Identifying Candida auris transmission in a hospital outbreak investigation using whole-genome sequencing and SNP phylogenetic analysis.

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.

COVID-19 outbreak and genomic investigation in an inpatient behavioral health unit.

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.

Monkeypox-Associated Central Nervous System Disease: A Case Series and Review.

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.

Tecovirimat Use in Ambulatory and Hospitalized Patients With Monkeypox Virus Infection.

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.

Impact of early antimicrobial stewardship intervention in patients with positive blood cultures: results from a randomized comparative study.

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.

An unusual case of Staphylococcus pasteuri osteomyelitis.

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.

Successful treatment of a Candida auris intra-articular infection.

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.

Inappropriate Clostridium difficile Testing and Consequent Overtreatment and Inaccurate Publicly Reported Metrics.

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.

Hand Hygiene: An Update.

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.

Respiratory syncytial virus outbreak on an adult stem cell transplant unit.

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.

The burden of mucosal barrier injury laboratory-confirmed bloodstream infection among hematology, oncology, and stem cell transplant patients.

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.

Influence of ACB complex genospecies on clinical outcomes in a U.S. hospital with high rates of multidrug resistance.

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.

Use of acid-fast bacilli staining to determine the need for airborne infection isolation precautions: a comparison of respiratory specimens.

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.

Outcomes of an enhanced surveillance program for carbapenem-resistant Enterobacteriaceae.

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.

Prospective approach to managing antimicrobial drug shortages.

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.

Evaluation of postprescription review and feedback as a method of promoting rational antimicrobial use: a multicenter intervention.

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.

The impact of anti-infective drug shortages on hospitals in the United States: trends and causes.

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.