Audiologic Monitoring Mdr Tb

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BMC Ear, Nose and Throat
Disorders
Open Access
Research article
Audiologic monitoring of multi-drug resistant tuberculosis patients
on aminoglycoside treatment with long term follow-up
Prahlad Duggal*
1
and Malay Sarkar
2
Address:
1
Department of Otolaryngology, Dr. Rajinder Prasad Govt. Medical College, Tanda, Kangra, Himachal Pradesh, India and
2
Department
of Pulmonary Medicine, Dr. Rajinder Prasad Govt. Medical College, Tanda, Kangra, Himachal Pradesh, India
Email: Prahlad Duggal* - [email protected]; Malay Sarkar - [email protected]
* Corresponding author
Abstract
Background: Multi-drug resistant tuberculosis has emerged as a significant problem with the
resurfacing of tuberculosis and thus the need to use the second line drugs with the resultant
increased incidence of adverse effects. We discuss the effect of second line aminoglycoside anti-
tubercular drugs on the hearing status of MDR-TB patients.
Methods: Sixty four patients were put on second line aminoglycoside anti-TB drugs. These were
divided into three groups: group I, 34 patients using amikacin, group II, 26 patients using kanamycin
and group III, 4 patients using capreomycin.
Results: Of these, 18.75% of the patients developed sensorineural hearing loss involving higher
frequencies while 6.25% had involvement of speech frequencies also. All patients were seen again
approximately one year after aminoglycoside discontinuation and all hearing losses were
permanent with no threshold improvement.
Conclusion: Aminoglycosides used in MDR-TB patients may result in irreversible hearing loss
involving higher frequencies and can become a hearing handicap as speech frequencies are also
involved in some of the patients thus underlining the need for regular audiologic evaluation in
patients of MDR-TB during the treatment.
Background
Tuberculosis is one of the leading infectious diseases in
the world and is responsible for more than two million
deaths and nine million new cases annually [1]. Emer-
gence of resistance to drugs used to treat tuberculosis and
particularly multi-drug resistant (MDR-TB) has become
an obstacle to effective global TB control [2]. Incomplete
and inadequate treatment is the most important factor
leading to its development, suggesting that it is often a
man-made problem [3]. Inappropriate treatment results
in unacceptably low cure rates and the continued spread
of tuberculosis in the community because of selection of
M. tuberculosis isolates that are resistant to anti- tubercu-
lar drugs [4]. Taking into consideration the high success
rate of TB treatment under DOT policy (Directly Observed
Treatment), the principal cause for the generation of drug
resistant TB generally appears to lie in the low degree of
patient compliance with treatment [5]. Most of the prob-
lems from which drug-resistance originates are related to
the length of treatment (especially considering tolerability
and adherence), the longer time that is required to treat
MDR-TB results in an additional risk of poor treatment
Published: 12 November 2007
BMC Ear, Nose and Throat Disorders 2007, 7:5 doi:10.1186/1472-6815-7-5
Received: 4 April 2007
Accepted: 12 November 2007
This article is available from: http://www.biomedcentral.com/1472-6815/7/5
© 2007 Prahlad and Malay; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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adherence and thus of treatment failure [6]. Two other
major issues of importance which affect the outcome in
MDR-TB compared to drug-susceptible disease are the
increased cost (up to 100 times higher) and higher toxicity
[7,8].
By definition, chemotherapy of MDR-TB cannot rely upon
isoniazid and rifampicin, the two most powerful drugs for
the treatment of tuberculosis [9]. Thus, depending on the
individual susceptibility pattern, residual first-line oral
drugs must be appropriately combined with additional
second line drugs comprising injectable aminoglycosides
(amikacin, kanamycin, capreomycin), fluoroquinolones
(ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin, gat-
ifloxacin), old bacteriostatic second line anti-tuberculosis
agents (ethionamide, protionamide, cycloserine, para-
amino salicylic acid, thiocetazone) and anti-tuberculosis
agents with unclear efficacy (clofazimine, amoxicillin/cla-
vuanate, clarithromycin, linezolid) [2].
A crucial issue related to long-term administration of the
injectable group is toxicity. Ototoxicity and nephrotoxic-
ity are well recognized as dose-related adverse effects of
aminoglycosides [10]. Ototoxicity and nephrotoxicity
have been of major concern because of the narrow thera-
peutic range of these agents and the wide variability in
pharmacokinetics among patients [11]. Amikacin is a
semi-synthetic aminoglycoside and shows excellent activ-
ity against Mycobacterium tuberculosis and atypical
mycobacteria and has been used in the treatment of dis-
seminated atypical Mycobacterium infection in AIDS
patients [12].
Kanamycin, an antibiotic elaborated by Streptomyces
kanamyceticus has shown activity against Mycobacterium
tuberculosis. But as the therapy of this disease is pro-
tracted and involves the administration of large total
doses of the drug, with the risk of ototoxicity and nephro-
toxicity, kanamycin should be used only in infection with
organisms that are resistant to the more commonly used
agents [12]. It is more toxic to cochlea with well docu-
mented ototoxicity [13,14] but is still being commonly
used in clinical settings like ours (in developing countries)
for MDR-TB where cost considerations are a major factor
in patient compliance (because of having one fourth the
cost of amikacin and one tenth the cost of capreomycin).
Capreomycin is an antimicrobial cyclic peptide elabo-
rated by Streptomyces capreolus and is effective both in
vitro and in experimental tuberculosis. It has proven to be
of value in the therapy of 'resistant' or treatment failure
tuberculosis when given with ethambutol or isoniazid
[15]. The toxicity profile of capreomycin is similar to that
of aminoglycosides and has been discussed along with
aminoglycosides in the present study [16]. Cost of therapy
with capreomycin is quite high compared to amikacin
and kanamycin and is used only in few patients of MDR-
TB showing resistance to amikacin and kanamycin. Initial
ototoxic drug exposure typically affects cochlear regions
coding the high frequencies. Continued exposure results
in spread of damage to progressively lower frequencies.
Early identification of ototoxic hearing loss provides phy-
sicians the opportunity to adjust the therapeutic treatment
in order to minimize or prevent hearing loss requiring
rehabilitation, depending on a patient's overall treatment
picture [17,18]. The present study was conducted to study
the effect of second line aminoglycosides (amikacin, kan-
amycin and capreomycin) on the hearing status in
patients of MDR-TB after long term use as a part of multi-
drug therapy.
Methods
A total of 64 patients were included in the study who com-
pleted treatment for MDR-TB from April 2000 to Septem-
ber 2006 using second line drugs and fulfilled the criteria
described below. Treatment regimens followed were
based on drug susceptibility testing and previous treat-
ment history. All the relevant data were recorded on MDR-
TB patient sheets including the baseline and follow-up
investigations. Baseline pre-treatment pure tone audiom-
etry was performed on all the patients and repeated every
two months until completion of therapy. Other baseline
investigations including renal function and liver function
tests were also performed on all the patients. These were
not repeated during the therapy unless some specific com-
plaint or clinical suspicion was present. Patients with
abnormal pre-treatment renal functions were excluded
from the study group. Serum aminoglycosides levels were
not measured during the course of therapy as the costs
involved did not permit them. Repeat renal function tests
were performed in all the patients with complaint/audio-
logic evidence of hearing loss after start of aminoglycoside
treatment. Those patients with any abnormality in
repeated renal function tests were excluded from the study
and were managed in consultation with the medical spe-
cialist. The treatment regimens used were in accordance
with the standard recommended protocols with necessary
permissions and informed consent of all the patients in
the study was obtained.
Complete otolaryngologic examination was done as a part
of pre-treatment clinical examination in all the patients.
Those patients with any pre-treatment evidence of hearing
loss on history, clinical assessment (patients with evi-
dence of infective pathology in ear were excluded) or pure
tone audiometry, whether conductive (A-B gap > 10 dB)
or sensorineural were excluded. Baseline pure tone audio-
grams between 125 Hz and 8000 Hz were performed for
all the patients in a sound treated room. Baseline, in addi-
tion to follow-up audiological testing, included both air-
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and bone-conduction threshold measurements in all the
patients. All the patients who had received any ototoxic
drug as a part of previous regimen were excluded from the
study.
The criteria used for determining ototoxic threshold shift
from baseline audiogram were: (1) 20 dB or greater
decrease at any one test frequency, (2) 10 dB or greater
decrease at any two adjacent frequencies, or (3) loss of
response at three consecutive frequencies where responses
were previously obtained (ASHA, 1994)[19]. All the
changes were confirmed by retest on the same day. These
patients were divided into three groups depending upon
the ototoxic aminoglycoside used. Group I (n = 34)
patients received amikacin (15 mg/kg per day, intramus-
cular, single daily dose), group II (n = 26) patients
received kanamycin (15 mg/kg per day, intramuscular,
single daily dose) and group III (n = 4) patients received
capreomycin (15 mg/kg per day, intramuscular, single
daily dose) as a part of complete regimen comprising of
one injectable (aminoglycoside), one quinolone with a
minimum of five drugs depending on the drug sensitivity
testing and the costs involved. Streptomycin was not used
because of high resistance in these patients on drug sensi-
tivity testing. Those patients receiving two ototoxic drugs
were excluded from the study. Total duration of therapy in
all the patients ranged from 18 to 24 months after sputum
smear/culture conversion and aminoglycoside was used
for six months after sputum conversion.
Audiometry findings were considered under three catego-
ries; 'normal' (N) defined by patients with pure tone audi-
ograms showing air-conduction thresholds up to 20 ± 5
dB HL at all the tested frequencies from 125 Hz to 8000
Hz with air-bone gap of ≤ 10 dB; 'high frequency loss'
(HFL) defined by (1) a 20 dB or greater decrease at any of
the three frequencies; 4000, 6000 and 8000 Hz, (2) 10 dB
or greater decrease at any two adjacent frequencies in
above range, (3) loss of response at all the three frequen-
cies (4000, 6000 and 8000 Hz) where responses were pre-
viously obtained; and 'flat' (FLAT) when in addition to
HFL, above criteria were also fulfilled in the frequencies
ranging from 250 to 3000 Hz. All the pure tone threshold
shifts were recorded at each frequency tested with refer-
ence to the baseline pure tone threshold at the same fre-
quency. Ototoxic aminoglycoside was stopped in patients
complaining of or showing audiological evidence of hear-
ing loss (based on ASHA's criteria used for determining
ototoxic threshold shift, 1994) and substituted with other
second line drug/drugs depending upon the drug sensitiv-
ity testing. The data so obtained was analyzed for various
epidemiological factors and hearing status in each group
after completion of therapy and data were reported as
mean and standard deviations.
Results
All the patients in this study were in the age group of 17
to 65 years (mean age = 39.9 ± 13.5 years) with males con-
stituting 60.9% and females constituting 39.1% (n = 64).
Majority of the patients were from rural background
(68.7%) while 31.2% were from urban areas (n = 64).
Majority (65.6%) of the patients were from low socio-eco-
nomic status (n = 64). Overall incidence of HFL was
18.75% while incidence of FLAT loss was 6.25% in the
present study (n = 64). The mean duration of therapy was
20.3 ± 0.25 months after smear/culture conversion (range
was 18–24 months) while aminoglycosides were contin-
ued for 6 months (180 days) post conversion in the initial
phase. Total duration of aminoglycoside use was 233.3 +
106.6 days while duration of audiologic follow-up after
discontinuation of aminoglycoside use was 376.7 ± 42
days.
Seven patients (20.6%, n = 34) of group I (amikacin)
showed sensorineural hearing loss (SNHL) involving the
higher frequencies (HFL). Amikacin was stopped on the
first report of hearing loss and patient shifted to another
of the second line drug. Follow-up audiogram showed
development of FLAT loss in two (5.9%, n = 34) of these
patients, (Subject # 2) at six months (pure tone audio-
gram at 6 months, PTA6) and (Subject # 4) at 10 months
(pure tone audiogram at 10 months, PTA10) (Table 1).
Duration of aminoglycoside use in group I was 235 ± 40
days (n = 34) while duration of aminoglycoside use in
seven patients of group I which developed ototoxicity (n
= 7) was 163 ± 45 days (as amikacin was discontinued on
first report of hearing loss).
Four patients (15.4%, n = 26) of group II (kanamycin)
had SNHL involving higher frequencies (HFL). In two
(7.7%, n = 26) patients lower frequencies were also
involved (FLAT) even when Subject # 8 had injectable
drug stopped at 4 months while Subject # 10 had the drug
stopped on report of high frequency loss at 6 months
(Table 1). Duration of aminoglycoside use in group II was
237 ± 34 days (n = 26) while duration of aminoglycoside
use in four patients of group II which developed ototoxic-
ity (n = 4) was 165 ± 30 days (as kanamycin was discon-
tinued on first report of hearing loss).
One of the patients of group III (25.0%, n = 4) developed
sensorineural hearing loss involving high frequencies
(HFL) at 4 months (Table 2) and capreomycin was substi-
tuted with other second line drug based on drug sensitiv-
ity testing. Mean duration of aminoglycoside use in group
III was 215 ± 64 (n = 4) days. Duration of capreomycin
use in single patient with HFL (Subject # 12) was 120
days. None of the patients had any recovery in pure-tone
thresholds after stopping the injectable treatment. Group-
wise mean loss shown by patients with ototoxic threshold
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shift (Group I, n = 7; Group II, n = 4, Group III, n = 1) at
different frequencies tested in the present study is shown
in Table 3. Mean loss (average decrease in pure tone
threshold from baseline at each frequency tested in
patients with ototoxic threshold shift in each group) in
seven patients of group I fulfilled the criteria (ASHA'
1994) for ototoxic threshold shift in frequencies range of
4000–8000 Hz (HFL) but not in the frequency range from
250–3000 Hz. Mean loss in four patients of group II ful-
filled the criteria for ototoxic threshold shift in both the
frequency ranges i.e. 4000–8000 Hz (HFL) and 250–3000
Hz. As sample size for group III was small, the data was
not further analyzed but a note of ototoxic threshold shift
in 4000–8000 Hz range was made. Studies with larger
number of patients using capreomycin are required but
higher cost of the therapy with capreomycin limits its use
in large number of patients in our setting.
Discussion
MDR-TB is a growing problem throughout the world [20].
The selection of drug resistant M. tuberculosis depends on
the frequency of the specific drug-resistant mutants in the
initially drug-susceptible bacterial population. As a conse-
quence, the chance of selecting such mutants is highest in
the case of mono-therapy [4] and this is the rationale of
combination chemotherapy both in case of drug-suscepti-
ble as well as MDR-TB even at the cost of adverse drug
reactions so that mutants resistant to a single drug are not
easily selected by mono-therapy. Adherence to treatment
is a critical factor in the management of MDR-TB and
adverse events associated with second line drugs could
have a severe impact on adherence because long term use
of second line drugs is required in MDR-TB ranging from
18–24 months [21]. A large literature exists on the adverse
Table 1: Audiometry findings, present regimen and length of aminoglycoside use in group I(n = 7) and II (n = 4) patients showing
audiological evidence of hearing loss
Sr. No. (Group) Length of
treatment (Days)
Present regimen
(Drugs)
PTA0 PTA2 PTA4 PTA6 PTA8 PTA10 PTAc
1 (I) 180 A, F, E, P, Py N N N HFL HFL HFL HFL
2 (I) 60 A, F, E, P, Py N HFL HFL HFL FLAT FLAT FLAT
3 (I) 180 A, F, E, P, Py N N N HFL HFL HFL HFL
4 (I) 180 A, F, E, P, Py N N N HFL HFL FLAT FLAT
5 (I) 180 A, F, E, P, Py N N N HFL HFL HFL HFL
6 (I) 180 A, F, E, P, Py N N N HFL HFL HFL HFL
7 (I) 180 A, F, E, P, Py N N N HFL HFL HFL HFL
8 (II) 120 K, F, E, P, Py N N N HFL FLAT FLAT FLAT
9 (II) 180 K, F, E, P, Py N N N HFL HFL HFL HFL
10 (II) 180 K, F, E, P, Py N N N HFL HFL FLAT FLAT
11 (II) 180 K, F, E, P, Py N N N HFL HFL HFL HFL
A = amikacin, F = flouroquinolone, E = ethionamide, P = Para-amino salicylic acid, Py = Pyrazinamide, K = kanamycin, Days = days of aminoglycoside
use in present regimen, PTA0 = baseline pure tone audiogram, PTA2 = pure tone audiogram after 2 months of aminoglycoside use, PTA4 = pure
tone audiogram after 4 months of aminoglycoside use, PTA6 = pure tone audiogram after 6 months of aminoglycoside use, PTA8 = pure tone
audiogram after 8 months of aminoglycoside use, PTA10 = pure tone audiogram after 10 months of aminoglycoside use, PTAc = pure tone
audiogram after completion of therapy for MDR-TB, N = Normal, HFL = High frequency loss (hearing loss involving frequencies of 4000, 6000 and
8000 Hz), FLAT = Hearing loss involving frequencies in range of 250–3000 Hz along with involvement of 4000, 6000 and 8000 Hz (Criteria for
hearing loss as defined in methods section).
Table 2: Audiometry findings, present regimen and length of aminoglycoside use in all four patients using capreomycin (Group III)
Sr. No. Length of treatment (Days) Present regimen (Drugs) PTA0 PTA2 PTA4 PTA6 PTA8 PTA10 PTAc
1 247 C, F, E, P, Clo N N N N N N N
2 254 C, F, E, P, Clo N N N N N N N
3* 120 C, F, E, P, Clo N N HFL HFL HFL HFL HFL
4 240 C, F, E, P, Clo N N N N N N N
C = capreomycin, F = flouroquinolone, E = ethionamide, P = Paraminosalicylic acid, Clo = Clofazimine, Days = days of aminoglycoside use in
present regimen, PTA0 = baseline pure tone audiogram, PTA2 = pure tone audiogram after 2 months of aminoglycoside use, PTA4 = pure tone
audiogram after 4 months of aminoglycoside use, PTA6 = pure tone audiogram after 6 months of aminoglycoside use, PTA8 = pure tone audiogram
after 8 months of aminoglycoside use, PTA10 = pure tone audiogram after 10 months of aminoglycoside use, PTAc = pure tone audiogram after
completion of therapy for MDR-TB, N = Normal, HFL = High frequency loss (hearing loss involving frequencies of 4000, 6000 and 8000 Hz), FLAT
= Hearing loss involving frequencies in range of 250–3000 Hz along with involvement of 4000, 6000 and 8000 Hz (Criteria for hearing loss as
defined in methods section). * Patient in group III with audiological evidence of hearing loss
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effects of anti-tuberculosis medications, which range from
minor to life threatening [10,22-24].
The main constraint to the administration of aminoglyco-
sides are risks of nephrotoxicity and ototoxicity [24]. Oto-
toxicity is the major irreversible toxicity of
aminoglycosides. Cochlear damage can produce perma-
nent hearing loss, while damage to vestibular apparatus
results in dizziness, ataxia and/or nystagmus. Aminogly-
cosides appear to generate free radicals within the inner
ear, with subsequent permanent damage to sensory cells
and neurons resulting in permanent hearing loss [14]. The
other major limitation to the clinical use of aminoglyco-
sides continues to be concern for the development of
nephrotoxicity. Nephrotoxicity has been defined as an
increase in the baseline serum creatinine concentration of
0.5 mg/dl or a 50% increase, whichever is greater, on two
consecutive occasions any time during therapy or up to 1
week after the cessation of therapy [25]. Evidence from
studies with animals and humans has demonstrated a cor-
relation between the nephrotoxic effect of aminoglyco-
sides and the accumulation of these drugs in the cortex of
kidney [26-28].
The present study evaluates the effect of parenteral second
line aminoglycosides namely amikacin, kanamycin and
capreomycin on hearing status of MDR-TB patients. We
report a hearing loss documented by pure tone audiome-
try in 18.75% patients of MDR-TB using a single
parenteral second line aminoglycoside involving higher
frequencies (4000 to 8000 Hz) to start with and progress-
ing to involve lower frequencies (500, 1000, 2000 and
3000 Hz) in 6.25% thus affecting the speech comprehen-
sion of the patient (n = 64). Speech comprehension can
also be affected with hearing loss in the 4000 Hz range
and may adversely affect communication especially in sit-
uations like environments with back ground noise [29].
The loss once developed has been found to be irreversible
and none of the patients in the present study showed any
improvement after stopping the therapy.
Ototoxicity is determined by comparing baseline data,
ideally obtained prior to ototoxic drug administration, to
the results of subsequent monitoring tests. Detecting
changes in pure tone thresholds directly using serial audi-
ograms is considered the most effective indicator of oto-
toxic hearing loss, particularly when ultra-high frequency
thresholds are included [17,18]. Monitoring audiological
evaluations after the baseline evaluations have been rec-
ommended 1–2 times per week for patients receiving oto-
toxic antibiotics [17,18,25]. Other approaches to
audiologic monitoring for ototoxicity are high frequency
audiometry and otoacoustic emissions [30].
In the present study, pure tone audiometry was performed
every other month for each patient until the completion
of therapy. Because aminoglycoside ototoxicity can
progress after discontinuation of the drug [13], we also
performed audiometric follow-up in all patients for an
average of over one year after drug discontinuation. This
long term follow-up confirmed that all aminoglycoside-
induced hearing loss in this patient population was per-
manent and not reversible. Persistence of toxicity of sera
has been reported up to one year in patients using
aminoglycosides even after stopping the ototoxic drug
[31]. Twice weekly audiograms as recommended were not
performed in the present study because of cost involved
and the inability of the patients from far distant places to
report twice weekly at our center where facilities for con-
ventional assessment of hearing are available. It is not
common to find equipment for audiometry as well as
trained staff at peripheral centers in developing country
like ours. Conventional frequency range (250–8000 Hz)
was used in the present study as only conventional audi-
ometers with frequency range between 125 and 8000 Hz
are available with us owing to low cost compared to high
frequency equipment.
Different studies have reported hearing loss as an adverse
drug reaction in patients of MDR-TB ranging from 6–18%
[21,22,31]. The finding that higher frequencies are
involved before the lower frequencies may be used as a
monitoring procedure for the detection of ototoxicity and
has the potential for minimizing irreversible communica-
tion deficits in patients receiving aminoglycoside therapy
[32]. In all the patients showing hearing loss, the
aminoglycoside was stopped and changed to another sec-
ond line drug done. Incidence of hearing loss may have
been reduced because the aminoglycoside was stopped
immediately at the outset of ototoxicity and substituted
with another second line drug. All the patients included in
the present study completed the remaining part of the
Table 3: Mean loss in patients with ototoxic threshold shift in group I (n = 7), group II (n = 4) and group III (n = 1) at different
frequencies tested
Group 250 Hz 500 Hz 1000 Hz 2000 Hz 3000 Hz 4000 Hz 6000 Hz 8000 Hz
I 3 ± 5.7 2 ± 5.7 3 ± 3.8 5 ± 5 8 ± 8.6 17 ± 12.5 29.3 ± 9.3 34.3 ± 8.5
II 2.5 ± 5 5 ± 7.1 10 ± 9.1 16.25 ± 10.3 20 ± 14.7 27.5 ± 10.4 30 ± 7.9 33.75 ± 16
III - - 5 5 10 30 35 45
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therapy. Other authors have also reported changing to
other second line drugs and completion of full therapy
[21,22].
A number of otoprotective agents are being investigated
for protection against hearing loss induced by cisplatin,
carboplatin, aminoglycosides or noise exposure. These
agents delivered either before or in combination with oto-
toxic drugs may help to prevent ototoxicity. D-methio-
nine as an otoprotective agent has shown protection
against amikacin induced ototoxicity [33].
There is evidence that aminoglycoside accumulation in
the kidney may be related to the dosing schedule i.e.
administration of larger doses less frequently may reduce
the level of drug accumulation in the kidney and has been
prospectively shown to reduce the nephrotoxic potentials
of aminoglycosides [25]. Conventional multiple daily
dosing is being gradually abandoned in favor of once
daily dosing and results from meta-analysis of rand-
omized clinical trials show diminished [34] or compara-
ble [35-38] nephrotoxicity, better [35,36,39] or
comparable [34,37,38] efficacy and comparable [34-
36,38,39] ototoxicity with once daily dosing among
adults. Once daily dosing has been used in all the patients
in the present study but individualized dosing based on
monitoring of serum levels of aminoglycosides has not
been used in present study.
Individualized aminoglycoside dosing guided by targeted
peak and trough concentrations in serum on the basis of
the patient's individual pharmacokinetics parameters and
standard equations has been related to decreased toxicity
[40]. An association of ototoxicity with nephrotoxicity
and with an elevated mean trough aminoglycoside serum
level has been observed in patients treated with aminogly-
cosides [41]. Because of economic constraints and the
non-affordability by the patients, serum levels of
aminoglycosides during the therapy were not measured in
the present study. But with individualized dosing based
on patient's individual pharmacokinetic monitoring
guided by targeted peak and trough concentrations, side
effects could probably be avoided in some cases.
First row outer hair cells (OHCs) in the basal turn tend to
be affected earlier than inner apical cells and type I cells
are affected before type II cells. The progression of hair cell
loss in cochlea tends to be from basal to apical and from
OHCs to inner hair cells (IHCs) to supporting cells to
more central neural structures like spiral ganglion cells
[42]. This stepwise progression of damage explains the
clinical findings of high frequency hearing loss occurring
first with ototoxic drugs.
Conclusion
Audiologic changes have been reported in patients of
MDR-TB using second line aminoglycosides which can
potentially affect the communication ability of the
patient. But careful audiologic monitoring may help in
limiting this damage which once developed is permanent.
Thus otologists and audiologists can have an important
role in the management of MDR-TB in preventing the
treatment related morbidity.
Competing interests
The author(s) declare that they have no competing inter-
ests.
Authors' contributions
DP participated in the study design, carried out audiolog-
ical work and helped in drafting the manuscript. SM con-
ceived of the study, outlined and carried out the
management of the patients under study. Both the
authors have read and approved the final manuscript.
Acknowledgements
We gratefully acknowledge Dr. Praveen K Sharma, Assistant Professor,
Department of Pharmacology, Dr. R. P. Govt. Medical College, Tanda, Kan-
gra, Himachal Pradesh, India for valuable help in pharmacological details and
statistical analysis.
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