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Transfusion-transmitted bacterial infection

Transfusion-transmitted bacterial infection
Literature review current through: Jan 2024.
This topic last updated: Oct 27, 2023.

INTRODUCTION — Transfusion-transmitted bacterial infection (TTBI) is a complication of transfusion in which a bacterial pathogen from a transfused blood component causes symptomatic disease in the transfusion recipient. The risk of TTBI is greatest with platelet transfusion.

This topic reviews definitions, epidemiology, risk factors, prevention, and immediate interventions for TTBI. Separate topics present an overview of transfusion reactions and summarize routine evaluation of blood donors, testing of blood components, and pathogen inactivation methods:

Transfusion reactions – (See "Approach to the patient with a suspected acute transfusion reaction".)

Blood donor testing

History – (See "Blood donor screening: Medical history".)

Laboratory testing – (See "Blood donor screening: Laboratory testing".)

Other protections – (See "Blood donor screening: Overview of recipient and donor protections".)

Pathogen inactivation – (See "Pathogen inactivation of blood products".)

DEFINITIONS — Evolving definitions make it challenging to track the epidemiology of transfusion-transmitted bacterial infection (TTBI) and to accurately evaluate case reporting.

TTBI is a subset of transfusion-transmitted infection (TTI); TTBI refers to TTI caused by bacterial organisms. The following classifications for TTI are included in a 2021 biovigilance protocol from the National Healthcare Safety Network (NHSN) of the Centers for Disease Control and Prevention (CDC) in the United States [1]:

Case definitions – Definitive cases are those for which there is laboratory evidence of a pathogen in the transfusion recipient. Possible cases are those with an illness that is temporally associated with the transfusion but for which no pathogen is detected in the recipient and other adverse transfusion reactions (such as allergic or hemolytic reactions) have been excluded.

Severity

Nonsevere TTBI does not cause permanent organ damage or impairment but does require medical intervention.

Severe reactions are those that lead to hospitalization, prolong hospital stay, require medical or surgical intervention to prevent organ damage, and/or cause persistent disability or incapacity due to organ dysfunction. Severe TTBI may also be referred to as a septic transfusion reaction or transfusion-associated sepsis.

Life-threatening reactions are those that require a major intervention such as hemodynamic or respiratory support (intubation) to prevent death.

Imputability – Imputability refers to the confidence that the infection came from the transfusion. Criteria for definite TTI include evidence of the pathogen in the transfused component, in the donor at the time of donation, in another component from the same donation, or in another recipient of a component from the same donation. In addition, there must not be any other exposure of the recipient to the pathogen, the recipient must not have been infected with the pathogen prior to receiving the transfusion, or there must be evidence that the specific bacterial organism in the component is the same as the organism in the recipient (by DNA testing or extended phenotypic comparison).

These case definitions can be used for clinical care as well as for case reporting. (See 'Case reporting' below.)

Other groups, such as the United Kingdom Serious Hazards of Transfusion (SHOT) program, define TTBI as the isolation of the same pathogen from the donor or the donated blood component and the transfusion recipient, with no evidence of infection prior to transfusion nor any reasonable alternative explanation for the infection [2].

In distinction from TTI, the term contamination may be used for a positive bacterial culture (or other test for viable organisms) from the blood product. Positive bacterial cultures are not definitive for TTBI: some may represent "false positives" in which contaminating organisms were introduced when the sample of the product was taken for culture or during or plating of the culture, while others may reveal an organism in the product that is unlikely to cause clinical disease in the recipient.

Not all blood products that contain viable organisms cause infection or disease in the recipient. In one study involving apheresis platelet products, the rate of positive cultures was 112 to 252 per million donations, whereas the rate of septic transfusion reactions was 9 per million donations, a >10-fold difference [3].

EPIDEMIOLOGY

Incidence — TTBI is much more common than transfusion-transmitted viral infections.

As an example, transfusion-transmitted hepatitis C virus (HCV) occurs in <1 per million (table 1), whereas the incidence of TTBI from platelets can be as high as 1 in 50,000 to 1 in 100,000 (10 to 20 times higher).

Estimates of TTBI incidence vary depending on several factors, especially the definitions used, the extent of mitigation measures, and the specific blood product that is transfused. (See 'Definitions' above and 'Prevention' below.)

Definitions – The incidence is highest in studies that report rates of bacterial contamination of the blood component and lower when more stringent criteria are applied (positive culture from the transfusion recipient, transfusion-associated sepsis). (See 'Definitions' above.)

Extent of mitigation measures – Rates of TTBI are higher with active surveillance (testing components at the time of issue, prior to transfusion, for the presence of bacterial organisms) than with passive surveillance (relying on clinicians to report transfusion-related adverse events and investigating them once they occur) [4]. Active surveillance consumes more time and resources but reduces the risk of transfusing a contaminated unit.

Methods to limit introduction of bacteria during collection, processing, and sampling of platelet products have been emphasized in the United States since 2019, although implementation has been delayed due to the coronavirus disease 2019 (COVID-19) pandemic. Rates of TTBI declined following institution of routine platelet culturing and are expected to decline further as these new measures are introduced. (See 'Platelet-specific guidance and requirements' below.)

In low-income and middle-income countries where routine surveillance (primary culture) or other mitigation processes are not in regular use, rates of TTI are higher. The few studies done in Africa show higher rates of TTBI compared with rates in high-income countries. As an example, in a 2021 survey of members of the African Society for Blood Transfusion (AfSBT), only 14 of 38 respondents (37 percent) reported using measures routinely used in high-income countries (such as diversion pouches for blood collection) and only 8 (21 percent) reported using bacterial culture of platelet units [5].

It is likely that the rate of TTBI from platelets will decline further once additional measures such as bacterial culture following high-volume delayed sampling (for platelets) or pathogen-inactivation are routinely used. (See 'Platelet-specific guidance and requirements' below.)

Reporting – There is an artifactually low incidence of TTBI in the context of underreporting. This is almost certainly the case in low- and middle-income countries where post-transfusion surveillance is severely lacking.

Blood product

Platelets – The incidence of TTBI is higher with platelet products than other components; platelets are stored at room temperature in bags that allow gas exchange, to prevent platelet activation and keep the platelets viable. (See "Platelet transfusion: Indications, ordering, and associated risks", section on 'Storage'.)

Estimates of bacterial contamination of platelets using passive surveillance data (based on recognized adverse reactions post transfusion) suggest an incidence of 1 in 1500 to 1 in 3000; estimated rates from active surveillance (based on culturing platelet components prior to transfusion) are as much as 10-fold higher [3,4,6]. Nonfatal TTBI rates are estimated at 1 in 100,000, whereas rates of fatal septic transfusion reactions are estimated at 1 in 500,000.

In a 2018 study from a single institution where platelet units underwent primary culture, the rate of blood culture-positive transfusion reactions from platelets was approximately 1 in 10,000 [7].

RBCs and plasma – The relative incidence of TTBI with red blood cell (RBC) units and plasma units is much lower than with platelets (20-fold lower in one study) [7].

Fatality rates — Fatalities from TTBI are reported by the US Food and Drug Administration (FDA). Following the introduction of mitigation measures such as bacterial culture or pathogen inactivation, the number of annual fatalities has been low (for definite causality based on conclusive evidence, 2 in 2019, 3 in 2020) [8-10]. Cases with probable and possible TTBI-related fatality are also reported.

Studies conducted before these mitigation measures were instituted (when the fatality rate was higher and risk factors for fatality were easier to identify) found the following associations:

Infection with Gram-negative organisms was associated with the greatest risk of death in one study (odds ratio [OR] 7.5, 95% CI 1.3-64.2) [11]. Gram-negative rods accounted for all six deaths in another study [12].

TTBI from RBC transfusions is more likely to be due to Gram-negative organisms (eg, Yersinia enterocolitica) and thus more likely to be fatal [13-15].

MICROBIOLOGY

Organisms — Gram-positive organisms are more common than gram-negative organisms (table 2). Most cases of contamination are due to gram-positive organisms such as skin and mucosal flora (eg, coagulase negative Staphylococcus species) that are introduced into platelets at time of collection. Some bacteria (eg, certain strains of S. aureus and S. capitis) have been shown to have virulence factors that favor their pathogenicity, such as the ability to form biofilms and measures that facilitate host immune evasion [16,17].

In a 2017 study from the American Red Cross that evaluated 375 confirmed cases of positive bacterial cultures from apheresis platelet products, the most common organisms were [3]:

Streptococcus species (S. viridans, S. bovis, and beta hemolytic streptococci) – 39 to 48 percent

Coagulase-negative staphylococcus – 21 to 24 percent

S. aureus – 4 to 9 percent

Escherichia coli – 8 to 9 percent

Other gram-negative organisms (Klebsiella, Serratia, Bacillus, and Enterobacter species) – 2 to 7 percent

Other organisms such as Enterococcus species and Listeria monocytogenes – 0 to 2 percent

In a 2019 study from the National Healthcare Safety Network (NHSN) in the United States that evaluated 37 definitive TTBIs, the most common organisms were [18]:

S. aureus – 38 percent

Coagulase-negative staphylococcus – 22 percent

S. viridans – 11 percent

E. coli – 8 percent

Treponema pallidum is a transfusion-transmissible bacterium, but it is not considered to be an organism that causes TTBI, given that it causes a distinct clinical syndrome (syphilis) rather than an acute/septic transfusion reaction. (See "Blood donor screening: Laboratory testing", section on 'Syphilis' and "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in patients without HIV".)

Sources — Bacterial sources include the donor (bloodstream or skin flora), the phlebotomist (skin flora), or the storage and handling of equipment (eg, contaminated water baths used to thaw frozen plasma or storage bags) [19,20]. Contamination may also occur when the unit is sampled to investigate a suspected transfusion reaction, whereby the source is from the technologist rather than the donor or the product.

Other sources have included:

Pet animals – Notable case reports have described infection with organisms that are carried by the donor's pet (Salmonella from a pet snake and Pasteurella from pet cats) [21,22].

Manufacturing facilities – A 2023 report described polymicrobial sepsis in seven patients, three of whom died, following transfusion of apheresis platelets during the period from 2018 to 2022 [23]. The platelets were found to contain Acinetobacter calcoaceticus baumannii complex (ACBC), Staphylococcus saprophyticus, Leclercia adecarboxylata, Enterobacter species, and/or Bacillus species. They came from six separate apheresis platelet donors from six different states; four had been pathogen-reduced and three had undergone bacterial culture prior to transfusion. Following an investigation by the Centers for Disease Control and Prevention (CDC), the source was determined to be the manufacturer of the platelet collection sets, where deficiencies were found in environmental controls and sterility assurance processes. (See "Acinetobacter infection: Epidemiology, microbiology, pathogenesis, clinical features, and diagnosis".)

A similar report from 2019 described four patients infected with ACBC and S. saprophyticus, one of whom died [24]. One of the units had undergone pathogen reduction. In this report, three separate donors were involved, and DNA sequencing revealed the organisms to have differed genetically, suggesting three independent sources.

Damage to collection bags – The containers in which platelets are stored can become damaged (scratched, pierced, cut) during manufacture, transport, or storage, leading to leaks and environmental contamination, although this is rare. Manufacturing defects are typically identified during inspection at the manufacturing facility, but damage can occur after the product has left the facility. A 2022 report reviewed reports of 23 apheresis platelet container defects, including one that led to fatal TTBI [25]. The unit had been visually inspected and no defects were apparent, but an independent laboratory identified a leak in the bag. Based on the 23 reports from >500,000 apheresis platelet sets, the overall defect rate was determined to be 44 per 1 million; the implicated bags were removed from inventory and implicated units were not transfused.

There are challenges in interpreting culture results that include known environmental contaminants and skin commensals. As an example, Cutibacterium (formerly Propionibacterium) acnes is sometimes cultured from platelet units, but it is unclear how often it causes overt clinical reactions in the transfusion recipient. Vigilance is prudent when interpreting culture results, given the potential risk of a large inocula of any bacteria infused into a high-risk recipient.

RISK FACTORS

Product, collection method, and storage conditions — Platelets and plasma can be collected by apheresis or prepared from whole blood donations.

Platelets – Apheresis platelets are considered to be lower risk for TTBI since they are a single donation rather than a pooled product from several donors. However, a 2017 study that compared bacterial contamination rates in 186,737 apheresis platelet concentrates and 601,988 whole blood-derived platelet concentrates did not find an appreciable difference [26].

A 2017 study that compared two apheresis platelet collection devices found that one of the devices was associated with almost twofold greater likelihood of bacterial contamination and a nearly fourfold higher rate of septic transfusion reactions than the other [3]. A 2023 report identified polymicrobial sepsis from one apheresis collection set manufacturer [23]. (See 'Microbiology' above.)

Platelets are routinely stored at room temperature in gas permeable bags to prevent their activation and to support their normal metabolic functions. However, room temperature storage also facilitates growth of bacterial organisms. (See "Platelet transfusion: Indications, ordering, and associated risks", section on 'Room temperature storage'.)

The role of storage duration is challenging to assess. The majority of TTBI cases (and fatalities) occur with day 4 to day 5 platelets; however, this may reflect the timing with which platelets are administered since most platelets are transfused on day 4 or day 5 [18,27,28].

The storage medium used for platelet transfusion may affect the risk of TTBI. One study reported a fourfold increased incidence of TTBI with platelet concentrates stored in platelet-additive solution compared with platelet concentrates stored in plasma [29].

Plasma and Cryoprecipitate – Compared to platelets, the risk of TTBI is lower from plasma and Cryoprecipitate, as these products are not stored at room temperature, but risk has been demonstrated using in vitro studies [30]. Pathogen-inactivated Cryoprecipitate is available in some jurisdictions, as discussed separately. (See "Pathogen inactivation of blood products", section on 'Cryoprecipitate'.)

Recipient health status — The immune status, overall health, and recent or current use of antibiotics at the time of transfusion may alter the risk of a clinically significant reaction.

Platelet transfusions are often used in patients with immunocompromised status (hematologic malignancy or receiving chemotherapy). One study that performed a multivariable analysis found that pancytopenia as the indication for transfusion was associated with a higher risk of TTBI compared with anemia as the indication [12].

It is possible that individuals who are already receiving antibiotics for another reason at the time of transfusion may have a lower risk of TTBI [31,32].

PREVENTION

Reducing risk of bacteria in the product — There are opportunities to reduce the risk of bacterial contamination at each stage of the platelet transfusion process:

Manufacturer of the collection set (See 'Sources' above.)

Blood donation facility and blood donor (See 'Donor screening, skin preparation, and sample handling' below.)

Transfusing facility (See 'Strategies at the bedside' below.)

Donor screening, skin preparation, and sample handling

Donor – Donors undergo medical history screening at the blood collection facility and are deferred if they are feeling ill or have symptoms of active infection. (See "Blood donor screening: Medical history", section on 'General symptoms of active infection'.)

Some countries (but not the United States) defer all donors for one to seven days after dental extractions.

Skin preparation – Attention to sterile technique is essential during blood collection and processing.

The preferred skin disinfection solution is a product combining 2% chlorhexidine (CHX) in 70% isopropyl alcohol (IPA), an approach endorsed by the World Health Organization (WHO) and the Association for the Advancement of Blood & Biotherapies (AABB) [33]. (See "Detection of bacteremia: Blood cultures and other diagnostic tests", section on 'Skin antisepsis and collection technique'.)

This approach is supported by a prospective, nonrandomized study from 2011 that compared a single swab containing 2% chlorhexidine plus 70% isopropyl alcohol (2% CHX/70% IPA) with a control (standard practice) two-swab process (30-second swab with 7.5% povidone-iodine [P-I] followed by a 30-second spiral swab with 10% P-I) [34]. The single swab 2% CHX/70% IPA method was more effective in skin decontamination (rate of initial positive bacterial cultures 143 per million versus 321 per million for controls; odds ratio [OR] 0.44, 95% CI 0.23-0.86).

In one study that compared bacterial contaminants before and after the change in skin preparation technique (two-swab process with P-I, during the period from 2007 to 2011, versus one-swab process with 2% CHX/IPA during 2012 to 2017), the average number of bacterial contaminants decreased from 4.2 per year to 0.8 per year, although this does not prove causality [35]. Despite these measures, a low number of bacteria may still enter a blood component during phlebotomy [36].

Diversion of first aliquot – The initial volume of blood collected from the donor is considered to be at highest risk for contamination, and many centers divert the first aliquot (15 to 40 mL) of donor blood. This prevention strategy has been proven to be effective in reducing bacterial contamination of blood products [37,38].

Leukoreduction – Prestorage leukoreduction, which is routine in most blood centers in the United States and other high-resource countries, may have also decreased rates of TTBI. (See "Practical aspects of red blood cell transfusion in adults: Storage, processing, modifications, and infusion", section on 'Pre-storage leukoreduction' and "Platelet transfusion: Indications, ordering, and associated risks", section on 'Leukoreduction'.)

Platelet-specific guidance and requirements — Platelets have the highest risk (more than 10-fold greater than red blood cells [RBCs] or plasma) of TTBI (see 'Incidence' above). Thus, additional mitigation processes have been added over time to further reduce the risk of TTBI from platelet transfusions [35]. The advantages and disadvantages of different strategies are summarized in the table (table 3).

Primary culture (introduced in the United States in 2004 and 2007) – This refers to testing for bacterial contamination in the platelet unit no sooner than 24 hours after collection (typically performed 24 to 36 hours after collection); it was introduced for apheresis platelets in 2004 and extended to whole blood-derived pooled platelets in 2007. Studies have demonstrated that primary culture was able to reduce the rate of bacterial contamination significantly (at one institution, 1511 per million before primary culture was instituted versus 348 per million afterwards) [35]. Other studies have also shown a benefit in reducing TTBI [39,40].

Mitigation options introduced in the United States in 2019 – TTBI can occur despite the use of primary culture because the initial inoculum was too small or the contaminating organisms were slow-growing, thus risking false-negative cultures in the first 24 to 36 hours after collection. Large volume delayed sampling (use of 16 mL rather than 8 mL and delaying culture beyond 24 to 36 hours) addresses both of these elements.

In response to the observation that TTBI remained a leading cause of transfusion-associated morbidity and mortality despite the widespread use of primary culture, the US Food and Drug Administration (FDA) introduced further mitigation methods to reduce bacterial contamination of platelets in 2019 [41,42]. The implementation timeframe was extended due to the COVID-19 pandemic.

Transfusion services that provide platelet components have the option to use either enhanced bacterial culture methods or pathogen-inactivated platelets. Per the FDA guidance, culture can be performed as a one-step or a two-step process [42]:

One-step process – Perform large volume delayed sampling no sooner than 36 hours after collection. "Large volume" implies use of a sample volume of at least 16 mL, rather than 8 mL for standard volume. The sample is then inoculated into aerobic and anerobic culture media. Cultures should be incubated for at least 12 hours prior to releasing the unit. Units processed in this manner have a shelf life of five days.

– or –

Perform large volume delayed sampling no sooner than 48 hours after collection, inoculate into aerobic and anaerobic media, cultured for at least 12 hours prior to release. These units have a shelf life of seven days.

– or –

Use a pathogen-reduced platelet product rather than performing secondary culture.

Two-step process – Perform primary culture no sooner than 24 hours after collection or large volume delayed sampling no sooner than 36 hours after collection.

– and –

Perform secondary culture no sooner than day 3; units outdate at day 5, or perform a point-of-release test (eg, an assay for bacterial components such as lipopolysaccharide [LPS]) within 24 hours of transfusion, or (for apheresis platelets only) perform secondary culture no sooner than day 4; units outdate at day 7. The two-step process has the advantage of extending shelf life but requires additional labor and complexity (culturing the unit at the collecting facility and again at the receiving facility), and it is not widely used.

Evidence to support these enhanced culture methods include studies prior to the use of secondary culture demonstrating that primary culture alone has a low sensitivity and may miss some contaminated units [43]. As discussed previously, doubling the sample volume used for bacterial culture was shown to improve sensitivity [38].

Pathogen inactivation treatments – UpToDate contributors use the term "pathogen inactivation" to refer to the procedures and "pathogen reduced" to refer to the blood components. Pathogen inactivation treatments for platelets involve addition of chemicals that damage nucleic acids followed by exposure to ultraviolet light; this is done shortly after platelets are collected. The goal is to inactivate or sufficiently reduce a variety of pathogens present in the unit so that the unit cannot cause TTBI.

These treatments can inactivate different types of microorganisms including viruses, bacteria, and parasites, and they have the potential to inactivate emerging pathogens for which blood components are not screened. The main disadvantage is increased cost.

Technical details and supporting evidence for pathogen inactivation are presented separately. (See "Pathogen inactivation of blood products", section on 'Platelets'.)

Immunoassay – In a 2011 study that used a rapid, lateral-flow immunoassay, performed on the date of issue, to evaluate 27,620 apheresis platelet units released as culture negative, nine units had a positive immunoassay test and subsequent positive confirmatory cultures [44].

Changes to storage time – The shelf life of platelets is short relative to other blood components, resulting in greater pressure to maintain inventory. Data to determine the effect of storage duration on the risk of TTBI are challenging to evaluate. The FDA allowed the storage time to be increased from five days to seven days, but an increase in septic transfusion reactions led the FDA to return to the five-day storage period in the mid-1980s. As noted in the discussions above, platelet products subjected to certain mitigation methods can have a shelf life extended to day 7.

Strategies at the bedside

Visual inspection – Visual inspection of the unit is the final step prior to transfusion that can be used to protect recipients from receiving platelet units with bacterial growth. Although not all abnormal-appearing units will have bacterial contamination, visual inspection can sometimes identify contaminated units due to discoloration or noticeable aggregates [45].

Occasional "near miss" incidents have been reported in which a contaminated platelet unit was intercepted and discarded due to abnormalities on visual inspection [46].

Monitoring the recipient – TTBI typically presents acutely. Standard monitoring includes vital signs and clinical assessment. Patients should be encouraged to report any unusual symptoms, especially development of fever, chills, nausea, vomiting, or following transfusion. (See "Practical aspects of red blood cell transfusion in adults: Storage, processing, modifications, and infusion", section on 'Administering the transfusion' and 'Typical presentation and clinical findings' below.)

Investigational strategies for prevention — Other strategies that are not in widespread use but might benefit from further study include:

Use of cold-stored platelets – Cold storage of platelets is under investigation and may improve shelf life. This approach may also address the increased risk of TTBI from platelets. (See "Platelet transfusion: Indications, ordering, and associated risks", section on 'Cold storage (investigational)'.)

Molecular (DNA) testing – DNA testing for specific bacterial pathogens is being studied for certain research and clinical indications [47-49]. DNA testing may have a higher sensitivity than culture-based techniques, and it has the potential to reduce TTBI from platelet-products and to increase shelf life [44,49]. Additional study is needed.

EVALUATION AND MANAGEMENT

Typical presentation and clinical findings — Clinical manifestations of TTBI can be highly variable and range from asymptomatic to fatal septic shock. Potential explanations for the variation in presentation of TTBI include the size of the bacterial inoculum, bacterial virulence, the recipient's immune status and underlying condition, and treatments the individual is receiving.

Signs and symptoms may be nonspecific and may overlap both with other transfusion reactions and/or with the patient's underlying condition, making it challenging to distinguish between TTBI and other causes of the patient's symptoms, especially in the initial few hours (table 4). Clinicians managing patients who become unwell during or following blood product administration must maintain a high degree of vigilance for TTBI as well as other transfusion reactions. (See 'Distinction from other transfusion reactions' below.)

Common signs of a septic transfusion reaction include:

Fever >39°C

Temperature increase of >2°C within a few hours following transfusion

Rigors

Tachycardia (heart rate >120 beats per minute)

Heart rate increase of ≥40 beats per minute within a few hours following transfusion

Rise or fall in systolic blood pressure (>30 mmHg)

TTBI can also occur in the absence of the above findings. A study from the early 1990s reported fever in 80 percent, chills in 53 percent, hypotension in 37 percent, and nausea or vomiting in 26 percent [50]. In a study from 2001 that included 41 cases of TTBI, 19 patients had minor symptoms, 16 had life-threatening severe sepsis or shock but recovered, and 6 patients died [12]. Fever and chills were the most common symptoms. Abdominal pain, back pain, nausea, vomiting, and hypothermia were also reported. No difference in the severity of clinical features with different blood components was observed.

The interval between the start of the transfusion and development of symptoms likely reflects the size of the inoculum, organism, and patient's underlying medical conditions.

Immediate interventions — Initial actions do not require distinction between TTBI and other serious transfusion reactions such as acute hemolytic reactions or anaphylaxis:

Stop the transfusion immediately.

Maintain a patent intravenous line and provide supportive/resuscitative care (hemodynamic, respiratory) as needed.

Notify the blood bank of a transfusion reaction and discuss the possibility that another patient may be affected (at risk of receiving a contaminated product if a contaminated component was split, or at risk of receiving an incorrect product if products were switched for two recipients).

Save the unused product and bag and return to the blood bank for testing (or coordinate with the blood bank or transfusion service to ensure that samples are sent to the proper place). In our institution, the blood bank coordinates sending samples to the microbiology laboratory; other institutions may have different policies.

If TTBI is suspected, collect two sets of blood cultures by venipuncture.

Evaluate for an acute hemolytic reaction. (See 'Laboratory testing/cultures' below.)

If there is a high suspicion for TTBI, begin empiric antibiotic therapy after cultures are obtained (do not delay while awaiting results).

The choice of antibiotics should be determined by information from the gram stain (if available) and local resistance patterns. Vancomycin plus a broad-spectrum beta-lactam (piperacillin-tazobactam, cefepime) should provide coverage for the most likely gram-positive and gram-negative organisms. Antibiotics can be stopped, narrowed, or expanded depending on culture results and the patient's clinical course. (See 'Antibiotic therapy' below.)

In addition to evaluating the unused component, the transfusion medicine service or blood bank can determine if other products may be affected, such as red blood cell (RBC) and plasma units from whole blood donations or additional apheresis platelet units from an apheresis platelet donation. All products from the same donation should be quarantined. Once the evaluation is completed, they can notify the appropriate agency. (See 'Case reporting' below.)

If there is equipoise regarding the likelihood of TTBI or sepsis from another source, the antibiotic choice may be targeted to other likely sources, as discussed separately. (See "Evaluation and management of suspected sepsis and septic shock in adults", section on 'Empiric antibiotic therapy (first hour)'.)

Most institutions have protocols for management of patients with suspected TTBI. Appropriate care involves close cooperation and communication between the clinicians caring for the patient, transfusion medicine service or blood bank, infectious diseases service, and microbiology laboratory.

Distinction from other transfusion reactions — The table summarizes differences among transfusion reactions (table 4).

Details are presented separately. (See "Approach to the patient with a suspected acute transfusion reaction", section on 'Initial patient assessment'.)

Laboratory testing/cultures

Cultures – Two blood cultures should be done to identify an infectious pathogen in the recipient, which is required to make a definite diagnosis (see 'Definitions' above):

The yield from cultures varies. In one study of 158 cases of suspected TTBI, there was a positive culture in the blood product and/or recipient in 77 percent of cases [12]. A gram stain of the residual contents of the blood product was positive in 56 percent of cases.

Results of positive cultures are used to adjust antibiotic therapy. Antibiotics are typically discontinued if an alternate diagnosis is made.

Testing for other transfusion reactions – One of the major considerations in the differential diagnosis of TTBI is an acute hemolytic transfusion reaction (AHTR), typically due to ABO incompatibility. This is evaluated by confirming the unit was administered to the intended recipient (rather than mistransfused due to a clerical error). Laboratory testing includes antiglobulin testing (Coombs testing), repeating the type and crossmatch, and testing for free heme in serum and urine. Close coordination between the treating clinicians and the transfusion service is important to coordinate this testing. (See "Hemolytic transfusion reactions", section on 'Evaluation and immediate management of AHTR'.)

Antibiotic therapy — Broad spectrum antibiotics are started empirically when there is a high suspicion for TTBI, guided by the gram stain of the implicated product if applicable. (See 'Immediate interventions' above.)

Once culture results and the results of testing for other transfusion reactions are available, antibiotics can be narrowed, expanded, or discontinued:

If a specific organism is identified, antibiotics can be narrowed to cover that organism.

If the patient is experiencing clinical deterioration, the antibiotics can be expanded.

If an alternative explanation explains the patient's clinical findings and cultures of the blood product were negative, antibiotics can be discontinued.

Antibiotic selection is discussed in more detail separately. (See "Evaluation and management of suspected sepsis and septic shock in adults", section on 'Empiric antibiotic therapy (first hour)'.)

Asymptomatic patient with notification of a positive culture from the blood collection center — Another clinical scenario is when a patient is clinically well, but either the blood collection center notifies the hospital that a platelet unit has a positive culture (after it has already been released to a hospital and transfused) or a gram stain and/or culture is positive on a co-component during investigation of a suspected transfusion reaction on another patient.

The decision to start antibiotics in such a case is individualized, realizing that the positive culture may represent a contaminant introduced during sampling of the unit, and the patient may not warrant changes in management.

If the patient is at high risk for infection (due to neutropenia), they may warrant increased surveillance and blood cultures; antibiotics may be started pending the blood culture results. However, the positive culture may be a sampling-induced contaminant, and the patient may not warrant additional interventions.

If the patient has an unexplained increase in white blood cell (WBC) count or high C-reactive protein (CRP) or if they will be away from direct medical care, it may be reasonable to obtain blood cultures and start empiric antibiotics pending the blood culture results.

Case reporting — Case reporting protects patients, since most apheresis platelet units are divided among several recipients, and another individual could be at risk for receiving a platelet unit from the same collection. Reporting also allows agencies to track the incidence of TTBI, determine whether mitigation processes are effective, identify new infectious pathogens, and maintain the safety of the blood supply.

Local requirements for case reporting should be followed. The transfusion medicine service usually submits the incident report. Many countries have robust hemovigilance systems. In the United States, all adverse transfusion reactions should be reported to the Centers for Disease Control and Prevention (CDC). Incident forms and instructions are provided on the CDC website [51,52].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Transfusion and patient blood management".)

SUMMARY AND RECOMMENDATIONS

Terminology and case definitions – Definitions of transfusion-transmitted bacterial infection (TTBI) vary depending on the clinical severity, which can range from bacterial contamination of the blood product without disease in the recipient to fatal septic transfusion reactions. The National Healthcare Safety Network (NHSN) differentiates definitive from possible cases and grades the confidence in the diagnosis. (See 'Definitions' above.)

Incidence and implicated blood products – The incidence of TTBI depends on definitions and extent of surveillance and reporting. Overall, platelet products carry the highest risk of TTBI. (See 'Epidemiology' above.)

Microbiology and risk factors – Gram-positive organisms, especially Staphylococcus and Streptococcus species, are more common than gram-negative organisms (table 2). Gram-negative sepsis is more likely to be fatal. Risk factors include storage conditions and immunocompromise in the recipient. (See 'Microbiology' above and 'Risk factors' above.)

Prevention

Preparation of the unit – Manufacturers and donation facilities must adhere to quality controls. Donors undergo medical history screening and are deferred if they have symptoms of active infection. The preferred skin disinfection solution is a product combining 2% chlorhexidine (CHX) in 70% isopropyl alcohol (IPA). Many blood collection centers divert the first aliquot of donor blood. (See 'Donor screening, skin preparation, and sample handling' above.)

Mitigation procedures for platelets – Primary culture of platelet units has been in place in the United States for decades. Guidance from the US Food and Drug Administration (FDA) published in 2019 specifies a choice of additional mitigation measures including large volume delayed sampling and use of pathogen-inactivated platelet products (table 3). (See 'Platelet-specific guidance and requirements' above.)

Administering the transfusion – Visual inspection may intercept a contaminated unit prior to transfusion. Patient monitoring may identify TTBI at an earlier stage and facilitate faster intervention. (See 'Strategies at the bedside' above.)

Management

Evaluation – Typical findings of TTBI (fever, rigors, tachycardia, hypotension, nausea) are nonspecific and may indicate one of several types of transfusion reactions. (See 'Distinction from other transfusion reactions' above.)

Immediate actions – Initial actions do not require distinction between TTBI and other serious reactions (see 'Immediate interventions' above and 'Distinction from other transfusion reactions' above):

-Stop the transfusion.

-Maintain a patent intravenous line and provide supportive/resuscitative care (hemodynamic, respiratory) as needed.

-Notify the blood bank of a transfusion reaction and possibility of other patients at risk.

-Save the product and return the unused portion to the blood bank for testing.

-If TTBI is strongly suspected, provide empiric antibiotics after cultures are obtained (do not delay while awaiting results).

Antibiotics – If empiric antibiotics are used, selection is determined by the gram stain and local resistance patterns. Vancomycin plus a broad-spectrum beta-lactam (piperacillin-tazobactam, or cefepime) should provide coverage for the most likely gram-positive and gram-negative organisms. Antibiotics can be narrowed, expanded, or discontinued depending on the patient's clinical course, culture results, and results of other evaluations. (See 'Antibiotic therapy' above.)

Reporting – TTBI should be reported to appropriate organizations. (See 'Case reporting' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Graeme MacLaren, MBBS, MSc, FRACP, FCICM, who contributed to earlier versions of this topic review.

  1. National Healthcare Safety Network Biovigilance Component Hemovigilance Module Surveillance Protocol. Centers for Disease Control. Available at: https://www.cdc.gov/nhsn/pdfs/biovigilance/bv-hv-protocol-current.pdf (Accessed on September 12, 2022).
  2. Definitions of current SHOT reporting categories & what to report. Serious Hazards of Transfusion. January 2022. https://www.shotuk.org/wp-content/uploads/myimages/SHOT-Definitions-active-Jan-2022.pdf (Accessed on June 14, 2022).
  3. Eder AF, Dy BA, DeMerse B, et al. Apheresis technology correlates with bacterial contamination of platelets and reported septic transfusion reactions. Transfusion 2017; 57:2969.
  4. Hong H, Xiao W, Lazarus HM, et al. Detection of septic transfusion reactions to platelet transfusions by active and passive surveillance. Blood 2016; 127:496.
  5. Ahmad Y, Heroes AS, Hume HA, et al. Bacterial contamination of blood products in Africa. Transfusion 2021; 61:767.
  6. Busch MP, Bloch EM, Kleinman S. Prevention of transfusion-transmitted infections. Blood 2019; 133:1854.
  7. Erony SM, Marshall CE, Gehrie EA, et al. The epidemiology of bacterial culture-positive and septic transfusion reactions at a large tertiary academic center: 2009 to 2016. Transfusion 2018; 58:1933.
  8. Fatalities Reported to FDA Following Blood Collection and Transfusion. US Food and Drug Administration. Available at: https://www.fda.gov/media/147628/download (Accessed on September 05, 2022).
  9. Fatalities Reported to FDA Following Blood Collection and Transfusion: Annual Summary for Fiscal Year 2020. US Food and Drug Administration. Available at: https://www.fda.gov/media/160859/download (Accessed on September 05, 2022).
  10. Fatalities Reported to FDA Following Blood Collection and Transfusion. US Food and Drug Administration, 2021. https://www.fda.gov/media/172382/download?attachment (Accessed on October 23, 2023).
  11. Kuehnert MJ, Roth VR, Haley NR, et al. Transfusion-transmitted bacterial infection in the United States, 1998 through 2000. Transfusion 2001; 41:1493.
  12. Perez P, Salmi LR, Folléa G, et al. Determinants of transfusion-associated bacterial contamination: results of the French BACTHEM Case-Control Study. Transfusion 2001; 41:862.
  13. Centers for Disease Control and Prevention (CDC). Red blood cell transfusions contaminated with Yersinia enterocolitica--United States, 1991-1996, and initiation of a national study to detect bacteria-associated transfusion reactions. MMWR Morb Mortal Wkly Rep 1997; 46:553.
  14. Guinet F, Carniel E, Leclercq A. Transfusion-transmitted Yersinia enterocolitica sepsis. Clin Infect Dis 2011; 53:583.
  15. Funk MB, Lohmann A, Guenay S, et al. Transfusion-Transmitted Bacterial Infections - Haemovigilance Data of German Blood Establishments (1997-2010). Transfus Med Hemother 2011; 38:266.
  16. Alabdullatif M, Ramirez-Arcos S. Biofilm-associated accumulation-associated protein (Aap): A contributing factor to the predominant growth of Staphylococcus epidermidis in platelet concentrates. Vox Sang 2019; 114:28.
  17. Maria Loza Correa, Sandra Ramirez-Arcos. Detection of bacterial adherence and biofilm formation on medical surfaces. In: Biofilms and Implantable Medical Devices: Infection and Control, 1, Ying Deng, Wei Lv (Eds), Elsevier, 2016. p.181-193.
  18. Haass KA, Sapiano MRP, Savinkina A, et al. Transfusion-Transmitted Infections Reported to the National Healthcare Safety Network Hemovigilance Module. Transfus Med Rev 2019; 33:84.
  19. Kou Y, Pagotto F, Hannach B, Ramirez-Arcos S. Fatal false-negative transfusion infection involving a buffy coat platelet pool contaminated with biofilm-positive Staphylococcus epidermidis: a case report. Transfusion 2015; 55:2384.
  20. Loza-Correa M, Kou Y, Taha M, et al. Septic transfusion case caused by a platelet pool with visible clotting due to contamination with Staphylococcus aureus. Transfusion 2017; 57:1299.
  21. Bryant BJ, Conry-Cantilena C, Ahlgren A, et al. Pasteurella multocida bacteremia in asymptomatic plateletpheresis donors: a tale of two cats. Transfusion 2007; 47:1984.
  22. Jafari M, Forsberg J, Gilcher RO, et al. Salmonella sepsis caused by a platelet transfusion from a donor with a pet snake. N Engl J Med 2002; 347:1075.
  23. Kracalik I, Kent AG, Villa CH, et al. Posttransfusion Sepsis Attributable to Bacterial Contamination in Platelet Collection Set Manufacturing Facility, United States. Emerg Infect Dis 2023; 29:1979.
  24. Jones SA, Jones JM, Leung V, et al. Sepsis Attributed to Bacterial Contamination of Platelets Associated with a Potential Common Source - Multiple States, 2018. MMWR Morb Mortal Wkly Rep 2019; 68:519.
  25. Gammon RR, Reik RA, Stern M, et al. Acquired platelet storage container leaks and contamination with environmental bacteria: A preventable cause of bacterial sepsis. Transfusion 2022; 62:641.
  26. Ramirez-Arcos S, DiFranco C, McIntyre T, Goldman M. Residual risk of bacterial contamination of platelets: six years of experience with sterility testing. Transfusion 2017; 57:2174.
  27. Benjamin RJ. Transfusion-related sepsis: a silent epidemic. Blood 2016; 127:380.
  28. Bacterial Risk Control Strategies for Blood Collection Establishments and Transfusion Services to Enhance the Safety and Availability of Platelets for Transfusion. US Food and Drug Administration. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/bacterial-risk-control-strategies-blood-collection-establishments-and-transfusion-services-enhance (Accessed on September 13, 2022).
  29. Kreuger AL, Middelburg RA, Kerkhoffs JH, et al. Storage medium of platelet transfusions and the risk of transfusion-transmitted bacterial infections. Transfusion 2017; 57:657.
  30. Ramirez-Arcos S, Jenkins C, Sheffield WP. Bacteria can proliferate in thawed cryoprecipitate stored at room temperature for longer than 4 h. Vox Sang 2017; 112:477.
  31. Martínez F, Tarrand J, Lichtiger B. Impact on patient outcome following transfusion of bacterially contaminated platelets: the M.D. Anderson Cancer Center experience. Am J Clin Pathol 2010; 134:207.
  32. Fenwick AJ, Gehrie EA, Marshall CE, et al. Secondary bacterial culture of platelets to mitigate transfusion-associated sepsis: A 3-year analysis at a large academic institution. Transfusion 2020; 60:2021.
  33. WHO guidelines on drawing blood: best practices in phlebotomy http://whqlibdoc.who.int/publications/2010/9789241599221_eng.pdf (Accessed on September 29, 2011).
  34. Benjamin RJ, Dy B, Warren R, et al. Skin disinfection with a single-step 2% chlorhexidine swab is more effective than a two-step povidone-iodine method in preventing bacterial contamination of apheresis platelets. Transfusion 2011; 51:531.
  35. Kundrapu S, Srivastava S, Good CE, et al. 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. Transfusion 2020; 60:974.
  36. Benjamin RJ, Dy B, Perez J, et al. Bacterial culture of apheresis platelets: a mathematical model of the residual rate of contamination based on unconfirmed positive results. Vox Sang 2014; 106:23.
  37. Liumbruno GM, Catalano L, Piccinini V, et al. Reduction of the risk of bacterial contamination of blood components through diversion of the first part of the donation of blood and blood components. Blood Transfus 2009; 7:86.
  38. Eder AF, Kennedy JM, Dy BA, et al. Limiting and detecting bacterial contamination of apheresis platelets: inlet-line diversion and increased culture volume improve component safety. Transfusion 2009; 49:1554.
  39. Thyer J, Perkowska-Guse Z, Ismay SL, et al. Bacterial testing of platelets - has it prevented transfusion-transmitted bacterial infections in Australia? Vox Sang 2018; 113:13.
  40. McDonald C, Allen J, Brailsford S, et al. Bacterial screening of platelet components by National Health Service Blood and Transplant, an effective risk reduction measure. Transfusion 2017; 57:1122.
  41. FDA guidance for industry, December 2020: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/bacterial-risk-control-strategies-blood-collection-establishments-and-transfusion-services-enhance (Accessed on July 17, 2022).
  42. Bacterial Risk Control Strategies for Blood Collection Establishments and Transfusion Services to Enhance the Safety and Availability of Platelets for Transfusion. US Food and Drug Administration. Available at: https://www.fda.gov/media/123448/download (Accessed on September 07, 2022).
  43. Murphy WG, Foley M, Doherty C, et al. Screening platelet concentrates for bacterial contamination: low numbers of bacteria and slow growth in contaminated units mandate an alternative approach to product safety. Vox Sang 2008; 95:13.
  44. Jacobs MR, Smith D, Heaton WA, et al. Detection of bacterial contamination in prestorage culture-negative apheresis platelets on day of issue with the Pan Genera Detection test. Transfusion 2011; 51:2573.
  45. Satake M, Kozakai M, Matsumoto M, et al. Platelet safety strategies in Japan: impact of short shelf life on the incidence of septic reactions. Transfusion 2020; 60:731.
  46. Brailsford SR, Tossell J, Morrison R, et al. Failure of bacterial screening to detect Staphylococcus aureus: the English experience of donor follow-up. Vox Sang 2018.
  47. Sen K. Rapid identification of Yersinia enterocolitica in blood by the 5' nuclease PCR assay. J Clin Microbiol 2000; 38:1953.
  48. Ribault S, Harper K, Grave L, et al. Rapid screening method for detection of bacteria in platelet concentrates. J Clin Microbiol 2004; 42:1903.
  49. Harm SK, Delaney M, Charapata M, et al. Routine use of a rapid test to detect bacteria at the time of issue for nonleukoreduced, whole blood-derived platelets. Transfusion 2013; 53:843.
  50. Morduchowicz G, Pitlik SD, Huminer D, et al. Transfusion reactions due to bacterial contamination of blood and blood products. Rev Infect Dis 1991; 13:307.
  51. CDC incident form https://www.cdc.gov/nhsn/forms/57.305_hemovigilance_incident_blank.pdf (Accessed on July 17, 2022).
  52. CDC instructions https://www.cdc.gov/nhsn/forms/instr/57.305-TOI-8_1.pdf (Accessed on July 17, 2022).
Topic 3805 Version 39.0

References

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