Optimal treatment time with systemic antimicrobial therapy in odontogenic infections affecting the jaws: a systematic review

Abstract

Objectives

This systematic review aimed to analyze the existing literature to determine the most effective and safe duration of antimicrobial treatment in odontogenic infections of the mandible, addressing a critical gap in clinical guidelines regarding optimal treatment duration.

Materials and methods

A systematic review protocol was registered in PROSPERO (CRD42024551258), and a comprehensive search was conducted in databases including PubMed, Web of Science, Scopus, ScienceDirect, Embase, and Google Scholar for articles published up to June 16, 2024. Randomized clinical trials (RCTs) evaluating different durations of antimicrobial treatment were prioritized.

Results

The database search yielded 3,446 articles. After removing duplicates using Rayyan© software, 2,653 articles remained, of which 26 met the inclusion criteria. Following a thorough evaluation, 8 studies were deemed highly relevant and included in the final analysis. The findings suggest that shorter antibiotic regimens, typically ranging from 3 to 5 days, are effective when combined with surgical interventions, minimizing complications and bacterial resistance.

Conclusions

The evidence indicates that the choice of antibiotic regimen and its duration should be tailored to the patient’s clinical condition, the severity of the infection, and local bacterial resistance patterns. While amoxicillin and its derivatives are effective for most cases, alternative antibiotics such as ciprofloxacin or metronidazole may be more suitable in specific scenarios. These findings highlight the importance of individualized treatment plans and the need for further randomized clinical trials to refine evidence-based guidelines.

Highlights

This article sought to investigate the ideal duration of antimicrobial therapy in odontogenic jaw infections through a systematic review of primary articles, focusing on randomized clinical trials. The literature suggests that the choice of antibiotic regimen should take into account factors specific to the patient, the infection and local bacterial sensitivity. Although amoxicillin is often effective, alternative antibiotics such as ciprofloxacin or metronidazole may be more appropriate in certain situations. Careful administration of antibiotics can improve clinical outcomes and reduce bacterial resistance. More randomized clinical trials are needed to refine these guidelines and ensure evidence-based clinical practices.

Introduction

Odontogenic infections, originating from the teeth and surrounding structures, present a significant challenge in dental practice due to their potential severity and complexity. These infections are often multimicrobial, involving facultative and anaerobic bacteria, necessitating precise antimicrobial selection. This systematic review aims to assess the duration and efficacy of antimicrobial therapy in these infections, balancing efficacy with the risks of bacterial resistance and adverse effects. Odontogenic infections in the jaws are a major challenge in dental practice, due to their potential severity and the complexity of treatment. These infections, which originate in the teeth or their supporting tissues, can range from localized conditions, such as periapical abscesses, to broader infections involving several facial spaces [1,2,3,4,5].

The most common symptoms include severe pain, swelling, sensitivity to touch, fever, bad breath and difficulty opening the mouth (trismus). In more serious cases, the infection can spread to other areas of the head and neck, causing serious complications such as Ludwig’s angina, which is an infection of the submandibular and sublingual spaces and can compromise the airways [2, 6, 7].

Effective management of these infections is therefore essential to avoid severe complications. Antimicrobial therapy plays a crucial role in the treatment of odontogenic infections, being used to control bacterial proliferation and prevent the spread of infection [8, 9].

These infections are typically multimicrobial, involving a combination of facultative and anaerobic species. The facultative Streptococcus viridans group, which includes S. anginosus, S. intermedius and S. constellatus, are Gram-positive commensal bacteria abundant in the mouth and often associated with cellulitis and orofacial abscesses. After a few days, anaerobes such as Prevotella and Porphyromonas predominate. Most of the facultative streptococci that cause odontogenic infections are sensitive to penicillin; however, approximately a quarter of Prevotella and Porphyromonas strains are resistant to penicillin [10, 11] (Chunduri et al., 2012; Reyes JVM, Dondapati M, Ahmad S, Song D, Lieber JJ, Pokhrel NB).

Thus, the choice of the appropriate antimicrobial depends on different factors, including the severity of the infection, the local bacterial resistance profile and the patient’s characteristics, such as allergies and comorbidities [12]. The duration of antimicrobial treatment is a critical aspect for the efficacy and safety of the management of odontogenic infections. The current trend favors shorter courses, usually between 3 and 5 days, especially when combined with surgical intervention, such as abscess drainage or tooth extraction. Studies indicate that shorter courses are equally effective and present a lower risk of developing bacterial resistance and adverse effects, while longer courses may be necessary in cases of severe or complicated infections [5, 13, 14].

The appropriate choice and adjustment of antibiotic therapy is crucial in the management of odontogenic infections. Given the multimicrobial nature of these infections, an initial empirical approach based on local patterns of bacterial resistance is often necessary. However, accurate identification of the pathogens involved and antimicrobial sensitivity testing can guide the selection of antibiotics more effectively [15, 16]. Monitoring and adjusting antimicrobial therapy is essential to ensure complete eradication of the infection, minimize the risk of bacterial resistance and reduce adverse effects. Recent studies have explored the efficacy of different antimicrobial regimens and the need for adjustments based on patient’s clinical response. This aspect of antibiotic therapy is fundamental to improving clinical outcomes and optimizing the use of antibiotics in dental practice [17, 18].

This systematic review aims to analyze the existing literature to determine the most effective and safe duration of antimicrobial treatment in odontogenic jaw infections. By synthesizing evidence from clinical studies, we aim to provide evidence-based recommendations that can guide clinical practice and improve patient outcomes. In addition, the review will address the impacts of treatment duration on bacterial resistance and associated adverse events, providing a comprehensive and up-to-date overview of the management of these infections.

Materials and methods

Development and registration of the systematic review protocol

The protocol for this systematic review included defining the start and end dates of the study, formulating the research question and selecting the databases. The PICOS methodology (Population, Intervention, Comparison, Outcomes and Type of Study) was used, with well-defined inclusion and exclusion criteria, detailed search strategies, and methods for screening, extracting and analyzing the data. Tools for assessing risk of bias and study quality were also specified. The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) [19], guaranteeing transparency and methodological integrity, under the number CRD42024551258.

Research question

Table 1 shows the PICOS tool used to formulate the research question.

Table 1 Acronym PICOS

Therefore, the research question posed was “What is the ideal time for treatment with antimicrobial therapy in individuals affected by odontogenic jaw infections?“. This question seeks to determine the most effective duration of antimicrobial treatment in order to minimize bacterial resistance, optimize clinical results and reduce side effects. The investigation considers variables such as the severity of the infection, the clinical response of the patients and current evidence-based recommendations.

Registration protocol

The study was registered with PROSPERO under the number CRD42024551258. This registration aimed to guarantee the transparency and methodological integrity of this review, ensuring that all planned procedures were clearly documented and accessible. The inclusion of the study in PROSPERO can also facilitate comparison with similar reviews and promotes confidence in the results presented, reinforcing the credibility and scientific quality of the research.

Search strategy, databases and article selection

Systematic literature searches were conducted in the following databases: PubMed, Web of Science, Scopus, ScienceDirect, Embase and Google Scholar. The search included articles published up to June 16, 2024. To optimize the searches, search terms were combined with Boolean operators (AND and OR). The databases were accessed through the CAPES journal portal, using a login on the CAFE platform. In the PubMed database, the “advanced search by MeSH topics and MeSH terms” filter was used.

The methodological quality of the selected articles was assessed by two independent researchers, considering the title and abstract (when available). The aim was to check whether the articles met the inclusion criteria. When the abstract did not provide enough information, the full text of the article was read. After individual assessments, the researchers reached a consensus on which studies should be included for full analysis.

Data were extracted systematically by two independent reviewers. A standardized form was used to collect information such as author, year of publication, country, study design, sample size, type of antimicrobial evaluated, duration of treatment, main results and conclusions. After extraction, data were compared to ensure consistency. Discrepancies were resolved by consensus or with the participation of a third reviewer. Data analysis was performed qualitatively, highlighting patterns between studies, and quantitatively, when applicable, to assess trends or relevant differences related to duration and efficacy of treatments. Tools such as RoB 2.0 were used to assess the risk of bias of the included studies, reinforcing the validity of the findings.

Study selection

The inclusion criteria covered primary articles investigating the optimal duration of antimicrobial therapy in odontogenic jaw infections. Preferably randomized clinical trials (RCTs) that looked at different durations of antimicrobial treatment.

Studies that did not mention the duration of antimicrobial therapy in adult odontogenic jaw infections, case reports, case series or studies without control groups or comparison arms, cross-sectional studies or retrospective analyses without appropriate controls, abstracts, conference proceedings or unpublished studies without sufficient methodological details for evaluation were excluded. In addition, articles that only summarized secondary data, such as systematic reviews and meta-analyses, as well as studies not conducted on humans, were discarded. Studies whose published data was inadequate in relation to primary and secondary outcome measures were also excluded.

The languages ​​considered for inclusion in this review were articles published in English, Portuguese and Spanish, due to the wide scientific dissemination of these languages ​​and the ease of interpretation by the reviewers.

Risk of bias and quality assessment

Three reviewers independently assessed the quality of each article. There was no divergence in the included studies. Due to the homogeneity in the design of the included studies, version 2 of the Cochrane risk of bias tool for randomized trials (RoB 2) was used, which is the recommended tool for this assessment [20].

Results

Selection of studies

The strategic search of the databases identified n = 3,446 studies. After removing duplicates using the Rayyan© software [21], n = 2,653 articles remained, of which n = 26 met the inclusion criteria. After careful evaluation based on the inclusion and exclusion criteria, n = 8 studies were considered highly relevant and included in the systematic review, as shown in Table 2. Figure 1 shows the database search flowchart.

Fig. 1

Literature search flowchart, adapted from PRISMA 2020. Source: Authors (2024) , adapted from PRISMA [22].

Risk of bias analysis

In this study, the risk of bias was assessed using version 2 of the Cochrane tool for risk of bias in randomized trials (RoB 2) [21]. By analyzing each study included individually, it was identified that they all presented a low risk of bias, as shown in Fig. 2.

Fig. 2

Individual bias analysis of each included study. Source: Authors (2024) , adapted from the ROB-2 tool [21].

Table 2 Articles that made up this systematic review

Discussion

The administration of systemic antibiotics in the treatment of odontogenic jaw infections is a topic of great clinical relevance. Several studies have investigated the efficacy of different antibiotics and their administration protocols, seeking to optimize therapeutic results and minimize adverse effects.

In the study by Natarajan et al. [23], the efficacy of amoxicillin and ciprofloxacin in the post-surgical treatment of transalveolar extraction was compared, and the findings showed that ciprofloxacin resulted in a lower incidence of post-surgical infection compared to amoxicillin. Furthermore, the literature reports that in maxillary sinus lift surgeries, based on antibiograms of positive cultures, the antibiotics that were most effective against possible complications were: ampicillin, amoxicillin-clavulanate and ciprofloxacin [24]. These findings suggest that ciprofloxacin may be a more effective choice in specific contexts, although the choice of antibiotic should always consider bacterial resistance and patient profiles.

Bali et al. [25] investigated the use of metronidazole as part of an empirical regimen after incision and drainage of odontogenic infections. The results showed that there was no significant difference in the resolution of the infection between the groups that used different antibiotics. However, the study highlighted the importance of basing the prescription of metronidazole on the assessment of clinical and laboratory markers of infection, suggesting that empirical use may not be necessary in all cases. Similarly, a study carried out by analyzing the medical records of patients affected by odontogenic infections concluded that Ceftriaxone and Metronidazole were the antibiotics of choice for the majority of cases [26].

According to Igoumenakis et al. [27] it is important to emphasize the importance of extracting the causative tooth in the rapid resolution of odontogenic infections. This study suggests that early removal of the infected tooth can accelerate clinical and biochemical recovery, supporting a more aggressive treatment approach in cases of severe infections.

In two studies conducted by Matijević et al. [28] the efficacy of amoxicillin and ampicillin in reducing the duration of clinical symptoms of acute dentoalveolar abscesses was demonstrated when administered after initial surgical treatment. Both antibiotics showed high bacterial sensitivity, reinforcing the usefulness of these agents in the management of acute odontogenic infections.

In the study by Mohanty et al. [29], the efficacy of postoperative antibiotic protocols in maxillofacial fractures was evaluated, concluding that a single perioperative dose of antibiotics is effective in minimizing postoperative complications. These findings question the need for prolonged antibiotic regimens, pointing to the importance of further research into comminuted and complex fractures.

Luaces-Rey et al. [30] investigated different amoxicillin administration regimens after third molar removal, concluding that postoperative therapy does not offer significant benefits over the short prophylactic regimen. This conclusion highlights the need to identify patients who have benefited most from antibiotic use in order to avoid bacterial resistance and other adverse effects. Thus, removing sources of infection in the oral cavity and maintaining periodontal health, along with a careful surgical technique, are fundamental elements for uncomplicated tooth extractions. It is important to note that tooth extraction in patients with good systemic health generally does not require antibiotic therapy [31].

Thus, the efficacy of amoxicillin/clavulanic acid in preventing infectious and inflammatory complications after third molar extraction was confirmed in the study by Arteagoitia et al. [32], but they warned against indiscriminate prescription of this regimen, suggesting a more judicious approach.

Finally, Salim et al. [33] compared amoxicillin and cephedrine in the treatment of oral and dental infections, concluding that amoxicillin is superior in terms of efficacy and lower incidence of adverse effects.

Thus, in line with the above, it can be seen that Matijević et al. [34], Luaces-Rey et al. [30], Arteagoitia et al. [32] and Salim et al. [33] agree that amoxicillin and its derivatives, such as amoxicillin/clavulanic acid, are effective in the management of odontogenic infections. These studies highlight the effectiveness of these antibiotics in reducing the duration of symptoms and preventing infectious complications.

In addition, Mohanty et al. [29] and Luaces-Rey et al. [30] suggest that a single perioperative dose of antibiotics may be sufficient to minimize postoperative complications, questioning the need for prolonged regimens.

Natarajan et al. [23] found that ciprofloxacin had a lower incidence of postoperative infection compared to amoxicillin, suggesting a superior efficacy of ciprofloxacin in specific contexts. In contrast, the studies by Matijević et al. [34] and Salim et al. [33] highlighted the high efficacy of amoxicillin and its derivatives, indicating that the response to treatment may vary according to the type of infection and the patient profile. These conclusions suggest that although ciprofloxacin may be preferred in certain cases due to its superior efficacy, amoxicillin remains an effective and widely used option, especially in odontogenic infections and in patients without specific contraindications. The choice of antibiotic should therefore be personalized, taking into account the type of infection, the patient’s profile and bacterial susceptibility.

In the study by Bali et al. [25], the efficacy of metronidazole was demonstrated in odontogenic infections treated with drainage. The study compared patients who received metronidazole after drainage with those who discontinued the antibiotic. The results showed that there was no significant difference in the resolution of the infection between the two groups. This suggests that, after effective drainage, the continued addition of metronidazole may not be necessary for all patients. The conclusion is that the administration of metronidazole should be observed on a case-by-case basis, and can be avoided in situations where adequate drainage has already been performed, especially in healthy patients without complications.

The selection of the ideal antibiotic for the management of odontogenic infections should consider the spectrum of action, pharmacokinetics, safety profile and local patterns of bacterial resistance. Amoxicillin is often used as the first choice due to its efficacy against gram-positive and some gram-negative bacteria, although emerging resistance is a challenge. The combination of amoxicillin with clavulanic acid expands the spectrum of action to include β-lactamase-producing organisms and is indicated for more severe cases. Alternatives such as clindamycin, effective against anaerobes and gram-positive bacteria, are recommended for patients allergic to penicillins, although there is a risk of colitis associated with Clostridioides difficile. Metronidazole is detrimental for infections dominated by anaerobes, usually in combination with other antibiotics. Cephalosporins may be an option in cases of penicillin allergy, but with possible cross-reactivity, while macrolides, such as azithromycin, offer alternative coverage, limited by increasing bacterial resistance. Individualization of antimicrobial therapy based on the type of infection, patient profile, and bacterial sensitivity is essential to improve clinical outcomes and minimize the risk of antimicrobial resistance [1, 35].

Conclusion

The results of this study indicate that the optimal duration of antibiotic therapy for odontogenic jaw infections is highly dependent on the clinical scenario, including the severity of the infection, patient-specific factors, and the presence of local bacterial resistance. Although amoxicillin and its derivatives remain effective and widely used options, evidence suggests that shorter durations of treatment, typically ranging from 3 to 5 days, may be sufficient in most cases, particularly when combined with appropriate surgical interventions such as drainage or tooth extraction. These shorter regimens not only demonstrate comparable efficacy but also help minimize the risk of bacterial resistance and adverse effects. However, the limited availability of high-quality randomized controlled trials directly addressing the optimal duration of therapy highlights the need for further research. Future studies should focus on refining evidence-based recommendations for treatment duration to ensure optimal patient care and global applicability.