Review
Acinetobacter baumannii: a universal threat to public health?

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Abstract

Acinetobacter spp. are non-fermentative, strictly aerobic, Gram-negative microorganisms with a confusing taxonomic history. The Acinetobacter baumannii–Acinetobacter calcoaceticus complex is the species most commonly isolated from clinical specimens. It is ubiquitous in nature and has been found as part of the normal skin, throat and rectal flora as well as in food and body lice. It colonises patients in Intensive Care Units and contaminates inanimate hospital surfaces and devices as well as wounds, including war injuries. Although a frequent coloniser, Acinetobacter can be the cause of severe and sometimes lethal infections, mostly of nosocomial origin, predominantly ventilator-associated pneumonia. Bacteraemic infections are rare but may evolve to septic shock. Acinetobacter also emerges as a cause of nosocomial outbreaks and is characterised by increasing antimicrobial multiresistance. Antibiotic use, especially carbapenems and third-generation cephalosporins, is recognised as the most important risk factor for multiresistance. Described resistance mechanisms include hydrolysis by β-lactamases, alterations in outer membrane proteins and penicillin-binding proteins, and increased activity of efflux pumps. Today, Acinetobacter resistant to carbapenems, aminoglycosides and fluoroquinolones presents a challenge to the clinician. However, sulbactam, tigecycline and colistin represent the current therapeutic approaches, which are associated with satisfactory efficacy.

Introduction

Acinetobacter spp. have emerged in recent years as a major cause of nosocomial infections associated with significant morbidity and mortality [1], [2]. Considered to be a commensal of low-grade pathogenicity, i.e. an opportunistic microorganism, Acinetobacter was frequently ignored in the 1970s whenever isolated from clinical specimens [3]. However, interest in Acinetobacter has grown rapidly in the last 20 years, a fact attributed to: (i) the worldwide expansion of Intensive Care Units (ICUs) that led to a change in the type of infections caused by Acinetobacter; and (ii) the emergence of multidrug-resistant (MDR) strains, some of which nowadays are pan-resistant to antibiotics with the exception of colistin [4], [5], [6], [7], [8]. Developing resistance patterns have prompted the suggestion that we are closer to the end of the antibiotic era with Acinetobacter than with meticillin-resistant Staphylococcus aureus (MRSA) [9].

This review focuses on the epidemiology and resistance surveillance of Acinetobacter baumannii as well as current mechanisms of resistance and their clinical impact. In addition, current strategies in therapeutic efforts and control of this universal threat to public health are reviewed.

Section snippets

Taxonomy

Acinetobacter spp. are non-fermentative, strictly aerobic, non-motile, non-pigmented, catalase-positive and oxidase-negative Gram-negative coccobacilli, usually occurring in diploid formation or in chains of variable length that grow on usual laboratory media [10]. The taxonomic history of Acinetobacter spp. appears confusing since they have been classified variously, moving from the family Neisseriaceae to the family Moraxellaceae under the names Moraxella, Herellea, Mima, Achromobacter and

Global epidemiology

Acinetobacter baumannii has been recovered from soil, water, animals and humans, being ubiquitous in nature [13]. Acinetobacter spp. are normal inhabitants of the human skin in the community but are also frequently isolated from the respiratory tract of hospitalised patients [14]. Throat carriage may occur in up to 10% of community residents with excessive alcohol consumption [15]. It has been suggested that human skin could be the source of severe A. baumannii infections such as bacteraemia

Resistance surveillance and risk factors

Acinetobacter baumannii is nowadays emerging as a cause of numerous global outbreaks as well as an endemic strain in ICUs with rising resistance rates. MDR A. baumannii have been reported from hospitals in Europe, the USA, China, Hong Kong, Korea and Japan as well as from remote areas such as the South Pacific [2].

The British Society for Antimicrobial Chemotherapy (BSAC) surveillance data illustrate increasing resistance trends since 2002 in A. baumannii, with >30% of bacteraemic isolates in

Mechanisms of resistance

The recent emergence of A. baumannii strains multiresistant to many classes of antibiotics has been attributed to its rapid ability to accumulate resistance mechanisms as well as being well suited for genetic exchange. Therefore, Acinetobacter belongs to a unique class of Gram-negative bacteria that are characterised as ‘naturally transformable’ [2]. Recently, in a carbapenem-susceptible and extended-spectrum β-lactamase (ESBL)-producing A. baumannii clinical isolate, the largest antibiotic

The clinical impact of Acinetobacter infections

Nowadays, Acinetobacter has gained great interest owing to the worldwide emergence of MDR or even pan-resistant strains that either become endemic or suddenly cause outbreaks of infection, usually in ICUs [8], [87]. The occurrence in recent years of fulminant community-acquired as well as nosocomial pneumonia and VAP indicate the potential of Acinetobacter to cause invasive infections [1]. Like other Gram-negative bacilli, Acinetobacter produces a similar lipopolysaccharide that is responsible

Therapeutic approach

In March 2003, the Infectious Diseases Society of America (IDSA) established the Antimicrobial Availability Task Force (AATF), which prepared a report entitled ‘Bad bugs, no drugs. As antibiotic discovery stagnates… a public health crisis brews’, proposing potential solutions to the dreadful problem of decreasing antibiotic development [104].

The current particularly problematic MDR pathogens, as also identified by the AATF, are A. baumannii and Pseudomonas aeruginosa. Despite the fact that A.

Epilogue

Today, while clinicians confront the worst situation trying to combat even pan-resistant isolates such as Acinetobacter, the industry curtails the development of new antibiotics. A concerted effort by industry, government and academies is urgently required to improve the situation [6]. In the meantime, what is left for the clinician? Proper application of infection control measures and particularly of ‘hand hygiene’ as well as better antibiotic stewardship in order to slow the development of

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