Impact of blood donation biovigilance and transfusion-transmitted infections on organ transplantation.

Over 118 million blood donations are collected globally each year. Recipients of blood products include those who experience major trauma or surgery, have acute blood loss and anemia, or impaired bone marrow function. Solid organ transplant recipients often require transfusion of blood products which places them at risk of transfusion-associated adverse events including transfusion-transmitted infection. National hemovigilance networks have documented low rates of transfusion-transmitted infection in the general population. Incidence transfusion-transmitted infection continues to occur in solid organ transplant patients and arises mainly from existing gaps in blood donor biovigilance processes. Emerging infectious diseases have highlighted existing gaps in the donor-recipient pathway to administering safe blood products. This article reviews the current process and regulatory oversight of blood donor biovigilance, including donor screening and microbiological testing, highlights cases of transfusion-transmitted infection documented in the literature, and addresses ways in which biovigilance may be improved, with a focus on the impact of solid organ transplantation.

Central line associated and primary bloodstream infections.

PURPOSE OF REVIEW: Primary and intravascular catheter-associated bloodstream infections (CA-BSIs) represent an important clinical entity in the intensive care unit (ICU) being associated with significant morbidity and mortality. The purpose of this review was to examine the recently published data on epidemiology and management of CA-BSI and other primary BSIs specifically within the context of the ICU. RECENT FINDINGS: In critically ill patients, the pooled prevalence of primary and CA-BSI from contemporary studies was 19.7-40.7% and 26.4-37.3% of all BSIs, respectively. Failure to achieve source control (i.e., removal of catheter in CA-BSI) is associated with higher mortality. Higher severity scores and durations of ICU stay and catheter insertion are well established risk factors for CA-BSI. The use of prevention bundles when inserting a central venous line is able to reduce CA-BSI incidence from 4 to 1.6 episodes per 1000 central venous catheter days. Differential time-to-positivity of paired blood cultures may assist in the diagnosis of CA-BSI. SUMMARY: Primary BSI is frequently observed in ICU cohorts and has a poor effect on outcome. Surveillance for BSI among patients admitted to ICUs is fundamental to inform healthcare service delivery, design preventive approaches, to track resistance, and detect emerging pathogens.

Scedosporium species and Lomentospora prolificans fungaemia is uniformly fatal in patients with haematological malignancy.

Scedosporium and Lomentospora species are environmental moulds that are virulent in immunocompromised hosts and rarely cause bloodstream infection (BSI). Patients with Scedosporium and Lomentospora species BSI were identified by the state public laboratory service in Queensland, Australia, over a 20-year period. Twenty-two incident episodes occurred among 21 residents; one patient had a second episode 321 days following the first. Of these, 18 were Lomentospora prolificans, three were Scedosporium apiospermum complex and one was a nonspeciated Scedosporium species. Seventeen (81%) patients died during their index admission, and all-cause mortality at 30, 90 and 365 days was 73%, 82% and 91% respectively. All 20 patients with haematological malignancy died within 365 days of follow-up with a median time to death of 9 days (interquartile range, 6-20 days) following diagnoses of BSI.

Comparison of Low-Level to High-Level Disinfection in Eliminating Microorganisms From Ultrasound Transducers Used on Skin: A Noninferiority Randomized Controlled Trial.

INTRODUCTION: There is a lack of international consensus as to whether high- or low-level disinfection (HLD or LLD) is required for ultrasound (US) transducers used during percutaneous procedures. This study compared the effectiveness of LLD to HLD on US transducers contaminated with microorganisms from skin. METHODS: Two identical linear US transducers repeatedly underwent either LLD or HLD during the study. Randomization determined which of these transducers was applied to left and right forearms of each participant. Swabs taken from transducers before and after reprocessing were plated then incubated for 4-5 days, after which colony forming units (CFU) were counted and identified. The primary hypothesis was the difference in the proportion of US transducers having no CFUs remaining after LLD and HLD would be less than or equal to the noninferiority margin of -5%. RESULTS: Of the 654 recruited participants 73% (n = 478) had microbial growth from both transducers applied to their left and right forearms before reprocessing. These were included in the paired noninferiority statistical analysis where, after disinfection, all CFUs were eliminated in 100% (95% CI: 99.4-100.0%) of HLD transducer samples (n = 478) and 99.0% (95% CI: 97.6-99.7%) of LLD transducer samples (n = 473). The paired difference in the proportion of transducers having all CFUs eliminated between LLD and HLD was -1.0% (95% CI: -2.4 to -0.2%, P-value <.001). CONCLUSIONS: Disinfection with LLD is noninferior to HLD when microorganisms from skin have contaminated the transducer. Therefore, using LLD for US transducers involved in percutaneous procedures would present no higher infection risk compared with HLD.

Aspergillus Species Causing Invasive Fungal Disease in Queensland, Australia.

BACKGROUND: Aspergillus species are important causes of invasive fungal disease, particularly among those with an impaired immune system. Increasing reports have revealed a rising incidence of antifungal drug resistance among Aspergillus spp., particularly among cryptic species. Understanding local antifungal susceptibility patterns is paramount to delivering optimal clinical care. METHODS: Aspergillus spp. recovered from clinical specimens between 2000 and 2021 from Pathology Queensland were collected. Aspergillus spp. were identified routinely morphologically, and where there was ambiguity or a lack of sporulation, by sequencing of the internal transcribed spacer (ITS) region. All Aspergillus spp. that underwent antifungal susceptibility testing according to the CLSI M38-A3 method and were recorded and included in the study. Amphotericin B, voriconazole, posaconazole, isavuconazole, micafungin, caspofungin, and anidulafungin were tested. Pathology Queensland services all public healthcare facilities in Queensland, Australia. RESULTS: 236 Aspergillus spp. were identified from clinical specimens during the study period. The most frequent species identified were Aspergillus section Fumigati (n = 119), Aspergillus section Flavi (n = 35), Aspergillus terreus (n = 32) and Aspergillus niger (n = 29). Overall, MIC50/90 values for voriconazole, posaconazole, itraconazole, and isavuconazole were 0.25/1, 0.25/0.5, 0.25/0.5, and 0.5/2 mg/L respectively. Echinocandins demonstrated low MIC values overall with micafungin and anidulafungin both having an MIC50/90 of 0.015/0.03 mg/L. A total of 15 cryptic species were identified; high triazole MIC values were observed with a voriconazole MIC50/90 of 2/8 mg/L. From 2017 to 2021 we observed an increase in incidence of isolates with high voriconazole MIC values. There was no difference in voriconazole MIC values between Aspergillus spp. acquired in North Queensland when compared to Southeast Queensland, Australia. CONCLUSION: Increasing reports of antifungal resistance among Aspergillus spp. is concerning and warrants further investigation both locally and worldwide. Active surveillance of both the emergence of different Aspergillus spp. and changes in antifungal susceptibility patterns over time is crucial to informing clinicians and treatment guidelines.

Shewanella spp. Bloodstream Infections in Queensland, Australia.

The epidemiology of bloodstream infections caused by Shewanella spp. is not well defined. Our objective was to define the incidence and determinants of Shewanella spp. bloodstream infections by using population-based surveillance in Queensland, Australia during 2000‒2019. The incidence was 1.0 cases/1 million persons annually and was highest during summer and in the tropical Torres and Cape region. Older persons and male patients were at highest risk. At least 1 concurrent condition was documented in 75% of case-patients, and 30-day all cause case-fatality rate was 15%. Aging populations in warm climates might expect an increasing burden of these infections.

Pasteurella species bloodstream infections in Queensland, Australia, 2000-2019.

Pasteurella species are infrequent but potentially severe causes of bloodstream infection (BSI). The objective of this study was to determine the incidence, risk factors, and outcomes of Pasteurella species BSI in a large Australian population. Retrospective, laboratory-based surveillance was conducted in Queensland, Australia (population ≈ 5 million) during 2000-2019, and clinical and outcome information was established by linkage to state hospital admissions and vital statistics databases. During more than 86 million person-years of surveillance, 272 incident Pasteurella species BSI occurred for an overall age- and sex-standardized annual incidence of 3.3 per million residents. The incidence of Pasteurella species BSI was highest in recent years and older individuals were at greatest risk. The median (interquartile range) Charlson Comorbidity Index was 2 (0-4) with scores of zero, 1, 2, and 3 + observed in 81 (30%), 37 (14%), 44 (16%), and 110 (40%) of cases. The 30-day all-cause case fatality was 9% (24/272) and patients who died had more comorbidities and were less likely to have community-associated disease. Although Pasteurella species are infrequent causes of BSI, older individuals and those with comorbidities are at highest risk. The burden of this disease may be expected to increase with an aging and more comorbid population.

An Australian perspective on antimicrobial stewardship programs and transplantation.

BACKGROUND: Over 1000 solid-organ and close to 2000 stem-cell transplants are performed annually in Australia. METHODS: Antimicrobial stewardship activities in transplant units in Australia were reviewed. RESULTS: All health service organizations, and thus all transplant centers, in Australia are required to have an antimicrobial stewardship program. Despite this, in one recent survey, 23.5% of hospital antibiotic prescriptions were inappropriate. Vigorous efforts are being made to implement antifungal stewardship in Australian transplant programs, with guidelines for implementation published in December 2021. These guidelines include therapeutic antifungal drug monitoring and diagnostic stewardship as it pertains to the investigation of suspected invasive fungal infections. CONCLUSIONS: Infections with multidrug resistant pathogens and invasive fungi are sporadic issues in Australian transplant units, but stewardship efforts can optimize patient outcomes.

Risk factors, treatment and outcomes of subacute thyroiditis secondary to COVID-19: a systematic review.

BACKGROUND: COVID-19 is known to cause an acute respiratory illness, although clinical manifestations outside of the respiratory tract may occur. Early reports have identified SARS-CoV-2 as a cause of subacute thyroiditis (SAT). METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, Web of Science and PubMed databases were queried in February 2021 for studies from December 2019 to February 2021. MeSH search terms 'COVID-19', 'SARS-CoV-2' and 'coronavirus' along with search terms 'thyroiditis', 'thyrotoxicosis' and 'thyroid' were used. Descriptive statistics for continuous variables and proportions for categorical variables were calculated. RESULTS: Fifteen publications reporting on 17 individual cases of COVID-19-induced SAT were identified. Age ranged from 18 to 69 years. The majority (14 of 17; 82%) of cases were female. The delay between onset of respiratory symptoms and diagnosis of SAT ranged from 5 to 49 days (mean, 26.5). Systemic inflammatory response syndrome related to viral infection was uncommonly reported at the time of SAT diagnosis. Thyroid ultrasonography frequently reported an enlarged hypoechoic thyroid with decreased vascularity and heterogenous echotexture. Elevated C-reactive protein (CRP) was common at the time of SAT diagnosis, with results ranging from 4.5 to 176 mg/L (mean, 41 mg/L). Antithyroid antibodies were frequently negative. SAT-specific treatment included corticosteroids for 12 of 17 (70.5%) patients. Most returned to normal thyroid status. CONCLUSION: COVID-19-associated SAT may be difficult to identify in a timely manner due to potential absence of classic symptoms, as well as cross-over of common clinical features between COVID-19 and thyrotoxicosis.

Completing the Picture-Capturing the Resistome in Antibiotic Clinical Trials.

Despite the accepted dogma that antibiotic use is the largest contributor to antimicrobial resistance (AMR) and human microbiome disruption, our knowledge of specific antibiotic-microbiome effects remains basic. Detection of associations between new or old antimicrobials and specific AMR burden is patchy and heterogeneous. Various microbiome analysis tools are available to determine antibiotic effects on microbial communities in vivo. Microbiome analysis of treatment groups in antibiotic clinical trials, powered to measure clinically meaningful endpoints would greatly assist the antibiotic development pipeline and clinician antibiotic decision making.

An update on cefepime and its future role in combination with novel ß-lactamase inhibitors for MDR Enterobacterales and Pseudomonas aeruginosa.

Cefepime, a wide-spectrum ß-lactam antibiotic, has been in use for the treatment of serious bacterial infections for almost 25 years. Since its clinical development, there has been a dramatic shift in its dosing, with 2 g every 8 hours being preferred for serious infections to optimize pharmacokinetic/pharmacodynamic considerations. The advent of ESBLs has become a threat to its ongoing use, although future coadministration with ß-lactamase inhibitors (BLIs) under development is an area of intense study. There are currently four new cefepime/BLI combinations in clinical development. Cefepime/zidebactam is generally active against MBL-producing Enterobacterales and Pseudomonas aeruginosa, in vitro and in animal studies, and cefepime/taniborbactam has activity against KPC and OXA-48 producers. Cefepime/enmetazobactam and cefepime/tazobactam are potential carbapenem-sparing agents with activity against ESBLs. Cefepime/enmetazobactam has completed Phase III and cefepime/taniborbactam is in Phase III clinical studies, where they are being tested against carbapenems or piperacillin/tazobactam for the treatment of complicated urinary tract infections. While these combinations are promising, their role in the treatment of MDR Gram-negative infections can only be determined with further clinical studies.

Modern Clinician-initiated Clinical Trials to Determine Optimal Therapy for Multidrug-resistant Gram-negative Infections.

Treatment options for multidrug-resistant (MDR) gram-negative infection are growing. However, postregistration, pragmatic, and clinician-led clinical trials in this field are few, recruit small sample sizes, and experience deficiencies in design and operations. MDR gram-negative therapeutic trials are often inefficient, only evaluating a single antibiotic or strategy at a time. Novel clinical trial designs offer potential solutions by attempting to obtain clinically meaningful conclusions at the end or during a trial, for many treatment strategies, simultaneously. An integrated, consensus approach to MDR gram-negative infection trial design is crucial.

Achromobacter Infections and Treatment Options.

Achromobacter is a genus of nonfermenting Gram-negative bacteria under order Burkholderiales Although primarily isolated from respiratory tract of people with cystic fibrosis, Achromobacter spp. can cause a broad range of infections in hosts with other underlying conditions. Their rare occurrence and ever-changing taxonomy hinder defining their clinical features, risk factors for acquisition and adverse outcomes, and optimal treatment. Achromobacter spp. are intrinsically resistant to several antibiotics (e.g., most cephalosporins, aztreonam, and aminoglycosides), and are increasingly acquiring resistance to carbapenems. Carbapenem resistance is mainly caused by multidrug efflux pumps and metallo-ß-lactamases, which are not expected to be overcome by new ß-lactamase inhibitors. Among the other new antibiotics, cefiderocol, and eravacycline were used as salvage therapy for a limited number of patients with Achromobacter infections. In this article, we aim to give an overview of the antimicrobial resistance in Achromobacter species, highlighting the possible place of new antibiotics in their treatment.

Is Ceftazidime/Avibactam an Option for Serious Infections Due to Extended-Spectrum-ß-Lactamase- and AmpC-Producing Enterobacterales?: a Systematic Review and Meta-analysis.

Carbapenem-sparing regimens are needed for the treatment of infections caused by extended-spectrum-ß-lactamase (ESBL)- and AmpC-producing members of the Enterobacterales We sought to compare the clinical efficacy of ceftazidime/avibactam and carbapenems against ESBL- and AmpC-producing Enterobacterales species. A systematic review and meta-analysis of randomized controlled trials comparing ceftazidime/avibactam with carbapenems for the treatment of ESBL- and AmpC-producing Enterobacterales was conducted. Five randomized controlled trials (RCTs) with ESBL- and AmpC-specific outcome data were compiled. Of the 246 patients infected with an ESBL-producing microorganism in the ceftazidime/avibactam arm, 224 (91%) had a clinical response at test of cure (TOC), versus 240 of 271 (89%) patients in the carbapenem arm (risk ratio [RR], 1.02; 95% confidence interval [CI], 0.97 to 1.08; P = 0.45; I2 = 0%). Clinical response rates for AmpC producers in the ceftazidime/avibactam and carbapenem arms were 32/40 (80%) and 37/42 (88%), respectively (RR, 0.91; 95% CI, 0.76 to 1.10; P = 0.35; I2 = 0%). Microbiological response and mortality rates were not reported specifically for ESBL/AmpC producers. Ceftazidime/avibactam may be a carbapenem-sparing option for the treatment of mild to moderate complicated urinary tract and intra-abdominal infections caused by ESBL-producing Enterobacterales species, and the data are too limited to provide any conclusive recommendations for the AmpC producers. Care should be taken before extrapolating this to severe infections, given that the representation of this population in the reviewed studies was negligible. Ceftazidime/avibactam is a costly drug active against carbapenem-resistant microorganisms and should be used judiciously to preserve its activity against them.

Oral cephalosporin and ß-lactamase inhibitor combinations for ESBL-producing Enterobacteriaceae urinary tract infections.

ESBL-producing Enterobacteriaceae as uropathogens have given rise to a sizeable amount of global morbidity. Community and hospital surveillance studies continue to report increasing proportions of these organisms as causes of urinary tract infection (UTI). Due to limited treatment options and the presence of cross-resistance amongst oral antibiotics of different classes, patients often require IV therapy, thereby increasing healthcare costs and reducing the effectiveness of delivering healthcare. Oral cephalosporin antibiotics are well known for their ability to achieve high urinary concentrations, in addition to achieving clinical success for treatment of uncomplicated UTI with a drug-susceptible pathogen. Novel cephalosporin/ß-lactamase inhibitor combinations have been developed and demonstrate good in vitro activity against ESBL-producing isolates. A pooled analysis of in vitro activity of existing oral cephalosporin/clavulanate combinations in ESBL-producing Enterobacteriaceae has shown MIC50s of 0.5-1, 0.125-1 and 0.25 mg/L for cefpodoxime, ceftibuten and cefixime, respectively. A novel cyclic boronic acid ß-lactamase inhibitor, QPX7728, was able to produce MIC50 values of 0.5 and ≤0.06 mg/L when paired with cefpodoxime and ceftibuten, respectively. Other novel combinations, cefpodoxime/ETX0282 and ceftibuten/VNRX7145, have also demonstrated excellent activity against ESBL producers. Clinical trials are now awaited.

Acute kidney injury in acute Q fever.

Coxiella burnetii infection is not known to involve directly the kidneys. Kidney injury associated with Q fever usually manifests in the setting of chronic infection or endocarditis with development of immune complex deposition. Acute kidney injury (AKI) in the context of acute Q fever infection may be more pathologically heterogeneous. We describe two cases of severe AKI secondary to acute Q fever infection, each with marked differences in pathological characteristics, and clinical course.