Outbreaks of Infection in Intensive Care Units- Usefulness of Molecular Techniques for Outbreak Analysis

(1)

Outbreaks of Infection in Intensive Care Units- Usefulness of Molecular Techniques for Outbreak Analysis

V. D

AMJANOVIC

, X. C

ORBELLA

, J.I.

VAN DER

S

POEL

, H.K.F.

VAN

S

AENE

Introduction

In the first edition of the book Infection Control in ICU (1998) we described our experience with four outbreaks of infection on a neonatal intensive care unit (NICU) [1]. Subsequently we analyzed ten outbreaks of infection due Pseudomonas aeruginosa on NICU. For that exercise, we designed a frame- work for the description and analysis of an outbreak of infection based on 13 pieces of information [2]. This particular framework serves as the basis of this chapter.

This chapter describes the analysis of a total of 57 outbreaks [3–59] occur- ring on not only NICU [3–27] but also on pediatric (PICU) [28–37] and adult intensive care units (AICU) [38–59]. These 57 outbreaks were selected for their employment of molecular techniques in the analysis of the micro-organ- isms involved in the outbreaks. Traditionally, all isolates obtained during the outbreak were required to be identical to be the cause of the outbreak. Several techniques, including serotyping, biotyping, and antibiogram, were applied, but were not found to be reliable. The recent advent of molecular techniques has greatly improved the determination of outbreak isolates. These tech- niques are currently accepted as the gold standard. The three objectives of this analysis of 57 outbreaks are: (1) to assess whether outbreaks are invari- ably due to one clone of an outbreak strain; (2) to evaluate the impact of molecular techniques on the analysis of all key data relevant to the outbreak;

(3) to clarify the contribution of molecular techniques to the management of an outbreak.

Chapter 13

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Methods of Analysis of Outbreaks

Search Strategy

We searched for outbreak reports published between 1 January 1990 and 30 June 2002. Studies were identified through Medline. The MeSH keywords used were ‘intensive care unit’, ‘adult ICU’, ‘pediatric ICU’ and ‘neonatal ICU’, and

‘outbreaks’. All studies that tested the strains involved using molecular biologi- cal techniques were selected.

Definitions

Definitions were given for the key data (Table 1) that were not readily available in the outbreak reports: morbidity, carriage rate, information on the type of outbreak, i.e., endogenous versus exogenous development and clonality.

For the calculation of morbidity the following definition was used.

Morbidity was defined in this study as the number of patients who developed an infection due to the outbreak strain divided by the total number of patients who were carriers of the outbreak strain in nose, throat, and/or gut, i.e., endoge- nous pathogenesis [1, 2]. In case of an exogenous infection, morbidity was defined as the number of patients who developed an exogenous infection divid- ed by the number of patients who acquired the outbreak strain in normally sterile sites such as blood, lower airways, bladder, and wounds.

In many studies the term colonization was used to refer to persistence of the outbreak strain in the patient. In this analysis carriage was used (Table 1). With regard to the type of the outbreak, the terms endogenous and exogenous were only used following interpretation of the evidence from the cited report.

An outbreak was considered to be monoclonal, if one clone amongst the oth- ers investigated was the cause of the outbreak. Polyclonal outbreaks were due to more than one clone. Those with one predominant strain were distinguished from those without one predominant strain.

Framework of the Analysis

The original framework was comprised of 13 key data [2]. Two key data were added to the present analysis: (1) clonality results (monoclonal/polyclonal) were added to the endogenous or exogenous type of outbreak and (2) risk fac- tor analysis (case-control studies). All 57 outbreaks were screened for 15 differ- ent key data related to the three elements crucial in the development of an out- break of infection: source/organism, transmission, and susceptible host.

248 V. Damjanovic, X. Corbella, J.I. van der Spoel, H.K.F. van Saene Vol.Infection/1 ok 8-02-2005 15:59 Pagina 248

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Table Presentation (Table 1)

In total, 57 outbreaks, 25 on the NICU [3–27], 10 on the PICU [28–37], and 22 on the AICU [38–59], were retrieved from the literature. The causative micro- organisms were presented in the following order: in alphabetical order aerobic Gram-negative bacilli (AGNB), yeasts, methicillin-sensitive (MSSA) and resist- ant Staphylococcus aureus (MRSA), coagulase-negative staphylococci, Bacillus cereus, and Enterococcus faecium. Within the same outbreak strain, outbreaks were presented chronologically, and in cases of the same year, the outbreaks were tabled using the first author in alphabetical order. There were two out- breaks of carriage, not infection, due to Klebsiella oxytoca [15] and P. aerugi- nosa [33] and one pseudo-outbreak caused by Staphylococcus epidermidis [26].

Results

Table 1 shows the 15 key data for the three different types of intensive care:

NICU, PICU, and AICU.

Neonatal Intensive Care Unit

There were 13 outbreaks that were retrieved from the first half of the 1990s; the other 12 originated from the second part of the decade. Half of the outbreaks (13) were reported from Europe, 8 from North America (7 from USA), and 2 each from Australia and Africa. Six outbreaks that lasted for less than 2 months were retrieved. There were 11 studies describing outbreaks with duration vary- ing between 2 months and 1 year. Only 3 studied outbreaks lasting between 1 and 2 years and 4 prospective outbreaks of longer than 2 years were found in the literature search. One study did not report the duration of the outbreak.

Of the reported outbreaks, 60% were caused by Klebsiella (5), Enterobacter (4), Acinetobacter (3), and Pseudomonas (3). Application of molecular tech- niques was a criterion for inclusion in the analysis. Three studies from the early 1990s used plasmid profile analysis. All other studies employed analysis of chromosomal DNA, the majority of which were pulsed-field gel electrophoresis (PFGE) (7), arbitrary primed polymerase chain reaction (PCR) (4), and several other PCR variations (4). Different clones were labeled with different capital let- ters, e.g., A, B, C, etc. In the case of minor genetic variation, the capital letters were followed by an apostrophe, e.g., A’, B’, C’, etc. Unique and different clones were denoted by X. Generally, more than 10 isolates were tested (19/25 out- breaks, 76%) in each of the outbreaks.

Usefulness of Molecular Techniques for Outbreak Analysis 249 Vol.Infection/1 ok 8-02-2005 15:59 Pagina 249

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250 V. Damjanovic, X. Corbella, J.I. van der Spoel, H.K.F. van Saene

Table 1.Main characteristics (key data) of outbreak infection in intensive care units (ICU)

RDS, respiratory distress syndrome; S, sensitive; R, resistant; SXT, cotrimoxazole; RTI, respiratory tract infection; UTI, urinary tract infection. Letter A, B = different clones;

A’, B’ = minor genetic variation; X, unique, different from each other and from separate clones;

*Surveillance cultures include throat and/or rectum (others) [3] Nijmegen

(Netherlands) 1998, 1999

2-year Prospective

study Location year

duration

Organism

Species and strain clonality no. identical/

no. tested

Sensitivity to antibiotics used as

1st line

Source Mode of

transmission

[4] Ghent (Belgium)

1993 1st outbreak

1 month 2nd outbreak

2 months

[5] Leiden (Netherlands)

1995 2 weeks

Acinetobacter junii 12A, 4B/18

2X

Not stated R to β-lactams

Not found

Not identified Not stated

S not mentioned Not stated Decreased

S to ampicillin, cefuroxime,

colistin + SXT

Not found

Not identified

Not identified 1st outbreak

Acinetobacter junii 4/4 2nd outbreak Acinetobacter

baumannii 6/6

Not stated Resistant to amoxicillin cefuroxime

Not found

Inanimate Animate

Not found

Hands of staff presumed Acinetobacter

(genomospecies 3 predominant) 29A,3B,3C/38; 3X

(5)

Usefulness of Molecular Techniques for Outbreak Analysis 251

Neonates Type of

outbreak Endogenous or exogenous:

monoclonal or polyclonal Surveillance

cultures*

% carriage rate

Before outbreak

During outbreak

Outbreak control measures

590-3, 310

Not stated

Not mentioned

6 Septicemia

Not reported 0

+

0

+

25

? Polyclonal

(2 infants infected with 2 strains) Prematurity

Prematurity 4, 3 colonized

1 RTI 6 5 colonized

1 RTI

? 3 died due to other causes

? 0

-- -- -- --

? Monoclonal

Not reported

Not reported Prematurity

and RDS

18, Septicemia, pneumonia

? Not reported

--

-- (Env.)

--

Secondary endogenous polyoclonal (one predomi-

nant)

Strict hygiene, carbapenem

treatment

‘disinfection’

of wounds

cont.➝ Average,

or range birth weight (g)

Susceptibility

No. of infected neonates

Predo- minant infection

% Morbidity

% Mortality Predo-

minant underlying

condition

(6)

[6] South Miami (USA) 1984-1988

4 years

[7] Non-USA hospital

? USA hospital

?

Enterobacter sakazakii

26/27 (3 patients, 24 formula)

5/5 (3 patients, 1 formula, 1 blender)

Not stated R to cephalo-

sporins

Not stated R to cephalo-

sporins

Contami- nated dried infant formula Contami-

nated dried infant formula

--

Direct from the source

Direct from the source Not stated

R to kanamycin,

streptomy- cin, mezlocillin

Authors: Parallel strain groups in NICU infants and outside of NICU

supports a theory of multiple source introduction of different C. diversus strains into the NICU rather than repeated intra-NICU

spread of a few strains Source not found Citrobacter diversus

NICU infants:

7A,5B/16; 3X (2 from 1 infant) Other than NICU

infants (community):

4A,3A’, 3B,3B’/16; 3X Table 1. cont.➝

Location year duration

Organism

no. tested

1st line

Source Mode of

transmission

Inanimate Animate

NEC, necrotising enterocolitis; CHD, congenital heart disease; CRF, chronic renal failure;

[8] London (UK) 1992-1993

3 months

Not stated R to penicillins

+ cephalo-

sporins

Blood gas analyzer

-- Hands of staff presumed Enterobacter cloacae

8/8

(7)

Not stated

Not mentioned

Not stated

100 33

? 0

Exogenous monoclonal

Not stated but presumably

by destro- ying the external

source (dried Formula) Not

mentioned

Not mentioned

3 Meningitis

3 Septicemia

18 (includes colonized)

UTI Septicemia,

meningitis

Primary endogenous

polyclonal

Nurse- patient cohorting, no efficacy was evident

? Not reported Neonates

Average, or range birth weight (g)

Susceptibility

% Morbidity

% Mortality Predo-

minant underlying

condition

Type of outbreak Endogenous or exogenous:

monoclonal or polyclonal

Outbreak control measures Surveillance

cultures*

% carriage rate

Before outbreak

During outbreak

+

?

+

?

-- --

Not stated

Prematurity 5 Septicemia

?

0

--

+ (axilla,

groin, tracheal

secre- tion, environ-

ment)

?

? Monoclonal

Gloves when using the machine.

Disinfection of the sampling port of the

machine Vol.Infection/1 ok 8-02-2005 15:59 Pagina 253

(8)

Organism

no. tested

1st line

Source Mode of

transmission

[9] Nijmegen (Netherlands)

1993 3 months

[10] Gauteng (South Africa)

1996 2 months

Enterobacter cloacae 10/13; 3X;

Identical: 3 patients, 6 environment, 1 hands of staff

Not stated R to penicillins

+ cephalo-

sporins

Amino acid cocktail solution (not sealed bottles)

-- Admini-

stration of amino

acid cocktail Not stated

R to cephalo-

sporins

-- One

neonate

‘cross contamina-

tion’

according to authors Enterobacter

cloacae 24A,5B,4C,2D/38;

3X

Inanimate Animate

[11] Durban (South Africa)

1989 3 weeks

Klebsiella pneumoniae Serotype X17, all identical plasmid

profiles

Not stated R to many including amikacin

and cephalo-

sporins

-- Neonates Hands of staff

[12] London (UK) 1992 4 months

Klebsiella pneumoniae All identical (number not stated)

Not stated R to cephalospo-

rins, β-lactam + β-lactamase inhibitor combina-

tions

-- Neonates (gut carriage)

Hands of staff presumed Table 1. cont.➝

(9)

Neonates Type of

cultures*

% carriage rate

Before outbreak

During outbreak

Not stated

NEC 9

Septicemia

Retrieving all suspected solutions;

emphasis on hand washing

? 100 (?NEC)

--

-- (Environ

-ment) --

Exogenous monoclonal

1400 Prematurity RDS

3 Septicemia

(2) Pneumonia

(1)

Isolation;

hand disinfec-

tion;

disinfection of ventilator

tubing 33

0

-- --

(Nasal, umbilical, environ-

ment)

Secondary endogenous monoclonal

16 days to 8 months

CHD CRF

14 Wound, septicemia

Restricting admission;

isolation of infected

and colonized

patients;

strict hand washing

? 21.4

-- --

? Monoclonal Prematurity 6

colonized or infected

? Not reported

-- --

Secondary endogenous

polyclonal (one predomi-

nant)

Barrier isolation,

aseptic techniques,

hand washing Average,

Susceptibility

% Morbidity

% Mortality Predo-

minant underlying

condition

(10)

Organism

no. tested

1st line

Source Mode of

transmission

[13] Parramatta (Australia)

1995-1996 8 months

[14]

Amsterdant (Netherlands)

1997 4 mohths

Klebsiella pneumoniae

8/9; 1X

Not stated R to gentamicin

β-lactamsand

-- Neonates Hands of staff presumed R to

vancomycin and gentamicin

-- Neonates Hands of staff presumed Klebsiella

pneumoniae 4/5; 1X

Inanimate Animate

[15] Saint Etienne (France) 1996-1997

6 months

Klebsiella oxytoca NICU = 1 clone PBU = different

clone (figures not given)

Not stated R to amoxicillin,

ticarcillin, piperacillin;

S to aminoglycosides,

fluoro- quinolones

-- Neonates Enteral feeding procedure

[16] Freiburg (Germany)

1991-1992 5 months

Pseudomonas aeruginosa Patients: 2A, 1B/3

Tap water (8 faucets):

17A,5B,6C,3D/38

Not stated S not mentioned

Tap water from faucets

on the ward

-- Directly from tap water with

which neonates were bathed Table 1. cont.➝

CCS, case-control study; PBU, premature baby unit

CCS, low birth weight, shorter gestational age and length of stay were risk factors;

(11)

Neonates Type of

cultures*

% carriage rate

Before outbreak

During outbreak

600-3700

627-1720 Prematurity 3 Pneumonia

(2) Septicemia

(1)

Replacing gentamicin

with amikacin,

hand disinfection 23.1

30

--

+ (Environ

-ment)

?

‘Low birth weight’

Prematurity PBU: 30 carriers NICU:

numbers not given

Hand washing, isolation, cohorting, using gloves

during feeding conlrolled the outbreak

?

Not reported

+

?

+

?

Outbreak of

‘carriage’, independent monoclonal in

each of the two units

Not stated

Prematurity 3 Septicemia

(1) Meningitis

(1) Pneumonia

(1)

Faucets aera- tors changed twice weekly and autocla- ved (colonization redu- ced but Pseu- domonas still present in tap water)

?

0

-- --

Exogenous monoclonal (faucets car- rying the infec-

ting strain in proximity to the infected patients) Gastro-

intestinal surgery,

NEC

7 Septicemia

? 28.6

-- --

? Monoclonal

Altering empiric antibiotic treatment to

imipenem and vancomycin, hand- washing Average,

Susceptibility

% Morbidity

% Mortality Predo-

minant underlying

condition

(12)

Organism

no. tested

1st line

Source Mode of

transmission

[17] Melborne (Australia)

? 10 months

[18] Oklaoma City (USA) 1997-1998 1 year 3 months

Pseudomonas aeruginosa Neonates: 15A,3B/20

Staff: 2A,1B/3

-- Neonates Staff fingers/nails Not stated

R to ticarcillin,

ticarcillin + clavulanic

acid

Blood gas analyzer

Patients Hands of staff presumed Pseudomonas

aeruginosa 16A,2B,1C/I9

Inanimate Animate

[19] Mexico City (Mexico)

1995 5 months

Serratia marcescens 24A,4B/33

Not stated R to ampi-

cillin, aminoglycosides, aztreonam,

SXT

-- Index case from another hospital

[20] Ghent (Belgium) 1991-1993 1 year 10 months

Sphingomonas paucimobilis

Neonates (temp probes): 26/31

Environmental contacts: 5X

Not stated R to piperacil-

lin, aztreonam, temocillin, polymyxin

B

The ventilator tempera-

ture for probes

-- Contamin- ated droplets

from the temperature

probe flowing back

to the endotracheal

tube Table 1. cont.➝

Cross-transmission between patients

CCS, exposure to two nurses both with long finger nails (one natural and one artificial) were risk factors for acquiring colonization/infection with P. aeruginosa

(13)

Neonates Type of

cultures*

% carriage rate

Before outbreak

During outbreak

1760

500->2500 Prematurity 34 Septicemia, endotracheal colonization

Improved hand was-

hing;

restriction of use of long finger nails 33

50

--

-- (Environ

-ment) --

? Polyclonal (oligoclonal)

Not stated

Not mentioned

23 Septicemia

Strict hand washing, cohorting, wearing glovesduring

catheter manipula-

tion

? Not reported

-- --

? Polyclonal (one predomi-

nant)

Not stated

Not mentioned

85 with tracheal colonization (no infection)

Hand disinfection (did not control the oubreak), steam sterilization of the ventilator temperature

probes did 0

0

--

-- --

Exogenous monoclonal Prematurity 16

Septicemia, pneumonia

? 3

-- --

+ (nose)

?

nant)

Vigilant hand washing Average,

Susceptibility

% Morbidity

% Mortality Predo-

minant underlying

condition

(14)

Organism

no. tested

1st line

Source Mode of

transmission

[21] Winston- Salem (USA) 1990 5 weeks

[22] Liverpool (UK) 1990 4.5 months

Candida parapsilosis 19A,11B/30

Intrinsically R to all antibio-

tics

-- Neonates (gut carriage)

Hands of staff presumed Intrinsically

R to all antibio-

tics

Retrograde syringes

in TPN

-- Retrograde medication administra-

tion Candida albicans

3A/5; 2X

Inanimate Animate

[23] New York (USA)

1989 3 months

MRSA 8A,2B/1O

Not stated R to methicillin Table 1. cont.➝

HMD, hyaline membrane disease; IVH intraventricular hemorrhage; CLD, chronic lung disease; SDD, selective decontamination of the digestive tract

‘the spread of more than a single strain of MRSA among hospitali- zed patients or from health care worker’s suggested by the authors

Source not found Vol.Infection/1 ok 8-02-2005 15:59 Pagina 260

(15)

Neonates Type of

cultures*

% carriage rate

Before outbreak

During outbreak

1400

1002 Prematurity, HMD, IVH,

CLD

6 Candidemia

Cohorting carriers, enhanced

level of hygiene,

SDD with nystatin 20

33

+ 10%

+ 40% at

peak;

10% to- wards

end

nant)

550-3487 Prematurity 10 Septicemia, meningitis, osteomye-

litis

Cohorting of infected and colonized

infants.

Hexachloro- phene

hand washing

?

30

--

-- (nose +

groin) 20

nant) Patent

ductus arteriosus,

4 had surgical

repair

5 Candidemia

100

40

--

Exogenous

monoclonal

Cohorting infected and

exposed infants, use of gloves for all infant contact,

chlorhexidine for hand washing. Us- ing syringes only once and

IV tubing changes every 24 h terminat-

ed the outbreak Average,

Susceptibility

% Morbidity

% Mortality Predo-

minant underlying

condition

(16)

Organism

no. tested

1st line

Source Mode of

transmission

[24] Dallas (USA) 1988-1991

3 years

[25] Leeds (UK) 1992-1996

5 years

Staphylococcus aureus MSSA

38/40

Not stated R to peni-

cillin

Staff nasal carriers

Hands of staff Not stated

R to methicillin

-- Neonates Hands of staff presumed MRSA

35/36

Inanimate Animate

[26] New York (USA)

? 3 months

Staphylococcus epidermidis 2A,2B,2C/15; 9X

-- Not

found

Not identified

[27]

Amsterdam (Netherlands)

1998 3 months

Bacillus cereus 35/35 (infected + coloni-

zed neonates, balloons + nurses)

Balloons used in manual ventilation

Neonates Blowing the organism into the respira-

tory tract;

hands of staff Table 1. cont.➝

ICN, infection control nurse

Not stated R to oxacil-

lin, eryth- romycin, cefuroxime + gentamicin

CCS, lower gestational age and birth weight and longer total length of stay were risk factors,

(17)

Neonates Type of

cultures*

% carriage rate

Before outbreak

During outbreak

Not stated

<1500 (175 neonates)

Prematurity Hand

hygiene

? Not reported

--

-- (Staff nasal environ-

ment)

? Monoclonal

675-1588 Immaturity 12 Septicemia

NEC

Prevention of intrava-

scular catheter colonization

? Not reported

-- --

?

‘pseudo-outbreak’ no single endemic

strain 825-2780 RDS(2)

Perinatal asphyxia

(1) Prematurity

3 Septicemia (35 respiratory tract coloniza-

tion)

Sterilization of the balloons 7.9

33.3

--

+ (umbili-

cus, armpits)

?

Secondary endogenous monoclonal Not

mentioned

43 (including colonized) Septicemia, meningitis,

osteo- myelitis

?

Not reported

-- --

+ (Anterior

nares, axillae)

40

?

Monoclonal

Dedication of an ICN to

tighten infection

control practices.

Triple dye application to umbilical stumps of all

infants on admission to

NICU Average,

Susceptibility

% Morbidity

% Mortality Predo-

minant underlying

condition

202 (including

colonization) Conjuncti-

vitis, RTI, septicemia

(18)

Organism

no. tested

1st line

Source Mode of

transmission

[28] Paris (France) Pediatric Burns Unit

1996 2 months

[29] Taipei (Taiwan)

1987 1 month 1988-1989

2 months

Enterobacter cloacae Cluster 1: 4A/4 Cluster 2: 9B/9 4 isolates blood, 5 distilled water

Not stated 1st outbreak S to cephalosporins +

aminoglycosides

2nd outbreak R to β-lac-

tams + aminoglycosides

Cluster 1?

Cluster 2:

distilled water, respira-

tory humidi-

fier

-- Contami-

nated distilled

water Not stated

Antibiotics not used, poor sensiti-

vity to chlorhe-

xidine

Diluted solution-

of chlorhe-

xidine

-- Treatment with contamina-

ted spray Alcaligenes

xylosoxidans 12/12

Inanimate Animate

[30] Madrid (Spain) 1997-1998

8 months

10/10

Not stated R to 3rd generation

cephalosporins, aminoglycosides commonly

used (gentami-

cin + tobramyci-

nin)

-- Index

case (16-day-

old neonate)

Not identified Table 1. cont.➝

CCS, age<12 weeks and prior treatment with 3 rd generation cephalosporins and aminoglycosides were risk factors for colonization/infection with multi- resistant K. pneumoniae

(19)

Pediatrics Type of

cultures*

% carriage rate

Before outbreak

During outbreak

6.9 years 9 months

to 15 years

? ?

All 8 children

required ventilation

Cluster 1:

4 septice- mias Cluster 2:

4 septice- mias

Changing distilled

water container

? Not reported

-- --

1 Exogenous monoclonal 2 Exogenous monoclonal

1 day to 5 years

Surgery for congenital

heart abnormali-

ties

4 (6 colonized)

Bacteremia

Patient isolation, gloves,

gowns etc during proce-

dures, cleaning + disin-

fection of environmen-

tal equipment.

Restricted use of 3rd generation cepha-

losporins + aminoglycosides

?

25

+

?

+

?

Monoclonal

Burns 6

Wounds

100

0

--

Exogenous

monoclonal

Deconta- mination of

the atomi- zers, chlorhe-

xidine dilu- tion under

aseptic conditions Average,

and/or range age

Susceptibility

No. of infected children

% Morbidity

% Mortality Predo-

minant underlying

condition

(20)

Organism

no. tested

1st line

Source Mode of

transmission

[31] Omaha (USA) 1997-1999 21 months

[32] Taoyman (Taiwan) 1997 5 months

1998 1 month

Klebsiella pneumoniae 21A/39; 15X A = 8 patients,

1 rectal swab from carrier, 10 sink swabs, 2 hands of staff

Not stated R to β-lactams and gentamicin

Hand- washing

sinks

-- Hands

of staff Not stated

R to extended spectrum β-lactams

Not found

Not identified Klebsiella

pneumoniae 14/23; 9X

Inanimate Animate

[33] Paris (France)

1989 2 months

Pseudomonas aeruginosa

11/13; 2X 5 patients with identical strain

R to tobramycin, S to colistin used in total digestive decontam-

ination

-- Patients with fecal carriage

Hands of staff suggested by authors

[34]

Johannesburg (South Afiica)

Pediatric oncology unit

3 months

Pseudomonas pickettii 3A,2B/6; 1 X

R to β-lactams, S to amino-

glycosides

‘sterile’

distilled water

-- Flushing the patients indwelling

Hickman lines with contamina-

ted water Table 1. cont.➝

(21)

Pediatrics Type of

cultures*

% carriage rate

Before outbreak

During outbreak

2.0 years (0.4-11.6)

5-70 days Prematurity 8 Bacteremia

Reinforcing hand- washing, cohorting infected patients, disinfecting

sinks with bleach, reducing the

splatter

?

0

--

-- (Environ

-ment)

?

? Secondary endogenous monoclonal

3 months - 6 years

Immuno- deficiency

Not mentioned

?

Not reported

+

?

+

?

Monoclonal

‘Outbreak of carriage’

19 months - 9 years

Nephro- blastoma,

neuro- blastoma

7 Septicemia

The use of contamina-

ted water discontinued 100

0

-- --

Exogenous

nant) Liver +

intestinal transplants

23 UTI, bacteremia,

RTI

56 20

-- --

nant)

Not mentioned Average,

and/or range age

Susceptibility

% Morbidity

% Mortality Predo-

minant underlying

condition

6 with gut carriage including 4 undergoing total digestive deconta-

mination (vancomycin,

tobramycin, colistin)

(22)

Organism

no. tested

1st line

Source Mode of

transmission

[37]

Philadelphia (USA)

1995 8 months

[35]

Mexico City (Mexico)

1997 2 months

P1CU

Pseudomonas aeruginosa 14A, 2B,7x/23

Not stated R to β-lactams + aminoglycosides

Not found

Cross- contam-

ination suggested

by authors

Not stated Sensitivity

not mentioned

Not found

Hands of staff suggested by authors Serratia marcescens

‘Heterogenicity of strains demonstrated’

(data not given)

Inanimate Animate

[36] Vancouver (Canada) 1991-1992

? 8 months

Serratia marcescens 5A,4B,2C,1D/12

Not stated 3/12 R to cephalosporins

Not found

‘Respiratory care suction involved’

Table 1. cont.➝

CCS, surgery >3 h and exposure to one particular person were risk factors Vol.Infection/1 ok 8-02-2005 15:59 Pagina 268

(23)

Pediatrics Type of

cultures*

% carriage rate

Before outbreak

During outbreak

0-545 days

6 years Congenital heart, neurologi-

cal, lung and neo-

plastic diseases

11 Septicemia

?

Not reported

--

+ (Environ

-ment)

?

Polyclonal (one predomi-

nant)

1 month - 5 years

Post open heart, post neuro-

surgery

12 (or coloni-

zed) Bacteremia

(6)

Change in disinfectant for respiratory component to l% final concentra-

tion of gluteral-

dehyde

?

Not reported

--

?

Polyclonal

Cardiac disease or

surgical procedure

8 (+ 6 coloni-

zed) Bacteremia,

UTI

?

Not reported

--

?

Polyclonal

Contact isolation precautions,

hand washing, environmental cleaning

cont.➝ Average,

and/or range age

Susceptibility

% Morbidity

% Mortality Predo-

minant underlying

condition

Strict hand washing, gloves

during any catheter manipula- tion, super- vision of antibiotic

use Vol.Infection/1 ok 8-02-2005 15:59 Pagina 269

(24)

Organism

no. tested

1st line

Source Mode of

transmission

[40] Cork (Ireland)

1993 2 x 3 months

[38]

Nottingham (UK) 1992-93 6 months

Acinetobacter spp.

9/10

+ aminoglycosides

Not found

Not identified

Not found

Not identified Acinetobacter

baumannii 6A, 6B/29

17X

Inanimate Animate

[39] Houston (USA)

1992 10 weeks

Acinetobacter baumannii

16/16 (also 9/9 from two

other Houston hospitals but S to ciprofloxacin)

R to β-lactams

+ aminoglycosides (only S to imipenem/

cilastin)

-- Index

patient with acute pneumo-

nia

CCS, therapy with 3rd generation cephalosporins, placement of central venous catheters and total parenteral nutrition were risk factors

(25)

Adults Type of

cultures*

% carriage rate

Before outbreak

During outbreak

? 40.4 17-73

Multiple trauma, head injury/

neuro-surgery, post operative support

11 26 coloni-

zed Pneumonia

(8), bacteremia

(3), wounds

?

36

--

-- (Environ

-ment)

--

?

Monoclonal

55 ?

24/25 (96%) used mechanical

ventilation 9 (+ 16 colo-

nized) Pneumonia

(5) bacteremia

(6)

Contact isolation.

A cohort of nurses for A. bau- mannii +ve patients, hand washing, equip-

ment not shared out-

side the cases, pro- per control of antibio-

tics 36

52

--

?

Monoclonal (The concur- rent isolation of a single clone in several

hospitals due to circulation

of staff and patients

amongst hospitals)

? 28

Wounds

? Not reported

--

?

Polyclonal

Rigidity enforced Average,

and/or range age

Susceptibility

No. of infected patients

% Morbidity

% Mortality Predo-

minant underlying

condition

Isolation, cohort nur-

sing, disposable

aprons + gloves,

hand washing

with chlorhexidi-

ne, closure of the unit Vol.Infection/1 ok 8-02-2005 15:59 Pagina 271

(26)

Organism

no. tested

1st line

Source Mode of

transmission

[43] Barcelona (Spain) 1997-1998 18 months prospective

study [41] Nedlands

(Australia) 1993-1994 2 years

Acinetobacter baumannii 41A, 5B/46

Not stated R to β-lactams + aminoglycosides clone B also

resistant to ciprofloxa-

cin

-- Hand

carriage

Hands of staff

R to carbapenem (in 62% of patients) also R to other β-lactams,

aminoglycosides, ciprofloxacin

Environ- ment (secondary to contami-

nation)

Patients ‘Horizontal’

Acinetobacter baumannii Authors example:

1A,2B,1C,6D,2E/12 6m before intervention:

25D,4E/29 6m after interven-

tion: 4D,12E/16

Inanimate Animate

Acinetobacter baumannii

18/18

Not stated Multi-drug

R, S only to imipenem + amikacin

Not found

Risk factors: previous carriage, carbapenems, admission to unit with a high density of patients with the outbreak strain

CCS, surgery >3 h and exposure to one particular person were risk factors [42] Nashville

(USA) SICU 1998 5 months

(2 without intervention,

when attack rate rose from 3

to 16/100 patient/month)

(27)

Adults Type of

cultures*

% carriage rate

Before outbreak

During outbreak

48.7 with CR 57.3 with

CS 51 16-79

Multiple trauma, head injury, cardiac surgery

27 (+18 colo-

nized) Pneumonia

60

0

--

nant)

41 Traumas 18

Pneumonia, bacteremia,

wound

Strict infection

control measures Daily

point prevalen-

ce deter- mined

Not reported

--

+ (Environ

-ment)

?

Monoclonal

Polytrauma, major digestive

surgery, cardio-pul-

monary surgery

189 (+124 colonized) RTI, bacteremia, wounds

1

20 (with CR)

21 (with CS)

--

+

?

Not elucidated Polyclonal- one predominant before interven-

tion, the other during intervention

Sequential closure for decontamination;

redesign of the units;

education + hand washing; restriction of carbapenem use Average,

and/or range age

Susceptibility

% Morbidity

% Mortality Predo-

minant underlying

condition

CR, carbapenem resistant strains; CS, carbapenem sensitive strains

Hand washing, protective clothing, decontam-

ination of equipment, use of gen- tamincin + cephalo-

sporins restricted Vol.Infection/1 ok 8-02-2005 15:59 Pagina 273

(28)

Organism

no. tested

1st line

Source Mode of

transmission

[44] Marseille (France) 1994-1995

7 months

[45] Brussels (Belgium) 1994-1995 9 months

Enterobacter aerogenes

24/24

Not stated, Multi-drug

R, including

the emergence

of imipenem resistance

-- Index

case patient

Hands of staff Highly R to

fluoro- quinolones

after treatment

Not found

Not identified Enterobacter

cloacae 21/21

Inanimate Animate

[46] Athens (Greece) 1994-1995

3 months

6/6

Not found

Not identified

[47] Sao Paolo (Brazil)

1991 3 months

7/14

Not stated R to aminogly-

cosides, extended spectrun β-lactams,

fluoro- quinolones

Not found

‘Nosocomially acquired’

–sample ≥ 48 h after admission

CCS, no risk factors identified

(29)

Adults Type of

cultures*

% carriage rate

Before outbreak

During outbreak

?

56.5 Multiple traumas, respiratory

failure, cardiac surgery

15 Pneumonia,

UTI, Bacteremia (19 coloni-

zed)

44

38

--

+ (Hands

of ICU workers)

?

Secondary exogenous

monoclonal

? ? ? ?

Not reported

-- --

? Monoclonal

? ? 14

RTI, surgical wounds

? After the ICU recon-

struction

‘the control measures reemphasi-

zed’

? Not reported

--

+

?

Monoclonal Acute renal

and respiratory

failure

15 RTI UTI

? Not reported

-- --

?

Monoclonal

Reducing the prescrip-

tion of fluoro- quinolones

cont.➝ Average,

and/or range age

Susceptibility

% Morbidity

% Mortality Predo-

minant underlying

condition

6 Bacteremia

Isolation, hand disinfection, tube sterilisation of mechanical ventila-

tors every 48h, cohort

nursing of colonized patients (gut

carriers) Vol.Infection/1 ok 8-02-2005 15:59 Pagina 275

(30)

Organism

no. tested

1st line

Source Mode of

transmission

[48] Iowa (USA)

1990 1 month

[49] Freiburg (Germany)

1992 2 months

3A, 2B/5

-- Index

patient

Not identified Not stated

S not mentioned

Not found

Hands of a nurse Pseudomonas

aeruginosa Patents: 3A/4

Nurse: 1A/1

Inanimate Animate

[50] Maastricht (Netherlands)

1994-1995 10 months

Pseudomonas aeruginosa 5A, 3B/50, 42X

R to Amoxicillin/

clavulanic acid S to gentamicin

-- Carriers on admis-

sion

Not identified

[51] Pau (France) 1995-1998

3 years

15/15

R to ceftazidime

S to amikacin

-- Index

patient with pneumo-

nia

Not identified

[52] Varese (Italy) 1998-1999 10 months

4A,4A’/8

Not stated R to amino-

glycosides, β-lactams + ciproflo-

xacin

-- Index

patient

(31)

Adults Type of

cultures*

% carriage rate

Before outbreak

During outbreak

31-87

? 19-71

Heart, lung + bowel disease

5 SWI (1) VAP (5)

?

? 0

-- --

polyclonal

58 17-93

Medical surgical trauma

? many carriers VAP

?

? Not reported

+ + Primary

endogenous polyclonal

57.5 Brain + lung disease

64 RTI in mechani-

cally ventilated

Treatment with cefepime, amikacin combina- tion and

hygiene measures

? 31

--

monoclonal Motor

vehicle accidents

9 RTI, surgical wounds

30%

Not reported

--

+ (Hand, of staff)

?

Monoclonal

Careful hand washing between contact with

different patients Average,

and/or range age

Susceptibility

% Morbidity

% Mortality Predo-

minant underlying

condition

? ? 18

Sepsis UTI

Strict hygiene, carbapenem treatment ‘disin-

fection’

of wounds

? Not reported

--

Secondary endogenous monoclonal The main daily

prevalence 34%

SWI, surgical wound infection; VAP, ventilator associated pneumonia Vol.Infection/1 ok 8-02-2005 15:59 Pagina 277

(32)

MICU, medical ICU; SICU, surgical ICU; OHU, open heart unit

Organism

no. tested

1st line

Source Mode of

transmission

[53] Kaysen (Turkey) ICUS 2000

3 months

[54] Richmond (USA) 1998-1999 10 months

Serratia marcescens (and Enterobacter cloacae in 25% of pa-

tients) S. marcescens 24/25 E. cloacae 7/7

Parenteral narcotic (fentanyl)

contaminated by a

therapist

-- Infusion of contaminated narcotic Not stated

R to many, S to amikacin,

ciprofloxacin, imipenem

Not found

Conta- minated

theater linen Serratia marcescens

(in 15 patients) misc AGNB in 5

patients S. marcescens 9/9

Inanimate Animate

[55] Albany, NY (USA)

1991 2 months

MRSA 5/7 (4 from patients, 1 from a nurse identical)

Not stated R to methicillin, eryth-

romycin, ciprofloxacin

-- Patients Using a common

bathtub

[56] New York (USA) 1988-1991

3 years

MRSA Cluster I:

Labour + delivery, Summer 1988 - 12 (4

patients, 4 staff; 4 environment) /12 Cluster 2: MICU, Spring 1990 - 6A, 2B/10, 2X (all patients)

Cluster 3: OHU, Fall 1990 5A/6, X

(3 patients, 2 environment) SICU: 4B,2C/6, 1X

Not stated R to methicillin Not stated

R to methicillin

Not found

Not found Index patient

Not found

Not identified

CCS, length of stay, fentanyl administration and exposure to two particular respiratory therapists were risk factors

(33)

Adults Type of

cultures*

% carriage rate

Before outbreak

During outbreak

Not stated

7 Surgery

for trauma

26 Septicemia

31%

(8 patients had polymi-

crobial septicemia)

Termination of employment of the implicated health care wolker 100

12

--

-- (Environ

-ment) --

Exogenous

monoclonal

? Psoriasis, skin ulcers, AIDS

7 Bacteremia

The use of the bathtub discontinued 21.2

0

-- --

? Monoclonal

?

7 neonates, 8 mothers (1 mother infected,

others colonized)

7 (2 bacteremia,

5 colonized) 5 wounds 3 wounds

All clusters:

patient isolation, screening of staff, topical bacitracin to carriers of MRSA, educating

staff 6.7

0 28.6

0

? 0

-- -- -- -- -- -- -- --

? Monoclonal (unrelated to other clones) Polyclonal (one

predominant) Monoclonal Polyclonal (one

predominant) AVR

MVR Bypass

17 Bacteremia, mediastinitis

7

30

--

Exogenous

monoclonal Average,

and/or range age

Susceptibility

% Morbidity

% Mortality Predo-

minant underlying

condition

Review of the central steri1isation

unit with strict control measu-

res for effective sterilization Vol.Infection/1 ok 8-02-2005 15:59 Pagina 279

(34)

Organism

no. tested

1st line

Source Mode of

transmission

[59] Valhalla (USA) 1991-1992

1 year [57] Barcelona

(Spain) 1991-1992 14 months

MRSA & MSSA MRSA 10A,2A’/13; 1X MSSA showed great

molecular variability

Not stated MRSA R to methicillin MSSA S to methicillin

Not found

Patients Not identified

R to ampicillin, gentamicin, vancomycin

-- Not

found

Not identified Enterococcus

faecium 8’ closely related/8

(blood and stool isolates)

Inanimate Animate

MRSA 6A,5A'/21

10X

Not stated R to methicillin

+ fucidic acid

Not found

CCS, carriage with MRSA as opposed to MSSA was a risk factor for septicemia [58] Oslo

(Norway) 1995-1996 10 months ICU of a neurosurgical

unit

(35)

Adults Type of

cultures*

% carriage rate

Before outbreak

During outbreak

36 (infected)

58.5 (stool carriers) MRSA 47.2 MSSA 42.6

MRSA +MSSA

COPD polytrauma, malignancy, liver disease

38 24 MRSA (of

63 carriers 14 MSSA (8

of 84 carriers, 6 of 341 non car-

riers) Bacteremia all infected patients

MRSA 38 28.5 MSSA

9.5 23.8

-- (Nose)

--

-- (Nose) MRSA 13 MSSA

17

Primary and secondary endogenous

MRSA polyclonal (one predomi-

nant)

1-78 (15 adults)

Accidents 17 (3A + 2A’

clone) wounds

Single room isolation,

staff + visitors wore gloves,

gowns + masks,

topical mupirocin

? Not reported

--

+ (Nose, hands)

?

? Monoclonal

(5 patient + 5 staff carriers)

Acute leukemia

7 Bacteremia

1.7 30%

-- --

+ 13

Contact isolation Average,

and/or range age

Susceptibility

% Morbidity

% Mortality Predo-

minant underlying

condition

Attempts to eradicate carrier state

COPD, chronic obstructive pulmonary disease

(36)

Based on the results of outbreak strain clonality, two subgroups were iden- tified in each group–monoclonal and polyclonal outbreaks. Monoclonality may include either all identical strains or one clone amongst several unique strains.

Polyclonality may occur with or without one predominant strain.

Of 25 outbreaks, 21 (84%) did not describe the first-line antibiotics as empirical therapy. Of the 4 reports that mentioned the first-line antimicrobials, the outbreak strain was invariably resistant to the first-line treatment, which included β-lactams and aminoglycosides [11], aminoglycosides and glycopep- tides [13], and all antibiotics in the two Candida outbreaks [21, 22]. Of 21 stud- ies that did not mention the first-line antibiotics, 18 reported sensitivity to the commonly used antimicrobials. Resistance of the outbreak strain varied from outbreak to outbreak, being most common to β-lactams [3, 5, 7–10, 15, 17, 23–25]. Several outbreaks were due to multiple resistant strains, which includ- ed β-lactams and aminoglycosides [6, 14, 19], β-lactams and polymyxins [20], β-lactams and β-lactamase inhibitor combinations [12], and β-lactams, amino- glycosides, and macrolides [26]. Four of six multiple resistant strains (β-lac- tams and others) were monoclonal [4, 12, 14, 20]. One was polyclonal with one predominant strain [19]. The remaining ‘multiple resistant strain’ actually belonged to several strains of S. epidermidis causing a ‘pseudo-outbreak’ [26].

Sensitivity was not mentioned in three studies [16, 18, 27].

In 5 outbreaks (22%), the source was not identified (Table 1). Inanimate sources of the outbreak strain were identified in 6 reports (Table 1). Animate sources were reported in 10 studies (Table 1). Both inanimate and animate sources were involved in 2 outbreaks [17, 27].

Of the 25 reports, the mode of transmission was not mentioned in 3 publi- cations. Three authors used vague terms including ‘cross-transmission’ follow- ing their own interpretation. In 7 reports the mode of transmission was direct- ly from the external source (exogenous pathogenesis). Twelve reports blamed the hands of health care workers as the vehicle of the outbreak strains, although that mode of transmission was microbiologically proven in only 4 reports.

Table 2.Source and clonality of outbreak strain in 54 outbreaks

Source Monoclonal Polyclonal

Inanimate 10 (30.5%) 1 (5%)

Animate 12 (36%) 8 (38%)

Inanimate + animate 1 (3%) 2 (10%)

Not identified 10 (30.5%) 10 (47%)

33 (61%) 21 (39%)

(37)

Half (12) of the outbreak reports did not mention birth weight as a suscep- tibility factor. Twelve quoted low birth weight (<1,500 g) and 1 reported the age. More than 70% (18) of the manuscripts mentioned the underlying condi- tion. Prematurity was identified as the main risk factor in 12 reports. In the remaining outbreak studies, underlying diseases, including necrotizing entero- colitis, respiratory distress syndrome, congenital heart disease, and chronic renal failure, were identified.

Without any exception all reports mentioned the number of infected babies with the predominant infection. Serious infections, including pneumonia, sep- ticemia, and meningitis, were described in 20 reports. In 9 reports colonized patients were included in the number of affected children.

Data on morbidity were not given in 17 studies. Six studies reported mor- bidity rates between 0% (i.e., only carriage) and 33%. Two outbreaks, invariably of exogenous pathogenesis, gave 100% morbidity rates. The mortality rate was not reported in 7 studies. In 6 reports no patients died. Ten outbreaks men- tioned a mortality between 21% and 50%, whilst mortality was 100% in only 1 outbreak following the injection of a contaminated amino acid solution [10].

There was no particular pattern of mortality rates between monoclonal and polyclonal outbreaks, with the exception of the monoclonal exogenous out- break due to the injection of a solution contaminated with Enterobacter cloacae, resulting in 100% mortality [10].

Surveillance cultures were not performed in 10 outbreaks; if obtained, sur- veillance cultures were taken during the outbreak. Environment (7), nose (4), lower airway secretions (3), and surface cultures (umbilical, groin, axilla) (6) were taken in a total of 15 outbreaks. Only 4 studies reported surveillance cul- tures before and during outbreak. Carriage rates were calculated for MRSA in the nose during 2 outbreaks [23, 24] giving 20% and 40% of nasal carriage of MRSA, and only 1 described 10% and 40% of Candida carriage before and dur- ing the outbreak [22].

Amongst the NICU outbreaks, there was 1 outbreak of carriage [15] and 1

pseudo-outbreak [26]. Of the 23 outbreaks, the pathogenesis was endogenous in

7 [3, 6, 9, 11, 14, 22, 27] (Table 1). With regard to clonality there were 3 mono-

clonal, 3 polyclonal with one predominant strain, and 1 polyclonal without pre-

dominant strains. The pathogenesis was exogenous in 5 reports, all monoclon-

al [7, 10, 16, 20, 21]. Details of the pathogenesis were absent in 11 outbreaks: 6

monoclonal outbreaks [4, 8, 12, 13, 24, 25], 4 polyclonal with one predominant

strain [17–19, 23], and 1 polyclonal outbreak without one predominant strain

[5]. Because of limited data on the pathogenesis, further analysis was related to

clonality. Monoclonal outbreaks were equally distributed amongst outbreaks of

short (<2 months) and long (>2 months) duration. Amongst 9 polyclonal out-

breaks, only 1 (11%) was of short duration [5]. Species were proportionally

(38)

due to Klebsiella spp., which were monoclonal in all 5 retrieved outbreaks.

Sensitivity to first-line antibiotics when reported was comparable in mono- and polyclonal outbreaks. Both animate and inanimate sources were involved in 2 outbreaks [17, 27]. However, monoclonal outbreaks differed in sources accord- ing to the species. All Klebsiella strains originated from animate sources, and most Pseudomonas and Enterobacter spp. came from inanimate sources (Table 1). The extent of outbreaks in terms of number of patients and predominant infections did not differ in monoclonal and polyclonal outbreaks. There was no difference in morbidity rate between mono- and polyclonal outbreaks, except for outbreaks of exogenous development, where 100% morbidity was observed in two monoclonal outbreaks [7, 21]. In outbreaks where mortality was not reported, 4 were monoclonal and 3 were polyclonal. The 6 outbreaks without mortality were due to 5 monoclonal strains and 1 polyclonal strain. In 11 stud- ies where the mortality was reported, 8 were monoclonal and 3 polyclonal.

Excluding the 100% mortality in the exogenous monoclonal outbreak [10], mortality rates varied from 20% to 50%.

No details were given of outbreak control measures in 2 outbreaks. In 1 of these the main aim was to compare various typing methods, including molecu- lar techniques, applied to the outbreak isolates [4]. In the other study only molecular techniques were compared [5].

With an animate source, hand washing was the main intervention, alone in 7 reports and combined with other measures, including cohorting and gloves, in 5 studies. In addition to the above maneuvers, 1 outbreak changed antibiotic policy [13] and the other used selective decontamination of the digestive tract [22]. With an inaminate source, removal of the vehicle of the outbreak strain was implemented in 2 outbreaks. Care of equipment was the main outbreak control measure in 6 reports.

Of the 25 analyzed outbreaks in NICU, only 3 [14, 18, 27] performed a case- control study for outbreaks of Klebsiella pneumoniae, P. aeruginosa, and B.

cereus. The risks factors were long finger nails of the health care workers in the P. aeruginosa outbreak [18] and low gestational age, birth weight, and total length of stay in the K. pneumoniae [14] and B. cereus outbreaks [27].

Pediatric Intensive Care Unit

Between 1991 and 1995, 5 outbreaks, 1 of which was an outbreak of carriage [33]

were described, and 5 between 1996 and 2001. There were 4 outbreaks in units in the United States, 3 European units, 2 Asian, and 1 African pediatric ICU.

Four outbreaks lasted for less than 2 months, 5 between 2 and 8 months, and 1 21 months.

All outbreaks reported from PICU were due to aerobic AGNB, including

Klebsiella (3), Pseudomonas (3), Serratia (2), Alcaligenes, and Enterobacter (1

284 V. Damjanovic, X. Corbella, J.I. van der Spoel, H.K.F. van Saene Vol.Infection/1 ok 8-02-2005 15:59 Pagina 284

(39)

each). More than 10 isolates were tested for clonality in 6 outbreaks. In 1 out- break the number of isolates was not given. Only 1 study in 1991 used plasmid profile analysis. In the other reports chromosomal DNA techniques were used in half, including PFGE.

The sensitivity pattern was stated in only two studies [33, 34]. In the first study that reported an outbreak of carriage, the outbreak strain of P. aeruginosa was resistant to tobramycin, used as a component of total digestive decontami- nation in immunodeficient children [33]. In the second, where contaminated distilled water was the source of the outbreak strain of P. pickettii, this strain was resistant to β-lactams, but sensitive to aminoglycosides [34]. Of 8 studies that did not mention the first-line antibiotics, 6 reported sensitivity. The out- break strain from 2 outbreaks was resistant to β-lactams [31, 36], and from the remaining 4 outbreaks the outbreak strain was resistant to β-lactams and aminoglycosides [29, 30, 32, 35]. Three of the latter multiple resistant strains were monoclonal, and 1 was polyclonal with a predominant strain [35].

The source was not identified in 4 outbreaks [31, 35–37]. The source was ani- mate in 1 study [30] (Table 1). Four studies identified the source as inanimate [28, 29, 32, 34] (Table 1). Transmission direct from the external source was the mode of spreading in 4 outbreaks. Hands of the staff were implicated in 2 reports, and the mode of transmission was not identified in 3 outbreaks.

Age varying between 1 day and 15 years was mentioned as a risk factor in 8 studies; 2 studies did not mention age. Surgery was the main underlying condi- tion in 5 outbreaks and neoplastic disease in 2 studies. The number of infected children varied from 8 to 23 in the 9 pediatric ICU outbreaks. Septicemia was the most common infection by 80%.

Seven outbreaks did not mention the morbidity. The morbidity was 100% in the 2 outbreaks of exogenous infection [28, 34]. One remaining outbreak showed a 56% morbidity [31]. Half of the pediatric outbreaks did not report mortality. No children died in 3 outbreaks. The mortality rate was 20% and 25%

Outbreaks of Infection in Intensive Care Units- Usefulness of Molecular Techniques for Outbreak Analysis