Respiratory tract infection with SARS-CoV-2 results in varying immunopathology underlying COVID-19. We examine cellular, humoral and cytokine responses covering 382 immune components in longitudinal blood and respiratory samples from hospitalized COVID-19 patients. SARS-CoV-2-specific IgM, IgG, IgA are detected in respiratory tract and blood, however, receptor-binding domain (RBD)-specific IgM and IgG seroconversion is enhanced in respiratory specimens. SARS-CoV-2 neutralization activity in respiratory samples correlates with RBD-specific IgM and IgG levels. Cytokines/chemokines vary between respiratory samples and plasma, indicating that inflammation should be assessed in respiratory specimens to understand immunopathology. IFN-α2 and IL-12p70 in endotracheal aspirate and neutralization in sputum negatively correlate with duration of hospital stay. Diverse immune subsets are detected in respiratory samples, dominated by neutrophils. Importantly, dexamethasone treatment does not affect humoral responses in blood of COVID-19 patients. Our study unveils differential immune responses between respiratory samples and blood, and shows how drug therapy affects immune responses during COVID-19.

Infections caused by carbapenemase‐producing Enterobacteriaceae (CPE) are an emerging threat in both solid organ and stem cell transplant recipients. Invasive CPE infections in transplant recipients are associated with a high mortality, often due to limited therapeutic options and antibacterial toxicities. One of the most therapeutically challenging group of CPE are the metallo‐β‐lactamase (MBL)‐producing Gram‐negative bacteria, which are now found worldwide, and often need treatment with older, highly toxic antimicrobial regimens. Newer β‐lactamase inhibitors such as avibactam have well‐established activity against certain carbapenemases such as Klebsiella pneumoniae carbapenemases (KPC), but have no activity against MBL‐producing organisms. Conversely, aztreonam has activity against MBL‐producing organisms but is often inactivated by other co‐existing β‐lactamases. Here, we report four cases of invasive MBL‐CPE infections in transplant recipients caused by IMP‐4‐producing Enterobacter cloacae who were successfully treated with a new, mechanism‐driven antimicrobial combination of ceftazidime/avibactam with aztreonam. This novel antimicrobial combination offers a useful treatment option for high‐risk patients with CPE infection, with reduced drug interactions and toxicity.

We report bilateral cerebellar abscesses in a neonate with Citrobacter freundii meningitis. The mortality and morbidity of Citrobacter abscess is high. Rapidly developing drug resistance may play a role as illustrated by our case.

Background: Antimicrobial resistance (AMR) in Helicobacter pylori is a global concern.The AMR data to inform the Australian Therapeutic Guidelines are based on data over 20 years old.Aims: To evaluate the frequency of AMR in H. pylori isolates from gastric biopsy specimens received in our laboratory in Melbourne, Australia. To review the literature on resistance rates in Australia and compare historic data.Methods: A retrospective, observational study summarising AMR rates in all H. pylori isolates from our laboratory from 2015 to June 2020. Microbiology laboratory in metropolitan Melbourne, Australia, receiving referrals from private hospitals, gastroenterology clinics and endoscopy suites. Population minimum inhibitory concentration distributions and frequency of resistance to clarithromycin, amoxicillin, metronidazole and tetracycline in H. pylori isolates.Results: Three hundred and eighty-six H. pylori isolates with susceptibility testing data were identified. The frequency of resistance in this cohort was: clarithromycin 89.9%, amoxicillin 23.5%, metronidazole 66.1% and tetracycline 4.4%. Comparison with historical data may suggest increasing AMR rates in Australia. The main limitation is the lack of treatment history to correlate AMR results.Conclusions: Definitive conclusions from this cohort cannot be made, but trends suggest rising levels of primary H. pylori AMR rates in Australia. This has important implications for empirical treatment decision making and treatment outcomes. Primary H. pylori AMR requires dedicated studies and current Australian therapeutic guideline recommendations may require re-evaluation. We propose considerations for improving the management of H. pylori in Australia. A centralised public health approach to H. pylori AMR surveillance should be established.

A total of 1080 individual patient samples (158 positive serology samples from confirmed, predominantly mildly symptomatic COVID-19 patients and 922 serology negative including 496 collected pre-COVID) from four states in Australia were analysed on four commercial SARS-CoV-2 serological assays targeting antibodies to different antigens (Roche Elecsys and Abbott Architect: nucleocapsid; Diasorin Liaison and Euroimmun: spike). A subset was compared to immunofluorescent antibody (IFA) and micro-neutralisation. Sensitivity and specificity of the Roche (n = 1033), Abbott (n = 806), Diasorin (n = 1034) and Euroimmun (n = 175) were 93.7%/99.5%, 90.2%/99.4%, 88.6%/98.6% and 91.3%/98.8%, respectively. ROC analysis with specificity held at 99% increased the sensitivity for the Roche and Abbott assays from 93.7% to 98.7% (cut-off 0.21) and 90.2% to 94.0% (cut-off 0.91), respectively. Overall seropositivity of samples increased from a maximum of 23% for samples 0-7days-post-onset of symptoms (dpos), to 61% from samples 8-14dpos and 93% from those >14dpos. IFA and microneutralisation values correlated best with assays targeting antibodies to spike protein with values >80 AU/mL on the Diasorin assay associated with neutralising antibody. Detectable antibody was present in 22/23 (96%), 20/23 (87%), 15/23 (65%) and 9/22 (41%) patients with samples >180dpos on the Roche, Diasorin, Abbott and microneutralisation assays respectively. Given the low prevalence in this community, two-step algorithms on initial positive results saw an increase in the positive predictive value (PPV) of positive samples (39%-65% to ≥98%) for all combinations. Similarly accuracy increased from a range of 98.5%-99.4% to ≥99.8% assuming a 1% seroprevalence. Negative predictive value (NPV) was high (≥99.8%) regardless of which assay was used initially.

The diagnosis of central nervous system (CNS) infection relies upon analysis of cerebrospinal fluid (CSF). We present 4 cases of CNS infections associated with basal meningitis and hydrocephalus with normal ventricular CSF but grossly abnormal lumbar CSF. We discuss CSF ventricular-lumbar composition gradients, putative pathophysiological mechanisms, and highlight clinical clues for clinicians.

Mycobacterium abscessus is an emerging cause of invasive infection in the immunosuppressed population. We report a case of M. abscessus bloodstream and catheter tunnel infection localized by positron emission tomography/computer tomography (PET/CT) in an allogeneic haematopoietic stem cell transplant recipient. This case highlights the difficulties in treating invasive M. abscessus infection and the potential role of PET/CT in localizing infection and guiding therapy in this population. K E Y W O R D S bacteremia, catheter-related infection, hematopoietic stem cell transplantation, Mycobacterium abscessus

Cytomegalovirus (CMV) infection is a significant cause of morbidity and mortality after solid organ transplantation. There has been a significant shift in disease epidemiology with the introduction of antiviral prophylaxis, with CMV disease occurring later and clinical presentations more atypical. We describe two cases of very late‐onset CMV disease where first disease occurred 15 and 18 years post–renal transplantation, with both cases complicated by antiviral drug resistance. We subsequently review the published cases and literature of very late‐onset CMV disease (onset > 10 years post–solid organ transplantation) as an increasingly recognized phenomenon which is emerging as an important aspect in improving long‐term patient outcomes in the current era of renal transplantation.