88 J Gandhara Med Dent Sci
October - December 2025
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ORIGINAL ARTICLE
DELAYED CLINICAL RESPONSE OF DEEP FACIAL INFECTIONS DUE TO PRIOR
UNREGULATED ANTIBIOTICS USE ASSESSED BY CRP LEVELS IN A TERTIARY CARE
HOSPITAL
Nuzhat Rahil1, Sana Wazir2, Amina Ifthekhar3, Ashwina Rahil4
ABSTRACT
OBJECTIVES
This study aimed to assess the efficacy of serum CRP levels as monitoring
tools for patients with fascial space infections who had a delayed clinical
response to initial treatment, as per guidelines, due to prior unregulated
antibiotics.
METHODOLOGY
This case series study was conducted at Lady Reading Hospital’s
Department of Oral and Maxillofacial Surgery and Ophthalmology from
January 2024 to March 2025, with ethics approval and informed consent
obtained from 35 participants with fascial space infections requiring
hospitalization and prior antibiotic use. Those with recurrent infections,
trauma, or chronic conditions were excluded. Diagnosis involved a
comprehensive history, clinical examination, and imaging studies (OPG for
odontogenic infections and CT for non-odontogenic infections). Infection
severity was tracked through C-reactive protein (CRP) levels measured at
admission, day three, and discharge. Initial treatment followed clinical
guidelines, utilizing first-line antibiotics and incision and drainage. If CRP
levels did not decrease, the antibiotic regimen was adjusted, leading to
improved outcomes. Data were analyzed using SPSS.
RESULTS
The most commonly involved space was the submandibular space (31%),
followed by unilateral and bilateral submandibular, sublingual, and
submental spaces (20%). Orbital cellulitis was observed in 17% of patients.
When asked about the prior unregulated use of antibiotics, 65.7% of patients
admitted to having used them. The Mean CRP on the day of admission was
15.46 mg/dl with a SD of 6.42. The follow-up means CRP on the 3rd day of
admission was 15.17mg/dl with SD 9.77, showing a poor response to initial
treatment in 54.3% of the patients. The mean CRP on the day of discharge
and after the change of antibiotic was markedly reduced, with a mean of
3.2mg/dl and SD of 3.7, showing resolution of infection.
CONCLUSION
Delays in infection resolution lead to longer hospital stays and increased
antibiotic resistance. Urgent action is needed to establish national antibiotic
programs, implement public awareness campaigns, and enforce stricter
regulations on antibiotic use to improve outcomes and reduce antibiotic
resistance.
KEYWORDS: Antibiotics, Infection, Facial Spaces, CRP , Clinical Response
How to cite this article
Rahil N, Wazir S, Ifthekhar A, Rahil
A. Delayed Clinical Response of Deep
Facial Infections Due to Prior
Unregulated Antibiotics Use Assessed
by Crp Levels in A Tertiary Care
Hospital. J Gandhara Med Dent Sci.
2025;12(4):88-92.https://doi.org/10.37760
Date of Submission: 26-05-2025
Date Revised: 20-09-2025
Date Acceptance: 24-09-2025
1Assistant Professor/Chairperson,
Department of Ophthalmology, MTI
Lady
3Trainee Medical Officer, Oral and
Maxillofacial Surgery, MTI Lady
Reading Hospital, Peshawar
4Trainee Medical Officer, Operative
Dentistry, MTI Lady Reading Hospital,
Peshawar
Correspondence
2Sana Wazir, Assistant Professor, Oral
and Maxillofacial Surgery, MTI Lady
Reading Hospital, Peshawar
+92-332-9059251
wazirkhansana@gmail.com
INTRODUCTION
Orofacial and neck infections, whether odontogenic or
non-odontogenic, can spread in unpredictable ways
because of the anatomical connectivity of potential
spaces. Potential spaces act as areas of least resistance
for the spread of infection.1 Due to the anatomical
relationships, these infections can range from minor,
locally confined infections to serious, organ and life-
threatening illnesses as they include the origin of the
upper airway and may extend to possible spaces created
by the lower head and upper cervical fascial planes,
such as the buccal, sublingual, submandibular,
temporal, masseteric, canine, and parapharyngeal,
which further exhibit fatal complications like
mediastinitis, cavernous sinus thrombosis, and brain
abscess if left untreated.2 Since these infections remain
the primary cause of morbidity and mortality,
maxillofacial surgeons continue to face significant
challenges despite significant improvements in health
services.3 Fever, swelling, trismus, pain, and, at a later
stage, dysphagia, dyspnea, and voice changes are part
/jgmds.12-4.734
89J Gandhara Med Dent Sci
October - December 2025
of the classic clinical presentation. This infection
quickly progresses from a localized to a deep neck-
space infection that compromises the airway.
Odontogenic infections can result in toxicity and
potentially fatal conditions such as respiratory distress,
reduced consciousness, meningitis, cavernous sinus
thrombosis, and impaired vision.1 Maxillofacial
infections are now far more severe than they were in the
past, necessitating early diagnosis and more aggressive
treatment. For early diagnosis and monitoring of
treatment response, we frequently use clinical
laboratory tests. The most widely used traditional
laboratory tests for identifying acute inflammation and
tracking the response to treatment are C-reactive
protein (CRP), erythrocyte sedimentation rate (ESR),
and white blood cell (WBC) counts.4 Only trace
amounts of C-reactive protein (CRP) are found in
healthy, normal people. It plays a role in the innate
immune system's processes of complement activation,
antigen clearance, and activation-mediated
phagocytosis. It is a good indicator of the degree of
tissue damage and inflammation, and the most effective
single screening test for an acute-phase reaction. Within
48 hours, the serum concentration peaks, first
surpassing 5 mg/l in 6 hours. Regardless of health or
illness, CRP has a plasma half-life of roughly 19 hours.
Consequently, the intensity of the pathological process,
which determines the plasma CRP concentration, is
directly reflected in the stimulus that causes the
secretion.5 Empirical antibiotics use and incision and
drainage are the main treatment options, but
understanding the microorganisms involved and their
sensitivity pattern is also crucial. Sometimes, despite
incision and drainage, antibiotic use, and other
treatments, the patient's condition remains unchanged.
This could be because the bacterial strains are resistant,
leading to the ineffective use of antibiotics. A broad
range of facultative anaerobes, including the
Streptococci viridians and Streptococcus anginosus
groups, as well as strict anaerobes, particularly
anaerobic cocci and species of Prevotella and
Fusobacterium, are present in the pathological process
of odontogenic infection. Gram-positive cocci and
strictly anaerobic gram-negative rods are the primary
isolates.6 Antibiotic misuse-recognized globally as a
major contributor to antimicrobial resistance-includes
practices such as self-medication, obtaining antibiotics
without a prescription, and poor adherence to treatment
regimens, such as skipping doses or not completing the
full course. Multiple factors contribute to these
behaviors, but organizations like the WHO emphasize
promoting responsible antibiotic use among patients as
a critical strategy to combat antimicrobial resistance.7
Deep facial infections are potentially life-threatening
and require timely recognition and management. In
many low- and middle-income countries, including
Pakistan, over-the-counter and unregulated antibiotic
use is common. Such indiscriminate exposure can mask
clinical signs, alter the local microbiological profile,
and delay the apparent clinical response to standard
therapy. C-reactive protein (CRP) is a sensitive
biomarker of inflammation and a valuable tool for
monitoring treatment response. Evaluating the pattern
of delayed clinical improvement in relation to prior
unsupervised antibiotic use and correlating it with CRP
levels can provide valuable insight into the impact of
inappropriate antibiotic practices. This case series
highlights the public health implications of antibiotic
misuse and underscores the need for strengthened
antibiotic stewardship and early, evidence-based
management protocols for deep facial infections in
resource-limited settings.
METHODOLOGY
This case series study was conducted in the Department
of Oral and Maxillofacial Surgery and Ophthalmology
at Lady Reading Hospital from January 2024 to March
2025. The study was initiated after obtaining approval
from the institutional ethics committee, with reference
number 219/LRH/MTI dated May 26, 2025, and written
informed consent was obtained from all participants. A
total of 35 patients, representing both genders and a
wide range of ages, ethnicities, and geographical
backgrounds, were included. All participants were
admitted with fascial space infections requiring hospital
management and had a history of prior antibiotic use
before presentation. Patients with recurrent infections,
infections secondary to trauma, or those with chronic
medical conditions were excluded. Diagnosis of a
fascial space infection was based on a detailed history,
including documentation of any previous unregulated
antibiotic use, and a comprehensive clinical
examination to assess signs of infection. For
odontogenic infections, the diagnosis was confirmed
with an orthopantomogram (OPG), while non-
odontogenic infections were evaluated using a CT scan.
The severity of the acute-phase infection was monitored
by serial measurements of C-reactive protein (CRP)
taken at three time points: admission, the third day of
hospitalization, and discharge. Initial treatment
followed standard clinical guidelines, including the use
of antibiotics and incision-and-drainage procedures
when indicated. First-line antibiotics included
amoxicillin with clavulanic acid or cephalosporins, in
combination with metronidazole. The response to the
initial antibiotic therapy was evaluated through serial
CRP measurements and clinical indicators of infection.
When CRP levels failed to decline and there was no
clinical improvement, the antibiotic regimen was
Delayed Clinical Response of Deep Facial Infections
90 J Gandhara Med Dent Sci
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modified. The alternative treatment proved effective, as
evidenced by a reduction in CRP levels and
improvement in clinical symptoms. All data were
recorded on a predesigned proforma. Statistical analysis
was carried out using SPSS software (version 25). To
begin with, the data distribution was checked for
normality by examining the skewness and kurtosis
values. Descriptive statistics were then applied:
'categorical variables, such as patients age groups and
gender, were summarized as frequencies and
percentages, while continuous (scale) variables were
expressed as means with their corresponding standard
deviations. To evaluate the effect of treatment, a paired
sample t-test was used to compare serial CRP levels,
specifically, the CRP measured on the third day after
the initial antibiotic therapy and the CRP level after the
antibiotic regimen was changed. A p-value of less than
0.05 was considered statistically significant.
Additionally, a bivariate correlation analysis was
conducted to investigate the relationship between the
CRP level at admission and the CRP level on the third
day of initial treatment. This analysis helped to assess
how well the patients were responding to the first
course of antibiotics given at admission.
RESULTS
A total of 35 patients with facial space infection were
enrolled in this prospective cross-sectional study. The
frequencies of females (51.4%) outnumber the males
(48.6%) by almost 3%. The mean age is 25.71 years ±
18.8 years, with a minimum of 4 years and a maximum
of 65 years, as the age bracket was open and not
defined by a specific number. The most commonly
involved space was the submandibular space (31%),
followed by unilateral and bilateral submandibular,
sublingual, and submental spaces (20%), as shown in
Table 1. Orbital cellulitis was observed in 17% of
patients (Figure 1). When asked about the prior
unregulated use of antibiotics, 65.7% of patients
admitted to having used them. The Mean CRP on the
day of admission was 15.46 mg/dl with a SD of 6.42.
After admission, the management guidelines were
followed, which include initial antibiotics
(Amoxicillin/cephalosporin and metronidazole) plus
incisional drainage where indicated. The follow-up
means CRP on the 3rd day of admission was 15.17mg/dl
with SD 9.77, showing a poor response to initial
treatment in 54.3% of the patients. Due to no response
to the initial treatment decision, a change in antibiotic
was made, as shown in Table No. 2. The mean CRP on
the day of discharge and after the change of antibiotic
was markedly reduced, with the mean of 3.2mg/dl and
SD of 3.7, showing resolution of infection. Inferential
statistical analysis using a paired sample t-test on serial
CRPs reveals that, with a 95% confidence interval, the
p-value is statistically significant (p < 0.001). On the
correlation analysis, the correlation coefficient was
(r=0.722). The p-value was statistically significant,
indicating that patients with a high level of CRP on
admission had a high CRP level after initial antibiotic
use, suggesting a lack of response to treatment due to
the unregulated use of antibiotics.
Figure: 1 Child presenting with severe left periorbital swelling
and necrotic changes consistent with advanced orbital cellulitis.
Table 1: Distribution of Anatomical Spaces Involved in Deep
Facial Infections
Space involved Frequency (n) %age
Orbital 06 17.1
Periorbital 03 8.6
Buccal 01 2.9
Submandibular 11 31.4
Unilateral 07 20.0
Bilateral 07 20.0
Percentages are based on the total sample of 35
patients.
Table 2: Frequency of Postoperative Complications
Complication Frequency
(n)
%age
Vancomycin and Metro 01 2.9
Meropenem and Metro 04 11.4
linezolid and Metro 11 31.4
Moxifloxacin and Metro 02 5.7
No change in the Antibiotic 17 48.6
Percentages are calculated from a total sample size of
35 patients.
Table 3: Comparing CRP on the Third Day of Admission with
Variable
Compared
Mean
Difference
(mg/L)
95% CI of
Difference
t (df =34)
P-
Value
CRP at Discharge
CRP (3rd day)
vs. CRP
(discharge)
11.89 ± 8.11
9.10 to
14.68
8.67 <0.001
Notes: Values are mean ± standard deviation unless
otherwise indicated. Paired-samples t-test shows a
(mg/L)
rdsignificant reduction in CRP between the 3 day and
discharge.
Delayed Clinical Response of Deep Facial Infections
91J Gandhara Med Dent Sci
October - December 2025
Table 4: Pearson correlation between CRP on admission and
CRP on the 3rd day of admission
Variables Pearson
Correlation (r)
P-value n
CRP on admission
vs. CRP on 3rd day
0.722 <0.001 35
Note: Pearson correlation shows a strong positive
association between CRP levels on admission and on
the 3rd day of admission. Correlation is significant at
the 0.01 level (two-tailed).
DISCUSSION
Fascial space infections of the maxillofacial region can
result in prolonged illness, leading to unpredictable
results and serious complications, even death, despite
the use of antibiotics.8 Inappropriate and unregulated
use of antibiotics is widespread in underdeveloped
countries like Pakistan, creating adverse clinical and
economic threats to the health of the patient.9 In our
study, 65.7% have used self-prescribed broad-
spectrum antibiotics due to the easy availability of over-
the-counter antibiotics, increasing antimicrobial
resistance (AMR). Misuse of antibiotics is the primary
factor contributing to antimicrobial resistance,
according to a study. Approximately 50% of global
antibiotics cannot be adequately justified.10 The
inappropriate use of antibiotics is evident through
multiple factors, one of which is the critical condition
of the patient when they present to the hospital.
Similarly, in our study, 54.3% of patients did not
respond to the initial treatment given according to the
guidelines, and their markers of infection remained
elevated despite antibiotic use. CRP is the primary
indicator of an acute phase reaction, with a short
lifespan of 5 to 6 hours, and can be used to diagnose
and monitor the response to treatment.11 According to a
study, the serum concentration of CRP increases up to
"000 fol" within a few hours of clinical presentation,
and it continues to increase if the clinical response to
treatment is poor.12 In our study, similar results were
observed, with a mean CRP level of 15.46 ± 6.42 on the
day of admission. Notably, this level did not decline, as
evidenced by the mean CRP on the 3rd day of
admission, which was 15.17 ± 9.77, indicating a poor
response in 54.3% of patients. A study conducted by G.
Mahesh et al. concluded that serum C-reactive protein
is an immediate effect of treatment in normal
circumstances and can be used as a monitoring tool for
deep fascial space infections.13 Due to the poor clinical
response to the first antibiotic in 54.3% of cases, as
indicated by the CRP level, due to resistance to the
recommended antibiotic, the decision was made to
switch to non-resistant and undocumented medications.
Another study reported that the rising rate of antibiotic
resistance is alarming.9 In our study, the most common
space involved was the submandibular space (31%),
followed by unilateral and bilateral submandibular,
submental, and sublingual spaces, at 20% and 17%,
respectively, with orbital cellulitis accounting for 20%.
Similar findings were observed in a local study, with
submandibular space involvement was 41.7% of the
cases.14 In another study, orbital cellulitis was found to
occur in 15% of pediatric patients, a rate similar to that
observed in your study.15 This study reveals that fascial
space infections are more prevalent in early childhood,
particularly among children under 10 years old, and
again in individuals in their fifth decade of life, a period
often associated with a reduced immune response.
Similar trends have been reported in other studies as
well.16,17,18 Antibiotic misuse-recognized globally as a
major contributor to antimicrobial resistance
encompasses practices such as self-medication,
obtaining antibiotics without a prescription, and poor
adherence to treatment regimens, including skipping
doses or not completing the full course. Multiple factors
contribute to these behaviors, but organizations like the
WHO emphasize promoting responsible antibiotic use
among patients as a critical strategy to combat
antimicrobial resistance.
LIMITATIONS
Our study has some limitations, including the data
being collected from a single tertiary care hospital,
which limits the generalizability of the findings to other
regions or healthcare settings. A small sample size of
only 35 patients, the study may lack the statistical
power to detect subtle associations or patterns.
Information regarding prior unregulated antibiotic use
was based on patient recall, which may introduce recall
bias or underreporting.
CONCLUSIONS
This study demonstrates that patients with deep fascial
space infections, as objectively determined by
persistently elevated C-reactive protein levels after
initial management, exhibit a delayed clinical response
due to prior use of unregulated and uncontrolled
antibiotics. In low- and middle-income countries like
Pakistan, the results highlighted the adverse effects of
self-medication and easy access and availability of
over-the-counter antibiotics, unlike in the West. Delays
in infection resolution not only result in more extended
hospital stays but also exacerbate antibiotic resistance.
To improve clinical outcomes and prevent the
development of resistance patterns in these vulnerable
settings, there is an urgent need for national antibiotic
dispensing programs, public awareness campaigns, and
robust regulations on antibiotic usage.
Delayed Clinical Response of Deep Facial Infections
92 J Gandhara Med Dent Sci
October - December 2025
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AUTHORS CONTRIBUTION
The authors accept responsibility for all aspects of the work
and will ensure that any concerns regarding the accuracy or
integrity of any part are properly investigated and resolved.
CONFLICT OF INTEREST: None
FUNDING SOURCES: None
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Nuzhat Rahil - Concept & Design; Data Acquisition; Data
Analysis/Interpretation; Drafting Manuscript; Critical
Revision; Final Approval
Sana Wazir - Concept & Design; Data Acquisition; Data
Analysis/Interpretation; Drafting Manuscript; Critical
Revision; Supervision; Final Approval
Amina Ifthekhar - Concept & Design; Data Acquisition; Data
Analysis/Interpretation; Drafting Manuscript; Final Approval
Ashwina Rahil - Concept & Design; Data Acquisition; Data
Analysis/Interpretation; Drafting Manuscript; Final Approval
Delayed Clinical Response of Deep Facial Infections