David Looke

Overcrowding and understaffing in modern health-care systems: Key determinants in meticillin-resistant Staphylococcus aureus transmission

Recent decades have seen the global emergence of meticillin-resistant Staphylococcus aureus (MRSA), causing substantial health and economic burdens on patients and health-care systems. This epidemic has occurred at the same time that policies promoting higher patient throughput in hospitals have led to many services operating at, or near, full capacity. A result has been limited ability to scale services according to fluctuations in patient admissions and available staff, and hospital overcrowding and understaffing. Overcrowding and understaffing lead to failure of MRSA control programmes via decreased health-care worker hand-hygiene compliance, increased movement of patients and staff between hospital wards, decreased levels of cohorting, and overburdening of screening and isolation facilities. In turn, a high MRSA incidence leads to increased inpatient length of stay and bed blocking, exacerbating overcrowding and leading to a vicious cycle characterised by further infection control failure. Future decision making should use epidemiological and economic evidence to evaluate the effect of systems changes on the incidence of MRSA infection and other adverse events.

Control of fluoroquinolone resistance through successful regulation, Australia.

Restricted Fluoroquinolone use in humans and food animals has result in low rates of resistance in human pathogens

Virulence properties of asymptomatic bacteriuria Escherichia coli.

In asymptomatic bacteriuria (ABU), bacteria colonize the urinary tract without provoking symptoms. Here, we compared the virulence properties of a collection of ABU Escherichia coli strains to cystitis and pyelonephritis strains. Specific urinary tract infection (UTI)-associated virulence genes, hemagglutination characteristics, siderophore production, hemolysis, biofilm formation, and the ability of strains to adhere to and induce cytokine responses in epithelial cells were analyzed. ABU strains were phylogenetically related to strains that cause symptomatic UTI. However, the virulence properties of the ABU strains were variable and dependent on a combination of genotypic and phenotypic factors. Most ABU strains adhered poorly to epithelial cells; however, we also identified a subgroup of strongly adherent strains that were unable to stimulate an epithelial cell IL-6 cytokine response. Poor immune activation may represent one mechanism whereby ABU E. coli evade immune detection after the establishment of bacteriuria.

Severe photosensitivity causing multifocal squamous cell carcinomas secondary to prolonged voriconazole therapy

A 32-year-old woman was treated with long-term voriconazole therapy for recurrent aspergillosis associated with chronic granulomatous disease. A short time after commencement of voriconazole therapy, a severe photosensitivity reaction developed. Continued voriconazole exposure led to the development of multifocal facial squamous cell carcinomas. The photosensitivity reaction resolved after the patient changed therapy to posaconazole.

Catheter-associated bloodstream infection incidence and risk factors in adults with cancer: a prospective cohort study

Central venous catheter-associated bloodstream infections (CABSIs) cause considerable morbidity in patients with cancer. We determined the incidence and risk factors for CABSI by performing a prospective observational cohort study of all adult patients requiring a central venous access device (CVAD) in a haematology-oncology unit. All CVADs were inserted under ultrasound guidance by trained operators in a dedicated interventional radiology facility. A total of 1127 CVADs were assessed in 727 patients over 51,514 line-days. The rate of CABSI per 1000 line-days was 2.50. Factors associated with CABSI included: type of CVAD, greatest for non-tunnelled lines [hazard ratio (HR): 3.50; P < 0.0001] and tunnelled lines (HR: 1.77; P = 0.011) compared to peripherally inserted central venous catheter (PICC) lines; patient diagnosis, greatest for aggressive haematological malignancies (HR: 3.17; P = 0.0007) and least for oesophageal, colon and rectal cancers (HR: 0.29; P = 0.019) compared to other solid tumours; side of insertion, greatest for right-sided lines (HR: 1.60; P = 0.027); and number of prior line insertions (HR: 1.20; P = 0.022). In patients with aggressive haematological malignancies there was significantly more CABSI with non-tunnelled lines (HR: 3.9; P < 0.001) and a trend to more CABSI with tunnelled lines (HR: 1.43; P = 0.12) compared to patients with PICC lines, as well as increased CABSI for right-sided insertions (HR: 1.62; P = 0.047). This study highlights the utility of a standardised CABSI surveillance strategy in adult patients with cancer, provides further data to support the use of PICC lines in such patient populations, and suggests that the side of line insertion may influence risk of CABSI.

Identification of Type 3 Fimbriae in Uropathogenic Escherichia coli Reveals a Role in Biofilm Formation

Catheter-associated urinary tract infection (CAUTI) is the most common nosocomial infection in the United States. Uropathogenic Escherichia coli (UPEC), the most common cause of CAUTI, can form biofilms on indwelling catheters. Here, we identify and characterize novel factors that affect biofilm formation by UPEC strains that cause CAUTI. Sixty-five CAUTI UPEC isolates were characterized for phenotypic markers of urovirulence, including agglutination and biofilm formation. One isolate, E. coli MS2027, was uniquely proficient at biofilm growth despite the absence of adhesins known to promote this phenotype. Mini-Tn5 mutagenesis of E. coli MS2027 identified several mutants with altered biofilm growth. Mutants containing insertions in genes involved in O antigen synthesis (rmlC and manB) and capsule synthesis (kpsM) possessed enhanced biofilm phenotypes. Three independent mutants deficient in biofilm growth contained an insertion in a gene locus homologous to the type 3 chaperone-usher class fimbrial genes of Klebsiella pneumoniae. These type 3 fimbrial genes (mrkABCDF), which were located on a conjugative plasmid, were cloned from E. coli MS2027 and could complement the biofilm-deficient transconjugants when reintroduced on a plasmid. Primers targeting the mrkB chaperone-encoding gene revealed its presence in CAUTI strains of Citrobacter koseri, Citrobacter freundii, Klebsiella pneumoniae, and Klebsiella oxytoca. All of these mrkB-positive strains caused type 3 fimbria-specific agglutination of tannic acid-treated red blood cells. This is the first description of type 3 fimbriae in E. coli, C. koseri, and C. freundii. Our data suggest that type 3 fimbriae may contribute to biofilm formation by different gram-negative nosocomial pathogens.

Nematode symbiont for Photorhabdus asymbiotica

Photorhabdus asymbiotica is an emerging bacterial pathogen that causes locally invasive soft tissue and disseminated bacteremic infections in the United States and Australia. Although the source of infection was previously unknown, we report that the bacterium is found in a symbiotic association with an insect-pathogenic soil nematode of the genus Heterorhabditis.

Experimentally Induced Blood-Stage Plasmodium vivax Infection in Healthy Volunteers

BACKGROUND Major impediments to development of vaccines and drugs for Plasmodium vivax malaria are the inability to culture this species and the extreme difficulty in undertaking clinical research by experimental infection. METHODS A parasite bank was collected from a 49-year-old woman with P. vivax infection, characterized, and used in an experimental infection study. RESULTS The donor made a full recovery from malaria after collection of a parasite bank, which tested negative for agents screened for in blood donations. DNA sequence analysis of the isolate indicated that it was clonal. Two subjects inoculated with the isolate became polymerase chain reaction positive on days 8 and 9, with onset of symptoms and positive blood smears on day 14, when they were treated with artemether-lumefantrine, with rapid clinical and parasitologic response. Transcripts of the parasite gene pvs25 that is expressed in gametocytes, the life cycle stage infectious to mosquitoes, were first detected on days 11 and 12. CONCLUSIONS This experimental system results in in vivo parasite growth, probably infectious to mosquitoes. It offers the opportunity to undertake studies previously impossible in P. vivax that will facilitate a better understanding of the pathology of vivax malaria and development of antimalarial drugs and vaccines. Trial Registration. ANZCTR: 12612001096842.

INTRADERMAL RECOMBINANT HEPATITIS B VACCINE FOR HEALTHCARE WORKERS WHO FAIL TO RESPOND TO INTRAMUSCULAR VACCINE

OBJECTIVE To study the humoral immune responses, safety, and tolerability of intradermal recombinant hepatitis B vaccination in healthcare workers (HCWs) nonresponsive to previous repeated intramuscular vaccination. DESIGN An open, prospective, before-after trial. SETTING A tertiary referral hospital and surrounding district health service in Queensland, Australia. PARTICIPANTS Hospital and community HCWs nonresponsive to previous intramuscular hepatitis B vaccination. METHODS Intradermal recombinant hepatitis B vaccine was administered every second week for a maximum of 4 doses. Hepatitis B surface antibody (anti-HBs) responses were assessed 2 weeks after each dose. RESULTS Protective anti-HBs levels developed in 17 (94%) of 18 study subjects. Three doses resulted in seroconversion of all responding subjects and the highest geometric mean antibody concentration. The vaccine was well tolerated. CONCLUSION More than 90% of previously nonresponsive HCWs responded to intradermal recombinant hepatitis B vaccine with protective anti-HBs levels.

Review article: Animal bites: an update for management with a focus on infections.

Animal bites are a significant public health problem, with an estimated 2% of the population bitten each year. The majority of bites are from dogs and risk factors include young children, men, certain dog breeds and unrestrained dogs. The risk of infection following bites differs among animal species and is dependent on animal dentition and oral flora. Recent studies have demonstrated a broad range of pathogens isolated from infected bite wounds, with Pasteurella species being the predominant isolate from dog and cat bite wounds. Controversy exists about the use of prophylactic antibiotics; however, they are currently only recommended for high‐risk bite wounds. Two fatal cases of Australian bat lyssavirus have been reported and bats are the only identified reservoir in Australia. All bat bites are of high risk and should receive post‐exposure prophylaxis for rabies. Workers handling bats should be offered routine immunization.