Enterobacter aerogenes

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Enterobacter aerogenes Piagnerelli M 1, Carlier E 1, Deplano A 3, Lejeune P 1, Govaerts D 2 1 Departments of Intensive Care and 2 Microbiology, A. Vésale Hospital. 6110 Montigny-le-Tilleul. 3 Department of Microbiology, Erasme University Hospital. 1070 Brussels. Belgium.

An increase of Enterobacter aerogenes infections has been reported in european ICUs De Gheldre Y. et al. J. Clin. Microbiol., 1997 ; 35 :152-160 160 Jalaluddin S. et al. J. Clin. Microbiol., 1998 ; 36 : 1846-1852 1852 Ronveaux O. et al. Clin. Microbiol.. Infect. 1999; 5 : 622-627 627

An increase of Enterobacter aerogenes infections has been reported in european ICUs De Gheldre Y. et al. J. Clin. Microbiol., 1997 ; 35 :152-160 160 Jalaluddin S. et al. J. Clin. Microbiol., 1998 ; 36 : 1846-1852 1852 Ronveaux O. et al. Clin. Microbiol.. Infect. 1999; 5 : 622-627 627 Enterobacter aerogenes is actually considered as the third Gram-negative bacilli in cause of nosocomial infections after Escherichia coli and Pseudomonas aeruginosa Glupczynski Y.et al. Acta Clin. Belgica, 1998 ; 53 : 28-38

0,7 0,6 Incidence (%) 0,5 0,4 (NB MREA/100 0,3 admissions) 0,47 0,52 0,6 0,4 0,48 0,37 0,36 0,2 0,1 0 1995 1996 1997 1998 1999 2000 2001 ANNEES

Comparison ICU > < other units : 1995 RR= 7.39, IC 95% (4.17 13.10) / p = 10-6 1996 RR= 8.24, IC 95% (4.78 14.19) / p = 10-6 1997 RR= 6.53, IC 95% (3.81 11.19) / p = 10-6 1998 RR= 4.0, IC 95% (1.91 8.37) / p = 10-5 1999 RR= 2.11, IC 95% (0.95-4.68) / p = 0.06 2000 RR= 4.06, IC 95% (1.95 8.45) / p = 10-6 2001 RR= 1.24, IC 95% (0.38 4.02) / p = 0.72

Hospital outbreak Piagnerelli et al. Infect. Control. Hosp. Epidemiol.. 2000; 21 : 651-653 653 30-bed geriatric acute unit. During 3 months (1998). 12 patients colonized/infected infected by MREA. Risk factors : central and urinary catheters. Identical clone by PFGE study.

Hospital outbreak Piagnerelli et al. Infect. Control. Hosp. Epidemiol.. 2000; 21 : 651-653 653 Contact isolation after detection of the second patient 6 new nosocomial cases Decision to close the unit to new admissions.

ICU outbreak Carlier et al. Crit.. Care 1997, 1 : P 35 February 1996, over a 3-day 3 period. 4 patients colonized at multiple sites. Colonization ultimately progressed to infection in 3 patients. 75 % mortality. Identical clone by RAPD study.

Risk Factors of Colonization/Infection in ICU Piagnerelli et al. Crit.. Care 1998, 2 : P 97 A 3 month prospective study (1995). Perineal swabs the admission day, discharge and on a weekly basis. 146 patients. 9.6 % colonization. Risk factors : - corticoid therapy - ICU length of stay - SAPS II Mortality : 43 %

To determine the frequency of colonization by E.a. in ICU patients hospitalized more than 48 hours.

To determine the frequency of colonization by E.a. in ICU patients hospitalized more than 48 hours. To evaluate the risk-factors of infection in colonized patients by the same bacteria.

PFGE was used to determine the genotypes of isolates.

PFGE was used to determine the genotypes of isolates. To determine risks of infection in colonized patients to develop in the future optimal preventive policies in these patients.

From January to September 1998 Perineal swabs on admission, weekly and on discharge

Colonization : isolation of E.a. in the absence of signs or symptoms of infections. Infection : isolation from a normally sterile body site, concurrent with accompanying signs and symptoms of infection.

Antimicrobial susceptibility Resistance 2/3 : ceftazidime, ciprofloxacin, amikacin. Clonality using PFGE SMaI digested DNA of Staphylococus aureus NCTC 8325 Strains with more than 70 % similarity were considered identical

Screening of 204 patients : 24 (11.4 %) were colonized by MREA 8 became infected during their ICU stay 2 infected without prior colonization

52 strains : for clinical infected - 7 respiratory tract - 4 urinary tract - 1 wound infection - 1 blood infection - 24 rectal swabs : for colonization

Antimicrobial Susceptibility Ceftazidime- R 76 % Ciprofloxacin- R 59 % ESBL + 66 % 47 % clone 1 17 % clone 2

RESULTS OF THE ANALYSIS OF RISK FACTORS FOR EA COLONIZATION Patients without colonization With colonization RR CI 95 p N = 170 (%) N = 24 (%) Male 101 (59) 14 (58) 0.98 0.68-1.41 0.92 Mean age 69 79.5 0.09 Admission via Long term 7 (4) 1 (4) 1.01 0.13-7.87 0.99 Other unit 106(62) 18(75) 1.2 0.93-1.56 0.23 Home 55 (32) 4(17) 0.52 0.21-1.29 1.29 0.12

RESULTS OF THE ANALYSIS OF RISK FACTORS FOR EA COLONIZATION Patients without colonization With colonization RR CI 95 p N = 170 (%) N = 24 (%) Chronic dis. 108 (63) 13 (54) 0.85 0.58-1.25 0.38 SAPS II 35 42 0.03* Surgery 46(27) 11(46) 1.69 1.03-2.79 0.06 Infection on ICU admission 74 (43) 14 (58) 1.34 0.92-1.96 0.17 AB 124(73) 22(92) 1.26 1.08-1.46 1.46 0.047* Corticoids 74 (43) 10(42) 0.96 0.58-1.58 0.86

RESULTS OF THE ANALYSIS OF RISK FACTORS FOR EA COLONIZATION Patients without colonization With colonization RR CI 95 p N = 170 (%) N = 24 (%) IS 3 (2) 1 (4) 2.36 0.26-21.8 21.8 0.44 CVP 155(92) 24(100) 1.1 1.05-1.15 1.15 0.13 Arterial Line 153(90) 23(96) 1.06 0.97-1.17 0.36 Surgical drain 43 (25) 10 (42) 1.65 0.96-2.82 0.09 Urinary cath 146(86) 22 (92) 1.07 0.93-1.22 0.44 Nasogastric tube 95 (56) 18(75) 1.34 1.03-1.75 1.75 0.08

RESULTS OF THE ANALYSIS OF RISK FACTORS FOR EA COLONIZATION Patients without colonization With colonization RR CI 95 p N = 170 (%) N = 24 (%) Endoscopy 55 (32) 15 (62) 1.93 1.32-2.8 2.8 0.004* MV 73(43) 16(67) 1.55 1.11-2.16 0.029* Hosp/ICU (days) 1.0 6.5 0.028* ICU stay Days 5 9 0.003* Mortality 33(19) 8 (33) 1.72 0.9-3.27 0.12

RESULTS OF THE ANALYSIS OF RISK FACTORS FOR EA INFECTION Colonized Patients Infected Patients RR CI 95 p N = 24 (%) N = 10 (%) Male 14 (58) 6 (60) 1.03 0.56-1.89 0.93 Mean age 76.5 63.5 0.039* Admission via Long term 1 (4) 0 (0) 0 0-45.4 0.52 Other unit 18(75) 5(50) 0.67 0.34-1.29 0.16 Home 4 (17) 5(50) 3.0 1.01-8.91 0.047*

RESULTS OF THE ANALYSIS OF RISK FACTORS FOR EA INFECTION Colonized Patients Infected Patients RR CI 95 p N = 24 (%) N = 10 (%) Chronic dis. 13 (54) 9 (90) 1.66 1.09-2.53 0.049* SAPS II 42 44.5 0.97 Surgery 11(46) 4 (40) 0.87 0.36-2.09 0.76 Infection on ICU admission 14 (58) 5 (50) 0.86 0.42-1.74 0.66 AB 22(92) 10(100) 1.09 0.97-1.23 0.35 Corticoids 10 (42) 5(50) 1.2 0.55-2.62 0.66

RESULTS OF THE ANALYSIS OF RISK FACTORS FOR EA INFECTION Colonized Patients Infected Patients RR CI 95 p N = 24 (%) N = 10 (%) IS 1(4) 0 (0) 0 0-45.4 0.52 CVP 24 (100) 10 (100) Arterial Line 23(96) 10 (100) 1.04 0.96-1.13 0.52 Surgical drain 10 (42) 4 (40) 0.96 0.39-2.35 0.93 Urinary cath 22 (92) 10 (100) 1.09 0.97-1.23 0.35 Nasogastric tube 18 (75) 10 (100) 1.33 1.06-1.68 0.86

RESULTS OF THE ANALYSIS OF RISK FACTORS FOR EA INFECTION Colonized Patients Infected Patients RR CI 95 p N = 24 (%) N = 10 (%) Endoscopy 15 (62) 10 (100) 1.5 1.17-2.18 0.026* MV 16 (67) 10 (100) 1.5 1.13-1.99 1.99 0.039* Hosp/ICU (days) 6.5 2.5 0.5 ICU stay Days 9 31 0.007* Mortality 8 (33) 3 (30) 0.9 0.3-2.71 0.85

Figure 2 PFGE ANALYSIS ( 52 samples) 20 40 60 80 100 44 51 1 3 43 2 4 9 5 49 16 17 6 7 8 26 35 25 24 31 32 20 21 34 36 33 37 42 47 48 41 38 40 39 52 53 50 19 22 23 18 29 30 27 28 11 12 10 46 13 15 14 1 2 3 4 28 strains 17 strains 5

Attack rate of colonization or infection of 28 % for clone 1 of 20 % for clone 2 7 / 8 infected patients had the same genomic profile for colonization and infection

Risk factors for infection were not new : De Gheldre et al. J. Clin. Microbiol., 1997 ; 35 :152-160. 160. Carlier et al. Crit.. Care, 1997 ;1 (suppl( suppl.. 1) : P 35.

Risk factors for infection were not new : De Gheldre et al. J. Clin. Microbiol., 1997 ; 35 :152-160. 160. Carlier et al. Crit.. Care, 1997 ;1 (suppl( suppl.. 1) : P 35. Prolonged ICU stay and invasive procedures, especially pulmonary procedures endotracheal intubation - mechanical ventilation - bronchoscopy most infections were pulmonary

PFGE analysis :

PFGE analysis : 2 principal clones as described in studies in Belgian hospitals De Gheldre Y. et al. J. Clin. Microbiol., 1997 ; 35 :152-160. 160. Jalaluddin S.et al. J. Clin. Microbiol., 1998 ; 36 : 1846-1852. 1852.

Colonization is a prerequiste of infection Infection is usually due to the same clone causing prior colonization.