Risk factors for mortality in patients with ventilator-associated pneumonia caused by carbapenem-resistant Enterobacteriaceae

Abstract Background: The ideal therapeutic option for ventilator associated pneumonia caused by carbapenem-resistant Enterobacteriaceae is not defined. The aim of this study was to assess mortality-associated risk factors in patients with VAP by CRE and determine the outcome of several treatment options. Methods: This was a retrospective study performed in two tertiary hospitals involving patients with VAP caused by CRE between January 2010 and August 2014. The outcomes were mortality within 30 days of VAP diagnosis and overall mortality during hospital admission. Risk factors for mortality were assessed by comparing variables of survivors and non-survivors. Results: One hundred and twelve patients with CRE-VAP were included, 73 (65%) male, median age 56 years. The 30-day mortality was 57.1% and the overall hospital mortality was 67%. In the binary logistic regression analysis, only age >50 years was independently associated to increased mortality. Polymyxin was the most used drug (47.5%), followed by tigecycline (29.2%) and aminoglycosides (2.4%). Combined therapy with two active drugs was used by 17 patients (20.8%). No therapeutic option was independently associated to survival. However, combined therapy with two active drugs was superior to the therapy with a single active drug when inappropriate therapy was the comparator (p = 0.044). The addition of carbapenem was not associated with increased survival. Conclusion: The best therapeutic option for VAP by CRE is still not completely defined, but the therapy with at least two active drugs was superior in this study.

Validação do teste de inibição pelo ácido aminofenilborônico para triagem de Klebsiella pneumoniae carbapenemases (KPC) / Validation of inhibition test by aminophenyl boronic acid to Klebsiella pneumoniae carbapenemases (KPC) screening

INTRODUÇÃO: A produção de enzimas Klebsiella pneumoniae carbapenemase (KPC) tem se tornado um importante e preocupante mecanismo de resistência, e ensaios que combinem alta sensibilidade e alta especificidade para a detecção dessas enzimas são escassos. OBJETIVO: Validar o teste de inibição pelo ácido 3-aminofenilborônico como método de triagem fenotípica de cepas produtoras de enzima KPC, comparando os resultados obtidos com os de testes confirmatórios por reação em cadeia da polimerase (PCR). METODOLOGIA: Avaliou-se o uso do ácido 3-aminofenilborônico impregnado em discos de antibióticos de imipenem, meropenem e ertapenem. Foram testadas 36 cepas positivas e 12 negativas, todas confirmadas por PCR. Foram ainda testadas três concentrações diferentes de ácido borônico: 300, 400 e 600 µg. RESULTADOS: Entre as cepas positivas testadas, o resultado mais adequado se deu com a adição do composto em disco contendo ertapenem, com especificidade de 100%, porém com sensibilidade de apenas 50%. CONCLUSÃO: Novos estudos são necessários, sobretudo no que diz respeito à padronização da técnica e aos insumos utilizados, pois o método se revela promissor na triagem de cepas produtoras de KPC.

INTRODUCTION: The production of Klebsiella pneumoniae carbapenemases enzymes (KPC) has become an important and worrisome resistance mechanism. Furthermore, tests that combine high sensitivity and high specificity for the detection of these enzymes are scarce. OBJECTIVE: To validate the inhibition test by 3-aminophenyl boronic acid as a phenotypic screening method for KPC-producing strains by comparing the results with confirmatory polymerase chain reaction testing (PCR). METHODS: We evaluated the use of 3-aminophenyl boronic acid applied on disks with imipenem, meropenem and ertapenem antibiotics. 36 strains were positive and 12 were negative, all confirmed by PCR. Three different concentrations of boronic acid were also tested: 300, 400 and 600 µg. RESULTS: Among the positive strains, the results were more accurate with the addition of the compound to the ertapenem disk, presenting 100 % specificity and 50% sensitivity. CONCLUSION: Further studies are required, mainly regarding the standardization of the technique and materials, since the method seems to be promising as to the screening of KPC strains.

Risk factors for KPC-producing Klebsiella pneumoniae bacteremia

The molecular epidemiology of carbapenemase-producing Klebsiella pneumoniae (KPC) has been largely investigated, but limited clinical information is available. A case-control study was performed to evaluate the risk factors for KPC bacteremia in hospitalized patients. Cases were patients with KPC bacteremia and controls were patients with non-KPC bacteremia. A total of 85 patients were included, 18 (21.2%) were KPC, and 67 (78.8%) were non-KPC (40 [59.7%] of them were extended-spectrum beta-lactamase producers). All KPC isolates were type 2 producers. These isolates belong to five distinct clones. Multivariate analysis showed that age (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.02 - 1.11; p = 0.004), presence of mechanical ventilation (OR, 11.1; 95% CI, 1.92 - 63.3; p = 0.007) and fluoroquinolone exposure during hospitalization (OR, 28.9; 95% CI, 1.85 - 454.6; p = 0.02) were independent risk factors for KPC in patients with K. pneumoniae bacteremia. Factors associated with severity of illness, such as age and mechanical ventilation, seem to be the main risks factors for KPC. Fluoroquinolones use might be a risk factor for KPC bacteremia. Further investigations on risk factors for KPC are warranted.