JAC Advance Access originally published online on April 20, 2006
Journal of Antimicrobial Chemotherapy 2006 57(6):1251-1254; doi:10.1093/jac/dkl130
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Comparison of mortality of patients with Acinetobacter baumannii bacteraemia receiving appropriate and inappropriate empirical therapy
1 Alfa Institute of Biomedical Sciences (AIBS) Athens, Greece 2 Department of Medicine, Henry Dunant Hospital Athens, Greece 3 Department of Medicine, Tufts University School of Medicine Boston, MA, USA 4 Department of Microbiology, Henry Dunant Hospital Athens, Greece
*Correspondence address. Alfa Institute of Biomedical Sciences (AIBS), 9 Neapoleos Street, 151 23 Marousi, Greece. Tel: +30-694-611-0000; Fax: +30-210-683-9605; E-mail: m.falagas{at}aibs.gr
Received 20 January 2006; returned 24 February 2006; revised 10 March 2006; accepted 20 March 2006
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Abstract |
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Objectives: To evaluate the effect of inappropriate empirical antimicrobial treatment on the mortality of patients with Acinetobacter baumannii bacteraemia.
Methods: Retrospective cohort study of patients with A. baumannii bacteraemia hospitalized at the Henry Dunant hospital from January 2002 to December 2004.
Results: Among 40 patients with A. baumannii bacteraemia, 22 (55%) and 18 (45%) received inappropriate and appropriate antibiotic therapy, respectively, during the 3 day period after obtaining the blood culture(s) from which the pathogen was isolated. Failure to cure the infection was more common in the first group [16/22 patients (72.7%) versus 5/18 (27.8%), P = 0.005]. Although without statistical significance, probably due to the small number of studied patients, considerably increased mortality was noted in the first group compared with the second group [13/22 patients (59.1%) versus 6/18 (33.3%), P = 0.10].
Conclusions: A. baumannii bacteraemia was associated with worse outcome regarding the cure of infection in patients who received inappropriate empirical antimicrobial treatment compared with those who received appropriate treatment.
Keywords: appropriate therapy , inadequate therapy , Gram-negative bacteria , bloodstream infections , antimicrobial treatment
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Introduction |
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Acinetobacter baumannii has become a major nosocomial pathogen in many hospitals in various parts of the world. Infections due to A. baumannii are associated with considerable morbidity and mortality. However, there has been continuous controversy regarding the mortality directly attributed to this infection.1,2 This is because A. baumannii infections frequently develop in critically ill patients who have significant comorbidity.
Nevertheless, A. baumannii, an otherwise commensal in nature, is a Gram-negative bacterium associated with a variety of serious infections in the hospital setting, especially in intensive care units. High levels of resistance to most classes of antibiotic is common in A. baumannii infections.2 Thus it is also common that inappropriate antibiotics (i.e. no in vitro susceptibility of A. baumannii to these antibiotics) are employed at some stage in the management of these infections. In the present study we sought to examine the impact of inappropriate empirical antimicrobial treatment on the mortality of patients with A. baumannii bacteraemia.
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Patients and methods |
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A retrospective cohort study was performed in patients with A. baumannii bacteraemia hospitalized at the Henry Dunant, a 450 bed tertiary-care hospital in Athens, Greece, during January 2002 to December 2004. The patients were identified through the microbiology electronic databases. Two physicians (S. K. K. and G. Z.) reviewed records of all patients and collected data including demographic and clinical characteristics, comorbidity and the administered antibiotic treatment throughout hospitalization. The study was approved by the Institutional Review Board (IRB) of the hospital.
Bacteraemia was defined according to criteria established by the Centers for Disease Control and Prevention.3 The observation period to evaluate the adequacy of the empirical antimicrobial treatment was defined as 72 h from the time of collection of the blood specimen cultures from which A. baumannii was isolated. The empirical antimicrobial therapy was considered as appropriate if at least one drug to which the isolated A. baumannii was in vitro susceptible was included in the initial empirical treatment. Such a drug had to be administered for at least 72 h from the time that the blood specimen cultures were drawn in order for the empirical treatment to be considered as appropriate. The administration of antimicrobial agents to which the isolated A. baumannii was in vitro resistant or intermediately susceptible was considered as inappropriate empirical treatment. The definition of outcomes including response of the infection as well as the microbiological methods used to evaluate susceptibility of the isolated A. baumannii to various antimicrobial agents have been reported previously.4 Specifically, cure was defined as resolution of presenting symptoms and signs of the infection by the end of antimicrobial treatment administered for the specific episode of infection, improvement was defined as partial resolution of presenting symptoms and signs of the infection, and failure was defined as persistence or worsening of presenting symptoms and/or signs of the infection during antibiotic treatment.
The comparison of the distribution of variables in the compared groups was performed with the 
2 test or Fisher exact test for categorical variables and Student's t-test or the Mann–Whitney test for normally and non-normally distributed continuous variables, respectively. All statistical analyses were performed using SPSS 11.0 (SPSS Inc., Chicago, IL, USA).
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Results |
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From January 2002 to December 2004, 47 patients were identified to have A. baumannii bacteraemia. Seven patients were excluded from further analyses; two of them were excluded because they did not receive antimicrobial treatment during the 3 day period after obtaining the blood culture from which the pathogen was isolated, due to extensive allergic reaction to previously administered antibiotics, four because they died before completing 72 h of empirical antimicrobial treatment and one because incomplete data were available. Thus, 40 patients were further analysed. Among these, 22 patients (55%) received inappropriate (Group 1) and 18 patients (45%) appropriate antibiotic therapy (Group 2), according to the study definitions. From the 22 patients who received inappropriate treatment, 18 had A. baumannii bacteraemia without any evidence of another focus of infection (i.e. primary), while in 4 patients bacteraemia was secondary to another infection (2 patients had respiratory tract infection, 1 patient urinary tract infection and another patient wound infection). In the group of patients who received appropriate antimicrobial therapy, 11 had primary bacteraemia, whereas 6 had A. baumannii bacteraemia due to respiratory tract infection and 1 patient bacteraemia due to abdominal infection.
Patients in Group 1 (inappropriate treatment) received the following antibiotics (in parentheses is the number of patients receiving the medication): ampicillin/sulbactam (1), piperacillin/tazobactam (9), ceftriaxone (2), imipenem/cilastatin (2), meropenem (9), ciprofloxacin (11), amikacin (3), gentamicin (4) and trimethoprim/sulfamethoxazole (2). Patients in Group 2 (appropriate treatment) received ampicillin/sulbactam (1), piperacillin/tazobactam (1), ceftriaxone (2), imipenem/cilastatin (3), meropenem (7), ciprofloxacin (2), amikacin (2) and colistin (13). One patient in each treatment group received empirical therapy with ampicillin/sulbactam; the A. baumannii strain that was isolated from the patient included in the inappropriate group was in vitro resistant to the drug (MIC 
64 mg/L), while the strain that was isolated from the patient in the appropriate group was in vitro susceptible to ampicillin/sulbactam (MIC = 8 mg/L). The use of piperacillin/tazobactam, meropenem and ciprofloxacin was more common in Group 1, whereas colistin was used exclusively in Group 2.
There was a significant number of the A. baumannii blood isolates with an increased spectrum of antimicrobial resistance. A total of 13 A. baumannii blood isolates in the inappropriate treatment group and 8 A. baumannii blood isolates in the appropriate treatment group had in vitro susceptibility only to polymyxins. There was an additional number of five isolates in the inappropriate treatment group and two isolates in the appropriate treatment group with in vitro susceptibility to polymyxins and to one additional antibiotic class (either a carbapenem or an aminoglycoside).
In the subgroup of patients that received inappropriate empirical antibiotic therapy in which imipenem or meropenem was included as part of the treatment, two strains of A. baumannii were in vitro resistant to imipenem (MIC 16 mg/L), seven strains were in vitro intermediate susceptible to meropenem (MIC = 8 mg/L), one strain was in vitro resistant to meropenem (MIC 16 mg/L) and one strain was in vitro susceptible to meropenem (MIC = 4 mg/L). In the group of patients that received appropriate antimicrobial therapy, one strain of A. baumannii was in vitro resistant (MIC 16 mg/L), one strain was in vitro intermediate susceptible (MIC = 8 mg/L) and one strain was in vitro susceptible to imipenem (MIC = 4 mg/L), while four strains were in vitro susceptible (three strains had MIC = 4 mg/L and one strain had MIC = 0.5 mg/L), two strains were in vitro intermediate susceptible (MIC = 8 mg/L) and one strain was in vitro resistant (MIC 16 mg/L) to meropenem.
The distribution of demographic and clinical characteristics of the 40 analysed patients according to the adequacy of the empirical antimicrobial treatment is shown in Table 1. None of the examined variables was statistically significantly different between the two groups of patients, except that heart disorders were more commonly found in the group of patients that received inappropriate empirical antimicrobial therapy (77.2% versus 38.9%, P = 0.01).
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Failure to cure or improve the infection was more common in the group of patients who received inappropriate empirical treatment [16/22 patients (72.7%) versus 5/18 (27.8%), P = 0.005]. The in-hospital mortality of patients who received inappropriate and appropriate antimicrobial therapy was 59.1% (13/22 patients) and 33.3% (6/18 patients), respectively (P = 0.10). Thus, an increased mortality of 25.8% was found in patients who received inappropriate therapy, although not statistically significant. We also performed a secondary analysis of mortality at day 14 of antimicrobial therapy. The 14 day mortality of patients who received inappropriate and appropriate antimicrobial therapy was 50% (11/22 patients) and 22% (4/18 patients), respectively (P = 0.07). A multivariable backward logistic regression model that included age, appropriate or inappropriate treatment, heart dysfunction and APACHE II score as independent variables showed that only age was associated with mortality (OR 1.09, 95%CI 1.02–1.16).
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Discussion |
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There are a few studies examining whether excess mortality is attributable directly to A. baumannii bacteraemia and whether inappropriate empirical therapy has any impact on the prognosis. Inappropriate antimicrobial therapy was found to be independently associated with mortality in patients with A. baumannii bacteraemia (P < 0.01) in a prospective observational study.2 Also, in a case–control study of adult burn patients with or without A. baumannii bloodstream infections (cases and controls, respectively), the crude mortality among cases was more than twice that of controls (31% versus 14%, respectively), though no specific comment was made regarding appropriate or inappropriate therapy.5 In a matched cohort study, it was shown that 10 patients with A. baumannii bacteraemia treated inappropriately, or in whom antibiotic therapy was initiated more than 48 h after the onset of infection, had higher mortality, although not statistically significant, than 35 patients with appropriately treated A. baumannii bacteraemia (50% versus 36.7% mortality).1 Also, in a prospective study of 133 patients the attributable mortality of bacteraemia due to A. baumannii was 25.6%. In the multivariable analysis of this study, inappropriate antibiotic therapy, septic shock and high morbidity score were associated with a worse prognosis.6
In conclusion, our data suggested that A. baumannii bacteraemia was associated with worse outcome regarding the cure of infection in patients who received inappropriate empirical antimicrobial treatment compared with those who received appropriate treatment. In addition, mortality was higher in this group of patients, although not statistically significant, probably due to the small number of studied patients. In hospitals where the majority of A. baumannii isolates are multiresistant, the use of more aggressive empirical antimicrobial treatment may be justified from the outset (at the time blood cultures are taken from the patient) to try to improve the grave prognosis of patients with A. baumannii bacteraemia. This may be particularly true in the intensive care setting.
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Transparency declarations |
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None to declare (no conflicts of interest).
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Acknowledgements |
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Funding: none.
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References |
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1 Blot S, Vandewoude K, Colardyn F. (2003) Nosocomial bacteremia involving Acinetobacter baumannii in critically ill patients: a matched cohort study. Intensive Care Med 29:471–5.[Medline]
2 Cisneros JM, Reyes MJ, Pachon J, et al. (1996) Bacteremia due to Acinetobacter baumannii: epidemiology, clinical findings, and prognostic features. Clin Infect Dis 22:1026–32.[Web of Science][Medline]
3 Gaynes RP and Horan TC. (1996) Surveillance of nosocomial infections. Appendix A: CDC definitions of nosocomial infections. In Mayhall CG (Ed.). Hospital Epidemiology and Infection Control (Williams & Wilkins, Baltimore) pp. 1–14.
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Kasiakou SK, Michalopoulos A, Soteriades ES, et al. (2005) Combination therapy with intravenous colistin for management of infections due to multidrug-resistant Gram-negative bacteria in patients without cystic fibrosis. Antimicrob Agents Chemother 49:3136–46.
5 Wisplinghoff H, Perbix W, Seifert H. (1999) Risk factors for nosocomial bloodstream infections due to Acinetobacter baumannii: a case-control study of adult burn patients. Clin Infect Dis 28:59–66.[Web of Science][Medline]
6 Rodriguez-Bano J, Pascual A, Galvez J, et al. (2003) Acinetobacter baumannii bacteremia: clinical and prognostic features. Enferm Infecc Microbiol Clin 21:242–7.[CrossRef][Medline]
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