Clinical and economic evaluation of blood culture whole process optimisation in critically ill adult patients with positive blood cultures.

OBJECTIVES: Optimising blood culture processing is important to ensure that bloodstream infections are accurately diagnosed while minimising adverse events caused by antibiotic abuse. This study aimed to evaluate the impact of optimised blood culture processes on antibiotic use, clinical outcomes and economics in intensive care unit (ICU) patients with positive blood cultures. METHODS: From March 2020 to October 2021, this microbiology laboratory implemented a series of improvement measures, including the clinical utility of Fastidious Antimicrobial Neutralization (FAN® PLUS) bottles for the BacT/Alert Virtuo blood culture system, optimisation of bottle reception, graded reports and an upgraded laboratory information system. A total of 122 ICU patients were included in the pre-optimisation group from March 2019 to February 2020, while 179 ICU patients were included in the post-optimisation group from November 2021 to October 2022. RESULTS: Compared with the pre-optimisation group, the average reporting time of identification and antimicrobial sensitivity was reduced by 16.72 hours in the optimised group. The time from admission to targeted antibiotic therapy within 24 hours after receiving both the Gram stain report and the final report were both significantly less in the post-optimisation group compared with the pre-optimisation group. The average hospitalisation time was reduced by 6.49 days, the average antimicrobial drug cost lowered by $1720.85 and the average hospitalisation cost by $9514.17 in the post-optimisation group. CONCLUSIONS: Optimising blood culture processing was associated with a significantly increased positive detection rate, a remarkable reduction in the length of hospital stay and in hospital costs for ICU patients with bloodstream infections.

Rapid Detection of Carbapenemase-producing Enterobacteriaceae From Blood Culture Bottles of Known CPE Carriers: Real-world Experience.

We used a rapid antigen test for the detection of carbapenemases directly from positive blood culture bottles of pediatric hemato-oncologic patients, known carriers of carbapenemase-producing enterobacteriaceae. Resistance mechanism was detected within 15 minutes of observing Gram-negative bacilli from a positive bottle, leading to treatment modification. This simple-to-use, inexpensive assay shortens the interval between empiric to tailored antimicrobial therapy.

Current Clinical Methods for Detection of Peri-Prosthetic Joint Infection.

Background: Currently, one of the most pressing problems in the field of orthopedic surgery is peri-prosthetic joint infection [PJI]. While there are numerous ways to detect PJI, current clinical detection methods differ across institutions and have varying criteria and protocols. Some of these methods include the Modified Musculoskeletal Infection Society system, culturing, polymerase chain reaction, the determination of the presence of certain biomarkers, testing for the presence of alpha defensin peptides, and leukocyte level testing. Methods: This review summarizes the most recent publications in the field of PJI detection to highlight current strengths as well as provide future directions to find the system for the quickest, cost-effective, and most accurate way to diagnose these types of infections. Results: The results of this literature review suggest that, while each method of diagnosis has its advantages, each has various drawbacks as well. Current methods can be expensive, take days to weeks to complete, be prone to contamination, and can produce ambiguous results. Conclusions: The findings in this review emphasize the need for a more comprehensive and accurate system for diagnosing PJI. In addition, the specific comparison of advantages and drawbacks can be useful for researchers and clinicians with goals of creating new diagnostic tests for PJIs, as well as in clinical scenarios to determine the correct treatment for patients.

A simplified blood culture sampling protocol for reducing contamination and costs: a randomized controlled trial.

OBJECTIVES: Blood culture contamination carries risks for patients, such as unnecessary antimicrobial therapy and other additional hazards and costs. One method shown to be effective in reducing contamination is initial blood specimen diversion during collection. We hypothesized that initial blood specimen diversion without a designated device or procedure would suffice for reduction in blood culture contamination rate. METHODS: From 1 September 2017 through to 6 September 2018, we conducted a randomized controlled trial to assess the effect of an initial-specimen diversion technique (ISDT) on the rate of blood-culture contamination by changing the order of sampling using regular vacuum specimen tubes instead of commercially available sterile diversion devices. We included adults from whom the treating physician planned to take blood cultures and additional blood chemistry tests. Additionally, we evaluated the potential economic benefits of an ISDT. This was a researcher-initiated trial, Clinicaltrials.gov NCT03088865. RESULTS: In all, 756 patients were enrolled. This method, compared with the standard procedure in use at our medical centre, reduced contamination by 66% (95% CI 17%-86%), from 20/400 (5%) with the standard method to 6/356 (1.6%) with the ISDT, without compromising detection of true bloodstream infection and at no additional cost. Hospital-wide implementation of ISDT was associated with a 1.1% saving in hospitalization days. CONCLUSIONS: We offer this novel approach as a simple, cost-effective measure to reduce risks to patient safety from contaminated blood cultures, without the need for using costly devices.

Advances in Rapid Molecular Blood Culture Diagnostics: Healthcare Impact, Laboratory Implications, and Multiplex Technologies.

BACKGROUND: For far too long, the diagnosis of bloodstream infections has relied on time-consuming blood cultures coupled with traditional organism identification and susceptibility testing. Technologies to define the culprit in bloodstream infections have gained sophistication in recent years, notably by application of molecular methods. CONTENT: In this review, we summarize the tests available to clinical laboratories for molecular rapid identification and resistance marker detection in blood culture bottles that have flagged positive. We explore the cost-benefit ratio of such assays, covering aspects that include performance characteristics, effect on patient care, and relevance to antibiotic stewardship initiatives. SUMMARY: Rapid blood culture diagnostics represent an advance in the care of patients with bloodstream infections, particularly those infected with resistant organisms. These diagnostics are relatively easy to implement and appear to have a positive cost-benefit balance, particularly when fully incorporated into a hospital's antimicrobial stewardship program.

Time to clinical response in sepsis associated with an algorithm for blood-culture pathogen identification using matrix-assisted laser desorption ionization time-of-flight mass spectroscopy.

PURPOSE: Antimicrobial stewardship programs (ASPs) can be aided by using rapid diagnostics (RDT). However, there are limited data evaluating the impact of ASPs and RDT on sepsis outcomes in the setting of the new Sepsis-3 guidelines. This study evaluates the impact of a low-resource method for ASPs with RDT on sepsis outcomes. METHODS: This was a prospective, quasi-experimental study with a retrospective double pretest. Patients ≥ 18 years old with sepsis and concurrent bacteremia or fungemia were included; patients who were pregnant, had polymicrobial septicemia or who were transferred from an outside hospital were excluded. In the first pretest (O1), polymerase chain reaction was used to identify Staphylococcal species from positive blood cultures, and traditional laboratory techniques were used to identify other species. Matrix-assisted laser desorption ionization time-of-flight mass spectroscopy and FilmArray were implemented in the second pretest (O2), and twice daily blood culture review was implemented in the posttest (O3). RESULTS: A total of 394 patients (157 in O1, 176 in O2, 61 in O3) were enrolled. Clinical response was 73.2%, 83.5%, and 88.5% in O1, O2, and O3, respectively, p = 0.013. By Cox regression, the O3 was associated with improved time to clinical response (hazard ratio, 1.388; 95% confidence interval, 1.004-1.919) as compared with O1. Mortality, hospital length of stay, and intensive care unit length of stay were unchanged between groups. CONCLUSION: Twice-daily blood culture review may be useful for implementing rapid diagnostics within low-resource ASPs. Further research is needed to identify the optimal method of blood culture follow-up within low-resource settings.

Cost-effectiveness of molecular diagnostic assays for the therapy of severe sepsis and septic shock in the emergency department.

OBJECTIVES: Sepsis presents a major burden to the emergency department (ED). Because empiric inappropriate antimicrobial therapy (IAAT) is associated with increased mortality, rapid molecular assays may decrease IAAT and improve outcomes. We evaluated the cost-effectiveness of molecular testing as an adjunct to blood cultures in patients with severe sepsis or septic shock evaluated in the ED. METHODS: We developed a decision analysis model with primary outcome the incremental cost-effectiveness ratio expressed in terms of deaths averted. Costs were dependent on the assay price and the patients' length of stay (LOS). Three base-case scenarios regarding the difference in LOS between patients receiving appropriate (AAT) and IAAT were described. Sensitivity analyses regarding the assay cost and sensitivity, and its ability to guide changes from IAAT to AAT were performed. RESULTS: Under baseline assumptions, molecular testing was cost-saving when the LOS differed by 4 days between patients receiving IAAT and AAT (ICER -$7,302/death averted). Our results remained robust in sensitivity analyses for assay sensitivity≥52%, panel efficiency≥39%, and assay cost≤$270. In the extreme case that the LOS of patients receiving AAT and IAAT was the same, the ICER remained≤$20,000/death averted for every studied sensitivity (i.e. 0.5-0.95), panel efficiency≥34%, and assay cost≤$313. For 2 days difference in LOS, the bundle approach was dominant when the assay cost was≤$135 and the panel efficiency was≥77%. CONCLUSIONS: The incorporation of molecular tests in the management of sepsis in the ED has the potential to improve outcomes and be cost-effective for a wide range of clinical scenarios.

Cost-effectiveness of rapid diagnostic assays that perform directly on blood samples for the diagnosis of septic shock.

Molecular diagnostic assays that test directly whole blood provide the ability to decrease inappropriate antimicrobial therapy and improve survival in patients with septic shock. We developed a decision analysis model to evaluate the cost-effectiveness of the addition of molecular assays to blood cultures in adults admitted to medical ICUs with septic shock. Under baseline assumptions, the use of molecular diagnostic methods was cost-saving in all cases that the length of hospital stay differed by 2 and 4 days between patients receiving appropriate and inappropriate antimicrobial therapy. In the case that the length of stay was the same, the use of molecular methods was cost-effective with an estimated incremental cost-effectiveness ratio (ICER) < $3000 per death averted. In the extreme that the length of stay between the 2 groups was the same, the highest cost reached was when the cost of the assay was $1000, with the estimated ICER being < $20,000 per death averted.

Economic health care costs of blood culture contamination: A systematic review.

BACKGROUND: Blood culture contamination with gram-positive organisms is a common occurrence in patients suspected of bloodstream infections, especially in emergency departments. Although numerous research studies have investigated the cost implications of blood culture contamination, a contemporary systematic review of the literature has not been performed. The aim of this project was to perform a systematic review of the published literature on the economic costs of blood culture contamination. METHODS: PubMed was searched (January 1, 1978, to July 15, 2018) using the search terms "blood culture contamination" or "false-positive blood cultures." Articles were title searched and abstracts were reviewed for eligible articles that reported immediate or downstream economic costs of blood culture contamination. RESULTS AND DISCUSSION: The PubMed search identified 151 relevant articles by title search, with 49 articles included after abstract review. From the studies included, overall blood culture contamination rates ranged from 0.9%-41%. Up to 59% of patients received unnecessary treatment with parenteral vancomycin as a result of blood culture contamination, resulting in increased pharmacy charges between $210 and $12,611 per patient. Increases in total laboratory charges between $2,397 and $11,152 per patient were reported. Attributable hospital length of stay increases due to blood culture contamination ranged from 1-22 days. CONCLUSIONS: This systematic review of the literature identified several areas of health care expenditure associated with blood culture contamination. Interventions to reduce the risk of blood culture contamination would avoid downstream economic costs.

Prospective evaluation of rapid antimicrobial susceptibility testing by disk diffusion on Mueller-Hinton rapid-SIR directly on blood cultures.

BACKGROUND: With the worldwide spread of antibiotic resistance, delivering antibiotic susceptibility test (AST) results in a timely manner represents a major challenge. In cases of sepsis, rapid AST may facilitate early optimization of empiric antibiotic therapy. Disc diffusion is a well-standardized AST method, however 16 to 24 h are required to achieve an overall AST profile according to antimicrobial societies. METHODS: In this prospective pilot study, we evaluated the performance of Mueller-Hinton-Rapid-SIR (MHR-SIR) agar after 6-8 h of incubation in comparison with standard MH agar after 16 h of incubation directly on positive blood cultures caused by Enterobacteriaceae and Staphylococcus aureus from routine clinical microbiology. A total of 133 positive blood samples including 110 Enterobacteriaceae (83%) and 23 Staphylococcus aureus (17%) were tested in parallel by two direct AST methods, each using EUCAST breakpoints. For each combination bacterium and antibiotic, we compared the categorical agreement and the correlation between the diameters obtained by MHR-SIR and by standard MH. RESULTS: Our results showed 97.7% categorical agreement for Enterobacteriaceae, with 1.4% minor errors, 0.4% major errors and 0.5% very major errors. For S. aureus, we observed 97.8% categorical agreement, 1.9% minor errors, 0.3% major errors and no very major errors. CONCLUSION: Our results showed excellent categorical agreement and correlations between diameters for MHR-SIR and standard MH methods. MHRSIR can predict the result of overall AST profile within 6-8 h with reliable results. AST is obtained on the same day the blood culture becomes positive, with a very moderate cost.

Variation in Diagnostic Test Use and Associated Outcomes in Staphylococcal Scalded Skin Syndrome at Children's Hospitals.

OBJECTIVES: The incidence of staphylococcal scalded skin syndrome (SSSS) is rising, but current practice variation in diagnostic test use is not well described. Our aim was to describe the variation in diagnostic test use in children hospitalized with SSSS and to determine associations with patient outcomes. METHODS: We performed a retrospective (2011-2016) cohort study of children aged 0 to 18 years from 35 children's hospitals in the Pediatric Health Information System database. Tests included blood culture, complete blood count, erythrocyte sedimentation rate, C-reactive protein level, serum chemistries, and group A streptococcal testing. K-means clustering was used to stratify hospitals into groups of high (cluster 1) and low (cluster 2) test use. Associations between clusters and patient outcomes (length of stay, cost, readmissions, and emergency department revisits) were assessed with generalized linear mixed-effects modeling. RESULTS: We included 1259 hospitalized children with SSSS; 84% were ≤4 years old. Substantial interhospital variation was seen in diagnostic testing. Blood culture was the most commonly obtained test (range 62%-100%), with the most variation seen in inflammatory markers (14%-100%). Between hospital clusters 1 and 2, respectively, there was no significant difference in adjusted length of stay (2.6 vs 2.5 days; P = .235), cost ($4752 vs $4453; P = .591), same-cause 7-day readmission rate (0.8% vs 0.4%; P = .349), or emergency department revisit rates (0.1% vs 0.6%; P = .148). CONCLUSIONS: For children hospitalized with SSSS, lower use of diagnostic tests was not associated with changes in outcomes. Hospitals with high diagnostic test use may be able to reduce testing without adversely affecting patient outcomes.

Adverse Economic Impact Associated With Blood Culture Contamination in a Pediatric Emergency Department.

BACKGROUND: Blood culture contamination (BCC) leads to unnecessary interventions including hospitalization, antibiotic administration and additional laboratory tests. Previous studies in adults revealed that BCC was associated with unnecessary financial expenditures. However, information pertaining to the pediatric population is limited. Therefore, we investigated the details of the adverse economic impact associated with BCC in a pediatric emergency department (ED) in Japan. METHODS: This study was a retrospective, observational study. We collected data on blood cultures performed in patients 18 years of age in a pediatric ED. Medical records of patients with positive blood cultures were reviewed, and the information regarding adverse events related to BCC was extracted. Medical costs related to BCC were estimated from the data. RESULTS: In total, 13,139 sets of blood cultures were performed from April 2013 to June 2016, and 141 cases (1.1%) of BCC were identified. Among these, 106 patients (75%) experienced at least 1 adverse event associated with BCC. The total medical cost due to BCC was 4,076,713 Japanese yen. Multifaceted approaches targeting ED physicians including lectures on optimal blood collection methods and monthly feedback on BCC rates were effective in reducing the BCC rate and its related costs. CONCLUSIONS: Interventions associated with BCC were common and accounted for significant adverse economic impact on pediatric patients. Regular education and monitoring were effective in reducing BCC and its related costs.

Follow-up Blood Cultures in Gram-Negative Bacteremia: Are They Needed?

BACKGROUND: Bloodstream infections remain a major cause of morbidity and mortality. Gram-negative bacilli (GNB) bacteremia is typically transient and usually resolves rapidly after the initiation of appropriate antibiotic therapy and source control. The optimal duration of treatment and utility of follow-up blood cultures (FUBC) have not been studied in detail. Currently, the management of gram-negative bacteremia is determined by clinical judgment. To investigate the value of repeat blood cultures, we analyzed 500 episodes of bacteremia to determine frequency of FUBC and identify risk factors for persistent bacteremia. METHODS: Of 500 episodes of bacteremia, we retrospectively analyzed 383 (77%) that had at least 1 FUBC. We sought information regarding presumed source of bacteremia, antibiotic status at the time of FUBC, antibiotic susceptibility, presence of fever, comorbidities (intravenous central lines, urinary catheters, diabetes mellitus, AIDS, end-stage renal disease, and cirrhosis), need for intensive care, and mortality. RESULTS: Antibiotic use did not affect the rate of positivity of FUBC, unless bacteria were not sensitive to empiric antibiotic. Fever on the day of FUBC was associated with higher rates of positive FUBC for gram-positive cocci (GPC) but not GNB. Mortality and care in the intensive care unit were not associated with positive FUBC. Seventeen FUBC and 5 FUBC were drawn for GNB and GPC to yield 1 positive result. CONCLUSIONS: FUBC added little value in the management of GNB bacteremia. Unrestrained use of blood cultures has serious implications for patients including increased healthcare costs, longer hospital stays, unnecessary consultations, and inappropriate use of antibiotics.

Impact of rapid identification of positive blood cultures using the Verigene system on antibiotic prescriptions: A prospective study of community-onset bacteremia in a tertiary hospital in Japan.

BACKGROUND: Rapid identification of positive blood cultures is important for initiation of optimal treatment in septic patients. Effects of automated, microarray-based rapid identification systems on antibiotic prescription against community-onset bacteremia (COB) remain unclear. METHODS: We prospectively enrolled 177 patients with 185 COB episodes (occurring within 72 h of admission) over 17 months. Bacteremia episodes due to gram-positive bacteria (GP) and gram-negative bacteria (GN) in the same patient were counted separately. For GP bacteremia, patients with ≥2 sets of positive blood cultures were included. The primary study objective was evaluating the rates of antibiotic prescription changes within 2 days of rapid identification using the Verigene system. RESULTS: Bacteremia due to GN and GP included 144/185 (77.8%) and 41/185 (22.2%) episodes, respectively. Antibiotic prescription changes occurred in 51/185 cases (27.6% [95%CI:21.3-34.6%]) after Verigene analysis and 70/185 cases (37.8% [30.8-45.2%]) after conventional identification and susceptibility testing. Prescription changes after Verigene identification were more frequent in GP (17/41[41.5%]) than in GN (34/144[23.5%]). Among bacteremia due to single pathogen targeted by Verigene test, bacterial identification agreement between the two tests was high (GP: 38/39[97.4%], GN: 116/116[100%]). The Verigene test correctly predicted targeted antimicrobial resistance. The durations between the initiation of incubation and reporting of the results for the Verigene system and conventional test was 28.3 h (IQR: 25.8-43.4 h) and 90.6 h (68.3-118.4 h), respectively. In only four of the seven episodes of COB in which two isolates were identified by conventional tests, the Verigene test correctly identified both organisms. CONCLUSION: We observed a high rate of antibiotic prescription changes after the Verigene test in a population with COB especially in GP. The Verigene test would be a useful tool in antimicrobial stewardship programs among patients with COB.

Addressing the risk of bacterial contamination in platelets: a hospital economic perspective.

BACKGROUND: Bacterially contaminated platelets (PLTs) remain a serious risk. The Food and Drug Administration has issued draft guidance recommending hospitals implement secondary testing or transfuse PLTs that have been treated with pathogen reduction technology (PRT). The cost implications of these approaches are not well understood. STUDY DESIGN AND METHODS: We modeled incurred costs when hospitals acquire, process, and transfuse PLTs that are PRT treated with INTERCEPT (Cerus Corp.) or secondary tested with the PLT PGD Test (Verax Biomedical). RESULTS: Hospitals will spend $221.27 (30.0%) more per PRT-treated apheresis PLT unit administered compared to a Zika-tested apheresis PLT unit that is irradiated and PGD tested in hospital. This difference is reflected in PRT PLT units having: 1) a higher hospital purchase price ($100.00 additional charge compared to an untreated PLT); 2) lower therapeutic effectiveness than untreated PLTs among hematologic-oncologic patients, which contributes to additional transfusions ($96.05); or 3) fewer PLT storage days, which contributes to higher outdating cost from expired PLTs ($67.87). Only a small portion of the incremental costs for PRT-treated PLTs are offset by costs that may be avoided, including primary bacterial culture, secondary bacterial testing ($26.65), hospital irradiation ($8.50), Zika testing ($4.47), and other costs ($3.03). CONCLUSION: The significantly higher cost of PRT-treated PLTs over PGD-tested PLTs should interest stakeholders. For hospitals that outdate PLTs, savings associated with expiration extension to 7 days by adding PGD testing will likely be substantially greater than the cost of implementing PGD-testing. Our findings might usefully inform a hospital's decision to select a particular blood safety approach.

Routine Workup of Postoperative Pyrexia Following Total Joint Arthroplasty Is Only Necessary in Select Circumstances.

BACKGROUND: It is unclear when routine workup of postoperative pyrexia (POP) following total joint arthroplasty (TJA) should be performed. METHODS: A retrospective electronic database search was conducted on 25,558 consecutive patients undergoing primary or revision TJA between June 2001 and June 2013. We identified patient demographics, procedure type, characteristics of feverish patients, and febrile complications. The estimated costs for chest x-ray (CXR), urinalysis, urine culture, and blood culture were investigated. RESULTS: POP occurred in 46% of TJAs. A total of 11,589 separate workups were performed in 90.5% of POP patients, of which 2.4% were positive. Urinalysis, urine culture, blood culture, and CXR were positive in 38.7%, 9.5%, 7.0%, and 0.2%, respectively. Febrile complications occurred in 4.5% and the infectious complications rate was 2.0%. The positive rate of fever workups was significantly higher in patients with the first POP occurring after postoperative day 3, POP > 102°F, multiple fever spikes, and patients undergoing revision TJA. Multivariate logistic regression revealed that the time of first POP, the maximum temperature, multiple fever spikes, and revision TJA were independent predictors of febrile complications. The estimated cost for 11,319 negative workups in patients with POP was $4,636,976.80, with CXR costing $4,613,182.00. CONCLUSION: Selective workup of POP following TJA should be performed in patients with higher temperatures, fever occurring after postoperative day 3, those with multiple fever spikes, and those undergoing revision TJA. CXR with an extremely low positive rate should not routinely be ordered.

Preparation of positive blood cultures for direct MALDI-ToF MS identification.

MALDI-ToF MS can be used to identify microorganisms directly from blood cultures. This study compared two methods of sample preparation. Similar levels of genus- (91% vs 90%) and species-level identifications (79% vs 74%) were obtained with differential centrifugation and SDS methods. The SDS method is faster and requires minimal handling.