|
Suspected transfusion transmitted infection.Initial information received: 31-jul-2023, 09-aug-2023, 17-aug-2023, 18-aug-2023, 23-aug-2023 (in).Executive summary: the patient involved in this report is a 72-year-old male.· product complaint #: (b)(4).· manufacturing blood center: haema ag lvv, berlin.· intercept product code #: int2504 b.· collection instrument: trima.· suspension medium: acda/terumo bct.· apheresis kit lot #: not reported.· pas intersol lot #: 22111701f1.· product type: platelets.· implicated component product code #: not reported.· illuminator serial #: (b)(6).· implicated unit donation id # (din#):(b)(6).· intercept blood system for platelets processing set lot#: ce23a19l71.On 31-jul-2023, cerus received a spontaneous report of suspected transfusion transmitted bacillus cereus (b.Cereus) with an intercept platelet component (pc) [pt: transmission of an infectious agent via product] from the cerus vp of global scientific and medical affairs.He was in communication with the chief medical officer (cmo) of haema ag in germany and relayed the information to cerus customer care team.This event of suspected transfusion transmitted b.Cereus was associated with one of the two units of intercept pc (din# (b)(6); implicated unit blood component processing set lot#: ce23a19l71) manufactured from a double apheresis platelet collection transfused to two patients.The other patient who received the implicated co-component intercept pc (din# (b)(6) was reported to cerus at the same time.Additional information on the initial report was received on 09-aug-2023 from (b)(6).Donor information: the donor of the implicated unit (din#:(b)(6) was a 61-year-old, male with no history of positive bacterial detection with platelet donation.He donated a double apheresis platelet and a single apheresis plasma component on (b)(6) 2023.No further information about the donor was reported.Apheresis platelet and plasma samples from a subsequent donation on (b)(6) 2023 were cultured on (b)(6)2023 with negative results on (b)(6) 2023.Gram stain was not performed.Haema ag uses descoderm, a 70% propanol skin disinfectant for blood donations.Implicated unit collection and manufacturing information: on (b)(6) 2023 from 13:02h to 14:09h, a double apheresis platelet and single apheresis plasma collection was performed on a trima (apheresis collection kit lot # was not reported) at (b)(6), germany.The apheresis platelets were suspended in acda/terumo bct platelet container (lot#: 23063010 expiration date: 01-mar-2025).On the same day, the implicated unit was treated with an intercept blood system dual storage (ds) processing set (product code #: int2504b, processing set lot#: processing set lot#: ce23a19l71, set expiration date: 31-dec-2024) and illuminated with the intercept illuminator serial number (b)(6) from 17:27h - 17:33h (3.5 hours after the end of collection) at (b)(6), germany.There were no device malfunctions of irregularities associated with the intercept treatment process reported by (b)(6), germany.On (b)(6) 2023, (b)(6) provided a summary of microbiological investigation that did not identify any environmental source of the b.Cereus.As part of the investigation, they performed skin swabs from the antecubital area of the donor arm, swab samples of external storage location, manufacturing site and have ongoing hygiene monitoring of blood donation center, manufacturing site and laboratory.There were no reports of b.Cereus contamination at (b)(6) in the last 3 years.Blood component(s) information: implicated intercept pc transfused to the patient on (b)(6) 2023.On (b)(6) 2023 the residual bag of the implicated intercept pc din# (b)(6) was received at laboratory of (b)(6) unsealed along with the transfusion kit.On the same day, the residual bag was rinsed with sterile saline and the rinse solution was cultured and grew b.Cereus var.Cereus under aerobic and anaerobic conditions.The hours to positive blood culture results were reported as aerobic: 17:56h (7 h 43 min) and anaerobic: 16:26h (6 h 13 min), determined by the reporter as rapid growth.Antigram of the b.Cereus var.Cereus indicated sensitivity at standard dose against imipenem, meropenem, clindamycin, vancomycin linezolid and sensitivity at higher dose against levofloxacin.Co-components of the implicated intercept pc on (b)(6) 2023 (day 5 of storage), the implicated co-component of intercept pc (din#(b)(6)) was transfused to another patient who subsequently experienced a serious adverse event that was ultimately fatal, ascribed to a suspected b.Cereus septic transfusion reaction with an intercept pc.Refer to (b)(4) for full details about this patient's investigation.The apheresis plasma co-component was quarantined, not transfused and cultured with negative result.Patient clinical course: this report involved a 72-year-old male patient with a history of aml and thrombocytopenia, who experienced a serious adverse event of suspected transfusion transmitted b.Cereus following the transfusion of intercept pc.On (b)(6) 2023 at 09:30am, the patient received the implicated intercept pc transfusion (din#:(b)(6) for thrombocytopenia.This transfusion episode took place at an outpatient transfusion center, thus limited clinical and laboratory information were obtainable for evaluation.The full unit of 199 milliliters (ml) was transfused.The patient's pre-transfusion vitals were reported as unknown but there were no signs or symptoms suggestive of infection or sepsis.Post-transfusion, his body temperature increased by > 1 °c (reported as sub-febrile temperature) and elevated to a max of 39.5 °c at a later time.He also developed chills/rigors, nausea/vomiting, malaise and diarrhea but no evidence of hypotension.The patient was subsequently admitted to the hospital as a cautionary measure where he received amoxicillin and clavulanic acid empiric antibiotic treatment for suspected transfusion transmitted infection.The patient's blood was cultured on 3 separate days ((b)(6)2023, (b)(6) 2023, (b)(6) 2023) and all samples tested negative for pathogens.It is unknown whether or not the first culture taken on (b)(6) 2023 was done prior or after initiating antibiotics.On (b)(6) 2023 the patient recovered from the transfusion reaction and was discharged from the hospital.Investigations: cerus investigation: on 01-aug-2023, cerus sent the transfusion reaction form (frm 00785) to the representative at (b)(6) in germany to provide additional information.On 09-aug-2023, cerus received the completed transfusion reaction form (frm 00785) from the representative at(b)(6) in germany.On 09-aug-2023, cerus completed a batch record review for (intercept product code #: int2504b, processing set lot#: ce23a19l71).The review of the batch records for the finished goods did not indicate any out-of-limit results during testing and controls.The product met all quality requirements and specifications at the time of release.This batch was released on 17-mar-2023.There were no other complaints for lot ce23a19l71.The total batch size was (b)(4) processing sets.On 17-aug-2023 and 18-aug-2023, cerus held two conference calls with dr.(b)(6) and dr.(b)(6) , at (b)(6) in germany.Additional clinical information and clarifications were obtained from (b)(6) regarding this adverse event report which have been incorporated in this narrative.Assessments: reporter assessment: 1.Transfusion transmitted b.Cereus with intercept pc [pt: transmission of an infectious agent via product] the reporter assessed the event as severe in severity and serious due to hospitalization.Causality was assessed as possible in relation to the intercept blood system for platelets device and possible in relation to the transfused intercept pc.Cerus medical reviewer (mr) assessment: 1.Transfusion transmitted b.Cereus with intercept pc [pt: transmission of an infectious agent via product] the cerus mr assessed the event as serious due to hospitalization.The causality was assessed as unlikely in relation to a defect in the intercept blood system for platelets device since there were no indication of device malfunction, compromise of the platelet processing set or the pathogen inactivation process from (b)(6) and cerus.Bacillus cereus is a common environmental spore-forming organism that may be found on the skin.Bacillus cereus is effectively inactivated in the vegetative state but the spore form is known to be relatively resistant to the intercept process and this is stated in the manufacturers' technical datasheet.Transmission of b.Cereus contaminated platelets is a rare but known complication, even when the intercept process is performed appropriately.The causality was assessed as possible in relation to the transfused intercept pc, although other causes cannot be definitively ruled out.The patient developed multiple signs and symptoms suggestive of a transfusion reaction with fever being the most prominent, one cannot definitively conclude this is due to b.Cereus infection because the patient never became hypotensive, and the first blood culture taken on the same date as the transfusion reaction was negative.The documented signs and symptoms immediately post-transfusion are more suggestive of underlying disease and/or febrile non-hemolytic transfusion reaction.While we recognize that the subsequent two negative blood cultures could be the effect of the patient being on antibiotic, this should still be considered as circumstantial evidence against b.Cereus infection.The clinical team performed multiple cultures on the patient, none were performed on the bag immediately post-transfusion, suggesting that they did not suspect a septic transfusion reaction at the time.The positive b.Cereus culture result from the residual platelet bag was from a sample taken 8 days after the transfusion, and then only after the report of sepsis in the recipient of the split sister unit.Since it was reported that the residual bag was left unsealed and had protracted storage time under unknown storage conditions, it is entirely possible the positive bag culture result is due to environmental contamination after the transfusion episode.Although the antigram for this implicated intercept pc demonstrated similar sensitivities as the implicated co-component intercept pc transfused to another patient (please reference(b)(4), b.Cereus is a common environmental contaminant, and genotyping of the strain isolated from the patient and the bags would be required to implicate the platelet product in a septic reaction even in the presence of similar antibiotic sensitivity.The co-component apheresis plasma was cultured with negative result, arguing against gross contamination at the time of collection.Finally, propanol-based skin disinfectant is not a robust bactericidal agent against bacillus sp.Spores, thus the possibility of a true contamination event due to ineffective skin prep still exist but cannot be fully corroborated given the limited clinical information and lack of adequate residual platelet and patient positive culture samples for further analysis.The cerus medical reviewer considered the listedness for the event to be listed for transfused intercept blood system for platelets device and intercept pc based on applicable cerus safety reference information.
|
