Molecular Epidemiology of Acinetobacter Species
In the past decades, there has been an increasing interest in the molecular epidemiology of bacteria. Data generated by a variety of phenotypic and genotypic methods can be used to identify the routes of transmission, both in a localized outbreak situation as well as in interhospital or cross-country spread.
To date, there are three clinically important Acinetobacter species: Acinetobacter baumannii and the unnamed Acinetobacter genomic species 3 and 13TU. Among those, A. baumannii is the most significant nosocomial pathogen especially in patients with impaired host defenses in the intensive care unit, and has been implicated in nearly all kinds of infections including severe nosocomial infections such as bloodstream infection (BSI), pneumonia, and meningitis. In those infections, mortality rates as high as 64% have been reported. Similar to methicillin-resistant Staphylococcus aureus (MRSA), major epidemiologic features of these organisms include their propensity for clonal spread, their involvement in hospital outbreaks as well as resistance to multiple antimicrobial agents.
Only after 1986, when the taxonomy of the genus Acinetobacter was revised and molecular methods provided the necessary tools to identify Acinetobacter at the species level, detailed studies of the epidemiology of the different members of this genus became possible.
Among the variety of molecular methods developed, some – such as plasmid profile analysis and pulsed-field gel electrophoresis (PFGE) – could be used for typing purposes only, while others – such as ribotyping and AFLP – were primarily developed for species identification. To the present day, PFGE remains the gold standard for epidemiological strain typing not only for Acinetobacter species but also for bacteria in general. PCR-based methods – such as randomly amplified polymorphic DNA-PCR (RAPD-PCR) and repetitive extragenic palindromic (REP) PCR – are generally not only easier to perform and less expensive, but they also tend to be less discriminative and less reproducible.
Molecular typing methods have provided important information on the hospital epidemiology of A. baumannii and also, to a far lesser extent, on the epidemiology of other Acinetobacter species. Insights gained through these methods included the mode of spread and the role of hospital personnel and environmental surfaces in their transmission. Outbreaks of A. baumannii involving patients within the same unit, the same hospital, or even different hospitals, cities or countries have been documented.
With the application of newer, sequence-based methods such as multi-locus sequence typing (MLST) or PCR/electrospray ionization mass spectrometry (PCR/ESI-MS) to A. baumannii, further insight into the population structure of A. baumannii might be gained. In addition, pending questions such as whether there are a few predominant clonal lineages that are responsible for the epidemic spread of multidrug-resistant A. baumannii within hospitals and across countries might be answered in the near future.
KeywordsAmplify Fragment Length Polymorphism Molecular Epidemiology Acinetobacter Baumannii Epidemic Spread Acinetobacter Species
- Bou, G., Cervero, G., Dominguez, M.A., Quereda, C., and Martinez-Beltran, J. (2000). PCR-based DNA fingerprinting (REP-PCR, AP-PCR) and pulsed-field gel electrophoresis characterization of a nosocomial outbreak caused by imipenem- and meropenem-resistant Acinetobacter baumannii. Clin. Microbiol. Infect. 6, 635–643.PubMedGoogle Scholar
- Brisse, S., Milatovic, D., Fluit, A.C., Kusters, K., Toelstra, A., Verhoef, J., and Schmitz, F.J. (2000). Molecular surveillance of European quinolone-resistant clinical isolates of Pseudomonas aeruginosa and Acinetobacter spp. Using automated ribotyping. J. Clin. Microbiol. 38, 3636–3645.PubMedGoogle Scholar
- Coelho, J.M., Turton, J.F., Kaufmann, M.E., Glover, J., Woodford, N., Warner, M., Palepou, M.F., Pike, R., Pitt, T.L., Patel, B.C., and Livermore, D.M. (2006). Occurrence of carbapenem-resistant Acinetobacter baumannii clones at multiple hospitals in London and Southeast England. J. Clin. Microbiol. 44, 3623–3627.PubMedGoogle Scholar
- Dortet, L., Legrand, P., Soussy, C. J., and Cattoir, V. (2006). Bacterial identification, clinical significance, and antimicrobial susceptibilities of Acinetobacter ursingii and Acinetobacter schindleri, two frequently misidentified opportunistic pathogens. J. Clin. Microbiol. 44, 4471–4478.PubMedGoogle Scholar
- Ecker, J.A., Massire, C., Hall, T.A., Ranken, R., Pennella, T.T., Agasino, I.C., Blyn, L.B., Hofstadler, S.A., Endy, T.P., Scott, P.T., Lindler, L., Hamilton, T., Gaddy, C., Snow, K., Pe, M., Fishbain, J., Craft, D., Deye, G., Riddell, S., Milstrey, E., Petruccelli, B., Brisse, S., Harpin, V., Schink, A., Ecker, D.J., Sampath, R., and Eshoo, M.W. (2006). Identification of Acinetobacter species and genotyping of Acinetobacter baumannii by multilocus PCR and mass spectrometry. J. Clin. Microbiol. 44, 2921–2932.PubMedGoogle Scholar
- Garcia-Garmendia, J.L., Ortiz-Leyba, C., Garnacho-Montero, J., Jimenez-Jimenez, F.J., Perez-Paredes, C., Barrero-Almodovar, A.E., and Gili-Miner, M. (2001). Risk factors for Acinetobacter baumannii nosocomial bacteremia in critically ill patients: a cohort study. Clin. Infect. Dis. 33, 939–946.PubMedGoogle Scholar
- Grundmann, H.J., Towner, K.J., Dijkshoorn, L., Gerner-Smidt, P., Maher, M., Seifert, H., and Vaneechoutte, M. (1997). Multicenter study using standardized protocols and reagents for evaluation of reproducibility of PCR-based fingerprinting of Acinetobacter spp. J. Clin. Microbiol. 35, 3071–3077.PubMedGoogle Scholar
- Hartstein, A.I., Morthland, V.H., Rourke, J.W., Jr., Freeman, J., Garber, S., Sykes, R., and Rashad, A.L. (1990). Plasmid DNA fingerprinting of Acinetobacter calcoaceticus subspecies anitratus from intubated and mechanically ventilated patients. Infect. Control Hosp. Epidemiol. 11, 531–538.PubMedGoogle Scholar
- Hartstein, A.I., Rashad, A.L., Liebler, J.M., Actis, L.A., Freeman, J., Rourke, J.W., Jr., Stibolt, T.B., Tolmasky, M.E., Ellis, G.R., and Crosa, J.H. (1988). Multiple intensive care unit outbreak of Acinetobacter calcoaceticus subspecies anitratus respiratory infection and colonization associated with contaminated, reusable ventilator circuits and resuscitation bags. Am. J. Med. 85, 624–631.PubMedGoogle Scholar
- Karlowsky, J.A., Draghi, D.C., Jones, M.E., Thornsberry, C., Friedland, I.R., and Sahm, D.F. (2003). Surveillance for antimicrobial susceptibility among clinical isolates of Pseudomonas aeruginosa and Acinetobacter baumannii from hospitalized patients in the United States, 1998 to 2001. Antimicrob. Agents Chemother. 47, 1681–1688.PubMedGoogle Scholar
- Koeleman, J.G., Stoof, J., Biesmans, D.J., Savelkoul, P.H., and Vandenbroucke-Grauls, C.M. (1998). Comparison of amplified ribosomal DNA restriction analysis, random amplified polymorphic DNA analysis, and amplified fragment length polymorphism fingerprinting for identification of Acinetobacter genomic species and typing of Acinetobacter baumannii. J. Clin. Microbiol. 36, 2522–2529.PubMedGoogle Scholar
- Koeleman, J.G., Stoof, J., Van Der Bijl. M.W., Vandenbroucke-Grauls, C.M., and Savelkoul, P.H. (2001b). Identification of epidemic strains of Acinetobacter baumannii by integrase gene PCR. J. Clin. Microbiol. 39, 8–13.Google Scholar
- Koeleman, J.G., van der Bijl, M.W., Stoof, J., Vandenbroucke-Grauls, C.M., and Savelkoul, P.H. (2001a). Antibiotic resistance is a major risk factor for epidemic behavior of Acinetobacter baumannii. Infect. Control Hosp. Epidemiol. 22, 284–288.Google Scholar
- Landman, D., Quale, J.M., Mayorga, D., Adedeji, A., Vangala, K., Ravishankar, J., Flores, C., and Brooks, S. (2002). Citywide clonal outbreak of multiresistant Acinetobacter baumannii and Pseudomonas aeruginosa in Brooklyn, NY: the preantibiotic era has returned. Arch. Intern. Med. 162, 1515–1520.PubMedGoogle Scholar
- Loubinoux, J., Mihaila-Amrouche, L., Le Fleche, A., Pigne, E., Huchon, G., Grimont, P.A., and Bouvet, A. (2006). Bacteremia caused by Acinetobacter ursingii. J Clin Microbiol. 41,1337–1338.Google Scholar
- Maiden, M.C., Bygraves, J.A., Feil, E., Morelli, G., Russell, J.E., Urwin, R., Zhang, Q., Zhou, J., Zurth, K., Caugant, D.A., Feavers, I.M., Achtman, M., and Spratt, B.G. (1998). Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. Proc. Natl. Acad. Sci. U. S. A. 95, 3140–3145.PubMedGoogle Scholar
- Naas, T., Coignard, B., Carbonne, A., Blanckaert, K., Bajolet, O., Bernet, C., Verdeil, X., Astagneau, P., Desenclos, J.C., and Nordmann, P. (2006b). VEB-1 Extended-spectrum beta-lactamase-producing Acinetobacter baumannii, France. Emerg. Infect. Dis. 12, 1214–1222.Google Scholar
- Nemec, A., De Baere, T., Tjernberg, I., Vaneechoutte, M., van der Reijden, T.J., and Dijkshoorn, L. (2001). Acinetobacter ursingii sp. nov. and Acinetobacter schindleri sp. nov., isolated from human clinical specimens. Int. J. Syst. Evol. Microbiol. 51, 1891–1899.Google Scholar
- Nemec, A., Dijkshoorn, L., and van der Reijden, T.J. (2004a). Long-term predominance of two pan-European clones among multi-resistant Acinetobacter baumannii strains in the Czech Republic. J. Med. Microbiol. 53, 147–153.Google Scholar
- Nemec, A., Dolzani, L., Brisse, S., van den Broek, P., and Dijkshoorn, L. (2004b). Diversity of aminoglycoside-resistance genes and their association with class 1 integrons among strains of pan-European Acinetobacter baumannii clones. J. Med. Microbiol. 53, 1233–1240.Google Scholar
- Rhomberg, P.R., Fritsche, T.R., Sader, H.S., and Jones, R.N. (2006). Clonal occurrences of multidrug-resistant Gram-negative bacilli: report from the Meropenem Yearly Susceptibility Test Information Collection Surveillance Program in the United States (2004). Diagn. Microbiol. Infect. Dis. 54, 249–257.PubMedGoogle Scholar
- Schulte, B., Goerke, C., Weyrich, P., Grobner, S., Bahrs, C., Wolz, C., Autenrieth, I.B., and Borgmann, S. (2005). Clonal spread of meropenem-resistant Acinetobacter baumannii strains in hospitals in the Mediterranean region and transmission to South-west Germany. J. Hosp. Infect. 61, 356–357.PubMedGoogle Scholar
- Seifert, H., Boullion, B., Schulze, A., and Pulverer, G. (1994a). Plasmid DNA profiles of Acinetobacter baumannii: clinical application in a complex endemic setting. Infect. Control Hosp. Epidemiol. 15, 520–528.Google Scholar
- Seifert, H., Dolzani, L., Bressan, R., van der, R.T., van Strijen, B., Stefanik, D., Heersma, H., and Dijkshoorn, L. (2005). Standardization and interlaboratory reproducibility assessment of pulsed-field gel electrophoresis-generated fingerprints of Acinetobacter baumannii. J. Clin. Microbiol. 43, 4328–4335.PubMedGoogle Scholar
- Seifert, H., Schulze, A., Baginski, R., and Pulverer, G. (1994b). Plasmid DNA fingerprinting of Acinetobacter species other than Acinetobacter baumannii. J. Clin. Microbiol. 32, 82–86.Google Scholar
- Seifert, H., Strate, A., Schulze, A., and Pulverer, G. (1994c). Bacteremia due to Acinetobacter species other than Acinetobacter baumannii. Infection. 22, 379–385.Google Scholar
- Snelling, A.M., Gerner-Smidt, P., Hawkey, P.M., Heritage, J., Parnell, P., Porter, C., Bodenham, A.R., and Inglis, T. (1996). Validation of use of whole-cell repetitive extragenic palindromic sequence-based PCR (REP-PCR) for typing strains belonging to the Acinetobacter calcoaceticus-Acinetobacter baumannii complex and application of the method to the investigation of a hospital outbreak. J. Clin. Microbiol. 34, 1193–1202.PubMedGoogle Scholar
- Struelens, M.J., Carlier, E., Maes, N., Serruys, E., Quint, W.G., and van Belkum, A. (1993). Nosocomial colonization and infection with multiresistant Acinetobacter baumannii: outbreak delineation using DNA macrorestriction analysis and PCR-fingerprinting. J. Hosp. Infect. 25, 15–32.PubMedGoogle Scholar
- Turton, J.F., Kaufmann, M.E., Gill, M.J., Pike, R., Scott, P.T., Fishbain, J., Craft, D., Deye, G., Riddell, S., Lindler, L.E., and Pitt, T.L. (2006). Comparison of Acinetobacter baumannii isolates from the United Kingdom and the United States that were associated with repatriated casualties of the Iraq conflict. J. Clin. Microbiol. 44, 2630–2634.PubMedGoogle Scholar
- Vaneechoutte, M., Elaichouni, A., Maquelin, K., Claeys, G., Van Liedekerke, A., Louagie, H., Verschraegen, G., and Dijkshoorn, L. (1995). Comparison of arbitrarily primed polymerase chain reaction and cell envelope protein electrophoresis for analysis of Acinetobacter baumannii and A. junii outbreaks. Res. Microbiol. 146, 457–465.Google Scholar
- Vila, J., Ruiz, J., Navia, M., Becerril, B., Garcia, I., Perea, S., Lopez-Hernandez, I., Alamo, I., Ballester, F., Planes, A.M., Martinez-Beltran, J., and de Anta, T.J. (1999). Spread of amikacin resistance in Acinetobacter baumannii strains isolated in Spain due to an epidemic strain. J. Clin. Microbiol. 37, 758–761.PubMedGoogle Scholar
- von Dolinger, D.B., Oliveira, E.J., Abdallah, V.O., Costa Darini, A.L., and Filho, P.P. (2005). An outbreak of Acinetobacter baumannii septicemia in a neonatal intensive care unit of a university hospital in Brazil. Braz. J. Infect. Dis. 9, 301–309.Google Scholar
- Wisplinghoff, H., Edmond, M.B., Pfaller, M.A., Jones, R.N., Wenzel, R.P., and Seifert, H. (2000). Nosocomial bloodstream infections caused by Acinetobacter species in United States hospitals: clinical features, molecular epidemiology, and antimicrobial susceptibility. Clin. Infect. Dis. 31, 690–697.PubMedGoogle Scholar
- Wisplinghoff, H., Rosato, A.E., Enright, M.C., Noto, M., Craig, W., and Archer, G.L. (2003). Related clones containing SCCmec type IV predominate among clinically significant Staphylococcus epidermidis isolates. Antimicrob. Agents Chemother. 47, 3574–3579.Google Scholar
- Zarrilli, R., Crispino, M., Bagattini, M., Barretta, E., Di Popolo, A., Triassi, M., and Villari, P. (2004). Molecular epidemiology of sequential outbreaks of Acinetobacter baumannii in an intensive care unit shows the emergence of carbapenem resistance. J. Clin. Microbiol. 42, 946–953.PubMedGoogle Scholar