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.

Effect of daily chlorhexidine bathing on hospital-acquired infection.

BACKGROUND: Results of previous single-center, observational studies suggest that daily bathing of patients with chlorhexidine may prevent hospital-acquired bloodstream infections and the acquisition of multidrug-resistant organisms (MDROs). METHODS: We conducted a multicenter, cluster-randomized, nonblinded crossover trial to evaluate the effect of daily bathing with chlorhexidine-impregnated washcloths on the acquisition of MDROs and the incidence of hospital-acquired bloodstream infections. Nine intensive care and bone marrow transplantation units in six hospitals were randomly assigned to bathe patients either with no-rinse 2% chlorhexidine-impregnated washcloths or with nonantimicrobial washcloths for a 6-month period, exchanged for the alternate product during the subsequent 6 months. The incidence rates of acquisition of MDROs and the rates of hospital-acquired bloodstream infections were compared between the two periods by means of Poisson regression analysis. RESULTS: A total of 7727 patients were enrolled during the study. The overall rate of MDRO acquisition was 5.10 cases per 1000 patient-days with chlorhexidine bathing versus 6.60 cases per 1000 patient-days with nonantimicrobial washcloths (P=0.03), the equivalent of a 23% lower rate with chlorhexidine bathing. The overall rate of hospital-acquired bloodstream infections was 4.78 cases per 1000 patient-days with chlorhexidine bathing versus 6.60 cases per 1000 patient-days with nonantimicrobial washcloths (P=0.007), a 28% lower rate with chlorhexidine-impregnated washcloths. No serious skin reactions were noted during either study period. CONCLUSIONS: Daily bathing with chlorhexidine-impregnated washcloths significantly reduced the risks of acquisition of MDROs and development of hospital-acquired bloodstream infections. (Funded by the Centers for Disease Control and Prevention and Sage Products; ClinicalTrials.gov number, NCT00502476.).

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.

Correlations of antibiotic use and carbapenem resistance in enterobacteriaceae.

Epidemiological studies have shown a link between carbapenem use and resistance; however, the clinical relationship between antibiotic consumption and the epidemiology of carbapenem-intermediate or -resistant Enterobacteriaceae (CIRE) remains unclear. This study sought to analyze temporal antibiotic consumption trends for relationships with incident CIRE. In total, 310,892 days of therapy and 55 deduplicated CIRE were analyzed. When conservative corrections were applied for multiple comparisons, carbapenem class use and piperacillin-tazobactam use retained significant positive and negative relationships with the incidence of CIRE, respectively.

Carbapenem-resistant Enterobacterales standardization across a large health care system.

Carbapenem-resistant Enterobacterales (CRE) are multidrug resistant organisms that pose a significant risk in the health care setting. Standardized identification ensures prompt isolation and is imperative to maintain patient safety.

A population pharmacokinetic model of polymyxin B based on prospective clinical data to inform dosing in hospitalized patients.

OBJECTIVES: To develop a population pharmacokinetic (PK) model with data from the largest polymyxin B-treated patient population studied to date to optimize its dosing in hospitalized patients. METHODS: Hospitalized patients receiving intravenous polymyxin B for ≥48 hours were enrolled. Blood samples were collected at steady state and drug concentrations were analysed by liquid chromotography tandem mass spectrometry (LC-MS/MS). Population PK analysis and Monte Carlo simulations were performed to determine the probability of target attainment (PTA). RESULTS: One hundred and forty-two patients received intravenous polymyxin B (1.33-6 mg/kg/day), providing 681 plasma samples. Twenty-four patients were on renal replacement therapy, including 13 on continuous veno-venous hemodiafiltration (CVVHDF). A 2-compartment model adequately described the PK with body weight as a covariate on the volume of distribution that affected Cmax, but it did not impact clearance or exposure. Creatinine clearance was a statistically significant covariate on clearance, although clinically relevant variations of dose-normalized drug exposure were not observed across a wide creatinine clearance range. The model described higher clearance in CVVHDF patients than in non-CVVHDF patients. Maintenance doses of ≥2.5 mg/kg/day or ≥150 mg/day had a PTA ≥90% (for non-pulmonary infections target) at a steady state for minimum inhibitory concentrations ≤2 mg/L. The PTA at a steady state for CVVHDF patients was lower. DISCUSSION: Fixed loading and maintenance doses of polymyxin B seemed to be more appropriate than weight-based dosing regimens in patients weighing 45-90 kg. Higher doses may be needed in patients on CVVHDF. Substantial variability in polymyxin B clearance and volume of distribution was found, suggesting that therapeutic drug monitoring may be indicated.

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.

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.

Occupational COVID-19 exposures and secondary cases among healthcare personnel.

Throughout the COVID-19 pandemic, healthcare personnel (HCP) have been at high risk of exposure to SARS-CoV-2, both from patients and co-workers. This paper summarizes occupational exposures to SARS-CoV-2 and secondary cases among HCP at a large health system. Key findings indicate that transmission of COVID-19 to HCP is low, especially with close adherence to PPE guidelines, but lapses in infection prevention practices, including dining together and omitting eye protection during patient care, especially at times when COVID-19 is circulating widely in the community increase the risk of exposure and subsequent transmission to HCP.

The value of repeat patient testing for SARS-CoV-2: real-world experience during the first wave.

INTRODUCTION: Reports of false-negative quantitative reverse transcription PCR (RT-qPCR) results from patients with high clinical suspension for coronavirus disease 2019 (COVID-19), suggested that a negative result produced by a nucleic acid amplification assays (NAAs) did not always exclude the possibility of COVID-19 infection. Repeat testing has been used by clinicians as a strategy in an to attempt to improve laboratory diagnosis of COVID-19 and overcome false-negative results in particular. AIM: To investigate whether repeat testing is helpful for overcoming false-negative results. METHODS: We retrospectively reviewed our experience with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, focusing on the yield of repeat patient testing for improving SARS-CoV-2 detection by NAA. RESULTS: We found that the yield from using repeat testing to identify false-negative patients was low. When the first test produced a negative result, only 6 % of patients tested positive by the second test. The yield decreased to 1.7 and then 0 % after the third and fourth tests, respectively. When comparing the results produced by three assays, the Centers for Disease Control and Prevention (CDC) SARS CoV-2 RT-qPCR panel, Xpert Xpress CoV-2 and ID NOW COVID-19, the ID NOW assay was associated with the highest number of patients who tested negative initially but positive on repeat testing. The CDC SARS CoV-2 RT-qPCR panel produced the highest number of indeterminate results. Repeat testing resolved more than 90 % of indeterminate/invalid results. CONCLUSIONS: The yield from using repeat testing to identify false-negative patients was low. Repeat testing was best used for resolving indeterminate/invalid results.

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.

The intersection of hand hygiene, infusion pump contamination, and high alarm volume in the health care environment.

BACKGROUND: Researchers have found that lack of hand hygiene and environmental contamination are sources of infection transmission in the health care environment. One factor that may lead to lack of hand hygiene is alarm fatigue, the sensory overload that results when clinicians are exposed to an excessive number of alarms, causing them to silence alarms without taking proper precautions. In this study, we report hand hygiene compliance and infusion pump contamination in the context of infusion pump alarm prevalence. METHODS: Health care worker hand hygiene audits were conducted to determine percent compliance. Cultures were obtained from infusion pumps to determine environmental contamination. The frequency of alarms from August 4, 2019 to September 7, 2019 was determined. RESULTS: Hand hygiene compliance ranged from 50% to 87%. Pump contamination ranged from 20% to 70% per unit. A total of 116, 872 infusion pump alarms sounded in the hospital. DISCUSSION: Pumps were contaminated primarily with skin flora. This was demonstrated in the context of poor hand hygiene compliance and a high number of alarms, indicative of alarm fatigue. CONCLUSIONS: The intersection of a high prevalence of infusion pump alarms and poor hand hygiene resulting in bacterial contamination of pumps could be a source of health care-associated infection transmission for patients.

Improved surveillance for surgical site infections after orthopedic implantation procedures: extending applications for automated data.

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.

Cost-effectiveness analysis of an antimicrobial stewardship team on bloodstream infections: a probabilistic analysis.

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.

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.

Persistent Staphylococcus aureus bacteremia: an analysis of risk factors and outcomes.

BACKGROUND: Persistent Staphylococcus aureus bacteremia (pSAB) is an emerging problem among hospitalized patients. We studied key clinical characteristics and outcomes associated with pSAB to better define the epidemiological features of this increasingly recognized clinical entity. METHODS: A retrospective case-control study of patients hospitalized with SAB between January 1, 2001, and September 30, 2004, was conducted to compare the clinical characteristics, management, and outcomes of patients with pSAB (> 7 days of bacteremia) with those of a cohort of patients with nonpersistent SAB (< 3 days of bacteremia). Patients with 4 to 6 days of bacteremia were excluded from the analysis. To detect a potential association between reduced susceptibility to vancomycin and persistent methicillin-resistant SAB, vancomycin susceptibilities were confirmed using standard dilution methods. RESULTS: Eighty-four patients with pSAB and 152 patients with nonpersistent SAB were included in the analysis. Methicillin resistance (odds ratio [OR], 5.22; 95% confidence interval [CI], 2.63-10.38), intravascular catheter or other foreign body use (OR, 2.37; 95% CI, 1.11-3.96), chronic renal failure (OR, 2.08; 95% CI, 1.09-3.96), more than 2 sites of infection (OR, 3.31; 95% CI, 1.17-9.38), and infective endocarditis (OR, 10.30; 95% CI, 2.98-35.64) were independently associated with pSAB. The mean time to device removal was significantly longer in patients with pSAB than in patients with nonpersistent SAB (4.94 vs 1.64 days; P < .01). There was no evidence of reduced vancomycin susceptibility among persistent methicillin-resistant S aureus isolates. Clinical outcomes were significantly worse among patients with pSAB. CONCLUSIONS: Many hospitalized patients may be at risk for pSAB. Aggressive attempts to minimize the risk of complications and poor outcomes associated with pSAB, such as early device removal, should be encouraged.

Implementation of a cefazolin-based stewardship pathway for methicillin-susceptible Staphylococcus aureus bloodstream infections paired with infectious diseases consultation.

Methicillin-susceptible Staphylococcus aureus (MSSA) infections have been successfully treated both with cefazolin and antistaphylococcal penicillins; cefazolin appears effective in MSSA bloodstream infections (BSIs). Thus, our antimicrobial stewardship programme (ASP) implemented a clinical pathway supporting cefazolin use in MSSA-BSIs and restricting oxacillin use to infectious diseases (ID) consultation due to cefazolin's lower cost and more convenient dosing. This before and after quasi-experimental study was conducted to describe the impact on outcomes and process of care measures associated with implementing this pathway among patients with MSSA-BSI. Definitive treatment with cefazolin increased over the study period from 17.3% to 69.8% post-implementation. Clinical failure (5.8% vs. 2.3%; P = 0.62) and in-hospital mortality (3.8% vs. 0%; P = 0.50) were rare pre- and post-implementation. Median hospital length of stay among survivors was similar between pre- and post-implementation periods (P = 0.31). Duration of bacteraemia [median (IQR) 3 (2-4) days vs. 2 (2-3) days; P = 0.002] and rates of re-infection after culture clearance (9.6% vs. 0%; P = 0.06) were reduced post-implementation. Frequency of source control (P = 0.71) and time to source control (P = 0.52) were similar between study periods. Significant increases in ID consultations (33.3% [3/9] vs. 73.3% [22/30]; P = 0.047) and median (IQR) 24-h daily doses [2 (1-3) g vs. 6 (3-6) g; P < 0.01] were seen for patients treated with cefazolin post-implementation. ASPs may find implementation of a similar pathway to be an effective means of improving the care of patients infected with MSSA.

A multicenter intervention to prevent catheter-associated bloodstream infections.

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.

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.