Though oral infection is a common finding, the therapist should know the special characteristics of the oral cavity and its local microflora. A distinct number of aerobic and anaerobic species are regularly observed and described. The bacteria identified in the bone specimens comprised Gram-positive and Gram-negative organisms. These also include aerobes, although anaerobes and facultative anaerobes dominate [8]. Anaerobic species are from the Peptostreptococcus, Prevotella, Fusobacterium, Gemella, and Porphyromonas genera. Aerobic species are Streptococcus, Staphylococcus, and Corynebacterium. Each of these microorganisms occupies a different microniche, but the prevailing balance is easily disturbed. Especially pathogenic or opportunistic bacteria (Actinomyces, Prevotella intermedia), yeasts (Candida sp. Histoplasma capsulatum), viruses, and parasites profit from any disturbance of the equilibrium and can then harm the organism [10]. Denaturing gradient gel electrophoresis profile and dice coefficient described 3 predominant genera in MRONJ, namely, Streptococcus, Eubacterium, and Pseudoramibacter [3].

The biofilms in these patients have a distinct combination of species/phylotypes, segregating a population with compositional changes but maintaining functional similarity of acid production [2]. The development of biofilms on the surface of the exposed bone may account for the poor response to systemic antimicrobial therapy as described above [19]. Bone specimens from MRONJ-affected sites showed large areas of occluded biofilms comprising mainly bacteria, and occasionally yeast, embedded in extracellular polymeric substance. The number of bacteria in these biofilms ranged from 2 to 15 and included species from genera Fusobacterium, Bacillus, Actinomyces, Staphylococcus, Streptococcus, and Selenomonas and 3 different types of treponemes [8]. The phyla described by Ji et al. found in MRONJ lesions are Acinetobacter, Bacteroidetes, Chloroflexi, Cyanobacteria, Firmicutes, Fusobacteria, Proteobacteria, and Synergistetes [2]. Badros et al. identified Prevotella, Porphyromonas, Fusobacterium, Peptostreptococcus, Streptococcus sp., and Eikenella species [20]. MRONJ site biofilm contained predominantly Fusobacterium, Actinomyces, Staphylococcus, Streptococcus, Selenomonas, and Treponema species as reported by Sedghizadeh and coworkers [8]. These different research teams demonstrated similarities but also differences in their findings. Though principally microbial cultures from the areas of infected exposed bone will show normal oral microbes, it must be taken into consideration that in cases with extensive soft-tissue involvement, microbial culture data may facilitate the selection of an appropriate antibiotic [19]. Awareness, however, must be drawn to the length of time the bone was exposed to the oral cavity as nonpermanent bacteria species may infect the bone as the nature of the biofilm is expected to change and adapt within time [8]. Interestingly, some histopathological examinations have even indicated that edentulous jaws contain regions of necrotic bone and microbial biofilm formation even after one year of tooth extraction and mucosal healing resulting eventually in MRONJ formation [21].

Actinomyces species are frequently observed in MRONJ. Actinomyces is regularly observed in histological bone specimens (Fig. 11.1) of MRONJ patients. In 70 to 100 % of all cases, Actinomyces is present [22–24]. In the beginning of the MRONJ discussion, Actinomyces was considered to be a particular complication [24] and to be an underestimated agent in the pathogenesis of MRONJ [11].

Actinomyces is a non-spore-forming, anaerobic, or microaerophilic bacterial species of the genus Actinomyces. Actinomyces spp. are Gram-positive, pleomorphic, and commonly delicately filamentous microbes. Actinomyces can be commonly found in gingivodental crevices [11, 24] and must be suspected as an opportunistic infection [10, 24, 25]. Mucosal disruption is also the key step in pathogenesis. Histologically Actinomyces can form clumps called sulfur granules [11]. Even though Actinomyces spp. were frequently found in exposed necrotic bone, however, the development of MRONJ also occurs in its absence [22, 24].

Infections with Candida spp. are also described regularly. Infections with other fungal spores and hyphae have been observed also frequently (Fig. 11.3) [24], but yeasts that have been identified consistently included Candida spp. [8, 10, 26]. Analysis of oral lesions demonstrated a correlation between higher Candida colonization and the severity of the lesion [27].

It must be taken into consideration that most of the addressed bacteria are strictly dependent on the culture-dependent methods used. Though most of the infectious diseases of the oral and maxillofacial regions are caused by polymicrobial infections of anaerobes and all causative bacteria may not be cultivable by the method used, they cannot be excluded or denied. Therefore, critical analysis of the identified bacteria and yeasts must be compared with the clinical success by antibiotic and antiyeast therapy. An antibiotic regime that does not support the microbiology findings could show a good clinical success and vice versa. Therefore, the clinical outcome is the leading sign for the antibiotic regime.

Early in 2005, Bamias et al. described that treatment with antibiotics resulted in transient improvement of MRONJ after multiple courses of antibiotics. It is possible to improve the infectious symptoms in the majority of cases with antibiotics. It is also evident in most cases that the purulent discharge and pain recurred after discontinuation of the antibiotics [28]. The time till the relapse and worsening of the infectious symptoms may vary.