BackgroundTo describe the clinical and microbiological data of carbapenem-resistant Enterobacteriaceae (CRE) infections, the treatment used, hospital- and infection-related mortality, and risk factors for death.MethodsA prospective cohort conducted from March 2011 to December 2012. Clinical, demographic, and microbiological data such as in vitro sensitivity, clonality, carbapenemase gene mortality related to infection, and overall mortality were evaluated. Data were analyzed using Epi Info version 7.0 (CDC, Atlanta, GA, USA) and SPSS (Chicago, IL, USA).ResultsOne hundred and twenty-seven patients were evaluated. Pneumonia, 52 (42 %), and urinary tract infections (UTI), 51 (40.2 %), were the most frequent sites of infection. The isolates were polyclonal; the Bla KPC gene was found in 75.6 % of isolates, and 27 % of isolates were resistant to colistin. Mortality related to infection was 34.6 %, and was higher among patients with pneumonia (61.4 %). Combination therapy was used in 98 (77.2 %), and monotherapy in 22.8 %; 96.5 % of them were UTI patients. Shock, age, and dialysis were independent risk factors for death. There was no difference in infection-related death comparing colistin-susceptible and colistin-resistant infections (p = 0.46); neither in survival rate comparing the use of combination therapy with two drugs or more than two drugs (p = 0.32).ConclusionsCRE infection mortality was higher among patients with pneumonia. Infections caused by colistin-resistant isolates did not increase mortality. The use of more than two drugs on combination therapy did not show a protective effect on outcome. The isolates were polyclonal, and the bla KPC gene was the only carbapenemase found. Shock, dialysis, and age over 60 years were independent risk factors for death.

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Susceptibility of ceftazidime-avibactam and in vitro synergy with meropenem were investigated using disk approximation and time-kill assays against 11 multiresistant Acinetobacter baumannii isolates harboring oxacillinases and 5 Serratia marcescens isolates carrying blaKPC-2. Ceftazidime-avibactam was very active and synergistic with meropenem against multiresistant S. marcescens isolates. On the other hand, only the A. baumannii isolates coharboring blaOXA-23 and blaOXA-117 displayed synergy. The disk approximation technique presented good sensitivity for synergism in S. marcescens infection.

Background: The use of combined antibiotic therapy has become an option for infections caused by multidrugresistant (MDR) bacteria. The time-kill (TK) assay is considered the gold standard method for the evaluation of in vitro synergy, but it is a time-consuming and expensive method. The purpose of this study was to evaluate two methods for testing in vitro antimicrobial combinations: the disk diffusion method through disk approximation (DA) and the agar gradient diffusion method via the MIC:MIC ratio. The TK assay was included as the gold standard. MDR Gram-negative clinical isolates (n = 62; 28 Pseudomonas aeruginosa, 20 Acinetobacter baumannii, and 14 Serratia marcescens) were submitted to TK, DA, and MIC:MIC ratio synergy methods. Results: Overall, the agreement between the DA and TK assays ranged from 20 to 93%. The isolates of A. baumannii showed variable results of synergism according to TK, and the calculated agreement was statistically significant in this species against fosfomycin with meropenem including colistin-resistant isolates. The MIC:MIC ratiometric agreed from 35 to 71% with TK assays. The kappa test showed good agreement for the combination of colistin with amikacin (K = 0.58; P = 0.04) among the colistin-resistant A. baumannii isolates. Conclusions: The DA and MIC:MIC ratiometric methods are easier to perform and might be a more viable tool for clinical microbiology laboratories.

The use of combined antibiotic therapy has become an option for infections caused by multidrug-resistant (MDR) bacteria. Time-kill (TK) assay is considered the gold standard method for evaluation of in vitro synergy; moreover, it is time-consuming and an expensive method. The purpose of this study was to evaluate in vitro synergy using the disk diffusion method through disk approximation (DA), and agar gradient diffusion method by MIC:MIC ratio, as both can be used routinely in clinical microbiology laboratories. Sixty-two MDR Gram-negative clinical isolates (28 Pseudomonas aeruginosa , 20 Acinetobacter baumannii and 14 Serratia marcescens ) were submitted to TK, DA, and MIC:MIC ratio synergy methods. Overall, the agreement between the DA and TK assays ranged from 20 to 93%. As the isolates of A. baumannii showed variable results of synergism according to TK, the calculated agreement was statistically significant in this species against fosfomycin with meropenem, including colistin-resistant isolates. MIC: MIC ratio method showed agreement range from 35 to 71% with TK assays. The kappa test showed a good agreement for the combination of colistin with amikacin (K = 0.58; P = 0.04) among the colistin-resistant A. baumannii isolates. The DA and MIC:MIC ratio methods are easier to perform and may be a more viable tool for clinical microbiology laboratories.

LISTA DE ABREVIATURAS, SÍMBOLOS E SIGLAS µg Micrograma µL Microlitro AMI Amicacina AmpC β-lactamases da classe C de Ambler ANVISA Agência Nacional de Vigilância Sanitária arnB UDP-Ara4O aminotransferase arnC Ara4FN transferase ATCC American Type Culture Collection bla Gene codificador de β-lactamases CAZ Ceftazidima CIF Concentração Inibitória Fracional CIM Concentração inibitória mínima CLSI Clinical and Laboratory Standards Institute CL Colistina Cols Colaboradores CVE Centro de Vigilância Epidemiológica CZA Ceftazidima-avibactam ETP 1. INTRODUÇÃO

The use of combined antibiotic therapy has became an option for infections caused by multidrug-resistant (MDR) bacteria. Time-kill (TK) assay is the gold standard method for evaluation of in vitro synergy; however, it is a time consuming and expensive method. The purpose of this study was to evaluate in vitro synergy using ETEST and disk diffusion methods that can be used routinely in clinical microbiology laboratories. Sixty-two MDR Gram-negative clinical isolates (28 Pseudomonas aeruginosa, 20 Acinetobacter baumannii and 14 Serratia marcescens) were submitted to TK, disk approximation (DA) and MIC:MIC ratio synergy methods. Overall, the agreement between the DA and TK assays for P. aeruginosa and S. marcescens isolates ranged from 57 to 93%. MIC:MIC ratio concordance with TK ranged from 57 to 71%. The best agreement with the TK assay was observed using DA method for A. baumannii isolates for the combination of fosfomycin with meropenem (80%; k= 0,60; P= 0,003). The concordance was also higher for combinations with colistin for colistin-resistant A. baumannii isolates by DA and MIC:MIC ratio methods. The DA and MIC:MIC ratio methods are easier to perform and may be a more viable tool for clinical microbiology laboratories. Moreover, more studies with large collection of strains are needed to evaluate these assays.