An overview of Acinetobacter baumannii: deciphering this amazing pathogen

The genus Acinetobacter comprises several groups of closely related species^(1,2), including the Acinetobacter calcoaceticus-baumannii complex that was initially proposed in 1991⁽³⁾. At that time, it had not yet been described what would become one of the most important multidrug-resistant pathogen, Acinetobacter baumannii⁽⁴⁾. In the following decades, A. baumannii became one of the most prevalent and well adapted pathogen to the nosocomial environment⁽⁵⁾. This adaptive ability is probably a consequence of its evolutionary exposure to selective pressure of antimicrobials, over a long period, in the complex and competitive environment^(4,5).

In the last 20 years, outbreaks caused by carbapenem-resistant A. baumannii isolates have become a major worldwide concern⁽⁴⁾, and infections caused by such pathogen are associated with increased morbidity and mortality⁽⁶⁾. According to the SENTRY antimicrobial surveillance program for Latin America, carbapenem resistance rates increased almost 60% in just one decade among Brazilian A. baumannii isolates, from 12.6% between 1997 and 1999 to 71.4% between 2008 and 2010⁽⁷⁾. Due to the multidrug resistance phenotype frequently verified among the major A. baumannii clones (CC79, CC15, and CC1) disseminated in Brazil^{(8, 9)}, the therapeutic options to treat those infections are drastically limited⁽¹⁰⁾. Since the development of new drugs does not follow the speed and evolution of antimicrobial resistance expressed by Gram-negative bacilli, the polymyxins are generally the only clinically effective antimicrobials^{(10, 11)}, despite of toxicity, which have limited their use in the clinical practice^(12,13).

The production of carbapenem-hydrolyzing class D β-lactamase (CHDLs) is, by far, the most prevalent carbapenem resistance mechanism in A. baumannii^{(14, 15)}. These enzymes weakly hydrolyze carbapenems and have no activity against the third-generation cephalosporins⁽¹⁴⁾. Thus, the presence of insertion sequences, which carry a strong promoter, are required to overexpress the vast majority of genes encoding for such group of β-lactamases⁽¹⁴⁾, as well as the chromosomal encoded ampC⁽⁸⁾. Somehow, along its evolutionary course, A. baumannii uniquely developed insertion sequences into its genome in order to rearrange the expression of different genes according to need and, to a lesser extent, to the energy cost^{(16, 17)}. The presence of multiple copies in the sequenced A. baumannii genomes confirms the importance of these mobile genetic elements for its adaptation and survival in the nosocomial environment^{(17, 18)}.

The spread of clones carrying bla_OXA-23 gene^(8,9) and, to a lesser extent, bla_OXA-143 ⁽¹⁹⁾, has been considered the responsible for the high carbapenem resistance rates (77.4%) verified in A. baumannii isolates recovered from bloodstream infections among Brazilian intensive care units at 2015, according to the last bulletin of the Brazilian Health Surveillance Agency [Agência Nacional de Vigilância Sanitária (Anvisa)]⁽²⁰⁾. Recently, bla_OXA-72 has emerged as one the most frequent CHDL encoding gene found among carbapenem-resistant A. baumannii isolates retrieved in Brazilian hospitals⁽²¹⁾, demonstrating the change in the epidemiology of carbapenem resistance in our country⁽²²⁾. Considering the continental proportions of Brazil, which contributes with the diversity of carbapenemases encoding genes and clones found in our territory^{(8,9,19,21,22)}, epidemiological studies that aimed to characterize the antimicrobial resistance mechanisms of Acinetobacter spp. causing infections in hospitalized patients from distinct Brazilian regions are essential. One of the articles included in this edition evaluated the antimicrobial susceptibility profile and carbapenem-resistant determinants in a large collection of A. baumannii isolates retrieved from distinct Brazilian states. The authors described interesting and original results, as the inter-hospital spread of an emergent CHDL encoding gene across three Brazilian states, as well as the resistance to an important class of antimicrobial agents considered the optimal option to treat the infections caused by multidrugresistant A. baumannii isolates. I hope you enjoy the reading.

REFERENCES

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  Visca P, Seifert H, Towner KJ. Acinetobacter infection--an emerging threat to human health. IUBMB Life. 2011; 63: 1048-54.
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  Henig O, Weber G, Hoshen MB, et al. Risk factors for and impact of carbapenem-resistant Acinetobacter baumannii colonization and infection: matched case-control study. Eur J Clin Microbiol Infect Dis. 2015; 34: 2063-8.
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  Gales AC, Castanheira M, Jones RN, Sader HS. Antimicrobial resistance among Gram-negative bacilli isolated from Latin America: results from SENTRY Antimicrobial Surveillance Program (Latin America, 2008-2010). Diagn Microbiol Infect Dis. 2012; 73: 354-60.
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  Cardoso JP, Cayô R, Girardello R, Gales AC. Diversity of mechanisms conferring resistance to β-lactams among OXA-23-producing Acinetobacter baumannii clones. Diagn Microbiol Infect Dis. 2016; 85: 90-7.
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  Chagas TP, Carvalho KR, de Oliveira Santos IC, Carvalho-Assef AP, Asensi MD. Characterization of carbapenem-resistant Acinetobacter baumannii in Brazil (2008-2011): countrywide spread of OXA-23-producing clones (CC15 and CC79). Diagn Microbiol Infect Dis. 2014; 79: 468-72.
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  Vila J, Pachón J. Therapeutic options for Acinetobacter baumannii infections: an update. Expert Opin Pharmacother. 2012; 13: 2319-36.
• ¹¹
  Rigatto MH, Vieira FJ, Antochevis LC, Behle TF, Lopes NT, Zavascki AP. Polymyxin B in combination with antimicrobials lacking in vitro activity versus polymyxin B in monotherapy in critically ill patients with Acinetobacter baumannii or Pseudomonas aeruginosa infections. Antimicrob Agents Chemother. 2015; 59: 6575-80.
• ¹²
  Ahmed MU, Velkov T, Lin YW, et al. Potential toxicity of polymyxins in human lung epithelial cells. Antimicrob Agents Chemother. 2017; 61(6).
• ¹³
  Pogue JM, Ortwine JK, Kaye KS. Are there any ways around the exposure-limiting nephrotoxicity of the polymyxins? Int J Antimicrob Agents. 2016; 48: 622-6.
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  Poirel L, Naas T, Nordmann P. Diversity, epidemiology, and genetics of class D beta-lactamases. Antimicrob Agents Chemother. 2010; 54: 24-38.
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  Walther-Rasmussen J, Hoiby N. OXA-type carbapenemases. J Antimicrob Chemother. 2006; 57: 373-83.
• ¹⁶
  Pagano M, Martins AF, Barth AL. Mobile genetic elements related to carbapenem resistance in Acinetobacter baumannii. Braz J Microbiol. 2016; 47: 785-92.
• ¹⁷
  Wright MS, Mountain S, Beeri K, Adams MD. Assessment of insertion sequence mobilization as an adaptive response to oxidative stress in Acinetobacter baumannii using IS-seq. J Bacteriol. 2017; 199(9). pii:: e00833-16.
• ¹⁸
  Adams MD, Bishop B, Wright MS. Quantitative assessment of insertion sequence impact on bacterial genome architecture. Microb Genom. 2016; 2(7): e000062.
• ¹⁹
  Mostachio AK, Levin AS, Rizek C, Rossi F, Zerbini J, Costa SF. High prevalence of OXA-143 and alteration of outer membrane proteins in carbapenemresistant Acinetobacter spp. isolates in Brazil. Int J Antimicrob Agents. 2012; 39: 396-401.
• ²⁰
  Agência Nacional de Vigilância Sanitária (Anvisa). Rede nacional de monitoramento da resistência microbiana em serviços de saúde - Rede RM. Boletim informativo: segurança do paciente e qualidade em serviço de saúde nº 12. Relatório da resistência microbiana em infecções primárias de corrente sanguínea confirmadas laboratorialmente relacionadas ao uso de cateter venoso central em unidades de terapia intensiva (2014). Available at: http://www20.anvisa.gov.br/segurancadopaciente/index.php/publicacoes/item/12 [access in: December 13, 2017].
  » http://www20.anvisa.gov.br/segurancadopaciente/index.php/publicacoes/item/12
• ²¹
  Pagano M, Rocha L, Sampaio JL, Martins AF, Barth AL. Emergence of OXA-72-producing Acinetobacter baumannii belonging to high-risk clones (CC15 and CC79) in different Brazilian states. Infect Control Hosp Epidemiol. 2017; 38: 252-4.
• ²²
  Vasconcelos AT, Barth AL, Zavascki AP, et al. The changing epidemiology of Acinetobacter spp. producing OXA carbapenemases causing bloodstream infections in Brazil: a BrasNet report. Diagn Microbiol Infect Dis. 2015; 83: 382-5.

Publication Dates

• Publication in this collection
  Nov-Dec 2017