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Journal of Hospital Infection (2009) 73, 143e150

Available online at www.sciencedirect.com

www.elsevierhealth.com/journals/jhin

Risk factors and impact of nosocomial


Acinetobacter baumannii bloodstream infections
in the adult intensive care unit: a caseecontrol
study
T.-N. Jang a,b,c,*, S.-H. Lee b, C.-H. Huang a,b,c, C.-L. Lee b, W.-Y. Chen a
a
Section of Infectious Diseases, Department of Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei,
Taiwan
b
Infection Control Committee, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
c
School of Medicine, Catholic Fu-Jen University, Taipei, Taiwan

Received 16 January 2009; accepted 10 June 2009


Available online 27 August 2009

KEYWORDS Summary During a nine-year study period, 96 episodes of nosocomial


Acinetobacter bloodstream infection (BSI) due to Acinetobacter baumannii were
baumannii; identified in the adult intensive care units (ICUs) of Shin Kong Wu Ho-Su
Bloodstream infection;
Memorial Hospital. Seventy-seven (80.2%) of these were available for
Intensive care unit;
Risk factors
matching in terms of age, sex, primary diagnosis of ICU admission, ICU
ward, and disease severity. Univariate analysis showed that central venous
catheter use, ventilator use, prior A. baumannii colonisation, and respira-
tory and cardiovascular organ failure were significantly associated with
acquiring A. baumannii BSI in the ICU. By multivariate analysis, only prior
A. baumannii colonisation [odds ratio (OR): 3.81; P < 0.001] and cardiovas-
cular failure (OR: 2.24; P ¼ 0.04) were identified as independent risk
factors. The lower respiratory tract (32/77; 41.6%) was the most frequent
source of infection, followed by intravascular catheters (13/77; 16.9%).
Cumulative survival curves for patients with A. baumannii BSI and control
patients showed no significant difference (30 day crude mortality: 29.9%
and 27.3%, respectively; P ¼ 0.916). However, the mean length of ICU
and hospital stay and mean hospital cost of patients with A. baumannii
BSI significantly increased, with an estimated 8.7 days excess length of
ICU stay, 19.1 days excess hospital stay, and US $8480 extra hospital costs.
Imipenem and meropenem remained the most active antimicrobial agents,

* Corresponding author. Address: Section of Infectious Diseases, Department of Medicine, Shin Kong Wu Ho-Su Memorial Hospital,
95 Wen Chang Road, Shih Lin District, Taipei 111, Taiwan. Tel: þ886 228 33 2211; fax: þ886 228 33 1111.
E-mail address: m002137@ms.skh.org.tw

0195-6701/$ - see front matter ª 2009 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.jhin.2009.06.007
144 T.-N. Jang et al.

both with 95.5% susceptibility (MIC50 ¼ 0.25 and 0.5, respectively). Improv-
ing hand hygiene of healthcare workers and aseptic care of vascular
catheters and endotracheal tubes are important measures to prevent
A. baumannii colonisation and decrease the incidence of BSI.
ª 2009 The Hospital Infection Society. Published by Elsevier Ltd. All rights
reserved.

Introduction patients. During the study period (October 1997


through September 2006), patients in the ICUs
Acinetobacter baumannii, previously known as with one or more positive A. baumannii blood cul-
Acinetobacter calcoaceticus variant anitratus, is a tures were evaluated. Only adults (aged 18
non-fermenting Gram-negative aerobic coccobacil- years) were included in the study.
lus found extensively in the natural environment. It
can survive environmental desiccation for weeks, Case
a characteristic that promotes transmission through
fomites in hospitals.1 Recently, it has emerged as an A case of clinically significant A. baumannii BSI was
important nosocomial pathogen mainly affecting defined as any patient with one or more blood cul-
patients with impaired host defences in the inten- tures positive for A. baumannii, where clinical ev-
sive care unit (ICU) setting.2 Moreover, of particular idence of infection was present, such as fever,
concern is the increasing prevalence of A. baumannii leucocytosis, chills, and rigors, and where these
isolates with resistance to many of the commercially symptoms were present for more than 8 h. Nosoco-
available antibiotics, including cephalosporins, mial ICU-acquired BSI was defined as the isolation
aminoglycosides, quinolones, and carbapenems.3 of one or more positive blood cultures in a patient
Clinical infections caused by A. baumannii in- occurring 48 h after admission to the ICU.
clude pneumonia, meningitis, endocarditis, peri-
tonitis, skin and soft-tissue infections, bloodstream Control
infections (BSIs), and catheter-related and urinary
tract infections.4 Clinical manifestations of Each significant A. baumannii BSI case was
A. baumannii BSI may range from benign transient matched with a control patient without A. bau-
bacteraemia to fulminant disease and septic shock mannii BSI after controlling for age (within one de-
associated with an overall mortality (a crude mor- cade), sex, primary diagnosis of ICU admission, ICU
tality rate) as high as 46%.5,6 ward, and disease severity [Acute Physiological As-
Although various predisposing factors have sessment and Chronic Health Evaluation (APACHE
been analysed in different series, long-term II) score 5 points]. Control patients were re-
caseecontrol studies in a large cohort of critically quired to have had an ICU stay at least as long as
ill patients to determine the risk factors for the matched case patient’s stay before the onset
ICU-acquired A. baumannii BSI are rare. To improve of A. baumannii BSI. To ensure the same duration
the understanding of risk factors and clinical and of risk exposure, this time was called T0 and
economic impact associated with A. baumannii defined as follows: for case patients, T0 was the
BSI, this nine-year retrospective matched casee time the first A. baumannii positive blood sample
control study was conducted in the adult ICU of was obtained; and for control patients, T0 was
Shin Kong Wu Ho-Su Memorial Hospital. the time from ICU admission to the time at which
the matched case patient had his or her first blood
culture positive for A. baumannii.7
Methods
Clinical parameters
Setting
Recent surgery was defined as a surgical procedure
Shin Kong Wu Ho-Su Memorial Hospital is a 921-bed performed within 14 days of the onset of
tertiary care centre in the city of Taipei, Taiwan. A. baumannii BSI. Prior antibiotic therapy was de-
Its ICUs (medical, surgical, neurological and fined as the use of a systemic antimicrobial agent
neurosurgical, respiratory and advanced ICUs) for at least 48 h within the preceding 10 days. Col-
have a total of 58 beds for critically ill adult onisation and infection were defined according to
patients with an annual occupancy of about 2700 previously published criteria for the study of
Risk factors for A. baumannii bloodstream infections 145

nosocomial infections.8 The diagnosis of pneumo- tailed and P < 0.05 was considered statistically sig-
nia due to A. baumannii required new or progres- nificant. Survival curves were prepared using the
sive infiltrates on chest radiographic examination KaplaneMeier method and univariate survival dis-
and the isolation of A. baumannii from a blood cul- tributions were compared using the log rank test.
ture. If pulmonary infiltrates were absent and the The SPSS software package, version 13.0 (SPSS
same A. baumannii strain was cultured from blood Inc., Chicago, IL, USA) was used for all analyses.
and sputum or bronchial secretions, the patient
was categorised as tracheobronchitis and bacter-
aemia. Catheter-related bacteraemia was diag-
nosed when the same organism was isolated in Results
blood cultures and in semiquantitative catheter
tip cultures (15 or more colonies), and if no During the nine-year study period, 106 episodes of
primary site other than the intravascular catheter nosocomial BSI due to A. baumannii in the adult
was identified. The presence of organ system ICUs were found. Of these, 10 episodes did not ful-
failure was evaluated by using the criteria fil the criteria and were excluded from the study. A
described by Fagon et al.9 Antimicrobial therapy total of 96 episodes of significant nosocomial BSI
was considered to be appropriate if one or more were identified, with an infection rate of 0.56 ep-
antimicrobial agents were active in vitro against isodes per 1000 patient-days. The incidence was
A. baumannii when the agent(s) was given at an relatively stable with 10.7  5 cases per year.
adequate dosage via an appropriate route for at The mean interval between ICU admission and
least two days within three days of obtaining identification of A. baumannii BSI was
a blood culture. Mortality was defined as death 16.05  14.85 days. Of these, 77 cases were
within 30 days of the first positive blood culture. matched according to the specified criteria and
were enrolled in the study. The characteristics of
Antimicrobial susceptibility testing cases and their matched controls are shown in
Table I. The average age, sex ratios and primary
ICU admission diagnosis were almost the same.
Blood specimens were obtained by percutaneous
The mean APACHE II scores of cases and controls
venepuncture and inoculated in a two-bottle blood
were 22.48  5.88 and 22.18  6.27, respectively,
culture system (Organon Teknika, Durham, NC,
which indicated no difference in disease severity
USA). A. baumannii was identified with the auto-
between the two groups.
matic API 20NE system (API-BioMérieux, LaBalme
Risk factors for acquiring A. baumannii BSI in
Les Grotles, France). Isolates identified as mem-
the ICU are shown in Table II. By univariate analy-
bers of the A. baumannii/calcoaceticus complex
ses, the following variables were significantly asso-
were grouped with A. baumannii. Minimum inhibi-
ciated with A. baumannii BSI in the ICU: central
tory concentrations (MICs) of antimicrobial agents
venous catheter use, ventilator use, prior A. bau-
for the isolates were determined by the agar dilu-
mannii colonisation, and respiratory and cardio-
tion method using the guidelines of the Clinical
vascular organ failure. Variables identified as
and Laboratory Standards Institute.10
significant risk factors were included in the step-
wise logistic regression analyses. After adjustment
Statistical analysis for confounding factors, only prior A. baumannii
colonisation [odds ratio (OR): 3.81; P < 0.001]
Proportions were compared by the c2-test or Fish- and cardiovascular failure (OR: 2.24; P ¼ 0.04)
er’s exact test, as appropriate, whereas continu- were independent risk factors associated with
ous variables were compared using independent A. baumannii BSI.
samples t-test. The length of hospital stay and Sources of infection were identified in 58.4% (45/
costs of hospitalisation were compared between 77) of the cases. The respiratory tract (32; 41.6%)
case patients and control patients. Hospital costs was the most frequent source, followed by intra-
were obtained from each patient’s invoice. The vascular catheter (13; 16.9%). For the rest (32;
excess length of stay and extra costs attributed 41.6%), the source of infection could not be identi-
to A. baumannii infection were defined as the dif- fied. Of the 32 cases originating from the respiratory
ferences between cases and controls. To deter- tract, 27 cases were diagnosed as having ventilator-
mine independent risk factors, a multivariate associated pneumonia. The remaining five cases
logistic regression model was used. All variables were classified as tracheobronchitis due to no
with P < 0.05 on univariate analysis were included obvious new or progressive pulmonary infiltration
in the multivariate model. All P-values were two- on chest radiographic examination.
146 T.-N. Jang et al.

Table I Demographic data and primary diagnosis of cases and matched controls
Parameter Cases (%) Controls (%) P-value
N ¼ 77 N ¼ 77
Agea 69.24  14.63 69.75  14.14 0.827
Male sex 33 (42.9) 33 (42.9) NS
Primary ICU admission diagnosis
Pneumonia 21 (27.3) 21 (27.3) NS
Intracranial haemorrhage 13 (16.9) 14 (18.2) NS
Sepsis 8 (10.4) 8 (10.4) NS
Respiratory failure 7 (9.1) 7 (9.1) NS
Acute myocardial infarction 5 (6.5) 4 (5.2) NS
Gastrointestinal bleeding 4 (5.2) 4 (5.2) NS
Coronary artery disease 2 (2.6) 3 (3.9) NS
Craniotomy 3 (3.9) 3 (3.9) NS
Acute cholecystitis 2 (2.6) 2 (2.6) NS
Aortic aneurysm 2 (2.6) 2 (2.6) NS
Intra-abdominal surgery 2 (2.6) 2 (2.6) NS
Shock 2 (2.6) 2 (2.6) NS
Cerebral infarct 2 (2.6) 1 (1.3) NS
Othersb 4 (5.2) 4 (5.2) NS
APACHE II scorea 22.48  5.88 22.18  6.27 NS
Duration of ICU stay (days)a 35.49  29.66 26.78  19.87 0.034
Duration of hospital stay (days)a,c 77.08  70.56 58.01  42.31 0.045
Costs of hospitalisation (US $)a,c 30,651  23,495 22,171  14,756 0.009
ICU, intensive care unit; APACHE, Acute Physiological Assessment and Chronic Health Evaluation.
a
Mean  SD.
b
Others, including chronic obstructive pulmonary disease with acute exacerbation, hyperosmolar hyperglycaemic state, heart
failure, and multiple traumatic injury.
c
Seventy-six matched caseecontrol pairs were included in the analysis of hospital stay and cost.

The mean time (SD) from infection to death was tested antimicrobials, imipenem and meropenem
10.26  9.33 days. The crude 30 day mortality rates were the most active against A. baumannii,
for the case and control patients were 29.9% (23/77) followed by ampicillin-sulbactam, levofloxacin,
and 27.3% (21/77), respectively. Thus, the esti- cefepime, ciprofloxacin, ceftazidime and piperacil-
mated attributable mortality rate due to A. bau- lin-tazobactam. Forty-nine out of 77 cases had
mannii BSI was only 2.6%. Cumulative survival received early appropriate antibiotic treatment.
curves for patients with A. baumannii BSI and con- Of these, piperacillin-tazobactam was used in 10
trol patients are compared in Figure 1. The differ- (20.4%) patients, ceftazidime in 10 (20.4%), fluoro-
ence of 30 day mortality between the two groups quinolones in 10 (20.4%), piperacillin in six (12.2%)
was not significant (P ¼ 0.916; log rank test). The and carbapenems in five patients (10.2%). In 10
mean length of ICU stay (SD) for patients with cases, aminoglycosides were used in combination.
A. baumannii BSI was 35.49  29.66 days, and was Patients who received early appropriate antibiotic
26.78  19.87 days for the matched controls treatment had a lower mortality rate than those
(P ¼ 0.034). The mean length of total hospital stay who received inappropriate antibiotic treatment
(SD) was 77.08  70.56 days for the cases and (24.5% vs 39.3%). However, the difference was not
58.01  42.31 days for the controls (P ¼ 0.045), significant.
and the mean costs of hospitalisation (SD) were
US $30,651  23,495 and $22,171  14,756 for the
cases and controls, respectively (P ¼ 0.009). Thus, Discussion
A. baumannii BSI patients had 8.7 and 19.1 days ex-
cess length of ICU and hospital stay, respectively, A. baumannii was previously considered an organ-
and $8480 extra hospital costs, compared with ism of low virulence.6 It is now increasingly re-
matched controls (Table I). ported as an important nosocomial pathogen
Among the 77 enrolled A. baumannii BSI cases, 67 implicated in outbreaks of respiratory, blood, cen-
isolates were retrieved for MIC, MIC50, MIC90, and tral nervous system, and wound infections.6,11e14
susceptibility studies (Table III). Among the 11 In one report from an Israeli teaching hospital,
Risk factors for A. baumannii bloodstream infections 147

Table II Risk factors in acquiring A. baumannii bloodstream infection in the intensive care unit by univariate
analysis
Risk factors Cases (%) Controls (%) P-value Odds ratio
N ¼ 77 N ¼ 77 (95% CI)
Invasive procedures
Central venous catheter 74 (96.1) 64 (83.1) 0.017 5.01 (1.37e18.37)
Arterial catheter 44 (57.1) 32 (41.6) 0.076 1.88 (0.99e3.56)
Ventilator 73 (94.8) 64 (83.1) 0.004 3.71 (1.15e11.94)
Chest tube 4 (5.2) 5 (6.5) 1.000 0.79 (0.20e3.06)
Nasogastric tube 74 (96.1) 72 (93.5) 0.719 1.71 (0.40e7.43)
Abdominal drain 7 (9.1) 11 (14.3) 0.452 0.60 (0.22e1.64)
Urinary catheter 70 (90.9) 67 (87.0) 0.607 1.49 (0.54e4.15)
Total parenteral nutrition 4 (5.2) 8 (10.4) 0.367 0.47 (0.14e1.64)
Recent major surgery 23 (29.9) 22 (28.6) 1.000 1.07 (0.53e2.13)
Prior antibiotic treatment 75 (97.4) 76 (98.7) 1.000 0.49 (0.04e5.56)
Third-generation cephalosporins 25 (32.5) 19 (24.7) 0.372 1.47 (0.73e2.97)
Fluoroquinolones 14 (18.2) 17 (22.1) 0.688 0.79 (0.36e1.73)
Aminoglycosides 35 (45.5) 45 (58.4) 0.147 0.59 (0.31e1.12)
Immunosuppression 17 (22.1) 10 (13.0) 0.204 1.90 (0.81e4.47)
Neutropenia 1 (1.3) 0 (0.0) 1.000 NA
Prior A. baumannii colonisation 40 (52.0) 16 (20.8) <0.001 4.12 (2.03e8.38)
Organ failures
Respiratory 33 (42.9) 18 (23.4) 0.017 2.46 (1.23e4.92)
Cardiovascular 36 (46.8) 18 (23.4) 0.004 2.88 (1.44e5.75)
Renal 29 (37.7) 25 (32.5) 0.612 1.26 (0.65e2.44)
Hepatic 4 (5.2) 6 (7.8) 0.744 0.65 (0.18e2.39)
CI, confidence interval; NA, not available.

acinetobacter had advanced from the fourth most


common bacterium resulting in bloodstream infec-
1.0 tions in 1997 to the most frequent cause in 2002.15
In addition to an ICU stay, risk factors for
A. baumannii colonisation and infection are recent
0.8 surgery, central vascular catheterisation, tracheos-
tomy, mechanical ventilation, enteral feedings,
APACHE II score, underlying malignancy, prior
Cumulative survial

infection, organ system failure, prolonged hospital-


0.6
isation, and prior antibiotic use (in particular,
third-generation cephalosporins and aminoglyco-
sides).5,11,16e19 Most of these potential risk factors
0.4 have been identified by univariate analysis but are
not part of a caseecontrol study, and thus may
simply reflect underlying disease severity or
a need for critical care. A prospective cohort study
0.2
in the ICU has demonstrated that immunosuppres-
sion, unscheduled hospital admission, respiratory
failure on ICU admission, previous antimicrobial
0.0 therapy, previous sepsis in the ICU, and invasive
procedures index are independently associated
0 5 10 15 20 25 30
with A. baumannii BSI.20 Grupper et al.’s three-
Day after T0
year prospective caseecontrol study found that
Figure 1 Cumulative survival curves of patients with mechanical ventilator use, central venous catheter
Acinetobacter baumannii bloodstream infection (solid in place, and previous antibiotic treatment were
line) and their matched control patients (dashed line) significantly associated with acinetobacter BSI in
(P ¼ 0.916; log rank test). univariate analysis.7
148 T.-N. Jang et al.

Table III Minimum inhibitory concentration (MIC), MIC50, MIC90 values and susceptibilities of 67 bloodstream
infection isolates to 11 antibiotics
Antimicrobial agents MIC (mg/mL) CLSI Susceptibility
breakpoints rate (%)
(mg/mL)
Range 50% 90% Sensitive
Ampicillin-sulbactam 0.5 to >256 4 32 8/4 77.6
Piperacillin-tazobactam 2 to >128 16 128 16/4 59.7
Ceftazidime 1 to >256 8 256 8 59.7
Cefepime 0.5 to 256 4 64 8 62.7
Aztreonam 2 to 256 32 128 8 a 7.5
Imipenem 0.03 to 32 0.25 2 4 95.5
Meropenem 0.125 to 64 0.5 1 4 95.5
Amikacin 1 to >256 8 >256 16 58.2
Levofloxacin 0.06 to 32 0.25 16 2 71.6
Ciprofloxacin 0.25 to >256 0.5 128 1 59.7
Colistin 1 to 128 2 8 2 53.7
a
No definite Clinical and Laboratory Standards Institute (CLSI) breakpoint was available but we used 8 as the breakpoint
according to those of third-generation cephalosporins.

In the present study, prior antibiotic therapy for death.25 An earlier study of acinetobacter bac-
and immunosuppression were similar in both teraemia also reported that outcome of the infec-
groups. None of the invasive procedures, including tion correlated more closely with the type of
recent major surgery, was identified as a risk underlying illness than with other factors.12
factor by multivariate analysis. Only prior A. bau- In this study design, adequate matching be-
mannii colonisation and cardiovascular organ fail- tween case patients and control patients elimi-
ure were the independent risk factors associated nated the influence of comorbid conditions.
with A. baumannii BSI. Prior A. baumannii coloni- Mortality attributable to A. baumannii BSI was
sation had the strongest association with the only 2.6%, while the cumulative survival curves
acquisition of A. baumannii BSI (OR: 3.81; for patients with A. baumannii BSI and control pa-
P < 0.001). This finding was consistent with a previ- tients showed no significant difference. This result
ous caseecontrol study in which prior colonisation is similar to a previous caseecontrol study in ICU
with A. baumannii was identified as the most sig- which also showed that A. baumannii bacteraemia
nificant independent risk factor of A. baumannii is not associated with a significantly increased
BSI (OR: 26.23; P ¼ 0.0002) in a burns ICU.21 mortality rate in critically ill patients.26 Another
An intravascular catheter and the lower re- caseecontrol study in a burns ICU also revealed
spiratory tract are two major portals of entry for that only 7% death was directly related to A. bau-
A. baumannii, with the respiratory tract as the mannii bacteraemia.21 These investigators con-
leading infection source in this (41.6%) and other cluded that A. baumannii was an opportunistic
studies whereas the intravascular catheter was pathogen and that underlying illnesses seemed to
the leading infection source in other investiga- play a more important role than the infection itself
tions.6,7,12,22e24 The source of A. baumannii BSI as the cause of death.
cannot be identified in 41.6% of cases in the pres- Although the mortality rate of A. baumannii BSI
ent study. This is comparable to previous reports in did not show significant difference compared with
which the source of A. baumannii BSI was undeter- the controls, the mean length of ICU and hospital
mined in 36.9e38% of cases.7,22 stay and mean hospital cost significantly in-
Mortality in the current series is 29.9% and creased, with an estimated 8.7 days excess length
comparable to the range of 22e46% reported in of ICU stay, 19.1 days excess hospital stay, and
other published series.5,12,22e24 Nevertheless, US $8480 extra hospital cost. These results were
crude mortality rates reflect deaths due to pa- similar to those of a previous caseecontrol study
tients’ underlying diseases as well as deaths due of nosocomial BSI in critically ill patients that re-
to infections. Our previous study of nosocomial vealed extra ICU stay of 8 days, hospital stay of
Gram-negative BSI in the critically ill revealed un- 24 days, and hospital costs of $40,890 among
derlying illnesses as the independent risk factors survivors.27
Risk factors for A. baumannii bloodstream infections 149

In recent years, the emergence of carbapenem- risk factor in acquiring A. baumannii BSI in criti-
resistant or even pandrug-resistant A. baumannii cally ill patients. The lower respiratory tract and
has been an increasing problem for both the con- intravascular catheters are the most frequently
trol and treatment of nosocomial infections.3 A re- identified sources of this infection. Improving
port of 399 episodes of acinetobacter BSI from a UK hand hygiene of healthcare workers and aseptic
tertiary care centre showed carbapenem resis- care of vascular catheters and endotracheal tubes
tance rising from 0% in 1998 to 55% in 2006.28 In are important measures to prevent A. baumannii
Taiwan, carbapenem-resistant A. baumannii was colonisation and reduce the incidence of BSI. Strict
also prevalent. A previous study in a university hos- antibiotic control is the most important measure in
pital showed that the incidence of carbapenem-re- the prevention of drug resistance and in reducing
sistant A. baumannii as causes of nosocomial the impact of growing A. baumannii BSI.
infection increased from 5.88% in 1993 to 21.5%
in 2000. The study also mentioned that this trend
correlated with the increasing use of carbapenem
Conflict of interest statement
and ciprofloxacin, but not with the use of
None declared.
extended spectrum cephalosporins and aminogly-
cosides.3 A caseecontrol study of multidrug-resis-
Funding sources
tant A. baumannii BSI from southern Taiwan
None.
showed that the group with resistant strains had
a 21.8% attributable mortality.29
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