Cost-effectiveness of interventions to improve hand hygiene in healthcare workers in middle-income hospital settings: a model-based analysis.

BACKGROUND: Multi-modal interventions are effective in increasing hand hygiene (HH) compliance among healthcare workers, but it is not known whether such interventions are cost-effective outside high-income countries. AIM: To evaluate the cost-effectiveness of multi-modal hospital interventions to improve HH compliance in a middle-income country. METHODS: Using a conservative approach, a model was developed to determine whether reductions in meticillin-resistant Staphylococcus aureus bloodstream infections (MRSA-BSIs) alone would make HH interventions cost-effective in intensive care units (ICUs). Transmission dynamic and decision analytic models were combined to determine the expected impact of HH interventions on MRSA-BSI incidence and evaluate their cost-effectiveness. A series of sensitivity analyses and hypothetical scenarios making different assumptions about transmissibility were explored to generalize the findings. FINDINGS: Interventions increasing HH compliance from a 10% baseline to ≥20% are likely to be cost-effective solely through reduced MRSA-BSI. Increasing compliance from 10% to 40% was estimated to cost US$2515 per 10,000 bed-days with 3.8 quality-adjusted life-years (QALYs) gained in a paediatric ICU (PICU) and US$1743 per 10,000 bed-days with 3.7 QALYs gained in an adult ICU. If baseline compliance is not >20%, the intervention is always cost-effective even with only a 10% compliance improvement. CONCLUSION: Effective multi-modal HH interventions are likely to be cost-effective due to preventing MRSA-BSI alone in ICU settings in middle-income countries where baseline compliance is typically low. Where compliance is higher, the cost-effectiveness of interventions to improve it further will depend on the impact on hospital-acquired infections other than MRSA-BSI.

TLR4 genetic variation is associated with inflammatory responses in Gram-positive sepsis.

OBJECTIVES: To identify important pathogen recognition receptor (PRR) pathways regulating innate immune responses and outcome in Staphylococcus aureus sepsis. METHODS: We analysed whether candidate PRR pathway genetic variants were associated with killed S. aureus-induced cytokine responses ex vivo and performed follow-up in vitro studies. We tested the association of our top-ranked variant with cytokine responses and clinical outcomes in a prospective multicentre cohort of patients with staphylococcal sepsis. RESULTS: An intronic TLR4 polymorphism and expression quantitative trait locus, rs1927907, was highly associated with cytokine release induced by stimulation of blood from healthy Thai subjects with S. aureus ex vivo. S. aureus did not induce TLR4-dependent NF-κB activation in transfected HEK293 cells. In monocytes, tumor necrosis factor (TNF)-α release induced by S. aureus was not blunted by a TLR4/MD-2 neutralizing antibody, but in a monocyte cell line, TNF-α was reduced by knockdown of TLR4. In Thai patients with staphylococcal sepsis, rs1927907 was associated with higher interleukin (IL)-6 and IL-8 levels as well as with respiratory failure. S. aureus-induced responses in blood were most highly correlated with responses to Gram-negative stimulants whole blood. CONCLUSIONS: A genetic variant in TLR4 is associated with cytokine responses to S. aureus ex vivo and plasma cytokine levels and respiratory failure in staphylococcal sepsis. While S. aureus does not express lipopolysaccharide or activate TLR4 directly, the innate immune response to S. aureus does appear to be modulated by TLR4 and shares significant commonality with that induced by Gram-negative pathogens and lipopolysaccharide.

Comparison of community-onset Staphylococcus argenteus and Staphylococcus aureus sepsis in Thailand: a prospective multicentre observational study.

Staphylococcus argenteus is a globally distributed cause of human infection, but diagnostic laboratories misidentify this as Staphylococcus aureus. We determined whether there is clinical utility in distinguishing between the two. A prospective cohort study of community-onset invasive staphylococcal sepsis was conducted in adults at four hospitals in northeast Thailand between 2010 and 2013. Of 311 patients analysed, 58 (19%) were infected with S. argenteus and 253 (81%) with S. aureus. Most S. argenteus (54/58) were multilocus sequence type 2250. Infection with S. argenteus was more common in males, but rates of bacteraemia and drainage procedures were similar in the two groups. S. argenteus precipitated significantly less respiratory failure than S. aureus (5.2% versus 20.2%, adjusted OR 0.21, 95% CI 0.06-0.74, p 0.015), with a similar but non-significant trend for shock (6.9% versus 12.3%, adjusted OR 0.46, 95% CI 0.15-1.44, p 0.18). This did not translate into a difference in death at 28 days (6.9% versus 8.7%, adjusted OR 0.80, 95% CI 0.24-2.65, p 0.72). S. argenteus was more susceptible to antimicrobial drugs compared with S. aureus, and contained fewer toxin genes although pvl was detected in 16% (9/58). We conclude that clinical differences exist in association with sepsis due to S. argenteus versus S. aureus.