MAUDE data represents reports of adverse events involving medical devices. This maude entry was filed from a foreign,health professional,u report with the FDA on 2016-01-15 for INTERCEPT BLOOD SYSTEM FOR PLATELETS manufactured by Cerus Corporation.
[36105496]
Cerus medical preliminary assessment ((b)(6) initial report): the adverse event report (aer) describes a case of an (b)(6)man who suffered an acute reaction 35 minutes after initiating an apheresis platelet transfusion (symptoms included fever (39. 5? C); hypertension (baseline 130/80 mmhg; post reaction 158/69 mmhg); tachycardia (baseline 78/min post reaction 148/min); shivering; and dyspnea). Bacterial culture of the residual component and patient apparently revealed klebsiella pneumoniae with an identical antibiotic resistance profile. These findings are in keeping with a severe septic transfusion reaction. In considering the relatedness to transfusion, it is plausible that the contamination of the platelet product occurred after the sterile integrity of the component was compromised by "spiking" the bag for transfusion, and contamination occurred by retrograde flow from a bacteremia in the patient. The patient in this case was an elderly man ((b)(6) on recently-initiated, high dose steroid therapy (spiricort 50mg). A subclinical urinary tract infection with klebsiella pneumoniae is plausible, despite the lack of symptoms prior to transfusion, and was not ruled out. The following factors favor this interpretation:? There was a 6 hour delay between spiking the component and bacterial culture sampling. The delay would have allowed bacterial growth in the platelet component if it were contaminated at the time of spiking for transfusion. ? The concentration of klebsiella pneumoniae was low at the time of sampling. The microbiology report states a finding of "+/- cells, negative microorganisms" and the laboratory sop confirms that a gram stain is routinely performed. Gram staining has a sensitivity to detect bacteria at concentrations of >10^5 cfu/ml. A negative result implies a low concentration (<10^5 cfu/ml) of bacteria 6 hours after the sterile integrity of the product was compromised by spiking. ? Klebsiella pneumoniae grows rapidly under blood culture conditions. The time to positive culture was 10. 6 hours, whereas fang et al report that the time to positive culture of three independent klebsiella spp. Strains isolated 24 hours after collection of apheresis platelets was a mean of 7. 7 + 1. 8 hours(1). The data suggest a lower bacterial contamination in this case where the sample was taken 5 days after collection. This is in keeping with contamination of the platelet component at the time of transfusion. ? The patient was reported to have a pre transfusion platelet count of 33 g/l and a post transfusion platelet count of 62 g/l. It is unlikely that a heavily contaminated platelet component would result in such a robust increase in platelet count. ? Culture of the split platelet component revealed failed to reveal contamination, suggesting that it is less likely that the platelet component was contaminated at the time of collection. An alternative explanation is that the platelet component was contaminated and was the source of the bacterial sepsis upon transfusion. Contamination after pathogen inactivation treatment with the intercept blood system (ibs) but before transfusion cannot be ruled out, but seems unlikely, given the integrity of the closed system and routine inspection of the component during handling. Contamination during collection with klebsiella pneumoniae is a major risk of platelet transfusion and a frequent cause of fatal reactions before interventions to detect or inactivate bacteria were implemented in the us(2). Asymptomatic, low concentration donor bacteremia is thought to be the underlying etiology. The blood center investigation suggests that the ibs process was performed according to standard procedures and no non-conformities were detected. The possibility that this particular klebsiella pneumoniae strain is resistant to treatment by the ibs is plausible, but deemed unlikely for the following reasons:? The instructions for use for the ibs document a 5. 8 log10 bacterial reduction efficacy for klebsiella pneumoniae under standardized laboratory conditions. While the concentration of bacteria at the time of ibs treatment in this case is unknown, multiple experiments have documented that the ibs incorporates robust inactivation of klebsiella pneumoniae that exceed this limit under routine clinical conditions:? Schmidt et al document that multiple (3) replicates of apheresis platelets contaminated 100 cfu (~0. 4 cfu/ml) or 1,000 cfu (~4 cfu/ml) per component with each of two strains of klebsiella pneumoniae were completely inactivated by ibs treatment 12 hours after contamination(3). Sterility was confirmed by culture 7 days after ibs treatment. At the time of ibs treatment, the concentrations of bacteria were documented to be 10^4 -10^6 cfu/ml in a 250 ml platelet component, implying a bacterial load of 106-108 bacteria per component. ? Nussbaumer at al document that apheresis platelets inoculated with 4, 50 or 250 cfu of klebsiella pneumoniae and treated with ibs 18-20 hours later, showed negative cultures when performed 5 days after contamination(4). The bacterial concentrations at the time of ibs treatment were not documented. ? Wagner et al contaminated multiple replicates (3) of apheresis platelets with <100 cfu of each of two klebsiella pneumoniae strains and treated with the ibs 24 hours after contamination, when the bacterial load was documented to be 10^5. 5-10^6. 5 cfu/component(5). No positive cultures were detected when cultures were performed on day 7 after collection. Cerus will attempt to retrieve samples of the klebsiella pneumoniae strain implicated in this case and perform bacterial growth and pathogen inactivation studies to determine susceptibility to inactivation. Taken together, all indications are that the ibs system was performed according to procedure, and was capable of inactivating high levels of the klebsiella pneumoniae species implicated in this transfusion reaction. Other causes of the reaction have not been ruled out. We conclude that failure of the ibs treatment to completely inactivate the bacteria was possibly related to this transfusion reaction and cannot be ruled out at this time. Further investigations are underway and will be described in our final report. (b)(6). References c. T. Fang et al. , detection of bacterial contamination in apheresis platelet products: american red cross experience, 2004. Transfusion 45, 1845 (dec, 2005). M. T. Niu, m. Knippen, l. Simmons, l. G. Holness, transfusion-transmitted klebsiella pneumoniae fatalities, 1995 to 2004. Transfus med rev 20, 149 (apr, 2006). M. Schmidt et al. , evaluation of the effectiveness of a pathogen inactivation technology against clinically relevant transfusion-transmitted bacterial strains. Transfusion 55, 2104 (sep, 2015). W. Nussbaumer et al. , prevention of transfusion of platelet components contaminated with low levels of bacteria: a comparison of bacteria culture and pathogen inactivation methods. Transfusion 47, 1125 (jul, 2007). S. J. Wagner et al. , inactivation of bacteria in apheresis platelets with pathogen reduction performed 24 hours after inoculation. Vox sanguinis [abstract 4d-s27-06), (2015). The timeline reveals that the patient suffered an acute transfusion reaction, as described above, on (b)(6) from 11:05- 16:10 h and was treated with antihistamines (tavegyl 2mg) and steroids (solumedrol 40 mg) only, during that time. He was considered fully recovered at 16:10 h on (b)(6). His post transfusion platelet count was taken at 11:20 h, soon after the transfusion was stopped and was measured at 62 g/l, a substantial increment from the pretransfusion count of 33 g/l taken at 5:00 h that morning. The residual platelet component was received at the microbiology laboratory at 16:32 h on (b)(6) and was discovered to be positive 10. 6 hours later, presumably in the early morning of (b)(6). A blood culture was taken from the patient on (b)(6) at 13:15 h and resulted positive after 9. 1 hours incubation with klebsiella pneumoniae. The patient was apparently asymptomatic between 16:10 h on (b)(6) and 18:30 h on (b)(6) when he received a second uneventful platelet transfusion. At this time he was in the ent ward. The patient's urine was cultured on (b)(6) at 14:00 h. No growth was detected. The patient was in a surgical inpatient ward at this time. Presumably in response to the positive platelet bacterial culture on (b)(6), the patient's blood was cultured at 18:15 h on (b)(6). The sample was taken in a medical inpatient ward and was received at the microbiology laboratory at 8:02 h on (b)(6). Klebsiella pneumoniae bacteria grew within 1. 6 hours of culture. The patient received a first injection of antibiotic (rocefin [ceftriaxone] 250 mg) at 20:00 h on (b)(6), more than 24 hours after the transfusion reaction had ended. Cerus medical assessment (follow up): the aer describes a case of an (b)(6) man who suffered an acute reaction 35 minutes after initiating an apheresis platelet transfusion (symptoms included fever (39. 5? C); hypertension (baseline 130/80 mmhg; post reaction 158/69 mmhg); tachycardia (baseline 78/min post reaction 148/min); shivering; and dyspnea). The patient was treated with antihistamines (tavegyl 2mg) and steroids (solumedrol 40 mg), presumably for an "allergic reaction". All symptoms resolved by 16:10 h that day. Bacterial culture of the residual component received in the laboratory 6 hours after the transfusion began, and also the patient blood taken during the reaction, revealed klebsiella pneumoniae with an identical antibiotic resistance profile. These findings are in keeping with a severe septic transfusion reaction. In considering the relatedness to transfusion, it is plausible that the contamination of the platelet product occurred after the sterile integrity of the component was compromised by "spiking" the bag for transfusion, and contamination occurred by retrograde flow from a bacteremia in the patient. The patient in this case was an elderly man ((b)(6)) on recently-initiated, high dose steroid therapy (spiricort 50mg). A subclinical infection with klebsiella pneumoniae is plausible, despite the lack of symptoms prior to transfusion, and was not ruled out. The following factors favor this interpretation:? The patient appears to have been asymptomatic after the end of the initial reaction at 16:10 h on (b)(6) 2015 without antibiotic therapy and despite later documented sepsis, in keeping with the subclinical nature of his infection. ? There was a 6 hour delay between spiking the component and bacterial culture sampling. The delay would have allowed bacterial growth in the platelet component if it were contaminated at the time of spiking for transfusion. ? The concentration of klebsiella pneumoniae was low at the time of sampling. The microbiology report states a microscopy finding of "+/- cells, negative microorganisms" and the laboratory sop confirms that a gram stain is routinely performed. Gram staining has a sensitivity to detect bacteria at concentrations of >10^5 cfu/ml. A negative result implies a low concentration (<10^5 cfu/ml) of bacteria 6 hours after the sterile integrity of the product was compromised by spiking. ? Klebsiella pneumoniae grows rapidly under blood culture conditions. The time to positive culture was 10. 6 hours, whereas fang et al report that the time to positive culture of three independent klebsiella spp. Strains isolated 24 hours after collection of apheresis platelets was a mean of 7. 7 + 1. 8 hours(1). The patient's blood specimen was positive 9. 1 hours after initial incubation, re-emphasizing the rapid growth of this organism and suggesting a higher concentration of bacteria in the patients' blood than in the residual platelet component. The data suggest a low bacterial contamination in this case where the sample was taken 5 days after collection. This is in keeping with contamination of the platelet component at the time of transfusion. ? The patient was reported to have a pre transfusion platelet count of 33 g/l and a post transfusion platelet count of 62 g/l. It is unlikely that a heavily contaminated platelet component would result in such a robust increase in platelet count. ? Culture of the split platelet and concurrent plasma components failed to reveal contamination, suggesting that it is less likely that the platelet component was contaminated at the time of collection. An alternative explanation is that the platelet component was contaminated and was the source of the bacterial sepsis upon transfusion. Contamination after pathogen inactivation treatment with the intercept blood system (ibs) but before transfusion cannot be ruled out, but seems unlikely, given the integrity of the closed system and routine inspection of the component during handling. Contamination during collection with klebsiella pneumoniae is a major risk of platelet transfusion and a frequent cause of fatal reactions before interventions to detect or inactivate bacteria were implemented in the us(2). Asymptomatic, low concentration donor bacteremia is thought to be the underlying etiology. The blood center investigation suggests that the ibs process was performed according to standard procedures and no non-conformities were detected. The possibility that this particular klebsiella pneumoniae strain is resistant to treatment by the ibs is plausible, but deemed unlikely for the following reasons: the instructions for use for the ibs document a bacterial reduction efficacy for klebsiella pneumoniae of 5. 8 log10 (us package insert) or >5. 6 log10 (european technical data sheet) under standardized laboratory conditions. While the concentration of bacteria at the time of ibs treatment in this case is unknown, multiple experiments have documented that the ibs incorporates robust inactivation of klebsiella pneumoniae that exceed this limit under routine clinical conditions:? Schmidt et al document that multiple (3) replicates of apheresis platelets contaminated 100 cfu (~0. 4 cfu/ml) or 1,000 cfu (~4 cfu/ml) per component with each of two strains of klebsiella pneumoniae were completely inactivated by ibs treatment 12 hours after contamination(3). Sterility was confirmed by culture 7 days after ibs treatment. At the time of ibs treatment, the concentrations of bacteria were documented to be 10^4 -10^6 cfu/ml in a 250 ml platelet component, implying a bacterial load of 10^6-10^8 bacteria per component. ? Nussbaumer at al document that apheresis platelets inoculated with 4, 50 or 250 cfu of klebsiella pneumoniae and treated with ibs 18-20 hours later, showed negative cultures when performed 5 days after contamination(4). The bacterial concentrations at the time of ibs treatment were not documented. ? Wagner et al contaminated multiple replicates (3) of apheresis platelets with <100 cfu of each of two klebsiella pneumoniae strains and treated with the ibs 24 hours after contamination, when the bacterial load was documented to be 10^5. 5-10^6. 5 cfu/component(5). No positive cultures were detected when cultures were performed on day 7 after collection. Cerus will attempt to retrieve samples of the klebsiella pneumoniae strain implicated in this case and perform bacterial growth and pathogen inactivation studies to determine susceptibility to inactivation. Taken together, all indications are that the ibs system was performed according to procedure, and was capable of inactivating high levels of the klebsiella pneumoniae species implicated in this transfusion reaction. Other causes of the reaction have not been ruled out. Failure of the ibs treatment to completely inactivate the bacteria was possibly related to this transfusion reaction and cannot be ruled out. However other probable causes include underlying patient sepsis and retrograde contamination of the platelet component at the time of transfusion (b)(6) references c. T. Fang et al. , detection of bacterial contamination in apheresis platelet products: american red cross experience, 2004. Transfusion 45, 1845 (dec, 2005). M. T. Niu, m. Knippen, l. Simmons, l. G. Holness, transfusion-transmitted klebsiella pneumoniae fatalities, 1995 to 2004. Transfus med rev 20, 149 (apr, 2006). M. Schmidt et al. , evaluation of the effectiveness of a pathogen inactivation technology against clinically relevant transfusion-transmitted bacterial strains. Transfusion 55, 2104 (sep, 2015). W. Nussbaumer et al. , prevention of transfusion of platelet components contaminated with low levels of bacteria: a comparison of bacteria culture and pathogen inactivation methods. Transfusion 47, 1125 (jul, 2007). S. J. Wagner et al. , inactivation of bacteria in apheresis platelets with pathogen reduction performed 24 hours after inoculation. Vox sanguinis [abstract 4d-s27-06), (2015).
Patient Sequence No: 1, Text Type: N, H10
[36105497]
This adverse event report (aer) is a regulatory authority case sent by (b)(6) to cerus on (b)(6) 2015 (originally reported to (b)(6) 2015) and concerns an (b)(6) male patient at the luzerner kantonspital with thrombocytopenia and anemia of unknown cause (differential diagnoses: immune thrombocytopenia, myelodysplastic syndrome - mds). Patient was scheduled for an ear-nose-throat surgery and received one platelet concentrate (pc) unit on "(b)(6) 2016" (10:30 h) prophylactically. Platelet count prior to transfusion was 33g/l and post transfusion was 62 g/l. Surgery was cancelled due to severe transfusion reaction (tr) characterized by the following symptoms: chills, fever (39. 5? , dyspnea, rise of blood pressure (baseline was 130/80 mmhg post transfusion 158/69 mmhg) and tachycardia (baseline 78/min post transfusion148/min). Tr started at 11:05 hours and lasted until 16:10 hours on (b)(6) 2015. Blood culture of the patient and the culture of the empty bag of the pc (received by the microbiology laboratory at 16:32 on (b)(6) 2015) grew ampicillin and cefuroxime resistant klebsiella pneumoniae (same antibiotic resistance sensitivity pattern) after being incubated for 10. 5 hours. Sample for platelet bag culture was taken according to internal sop- in this case 10-20 ml of platelets were extracted from the transfusion bag in a sterile manner and were transferred to the culture bottles, the remainder of the samples were kept in the fridge at 4 degrees celsius. The sample was taken from a primary bag via sterile port. The patient did not show any evidence of sepsis before transfusion, or evidence of pneumonia or other local infection caused by klebsiella spp. A blood culture was not performed before transfusion. The hospital had not observed any sepsis case of the same klebsiella spp. Strain in 2015. The patient was taking spiricort 50 mg (prednisolone) since (b)(6) 2015 and received the following medications post transfusion: an antibiotic (unknown drug), tavegyl (clemastine) 2 mg i. V. , solumedrol (methylprednisolone) 40 mg single shot i. V. The pc came from a double platelet apheresis collection donated on (b)(6) 2015 by a (b)(6) female donor (with a past history of apheresis and full blood donations) who was fully acceptable for donation according to the guidelines/sops from the blood services in switzerland. Collection was performed with a blood cell separator trima accel (terumobct ) and specific bags to collect platelets and plasma (terumo set nr. 80 410). Donation ended at 10:25 hours, lasting 64 min. Two sets of platelet components (pc1 and pc2) were separated prior to sealing the small volume pi-sets. Sterile connections were performed with tscd ii (sterile docking device terumobct); connections were checked and controlled according to sop. The final product was kept on tc-flat incubator under agitation and controlled temperature -products were kept until transfusion on (b)(6) 2015 at 10:30 h, i. E. 4 days and 17 hours after treatment (119. 5 hours [5 days] after collection). All personnel in charge had not reported being sick. The time between donation and pathogen inactivation was 6 hours. Donor was not sick prior and post donation. A telephone control call did not reveal any illness post donation. There are no previous reports of transfusion reactions from the recipients of blood components from this repeat donor. The second pc (pc2) was transfused to another patient on day 5 after collection without any documented transfusion reaction; however, that patient was on antibiotic therapy due to his underlying disease. Culture of the pc2 bag was negative: no germs/bacteria could be detected. The plasma obtained from this donation was also tested, no bacteria could be found. Initial reporter's assessment (blood center physician: dr (b)(6), free translation from german by dr. (b)(6), german-speaking cerus medical reviewer): the blood center physician assessed the relatedness of the events of chills, fever, dyspnea, increased blood pressure, tachycardia and suspected septic transfusion reaction as "probable" to the ibs treated platelet component. Investigation of all steps of production did not show any non-conformities. Storage receipt control of all critical material used and additional control of all certificates with special emphasis on sterility proof, did not find any non-conformities. Temperature controls of storage rooms, used materials, interim and end-products were equally conformant. The donor was fully acceptable for donation according to guidelines of the swiss blood services and did not get sick after donation. Microbiologic investigations showed bacterial growth of klebsiella pneumoniae for pc1. For pc2 and plasma, no bacterial growth was detected (see notification tr nr. Tr-1286). The high number of bacteria detected in pc1 is especially astounding. Time to positivity was 10. 6 hours (which is the time gap from placing the blood culture bottle into the automat and a positive signal and correlates with the number of bacteria within the culture). The following sources of bacterial contamination may be considered: bacteremia of donor: a bacteremia of the donor would have infected most probably all products to the same extent, especially both pcs (platelet components) as these were equally distributed into two separate bags from the collection bag. At the time of notification, 8 days post donation, it was not practical to take a blood culture from the donor. Transient bacteremia is possible at any time in carriers of bacteria - klebsiella pneumoniae is frequently found in the normal flora of oral mucosa and gastrointestinal tract. It would be interesting to know the number of bacteria in a carrier that can lead to clinical symptoms. It would be useful to take a mouth swab and blood cultures next time this donor donates blood. Should there be growth, sequencing will be initiated. If the sequencing results do not match the klebsiella strain seen in the patient, then the donor can be ruled out as a "source" of contamination in this case. In case of a match, it would be assumed that there was an error somewhere or insufficient pathogen inactivation of the product in question. Contaminated bag system during platelet withdrawal: in this case, only one of the end-product bags was contaminated. In addition, contamination should have been sufficiently high that depletion capacity was insufficient. It remains to be questioned if the bag system should be controlled, although sterility was documented (certificate of charge). This charge is in use without any further occurrences. Contaminated bag system of package inactivation (pi): in this case, the pi bag could have been contaminated to such an extent that the depletion capacity was insufficient or the bag with the amotosalen adsorber could be have been contaminated (at the time of pi it was dry). Sterility was documented (certificate of the charge). It remains to be questioned if the bag system should be investigated. This charge is currently in use without any further events. Contaminated solutions: in this case, the solutions acd or intersol could have been contaminated to such an extent that the depletion capacity was insufficient. In which case all three products should have been contaminated (at least the two pcs). Sterility was documented (certificate of the charge). It remains to be questioned if the bag system should be investigated. This charge is currently in use without any further events. No or insufficient amount of amotosalen: staff opened the breakable outlet for addition of amotosalen before the platelet fluid entered the bag. If there were no amotosalen, that would have been detected then. An insufficient amount of amotosalen cannot be excluded, although it is pretty unlikely it would have not been detected. Insufficient illumination: service in the illuminator takes place every 6 months and it has taken place in may and november (after this event) and did not show any non-conformities. Therefore, insufficient illumination seems to be very unlikely. Leakage of the bag in question during process prior to pi: contamination should have been to such an extent that the depletion capacity was insufficient. All bags are visually checked for leakages by our staff. A leakage would have been detected, but a "non-detection" can never be ruled out. Leakage after pi: bags are visually checked for leakages. A leakage would have been detected, but a "non-detection" can never be ruled out. Contamination by the patient: it is known that klebsiella pneumoniae induces nosocomial pneumonia in immune incompetent patients in hospital wards. The recipient was on steroidal drug therapy due to his itp. He could have acquired the bacteria prior to the transfusion. This however does not seem likely as the patient was completely asymptomatic until the time of transfusion. A retrograde contamination by transfusion disposables is possible, but so far, to the physician's knowledge, it has only been described for viruses. It remains to be explored if such a contamination by bacteria has been reported. Contamination during the process of collecting blood for blood culture: a contamination during preservation, during interim storage prior to cultivation, during transport or during cultivation by staff members cannot be ruled out. Following intensive discussions, including representatives from (b)(6), it seems that a contamination based on a bacteremia of the donor (please refer to 1. ) seems to be most likely and plausible. Strains of klebsiella pneumoniae replicate at different rates, but they generally occur at an average of 20-30 minutes at 37? As the products have been stored at room temperature (22? C? 2? C) replication time is slower. Postulating a bacteremia causing a primary concentration of 10^2 cfus/ml in the bag, bacterial concentration would have been approximately 4 x 10^5 cfus/ml given an estimated generation time of 30 minutes after 6 hours (pi was done 6 hours post donation). The extent of inactivation for the intercept procedure is indicated to be a log-reduction of >5. 6 by cerus technical data sheet. Therefore, the pathogen inactivation could have been in a threshold region after 6 hours. It seems possible, that pi was effective for pc 2 but not for pc 1. Further steps: as described in item 1. Above, the blood bank will perform an oral swab of the donor at the beginning of the next year during her next donation and a blood culture as well. Should klebsiella pneumoniae be found, sequencing and comparison of all three strains (pc, patient and donor) will take place. Additionally, to exclude the possibility of contamination occurring during phlebotomy, an oral swab of the phlebotomist will be taken as well. All results and conclusions will be communicated as an follow up to this report.
Patient Sequence No: 1, Text Type: D, B5
[42798748]
On (b)(6) 2016, dr. (b)(6), a (b)(6)-speaking cerus medical reviewer, contacted the blood center physician (dr (b)(6)) and shared with her all the investigation findings described in the above narrative. On (b)(6) 2016, cerus received information that the bag used in the patient's transfusion would be sent to cerus. On (b)(6) 2016 cerus ((b)(4)) received the following items from the (b)(6): one empty intercept platelet component (pc1) bag associated with the potential transfusion reaction (tr); 1 plasma bag containing residual plasma (not pathogen inactivated) from the same donation as pc1, and 3 bacterial culture vials ((b)(6)). (b)(6) isolate was recovered from a rectal swab taken from the donor approximately six weeks after the implicated platelet donation. (b)(6) isolate came from the platelet recipient ((b)(6) male patient). (b)(6) isolate came from the implicated intercept pc bag (pc1). The (b)(6) stated that prior to sending the empty blood bag (pc1) and plasma bag to cerus they had performed a bacterial culture on each bag, and these were culture negative. On (b)(6) 2016, further written information was received from (b)(6). Translation into english was provided by dr. (b)(6), a cerus medical reviewer fluent in (b)(6). This update included a material vigilance report and results of a microbiology investigation. The material vigilance report concluded that the (b)(6) female donor of the implicated collection had a history of 61 prior apheresis and whole blood donations, and was an acceptable donor on the day of donation, according to the guidelines of the (b)(6) blood services. A telephone interview did not reveal post donation illness. There were no abnormalities noted during, or after donation. Neither the phlebotomist, nor the nursing staff involved in the platelet collection reported illness. A blood bank investigation of all production steps did not show non-conformities. Storage of all critical material was appropriate and conformant. Temperature controls of storage rooms, of materials used, and all the interim and final products were equally conformant. Microbiology investigation consisted of culture of throat and rectal swabs taken from the phlebotomist and donor, and a urine culture and blood culture from the donor. Previous microbiology investigation had shown no bacterial growth for pc2 and plasma bag. All cultures from the phlebotomist were negative for klebsiella pneumoniae. Blood and urine cultures obtained from the donor were negative. The rectal swab from the pc donor, cultured under conditions that would favor only the growth of gram negative bacteria, showed growth of a k. Pneumoniae strain. Antibiotic sensitivity profile demonstrated that this klebsiella strain was sensitive to all antibiotics tested with the exception of ampicillin. Three k. Pneumoniae strains (from the patient's blood culture, empty platelet bag of the transfused platelets ([tk1, aka pc1] and donor's rectal swab) were analyzed by pulsed-field gel electrophoresis after subjecting to the xbal restriction enzyme. A comparison between the blood bag (pc1) and patient's blood culture isolates showed a similarity of 97. 2%. Hence, both isolates were considered associated. The rectal swab isolate from the donor differed from the other isolates (similarity ~ 40. 3%), showing that the donors' rectal swab isolate was not related to the patient and donor pc isolates. Based on the results of the material vigilance report and the microbiology investigation, dr (b)(6) concluded that the donor could be ruled out as source of the pc contamination, and that retrograde contamination of the pc by contaminated blood from the recipient, was the most likely cause of the pc unit contamination. On (b)(6) 2016 the microbiology department at cerus reported the results of the investigation conducted with the bags and vials received on 05-feb-2016. The investigation included: preparation of initial bacterial stocks; growth kinetics in non-selective media; confirmation of bacterial identity by 16s ribosomal dna and bacterial membrane fatty acid methyl ester (fame) analysis; antibiotic susceptibility testing; pathogen inactivation studies; and assessment of growth kinetics in platelets suspended in additive solution (pas-3). The empty intercept platelet bag (pc1) and the concurrent plasma bag from the implicated donation were cultured and found negative for bacterial growth, confirming the results obtained by the (b)(6) blood bank. The 3 vials ((b)(6) [isolate from a donor rectal swab]; (b)(6) [isolate from recipient/patient]; and 61215 [isolate from pc1]) were cultured and all tested positive for klebsiella pneumoniae (confirmed by dna and fame analysis). Bacterial strains demonstrated differing growth kinetics when grown under identical conditions in non-selective liquid media (lb broth). Patient (isolate (b)(6)) and pc bag (isolate (b)(6)) strains showed an identical growth pattern, while the donor rectal swab strain (isolate (b)(6)) revealed a slower rate of growth. Donor rectal swab sample (01645) revealed two colony morphologies (a= translucent and b= dense), both "a" and "b" cultures were identified as klebsiella pneumoniae-rhinoscleromatus (using a 16s ribosomal dna test) and klebsiella-pneumoniae-pneumoniae-gc subgroup c (using the fame test). The patient strain and the pc bag strain were identical: klebsiella pneumoniae- rhinoscleromatus (by 16s ribosomal dna test) and klebsiella-pneumoniae-pneumoniae-gc subgroup b (by fame test). Patient and pc1 strain 16s ribosomal dna sequencing showed a 99% match. The antibiotic susceptibility screen using 11 antibiotics revealed that the donor rectal swab strain (isolate (b)(6)) and patient strains (isolate (b)(6)) had different profiles, while the patient (isolate (b)(6)) and the intercept pc1 bag (isolate (b)(6)) strains were identical. Patient and pc1 bag strains were susceptible to all the antibiotics tested except to ampicillin (resistant) and cefuroxime (intermediate resistance). These results were similar to those reported by the (b)(6) blood bank. In the cerus analysis, the donor rectal swab strain showed resistance to all antibiotics tested. Susceptibility data from the donor rectal swab strain obtained at cerus were different from that reported by the (b)(6) blood bank. A second sample of the donor rectal swab will be obtained from (b)(6) and the antibiotic susceptibility testing will be repeated in order to resolve the discrepancy. Two independent replicate pathogen inactivation experiments with the intercept blood system for platelets (small volume set) in pas-3 were performed with the 5 k. Pneumoniae isolates (donor rectal swab mixed colonies [isolate (b)(6)]; donor rectal swab colony type "a" [isolate (b)(6)]; donor rectal swab colony type "b" [isolate (b)(6)]; pc bag [isolate (b)(6)]; and patient [isolate (b)(6)]). Bacterial cultures were prepared as per internal cerus standard procedures: a single colony of each bacterial strain was inoculated into lb broth and the flask was incubated at 37? C with aeration and agitation. Stationary phase culture was added to the pc unit targeting a final concentration of ~6 log10 cfu/ml of bacteria in the unit. Results showed effective pathogen reduction to the limit of detection with greater than or equal to 6 log10 reduction for all strains and replicates tested (isolate (b)(6) [>7. 1 log10 reduction], isolate (b)(6) [6. 9 log10 reduction] and isolate (b)(6) [7. 4 log10 reduction]). Growth kinetics were evaluated in platelet components suspended in 65% pas-3/35% plasma, which is the same medium that the platelets were administered to the patient, in 2 experiments in order to assess the concentrations of k. Pneumoniae that might be attained within 6 hrs of contamination. In the first experiment, klebsiella strains recovered from the donor rectal swab, patient and pc1 were inoculated at ~100-150 cfu/unit and the contaminated pc units were stored at 22? C with agitation in a platelet shaker. The bacterial titer was determined by plating assay over a period of 5 days. All strains only reached high concentrations (>108 log10 cfu/ml) after 5 day of room temperature storage, but showed low titers (<101log10 cfu/ml) at the time of the first assessment at 5-14 hrs after inoculation. In the second growth kinetics experiment, the klebsiella strains recovered from patient's blood culture (isolate (b)(6)) and pc1 (isolate (b)(6)) were evaluated. Platelets in 65% pas-3/35% plasma were inoculated with either ~100 cfu or ~1000 cfu per unit for each strain. After bacterial inoculation, platelet units were incubated at 22? C with agitation. The bacterial titer in each unit was monitored for up to 24 hrs by plating assay at 3h, 6h, ~9h, and 24h after inoculation, in order to model the 6 hour delay between collection and prt treatment in the clinical case. At each time point, a 10ml of platelet sample was withdrawn from each unit and plated immediately on a non-selective media. After 8 hrs of incubation, growth of both klebsiella sp. Isolates was detectable but low (<100 log10cfu/ml) in all replicates and well below the inactivation threshold of intercept for the klebsiella strains (>6. 0 log10). Cerus medical assessment: the combined investigations by the (b)(6) and cerus showed no evidence of non-conformity for the ibs process or failure of the system. The bacterial isolates from the patient blood culture and pc1 bag associated with this transfusion reaction were found to be identical. The intercept blood system was capable of inactivating high levels of this klebsiella pneumoniae strain. Growth studies suggest that the klebsiella strain was not capable of achieving high levels of contamination within a 6 hour period between collection and pathogen inactivation, and furthermore that there was a 5-6 log; (one hundred thousand-fold to one million fold) excess inactivation capacity between the highest levels reached after 6 hrs of room temperature storage in conditions simulating the ones for the administered unit. The medical reviewer concurs with the reporter that the available evidence suggests that the transfused intercept-treated pc component (pc1) was not the cause of the patients' transfusion reaction, although causality cannot be categorically excluded. It is more likely that the patient was septic with k. Pneumoniae prior to the transfusion, and contamination of the pc bag occurred by retrograde contamination of the platelet concentrate by the recipient's blood after the integrity of the component had been compromised at the bedside.
Patient Sequence No: 1, Text Type: D, B5
[61417762]
On 7-apr-2016 cerus received another sample obtained from the pc donor (2nd rectal swab sample). On 18-apr-2016 cerus' microbiology team reported the results of the antibiotic resistance profile test conducted by mqa (same lab that performed the previous antibiotic resistance profile tests for cerus). The results matched those obtained by the (b)(6): susceptible to all antibiotics tested with the exception of ampicillin (resistant). This additional information provides further confirmation of previous conclusion by cerus. The combined investigations by the (b)(6) and cerus showed no evidence of non-conformity for the ibs process or failure of the system. Cerus concurs with dr. (b)(6) assessment that the available evidence suggests that the transfused intercept-treated pc component (pc1) was not the cause of the patients' transfusion reaction, although causality cannot be categorically excluded. It is more likely that the patient was septic with k. Pneumoniae prior to the transfusion, and contamination of the pc bag occurred by retrograde contamination of the platelet concentrate by the recipient's blood after the integrity of the component had been compromised at the bedside.
Patient Sequence No: 1, Text Type: N, H10
[61417765]
On 7-apr-2016 cerus received another sample obtained from the pc donor (2nd rectal swab sample). On 18-apr-2016 cerus' microbiology team reported the results of the antibiotic resistance profile test conducted by mqa (same lab that performed the previous antibiotic resistance profile tests for cerus). The results matched those obtained by the (b)(6): susceptible to all antibiotics tested with the exception of ampicillin (resistant). This additional information provides further confirmation of previous conclusion by cerus. The combined investigations by the (b)(6) and cerus showed no evidence of non-conformity for the ibs process or failure of the system. Cerus concurs with dr. (b)(6) assessment that the available evidence suggests that the transfused intercept-treated pc component (pc1) was not the cause of the patients' transfusion reaction, although causality cannot be categorically excluded. It is more likely that the patient was septic with k. Pneumoniae prior to the transfusion, and contamination of the pc bag occurred by retrograde contamination of the platelet concentrate by the recipient's blood after the integrity of the component had been compromised at the bedside.
Patient Sequence No: 1, Text Type: D, B5
| Report Number | 3003925919-2016-00001 |
| MDR Report Key | 5370757 |
| Report Source | FOREIGN,HEALTH PROFESSIONAL,U |
| Date Received | 2016-01-15 |
| Date of Report | 2015-12-14 |
| Date of Event | 2015-11-16 |
| Date Mfgr Received | 2015-12-14 |
| Date Added to Maude | 2016-01-15 |
| Event Key | 0 |
| Report Source Code | Manufacturer report |
| Manufacturer Link | Y |
| Number of Patients in Event | 0 |
| Adverse Event Flag | 3 |
| Product Problem Flag | 3 |
| Reprocessed and Reused Flag | 3 |
| Health Professional | 3 |
| Initial Report to FDA | 3 |
| Report to FDA | 3 |
| Event Location | 3 |
| Manufacturer Contact | CAROL MOORE |
| Manufacturer Street | 2550 STANWELL DRIVE |
| Manufacturer City | CONCORD CA 94520 |
| Manufacturer Country | US |
| Manufacturer Postal | 94520 |
| Manufacturer Phone | 9258766819 |
| Manufacturer G1 | FENWAL FRANCE SAS |
| Manufacturer Street | ETAILLE, 36-400 |
| Manufacturer City | LA CH |
| Manufacturer Country | FR |
| Single Use | 3 |
| Previous Use Code | 3 |
| Event Type | 3 |
| Type of Report | 3 |
| Brand Name | INTERCEPT BLOOD SYSTEM FOR PLATELETS |
| Generic Name | INTERCEPT PLATELETS |
| Product Code | PJF |
| Date Received | 2016-01-15 |
| Returned To Mfg | 2016-02-05 |
| Operator | HEALTH PROFESSIONAL |
| Device Availability | R |
| Device Age | DA |
| Device Eval'ed by Mfgr | Y |
| Device Sequence No | 1 |
| Device Event Key | 0 |
| Manufacturer | CERUS CORPORATION |
| Manufacturer Address | 2550 STANWELL DRIVE CONCORD CA 94520 US 94520 |
| Patient Number | Treatment | Outcome | Date |
|---|---|---|---|
| 1 | 0 | 1. Required No Informationntervention | 2016-01-15 |