PERSPECTIVES

J Oral Maxillofac Surg

74:1512-1513, 2016

Dental Care Professionals Should Avoid

the Administration of Amoxicillin in
Healthy Patients During Third Molar
Surgery: Is Antibiotic Resistence the
Only Problem?
Othoniel H. Aragon-Martinez, PhD,* Mario A. Isiordia-Espinoza, DDS, PhD,y
Francisco J. Tejeda Nava, DDS, MSc,z and Saray Aranda Romo, DDS, PhDx
The mouth contains over 200 different bacterial species; consequently, invasive oral procedures may produce local or distant infections. Local infections are
commonly caused by several types of bacteria
including periodontal pathogens (Treponema), anaerobic gram-negative bacteria (Prevotella spp and Fusobacterium spp), and aerobic gram-positive organisms
(viridans streptococci), whereas distant complications
are usually produced by gram-positive bacteria such as
viridans streptococci. The onset of distal complications depends on the bacterial load, duration of
bacteremia, type of bacteria, and predisposition of
the patient. However, a healthy immune system has
the capacity for the bacterial eradication from the
bloodstream.1
In this direction, the use of a b-lactam antibiotic such
as amoxicillin for third molar surgery is a common
practice of oral care professionals to prevent infections. Amoxicillin dosages are from 1 to 2 g before
the operation or 500 mg every 8 hours during a 5- to
7-day period postoperatively. However, the information obtained from high-quality clinical trials has
shown that amoxicillin is not effective to reduce the
risk of wound infections supported by an overall
odds ratio of 0.26 with a 95% confidence interval of
0.06 to 1.17 and probability of 0.08 alongside inadequate values for the absolute risk reduction and number needed to treat. Similar results were obtained

from the individual analyses of preoperative and postoperative amoxicillin data.2 The inactivation of amoxicillin is the most plausible cause for the therapeutic
failure because gram-negative organisms in the oral
wound produce b-lactamases.1
Recent evidence has shown that the administration
of 250 mg of amoxicillin in healthy volunteers every
8 hours for 7 days produces an important incidence
of antibiotic resistancerelated genes in the intestinal
metagenome after the treatment course whereas the
saliva metagenome remains stable. The amoxicillin
exposure modifies 14% of the Kyoto Encyclopedia of
Genes and Genomes (KEGG) orthologous groups in
feces; however, this difference is lost in the first
month. The gene load is increased, exhibiting a
pattern of protection against antibiotics, which
include genes for b-lactamases, efflux pumps, and
other enzymes. This transient disturbance by amoxicillin may contribute to the spread of antibiotic resistance.3 Consequently, unnecessary antibiotic use
promotes bacterial resistance, and the human microbiome exposed extensively to antimicrobials has
become a significant reservoir of resistance genes.4
The development of microbial resistance to antibiotics
is reported commonly to justify the disuse of antimicrobial agents in oral and maxillofacial surgery, but
dental care professionals should take into account dysbiosis, which is another major health problem.

*Research Assistant, Department of Pharmacology, School of

Address correspondence and reprint requests to Dr Aranda: Fac-

Medicine, University of San Luis Potos, San Luis Potos, Mexico.

yProfessor, Department of Pharmacology, School of Dentistry,

ultad de Estomatologa, Universidad Aut

onoma de San Luis Potos,
Manuel Nava No. 2, Col Universitaria, San Luis Potos, SLP 78290,

University of Baja California, Mexicali, Mexico.

Mexico; e-mail: sarayaranda@fest.uaslp.mx

zProfessor, Diagnostic Clinic, Dentistry School, University of San

Luis Potos, San Luis Potos, Mexico.
xDepartment

Head, Diagnostic

2016 American Association of Oral and Maxillofacial Surgeons

0278-2391/16/30126-4

Clinic,

Dentistry

School,

http://dx.doi.org/10.1016/j.joms.2016.04.026

University of San Luis Potos, San Luis Potos, Mexico.

1512

1513

ARAGON-MARTINEZ ET AL

Dysbiosis is a detrimental modification in the

composition of the microbiome alongside altered
microflora functions, which can be produced by antibiotic exposure, type of diet, lifestyle habits, and other
factors. In this way, amoxicillin administration
(500 mg every 8 hours for 5 days) in healthy volunteers
causes marked alterations in the dominant profile of
fecal microbiota within the treatment course, returning to the original profile within 60 days. The evaluations of dominant species diversity using the V6 to
V8 regions of 16S rRNA genes have ranges of similarity
compared with the original profile from 93.2 to 99.1%,
from 76.2 to 98.1%, from 62.1 to 82%, from 46.2 to
94.8%, from 65.6 to 95.5%, and from 66.4 to 98.1%
on days 1, 2, 3, 4, 30, and 60, respectively.5 In this
manner, important alterations with a similarity coefficient of less than 70% may persist for at least 2 months.
Dysbiosis in the short- and long-term can produce
harmful changes in health, including the accumulation
of antimicrobial resistances as mentioned in prior lines
for amoxicillin, increased susceptibility to infectious
diseases, altered immune homeostasis, and deregulated metabolism.4 For example, the administration
of 750 mg of amoxicillin every 8 hours during a
7-day period in patients after third molar extraction
may produce a delayed onset of local infection. This
infection appears between 16 and 79 days after the
extraction. Fusobacterium sp and Prevotella sp are
commonly implicated in this type of infection and
these bacteria have a resistance profile to amoxicillin.2
Thus this information suggests that prior amoxicillin
exposure may predispose the oral microbiome to
establish a delayed-onset infection.
In addition, the use of amoxicillin has been associated with increased incidences of asthma and rash in
infants and toddlers, which are likely related to gut dysbiosis. Moreover, b-lactams increase the rate of sugar
metabolism via high activation of glycolysis and
pentose phosphate reactions alongside unbalanced
hydrolytic capacity for sugars in the gastrointestinal
tract, promoting digestion and energy extraction
from dietary carbohydrates and fermentation of their

final metabolites. All these are major factors contributing to underlying mechanisms for unhealthy conditions, such as metabolic syndrome and obesity.4
Moreover, the use of amoxicillin in adult patients during dental surgery may produce diarrhea, gastric pain,
and nausea.2 These adverse events might be linked to
dysbiosis because the intestinal microbiota composition is related to disorders involving the processes of
inflammation and autoimmunity.4 As discussed earlier,
the present information suggests that intestinal and
oral microbiota changes under the amoxicillin exposure, returning to the original species profile within
2 months; however, these microflora modifications
may continue for a prolonged period in some patients,
increasing the risk of the establishment of dysbiosisrelated diseases.
In our opinion, the use of amoxicillin has no scientific evidence of benefit in preventing a local infection
during third molar surgery, whereas this antibiotic
exposure may produce deleterious effects, such as
dysbiosis-related diseases and potential infections
with resistance pathogens, in the healthy patient.
Therefore, amoxicillin therapy is not justified for this
type of oral surgery.

References
1. Maestre Vera JR, G
omez-Lus Centelles ML: Antimicrobial prophylaxis in oral surgery and dental procedures. Med Oral Patol Oral
Cir Bucal 12:E44, 2007
2. Isiordia-Espinoza MA, Aragon-Martinez OH, Martnez-Morales JF,
et al: Risk of wound infection and safety profile of amoxicillin
in healthy patients which required third molar surgery: A systematic review and meta-analysis. Br J Oral Maxillofac Surg 53:796,
2015
3. Zaura E, Brandt BW, Teixeira de Mattos MJ, et al: Same exposure
but two radically different responses to antibiotics: Resilience
of the salivary microbiome versus long-term microbial shifts in
feces. MBio 6:e01693, 2015
4. Francino MP: Antibiotics and the human gut microbiome: Dysbioses and accumulation of resistances. Front Microbiol 6:1543,
2016
5. De La Cochetiere MF, Durand T, Lepage P, et al: Resilience of the
dominant human fecal microbiota upon short-course antibiotic
challenge. J Clin Microbiol 43:5588, 2005