Low rates of complications and ß-lactam resistance in viridans group streptococci bloodstream infection among cancer patients receiving chemotherapy.

BACKGROUND: Viridans group streptococci (VGS) bloodstream infection (BSI) frequently occurs in cancer patients receiving chemotherapy, and is associated with infective endocarditis (IE) in up to 20% of cases in the general population. OBJECTIVES: In cancer patients receiving chemotherapy with VGS BSI, we aimed to: (i) determine the incidence of infective complications including IE, (ii) assess the utility of echocardiography in this patient population, (iii) determine the duration and type of antimicrobial therapy received for monomicrobial infections, and (iv) determine the evolution of antimicrobial resistance. METHODS: VGS BSIs (excluding Streptococcus pneumoniae and Streptococcus pseudopneumoniae) in cancer patients receiving chemotherapy were identified from a statewide public pathology database between 2013 and 2022 at our tertiary centre. Medical records were accessed for clinical, microbiological and radiological data. RESULTS: Of 581 patient episodes screened, 183 episodes involving 171 patients met inclusion criteria. Of these, 51% were bone marrow transplantation (BMT) patients, 40% were non-BMT haematology patients, and 8% were solid organ malignancy patients. The median age was 55 years, and 96% were neutropenic at the time of blood culture collection. A transthoracic echocardiogram was performed for 71% of episodes, and one patient met modified Duke's criteria for definite IE, although this diagnosis was not suspected on clinical grounds. Other complications were uncommon. Benzylpenicillin resistance was rare (2.9%) and did not change over time. Most episodes (75%) were treated with piperacillin/tazobactam. For monomicrobial BSIs, the median antibiotic duration was 5 days (IQR 2-7) post-neutropenia resolution. CONCLUSIONS: Infective complications and antimicrobial resistance are rare in cancer patients with VGS BSI. This may provide a safe opportunity to limit both investigations (e.g. echocardiogram) and prolonged exposure to broad-spectrum antimicrobials.

ANZTCT practice statement: sinusoidal obstruction syndrome/veno-occlusive disease diagnosis and management.

Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication which can develop after haemopoietic stem cell transplantation (HSCT) and some antibody-drug conjugates. Several SOS/VOD diagnostic and management guidelines exist, with the most recent and refined being the European Society for Blood and Marrow Transplantation adult and paediatric guidelines. Timely diagnosis and effective management (including the availability of therapeutic options) significantly contribute to improved patient outcomes. In Australia and New Zealand, there is variability in clinical practice and access to SOS/VOD therapies. This review aims to summarise the current evidence for SOS/VOD diagnosis, prevention and treatment and to provide recommendations for SOS/VOD in the context of contemporary Australasian HSCT clinical practice.

PET assessment of acute gastrointestinal graft versus host disease.

Acute gastrointestinal graft versus host disease (GI-GVHD) is a common complication following allogeneic haematopoietic cell transplantation (HCT), and is characterised by severe morbidity, frequent treatment-refractoriness, and high mortality. Early, accurate identification of GI-GVHD could allow for therapeutic interventions to ameliorate its severity, improve response rates and survival; however, standard endoscopic biopsy is inadequately informative in terms of diagnostic sensitivity or outcome prediction. In an era where rapid technological and laboratory advances have dramatically expanded our understanding of GI-GVHD biology and potential therapeutic targets, there is substantial scope for novel investigations that can precisely guide GI-GVHD management. In particular, the combination of tissue-based biomarker assessment (plasma cytokines, faecal microbiome) and molecular imaging by positron emission tomography (PET) offers the potential for non-invasive, real-time in vivo assessment of donor:recipient immune activity within the GI tract for GI-GVHD prediction or diagnosis. In this article, we review the evidence regarding GI-GVHD diagnosis, and examine the potential roles and translational opportunities posed by these novel diagnostic tools, with a focus on the evolving role of PET.

Favourable survival in "Discordant" acute gastrointestinal graft versus host disease (GI-GVHD) is explained by mild clinical course and treatment-responsive disease.

We have previously reported that haematopoietic progenitor cell transplantation recipients with biopsy-negative acute Gastrointestinal Graft versus Host Disease (Discordant GVHD) demonstrate superior survival compared to "True Positive" cases. We aimed to elucidate this discrepancy by examining clinical and laboratory predictors of survival among patients treated for True Positive or Discordant GVHD. Data were obtained by retrospective chart review. At diagnosis, the incidence of severe symptoms, hypoalbuminaemia, hyperbilirubinaemia, and poor performance status were recorded. Following treatment, the incidence of non-response to first-line corticosteroids was assessed. Differences between cohorts were compared using Fisher's exact test. 74 patients were identified, comprising 55 (74%) True Positive and 19 (26%) Discordant GVHD cases. True Positive cases were significantly more likely to have baseline severe symptoms (84% vs. 36%; p = 0.0002) and hypoalbuminaemia (94% vs. 75%; p = 0.023). There was no significant difference between cohorts in terms of hyperbilirubinaemia or performance status. Non-response to corticosteroid therapy was observed significantly more frequently in the True Positive cohort (55% vs. 11%; p = 0.001). In summary, the superior survival observed in Discordant GVHD is explained by a less severe GI-GVHD phenotype at diagnosis and a greater likelihood of response to corticosteroids. Further research is warranted to explain biological mechanisms for these findings.

Diagnostic Utility of Endoscopy and Biopsy in Suspected Acute Gastrointestinal Graft-versus-Host Disease after Hematopoietic Progenitor Cell Transplantation.

Acute gastrointestinal graft-versus-host disease (GI-GVHD) after hematopoietic progenitor cell transplantation (HPCT) is a common and life-threatening complication. Endoscopic biopsy of the GI tract (GIT) is required for diagnosis. However, clear evidence to optimize this diagnostic approach is lacking, leading to variation in diagnostic sensitivity between institutions. We aimed to assess the clinical, endoscopic, and histologic findings of endoscopies performed for suspected acute GI-GVHD at our institution to better define the optimal use of this strategy. We performed a retrospective cohort study of adults who had undergone endoscopy for suspected acute GI-GVHD within 180 days after allogeneic HPCT for hematologic malignancy between 2011 and 2016. Details included symptoms at time of referral for endoscopy, type of procedure performed, macroscopic findings on endoscopy, and histologic findings after gut biopsy. Correlation was made with clinical GVHD severity scores. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated and compared for each procedure. Predictors of histologic GVHD and overall survival were also compared. Of the 123 patients included, acute GI-GVHD occurred in 59 (48%). Lower endoscopy demonstrated greater sensitivity than upper endoscopy (50% versus 39%). Single upper endoscopy for upper symptoms alone had the lowest yield of GI-GVHD (14%). Combination upper and lower endoscopy demonstrated strong histologic concordance between upper and lower procedures. The addition of upper endoscopy to lower endoscopy only identified an extra 2 (4%) cases of GVHD. Advanced age and the presence of lower GIT symptoms were the only pre-endoscopy predictors of histologic GVHD on multivariate analysis. Patients with isolated upper histologic GVHD showed similar survival to patients with negative biopsies. Endoscopy and biopsy only identified 74% of those ultimately requiring treatment for acute GI-GVHD. Acute GI-GVHD remains a clinical diagnosis supported by available histologic evidence. Isolated upper GI-GVHD is rare, and in the absence of lower GIT symptoms, routine upper endoscopy does not significantly improve diagnostic yield for histologic GVHD. Overall, endoscopy and biopsy underdiagnoses 26% of clinical GI-GVHD, highlighting a need for research into novel diagnostic strategies.