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Aim: The orphan drug auranofin was recently found to exhibit antimicrobial properties. Materials & methods: We explored the efficacy of auranofin by evaluating the minimal inhibitory concentration against a collection of over 500 clinical isolates derived from multiple institutions, inclusive of drug resistant strains. Our evaluation also included continuous exposure of bacteria to auranofin. Results & conclusion: We found that minimal inhibitory concentrations ranged between 0.125 and 1 mg/l, exerting robust antimicrobial activity against a sizeable clinical collection of the bacteria. Further, we evaluated the propensity of the methicillin-resistant Staphylococcus aureus strain MW2 to develop resistance through extended exposure to auranofin. After 25 days, the bacteria remained susceptible. Our data suggest that resistance mechanisms do not currently exist to block auranofin antimicrobial activity.

Using a rigorously collected data set of antimicrobial use among patients receiving chronic hemodialysis, antimicrobial use was calculated using 3 different methodologies: daily defined dose, days of therapy, and start-stop days. Estimates of antimicrobial use varied by as much as 10-fold, depending on the type of antimicrobial. Infect Control Hosp Epidemiol 2017;38:360-363.

Purpose of Review: Rates of multidrug-resistant organisms (MDRO), including methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and multidrug-resistant gram-negative bacteria, continue to rise among the population of chronic hemodialysis. Antimicrobial exposure is the main risk factor for MDRO emergence and dissemination. Up to 30% of antimicrobial doses administered in out-patient dialysis units may not be indicated. Antimicrobial stewardship programs (ASP) improve antimicrobial prescribing patterns. The purpose of this review is to highlight the key elements and interventions of ASP., Recent Findings: The Infectious Disease Society of America and the Society of Healthcare Epidemiology of America have provided evidence-based guidelines for the development and implementation of an ASP. Many of their recommendations can be adapted to the out-patient dialysis setting., Summary: Developing and implementing an ASP by following key elements and interventions in the out-patient dialysis setting can lead to reduced mortality, adverse events, costs, and improvement in antimicrobial susceptibility rates.

Background: Antimicrobial use is common among patients receiving chronic hemodialysis (CHD) and may represent an important antimicrobial stewardship opportunity. The objective of this study is to characterize CHD patients at increased risk of receiving antimicrobials, including not indicated antimicrobials., Methods: We conducted a prospective cohort study over a 12-month period among patients receiving CHD in 2 outpatient dialysis units. Each parenteral antimicrobial dose administered was characterized as indicated or not indicated based on national guidelines. Patient factors associated with receipt of antimicrobials and receipt of ≥1 inappropriate antimicrobial dose were analyzed., Results: A total of 89 of 278 CHD patients (32%) received ≥1 antimicrobial doses and 52 (58%) received ≥1 inappropriately indicated dose. Patients with tunneled catheter access, a history of colonization or infection with a multidrug-resistant organism, and receiving CHD sessions during daytime shifts were more likely to receive antimicrobials (odds ratio [OR], 5.16; 95% confidence interval [CI], 2.72-9.80; OR, 5.43; 95% CI, 1.84-16.06; OR, 4.59; 95% CI, 1.20-17.52, respectively). Patients with tunneled catheter access, receiving CHD at dialysis unit B, and with a longer duration of CHD prior to enrollment were at higher risk of receiving an inappropriately indicated antimicrobial dose (incidence rate ratio, 2.23; 95% CI, 1.16-4.29; incidence rate ratio, 2.67; 95% CI, 1.34-5.35; incidence rate ratio, 1.11; 95% CI, 1.01-1.23, respectively)., Conclusions: This study of all types of antimicrobials administered in 2 outpatient dialysis units identified several important factors to consider when developing antimicrobial stewardship programs in this health care setting., (Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.)

Purpose: Methodological approaches to examine the association between antimicrobial exposure and multidrug-resistant organism (MDRO) acquisition are complex. This report's objectives are to review approaches used in and findings of prior studies in the long-term care setting, illustrate how these challenges were addressed in a recently completed large prospective study, and discuss strategies for future studies., Methods: Key design and analytic approaches used in studies conducted since 2000 examining the association between antimicrobial exposure and MDRO acquisition in the long-term care setting were reviewed. The Study of Pathogen Resistance and Exposure to Antimicrobials in Dementia (SPREAD) in nursing home residents in Boston from 2009 to 2014 is used to illustrate how to approach these challenges., Results: Prior investigations reporting the association between antimicrobial exposure and MDRO acquisition vary considerably in their approaches. In SPREAD, grouped-time hazard models with complementary log-log link function were used to model acquisition accounting for clustering within facilities using generalized estimating equations and including all days of exposure before acquisition., Conclusions: Future studies in these populations should make use of all available acquisition status data, incorporate the timing of antimicrobial exposure relative to acquisition, and collect detailed covariate information that facilitates examining confounding by indication., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Patients receiving chronic hemodialysis (CHD) are among the most vulnerable to infections caused by multidrug-resistant organisms (MDRO), which are associated with high rates of morbidity and mortality. Current guidelines to reduce transmission of MDRO in the out-patient dialysis unit are targeted at patients considered to be high-risk for transmitting these organisms: those with infected skin wounds not contained by a dressing, or those with fecal incontinence or uncontrolled diarrhea. Here, we hypothesize that targeting patients receiving antimicrobial treatment would more effectively reduce transmission and acquisition of MDRO. We also hypothesize that environmental contamination plays a role in the dissemination of MDRO in the dialysis unit. To address our hypotheses, we built an agent-based model to simulate different treatment strategies in a dialysis unit. Our results suggest that reducing antimicrobial treatment, either by reducing the number of patients receiving treatment or by reducing the duration of the treatment, markedly reduces overall colonization rates and also the levels of environmental contamination in the dialysis unit. Our results also suggest that improving the environmental decontamination efficacy between patient dialysis treatments is an effective method for reducing colonization and contamination rates. These findings have important implications for the development and implementation of future infection prevention strategies.

Objectives: To determine whether antimicrobial treatment for suspected urinary tract infections (UTIs) improves survival in nursing home residents with advanced dementia., Design: Prospective cohort study., Setting: Thirty-five nursing homes in Boston, Massachusetts., Participants: Nursing home residents who experienced at least one suspected UTI over a 12-month period (N = 110); mean participant age 86.4 ± 6.2, 84% female., Measurements: Analyses were at the level of the UTI episode. Antimicrobial treatment for each suspected UTI was categorized as none, oral, intramuscular, or intravenous or hospitalization. Survival was calculated from the date of suspected UTI episode until death or last known follow-up date. Covariates included resident and episode characteristics. Cox proportional hazards regression was used to examine the association between treatment group and risk of death after adjusting for covariates., Results: Residents experienced 196 suspected UTIs over the follow-up period; 33% (n = 36) died during follow-up. There was no antimicrobial use for 25.0% of the 196 suspected UTIs, oral antimicrobial use in 59.7%; intramuscular antimicrobial use in 9.2%, and intravenous antimicrobial use or hospital transfer in 6.1%. After multivariable adjustment, antimicrobial treatment was not significantly associated with mortality (oral, adjusted hazard ratio for death (AHR) = 1.09, 95% confidence interval (CI) = 0.43-2.75; intramuscular, AHR = 0.66, 95% CI = 0.08-5.66; intravenous or hospitalization, AHR = 1.83, 95% CI = 0.44-7.60)., Conclusion: Although the majority of suspected UTIs that nursing home residents with advanced dementia experienced were treated with antimicrobials, treatment was not associated with survival., (© 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.)

Objective: To quantify the extent of inter- and intra-nursing home transmission of multidrug-resistant gram-negative bacteria (MDRGN) among residents with advanced dementia and characterize MDRGN colonization among these residents., Design: Prospective cohort study., Setting: Twenty-two nursing homes in the greater Boston, Massachusetts, area., Patients: Residents with advanced dementia., Methods: Serial rectal surveillance cultures for MDRGN and resident characteristics were obtained every 3 months for 12 months or until death. Molecular typing of MDRGN isolates was performed by pulsed-field gel electrophoresis., Results: A total of 190 MDRGN isolates from 152 residents with advanced dementia were included in the analyses. Both intra- and inter-nursing home transmission were identified. Genetically related MDRGN strains, recovered from different residents, were detected in 18 (82%) of the 22 nursing homes. The percent of clonally related strains in these nursing homes ranged from 0% to 86% (average, 35%). More than 50% of strains were clonally related in 3 nursing homes. Co-colonization with more than 1 different MDRGN species occurred among 28 residents (18.4%). A total of 168 (88.4%), 20 (10.5%), and 2 (1.0%) of MDRGN isolates were resistant to 3, 4, and 5 different antimicrobials or antimicrobial classes, respectively., Conclusions: MDRGN are spread both within and between nursing homes among residents with advanced dementia. Infection control interventions should begin to target this high-risk group of nursing home residents.

Antimicrobial exposure contributes to the emergence and spread of multidrug-resistant organisms. As rates of colonization and infection with these organisms are among the highest in the population of chronic hemodialysis patients and antimicrobial exposure among this patient population is extensive, it is imperative to prescribe antimicrobials judiciously. Thirty to forty percent of chronic hemodialysis patients receive at least one dose of antimicrobials in outpatient centers over a one-year period. Up to 30% of these antimicrobials are prescribed inappropriately, as per national guidelines. The predominant reasons include (i) failure to de-escalate to a more narrow-spectrum antimicrobial, (ii) criteria for infection, especially skin and soft tissue infections, are not met, and (iii) indications and duration for surgical prophylaxis for minor vascular-access-related procedures do not follow recommended guidelines. Vancomycin, third- or fourth-generation cephalosporins and cefazolin are the most common antimicrobials or antimicrobial classes prescribed inappropriately. Antimicrobial stewardship programs reduce both inappropriate antimicrobial exposure and associated costs. Effective strategies include (i) education, (ii) guidelines and clinical pathways, (iii) antimicrobial order forms, (iv) de-escalation therapy, and (v) prospective audit and feedback. Dialysis centers need to identify a team of individuals that will lead the antimicrobial stewardship program. Administrative and financial support for this team is essential. After implementation of the program, regular monitoring for compliance with strategies, and identifying factors that are preventing compliance are necessary. The efficacy of the program should also be evaluated at regular intervals through process and outcome measures., (© 2013 Wiley Periodicals, Inc.)

Objective: To quantify and characterize overall antimicrobial use, including appropriateness of indication, among patients receiving chronic hemodialysis., Design: Retrospective and prospective observational study., Setting: Two outpatient hemodialysis units., Patients: All patients receiving chronic hemodialysis., Methods: The rate of parenteral antimicrobial use (number of doses per 100 patient-months) was calculated retrospectively from September 2008 through July 2011. Indication and appropriateness of antimicrobial doses were characterized prospectively from August 2010 through July 2011. Inappropriate administration was defined as occasions when criteria for infection based on national guidelines were not met, failure to choose a more narrow-spectrum antimicrobial on the basis of culture data, or occasions when indications for surgical prophylaxis were not met., Results: Over the 35-month retrospective study period, the rate of parenteral antimicrobial use was 32.9 doses per 100 patient-months. Vancomycin was the most commonly prescribed antimicrobial, followed by cefazolin and third- or fourth-generation cephalosporins. Over the 12-month prospective study, 1,003 antimicrobial doses were prescribed. Among the 926 (92.3%) doses for which an indication for administration was available, 276 (29.8%) were classified as inappropriate. Of these, a total of 146 (52.9%) did not meet criteria for infection, 74 (26.8%) represented failure to choose a more narrow-spectrum antimicrobial, and 56 (20.3%) did not meet criteria for surgical prophylaxis. The most common inappropriately prescribed antimicrobials were vancomycin and third- or fourth- generation cephalosporins., Conclusions: Parenteral antimicrobial use was extensive, and as much as one-third was categorized as inappropriate. The findings of this study provide novel information toward minimizing inappropriate antimicrobial use.

Resistance to antimicrobials continues to increase worldwide. Data suggest that older patients are among the main reservoirs of multidrug-resistant organisms (MDROs) in the hospital. We hypothesized that older patients (≥ 65 years of age) are more likely to harbor MDRO at hospital admission. We compared rates of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and multidrug-resistant gram-negative bacteria (MDRGN) recovered from clinical cultures within the first 48 h of admission to an adult acute care hospital between the elderly (≥ 65 years old) and young per 1000 age-stratified admissions over a 12-year study period. Trends in antimicrobial resistance, sites of recovery and species for MDRGN were also characterized. An average of 7534 positive bacterial cultures were collected per year. The admission prevalence per 1000 age-stratified admissions was consistently higher among the elderly for all three MDRO under investigation. Among the elderly, the admission prevalence increased significantly for VRE (0.89 in 1998 to 3.62 in 2009 per 1000 admissions; p < 0.001) and MDRGN (1.41 in 1998 to 11.33 in 2009 per 1000 admissions; p < 0.001). Percentage resistant for all three MDRO increased as well. These data suggest that elderly patients are contributing substantially to the influx of MDRO into the hospital setting., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

The contribution of horizontal gene transmission (HGT) in the emergence and spread of extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacteria during periods of endemicity is unclear. Over a 12-month period, rectal colonization with SHV-5- and SHV-12-producing Escherichia coli and Klebsiella pneumoniae was quantified among a cohort of residents in a long-term care facility. Demographic and clinical data were collected on colonized residents. Transferability of SHV-encoding plasmids and pulsed-field gel electrophoresis were performed to quantify the contribution of HGT and cross-transmission, respectively. A total of 25 (12%) of 214 enrolled patients were colonized with 11 SHV-5- and 17 SVH-12-producing E. coli and K. pneumoniae. Clonally related isolates were detected among multiple residents residing on the same and different wards. Among 12 clonally distinct isolates, HGT of SHV-5- and SHV-12-encoding plasmids was identified among 6 (50%) isolates. HGT among clonally distinct strains contributes to the transmission dynamics of these ESBL-producing Gram-negative bacteria and should be considered when evaluating the spread of these pathogens., (Copyright © 2012 Elsevier Inc. All rights reserved.)

To quantify the sensitivity of surveillance cultures for the detection of multidrug-resistant gram-negative (MDRGN) bacteria, perianal/rectal swabs were collected from patients with positive clinical cultures for MDRGN species. Surveillance cultures identified colonization with the same genetically related MDRGN species in 29 of 37 MDRGN clinical culture isolates (78%). There was a trend toward less antimicrobial exposure among patients with false-negative surveillance culture results (P = .06)., (Copyright © 2012 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

Purpose of Review: Antimicrobial-resistant bacteria (ARB) including resistant strains of Staphylococcus aureus, enterococci, and Gram-negative bacteria have the potential to cause serious infections among patients requiring chronic hemodialysis (CHD). The purpose of this article is to review novel ARB, which have emerged in this patient population, their mechanisms of transmission, and preventive efforts aimed at limiting their dissemination., Recent Findings: New strains of ARB, including community-acquired methicillin-resistant S. aureus, S. aureus strains with reduced susceptibility to vancomycin, vancomycin-resistant S. aureus and multidrug-resistant Gram-negative bacteria (MDRGN), are emerging among the CHD population. Extended-spectrum β-lactamase Gram-negative bacteria (ESBLGN) are among the most common MDRGN strains. These ESBLGN are resistant to the great majority of antimicrobials. The carbapenems remain the only optimal antimicrobial choice to treat ESBLGN infections. Intrafacility spread of ARB in dialysis units occurs between patients through contaminated hands and clothes of healthcare workers (HCWs), as well as contaminated inanimate surfaces. Spread of ARB to family members of both patients and HCWs has also been documented., Summary: Colonization and infection with ARB continues to present a significant threat to patients receiving CHD. Interventions to reduce the spread of ARB should include infection control measures and judicious use of antimicrobials.

Multidrug-resistant organisms (MDRO) continue to spread in hospitals globally, but the population-level impact of recommended preventive strategies and the relative benefit of individual strategies targeting all MDRO in the hospital setting are unclear. To explore the dynamics of MDRO transmission in the hospital, we develop a model extending data from clinical individual-level studies to quantify the impact of hand hygiene, contact precautions, reducing antimicrobial exposure and screening surveillance cultures in decreasing the prevalence of MDRO colonization and infection. The effect of an ongoing increase in the influx of patients colonized with MDRO into the hospital setting is also quantified. We find that most recommended strategies have substantial effect in decreasing the prevalence of MDRO over time. However, screening for asymptomatic MDRO colonization among patients who are not receiving antimicrobials is of minimal value in reducing the spread of MDRO.

Introduction: Clostridium difficile-associated disease (CDAD) is treated using antibiotics, which often leads to the emergence of antibiotic-resistant bacteria such as vancomycin-resistant enterococci (VRE). This study estimated the impact of a non antibiotic treatment for CDAD on VRE prevalence., Methods: A previously published model describing the impact of in-hospital antibiotic use on VRE prevalence was adapted to include CDAD treatment. Simulations compared the prevalence of VRE when nonantibiotic versus antibiotic therapy was used., Results: Nonantibiotic treatment in 50% of CDAD patients resulted in an 18% relative reduction in the prevalence of VRE colonization compared with antibiotic use only. Sensitivity analysis found the model to be most sensitive to rates of antibiotic initiation and discontinuation, prevalence of VRE in admitted patients, length of stay of colonized patients, probability of CDAD acquisition, and hand-washing compliance., Conclusion: Nonantibiotic treatment of patients hospitalized with CDAD may significantly reduce the incidence of VRE colonization.

Background: The characteristics of co-colonization with multiple different species of multidrug-resistant gram-negative bacteria (MDRGN) have not been fully elucidated. Quantifying the prevalence of co-colonization and those patients at higher risk of co-colonization may have important implications for strategies aimed at limiting the spread of MDRGN., Methods: To determine the prevalence of MDRGN colonization, rectal swabs were obtained from 212 residents residing in a 600-bed long-term care facility. Co-colonization was defined as colonization with ≥2 different MDRGN species. Co-colonized residents were compared with residents colonized with a single MDRGN species to identify factors associated with an increased risk for co-colonization. Molecular typing was performed to determine the contribution of cross transmission to the co-colonized state., Results: A total of 53 (25%) residents was colonized with ≥1 MDRGN. Among these, 11 (21%) were colonized with ≥2 different species of MDRGN. A global deterioration score of ≥5 representing advanced dementia and an increased requirement for assistance from health care workers was significantly associated with co-colonization (P = .05). Clonally related MDRGN strains were identified among 7 (64%) co-colonized residents., Conclusion: The prevalence of co-colonization with ≥2 different MDRGN is substantial. Cross transmission of MDRGN is a major contributor to the co-colonized state., (Copyright © 2011 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

Background and Objective: An improved understanding of the transmission dynamics of multidrug-resistant (MDR) gram-negative bacteria and the mechanism of acquisition in long-term care facilities (LTCFs) could aid in the development of prevention strategies specific to LTCFs. We thus investigated the incidence of acquisition of these pathogens among an LTCF population., Design: Prospective cohort study., Setting: Three separate wards at a 600-bed LTCF in metropolitan Boston, Massachusetts, during the period October 31, 2006, through October 22, 2007., Participants: One hundred seventy-two LTCF residents., Methods: A series of rectal samples were cultured to determine acquisition of MDR gram-negative bacteria, defined as absence of MDR gram-negative bacterial colonization at baseline and de novo recovery of MDR gram-negative bacteria from a follow-up culture. Molecular typing was performed to identify genetically linked strains. A nested matched case-control study was performed to identify risk factors associated with acquisition., Results: Among 135 residents for whom at least 1 follow-up culture was performed, 52 (39%) acquired at least 1 MDR gram-negative organism during the study period. Thirty-two residents (62%) had not been colonized at baseline and had acquired at least 1 MDR gram-negative species at follow-up culture, and 20 residents (38%) were colonized at baseline and had acquired at least 1 MDR gram-negative species at follow-up culture. The most common coresistance pattern was resistance to extended-spectrum penicillins, ciprofloxacin, and gentamicin (57 isolates [42.5%]). Genetically related strains of MDR gram-negative bacteria were identified among multiple residents and between roommates. On conditional logistic regression analysis, antibiotic exposure during the study period was significantly associated with acquisition of MDR gram-negative bacteria (odds ratio, 5.6 [95% confidence interval, 1.1-28.7]; P = .04)., Conclusions: Acquisition of MDR gram-negative bacteria occurred frequently through resident-to-resident transmission. Existing infection control interventions need to be reevaluated.

An outbreak of acute respiratory disease due to human adenovirus and a resulting increase in mortality occurred in a long-term care facility for the elderly. By use of viral culture and polymerase chain reaction, not a rapid antigen test, the virus was detected. Human adenovirus infection can occur in elderly individuals, but detection by rapid antigen testing may be limited.

We investigate the in-hospital transmission dynamics of two methicillin-resistant Staphylococcus aureus (MRSA) strains: hospital-acquired methicillin resistant S. aureus (HA-MRSA) and community-acquired methicillin-resistant S. aureus (CA-MRSA). Under the assumption that patients can only be colonized with one strain of MRSA at a time, global results show that competitive exclusion occurs between HA-MRSA and CA-MRSA strains; the strain with the larger basic reproduction ratio will become endemic while the other is extinguished due to competition. Because new studies suggest that patients can be concurrently colonized with multiple strains of MRSA, we extend the model to allow patients to be co-colonized with HA-MRSA and CA-MRSA. Using the extended model, we explore the effect of co-colonization on competitive exclusion by determining the invasion reproduction ratios of the boundary equilibria. In contrast to results derived from the assumption that co-colonization does not occur, the extended model rarely exhibits competitive exclusion. More commonly, both strains become endemic in the hospital. When transmission rates are assumed equal and decolonization measures act equally on all strains, competitive exclusion never occurs. Other interesting phenomena are exhibited. For example, solutions can tend toward a co-existence equilibrium, even when the basic reproduction ratio of one of the strains is less than one., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

BACKGROUND: Community-acquired methicillin-resistant Staphylococcus aureus (CA- MRSA), a novel strain of MRSA, has recently emerged and rapidly spread in the community. Invasion into the hospital setting with replacement of the hospital-acquired MRSA (HA-MRSA) has also been documented. Co-colonization with both CA-MRSA and HA-MRSA would have important clinical implications given differences in antimicrobial susceptibility profiles and the potential for exchange of genetic information. METHODS: A deterministic mathematical model was developed to characterize the transmission dynamics of HA-MRSA and CA-MRSA in the hospital setting and to quantify the emergence of co-colonization with both strains RESULTS: The model analysis shows that the state of co-colonization becomes endemic over time and that typically there is no competitive exclusion of either strain. Increasing the length of stay or rate of hospital entry among patients colonized with CA-MRSA leads to a rapid increase in the co-colonized state. Compared to MRSA decolonization strategy, improving hand hygiene compliance has the greatest impact on decreasing the prevalence of HA-MRSA, CA-MRSA and the co-colonized state. CONCLUSIONS: The model predicts that with the expanding community reservoir of CA-MRSA, the majority of hospitalized patients will become colonized with both CA-MRSA and HA-MRSA.

Recently, we [E.M.C. D’Agata, G.F. Webb, M.A. Horn, R.C. Moellering Jr., and S. Ruan, Modellingthe invasion of community-acquired methicillin-resistant Staphylococcus aureus into the hospital setting, Clin. Infect. Dis. 48 (2009), pp. 274–284] proposed a deterministic mathematical model to characterize the factors contributing to the replacement of hospital-acquired methicillin-resistant Staphylococcus aureus(HA-MRSA) with the community-acquired MRSA (CA-MRSA) and to quantify the effectiveness of interventionsaimed at limiting the spread of CA-MRSA in the hospital setting. Numerical simulations of the model strongly suggest that CA-MRSA will become the dominant MRSA strain in the hospital setting. In this companion paper, we provide steady-state analysis and more numerical simulations of the model. It is shown that when no colonized or infected patients enter the hospital, competitive exclusion of HA-MRSA by CA-MRSA will occur with increased severity of CA-MRSA infections resulting in longer hospitalizations and a larger in-hospital reservoir of CA-MRSA. Improving compliance with hand hygiene and decolonization of CA-MRSA carriers are effective control strategies.

Objective: To characterize the clinical and molecular epidemiology of multidrug-resistant (MDR) organisms in residents, in healthcare workers (HCWs), and on inanimate surfaces at a long-term care facility (LTCF)., Design: Point-prevalence study in 4 separate wards at a 600-bed urban LTCF that was conducted from October 31, 2006 through February 5, 2007., Participants: One hundred sixty-one LTCF residents and 13 HCWs., Methods: Nasal and rectal samples were obtained for culture from each resident, selected environmental surfaces in private and common rooms, and the hands and clothing of HCWs in each ward. All cultures were evaluated for the presence of MDR gram-negative bacteria, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant enterococci. Clinical and demographic information were collected for each enrolled resident. Molecular typing was performed to identify epidemiologically related strains., Results: A total of 37 (22.8%), 1 (0.6%), and 18 (11.1%) residents were colonized with MDR gram-negative bacteria, vancomycin-resistant enterococci, and methicillin-resistant S. aureus, respectively. MDR gram-negative bacteria were recovered from 3 (1.8%) of the 175 environmental samples cultured, all of which were obtained from common areas in LTCF wards. One (7.7%) of the 13 HCWs harbored MDR gram-negative bacteria. Molecular typing identified clonally related MDR gram-negative strains in LTCF residents. After multivariable analysis, length of hospital stay of at least 4 years, fecal incontinence, and antibiotic exposure for at least 8 days were independent risk factors associated with harboring MDR gram-negative bacteria among LTCF residents., Conclusions: The prevalence of MDR gram-negative bacteria is high among LTCF residents and exceeds that of vancomycin-resistant enterococci and methicillin-resistant S. aureus. Common areas in LTCFs may provide a unique opportunity for person-to-person transmission of MDR gram-negative bacteria.

Aim: Transplant recipients are at risk for hospital-acquired infections (HAIs), including those caused by Pseudomonas aeruginosa. Of all HAIs, bloodstream infection (BSI) remains one of the most life-threatening., Methods: Over a 10-year period, we studied 503 patients, including 149 transplant recipients, with pseudomonal BSI from the University of Pittsburgh Medical Center. Trends in antimicrobial susceptibility, risk factors for multidrug resistance (MDR), and outcomes were compared between transplant and non-transplant patients., Results: Resistance to all antibiotic classes was significantly greater in pseudomonal blood culture isolates from transplant compared with non-transplant patients (P<0.001). Of isolates from transplant recipients (n=207), 43% were MDR, compared with 18% of isolates from non-transplant patients (n=391) (odds ratio [OR] 3.47; 95% confidence interval [CI] 2.34-5.14, P<0.001). Among all patients, independent risk factors for MDR P. aeruginosa BSI included previous transplantation (OR 2.38; 95% CI 1.51-3.76, P<0.001), hospital-acquired BSI (OR 2.41; 95% CI 1.39-4.18, P=0.002), and prior intensive care unit (ICU) admission (OR 2.04; 95% CI 1.15-3.63, P=0.015). Mortality among transplant recipients was 42%, compared with 32% in non-transplant patients (OR 1.55; 95% CI 0.87-2.76, P=0.108). For transplant recipients, onset of BSI in the ICU was the only independent predictor of mortality (OR 8.00; 95% CI 1.71-37.42, P=0.008)., Conclusions: Transplant recipients are at greater risk of MDR P. aeruginosa BSI, with an appreciable mortality. Future management must concentrate on the implementation of effective preventative strategies.

Background: The characteristics of colonization with multidrug-resistant gram-negative bacteria (MDRGNB) in the gastrointestinal tract have not been well defined. Characterizing the duration of colonization, clearance of colonization, and frequency of cocolonization would provide important information for the development of interventions targeting the prevention of MDRGNB spread., Methods: From 31 October 2006 through 22 October 2007, serial rectal cultures were obtained every 3-4 weeks from residents of a long-term care facility. Clearance of colonization was defined as > or = 2 consecutive cultures from which MDRGNB were not recovered. Factors associated with clearance of colonization were analyzed using time-to-event methods., Results: Thirty-three patients colonized with 57 MDRGNB isolates were followed up for a median of 211 days (range, 63-356 days). Twenty (61%) of the patients were colonized with > or = 1 different MDRGNB species (median, 2 strains; range, 1-4 strains). The median duration of MDRGNB colonization was 144 days (range, 41-349 days). Clearance of colonization with all MDRGNB strains occurred in 3 patients (9%). Clearance of MDRGNB colonization, calculated by colonizing strain, occurred in 22 (39%) of 57 MDRGNB colonization episodes, with a rate of colonization clearance of 2.6 episodes per 1000 days. Clearance of multidrug-resistant Proteus mirabilis colonization occurred in 1 (6.7%) of 15 episodes, compared with clearance of 21 (50%) of 42 colonization episodes due to other MDRGNB species (hazard ratio, 0.1; 95% confidence interval, 0.01-0.78; P = .03)., Conclusions: Patient colonization with MDRGNB is prolonged, and a substantial proportion of patients are colonized with multiple MDRGNB species. Multidrug-resistant P. mirabilis may have a survival advantage in the gastrointestinal tract, compared with other MDRGNB species.

Background: Multidrug-resistant (MDR) gram-negative bacteria are reported increasingly frequently among isolates recovered from elderly patients. The clinical epidemiology of bloodstream infection (BSI) due to MDR gram-negative bacteria among elderly patients is unknown., Objective: To characterize the clinical epidemiology of BSI due to MDR gram-negative bacteria among elderly patients at hospital admission in an effort to provide a greater understanding of these serious infections and ultimately to improve patient outcomes., Design: Case-control study., Setting: Tertiary care hospital in Boston, Massachusetts., Patients: Patients 65 years of age and older., Methods: From 1999 to 2007, computerized medical records were reviewed for BSI due to MDR gram-negative bacteria within 48 hours of hospital admission. Risk factors for BSI due to these bacteria were identified., Results: MDR gram-negative bacteria were recovered from 61 (8%) of 724 elderly patients with BSI caused by gram-negative bacteria. Over the 8 1/2-year study period, the percentage of MDR gram-negative bacteria among bloodstream isolates increased from 2 (1%) of 199 to 34 (16%) of 216. Empiric therapy was ineffective for 38 (63%) of 60 patients with BSI caused by MDR gram-negative bacteria. The variables independently associated with BSI due to these bacteria were as follows: residency in a long-term care facility (odds ratio [OR], 4.9 [95% confidence interval {CI} 1.6-14.9]; P= .006), presence of an invasive device (OR, 6.0 [95% CI, 1.5-23.5]; P= .01), severe sepsis (OR, 7.9 [95% CI, 1.7-37.1]; P= .009), and delayed initiation of effective therapy (OR, 12.8 [95% CI, 3.9-41.1]; P= .001)., Conclusion: The 16-fold increase in BSI due to MDR gram-negative bacteria at hospital admission among elderly patients, especially among those who resided in long-term care facilities prior to admission, contributes further to the expanding body of evidence that these patients are the main reservoirs of MDR gram-negative bacteria. Given their contribution to the influx of antimicrobial-resistant bacteria in the hospital setting, infection control interventions that target this high-risk group need to be considered.

The utility of peptide nucleic acid fluorescence in situ hybridization (PNA FISH) for the detection of Acinetobacter spp. and Pseudomonas aeruginosa was evaluated on broth suspensions and spiked blood cultures of ATCC strains and clinical isolates with select gram-negative rods. After testing 60 clinical isolates, PNA FISH had a sensitivity and specificity of 100% and 100%, respectively, for Acinetobacter spp. and 100% and 95%, respectively, for P. aeruginosa. PNA FISH was able to detect both pathogens simultaneously and directly from spiked blood cultures.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) has traditionally been associated with infections in hospitals. Recently, a new strain of MRSA has emerged and rapidly spread in the community, causing serious infections among young, healthy individuals. Preliminary reports imply that a particular clone (USA300) of a community-acquired MRSA (CA-MRSA) strain is infiltrating hospitals and replacing the traditional hospital-acquired MRSA strains. If true, this event would have serious consequences, because CA-MRSA infections in hospitals would occur among a more debilitated, older patient population., Methods: A deterministic mathematical model was developed to characterize the factors contributing to the replacement of hospital-acquired MRSA with CA-MRSA and to quantify the effectiveness of interventions aimed at limiting the spread of CA-MRSA in health care settings., Results: The model strongly suggests that CA-MRSA will become the dominant MRSA strain in hospitals and health care facilities. This reversal of dominant strain will occur as a result of the documented expanding community reservoir and increasing influx into the hospital of individuals who harbor CA-MRSA. Competitive exclusion of hospital-acquired MRSA by CA-MRSA will occur, with increased severity of CA-MRSA infections resulting in longer hospitalizations and a larger in-hospital reservoir of CA-MRSA., Conclusions: Improving compliance with hand hygiene and screening for and decolonization of CA-MRSA carriers are effective strategies. However, hand hygiene has the greatest return of benefits and, if compliance is optimized, other strategies may have minimal added benefit.

Objectives: To quantify the prevalence, risk factors, and mode of transmission associated with colonization by multidrug-resistant gram-negative bacteria (MDRGN) in the long-term care (LTC) setting., Design: Cross-sectional., Setting: Four nursing units in a 648-bed LTC facility in Boston, Massachusetts., Participants: Eighty-four long-term care residents., Measurements: Nasal and rectal swabs were obtained to determine colonization with MDRGN; if present, molecular typing was performed. The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) was also determined. Demographic and clinical characteristics were obtained from the medical record. Multivariable analysis was used to identify factors independently associated with MDRGN colonization., Results: A total of 51%, 28%, and 4% subjects were colonized with MDRGN, MRSA, and VRE, respectively. After multivariable adjustment, advanced dementia (adjusted odds ratio (AOR)=2.9, 95% confidence interval (CI)=1.2-7.35, P=.02) and nonambulatory status (AOR=5.7, 95% CI=1.1-28.9, P=.04) were the only independent risk factors for harboring MDRGN. Molecular typing indicated person-to-person transmission., Conclusion: Colonization with MDRGN is common in the LTC setting. A diagnosis of advanced dementia is a major risk factor for harboring MDRGN.

Background and Objectives: Multidrug-resistant gram-negative bacteria are rapidly spreading throughout the world. The epidemiology of multidrug-resistant gram-negative bacteria in patients who require chronic hemodialysis has not been previously studied., Design, Setting, Participants, & Measurements: A prospective cohort study of an outpatient hemodialysis unit was conducted. Serial surveillance cultures for multidrug-resistant gram-negative bacteria, vancomycin-resistant enterococci, and methicillin-resistant Staphylococcus aureus were collected from patients who were undergoing chronic hemodialysis., Results: Nineteen (28%) of the 67 enrolled patients were colonized with one or more antimicrobial-resistant bacteria at study enrollment. Eleven (16%), nine (13%), and three (5%) patients were colonized with multidrug-resistant gram-negative bacteria, vancomycin-resistant enterococci, and methicillin-resistant Staphylococcus aureus, respectively. Independent risk factors associated with harboring multidrug-resistant gram-negative bacteria at enrollment were residence in a long-term care facility and antibiotic exposure for > or = 7 d in the previous 3 mo. Twenty-two (40%) of 55 patients who had follow-up cultures acquired at least one antimicrobial-resistant bacterium. A total of 20, 15, and 13% of patients acquired multidrug-resistant gram-negative bacteria, vancomycin-resistant enterococci, and methicillin-resistant Staphylococcus aureus, respectively. Antibiotic exposure was the only independent risk factor for multidrug-resistant gram-negative bacteria acquisition. Endogenous multidrug-resistant gram-negative bacteria acquisition was detected among 69% of acquired multidrug-resistant gram-negative bacterial strains., Conclusions: The prevalence and acquisition of multidrug-resistant gram-negative bacteria surpassed that of vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. Endogenous acquisition, as opposed to patient-to-patient spread, was the predominant mechanism of acquisition. Residence in a long-term care facility and antibiotic exposure may be important factors promoting the spread of multidrug-resistant gram-negative bacteria among this patient population.

Background: The emergence and ongoing spread of antimicrobial-resistant bacteria is a major public health threat. Infections caused by antimicrobial-resistant bacteria are associated with substantially higher rates of morbidity and mortality compared to infections caused by antimicrobial-susceptible bacteria. The emergence and spread of these bacteria is complex and requires incorporating numerous interrelated factors which clinical studies cannot adequately address., Methods/principal Findings: A model is created which incorporates several key factors contributing to the emergence and spread of resistant bacteria including the effects of the immune system, acquisition of resistance genes and antimicrobial exposure. The model identifies key strategies which would limit the emergence of antimicrobial-resistant bacterial strains. Specifically, the simulations show that early initiation of antimicrobial therapy and combination therapy with two antibiotics prevents the emergence of resistant bacteria, whereas shorter courses of therapy and sequential administration of antibiotics promote the emergence of resistant strains., Conclusions/significance: The principal findings suggest that (i) shorter lengths of antibiotic therapy and early interruption of antibiotic therapy provide an advantage for the resistant strains, (ii) combination therapy with two antibiotics prevents the emergence of resistance strains in contrast to sequential antibiotic therapy, and (iii) early initiation of antibiotics is among the most important factors preventing the emergence of resistant strains. These findings provide new insights into strategies aimed at optimizing the administration of antimicrobials for the treatment of infections and the prevention of the emergence of antimicrobial resistance.

Infections caused by antibiotic-resistant pathogens are a global public health problem. Numerous individual- and population-level factors contribute to the emergence and spread of these pathogens. An individual-based model (IBM), formulated as a system of stochastically determined events, was developed to describe the complexities of the transmission dynamics of antibiotic-resistant bacteria. To simplify the interpretation and application of the model's conclusions, a corresponding deterministic model was created, which describes the average behavior of the IBM over a large number of simulations. The integration of these two model systems provides a quantitative analysis of the emergence and spread of antibiotic-resistant bacteria, and demonstrates that early initiation of treatment and minimization of its duration mitigates antibiotic resistance epidemics in hospitals.

Despite the high prevalence of meticillin-resistant Staphylococcus aureus (MRSA) infections among the elderly, outcomes of nosocomial MRSA bloodstream infections (BSI) for this patient population have not been fully examined. We performed a case-control study to compare outcomes of hospital-acquired MRSA BSI among patients >/=65 years of age (cases) with those younger than 65 years of age (controls). In a 430-bed tertiary-care teaching hospital, 100 hospitalized patients >/=18 years of age with S. aureus BSI were included in the study. Measurements obtained were: comorbidities, severity of illness at presentation, antibiotic therapy, haematogenous complications and mortality. Overall mortality was significantly higher among cases than controls [36% vs 12%; odds ratio (OR) 4.1, 95% confidence interval (CI) 1.4-14, P<0.01]. A pulmonary source was identified more frequently among elderly patients compared with younger controls (34% vs 16%; OR 2.7, 95%CI 1.1-8.1, P=0.04). On logistic regression, the following variables were independently associated with MRSA BSI among elderly patients: admission to a medical ward (OR 3.1, 95%CI 1.3-7.6, P=0.02), non-central-venous-catheter-related BSI (OR 3, 95%CI 1.2-7.6, P=0.02) and death (OR 3.7, 95%CI 1.3-11, P=0.02). Among patients who received vancomycin, more cases were treated with a reduced dose of vancomycin due to renal insufficiency compared with controls (64% vs 31%; OR 4, 95%CI 2-9, P=0.01). These data suggest that MRSA BSI is associated with significant mortality among the elderly population. Preventing MRSA acquisition among this patient population is of paramount importance.

Background: Case-control studies analyzing antibiotic exposure as a risk factor for antimicrobial resistance usually assume single-drug resistance in the bacteria under study, even though resistance to multiple antimicrobials may be present. Since antibiotic selection pressures differ depending on the susceptibility profile of the antimicrobial-resistant bacteria, an accurate assessment of whether exposure to an individual antimicrobial is a risk factor for the emergence of resistance should distinguish between single-drug-resistant and multidrug-resistant bacteria., Objective: To determine whether the exposures to individual antibiotics that were identified as independent risk factors in case-control studies differed depending on whether single-drug-resistant or multidrug-resistant bacteria were evaluated., Design: Two retrospective case-control studies were performed with data on patients harboring Pseudomonas aeruginosa strains resistant only to ciprofloxacin (CRPA) and patients harboring P. aeruginosa strains resistant to ciprofloxacin and other antibiotics (multidrug-resistant P. aeruginosa [MDR-PA]). These 2 groups were compared with patients not harboring P. aeruginosa., Setting: Two tertiary care hospitals., Results: A total of 41 patients harboring CRPA and 151 patients harboring MDR-PA were identified and matched to 192 control subjects. By conditional logistic regression, independent risk factors associated with presence of CRPA were nonambulatory status (OR, 5.6 [95% confidence interval {CI}, 1.4-23]; P=.02) and prior ciprofloxacin exposure (OR, 5.0 [95% CI, 1.2-21]; P=.03). Independent risk factors for presence of MDR-PA were a Charlson score greater than 2 (OR, 3.3 [95% CI 1.8-6.0]; P<.001) and exposure to quinolones (OR, 2.8 [95% CI, 1.2-5.0]; P=.001), third- and fourth-generation cephalosporins (OR, 3.5 [95% CI, 1.7-7.1]; P<.001), imipenem (OR, 3.8 [95% CI, 1.2-12.1]; P=.02), and/or aminoglycosides (OR, 2.3 [95% CI, 1.04-5.1]; P=.04)., Conclusion: There were substantial differences in exposure to individual antimicrobials between patients harboring CRPA and patients harboring MDR-PA. Future case-control studies addressing risk factors for single-drug-resistant bacteria should consider the complete susceptibility profile of the bacteria under investigation.

Background: Treatment of acute human immunodeficiency virus type 1 (HIV-1) infection may have unique immunologic, virological, and clinical benefits. However, the timing of treatment, optimal starting regimens, and expected response to therapy have not been defined.Methods. One hundred two subjects treated during acute and early HIV-1 infection were observed prospectively to determine the effect of time elapsed before initiation of therapy on time to virological suppression and absolute CD4+ cell count. Subjects were divided into pre- and postseroconversion groups on the basis of HIV-1 antibody status at the time of initiation of treatment. Absolute CD4+ cell counts were compared between these groups and with those of historical untreated persons who had experienced seroconversion. Potential predictors of time to virological suppression and CD4+ cell count at > or =12 months were assessed., Results: Ninety-nine (97%) of 102 subjects achieved virological suppression. The median time to suppression was 11.1 weeks (95% confidence interval, 9.4-14.9) and was independent of initial regimen. The mean CD4+ cell count at 12 months was 702 cells/mm3 (95% confidence interval, 654-750 cells/mm3) and showed an increasing trend over 60 months. Treated subjects demonstrated a statistically significant gain in the CD4+ cell count, compared with untreated historical control subjects, at > or =12 months. Comparable virological and immunologic outcomes were seen in the pre- and postseroconversion groups. Baseline virus load and nadir CD4+ cell count predicted time to virological suppression and CD4+ cell count at > or =12 months, respectively., Conclusions: Early treatment of HIV-1 infection is well tolerated and results in rapid and sustained virological suppression. Preservation of CD4+ cell counts may be achieved with early therapy, independent of seroconversion status. Protease inhibitor-based and nonnucleoside reverse-transcriptase inhibitor-based regimens show comparable performance in tolerability, time to virological suppression, and CD4+ cell count when used as a first regimen.

Background: Mathematical modeling can be used to describe the interdependent and dynamic interactions that contribute to the transmission dynamics of vancomycin-resistant enterococci (VRE). A model was developed to quantify the contribution of antibiotic exposure and of other modifiable factors to the dissemination of VRE in the hospital setting., Methods: The model consists of 4 compartments: patients colonized with VRE receiving and not receiving antibiotics and uncolonized patients receiving and not receiving antibiotics. A series of differential equations describe the movement between these compartments. Baseline parameter estimates were obtained from pharmacy, infection-control, and clinical databases., Results: The main predictions of this model are that (1) preventing the initiation or enhancing the discontinuation of unnecessary antimicrobial therapy will have a greater impact if it is targeted to patients who are not colonized with VRE; (2) increasing the number of patients harboring VRE at the time of hospital admission substantially increases the endemic prevalence of VRE; and (3) eliminating the influx of VRE results in the eradication of this pathogen from the hospital. A decrease in the endemic prevalence of VRE also occurs with a decrease in the length of hospital stay of colonized patients, increased hand hygiene compliance, and a lower ratio of health-care workers : patients., Conclusion: This mathematical model provides a framework to assist in targeting necessary interventions aimed at limiting the spread of VRE.

The emergence of drug-resistant strains of bacteria is an increasing threat to society, especially in hospital settings. Many antibiotics that were formerly effective in combating bacterial infections in hospital patients are no longer effective because of the evolution of resistant strains, which compromises medical care worldwide. In this article, we formulate a two-level population model to quantify key elements in nosocomial (hospital-acquired) infections. At the bacteria level, patients infected with these strains generate both nonresistant and resistant bacteria. At the patient level, susceptible patients are infected by infected patients at rates proportional to the total bacteria load of each strain present in the hospital. The objectives of this paper are to analyze the dynamic elements of nonresistant and resistant bacteria strains in epidemic populations in hospital environments and to provide understanding of measures to avoid the endemicity of resistant antibiotic strains.

Background: The prevalence of multidrug resistance (MDR) among gram-negative bacilli is rapidly increasing. Quantification of the prevalence and the common antimicrobial coresistance patterns of MDR gram-negative bacilli (MDR-GNB) isolates recovered from patients at hospital admission, as well as identification of patients with a high risk of harboring MDR-GNB, would have important implications for patient care., Methods: Over a 6-year period, patients who harbored MDR-GNB (i.e., patients who had MDR-GNB isolates recovered from clinical cultures within the first 48 h after hospital admission) were identified. "MDR-GNB isolates" were defined as Pseudomonas aeruginosa, Escherichia coli, Enterobacter cloacae, and Klebsiella species isolates with resistance to at least 3 antimicrobial groups. A case-control study was performed to determine the independent risk factors for harboring MDR-GNB at hospital admission., Results: Between 1998 and 2003, the prevalence of MDR-GNB isolates recovered from patients at hospital admission increased significantly for all isolate species (P < .001), with the exception of P. aeruginosa (P = .09). Of 464 MDR-GNB isolates, 12%, 35%, and 53% of isolates were coresistant to 5, 4, and 3 antimicrobial groups, respectively. Multivariable analysis identified age > or = 65 years (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.1-7.4; P < .04), prior exposure to antibiotics for > or = 14 days (OR, 8.7; 95% CI, 2.5 -30; P < .001), and prior residence in a long-term care facility (OR, 3.5; 95% CI, 1.3-9.4; P < .01) as independent risk factors for harboring MDR-GNB at hospital admission., Conclusion: A substantial number of patients harbor MDR-GNB at hospital admission. Identification of common coresistance patterns among MDR-GNB isolates may assist in the selection of empirical antimicrobial therapy for patients with a high risk of harboring MDR-GNB.

Objective: To examine and quantify the temporal trends of nosocomial multidrug-resistant, gram-negative bacilli., Design: A 9-year surveillance study was conducted. Multidrug resistance was defined as resistance to 3 or more antimicrobial classes., Setting: Tertiary-care institution., Results: From 1994 to 2002, multidrug-resistant, gram-negative bacilli increased from 1% to 16% for multidrug-resistant Pseudomonas aeruginosa, 4% to 13% for multidrug-resistant Enterobacter species, 0.5% to 17% for multidrug-resistant Klebsiella species, 0% to 9% for multidrug-resistant Proteus species, and 0.2% to 4% for multidrug-resistant Escherichia coli (P < or = .05). The most common pattern of multidrug resistance was co-resistance to quinolones, third-generation cephalosporins, and aminoglycosides., Conclusion: The rapid rise of multidrug-resistant, gram-negative bacilli may warrant infection control programs to include these pathogens in strategies aimed at limiting the emergence and spread of antimicrobial-resistant pathogens.

Background: The goal of this study was to develop a validated prediction rule for identification of patients harboring vancomycin-resistant enterococci (VRE) at hospital admission., Methods: A model for the prediction of patients harboring VRE at admission was created and validated by assigning weighted point values to independent risk factors associated with harboring VRE at admission, in 2 different cohorts of patients from 2 tertiary care hospitals in Boston, Massachusetts. Patients with VRE isolated from clinical culture samples collected within 48 h of hospital admission were compared with patients not harboring VRE. To assess the diagnostic accuracy of the prediction rule, the main outcome measures were patient demographic characteristics, comorbid illnesses, hospitalizations, and antibiotic exposure., Results: A total of 412 patients were enrolled. A risk index score was derived by using the following 6 independent risk factors associated with VRE recovery within 48 h of hospital admission: previous isolation of methicillin-resistant Staphylococcus aureus (MRSA), whether the patient was receiving long-term hemodialysis, transfer from a long-term care facility, antibiotic exposure, prior hospitalization, and age >60 years. On the basis of a point score >or=10, the sensitivity, specificity, and positive and negative predictive values of this prediction rule were 44%, 98%, 81%, and 90%, respectively., Conclusions: This validated clinical prediction rule provides a novel strategy for the identification of patients at high risk of harboring VRE at hospital admission. Implementation of this rule may reduce the influx of VRE into health care institutions and the overall prevalence of VRE, by targeting VRE-screening measures and contact isolation precautions for these high-risk patients.

To analyze risk factors for the development of adult poststernotomy surgical site infections (SSIs), we performed a retrospective case-control study at a tertiary care hospital. Case patients with poststernotomy SSI between June 1999 and January 2001 were matched to control subjects without poststernotomy SSI according to date of procedure and age. Data were collected on known SSI risk factors. Of 711 procedures, we identified 38 cases with SSI and 114 matched controls. Univariate analysis revealed that receipt of transfused blood (odds ratio [OR], 3.19; 95% confidence interval [CI], 1.54-6.62), diabetes (OR, 2.90; 95% CI, 1.27-6.59), length of stay before hospitalization (OR, 1.19 per day; 95% CI, 1.02-1.37 per day), and American Society of Anesthesia score (OR, 2.19; 95% CI, 1.04-4.64) were significantly associated with SSI. Multivariate analysis revealed that transfusion (OR, 3.21; 95% CI, 1.41-7.31) and diabetes (OR, 3.65; 95% CI, 1.42-9.36) were predictors for SSI. The exact role of blood transfusion in the pathogenesis of SSI, whether as a direct immunosuppressant or a surrogate marker for morbidity, remains unresolved.

A systematic review of the English-language literature was performed to determine the overall benefit of mupirocin therapy in reducing the rate of Staphylococcus aureus infection among patients undergoing hemodialysis (HD) or peritoneal dialysis (PD). Included studies met the following criteria: they were randomized clinical trials or cohort studies; cohorts consisted of adults (age, > or =18 years) requiring HD or PD; mupirocin therapy was administered to the treatment group, and placebo or no therapy was administered to the control group; and the primary outcome of interest was the difference in the number of S. aureus infections among mupirocin-treated and -untreated patients. Ten studies described in 9 articles were analyzed. A total of 2445 patients were included in the analysis. Use of mupirocin reduced the rate of S. aureus infections by 68% (95% confidence interval [CI], 57%-76%) among all patients undergoing dialysis; risk reductions were 80% (95% CI, 65%-89%) among patients undergoing HD and 63% (95% CI, 50%-73%) among patients undergoing PD. When data were stratified by type of infection, S. aureus bacteremia was found to be reduced by 78% among patients undergoing HD, and peritonitis and exit-site infections were found to be reduced by 66% and 62%, respectively, among patients undergoing PD. Mupirocin prophylaxis substantially reduces the rate of S. aureus infection in the dialysis population. Optimal regimens that minimize the emergence of mupirocin resistance need to be explored.

We performed 2 case-control studies among 108 patients with true coagulase-negative staphylococcal (CoNS) bacteremia diagnosed within 48 h of hospital admission. Seventy-nine patients (73%) with methicillin-resistant (MR) CoNS bacteremia and 29 patients (27%) with methicillin-susceptible (MS) CoNS bacteremia were compared with 79 randomly selected control patients without CoNS bacteremia. The presence of a central venous catheter was an independent risk factor for both MR- and MS-CoNS bacteremia (P<.001). Patients with MR-CoNS bacteremia were more frequently admitted from health care facilities (P=.02), more likely to have had previous MR Staphylococcus aureus infection or colonization (P=.02), and more likely to have received antibiotics in the previous 30 days (P=.02). The probability that bacteremia was caused by an MR strain, rather than an MS strain, was 62% among patients admitted from the community and 84% among patients admitted from health care facilities. This study identified epidemiological characteristics that can be used to distinguish between MR- and MS-CoNS bacteremia and found high rates of methicillin resistance among CoNS isolates recovered from patients admitted from the community, as well as from health care facilities.

Numerous antimicrobial-resistant pathogens (ARPs) have emerged among patients who undergo chronic hemodialysis (CHD), including vancomycin-resistant enterococci, vancomycin-resistant coagulase-negative staphylococci, Staphylococcus aureus with reduced susceptibility to vancomycin, and linezolid-resistant S. aureus. In June 2002, the first isolate of vancomycin-resistant S. aureus (minimum inhibitory concentration of vancomycin, > or =32 microg/mL) was isolated in the United States from a patient who required CHD. Frequent administration of antibiotics and repeated exposure to settings conducive to cross-transmission contribute to a patient population at considerable risk of harboring ARPs. Dissemination of ARPs among patients who are undergoing CHD is facilitated by the requirement for regular hemodialysis in a closed setting in which health care workers provide concurrent care to multiple patients. Frequent hospitalizations in this patient population further contribute to acquisition of ARPs and to the spread of ARPs to other hospitalized patients. The epidemiology of antimicrobial-resistant, gram-positive pathogens in patients undergoing CHD is reviewed, and recommendations for limiting further dissemination are provided.

The transmission dynamics of vancomycin-resistant enterococci (VRE) and factors contributing to their dissemination are complex. Mathematical modeling was used to simulate patterns of dissemination among patients and health care workers (HCWs) and to quantify the contribution of specific factors and infection control interventions on the endemic prevalence (EP) of VRE in a long-term hemodialysis unit. The model predicted that (1) an EP of 12% would be reached over time, regardless of the number of patients initially colonized, (2) endemicity would be sustained by the constant influx of newly colonized patients discharged from the hospital, (3) duration of VRE gastrointestinal colonization would have the most impact on the number of secondary cases, increasing the EP to a maximum of 70%, and (4) decreasing the patient:HCW ratio or improving hand hygiene would decrease the EP to 3%. Decreasing the duration of colonization, limiting hospital acquisition of VRE, and improving compliance with hand hygiene in the hemodialysis unit may decrease the rapidly rising rates of VRE in the patient population.

The clinical and molecular epidemiology of penicillin-resistant Streptococcus pneumoniae and the diagnostic accuracy of a six-primer PCR assay in identifying penicillin resistance were analyzed by using clinical isolates recovered over a 10-year period in middle Tennessee. The prevalence of non-penicillin-susceptible S. pneumoniae isolates (MIC, > or =0.1 microg/ml) increased from 10% in 1990 to 70% in 1999 (P < 0.001). Among S. pneumoniae isolates for which the penicillin MIC was > or =2 microg/ml (highly penicillin-resistant S. pneumoniae [PRSP]), 23 and 5% were resistant to at least three and at least five other antimicrobial classes, respectively. Pulsed-field gel electrophoresis identified 13 unique strain types, with type B accounting for 33% of PRSP isolates. The sensitivity, specificity, and negative and positive predictive values of the PCR assay in detecting PRSP were 99, 100, 99, and 100%, respectively. Penicillin resistance is rapidly increasing among S. pneumoniae isolates in Tennessee. The simultaneous detection of S. pneumoniae and high-level penicillin resistance can be accurately performed with the six-primer PCR assay.

The diagnostic accuracy of the rectal swab (RS) culture method in identifying gastrointestinal colonization with vancomycin-resistant enterococci (VRE) is not known. Serial quantitative stool cultures, skin cultures, and RS cultures were performed for patients with VRE infections to assess the false-negative rate of the RS and the prevalence of skin colonization, a prerequisite for cross-transmission, at varying VRE stool densities. A total of 35 stool samples were obtained from 13 patients. The sensitivity of the RS culture was 58%; it ranged from 100%, at VRE densities of > or =7.5 log10 colony forming units (cfu) per gram of stool, to 0%, at densities of < or =4.5 log10 cfu per gram of stool. Skin colonization was detected at these low VRE stool densities, but it was more common at higher VRE densities (P<.001). Antibiotic exposure was significantly associated with higher VRE stool densities (P<.001). The high false-negative rate of the RS may be contributing to the continued increase in the prevalence of VRE.

Background and Objective: In the United States, vancomycin-resistant enterococci (VRE) are predominantly acquired in the hospital. The extent of dissemination of VRE into the community in the United States has not been examined. Our objective was to determine the prevalence of VRE among nonhospitalized patients., Methods: We conducted a cross-sectional surveillance study in an ambulatory care clinic. One hundred ambulatory patients participated in the study. Measurements included a written questionnaire on patient demographics, clinical data, and prior exposure to health care settings and antibiotics; rectal swabs; pulsed-field gel electrophoresis; and polymerase chain reaction genotyping., Results: Three of 100 subjects (3%) were colonized with VRE, including one person who did not have any exposure to a health care setting or antibiotics., Conclusions: VRE was recovered from nonhospitalized patients. Physicians should be alert to the potential of VRE transmission in the ambulatory care setting.

Objective: To compare molecular typing by amplified fragment-length polymorphism (AFLP) analysis with pulsed-field gel electrophoresis (PFGE) with respect to the ability to differentiate between epidemiologically related and unrelated isolates of common nosocomial pathogens recovered during a period of endemicity., Design: Retrospective laboratory analysis., Setting: Tertiary-care institution., Methods: 17 isolates of Acinetobacter baumannii, 22 isolates of Pseudomonas aeruginosa, and 22 vancomycin-resistant Enterococcusfaecium (VRE) were typed by both methods., Results: AFLP generated comparable results to PFGE for A baumannii and P aeruginosa isolates; both methods identified epidemiologically related and unrelated isolates. However, strain typing of VRE isolates produced discordant results between the two methods. PFGE identified 10 different strain types and differentiated between all epidemiologically related and unrelated isolates. In contrast, AFLP generated only five different strain types, three of which contained both epidemiologically related and unrelated isolates., Conclusion: Molecular typing by AFLP is comparable to PFGE for A baumannii and P aeruginosa isolates. For VRE isolates, however, PFGE remains the method of choice.