Impact of air decontamination by use of Plasmers

on the occurrence of invasive aspergillosis in patients at risk in hematological ward

Aho Glélé LS**, Lafon I*, Ferrant M *, Barry M *, Astruc K**, Bonnin A***, Caillot D*

Hematology; ** Epidemiology and Hospital hygiene; *** MycologyDijon (France)

Denver, June 2008

Context

Aspergillosis

• Aspergillus spp. and other moulds – => Life-threatening opportunistic infections

• In immunocompromised patients

• Indoor contamination and construction work– => Liberate fungal spores

• Major source of nosocomial aspergillosis

Aspergillosis

• In immunocompromised patients– Respiratory tract colonization by Aspergillus is

associated with increased risk of invasive aspergillosis (IA)

» Wald A et al.. J Infect Dis 1997;175:1459-66

» Perfect JR et al. Clin Infect Dis 2001;33:1824-33

Aspergillosis

• Incidence rates of IA– Range from 4-26% in allogenic bone marrow

transplant patients – 5-25% in acute leukemia patients

• IA associated mortality rates – Range from 74-92%

» Denning DW.Clin Infect Dis 1998;26:781-805

» Singh N et al. Clin Microbiol Rev 2005;18:44-69

» Latge´ JP. Clin Microbiol Rev 1999;12:310-350

Previous study : Indoor fungal contamination surveillance program

• Implemented one year before building work– To establish baseline levels of contamination

• Prospective examination of air and surface fungal contamination – Following use, or not, of plasmer units – Adult and paediatric haematology units

• plasmer treated rooms – Significant reductions in overall fungal

contamination • For air and surface samples

– In both clinical units

• For A. fumigatus in the air

• plasmer units may provide an efficient method for reducing indoor fungal contamination in hospitals

» Sixt et al. J hosp Infect 2006; 65(2):156-62

Previous study : Indoor fungal contamination surveillance program

Objectives

Objectives

• To assess the impact of air decontamination

by use of Plasmers on the occurrence of invasive aspergillosis

• In patients at risk – In hematological ward

• i.e follows next study– Clinical outcome instead of environnemental

microbiologic outcome

Setting

Setting : Dijon hospital

• Tertiary care institution– Northeast France

• Hospital involved in a renovation program – Construction of two buildings adjacent to

clinical units receiving patients at high risk of fungal infection

– Hematology unit

– Infectious Diseases unit

Flow

Flow

Flow

Flow

Flow

Flow

Nurses Room 10(4)

Room 1

Nurses

Hematologyward

UniversityHospital

Dijon

« Protected » Sector

Plasmair®1 by room

Since07/20/2004

Conventional Sector

Room 10(4)

Room 10(4)

Room 1

Room 1

Room 2

Room 2 Room 1

Room 1

Room 1

Room 1

Room 1

Room 1

Room 1

Room 1

Participants

Participants

• Inclusion– Acute Myeloid leukemia (AML)– Acute Lymphoid leukemia (ALL)– See flow chart

• Non inclusion– Burkitt

• n=3

From 01/01/2000 to /12/31/2007

Proven IPA n = 17 (27%)

Probable IPA n = 41 (65%)

Possible IPA n = 5 (8%)

63 IPA(occurred in the department of hematology)

MSG & IFIG/EORTC criteria

798 episodes of aplasia at very high risk of aspergillosis

435 patients with AML or ALL

Intervention and methods

Intervention : plasmer

Mobile air-decontamination unit :

• Not based on filtration

• Destruction of airborne organisms through a three-step process – Exposure to high electric fields

• Deform and alter membrane or cell-wall

– Subsequent bombardment with positive and negative ions

• Destroy internal structures

– Electrostatic nano-filtration

Intervention: plasmer

• Electricity supply

• Three modes of activity – Correspond to increasing air-exchange capacity

and increasing noise

• Cost – One unit : about 17 000 Euros

• Maintenance needed– As for all kind of devices…

Intervention: others devices

• Standard Room

• Filtration and positive air-pressure– Laminar Flow– Class 104

» Federal Standard 209D

Methods

• Diagnostic– MSG & IFIG/EORTC criteria

» Ascioglu et al. Clin Infect Dis. 2002: 7-14

• Statistical analysis– Univariate analysis

• Before and after plasmers comparisons

• Classical tests, as appropriate– Fischer exact test, chi2 test

– Kruskall Wallis, T-test

Methods: multivariate analysis

• Variable to explain– Occurrence of IPA (probability of)

• Explanatory variables – Age (A)– Sex (S)– Type of leukemia (L; AML or ALL)– De novo patient (DN; Yes or No)– Duration of Leucopenia (DL; days)– Construction Work (CW; Yes or No)– Date of diagnosis (T; year)– Type of Device (TD; none, 10(4) class, plasmer,

laminar flow)

Methods: multivariate analysis

• Model– P(Occurrence of IPA) = f(TD, A, S, L, DN,

DL, CW, T, )– f: logistic link– Correlated data

• Use of GEE or mixed model – Correlation matrix = exchangeable

• Check of loglinearity

– Forced variable in the model : date of diagnosis• Non randomized study

Methods: multivariate analysis

• Time of diagnosis (T; year)– Continuous– Discrete

• Duration of leucopenia (DL; days)– Data collection not complete

• Listwise deletion

• Median imputation

• 3 classes : < Median, >= Median, « Missing »

Results

Univariate analysis

From 01/01/2000 to 07/20/2004

Probable IPA

n = 20 (80%)

Possible IPA n = 0

28 IPA (6.8%)

407 Aplasia AML/ALL(236 pts)

From 07/20/2004 to 12/31/2007

Proven IPA

n = 9 (26%)

Probable IPA

n = 21 (60%)

Possible IPA

n = 5 (14%)

35 IPA (8.7%)

391 Aplasia AML/ALL(199 pts)

Proven IPAn = 8 (20%)

Results

Baseline characteristics

Population under studyBefore Plasmairs®

After Plaismairs

®

P

Patients 236 199 -

Aplaisia 407 391 -

Age 55 (17-81) 56 (16-86) ns

AML 321 (79%) 303 (78%) ns

ALL 86 (21%) 88 (22%) ns

Laminar Flow sector

231 (57%) 197 (50%) ns

Class 104 Sector 90 (22%) 86 (22%) ns

Standart Sector

Plasmairs

86 (21%)-

-108 (28%)

--

IPA 28 (6.8%) 35 (8.7%) ns

De novo IPA 12/187 (6.4%) 17/176 (9.6%) ns

Patients’s characteristics (Aspergillosis)

BAL: BronchoAlveolar Lavage; ME: Microscopic Examination; Asperg. Ag: Aspergillus Antigen

Before Plasmairs® After Plaismairs® P

Invasive Aspergillosis (IA) 28 35 -

IPA 26/28 33/35 ns

Male vs Female 16 vs 11 20 vs 15 ns

Age 58 (27-76) 64 (22-75)

Hematol.Prog.disease 13/28 18/35 ns

Hospitalization before IA (d)

21 (8-54) 21 (10-63) ns

Neutropenia before IA (d) 17 (11-60) 18 (10-90) ns

Hospitalization after IA(d) 17 (2-85) 15 (2-40) ns

Neutropenia after IA (d) 8 (0-83) 8 (0-40) ns

BAL + (culture or ME) 9/23 5/29 ns

Asperg Ag + (in BAL) 20/23 20/29 ns

Asperg Ag + (in Sera) 20/27 21/35 ns

Pathological exam + 8 9 ns

Treatment and evolution of patients with aspergillosis

Before Plasmairs®

After Plaismairs®

P

Invasive Aspergillosis (IA) 28 35

Antifungal monotherapy 5/28 14/35 0.04

Combination antifungal therapy

23/28 21/35 0.04

Associated Surgery 3/28 3/35 ns

Aspergillosis response (CR+PR) 

22/28 (79%) 29/35(83%) ns

Hematological complete response

13/28 (46%) 20/35 (57%) ns

Median survival (weeks) 31 (1-422) 34 (1-191) ns

Survival at 12 weeks 18/28 (64%) 30/35 (86%)* 0.04

Death with aspergillosis 6/28 (21%) 7/35 (20%) ns

From 01/01/2000 to 20/07/2004 (Before plasmairs®)

Laminar Flow3.9 %

9 IA / 231 Aplasia

104 Class5.6 %

5 IA / 90 Aplasia

Standard16.3 %

14 IA / 86 Aplasia

NS

Invasive aspergillosis incidence

Laminar Flow ≈ 104 Class >> Standard

P < 0.001 P = 0.03

From 07/20/2004 to 12/31/2007 (with plasmair®; without and then with construction work in the hospital)

Laminar Flow5.6 %

11 IA / 197 Aplasia

104 Class10.5 %

9 IA / 86 Aplasia

plasmair®13.8 %

15 IA / 108 Aplasia

NS

Invasive aspergillosis incidence

Laminar Flow > plasmer®

P = 0.02 NS

plasmer ® ≈ 104 Class

From 07/20/2004 to 12/31/2006 (with plasmair®; without construction work in the hospital)

Laminar Flow5.7 %

8 IA / 141 Aplasia

104 Class8.5 %

5 IA / 59 Aplasia

plasmair®12.8 %

10 IA / 78 Aplasia

NS

Invasive aspergillosis incidence

Laminar Flow > ≈ plasmer®

P = 0.06 NS

plasmer ® ≈ 104 Class

From 01/01/2007 to 12/31/2007 (with plasmair®; with construction work in the hospital)

Laminar Flow5.3 %

3 IA / 56 Aplasia

104 Class14.8 %

4 IA / 27 Aplasia

plasmair®16.7 %

5 IA / 30 Aplasia

P = NS

Invasive aspergillosis incidence

Laminar Flow > = plasmer®

P = 0.08 P = NS

plasmer ® ≈ 104 Class

Laminar Flow5.7 %

8 IA / 141 Aplasia

104 Class8.5 %

5 IA / 59 Aplasia

plasmairs®12.8 %

10 IA / 78 Aplasia

All sectors8.3 %

23 IA / 278 Aplasia

From 07/20/2004 to 12/31/2006 From 01/01/2007 to 12/31/2007

Impact of construction work in the university hospitalDuring construction With plasmairs®

Laminar Flow5.3 %

3 IA / 56 Aplasia

104 Class14.8 %

4 IA / 27 Aplasia

plasmairs®16.7 %

5 IA / 30 Aplasia

All sectors10.6 %

12 IA / 113 Aplasia

P = NS

P = NS

P = NS

P = NS

Results

Multivariate analysis

Methods: multivariate analysis

• Duration of leucopenia (DL; days)– 7.43 % « missing data » (1-(735/794))– Missing At Random

• Sex, Type of device, API, Time, Construction Work

Results of the model

Significant

– Age (A)

– Duration of Leucopenia (DL; days)

– Time of diagnosis (T; year)

– Type of Device (TD; none, 10(4) class, plasmer, laminar flow)

Not significant

– Sex (S)

– Type of leukemia (L; AML or ALL)

– de novo patient

(DN; Yes or No)

– Construction Work (CW; Yes or No)

Model 1 (Time continuous; logit)

Variables Odds Ratio (OR)

p

Duration of leucopenia 1.053 0.0001

Age 1.022 0.031

Time (continuous) 1.099 0.270

Type of deviceNoneplasmer Class 10(4)Laminar Flow

Ref.3469.2015.1569

-----0.0560.00010.0001

Model 2 (Time discrete; GEE)

Variables Coefficient p

Duration of leucopenia 0.0067 0.001

Age 0.0014 0.012

Time (discrete) -- 0.18

Type of deviceNoneplasmer Class 10(4)Laminar Flow

ref-0.0834-0.1495-0.1552

ref0.0600.00010.0001

Model 3 (Time discrete and duration of leucopenia with median substitution; GEE)

Variables Coefficient p

Duration of leucopenia(Median substitution)

0.0068 0.0001

Age 0.0012 0.013

Time (discrete) - 0.367

Type of device

None

plasmer

Class 10(4)

Laminar Flow

ref

-0.075

-0.1280

-0.1371

ref

0.066

0.0001

0.0001

Model 4 (Time continuous and duration of leucopenia with 3 classes; GEE)

Variables Coefficient p

Duration of leucopenia(reference : < median)

0.0578 0.0001

Age 0.00138 0.011

Time (continuous) 0.01034 0.022

Type of device

None

plasmer

Class 10(4)

Laminar Flow

ref

-0.0833

-0.1340

-0.1429

ref

0.045

0.0001

0.0001

Discussion

Discussion

Multivariate analysis

• Duration of leucopenia– Major risk factor– Missing values

• Effect of Plamairs remains significant under sensitivity analysis

Discussion

What about others devices ?

• Example Photoclean®– http://www.photocleanquartz.com/– Under evaluation in medical area

Discussion

Limits of the study

• Randomization– It would be better for internal validity

• But, no randomized study available for the reference device (Laminar flow)

» Humphreys H. J Hosp Infect 2004.56:93-100

• Power– Sample size not determined a priori

• IPA is a rare disease– Multicentric study needed ?

Discussion

Limits of the study

• Outcome measure– Plan to take into account time to event – « Missing » values for duration of leucopenia– Only simple imputation methods used

• No multiple imputation or Maximum likelihood-based procedures

– = > Recover the data !

Conclusion

Conclusion

• plasmers seems to prevent IPA

• Results must be confirmed– « Missing values » for duration of leucopenia– Taking into account time to event

Thank you for your attention