In vitro activity of antimicrobial agents against multidrug- and extensively drug-resistant Acinetobacter baumannii

Abstract

Acinetobacter baumannii is a leading cause of complicated infections in the hospital environment, particularly among severely ill patients [1]. The crude mortality attributed to Acinetobacter species causing bloodstream infections is higher than 50 % [2]. Carbapenems have been one of the main antimicrobial classes used against A. baumannii infections [3], but the emergence and dissemination of carbapenemases have diminished the utility of this class of drugs from an already limited list of existing treatment options [4]. In Brazil, it is known that carbapenem-resistant A. baumannii is considered endemic [5], and the main lineages circulating in that country are those belonging to the clonal complexes (CCs) CC1, CC15 and CC79 [6,7]. Among the alternatives for the treatment of infections due to carbapenem-resistant A. baumannii, polymyxins and other non-blactam agents, such as tetracyclines, may be valuable options [3]. Given the increasing rates of multidrug-(MDR) and extensively drug-resistant (XDR) A. baumannii [8], determination of the antimicrobial susceptibility of alternative agents is needed to assess the availability of potential therapeutic options. Thus, the aim of this study was to assess the in vitro activity of antimicrobial agents against carbapenemresistant A. baumannii isolates recovered from clinical specimens of patients from several hospitals in the state of São Paulo, Brazil.A total of 71 A. baumannii isolates recovered from clinical specimens of non-duplicate patients attending 64 different health institutions located in 23 different cities across the state of São Paulo, Brazil, referred to the Instituto Adolfo Lutz from 2008 to 2013 were evaluated. The Instituto Adolfo Lutz, a public health laboratory of São Paulo State, Brazil, receives MDR pathogens, as a reference laboratory, from hospitals across the state of São Paulo on an ongoing and voluntary basis for identification and antimicrobial susceptibility testing. Isolates were mostly recovered from blood or vascular catheter (47.9 %), cerebrospinal fluid (21.9 %), tracheal secretion (13.7 %) and urine (12.3 %); remaining sources were bronchoalveolar lavage, peritoneal fluid and unidentified source (1.4 %, each). Species identification was confirmed by sequencing analysis of the 16S-23S rRNA gene spacer region (internal transcribed spacer) [9]. Antimicrobial susceptibility was determined by disc diffusion methodology [10] for amikacin, gentamicin, tobramycin, ciprofloxacin, levofloxacin, piperacillin-tazobactam, ticarcillin-clavulanate, cefotaxime, cefepime, ceftazidime and trimethoprim-sulfamethoxazole. The MIC values were determined for imipenem, meropenem, ampicillin-sulbactam and minocycline (Sigma-Aldrich) using the broth microdilution technique [11]. Polymyxin B and colistin susceptibilities were determined by agar dilution [11]; tigecycline susceptibility was assessed by Etest (bioM erieux) in freshly prepared Mueller-Hinton agar (Oxoid). MIC values that inhibited 50 % (MIC 50 ) and 90 % (MIC 90 ) of the population were calculated, ...

Emergence and Persistence of High-Risk Clones Among MDR and XDR A. baumannii at a Brazilian Teaching Hospital

“…Among the CRAB isolates from a single hospital, we identified the predominance of CC79 (49.5%), CC1 (10.3%), and CC15 (9.3%), corresponding to 69.2% of all the isolates evaluated over the entire period. This finding is well documented in Brazil as well as the occurrence of isolates belonging to the CC25, which seems to configure an emerging clone in our country (Chagas et al, 2014; Campos et al, 2015; Camargo et al, 2016; Provasi Cardoso et al, 2016; Vasconcellos et al, 2017a,b; Royer et al, 2018), although ST25 has already been detected worldwide (Sahl et al, 2015). ST107 was also identified, corresponding to the two isolates carrying OXA-231, which reinforces the association between ST107 and OXA-231 in Brazil (Camargo et al, 2016; Rodrigues-Costa et al, 2018).…”

“…Despite the controversies, tigecycline can be considered one of the few therapeutic options for treatment of MDR infection in skin and soft tissue infections and meningitis (Montravers et al, 2013; Kooli et al, 2016; Lauretti et al, 2017). Still tigecycline is not recommended for the treatment of ventilator-associated pneumonia and BSI (http://www.fda.gov/drugs/drugsafety/ucm224370.htm), we evaluate the tigecycline activity in our BSI isolates with surveillance purposes and no resistance was observed, even this phenotype becomes progressively more common in A. baumannii in several countries (Navon-Venezia et al, 2007; Al-Sweih et al, 2011; Montravers et al, 2013; Sun et al, 2013; Provasi Cardoso et al, 2016; Vasconcellos et al, 2017a; Royer et al, 2018).…”

“…Although the study performed by Wang and colleagues had demonstrated a higher susceptibility rate to minocycline by microdilution method in CRAB compared to epsilometric method, MIC values identified in the isolates of this study were far below the intermediate value for this drug, confirming their susceptibilities (Wang et al, 2016). This antimicrobial is commonly effective against carbapenem-resistant Acinetobacter baumannii (Lashinsky et al, 2017; Poirel et al, 2017), although resistance is already being observed (Cheah et al, 2016; Pournaras et al, 2017; Vasconcellos et al, 2017a). On the other hand, resistance rates to other antimicrobial classes were remarkable.…”

Caracterização genética e perfil de sensibilidade antimicrobiana de cepas multirresistentes de Acinetobacter baumannii presentes em um hospital de ensino

“…Embora relatos pontuais indiquem que este gene pode estar associado a plasmídeos e, por este motivo, transferir-se horizontalmente a outras espécies (Chen et al, 2010;Lee et al, 2009;Saranathan et al, 2014), esta metodologia é aceita e foi validada por diferentes autores (Camargo et al, 2016;Chen et al, 2014;Ghajavand et al, 2015 Acinetobacter baumannii resistentes a carbapenêmcios, muito embora uma crescente resistência já esteja sendo observada, inclusive no Brasil (Cheah et al, 2016;Clímaco et al, 2013;Genteluci et al, 2017;Liu et al, 2016;Pournaras et al, 2017;Wang et al 2016). Não foi verificada resistência a tigeciclina, apesar de este fenótipo mostrar-se progressivamente mais usual em A. baumannii no país (Cardoso et al, 2016;Vasconcellos et al, 2017b). A progressão de tal resistência culminou na publicação de uma meta-análise que desaconselha o tratamento baseado nesse fármaco para infecções por A.…”

“…Ainda assim, no presente trabalho, 35,7% dos isolados foram considerados intermediários, um possível indício do rumo de Acinetobacter à resistência a tigeciclina. Essa tendência tem sido notada também no cenário mundial, visto o crescente registro de A. baumannii com valores intermediários ou resistentes à tigeciclina, muito embora este ainda seja um fármaco de escolha para o tratamento de infecções por A. baumannii MDR ou XDR (Nowak et al, 2017;Park et al, 2017;Vasconcellos et al 2017b, Vega e Dowzicky, 2017).…”