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.
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