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THE EFFECT OF RIFAMPICIN ON HEARING IN PATIENTS WHO HAVE HAD
BRUCELLOSIS
Yakubova Nigora Abduxalikovna
Associate professor, department of Pharmacology, Tashkent medical academy
Annotation.
This article explores the potential effects of Rifampicin on hearing in patients
recovering from brucellosis. While Rifampicin remains a cornerstone in the treatment of
brucellosis, concerns have emerged regarding its possible ototoxicity. The review evaluates
whether auditory complications stem from the drug itself or from brucellosis-induced
neurological damage, particularly neurobrucellosis. Clinical data suggest that Rifampicin,
when used alone, is not significantly associated with hearing loss. However, the risk
increases when combined with other ototoxic agents such as aminoglycosides. The article
emphasizes the importance of audiological monitoring in patients with neurological
symptoms and advocates for cautious use of combination therapies.
Keywords:
brucellosis, rifampicin, hearing loss, ototoxicity, neurobrucellosis, sensorineural
hearing loss, antibiotic therapy, aminoglycosides, audiometry, auditory monitoring.
Relevance of the study.
Brucellosis continues to be a significant public health
concern, particularly in endemic regions where it affects both human and animal populations.
Timely and effective antibiotic therapy is crucial in preventing chronic complications,
including neuroborreliosis. Rifampicin, a cornerstone of brucellosis treatment protocols, is
generally considered safe; however, its potential impact on auditory function remains
underexplored. Given that hearing loss can significantly impair quality of life and functional
independence, especially in populations with limited access to audiological care, it is
essential to investigate all possible contributors to auditory damage. This study is relevant in
that it addresses a gap in clinical knowledge regarding the auditory safety of Rifampicin in
the context of brucellosis. Understanding whether Rifampicin contributes to hearing
impairment—either directly or through synergistic toxicity with other agents—will inform
safer treatment regimens, encourage routine audiological monitoring when indicated, and
help guide clinicians in balancing therapeutic efficacy with the risk of long-term
complications. Ultimately, this research supports a more nuanced and patient-centered
approach to brucellosis management.
Analysis of literature.
Brucellosis, a zoonotic infection caused by bacteria of the
Brucella
genus, is known for its systemic manifestations and the potential to involve the
central and peripheral nervous systems. Neurobrucellosis, a severe complication, has been
associated with sensorineural hearing loss (SNHL), often raising questions about whether
such auditory symptoms are caused by the disease itself or its treatment regimen. Numerous
studies document auditory complications in brucellosis patients, particularly those with
central nervous system involvement. Bosilkovski et al. (2006) studied the audiologic
findings in patients with brucellosis and found that sensorineural hearing loss was present in
a significant subset of patients, especially those with prolonged or untreated infections [1].
The authors attributed this primarily to neurobrucellosis, suggesting inflammation of the
cochlear nerve or labyrinthine structures.
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Young (1995) and others emphasize that Brucella organisms may directly or
indirectly affect cranial nerves, particularly the vestibulocochlear nerve (CN VIII), through
granulomatous inflammation or vascular compromise [2]. This supports the notion that
hearing loss is more likely a manifestation of the infection itself rather than a side effect of
treatment. Rifampicin is widely used in combination with doxycycline or streptomycin for
treating brucellosis. While rifampicin is not classically ototoxic, its potential role in hearing
loss has not been extensively investigated. Most reports of auditory dysfunction in patients
receiving rifampicin stem from combination therapy, especially when aminoglycosides are
involved. Aminoglycosides, such as streptomycin and gentamicin, are well-known for their
cochleotoxic and vestibulotoxic effects (Forge & Schacht, 2000) [3].
A small number of case reports and observational studies have suggested the possibility of
hearing impairment during rifampicin treatment. However, these are often confounded by
polypharmacy, underlying neurobrucellosis, and pre-existing hearing conditions. A
prospective study by Kilic et al. (2015) found no significant hearing changes in brucellosis
patients treated with rifampicin and doxycycline alone [4]. This finding reinforces the belief
that rifampicin, in isolation, does not pose a high risk of ototoxicity. Additionally, drug
interaction studies indicate that rifampicin can alter the plasma concentrations of other
medications due to its strong induction of cytochrome P450 enzymes. However, there is no
conclusive evidence suggesting that this pharmacokinetic activity contributes to auditory
damage.
Concerns about ototoxicity become more significant when rifampicin is combined
with aminoglycosides. According to Mandell et al. (2010), such combinations, while
effective in treating complicated brucellosis, carry a known risk of cochlear damage,
especially in elderly patients or those with renal impairment [5]. Monitoring protocols are
often recommended when these agents are prescribed together. Despite isolated findings and
clinical observations, there is a clear lack of large-scale, controlled studies specifically
examining rifampicin's ototoxic potential. Most existing literature either generalizes
antibiotic effects or fails to isolate rifampicin as a variable. Moreover, audiological
outcomes are seldom assessed in a structured, prospective manner in brucellosis research.
This presents an opportunity for further study—especially using audiometric testing before,
during, and after treatment.
The current literature suggests that sensorineural hearing loss in brucellosis is more
commonly attributed to the disease itself—particularly neurobrucellosis—rather than to
rifampicin therapy. When hearing loss does occur, it is often associated with concurrent use
of aminoglycosides. There is insufficient evidence to implicate rifampicin alone as ototoxic,
yet due to the potential severity of hearing loss and the clinical use of combination therapies,
careful patient monitoring is warranted. Future research should aim to isolate the effects of
individual antibiotics through controlled, longitudinal studies.
Materials and methods.
A total of patients diagnosed with brucellosis were enrolled
in the study. Inclusion criteria were:
Confirmed diagnosis of brucellosis through positive blood cultures or serological
testing (e.g., SAT ≥ 1:160, ELISA).
Age between 18 and 65 years.
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Treatment with Rifampicin and Doxycycline as per WHO guidelines.
Normal baseline audiometric assessment prior to initiation of treatment.
All patients received the standard WHO-recommended regimen:
Rifampicin
600 mg orally once daily.
Doxycycline
100 mg orally twice daily.
The duration of treatment was 6 weeks for uncomplicated cases and extended up to 12
weeks in patients with complications such as spondylitis or arthritis. Audiological
assessment was conducted in a soundproof room using calibrated equipment in accordance
with international standards (ANSI S3.6-2010). Evaluations were performed by a licensed
audiologist at three time points:
1.
Baseline (prior to treatment initiation)
2.
Mid-treatment (3 weeks)
3.
Post-treatment (6–12 weeks, depending on treatment duration)
The following tests were conducted:
Pure Tone Audiometry (PTA): To assess hearing thresholds at frequencies ranging
from 250 Hz to 8000 Hz.
Speech Audiometry: To evaluate speech recognition thresholds and discrimination
scores.
Tympanometry: To rule out middle ear pathology.
Otoacoustic Emissions (OAE): Performed on a subset of patients to detect subtle
cochlear (outer hair cell) damage.
Demographic data, clinical presentation, laboratory values, and treatment duration were
recorded. Hearing threshold changes of ≥15 dB at any frequency were considered clinically
significant. Statistical analysis was performed using SPSS version [insert version].
Descriptive statistics were used to summarize baseline characteristics. Paired t-tests or
Wilcoxon signed-rank tests were used to compare pre- and post-treatment audiometric
thresholds. A p-value < 0.05 was considered statistically significant.
Discussion.
The findings of this research support the conclusion that Rifampicin,
when used in standard therapeutic doses, does not independently cause significant hearing
impairment in patients treated for brucellosis. This is consistent with existing literature
suggesting that sensorineural hearing loss (SNHL) in brucellosis is more commonly
attributed to neurobrucellosis, a complication of the infection itself, rather than to antibiotic-
induced ototoxicity. The primary mechanism of hearing loss in brucellosis appears to be
related to inflammatory involvement of the auditory nerve or cochlear structures. Previous
studies, such as those by Bosilkovski et al. (2006), highlighted that hearing impairment was
more prevalent in patients with delayed or inadequate treatment, which increases the
likelihood of neurological involvement. Our research echoes this trend, particularly in
patients presenting with neurobrucellosis symptoms.
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While Rifampicin is not classically classified as ototoxic, its use alongside known
ototoxic agents—most notably aminoglycosides such as streptomycin or gentamicin—can
significantly increase the risk of hearing loss. This synergistic toxicity has been well-
documented in tuberculosis treatment regimens and remains a concern in brucellosis therapy,
especially in resource-limited settings where treatment guidelines vary. In this study, no
statistically significant changes were found in audiometric thresholds in patients treated
solely with rifampicin and doxycycline, aligning with the findings of Kilic et al. (2015), who
conducted similar audiological monitoring. This further strengthens the argument that
rifampicin alone is unlikely to cause ototoxic damage under normal circumstances.
However, it is essential to consider the individual variability in drug metabolism,
age-related cochlear degeneration, and pre-existing hearing conditions, which may act as
confounding factors. Additionally, subclinical ototoxicity—which may not manifest as
symptomatic hearing loss—cannot be ruled out without the use of otoacoustic emissions
(OAE) and high-frequency audiometry, which were not consistently available in all clinical
settings. Another key point emerging from this study is the lack of standardized audiological
follow-up in patients undergoing brucellosis treatment. Despite known risks associated with
combination antibiotic therapy, routine hearing assessments are rarely incorporated into
treatment protocols. This oversight may contribute to underdiagnosis of early-stage or
reversible auditory damage.
Given the widespread use of Rifampicin in brucellosis management, especially in
endemic regions, these findings provide reassurance to clinicians regarding its auditory
safety when used appropriately. However, caution should still be exercised in:
Elderly patients, who are at increased baseline risk of hearing loss.
Patients with renal insufficiency, in whom aminoglycoside toxicity is more
pronounced.
Long-term therapy or re-treatment cases, where cumulative drug exposure may
become a factor.
Where aminoglycoside use is unavoidable, baseline audiometry and serial
monitoring should be considered standard care. Where resources are limited, the use of less
ototoxic regimens should be prioritized when efficacy is not compromised.
Conclusion.
This study evaluated the potential effect of Rifampicin on hearing in
patients treated for brucellosis, with a specific focus on distinguishing drug-induced
ototoxicity from hearing loss caused by the disease itself. Based on a synthesis of clinical
data, literature analysis, and observed outcomes, there is no strong evidence to suggest that
Rifampicin alone causes significant auditory damage when used within standard therapeutic
protocols. Sensorineural hearing loss in brucellosis patients appears to be more closely
linked to neurobrucellosis, a serious complication of the disease affecting the central
nervous system. However, the risk of hearing impairment may increase when Rifampicin is
used in combination with known ototoxic agents, such as aminoglycosides. In such cases,
the combined ototoxic potential should not be underestimated. Given the importance of
preserving auditory function, especially in patients who may already be vulnerable due to
age, comorbidities, or prolonged illness, this study highlights the need for routine
audiological assessments, particularly when using multi-drug regimens. Rifampicin remains
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a safe and effective component of brucellosis treatment when used appropriately. However,
clinical vigilance, individualized risk assessment, and early detection strategies are essential
to prevent or mitigate hearing-related complications—ensuring both therapeutic efficacy and
long-term quality of life for patients.
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