•Time to culture NTM organism ranged from 2 to 27 days.•Consider prolonged culture to 14 days in culture negative peritonitis.•We recommend 6 week mycobacterial culture where NTM infection suspected.
...Peritonitis remains a significant cause of peritoneal dialysis (PD)-associated morbidity, and technique failure. Non-tuberculous mycobacteria (NTM), commonly found in the environment (soil and water sources), are a rare cause of PD peritonitis, particularly important to consider in culture negative peritonitis.
Cases were identified via a search of the local microbiology laboratory database system between 01/01/2011 and 01/01/2020 at the Queen Elizabeth Hospital Birmingham, UK. Cases were identified by isolation of a Mycobacterium sp. other than Mycobacterium tuberculosis complex either from a PD exit site culture or from PD peritoneal fluid culture. We identified nine cases of peritonitis and one of isolated exit site infection (ESI).
Clinical presentation was similar to peritonitis caused by usual bacterial pathogens. Of the peritonitis cases, three were due to M. chelonae, three M. fortuitum, two M. abscessus and one M. chimera. The ESI was caused by M. fortuitum. The peritoneal fluid microscopy showed a neutrophil predominance. In 80 % of the cases in our cohort, the microorganism was identified from the culture of the first peritoneal dialysis (PD) fluid sample, however the time to identification from culture ranged from 2 to 27 days. All mycobacteria were grown from standard culture media, except for M. chimera which required a specialist mycobacterial liquid culture system. All cases of peritonitis underwent PD catheter removal with conversion to haemodialysis. Treatment length and antibiotic combinations varied significantly, with some cases being successfully treated with courses as short as 4 weeks. Significant antibiotic related side effects including hearing loss and QTc prolongation were noted.
We would recommend extending standard microbiological cultures of culture negative peritonitis to 2 weeks and employing mycobacterial culture media incubated for 6–10 weeks as would be standard for mycobacterial investigations, prior to exclusion of NTM as a causative organism of peritonitis.
•VLA2001 is a whole-virus, inactivated, adjuvanted COVID-19 vaccine candidate.•VLA2001 induces neutralizing antibodies and T-cell responses against COVID-19.•VLA2001 is well tolerated in adults aged ...18–55 years, with no safety signal of concern being identified.•Comparison of three different dose levels allowed identification of optimum dosage for further clinical investigation.
We aimed to evaluate the safety and optimal dose of a novel inactivated whole-virus adjuvanted vaccine against SARS-CoV-2: VLA2001.
We conducted an open-label, dose-escalation study followed by a double-blind randomized trial using low, medium and high doses of VLA2001 (1:1:1). The primary safety outcome was the frequency and severity of solicited local and systemic reactions within 7 days after vaccination. The primary immunogenicity outcome was the geometric mean titre (GMT) of neutralizing antibodies against SARS-CoV-2 two weeks after the second vaccination. The study is registered as NCT04671017.
Between December 16, 2020, and June 3, 2021, 153 healthy adults aged 18–55 years were recruited in the UK. Overall, 81.7% of the participants reported a solicited AE, with injection site tenderness (58.2%) and headache (46.4%) being the most frequent. Only 2 participants reported a severe solicited event. Up to day 106, 131 (85.6%) participants had reported any AE. All observed incidents were transient and non-life threatening in nature. Immunogenicity measured at 2 weeks after completion of the two-dose priming schedule, showed significantly higher GMTs of SARS-CoV-2 neutralizing antibody titres in the highest dose group (GMT 545.6; 95% CI: 428.1, 695.4) which were similar to a panel of convalescent sera (GMT 526.9; 95% CI: 336.5, 825.1). Seroconversion rates of neutralizing antibodies were also significantly higher in the high-dose group (>90%) compared to the other dose groups. In the high dose group, antigen-specific IFN-γ expressing T-cells reactive against the S, M and N proteins were observed in 76, 36 and 49%, respectively.
VLA2001 was well tolerated in all tested dose groups, and no safety signal of concern was identified. The highest dose group showed statistically significantly stronger immunogenicity with similar tolerability and safety, and was selected for phase 3 clinical development.
