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Acinetobacter bacteraemia in a teaching hospital, 1989–1998
European Journal of Internal Medicine 12 (2001) 425–429 www.elsevier.com / locate / ejim
Original article
Acinetobacter bacteraemia in a teaching hospital, 1989–1998 c d ´ Palomo a , P. Matorras b , C. Fernandez-Mazarrasa ´ ´ ´ C. Valero a , J.D. Garcıa , C. Gonzalez Fernandez , ˜ a ,* M.C. Farinas
b
a ´ de Valdecilla, Avd. Valdecilla s /n, 39008 Santander, Spain Infectious Diseases Unit, Hospital Universitario Marques ´ de Valdecilla, Avd. Valdecilla s /n, 39008 Santander, Spain Department of Internal Medicine, Hospital Universitario Marques c ´ de Valdecilla, Avd. Valdecilla s /n, 39008 Santander, Spain Department of Microbiology, Hospital Universitario Marques d ´ de Valdecilla, Avd. Valdecilla s /n, 39008 Santander, Spain Intensive Care Medicine, Hospital Universitario Marques
Received 4 September 2000; received in revised form 1 March 2001; accepted 13 March 2001
Abstract Background: The mortality rate from bacteraemia is one of the highest among infections in hospitals, especially in the intensive care unit (ICU). Recently, an increase in nosocomial bacteraemia caused by gram-negative resistant pathogens has been observed. In this work we review the clinical and laboratory findings of adult patients with Acinetobacter bacteraemia in order to identify risk factors associated with mortality. Methods: A retrospective review of the medical records of patients with Acinetobacter bacteraemia identified by blood cultures from the Diagnostic Microbiology Laboratory was conducted between January 1989 and March 1998. Results: We identified 59 cases of Acinetobacter bacteraemia. Most of the infections (71%) were nosocomial; the majority occurred in the Department of Internal Medicine (28.8%), followed by Haematology (27%) and the ICU (23%). A. lwoffii was isolated in 52.5% of cases and A. baumannii in 47.5%. The related mortality was 17%. Staying in the ICU was associated with A. baumannii bacteraemia (P , 0.004). An intravascular catheter was the leading source of infection (37%). Main risk factors were mechanical ventilation (28%), parenteral nutrition (23%) and the presence of a urinary catheter (22%). In the multivariate analysis the independent prognostic factors for mortality were the presence of shock (P , 0.05) and the severity of the underlying disease, according to the classification of McCabe (P , 0.05). Conclusions: The incidence of Acinetobacter bacteraemia has increased in the last decade, mainly since 1995. The development of septic shock and the severity of the underlying disease appear to be associated with an increase in mortality. 2001 Elsevier Science B.V. All rights reserved. Keywords: Bacteraemia; Acinetobacter
1. Introduction Bacteraemia is currently one of the infections with the highest mortality in hospitals [1,2]. In recent years, an increase in patients with nosocomial bacteraemia caused by gram-positive organisms has been observed [1]. However, contrary to expectations, the number of cases of gram-negative bacteraemia have barely fallen, due to the rise in resistant pathogens such as Acinetobacter [3,4]. *Corresponding author. Fax: 134-942-202660. ˜ E-mail address: [email protected] (M.C. Farinas).
These gram-negative bacteria are opportunist pathogens, highly resistant to antimicrobial agents. Clinical illnesses associated with Acinetobacter include pneumonia, meningitis, peritonitis, endocarditis and infections of the urinary tract and skin [5–7]. Patients are more susceptible to these illnesses when treated with an endovenous catheter, mechanical ventilation or when located in an ICU [2,8–11]. The fact that published series on bacteraemia from Acinetobacter are scarce and that the few existing studies have found varied infection rates led us to review our university teaching hospital’s records on Acinetobacter episodes in the last 9 years, analysing clinical and mi-
0953-6205 / 01 / $ – see front matter 2001 Elsevier Science B.V. All rights reserved. PII: S0953-6205( 01 )00150-9
426
C. Valero et al. / European Journal of Internal Medicine 12 (2001) 425 – 429
crobiologic aspects, risk factors and predictors of mortality.
2. Patients and methods This study was conducted at an 1100-bed university hospital from January 1989 to March 1998. Cases were identified by retrospective review of all blood culture isolates reported as Acinetobacter by the Diagnostic Microbiology Laboratory during the 9-year period. Information collected from the clinical records included patient age, sex, average hospital stay, attending unit, risk factors, underlying diseases, date and source of bacteraemia, presence of organisms other than Acinetobacter, initial antibiotic used, complications, clinical outcome and, if applicable, cause of death. Contaminants were organisms isolated from single positive blood cultures that were not associated with clinical symptoms [12]. These contaminants were excluded from the study.
2.1. Microbiological methods Blood cultures were processed by the microbiology laboratory using the Bactec system (Becton Dickinson, Cockeysville, MD, USA). Identification of the micro-organisms, as well as their sensitivity to antimicrobial agents, was carried out with the Microscan system (Autoscan), using the panel Neg combo 61, and following National Committee for Clinical Laboratory Standards (NCCLS) criteria [13].
respiratory infection and the sputum culture or respiratory secretions showed Acinetobacter, as well as in cases in which chest X-ray showed pulmonary infiltration, which was later resolved with the antibiotic treatment established for the bacteraemia. In cases involving cellulitis or infections from surgical injury, these were considered bacteraemia foci in the absence of any other obvious source. The diagnoses of endocarditis met Duke’s criteria [15]. Inflammatory response syndrome, sepsis and septic shock were diagnosed according to the criteria established by the Intensive Care and Respiratory Society, established at the Chicago Consensus Conference [16]. The presence of associated underlying illness was categorised by criteria set forth by McCabe and Jackson [17]. We analysed the antibiotic treatment administered in all episodes after the results of antimicrobial susceptibility testing became available. Appropriate therapy was defined as administration for at least 24 h of an antibiotic to which the organism was susceptible; the antibiotic was administered after collection for culture [12]. Death was considered bacteraemia-related if it occurred in the phase of active infection and without evidence of any other attributable cause.
2.3. Statistical analysis The chi-square test and Fisher’s test were used. Differences were considered significant by chi-square if P , 0.05 (two-sided). Multivariate analysis of the predictive factors of mortality was carried out using logistic regression analysis.
2.2. Parameters Episodes were categorised as community or nosocomially acquired following the Centres for Diseases Control (CDC) definitions [14]. The following parameters were considered risk factors for bacteraemia: presence of central venous catheter, orotracheal intubation, parenteral nourishment, urinary or nasogastric intubation at least 48 h before blood culture; bone marrow or solid organ transplant in the previous month; chemotherapy or cytotoxic treatment in the previous 6 weeks; treatment with corticosteroids or antibiotics in the previous 2 weeks; and surgery, the presence of neutropenia (granulocytes ,500 cells / mm 3 ), or an acute cerebrovascular event in the week prior to positive blood cultures. The bacteraemia was attributed to a central venous catheter when there were local signs of phlebitis at the insertion site or when the catheter was withdrawn and the sepsis manifestation was resolved in less than 48 h without evidence of other bacteraemia foci. The infection was considered urinary if Acinetobacter was isolated in the urine or if clinical signs of urinary infection were reported within the context of the bacteraemia episode. Focus was deemed respiratory when the clinical picture indicated
3. Results Over the 9 years covered in our study, we detected 59 patients with Acinetobacter bacteraemia (1.8 episodes per 10 000 admissions). The year-by-year distribution was not homogenous, with a clear increase after 1995 (8.9 per 10 000 admissions). The average age of the patients was 50.5623 years, and 66% were male. Acquisition was nosocomial in 42 cases (71%), and community in 17 patients (29%). The highest number of cases was recorded in the Department of Internal Medicine, with 17 patients (28.8%), followed by Haematology, with 16 patients (27%), and the ICU, with 14 (23%). The accumulated percentage of the three departments was 84%. The average hospital stay was 29.5621.8 days (range 1–95 days). The average number of blood cultures extracted from each patient was 3.6 (of which Acinetobacter was isolated in 2.4). A. lwoffii was isolated in 52.5% of the bacteraemias (31 cases) and A. baumannii in 47.5% (28 cases). One-third of the bacteraemias were polymicrobial (35.5%); the isolated organisms associated with Acinetobacter were Staphylococcus epidermidis (15 cases),
C. Valero et al. / European Journal of Internal Medicine 12 (2001) 425 – 429
Enterococcus faecalis (two cases), Stenotrophomonas maltophilia (two cases) and Escherichia coli, Pseudomonas aeruginosa, S. haemolyticus and S. equorum (one case each). In the majority of cases (19 patients), Acinetobacter was associated with only one organism. Complications were studied according to species, and there were only significant differences in the case of septic shock, in favour of A. baumannii (P , 0.05). An analysis of the species’ distribution in the different departments showed that 93% of the bacteraemia episodes in the ICU were due to A. baumannii, compared with 41% in the Department of Internal Medicine and 19% in Haematology. The source of Acinetobacter bacteraemia was an intravascular catheter in 22 cases (37%), respiratory in 11 cases (11.6%), and a soft tissue infection in four cases (6.7%). In nearly one-third of the cases, the focus was unknown (30.5%). Forty-four patients developed sepsis (75%) and another nine developed septic shock (15%). Only one patient was diagnosed as having endocarditis of the native mitral valve due to A. lwoffii. In the remaining patients there was either no evidence of endocarditis (12%) or it was not studied (86%). Malignant diseases (haematological in 15 cases and solid in 10 cases) and chronic obstructive lung disease (five cases) were the major underlying conditions. Eight patients had suffered a polytraumatism. Following McCabe’s classification, 18 patients had a nonfatal disease (30%), 31 an ultimately fatal disease (53%) and 10 a rapidly fatal disease (17%). The risk factors were distributed as follows: mechanical ventilation in 17 patients (28%), parenteral nourishment in 14 (23%) and urinary catheter in 13 (22%). More than half of the patients (54%) had received treatment with antibiotics in the 15 days prior to the onset of bacteraemia and 11 patients (18.6%) underwent surgery. Risk factors associated with A. baumannii bacteraemia are shown in Table 1. In the multivariate analysis, only the stay in the ICU was associated with A. baumannii bacteraemia (P , 0.05). Forty-eight patients (81%) received antibiotic treatment, the majority with one antibiotic. Only 30% of the treatments were considered appropriate. In our cases, no resistance to imipenem was observed. Resistance to third-
427
Table 2 Univariate analysis of factors influencing mortality among patients with Acinetobacter bacteraemia No. of patients who died / total No. patients (%)
Pa
Acinetobacter A. baumannii A. lwoffii
7 / 28 (25) 3 / 31 (30)
NS
Sepsis Yes No
10 / 44 (23) 0 / 15 (0)
,0.05
Septic shock Yes No
7 / 9 (77) 3 / 50 (6)
,0.05
McCabe’ s classification Nonfatal Ultimately fatal Rapidly fatal
0 / 18 (0) 2 / 31 (6) 8 / 10 (80)
Urinary tract catheter Yes No
5 / 13 (38) 5 / 46 (11)
Variable
,0.05
,0.05
Leukocyte count ( . 12 000 or , 2000) Yes 9 / 33 (27) No 1 / 26 (4)
,0.05
Albumin ( g /dl) $3.5 #3.4
,0.05
2 / 31 (6) 8 / 28 (28)
NS, not significant. a Univariate analysis.
generation cephalosporins was 50–75% for A. baumannii and 2–6% for A. lwoffii. Seventeen patients died (overall mortality 28.8%). In 10 cases, death was related to bacteraemia (17%) and in seven it was due to other causes. The average survival time of the patients who died was 1.8 days from the date of the blood culture. The predictive factors for mortality in the univariate analysis are shown in Table 2. In the multivariate analysis, predictors for mortality were the presence of shock (P , 0.05) and the higher severity of the underlying
Table 1 Univariate analysis of risk factors influencing mortality according to Acinetobacter species
Mechanical ventilation Parenteral nutrition Urinary catheter Immunosuppression Neutropenia ICU a
Univariate analysis.
No. of patients with the risk factor / total
A. baumannii No. (%)
A. lwoffii No. (%)
Pa
17 / 59 14 / 59 13 / 59 22 / 58 16 / 59 14 / 59
15 11 11 7 4 13
2 3 2 15 12 1
0.000 0.008 0.003 0.056 0.03 0.000
(88) (79) (85) (32) (25) (93)
(12) (21) (15) (22) (75) (7)
C. Valero et al. / European Journal of Internal Medicine 12 (2001) 425 – 429
428
Table 3 Multivariate logistic regression analysis predicting mortality in patients with Acinetobacter bacteraemia Variable
Coefficient
Standard error of the coefficient
95% CI
P
McCabe Shock Constant
3.77 3.15 211.09
1.28 1.36 3.36
1.20–6.33 0.42–5.88
0.005 0.024
No. of observations 59; model chi-square 35.11; significance 0.0000. CI, confidence interval.
disease according to McCabe’s classification (P , 0.05; Table 3).
4. Discussion In the past decade, the rate of bacteraemia due to Acinetobacter infection has clearly risen, mainly in ICUs. These rates vary from one hospital to another in relation to the type of patients involved. In a recent study on bacteraemias in ICUs, Acinetobacter represented 3.8% of the total, and 12% of those were caused by gram-negative bacteria [2]. In our hospital, the overall rate of Acinetobacter bacteraemia was 1.8 per 10 000 admissions. The rate of Acinetobacter bacteraemia varies according to the published series from 0.3 / 1000 to 1.8 / 1000 [12,18]. The rate was even higher (10.4% of admissions) in a study conducted in ICUs only [19]. These variations can be explained, in part, by different risk factors and transmission mechanisms in the different hospitals. As expected, Acinetobacter spp. bacteraemia in our study was mainly nosocomial (71%), which is somewhat lower than in other studies. A noteworthy difference was that the highest number of cases came from the Department of Internal Medicine (29%), followed by Haematology (27%) and the ICU (23%). Studies conducted in other hospitals have reported that ICUs are clearly the prominent source of bacteraemia due to Acinetobacter [20,21]. This may partly be explained by the fact that, in other series, the rate of community-acquired bacteraemia infections was low, whereas in our study it reached 30%. If we consider only nosocomial bacteraemias, the order is reversed, and the department that recorded the greatest number of cases was the ICU with 31%, followed by the Department of Internal Medicine with 24%. We found that more than half of the bacteraemias were due to A. lwoffii, whereas most studies in the literature focus on A. baumannii, with only a few reports on infections due to A. lwoffii. In fact, in a study of 584 Acinetobacter-positive samples, 72.9% were A. baumannii and only 3.6% were A. lwoffii [22]. We do not have an explanation for the discrepancy between this tendency and our finding. Central venous catheters were the most frequent source of cases (37%); rates reported in the literature range from
11 to 46% [12,18]. A. lwoffii has traditionally been associated more with catheter-related infection, and these bacteraemias have tended to have a more benign evolution. Seifert et al. [8] described 13 cases of bacteraemia due to A. johnsonnii (A. calcoaceticus var. lwoffii) associated with catheterisation, highlighting their positive evolution when the catheter was withdrawn, regardless of whether appropriate antibiotics were administered. We did not find any association between the species of Acinetobacter and catheter-related bacteraemia, nor was mortality related to bacteraemia after catheterisation. These results are similar to those of Beck-Sague et al. [19], who reported on 72 patients with catheter-related A. baumannii bacteraemia and who found that their mortality rate was not higher than that in a control group. In our study, the respiratory focus was the second most frequent (11.6%), although the literature shows rates ranging from 31 to 71% [18,20]. This is attributable to the fact that the number of bacteraemias due to Acinetobacter found in ICUs is low, and respiratory focus is most frequent in these units. In a high percentage of our cases (30%), the focus of infection was unknown; this figure is similar to those reported in other studies [11]. Endocarditis due to Acinetobacter is uncommon, has a high mortality rate and has mostly been described in patients with predisposing risk factors [7,23]. Mechanical ventilation, parenteral nutrition and the presence of a urinary catheter were the most frequent invasive processes to which our patients were submitted. The rate of these processes was lower than those reported in other studies [18,19,24–26]. The clinical manifestations of bacteraemia were non-specific. Septic shock was presented by 15% of our patients, similar to figures reported in other studies which describe septic shock in 25–30% of cases [18,20]. In our series, bacteraemia-related mortality was low (17%) compared to other studies, with rates of 19 and 32% [18,20]. This may be due to the relatively high number of community-acquired bacteraemia infections or to a predominance of A. lwoffii infections. The development of septic shock and the severity of the underlying disease were associated with an increase in mortality. The present study thus confirms that bacteraemia due to Acinetobacter is a major nosocomial infection which is associated with high morbidity and mortality. Together with Acinetobacter’s high resistance to antibiotics, this indicates that further study is needed to determine the best strategies for both prevention and treatment of these infections.
References [1] Vincent JL, Bihari DJ, Suter PM, Bruining HA, White J, NicolasChanoin MH et al. The prevalence of nosocomial infection in intensive care units in Europe. Results of the European Prevalence
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Original article
Acinetobacter bacteraemia in a teaching hospital, 1989–1998 c d ´ Palomo a , P. Matorras b , C. Fernandez-Mazarrasa ´ ´ ´ C. Valero a , J.D. Garcıa , C. Gonzalez Fernandez , ˜ a ,* M.C. Farinas
b
a ´ de Valdecilla, Avd. Valdecilla s /n, 39008 Santander, Spain Infectious Diseases Unit, Hospital Universitario Marques ´ de Valdecilla, Avd. Valdecilla s /n, 39008 Santander, Spain Department of Internal Medicine, Hospital Universitario Marques c ´ de Valdecilla, Avd. Valdecilla s /n, 39008 Santander, Spain Department of Microbiology, Hospital Universitario Marques d ´ de Valdecilla, Avd. Valdecilla s /n, 39008 Santander, Spain Intensive Care Medicine, Hospital Universitario Marques
Received 4 September 2000; received in revised form 1 March 2001; accepted 13 March 2001
Abstract Background: The mortality rate from bacteraemia is one of the highest among infections in hospitals, especially in the intensive care unit (ICU). Recently, an increase in nosocomial bacteraemia caused by gram-negative resistant pathogens has been observed. In this work we review the clinical and laboratory findings of adult patients with Acinetobacter bacteraemia in order to identify risk factors associated with mortality. Methods: A retrospective review of the medical records of patients with Acinetobacter bacteraemia identified by blood cultures from the Diagnostic Microbiology Laboratory was conducted between January 1989 and March 1998. Results: We identified 59 cases of Acinetobacter bacteraemia. Most of the infections (71%) were nosocomial; the majority occurred in the Department of Internal Medicine (28.8%), followed by Haematology (27%) and the ICU (23%). A. lwoffii was isolated in 52.5% of cases and A. baumannii in 47.5%. The related mortality was 17%. Staying in the ICU was associated with A. baumannii bacteraemia (P , 0.004). An intravascular catheter was the leading source of infection (37%). Main risk factors were mechanical ventilation (28%), parenteral nutrition (23%) and the presence of a urinary catheter (22%). In the multivariate analysis the independent prognostic factors for mortality were the presence of shock (P , 0.05) and the severity of the underlying disease, according to the classification of McCabe (P , 0.05). Conclusions: The incidence of Acinetobacter bacteraemia has increased in the last decade, mainly since 1995. The development of septic shock and the severity of the underlying disease appear to be associated with an increase in mortality. 2001 Elsevier Science B.V. All rights reserved. Keywords: Bacteraemia; Acinetobacter
1. Introduction Bacteraemia is currently one of the infections with the highest mortality in hospitals [1,2]. In recent years, an increase in patients with nosocomial bacteraemia caused by gram-positive organisms has been observed [1]. However, contrary to expectations, the number of cases of gram-negative bacteraemia have barely fallen, due to the rise in resistant pathogens such as Acinetobacter [3,4]. *Corresponding author. Fax: 134-942-202660. ˜ E-mail address: [email protected] (M.C. Farinas).
These gram-negative bacteria are opportunist pathogens, highly resistant to antimicrobial agents. Clinical illnesses associated with Acinetobacter include pneumonia, meningitis, peritonitis, endocarditis and infections of the urinary tract and skin [5–7]. Patients are more susceptible to these illnesses when treated with an endovenous catheter, mechanical ventilation or when located in an ICU [2,8–11]. The fact that published series on bacteraemia from Acinetobacter are scarce and that the few existing studies have found varied infection rates led us to review our university teaching hospital’s records on Acinetobacter episodes in the last 9 years, analysing clinical and mi-
0953-6205 / 01 / $ – see front matter 2001 Elsevier Science B.V. All rights reserved. PII: S0953-6205( 01 )00150-9
426
C. Valero et al. / European Journal of Internal Medicine 12 (2001) 425 – 429
crobiologic aspects, risk factors and predictors of mortality.
2. Patients and methods This study was conducted at an 1100-bed university hospital from January 1989 to March 1998. Cases were identified by retrospective review of all blood culture isolates reported as Acinetobacter by the Diagnostic Microbiology Laboratory during the 9-year period. Information collected from the clinical records included patient age, sex, average hospital stay, attending unit, risk factors, underlying diseases, date and source of bacteraemia, presence of organisms other than Acinetobacter, initial antibiotic used, complications, clinical outcome and, if applicable, cause of death. Contaminants were organisms isolated from single positive blood cultures that were not associated with clinical symptoms [12]. These contaminants were excluded from the study.
2.1. Microbiological methods Blood cultures were processed by the microbiology laboratory using the Bactec system (Becton Dickinson, Cockeysville, MD, USA). Identification of the micro-organisms, as well as their sensitivity to antimicrobial agents, was carried out with the Microscan system (Autoscan), using the panel Neg combo 61, and following National Committee for Clinical Laboratory Standards (NCCLS) criteria [13].
respiratory infection and the sputum culture or respiratory secretions showed Acinetobacter, as well as in cases in which chest X-ray showed pulmonary infiltration, which was later resolved with the antibiotic treatment established for the bacteraemia. In cases involving cellulitis or infections from surgical injury, these were considered bacteraemia foci in the absence of any other obvious source. The diagnoses of endocarditis met Duke’s criteria [15]. Inflammatory response syndrome, sepsis and septic shock were diagnosed according to the criteria established by the Intensive Care and Respiratory Society, established at the Chicago Consensus Conference [16]. The presence of associated underlying illness was categorised by criteria set forth by McCabe and Jackson [17]. We analysed the antibiotic treatment administered in all episodes after the results of antimicrobial susceptibility testing became available. Appropriate therapy was defined as administration for at least 24 h of an antibiotic to which the organism was susceptible; the antibiotic was administered after collection for culture [12]. Death was considered bacteraemia-related if it occurred in the phase of active infection and without evidence of any other attributable cause.
2.3. Statistical analysis The chi-square test and Fisher’s test were used. Differences were considered significant by chi-square if P , 0.05 (two-sided). Multivariate analysis of the predictive factors of mortality was carried out using logistic regression analysis.
2.2. Parameters Episodes were categorised as community or nosocomially acquired following the Centres for Diseases Control (CDC) definitions [14]. The following parameters were considered risk factors for bacteraemia: presence of central venous catheter, orotracheal intubation, parenteral nourishment, urinary or nasogastric intubation at least 48 h before blood culture; bone marrow or solid organ transplant in the previous month; chemotherapy or cytotoxic treatment in the previous 6 weeks; treatment with corticosteroids or antibiotics in the previous 2 weeks; and surgery, the presence of neutropenia (granulocytes ,500 cells / mm 3 ), or an acute cerebrovascular event in the week prior to positive blood cultures. The bacteraemia was attributed to a central venous catheter when there were local signs of phlebitis at the insertion site or when the catheter was withdrawn and the sepsis manifestation was resolved in less than 48 h without evidence of other bacteraemia foci. The infection was considered urinary if Acinetobacter was isolated in the urine or if clinical signs of urinary infection were reported within the context of the bacteraemia episode. Focus was deemed respiratory when the clinical picture indicated
3. Results Over the 9 years covered in our study, we detected 59 patients with Acinetobacter bacteraemia (1.8 episodes per 10 000 admissions). The year-by-year distribution was not homogenous, with a clear increase after 1995 (8.9 per 10 000 admissions). The average age of the patients was 50.5623 years, and 66% were male. Acquisition was nosocomial in 42 cases (71%), and community in 17 patients (29%). The highest number of cases was recorded in the Department of Internal Medicine, with 17 patients (28.8%), followed by Haematology, with 16 patients (27%), and the ICU, with 14 (23%). The accumulated percentage of the three departments was 84%. The average hospital stay was 29.5621.8 days (range 1–95 days). The average number of blood cultures extracted from each patient was 3.6 (of which Acinetobacter was isolated in 2.4). A. lwoffii was isolated in 52.5% of the bacteraemias (31 cases) and A. baumannii in 47.5% (28 cases). One-third of the bacteraemias were polymicrobial (35.5%); the isolated organisms associated with Acinetobacter were Staphylococcus epidermidis (15 cases),
C. Valero et al. / European Journal of Internal Medicine 12 (2001) 425 – 429
Enterococcus faecalis (two cases), Stenotrophomonas maltophilia (two cases) and Escherichia coli, Pseudomonas aeruginosa, S. haemolyticus and S. equorum (one case each). In the majority of cases (19 patients), Acinetobacter was associated with only one organism. Complications were studied according to species, and there were only significant differences in the case of septic shock, in favour of A. baumannii (P , 0.05). An analysis of the species’ distribution in the different departments showed that 93% of the bacteraemia episodes in the ICU were due to A. baumannii, compared with 41% in the Department of Internal Medicine and 19% in Haematology. The source of Acinetobacter bacteraemia was an intravascular catheter in 22 cases (37%), respiratory in 11 cases (11.6%), and a soft tissue infection in four cases (6.7%). In nearly one-third of the cases, the focus was unknown (30.5%). Forty-four patients developed sepsis (75%) and another nine developed septic shock (15%). Only one patient was diagnosed as having endocarditis of the native mitral valve due to A. lwoffii. In the remaining patients there was either no evidence of endocarditis (12%) or it was not studied (86%). Malignant diseases (haematological in 15 cases and solid in 10 cases) and chronic obstructive lung disease (five cases) were the major underlying conditions. Eight patients had suffered a polytraumatism. Following McCabe’s classification, 18 patients had a nonfatal disease (30%), 31 an ultimately fatal disease (53%) and 10 a rapidly fatal disease (17%). The risk factors were distributed as follows: mechanical ventilation in 17 patients (28%), parenteral nourishment in 14 (23%) and urinary catheter in 13 (22%). More than half of the patients (54%) had received treatment with antibiotics in the 15 days prior to the onset of bacteraemia and 11 patients (18.6%) underwent surgery. Risk factors associated with A. baumannii bacteraemia are shown in Table 1. In the multivariate analysis, only the stay in the ICU was associated with A. baumannii bacteraemia (P , 0.05). Forty-eight patients (81%) received antibiotic treatment, the majority with one antibiotic. Only 30% of the treatments were considered appropriate. In our cases, no resistance to imipenem was observed. Resistance to third-
427
Table 2 Univariate analysis of factors influencing mortality among patients with Acinetobacter bacteraemia No. of patients who died / total No. patients (%)
Pa
Acinetobacter A. baumannii A. lwoffii
7 / 28 (25) 3 / 31 (30)
NS
Sepsis Yes No
10 / 44 (23) 0 / 15 (0)
,0.05
Septic shock Yes No
7 / 9 (77) 3 / 50 (6)
,0.05
McCabe’ s classification Nonfatal Ultimately fatal Rapidly fatal
0 / 18 (0) 2 / 31 (6) 8 / 10 (80)
Urinary tract catheter Yes No
5 / 13 (38) 5 / 46 (11)
Variable
,0.05
,0.05
Leukocyte count ( . 12 000 or , 2000) Yes 9 / 33 (27) No 1 / 26 (4)
,0.05
Albumin ( g /dl) $3.5 #3.4
,0.05
2 / 31 (6) 8 / 28 (28)
NS, not significant. a Univariate analysis.
generation cephalosporins was 50–75% for A. baumannii and 2–6% for A. lwoffii. Seventeen patients died (overall mortality 28.8%). In 10 cases, death was related to bacteraemia (17%) and in seven it was due to other causes. The average survival time of the patients who died was 1.8 days from the date of the blood culture. The predictive factors for mortality in the univariate analysis are shown in Table 2. In the multivariate analysis, predictors for mortality were the presence of shock (P , 0.05) and the higher severity of the underlying
Table 1 Univariate analysis of risk factors influencing mortality according to Acinetobacter species
Mechanical ventilation Parenteral nutrition Urinary catheter Immunosuppression Neutropenia ICU a
Univariate analysis.
No. of patients with the risk factor / total
A. baumannii No. (%)
A. lwoffii No. (%)
Pa
17 / 59 14 / 59 13 / 59 22 / 58 16 / 59 14 / 59
15 11 11 7 4 13
2 3 2 15 12 1
0.000 0.008 0.003 0.056 0.03 0.000
(88) (79) (85) (32) (25) (93)
(12) (21) (15) (22) (75) (7)
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428
Table 3 Multivariate logistic regression analysis predicting mortality in patients with Acinetobacter bacteraemia Variable
Coefficient
Standard error of the coefficient
95% CI
P
McCabe Shock Constant
3.77 3.15 211.09
1.28 1.36 3.36
1.20–6.33 0.42–5.88
0.005 0.024
No. of observations 59; model chi-square 35.11; significance 0.0000. CI, confidence interval.
disease according to McCabe’s classification (P , 0.05; Table 3).
4. Discussion In the past decade, the rate of bacteraemia due to Acinetobacter infection has clearly risen, mainly in ICUs. These rates vary from one hospital to another in relation to the type of patients involved. In a recent study on bacteraemias in ICUs, Acinetobacter represented 3.8% of the total, and 12% of those were caused by gram-negative bacteria [2]. In our hospital, the overall rate of Acinetobacter bacteraemia was 1.8 per 10 000 admissions. The rate of Acinetobacter bacteraemia varies according to the published series from 0.3 / 1000 to 1.8 / 1000 [12,18]. The rate was even higher (10.4% of admissions) in a study conducted in ICUs only [19]. These variations can be explained, in part, by different risk factors and transmission mechanisms in the different hospitals. As expected, Acinetobacter spp. bacteraemia in our study was mainly nosocomial (71%), which is somewhat lower than in other studies. A noteworthy difference was that the highest number of cases came from the Department of Internal Medicine (29%), followed by Haematology (27%) and the ICU (23%). Studies conducted in other hospitals have reported that ICUs are clearly the prominent source of bacteraemia due to Acinetobacter [20,21]. This may partly be explained by the fact that, in other series, the rate of community-acquired bacteraemia infections was low, whereas in our study it reached 30%. If we consider only nosocomial bacteraemias, the order is reversed, and the department that recorded the greatest number of cases was the ICU with 31%, followed by the Department of Internal Medicine with 24%. We found that more than half of the bacteraemias were due to A. lwoffii, whereas most studies in the literature focus on A. baumannii, with only a few reports on infections due to A. lwoffii. In fact, in a study of 584 Acinetobacter-positive samples, 72.9% were A. baumannii and only 3.6% were A. lwoffii [22]. We do not have an explanation for the discrepancy between this tendency and our finding. Central venous catheters were the most frequent source of cases (37%); rates reported in the literature range from
11 to 46% [12,18]. A. lwoffii has traditionally been associated more with catheter-related infection, and these bacteraemias have tended to have a more benign evolution. Seifert et al. [8] described 13 cases of bacteraemia due to A. johnsonnii (A. calcoaceticus var. lwoffii) associated with catheterisation, highlighting their positive evolution when the catheter was withdrawn, regardless of whether appropriate antibiotics were administered. We did not find any association between the species of Acinetobacter and catheter-related bacteraemia, nor was mortality related to bacteraemia after catheterisation. These results are similar to those of Beck-Sague et al. [19], who reported on 72 patients with catheter-related A. baumannii bacteraemia and who found that their mortality rate was not higher than that in a control group. In our study, the respiratory focus was the second most frequent (11.6%), although the literature shows rates ranging from 31 to 71% [18,20]. This is attributable to the fact that the number of bacteraemias due to Acinetobacter found in ICUs is low, and respiratory focus is most frequent in these units. In a high percentage of our cases (30%), the focus of infection was unknown; this figure is similar to those reported in other studies [11]. Endocarditis due to Acinetobacter is uncommon, has a high mortality rate and has mostly been described in patients with predisposing risk factors [7,23]. Mechanical ventilation, parenteral nutrition and the presence of a urinary catheter were the most frequent invasive processes to which our patients were submitted. The rate of these processes was lower than those reported in other studies [18,19,24–26]. The clinical manifestations of bacteraemia were non-specific. Septic shock was presented by 15% of our patients, similar to figures reported in other studies which describe septic shock in 25–30% of cases [18,20]. In our series, bacteraemia-related mortality was low (17%) compared to other studies, with rates of 19 and 32% [18,20]. This may be due to the relatively high number of community-acquired bacteraemia infections or to a predominance of A. lwoffii infections. The development of septic shock and the severity of the underlying disease were associated with an increase in mortality. The present study thus confirms that bacteraemia due to Acinetobacter is a major nosocomial infection which is associated with high morbidity and mortality. Together with Acinetobacter’s high resistance to antibiotics, this indicates that further study is needed to determine the best strategies for both prevention and treatment of these infections.
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