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Inf Nosocomiale Bgn 2002

Inf Nosocomiale Bgn 2002

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Published by Ana-Maria Mîrcă
microbiologie
microbiologie

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Published by: Ana-Maria Mîrcă on Jul 15, 2014
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1600
 
 CID 2002:34 (15 June)
 
 Blot et al.
M A J O R A R T I C L E
Nosocomial Bacteremia Caused by Antibiotic-Resistant Gram-Negative Bacteria in Critically Ill Patients: Clinical Outcome and Lengthof Hospitalization
Stijn Blot,
1
Koenraad Vandewoude,
1
Dirk De Bacquer,
2
and Francis Colardyn
1
1
Department of Intensive Care, Ghent University Hospital, and
 2
Department of Public Health, Ghent University, Ghent, Belgium
Population characteristics and outcomes were retrospectively compared for critically ill patients with noso-comial bacteremia caused by antibiotic-susceptible (AB-S; ) or antibiotic-resistant (AB-R; )
p
208
 
p
120gram-negative bacteria. No significant differences in severity of illness and comorbidity factors were seenbetween groups. Patients with bacteremia caused by AB-R strains had a longer hospitalization before theonsetof the bacteremia. The in-hospital mortality for patients with bacteremia caused by AB-S strains was 41.8%;for patients infected with AB-R strains, it was 45.0% ( ). A multivariate survival analysisdemonstrated
p
.576that older age ( ), a high-risk source of bacteremia (abdominal and lower respiratory tract;
p
.009
 
p
), and a high acute physiology and chronic health evaluation II–related expected mortality ( ) were.031
 
p
.032independently associated with in-hospital mortality ( ). Antibiotic resistance in nosocomial bacteremia
!
.05caused by gram-negative bacteria does not adversely affect the outcome for critically ill patients.
The widespread use of broad-spectrum antibiotics isthe principal factor in the emergence of antibiotic re-sistance. Consequently, in intensive care units (ICUs),where the use of antibiotics is considerably greaterthanin general wards [1], dealing with antibiotic-resistantmicroorganisms is an almost daily challenge. This mustbe considered a major problem, because the develop-ment of newer and more-potentantibioticscannotkeepup with the increase in antibiotic resistance.In ICUs, gram-negative bacteria are responsible for a
Received 3 December 2001; revised 1 February 2002; electronically published23 May 2002.Presented in part: 14th Annual Congress of the European Society of IntensiveCare Medicine, Geneva, 30 September–3 October 2001.Financial support: Fund for Scientific Research, Flanders, Belgium (specialdoctoral grant 1.9.205.02N00 to S.B.).Reprints or correspondence: Dr. Stijn Blot, Dept. of Intensive Care, GhentUniversity Hospital, De Pintelaan 185, B-9000 Ghent, Belgium (stijn.blot@rug.ac.be).
Clinical Infectious Diseases 2002;34:1600–6
 2002 by the Infectious Diseases Society of America. All rights reserved.1058-4838/2002/3412-0009$03.00
considerable percentageofallbloodstreaminfections[2].In ICUs in the United States and Europe, patterns of reduced susceptibility to antibiotics were found amonggram-negativebacteria[3,4].Despitethehighprevalenceof antibiotic resistance among gram-negative bacteriacausing bacteremia, the clinical consequences of resis-tance remain unclear. The main objective of our study was to evaluate the relationship between antibiotic re-sistance in gram-negative bacteria causing bacteremiaand the clinical outcomes for critically ill patients. Sec-ondary objectives were to compare the length of the ICUstay and hospitalization for patients with bacteremiacaused by antibiotic-susceptible (AB-S) or antibiotic-resistant (AB-R) gram-negative strains.
METHODS
Setting.
 This study was performed in the ICU of the1060-bed Ghent University HospitalinGhent,Belgium.The ICU has 54 beds and includes a medical and sur-gical ICU, an ICU for cardiac surgery, and an ICU for
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Bacteremia Caused by Resistant Microorganisms
 
 CID 2002:34 (15 June)
 
 1601
severely burned patients. No significant changes in mean ageof patients, length of the ICU stay, or acute physiology andchronic health evaluation (APACHE) II score [5] wereobservedduring the study period.
Study design and data collection.
 We conducted a retro-spective, observational cohort study that included ICU patientswith nosocomial, microbiologically documented bacteremiacaused by gram-negative bacteria. We compared data from pa-tients with bacteremia caused by AB-S gram-negative bacteriawith data from patients with bacteremia caused by AB-R gram-negative bacteria. In-hospital mortality (mortality rate for 3evaluation points) was the principal outcome variable evalu-ated. We also assessed secondary outcomes, including lengthof stay in the ICU and in the hospital and prevalence of acuteorgan failure.The study included critically ill adult patients who were ad-mitted to the ICU during a 9-year period (January 1992–December 2000). All microbiologically documented nosoco-mial bloodstream infections are prospectively screened by thecenter for infection control. This hospital-wide case-based sur-veillance program was used to perform a retrospective searchfor ICU patients with bacteremia caused by gram-negativebac-teria. Every patient whose ICU stay was complicated by thisbloodstream infection was assessed in our analysis. For ICUpatients who developed
 1
1 case of bacteremia caused by gram-negative bacteria, only the first episode was considered.Patientswith hemocultures that yielded
 1
1 type of gram-negative bac-teria of which at least 1 strain was AB-R were included in theAB-R group.
Definitions.
 Bacteremia was considered to be nosocomialwhen it was diagnosed at least 48 h after hospital admission.“Gram-negative bacteremiawas defined as the presence of gram-negative bacteria in the blood, documented by at least 1positive hemoculture. Hemocultures were routinely performedwhen the patient’s temperature was
 1
38.4
C or when infectionwas suspected on clinical grounds; blood samples were pro-cessed following the BacT/Alert (Organon Teknika) procedure.A 10-mL blood culture inoculum was standard. “Antibioticresistance” was defined as in vitro resistance to ceftazidime. Inour hospital, ceftazidime resistance is considered to be an in-dicator of epidemic extended-spectrum
b
-lactamase–producingstrains or hyperproducers of 
 b
-lactamases, and, therefore, it isa sign of infection with organisms that are resistant to multipledrugs [6, 7]. Because susceptibility patterns for
 Pseudomonas aeruginosa 
 vary, such isolates were considered to be AB-R whenresistance to one of the following antipseudomonal antibioticswas seen: piperacillin, ciprofloxacin, ceftazidime, and imipen-em [8].Antibiotic resistance was determined according to methodsfor disk-diffusion testing recommended by the National Com-mittee for Clinical Laboratory Standards [9]. For the sake of convenience, cases of bacteremia were designated “AB-S bac-teremia” or “AB-R bacteremia,” depending on the antibiotic-resistance status of the isolated organisms. During the study period, no changes in microbiologic laboratorytechniqueswereseen. The source of the bacteremia was determined by intensivecare physicians and microbiologists, on the basisof theisolationof gram-negative bacteria from the presumed portal of entry and clinical evaluation. For the purpose of analysis, sources of bacteremia were divided into 3 categories: low risk (associatedmortality,
30%), which were sinus, urinary tract, intravenouscatheter, and soft-tissue sources; intermediate risk (associatedmortality, 31%–50%), which were primary sources of bacte-remia; and high risk (associated mortality,
 1
50%), which werelower respiratory tract and abdominal sources. Patients with
1
1 possible source of bacteremia (e.g., 1 low-risk and 1 high-risk source) were considered to have a high-risk source.Antibiotic therapy was considered to be “appropriate” if thedrugs used had in vitro activity against the isolated strain. Weconsidered antibiotic therapy to be “inadequate” if the drugsused did not have in vitro activity against the isolated strainor if the patient did not receive antibiotic treatment. The delay in the initiation of appropriate antibiotic treatment was cal-culated from the day of onset of bacteremia. “Acute respiratory failure” was defined as ventilator dependence; “acute renal fail-ure,” as the need for renal replacement therapy; and “hemo-dynamic instability,” as the need for vasopressive or inotropicsupport during the ICU stay. For the comparison of outcomes,survival status was evaluated at 14 and 28 days after the onsetof bacteremia and at the end of thehospitalstay(all3evaluationpoints are included in in-hospital mortality).
Statistical analysis.
 Continuous variables are given asor as median (lower–upper quartile), dependingmean
SDon the distribution. Comparative analyses were done with theMann-Whitney 
 
 test or the
 x
2
test, as appropriate. Survivalcurves were prepared by means of the Kaplan-Meier method,and univariate survival distributions were compared by the log-rank test. To assess the relationship between in-hospital mor-tality and a set of independent variables, a multivariatesurvivalanalysis was used (Cox proportional hazard model); hazardratios and 95% CIs are reported. In this multivariate analysis,continuous variables were handled continuously. Variables en-tered in the Cox regression model were required to have aplausible relationship with mortality, to avoid spurious asso-ciations. Statistical analyses were performed using Statistica,version 4.5 (StatSoft), and SPSS, version 9.0. All tests were 2tailed; was considered to be statistically significant.
!
.05
RESULTS
During the study period, 29,727 patients were admitted to theICU. Among these, 328 patients were identifiedashavinggram-
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1602
 
 CID 2002:34 (15 June)
 
 Blot et al.
Table 1. Characteristics of hospitalized, critically ill patients who had nosocomial bacteremia caused by gram-negative bacteria.
CharacteristicOutcome of hospital stay Type of bacteremiaDeath(
n
p
141)Survival(
n
p
187)
 
AB-S(
n
p
208)AB-R(
n
p
120)
 
Age, mean years
 
 SD 59
 
 14.3 49
 
 18.1
 !
.001 54
 
 17.4 52
 
 16.9 .303APACHE II score, mean
 
 SD 26
 
 9.4 22
 
 8.0
 !
.001 23
 
 9.0 23
 
 8.6 .814APACHE II–related expected mortality, mean %
 SD 50
 
 29.0 36
 
 25.1
 !
.001 41
 
 28.2 44
 
 27.3 .305Acute renal failure, % of patients 38.3 16.0
 !
.001 25.0 26.7 .431Hemodynamic instability, % of patients 86.5 75.9 .017 77.9 85.0 .117Acute respiratory failure, % of patients 95.7 92.0 .021 92.4 95.8 .227Ventilator dependence, median days (lower–upperquartile) 17 (628) 21 (834) .165 16 (527) 23 (1238)
 !
.001Length of ICU stay, median days(lower–upper quartile)Before onset of bacteremia 10 (318) 13 (624) .009 8 (3.517) 18 (933)
 !
.001After onset of bacteremia 8 (317) 12 (525) .002 10 (319) 11 (520) .321Total 18 (934) 28 (1446)
 !
.001 21 (940) 28.5 (1648)
 !
.001Length of hospitalization, median days(lower–upper quartile)Before onset of bacteremia 13 (527) 16 (727) .428 11 (522) 23 (1141)
 !
.001After onset of bacteremia 10 (321) 59 (28117)
 !
.001 27 (963.5) 35 (1077) .333Total 29 (1554) 76 (44144)
 !
.001 47 (2285) 60 (30130) .007Mortality at 14 days, % of patients 61.0 0 26.0 26.7 .550Mortality at 28 days, % of patients 81.0 0 34.1 35.8 .756In-hospital mortality, % of patients 100 0 41.8 45.0 .576
NOTE.
 AB-R, antibiotic resistant; AB-S, antibiotic susceptible; APACHE, acute physiology and chronic health evaluation; ICU, intensive care unit.
negative bacteremia and were included in the study cohort (aprevalence of 11.0 cases of gram-negative bacteremia per 1000ICU admissions). The mean age of the patients was 54
 years. The mean APACHE II score was , and the17.2 23
8.9mean APACHE II–related expected mortality was 42%
. Fifty-four percent of the patients were admitted to the27.8%ICU after a surgical procedure; 75% of these patients had non-elective surgery. Twenty percent of the patients were admittedafter experiencing trauma.Among the 328 cases of bacteremia included in the analysis,369 gram-negative isolates were identified. The most frequently detected gram-negative microorganisms were
 Escherichia coli 
( ),
 Enterobacter 
 species ( ),
 P. aeruginosa 
 (
p
71
 
p
68
 
p
),
 Klebsiella 
 species ( ),
 Acinetobacter 
 species ( ),62
 
p
52
 
p
51and
 Serratia 
 species ( ). In 36.6% (120 of 328) of the
p
27cases of bacteremia, the strain involved was AB-R. During thestudy period, the yearly rate of AB-R bacteremia remainedstable ( ) (data not shown).
p
.495
Outcome of hospital stay.
 Mortality rates at 14 days, at28 days, and at the end of the hospital stay were, respectively,26%, 35%, and 43%. The characteristics of the patients whodied in the hospital and the characteristics of those who sur-vived are compared in table 1. Patients who died in the hospitalgenerally were older and had higher APACHE II scores andAPACHE II–related expected mortality, and the prevalence of organ failure was also higher in this group. These patients hada shorter ICU stay and a shorter hospitalization. Of all bac-teremia-associated factors, only infection with
 P. aeruginosa 
and high-risk sources of bacteremiaweremoreprevalentamongnonsurvivors (table 2).
Patients with AB-S bacteremia versus those with AB-R bac- teremia.
 The population characteristics of patients withAB-S gram-negative bacteremia and those with AB-R gram-neg-ative bacteremia are listed in tables 1 and 2. Polymicrobialbloodstream infections were more likely to occur in the AB-R group. Furthermore, no important differences in severity of illness were found, but patients with AB-R bacteremia hada longer stay in the ICU, as well as in the hospital. This seemsto be the consequence of a longer hospitalization before theonset of the bacteremia; length of stay (both in ICU andhospital) after the onset of the bacteremia was not different.Antibiotic resistance was not associated with higher mor-tality rates (table 1). Figure 1 shows the survival curves forboth groups from the onset of bacteremia to the end of hos-
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