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The attention and resources being dedicated to improving sepsis care are welcome. The policy response to this apparent epidemic, however, ought to be tempered by recognition that we do not yet have reliable tools for measuring sepsis incidence. Sepsis, the syndrome of dysregulated inflammation that occurs with severe infection, affects millions of people worldwide each year. Multiple studies suggest that the incidence of sepsis is dramatically increasing. According to the Centers for Disease Control and Prevention (CDC), for example, sepsis rates doubled between 2000 and 2008. 1 In 2010, sepsis was the 11th leading cause of death in the United States, 2 and in 2011, it was the single most expensive condition treated in hospitals. 3 This apparent explosion in sepsis is spurring high-profile initiatives to promote earlier recognition and better treatment. Standardized screening protocols, bundled order sets, and algorithms for . . .

BackgroundThe diagnosis and management of pneumonia is often challenging due to its overlapping clinical presentations with other respiratory illnesses, low pathogen identification rates, and slow turnaround time of conventional bacterial cultures. These factors contribute to both inadequate empiric therapy and overuse of broad-spectrum antibiotics, which can negatively impact outcomes. Recently, multiplex polymerase chain reaction (mPCR) assays capable of rapidly detecting multiple bacterial respiratory pathogens and resistance genes have emerged. However, their clinical utility in pneumonia management remains uncertain.ObjectiveTo assess the utility of bacterial mPCR assays in pneumonia diagnosis, their impact on antimicrobial usage, and their effect on patient outcomes.MethodsA comprehensive literature review was conducted using MEDLINE to identify observational studies and randomised controlled trials (RCTs) evaluating the accuracy and clinical impact of bacterial mPCR tests for pneumonia.ResultsBacterial mPCR assays demonstrate high sensitivity for pathogen detection, rapid turnaround compared to conventional cultures, and the ability to identify many common resistance genes. They may also improve pathogen detection in patients who received empirical antibiotics prior to specimen collection. However, mPCRs do not detect all potential pathogens, cannot reliably differentiate colonisation from infection, and may show discordance between genetic and phenotypic resistance. mPCR panels also generally require lower respiratory tract specimens, limiting their utility since many pneumonia patients cannot produce adequate sputum. Observational studies and RCTs suggest that mPCR may help optimise antibiotic selection, but RCTs have not clearly demonstrated reductions in overall antibiotic use or improved clinical outcomes including mortality. Implementation of mPCR without structured antimicrobial stewardship may limit clinical impact.ConclusionsBacterial mPCR assays offer rapid and sensitive pathogen detection, but their integration into pneumonia management requires careful consideration of clinical context and expert antimicrobial stewardship guidance. Future research should focus on optimising their diagnostic and therapeutic applications, evaluating cost-effectiveness, and assessing patient-centered outcomes.

Abstract Background Resistance to all first-line antibiotics necessitates the use of less effective or more toxic \"reserve\" agents. Gram-negative bloodstream infections (GNBSIs) harboring such difficult-to-treat resistance (DTR) may have higher mortality than phenotypes that allow for ≥1 active first-line antibiotic. Methods The Premier Database was analyzed for inpatients with select GNBSIs. DTR was defined as intermediate/resistant in vitro to all ß-lactam categories, including carbapenems and fluoroquinolones. Prevalence and aminoglycoside resistance of DTR episodes were compared with carbapenem-resistant, extended-spectrum cephalosporin-resistant, and fluoroquinolone-resistant episodes using CDC definitions. Predictors of DTR were identified. The adjusted relative risk (aRR) of mortality was examined for DTR, CDC-defined phenotypes susceptible to ≥1 first-line agent, and graded loss of active categories. Results Between 2009-2013, 471 (1%) of 45011 GNBSI episodes at 92 (53.2%) of 173 hospitals exhibited DTR, ranging from 0.04% for Escherichia coli to 18.4% for Acinetobacter baumannii. Among patients with DTR, 79% received parenteral aminoglycosides, tigecycline, or colistin/polymyxin-B; resistance to all aminoglycosides occurred in 33%. Predictors of DTR included urban healthcare and higher baseline illness. Crude mortality for GNBSIs with DTR was 43%; aRR was higher for DTR than for carbapenem-resistant (1.2; 95% confidence interval, 1.0-1.4; P = .02), extended-spectrum cephalosporin-resistant (1.2; 1.1-1.4; P = .001), or fluoroquinolone-resistant (1.2; 1.0-1.4; P = .008) infections. The mortality aRR increased 20% per graded loss of active first-line categories, from 3-5 to 1-2 to 0. Conclusion Nonsusceptibility to first-line antibiotics is associated with decreased survival in GNBSIs. DTR is a simple bedside prognostic measure of treatment-limiting coresistance. Resistance to all first-line agents or difficult-to-treat resistance (DTR) was observed in 1% of gram-negative bacteremias. DTR was identified at half the hospitals; nearly 80% of patients with DTR received \"reserve\" agents. Mortality risk increased with decreasing active first-line categories.

The prevalence and effects of inappropriate empirical antibiotic therapy for bloodstream infections are unclear. We aimed to establish the population-level burden, predictors, and mortality risk of in-vitro susceptibility-discordant empirical antibiotic therapy among patients with bloodstream infections. Our retrospective cohort analysis of electronic health record data from 131 hospitals in the USA included patients with suspected—and subsequently confirmed—bloodstream infections who were treated empirically with systemic antibiotics between Jan 1, 2005, and Dec 31, 2014. We included all patients with monomicrobial bacteraemia caused by common bloodstream pathogens who received at least one systemic antibiotic either on the day blood cultures were drawn or the day after, and for whom susceptibility data were available. We calculated the prevalence of discordant empirical antibiotic therapy—which was defined as receiving antibiotics on the day blood culture samples were drawn to which the cultured isolate was not susceptible in vitro—overall and by hospital type by using regression tree analysis. We used generalised estimating equations to identify predictors of receiving discordant empirical antibiotic therapy, and used logistic regression to calculate adjusted odds ratios for the relationship between in-hospital mortality and discordant empirical antibiotic therapy. 21 608 patients with bloodstream infections received empirical antibiotic therapy on the day of first blood culture collection. Of these patients, 4165 (19%) received discordant empirical antibiotic therapy. Discordant empirical antibiotic therapy was independently associated with increased risk of mortality (adjusted odds ratio 1·46 [95% CI, 1·28–1·66]; p<0·0001), a relationship that was unaffected by the presence or absence of resistance or sepsis or septic shock. Infection with antibiotic-resistant species strongly predicted receiving discordant empirical therapy (adjusted odds ratio 9·09 [95% CI 7·68–10·76]; p<0·0001). Most incidences of discordant empirical antibiotic therapy and associated deaths occurred among patients with bloodstream infections caused by Staphylococcus aureus or Enterobacterales. Approximately one in five patients with bloodstream infections in US hospitals received discordant empirical antibiotic therapy, receipt of which was closely associated with infection with antibiotic-resistant pathogens. Receiving discordant empirical antibiotic therapy was associated with increased odds of mortality overall, even in patients without sepsis. Early identification of bloodstream pathogens and resistance will probably improve population-level outcomes. US National Institutes of Health, US Centers for Disease Control and Prevention, and US Agency for Healthcare Research and Quality.

Strategic MaskingWith the end of the Covid-19 public health emergency, health care facilities could reimagine masking polices to protect patients from the full array of nosocomial respiratory viral infections.

Some patients are avoiding essential care for fear of contracting coronavirus disease 2019 (COVID-19) in hospitals. There are few data, however, on the risk of acquiring COVID-19 in US hospitals. To assess the incidence of COVID-19 among patients hospitalized at a large US academic medical center in the 12 weeks after the first inpatient case was identified. This cohort study included all patients admitted to Brigham and Women's Hospital (Boston, Massachusetts) between March 7 and May 30, 2020. Follow-up occurred through June 17, 2020. Medical records for all patients who first tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse-transcription polymerase chain reaction (RT-PCR) on hospital day 3 or later or within 14 days of discharge were reviewed. A comprehensive infection control program was implemented that included dedicated COVID-19 units with airborne infection isolation rooms, personal protective equipment in accordance with US Centers for Disease Control and Prevention recommendations, personal protective equipment donning and doffing monitors, universal masking, restriction of visitors, and liberal RT-PCR testing of symptomatic and asymptomatic patients. Whether infection was community or hospital acquired based on timing of tests, clinical course, and exposures. Over the 12-week period, 9149 patients (mean [SD] age, 46.1 [26.4] years; median [IQR] age, 51 years [30-67 years]; 5243 female [57.3%]) were admitted to the hospital, for whom 7394 SARS-CoV-2 RT-PCR tests were performed; 697 COVID-19 cases were confirmed, translating into 8656 days of COVID-19-related care. Twelve of the 697 hospitalized patients with COVID-19 (1.7%) first tested positive on hospital day 3 or later (median, 4 days; range, 3-15 days). Of these, only 1 case was deemed to be hospital acquired, most likely from a presymptomatic spouse who was visiting daily and diagnosed with COVID-19 before visitor restrictions and masking were implemented. Among 8370 patients with non-COVID-19-related hospitalizations discharged through June 17, 11 (0.1%) tested positive within 14 days (median time to diagnosis, 6 days; range, 1-14 days). Only 1 case was deemed likely to be hospital acquired, albeit with no known exposures. In this cohort study of patients in a large academic medical center with rigorous infection control measures, nosocomial COVID-19 was rare during the height of the pandemic in the region. These findings may inform practices in other institutions and provide reassurance to patients concerned about contracting COVID-19 in hospitals.

Hospitalized patients are at risk for developing hospital acquired infections. Active surveillance for bacterial colonization is effective at preventing infection but is resource-intensive and limited to high-risk units and a subset of high-risk pathogens. Colonization pressure, defined as the prevalence of an organism among ward co-occupants, has been associated with hospital acquired infection and can be calculated in real-time using data in the electronic health record, but its use by infection control programs has been limited. As a proof-of-concept study, we built an open source informatics tool to model the impact of colonization pressure on nosocomial acquisition for a wide range of drug susceptible and resistant pathogens using electronic health record data from a large integrated health system in the Northeast United States, collected between May 2015 and July 2024. Using a matched case-control design, we show a consistent positive association between colonization pressure for an organism and nosocomial acquisition of that organism, regardless of whether that organism was drug susceptible or resistant. We also observed significant positive relationships between disparate organisms (e.g., colonization pressure from vancomycin resistant Enterococcus faecium and hospital acquisition of extended-spectrum beta-lactamase producing Klebsiella pneumoniae ) as well as negative associations, primarily between organisms that inhabit distinct niches, such as colonization pressure from drug resistant Pseudomonas aeruginosa and hospital acquisition of vancomycin susceptible Enterococcus faecalis . Our results suggest nosocomial transmission of potential pathogens is widespread in a tertiary care hospital system with advanced infection control programs. We have made the software and our patient-level dataset publicly available to support future research and infection control interventions. Hospitalised patients are at risk of acquiring infections, and the risk increases when there is a higher prevalence among ward co-occupants, known as colonisation pressure. Here, the authors built an open-source tool for passive surveillance of colonisation pressure across a health system in the United States and assess impacts on infection risk for a range of pathogens.

Purpose of ReviewEarly antibiotic administration is the cornerstone of sepsis treatment guidelines and quality measures. We summarize recent key literature on sepsis definitions and screening, time-to-antibiotics and outcomes, and dosing considerations.Recent FindingsCurrent sepsis clinical criteria have limited utility for identifying patients who warrant urgent broad-spectrum antibiotics because they include a very heterogeneous population, including many patients later found to have non-infectious syndromes or mild transient illnesses. The best available evidence supports immediate antibiotic administration (within 1 h) for patients with septic shock. Many sepsis patients without shock likely benefit from early antibiotics as well, but further high-quality studies are needed to precisely delineate the magnitude of benefit among potential subgroups and the time windows beyond which delays lead to worse outcomes. Time from antibiotic order-to-infusion and the order of antibiotic administration (i.e., beta-lactam before vancomycin) are two additional care processes found to be associated with outcomes. Empiric antibiotic choices should be informed by patients’ likely site of infection, prior microbiology, comorbidities, severity of illness, and allergy profiles, and the development of better antibiotic resistance predictive models and novel rapid antimicrobial susceptibility testing hold promise for mitigating risks of both inadequate and unnecessarily broad antibiotic therapy. Lastly, incorporating established pharmacokinetic and pharmacodynamic principles, including aggressive loading doses and prolonged beta-lactam infusions, is critical to optimize clinical outcomes.SummaryA systematic approach to deciding who needs early versus immediate antibiotics, which agents to choose, and how to properly dose them may improve sepsis outcomes while minimizing antibiotic-related adverse events.

Background: Tuberculosis transmission in healthcare is poorly understood. Exposure definitions for patients and healthcare workers tend to be based on custom rather than data leading to many people being flagged for evaluation despite few infection transmission events. We reviewed the medical literature to identify and quantify risk factors for tuberculosis transmission in healthcare to guide risk-stratification and inform exposure definitions. Methods: We reviewed MEDLINE, EMBASE, CINAHL and Cochrane databases from inception to December 10, 2024. We included studies reporting tuberculosis transmission from infected adult patients to healthcare workers and other patients in both inpatient and outpatient settings. We evaluated 12 transmission risk factors: contact factors (exposure duration, proximity of exposure, mask use, room ventilation), patient factors (smear positivity, NAAT positivity, cavitary pulmonary disease, respiratory symptoms), and procedure factors (intubation, bronchoscopy, sputum collection, and other procedures). Results: A total of 6,695 studies were identified of which 49 met inclusion criteria. Contact factors associated with increased risk of transmission included poor room ventilation (≤ 2 air exchanges per hour, 60-70% air recirculation without high efficiency filtration, high ambient carbon dioxide levels with median 660-800 parts per million) and positive pressure air flow from poorly ventilated rooms to nearby clinical spaces. Most ventilation-related transmissions occurred before modern healthcare ventilation standards were implemented. Sustained proximity to infected patients was associated with patient-to-patient transmission via shared rooms (4 transmissions/90 exposures, minimum exposure ≥16 hours) and prolonged residence adjacent to a poorly ventilated standard pressure room (42 transmissions/430 exposures, minimum exposure ≥24 hours). Amongst 766 cases of tuberculosis transmission from patients to healthcare workers, risk factors included prolonged patient contact (median 6 hours, minimum 30 minutes), failure to wear an N95 respirator, and face-to-face patient care (28% of transmissions were associated with face-to-face patient contact, 21% of transmissions were associated with working on the same unit without direct patient contact, and contact details were unknown in 52% of transmissions). Patient factors associated with increased transmission included cavitary disease (OR 1.90, 95% CI 1.26-2.84). Transmission risk was similar for smear-positive and smear-negative patients undergoing aerosol-generating procedures without airborne precautions (17/111 smear negative exposures led to transmission vs 32/166 smear positive exposures, 15% vs 19%). All transmissions to healthcare workers associated with intubation, bronchoscopy and induced sputum collection occurred without airborne precautions. Conclusions: Detailed review of the circumstances around nosocomial tuberculosis exposure helps identify transmission risk factors that can inform more evidence-based, detailed and individualized exposure definitions.

Introduction Claims-based analyses report that the incidence of sepsis-associated organ dysfunction is increasing. We examined whether coding practices for acute organ dysfunction are changing over time and if so, whether this is biasing estimates of rising severe sepsis incidence and severity. Methods We assessed trends from 2005 to 2013 in the annual sensitivity and incidence of discharge ICD-9-CM codes for organ dysfunction (shock, respiratory failure, acute kidney failure, acidosis, hepatitis, coagulopathy, and thrombocytopenia) relative to standardized clinical criteria (use of vasopressors/inotropes, mechanical ventilation for ≥2 consecutive days, rise in baseline creatinine, low pH, elevated transaminases or bilirubin, abnormal international normalized ratio or low fibrinogen, and decline in platelets). We studied all adult patients with suspected infection (defined by ≥1 blood culture order) at two US academic hospitals. Results Acute organ dysfunction codes were present in 57,273 of 191,695 (29.9 %) hospitalizations with suspected infection, most commonly acute kidney failure (60.2 % of cases) and respiratory failure (28.9 %). The sensitivity of all organ dysfunction codes except thrombocytopenia increased significantly over time. This was most pronounced for acute kidney failure codes, which increased in sensitivity from 59.3 % in 2005 to 87.5 % in 2013 relative to a fixed definition for changes in creatinine ( p = 0.019 for linear trend). Acute kidney failure codes were increasingly assigned to patients with smaller creatinine changes: the average peak creatinine change associated with a code was 1.99 mg/dL in 2005 versus 1.49 mg/dL in 2013 ( p <0.001 for linear decline). The mean number of dysfunctional organs in patients with suspected infection increased from 0.32 to 0.59 using discharge codes versus 0.69 to 0.79 using clinical criteria ( p <0.001 for both trends and comparison of the two trends). The annual incidence of hospitalizations with suspected infection and any dysfunctional organ rose an average of 5.9 % per year (95 % CI 4.3, 7.4 %) using discharge codes versus only 1.1 % (95 % CI 0.1, 2.0 %) using clinical criteria. Conclusions Coding for acute organ dysfunction is becoming increasingly sensitive and the clinical threshold to code patients for certain kinds of organ dysfunction is decreasing. This accounts for much of the apparent rise in severe sepsis incidence and severity imputed from claims.