PMID: 8561477, Kolenbrander PE (2000) Oral microbial communities: biofilms, interactions, and genetic systems. Despite being considered a periodontopathogen, A. actinomycetemcomitans can frequently be detected in periodontally healthy individuals, suggesting variability in its virulence 20 . Initial treatment was with amoxicillin and netilmicin, but by day 8 difficulties with venous access necessitated a switch to an oral agent. In: Gorbach SL, Bartlett JG, Blacklow NR, editors. 3. A wide variety of infections due to A. actinomycetemcomitans are reported in the literature, including endophthalmitis (5, 28, 57 ), cerebral abscess (55, 63, 75), septicemia during pregnancy (58), pulmonary and chest wall infection (8, 41, 69, 74), pericarditis (26, 75), septic arthritis (14, 40), vertebral osteomyelitis (29, 42) and chronic lymphadenitis (24). Aggregatibacter actinomycetemcomitans is also encountered in its traditional role as a companion to Actinomyces in actinomycosis (33, 41, 66, 75). Clin Micro Rev 2001;14:177-207. [PubMed], 7. Burgess RC. Strains with fimbriae adhere three to four folds better. Reactivity to A. actinomycetemcomitans correlated with … A wide variety of treatments have been used, generally successfully. These 3 species have recently been transferred to the new genusAggregatibacter within the family Pasteurellaceae (45). Aggregatibacter actinomycetemcomitans is a small, fastidious, non-motile, non-encapsulated, slow-growing, capnophilic, Gram-negative cocco-bacillus. Agar dilution MICs have been obtained using an inoculum of 104 CFU/spot on Mueller-Hinton Haemophilustest medium (47, 48, 52), Mueller-Hinton agar supplemented with rabbit blood (22), trypticase soy agar with sheep blood (46) incubated in 5% -10% CO2, or Wilkens-Chalgren agar incubated anaerobically (17, 59), with results read at 24 hours (46) or 48 hours (17, 22, 47, 48, 52, 59). The organism has a number of means of evading host defences, which include: (i) production of leukotoxin; (ii) producing immunosuppressive factors; (iv) secreting proteases capable of cleaving IgG; and (v) producing Fc-binding. Hammerberg O, Gregson DB, Gopaul D, Lampe H. Recurrent cervical and submandibular lymphadenitis due to Actinobacillus actinomycetemcomitans. Oral MicrobiolImmunol. PMID: 17412552. Vaccines are not available for Aggregatibacter actinomycetemcomitans. The erythromycin MBCs for 60% of the isolates were three- to fourfold higher than the corresponding MIC. Aggregatibacter Actinomycetemcomitans-Induced Hypercitrullination Links Periodontal Infection to Autoimmunity in Rheumatoid Arthritis. The MIC of ciprofloxacin for the isolate was 0.019mg/L and the steady state serum concentration achieved was 4.1mg/L (2). Ofloxacin has been used successfully to complete therapy in a case of native mitral valve endocarditis. The distribution of the bacteria was studied in healthy normals, patients with adult periodontitis, diabetics, and those with LJP. 1992;7: 338–43. J Periodontal 1999:70:888-892. [PubMed], 35. Am J Med 1988;85:104-107. [PubMed], 38. 1995;63:2612–18. Eur J Clin Microbiol Infect Dis 1998;17:104-107. [PubMed], 37. 4 Korostoff J, Yamaguchi N, Miller M, Kieba I, Lally ET. Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Treponema denticola / Prevotella intermedia Co-Infection Are Associated with Severe Periodontitis in a Thai Population. They are proteinaceous structures found on cell surfaces. Adhesion to epithelial and tooth surfaces is dependent on the presence of surface proteins and structures such as microvesicles and fimbriae. Key tests for discrimination between A. actinomycetemcomitans and V-factor independent strains of Aggregatibacter aphrophilus are catalase, ONPG and fermentation of lactose, sucrose and trehalose (45). Actinobacillus actinomycetemcomitans pneumonia with possible septic embolization [Letter]. Clin Infect Dis 1996; 23:657-658. [PubMed], 14. Das M, Badley AD, Cockerill FR, Steckelberg JM, Wilson WR. Studies have suggested that A. actinomycetemcomitans is involved in the aetiology of aggressive periodontitis as well as in chronic periodontitis. determined values of penicillin G, ampicillin, cefazolin, tetracycline and chloramphenicol for an isolate from a patient with pericarditis. In vitro activity of antibiotics alone and in combination against Actinobacillus actinomycetemcomitans. Konig et al . Potts TV, Berry EM. Marshall C, McDonald M. Recurrent subacute bacterial endocarditis as a presentation of left atrial myxoma. Klinger R. Untersuchungen uber menschliche Aktinmykose. Rare Actinobacillus infection of the cavernous sinus causing painful ophthalmoplegia: case report. Because of their excellent bactericidal activity against A. actinomycetemcomitans, fluoroquinolones are likely to find a role in the treatment of periodontitis, albeit in combination with antibiotics having activity against anaerobes. There was no clinical response and the patient died. Aggregatibacter actinomycetemcomitans was recovered from blood cultures incubated for more than 14 days, including those taken during vancomycin treatment and just before death (20). A. actinomycetemcomitans is also resistant to clindamycin, therefore of the recommended prophylactic regimens for immediate-type penicillin allergic patients azithromycin or clarithromycin are the only agents with any activity against A. actinomycetemcomitans (15). Page MI, King EO. Aggregatibacter actinomycetemcomitans is a gram-negative, capnophilic coccobacillus 13, that is strongly associated with aggressive periodontitis (AgP) 14. Actinobacillus actinomycetemcomitans pneumonia with chest wall and subphrenic abscess. L Antimicrob Agents Chemother 1986;29:699-700. [PubMed], 21. The genetic diversity among different isolates of Aggregatibacter actinomycetemcomitans is great and its ability to express and release virulence factors varies. 32. Recommendations by the American Heart Association. Wilson M, McNab R, Henderson B. Bacterial disease mechanisms: an introduction to cellular microbiology. Annu Rev Microbiol 54: 413–437. Endocarditis due to Actinobacillus actinomycetemcomitans serotype c and patient immune response. Berbari EF, Cockerill FR, Steckelberg JM. Renton TF, Danks J, Rosenfeld JV. Antimicrob Agents Chemother 1980;17:943-946. Aggregatibacter actinomycetemcomitans is a Gram-negative opportunistic pathogen associated with rapidly progressing periodontitis and with extra-oral diseases, such as endocarditis [1–3]. Bacterial adhesion, which facilitates colonization is the key virulent mechanism. Stepanović S, ToÅ¡ić T, Savić B, Jovanović M, K’ouas G, Carlier J-P. Int J Syst Bacteriol 1983;33:765-771. For decades, Aggregatibacter actinomycetemcomitanshas been associated with aggressive forms of periodontitis in adolescents. (2013) Psl trails guide exploration and microcolony formation in Pseudomonas aeruginosa biofilms. Aggregatibacter actinomycetemcomitans is typically catalase positive and oxidase negative although occasional strains produce oxidase. Antimicrob Agents Chemother 1980;18:9-12. It has also been proposed that A.actinomycetemcomitans can produce super antigens, which have the ability to bring about T cell apoptosis by binding to T cell receptors [22,23]. Nature 497: 388–391. The extent to which these variables may influence the MIC for A. actinomycetemcomitans is not known, however, there was no difference observed in agar dilution MICs of cefixime and ciprofloxacin between incubation anaerobically or in 5% CO2 for 50 isolates (50). Invasion has been demonstrated in vivo and in vitro. MicrobPathog 45: 173–180. The distinctive name A. actinomycetemcomitansoriginates from it having been first isolated in association with Actinomyces israelii from patients with cervico-facial actinomycosis (31). Antagonism was seen as often as synergy when rifampicin was combined with penicillin, but was not seen in combination with cephalosporins (cephapirin or ceftriaxone). Deoxyribonucleic acid-deoxyribonucleic acid hybridisation analysis of Actinobacillus actinomycetemcomitans and Haemophilus aphrophilus. Characterization of an antiproliferative surface-associated protein from Actinobacillusactinomycetemcomitans which can be neutralized by sera from a proportion of patients with localized juvenile periodontitis. The aortic valve was the most commonly affected site (38/75; 50.7%) and in 10 cases vegetations were present on multiple valves. Aust Dent J 1996;41:12-15. [PubMed], 56. APMIS 2005;113:225-228. [PubMed], 64. Almost all the RTX leukotoxins are secreted except LtxA toxin of A. actinomycetemcomitans which is thought to be entirely cell associated; either bound to cell surface-associated nucleic acids [16] or within membranous vesicles which bud from bacterium’s surface [17,18]. Norskov-Lauritsen N and Kilian M. Reclassification of Actinobacillus actinomycetemcomitans, Haemophilus aphrophilus, Haemophilus paraphrophilus and Haemophilus segnis as Aggregatibacter actinomyctemcomitans gen. nov., comb. These authors note the absence of previous studies to determine which combinations of antibiotics are synergistic against A. actinomycetemcomitans and caution against the empirical use of most single agents, or any combination, to treat A. actinomycetemcomitans infection without supporting laboratory data (73). KuritaiOchiai T, Ochiai K, Ikeda T. Immunosuppressive effects induced by Actinobacillusactinomycetemcomitans: Effect on immunoglobulin production and lymphokine synthesis. Evaluation of three selective media for isolation of Aggregatibacteractinomycetemcomitans. Binder MI, Chua C, Kaiser PK, Mehta N, Isada CM. Aggregatibacter actinomycetemcomitans is a Gram-negative commensal bacterium of the oral cavity which has been associated with the pathogenesis of … Susceptibility to penicillin, amoxicillin, ampicillin, ticarcillin, and piperacillin is more variable (Table 1). Aggregatibacter actinomycetemcomitans is part of the normal oral flora and infection is endogenously acquired. This study aimed to assess the antimicrobial susceptibility of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Tannerella forsythia isolated from periodontitis patients to amoxicillin, metronidazole, azithromycin and moxifloxacin. J Hand Surg 1987;12:294-5. [PubMed]Â, 8. A cell stress protein, chaperonin 60 is considered to be a potent bone degrading molecule by stimulating bone resorption by acting as an osteoclast ‘growth factor’. A recent review of A. actinomycetemcomitans endocarditis found the mean time was 7.1 days (range 1-15 days) for 54 of the 102 cases where this information was available (49). Dental surgery may be indicated for cases of periodontitis. 54. reported values for isolates from 2 patients with PVE. 44. The hyperleukotoxin-producing A. actinomycetemcomitans strain demonstrates up-regulation of attachment genes, permitting it to attach better than the wild-type strain in competition with commensal bacteria for space on tooth surfaces.  During the last two decades, it has been shown that Aggregatibacter actinomycetemcomitans can be regarded as a major pathogen in destructive periodontal diseases (Slots et al. In a recent series of 45 patients with endocarditis due to HACEK organisms 2 patients died during treatment and thirteen had valve surgery during the first month after diagnosis. Strong evidence is available on the role of Aggregatibacter actinomycetemcomitans (A.a) as the causative agent of localised juvenile periodontitis (LJP), a disease characterised by rapid destruction of the tooth-supporting tissues. determined both MICs and MBCs of tetracyclines, macrolides, clindamycin, fluoroquinolones and metronidazole for 11 isolates of A. actinomycetemcomitans (39). Diskitis caused by Actinobacillus actinomycetemcomitans. Three studies have investigated the bactericidal activity of various antibiotics against several strains of A. actinomycetemcomitans (20, 39, 52). The most actively studied gene product of the organism is a leukotoxin and a member of the RTX (repeats in toxin) family whose cellular receptor is the integrin, LFA-1, thus accounting for its selective effect on leucocytes (although only those from primates) [13-15]. Periodontal disease is usually a chronic disease taking many months to develop. Infect Immun 67: 2627–2632. Prosthetic valve endocarditis due to A. actinomycetemcomitans was first described in 1972 (61). Endarteritis and mycotic aortic aneurysm caused by an oral strain of Actinobacillus actinomycetemcomitans. Paju S, Carlson P, Jousimies-Somer H, Asikainen S. Heterogeneity of Actinobacillus actinomycetemcomitans strains in various human infections and relationships between serotype, genotype and antimicrobial susceptibility. HACEK group endocarditis at the Riyadh Armed Forces Hospital. J Biol Chem. Scientific data clearly underlines its etiological role in localized aggressive periodontitis. Cell Microbiol, 269–275. This affirms to the possibility that the bacterium itself is toxic to the target cells. It is a major pathogen in juvenile periodontitis. Periodontitis; Leukotoxin; Lipopolysaccharide, Ragavendran R, Ramya V, Paddmanabhan P. Aggregatibacter Actinomycetemcomitans – Its Role in Periodontitis. Abstract T en systemically healthy subjects (ages 28 to 60 years) with untreated moderate to severe periodontal disease and evidence of presence of A. actinomycetemcomitans underwent standard mechanical periodontal treatment consisting of oral hygiene instruction and … The interaction between RTX toxins and target cells. The apoptosis of the target cells in response to A.actinomycetemcomitans leukotoxin is by a mechanism involving mitochondrial perturbation [19]. El Khizzi N, Kasab SA, Osoba AO. Actinobacillus actinomycetemcomitans prosthetic valve endocarditis. Yogev R, Shulman D, Shulman ST, Glogowski WG. A. actinomycetemcomitans and other members of the HACEK group (Haemophilus, Cardiobacterium, Eikenella and Kingella) are primarily associated with bacterial endocarditis. A. actinomycetemcomitans produces a 65-kDa macromolecule able to bind to the IL-10 receptor and henceforth can modulate monocyte/macrophage function as IL- 10 is considered to be a major macrophage de-activating cytokine. The greatest reduction in colony-forming units (minus 4 logs) after 24 hours incubation in an antibiotic concentration four times the MIC was seen with penicillin (range MIC 0.02-4µg/mL), gentamicin (0.1-10µg/mL) and ciprofloxacin (0.001-0.5µg/mL). [PubMed], 26. Pericarditis, pneumonia and brain abscess due to a combined Actinomyces-Actinobacillus actinomycetemcomitans infection. They therefore tested combinations of rifampicin with various ß-lactam antibiotics. doi: 10.1038/ nature12155 PMID: 23657259, Rupp ME, Fey PD (2001) In vivo models to evaluate adhesion and biofilm formation by Staphylococcus epidermidis. Orthopedics 1998;21:714-716.[PubMed]. 18 Pathogenesis of Aggregatibacter actinomycetemcomitans in Periodontitis The most common illness associated with A. actinomycetem- comitans is juvenile periodontal disease.A. 13. Authors: Susan L Taylor, MBChB, FRCPA,  Selwyn D R Lang, MBChB, FRACP, FRCPA. 2002; 32:1–13. They concluded that ciprofloxacin or cefixime might be used in combination with metronidazole to treat periodontitis in patients allergic to penicillins (50). 55. showed that rifampicin and ceftriaxone shared the lowest MIC90 value (1.6µg/mL) for 24 clinical isolates of A. actinomycetemcomitans (73). Various studies have associated Aggregatibacter actinomycetemcomitans, formerly known as Actinobacillus actinomycetemcomitans, with aggressive periodontitis. It has been well documented that biofilm bacteria predominate, numerically and metabolically, in virtually all nutrient-sufficient ecosystems, including the oral cavity [1,2]. The MBCs of clarithromycin were always the same or, at most, twofold higher than the corresponding MIC. Oral MicrobiolImmunol. Wilson ME. Endocarditis due to gram-negative bacteria: report of 56 cases. This work is licensed under a Creative Commons Attribution 4.0 International License. Cuende E, de Pablos M, Gomez M, Burgaleta S, Michaus L, Vesga JC. Aggregatibacter actinomycetemcomitans was first identified as a possible periodontal pathogen in 1975 in studies of localized juvenile periodontitis, now known as localized aggressive periodontitis (LAP) (36, 43). Respir Med 1992;86:341-343.  [PubMed], 67. van Winkelhoff AJ, Overbeek BP, Pavicic MJAMP, van den Bergh JPA, Ernst JPMG, de Graaff J. Long-standing bacteremia caused by oral Actinobacillus actinomycetemcomitans in a patient with a pacemaker. Scand J Infect Dis 2003;35:133-136. [PubMed], 6. In 1962 King and Tatum reviewed 33 isolates; 32 were not associated with diagnosed actinomycosis and 27 were isolated from blood (30). Comparative activities of cefuroxime, amoxicillin-clavulanic acid, ciprofloxacin, enoxacin, and ofloxacin against aerobic and anaerobic bacteria isolated from bite wounds. The combination of ceftriaxone and rifampicin would seem reasonable, but has not been clinically evaluated. Rev Infect Dis 1989;11:665-667. [PubMed] Â, 72. It is also suspected to be involved in chronic periodontitis. [PubMed], 65. Among children below the age of 11, A. actinomycetemcomitans has been isolated from 0-26% of periodontally healthy children and 40-100% of patients with prepubertal periodontitis or other types of early-onset periodontitis. A. actinomycetemcomitans has been isolated from 75-100% of the lesions of localized juvenile periodontitis. Tyrrell J, Noone P, Prichard JS. But it is considered to be a less significant cytokine inducer than the secreted protein. Oral MicrobiolImmunol. White PA, Wilson M, Nair SP, Kirby AC, Reddi K, Henderson B. A. actinomycetemcomitans (Aa) was first reported by Klinger in 1912 where he described a previously unknown Gram-negative microorganism that was found in actinomycotic lesions associated with Actinomyces, hence the latin word “comitans” in co… While these studies highlight the significance of exopolysaccharide, they also bring the genes encoding the exopolysaccharide to the forefront in the disease process. 62. Aggregatibacter actinomycetemcomitans , a microorganism associated with aggressive periodontitis, can result in tooth loss and systemic complications. Infective endocarditis due to unusual or fastidious microorgansims. only one of 13 patients with A. actinomycetemcomitans prosthetic valve endocarditis died and only two required surgical intervention during treatment (23). Though it was initially named as Actinobacillus actinomycetemcomitans, it was found that the bacterium is more similar to haemophilus than actinobacillus and hence it was reclassified under aggregatibacter as Aggregatibacter actinomycetemcomitans. Resistance profile survey of 50 periodontal strains of Actinobacillus actinomycetemcomitans. 4. However, that isolate fermented lactose and sucrose and was more likely to be Aggregatibacter aphrophilus (30). One showed an additive effect between ampicillin and gentamicin by time-kill curve and the other, absence of synergy between ampicillin and streptomycin (23). Yogev et al. It has been observed that microfilaments and microtubules for intracellular movement . Recent CLSI guidelines recommend cation-adjusted Mueller-Hinton broth with lysed horse blood, direct colony suspension equivalent to a 0.5 McFarland standard and incubation at 35°C in 5% CO2 for 24-48 hours (11). They penetrate gingival epithelium. Kugler et al. The repeated message is that laboratory susceptibility testing of A. actinomycetemcomitans is essential to enable treatment appropriate for a particular isolate and site of infection because susceptibility varies considerably, especially to ß-lactam agents. nov., Aggregatibacter aphrophilus comb. Surface entities like vesicles mediate aggregation. The mean time until detection of growth of A. actinomycetemcomitans in blood cultures was 5.5 days (range 2 - 9 days) in a review of 12 cases of prosthetic valve endocarditis (PVE) (23) and 4.4 days (range 3-7 days) in a series of 5 PVE (18). This leukotoxin is encoded by an operon belonging to the core genome of this bacterial species. [25] Bacterial components involved in Adhesion are called adhesins. found synergy in vitro between rifampicin and both penicillin and ceftriaxone, but not consistently and the combination of rifampicin and penicillin was just as commonly antagonistic (73). The process of intracellular movement and the cell spreading could be inhibited by agents that interfered with microtubule dynamics, suggesting that this bacterium when internalized interacts closely with the microtubules of the host cell . Unfortunately, vancomycin (2G per day) was also chosen as empirical treatment. doi: 10.1016/j.micpath.2008.05.007 PMID: 18573331, Vuong C, Voyich JM, Fischer ER, Braughton KR, Whitney AR, et al. In addition to valvular endocarditis, A. actinomycetemcomitans endarteritis has occurred in adults with previously undiagnosed aortic coarctation (27, 36) and infection of a left atrial myxoma is described (35). † A. actinomycetemcomitans showed susceptibility for amoxicillin and amoxicillin plus clavulanate, while 28% of the isolated strains were resistant to azithromycin and 61.7% towards metronidazole. Prosthetic valve endocarditis due to A. actinomycetemcomitans was successfully treated with oral ciprofloxacin 750mg every 12 hours for 8 weeks. For example, in several infection models, the exopolysaccharide PIA has been demonstrated to be relevant for the virulence of S. epidermidis [9,10,11]. J Infect 1997;34:69-74. [PubMed], 19. Infective endocarditis caused by HACEK microorganisms. Chen PB, Davern LB, Neiders ME, Reynolds HS, Zambon JJ. Available from: http://biomedpharmajournal.org/?p=3774>. Wayne PA: Clinical and Laboratory Standards Institute; 2007. Metronidazole appeared to have bactericidal activity, but both MICs and MBCs were high (MIC50 = MBC50 = 64µg/mL). However, DNA homology and 16S rRNA sequencing studies have demonstrated a close relationship to Haemophilus aphrophilus and Haemophilus segnis (10, 54). The overall mortality rate from A. actinomycetemcomitans endocarditis has been approximately 18% and is not increased with prosthetic valve involvement (23, 37, 49). A. actinomycetemcomitans has been reported to produce a number of, as yet unidentified, proteins with cell cycle-inhibitory activity causing arrest in the G2 phase of the cell cycle. In a survey of clinical microbiology laboratories using Septi-Chek blood culture bottles, the 538 respondents indicated that only 2/136 patients (1.5%) with bacteremia due to fastidious bacteria were first shown to be bacteremic following incubation of bottles for greater than 7 days (16). On agar, serum with bacitracin and vancomycin ( range MIC 16-120µg/mL ) was chosen. Indication for valve replacement ( 23 ) target cells Korostoff J, N. Affirms to the forefront in the disease process generally successfully subsequently named Haemophilus actinomycetemcomitans, species! Wakefield T, Reller LB, Carroll KC population with chronic periodontitis comitans ’ previously... Aggregatibacter actinomycetemcomitans is typically catalase positive and oxidase negative although occasional strains produce.! 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