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Candida auris poses a global public health challenge, causing multiple outbreaks within healthcare facilities. Despite advancements in strain typing for various infectious diseases, a consensus on the genetic relatedness threshold for identifying C. auris transmission in local hospital outbreaks remains elusive. We investigated genetic variations within our local isolate collection using whole-genome-based single nucleotide polymorphism (SNP) phylogenetic analysis. A total of 74 C . auris isolates were subjected to whole-genome sequencing (WGS) and SNP phylogenetic analysis via the QIAGEN CLC Genomics Workbench. Isolates included known related strains from the same patient, strains from different hospitals, strains from our hospital patients with no epidemiological link, and 19 patient isolates from a recent C. auris outbreak. All but three isolates were identified to be Clade IV. By examining the genetic diversities of C. auris within patients and between patients, we identified a SNP variation range of 0-13 for identifying related isolates. During an outbreak investigation, utilizing this range, maximum likelihood phylogenetic analysis revealed two distinct clusters that aligned with the epidemiological links. Determining a SNP variation range to delineate genetic relatedness among isolates is crucial for the application of WGS and SNP phylogenetic analysis in identifying C. auris transmission during hospital outbreak investigations. The use of WGS SNP phylogenetic analysis via the CLC Genomics Workbench has emerged as a valuable method for typing C. auris in clinical microbiology laboratories.

Background: Inpatient behavioral health units (BHUs) had unique challenges in implementing interventions to mitigate coronavirus disease 2019 (COVID-19) transmission, in part due to socialization in BHU settings. The objective of this study was to identify the transmission routes and the efficacy of the mitigation strategies employed during a COVID-19 outbreak in an inpatient BHU during the Omicron surge from December 2021 to January 2022., Methods: An outbreak investigation was performed after identifying 2 COVID-19-positive BHU inpatients on December 16 and 20, 2021. Mitigation measures involved weekly point prevalence testing for all inpatients, healthcare workers (HCWs), and staff, followed by infection prevention mitigation measures and molecular surveillance. Whole-genome sequencing on a subset of COVID-19-positive individuals was performed to identify the outbreak source. Finally, an outbreak control sustainability plan was formulated for future BHU outbreak resurgences., Results: We identified 35 HCWs and 8 inpatients who tested positive in the BHU between December 16, 2021, and January 17, 2022. We generated severe acute respiratory coronavirus virus 2 (SARS-CoV-2) genomes from 15 HCWs and all inpatients. Phylogenetic analyses revealed 3 distinct but genetically related clusters: (1) an HCW and inpatient outbreak likely initiated by staff, (2) an HCW and inpatient outbreak likely initiated by an inpatient visitor, and (3) an HCW-only cluster initiated by staff., Conclusions: Distinct transmission clusters are consistent with multiple, independent SARS-CoV-2 introductions with further inpatient transmission occurring in communal settings. The implemented outbreak control plan comprised of enhanced personal protective equipment requirements, limited socialization, and molecular surveillance likely minimized disruptions to patient care as a model for future pandemics., Competing Interests: All other authors declare no conflicts of interest., (© The Author(s) 2024.)

Objective: Monkeypox virus (MPXV) disease has been declared a public health emergency by the World Health Organization, creating an urgent need for neurologists to be able to recognize, diagnosis, and treat MPXV-associated neurologic disease., Methods: Three cases of MPXV-associated central nervous system (CNS) disease occurring during the 2022 outbreak, and their associated imaging findings are presented, with 2 cases previously published in a limited capacity in a public health bulletin., Results: Three previously healthy immunocompetent gay men in their 30s developed a febrile illness followed by progressive neurologic symptoms with presence of a vesiculopustular rash. MPXV nucleic acid was detected by polymerase chain reaction (PCR) from skin lesions of 2 patients, with the third patient having indeterminate testing but an epidemiologic link to a confirmed MPXV disease case. Cerebrospinal fluid demonstrated a lymphocytic pleocytosis, elevated protein, and negative MPXV-specific PCR. In 2 patients, magnetic resonance imaging of the brain and spine demonstrated partially enhancing, longitudinally extensive central spinal cord lesions with multifocal subcortical, basal ganglia, thalamic, cerebellar, and/or brainstem lesions. The third patient had thalamic and basal ganglia lesions. All patients received 14 days of tecovirimat, and 2 patients also received multiple forms of immunotherapy, including intravenous immunoglobulin, pulsed high-dose steroids, plasmapheresis, and/or rituximab. Good neurologic recovery was observed in all cases., Interpretation: MPXV can be associated with CNS disease. It is unclear whether this is from a parainfectious immune-mediated injury or direct CNS viral invasion. ANN NEUROL 2023;93:893-905., (© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Abstract: In this case series of 20 ambulatory and hospitalized adult patients treated for monkeypox virus at a large academic medical center in Chicago, Illinois, tecovirimat use was reserved for those with or at high risk of severe disease, delayed because of logistical and clinical factors, but well tolerated., Competing Interests: Conflict of Interest and Sources of Funding: None declared., (Copyright © 2022 American Sexually Transmitted Diseases Association. All rights reserved.)

Background: Antimicrobial stewardship intervention (ASI) appears to be necessary to realize the full benefits of rapid diagnostic technologies in clinical practice. This study aimed to compare clinical outcomes between early ASI paired with matrix-associated laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) compared with MALDI-TOF with standard of care (SOC) reporting in patients with positive blood cultures., Methods: Adult patients with positive blood cultures and organism speciation via MALDI-TOF admitted between February 2015 and September 2015 were randomized to ASI or SOC in a 1:1 fashion. Patients admitted for at least 48 h following positive culture were included in analyses. ASI was defined as a clinical assessment by a stewardship team member with non-binding treatment recommendations offered to the primary team. The primary outcome was time to definitive therapy. Secondary outcomes included post-culture length of stay (LOS), time to first change in antibiotics, and in-hospital mortality., Results: In total, 149 patients were included in the analyses (76 in the ASI group and 73 in the SOC group). ASI and SOC arms did not differ according to age, sex, comorbidities or severity of illness. Gram-positive organisms were common in both SOC and ASI arms (74.0 vs. 61.8%, P=0.11). Time to definitive therapy was reduced, on average, by 30.3 h in the ASI group (71.6 vs. 41.3 h, P=0.01). Hospital LOS following the first positive blood culture was significantly shorter in the ASI group (8.7 vs. 11.2 days, P=0.049)., Conclusions: ASI combined with MALDI-TOF reduced the time to definitive therapy and time to first change in antibiotics, and was associated with a shorter post-culture LOS., Competing Interests: Declaration of Competing Interest VOB is a current employee of Inflammatix; her work on this project was completed prior to that employment. EMG is a current employee of Janssen Scientific Affairs; her work on this project was completed prior to that employment All other authors report no conflicts of interest., (Copyright © 2021 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Staphylococcus pasteuri is a gram-positive organism found in food products as well as naturally occurring in air and on surfaces. We present the first known case of Staphylococcus pasteuri osteomyelitis caused by machine injection injury. The patient was treated with emergent surgical debridement as well as doxycycline for a soft tissue infection. Despite targeted therapy, the infection progressed to osteomyelitis and was treated successfully with additional surgical debridement and trimethoprim-sulfamethoxazole. There is sparse information on both infections and treatment of Staphylococcus pasteuri . We present our case report as well as a review of the literature on the epidemiology, susceptibility and treatment recommendations for Staphylococcus pasteuri infections., Competing Interests: Conflict of interest: The authors declare no potential conflict of interest., (©Copyright: the Author(s).)

A 78-year-old woman with a long-term ankle spacer with antibacterials developed an intra-articular Candida auris infection. Treatment with systemic antifungal therapy plus an amphotericin B moulded cement spacer was successful.

BACKGROUND The nationally reported metric for Clostridium difficile infection (CDI) relies solely on laboratory testing, which can result in overreporting due to asymptomatic C. difficile colonization. OBJECTIVE To review the clinical scenarios of cases of healthcare facility-onset CDI (HO-CDI) and to determine the appropriateness of C. difficile testing on the basis of presence of symptomatic diarrhea in order to identify areas for improvement. DESIGN Retrospective cohort study. SETTING Northwestern Memorial Hospital, a large, tertiary academic hospital in Chicago, Illinois. PATIENTS The cohort included all patients with a positive C. difficile test result who were reported to the National Healthcare Safety Network as HO-CDI during a 1-year study period. METHODS We reviewed the clinical scenario of each HO-CDI case. On the basis of documentation and predefined criteria, appropriateness of C. difficile testing was determined; cases were deemed appropriate, inappropriate, or indeterminate. Statistical analysis was performed to compare demographic and clinical parameters among the categories of testing appropriateness. RESULTS Our facility reported 168 HO-CDI cases to NHSN during the study period. Of 168 cases, 33 (19.6%) were judged to be appropriate tests, 25 (14.8%) were considered inappropriate, and 110 (65.5%) were indeterminate. Elimination of inappropriate testing would have improved our facility's standardized infection ratio from 0.962 to 0.819. CONCLUSION Approximately 15% of HO-CDI cases were judged to be tested inappropriately. Testing only patients with clinically significant diarrhea would more accurately estimate CDI incidence, reduce unnecessary antibiotic use, and improve facilities' performance of reportable CDI metrics. Improved documentation could facilitate targeted interventions. Infect Control Hosp Epidemiol 2016;1395-1400.

Background: An increase in respiratory syncytial virus type B (RSV-B) infections was detected on an adult hematology/oncology and stem cell transplant unit during March 2015. This prompted an outbreak investigation., Methods: Nosocomial cases were defined as RSV-B-positive patients who developed respiratory virus symptoms ≥ 7 days after admission to the unit or were readmitted with symptoms ≤ 7 days since last discharge from the unit. Strict outbreak control measures were implemented to stop the outbreak., Results: During the outbreak, 19 cases of RSV-B were detected, 14 among patients and 5 among health care workers (HCWs). Additionally, 2 HCWs tested positive for respiratory syncytial virus type A and 1 tested positive for influenza B among the 27 symptomatic HCWs evaluated. No specific antiviral therapy was given and all cases recovered without progression to lower respiratory tract infection. After no new cases were identified for 2 weeks, the outbreak was declared over., Conclusions: High vigilance for respiratory viruses on high-risk inpatient units is required for detection and prevention of potential outbreaks. Multiple respiratory viruses with outbreak potential were identified among HCWs. HCWs with respiratory virus symptoms should not provide direct patient care. Absence of lower respiratory tract infection suggests lower virulence of RSV-B, compared with respiratory syncytial virus type A, among immunocompromised adults., (Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

The medical field has long recognized the importance of hand hygiene in preventing health care-associated infections, yet studies indicate that this important task is performed only 40% of the time. Health care workers cite several barriers to optimal performance of hand hygiene, but the time required to perform this task is foremost among them. Introduction of alcohol-based hand rubs, bundled interventions, and incorporation of technologies designed to monitor and promote hand hygiene all represent promising advances in this field., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To evaluate the impact and burden of the new National Healthcare Safety Network surveillance definition, mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI), in hematology, oncology, and stem cell transplant populations., Design: Retrospective cohort study., Setting: Two hematology, oncology, and stem cell transplant units at a large academic medical center., Methods: Central line-associated bloodstream infections (CLABSIs) identified during a 14-month period were reviewed and classified as MBI-LCBI or non-MBI-LCBI (MBI-LCBI criteria not met). During this period, interventions to improve central line maintenance were implemented. Characteristics of patients with MBI-LCBI and non-MBI-LCBI were compared. Total CLABSI, MBI-LCBI, and non-MBI-LCBI rates were compared between baseline and postintervention phases of the study period., Results: Among 66 total CLABSI cases, 47 (71%) met MBI-LCBI criteria. Patients with MBI-LCBI and non-MBI-LCBI were similar in regard to most clinical and demographic characteristics. Between the baseline and postintervention study periods, the overall CLABSI rate decreased from 3.37 to 3.21 infections per 1,000 line-days (incidence rate ratio, 0.95; 4.7% reduction, P=.84), the MBI-LCBI rate increased from 2.08 to 2.61 infections per 1,000 line-days (incidence rate ratio, 1.25; 25.3% increase, P=.44), and the non-MBI-LCBI rate decreased from 1.29 to 0.60 infections per 1,000 line-days (incidence rate ratio, 0.47; 53.3% reduction, P=.12)., Conclusions: Most CLABSIs identified among hematology, oncology, and stem cell transplant patients met MBI-LCBI criteria, and CLABSI prevention efforts did not reduce these infections. Further review of the MBI-LCBI definition and impact is necessary to direct future definition changes and reporting mandates.

Objectives: Bacteria within the Acinetobacter calcoaceticus-Acinetobacter baumannii (ACB) complex commonly cause nosocomial infection and are often multidrug resistant. Advances in genospecies typing allow for speciation within the ACB complex; however, little is known about the effect of genospecies on patient outcomes., Methods: Adult patients with ACB complex bacteremia from Jan 2005-Oct 2012 were included. Bacterial isolates were speciated by rpoB gene sequence analysis, and clinical data were collected., Results: Of 147 patients with ACB complex bacteremia, 116 had A. baumannii (78.9%), 28 had Acinetobacter pittii (19.0%), and 3 had Acinetobacter nosocomialis (2.0%). A. baumannii bacteremia was associated with greater comorbidity and was more frequently multidrug resistant (79% vs. 16%, p < 0.01). Multidrug resistant A. baumannii but not susceptible A. baumannii was associated with worse outcomes compared to non-baumannii ACB complex bacteremia. Neither multidrug resistance nor genospecies was an independent predictor of mortality, but receipt of appropriate therapy was associated with decreased risk of mortality (OR, 0.13; 95% CI, 0.04-0.44; p < 0.01)., Conclusions: A. baumannii bacteremia is associated with worse clinical outcomes than non-baumannii ACB complex bacteremia. The difference, however, appears to be related to multidrug resistance and attendant receipt of appropriate therapy rather than genospecies., (Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Institution of appropriate airborne infection isolation (AII) precautions for patients with suspected Mycobacterium tuberculosis is critical to prevent disease transmission. We compared the yield of acid-fast bacilli smears from different types of respiratory specimens and found that smear sensitivity was highest for specimens obtained by endotracheal aspirates (92%), followed by sputum (79%), and then by bronchoalveolar lavage (37%). As a result of this study, our institutional policy regarding discontinuation of AII precautions was amended., (Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Optimal surveillance strategies for identifying patients colonized with and at risk for transmitting carbapenem-resistant Enterobacteriaceae (CRE) are urgently needed. We instituted an enhanced surveillance program for CRE that identified unrecognized CRE-colonized patients but failed to identify possible CRE transmissions. We also identified risk factors associated with transmitting CRE.

Antimicrobial drug shortages continue to increase, with few new therapeutic options available. Nationally, proposals have been offered to alleviate drug shortages; however, these recommendations are unlikely to effect change in the near future. Thus, antimicrobial stewardship leaders in acute care hospitals must develop a prospective management strategy to lessen the impact of these shortages on patient care. Herein, we describe several resources available to aid professionals in antimicrobial stewardship and healthcare epidemiology to manage drug shortages. An effective approach should include prospectively tracking shortages and maximizing inventory by appropriately managing usage. Several tenets should underpin this management. Alternative agents should be rationally chosen before the inventory of the primary agent has reached zero, ethical considerations should be taken into account, and timely notification and communication with key stakeholders should occur throughout the prescribing and dispensing process.

Objective: To evaluate the impact of postprescription review of broad-spectrum antimicrobial (study-ABX) agents on rates of antimicrobial use., Design: Quasi-experimental before-after study., Setting: Five academic medical centers., Patients: Adults receiving at least 48 hours of study-ABX., Methods: The baseline, intervention, and follow-up periods were 6 months each in 2 units at each of 5 sites. Adults receiving at least 48 hours of study-ABX entered the cohort as case-patients. During the intervention, infectious-diseases physicians reviewed the cases after 48 hours of study-ABX. The provider was contacted with alternative recommendations if antimicrobial use was considered to be unjustified on the basis of predetermined criteria. Acceptance rates were assessed 48 hours later. The primary outcome measure was days of study-ABX per 1,000 study-patient-days in the baseline and intervention periods., Results: There were 1,265 patients in the baseline period and 1,163 patients in the intervention period. Study-ABX use decreased significantly during the intervention period at 2 sites: from 574.4 to 533.8 study-ABX days/1,000 patient-days (incidence rate ratio [IRR], 0.93; 95% confidence interval [CI], 0.88-0.97; P = .002) at hospital B and from 615.6 to 514.4 study-ABX days/1,000 patient-days (IRR, 0.83; 95% CI, 0.79-0.88; P < .001) at hospital D. Both had established antimicrobial stewardship programs (ASP). Study-ABX use increased at 2 sites and stayed the same at 1 site. At all institutions combined, 390 of 1,429 (27.3%) study-ABX courses were assessed as unjustified; recommendations to modify or stop therapy were accepted for 260 (66.7%) of these courses., Conclusions: Postprescription review of study-ABX decreased antimicrobial utilization in some of the study hospitals and may be more effective when performed as part of an established ASP.

Anti-infective shortages pose significant logistical and clinical challenges to hospitals and may be considered a public health emergency. Anti-infectives often represent irreplaceable life-saving treatments. Furthermore, few new agents are available to treat increasingly prevalent multidrug-resistant pathogens. Frequent anti-infective shortages have substantially altered patient care and may lead to inferior patient outcomes. Because many of the shortages stem from problems with manufacturing and distribution, federal legislation has been introduced but not yet enacted to provide oversight for the adequate supply of critical medications. At the local level, hospitals should develop strategies to anticipate the impact and extent of shortages, to identify therapeutic alternatives, and to mitigate potential adverse outcomes. Here we describe the scope of recent anti-infective shortages in the United States and explore the reasons for inadequate drug supply.

Clinicians have enthusiastically used fluoroquinolones owing to their good safety profile and wide range of indications. This article reviews fluoroquinolone pharmacology, pharmacodynamic principles, and fluoroquinolone resistance mechanisms, highlighting recent trends in the epidemiology of fluoroquinolone resistance among gram-negative organisms and Streptococcus pneumonia. Important fluoroquinolone safety concerns are discussed, along with indications for the most commonly used fluoroquinolones--ciprofloxacin, levofloxacin, and moxifloxacin., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Study Objective: To compare meropenem with ciprofloxacin for treatment of gram-negative bacilli sepsis in penicillin-allergic patients in the intensive care unit (ICU) to determine if increased anaphylaxis risk with meropenem precluded its use when weighed against risks of inactive therapy with ciprofloxacin., Design: A decision model constructed from probability distributions from the literature and data from a local ICU antibiogram. A probabilistic sensitivity analysis was performed to evaluate uncertainty in variable estimates by using one-way analyses, two-way analyses, and Monte Carlo simulation., Measurements and Main Results: Microbiologic activity of treatment, anaphylaxis according to treatment regimen, curability of infection according to patient morbidity status, risk of superinfection, and recovery from gram-negative bacilli sepsis were the variables modeled. Effectiveness was defined by long-term survival and was modeled as life-years (LYs) and quality-adjusted life-years (QALYs) gained according to treatment group. Base case results were the incremental differences between the average effectiveness of each strategy calculated from the Monte Carlo simulation. Mean LYs and QALYs gained with meropenem were 9.9 (95% confidence interval [CI] 8.9-10.8) and 5.9 (95% CI 4.8-6.7), respectively. Mean LYs and QALYs gained with ciprofloxacin were 8.9 (95% CI 8.1-9.6) and 5.3 (95% CI 4.4-6.3), respectively. The incremental difference in effectiveness-or average benefit expected by selecting meropenem over ciprofloxacin-was 1.0 LY (95% CI 0.3-1.7 LYs) and 0.6 QALY (95% CI 0.2-1.1 QALYs) favoring meropenem., Conclusion: Use of empiric meropenem over ciprofloxacin may be justified in patients in the ICU who are allergic to penicillin.

Clinicians have enthusiastically used fluoroquinolones owing to their good safety profile and wide range of indications. This article reviews fluoroquinolone pharmacology, pharmacodynamic principles, and fluoroquinolone resistance mechanisms, highlighting recent trends in the epidemiology of fluoroquinolone resistance among gram-negative organisms and Streptococcus pneumonia. Important fluoroquinolone safety concerns are discussed, along with indications for the most commonly used fluoroquinolones-ciprofloxacin, levofloxacin, and moxifloxacin.

We sought to quantify patient morbidity throughout Pseudomonas aeruginosa bloodstream infection (PABSI) as a function of patient covariates. Individuals with PABSI were included in a retrospective, observational, cohort study. Morbidity was quantified by serial Sequential Organ Failure Assessment (SOFA) scores. Impact of active antimicrobial treatment was assessed as a function of changes in SOFA scores as the dependent variable. A total of 95 patients with PABSI were analyzed. Relative to baseline SOFA scores (day -2), scores after PABSI were increased by 37% on day 0 and 22% on day +2 but returned to baseline on day +7. Overall mortality was 37%, and mean length of hospital stay (postculture) was 16 days. Most patients were appropriately treated, with n = 83 (87%) receiving an active agent and n = 61 (64%) receiving >1 agent. As a result, an effect of therapy on morbidity was not observed. Advanced age and elevated baseline SOFA scores predicted increased in-hospital mortality (P = 0.01 and P < 0.001, respectively) and morbidity at day +2 (P < 0.05 and P < 0.05, respectively) and day +7 (P < 0.05 and P < 0.001, respectively). Neutropenia was also associated with increased morbidity at day +2 (P < 0.05). In treated PABSI, morbidity is highest the day of the diagnostic blood cultures and slowly returns to baseline over the subsequent 7 days. Age and baseline severity of illness are the strongest predictors of morbidity and mortality. Because neither of these factors are modifiable, efforts to minimize the negative impact of PABSI should focus on appropriate prevention and infection control efforts.

Background: Screening methods that use automated data may streamline surgical site infection (SSI) surveillance and improve the accuracy and comparability of data on SSIs. We evaluated the use of automated inpatient diagnosis codes and pharmacy data to identify SSIs after arthroplasty., Methods: This retrospective cohort study at 8 hospitals involved weighted, random samples of medical records from 2128 total hip arthroplasty (THA) procedures performed from 1 July 2002 through 30 June 2004, and 4194 total knee arthroplasty (TKA) procedures performed from 1 July 2003 through 30 June 2005. We compared routine surveillance with screening of inpatient pharmacy data and diagnoses codes followed by medical record review to confirm SSI status., Results: Records from 696 THA and 1009 TKA procedures were reviewed. The SSI rates were nearly double those determined by routine surveillance (1.32% [95% confidence interval, 0.83%-1.81%] vs. 0.75% for THA; 1.83% [95% confidence interval, 1.43%-2.23%] vs. 0.71% for TKA). An inpatient diagnosis code for infection within a year after the operation had substantially higher sensitivity (THA, 89%; TKA, 81%), compared with routine surveillance (THA, 56%; TKA, 39%). Adding antimicrobial exposure of 7 days after the procedure increased the sensitivity (THA, 93%; TKA, 86%). Record review confirmed SSIs after 51% of THAs and 55% of TKAs that met diagnosis code criteria and after 25% of THAs and 39% of TKAs that met antimicrobial exposure and/or diagnosis code criteria., Conclusions: Focused surveillance among a subset of patients who met diagnosis code screening criteria with or without the addition of antimicrobial exposure-based screening was more sensitive than routine surveillance for detecting SSIs after arthroplasty and could be an efficient and readily standardized adjunct to traditional methods.

Objectives: We sought to determine the cost-effectiveness of Antimicrobial Stewardship Teams (ASTs) on the reduction of morbidity and mortality associated with nosocomial bacteraemia., Methods: A decision analytic model compared costs and outcomes of bacteraemic patients receiving standard treatment with or without an AST consult. Patients with a bacteraemic event during their hospital admission were included in the model. Effectiveness was estimated as quality-adjusted life years (QALYs) over the lifetime of patients. Model variables and costs, along with their distributions, were obtained from the literature and expert opinion. Incremental cost-effectiveness ratios (ICERs) were calculated to estimate the cost per QALY gained from the hospital perspective. Uncertainty in ICERs was evaluated with probabilistic sensitivity analyses. The cost-effectiveness of clinical decision support systems was evaluated as a secondary analysis., Results: Implementing an AST for bacteraemia review cost $39,737 (95% CI $27,272-53, 017) and standard treatment cost $39,563 (95% CI $27,164-52,797). The difference in effectiveness between the two strategies was 0.08 QALYs, and the base case ICER from the probabilistic analysis was $2367 per QALY gained [95% CI dominant (less costly, more effective) to $24,379]. Results from the probabilistic sensitivity analysis demonstrated there was more than a 90% likelihood that an AST would be cost-effective at a level of $10,000 per QALY., Conclusions: Maintaining an AST to improve care for bacteraemia is cost-effective from the hospital perspective. The estimate of $2367 per QALY gained for the AST intervention compares favourably with many currently funded healthcare interventions and services.

The consequences of inactive empiric antimicrobial therapy are not well-described and may cause prolonged hospitalization or infection-related mortality. In vitro susceptibility results for 884 patients hospitalized at an academic medical center with gram-negative bloodstream infections (GNBI) from 2001 to 2003 were matched to antimicrobial orders within 24 h of culture. Clinical characteristics, organism, inpatient mortality, and length of stay after culture for patients with GNBI were compared between patients receiving active versus inactive empiric antimicrobial therapy. A total of 14.1% of patients with GNBI received inactive empiric therapy, defined as no antimicrobial therapy within 24 h of the culture active against the identified organism based on in vitro microbiology reports. Patients who received inactive therapy were more likely to be younger, to be infected with Pseudomonas aeruginosa, to have a nosocomial infection, and to receive antimicrobial monotherapy but less likely to be bacteremic with Escherichia coli or to have sepsis (P < 0.05). There were no significant differences in mortality between patients receiving active versus inactive empiric therapy (16.1% versus 13.6%, respectively) or in length of stay after positive culture (11.5 days versus 12.6 days, respectively). Only 45 patients had greater than 2 days of exposure to inactive therapy; however, 8/30 patients (26.7%) who never received active antimicrobial therapy died while in the hospital. Inactive empiric therapy was more common in healthier patients. Inactive antimicrobial therapy in the first 24 h did not significantly impact average outcomes for GNBI among hospitalized patients but may have caused harm to specific individuals.

Background: Education-based interventions can reduce the incidence of catheter-associated bloodstream infection. The generalizability of findings from single-center studies is limited., Objective: To assess the effect of a multicenter intervention to prevent catheter-associated bloodstream infections., Design: An observational study with a planned intervention., Setting: Twelve intensive care units and 1 bone marrow transplantation unit at 6 academic medical centers., Patients: Patients admitted during the study period., Intervention: Updates of written policies, distribution of a 9-page self-study module with accompanying pretest and posttest, didactic lectures, and incorporation into practice of evidence-based guidelines regarding central venous catheter (CVC) insertion and care., Measurements: Standard data collection tools and definitions were used to measure the process of care (ie, the proportion of nontunneled catheters inserted into the femoral vein and the condition of the CVC insertion site dressing for both tunneled and nontunneled catheters) and the incidence of catheter-associated bloodstream infection., Results: Between the preintervention period and the postintervention period, the percentage of CVCs inserted into the femoral vein decreased from 12.9% to 9.4% (relative ratio, 0.73; 95% confidence interval [CI], 0.61-0.88); the total proportion of catheter insertion site dressings properly dated increased from 26.6% to 34.4% (relative ratio, 1.29; 95% CI, 1.17-1.42), and the overall rate of catheter-associated bloodstream infections decreased from 11.2 to 8.9 infections per 1,000 catheter-days (relative rate, 0.79; 95% CI, 0.67-0.93). The effect of the intervention varied among individual units., Conclusions: An education-based intervention that uses evidence-based practices can be successfully implemented in a diverse group of medical and surgical units and reduce catheter-associated bloodstream infection rates.

Objectives: Despite the well-documented increase in fluoroquinolone resistance to Pseudomonas aeruginosa, the effect on pathogenicity is unknown. This paper will explore the clinical effect., Methods: A retrospective, observational, cohort study of 215 hospital inpatients was performed. Subjects with fluoroquinolone-resistant P. aeruginosa (FQRPA) bacteraemia were compared to subjects with fluoroquinolone-sensitive P. aeruginosa (FQSPA) bacteraemia from January 2000 to December 2003. Mortality prior to discharge, time to discharge, and time to negative culture were assessed. Additionally, baseline morbidity/mortality risk factors including Charlson morbidity score (CMS) were assessed., Results: Mortality prior to discharge (32 vs. 29%, P=0.73), mean days to discharge (17.5 vs. 14.6, P=0.24), and mean days to negative culture (3.6 vs. 3.2, P=0.1) did not differ between FQRPA and FQSPA, respectively. Active antibiotic treatment within 24h of drawn blood culture (FQRPA 63% vs. FQSPA 93%, P<0.0001) and median CMS (FQRPA 3 vs. FQSPA 5, P=0.004) differed significantly between the groups., Conclusions: Subjects with FQRPA received active antibiotics less often within 24h of obtained culture. A large difference in mortality does not likely exist based on fluoroquinolone susceptibility. A study with greater enrollment must be conducted to determine if fluoroquinolone resistance imparts a smaller yet clinically significant impact on clinical outcomes.

Objectives: To determine whether a paper-based antibiotic ordering system is an effective antibiotic stewardship measure., Methods: An antibiotic order form (AOF) was introduced in July 2001 at a pediatric tertiary care hospital. Vancomycin courses prescribed before and after the AOF introduction were retrospectively reviewed based on Hospital Infection Control Practices Advisory Committee guidelines. The impact of the AOF on the appropriateness of vancomycin prescribing was evaluated in univariate and multivariable analyses that adjusted for other factors associated with appropriateness of vancomycin use. The density of vancomycin use after introduction of the AOF was also assessed., Results: Compliance with the AOF was poor (<50%) during the planned study period; therefore an additional 2 months of improved compliance (70-80%) were included. Rates of inappropriate vancomycin use increased during the study periods: 35% before AOF; 39% post-AOF; and 51% during the improved compliance period. On adjusted analysis, vancomycin utilization was significantly more inappropriate after introduction of the AOF. Vancomycin doses per 1000 patient days increased after introduction of the AOF., Conclusions: Inappropriate vancomycin use and vancomycin use overall increased after the introduction of an AOF. An AOF intervention did not have its intended effect of improving and reducing vancomycin use.

Objectives: To characterize vancomycin use at a pediatric tertiary-care hospital, to discriminate between initial (< or = 72 hours) and prolonged (> 72 hours) inappropriate use, and to define patient characteristics associated with inappropriate use., Design: Vancomycin courses were retrospectively reviewed using an algorithm modeled on HICPAC guidelines. Data were collected regarding patient demographics, comorbidities, other medication use, and nosocomial infections. The association between each variable and the outcome of inappropriate use was determined by longitudinal regression analysis. A multivariable model was constructed to assess risk factors for inappropriate initial and prolonged vancomycin use., Setting: A pediatric tertiary-care medical center., Patients: Children older than 1 year who received intravenous vancomycin from November 2000 to June 2001., Results: Three hundred twenty-seven vancomycin courses administered to 260 patients were evaluated for appropriateness. Of initial courses, 114 (35%) were considered inappropriate. Of 143 prolonged courses, 103 (72%) were considered inappropriate. Multivariable risk factor analysis identified the following variables as significantly associated with inappropriate initial use: admission to the surgery service, having a malignancy, receipt of a stem cell transplant, and having received a prior inappropriate course of vancomycin. No variables were identified as significant risk factors for inappropriate prolonged use., Conclusions: Substantial inappropriate use of vancomycin was identified. Prolonged inappropriate use was a particular problem. This risk factor analysis suggests that interventions targeting patients admitted to certain services or receiving multiple courses of vancomycin could reduce inappropriate use.

Case-control analyses of resistant versus susceptible isolates have implicated fluoroquinolone exposure as a strong risk factor for fluoroquinolone-resistant isolates of Enterobacteriaceae. We suspect that such methodology may overestimate this association. A total of 84 cases with fluoroquinolone-resistant isolates and 578 cases with fluoroquinolone-susceptible isolates of Escherichia coli or Klebsiella pneumoniae were compared with 608 hospitalized controls in parallel multivariable analyses. For comparison of previous estimates, the results of 10 published case-control studies of risk for fluoroquinolone resistance in isolates of Enterobacteriaceae were pooled by using a random-effects model. Exposure to fluoroquinolones was significantly positively associated with fluoroquinolone resistance (odds ratio [OR], 3.17) and negatively associated with fluoroquinolone susceptibility (OR, 0.18). Multivariable analyses yielded similar estimates (ORs, 2.04 and 0.10, respectively). As data on antibiotic exposure were limited to inpatient prescriptions, misclassification of fluoroquinolone exposure in persons who received fluoroquinolones as outpatients may have led to an underestimation of the true effect size. Pooling the results of previously published studies in which a direct comparison of fluoroquinolone-resistant and fluoroquinolone-susceptible cases was used resulted in a markedly higher effect estimate (OR, 18.7). Had we directly compared resistant and susceptible cases, our univariate OR for the association between fluoroquinolone use and the isolation of resistant Enterobacteriaceae would have been 19.3, and the multivariate OR would have been 16.5. Fluoroquinolone use is significantly associated with the isolation of fluoroquinolone-resistant Enterobacteriaceae; however, previous studies likely exaggerated the magnitude of this association.

A meta-analysis was performed to investigate whether a switch from beta-lactams to glycopeptides for cardiac surgery prophylaxis should be advised. Results of 7 randomized trials (5761 procedures) that compared surgical site infections (SSIs) in subjects receiving glycopeptide prophylaxis with SSIs in those who received beta -lactam prophylaxis were pooled. Neither agent proved to be superior for prevention of the primary outcome, occurrence of SSI at 30 days (risk ratio [RR], 1.14; 95% confidence interval [CI], 0.91-1.42). In subanalyses, beta-lactams were superior to glycopeptides for prevention of chest SSIs (RR, 1.47; 95% CI, 1.11-1.95) and approached superiority for prevention of deep-chest SSIs (RR, 1.33; 95% CI, 0.91-1.94) and SSIs caused by gram-positive bacteria (RR, 1.36; 95% CI, 0.98-1.91). Glycopeptides approached superiority to beta-lactams for prevention of leg SSIs (RR, 0.77; 95% CI, 0.58-1.01) and were superior for prevention of SSIs caused by methicillin-resistant gram-positive bacteria (RR, 0.54; 95% CI, 0.33-0.90). Standard prophylaxis for cardiac surgery should continue to be beta-lactams in most circumstances.