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Background Early excision of burns reduces the incidence of local and systemic infections caused by colonising microorganisms, and reduces mortality and length of hospital stay. Appropriate antibiotic prophylaxis can reduce the risk of postoperative wound infections and skin graft loss. Antibiotic selection should be based on likely pathogens. However, there are few studies that have investigated the early pathogenic colonisers of acute burn wounds. Aim To describe pathogenic microorganisms found in acute burns and to make further recommendations on the use of early perioperative prophylactic antibiotics. Methods All burns patients admitted at the tertiary adult burns centre in Victoria over a 2-year period, who had surface swabs or tissue samples obtained from wounds within 24 h of injury were included in this retrospective cohort study. Pathogenic organisms were examined with respect to patient characteristics, burn characteristics, treatment provided and immediate exposure to environmental contaminants. Results Nearly one third of burns patients had wounds colonised with pathogenic microorganisms. Gram-negative bacteria were isolated from 52% of these. Staphylococcus aureus was the most common isolate. Pseudomonas and Enterobacter species were the most common gram-negatives. The only independent risk factor associated with early colonisation with gram-negative bacteria was per cent TBSA burn. Conclusion Increased colonisation of acute burn wounds with pathogenic gram-negative bacteria was associated with increased size of burn.

This study reviewed the demographics, presentation, management, complications and outcomes of acute epiglottitis post Haemophilus influenzae type-b vaccine introduction in Australia.Retrospective review of acute epiglottitis at four Victorian tertiary centres from 2011 to 2016 was conducted. Patient characteristics, presentation, investigations, management, complications and outcomes were recorded. Subgroup analysis aiming to identify risk factors for patients requiring acute airway management was performed.Eighty-seven adult and six paediatric cases were identified. The most frequent clinical findings in adults were sore throat (88.5%), dysphagia (71.3%), odynophagia (57.5%), dysphonia (56.3%) and fever (55.2%); 75.9% required intensive care unit admission. Airway compromise requiring intubation occurred in 27.6%, with 12.5% of these patients undergoing emergency surgical airways. Stridor, hypoxia, shortness of breath, odynophagia and lymphadenopathy were statistically more frequent amongst cases requiring airway intervention (P0.05). Cultures revealed mixed results with no aetiological pattern. H. influenzae type-b was never cultured. Amongst paediatric cases, fever, tachycardia and stridor were frequently observed and all were admitted to intensive care unit. Two of six required intubation and one underwent surgical intervention. There were no deaths, but one patient suffered a hypoxic brain injury.Modern epiglottitis is not the disease previously encountered by clinicians. With changing demographics and varying organisms, management is adapting to reflect this. Complications are rare, and symptomatology at presentation aids earlier recognition of patients who may require airway protection.

Acinetobacter baumannii is a common causative agent of hospital-acquired infections and a leading cause of infection in burns patients. Carbapenem resistant A. baumannii is considered a major public health threat and has been identified by the World Health Organization as the top priority organism requiring new antimicrobials. The most common mechanism for carbapenem resistance in A. baumannii is via horizontal acquisition of carbapenemase genes. In this study, we sampled 20 A. baumannii isolates from a patient with extensive burns, and characterized the evolution of carbapenem resistance over a 45-day period via Illumina and Oxford Nanopore sequencing. All isolates were multi-drug resistant, carrying two genomic islands that harboured several antibiotic resistance genes. Most isolates were genetically identical and represent a single founder genotype. We identified three novel non-synonymous substitutions associated with meropenem resistance: F136L and G288S in AdeB (part of the AdeABC efflux pump) associated with an increase in meropenem MIC to ≥8 μg/mL; and A515V in FtsI (PBP3, a penicillin-binding protein) associated with a further increase in MIC to 32 μg/mL. Structural modelling of AdeB and FtsI showed that these mutations affected their drug binding sites and revealed mechanisms for meropenem resistance. Notably, one of the adeB mutations arose prior to meropenem therapy but following ciprofloxacin therapy, suggesting exposure to one drug whose resistance is mediated by the efflux pump can induce collateral resistance to other drugs to which the bacteria has not yet been exposed.DATA SUMMARYAll raw genome sequences, including Illumina paired end short reads and Oxford Nanopore long reads, have been deposited in the SRA under project PRJNA396979. Individual accessions for each strain are provided in Table S1.The annotated genome assembly for strain A2, the reference genome for the founder genotype, has been submitted to GenBank under accession CP024124 (chromosome) and CP024125 (plasmid).Hybrid assemblies for strains A1, A3, A8, A13, A15, A17 and A20 are available in FigShare, doi: 10.4225/49/5987e14e9b530 (note they were not deposited in GenBank as they differ from A2 by only 1-4 SNPs as indicated).IMPACT STATEMENTSAcinetobacter baumannii is a highly drug resistant pathogen that is frequently found within intensive care units (ICUs) and especially impacts patients with severe burns. While several studies have examined the global population structure of A. baumannii, few have investigated within-host evolution of A. baumannii in direct response to antibiotic treatment in a single patient. Here, we analysed the genetic evolution of A. baumannii isolated from a patient with severe burns over the course of their stay in ICU. The A. baumannii population on this patient was highly drug resistant, carrying two distinct genomic islands encoding resistance to several antibiotics but not carbapenems. The bacterial population comprised four distinct subclades, two of which had evolved carbapenem resistance over the course of antibiotic treatment through novel mutations in genes associated with drug binding. One subclade was also transmitted to another patient on the ward. While carbapenem resistance is common in A. baumannii, this is generally attributed to horizontally transferred carbapenemase genes. These data provide evidence for carbapenem resistance arising in vivo via non-synonymous substitutions during a single infection episode, demonstrating carbapenem resistance can emerge in genetic isolation in response to exposure to carbapenems and other drugs.

Background Respiratory infections including influenza are a common cause of acute short-term morbidity in travellers and yet the risk of these infections is poorly defined. Objectives To estimate the incidence density of and risk factors for acute respiratory infections (ARIs) and influenza in Australian travellers to Asia. Study design Travel-clinic attendees were prospectively identified and completed questionnaires (demographic data, travel itinerary, health and vaccination history) and also provided pre and post-travel serological samples for Influenza A and B (complement fixation test). Returned travellers with an ARI provided nasopharyngeal specimens for RT-PCR identification of respiratory viruses. Results In this cohort ( n = 387) of predominantly (72%) short-term travellers, 58% were female, the median age was 37 years and 69% were tourists. ARIs occurred in 109 travellers (28%) translating to an incidence of 106.4 ARIs per 10,000 traveller days (95% confidence interval CI 88.6–126.7). The traveller type of missionary or aid worker was a risk factor for acquiring an ARI ( p = 0.03) and ARIs occurred early ( p = 0.001). Four travellers (1%) acquired influenza A during travel translating to an incidence density of 3.4 infections per 10,000 days of travel (95% CI 1.4–8.6). Influenza vaccination was reported in 49% of travellers with a 3.5-fold higher incidence of influenza in unvaccinated travellers compared to vaccinated travellers ( p = 0.883). Conclusions This is one of the largest prospective studies estimating the incidence of respiratory infections in travellers. These findings have important implications for practitioners advising prospective travellers and for public health authorities.

Background: Patients in the Intensive Care Unit (ICU) often have sub-therapeutic vancomycin levels in the initial stages of therapy. Loading doses have been demonstrated to overcome this problem. Aim: The aim of this study was to determine the impact of a standardised loading dose and increased clinician awareness of under-dosing on the achievement of early therapeutic vancomycin trough concentrations in the ICU. Methods: A pre- and post-intervention observational study was conducted in the ICU following the introduction of a 2-g vancomycin loading dose and demonstration of local under-dosing. All initial vancomycin trough levels were examined, except those from neurosurgical patients. Primary outcome measures were the proportion of patients achieving therapeutic vancomycin levels and mean trough concentrations. A year after introduction, a review was conducted to further assess the impact and sustainability of the intervention. Results: There were 31 courses of vancomycin in the pre-intervention period (no loading doses given) and 21 courses in the post-intervention period, of which 11 had a loading dose. In the pre-intervention group, 13% of courses achieved therapeutic concentrations. This increased to 33% in the post-intervention group (P= 0.08). A statistically significant increase in mean trough concentration, from 9.8 ± 6.6 mg/L to 14.9 ± 6.3 mg/L (P= 0.01), between the pre- and post-intervention groups was observed. During the follow-up period, results were similar to the post-intervention audit. Conclusion: A standardised loading dose is a simple and sustainable intervention that may improve early achievement of therapeutic vancomycin levels in critically ill patients. The clinical significance of this requires further study.

Severe immunodeficiency during primary human immunodeficiency virus (HIV) infection is unusual. Here, we characterized viral and immunological parameters in a subject presenting with Pneumocystis jirovecii pneumonia in the setting of prolonged primary HIV illness and delayed seroconversion. HIV antibody was only detected by enzyme-linked immunosorbent assay 12 months after presentation, and Western blot profiles remain indeterminate. Isolated virus was of R5 phenotype, exhibited poor viral fitness, but was otherwise unremarkable. Analysis of HIV antibody isotypes showed failure to mount a detectable HIV IgG response over nearly 2 years of infection, in particular IgG(1)- and IgG(3)-specific responses, despite normal responses to common infections and vaccines. Genetic analysis demonstrated homozygosity for part of an MHC haplotype containing susceptibility genes for common variable immunodeficiency (CVID) syndrome and other antibody deficiency disorders. Thus, a primary disorder of specific antibody production may explain exceptionally slow antibody development in an otherwise severe seroconversion illness. This highlights the need for multiparameter testing, in particular use of a fourth generation HIV test, for confirming HIV infection and underscores the importance of host factors in HIV pathogenesis.

The risk of Japanese encephalitis (JE) in travelers is unknown. In this prospective study, we investigated the incidence of JE in 387 short-term Australian travelers visiting Asia over a 32-month period from August 2007 to February 2010 by performing pre- and post-travel antibody testing. No travelers were infected with JE virus during travel, indicating a low risk of infection for short-term travelers.