Acinetobacter

Acinetobacter is a Gram-negative genus of bacteria belonging to the phylum Proteobacteria. Non-motile, Acinetobacter species are oxidase-negative, and occur in pairs under magnification. They are important soil organisms where they contribute to the mineralisation of, for example, aromatic compounds. Acinetobacter are an important source of infection in debilitated patients in hospital.

Identification
Using FLN, or Fluorescence-Lactose-Denitrification medium, to find the amount of acid produced by metabolism of glucose, different species of bacteria under this genus can be identified.

Microbiology
Species of the genus Acinetobacter are strictly aerobic nonfermentative gram-negative bacilli. They show preponderantly a coccobacillary morphology on nonselective agar. Rods predominate in fluid media, especially during early growth.

The morphology of Acinetobacter spp. can be quite variable in Gram stained human clinical specimens, and cannot be used to differentiate Acinetobacter from other common causes of infection.

Most strains of Acinetobacter, except some of the A. lwoffii strain, grow well on MacConkey agar (without salt). Although officially classifed as non-lactose fermenting, they are often partially lactose fermenting when grown on MacConkey agar. They are oxidase negative, nonmotile and usually nitrate negative.

Taxonomy
The genus Acinetobacter comprises 17 validly named and 14 unnamed (genomic) species. Some unrelated (genomic) species have common designations, while some other species seem to be congruent but have different names. The knowledge of the biology or ecology of acinetobacters at species level is limited. This is due to the fact that identification of acinetobacters at species level is difficult. A phenotypic species identification system has been described and a variety of genotypic methods has been explored and applied to investigate the diversity or phylogeny in the genus. These methods include high resolution fingerprinting with AFLP, PCR-RFLP with digestion of PCR amplified sequences, and analysis of various DNA sequences. Of these, AFLP analysis and amplified 16SrDNA ribosomal DNA restriction analysis have been validated with large numbers of strains of all described species. Nucleotide sequence based methods are expected to be the standard for identification in the near future.

However, because routine identification in the clinical microbiology laboratory is not (yet) possible, they are divided and grouped into three main complexes:
 * Acinetobacter calcoaceticus-baumanii complex: glucose-oxidising nonhemolytic, (A.baumannii can be identified by OXA-51 typing)
 * Acinetobacter lwoffii: glucose-negative nonhemolytic
 * Acinetobacter haemolyticus: hemolytic

Natural Habitat
Acinetobacter spp are widely distributed in nature. They are able to survive on various surfaces (both moist and dry) in the hospital environment, thereby being an important source of infection in debilitated patients. Occasional strains are isolated from foodstuffs and some are able to survive on various medical equipment and even on healthy human skin.

Clinical Significance
Acinetobacter species are generally considered nonpathogenic to healthy individuals. However, several species persist in hospital environments and cause severe, life-threatening infections in compromised patients. The spectrum of antibiotic resistances of these organisms together with their survival capabilities make them a threat to hospitals as documented by recurring outbreaks both in highly developed countries and elsewhere. An important factor for their pathogenic potential is probably an efficient means of horizontal gene transfer even though such a mechanism has so far only been observed and analyzed in Acinetobacter baylyi, a species that lives in the soil and has never been associated with infections.

Most infections occur in immunocompromised individuals, and the strain A. baumannii is the second most commonly isolated nonfermenting bacteria in human specimens.

Acinetobacter is frequently isolated in nosocomial infections and is especially prevalent in intensive care units, where both sporadic cases as well as epidemic and endemic occurrence is common. A. baumannii is a frequent cause of nosocomial pneumonia, especially of late-onset ventilator associated pneumonia. It can cause various other infections including skin and wound infections, bacteremia, and meningitis, but A. lwoffi is mostly responsible for the latter. A. baumannii can survive on the human skin or dry surfaces for weeks.

Ethanol has been found to stimulate the virulence of A. baumanniiin meiofaunal host model studies. Tests on infected nematode worms dosed with ethanol found that the worms laid fewer eggs and their life spans were only 80% of worms infected with a non-ethanol responsive strain of A. baumannii.

Since the start of the Iraq War, over 700 U.S. soldiers have been infected or colonized by A. baumannii. Four civilians undergoing treatment for serious illnesses at Walter Reed Army Medical Center in Washington, D.C., contracted A. baumannii infections and died. At Landstuhl Regional Medical Center, a U.S. military hospital in Germany, another civilian under treatment, a 63-year-old German woman, contracted the same strain of A. baumannii infecting troops in the facility and also died. These infections appear to have been hospital acquired. 

Treatment
Acinetobacter species are innately resistant to many classes of antibiotics, including penicillin, chloramphenicol, and often aminoglycosides. Resistance to fluoroquinolones has been reported during therapy and this has also resulted in increased resistance to other drug classes mediated through active drug efflux. A dramatic increase in antibiotic resistance in Acinetobacter strains has been reported by the CDC and the carbapenems are recognised as the gold-standard and/or treatment of last resort. Rather worryingly is an increase in resistance to the carbapenems which leaves very little treatment option although there some success reported with polymyxin B as well as the use of novel combinations of antibiotics. Acinetobacter species are unusual in that they are sensitive to sulbactam; sulbactam is most commonly used to inhibit bacterial ?-lactamase, but this is an example of the antibacterial property of sulbactam itself.

In November, 2004, the CDC reported an increasing number of A. baumannii bloodstream infections in patients at military medical facilities in which service members injured in the Iraq/Kuwait region during Operation Iraqi Freedom (OIF) and in Afghanistan during Operation Enduring Freedom (OEF) were treated. Most of these were multidrug-resistant. Among one set of isolates from Walter Reed Army Medical Center, 13 (35%) were susceptible to imipenem only, and two (4%) were resistant to all drugs tested. One antimicrobial agent, colistin (polymyxin E), has been used to treat infections with multidrug-resistant A. baumannii; however, antimicrobial susceptibility testing for colistin was not performed on isolates described in this report. Because A. baumannii can survive on dry surfaces for up to 20 days, they pose a high risk of spread and contamination in hospitals, potentially putting immune-compromised and other patients at risk for drug resistant infections that are often fatal and generally expensive to treat.

Identification
Schreckenberger PC, Daneshvar MI, Weyant RS, Hollis DG. Acinetobacter, Achromobacter, Chryseobacterium, Moraxella, and Other Nonfermentative Gram-Negative Rods. In: Murray PR, et al. (Eds.) Manual of Clinical Microbiology. 8 Ed. (2003) ASM Press, Washington DC, pp 749-779

Risk Factors

 * Garcia-Garmendia JL, Ortiz-Leyba C, Garnacho-Montero J, Jimenez-Jimenez FJ, Perez-Paredes C, Barrero-Almodovar AE, Gili-Miner M. Risk factors for Acinetobacter baumannii nosocomial bacteremia in critically ill patients: a cohort study. Clin Infect Dis. 2001 October 1;33(7):939-46.


 * Chen CH, Young TG, Huang CC. Predictive biomarkers for drug-resistant Acinetobacter baumannii isolates with bla(TEM-1), AmpC-type bla and integrase 1 genotypes. J Microbiol Immunol Infect. 2006 Oct;39(5):372-9. PMID: 17066198


 * Joshi SG, Litake GM, Satpute MG, Telang NV, Ghole VS, Niphadkar KB. Clinical and demographic features of infection caused by Acinetobacter species. Indian J Med Sci. 2006 Sep;60(9):351-60. PMID: 16940684


 * Robenshtok E, Paul M, Leibovici L, Fraser A, Pitlik S, Ostfeld I, Samra Z, Perez S, Lev B, Weinberger M. The significance of Acinetobacter baumannii bacteraemia compared with Klebsiella pneumoniae bacteraemia: risk factors and outcomes. J Hosp Infect. 2006 Nov;64(3):282-7. Epub 2006 August 22. PMID: 16930770

Resistance
General, ICU


 * Global / Large Area
 * Waites KB, Duffy LB, Dowzicky MJ. Antimicrobial susceptibility among pathogens collected from hospitalized patients in the United States and in vitro activity of tigecycline, a new glycylcycline antimicrobial. Antimicrob Agents Chemother. 2006 Oct;50(10):3479-84. [PMID: 17005838]
 * Jones ME, Draghi DC, Thornsberry C, Karlowsky JA, Sahm DF, Wenzel RP. Emerging resistance among bacterial pathogens in the intensive care unit - A European and North American Surveillance study (2000-2002). Ann Clin Microbiol Antimicrob. 2004 July 29;3:14.
 * Clark NM, Patterson J, Lynch JP 3rd. Antimicrobial resistance among gram-negative organisms in the intensive care unit. Curr Opin Crit Care. 2003 Oct;9(5):413-23.


 * Limited Region / One Hospital
 * Bayram A, Balci I. Patterns of antimicrobial resistance in a surgical intensive care unit of a university hospital in Turkey. BMC Infect Dis. 2006 October 25;6:155. PMID: 17064415
 * Dobrewski R, Savov E, Bernards AT, van den Barselaar M, Nordmann P, van den Broek PJ, Dijkshoorn L. Genotypic diversity and antibiotic susceptibility of Acinetobacter baumannii isolates in a Bulgarian hospital. Clin Microbiol Infect. 2006 Nov;12(11):1135-7. PMID: 17002615

Acinetobacter


 * MDR
 * Falagas ME, Koletsi PK, Bliziotis IA. The diversity of definitions of multidrug-resistant (MDR) and pandrug-resistant (PDR) Acinetobacter baumannii and Pseudomonas aeruginosa. J Med Microbiol. 2006 Dec;55(Pt 12):1619-29. PMID: 17108263
 * Nseir S, Di Pompeo C, Cavestri B, Jozefowicz E, Nyunga M, Soubrier S, Roussel-Delvallez M, Saulnier F, Mathieu D, Durocher A. Multiple-drug-resistant bacteria in patients with severe acute exacerbation of chronic obstructive pulmonary disease: Prevalence, risk factors, and outcome. Crit Care Med. 2006 Dec;34(12):2959-66. PMID: 17012911
 * Hujer KM, Hujer AM, Hulten EA, Bajaksouzian S, Adams JM, Donskey CJ, Ecker DJ, Massire C, Eshoo MW, Sampath R, Thomson JM, Rather PN, Craft DW, Fishbain JT, Ewell AJ, Jacobs MR, Paterson DL, Bonomo RA. Analysis of antibiotic resistance genes in multidrug-resistant Acinetobacter sp. isolates from military and civilian patients treated at the Walter Reed Army Medical Center. Antimicrob Agents Chemother. 2006 Dec;50(12):4114-23. Epub 2006 September 25. PMID: 17000742
 * Hsueh PR, Teng LJ, Chen CY, Chen WH, Yu CJ, Ho SW, et al. Pandrug-resistant Acinetobacter baumannii causing nosocomial infections in a university hospital, Taiwan. Emerg Infect Dis 2002 Aug;8. PMID: 12141969 Full text available from: http://www.cdc.gov/ncidod/EID/vol8no8/02-0014.htm
 * Mahgoub S, Ahmed J, Glatt AE. Underlying characteristics of patients harboring highly resistant Acinetobacter baumannii. Am J Infect Control. 2002 Nov;30(7):386-90.


 * Carbapenem Resistance
 * Coelho JM, Turton JF, Kaufmann ME, Glover J, Woodford N, Warner M, Palepou MF, Pike R, Pitt TL, Patel BC, Livermore DM. Occurrence of carbapenem-resistant Acinetobacter baumannii clones at multiple hospitals in London and Southeast England. J Clin Microbiol. 2006 Oct;44(10):3623-7. PMID: 17021090
 * Bogaerts P, Naas T, Wybo I, Bauraing C, Soetens O, Pierard D, Nordmann P, Glupczynski Y. Outbreak of infection by carbapenem-resistant Acinetobacter baumannii producing the carbapenemase OXA-58 in Belgium. J Clin Microbiol. 2006 Nov;44(11):4189-92. Epub 2006 September 6. PMID: 16957031
 * Jeong SH, Bae IK, Park KO, An YJ, Sohn SG, Jang SJ, Sung KH, Yang KS, Lee K, Young D, Lee SH. Outbreaks of imipenem-resistant Acinetobacter baumannii producing carbapenemases in Korea. J Microbiol. 2006 Aug;44(4):423-31. PMID: 16953178
 * Cisneros JM, Rodriguez-Bano J, Fernandez-Cuenca F, Ribera A, Vila J, Pascual A, Martinez-Martinez L, Bou G, Pachon J; Spanish Group for Nosocomial Infection (GEIH) for the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC). Risk-factors for the acquisition of imipenem-resistant Acinetobacter baumannii in Spain: a nationwide study. Clin Microbiol Infect. 2005 Nov;11(11):874-9.
 * Lee SO, Kim NJ, Choi SH, Hyong Kim T, Chung JW, Woo JH, Ryu J, Kim YS. Risk factors for acquisition of imipenem-resistant Acinetobacter baumannii: a case-control study. Antimicrob Agents Chemother. 2004 Jan;48(1):224-8. Erratum in: Antimicrob Agents Chemother. 2004 Mar;48(3):1070.


 * Cephalosporin Resistance
 * Lee K, Lim CH, Cho JH, Lee WG, Uh Y, Kim HJ, Yong D, Chong Y; KONSAR Group. High prevalence of ceftazidime-resistant Klebsiella pneumoniae and increase of imipenem-resistant Pseudomonas aeruginosa and Acinetobacter spp. in Korea: a KONSAR program in 2004. Yonsei Med J. 2006 October 31;47(5):634-45. PMID: 17066507

Therapy
Colistin

Montero A, Ariza J, Corbella X, Domenech A, Cabellos C, Ayats J, Tubau F, Ardanuy C, Gudiol F. Efficacy of colistin versus beta-lactams, aminoglycosides, and rifampin as monotherapy in a mouse model of pneumonia caused by multiresistant Acinetobacter baumannii. Antimicrob Agents Chemother. 2002 Jun;46(6):1946-52.

Reports suggest that this bacteria is susceptible to phage therapy. A phage directed against Acinetobacter showed a remarkable lytic activity both in vitro and in vivo: as few as 100 pfu of phage protected mice against Acinetobacter.

Biotechnology
Many of the characteristics of Acinetobacter ecology, taxonomy, physiology and genetics point to the possibility of exploiting its unique features for future applications. Acinetobacter strains are often ubiquitous, exhibit metabolic versatility, are robust and some provide convenient systems for modern molecular genetic manipulation and subsequent product engineering. These characteristics are being exploited in various biotechnological applications including biodegradation and bioremediation, novel lipid and peptide production, enzyme engineering, biosurfactant and biopolymer production and engineering of novel derivatives of these products. It is anticipated that progress in these fields will broaden the range of applications of Acinetobacter for modern biotechnology.