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Evolution of Acinetobacter Baumannii Infections and Antimicrobial Resistance

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Evolution of Acinetobacter Baumannii Infections and Antimicrobial Resistance Central European Journal of Clinical Research Volume 2, Issue 1, Pages 28-36 DOI: 10.2478/cejcr-2019-0005 REVIEW Evolution of Acinetobacter baumannii infections and antimicrobial resistance. A review Sonia Elena Popovici1, Ovidiu Horea Bedreag2, Dorel Sandesc2 1“Pius Branzeu” Emergency County Hospital, Timisoara, Romania 2 Faculty of Medicine, “Victor Babes” Univeristy of Medicine and Pharmacy, Timisoara, Romania Correspondence to: Sonia Elena Popovici, MD Clinic of Anesthesia and Intensive Care “Pius Branzeu” Emergency County Hospital, Timisoara, Romania, Bulevardul Liviu Rebreanu, Nr. 156, Cod 300723, Timișoara E-mail: [email protected] Conflicts of interests Nothing to declare Acknowledgment None Funding: This research did not receive any specific grant from funding agencies in the public, commercial or not-for profit sectors. Keywords: Acinetobacter baumannii, hospital-acquired, antimicrobial resistance. These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. Central Eur J Clin Res 2019;2(1):28-36 _________________________________________________________________________________ Received: 12.12.2018, Accepted: 15.01.2019, Published: 25.03.2019 Copyright © 2018 Central European Journal of Clinical Research. This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. in the hospital environment and the multitude of transmission possibilities raises serious issues Abstract regarding the management of these complex in- fections. The future lies in developing new and The emergence of multi-drug resistant targeted methods for the early diagnosis of A. Acinetobacter spp involved in hospital-acquired baumannii, as well as in the judicious use of an- infections, once considered an easily treatable timicrobial drugs. This review details the evolu- pathogen, is troublesome and an immense bur- tion of the pathogenicity of this microorganism, den for the modern medical systems worldwide. together with the changes that appeared in re- In the last 20 years the medical community re- sistance mechanisms and the advancements in corded an increase in the incidence and severi- molecular testing for the early detection of in- ty of these infections as therapeutic means tend fection. to be less and less effective on these strains. The ability of these bacteria to rapidly develop Introduction resistance to antimicrobial agents by continu- ously changing and adapting their mechanisms, The critically ill patient as one of the big- their ability to survive for long periods of time gest challenges in the medical world has a con- 28 Evolution of Acinetobacter baumannii antimicrobial resistance. A review stant need of complex management which also fections have been reported, especially in the involves the prevention and treatment of asso- case of hospital-acquired infections, raising a ciated infections. The length of stay in the ICU, red flag related to the lack of therapeutic means the mechanical ventilation time, the invasive for the ever-evolving multidrug-resistant strains techniques used, as well as the nutrition strate- of this bacterium. Together with technologi- gy all make the critically ill patient susceptible to cal advancements, in 1986 four new genomic infection and influence the clinical outcome and species were proposed after using DNA-DNA mortality rates. It was proven that the mortality hybridization: 3TU, 13 TU, Acinetobacter bau- risk is 2.48 times higher in critically ill patients mannii, and Acinetobacter calcoaceticus which with hospital-acquired infections especially in together form the “A. baumannii complex” [4], as the case of patients with respiratory disease [1]. they share common properties that make them Bacterial infections are a heavy burden hard to distinguish from each other. A. bauman- on the medical systems and on patients world- nii infections associated with medical interven- wide, with the most threatening being patho- tions were proven to have high-virulence which gens of the respiratory tract, enteric pathogens altered the belief that it was a low-virulence and HIV-associated infections. Finding new pathogen acting as an opportunist [5]. Their treatment options represents a constant chal- potential of rapidly developing resistance to lenge for the medical community, as the fight is antimicrobial agents, their capacity of surviving against the continuously evolving mechanisms in the hospital environment for long periods of of microbial resistance. New hope comes from time, and the numerous transmission mecha- the recent advances in the field of genetics, nisms have raised serious issues worldwide mainly DNA sequencing that offer the possibility regarding the treatment and management of of comparing the genomes of the same strains hospital-acquired Acinetobacter spp. infections over a period of time in order to identify genetic [6]. Wright et al. carried out a genomic analysis changes signifying the development of adapta- of A. baumannii isolated from the same patient tion techniques of the microorganism to certain during their hospital stay and have proven that drugs or to the environment [2]. Along the years antibiotic treatment and host response led to research groups have struggled to elucidate the enrichment in mutation [7]. resistance mechanisms of certain pathogens involved in acute infections, such as Neisseria Microbiology – current classification meningitidis, Pseudomonas aeruginosa, and and relevance in the clinical setting Acinetobacter baumannii, with a soft focus on their genomic evolution. The genus Acinetobacter encompass- es opportunistic pathogens, gram-negative Background coco-bacilli in pairs, with dimensions between 1 and 1.5 μm that do not present mobility, and The alarming increase in the incidence produce a catalase enzyme (catalase-positive) of infections determined by opportunistic micro- but does not produce cytochrome oxidase (ox- organisms, especially as epidemiologic events idase-negative) or urease. Regarding nutrition- such as nosocomial infections, have deter- al mechanisms these pathogens are aerobic, mined researchers in the fields of microbiology non-fermenting, and non-fastidious [8]. More re- and molecular biology to carry out studies on cent classification strategies have proposed to these certain types of pathogens. Acinetobacter classify the genus Acinetobacter as part of the baumannii is an ubiquitary bacterium that col- Moraxellaceae family and of the more extensive onizes over 40% of healthy adults that come Gammaproteobacteria class. into contact, with a higher incidence seen in the The A. baumannii complex includes the medical personnel. three most clinically important species that have Belonging to a wider class called Gam- been involved in community-acquired and hos- maproteobacteriae, germs in the Acinetobacter pital-acquired infections in humans, as well as a genus have long been considered as opportun- fourth specie, A. calcoaceticus, frequently found ists, usually involved in less severe infections. in water and soil that does not inflict diseases in Genus Acinetobacter as we nowadays call it the human population. Apart from the “Acineto- was first discovered in 1911 by Martinus Bei- bacter complex” Bouvet and Grimont, and lat- gerinck, as a gram-negative bacterium [3]. Only er Bouvet and Jeanjean [4], described further in 1970 was this pathogen recognized as being genospecies through DNA-hybridization includ- significantly involved in hospital infections, but ing: A. haemolyticus, A. johnosnii, A. junii, A. with a high sensitivity to common antimicrobials Iwoffii, and A. radioresistens. In the last two de- used at the time. However, in the last 30 years cades additional species have been identified, an increased incidence and severity of the in- but out of the total 10 only 3 are of human origin: 29 Evolution of Acinetobacter baumannii antimicrobial resistance. A review A. parvus, A. schindleri, and A.ursingii [9,10,11]. sence of specific structures in the chromosomal Up until now the following species of the Acine- or extra-chromosomal DNA sequence. Natural tobacter genus have been identified, with their variability does not influence these methods type and reference strains mentioned in the as much but they can be affected by insertion, brackets: A. baumannii (ATCC19606T) – with deletions, and point mutations. Fortunately the two genomic species, A.baylyi (DSM14961T), incidence of these defects is lower, and in many A. bouvetii (DSM 14961T), A. calcoaceticus cases they can represent diagnostic or epidemi- (ATCC 23055T) - one genomic specie, A. gern- ologic biomarkers. eri (DSM 14967T), A. grimontii (DSM 14968T), A. baumannii species present indige- A. haemolyticus (ATCC 17906T) with 4 genomic nous plasmids and therefore plasmid analysis species, A. johnsonii (ATCC 17909T) with 7 ge- is one method that has been used for the epi- nomic species, A. junii (ATCC 17908T) with 5 demiological typing but only after taking into ac- genomic species, A. lowffii(ACTC 15309, ATCC count that plasmids can be gained or lost in the 9957) with 8, respectively 9 genomic species, transformation process [16]. A. parvus (NPH384T), A. radioresistens (IAM Ribotyping, although labor-intensive 13186T) with 12 genomic species, A. schin- and with limited discriminatory power, has been dleri (NIPH1034T), A. tandoii (DSM 14970T),
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