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J Stomatol Oral Maxillofac Surg xxx (2020) xxx–xxx

Available online at

ScienceDirect
www.sciencedirect.com

Review

Microbiota of alveolar osteitis after permanent tooth extractions:

A systematic review
N. Riba-Terés a, A. Jorba-Garcı́a a, J. Toledano-Serrabona a,b, L. Aguilar-Durán a,
R. Figueiredo a,b,*,1, E. Valmaseda-Castellón a,b
a
Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
b
Idibell Institute, Barcelona, Spain

A R T I C L E I N F O A B S T R A C T

Article history: Alveolar osteitis (AO) or dry socket after dental extractions is a common postoperative complication
Received 22 June 2020 characterized by the presence of severe pain associated with an empty socket. Although some authors
Accepted 25 August 2020 consider AO to be related to an alteration of the blood clot, the underlying etiology remains unclear, and
recent reports suggest that bacteria might play an important role. A systematic review was made,
Keywords: compiling relevant references from PubMed, the Cochrane Library, Scopus and the Web of Science
Dry socket databases to determine which bacteria have been identified in AO sockets after dental extractions.
Alveolar osteitis
Papers published between 1980–2019, identifying the bacteria present in AO sockets after tooth
Etiology
Bacteria
extractions, were included. Data were displayed in tables, and a descriptive analysis was carried out.
Microbiology After the screening process, four papers were analyzed, comprising a total of 138 samples from
Dental extraction 138 patients with AO. The most commonly detected bacteria were Prevotella, Fusobacterium, Parvimonas
Third molar and Peptostreptococcus. Two studies also showed the microbiota of patients that developed AO after
dental extractions to be apparently different from that of patients without postoperative complications.
These results indicate that bacteria may play an important role in the pathogenesis of AO, though further
studies are needed to confirm these findings.
C 2020 Elsevier Masson SAS. All rights reserved.

1. Introduction ment of AO [1,4,5], the underlying etiology remains unclear, and

Alveolar osteitis (AO) or dry socket, is one of the most common
postoperative complications, with an estimated incidence of 5–
30% [1–4]. This disorder usually occurs between the first and the
fourth day after permanent tooth extraction, and is characterized
by acute and severe pain, without signs of infection or inflamma-
tion [1,3]. Clinically, AO is accompanied by a partially or totally
disintegrated blood clot within the alveolar socket, with or without
halitosis [2].
While smoking, mandibular teeth extractions, the female
gender, the use of oral contraceptives, inadequate intraoperative
irrigation, difficult or traumatic extractions and pre-existing
infections are some of the predisposing factors for the develop-
* Corresponding author at: Faculty of Medicine and Health Sciences, Campus de
Bellvitge. University of Barcelona, L’Hospitalet de Llobregat, C/Feixa Llarga s/n,
Pavelló Govern, 2 planta, Despatx 2.9, 08907 Barcelona, Spain.
E-mail address: ruibarbosa@ub.edu (R. Figueiredo).
1
Website: http://www.mastercirugiabucal.com.
many concepts are still the subject of debate.
Alveolar osteitis traditionally has been considered to be related
to an alteration in formation of the blood clot. According to Birn [6],
dry socket exhibits increased fibrinolytic activity and activation of
plasminogen to plasmin in the presence of tissue activators
(physiological substances such as tissue plasminogen activator or
non-physiological substances such as streptokinase and staphy-
lokinase). This in turn might result in premature loss of the intra-
alveolar blood clot after extraction, leaving the bony walls of the
socket exposed to the oral cavity [1].
Bacteria have also been suggested to play a role in AO,
supported by the fact that the latter shares most of the risk factors
of postoperative infections. Poor oral hygiene, pre-existing local
infection such as pericoronitis, and advanced periodontal disease
are examples that support this claim [3].
There are important clinical implications concerning the
possible infectious etiology of AO. Indeed, if AO is an infection
provoked by bacteria, prevention and treatment guidelines should
be reassessed and the prescription of antibiotics and antiseptics
might be indicated, especially in patients with risk factors. In this

https://doi.org/10.1016/j.jormas.2020.08.007
2468-7855/ C 2020 Elsevier Masson SAS. All rights reserved.

Please cite this article in press as: Riba-Terés N, et al. Microbiota of alveolar osteitis after permanent tooth extractions: A systematic
review. J Stomatol Oral Maxillofac Surg (2020), https://doi.org/10.1016/j.jormas.2020.08.007
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line, several clinical trials have shown that both topical and
systemic antibiotics and antiseptics significantly reduce the
occurrence of AO [1,3,4,7]. Within the entire spectrum of the oral
microbiome, the presence of fibrinolytic microorganisms which
may induce blood clot lysis in the dental alveolus, such as
Treponema denticola, Streptococcus, Staphylococcus, Prevotella,
Bacteroides and Peptostreptococcus, may be another plausible
etiological factor in AO [8–12].
Several methods have been used to analyze the composition of
the oral microbiota, including microscopy, culture testing, staining,
enzymatic assays, immunoassays, DNA sequencing, DNA–DNA
hybridization, Sanger sequencing and polymerase chain reaction
(PCR) tests. However, it is important to mention that a substantial
number of microorganisms may be overlooked when common
culture methods are employed [13]. In this respect, 16S ribosomal
RNA (16S rRNA) gene sequencing methods have been used in
recent studies to compare microbial communities in sockets with
AO and in normal healing sockets [1,14].
Very few studies have focused on the etiology of AO. On one
hand, some papers have reported that bacteria might induce
fibrinolytic activity and lysis of the blood clot [9,12]. On the other
hand, studies using next-generation sequencing (NGS) of 16S rRNA
are scarce in the dental field – a fact that can result in an
incomplete analysis of the implicated microbiota. The aim of the
present study therefore was to determine which bacteria have
been identified in the published studies referred to AO sockets after
dental extractions. Furthermore, in those studies that included a
control group, comparisons were made between the microbiota
present in AO sockets and in postoperative sites without
complications.
2. Materials and methods
The present systematic review was carried out according to the
‘‘Preferred Reporting Items for Systematic Reviews and Meta-
Analyses’’ (PRISMA) statement [15] and was registered on the
PROSPERO website (Reference: CRD42020183668).
2.1. Eligibility criteria
The PECOS factors [study population (P), exposure (E),
comparison (C), outcome variables (O) and study design (S)] were
as follows:
- (P) The study population consisted of patients subjected to
dental extraction, with a microbiology sample taken from a post-
extraction socket.
- (E) Diagnosis of AO.
- (C) Comparison was made with the microbiological samples
taken from sockets without postoperative complications. In
some cases, comparison was not possible due to the lack of a
control group.
- (O) Identified bacterial genera or species. When available,
abundance or frequency of microorganisms was also reported.
- (S) Randomized clinical trials or observational studies (case-
control, cohort, cross-sectional, case series) published between
1980–2019.
2.2. Information sources and screening process
Two independent examiners (N.R-T. and A.J-G.) conducted an
electronic search in PubMed (MEDLINE), the Cochrane Library,
Scopus and the Web of Science databases in April 2020. The search
strategy was ("Dry Socket"[Mesh] OR "alveolar osteitis" OR
Please cite this article in press as: Riba-Terés N, et al. Microbiota of alveolar osteitis after permanent tooth extractions: A systematic
review. J Stomatol Oral Maxillofac Surg (2020), https://doi.org/10.1016/j.jormas.2020.08.007
"alveolar periostitis" OR "dry socket" OR "alveolalgia" OR
"fibrinolytic osteitis" OR "fibrinolytic alveolitis") AND ("etiology"
[Subheading] OR "aetiology" OR "etiopathology" OR "etiological"
OR "aetiological" OR "etiopathogenesis" OR "bacteria"[Mesh] OR
"microbiology"[Mesh] OR "microbiota"[Mesh] OR "microorga-
nisms" OR "microbiome" OR "microbial" OR "microbiota" OR
"bacteria" OR "microbiology"). In addition, a cluster search from
the selected studies was carried out to identify possible eligible
items not included in the electronic search. Any discrepancy during
the article selection process was resolved thanks to an indepen-
dent investigator (RF). After reviewing the title and summary,
irrelevant studies were eliminated. Finally, those articles that after
evaluation of the full text did not meet the pre-established
inclusion criteria were likewise excluded. Cohen’s kappa coeffi-
cient was calculated in order to assess reviewer agreement.
2.3. Data extraction
Data collection was performed by three independent examiners
(N.R-T., A.J-G. and J.T-S.) using data extraction tables, and a
descriptive analysis was carried out. Whenever possible, the
following items were recorded: author/s, year of publication, city
(country), study design and details of the participants and the
microbiology. Authors were contacted when necessary for
clarification of missing information.
2.4. Quality assessment and data analysis
Two independent researchers (N.R-T.- R.F.) assessed the quality
of observational studies using the modified Newcastle Ottawa scale
(NOS) [16] and the modified Delphi technique [17]. In case-control
studies, NOS evaluates 8 items for three domains (Selection,
Comparability, Exposure). The total maximum score of these three
subsets is 9, and a study can be awarded a maximum of one star for
each numbered item within the Selection and Exposure categories,
while a maximum of two stars can be given for Comparability. The
studies which scored 7 were classified as high-quality studies.
Regarding case series, methodological quality was assessed by a
modified Delphi technique including 18 items. The studies which
scored 13 were classified as high-quality studies.
A descriptive analysis of the above-mentioned outcomes was
carried out using data extraction tables.
3. Results
3.1. Study selection
Out of 434 potential articles without any duplicate references,
6 full-text papers were screened, reviewing the titles and abstracts.
Two publications were excluded: one was removed because the
results did not allow identification of which bacteria were found in
AO patients [18], and the other was excluded because bacterial
genera and/or species were not reported [19]. Finally, four studies
[1,14,20,21] that assessed the microbiota of AO were included
(Fig. 1). The level of agreement between reviewers was 87.50%,
with a kappa index of 0.75.
3.2. Quality assessment
Case-control studies can be awarded up to 9 stars [16], and case
series can be classified based on an 18-criteria checklist [17] (Table
1). Case-control studies had a mean NOS of 7  0 stars, and case
series had a mean Delphi rating of 9.5  4.95. The main flaw in the
case-control studies was in the selection domain, since all of them did
not include representative cases.
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Fig. 1. PRISMA flow chart of the study selection process. AO: alveolar osteitis.

Table 1
Quality assessment of studies. The modified Newcastle Ottawa scale (NOS) and the modified Delphi technique were used. NA:
not applicable.

Please cite this article in press as: Riba-Terés N, et al. Microbiota of alveolar osteitis after permanent tooth extractions: A systematic
review. J Stomatol Oral Maxillofac Surg (2020), https://doi.org/10.1016/j.jormas.2020.08.007
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Table 2
Patient features of the selected studies. M: male, F: female, H: healthy, G: gingivitis, P: periodontitis, NR: not reported, L3M: lower third molar.

Shen et al. [14] Aguilar-Durán et al. [1] Soni et al. [20] Kiewlicz et al. [21]

Age 29.36 (24 45) 30 (19 35) 34.60 (18 62) (15 71)
Gender M 4 3 25 38
F 7 7 22 32
Smoker Yes NR 1 NR NR
No 9
Oral contraceptives in NR 2 0 NR
women
Oral hygiene H NR 4 NR NR
G 5
P 1
History of infection NR 6 NR NR
Pericoronitis 4
Surgical extraction Yes Only surgical extraction of L3M 6 NR NR
No 4
Surgeon experience NR Residents (1st-/2nd-/3rd-year resident) 5/3/2 NR NR

3.3. Data extraction and synthesis
Among the included studies, a total of 138 samples from
138 patients diagnosed with AO after tooth extraction were
analyzed. Some of these studies employed next-generation
sequencing techniques to perform bacterial identification [1,14]
while others used standard culture media [20,21] (Table 2).
3.4. Next-generation metagenomic techniques
Regarding the studies that used metagenomic techniques, a
total of 21 samples from 21 patients diagnosed with AO after tooth
extraction were analyzed. Shen et al. [14] described the identified
microorganism genera, while Aguilar-Duran et al. [1] reported the
species of each detected bacterium. Taxonomic results with the
sequenced pathogens of each study, with the species/genus and
the amount, are reported in Table 3.
Both of the aforementioned studies showed Prevotella, Fuso-
bacterium and Parvimonas to be among the most commonly
identified bacteria (Table 4). Additionally, these studies also
incorporated a control group that included bacterial samples of
sockets without postoperative complications [1,14]. In a normal
healing situation, Aguilar-Durán et al. [1] found a high proportion
of Prevotella (18%), Capnocytophaga (8%), Streptococcus (6%) and
Porphyromonas (5%), while Shen et al. [14] found a significantly
increased abundance of Aggregatibacter, Peptostreptococcaceae_-
XIG-7, Veillonella spp. and Treponema (Table 5).
Ten phyla, 23 classes, 38 orders, 63 families and 116 genera
were detected by Shen et al. [14]. At phylum level, more than 90%
of the sequences belonged to Bacteroidetes (2–67% of total
sequences), Firmicutes (11–64%), Fusobacterium (0.2–35%), Pro-
teobacteria (0.8–56%), Actinobacteria (0.1–68%) and Spirochaetes
spp. (0–12%). The remaining bacteria corresponded to Gracili-
bacteria_GN02, Saccharibacteria_TM7, SR1 and Synergistes spp.
(Table 3).
Aguilar-Durán et al. [1] found 151 different species: 55 of them
were only found in AO, 51 bacteria were specific to the control
group, and 44 were common to both groups.

Table 3
Description and comparison of selected studies. Highlighted cells indicate the most commonly identified bacteria in AO (alveolar osteitis) of each study, while bacteria in bold
indicate an abundance of >0.1% in the study of Shen et al. (15) and >0.5% in the study of Aguilar-Durán et al. (2).

Author (year), Design No. patients (No. Method Genus (strains) Species Abundance %
country dry sockets)

Shen et al. (14) Case-control 31 (11) Metagenomic technique Actinobacteria

(2019), China (Next-generation Aggregatibacter
sequencing (NGS) of 16S Atopobium
rRNA), using the Illumina Bacteroidetes
Miseq PE300 sequencing Dialister
platform Filifactor
Firmicutes
Fusobacterium 16%
Gracilibacteria_GN02
Johnsonella
Oribacterium
Parvimonas 7%
Peptostreptococcaceae_XIG-7
Peptostreptococcus
Prevotella 24%
Proteobacteria
Saccharibacteria_TM7
Slackia
Solobacterium
Spirochaetes
SR1
Streptococcus
Synergistes
Treponema
Veillonella

Please cite this article in press as: Riba-Terés N, et al. Microbiota of alveolar osteitis after permanent tooth extractions: A systematic
review. J Stomatol Oral Maxillofac Surg (2020), https://doi.org/10.1016/j.jormas.2020.08.007
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Table 3 (Continued )

Author (year), Design No. patients (No. Method Genus (strains) Species Abundance %
country dry sockets)

Aguilar-Durán et al. Case-control 20 (10) Metagenomic technique Abiotrophia Abiotrophia defective 246 (0.3%)
(1) (2019), Spain (next-generation Abiotrophia para- 487 (0.4%)
sequencing (NGS) of 16S adiacens
rRNA), using the Roche Acidithiobacillus Acidithiobacillus 117 (0.09%)
sequencing platform ferrooxidans
Actinomyces Actinomyces 3250 (3%)
odontolyticus
Actinomyces naeslundii 109 (0.09%)
Aggregatibacter Aggregatibacter segni 84 (0.09%)
Anaplasma Anaplasma 6 (<0.09%)
phagocytophilum
Atopobium Atopobium minutum 347 (0.3%)
Bacteroides Bacteroides acidifaciens 313 (0.3%)
Blautia Blautia producta 199 (0.2%)
Butyrate-producing bacterium Butyrate-producing 3 (<0.09%)
bacterium SM4/1
Butyrate-producing 328 (0.3%)
bacterium SS3/4
Butyricimonas Butyricimonas 152 (0.2%)
synergistica
Butyrivibrio Butyrivibrio hungatei 4759 (4%)
Candidatus Candidatus Desulforudis 405 (0.3%)
audaxviator MP104C
Capnocytophaga Capnocytophaga 509 (0.4%)
gingivalis
Capnocytophaga 1717 (1%)
ochracea
Capnocytophaga 201 (0.2)
sputigena
Chryseobacterium Chryseobacterium sp. 563 (0.5%)
KM
Clostridium Clostridium 24 (<0.09%)
aminobutyricum
Clostridium 975 (0.9%)
longisporum
Clostridium paradoxum 81 (0.09)
Clostridium sp. MK8 354 (0.3%)
Clostridium ultunense 1679 (1%)
Cytophaga Cytophaga sp. 3 (<0.09%)
MBIC04667
Desulfotomaculum Desulfotomaculum 84 (0.09%)
thermosapovorans
Dialister Dialister pneumosintes 1617 (1%)
Eikenella Eikenella corrodens 386 (0.3%)
Embryophyte Embryophyte 12 (<0.09%)
environmental sample
Eubacterium Eubacterium 5 (<0.09%)
cellulosolvens
Eubacterium hallii 738 (0.6%)
Eubacterium rectale 1159 (1%)
Eubacterium saburreum 346 (0.3%)
Eubacterium sp. WAL 1273 (1%)
17363
Flavobacterium Flavobacterium 638 (0.5%)
columnare
Flavobacterium 64 (0.09%)
denitrificans
Fusobacterium Fusobacterium 7 (<0.09%)
necrophorum
Fusobacterium 5109 (4%)
nucleatum
Fusobacterium 576 (0.5%)
nucleatum subsp.
animalis
Fusobacterium 1676 (1%)
nucleatum subsp.
polymorphum
Fusobacterium 1249 (1%)
periodonticum
Gemella Gemella morbillorum 300 (0.3%)
Granulicatella Granulicatella adiacens 559 (0.5%)
Granulicatella elegans 1182 (1%)

Please cite this article in press as: Riba-Terés N, et al. Microbiota of alveolar osteitis after permanent tooth extractions: A systematic
review. J Stomatol Oral Maxillofac Surg (2020), https://doi.org/10.1016/j.jormas.2020.08.007
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Table 3 (Continued )

Author (year), Design No. patients (No. Method Genus (strains) Species Abundance %
country dry sockets)

Haemophilus Haemophilus 2 (<0.09%)

haemolyticus
Haemophilus 1783 (2%)
parainfluenzae
Haemophilus sp. CCUG 69 (<0.09%)
15949
Halanaerobium Halanaerobium 930 (0.8%)
saccharolyticum subsp.
Saccharolyticum
Halothiobacillus Halothiobacillus 1039 (0.9%)
hydrothermalis
Lactobacillus Lactobacillus 4 (<0.09%)
catenaformis
Lactococcus Lactococcus lactis subsp. 30 (<0.09%)
lactis
Leptotrichia Leptotrichia hofstadii 385 (0.3%)
F0254
Leuconostoc Leuconostoc 819 (0.7%)
mesenteroides
Megasphaera Megasphaera 16 (<0.09%)
micronuciformis
Mitsuokella Mitsuokella multacida 6 (<0.09%)
Mycoplasma Mycoplasma salivarium 25 (<0.09%)
Neisseria Neisseria pharyngis 342 (0.3%)
Nymphaea Nymphaea alba 1030 (0.9%)
Parabacteroides Parabacteroides 109 (0.09%)
goldsteinii
Parvimonas Parvimonas micras 3149 (3%)
Peptostreptococcus Peptostreptococcus 343 (0.3%)
anaerobius
Porphyromonas Porphyromonas 59 (0.09%)
gingivalis
Porphyromonas 4982 (4%)
catoniae
Porphyromonas 1500 (1%)
endodontalis
Prevotella Prevotella buccae 7498 (7%)
Prevotella copri 68 (0.09%)
Prevotella denticola 1765 (2%)
Prevotella enoeca 45 (0.09%)
Prevotella intermedia 1870 (2%)
Prevotella loescheii 183 (0.2%)
Prevotella maculosa 91 (0.09%)
Prevotella 4079 (4%)
melaninogenica
Prevotella multiformis 5 (<0.09%)
Prevotella nanceiensis 1521 (1%)
Prevotella nigrescens 1696 (1%)
Prevotella oris 4060 (4%)
Prevotella oulorum 284 (0.3%)
Prevotella pallens 277 (0.3%)
Prevotella pleuritidis 942 (0.8%)
Prevotella ruminicola 45 (0.09%)
Prevotella salivae 186 (0.2%)
Prevotella veroralis 836 (0.7%)
Robinsoniella Robinsoniella 4723 (4%)
peoriensis
Roseburia Roseburia cecicola 369 (0.3%)
Selenomonas Selenomonas lacticifex 118 (0.09%)
Selenomonas 736 (0.6%)
ruminantium
Streptococcus 923 (0.8%)
Streptococcus 922 (0.8%)
intermedius
Streptococcus mitis 1516 (1%)
Streptococcus 171 (0.2%)
thermophilus
Tannerella Tannerella forsythia 1398 (1%)
Treponema Treponema 185 (0.2%)
lecithinolyticum
Treponema 1146 (1%)
maltophilum
Treponema medium 79 (0.09%)
uncultured alpha proteobacterium 39 (<0.09%)
uncultured bacterium 19,265 (17%)

Please cite this article in press as: Riba-Terés N, et al. Microbiota of alveolar osteitis after permanent tooth extractions: A systematic
review. J Stomatol Oral Maxillofac Surg (2020), https://doi.org/10.1016/j.jormas.2020.08.007
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Table 3 (Continued )

Author (year), Design No. patients (No. Method Genus (strains) Species Abundance %
country dry sockets)

uncultured beta proteobacterium 113 (0.09%)

uncultured Kingella sp. 750 (0.7%)
Unidentified 78 (0.09%)
unidentified proteobacterium 10 (<0.09%)
Veillonella Veillonella dispar 3368 (3%)
Veillonella rogosae 1460 (1%)
Soni et al. (20) Case series 47 (47) Culture media (Nutrient Enterococcus 7.4%
(2016), India agar, Blood agar, Staphylococcus Staphylococcus aureus 29.6%
MacConkey agar) Streptococcus 51.8%
Streptococcus + Staphylococcus Staphylococcus 11.1%
aureus + Streptococcus
viridans
Kiewlicz et al. (21) Case series 70 (70) Culture media (Tryptone Actinomyces (22)
(2004), Poland soya agar) Bacteroides (26)
Bifidobacterium (1)
Clostridium (2)
Eubacterium (6)
Fusobacterium (22)
Leptotrichia (3)
Mitsuokella (1)
Peptococcus (6)
Peptostreptococcus (50)
Porphyromonas (13)
Prevotella (48)
Propionibacterium (26)
Selenomonas (3)
Tissierella (1)
Veillonella (10)

Table 4
Most commonly identified bacteria in alveolar osteitis (%). The highlighted bacteria (in bold) have been identified in two or more studies.

Shen et al. [14] Aguilar-Durán et al. [1] Soni et al. [20] Kiewlicz et al. [21]

Prevotella (24%) Prevotella (23.95%) Streptococcus (51.8%) Peptostreptococcus

Fusobacterium (16%) Fusobacterium (6.59%) Prevotella
Bacteroides
Parvimonas (7%) Porphyromonas (5.09%) Staphylococcus aureus (29.6%) Propionibacterium
Fusobacterium
Peptostreptococcus Parvimonas (3%) Actinomyces

3.5. Culture media 4. Discussion

Considering the studies that used culture media to describe the
microbial profile of the wounds, a total of 117 samples from
117 patients diagnosed with AO after tooth extraction were
analyzed.
The study published by Soni et al. [20] included 47 patients with
AO, and S. aureus was found to be present in 29.6% of the patients,
Streptococcus in 51.8%, and Enterococcus in 7.4% of patients (Table
3).
Kiewlicz et al. [21] found the most common genera in AO to be
Peptostreptococcus, Prevotella, Bacteroides, Propionibacterium, Fuso-
bacterium and Actinomyces (Table 4). These authors [21] also
determined the susceptibility to antibiotics and chemotherapeutic
agents of the identified anaerobic bacteria present in AO samples of
70 patients. A total of 241 strains of anaerobic bacteria were
isolated from the swabs taken from AO sockets (Table 3). These
were characterized by high susceptibility to amoxicillin –
clavulanic acid, ampicillin with sulbactam, metronidazole, tinida-
zole and clindamycin. The anaerobes were less susceptible to
penicillin G, erythromycin and to most examined cephalosporins
(except strains from the genus Veillonella). Bacteroides strains were
frequently resistant to most of the tested antibacterial agents.
Based on the results obtained, the microbiota found in AO sites
differed considerably from that found in sockets with uneventful
healing. These observations do not allow us to rule out a possible
infectious etiology of dry socket, since bacteria may play an
important role in this disease condition.
The two studies that included a control group highlighted
that AO patients seem to have a specific microbiota. Also, three
of the included papers agreed that the most common bacteria
in dry sockets were Prevotella and Fusobacterium. These
findings are interesting, since these same bacteria are common
in third molars with pericoronitis – a well-established risk
factor for AO [11]. Parvimonas and Peptostreptococcus were also
mentioned in two of these studies as common microorganisms
(Table 4). Furthermore, Prevotella and Fusobacterium showed a
relatively high abundance at the affected sites in comparison
with normal healing sockets, which suggests that these
bacteria are likely to be associated with the onset or evolution
of AO. Likewise, Peptostreptococcus and Prevotella have been
cultured from blood samples of extraction sockets, suggesting
that these bacteria might colonize the socket wall and blood
clot in an early stage [22].

Please cite this article in press as: Riba-Terés N, et al. Microbiota of alveolar osteitis after permanent tooth extractions: A systematic
review. J Stomatol Oral Maxillofac Surg (2020), https://doi.org/10.1016/j.jormas.2020.08.007
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Table 5
Pathogens overrepresented in alveolar osteitis compared with the controls. The
highlighted bacteria (in bold) have been identified in both studies.
Shen et al. [14] Aguilar-Durán et al. [1]
Atopobium Butyrivibrio hungatei
Dialister Dialister pneumosintes
Filifactor Fusobacterium nucleatum
Fusobacterium Parviromas micra
Johnsonella Peptostreptococcus anaerobius
Oribacterium Prevotella intermedia
Parvimonas Prevotella melaninogenica
Peptostreptococcus Prevotella nigrescens
Prevotella Streptococcus intermedius
Slackia Streptococcus mitis
Solobacterium Veillonella rogosae
Next-generation sequencing of 16S rRNA allows the identifica-
tion of a huge number of bacteria that may remain unnoticed if
other methods are used. Since these techniques are recent, many
studies published in the past used culture media to identify the
microbiota of the wounds. This obviously results in a significant
difference with respect to the number of bacteria reported in the
most recent papers. Moreover, most of the microorganisms
identified in the AO samples were not found in the Human Oral
Microbiome Database [23] or the CORE Microbiome [24].
It is important to evaluate the role of these bacteria as a part of a
much more complex structure called oral biofilm. Generally, a
surface exposed to the oral cavity is covered by a layer of proteins,
enzymes and hydrophobic molecules. This layer allows the
attachment and development of initial colonizers which are
generally facultative grampositive cocci such as Streptococcus mitis,
Streptococcus sanguis or Streptococcus oralis [25]. The subsequent
attachment of bacteria with different properties eventually leads
to the formation of a mature biofilm in which pathological bacteria
are present [25]. It is important to stress that a bacterium included
in a biofilm expresses a different phenotype in comparison with its
planktonic state [26]. Thus, bacteria that develop in a biofilm have
more efficient metabolism, are more resistant to antimicrobial
agents, and have a more pathogenic behavior [27]. This aspect
must be taken into account when interpreting the most commonly
found microorganisms in the included studies (i.e., Prevotella,
Fusobacterium, Parvimonas and Peptostreptococcus).
Increased fibrinolytic activity can result in premature loss of the
intra-alveolar blood clot after extraction. Direct (physiological
substances such as tissue plasminogen activator) or indirect (non-
physiological substances such as streptokinase and staphylokinase
produced by bacteria) activation of the plasminogen pathway
leads to the formation of plasmin, which disintegrates the clot and
produce hyperalgesia – potentially providing an explanation for
the pain experienced by patients suffering from AO [28].
Most authors support the view that AO is associated with a
fibrinolytic process that leaves the bony walls of the socket
exposed to the oral cavity [1]. However, it should be taken into
account that this fibrinolytic activity can be induced by bacteria
[7]. Indeed, Streptococcus pyogenes and Fusobacterium may facili-
tate the activation of fibrinolytic activity [12,29]. Interestingly,
Leuconostoc mesenteroides found by Aguilar-Duran et al. in AO
samples is employed by pharmaceutical and chemical companies
due to its anticoagulant properties [30].
Moreover, AO has been observed after dental extractions in
patients with poor oral hygiene and previous plaque accumulation,
and several studies have shown a significant increase in
postoperative pain in these patients. Moreover, both topical and
systemic antibiotics and antiseptics significantly reduce the
occurrence of this complication [1,31–34]. All these factors, added
Please cite this article in press as: Riba-Terés N, et al. Microbiota of alveolar osteitis after permanent tooth extractions: A systematic
review. J Stomatol Oral Maxillofac Surg (2020), https://doi.org/10.1016/j.jormas.2020.08.007
to the fibrinolytic activity of some bacteria, underscore that
additional studies are needed to clarify this possible infectious
etiology.
In 1973, Birn [6] postulated that AO develops as a result of a
localized infection of the socket that could lead to a complete
absence of the blood clot or to the lysis of an initial clot. Nitzan [8,9]
in turn implicated bacteria as the causal agents of AO, even though
the condition does not manifest with all the typical features of
bacterial infections. In this same sense, Serrati et al. [35] reported
that bacteria or debris might stimulate monocytes/macrophages to
release cytokines, which can provoke an up-regulation of
urokinase-type plasminogen activator (uPA) and plasminogen
activator inhibitor 1 (PAI-1), leading to clot lysis. In addition,
Peptostreptococcus can activate plasmin and proteolytic capacity,
inducing intracellular signaling pathways that lead to an increased
production of proinflammatory cytokines, chemokines and MMP-9
by macrophages [36,37]. These effects might be more intense in
mixed infections of Peptostreptococcus and Prevotella [38].
Finally, if future research confirms that AO is an infection
caused by bacteria, prevention and treatment guidelines should be
changed and the prescription of antibiotics and antiseptics might
be especially useful in high-risk patients. In fact, there are already
several papers that seem to support the administration of both
antibiotics (topic and systemic) and antiseptics in order to reduce
the incidence of AO [31,39]. Ren and Malmstrom’s meta-analysis
[31] showed that pre-operative systemic antibiotics such as
amoxicillin and metronidazole were effective in reducing the
occurrence of AO after mandibular third molar removal [31]. On
the other hand, antiseptics like chlorhexidine and topical anti-
biotics (i.e. tetracycline) have also been pointed out as useful
prophylactic agents [39]. Finally, mechanical debridement of the
wound and irrigation with saline before suturing the flap might
also be beneficial.
The present review has some relevant limitations. Firstly, only
four studies were included, two of which had no control group. On
the other hand, different microbiological methods were employed
in the analyzed papers, which complicates the comparison of
results. Still, we believe this review is of great interest to
researchers and clinicians, since it stresses the need to perform
studies with larger samples and with a control group using next-
generation sequencing techniques to confirm the role of the
microbiota in the etiology of AO.
5. Conclusions
The most commonly identified bacteria in alveolar osteitis
sockets after dental extractions are Prevotella, Fusobacterium,
Parvimonas and Peptostreptococcus. The microbiota of patients who
develop alveolar osteitis after dental extractions seems to be
different from that of patients without postoperative complica-
tions, so bacteria may play an important role in the pathogenesis of
alveolar osteitis. If these findings are confirmed in future research,
prevention and treatment strategies for alveolar osteitis will have
to be reassessed.
Sources of funding and disclosure of conflicts of interests
None of the authors have any relevant financial relationship(s)
with this study.
- The authors Nina Riba-Terés, Adrià Jorba-Garcı́a, Jorge Toledano-
Serrabona and Laura Aguilar-Durán have received no grants,
personal fees or non-financial support.
- Prof. Dr. Rui Figueiredo reports grants, personal fees, and non-
financial support from MozoGrau (Valladolid, Spain) and
G Model
JORMAS-903; No. of Pages 9
N. Riba-Terés et al. / J Stomatol Oral Maxillofac Surg xxx (2020) xxx–xxx
Avinent (Santpedor, Spain), grants from Mundipharma Research
(Cambridge, UK), and personal fees from BioHorizons Ibérica
(Madrid, Spain), Inibsa Dental (Lliçà de Vall, Spain), Dentsply
implants Iberia (Barcelona, Spain), and Araguaney Dental
(Barcelona, Spain) outside the submitted work.
- Prof. Dr. Eduard Valmaseda-Castellón reports grants, personal
fees, and non-financial support from MozoGrau (Valladolid,
Spain) and Avinent (Santpedor, Spain), and personal fees from
BioHorizons Ibérica (Madrid, Spain), Inibsa Dental (Lliçà de Vall,
Spain) and Dentsply implants Iberia (Barcelona, Spain) outside
the submitted work.
Acknowledgments
This study has been carried out by the Odontologic and
Maxillofacial Pathology and Therapy research group of the
Bellvitge Biomedical Investigation Institute (Idibell), Barcelona
(Spain).
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