High-risk Escherichia coli clones that cause neonatal meningitis and association with recrudescent infection.

Neonatal meningitis is a devastating disease associated with high mortality and neurological sequelae. Escherichia coli is the second most common cause of neonatal meningitis in full-term infants (herein NMEC) and the most common cause of meningitis in preterm neonates. Here, we investigated the genomic relatedness of a collection of 58 NMEC isolates spanning 1974-2020 and isolated from seven different geographic regions. We show NMEC are comprised of diverse sequence types (STs), with ST95 (34.5%) and ST1193 (15.5%) the most common. No single virulence gene profile was conserved in all isolates; however, genes encoding fimbrial adhesins, iron acquisition systems, the K1 capsule, and O antigen types O18, O75, and O2 were most prevalent. Antibiotic resistance genes occurred infrequently in our collection. We also monitored the infection dynamics in three patients that suffered recrudescent invasive infection caused by the original infecting isolate despite appropriate antibiotic treatment based on antibiogram profile and resistance genotype. These patients exhibited severe gut dysbiosis. In one patient, the causative NMEC isolate was also detected in the fecal flora at the time of the second infection episode and after treatment. Thus, although antibiotics are the standard of care for NMEC treatment, our data suggest that failure to eliminate the causative NMEC that resides intestinally can lead to the existence of a refractory reservoir that may seed recrudescent infection.

Genomic characterisation reveals a dominant lineage of SARS-CoV-2 in Papua New Guinea.

The coronavirus disease pandemic has highlighted the utility of pathogen genomics as a key part of comprehensive public health response to emerging infectious diseases threats, however, the ability to generate, analyse, and respond to pathogen genomic data varies around the world. Papua New Guinea (PNG), which has limited in-country capacity for genomics, has experienced significant outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with initial genomics data indicating a large proportion of cases were from lineages that are not well defined within the current nomenclature. Through a partnership between in-country public health agencies and academic organisations, industry, and a public health genomics reference laboratory in Australia a system for routine SARS-CoV-2 genomics from PNG was established. Here we aim to characterise and describe the genomics of PNG's second wave and examine the sudden expansion of a lineage that is not well defined but very prevalent in the Western Pacific region. We generated 1797 sequences from cases in PNG and performed phylogenetic and phylodynamic analyses to examine the outbreak and characterise the circulating lineages and clusters present. Our results reveal the rapid expansion of the B.1.466.2 and related lineages within PNG, from multiple introductions into the country. We also highlight the difficulties that unstable lineage assignment causes when using genomics to assist with rapid cluster definitions.

Standard rectal swabs as a surrogate sample for gut microbiome monitoring in intensive care.

BACKGROUND: The purpose of this study was to investigate the use of routinely available rectal swabs as a surrogate sample type for testing the gut microbiome and monitoring antibiotic effects on key gut microorganisms, of patients hospitalised in an intensive care unit. A metagenomic whole genome sequencing approach was undertaken to determine the diversity of organisms as well as resistance genes and to compare findings between the two sampling techniques. RESULTS: No significant difference was observed in overall diversity between the faeces and rectal swabs and sampling technique was not demonstrated to predict microbial community variation. More human DNA was present in the swabs and some differences were observed only for a select few anaerobes and bacteria also associated with skin and/or the female genitourinary system, possibly reflecting sampling site or technique. Antibiotics and collections at different times of admission were both considered significant influences on microbial community composition alteration. Detection of antibiotic resistance genes between rectal swabs and faeces were overall not significantly different, although some variations were detected with a potential association with the number of human sequence reads in a sample. CONCLUSION: Testing the gut microbiome using standard rectal swab collection techniques currently used for multi-resistant organism screening has been demonstrated to have utility in gut microbiome monitoring in intensive care. The use of information from this article, in terms of methodology as well as near equivalence demonstrated between rectal swabs and faeces will be able to support and potentially facilitate the introduction into clinical practice.

Detection of the Omicron (B.1.1.529) variant of SARS-CoV-2 in aircraft wastewater.

On the 26th of November 2021, the World Health Organization (WHO) designated the newly detected B.1.1.529 lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) the Omicron Variant of Concern (VOC). The genome of the Omicron VOC contains more than 50 mutations, many of which have been associated with increased transmissibility, differing disease severity, and potential to evade immune responses developed for previous VOCs such as Alpha and Delta. In the days since the designation of B.1.1.529 as a VOC, infections with the lineage have been reported in countries around the globe and many countries have implemented travel restrictions and increased border controls in response. We putatively detected the Omicron variant in an aircraft wastewater sample from a flight arriving to Darwin, Australia from Johannesburg, South Africa on the 25th of November 2021 via positive results on the CDC N1, CDC N2, and del(69-70) RT-qPCR assays per guidance from the WHO. The Australian Northern Territory Health Department detected one passenger onboard the flight who was infected with SARS-CoV-2, which was determined to be the Omicron VOC by sequencing of a nasopharyngeal swab sample. Subsequent sequencing of the aircraft wastewater sample using the ARTIC V3 protocol with Nanopore and ATOPlex confirmed the presence of the Omicron variant with a consensus genome that clustered with the B.1.1.529 BA.1 sub-lineage. Our detection and confirmation of a single onboard Omicron infection via aircraft wastewater further bolsters the important role that aircraft wastewater can play as an independent and unintrusive surveillance point for infectious diseases, particularly coronavirus disease 2019.

Replication Kinetics of B.1.351 and B.1.1.7 SARS-CoV-2 Variants of Concern Including Assessment of a B.1.1.7 Mutant Carrying a Defective ORF7a Gene.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, is a readily transmissible and potentially deadly pathogen which is currently re-defining human susceptibility to pandemic viruses in the modern world. The recent emergence of several genetically distinct descendants known as variants of concern (VOCs) is further challenging public health disease management, due to increased rates of virus transmission and potential constraints on vaccine effectiveness. We report the isolation of SARS-CoV-2 VOCs imported into Australia belonging to the B.1.351 lineage, first described in the Republic of South Africa (RSA), and the B.1.1.7 lineage originally reported in the United Kingdom, and directly compare the replication kinetics of these two VOCs in Vero E6 cells. In this analysis, we also investigated a B.1.1.7 VOC (QLD1516/2021) carrying a 7-nucleotide deletion in the open reading frame 7a (ORF7a) gene, likely truncating and rendering the ORF7a protein of this virus defective. We demonstrate that the replication of the B.1.351 VOC (QLD1520/2020) in Vero E6 cells can be detected earlier than the B.1.1.7 VOCs (QLD1516/2021 and QLD1517/2021), before peaking at 48 h post infection (p.i.), with significantly higher levels of virus progeny. Whilst replication of the ORF7a defective isolate QLD1516/2021 was delayed longer than the other viruses, slightly more viral progeny was produced by the mutant compared to the unmutated isolate QLD1517/2021 at 72 h p.i. Collectively, these findings contribute to our understanding of SARS-CoV-2 replication and evolutionary dynamics, which have important implications in the development of future vaccination, antiviral therapies, and epidemiological control strategies for COVID-19.

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.

COVID-19 in a complex obstetric patient with cystic fibrosis.

We report the first case of COVID-19 in a pregnant patient with cystic fibrosis. We describe the diagnosis, clinical course and management of the patient and their family with regards to clinical, social and infection control measures around delivery. This case highlights the importance of the cooperation of multidisciplinary teams to achieve good clinical outcomes in complex patients with COVID-19.

A Case of Japanese Encephalitis with a Fatal Outcome in an Australian Who Traveled from Bali in 2019.

A severe case of Japanese encephalitis virus (JEV) infection, resulting in fatality, occurred in an unvaccinated Australian male traveler from Bali, Indonesia, in 2019. During hospitalisation in Australia, patient cerebrospinal fluid (CSF) yielded JEV-specific IgM antibodies and RNA, and an isolate of the virus. Ongoing transmission of JEV in Bali underscores this pathogen as a public health risk and the importance of appropriate health, vaccination and mosquito avoidance advice to prospective travelers to the region.

Testing for Common Respiratory Viruses in Children Admitted to Pediatric Intensive Care: Epidemiology and Outcomes.

OBJECTIVES: Viral infections are common in children, but there is a lack of data on severe viral infections in critically ill children. We investigated testing for viral infections in children requiring PICU admission and describe the epidemiology and outcomes. DESIGN: Multicenter retrospective study. Results of viral testing for nine respiratory viruses using polymerase chain reaction were collected. PARTICIPANTS: Children less than 16 years old nonelectively admitted to PICU over a 6-year period. SETTING: Two tertiary PICUs in Queensland, Australia. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Primary outcome was PICU length of stay. Secondary outcomes included need for and duration of intubation and mortality in PICU. Univariate and multivariate regression analyses were performed, adjusting for age, indigenous status, comorbidities, and severity of illness. RESULTS: Of 6,426 nonelective admissions, 2,956 (46%) were polymerase chain reaction tested for a virus of which 1,353 (46%) were virus positive. Respiratory syncytial virus was the most common pathogen identified (n = 518, 33%), followed by rhinovirus/enterovirus and adenovirus. Across all patients who underwent polymerase chain reaction testing, identification of a respiratory virus was not significantly associated with longer overall length of stay (multivariate odds ratio, 1.08; 95% CI, 0.99-1.17; p = 0.068) or longer intubation (p = 0.181), whereas the adjusted odds for intubation and mortality were significantly lower (p < 0.01). Subgroup analyses restricted to patients with acute respiratory infections (n = 1,241), bronchiolitis (n = 761), pneumonia (n = 311), confirmed bacterial infection (n = 345), and malignancy (n = 95) showed that patients positive for a virus on testing had significantly longer PICU length of stay (multivariate p < 0.05). In children with pneumonia, identification of a respiratory virus was associated with significantly increased duration of ventilation (p = 0.003). No association between positive test results for multiple viruses and outcomes was observed. CONCLUSION: Viral infections are common in critically ill children. Viral infections were associated with lower intubation and mortality rates compared with all children testing negative for viral infections. In several subgroups studied, identification of viral pathogens was associated with longer PICU length of stay while mortality was comparable. Prospective studies are required to determine the benefit of routine testing for respiratory viruses at the time of PICU admission.

Antimicrobial-associated harm in critical care: a narrative review.

The belief that, for the individual patient, the benefit of prompt and continued use of antimicrobials outweighs any potential harm is a significant barrier to improved stewardship of these vital agents. Antimicrobial stewardship may be perceived as utilitarian rationing, seeking to preserve the availability of effective antimicrobials by limiting the development of resistance in a manner which could conflict with the immediate treatment of the patient in need. This view does not account for the growing evidence of antimicrobial-associated harm to individual patients. This review sets out the evidence for antimicrobial-associated harm and how this should be balanced with the need for prompt and appropriate therapy in infection. It describes the mechanisms by which antimicrobials may harm patients including: mitochondrial toxicity; immune cell toxicity; adverse drug reactions; selection of resistant organisms within a given patient; and disruption of the microbiome. Finally, the article indicates how the harms of antimicrobials may be mitigated and identifies areas for research and development in this field.

Viral Respiratory Infections Diagnosed After PICU Admission.

OBJECTIVES: Reduction of nosocomial infections represents an increasingly recognized aspect of PICU benchmarking. We investigated the prevalence and outcomes of viral respiratory infections acquired during admission to PICU. DESIGN: Multicenter, statewide retrospective linkage study. SETTING: Tertiary PICU. PATIENTS: All children less than 16 years requiring PICU admission for greater than 48 hours from January 1, 2008, until December 31, 2013. INTERVENTION: Testing was performed in symptomatic patients using an extended panel polymerase chain reaction capturing nine respiratory viruses. Duration of intubation and total duration of respiratory support were primary outcomes. MEASUREMENTS AND MAIN RESULTS: Of 3,607 patients admitted to PICU for greater than 48 hours, 102 (2.8%) were diagnosed with a PICU-associated viral infection out of 702 patients (19.4%) undergoing viral testing, reflecting a rate of 2.8 PICU-associated viral infections per 1,000 PICU patient days. Compared with negative/untested patients, those with PICU-associated viral infections had greater intubation duration (median 164 vs 67; p< 0.001), longer respiratory support (204 vs 68 hr; p < 0.001), were more likely to require extracorporeal life support (odds ratio, 5.3; 2.7-10.3; p < 0.001), high-frequency oscillatory ventilation (odds ratio, 3.0; 1.7-5.4; p < 0.001), and inhaled nitric oxide (odds ratio, 2.7; 1.5-5.0; p = 0.001). When comparing patients with PICU-associated viral infection with patients who tested negative for respiratory viruses, no substantial difference in these outcomes was found. CONCLUSIONS: The acquisition of viral infections during PICU admission is less frequent compared with previous reports on bacterial and fungal hospital-acquired infections. We did not observe worse patient-centered outcomes when comparing virus positive versus tested but negative patients. Our findings challenge the clinical value of performing viral respiratory diagnostics in PICU patients evaluated for infection.

Severe Mycoplasma Pneumoniae Infection in Children Admitted to Pediatric Intensive Care.

Mycoplasma pneumoniae is a common cause of community-acquired pneumonia and may cause life-threatening disease in children. We identified 30 (0.3%) confirmed M. pneumoniae cases by clinical and laboratory criteria in 11,526 pediatric intensive care unit admissions. Outcomes were comparable to patients admitted with other infections (n=3005; P > 0.1). Our findings indicate that empiric antimicrobial coverage for M. pneumoniae infection in pediatric intensive care unit is rarely needed.

Early Blood Stream Infections after BMT are Associated with Cytokine Dysregulation and Poor Overall Survival.

The key complications of allogeneic bone marrow transplantation (BMT) remain graft-versus-host disease (GVHD) and opportunistic infection. We have analyzed the blood stream infections (BSIs) occurring between day -7 and day 100 in a cohort of 184 adult patients undergoing allogeneic BMT in our center. A total of 167 of the 184 patients (91%) had blood cultures collected, and 69 (38%) patients had a confirmed BSI. Enterobacteriaceae, Pseudomonas aeruginosa, Enterococcus spp., and viridans Streptococcus spp. were the most commonly isolated organisms. Gender, conditioning (myeloablative versus reduced intensity), and donor type (sibling versus unrelated) did not differ significantly between those with and without confirmed BSI. Elevated temperature (>38°C) at the time of culture collection was associated with an almost 2-fold increased likelihood of returning a positive blood culture. The absence of a BSI was associated with a significant improvement in overall survival at 2 years, due to a significant reduction in nonrelapse mortality predominantly unrelated to the primary BSI. The presence of a BSI before engraftment was associated with the dysregulation of IL-6 and IL-8. Our findings suggest that BSI early after BMT defines a group of high-risk patients with enhanced cytokine dysregulation and poor transplant outcome.

Impact of Viral Respiratory Pathogens on Outcomes After Pediatric Cardiac Surgery.

OBJECTIVES: Viral respiratory infection is commonly considered a relative contraindication to elective cardiac surgery. We aimed to determine the frequency and outcomes of symptomatic viral respiratory infection in pediatric cardiac surgical patients. DESIGN: Retrospective cohort study of children undergoing cardiac surgery. Symptomatic children were tested using a multiplex Polymerase Chain Reaction (respiratory virus polymerase chain reaction) panel capturing nine respiratory viruses. Tests performed between 72 prior to and 48 hours after PICU admission were included. Mortality, length of stay in PICU, and intubation duration were investigated as outcomes. SETTING: Tertiary PICU providing state-wide pediatric cardiac services. PATIENTS: Children less than 18 years admitted January 1, 2008 to November 29, 2014 for cardiac surgery. MEASUREMENTS AND MAIN RESULTS: Respiratory virus polymerase chain reaction was positive in 73 (4.2%) of 1,737 pediatric cardiac surgical admissions, including 13 children with multiple viruses detected. Commonly detected viruses included rhino/enterovirus (48%), adenovirus (32%), parainfluenza virus 3 (10%), and respiratory syncytial virus (3%). Pediatric Index of Mortality 2, Aristotle scores, and cardiopulmonary bypass times were similar between virus positive and negative/untested cohorts. Respiratory virus polymerase chain reaction positive patients had a median 2.0 days greater PICU length of stay (p < 0.001) and longer intubation duration (p < 0.001). Multivariate analysis adjusting for age, Aristotle score, cardiopulmonary bypass duration, and need for preoperative PICU admission confirmed that virus positive patients had significantly greater intubation duration and PICU length of stay (p < 0.001). Virus positive patients were more likely to require PICU admission greater than 4 days (odds ratio, 3.5; 95% CI, 1.9-6.2) and more likely to require intubation greater than 48 hours (odds ratio, 2.5; 95% CI, 1.4-4.7). There was no difference in mortality. No association was found between coinfection and outcomes. CONCLUSIONS: Pediatric cardiac surgical patients with a respiratory virus detected at PICU admission had prolonged postoperative recovery with increased length of stay and duration of intubation. Our results suggest that postponing cardiac surgery in children with symptomatic viral respiratory infection is appropriate, unless the benefits of early surgery outweigh the risk of prolonged ventilation and PICU stay.

Diagnostic testing in influenza and pertussis related paediatric intensive care unit admissions,Queensland, Australia, 1997-2013.

Severe respiratory infections make up a large proportion of Australian paediatric intensive care unit (ICU) admissions each year. Identification of the causative pathogen is important and informs clinical management. We investigated the use of polymerase chain reaction (PCR) in the ICU-setting using data collated by the Australian and New Zealand Paediatric Intensive Care (ANZPIC) Registry from five ICUs in Queensland, Australia. We describe diagnostic testing use among pertussis and influenza-related paediatric ICU admissions between 01 January 1997 and 31 December 2013.