In this retrospective analysis, the spectrum of the isolated pathogenic bacteria and their AMRs were evaluated. The most frequently isolated bacteria were Streptococcus, Prevotella, Staphylococcus and Fusobacterium spp. Notably, Enterobacter spp. were the fifth most commonly isolated bacteria. Differences in the microbial composition of the three patient groups (‘abscess’, ‘necrosis’ and ‘tumor’) were also assessed. In conclusion, patients with malignant tumors had significantly greater percentages of Enterobacter spp., Enterococcus spp., Pseudomonas spp. and beta-hemolytic streptococci than did the other two patient groups. Patients in the ‘abscess’ group had significantly lower percentages of Enterobacter spp., Enterococcus spp., Escherichia spp. and Klebsiella spp. than patients in the ‘necrosis’ and ‘tumor’ groups did. Compared with patients in the other groups, patients in the necrosis group had significantly greater percentages of Actinomyces spp. Among our findings regarding AMR, the particularly high resistance rates to clindamycin among Prevotella, Streptococcus and Staphylococcus spp. should be highlighted.

Comparison of the pathogen spectrum and AMR pattern to available worldwide data

Although the antimicrobial spectrum and AMR among patients with maxillofacial infections have been studied worldwide, the methodologies of these studies were unfortunately not consistent in terms of susceptibility testing or evaluation of the pathogen spectrum. Most of the studies were performed with a smaller population, and the bacterial spectrum was often divided into aerobes and anaerobes or gram-positive and gram-negative bacteria rather than being evaluated as a whole. Moreover, in some cases, resistance rates were reported for the entirety of the bacteria rather than individually for each genus, and the same guidelines were not adopted for the evaluation of susceptibility throughout the studies, making comparisons difficult.

In general, the bacteria most frequently isolated worldwide are Streptococcus spp., followed by Prevotella and Staphylococcus spp. [27,28,29,30,31,32,33,34,35,36,37]. This finding is in accordance with our results, although the spectrum of pathogens in our population exhibited greater diversity; thus, the percentage of streptococci was not as high. The majority of these studies focused only on odontogenic infections, which may explain the difference in diversity compared with our study. However, the pathogen spectrum in the ‘abscess’ group was also fairly different in composition compared with data from other countries, which could be expected owing to the changes in the microbiome in geographically distinct populations [38]. According to the literature, the microbes involved in SSIs in general are S. aureus, coagulase-negative staphylococci, E. coli, E. faecalis, and P. aeruginosa [39]. A study conducted in India specifically focused on SSIs in head and neck cancer patients revealed that Klebsiella spp., Acinetobacter spp., E. coli, S. aureus and Enterococcus spp. were the most common bacteria among the isolates from these patients [40], which is only somewhat similar to our results.

With respect to AMR, we compared our results only with studies in which the AMR of each genus was evaluated separately. Notably, even the European studies were not completely consistent with the EUCAST guidelines that our laboratory uses [24]. With respect to these limitations, we could draw relevant conclusions for only a few antibiotics. The resistance rate to clindamycin ranged from 13.7% [28] to 46% [35] in the viridans streptococci group. Resistance rates estimated in different parts of the world, specifically in the U.S. [29, 33], Germany [30] and Iraq [36], were consistent with our rates (35.2%). An outstanding result in our study was the 40.9% resistance rate of Prevotella spp. to clindamycin, which is substantially higher than the data in the literature, where the highest AMR rate was reported to be 22.5% [30, 31, 35, 36]. Notably, in almost every country, the resistance rate of S. aureus to vancomycin was 0%, including in our study, except for Iraq [36], where a remarkable 30.4% resistance rate was estimated. In terms of structure and scope, the study most similar to ours was conducted by Meinen et al. in Germany, in which they compared the data acquired from hospitals to those acquired from dental practices [27]; however, it should be noted that they reported only resistance rates to S. aureus, Streptococcus and Klebsiella spp. Compared with their results from hospital settings, we observed substantially higher resistance rates to clindamycin among both Streptococcus spp. (32.2% vs. 19.4%) and S. aureus (22.2% vs. 17%) and slightly higher percentages of MRSA (13.8% vs. 12.0%). However, in terms of Klebsiella spp., our outcomes were more similar to the data from dental practices, with a 4.1% resistance rate to third-generation cephalosporines, a 3.1% resistance rate to fluoroquinolones and no resistance to carbapenems.

The role of S. epidermidis in oral biofilm formation and its relationship with systemic diseases

One of the main virulence factors of S. epidermidis is biofilm formation, which is particularly associated with the colonization of surgical wounds or medical devices such as implants. Although S. epidermidis is mostly regarded as a commensal microorganism of human skin and mucosal surfaces, including the oral cavity, it can also emerge as an opportunistic pathogen, especially in immunocompromised patients or those undergoing surgery. There is evidence suggesting that S. epidermidis may function as a virulence gene reservoir that can potentially increase the pathogenic potential of S. aureus through horizontal gene transfer. S. epidermidis has emerged as one of the leading causes of nosocomial infections; however, it can also play a favorable role in suppressing the outgrowth of aggressive pathogens, primarily S. aureus. It can spread from the oral cavity to other body sites, potentially contributing to systemic infections such as infective endocarditis, prosthetic joint infections, and device-related osteomyelitis [11, 12, 41,42,43]. In addition to the inadequate oral hygiene encountered in the Hungarian population [23], other factors could also contribute to biofilm formation, which can also explain the relatively high percentage of S. epidermidis in our study compared with other studies [27]. These factors include titanium implants or osteosynthesis plates inserted intraorally, as well as surgical interventions breaking through the skin (e.g., extraoral incisions or neck dissections).

The relevance of oral pathogens in carcinogenesis

It has been estimated that 15–20% of human tumors can be induced by infections. The aim of some of the studies on this topic was to identify early diagnostic markers within the microbiome that could be helpful in the early detection of cancer. On the other hand, studies on the microbiome of cancer patients also revealed that patients undergoing chemoradiotherapy may have alterations in their oral microbiota induced by treatment, which can lead to other systemic health problems through the emergence of potential pathogens [10, 15, 18, 44].

There has been increasing concern regarding the possible role of Fusobacterium spp. in promoting carcinogenesis [18, 45,46,47,48,49]. Yosat et al. [50] reported that these bacteria were metabolically hyperactive in the oral microbiome of patients with OSCC. According to their research, Fusobacteria were significantly more active in tumor sites than in tumor-adjacent sites, and these authors also demonstrated the greatest upregulation of the expression of putative virulence factors. However, our results were not consistent with these findings, as patients with malignant tumors presented significantly lower percentages of Fusobacterium spp. than did those in the ‘abscess’ or ‘necrosis’ groups, although importantly, molecular biology techniques were utilized in the aforementioned studies. Cai et al. [51] reported an enrichment of Fusobacterium nucleatum in the tumor microenvironment compared with healthy sites, but interestingly, F. nucleatum enrichment was significantly associated with nonsmokers, nondrinkers and a better survival rate, suggesting that F. nucleatum enrichment can be an indicator of more favorable outcomes in oral cancer patients. Our results regarding the lower percentages of Fusobacterium spp. might support this theory, as Hungary has the highest mortality and morbidity rates of oral cancer patients in Europe and a considerably low overall 5-year survival rate, with smoking and alcohol consumption reported to be the most important risk factors [52, 53]. This assumption was further supported by the findings of Eun et al. [22], who reported that Prevotella spp. were enriched in the saliva of patients with lymph node metastasis, whereas Fusobacterium spp. were dominant in patients without metastasis. Other pathogens that are strongly associated with OSCC are P. aeruginosa [48], Porphyromonas gingivalis and Prevotella intermedia, but other bacterial genera, such as Actinomyces, members of the Enterobacteriaceae family, Haemophilus, Streptococcus and Veillonella, are also associated with oral cancer [54]. Although most studies have focused on either tumor surfaces or intratumoral tissue, many have reported overlapping bacterial genera, indicating a common core microbiota associated with OSCC. Gopinath et al. [55] and Nagy et al. [16] both found that tumor surfaces were enriched with genera such as Fusobacterium, Porphyromonas, and members of the Enterobacteriaceae family, whereas Gopinath noted that Prevotella and Treponema were more abundant within tumor tissue. Additionally, Nagy et al. reported elevated levels of Veillonella, Actinomyces, Clostridium, Haemophilus, and Streptococcus spp. in biofilms on tumor surfaces. Furthermore, Hooper et al. [17] found that the intratumoral microbiota was predominantly saccharolytic and aciduric, including Proteobacteria and genera such as Fusobacterium, Streptococcus, Prevotella, and Veillonella, which they suggested may reflect selective bacterial growth within carcinoma tissue. However, the presence of similar taxa on tumor surfaces raises the possibility that such bacteria may not be exclusively selected by the intratumoral environment and could instead result from bacterial migration from the surface. Our results are only partially in line with these findings, since these pathogens were not specifically increased in cancer patients; in fact, most patients in the cancer group had significantly lower percentages of these species than did patients in the abscess or necrosis groups, and only Enterobacter spp. and beta-hemolytic streptococci were present in significantly higher percentages in this particular patient group. We must note that the samples taken from these patients were not exclusively taken intraorally but also from neck surgical sites, but these sites are often connected to the oral wound, thereby resulting in infection [56]. Panghal et al. reported similar results to ours in their microbiological analysis of oral cancer patients [57], where the most prevalent bacteria were Staphylococcus spp., E. coli, K. pneumoniae and Proteus spp. Our results were also consistent with the outcomes of the study conducted by Jobbins et al. [58], who evaluated the oral pathogens of patients with advanced malignant diseases and reported that terminally ill patients presented an increase in coliform bacteria. In addition to the patients treated for oral cancer, the majority of the patients in the ‘necrosis’ group could also be considered terminally ill patients in our study, as the common underlying diseases of patients treated for osteonecrosis were usually breast cancer, prostate cancer or multiple myeloma. These patients often receive antiresorptive drugs, which might also cause a shift in the microbiota of the mouth, as the reduced resilience of the bone can lead to opportunistic infections. Various studies have focused on the role of periodontopathogens (e.g., Fusobacterium, Prevotella, and Porphyromonas spp.) and Actinomyces spp., but in a thorough evaluation of the results of these studies, we observed a considerable percentage of Proteobacteria in the isolates of these patients [59,60,61]. These findings are in accordance with our results, as the patients in the ‘necrosis’ group presented increased percentages of Actinomyces and Prevotella spp., and similar to the patients in the ‘tumor’ group, they also presented substantial percentages of Enterobacter, Enterococcus, Escherichia and Klebsiella spp. It has been previously suggested that coliform bacteria could be used as markers for underlying diseases, as these types of bacteria are practically absent from the oral cavity of healthy patients [13, 58]. A study by Karpinets et al. [62] revealed that the intratumoral microbiome of adenoid cystic carcinoma patients featured gut-like bacteria, with low diversity and colonization by Proteobacteria and other gut microbes, such as Enterococcus spp., which were negatively associated with patient survival compared with the bacteria typically found in the oral cavity. There is growing evidence suggesting that the oral microbiota may play a role in the development of diseases of the gastrointestinal system, such as colorectal cancer [63], but the reverse interaction between the oral cavity and the gut microbiome might be due to the lower resistance of the intratumoral microbiome to colonization by gut bacteria. Although we are aware that the generally stable oral microbiota of healthy individuals can be disrupted by various local and systemic diseases, the exact role of bacteria in the pathomechanisms of the aforementioned diseases is still unclear, despite the efforts of numerous studies. Furthermore, the oral microbiota can potentially influence the morbidity of patients who are already compromised, especially those with advanced disease, but further investigation is needed.

This study represents the first comprehensive microbiological evaluation of maxillofacial infections in Hungary and, to our knowledge, is the first to compare the pathogen spectrum between oral cancer patients and those treated for nonmalignant lesions, specifically abscesses and necrosis. Our results revealed significantly greater percentages of Enterobacterales among the clinical isolates of patients with oral cancer than among the other patient groups. The high abundance of Enterobacterales in oral cancer patients, coupled with the intrinsic resistance of many bacteria in this order to amoxicillin with clavulanic acid—the commonly used first-line empirical antibiotic therapy—highlights the need for targeted microbial surveillance, early detection, and personalized treatment strategies to prevent severe infections and complications during cancer treatment and recovery. Future studies are needed to determine whether Enterobacterales are present in intratumoral tissues, contributing to the development of SSIs, or if they are introduced as nosocomial infections during hospital care. Another key finding of our investigation was the high rate of clindamycin resistance, particularly among Prevotella, Streptococcus and Staphylococcus spp. The high resistance rates to clindamycin in head and neck infections highlight the need to reconsider its empirical use and promote a more personalized, susceptibility-based approach, emphasizing the importance of minimizing unnecessary antibiotic use to prevent AMR and improve patient outcomes. However, several limitations should be considered when interpreting these findings. Bacterial identification was based solely on conventional culturing techniques without the use of molecular diagnostic methods. While this may have limited the detection of uncultivable organisms, it is important to note that culture-based methods remain essential for phenotypic antimicrobial resistance profiling, which was a primary objective of the study. Variability in sample collection methods—specifically between intraoral and extraoral approaches—and the fact that the isolates from cancer patients in this study were often not obtained directly from intratumoral tissue may have influenced the microbiological findings. Additionally, detailed clinical background information was not consistently available for all patients, which prevented the inclusion of these data and limited the ability to explore associations between clinical factors, microbiological profiles and AMR rates. Future studies incorporating standardized sampling methods and molecular diagnostics, alongside complete clinical data, would provide a more nuanced understanding of pathogen diversity and resistance dynamics in head and neck infections.