Exebacase in Addition to Standard-of-Care Antibiotics for Staphylococcus aureus Bloodstream Infections and Right-Sided Infective Endocarditis: A Phase 3, Superiority-Design, Placebo-Controlled, Randomized Clinical Trial (DISRUPT).

BACKGROUND: Novel treatments are needed for Staphylococcus aureus bacteremia, particularly for methicillin-resistant S. aureus (MRSA). Exebacase is a first-in-class antistaphylococcal lysin that is rapidly bactericidal and synergizes with antibiotics. METHODS: In Direct Lysis of Staph Aureus Resistant Pathogen Trial of Exebacase (DISRUPT), a superiority-design phase 3 study, patients with S. aureus bacteremia/endocarditis were randomly assigned to receive a single dose of intravenous exebacase or placebo in addition to standard-of-care antibiotics. The primary efficacy outcome was clinical response at day 14 in the MRSA population. RESULTS: A total of 259 patients were randomized before the study was stopped for futility based on the recommendation of the unblinded Data Safety Monitoring Board. Clinical response rates at day 14 in the MRSA population (n = 97) were 50.0% (exebacase + antibiotics; 32/64) versus 60.6% (antibiotics alone; 20/33) (P = .392). Overall, rates of adverse events were similar across groups. No adverse events of hypersensitivity related to exebacase were reported. CONCLUSIONS: Exebacase + antibiotics failed to improve clinical response at day 14 in patients with MRSA bacteremia/endocarditis. This result was unexpected based on phase 2 data that established proof-of-concept for exebacase + antibiotics in patients with MRSA bacteremia/endocarditis. In the antibiotics-alone group, the clinical response rate was higher than that seen in phase 2. Heterogeneity within the study population and a relatively small sample size in either the phase 2 or phase 3 studies may have increased the probability of imbalances in the multiple components of day 14 clinical outcome. This study provides lessons for future superiority studies in S. aureus bacteremia/endocarditis. Clinical Trials Registration.NCT04160468.

Practical Guidance for Clinical Microbiology Laboratories: A Comprehensive Update on the Problem of Blood Culture Contamination and a Discussion of Methods for Addressing the Problem

In this review, we present a comprehensive discussion of matters related to the problem of blood culture contamination. Issues addressed include the scope and magnitude of the problem, the bacteria most often recognized as contaminants, the impact of blood culture contamination on clinical microbiology laboratory function, the economic and clinical ramifications of contamination, and, perhaps most importantly, a systematic discussion of solutions to the problem. We conclude by providing a series of unanswered questions that pertain to this important issue.

Effect of Algorithm-Based Therapy vs Usual Care on Clinical Success and Serious Adverse Events in Patients with Staphylococcal Bacteremia: A Randomized Clinical Trial.

Importance: The appropriate duration of antibiotics for staphylococcal bacteremia is unknown. Objective: To test whether an algorithm that defines treatment duration for staphylococcal bacteremia vs standard of care provides noninferior efficacy without increasing severe adverse events. Design, Setting, and Participants: A randomized trial involving adults with staphylococcal bacteremia was conducted at 16 academic medical centers in the United States (n = 15) and Spain (n = 1) from April 2011 to March 2017. Patients were followed up for 42 days beyond end of therapy for those with Staphylococcus aureus and 28 days for those with coagulase-negative staphylococcal bacteremia. Eligible patients were 18 years or older and had 1 or more blood cultures positive for S aureus or coagulase-negative staphylococci. Patients were excluded if they had known or suspected complicated infection at the time of randomization. Interventions: Patients were randomized to algorithm-based therapy (n = 255) or usual practice (n = 254). Diagnostic evaluation, antibiotic selection, and duration of therapy were predefined for the algorithm group, whereas clinicians caring for patients in the usual practice group had unrestricted choice of antibiotics, duration, and other aspects of clinical care. Main Outcomes and Measures: Coprimary outcomes were (1) clinical success, as determined by a blinded adjudication committee and tested for noninferiority within a 15% margin; and (2) serious adverse event rates in the intention-to-treat population, tested for superiority. The prespecified secondary outcome measure, tested for superiority, was antibiotic days among per-protocol patients with simple or uncomplicated bacteremia. Results: Among the 509 patients randomized (mean age, 56.6 [SD, 16.8] years; 226 [44.4%] women), 480 (94.3%) completed the trial. Clinical success was documented in 209 of 255 patients assigned to algorithm-based therapy and 207 of 254 randomized to usual practice (82.0% vs 81.5%; difference, 0.5% [1-sided 97.5% CI, -6.2% to ∞]). Serious adverse events were reported in 32.5% of algorithm-based therapy patients and 28.3% of usual practice patients (difference, 4.2% [95% CI, -3.8% to 12.2%]). Among per-protocol patients with simple or uncomplicated bacteremia, mean duration of therapy was 4.4 days for algorithm-based therapy vs 6.2 days for usual practice (difference, -1.8 days [95% CI, -3.1 to -0.6]). Conclusions and Relevance: Among patients with staphylococcal bacteremia, the use of an algorithm to guide testing and treatment compared with usual care resulted in a noninferior rate of clinical success. Rates of serious adverse events were not significantly different, but interpretation is limited by wide confidence intervals. Further research is needed to assess the utility of the algorithm. Trial Registration: ClinicalTrials.gov Identifier: NCT01191840.

Reduction in Blood Culture Contamination Through Use of Initial Specimen Diversion Device.

BACKGROUND: Blood culture contamination is a clinically significant problem that results in patient harm and excess cost. METHODS: In a prospective, controlled trial at an academic center Emergency Department, a device that diverts and sequesters the initial 1.5-2 mL portion of blood (which presumably carries contaminating skin cells and microbes) was tested against standard phlebotomy procedures in patients requiring blood cultures due to clinical suspicion of serious infection. RESULTS: In sum, 971 subjects granted informed consent and were enrolled resulting in 904 nonduplicative subjects with 1808 blood cultures. Blood culture contamination was significantly reduced through use of the initial specimen diversion device™ (ISDD) compared to standard procedure: (2/904 [0.22%] ISDD vs 16/904 [1.78%] standard practice, P = .001). Sensitivity was not compromised: true bacteremia was noted in 65/904 (7.2%) ISDD vs 69/904 (7.6%) standard procedure, P = .41. No needlestick injuries or potential bloodborne pathogen exposures were reported. The monthly rate of blood culture contamination for all nurse-drawn and phlebotomist-drawn blood cultures was modeled using Poisson regression to compare the 12-month intervention period to the 6 month before and after periods. Phlebotomists (used the ISDD) experienced a significant decrease in blood culture contamination while the nurses (did not use the ISDD) did not. In sum, 73% of phlebotomists completed a post-study anonymous survey and widespread user satisfaction was noted. CONCLUSIONS: Use of the ISDD was associated with a significant decrease in blood culture contamination in patients undergoing blood cultures in an Emergency Department setting. CLINICAL TRIALS REGISTRATION: NCT02102087.

Is bacteremic sepsis associated with higher mortality in transplant recipients than in nontransplant patients? A matched case-control propensity-adjusted study.

BACKGROUND: Sepsis is a serious complication of solid organ transplant (SOT). Evidence on survival differences between SOT recipients and non-SOT patients with sepsis is lacking. METHODS: This was a matched, case-control propensity-adjusted study. Conditional logistic regression was performed for risk factor analysis, and Cox proportional hazards regression for survival analysis. RESULTS: Three hundred sixty-nine patients (123 cases; 246 controls) diagnosed with blood culture-proven sepsis were matched 1:2 by age, sex, and hospital location. The distribution of allografts was 36.6% kidney, 34.1% liver, 13% kidney-pancreas, 7.3% small bowel/liver, 5.7% heart/lung, and 3.3% multivisceral. The conditional logistic regression showed that the following factors were significantly more frequently associated with SOT compared to non-SOT: higher number of comorbidities (odds ratio [OR] = 8.2 [95% confidence interval {CI}, 1.48-45.44], P = .016); higher Sepsis-related Organ Failure Assessment score (OR = 1.2 [95% CI, 1.07-1.32], P = .001); presence of nosocomial infection (OR = 36.3 [95% CI, 9.71-135.96], P < .0001); appropriate initial antibiotics (OR = 0.04 [95% CI, .006-.23], P < .0001); and lower white blood cell count (OR = 0.93 [95% CI, .89-.97], P < .0001). Cox proportional hazards regression showed that after all adjustments for clinical presentation, severity of illness, and types of infection, SOT recipients with sepsis had a significantly lower risk of death at 28 days (hazard ratio [HR] = 0.22 [95% CI, .09-.54], P = .001) and at 90 days (HR = 0.43 [95% CI, .20-.89], P = .025). CONCLUSIONS: The 28-day and 90-day mortality were significantly decreased for transplant recipients compared with nontransplant patients. These findings suggest that the immunosuppression associated with transplantation may provide a survival advantage to transplant recipients with sepsis through modulation of the inflammatory response.

Epidemiology and predictors of multidrug-resistant community-acquired and health care-associated pneumonia.

There are limited U.S. data describing the risk factors for multidrug-resistant organism (MDRO) isolation in community-acquired pneumonia (CAP) and health care-associated pneumonia (HCAP). However, concern for the presence of these pathogens drives the prescribing of empiric broad-spectrum antibiotics for CAP and HCAP. A retrospective study of all adults hospitalized with community-onset pneumonia (CAP and HCAP) at a large U.S. medical center from January 2010 to December 2011 was conducted. The objective was to ascertain the rate of pneumonia caused by MDROs and to evaluate whether HCAP is a risk factor for MDRO pneumonia. Univariate and propensity score-adjusted multivariate analyses were performed. A total of 521 patients (50.5% CAP and 49.5% HCAP) were included. The most common etiologies of pneumonia were primary viral and Streptococcus pneumoniae. MDROs were isolated in 20 (3.8%) patients overall, and MDROs occurred in 5.9% and 1.9% of HCAP and CAP patients, respectively. The presence of an MDRO was not associated with HCAP classification (odds ratio [OR]=1.95; 95% confidence interval [95% CI], 0.66 to 5.80; P=0.23) or with most of its individual components (hemodialysis, home infusion, home wound care, and ≥48-h hospitalization in the last 90 days). Independent predictors of MDRO included the following: Pseudomonas aeruginosa colonization/infection in the previous year (OR=7.43; 95% CI, 2.24 to 24.61; P<0.001), antimicrobial use in the previous 90 days (OR=2.90; 95% CI, 1.13 to 7.45; P=0.027), admission from a nursing home (OR=4.19; 95% CI, 1.55 to 11.31; P=0.005), and duration of hospitalization in the previous 90 or 180 days (P=0.013 and P=0.002, respectively). MDROs were uncommon in HCAP and CAP. HCAP did not predict MDRO isolation. Local etiology of community onset pneumonia and specific MDRO risk factors should be integrated into therapeutic decisions to prevent empirical overprescribing of antibiotics for methicillin-resistant Staphylococcus aureus (MRSA) and P. aeruginosa.

Association between vancomycin minimum inhibitory concentration and mortality among patients with Staphylococcus aureus bloodstream infections: a systematic review and meta-analysis.

IMPORTANCE: Staphylococcus aureus bacteremia (SAB) is a worldwide problem. It is unclear whether higher-vancomycin minimum inhibitory concentration (MIC) is associated with mortality. This potential association has direct consequences for patients and public health. DATA SOURCES: PubMed, Embase, the Cochrane Library, Evidence-based Medicine BMJ, and the American College of Physicians Journal Club were searched from inception through April 2014. STUDY SELECTION: Studies reporting mortality and vancomycin MIC in patients with SAB were included. DATA EXTRACTION AND SYNTHESIS: Two authors performed the literature search and the study selection separately. Random-effects modeling was used for all analyses. MAIN OUTCOMES AND MEASURES: All-cause mortality. FINDINGS: Among 38 included studies that involved 8291 episodes of SAB, overall mortality was 26.1%. The estimated mortality was 26.8% among SAB episodes (n = 2740) in patients with high-vancomycin MIC (≥1.5 mg/L) compared with 25.8% mortality among SAB episodes (n = 5551) in patients with low-vancomycin MIC (<1.5 mg/L) (adjusted risk difference [RD], 1.6% [95% CI, -2.3% to 5.6%]; P = .43). For the highest-quality studies, the estimated mortality was 26.2% among SAB episodes (n = 2318) in patients with high-vancomycin MIC compared with 27.8% mortality among SAB episodes (n = 4168) in patients with low-vancomycin MIC (RD, 0.9% [95% CI, -2.9% to 4.6%]; P = .65). In studies that included only methicillin-resistant S aureus infections (n = 7232), the mortality among SAB episodes (n = 2384) in patients with high-vancomycin MIC was 27.6% compared with mortality of 27.4% among SAB episodes (n = 4848) in patients with low-vancomycin MIC (adjusted RD, 1.6% [95% CI, -2.3% to 5.5%]; P = .41). No significant differences in risk of death were observed in subgroups with high-vancomycin MIC vs low-vancomycin MIC values across different study designs, microbiological susceptibility assays, MIC cutoffs, clinical outcomes, duration of bacteremia, previous vancomycin exposure, and treatment with vancomycin. CONCLUSIONS AND RELEVANCE: In this meta-analysis of SAB episodes, there were no statistically significant differences in the risk of death when comparing patients with S aureus exhibiting high-vancomycin MIC (≥1.5 mg/L) to those with low-vancomycin MIC (<1.5 mg/L), although the findings cannot definitely exclude an increased mortality risk. These findings should be considered when interpreting vancomycin susceptibility and in determining whether alternative antistaphylococcal agents are necessary for patients with SAB with elevated but susceptible vancomycin MIC values.

Should Blood Cultures Be Drawn Through an Indwelling Catheter?

There is no practical way to definitively diagnose a catheter-related bloodstream infection in situ if blood cultures are only obtained percutaneously unless there is the rare occurrence of purulent drainage from a central venous catheter insertion site. That is why the Infectious Diseases Society of America guidelines for diagnosis and management of catheter-related bloodstream infections and Infectious Diseases Society of America guidelines for evaluation of fever in critically ill patients both recommend drawing blood cultures from a central venous catheter and percutaneously if the catheter is a suspected source of infection. However, central venous catheter-drawn blood cultures may be more likely to be positive reflecting catheter hub, connector, or intraluminal colonization, and many hospitals in the United States discourage blood culture collection from catheters in an effort to reduce reporting of central-line associated bloodstream infections to the Centers for Disease Control and Prevention. As such, clinical decisions are made regarding catheter removal or other therapeutic interventions based on incomplete and potentially inaccurate data. We urge clinicians to obtain catheter-drawn blood cultures when the catheter may be the source of suspected infection.

Disinfection of vascular catheter connectors that are protected by antiseptic caps is unnecessary.

OBJECTIVE: Determination of whether vascular catheter disinfecting antiseptic-containing caps alone are effective at decreasing microbial colonization of connectors compared to antiseptic-containing caps plus a 5-second alcohol manual disinfection. SETTING: The study was conducted in a 718-bed, tertiary-care, academic hospital. PATIENTS: A convenience sample of adult patients across intensive care units and acute care wards with peripheral and central venous catheters covered with antiseptic-containing caps. METHODS: Quality improvement study completed over 5 days. The standard-of-care group consisted of catheter connectors with antiseptic-containing caps cleaned with a 5-second alcohol wipe scrub prior to culture. The comparison group consisted of catheter connectors with antiseptic-containing caps without a 5-second alcohol wipe scrub prior to culture. The connectors were pressed directly onto blood agar plates and incubated. Plates were assessed for growth after 48-72 hours. RESULTS: In total, 356 catheter connectors were cultured: 165 in the standard-of-care group, 165 in the comparison group, and 26 catheters connectors without an antiseptic-containing cap, which were designated as controls. Overall, 18 catheter connectors (5.06%) yielded microbial growth. Of the 18 connectors with microbial growth, 2 (1.21%) were from the comparison group, 1 (0.61%) was from the standard-of-care group, and 15 were controls without an antiseptic-containing cap. CONCLUSIONS: Bacterial colonization rates were similar between the catheter connectors cultured with antiseptic-containing caps alone and catheter connectors with antiseptic-containing caps cultured after a 5-second scrub with alcohol. This finding suggests that the use of antiseptic-containing caps precludes the need for additional disinfection.

KPC-4 Is encoded within a truncated Tn4401 in an IncL/M plasmid, pNE1280, isolated from Enterobacter cloacae and Serratia marcescens.

We describe the transfer of bla(KPC-4) from Enterobacter cloacae to Serratia marcescens in a single patient. DNA sequencing revealed that KPC-4 was encoded on an IncL/M plasmid, pNE1280, closely related to pCTX-M360. Further analysis found that KPC-4 was encoded within a novel Tn4401 element (Tn4401f) containing a truncated tnpA and lacking tnpR, ISKpn7 left, and Tn4401 IRL-1, which are conserved in other Tn4401 transposons. This study highlights the continued evolution of Tn4401 transposons and movement to multiple plasmid backbones that results in acquisition by multiple species of Gram-negative bacilli.

Clinical outcomes associated with blood-culture contamination are not affected by utilization of a rapid blood-culture identification system.

OBJECTIVE: Contaminated blood cultures result in extended hospital stays and extended durations of antibiotic therapy. Rapid molecular-based blood culture testing can speed positive culture detection and improve clinical outcomes, particularly when combined with an antimicrobial stewardship program. We investigated the impact of a multiplex polymerase chain reaction (PCR) FilmArray Blood Culture Identification (BCID) system on clinical outcomes associated with contaminated blood cultures. METHODS: We conducted a retrospective cohort study involving secondary data analysis at a single institution. In this before-and-after study, patients with contaminated blood cultures in the period before PCR BCID was implemented (ie, the pre-PCR period; n = 305) were compared to patients with contaminated blood cultures during the period after PCR BCID was implemented (ie, the post-PCR implementation period; n = 464). The primary exposure was PCR status and the main outcomes of the study were length of hospital stay and days of antibiotic therapy. RESULTS: We did not detect a significant difference in adjusted mean length of hospital stay before (10.8 days; 95% confidence interval [CI], 9.8-11.9) and after (11.2 days; 95% CI, 10.2-12.3) the implementation of the rapid BCID panel in patients with contaminated blood cultures (P = .413). Likewise, adjusted mean days of antibiotic therapy between patients in pre-PCR group (5.1 days; 95% CI, 4.5-5.7) did not significantly differ from patients in post-PCR group (5.3 days; 95% CI, 4.8-5.9; P = .543). CONCLUSION: The introduction of a rapid PCR-based blood culture identification system did not improve clinical outcomes, such as length of hospital stay and duration of antibiotic therapy, in patients with contaminated blood cultures.

Hospital return-to-work practices for healthcare providers infected with severe acute respiratory coronavirus virus 2 (SARS-CoV-2).

A survey of academic medical-center hospital epidemiologists indicated substantial deviation from Centers for Disease Control and Prevention guidance regarding healthcare providers (HCPs) recovering from coronavirus disease 2019 (COVID-19) returning to work. Many hospitals continue to operate under contingency status and have HCPs return to work earlier than recommended.

Nosocomial outbreak of SARS-CoV-2 delta variant among vaccinated healthcare workers and immunocompromised patients on a solid-organ transplant unit: Complexities of an epidemiologic and genomic investigation.

In September 2021, a cluster of 6 patients with nosocomial coronavirus disease 2019 (COVID-19) were identified in a transplant unit. A visitor and 11 healthcare workers also tested positive for severe acute respiratory coronavirus virus 2 (SARS-CoV-2). Genomic sequencing identified 3 separate introductions of SARS-CoV-2 with related transmission among the identified patients and healthcare workers.

Patient-specific risk factors contributing to blood culture contamination.

Objective: Contaminated blood cultures result in extended hospital stays and unnecessary antibiotic therapy. Patient-specific factors associated with blood culture contamination remain largely unexplored. Identifying patients at higher risk of blood culture contamination could alert healthcare providers to take extra precautionary measures to limit contamination in these patients, and thereby prevent associated adverse outcomes. We sought to identify patient-related factors that contribute to blood culture contamination in hospitalized patients. Design and setting: We conducted a secondary data analysis of a retrospective cohort study at an academic medical center. Patients: Study participants included 19,255 adult patients who had blood culture(s) performed during a hospital admission between June 2014 and December 2016. Methods: Data were analyzed to evaluate risk factors for blood culture contamination using logistic regression. Results: Among adult patients, we identified 464 contaminated episodes and 11,010 negative blood-culture episodes. Chronic obstructive pulmonary disease (adjusted odds ratio [AOR], 1.67; 95% confidence interval [CI], 1.20-2.34) and stay in an intensive care unit (ICU) during an admission (AOR, 1.41; 95% CI, 1.14-1.74) were associated with blood culture contamination. Other risk factors included race, body mass index, and admission from the emergency department. Subgroup analyses of patients admitted from the emergency department showed similar results. Conclusions: We identified patient-specific factors that increase the odds of false-positive blood cultures. By introducing mitigation strategies to limit contamination in patients with these risk factors, it may be possible to reduce the adverse clinical impact of blood culture contamination.

Evaluation of cycle threshold values at deisolation.

The decision to discontinue isolation in hospitalized patients with persistently positive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) molecular testing is nuanced. Improvement in clinical status should be evaluated with expert consultation when considering whether discontinuation of isolation is appropriate. The cycle threshold value may serve as a useful adjunct to this decision-making process.

Improving antibiotic prescribing for acute bronchitis in the ambulatory setting using a multifaceted approach.

Antibiotics are frequently prescribed inappropriately for acute respiratory infections in the outpatient setting. We report the implementation of a multifaceted outpatient antimicrobial stewardship initiative resulting in a 12.3% absolute reduction of antibiotic prescribing for acute bronchitis in primary care clinics receiving active interventions.

Vancomycin susceptibility trends and prevalence of heterogeneous vancomycin-intermediate Staphylococcus aureus in clinical methicillin-resistant S. aureus isolates.

Due to the rise in methicillin-resistant Staphylococcus aureus (MRSA) infections and widespread use of vancomycin, MRSA isolates with reduced susceptibility to vancomycin are emerging (i.e., MIC creep). However, the prevalence of heterogeneous vancomycin-intermediate S. aureus (hVISA) is unknown due to the difficulty in detecting this phenotype. Recently, Etest glycopeptide resistance detection (GRD) strips have been developed to detect hVISA. This study assessed vancomycin susceptibility in MRSA isolates and determined the prevalence of hVISA by Etest GRD and population analysis profile-area under the curve ratio (PAP-AUC). The genetic backgrounds of 167 MRSA isolates collected from 2000 to 2008 were identified by pulsed-field gel electrophoresis. Vancomycin MICs were determined using Etest and two broth microdilution assays, MicroScan and Sensititre. Etest GRD was performed on all isolates, and those exhibiting a hVISA phenotype were further tested by PAP-AUC. The vancomycin MIC modes remained consistent at 1 µg/ml, as assessed by Sensititre and MicroScan. Etest reported a significant increase (mode MIC = 1.5 µg/ml) in the MIC between 2000 and 2008 (P < 0.01); however, this increase did not reflect a ≥ 2-fold change. In addition, the slight MIC increase did not increase linearly from 2000 to 2008, suggesting biological fluctuation, and is inconsistent with the concept of MIC creep. Etest GRD identified six hVISA isolates, two of which were confirmed to be hVISA by PAP-AUC. In conclusion, reduced vancomycin susceptibility was not detected in our hospital over a 9-year period using three different MIC methodologies, and the hVISA incidence was 1.2%, as determined by Etest GRD and PAP-AUC.

Validation and comparison of clinical prediction rules for invasive candidiasis in intensive care unit patients: a matched case-control study.

INTRODUCTION: Due to the increasing prevalence and severity of invasive candidiasis, investigators have developed clinical prediction rules to identify patients who may benefit from antifungal prophylaxis or early empiric therapy. The aims of this study were to validate and compare the Paphitou and Ostrosky-Zeichner clinical prediction rules in ICU patients in a 689-bed academic medical center. METHODS: We conducted a retrospective matched case-control study from May 2003 to June 2008 to evaluate the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of each rule. Cases included adults with ICU stays of at least four days and invasive candidiasis matched to three controls by age, gender and ICU admission date. The clinical prediction rules were applied to cases and controls via retrospective chart review to evaluate the success of the rules in predicting invasive candidiasis. Paphitou's rule included diabetes, total parenteral nutrition (TPN) and dialysis with or without antibiotics. Ostrosky-Zeichner's rule included antibiotics or central venous catheter plus at least two of the following: surgery, immunosuppression, TPN, dialysis, corticosteroids and pancreatitis. Conditional logistic regression was performed to evaluate the rules. Discriminative power was evaluated by area under the receiver operating characteristic curve (AUC ROC). RESULTS: A total of 352 patients were included (88 cases and 264 controls). The incidence of invasive candidiasis among adults with an ICU stay of at least four days was 2.3%. The prediction rules performed similarly, exhibiting low PPVs (0.041 to 0.054), high NPVs (0.983 to 0.990) and AUC ROCs (0.649 to 0.705). A new prediction rule (Nebraska Medical Center rule) was developed with PPVs, NPVs and AUC ROCs of 0.047, 0.994 and 0.770, respectively. CONCLUSIONS: Based on low PPVs and high NPVs, the rules are most useful for identifying patients who are not likely to develop invasive candidiasis, potentially preventing unnecessary antifungal use, optimizing patient ICU care and facilitating the design of forthcoming antifungal clinical trials.

Prevention of Central-Line Associated Bloodstream Infections: 2021 Update.

Despite a large volume of research in prevention, central line-associated bloodstream infections and catheter-related bloodstream infections continue to cause significant morbidity, mortality, and increased health care costs. Strategies in prevention, including decision about catheter placement, insertion bundles, adherence to standard of care guidelines, and technologic innovations, shown to decrease rates of catheter-related bloodstream infections and central line-associated bloodstream infections are described in this update. The coronavirus disease 2019 pandemic has resulted in increased health care-acquired infections, including central line-associated bloodstream infections.