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Acinetobacter Spreads its Wings
Abstract & Commentary
By Ellen Jo Baron, PhD, D(ABMM), Professor Emerita, Stanford University School of Medicine; Interim Director, Clinical Virology Laboratory, Associate Director, Clinical Microbiology Laboratory, Stanford University Medical Center. Dr. Baron reports no financial relationships relevant to this field of study. This article originally appeared in the July 2010 issue of Infectious Disease Alert. It was edited by Stan Deresinski, MD, FACP, and peer reviewed by Timothy Jenkins, MD. Dr. Deresinski is Clinical Professor of Medicine, Stanford University; Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, and Dr. Jenkins is Assistant Professor of Medicine, University of Colorado, Denver Health Sciences Center. Dr. Deresinski serves on the speaker's bureau for Merck, Pharmacia, GlaxoSmithKline, Pfizer, Bayer, and Wyeth, and does research for Merck, and Dr. Jenkins reports no financial relationships relevant to this field of study.
Synopsis: Serious infections caused by Acinetobacter baumannii are appearing in the community, spread by patients who acquired the organism in the hospital setting, and conversely, the organism is being introduced into the hospital from long-term nursing care patient settings. Resistance to antimicrobial agents has increased over the six-year study period, along with the severity of disease.
Source: Sengstock DM, et al. Multidrug-resistant Acinetobacter baumannii: An emerging pathogen among older adults in community hospitals and nursing homes. Clin Infect Dis. 2010:50:1611-1616.
We have all watched as acinetobacter morphed from an infrequently seen isolate of little clinical consequence to a frightening pathogen. Microbiologists used to recover Acinetobacter lwoffii from vaginal secretions in the days when we thought, incorrectly, that gram-negative rods were pathogens in that site. Now we are faced with Acinetobacter baumannii, currently the most common Acinetobacter species seen in clinical samples, causing pneumonia, wound infections, urinary tract infections, and sepsis. The organism does not inherently have any toxins or cytolysins, and other conventional virulence factors have not been detected, as reviewed by Gordon and Wareham.1 Acinetobacter does form biofilms, a trait that no doubt helps it survive in the environment, from which it infects humans.2 And like Salmonella, Yersinia pestis, Bacillus anthracis, and other pathogenic siderophore-producing microbes, it accumulates iron from the environment and its host.3 Probably the most important reason for its increasing importance is its multidrug resistance. In fact, almost every hospital laboratory in the United States has isolated at least one A. baumannii that is resistant to every antimicrobial that can be tested. Carbapenem resistance due to the blaOXA-23 gene, common among injured Iraqi- and Afghanistan-conflict veterans, and spreading rapidly in the civilian population, was associated with prolonged stay in both the intensive care unit and the hospital, according to a recent report from a Veterans Administration system group studying patients at Walter Reed Army Medical Center.4 However, a recent study from an excellent healthcare system in Porto Alegre, Brazil, showed that the risk of 30-day mortality in patients infected with a carbapenem-resistant outbreak strain of A. baumannii was related more to the patient's underlying condition and severity of infection at presentation than to the use of inappropriate therapy.5 On the other hand, only one-third of the 66 patients received the correct therapy, due to many physicians underestimating the importance of the isolate. Early appropriate therapy has been shown in other studies to reduce mortality.6 And the major study summarized here also found increasing morbidity related to increasing antibiotic resistance.
Its role as a hospital-acquired pathogen is well described, but Sengstock and colleagues extended their study to include all patients older than 60 years from whom Acinetobacter was isolated by a central reference microbiology laboratory over the years 2003-2008.7 The laboratory serves four community hospitals in suburban Detroit. Only the first isolate from each patient was included in the database. The patient groups were divided into "community dwellings" and "nursing home dwellings"; patients admitted from long-term acute-care facilities were excluded, although the authors concluded that patients discharged to such facilities from hospitals were one source of multidrug-resistant Acinetobacter in the community. The 840 patients whose cultures were analyzed in the study included 560 community-dwelling (admitted from home) and 280 nursing home-dwelling (admitted from the nursing home) patients. Nosocomial infections were those acquired > 2 days after admission. Thus, the study allowed the authors to evaluate Acinetobacter prevalence in patients who acquired their infection in the hospital, in the community, or in a nursing home. More than half of cultures were from respiratory secretions (56%), but others came from wounds (22%), urine (12%), blood or catheter tip (10%), and stool (0.3%). These sources immediately bring up a potential problem, since Acinetobacter is certainly not a pathogen in stool. This is particularly bothersome with regard to sputum, where the organism is more often a colonizer than a pathogen. The publication reveals no information on laboratory protocols for determining significance of organisms and determining the extent of further workup, such as screening Gram stains of respiratory samples, a long-time proven method used to direct the culture processing of such samples.8 The authors acknowledge that colonization was not differentiated from infection.
Given that caveat, the findings about the organisms themselves are certainly valid. From a relatively low number during 2003-2006, but dramatically exploding in 2007, the percentage of strains resistant to imipenem and/or ampicillin/sulbactam rose from < 5% to > 30%, and the percentage of strains considered pan-resistant (resistant to all eight antibiotic classes tested: ampicillin/sulbactam, aztreonam, cephalosporins, aminoglycosides, quinolones, carbapenems, tetracycline, and trimethoprim/sulfamethoxazole) rose from < 3% to a high of > 20%. The relative percentages of pan-resistant Acinetobacter isolates recovered from patients whose infection was acquired nosocomially (defined as infections acquired by any patient after day two post-admission) and from patients admitted from nursing homes whose infection manifested within the first two days of admission (nursing home-dwelling) also rose steadily after 2005. In contrast, non-nosocomial isolates from community-dwelling patients showed relatively stable levels of pan resistance over the last three years of the study.
Even the overall numbers of Acinetobacter isolates increased from 189 in 2003 to 329 in 2007, and to 214 in 2008, a 25% increase among this older adult patient cohort (p < 0.001). And regardless of their previous habitat, patients with Acinetobacter infections had high rates of adverse outcomes. Only 25% of previously community-dwelling patients were released to home, with 31% being released to hospice care or were dying. Another 27% were released to acute-care, long-term care facilities. Fifty percent of previously nursing home-dwelling patients were released back to the home; 20% were transferred to other acute-care facilities, and 30% were referred to hospice or died. The authors found a direct correlation between increasing antibiotic resistance and adverse outcome, although they noted that they could not establish causation. Of note, half of community-dwelling patients whose infection was caused by a pan-resistant strain expired; another third went to long-term acute-care facilities, and only 6 of 45 patients were discharged to home. Patients discharged to nursing homes hosted strains of increasing resistance over the study period.
One message to take away from this large study is that both hospitals and long-term care facilities (nursing homes) are likely feeding resistant Acinetobacter to each other, which calls for a region-wide or system-wide strategy for reducing the spread of these strains. As has been witnessed with many other pathogens, failure to take measures early allows widespread dissemination of resistance factors. It may already be too late to prevent this under-rated pathogen from becoming the next MRSA or Clostridium difficile. And it may be stating the obvious to remind ourselves that while at least a few new antimicrobials are being developed for MRSA and C. difficile , Acinetobacter has yet to reach the "status" of meriting its very own antibiotic.
1. Gordon NC, Wareham DW. Multidrug-resistant Acinetobacter baumannii: Mechanisms of virulence and resistance. Int J Antimicrob Agents. 2010;35:219-226.
2. de Breij A, et al. Do biofilm formation and interactions with human cells explain the clinical success of Acinetobacter baumannii? PLoS One. 2010;5:e10732.
3. Dorsey CW, Beglin MS, Actis LA. Detection and analysis of iron uptake components expressed by Acinetobacter baumannii clinical isolates. J Clin Microbiol. 2003;41: 4188–4193.
4. Perez F, et al. Antibiotic resistance determinants in Acinetobacter spp and clinical outcomes in patients from a major military treatment facility. Am J Infect Control. 2010;38:63-65.
5. Prates CG, et al. Risk factors for 30-day mortality in patients with carbapenem-resistant Acinetobacter baumannii during an outbreak in an intensive care unit. Epidemiol Infect. 2010;1:1-8. [Epub ahead of print]
6. Erbay A, et al. Impact of early appropriate antimicrobial therapy on survival in Acinetobacter baumannii bloodstream infections. Int J Antimicrob Agents. 2009;34: 575-579.
7. Sengstock DM, et al. Multidrug-resistant Acinetobacter baumannii: An emerging pathogen among older adults in community hospitals and nursing homes. Clin Infect Dis. 2010;50:1611-1616.
8. Anevlavis S, et al. A prospective study of the diagnostic utility of sputum Gram stain in pneumonia. J Infect. 2009; 59:83-89.