Surveillance for donor-derived infections in Australia.

BACKGROUND: Systems for quality and safety assurance in organ donation and transplantation are vital, especially those that seek to minimize donor disease transmission. Australia has developed a national vigilance and surveillance system to identify, review, and analyze actual and potential donor-derived infections and other disease transmissions. METHODS: The system involves notification of incidents to the Australian Organ and Tissue Authority for review by a Vigilance and Surveillance Expert Advisory Committee (VSEAC). The VSEAC grades incidents, O makes recommendations, and issues communications both publicly and to the clinical donation and transplant sector. RESULTS: Annual notifications have increased since the inception of the system in 2012 until 2022. The vast majority relate to procedural aspects including donor assessment, information/data issues, and the recovery, offer, allocation, preservation and transportation of organs. Possible donor-derived disease accounted for 19% of all notifications, and those related to possible donor-derived infection only 12%. The VSEAC, as a result of reviewing these incidents, has made recommendations resulting in revisions to donor screening, organ allocation, packaging and transportation. The review of incidents has led to changes in clinical guidance for increased viral risk donor assessment, testing, and ensuing organ utilization and recipient surveillance. Guidance has also been reviewed for other infectious risks including strongyloides, human T-lymphotropic virus, and HEV. CONCLUSION: The Australian vigilance and surveillance system has enabled national retrospective reporting and evaluation of serious adverse events or reactions to identify trends and inform processes and guidelines, therefore improving the safety of donation and transplantation.

The Western Australian experience of COVID-19 after the borders reopened: evaluation of public health modelling predictions.

BACKGROUND: Western Australia (WA) serves as a unique global case study on the impact of coronavirus disease 2019 (COVID-19) on an isolated, prepared and highly vaccinated population. This study builds upon the study performed by House et al. through an extended data set. AIM: To examine the impact of COVID-19 at the only quaternary hospital in WA following the border opening from 3 March to 17 July 2022. PARTICIPANTS: A total of 257 adults were admitted with COVID-19 under either respiratory or the intensive care unit (ICU). OUTCOMES: Admission numbers, disease severity, ICU admission, prevalence of COVID-19 deterioration risk factors, length of stay and mortality. RESULTS: A total of 257 patients were admitted with COVID-19, under respiratory (81.7%) and ICU (18.3%). COVID-19 was the primary reason for admission for 67.7%. Ten patients died during the study, with seven deaths attributed to COVID pneumonitis. COVID-19 severity was 37.4% mild, 37.0% moderate, 18.3% severe and 7.4% critical. Risk factors for requiring ICU included incomplete immunisation status (P = 0.011), chronic kidney disease (P = 0.008) and Aboriginal and Torres Strait Islander (ATSI) ethnicity. The WA Department of Health predicted that the number of hospitalisations and ICU cases were significantly higher than the actual number of cases. CONCLUSION: The number of hospitalisations and ICU COVID-19 cases were significantly less than predicted, likely due to high population vaccination rates prior to border opening. The main risk factors for COVID-19 severity were incomplete immunisation and ATSI ethnicity.

Utilising organs from hepatitis C virus PCR-positive donors in Western Australia.

We transplanted six solid organs from three hepatitis C virus (HCV) polymerase chain reaction (PCR)-positive donors during 2018-2023. Recipients were treated with glecaprevir/pibrentasvir or sofosbuvir/velpatasvir for 4-12 weeks, with all six achieving sustained virological response without significant adverse events. As occurs in other jurisdictions, solid organ transplants from HCR PCR-positive donors can be safely utilised in Australia.

COVID-19 outcomes in haemopoietic stem cell transplant recipients in Western Australia: the value of vaccination and antiviral therapy.

Coronavirus-19 (COVID-19) mortality rates among haemopoietic stem cell transplant (HSCT) patients are high, ranging between 20% and 40%. We prospectively evaluated the mortality outcomes of COVID-19 in Western Australian HSCT patients. A total of 32/492 (6.5%) HSCT recipients contracted COVID-19 during the study, of whom 30/32 (94%) developed mild or asymptomatic disease. Two allogeneic HSCT patients were hospitalised for severe COVID-19; one patient died. Stringent healthcare, social isolation practices, aggressive vaccination programmes and rapid access to COVID-19 antivirals may have promoted mild COVID-19 illness in Western Australian HSCT patients, resulting in one of the lowest COVID-19 mortality rates in HSCT recipients worldwide.

Letermovir for pre-emptive cytomegalovirus therapy after allogeneic hematopoietic cell transplantation.

BACKGROUND: Cytomegalovirus (CMV) is a common cause of morbidity after allogeneic haematopoietic cell transplantation (alloHCT). Pre-emptive therapy (PET) with valganciclovir (VGC) is associated with haematological toxicity. METHODS: We included alloHCT patients from 2018 to 2021 where letermovir (LTV) was used for CMV PET because of cytopenias. RESULTS: Ten patients were included. Six received VGC prior to LTV. VGC was commenced at median d42, given for median 40 days. LTV was commenced at median d90, given for median 54 days. At commencement of antiviral, CMV viral load was higher for VGC at 3.7 log10 IU/mL, compared to LTV at 2.9 log10 IU/mL. Viral load reduction occurred at 0.18 log10 IU/mL per week for VGC, compared to 0.17 log10 IU/mL per week for LTV. There was no clinically significant CMV viremia after stopping LTV. Cytopenias improved on LTV. CONCLUSION: LTV was effective in controlling CMV viremia when it was given at a lower starting CMV viral load and later post alloHCT than VGC. Further study is required of LTV as upfront PET following alloHCT.

The unique COVID-19 experience in Western Australia: lessons learnt.

BACKGROUND: Western Australia (WA) was in a unique position to experience coronavirus disease 2019 (COVID-19) in a highly vaccinated and geographically isolated population. AIM: To describe the COVID-19 Omicron experience at the only quaternary hospital in WA following border opening from 3 March to 11 May 2022. PARTICIPANTS: A total of 158 adults with microbiologically confirmed COVID-19 were admitted to the respiratory or intensive care unit (ICU). OUTCOMES: Admission numbers, disease severity, prevalence of COVID-19 deterioration risk factors, immunisation status, severity of infection, immunosuppression and treatment regimen. RESULTS: One hundred fifty-eight COVID-19-positive patients were admitted to the respiratory ward (n = 123) and the ICU (n = 35) during the study period. COVID-19 infection was the primary admission reason in 32.9% of patients, 51.3% were male and the median age was 62 years. Aboriginal or Torres Strait Islanders (ATSI) were overrepresented (13.3%). Care was predominantly ward based (77.2%). Nearly half of the patients had mild COVID-19 (49.4%). Dexamethasone was the most common treatment provided to patients (58.2%). The median length of stay was 5.8 days (interquartile range, 5-15). Eight patients died during the study period (5.1%), with three of those deaths attributable to COVID-19. CONCLUSIONS: COVID-19 case numbers following WA state border opening were of lower care acuity and disease severity than predicted. Two-thirds of admissions were for other primary diagnoses, with incidental COVID detection. Hospital admissions were overrepresented by partially or unvaccinated patients and by ATSI Australians. An increase in social support along with general and geriatric medicine speciality input were required to treat hospitalised COVID-19 cases in the WA Omicron wave.

Prevalence of Blood-Borne Viruses and Predictors of Risk in Potential Organ Donors in Australia.

Internationally, the designation of a patient as an increased viral risk organ donor has been associated with lower utilisation rates. The actual prevalence of blood borne viruses in Australian potential organ donors, and the predictive performance of questionnaires administered to stratify this risk, remains unknown. We conducted a retrospective review of all patients who commenced workup for donation on the national database between 2014-2020. The prevalence of HIV, Active HBV and Active HCV in 3650 potential organ donors was 0.16%, 0.9%, and 2.2%, respectively. The behavioural risk profile was assessed in a subset of 3633 patients. Next-of-kin reported increased risk behaviours were associated with an increased prevalence of HCV but not of HIV or HBV (OR 13.8, p < 0.01, OR 0.3. p = 0.42, OR 1.5, p = 0.14). Furthermore, the majority of HIV and HBV infections occurred in potential donors without a disclosed history of increased risk behaviours. In this series, donors had a higher prevalence of HCV, and similar rates of HBV and HIV to the broader community. Behavioural transmission risks were poorly predictive of HIV and HBV. Rather than pre-transplantation behavioural risk screening, routine post-transplant recipient screening may provide a more powerful tool in mitigating the consequences of unexpected viral transmission.

Cidofovir-induced anterior uveitis in an allogeneic stem cell transplant recipient.

Anterior uveitis is a reported complication of intravenous cidofovir, almost exclusively described in human immunodeficiency virus (HIV) infected patients treated for cytomegalovirus retinitis. In this study, we report the case of an allogeneic stem cell transplant recipient with significant visual impairment and hypotony following administration of high-dose intravenous cidofovir for hemorrhagic cystitis due to BK virus.

QuantiFERON-cytomegalovirus to predict clinically significant cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Controlling cytomegalovirus (CMV) infection through prophylaxis or pre-emptive therapy remains an important contributor to outcomes after allogeneic hematopoetic stem cell transplant (alloHCT). Predicting clinically significant CMV infection (csCMVi) after day 100 remains a challenge. METHODS: We examined the abilty of the QuantiFERON-CMV assay (QFN-CMV) at day 100 (d100) and day 150 (d150) after alloHCT to predict csCMVi after these time points, with median follow-up of 3.1 years (range 1.3-4.3 years). RESULTS: In 46 transplants (donor seropositive (D+) recipient seronegative (R-) = 12, D+R+ = 25, D-R+ = 9; matched related = 13, unrelated donor = 32, haploidentical = 1), for the prediction of freedom from csCMVi >d100, QFN-CMVd100 (positive compared to negative/indeterminate) had sensitivity 62% (23/37), specificity 100% (9/9), positive predictive value 100% (23/23), and negative predictive value 39% (9/23). For the prediction of freedom from csCMVi >d150, QFN-CMVd150 (positive compared to negative/indeterminate) had sensitivity 62% (18/29), specificity 83% (5/6), positive predictive value 95% (18/19), and negative predictive value 31% (5/16). CONCLUSION: Positive QFN-CMV at d100 and d150 strongly predicted freedom from csCMVi after these time points. QFN-CMV could be utilized to predict the need for pre-emptive therapy and CMV viral load monitoring after day 100 post-alloHCT.

Antifungal use via outpatient parenteral antimicrobial therapy.

BACKGROUND: Antifungal administration via outpatient parenteral antimicrobial therapy (OPAT) is infrequent. As patients with invasive fungal infections (IFIs) receiving OPAT are at high risk of readmissions, careful, risk-based patient selection and monitoring is important. OBJECTIVES: To describe our experience managing IFIs via OPAT, including assessment of risk factors associated with unplanned readmissions. PATIENTS AND METHODS: A retrospective cohort study of outpatients from two tertiary hospitals in Western Australia managed with parenteral antifungals for the treatment of IFIs from 2012 to 2020. Outcomes assessed were unplanned OPAT-related readmissions; adverse events and achievement of treatment aim at the completion of OPAT. RESULTS: Forty-six patients were included, encompassing 696 OPAT days. Twenty-three (50%) patients received intravenous (IV) liposomal amphotericin B (L-AmB), 23 (50%) received IV echinocandins and one (2%) patient received IV fluconazole. One patient received both IV L-AmB and an echinocandin. Unplanned OPAT-related readmissions occurred in 13 (28%) patients and any adverse event occurred in 19 (41%), most commonly nephrotoxicity amongst patients receiving L-AmB. On univariate analysis, unplanned OPAT-related readmissions were more common in Mucorales infection, L-AmB doses of ≥5 mg/kg and otorhinolaryngologic (ENT) infections. At the completion of OPAT, attainment of treatment aims occurred in 28 (61%) patients. CONCLUSIONS: Patients receiving parenteral antifungals via OPAT experience high rates of unplanned readmissions and adverse events. Risk factor identification may facilitate optimal patient selection and establishment of treatment aims.

Fungal yield from sterile specimens.

Clinicians may not request fungal culture when it is indicated. For sterile specimens without a specific request for fungal culture, in addition to bacteriology media, we routinely incubated a Sabouraud dextrose agar (SAB) plate for 4 weeks. From 44635 sterile specimens from years 2011 to 2016, 2722 (6.1%) had fungal request. Fungi were identified from 1037 (2.3%) specimens, 292 (0.6%) from specimens with specific fungal request, 574 (1.3%) from bacteriology media, and 171 (0.4%) solely from SAB plate (of 171, 77 were deemed clinically significant and 55 were treated). Relying on request for fungal studies from sterile specimens underdiagnosed fungal infection. Routine fungal culture had a modest incremental yield at a moderately high cost. LAY SUMMARY: Routine fungal culture of sterile specimens had a modest incremental yield to routine bacteriology culture and specific fungal request at a moderately high financial cost.

High dose valaciclovir to prevent cytomegalovirus infection in allogeneic haematopoietic stem cell transplant recipients.

Cytomegalovirus (CMV) infection causes morbidity and mortality after allogeneic haematopoietic stem cell transplantation (HSCT). We investigated whether prophylaxis with high dose valaciclovir is effective at reducing the incidence of clinically significant CMV infection (csCMVi) within six months of allogeneic HSCT. Consecutive allogeneic HSCT recipients who received 2g valaciclovir orally four times daily from transplant until day 100 (prophylaxis group) were compared to subsequent patients who received no CMV prophylaxis (control group). Forty-nine patients in the prophylaxis group and 59 in the control group were included. The cumulative incidence of csCMVi at 6 months was 20% (95% confidence interval (CI): 9%-27%) in the prophylaxis group and 39% (95% CI: 26%-47%) in the control group (P = .009). There was no CMV disease in the prophylaxis group and three cases in the control group. There was no difference in time to neutrophil or platelet recovery nor graft failure between groups. On multivariable analysis, lack of high dose valaciclovir prophylaxis, positive recipient CMV IgG and age were associated with greater likelihood of csCMVi. There was no significant difference in acute graft versus host disease, non-relapse mortality or overall survival between groups. In this retrospective cohort study, high dose valaciclovir prophylaxis resulted in a lower incidence of csCMVi within six months of HSCT.

A novel highly bio-available itraconazole formulation (SUBA®-Itraconazole) for anti-fungal prophylaxis in lung transplant recipients.

BACKGROUND: Antifungal prophylaxis remains a mainstay of lung transplantation, given invasive fungal infection is a common and serious complication after lung transplantation. Choice of systemic agent to prevent invasive fungal infection varies between centers and funding of agents remains challenging. Our center has recently changed from posaconazole to a highly bioavailable formulation of itraconazole (SUBA®-itraconazole) at substantially reduced cost, but safety and toxicity require further assessment. A retrospective study of lung transplant patients receiving systemic antifungal prophylaxis from December 2016 through December 2019 following change from posaconazole to itraconazole as standard practice. 150 patients with lung transplants were managed in this time period, with 88 (59%) receiving at least 1 mold-active triazole during the study period. 48 (58%) of these patients received SUBA®-itraconazole; 68 (82%) received posaconazole and 10 (12%) received voriconazole. The average cost per patient during the study period was significantly lower on SUBA®-itraconazole (mean $1548/patient/6 month course) than posaconazole (mean $16 921.35/patient/6 month course). Target trough concentrations for prophylaxis of itraconazole > 0.5 mg/L and posaconazole > 0.7 mg/L were achieved on empiric dosing in 49% and 68% respectively. Overall trough itraconazole (0.50 vs 1.12 mg/L, P < .001) and posaconazole (1.37 vs 2.10 mg/L P < .001) concentrations were significantly lower in patients with cystic fibrosis. Calcineurin inhibitor dose changes on introduction or cessation were similar for SUBA®-itraconazole and posaconazole. Breakthrough invasive fungal infection and toxicity were rare. SUBA®-itraconazole is well-tolerated, associated with rare breakthrough invasive fungal infection, and lower cost. Prospective studies following general introduction are required to determine long-term safety, tolerability, and efficacy.

Consensus guidelines for the diagnosis and management of invasive candidiasis in haematology, oncology and intensive care settings, 2021.

Patients with haematological malignancies, haemopoietic stem cell transplant recipients and patients requiring admission to intensive care settings are at high risk for invasive candidiasis (IC). Over the past decade, there has been increased reporting of non-albicans species and fluconazole resistance in Australia. These guidelines provide updated evidence-based recommendations for the diagnosis and management of IC in adult and paediatric haematology, oncology and intensive care settings. Optimal pharmacological and non-pharmacological management are discussed. Recent studies strengthen the recommendation for an echinocandin agent as first-line therapy for high-risk patients with IC. Mortality benefit has also been demonstrated for non-pharmacological management, including removal of central venous catheters, infectious diseases consultation and use of care bundles. Healthcare facilities managing immunocompromised patient populations should therefore adopt implementation strategies for these multimodal interventions.

Early urinary tract infection after spinal cord injury: a retrospective inpatient cohort study.

STUDY DESIGN: Retrospective audit. OBJECTIVES: Examine factors associated with urinary tract infection (UTI), UTI incidence and impact on hospital length of stay (LOS) in new, inpatient adult traumatic spinal cord injury (SCI). SETTING: Western Australian Hospitals managing SCI patients. METHODS: Data on UTIs, bladder management and LOS were obtained from hospital databases and medical records over 26 months. Adherence to staff-administered intermittent catheterisation (staff-IC) was determined from fluid balance charts. RESULTS: Across the cohort (n = 70) UTI rate was 1.1 starts/100 days; UTI by multi-resistant organisms 0.1/100 days. Having ≥1 UTIs compared with none and longer duration of initial urethral indwelling catheterisation (IDC) were associated with longer LOS (p-values < 0.001). For patients with ≥1 UTIs (n = 43/70), longer duration of initial IDC was associated with shorter time to first UTI (1 standard deviation longer [SD, 45.0 days], hazard ratio (HR): 0.7, 95% confidence interval [CI] 0.5-1.0, p-value 0.044). In turn, shorter time to first UTI was associated with higher UTI rate (1 SD shorter [30.7 days], rate ratio (RR): 1.32, 95%CI 1.0-1.7, p-value 0.039). During staff-IC periods (n = 38/70), protocols were followed (85.7% ≤ 6 h apart, 96.1% < 8 h), but 26% of IC volumes exceeded 500 mL; occasional volumes > 800 mL and interruptions requiring temporary IDC were associated with higher UTI rates the following week (odds ratios (ORs): 1.6, 95%CI 1.1-2.3, p-value 0.009; and 3.9, 95%CI 2.6-5.9, p-value < 0.001 respectively). CONCLUSIONS: Reducing initial IDC duration and limiting staff-IC volumes could be investigated to possibly reduce inpatient UTIs and LOS. SPONSORSHIP: None.

Cytomegalovirus viremia in lung transplantation during and after prophylaxis.

BACKGROUND: Lung transplantation has a high risk of cytomegalovirus (CMV) viremia and disease. METHODS: Valganciclovir was planned for 6 months in CMV recipient seropositive (R+) lung transplants (LTs) and given long-term in D+R- LTs. CMV viremia was monitored regularly during and after prophylaxis in all patients. RESULTS: Of 137 LTs, 22 were D+R-, 49 D+R+, 43 D-R+, and 23 D-R-, with median follow up 4.1 years (IQR 2.1-6.2 years). CMV viremia at any time occurred in 44.5% of LTs. CMV viral load >103  c/mL was uncommon (9/77 episodes). CMV viremia occurred at median 665 days (IQR 271-1411 days), in 5.1% LTs <6 months, 20.3% LTs 6-12 months, and 35.8% LTs >12 months. CMV disease occurred in 6 (4.4%) LTs at an overall rate of 1.0 episode per 100 person-years: two of these cases were organ-specific disease, four were CMV syndrome. One case of ganciclovir-resistant CMV was diagnosed. D+R+ and D+R- LTs had higher viremia rates than the D-R+ group. No viremia occurred in D-R- LTs. CMV viremia was not associated with age, gender, type of LT, indication for LT, acute rejection, bronchiolitis obliterans syndrome, or mortality. CONCLUSIONS: Prophylaxis for 6 months in D+R+ and D-R+, and past 12 months in D+R- LTs, with long-term monitoring in all patients using a sensitive assay, and reinstitution of valganciclovir for low-level viremia was effective at markedly reducing the incidence of CMV disease. CMV D-R- LTs do not need routine CMV monitoring.

Epidemiology of invasive fungal infections in lung transplant recipients in Western Australia.

BACKGROUND: Invasive fungal infections (IFI) are common after lung transplantation with reported incidence of 8.1% to 16% at 12 months post-transplant, and 3-month all-cause mortality after IFI of 21.7%. METHODS: We performed a retrospective study of IFI and fungal colonization in lung transplants (LTs) from November 2004 to February 2017. RESULTS: 137 LTs were followed for a median 4.1 years (IQR 2.1-6.2 years). In addition to nebulized amphotericin for the transplant admission to all LTs, systemic mold-active azole was given to 80/130 (61.5%) LTs in the first 6 months post-transplant, 57/121 (47.1%) in the period 6-12 months after transplant, and 93/124 (75%) in the period more than 12 months post-transplant. Mold airways colonization was found in 81 (59.1%) LTs before and 110 (80.3%) LTs after transplantation. There were 13 IFIs for an overall incidence of 2.1 per 100 person-years, occurring at a median 583 days (IQR 182-1110 days) post-transplant, a cumulative incidence of 3.8% at 1 year, 7.6% at 3 years and 10.1% at 5 years post-transplant. All-cause 3-month mortality after IFI was 7.7%. Aspergillus species followed by Scedosporium apiospermum and Cryptococcus species were the commonest fungi causing IFI. CONCLUSIONS: In our cohort the rate of IFI was comparatively low, likely because of comprehensive early antifungal use and preemptive therapy at any time after transplant. Prospective studies of fungal colonization late after LT are required to determine the risks and benefits of watchful waiting compared to preemptive therapy.

Cytomegalovirus viraemia and mortality in renal transplant recipients in the era of antiviral prophylaxis. Lessons from the western Australian experience.

BACKGROUND: Cytomegalovirus (CMV) establishes a lifelong infection that is efficiently controlled by the immune system; this infection can be reactivated in case of immunosuppression such as following solid organ transplantation. CMV viraemia has been associated with CMV disease, as well as increased mortality and allograft failure. Prophylactic antiviral medication is routinely given to renal transplant recipients, but reactivation during and following cessation of antiviral prophylaxis is known to occur. The aims of this study were to assess the incidence, timing and impact of CMV viraemia in renal transplant recipients and to determine the level of viraemia associated with adverse clinical outcomes. METHODS: Data from all adult (18 years and over) Western Australian renal transplant recipients transplanted between 1 January 2007 and 31 December 2012 were obtained from the Australia and New Zealand Dialysis and Transplant registry and were supplemented with data obtained from clinical records. Potential risk factors for detectable CMV viraemia (≥600 copies/ml) and all-cause mortality were assessed using univariable analysis and Cox Proportional Hazards Regression. RESULTS: There were 438 transplants performed on 435 recipients. The following factors increased the risk of CMV viraemia with viral loads ≥600 copies/ml: Donor positive/Recipient negative status; receiving a graft from a deceased donor; and receiving a graft from a donor aged 60 years and over. CMV viraemia with viral loads ≥656 copies/ml was a risk factor for death following renal transplantation, as was being aged 65 years and above at transplant, being Aboriginal and having vascular disease. Importantly 37% of the episodes of CMV viraemia with viral loads ≥656 copies/ml occurred while the patients were expected to be on CMV prophylaxis. CONCLUSIONS: CMV viraemia (≥656 copies/ml) was associated with all-cause mortality in multivariable analysis, and CMV viraemia at ≥656 copies/ml commonly occurred during the period when renal transplant recipients were expected to be on antiviral prophylaxis. A greater vigilance in monitoring CMV levels if antiviral prophylaxis is stopped prematurely or poor patient compliance is suspected could protect some renal transplant recipients from adverse outcomes such as premature mortality.