Surgical infection and outbreaks Malcolm Richardson PhD, FSB, FRCPath Regional Mycology Reference Centre University Hospital of South Manchester, and The University of Manchester

Nosocomially vs. community-acquired IA Nosocomial Due to break in, or contamination of hospital water system Due to break in HEPA filtration system Due to construction or demolition work in the hospital Community-acquired Due to occupational activities Due to leisure activities Due to exposure to Aspergillus spores (minimum effective dose not known) Praz-Christinaz et al. Transplant Infect Dis 2007; 9:

53 outbreaks: affected patients: – 299 (65.3%) haematological malignancies – Route of transmission: air – Site of primary infection: lower respiratory tract (356 patients) – Surgical site infections (24 patients) – Skin infections (24 patients)

Nosocomial aspergillosis

Outbreaks update 2009 Weber et al. Medical Mycology 2009 >60 English literature

Species distrubution

Infection sites Pulmonary Post-operative – Cardiac surgery – Ophthalmic surgery – Dental surgery Cutaneous

Post-operative aspergillosis Dd paper >500 cases Cardiac surgery (n = 188 Ophthalmic surgery (n > 90) Dental surgery (n = 100) Wound infection (n = 22) Bronchial infections (n = 30) Orthopedic surgery (n = 42) Vascular prosthetic surgery (n = 22) Neurosurgery (n = 25) Source presumed to be airborne infection

20 healthy individuals Conventional and molecular analysis 74 culturable genera 11 non-culturable Aspergillus species: 35% 2010

Liver transplant recipient 11-days post-transplant: Aspergillus fumigatus deep-surgical site infection 2 patients: transplantation unit: pulmonary aspergillosis Debridement and changing of dressings: bioaerosols CID 2002

Events in the growth of Aspergillus

A w : Minimum water activity level at 25°C ERH: Equilibrium relative humidity A w < 0.80, ERH <80% A w < , ERH <80-90% A w >0.90, ERH >90% water

Air as a source of human infection Inhalation: most common portal of entry Temporal association between hospital-based outbreaks and construction Very little data on base-line concentrations Longitudinal studies show no correlation between sporadic cases of IA and changes in spore count

Concentrations of airborne Aspergillus compared to the incidence of invasive aspergillosis: lack of correlation 54-week air sampling period A. fumigatus and A. flavus: mean 1.83 cfu m -3 Individual samples: maximum: 11.6 cfu m -3 No correlation with season or ward 6 cases of IPA during sampling period No association with fluctuations in air count Conclusion: the available data do not provide a firm link between hospital exposure and an increased incidence of aspergillosis Hospenthal et al., Medical Mycology 1998.

Heavy excavation!

Ventilation as a source

Source of Aspergillus in the operating theatre

Surgical infection

A thermal ceiling as source of Aspergillus

Dust: a perfect home for Aspergillus! GM

Dust collection

Air sampling: SAS Super 100 and Duo

Acceptable levels HEPA filtered air: 0 Open ward:? General hospital areas: ? Outdoor air: highly variable/seasonal

Efficacy of prevention by HEPA filtration or laminar airflow against Aspergillus airborne contamination during hospital renovation Conclusions: – strong association between building renovation and an increase in environmental contamination – confirmation of the high efficacy of laminar airflow plus HEPA filtration and a high air-exchange rate – HEPA filtration alone did not prevent contamination during renovation – A standard protocol for aerobiological surveillance is needed Cornet et al. Infect Control Hosp Epidemiol 1999; 20:

Invasive aspergillosis related to construction and the utility of air sampling 8-bedded BMT unit 2 cases of IPA 5 cases of colonisation Coincided with major construction project on floor directly below unit High air counts before cleaning No isolation after construction stopped and deep cleaning Lai et al., 39th ICAAC, San Francisco 1999

Is air sampling necessary, if so, when? Determination of source: outbreaks occupants have symptoms, but no obvious building damage contamination suspected through air from other parts of the building

Malt extract agar Heptane Undecane Isoprene 2,4 Hexadiene 2-Methyl-1,3-pentadiene 1,3-Octadiene 2-Methyl-1-butanol 3-Methyl-1-butanol 2-Ethyl-1-hexanol Wood Methylpyrazine Acetone 2-Pentanon 2-Hexanone 2-Heptanone 4-Heptanone 2-Octanone 3-Octanone Acetophenone -Farnesene Aspergillus fumigatus Head-space solid-phase microextraction Fiedler et al Int J Hyg Environ Health

7-year sampling period: weekly: 978 samples Aspergillus spp. 16.7%: 1.8 cfu/m cfu/m 3 45 cases proven IA (2.29% allo; 0.36% auto HSCT) cases of IA analysed 14 and 28-days following high counts Conclusion: high counts did not predict risk of developing IA Rupp et al. JHI 2008.

Particle counting Hansen et al. JHI 2008; 70:

Particle counting IQAir Particle Scan Pro Airborne Laser Counter 0.3 m - 5 m

during demolition building was sealed and water sprayed to minimise dust emission particle and fungal concentrations monitored before and during demolition particle concentrations significantly higher during demolition no difference in moulds cultured at 37 0 C before and during demolition

Air quality monitoring of HEPA-filtered hospital rooms by particulate counting Anttila V-J, Nihtinen A, Kuutamo T, Richardson M

Air quality monitoring of HEPA-filtered hospital rooms by particulate counting Anttila V-J, Nihtinen A, Kuutamo T, Richardson M

Construction of an outbreak curve Line listing of all infected patients Evaluation of air ventilation system Regular particle counting Water damage/ingress assessment Possible common source exposure Air sampling Water analysis Settled dust analysis

AirInSpace: Immunair m 3 /hr rapid air decontamination not sensitive to exterior movement <1 cfu/m 3 Am J Infect Control 2007; 35:

Conclusions Overall mortality among patients involved in outbreaks: 50-60% Recent outbreaks due to internal construction or renovation with failure to control spread of contaminated dust Key interventions: surveillance and engineering controls Minimum effective dose of Aspergillus conidia is not known