Study protocol of associated criteria used in investigating septic transfusion reactions (STRs): A scoping review about available evidence.

BACKGROUND AND OBJECTIVE: Assessment criteria for septic transfusion reactions (STRs) are variable around the world. A scoping review will be carried out to find out, explore and map existing literature on STRs associated criteria. METHODS: This scoping review will include indexed and grey literatures available in English or French language from January 1, 2000, to December 31, 2021. Literature search will be conducted using four electronic databases (i.e., MEDLINE via PubMed, Web of Science, Science Direct, and Embase via Ovid), and grey literatures accompanying the research questions and objectives. Based on the inclusion criteria, studies will be independently screened by two reviewers for title, abstract, and full text. Extracted data will be presented in tabular form followed by a narrative description of inputs corresponding to research objectives and questions.

Limitations of current practices in detection of bacterially contaminated blood products associated with suspected septic transfusion reactions.

BACKGROUND: In the setting of suspected septic transfusion reactions, bacterial culture of both the transfused patient and the residual blood component is recommended. Primary bacterial contamination can occur at the time of component collection. Clinically insignificant "secondary contamination" can occur during post-transfusion component discard, retrieval for culture, or manipulation of the bag at the time of culture sampling. STUDY DESIGN AND METHODS: This retrospective, multi-center study analyzes positive residual component culture results and companion patient blood cultures from 15 hospitals, 1 blood center, and all cultured transfusion reactions within the province of Quebec, Canada, over a 5-year period. Imputability was assigned as "definite" (concordant growth), "possible" (discordant growth or lack of growth in patient culture), or "unable to assess" (patient not cultured). RESULTS: There were 373 positive component cultures from 360 unique transfusion reactions, with 276 (76.7%) companion patient blood cultures performed, of which 10 (2.8%) yielded the pathogen detected in the positive component. Of these 10 definite pathogens, 7 (2 Staphylococcus aureus, 3 other staphylococci, and 1 Streptococcus pyogenes and 1 Bacillus sp.) were associated with platelet and 3 (Aeromonas veronii, Staphylococcus epidermidis, and Enterococcus faecalis) with RBC transfusions. RBC and plasma components comprised 70% of positive component cultures. DISCUSSION: The process of performing residual component culture is vulnerable to secondary contamination. The significance of microorganisms recovered from component culture cannot be interpreted in isolation. In the context of low prevalence of primary contamination of blood components, the positive predictive value of a positive component culture result is very low.

Fatal sepsis associated with a storage container leak permitting platelet contamination with environmental bacteria after pathogen reduction.

BACKGROUND: Pathogen reduction technology and enhanced bacterial culture screening promise to significantly reduce the risk of transfusion-associated septic reactions due to contaminated platelets. Recent reports suggest that these interventions lack efficacy for post-collection and processing contamination with environmental organisms if the storage bag integrity is compromised. CASE REPORT: We report a fatal septic transfusion reaction in a 63-year-old patient with chronic kidney and liver disease who received a pathogen reduced platelet transfusion in anticipation of surgery. METHODS: The residual platelet concentrate was cultured, with the detected microorganisms undergoing 16S genotype sequencing. Separate pathogen reduction studies were performed on the recovered bacteria, including assessment for amotosalen photoproducts. The storage container was subjected to pressure testing and microscopic examination. Environmental culture screening was performed at the hospital. RESULTS: Gram negative rods were detected in the platelet unit and cultures of both platelet component and the patient's blood grew Acinetobacter baumannii complex, Leclercia adecarboxylata and Staphylococcus saprophyticus. These strains were effectively inactivated with >7.2, 7.7, and >7.1 log10 kill, respectively. The platelet storage container revealed a leak visible only on pressure testing. Hospital environmental cultures were negative and the contamination source is unknown. A. baumannii complex and S. saprophyticus 16S genotyping sequences were identical to those implicated in a previously reported septic reaction. CONCLUSION: Findings are compatible with post-processing environmental contamination of a pathogen reduced platelet concentrate via a non-visible, acquired storage container leak. Efforts are warranted to actively prevent damage to, and detect defects in, platelet storage containers, and to store and transport components in clean environments.

The impact of the sample time of secondary bacterial culture on the risk of exposure to contaminated platelet components: A mathematical analysis.

BACKGROUND: The US Food and Drug Administration (FDA) issued a guidance for bacterial risk control strategies for platelet components in September 2019 that includes strategies using secondary bacterial culture (SBC). While an SBC likely increases safety, the optimal timing of the SBC is unknown. Our aim was to develop a model to provide insight into the best time for SBC sampling. STUDY DESIGN AND METHODS: We developed a mathematical model based on the conditional probability of a bacterial contamination event. The model evaluates the impact of secondary culture sampling time over a range of bacterial contamination scenarios (lag and doubling times), with the primary outcome being the optimal secondary sampling time and the associated risk. RESULTS: Residual risk of exposure decreased with increasing inoculum size, later sampling times for primary culture, and using higher thresholds of exposure (in colony-forming units per milliliter). Given a level of exposure, the optimal sampling time for secondary culture depended on the timing of primary culture and on the expiration time. In general, the optimal sampling time for secondary culture was approximately halfway between the time of primary culture and the expiration time. CONCLUSION: Our model supports that the FDA guidance is quite reasonable and that sampling earlier in the specified secondary culture windows may be most optimal for safety.

The incremental benefit of anaerobic culture for controlling bacterial risk in platelets: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Septic transfusion reactions are a principal cause of transfusion-related mortality. The frequency of detectable bacterial contamination is greater in platelets compared to other blood components because platelets are stored at room temperature. Most strategies outlined in the September 2019 FDA guidance require both aerobic culture (AC) and anaerobic culture (AnC) testing. We performed a systematic review and meta-analysis in an effort to provide the best available estimate of the effectiveness of AnC. MATERIALS AND METHODS: Our analysis was performed according to published guidelines. Broad and context-specific meta-analyses of bacterial detection rates in platelets by AnC were performed to assess the practical effectiveness of AnC as a risk control measure. RESULTS: Seven studies with a total of 1 767 014 tested platelet components were included for analysis. With exclusion of positives due to Cutibacterium/Propionibacterium species and redundancy due to AC results, AnC detected 0·06 contamination events per thousand (EPT) components tested, twofold lower than the AC (0·12 EPT). CONCLUSION: Excluding Cutibacterium/Propionibacterium species, AnC detects occasional bacterial contamination events that are not detected by AC (~1 in 17 000 platelet components).

Clinical Case of a Transfusion-Associated Canine Mycoplasma haemocanis Infection in the Republic of Korea: A Case Report.

This report describes the first clinical case of a transfusion-associated Mycoplasma haemocanis infection in a dog in Korea. A 6-year-old male Maltese underwent a red blood cell transfusion for idiopathic immune-mediated hemolytic anemia. Eighteen days after the blood transfusion, the recipient's packed cell volume decreased and basophilic organisms were found on erythrocytes. A polymerase chain reaction and sequential analysis showed that both the donor dog and recipient dog had M. haemocanis. Six weeks after doxycycline administration, no organisms were detected and the recipient's anemia had improved.

Sepsis from an apheresis platelet contaminated with Acinetobacter calcoaceticus/baumannii complex bacteria and Staphylococcus saprophyticus after pathogen reduction.

BACKGROUND: Strategies to reduce platelet (PLT) bacterial contamination include donor screening, skin disinfection, sample diversion, bacterial culture, pathogen reduction (PR), and day-of-transfusion tests. We report bacterial sepsis following a pathogen-reduced PLT transfusion. CASE REPORT: An adult male with relapsed acute lymphoblastic leukemia was successfully treated for central catheter-associated Staphylococcus aureus bacteremia. A peripherally inserted central catheter (PICC) was placed. Chills, rigors, and flushing developed immediately after PICC-infused pathogen-reduced PLTs, progressing to septic shock requiring intensive care management. METHODS: PICC and peripheral blood (PB), transfused bag saline flushes (TBFs), environmental samples, and the pathogen-reduced untransfused co-component (CC) were cultured. Plasma metagenomic and bacterial isolate whole-genome sequencing; PLT mitochondrial DNA (mtDNA) testing of untransfused CC and TBF; CC testing for amotosalen (S-59)/S-59 photoproducts; isolate PR studies (INTERCEPT); and TBF polymerase chain reaction for recipient Y-chromosome DNA were performed. RESULTS: PB and PICC cultures grew Acinetobacter calcoaceticus/baumannii complex (ACBC). TBF was gram-positive; mass spectrometry identified ACBC and Staphylococcus saprophyticus (SS). CC Gram stain and cultures were negative. Environmental cultures, some done after decontamination, were ACBC/SS negative. Posttransfusion patient plasma and TBF ACBC sequences were genetically identical. No Y-chromosome signal was detected in TBF. S-59 photoproducts and evidence of mtDNA amplification inhibition were found in the CC. Spiking PR studies showed >5.9-log inactivation for both isolates. Donor skin cultures for Acinetobacter were negative. CONCLUSION: CC sterility, PR studies, residual S-59 photoproducts, and mtDNA amplification inhibition suggest successful PR. Unidentified environmental sources and inherent or acquired bag defects may have contributed to postmanufacturing pathogen-reduced PLT contamination.

Secondary bacterial culture of platelets to mitigate transfusion-associated sepsis: A 3-year analysis at a large academic institution.

BACKGROUND: In 2019, the United States Food and Drug Administration published its final recommendations to mitigate bacterial contamination of platelets. We sought to evaluate our secondary bacterial culture (SBC) strategy in light of those recommendations. STUDY DESIGN AND METHODS: A retrospective analysis was conducted of SBC data (October 2016-2019) at our institution. SBC was performed upon receipt (Day 3 after collection); 5 mL of platelet product was inoculated aseptically into an aerobic bottle and incubated at 35°C for 3 days. For 8 months, a 10-mL inoculum was trialed. No quarantine was applied. All positive cultures underwent Gram staining and repeat culture of the platelet product (if available). A probable true positive was defined as concordant positive culture between the initial and repeat culture. The incidence of probable true- and false-positive cultures were reported descriptively and differences evaluated by sampling volume. RESULTS: Over 3 years, 55 896 platelet products underwent SBC, yielding 30 initial positive results (approx. 1/1863 platelets); 25 (83.3%) signaled within 24 hours of SBC. The rates of probable true positive, false positive, and indeterminate for 5 mL were 0.027% (1/3771), 0.002% (1/45 251) and 0.018% (1/5656), respectively. The respective rates for 10 mL were 0.018% (1/5323), 0.07% (1/1521), and 0%. Seven of eight (87.5%) false-positive SBCs occurred with a 10-mL inoculum. No septic transfusion reactions were reported. CONCLUSION: SBC continues to interdict bacterially contaminated units of platelets. Our findings suggest higher rates of false positivity using large-volume inocula.

Residual bacterial detection rates after primary culture as determined by secondary culture and rapid testing in platelet components: A systematic review and meta-analysis.

BACKGROUND: Primary culture alone was a bacterial risk control strategy intended to facilitate interdiction of contaminated platelets (PLTs). A September 2019 FDA guidance includes secondary testing options to enhance safety. Our objective was to use meta-analysis to determine residual contamination risk after primary culture using secondary culture and rapid testing. STUDY DESIGN AND METHODS: A December 2019 literature search identified articles on PLT bacterial detection rates using primary culture and a secondary testing method. We used meta-analysis to estimate secondary testing detection rates after a negative primary culture. We evaluated collection method, sample volume, sample time, and study date as potential sources of heterogeneity. RESULTS: The search identified 6102 articles; 16 were included for meta-analysis. Of these, 12 used culture and five used rapid testing as a secondary testing method. Meta-analysis was based on a total of 103 968 components tested by secondary culture and 114 697 by rapid testing. The residual detection rate using secondary culture (DRSC ) was 0.93 (95% CI, 0.24-0.6) per 1000 components, while residual detection rate using rapid testing (DRRT ) was 0.09 (95% CI, 0.01-0.25) per 1000 components. Primary culture detection rate was the only statistically significant source of heterogeneity. CONCLUSION: We evaluated bacterial detection rates after primary culture using rapid testing and secondary culture. These results provide a lower and upper bound on real-world residual clinical risk because these methods are designed to detect high-level exposures or any level of exposure, respectively. Rapid testing may miss some harmful exposures and secondary culture may identify some clinically insignificant exposures.

Bacterial contamination and septic transfusion reaction rates associated with platelet components before and after introduction of primary culture: experience at a US Academic Medical Center 1991 through 2017.

BACKGROUND: The high incidence of septic transfusion reactions (STRs) led to testing being mandated by AABB from 2004. This was implemented by primary culture of single-donor apheresis platelets (APs) from 2004 and prestorage pooled platelets (PSPPs) from 2007. STUDY DESIGN/METHODS: Platelet (PLT) aliquots were cultured at issue and transfusion reactions evaluated at our hospital. Bacterial contamination and STR rates (shown as rates per million transfusions in Results) were evaluated before and after introduction of primary culture by blood centers that used a microbial detection system (BacT/ALERT, bioMerieux) or enhanced bacterial detection system (eBDS, Haemonetics). RESULTS: A total of 28,457 PLTs were cultured during pre-primary culture periods (44.7% APs; 55.3% at-issue pooled PLTs [AIPPs]) and 97,595 during post-primary culture periods (79.3% APs; 20.7% PSPPs). Forty-three contaminated units were identified in preculture and 34 in postculture periods (rates, 1511 vs. 348; p < 0.0001). Contamination rates of APs were significantly lower than AIPPs in the preculture (393 vs. 2415; p < 0.0001) but not postculture period compared to PSPPs (387 vs. 198; p = 0.9). STR rates (79 vs. 90; p = 0.98) were unchanged with APs but decreased considerably with pooled PLTs (826 vs. 50; p = 0.0006). Contamination (299 vs. 324; p = 0.84) and STR rates (25 vs. 116; p = 0.22) were similar for PLTs tested by BacT/ALERT and eBDS primary culture methods. A change in donor skin preparation method in 2012 was associated with decreased contamination and STR rates. CONCLUSION: Primary culture significantly reduced bacterial contamination and STR associated with pooled but not AP PLTs. Measures such as secondary testing near time of use or pathogen reduction are needed to further reduce STRs.

Financial analysis of large-volume delayed sampling to reduce bacterial contamination of platelets.

BACKGROUND: Effective and financially viable mitigation approaches are needed to reduce bacterial contamination of platelets in the US. Expected costs of large-volume delayed sampling (LVDS), which would be performed by a blood center prior to shipment to a hospital, were compared to those of pathogen reduction (PR), point-of-release testing (PORt), and secondary bacterial culture (SBC). METHODS: Using a Markov-based decision-tree model, the financial and clinical impact of implementing all variants of LVDS, PR, PORt, and SBC described in FDA guidance were evaluated from a hospital perspective. Hospitals were assumed to acquire leukoreduced apheresis platelets, with LVDS adding $30 per unit. Monte Carlo simulations were run to estimate the direct medical costs for platelet acquisition, testing, transfusion, and possible complications associated with each approach. Input parameters, including test sensitivity and specificity, were drawn from existing literature and costs (2018US$) were based on a hospital perspective. A one-way sensitivity analysis varied the assumed additional cost of LVDS. RESULTS: Under an approach of LVDS (7-day), the total cost per transfused unit is $735.78, which falls between estimates for SBC (7-day) and PORt. Assuming 20,000 transfusions each year, LVDS would cost $14.72 million annually. Per-unit LVDS costs would need to be less than $22.32 to be cheaper per transfusion than all other strategies, less than $32.02 to be cheaper than SBC (7-day), and less than $196.19 to be cheaper than PR (5-day). CONCLUSIONS: LVDS is an effective and cost-competitive approach, assuming additional costs to blood centers and associated charges to hospitals are modest.

Bacterial contamination rate of platelet components by primary culture: a systematic review and meta-analysis.

BACKGROUND: Platelets have the highest bacterial contamination risk of all blood components, and septic transfusion reactions remain a problem. A good estimate of contamination rates could provide information about residual risk and inform optimal testing strategies. We performed a systematic review and meta-analysis of platelet contamination rates by primary culture. STUDY DESIGN AND METHODS: A literature search in December 2019 identified articles on platelet contamination rates using primary culture. We used meta-analysis to estimate the overall rate of contamination and meta-regression to identify heterogeneity. We studied the following sources of heterogeneity: collection method, sample volume, positivity criteria, and study date. Contamination rate estimates were obtained for apheresis (AP), platelet rich plasma (PRP), and buffy coat (BC) collection methods. RESULTS: The search identified 6102 studies, and 22 were included for meta-analysis. Among these 22 studies, there were 21 AP cohorts (4,072,022 components), 4 PRP cohorts (138,869 components), and 15 BC cohorts (1,474,679 components). The overall mean contamination rate per 1000 components was 0.51 (95% CI: 0.38-0.67) including AP (0.23, 95% CI: 0.18-0.28), PRP, (0.38, 95% CI: 0.15-0.70), and BC (1.12, 95% CI: 0.51-1.96). There was considerable variability within each collection method. Sample volume, positivity criteria, and publication year were significant sources of heterogeneity. CONCLUSION: The bacterial contamination rate of platelets by primary culture is 1 in 1961. AP and PRP components showed a lower contamination rate than BC components. There is clinically significant between-study variability for each method. Larger sample volumes increased sensitivity, and bacterial contamination rates have decreased over time.

A suspected septic transfusion reaction associated with posttransfusion contamination of a platelet pool by vancomycin-resistant Enterococcus faecium.

BACKGROUND: Vancomycin-resistant enterococci (VRE) are antibiotic-resistant organisms associated with both colonization and serious life-threatening infection in health care settings. Contamination of platelet concentrates (PCs) with Enterococcus can result in transfusion-transmitted infection. CASE PRESENTATION: This report describes the investigation of a septic transfusion case involving a 27-year-old male patient with relapsed acute leukemia who was transfused with a 5-day-old buffy coat PC pool and developed fever and rigors. DISCUSSION: Microbiology testing and pulse-field gel electrophoresis (PFGE) was done on patient blood cultures obtained from peripheral and central lines. Microbiology and molecular testing were also performed on the remaining posttransfusion PC pool, which was refrigerated for 24 hours before microbiology testing. Red blood cell (RBC) and plasma units associated with the implicated PCs were screened for microbial contamination. Patient blood cultures obtained from peripheral and central lines yielded vancomycin-resistant Enterococcus faecium. Gram stain of a sample from the platelet pool was negative but coagulase-negative Staphylococcus (CNST) and VRE were isolated on culture. Antibiotic sensitivity and PFGE profiles of several VRE isolates from the patient before and after transfusion, and the PC pool, revealed that all were closely related. Associated RBC and plasma components tested negative for microbial contamination. CONCLUSIONS: Microbiological and molecular investigations showed a relationship between VRE isolated from the patient before and after transfusion, and therefore it is postulated that a patient-to-PC retrograde contamination (from either blood or skin) occurred. As the CNST isolated from the PC pool was not isolated from patient samples, its implication in the transfusion event is unknown.

Cutaneous manifestations of bartonellosis.

Bartonellosis are diseases caused by any kind of Bartonella species. The infection manifests as asymptomatic bacteremia to potentially fatal disorders. Many species are pathogenic to humans, but three are responsible for most clinical symptoms: Bartonella bacilliformis, Bartonella quintana, and Bartonella henselae. Peruvian wart, caused by B. bacilliformis, may be indistinguishable from bacillary angiomatosis caused by the other two species. Other cutaneous manifestations include maculo-papular rash in trench fever, papules or nodules in cat scratch disease, and vasculitis (often associated with endocarditis). In addition, febrile morbilliform rash, purpura, urticaria, erythema nodosum, erythema multiforme, erythema marginatus, granuloma annularis, leukocytoclastic vasculitis, granulomatous reactions, and angioproliferative reactions may occur. Considering the broad spectrum of infection and the potential complications associated with Bartonella spp., the infection should be considered by physicians more frequently among the differential diagnoses of idiopathic conditions. Health professionals and researchers often neglected this diseases.

Cutaneous manifestations of bartonellosis

Abstract Bartonellosis are diseases caused by any kind of Bartonella species. The infection manifests as asymptomatic bacteremia to potentially fatal disorders. Many species are pathogenic to humans, but three are responsible for most clinical symptoms: Bartonella bacilliformis, Bartonella quintana, and Bartonella henselae. Peruvian wart, caused by B. bacilliformis, may be indistinguishable from bacillary angiomatosis caused by the other two species. Other cutaneous manifestations include maculo-papular rash in trench fever, papules or nodules in cat scratch disease, and vasculitis (often associated with endocarditis). In addition, febrile morbilliform rash, purpura, urticaria, erythema nodosum, erythema multiforme, erythema marginatus, granuloma annularis, leukocytoclastic vasculitis, granulomatous reactions, and angioproliferative reactions may occur. Considering the broad spectrum of infection and the potential complications associated with Bartonella spp., the infection should be considered by physicians more frequently among the differential diagnoses of idiopathic conditions. Health professionals and researchers often neglected this diseases.

The BEST criteria improve sensitivity for detecting positive cultures in residual blood components cultured in suspected septic transfusion reactions.

BACKGROUND: Culturing residual blood components after suspected septic transfusion reactions guides management of patients and cocomponents. Current practice, accuracy of provider vital sign assessment, and performance of the AABB culture criteria are unknown. A multicenter international study was undertaken to investigate these issues and develop improved culture criteria. STUDY DESIGN AND METHODS: Retrospective data for all transfusion reactions resulting in residual blood component culture in 2016 were collected from participating hospitals. The performance of the AABB culture criteria were assessed for detection of positive culture results. Modifications to the AABB criteria including 1) recommending culturing in the setting of isolated high fevers, 2) defining hypotension and tachycardia using objective parameters, and 3) incorporating antipyretic use were tested to determine if modifications improved performance. Modifications associated with improvement were incorporate into the BEST criteria. The AABB and the BEST criteria were then tested against a data set enriched for positive culture results to determine which criteria were superior. RESULTS: Data were collected from 20 centers encompassing 779,143 transfusions, 3,187 reported transfusion reactions, and 1,104 cultured components. There was marked variation in reaction reporting and culturing rates (0.0%-100.0%). Of 35 total positive component cultures, only one of 35 (2.9%) had concordant patient cultures; 12 of 34 (35.3%) did not have patient cultures performed. The BEST criteria had better sensitivity for detection of a positive culture result compared to the AABB criteria (74% vs. 41%), although specificity decreased (45% vs. 65%). CONCLUSION: Compared to the AABB criteria, the BEST criteria have improved sensitivity for positive culture detection.

Recipient sepsis caused by Lactococcus garvieae contamination of platelets from a donor with colon cancer.

Lactococcus garvieae is a well-known fish pathogen that has low virulence in humans and is rarely isolated from the blood cultures of endocarditis patients. We describe herein the first reported case of transfusion-transmitted L. garvieae sepsis caused by a contaminated platelet concentrate from a donor who consumed raw octopus before blood donation. Retrospective examination of the laboratory results of the index donor revealed that his haemoglobin levels had been steadily decreasing, which led to the detection of a latent colon cancer. The donors with colon lesions involving a latent cancer may relate an asymptomatic bacteremia.