persistent (all cultures positive), intermittent (at least 1 but not all cultures positive), and noncarrier (no cultures positive). MRSA acquisition was defined by an initial negative culture followed by more than 2 positive cultures with no subsequent negative cultures. Epidemiologic data were collected to identify risk factors, and MRSA isolates were typed by pulsed-field gel electrophoresis (PFGE). RESULTS Among 412 residents at 3 LTCFs, overall MRSA prevalence was 58%, with similar distributions of carriage at all 3 facilities: 20% persistent, 39% intermittent, 41% noncarriers. Of 254 residents with an initial negative swab, 25 (10%) acquired MRSA over the 6 months; rates were similar at all 3 LTCFs, with no clusters evident. Multivariable analysis demonstrated that receipt of systemic antimicrobials during the study was the only significant risk factor for MRSA acquisition (odds ratio, 7.8 [95% confidence interval, 2.1-28.6]; P = .002). MRSA strains from acquisitions were related by PFGE to those from a roommate in 9/25 (36%) cases; 6 of these 9 roommate sources were persistent carriers. CONCLUSIONS MRSA colonization prevalence was high at 3 separate VA LTCFs. MRSA acquisition was strongly associated with antimicrobial exposure. Roommate sources were often persistent carriers, but transmission from roommates accounted for only approximately one-third of MRSA acquisitions.

Antimicrobial stewardship in long-term care facilities.

Although antimicrobial stewardship has been shown to improve microbiologic susceptibility patterns, decrease drug toxicities, and lower overall drug costs in the inpatient setting, there are few studies assessing programs in the long-term care (LTC) setting. Implementing antimicrobial stewardship programs in LTC settings can be challenging as the LTC setting houses a unique population of frail and older adults with several preexisting conditions and multiple risk factors for colonization with multidrug-resistant organisms. Antimicrobial stewardship has an important role in decreasing inappropriate antibiotic use, encouraging targeted treatment of specific disease states, and limiting the untoward effects and costs of antimicrobials in this vulnerable population.

Burden of Nursing Home-Onset Clostridium difficile Infection in the United States: Estimates of Incidence and Patient Outcomes

Background. Approximately 4 million Americans receive nursing home (NH) care annually. Nursing home residents commonly have risk factors for Clostridium difficile infection (CDI), including advanced age and antibiotic exposures. We estimated national incidence of NH-onset (NHO) CDI and patient outcomes. Methods. We identified NHO-CDI cases from population-based surveillance of 10 geographic areas in the United States. Cases were defined by C difficile-positive stool collected in an NH (or from NH residents in outpatient settings or ≤3 days after hospital admission) without a positive stool in the prior 8 weeks. Medical records were reviewed on a sample of cases. Incidence was estimated using regression models accounting for age and laboratory testing method; sampling weights were applied to estimate hospitalizations, recurrences, and deaths. Results. A total of 3503 NHO-CDI cases were identified. Among 262 sampled cases, median age was 82 years, 76% received antibiotics in the 12 weeks prior to the C difficile-positive specimen, and 57% were discharged from a hospital in the month before specimen collection. After adjusting for age and testing method, the 2012 national estimate for NHO-CDI incidence was 112 800 cases (95% confidence interval [CI], 93 400–131 800); 31 400 (28%) were hospitalized within 7 days after a positive specimen (95% CI, 25 500–37 300), 20 900 (19%) recurred within 14–60 days (95% CI, 14 600–27 100), and 8700 (8%) died within 30 days (95% CI, 6600–10 700). Conclusions. Nursing home onset CDI is associated with substantial morbidity and mortality. Strategies focused on infection prevention in NHs and appropriate antibiotic use in both NHs and acute care settings may decrease the burden of NHO CDI.

Utility of a Commercial PCR Assay and a Clinical Prediction Rule for Detection of Toxigenic Clostridium difficile in Asymptomatic Carriers

ABSTRACT A commercial PCR assay of perirectal swab specimens detected 17 (68%) of 25 asymptomatic carriers of toxigenic Clostridium difficile, including 93% with skin and/or environmental contamination. A clinical prediction rule, followed by PCR screening, could be used to identify carriers at high risk of C. difficile shedding.

Comparison of Disk Diffusion, VITEK 2, and Broth Microdilution Antimicrobial Susceptibility Test Results for Unusual Species of Enterobacteriaceae

ABSTRACT We compared the antimicrobial susceptibility testing results generated by disk diffusion and the VITEK 2 automated system with the results of the Clinical and Laboratory Standards Institute (CLSI) broth microdilution (BMD) reference method for 61 isolates of unusual species of Enterobacteriaceae. The isolates represented 15 genera and 26 different species, including Buttiauxella, Cedecea, Kluyvera, Leminorella, and Yokenella. Antimicrobial agents included aminoglycosides, carbapenems, cephalosporins, fluoroquinolones, penicillins, and trimethoprim-sulfamethoxazole. CLSI interpretative criteria for Enterobacteriaceae were used. Of the 12 drugs tested by BMD and disk diffusion, 10 showed >95% categorical agreement (CA). CA was lower for ampicillin (80.3%) and cefazolin (77.0%). There were 3 very major errors (all with cefazolin), 1 major error (also with cefazolin), and 26 minor errors. Of the 40 isolates (representing 12 species) that could be identified with the VITEK 2 database, 36 were identified correctly to species level, 1 was identified to genus level only, and 3 were reported as unidentified. VITEK 2 generated MIC results for 42 (68.8%) of 61 isolates, but categorical interpretations (susceptible, intermediate, and resistant) were provided for only 22. For the 17 drugs tested by both BMD and VITEK 2, essential agreement ranged from 80.9 to 100% and CA ranged from 68.2% (ampicillin) to 100%; thirteen drugs exhibited 100% CA. In summary, disk diffusion provides a reliable alternative to BMD for testing of unusual Enterobacteriaceae, some of which cannot be tested, or produce incorrect results, by automated methods.

A National Implementation Project to Prevent Catheter-Associated Urinary Tract Infection in Nursing Home Residents

Importance Catheter-associated urinary tract infection (UTI) in nursing home residents is a common cause of sepsis, hospital admission, and antimicrobial use leading to colonization with multidrug-resistant organisms. Objective To develop, implement, and evaluate an intervention to reduce catheter-associated UTI. Design, Setting, and Participants A large-scale prospective implementation project was conducted in community-based nursing homes participating in the Agency for Healthcare Research and Quality Safety Program for Long-Term Care. Nursing homes across 48 states, Washington DC, and Puerto Rico participated. Implementation of the project was conducted between March 1, 2014, and August 31, 2016. Interventions The project was implemented over 12-month cohorts and included a technical bundle: catheter removal, aseptic insertion, using regular assessments, training for catheter care, and incontinence care planning, as well as a socioadaptive bundle emphasizing leadership, resident and family engagement, and effective communication. Main Outcomes and Measures Urinary catheter use and catheter-associated UTI rates using National Healthcare Safety Network definitions were collected. Facility-level urine culture order rates were also obtained. Random-effects negative binomial regression models were used to examine changes in catheter-associated UTI, catheter utilization, and urine cultures and adjusted for covariates including ownership, bed size, provision of subacute care, 5-star rating, presence of an infection control committee, and an infection preventionist. Results In 4 cohorts over 30 months, 568 community-based nursing homes were recruited; 404 met inclusion criteria for analysis. The unadjusted catheter-associated UTI rates decreased from 6.78 to 2.63 infections per 1000 catheter-days. With use of the regression model and adjustment for facility characteristics, the rates decreased from 6.42 to 3.33 (incidence rate ratio [IRR], 0.46; 95% CI, 0.36-0.58; P < .001). Catheter utilization was 4.5% at baseline and 4.9% at the end of the project. Catheter utilization remained unchanged (4.50 at baseline, 4.45 at conclusion of project; IRR, 0.95; 95% CI, 0.88-1.03; P = .26) in adjusted analyses. The number of urine cultures ordered for all residents decreased from 3.49 per 1000 resident-days to 3.08 per 1000 resident-days. Similarly, after adjustment, the rates were shown to decrease from 3.52 to 3.09 (IRR, 0.85; 95% CI, 0.77-0.94; P = .001). Conclusions and Relevance In a large-scale, national implementation project involving community-based nursing homes, combined technical and socioadaptive catheter-associated UTI prevention interventions successfully reduced the incidence of catheter-associated UTIs.