Aggregatibacter actinomycetemcomitans (Actinobacillus actinomycetemcomitans)
Authors: Susan L Taylor, MBChB, FRCPA, Selwyn D R Lang, MBChB, FRACP, FRCPA
MICROBIOLOGY
The ‘Bacterium actinomycetem comitans’ was previously placed in the genus Actinobacillus. However, DNA homology and 16S rRNA sequencing studies have demonstrated a close relationship to Haemophilus aphrophilus and Haemophilus segnis (10, 54). 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. It is a commensal of the human mouth and can be recovered on culture of oral secretions in up to 20% of healthy people and in the great majority of those with localized juvenile periodontitis (44, 50, 62 ). A. actinomycetemcomitans grows slowly at 37oC, aerobically or anaerobically, in standard broth media or on non-inhibitory solid media provided there is an atmosphere of approximately 5% carbon dioxide. It has no requirement for either X or V factor. In liquid media the organism tends to grow in small granules adhering to the walls of the bottle (30) and this property is behind the name of the new genus Aggregatibacter (45). On agar, colonies generally become visible after 24 hours reaching approximately 3mm diameter after several days. Initially smooth, domed and translucent they become corrugated, star-shaped, adherent and may pit the agar.
Aggregatibacter actinomycetemcomitans is typically catalase positive and oxidase negative although occasional strains produce oxidase. It reduces nitrates to nitrites and is ONPG, urease and indole negative. It can ferment carbohydrates including glucose, fructose, maltose and mannose, and variably xylose, and mannitol. It is unable to ferment galactose, lactose, raffinose, sorbitol, sucrose, trehalose and glycerol (45). King and Tatum (30) identified two biochemical groups, the one fermenting mannitol but not xylose and the other xylose but not mannitol. Subsequently several biotypes and serotypes have been described and serotyping has been used to demonstrate that an isolate causing endocarditis was likely to have originated from the patient’s oral flora (53). 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).
EPIDEMIOLOGY
Aggregatibacter actinomycetemcomitans is part of the normal oral flora and infection is endogenously acquired. The distinctive name A. actinomycetemcomitansoriginates from it having been first isolated in association with Actinomyces israelii from patients with cervico-facial actinomycosis (31). It has subsequently been confirmed as present in at least 30% of actinomycotic lesions (29). For many years A. actinomycetemcomitans was not considered an independent pathogen. In 1951 it was reported as the sole pathogen in a human case of "lumpy jaw" (65). However, that isolate fermented lactose and sucrose and was more likely to be Aggregatibacter aphrophilus (30). In 1962 King and Tatum reviewed 33 isolates; 32 were not associated with diagnosed actinomycosis and 27 were isolated from blood (30).
CLINICAL MANIFESTATIONS
A. actinomycetemcomitans and other members of the HACEK group (Haemophilus, Cardiobacterium, Eikenella and Kingella) are primarily associated with bacterial endocarditis. A well-documented case of native valve endocarditis due to A. actinomycetemcomitans was reported in 1964 (38), and a subsequent review considered that 23 of 25 patients with A. actinomycetemcomitans bacteraemia had good evidence for the diagnosis of bacterial endocarditis (46). Prosthetic valve endocarditis due to A. actinomycetemcomitans was first described in 1972 (61). In a recent review of endocarditis due to rare and fastidious bacteria A. actinomycetemcomitans was the second most frequent agent of endocarditis in the HACEK group (6). Of 399 reported cases, the contribution of each species was Haemophilus parainfluenzae (66), H. influenzae (13),Aggregatibacter aphrophilus (99), A. actinomycetemcomitans (93), Cardiobacterium hominis (76), Eikenella corrodens (19), Kingella kingae (28) and Kingella denitrificans (5) (6).
The most recent review of A. actinomycetemcomitans endocarditis summarizes 102 cases (49). Previous heart disease was a risk factor for 76.5%. The mean duration of symptoms before hospital admission was 13 weeks (range 2 days to 60 weeks) for the 72 patients for whom this information was available. The aortic valve was the most commonly affected site (38/75; 50.7%) and in 10 cases vegetations were present on multiple valves. Complications, most commonly emboli or congestive heart failure, were reported in 49 (63%) of 78 cases and 18 patients died as a result of endocarditis. No recurrence of A. actinomycetemcomitans endocarditis was reported.
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).
In dentistry, the emphasis is on the involvement of A. actinomycetemcomitans in the pathogenesis of localized juvenile periodontitis and acute necrotising ulcerative gingivitis (60). 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. Localized juvenile periodontitis is one manifestation of the spectrum of early onset periodontitis in which severe periodontal attachment loss occurs in children, adolescents and young adults. This organism also occurs in adult forms of periodontitis, but less frequently (60).
Other infections in which A. actinomycetemcomitans has been implicated, and usually isolated in pure culture, include: brain abscess (55, 63, 75), cavernous sinus infection (64), endophthalmitis (5, 28, 57), lymphadenitis (24), septic arthritis (13, 40), osteomyelitis (1, 29, 42), tenosynovitis (7), pacemaker infection (67), pericarditis (26,75), pneumonia (41, 69, 74, 75), empyema, chest wall and subphrenic collections (8, 9), septicemia during pregnancy (58) and urinary tract infection (29).
LABORATORY DIAGNOSIS
The need to incubate blood cultures for 2 - 3 weeks before reporting them as negative has been emphasized in the past (20, 71). 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). However, the number of cases diagnosed using continuous-monitoring blood culture systems was not recorded. 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). A review of 45 cases of endocarditis caused by HACEK bacilli, including 33 native valve infections and 9 cases of A. actinomycetemcomitans, found the mean time until detection of growth in blood cultures was 3.4 days (range 1-10 days) (13).
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). Retrospective reviews of two extended incubation protocols using continuous-monitoring blood culture systems found that HACEK bacteria were not isolated beyond the routine 5 to 6.5 day incubation periods for the 407 and 215 blood cultures where extended incubation was physician requested (3, 51). Recent blood culture guidelines from CLSI recommend that if blood cultures remain negative at 5 days and the diagnosis of endocarditis is still under consideration, to subculture all bottles to chocolate agar (12).
PCR of the 16S rRNA gene and subsequent sequence analysis has been performed on an explanted mitral valve to confirm A. actinomycetemcomitans endocarditis in a blood culture negative case (70).
SUSCEPTIBILITY IN VITRO AND IN VIVO
Single Drugs
Aggregatibacter actinomycetemcomitans is usually susceptible to second, third and fourth generation cephalosporins, carbapenems, mezlocillin, aminoglycosides, fluoroquinolones, cotrimoxazole, rifampicin, chloramphenicol, tetracyclines, clarithromycin and azithromycin (Table 1). Susceptibility to penicillin, amoxicillin, ampicillin, ticarcillin, and piperacillin is more variable (Table 1). The addition of clavulanic acid to amoxicillin confers no advantage against this organism because it does not produce ß-lactamase (34, 46, 59, 68). A. actinomycetemcomitans is usually resistant to erythromycin and to clindamycin and is predictably resistant to methicillin and to vancomycin (Table 1).
The conditions used to obtain the MICs listed in Table 1 vary considerably with respect to medium, atmosphere and duration of incubation. 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). 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). Broth microdilution MICs were obtained using an inoculum of 5x104 CFU in trypticase soy broth with 0.1%NaHCO3 (supplemented with yeast extract and hemin (34)) incubated for 24 hours in 10% CO2 (73) or in air (34). Kugler et al. measured MICs using E-tests placed onto Brucella Blood agar swabbed with a 1.0 McFarland standard suspension of organism and incubated in 5% CO2 for 48 hours (32). 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).
Three studies have investigated the bactericidal activity of various antibiotics against several strains of A. actinomycetemcomitans (20, 39, 52). Eng et al. examined killing kinetics for 20 isolates following a case of endocarditis which developed despite vancomycin and erythromycin prophylaxis. 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). Cefotaxime (range MIC 0.2-0.5µg/mL), cefoxitin (0.2-4µg/mL), trimethoprim/sulphamethoxazole (0.08/5-1.6/100µg/mL) and erythromycin (0.12-4µg/mL) showed lesser degrees of bactericidal activity. Only vancomycin (range MIC 16-120µg/mL) was associated with a total absence of bactericidal activity (20). Miyake et al. determined both MICs and MBCs of tetracyclines, macrolides, clindamycin, fluoroquinolones and metronidazole for 11 isolates of A. actinomycetemcomitans (39). The MBCs of the fluoroquinolones were the same or little more than their MICs. In contrast, MBCs of tetracycline, minocycline, erythromycin and clindamycin were several times their MICs. Metronidazole appeared to have bactericidal activity, but both MICs and MBCs were high (MIC50 = MBC50 = 64µg/mL). Piccolomini et al. determined MBC values for 87 periodontitis-associated isolates of A. actinomycetemcomitans (52). The erythromycin MBCs ranged from 8-64µg/mL, with MBC50=8.0µg/mL and MBC90=32µg/mL. The erythromycin MBCs for 60% of the isolates were three- to fourfold higher than the corresponding MIC. Clarithromycin was more active with MIC50 = MBC50 = 0.5µg/mL, MIC90=2µg/mL and MBC90=4µg/mL. The MBCs of clarithromycin were always the same or, at most, twofold higher than the corresponding MIC.
A few case reports have performed MICs and MBCs for a small range of antimicrobials tested against the clinical isolate, with variable results for penicillin and ampicillin (23, 26, 29). Horowitz et al. determined values of penicillin G, ampicillin, cefazolin, tetracycline and chloramphenicol for an isolate from a patient with pericarditis. MBC values were four times the MIC in the case of the ß-lactam antibiotics, twice the MIC in the case of chloramphenicol and sixteen times the MIC in the case of tetracycline (26). Grace et al. reported values for isolates from 2 patients with PVE. One isolate had an ampicillin MIC=MBC= 4.0µg/mL, ceftriaxone MIC=MBC= <0.12µg/mL and gentamicin MIC=MBC=4.0µg/mL, the second isolate had an ampicillin MIC=1.0µg/mL, MBC=2.0µg/mL and gentamicin MIC=0.25µg/mL, MBC=0.5µg/mL (23). In a case of PVE from a series of infections reported by Kaplan et al., the A. actinomycetemcomitans had an ampicillin MIC=MBC=0.4µg/mL and penicillin MIC=MBC=0.8µg/mL (29).
Combination Drugs
Yogev et al. showed that rifampicin and ceftriaxone shared the lowest MIC90 value (1.6µg/mL) for 24 clinical isolates of A. actinomycetemcomitans (73). They therefore tested combinations of rifampicin with various ß-lactam antibiotics. No combination was consistently synergistic against the 12 isolates tested. Antagonism was seen as often as synergy when rifampicin was combined with penicillin, but was not seen in combination with cephalosporins (cephapirin or ceftriaxone). Indifference or additive effects were seen with rifampicin plus penicillin against 4 of 12 isolates, with rifampicin plus ceftriaxone against 9 of 12 isolates and with rifampicin plus cephapirin against all 12 isolates (73). 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).
Pavicic et al. studied various antimicrobials in combination with either metronidazole or its hydroxymetabolite against five A. actinomycetemcomitans strains (50). Beta-lactam antibiotics (penicillin G, cefixime and moxalactam) as well as ciprofloxacin, acted synergistically with both metronidazole and its hydroxymetabolite, whereas erythromycin, tetracycline and tobramycin showed indifferent or only additive effects. They concluded that ciprofloxacin or cefixime might be used in combination with metronidazole to treat periodontitis in patients allergic to penicillins (50).
Very few investigators have reported on the effect of combining an aminoglycoside with a ß-lactam against A. actinomycetemcomitans. Grace et al. demonstrated synergy between ampicillin and gentamicin by the checkerboard technique for a single isolate with ampicillin MIC=MBC = 4µg/mL and gentamicin MIC=MBC = 4µg/mL, but subsequently treated the patient with ceftriaxone (MIC=MBC= < 0.12µg/mL) and gentamicin (23). In their review of the literature they found only two reports of A. actinomycetemcomitans endocarditis that included synergy studies. One showed an additive effect between ampicillin and gentamicin by time-kill curve and the other, absence of synergy between ampicillin and streptomycin (23).
ANTIMICROBIAL THERAPY
Bacterial Endocarditis
Despite the paucity of evidence for synergy between penicillin or ampicillin and aminoglycosides against A. actinomycetemcomitans, most cases of A. actinomycetemcomitans endocarditis, whether native or prosthetic valve disease, have been treated with this combination for 4-6 weeks with largely satisfactory outcomes (14,19, 23, 29, 37, 49). 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. The proportion of patients who underwent surgical therapy was similar, regardless of the infecting organism (14). The review of endocarditis due to unusual or fastidious organisms by Berbari et al. found that medical treatment alone or associated with surgical treatment cured 82-87% of native and prosthetic valve endocarditis caused by HACEK organisms (4). The overall mortality rate from A. actinomycetemcomitans endocarditis has been approximately 18% and is not increased with prosthetic valve involvement (23, 37, 49). In the series reported by Grace et al. only one of 13 patients with A. actinomycetemcomitans prosthetic valve endocarditis died and only two required surgical intervention during treatment (23). Thus recovery of A. actinomycetemcomitans in prosthetic valve endocarditis is not itself an indication for valve replacement (23).
The use of combination treatment once the isolate is shown to be A. actinomycetemcomitans is more a matter of ‘usual practice’ than scientifically based.Cefamandole has been used successfully as monotherapy for A. actinomycetemcomitans prosthetic valve endocarditis (23). Ceftriaxone has excellent activity against most strains of A. actinomycetemcomitans (73) and its use is endorsed by an ad hoc writing group of the American Heart Association (72). Yogev et al. 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 combination of ceftriaxone and rifampicin would seem reasonable, but has not been clinically evaluated.
For the patient who is allergic to ß-lactam antibiotics, the most suitable agent is likely to be a fluoroquinolone. Prosthetic valve endocarditis due to A. actinomycetemcomitans was successfully treated with oral ciprofloxacin 750mg every 12 hours for 8 weeks. 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. Initial treatment was with amoxicillin and netilmicin, but by day 8 difficulties with venous access necessitated a switch to an oral agent. Ofloxacin 200mg tid (tds) was prescribed for 5 weeks. The MIC of ofloxacin for the isolate was 0.03mg/L by E-test and a peak serum ofloxacin concentration was 8.3mg/L (56).
The inappropriateness of vancomycin or erythromycin as treatment or prophylaxis for endocarditis due to A. actinomycetemcomitans has been emphasized by a report of endocarditis developing in a patient with penicillin allergy who was given prophylaxis with both vancomycin and erythromycin. Unfortunately, vancomycin (2G per day) was also chosen as empirical treatment. 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). Whether these agents are effective in preventing A. actinomycetemcomitans endocarditis has not been evaluated in animal experimental models.
Periodontitis
Periodontal disease is not caused by a single pathogen, but A. actinomycetemcomitans appears to have an important contributory role (60). Slots and Ting have reviewed the effectiveness of various therapies to suppress or remove subgingival A. actinomycetemcomitans. Scaling and root planning alone was unable to remove A. actinomycetemcomitans from localized juvenile periodontitis lesions. Tetracycline has been used for periodontal infections, but lacks bactericidal activity for most strains of A. actinomycetemcomitans and the clinical response has been variable. Systemic use of amoxicillin and metronidazole has been effective in treating A. actinomycetemcomitans-associated localized juvenile periodontitis and adult periodontitis and 7 days therapy with 250mg tid (tds) of amoxicillin and metronidazole is the current recommended (adult dosage) therapy (60). Azithromycin and clarithromycin have been shown to be more active in vitro than erythromycin (48, 52) and synergy has been demonstrated with either ß-lactams or ciprofloxacin in combination with metronidazole or its metabolite (50). 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.
Other Infections
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). A wide variety of treatments have been used, generally successfully. 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.
VACCINES
Vaccines are not available for Aggregatibacter actinomycetemcomitans.
ADJUNCTIVE THERAPY
Resection of infected tissue may be necessary for selected cases of invasive infection. Dental surgery may be indicated for cases of periodontitis.
REFERENCES
1. Antony B, Thomas S, Chandrashekar SC, Kumar MS, Kumar V. Osteomyelitis of the mandible due to Aggregatibacter actinomycetemcomitans. Indian J Pathol Microbiol 2009;52:115-116. [PubMed]
2. Babinchak TJ. Oral ciprofloxacin therapy for prosthetic valve endocarditis due to Actinobacillus actinomycetemcomitans. Clin Infect Dis 1995;21:1517-1518. [PubMed]
3. Baron EJ, Scott JD, Tompkins LS. Prolonged incubation and extensive subculturing do not increase recovery of clinically significant microorganisms from standard automated blood cultures. Clin Infect Dis 2005;41:1677-1680. [PubMed]
4. Berbari EF, Cockerill FR, Steckelberg JM. Infective endocarditis due to unusual or fastidious microorgansims. Mayo Clin Proc 1997;72:532-542. [PubMed]
5. Binder MI, Chua C, Kaiser PK, Mehta N, Isada CM. Actinobacillus actinomycetemcomitans endogenous endophthalmitis: Report of two cases and review of the literature. Scand J Infect Dis 2003;35:133-136. [PubMed]
6. Brouqui P, Raoult D. Endocarditis due to rare and fastidious bacteria. Clin Micro Rev 2001;14:177-207. [PubMed]
7. Burgess RC. Chronic tenosynovitis caused by Actinobacillus actinomycetemcomitans. J Hand Surg 1987;12:294-5. [PubMed]
8. Chao CL, Chang SC, Sheu JC, Luh KT. Transdiaphragmatic Actinobacillus actinomycetemcomitans infection; case report. Clin Infect Dis 1994;19:958-960. [PubMed]
9. Chen AC, Liu CC, Yao WJ, Chen CT, Wang JY. Actinobacillus actinomycetemcomitans pneumonia with chest wall and subphrenic abscess. Scand J Infect Dis 1995;27:289-290. [PubMed]
10. Chuba PJ, Bock R, Graf G, Adam T, Gobel U. Comparison of 16S rRNA sequences from the family Pasteurellaceae: phlyogenetic relatedness by cluster analysis. J Gen Microbiol 1988;134:1923-1930. [PubMed]
11. CLSI. Methods for antimicrobial dilution and disk susceptibility testing of infrequently isolated or fastidious bacteria; Approved guideline. CLSI document M45-A. Wayne PA: Clinical and Laboratory Standards Institute; 2006.
12. CLSI. Principles and procedures for blood cultures; Approved guideline. CLSI document M47-A. Wayne PA: Clinical and Laboratory Standards Institute; 2007.
13. Cuende E, de Pablos M, Gomez M, Burgaleta S, Michaus L, Vesga JC. Coexistence of pseudogout and arthritis due to Actinobacillus actinomycemcomitans. Clin Infect Dis 1996; 23:657-658. [PubMed]
14. Das M, Badley AD, Cockerill FR, Steckelberg JM, Wilson WR. Infective endocarditis caused by HACEK microorganisms. Annu Rev Med 1997;48:25-33.[PubMed]
15. Dajani AS, Taubert KA, Wilson W, Bolger AF, Bayer A, Ferrieri P, Gewitz MH, Shulman ST, Nouri S, Newburger JW, Hutto C, Pallasch TJ, Gage TW, Levison ME, Peter G, Zuccaro G Jr. Prevention of bacterial endocarditis. Recommendations by the American Heart Association. JAMA 1997;277:1794-1801. [PubMed]
16. Doern GV, Davaro R, George M, Campogne P. Lack of requirement for prolonged incubation of Septi-Chek blood culture bottles in patients with bacteremia due to fastidious organsims. Diagn Microbiol Infect Dis 1996;24:141-143. [PubMed]
17. Eick S, Pfister W, Straube E. Antimicrobial susceptibility of anaerobic and capnophilic bacteria isolated from odontogenic abscesses and rapidly progressive periodontitis. Int J Antimicrob Agents 1999;12:41-46. [PubMed]
18. El Khizzi N, Kasab SA, Osoba AO. HACEK group endocarditis at the Riyadh Armed Forces Hospital. J Infect 1997;34:69-74. [PubMed]
19. Ellner JJ, Rosenthal MS, Lerner PI, McHenry MC. Infective endocarditis caused by slow-growing, fastidious, gram-negative bacteria. Medicine 1979;58:145-158. [PubMed]
20. Eng RH, Smith SM, Goldstein EJC, Miyasaki KT, Quah SE, Buccini F. Failure of vancomycin prophylaxis and treatment for Actinobacillus actinomycetemcomitans endocarditis. Antimicrob Agents Chemother 1986;29:699-700. [PubMed]
21. Geraci JE, Wilson WR. Endocarditis due to gram-negative bacteria: report of 56 cases. Mayo Clin Proc 1982;57:145-148. [PubMed]
22. Goldstein EJ, Citron DM. Comparative activities of cefuroxime, amoxicillin-clavulanic acid, ciprofloxacin, enoxacin, and ofloxacin against aerobic and anaerobic bacteria isolated from bite wounds. Antimicrob Agents Chemother 1988;32:1143-1148. [PubMed]
23. Grace CJ, Levitz RE, Katz-Pollack H, Brettman LR. Actinobacillus actinomycetemcomitans prosthetic valve endocarditis. Rev Infect Dis 1988;10:922-929. [PubMed]
24. Hammerberg O, Gregson DB, Gopaul D, Lampe H. Recurrent cervical and submandibular lymphadenitis due to Actinobacillus actinomycetemcomitans. Clin Infect Dis 1993;17:1077-1078. [PubMed]
25 Hoffler U, Niederau W, Pulverer G. Susceptibility of Bacterium actinomycetem comitans to 45 antibiotics. Antimicrob Agents Chemother 1980;17:943-946.[PubMed]
26. Horowitz EA, Pugsley MP, Turbes PG, Clark RB. Pericarditis caused by Actinobacillus actinomycetemcomitans. J Infect Dis 1987;155:152-153. [PubMed]
27. Idir M, Denisi R, Parrens M, Roudaut R, Deville C. Endarteritis and false aneurysm complicating aortic coarctation. Ann Thorac Surg 2000;70:966-969. [PubMed]
28. Ishak MA, Zablit KV, Dumas J. Endogenous endophthalmitis caused by Actinobacillus actinomycetemcomitans. Can J Ophthalmol 1986;21:284-286. [PubMed]
29. Kaplan AH, Weber DJ, Oddone EZ, Perfect JR. Infection due to Actinobacillus actinomycetemcomitans: 15 cases and review. Rev Infect Dis 1989;11:46-63. [PubMed]
30. King EO, Tatum HW. Actinobacillus actinomycetemcomitans and Haemophilus aphrophilis. J Infect Dis 1962;111:85-94. [PubMed]
31. Klinger R. Untersuchungen uber menschliche Aktinmykose. Zentralbl Bakteriol Mikrobiol Hyg 1912;62:191-200.
32. Kugler KC, Biedenbach DJ, Jones RN. Determination of the antimicrobial activity of 29 clinically important compounds tested against fastidious HACEK group organisms. Diagn Microbiol Infect Dis 1999;34:73-76. [PubMed]
33. Kujjper EJ, Wiggerts HO, Jonker GJ, Schaal KP, de Gans J. Disseminated actinomycosis due to Actinomyces meyeri and Actinobacillus actinomycetemcomitans. Scand J Infect Dis 1992;24:667-672. [PubMed]
34. Madinier IM, Fosse TB, Hitzig C, Charbit Y, Hannoun LR. Resistance profile survey of 50 periodontal strains of Actinobacillus actinomycetemcomitans. J Periodontal 1999:70:888-892. [PubMed]
35. Marshall C, McDonald M. Recurrent subacute bacterial endocarditis as a presentation of left atrial myxoma. Aust NZ J Med. 1998;28:350. [PubMed]
36. Martin MC, Andres MT, Fierro JF, Mendez FJ. Endarteritis and mycotic aortic aneurysm caused by an oral strain of Actinobacillus actinomycetemcomitans. Eur J Clin Microbiol Infect Dis 1998;17:104-107. [PubMed]
37. Meyer DJ, Gerding DN. Favorable prognosis of patients with prosthetic valve endocarditis caused by gram-negative bacilli of the HACEK group. Am J Med 1988;85:104-107. [PubMed]
38. Mitchell RG, Gillespie WA. Bacterial endocarditis due to an Actinobacillus. J Clin Pathol 1964;17:511-512. [PubMed]
39. Mayake Y, Tsuruda K, Okuda K, Widowati, Iwamoto Y, Suginaka H. In vitro activity of tetracyclines, macrolides, quinolones, clindamycin and metronidazole against periodontopathic bacteria. J Periodont Res 1995:30:290-293. [PubMed]
40. Molina F, Echániz A, Durán MT, Diz-Lois F. Infectious arthritis of the knee due to Actinobacillus actinomycetemcomitans [Letter]. Eur J Clin Microbiol Infect Dis 1994;13:687-689. [PubMed]
41. Morris JF, Sewell DL. Necrotising pneumonia caused by mixed infection with Actinobacillus actinomycetemcomitans and Actinomyces israelii: case report and review. Clin Infect Dis 1994;18:450-452. [PubMed] Washington: American Society for Microbiology, 1999 ;561-571. [PubMed]
42. Nashi M, Venkatachalam AK, Unsworth PF, Muddu BN. Diskitis caused by Actinobacillus actinomycetemcomitans. Orthopedics 1998;21:714-716.[PubMed]
43. National Committee for Clinical Laboratory Standards. Performance standards for antimicrobial susceptibility testing; eleventh informational supplement. NCCLS document M100-S11, Wayne, Pennsylvania, 2001.
44. Nerad JL, Seville MT, Snydman DR. Miscellaneous Gram-negative bacilli: Acinetobacter, Cardiobacterium, Actinobacillus, Chromobacterium, Capnocytopaga, and others. In: Gorbach SL, Bartlett JG, Blacklow NR, editors. Infectious Diseases, 2nd edition. Philadelphia: WB Saunders Company, 1998;1871-1887.
45. Norskov-Lauritsen N and Kilian M. Reclassification of Actinobacillus actinomycetemcomitans, Haemophilus aphrophilus, Haemophilus paraphrophilus and Haemophilus segnis as Aggregatibacter actinomyctemcomitans gen. nov., comb. nov., Aggregatibacter aphrophilus comb. nov. and Aggregatibacter segnis comb. nov., and emended description of Aggregatibacter aphrophilus to include V factor-dependent and V factor-independent isolates. Int J Syst Bacteriol 2006;56:2135-2146. [PubMed]
46. Page MI, King EO. Infection due to Actinobacillus actinomycetemcomitans and Haemophilus aphrophilus. N Engl J Med 1966;275:181-188. [PubMed]
47. 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. J Clin Microbiol 2000;38:79-84. [PubMed]
48. Pajukanta R, Asikainen S, Saarela M, Alaluusua S, Jousimies-Somer H. In vitro activity of azithromycin compared with that of erythromycin against Actinobacillus actinomycetemcomitans. Antimicrob Agents Chemother 1992;36:1241-1243. [PubMed]
49. Paturel L, Casalta JP, Habib G, Nezri M, Raoult D. Actinobacillus actinomycetemcomitans endocarditis. Clin Microbiol Infect 2004;10:98-118. [PubMed]
50. Pavcic MJAMP, van Winkelhoff AJ, de Graaff J. In vitro susceptibilities of Actinobacillus actinomycetemcomitans to a number of antimicrobial combinations. Antimicrob Agents Chemother 1992;36:2634-2638. [PubMed]
51. Petti CA, Bhally HS, Weinstein MP, Joho K, Wakefield T, Reller LB, Carroll KC. Utility of extended blood culture incubation for isolation of Haemophilus, Actinobacilus, Cardiobacterium, Eikenella and Kingella organisms: a retrospective multicenter evaluation. J Clin Microbiol 2006;44:257-259.
52. Piccolomini R, Catamo G, di Bonaventura G. Bacteriostatic and bactericidal in vitro activities of clarithromycin and erythromycin against periodontopathic Actinobacillus actinomycetemcomitans. Antimicrob Agents Chemother 1998; 42:3000-3001. [PubMed]
53. Pierce CS, Bartholomew WR, Amsterdam D, Neter E, Zambon JJ. Endocarditis due to Actinobacillus actinomycetemcomitans serotype c and patient immune response. J Infect Dis 1984;149:479. [PubMed]
54. Potts TV, Berry EM. Deoxyribonucleic acid-deoxyribonucleic acid hybridisation analysis of Actinobacillus actinomycetemcomitans and Haemophilus aphrophilus. Int J Syst Bacteriol 1983;33:765-771.
55. Renton TF, Danks J, Rosenfeld JV. Cerebral abscess complicating dental treatment. Case report and review of the literature. Aust Dent J 1996;41:12-15. [PubMed]
56. Sailler L, Marchou B, Lemozy J, Bonnet E, Elias Z, Cuzin L, Massip P. Successful treatment of Actinobacillus actinomycetemcomitans endocarditis with ofloxacin. Clin Microbiol Infect 2000;6:55-56. [PubMed]
57. Schmidt ME, Smith MA, Levy CS. Endophthalmitis caused by unusual gram-negative bacilli: three case reports and review. Clin Infect Dis 1993;17:686-690. [PubMed]
58. Shalini S, Ganesh P, Anand AR. Actinobacillus actinomycetemcomitans septicemia during pregnancy (letter). Int J Gynaecol Obstet 1995;51:57-58. [PubMed]
59. Slots J, Evans RT, Lobbins PM, Genco RJ. In vitro antimicrobial susceptibility of Actinobacillus actinomycetemcomitans. Antimicrob Agents Chemother 1980;18:9-12.[PubMed]
60. Slots J, Ting M. Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in human periodontal disease: occurrence and treatment. Periodontology 2000, 1999;20:82-121. [PubMed]
61. Stauffer JL, Goldman MJ. Bacterial endocarditis due to Actinobacillus actinomycetemcomitans in a patient with a prosthetic aortic valve. California Medicine 1972;117:59-63. [PubMed]
62. Steinberg JP, Del Rio C. Other Gram-negative bacilli. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and practice of infectious diseases, 5th edition. New York: Churchill Livingstone, 2000:2459-2474.
63. Stepanović S, Tošić T, Savić B, Jovanović M, K’ouas G, Carlier J-P. Brain abscess due to Actinobacillus actinomycetemcomitans. APMIS 2005;113:225-228. [PubMed]
64. Tobias S, Lee JH, Tomford JW. Rare Actinobacillus infection of the cavernous sinus causing painful ophthalmoplegia: case report. Neurosurgery 2002;51:807-810.[PubMed]
65. Thjotta TL, Sydnes S. Actinobacillus actinomycetam comitans as the sole infecting agent in a human being. Acta Pathol Microbiol Scand 1951;28:27-35. [PubMed]
66. Tyrrell J, Noone P, Prichard JS. Thoracic actinomycosis complicated by Actinobacillus actinomycetemcomitans: case report and review of literature. 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. Clin Infect Dis 1993;16:216-218. [PubMed]
68. van Winkelhoff AJ, Winkel EG, Barendregt D, Dellemijn-Kippuw N, Stijne A, van der Velden U. ß-lactamase producing bacteria in adult periodontitis. J Clin Periodontal 1997;24:538-543. [PubMed]
69. Venkataramani A, Santo-Domingo NE, Main DM. Actinobacillus actinomycetemcomitans pneumonia with possible septic embolization [Letter]. Chest 1994;105:645-646.[PubMed]
70.Westling K, Vondracek M. Actinobacillus (Aggregatibacter) actinomycetemcomitans (HACEK) identified by PCR/16S rRNA sequence analysis from the heart valve in a patient with blood culture negative endocarditis. Scand J Infect Dis 2008; 40:981-996. [PubMed]
71. Wilson ME. Prosthetic valve endocarditis and paravalvular abscess caused by Actinobacillus actinomycetemcomitans [Letter]. Rev Infect Dis 1989;11:665-667. [PubMed]
72. Wilson WR, Karchmer AW, Dajani AS, Taubert KA, Bayer A, Kaye D, Bisno AL, Ferrieri P, Shulman ST, Durack DT. Antibiotic treatment of adults with infective endocarditis due to streptococci, enterococci, staphylococci, and HACEK microorganisms. JAMA 1995;274:1706-1713. [PubMed]
73. Yogev R, Shulman D, Shulman ST, Glogowski WG. In vitro activity of antibiotics alone and in combination against Actinobacillus actinomycetemcomitans. Antimicrob Agents Chemother 1986;29:179-181. [PubMed]
74. Yuan A, Yang P-C, Lee L-N, Chang D-B, Kuo S-H, Luh K-T. Actinobacillus actinomycetemcomitans pneumonia with chest wall involvement and rib destruction. Chest 1992;101:1450-1452. [PubMed]
75. Zijlstra EE, Swart GR, Godfroy FJM, Degener JE. Pericarditis, pneumonia and brain abscess due to a combined Actinomyces-Actinobacillus actinomycetemcomitans infection. J Infect 1992;25:83-87. [PubMed]
Tables
Table 1. In vitro susceptibilities of Actinobacillus actinomycetemcomitansa
| Antibiotic | n | Range | MIC50 | MIC90 | Breakpointb | % Susceptible | Reference |
|---|---|---|---|---|---|---|---|
| Amikacin | 24 | 0.8->25 | 6.25 | 25 | 73 | ||
| Amikacin | 14 | 3.1-12.5 | 3.1 | 12.5 | 25 | ||
| Gentamicin | 14 | 1.6-6.25 | 3.1 | 6.25 | 25 | ||
| Gentamicin | 20 | 0.1-10 | 19 | ||||
| Streptomycin | 37 | 0.75-12.5 | 1.5 | 3 | 48 | ||
| Tobramycin | 14 | 1.6-3.1 | 3.1 | 3.1 | 25 | ||
| Tobramycin | 5 | 2.0-3.3 | 2.5 | 3 | 51 | ||
| Amoxycillin | 16 | 0.5-16 | 2 | 16 | 16 | ||
| Amoxycillin | 50 | 0.06-8 | 0.25 | 2 | 36 | ||
| Amoxycillin | 73 | 0.12-2.0 | 0.5 | 1.0 | 49 | ||
| Amoxycillin clavulanate | 50 | 0.06-8 | 0.25 | 2 | < 4/2 | 36 | |
| Amoxycillin clavulanate | <14 | 0.06-0.5 | 0.25 | 0.5 | < 4/2 | 100 | 22 |
| Ampicillin | <14 | 0.06-0.5 | 0.25 | 0.5 | <1 | 100 | 22 |
| Ampicillin | 24 | <0.1->25 | 1.6 | 25 | <1 | 73 | |
| Ampicillin | 59 | 1-128 | 4 | 128 | <1 | 5 | 60 |
| Ampicillin | 37 | 0.37->100 | >100 | >100 | <1 | 48 | |
| Penicillin | 37 | 0.75->100 | >100 | >100 | 48 | ||
| Penicillin | 59 | 1-128 | 4 | 64 | 60 | ||
| Penicillin | 14 | 0.8->100 | 3.1 | 6.25 | 25 | ||
| Penicillin | 24 | <0.1->25 | 3.1 | 12.5 | 73 | ||
| Penicillin | 16 | 1-8 | 8 | 8 | 16 | ||
| Penicillin | 50 | 0.12-8 | 2 | 8 | 36 | ||
| Penicillin | 73 | 0.5-8.0 | 2.0 | 4.0 | 49 | ||
| Carbenicillin | 59 | 0.1-128 | 0.1 | 32 | 60 | ||
| Carbenicillin | 14 | 0.4->100 | 0.4 | 3.1 | 25 | ||
| Mezlocillin | 14 | 0.8->100 | 1.6 | 3.1 | 25 | ||
| Piperacillin | 24 | 0.4->25 | 12.5 | >25 | 73 | ||
| Ticarcillin | 24 | 0.2->25 | 6.2 | 12.5 | 73 | ||
| Ticarcillin | 14 | 0.4->100 | 0.8 | 3.1 | 25 | ||
| Ticarcillin | 5 | 0.25-0.5 | 0.38 | 34 | |||
| Cefadroxyl | <14 | 0.25-16 | 8 | 16 | 22 | ||
| Cefamandole | 14 | 0.8->100 | 3.1 | 3.1 | <4 | 93 | 25 |
| Cefazolin | 14 | 0.8->100 | 1.6 | 1.6 | 25 | ||
| Cefdinir | 5 | 0.047-0.19 | 0.125 | <1 | 100 | 34 | |
| Cefepime | 5 | 0.064-0.25 | 0.19 | <2 | 100 | 34 | |
| Cefixime | 50 | 0.3-2.2 | 0.8 | <1 | 51 | ||
| Cefotaxime | 14 | 0.1->100 | 0.4 | 0.4 | <2 | 93 | 25 |
| Cefotaxime | 5 | 0.023-0.064 | 0.032 | <2 | 100 | 34 | |
| Cefotaxime | 20 | 0.02-0.5 | <2 | 100 | 19 | ||
| Cefoxitin | 14 | 0.4->100 | 1.6 | 6.25 | 25 | ||
| Cefoxitin | 5 | 0.25-1.5 | 1 | 34 | |||
| Cefoxitin | 20 | 0.2-4 | 19 | ||||
| Cefpirome | 5 | 0.064-0.25 | 0.125 | 0.125 | 34 | ||
| Cefpodoxime | 5 | 0.032-0.19 | 0.125 | <2 | 100 | 34 | |
| Cefprozil | 5 | 0.38-3 | 1.5 | <8 | 100 | 34 | |
| Cefradine | 14 | 12.5-100 | 12.5 | 25 | 25 | ||
| Ceftazidime | 5 | 0.064-0.25 | 0.125 | <2 | 100 | 34 | |
| Ceftibuten | 5 | 0.023-0.19 | 0.032 | <2 | 100 | 34 | |
| Ceftriaxone | 24 | <0.1-3.1 | 0.2 | 1.6 | <2 | 73 | |
| Ceftriaxone | 5 | 0.006-0.023 | 0.006 | <2 | 100 | 34 | |
| Cefuroxime | <14 | 0.6-2 | 0.25 | 2 | <4 | 100 | 22 |
| Cefuroxime | 14 | 0.4->100 | 0.4 | 1.6 | <4 | 93 | 25 |
| Cefuroxime | 5 | 0.125-0.38 | 0.19 | <4 | 100 | 34 | |
| Cephalexin | 14 | 6.25->100 | 6.25 | 12.5 | 25 | ||
| Cephalexin | <14 | 0.5-16 | 4 | 8 | 22 | ||
| Cephalothin | 14 | 0.4->100 | 0.8 | 1.6 | 25 | ||
| Cephapirin | 24 | <0.1-6.2 | 0.4 | 3.1 | 73 | ||
| Imipenem | 5 | 0.25-0.75 | 0.38 | <4 | 100 | 34 | |
| Meropenem | 5 | 0.064-0.19 | 0.125 | <0.5 | 100 | 34 | |
| Chloramphenicol | 24 | 0.4-6.2 | 0.8 | 3.1 | <2 | 73 | |
| Chloramphenicol | 37 | <0.3-1.5 | 0.75 | 1.5 | <2 | 100 | 48 |
| Chloramphenicol | 59 | 1-2 | 1 | 1 | <2 | 100 | 60 |
| Ciprofloxacin | 50 | 0.001-0.02 | 0.01 | <1 | 100 | 51 | |
| Ciprofloxacin | 16 | <0.125-0.5 | <0.125 | 0.25 | <1 | 100 | 16 |
| Ciprofloxacin | 50 | 0.01-0.08 | 0.03 | 0.03 | <1 | 100 | 36 |
| Enoxacin | 11 | <0.03-1 | 0.12 | 0.5 | 41 | ||
| Ofloxacin | <14 | <0.03-0.25 | 0.06 | 0.06 | <2 | 100 | 22 |
| Ofloxacin | 11 | <0.03-0.125 | 0.06 | 0.06 | <2 | 100 | 41 |
| Tosufloxacin | 11 | <0.50 | <0.50 | <0.50 | 41 | ||
| Azithromycin | 79 | <0.25-2 | 1 | 2 | <4 | 100 | 50 |
| Azithromycin | 73 | 0.06-2.0 | 1.0 | 1.0 | <4 | 100 | 49 |
| Clarithromycin | 50 | 1-16 | 4 | 16 | <8 | 36 | |
| Clarithromycin | 87 | 0.12-8 | 0.5 | 2 | <8 | 100 | 53 |
| Erythromycin | 11 | 1-32 | 2 | 16 | 41 | ||
| Erythromycin | 59 | 0.1-128 | 8 | 32 | 60 | ||
| Erythromycin | 79 | 0.5-8 | 4 | 8 | 50 | ||
| Erythromycin | 50 | 0.25-128 | 2 | 4 | 36 | ||
| Erythromycin | 87 | 0.5-32 | 2 | 16 | 53 | ||
| Spiramycin | 50 | 0.25-128 | 32 | 64 | 36 | ||
| Pristinamycin | 50 | 0.5-2 | 1 | 2 | 36 | ||
| Clindamycin | 11 | 0.25->64 | 4 | >64 | 41 | ||
| Clindamycin | 14 | 1.6-12.5 | 6.25 | 12.5 | 25 | ||
| Clindamycin | 59 | 2-128 | 32 | 128 | 60 | ||
| Clindamycin | 16 | 1->16 | 16 | >16 | 16 | ||
| Rifampicin | 24 | <0.1-3.1 | 0.8 | 1.6 | <1 | 73 | |
| Rifampicin | 5 | 0.094-2 | 0.75 | <1 | 34 | ||
| Rifampicin | 14 | 0.2-0.8 | 0.4 | 0.8 | <1 | 100 | 25 |
| Doxycycline | 16 | 0.5-4 | 2 | 4 | 16 | ||
| Doxycycline | 14 | 0.4-3.1 | 1.6 | 3.1 | 25 | ||
| Minocycline | 59 | 0.1-4 | 1 | 1 | 60 | ||
| Minocycline | 14 | 0.2-1.6 | 0.8 | 1.6 | 25 | ||
| Minocycline | 11 | 0.125-4 | 0.25 | 2 | 41 | ||
| Tetracycline | 59 | 0.1-1 | 0.1 | 1 | <2 | 100 | 60 |
| Tetracycline | 37 | 0.37-3.1 | 3.1 | 3.1 | <2 | 48 | |
| Tetracycline | 14 | 0.4-1.6 | 1.8 | 1.6 | <2 | 100 | 25 |
| Tetracycline | 11 | 0.5-8 | 1 | 4 | <2 | 41 | |
| Tetracycline | 24 | 0.2-12.5 | 0.8 | 3.1 | <2 | 73 | |
| Tetracycline | 50 | 0.03-16 | 0.25 | 0.5 | <2 | 36 | |
| Tetracycline | 73 | 0.24-4.0 | 1.0 | 1.0 | <2 | 49 | |
| Trimethoprim/ Sulfamethoxazole | 20 | 0.08-5 | <0.5/9.5 | 19 | |||
| Trimethoprim/ Sulfamethoxazole | 5 | 0.023-0.125 | 0.047 | <0.5/9.5 | 100 | 34 | |
| Trimethoprim/ Sulfamethoxazole | 14 | 0.2-1.6 | 0.8 | 1.6 | <0.5/9.5 | 25 | |
| Metronidazole | 11 | 8->64 | 64 | >64 | 41 | ||
| Metronidazole | 16 | 8-32 | 16 | >32 | 16 | ||
| Metronidazole | 50 | 32->512 | 64 | 128 | 36 | ||
| Metronidazole | 59 | 0.1-64 | 0.1 | 16 | 60 | ||
| Metronidazole | 73 | 0.25-128 | 16 | 16 | 49 | ||
| Ornidazole | 50 | 1->512 | 4 | 16 | 36 | ||
| Tinidazole | 14 | 0.4->100 | 0.4 | 1.6 | 25 |
a Modified from (16, 22, 25, 34, 36, 41, 48, 49, 50, 51, 53, 60, 73).
b Current NCCLS susceptible MIC interpretive standards for Haemophilus spp. (µg/mL) (46)
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