JAC Advance Access originally published online on March 3, 2008
Journal of Antimicrobial Chemotherapy 2008 61(5):1183-1185; doi:10.1093/jac/dkn082
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Research letters |
Nosocomial bloodstream infections due to metallo-β-lactamase-producing Pseudomonas aeruginosa
1 Infectious Diseases Service, Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil 2 Microbiology Unit, Clinical Pathology Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil 3 Division of Infectious Diseases, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
* Corresponding author. Tel/Fax: +55-51-33621850; E-mail: azavascki{at}hcpa.ufrgs.br
Keywords: bacterial drug resistance , β-lactamases , mortality , bacteraemia
The worldwide emergence of metallo-β-lactamases (MBLs) has challenged antimicrobial therapy against Pseudomonas aeruginosa, a leading pathogen causative of nosocomial infections.1 In a recent cohort, we showed that the production of this type of enzyme was associated with increased mortality rates in patients with nosocomial infections due to P. aeruginosa.1
Bacterial bloodstream infections (BSIs) are serious infections associated with significant mortality and healthcare costs. Only two reports have analysed mortality of patients with MBL-producing P. aeruginosa (MBL-PA) BSIs.2,3 However, both were limited by a small number of patients and did not compare mortality rates with mortality rates of patients with MBL-PA and non-MBL-PA BSIs. Owing to the importance of BSI, in the current study, we describe the clinical characteristics, treatments and mortality of the subset of patients from our cohort with nosocomial MBL-PA BSIs.
Patients from a contemporary cohort performed at two tertiary-care teaching hospitals in Porto Alegre, southern Brazil,1 who presented positive blood cultures for P. aeruginosa were included in the study. Microbiological and molecular procedures are described in detail elsewhere.1 The Ethics Review Boards of both hospitals have approved this study. Written informed consent was obtained from each participant. Variables were compared using the 
2 or Fisher exact test for categorical variables and the Student's t-test for continuous variables. All tests were two-tailed and a P value 
0.05 was considered significant.
A total of 44 patients were included in the study. Twenty-one (47.7%) had MBL-PA BSIs (Table 1). The overall hospital mortality of patients with P. aeruginosa BSI was 52.3% (23 of 44): 61.9% (13 of 21) and 43.5% (10 of 23) for patients with MBL-PA and non-MBL-PA BSI, respectively [relative risk (RR), 1.42; 95% confidence interval (CI), 0.80–2.53; P = 0.36]. There was no statistically significant difference in mean age, sex, baseline diseases, presence of severe sepsis or septic shock and primary site of the bacteraemia, between patients with MBL-PA and non-MBL-PA BSI. However, administration of appropriate antibiotic therapy (antibiotic with in vitro susceptibility) tended to be less frequent in the MBL-PA group than in the non-MBL-PA group [11 (52.4%) of 21 patients and 18 (78.3%) of 23, respectively; P = 0.06]. This latter variable was a significant protective factor for hospital mortality [12 (41.4%) of 29 who received appropriate therapy and 11 (73.3%) of 15 who did not receive appropriate therapy; RR, 0.56; 95% CI, 0.33–0.96; P = 0.04]. Antibiotic resistance profiles are shown in Table 1. Clonal dissemination of these isolates was demonstrated in these institutions and SPM-1 was the MBL type.1
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Four (36.4%) of those 11 patients with MBL-PA BSIs who received appropriate antibiotic therapy and 9 (90.0%) of 10 who did not receive appropriate antibiotic therapy died (RR for mortality of inappropriate therapy, 2.48; 95% CI, 1.10–5.56; P = 0.02). No specific antibiotic agent was associated with lower mortality (P = 0.58). Among patients who received appropriate therapy, the mortality of those treated with combination therapy was 20% (1 of 5 patients) compared with 50% (3 of 6) of patients treated with a single agent (P = 0.35). The single patient who survived without appropriate therapy was a 48-year-old male patient with urinary tract infection who was treated with aztreonam (2 g every 8 h) plus ceftazidime (2 g every 8 h). This isolate was only susceptible to polymyxin B, but presented intermediate resistance to aztreonam (MIC = 16 mg/L; Etest, AB BIODISK, Solna, Sweden).
Although without statistical significance, MBL production by P. aeruginosa increased mortality of the specific group of patients with BSIs in this study. This higher mortality of MBL-PA BSIs might be explained by the considerable proportion of inappropriate antibiotic therapy in this group of patients.
Antimicrobial-resistant P. aeruginosa BSIs have been associated with higher overall mortality rates than those due to antimicrobial-susceptible isolates,4–6 although most of these differences have not reached statistical significance.4,6 This may be caused by the intrinsic virulence of P. aeruginosa regardless of antimicrobial resistance profile and a consequential high rate of organ dysfunction associated with BSIs caused by this organism.4 However, most of the studies assessing the impact of antimicrobial resistance on BSI mortality performed so far have lacked statistical power to detect minor differences in mortality between the groups.
The relatively small number of patients in our study did not permit any definitive conclusion about the optimal therapy for MBL-PA BSIs. However, polymyxin B should always be considered for the treatment of these severe infections, although aztreonam may also be considered if there is in vitro susceptibility. Combination therapy should be considered in addition and deserves further investigation to assess a potential superiority over monotherapy.7
In conclusion, P. aeruginosa BSIs are associated with high mortality rates. MBL production probably contributes to increasing these rates. Appropriate antimicrobial therapy may be the only modifiable factor able to improve outcomes for these patients. The optimal treatment of these infections must be further determined in other studies.
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 Top Funding Transparency declarationsReferences |
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—CAPES, Ministry of Education, Brazil, and Fundação de Incentivo a Pesquisa e Eventos—FIPE, Hospital de Clínicas de Porto Alegre.
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Transparency declarations |
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TopFundingTransparency declarationsReferences |
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A. P. Z. has received speaking honoraria from Forest Laboratories. All other authors: none to declare.
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References |
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1 Zavascki AP, Barth AL, Gonçalves AL, et al. The influence of metallo-β-lactamase production on mortality in nosocomial Pseudomonas aeruginosa infections. J Antimicrob Chemother (2006) 58:387–92.
2 Lee NY, Yan JJ, Lee HC, et al. Clinical experiences of bacteremia caused by metallo-β-lactamase-producing Gram-negative organisms. J Microbiol Immunol Infect (2004) 37:343–9.[Medline]
3
Marra AR, Pereira CA, Gales AC, et al. Bloodstream infections with metallo-β-lactamase-producing Pseudomonas aeruginosa: epidemiology, microbiology, and clinical outcomes. Antimicrob Agents Chemother (2006) 50:388–90.
4 Kang CI, Kim SH, Park WB, et al. Risk factors for antimicrobial resistance and influence of resistance on mortality in patients with bloodstream infection caused by Pseudomonas aeruginosa. Microb Drug Resist (2005) 11:68–74.[CrossRef][Web of Science][Medline]
5 Tacconelli E, Tumbarello M, Bertagnolio S, et al. Multidrug-resistant Pseudomonas aeruginosa bloodstream infections: analysis of trends in prevalence and epidemiology. Emerg Infect Dis (2002) 8:220–1.[Web of Science][Medline]
6 Scheetz MH, Bolon MK, Scarsi KK, et al. Lack of effect of fluoroquinolone resistance on mortality in subjects with Pseudomonas aeruginosa bacteraemia. J Infect (2006) 52:105–10.[CrossRef][Medline]
7
Zavascki AP, Goldani LZ, Li J, et al. Polymyxin B for the treatment of multidrug-resistant pathogens: a critical review. J Antimicrob Chemother (2007) 60:1206–15.
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