Bacterial Contamination Of Platelet Components Research Articles

Changing Strategies for the Detection of Bacteria in Platelet Components in Ireland: From Primary and Secondary Culture (2010-2020) to Large Volume Delayed Sampling (2020-2023).

Bacterial contamination of platelet components (PC) poses the greatest microbial risk to recipients, as bacteria can multiply over the course of PC storage at room temperature. Between 2010 and 2020, the Irish Blood Transfusion Service (IBTS) screened over 170,000 buffy coat-derived pooled (BCDP) and single-donor apheresis platelets (SDAPs) with the BACT/ALERT 3D microbial detection system (Biomerieux, L'Etoile, France), using a two-step screening protocol which incorporated primary and secondary cultures. Although the protocol was successful in averting septic transfusion reactions (STRs), testing large sample volumes at later time points was reported to improve detection of bacterial contamination. A modified large-volume delayed sampling (LVDS)-type protocol was adopted in 2020, which in the case of SDAP was applied to collections rather than individual splits (2020-2023, 44,642 PC screened). Rates of bacterial contamination for BCDP were 0.125% on Day-2, 0.043% on Day-4 vs. 0.191% in the post-LVDS period. SDAP contamination rates in the pre-LVDS period were 0.065% on Day-1, 0.017% on Day-4 vs. 0.072% in the post-LVDS period. Confirmed STRs were absent, and the interdiction rate for possibly contaminated SDAP was over 70%. In the post-LVDS period, BCDPs had a higher total positivity rate than SDAPs, 0.191% (1:525) versus 0.072% (1:1385), respectively, (chi-squared 12.124, 1 df, p = 0.0005). The majority of organisms detected were skin-flora-type, low pathogenicity organisms, including coagulase-negative staphylococci and Cutibacterium acnes, with little change in the frequency of clinically significant organisms identified over time. Both protocols prevented the issue of potentially harmful components contaminated (rarely) with a range of pathogenic bacteria, including Escherichia coli, Serratia marcesens, Staphylococcus aureus, and streptococci. Culture positivity of outdates post-LVDS whereby 100% of expired platelets are retested provides a residual risk estimate of 0.06% (95% CI 0.016-0.150). However, bacterial contamination rates in expired platelets did not demonstrate a statistically significant difference between the pre-LVDS 0.100% (CI 0.033-0.234) and post-LVDS 0.059% (0.016-0.150) periods (chi-squared = 0.651, 1 df, p = 0.42).

Bacterial contamination of platelet components

Bacterial contamination of platelet components

Current status of rapid bacterial detection methods for platelet components: A 20-year review by the ISBT Transfusion-Transmitted Infectious Diseases Working Party Subgroup on Bacteria.

Bacterial contamination of platelet components (PCs) poses a safety challenge for transfusion patients. Despite mitigation interventions, the residual risk of transfusion-transmitted bacterial infections remains predominant. PC safety can be improved either by pathogen reduction or by implementation of bacterial detection methods. Detection methodologies include culture methods and rapid detection methods. The current review focuses on currently available rapid detection methods. We reviewed published manuscripts since 2000 on rapid bacterial detection methods used for PC screening with result determination within 4 h. Methods meeting this criterion included Verax PGDprime, BacTx and nucleic amplification testing. The analytical and diagnostic sensitivity and specificity of these systems were assessed. The analytical sensitivity between the different detection methods ranged between 50 and 100,000 CFU/ml. The sample volume used by these testing systems varies between 0.5 and 1.0ml of PCs. A delay of at least 48 h before sampling enhances detectability. All rapid detection methods generate results in a timely manner, allowing testing to be performed before transfusion with optimal sensitivity. Rapid detection methods improve PC safety regarding bacterial contamination. The assays are optimal for rapidly growing bacteria, which are more likely to cause septic transfusion reactions in patients. Because of the reduced diagnostic sensitivity, the sample collection should be late in shelf-life and ideally just before transfusion. The major benefit of these methods is that the test result can be obtained before releasing PCs for transfusion or to be used in combination with other screening methods applied early during PC storage.

Mitigating the risk of transfusion-transmitted bacterial infections in hematology oncology patients.

e19047 Background: Hospital acquired infections create major logistical, financial, and patient safety concerns within the healthcare system. Bacterial contamination (BC) of platelet components (PCs) can lead to transfusion-transmitted bacterial infections (TTBI), central line-associated bloodstream infections, and sepsis, with long-term complications and/or death. In the US, hematopoietic stem cell transplant (HSCT) recipients require transfusion support until engraftment and together with hematology/oncology (hemonc.) patients receive the highest number of PCs/patient. FDA’s Guidance recommends approaches to reduce BC risk including the use of enhanced bacterial culture screening (EBSC) or pathogen reduction (PR) of platelets. Methods: The Miami Cancer Institute (MCI) implemented PR-PCs for all allogeneic HSCT patients. Irradiation, CMV testing, and bacterial screening have been discontinued for PR-PCs. Transfusion outcomes are being monitored using active hemovigilance (HV) reporting. Results: Considering the fatality risk associated with BC of PCs (1:200,000 – 1:1,000,000) despite the use of optimal skin cleansing, initial sample diversion, and primary bacterial culture, 1/2,880 PCs are still contaminated (Bloch et al.); further steps towards BC mitigation are needed. As the UK and US reported a residual BC risk of 5.4-9.4/million PCs after implementation of EBSC, PR may represent an alternative approach with other cumulative benefits. Indeed, national HV data from France, Switzerland and Belgium reported no sepsis transfusion reactions since PR implementation (Benjamin et al.). In addition, the risk of TA-GVHD and other TTI including emerging infectious diseases (EID) may be decreased after the inactivation of pathogens and leukocytes (Lanteri et al.). At MCI, the percentage of transfused PR-PCs has been increasing steadily from 7.9% in July 2019 to 22.2% in January 2021. Over a 19 month-period, a total of 9,296 PC were transfused including 1,677 PR-PCs. While non-PR-PCs were all irradiated and bacterially screened, PR-PC were neither irradiated nor bacterially screened. No cases of TA-GVHD or TTI were reported. A total of 27 mild, non-life-threatening platelet transfusion reactions were reported including 22 (81.5%) after non-PR PCs transfusion and 5 (18.5%) after PR-PC transfusion. In addition, the early release of transfusion-ready fresh PR-PCs 24-48 hours after collection has proven invaluable in providing clinicians and patients with blood continuity during the COVID-19 pandemic. Conclusions: Though certain measures have improved blood safety, the risk of TTI associated with PC transfusion remains a concern for vulnerable hemonc. patients. Using PR-PC is especially important to consider when patients undergo extensive life-saving therapies such as bone marrow transplants.

Bacterial Contamination of Platelet Units is an Under-Recognized Contributor to Healthcare-associated infections (HAIs)

BACKGROUND HAIs create a major logistical, financial and patient safety concerns within the healthcare system. Bacterial contamination of platelet components (PCs) is the most common, under recognized, infectious risk of transfusion and contributor to HAIs. Contaminated PCs can lead to central line-associated bloodstream infections, bacteremia, and sepsis, with major long term complications and/or death. While US blood centers employ primary bacterial culture screening (pBCS) today, FDA's Draft Guidance and Blood Products Advisory Committee recommend additional approaches to reduce continued risk including FDA-approved pathogen reduction technology (PRT). Our objective is to determine whether PRT is an effective means to reduce the infectious risk of PCs. METHODS We compiled national hemovigilance (HV) data (2006-2016) from the UK, France, Switzerland, Belgium and the US to examine use of pBCS and PRT with amotosalen/UVA and their associated reports of PC bacterial contamination and sepsis. RESULTS Introduction of pBCS decreased HV reports of PC bacterial contamination in the US by 72.5% (p 700,000 PRT PCs over the same time period. CONCLUSIONS pBCS does not eliminate the risk of bacterial contamination; In its Draft Guidance, FDA acknowledges this shortcoming and recommends further measures. In contrast, PRT inactivates a broad spectrum of pathogens present in PCs, regardless of low level contamination, eliminating the need for pBCS. PRT provides clinicians and patients with transfusion-ready PCs, mitigating the risk of transfusion-transmitted infections and representing an approach to increase hospital safety while reducing the financial challenges of transfusion-related HAIs.

Bacterial contamination of platelet components not detected by BacT/ALERT®.

To investigate the possible causes for false negative results in BacT/ALERT® 3D Signature System despite bacterial contamination of platelet units. The Northern Ireland Blood Transfusion Service (NIBTS) routinely extends platelet component shelf life to 7 days. Components are sampled and screened for bacterial contamination using an automated microbial detection system, the BacT/ALERT® 3D Signature System. We report on three platelet components with confirmed bacterial contamination, which represent false negative BacT/ALERT® results and near-miss serious adverse events. NIBTS protocols for risk reduction of bacterial contamination of platelet components are described. The methodology for bacterial detection using BacT/ALERT® is outlined. Laboratory tests, relevant patient details and relevant follow-up information are analysed. In all three cases, Staphylococcus aureus was isolated from the platelet residue and confirmed on terminal sub-culture using BacT/ALERT® . In two cases, S. aureus with similar genetic makeup was isolated from the donors. Risk reduction measures for bacterial contamination of platelet components are not always effective. Automated bacterial culture detection does not eliminate the risk of bacterial contamination. Visual inspection of platelet components prior to release, issue and administration remains an important last line of defence.

A Non-Invasive Method for the Detection of Bacterial Contamination of Platelet Apheresis Concentrates

AbstractAbstract 1177 Introduction:Allogeneic blood transfusion is a potential source of infection via a variety of known and unknown transmissible agents. Over the last three decades, pre-transfusion donor screening for viral agents has led to a dramatic reduction in the risk of virally transmitted diseases. Bacterial contamination, on the other hand, has proved more difficult to address and remains the most prevalent transfusion-associated infectious risk. This is especially true for platelet components whose storage conditions (22°C, for up to 5 days, with agitation) facilitate bacterial proliferation throughout the storage period. Reported here are the results of initial testing using a novel, noninvasive, real time, rapid screening device for the detection of bacterial contamination of platelet units. Methods and Results:This detection method is based on measuring absorption of an infrared beam that is transmitted through the gaseous atmosphere above the platelets. Living microorganisms produce metabolic gases such as carbon dioxide (CO2) during respiration. By means of infrared absorption the concentration of metabolic gases can be measured inside the platelet storage bag.The methodology consists of an apparatus which uses a tunable monochromatic mid-IR light source, IR detector and electronic signal processor. The light source emits light in frequency range overlapping at least with one absorption line of CO2gas. Use of the tunable light source allows the determination of metabolic gas concentration within the container without etalon use. In this method, the light from the light source is transmitted through the gaseous part of storage bag is measured by means of an IR detector. The concentration of CO2gas inside the platelet bag is determined by equilibrium conditions between the release rate and the rate of diffusion of the metabolic gases through the bag walls.Staphylococcus epidermidis obtained from the American Type Culture Collection (ATCC) were used to contaminate platelets bags. The bacterially inoculated apheresis platelets were agitated at 22°C and measurements were performed using a laser instrument. Each platelet unit was measured before and during bacterial contamination. Samples were taken from each contaminated platelet bag and a standard culture plate count was used for determining bacterial concentration in the platelet medium. Using this device we have succeeded to detect bacterial concentration of above 3*106 CFU/mL staphylococcus epidermidis (Figure 1). Conclusions:Although methods to detect platelet bacterial contamination have received much attention, bacterial contamination of platelet components remains a persistent problem. The methodology described in this report detects staphylococcus epidermidis in apheresis platelet bags. The method allows for testing in real time - at issue or during storage, and it provides immediate results.This device is expected to be successful in detecting most prevalent types of bacteria strains. The test is easy to perform and does not require pre-incubation of samples or handling of the bag's contents. The device is specific and sensitive, allowing bacteria screening, ensuring increased safety of platelet transfusions. The device is able to detect bacteria in platelets, and other blood constituents, through the storage bag, without contacting, harming, or handling the bag's contents. Since there is no direct interaction of the laser light beam with the platelet media and the laser power is low (approximately 10 mW) thermal effects are avoided.By allowing real-time, sensitive detection of bacterial contamination of platelet products, wastage can be reduced, platelet shortage can be alleviated and the adverse outcomes associated with platelet transfusion contamination can be prevented. Further studies are required to evaluate the sensitivity limits for the detection of other bacterial strains that have been reported to contaminate platelet products. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Bacterial contamination of platelet components: potential solutions to prevent transfusion-related sepsis

Bacterial contamination of platelet components (PC) is the most prevalent risk for transfusion-transmitted infection. Based on the recent studies with optimal culture methods of expired PC, the prevalence of bacterial contamination is estimated to occur in approximately one in 750 to one in 1000 PC. Only within the last few years have the magnitude of the risks and the range of clinical outcomes associated with bacterial contamination been extensively characterized. Despite increased recognition of bacterial contamination of PC, transfusion-related sepsis is infrequently reported. This has largely been attributed to passive reporting systems, and low levels of clinical awareness for transfusion-related sepsis by primary care physicians. The risk for transfusion of contaminated PC has generally been characterized per component. Importantly, because patients require repeated transfusions of PC during a period of transfusion-dependent thrombocytopenia, it is appropriate to express the risk to receive a contaminated PC on a patient exposure basis. Assuming that the average hematology oncology patient may receive seven PC during a 28-day period of support, the risk of exposure to a contaminated PC is in the range of one in 150 per patient. This level of risk would not be acceptable for other intravenous medications. With increased appreciation of the risk of bacterial contamination, methods were developed to limit the risk of transfusion-transmitted bacteremia. This article focuses on those interventions that have been implemented in routine practice. The most important methods employed to mitigate the risk are improved skin disinfection, initial blood draw diversion, bacterial detection and pathogen inactivation/reduction. These technologies are now undergoing increased use in the clinical practice of transfusion medicine. With increased use, additional data are being generated to more fully characterize the effects of these interventions. Improved disinfection, blood diversion and bacterial detection have decreased, but not resolved the risk of bacterial contamination. Pathogen inactivation/reduction offers the potential for a further substantial decrease of the risk for transfusion of PC contaminated with bacteria.

Bacterial contamination in platelets: incremental improvements drive down but do not eliminate risk

Bacterial contamination of platelet components (PCs) remains an important cause of transfusion-associated infectious risk. In 2004, Canadian Blood Services (CBS) implemented bacterial testing of PCs using the BacT/ALERT 3D system (bioMérieux). This system has been validated and implemented and continuous monitoring of culture rates allows gathering of data regarding true and false positives as well as false negatives. National data gathered between March 2004 and October 2010 from 12 CBS sites were analyzed to compare bacterial contamination rates across three platelet (PLT) preparation methods: apheresis, buffy coat, and PLT-rich plasma. Data were compared before and after implementation of protocol changes that may affect bacterial detection or contamination rates. Initial positive rates among the three production methods were significantly different, with apheresis PCs being the highest. The rates of confirmed positives among production methods did not differ significantly (p = 0.668). Increasing sample testing volumes from 4 to 6 mL to 8 to 10 mL significantly increased the rate of initial positives, while confirmed positives increased from 0.64 to 1.63 per 10,000, approaching significance (p = 0.055). Changing the skin disinfection method from a two-step to a one-step protocol did not significantly alter the rate of confirmed positives. During the period of data analysis, eight false-negative cases were reported, with five implicated in adverse transfusion reactions. Bacterial testing of PCs and implementation of improved protocols are incrementally effective in reducing the risk of transfusion of bacterially contaminated PLT concentrates; however, the continued occurrence of false-negative results means the risk has not been eliminated.

Bacterial contamination of platelet components: remaining risks after introduction of bacterial screening–authors’ reply

Bacterial contamination of platelet components: remaining risks after introduction of bacterial screening–authors’ reply

Bacterial contamination of platelet components: remaining risks after introduction of bacterial screening

Bacterial contamination of platelet components: remaining risks after introduction of bacterial screening

Detection of bacterial contamination of platelet components: six years' experience with the BacT/ALERT system.

Hemovigilance has shown that bacteria cause more fatalities than other infections together. Surveillance for detection of bacteria in platelets (PLTs) was initiated. Concomitantly, the storage period for PLTs was extended from 5 to 7 days to reduce cost. Analysis was performed of all cases of a positive signal in a screening procedure for contaminated PLTs taking into account results of confirmative cultures and results of culture from blood components including bacteria strains. Records were assessed from patients transfused with blood components issued before the screening culture became positive. Samples were collected from 22,057 PLT units. An initial reaction was seen in 84 (0.38%). Growth was confirmed in 70 of these. Of the associated PLT units, 26 had been issued or outdated at the time when the culture was found to be reactive, in 27 bacteria were found, and in 17 cultures were negative. The bacteria found were mainly from normal skin flora. Sixty-six patients received 75 blood components issued before the screening system alarmed. None of these patients had a transfusion reaction reported. The outdating fell to less than 5 percent. A screening system for detection of bacterial contamination was implemented without increase in cost owing to extension of storage time to 7 days. Transfusion of several contaminated blood components was prevented.

Blood donor selection and screening: strategies to reduce recipient risk.

Various measures are taken to ensure the safety of the blood supply. Donor selection begins with education of the public about transfusion-transmissible diseases. Potential donors must answer a questionnaire designed to identify specific risk factors for these infections. The questionnaire is the only line of protection against certain infections for which no testing is performed, such as malaria, babesiosis, leishmaniasis, and Chagas disease. All donations are tested for the presence of antibodies to HIV-1 and -2, HCV, HTLV and syphilis, the hepatitis B surface antigen (HbsAg), the p24 antigen (HIV), and also for HIV and HCV nucleic acids. The introduction of new and improved screening tests for transfusion-transmissible diseases has led to remarkable improvement in the safety of the blood supply, with substantial shortening of the window period for HIV, HCV, and HBV infections. The current challenge of the industry is to reduce even further the small but significant risk of bacterial contamination of platelet components. Finally, some safety measures are purely precautionary, such as the deferral of donors who have traveled to certain countries affected by the bovine spongiform encephalopathy (BSE).

Antibiotic‐labeled probes and microvolume fluorimetry for the rapid detection of bacterial contamination in platelet components: a preliminary report

Approximately 1 platelet in 2000 components is bacterially contaminated. Most commonly, contaminating organisms are gram positive skin saprophytes (such as Staphylococcus sp. or Bacillus sp.). A novel approach to the rapid diagnosis of gram positive contamination by the use of a fluorescence-labeled antibiotic probe with affinity for the gram positive cell was investigated. Two isolates of Staphylococcus epidermidis were inoculated into bags of Day 0 platelets. Quantitative cultures along with a semi-automated screening assay on a microvolume fluorimeter employing a fluorescence-conjugated vancomycin probe was performed for each day of storage. In addition, serial dilutions of the bacteria were added to sterile platelets to achieve a range spanning 10(1) to 10(8) CFUs per mL. All samples with a bacterial contamination of > or =10(5) CFU per mL were detected. Sterile samples were nonreactive. The entire procedure requires three pipetting steps and took less than 1 hour to perform. These preliminary results with the use of fluorescence-labeled antibiotics as probes combined with microvolume fluorimetry for the rapid detection of bacterial contamination of platelet components suggest that this is a promising approach. Further studies with additional organisms and alternative conjugates, bacteria, and antibiotics are underway.