an outbreak of aspergillosis in a general itu

Journal of Hospital Infection (1991) 18, 167-l 77

An outbreak of aspergillosis in a general ITU

H. Humphreys, E. M. Johnson, D. W. Warnock, S. M. Willatts*, R. J. Winter* and D. C. E. Speller

Department of Microbiology and *Intensive Therapy Unit, Bristol Royal Infirmary, Bristol BS.2 8HW

Accepted for publication 2 April 1991

Summary: Over a S-month period, six patients in a general intensive therapy unit became colonized by Aspergillus species including Aspergillus fumigatus, and invasive infection occured in at least two of them. Broncho- alveolar lavage was unhelpful in discriminating between infection and colonization. The source of infection was presumed to be disturbance of an accumulation of spores in fibrous insulation material above the perforated metal ceiling. Patients in such units without clearly identifiable defects of defence against infection may be at risk from aspergillosis. The risk can be reduced by improved hospital design, satisfactory ventilation and thorough regular cleaning of environmental surfaces.

Keywords: Intensive care unit; aspergillosis; Aspergillusfumigatus; bronchoalveolar lavage.

Introduction

Invasive aspergillosis is primarily an infection of severely immunocompromised patients but can also occur in alcoholics and diabetics.’ Nosocomial outbreaks of aspergillosis have become a well-recognized complication of construction work in or near hospital wards in which neutropenic patients are housed. In several reported outbreaks, building works adjacent to the unit in which the patients were accommodated led to contamination of the air.2v3 In other instances, the ventilation system for the unit drew contaminated air from neighbouring building sites”,’ or otherwise became contaminated.6,7

Invasive aspergillosis is most likely to develop in bone marrow transplant recipients followed by renal transplant recipients, patients with acute leukaemia and burn patients. s To date, nosocomial outbreaks of aspergillosis have not been a problem among non-immunocompromised patients. However, the occurrence of six cases of colonization which led to invasive infection in two, or possibly three patients, over a S-month period in the

Correspondence to: H. Humphreys.

0195-6701,‘91:07fll67+ I I SO3 0O;O

167

0 1991 The Hospml Infectmn Soc,rry

168 H. Humphreys et al.

Intensive Therapy Unit (ITU) of this hospital led us to investigate possible sources in an attempt to prevent further infections.

The outbreak of aspergillosis

ITU design and practice The ITU at Bristol Royal Infirmary has seven beds including one in an isolation room (Figure 1). There is no artificial ventilation system in the unit. Temperature control is achieved by a fan conductor heating system located at the end of the unit furthest from the main entrance and by opening and closing the many windows. The ITU and the nearby wards and offices have false ceilings, consisting of removable perforated metal panels with insulating fibre glass material, above which there is a space containing pipework and electrical wiring. Repairs to the pipework or investigation of electrical faults requires removal of the panels with disruption of the insulating material.

About 550 patients are admitted annually, the main reasons for admission being postoperative care, especially following major vascular surgery (but not cardiac surgery), gastrointestinal emergencies, major trauma and the requirement for mechanical ventilation and organ support. The care of the patients is supervised by the Department of Anaesthesia with one member (SMW) acting as the head of the unit. In general, patients are admitted to the isolation cubicle only when there is need for source or protective

I I Sluice ( Cubicle I I Sister Store office

v Doors Areo where recent construction work was carried out

0 0 Windows in ITU

I Beds in ITU * Position of electric fan

Figure 1. Plan of ITU and surrounding area.

Aspergillosis in a general ITU 169

isolation, but all the other beds are in regular use, with those patients requiring closest observation being accommodated nearest to the nurses’ station.

It happened that since July 1988 a study of the effect of selective decontamination of the digestive tract (SDD) on infectious morbidity and mortality in ITU patients had been taking place. Patients randomized to receive SDD had been treated with topical antimicrobial agents (amphotericin B, tobramycin and colistin) and with intravenous ceftazidime initially. As a part of the accompanying microbiological investigation, almost all patients who stayed in the unit for more than 48 h had respiratory tract and other specimens investigated for the presence of fungi.

Building works For 3 weeks, commencing 17 September 1989, minor building work was carried out in an area adjacent to the ITU, where a number of offices and stores are located. This involved the removal of walls and the erection of new partitions to allow the provision of an ‘on-call room’. This created a considerable amount of dust but this area was sealed off from the ITU by polythene partitions.

Colonized OY infected patients Table I gives details of the underlying illnesses, the laboratory diagnosis of aspergillus colonization or infection and the final outcome in the patients involved. Patient 1 was definitely infected as evidenced by tissue invasion demonstrated at autopsy. He was a 26-year-old male with Crohn’s disease requiring high dose corticosteroids (1 S-20 mg prednisone daily) who presented with a pyrexia of unknown origin and was hospitalized for a number of weeks on a general ward and then transferred to the ITU for mechanical ventilation. Aspergillus fumigatus was isolated from a tracheal aspirate taken 4 days ante mortem, but broncho-alveolar lavage (BAL) specimens on the same day did not yield the fungus. The tracheal aspirate result was therefore not considered to be significant. Pseudomonas aeruginosa and Flavobacterium meningosepticum had been isolated repeatedly from tracheal aspirate and BAL specimens previously, and therefore his antibiotic therapy (netilmicin and ceftazidime) was continued. Post-mortem examination revealed bilateral pleural effusions, bronchopneumonia and systemic vasculitis. Grocott silver stain revealed invasive aspergillosis in sections from lung and kidney and A. fumigatus was isolated from these tissues.

Patients 2 and 3 had severe chronic bronchitis, emphysema and asthma which required ventilation. Aspergillus fumigatus was isolated from tracheal aspirate and BAL fluid in patient 2 within a day of admission to the ITU but this was felt to represent colonization rather than infection or an allergic

Tabl

e 1.

Det

ails

of

pat

ient

s ei

ther

co

loni

zed

or

infe

cted

w

ith

Aspe

rgillu

s sp

. X

Cas

e Se

x:

No.

ag

e (in

ye

ars)

M:2

6

F:

77

M:7

4

Clin

ical

de

tails

Im

mun

o-

Inve

stig

atio

ns

Antif

unga

l O

utco

me

supp

ress

ive

ther

apy

F

ther

apy

8 u 2 R

espi

rato

ry

failu

re,

Cro

hn’s

di

seas

e

Cor

ticos

tero

ids

TA:

A.

fum

igat

as

isol

ated

on

ce

Non

e D

eath

in

IT

U

2 B

AL:

N

egat

ive

for

mic

rosc

opy

fn

and

cultu

re

thre

e tim

es

z PM

lu

ng

tissu

e:

A fu

mig

atus

tr

isol

ated

; hi

stol

ogic

al

evid

ence

of

tis

sue

inva

sion

Res

pira

tory

fa

ilure

, ch

roni

c br

onch

itis,

em

phys

ema

& as

thm

a

Cor

ticos

tero

ids

Res

pira

tory

fa

ilure

, ch

roni

c br

onch

itis,

em

phys

ema

& as

thm

a

Cor

ticos

tero

ids

TA:

A. f

umig

atus

is

olat

ed

twic

e N

one

Dis

char

ged

from

IT

U

BA

L:

posi

tive

mic

rosc

opy;

A.

fu

mig

atus

an

d A.

jla

vus

isol

ated

Pr

ecip

itins

: ne

gativ

e

TA:

A.

fum

igat

us

isol

ated

tw

ice

12 d

ays

of

iv D

eath

du

e to

re

spira

tory

B

AL:

ne

gativ

e by

m

icro

scop

y am

phot

eric

in

B fa

ilure

an

d cu

lture

M:

19

M:6

5

F:76

Mul

tiple

tra

uma

incl

udin

g th

orac

ic

inju

ries

follo

win

g ro

ad

traffi

c ac

cide

nt

Sept

ic

shoc

k po

st-

pros

tate

ctom

y (p

erfo

rate

d bl

adde

r),

pseu

do-

mem

bran

ous

colit

is

Elec

tive

post

-ope

rativ

e ve

ntila

tion,

el

ectiv

e ab

dom

inal

an

eury

sm

repa

ir

Non

e TA

: sc

anty

A.

fum

igat

us

2 w

eeks

of

iv

isol

ated

tw

ice

Dis

char

ged

from

IT

U

amph

oter

icin

B

BA

L:

posi

tive

cultu

re

for

A.

fum

igat

us

Prec

ipiti

ns:

posi

tive

(wea

k)

but

nega

tive

2 w

eeks

af

ter

treat

men

t

Non

e TA

: po

sitiv

e m

icro

scop

y fo

r as

perg

illus

once

; A.

fum

igat

us

isol

ated

tw

ice

PM

lung

tis

sue:

A.

fum

igat

us

isol

ated

; no

ev

iden

ce

of

tissu

e in

vasi

on

Non

e

Non

e TA

: A.

fum

igat

us

and

A.fla

vus

Non

e is

olat

ed

once

Dea

th

due

to

pseu

dom

embr

anou

s co

litis

Dis

char

ged

from

IT

U

Prec

ipiti

ns:

nega

tive

TA,

Trac

heal

as

pira

te;

BAL,

br

onch

oalv

eola

r la

vage

; PM

, po

st-m

orte

m.


state. Patient 3 was treated with alternate day amphotericin B for 12 days because of what was initially considered to be invasive infection. However his subsequent course and outcome suggested otherwise. Precipitin tests to A. fumigatus were negative in both patients. Both patients were on corticosteroids for asthma and this may have contributed to colonization with A. fumigatus.

Aspergillus fumigatus was recovered from the tracheal aspirate and BAL fluid of patient 4 three weeks after admission to the ITU following a road traffic accident which resulted in multiple injuries including major chest trauma. Prior to the recovery of Aspergillus from respiratory specimens he had been treated with a variety of antibiotics including cefuroxime, ceftazidime and vancomycin for presumed Gram-negative bacillary pneumonia, and Bacillus cereus septicaemia secondary to colonization of an intravascular cannula. He responded initially to these antibiotics but at the time of the BAL procedure he was pyrexial and had deteriorating blood gas concentrations and his chest X-ray showed new infiltrates. He was treated with intravenous amphotericin B for invasive aspergillosis and responded. Precipitin tests were positive but these became negative following his course of treatment.

Patients 5 and 6 had been in the unit for very short periods, 5 and 2 days respectively, when A. fumigatus was recovered from tracheal aspirates. Aspergillus was isolated from post-mortem lung tissue in patient 5 but despite histological evidence of acute pneumonia and bronchiolitis there was no evidence of tissue invasion.

Investigation of the outbreak Following isolation of A. fumigatus from patient 4 a retrospective review of the preceding three patients either colonized or infected with Aspergillus was undertaken.

Figure 2 outlines the time course of the outbreak, indicating the duration of stay on the ITU of the patients involved, the point at which AspergiZZus was isolated, and the various investigations carried out in the ITU. All the patients from whom Aspergillus was isolated were located at some stage during their ITU stay in the corner bed under the fan as indicated in Figure 1.

Air sampling was carried out on two occasions with a portable centrifugal air sampler (Biotest, RCS). During the 8-min sampling time 320 litres of air was projected onto agar strips (GK-A, Biotest). No moulds were isolated on either occasion, but owing to the relative inefficiency of this type of sampler, low concentrations of aspergillus spores might not have been detected. Moreover, as the sampling was performed several months after the adjacent building work had been completed, spores released during the reconstruction would have settled out. For this reason, dust lying on surfaces in the unit was sampled.

173 Aspergillosis in a general ITU

I

2 w

3”

41

7 Period of construction work

Timing of air samples

5A

61

Timing of environment01 swabs

‘Deep clean’ procedure

1 Case number, duration of ITU stay and when ospergillus isoloted

I I I I I I I I Sept act Nov Dee Jon Feb Mar Apr MOY

1989

Figure 2. Time course of outbreak.

1990

Horizontal surfaces were sampled by rubbing a moistened swab over an area of 5 cm* and then inoculating Sabouraud’s dextrose agar (SDA) plates. Samples of fibre glass insulating material from the ceiling void were shaken over SDA plates, or washed in sterile distilled water (1 g ml-‘) with plating of loo-p1 amounts of the washing on the surface of SDA plates. In further tests adhesive tape was used to attach SDA plates to the undersurface of the perforated ceiling panels for up to 24 h, inside and outside the ITU. Plates were assessed after 72 h at 37°C for the presence of moulds.

Aspergillus fumigatus and A. jlavus were isolated from shelves in a store-room and from the wall-mounted fan in the ITU itself. Various Aspergillus species including A. fumigatus, A. niger and A. ochraceus were isolated from the ceiling insulation material and dust samples (Figure 3) and from the ceiling above the ITU and the corridor, together with Absidia, Cladosporium and Penicillium species. Moulds were also recovered when plates were attached to the corridor ceiling outside the ITU and left for 6 hours; however, the adjacent ceiling had been disturbed during the sampling period. No moulds were recovered when plates were attached to the ITU ceiling but this had not been disturbed during the sampling period.

H. Humphreys et al.

Figure 3. Perforated metal ceiling with insulating fibre glass material.

Management of the outbreak Following recovery of Aspergillus from a number of patients and from the environmental swabs, all areas of the ITU underwent a ‘deep clean’ procedure (Figure 2). All patients were relocated during a weekend; the ceilings, floors, walls, fans, beds and shelves were cleaned with detergent and water. Subsequent environmental sampling of the areas from which Aspergillus had previously been isolated proved negative on two occasions.

The requirement for a larger ITU has led to plans to construct a new unit without false ceilings and incorporating an artificial ventilation system in the near future. In the interim, no ceiling panels may be removed without transfer of patients from the area. Respiratory specimens from all patients in the ITU are being examined for the presence of Aspergillus twice weekly. Following the initiation of these measures in March 1990 no further cases have occurred.

Discussion

Aspergillus was isolated from one or more tracheal aspirates from all six patients included in this outbreak, only one of whom would be regarded as being at significant risk for invasive aspergillosis (patient 1: high dose


corticosteroids). Primary invasive aspergillosis in a normal host is very uncommon and in a review of 25 cases occurring in ‘non-immunocompromised, non-neutropenic hosts’, only 11 had no underlying diseases.’ In immunosuppressed patients, when there is no pre-existing pulmonary disease, a positive coughed sputum culture together with pulmonary infiltrates has sufficient sensitivity and specificity to be useful in the clinical diagnosis of aspergillosis,” and requires immediate systemic antifungal treatment. Sputum cultures are often negative, however, and serological tests are frequently unhelpful in this group of patients, while histological evidence of invasive infection is often not obtainable. On the other hand, Aspergillus species may be cultured from the respiratory tract secretions in a proportion of normal people; a prospective screening of 3000 sputum samples in Cambridge, UK, revealed an incidence of 0.46% of positivity for Aspergillus, but the incidence was higher in immunosuppressed hosts and patients with chronic pulmonary disease.” To resolve this difficulty, bronchoscopic or transthoracic aspiration may be carried out.

Bronchoalveolar lavage (BAL) is a procedure recommended in the diagnosis of invasive aspergillosis, allowing the direct detection of aspergillus hyphae.‘* This procedure, however, was not helpful in this outbreak, being negative by microscopy and culture three times in patient 1, who had definite aspergillosis. In contrast, patient 2 had hyphae seen on microscopy and A. fumigatus and A. JEavus were subsequently isolated from BAL, but the clinical course was never consistent with a diagnosis of invasive aspergillosis. The significance of the positive cultures from tracheal aspirate and BAL in patient 4 and positive serology was supported by his lack of response to antibacterial agents. This patient was treated with amphotericin B and recovered. Patient 3 was also treated with amphotericin B after positive tracheal aspirate cultures, but the pathological significance of the Aspergillus cannot be determined.

Although bronchial biopsies might have improved the diagnostic yield, these were not taken in any of the patients. BAL and protected brush specimens are currently the most widely recognized techniques to diagnose lower respiratory tract infection and in our unit transbronchial biopsy is reserved to diagnose other inflammatory conditions of the lung parenchyma. Moreover, the possibility of making a diagnosis with biopsies rather than BAL has to be set against the greater risk of contamination with this procedure.

As patients likely to remain in the ITU for 48 h or longer had been screened for fungi in the respiratory tract during the preceding 17 months as part of a SDD trial, we can be confident that the outbreak was localized in time. There was no evidence to suggest that the use of SDD during this period precipitated the outbreak.

A number of factors probably contributed to the outbreak described here. Aspergillosis following construction work in or adjacent to units containing


neutropenic patients is well described. 2-5 It is generally accepted that aspergillus spores in a hospital environment do not constitute a risk to the majority of patients. A significant proportion of the non-neutropenic hospital population may be at risk especially those on corticosteroids and other immunosuppressive agents in the vicinity of recent construction work as recently described.13 Many ITU patients are immunosuppressed and must therefore be regarded as being at risk; the first patient detected in this outbreak had received high dose corticosteroids. Nevertheless, all patients requiring invasive organ support on a general ITU are particularly susceptible to infections including those caused by opportunist pathogens.

The work carried out in the areas adjacent to the ITU, albeit minor, may have caused an accumulation of fungal spores, while the frequent disruption of the perforated ceiling in the corridor adjacent to our unit, leading to the dissemination of aspergillus spores, seems likely to have been a major factor in our outbreak. Aspergillus species have been recovered from a variety of inanimate surfaces (e.g. window-sills and window-frames) and in one study carried out in a childrens hospital, 38% of samples yielded AspergilZus.‘4 Dust with high concentrations of Aspergihs accumulates in air ducts and other places which are not regularly cleaned and when disturbed may produce bursts of airborne A. fumigatus.‘5 An outbreak of aspergillus infections in cancer patients caused by contamination of dust above false ceilings, on pipes and in fireproofing materials has been described.16 Such a ceiling is now regarded as unsuitable in a bone marrow transplant unit where, in addition to a solid ceiling laminar air flow is important,8T’0 and the particular design of the ceilings on our unit (perforated metal with fibre glass insulation above it) seems unsuitable for any clinical areas.

Filters are an integral part of mechanical ventilation and should prevent patients from inhaling aspergillus spores; however, there are occasions when the circuit is broken, e.g. during physiotherapy when a bag with oxygen is used. It is probable that our patients inhaled aspergillus spores on such occasions and subsequently became colonized or infected.

Our experience shows the importance of providing safe ventilation systems in units for all high dependency patients. We agree with the need for increased awareness of aspergillus infection and vigilance in patients receiving immunosuppressive agents.13 When building works adjacent to a general ITU are taking place air and environmental monitoring for fungal spores may be indicated. Hospital design should avoid creation of areas where fungal spores may accumulate and later be dispersed, and should allow easy access to services. This report also emphasizes that accumulation of dust should be prevented by regular cleaning of all surfaces in clinical areas.

References

1. Bodey GP, Vartivarian S. Aspergillosis. EurJClin Microbial Infect Dis 1989; 8: 413-437. 2. Arnow PM, Anderson RL, Mainous PD, Smith EJ. Pulmonary aspergillosis during

hospital renovations. Am Rev Rap Dis 1978; 118: 49-53.


3. Barnes RA, Rogers TR. Control of an outbreak of nosocomial aspergillosis by laminar air-flow isolation. J Hasp Znfect 1989; 14: 89-94.

4. Lentino JR, Rosenkranz MA, Michaels JA, Kurup VP, Rose HD, Rytel lV’IW. Nosocomial aspergillosis. A retrospective review of airborne disease secondary to road construction and contaminated air conditioners. Am J Epidem 1982; 116: 430-437.

5. Rotstein C, Cummings M, Tidings J et al. An outbreak of invasive aspergillosis among allogeneic bonemarrow transplants: a case-control study. Znfect Control 1985; 6: 3477355.

6. Kyriakides GK, Zinneman HH, Hall WH et al. Immunologic monitoring and aspergillosis in renal transplant patients. Am J Surg 1976; 131: 246-252.

7. Ruutu P, Valtonen V, Tiittanen L et al. An outbreak of invasive aspergillosis in a haematologic unit. Stand J Infect Dis 1987; 19: 347-352.

8. Sherertz RJ, Belani A, Kramer BS et al. Impact of air filtration on nosocomial aspergillus infections. Unique risk of bone marrow transplant recipients. Am J Med 1987; 83: 709-718.

9. Karam GH, Griffin FM. Invasive pulmonary aspergillosis in nonimmunosuppressed, non-neutropenic hosts. Rev Znfect Dis 1986; 8: 357-363.

10. Rhame FS. Nosocomial aspergillosis: how much protection for which patients? Infect Control Hosp Epidemiol 1989; 10: 296-298.

11. Warren RE, Warnock DW. Clinical manifestations and management of aspergillosis in the compromised patient. In: Warnock DW, Richardson MD, Eds. Fungal Infection in the Compromised Patient. Chichester: John Wiley and Sons 1982; 119-153.

12. Kahn FW, Jones JM, England DM. The role of bronchoalveolar lavage in the diagnosis of invasive pulmonary aspergillosis. Am J Clin Pathol 1986; 86: 5 18-523.

13. Dewhurst AG, Cooper MJ, Khan SM, Pallett AP, Dathan JRE. Invasive aspergillosis in immunocompromised patients: potential hazard of hospital buiding work. Br Med J 1990; 301: 8022805.

14. Wadowsky RM, Benner SM. Distribution of the genus Aspergillus in hospital room air conditioners. Infection Control 1987; 8: 516-518.

15. Rhame FS, Streifel AJ, Kersey Jr JH, McGlave PB. Extrinsic risk factors for pneumonia in the patient at high risk of infection. Am J Med 1984; 76(5A): 42-52.

16. Aisner J, Schimpff SC, Bennett JE, Young VM, Wiernik PH. Aspergillus infections in cancer patients. Association with fireproofing materials in a new hospital. J Am Med Assoc 1976; 235: 41 l-412.

an outbreak of aspergillosis in a general itu

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