OVERVIEW: What every clinician needs to know

Pathogen name and classification

Acinetobacter species are gram-negative, non-fermenting, often coccobacillary bacteria that belong in the family Moraxellaceae. The genus currently comprises of 34 species, 25 of them have valid names and 9 are named by their genomic group, of which A. baumannii is the most important in human infections. A. baumannii is part of the A. calcoaceticus-A. baumannii complex, which includes A. calcoaceticus (genomic species 1, an environmental species of limited clinical significance), A. baumannii (genomic species 2), A. pittii (genomic species 3) and A. nosocomialis (genomic species 13TU), which are all genetically highly related and difficult to distinguish phenotypically. A. baumannii has been found to be associated with greater resistance to antibiotics and higher mortality among bacteremic patients compared with other genomic species.

What is the best treatment?

The preferred anti-infective agents for serious, invasive Acinetobacter infection is a carbapenem. More specifically, meropenem, doripenem, or imipenem. Ertapenem is not effective against Acinetobacter. Other agents such as sulbactam, aminoglycosides, quinolones, trimethoprim-sulfamethoxazole, tetracycline antibiotics may also be effective, but this depends on antimicrobial susceptibility testing. Last-line agents for carbapenem-resistant organisms include the polymyxin antibiotics (colistin or polymixin B) and tigecycline, which are often used in combination with other agents. See details below:

Antibiotic resistance is a major problem with Acinetobacter infections. It has a range of inherent resistance mechanisms that can be upregulated when required (antibiotic pressure), as well as a great ability to acquire resistance genes from other bacteria through mobile genetic elements such as plasmids.
In broad terms, the mechanisms underlying resistance are either enzymatic or non-enzymatic. The enzymatic are predominately β-lactamases (all Ambler classes), which are capable of breaking down all the β-lactam antibiotics (penicillins, cephalosporins, carbapenems, monobactams) but also includes enzymes that can break down aminoglycosides. The non-enzymatic mechanisms are changes to outer membrane porins or channels that allow the antimicrobial to enter the bacterial cell, efflux pumps that may efflux a single agent or multiple agents out of the cell, alteration of penicillin-binding proteins, and modification of the antimicrobial target, such as ribosomal or DNA gyrase modification.
The most common methods for detecting resistance are to perform antimicrobial susceptibility testing using internationally recognized laboratory standards. There are also validated methods for detection of β-lactamases using β-lactamase-inhibitors. For specific detection of resistance mechanisms, molecular methods such as PCR and sequencing are used to detect resistance genes.
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Alternative therapies include sulbactam (formulated as ampicillin-sulbactam in the United States), polymyxin class of antibiotics and tigecycline. A range of combination therapies have been studied in vitro and in animal models, and combinations including a carbapenem plus a polymyxin, even if the organism is resistant to the carbapenem, appears more active than polymyxin alone. Combinations with non-traditional antimicrobials have also been studied, the most common of these being the addition of rifampicin to a carbapenem and a polymyxin.

How do patients contract this infection, and how do I prevent spread to other patients?

Epidemiology

Acinetobacter species are widely distributed in nature and the hospital environment and can survive on moist and dry surfaces, and may be present in foodstuffs and on healthy skin. Interestingly, despite A. baumannii being the most clinically recognized species, it has not been found widely in environments outside the hospital setting.
A. baumannii has been implicated in hospital outbreaks and in the endemic spread of resistant clones throughout the world. In tropical climates, higher rates of colonization in healthy subjects are seen in the summer months compared with winter.
In a study of blood stream infections (BSI) from 52 US hospitals from 1995 to 2003, Acinetobacter species were the 10th most frequently isolated pathogen accounting for 1.3% of all BSI, of which A. baumannii accounted for two-thirds of the isolates. More recently, European ICU surveillance data from 2009 showed that the Acinetobacter spp. was implicated in ICU-acquired infections in 11.9 to 21.8% of the time, depending on location of infection.
Of greater concern is increasing resistance rates among A. baumannii isolates. In Europe, the rate of imipenem-resistance has been reported to be 47.1% during a 2008 – 2009 study, with highest rates in Turkey and Greece. US-wide surveillance data demonstrates that A. baumannii resistant to carbapenems has grown nearly eight times, going from 5.2% in 1999 to 40.8% in 2010, and increasing in all but one year during the period. During 2006 – 07, the SENTRY Antimicrobial Surveillance Program assessed 544 Acinetobacter species from 41 medical centers located in 10 countries in the Asia-Pacific region, of which 42.3% of the isolates were non-susceptible to imipenem or meropenem, most common in isolates recovered from Singapore.

Infection control issues

The spread of resistant clones between patients can be minimized by hand hygiene and contact precautions. Environmental reservoirs within the hospital environment may become apparent in an outbreak situation and may need targeted environmental cleaning with hydrogen peroxide and peracetic acid. Early case-control study and sampling of potential environmental reservoirs are often required early during an outbreak.
Prevention of acquisition of Acinetobacter species also lies largely with antibiotic stewardship in order to minimize the indiscriminate use of broad-spectrum antimicrobial agents. There is no vaccination available, and antibiotic prophylaxis runs the risk of further increasing the rates of resistance.

What host factors protect against this infection?

Intact skin and mucosal surfaces, and adequacy of neutrophil activity are key aspects of the host to protect against infection with Acinetobacter species.
Although initially considered non-pathogenic in healthy individuals, A. baumannii is now largely considered as an important pathogen implicated in hospital-acquired infections. This is especially true of those patients in the intensive care unit. The presence of indwelling urinary catheters, central venous lines, intubation, and exposure to broad-spectrum antibiotics are all important risk factors. Other risk groups include patients with a history of alcohol abuse, immunosuppression, peritoneal dialysis and neurosurgical intervention. A. baumannii infection of traumatic battlefield wounds in military personnel has been well described.

What are the clinical manifestations of infection with this organism?

Bloodstream infections

Most often associated with ICU-acquired bloodstream infections, with mortality up to 43.3%, exceeded only by Pseudomonas and Candida infections. Typically line-related or attributed to underlying pneumonia, urinary tract infection (UTI), or wound infections.
Hospital-acquired pneumonia

Majority of A. baumannii isolates are from the respiratory tracts of hospitalized patients. Ventilator-associated pneumonia (VAP) due to A. baumannii has been reported in 5% to 20% of ICU-acquired pneumonia.
Community-acquired pneumonia

Described in tropical regions of Australia and Asia, and most common during the rainy season and among those patients with a history of alcohol abuse and/or diabetes mellitus. Can have a fulminant course with secondary bacteremia and is associated with high mortality.
Skin and soft tissue infections

Reported extensively in traumatic battlefield wounds in the military population. Also seen in patients suffering burns and may be difficult to eradicate.
Urinary tract infections

Associated with catheter-associated infections or colonization.
Peritonitis

Reports of peritonitis complicating peritoneal dialysis in those patients with end-stage renal failure.
Meningitis

Most often related to hospital-acquired meningitis, especially reported post-neurosurgical interventions with external ventricular drain placement.
Endocarditis

A rarely reported pathogen in endocarditis, most often associated with prosthetic valves.

What common complications are associated with infection with this pathogen?

Gram-negative sepsis and septic shock may complicate A. baumannii infection of any organ. Antimicrobial resistance may increase the likelihood of a poor outcome given that standard antibiotic therapy may be ineffective at clearing the infection.

How should I identify the organism?

Microscopy reveals A. baumannii to be a non-motile, gram-negative coccobacillary rod. In clinical practice, A. baumannii may be difficult to decolorize on gram staining and can be initially falsely reported as gram-positive cocci from direct smears from blood culture bottles.
A. baumannii will grow on standard, non-selective agar after 24 – 48 hours incubation, making culture a sensitive method of identification. Appearance on horse blood agar is that of smooth, opaque (or white), mucoid colonies that are non-hemolytic and are smaller than that of Enterobacteriacaea. Growth on MacConkey agar appears as a non-lactose fermenter. Other laboratory aspects include oxidase, indole and esculin negativity, catalase positive and are able to oxidize glucose.
Most automated systems perform poorly to differentiate between different Acinetobacter spp. Vitek2, API 20E (bioMérieux, Marcy l’Etoile, France) and Phoenix (Becton Dickinson, Franklin Lakes, NJ, USA) systems will identify down to A. calcoaceticus-A. baumannii complex, but this leads to A. pittii and A. nosocomialis often erroneously identified as A. baumannii.
Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) systems appear to perform better at species differentiation than phenotypic systems.
Identification of clonal outbreaks can be identified using pulsed-field gel electrophoresis (PFGE), although this remains a time consuming and technically difficult exercise. Molecular typing systems using PCR technology have the ability to generate rapid and reproducible results. Whole genome sequencing has emerged as an extremely useful technique for establishing similarity among strains of Gram negative bacilli involved in outbreaks.

How does this organism cause disease?

A number of virulence and survival factors have been described with A. baumannii. Biofilm formation, induction of apoptosis of human cells, siderophores (sequestration of iron from human cells) and quorum sensing signal molecules are all important. Lipopolysaccharide synthesis not only protects the bacteria from host defenses, but also act as the major immunostimulatory factor through interaction with, and signaling by, the Toll-like receptors.

What is the Evidence?

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.. vol. 73. 2012. pp. 354-360. (Imipenem-resistant Acinetobacter spp. rates increased from 6.4%, 12.6%, and 0.0% in the 1997-1999 period to 84.9%, 71.4%, and 50.0% in 2008-2010 in Argentina, Brazil, and Chile, respectively. Oxacillinase [OXA]-producing Acinetobacter spp. was documented in Argentina [OXA-23 and -24], Brazil [OXA-23], Chile [OXA-58], and Mexico [OXA-24].)

Gales, AC, Jones, RN, Sader, HS. “Contemporary activity of colistin and polymyxin B against a worldwide collection of Gram-negative pathogens: results from the SENTRY Antimicrobial Surveillance Program (2006-09)”. J Antimicrob Chemother.. vol. 66. 2011. pp. 2070-2074. (An important reduction in imipenem susceptibility among Acinetobacter spp. and Klebsiella spp. was demonstrated in most geographical regions.)

Gu, Z, Han, Y, Meng, T. “Risk Factors and Clinical Outcomes for Patients With Acinetobacter baumannii Bacteremia”. Medicine (Baltimore).. vol. 95. 2016. pp. e2943(A 6-year retrospective study of 122 cases with monomicrobial A. baumannii bacteremia was conducted in China. The overall 14-day mortality rate was 40.2% [49 of 122 patients]. Independent predictors of 14-day mortality included severity of illness defined by Pitt Bacteremia Score [PBS] [Odds ratio 0.46], neutropenia [OR, 18], and malignancy [OR, 4.63].)

Jiang, Y, Resch, S, Liu, X. “The Cost of Responding to an Acinetobacter Outbreak in Critically Ill Surgical Patients”. Surg Infect (Larchmt).. vol. 17. 2016. pp. 58-64. (The hospital incurred $371,079 in excess costs as a result of an MDRA outbreak. Strategies to prevent and more effectively control such outbreaks are of substantial value.)

Sader, HS, Castanheira, M, Farrell, DJ, Flamm, RK, Mendes, RE, Jones, RN. “Tigecycline antimicrobial activity tested against clinical bacteria from Latin American medical centres: results from SENTRY Antimicrobial Surveillance Program (2011-2014)”. Int J Antimicrob Agents.. vol. 48. 2016. pp. 144-150. (Tigecycline was active against most strains of Acinetobacter spp. [MIC50/90, 1/2 microg/mL; 92.3/72.1% inhibited at

Zenati, K, Touati, A, Bakour, S, Sahli, F, Rolain, JM. “Characterization of NDM-1- and OXA-23-producing Acinetobacter baumannii isolates from inanimate surfaces in a hospital environment in Algeria”. J Hosp Infect.. vol. 92. 2016. pp. 19-26. (Carbapenemase-producing A. baumannii strains were recovered from inanimate surfaces in a hospital environment, surrounding patients, healthcare workers and visitors, associated with an Acinetobacter outbreak in an Algerian hospital.)

Zilberberg, MD, Kollef, MH, Shorr, AF. “Secular trends in Acinetobacter baumannii resistance in respiratory and blood stream specimens in the United States, 2003 to 2012: A survey study”. J Hosp Med.. vol. 11. 2016. pp. 21-26. (Resistance rates among Acinetobacter spp. to such last-resort antimicrobials as carbapenems and colistin are on the rise, whereas resistance to minocycline has declined. Nursing homes are a reservoir of resistant Acinetobacter spp.)

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Acinetobacter species