Incidence of aminoglycoside-induced hearing loss in HIV positive and HIV negative multidrug-resistant tuberculosis patients

Aims of the study: To document the incidence and severity of aminoglycoside-induced ototoxicity at Brooklyn Chest Hospital; To determine the prevalence of the 6 known aminoglycoside-induced deafness mutations in the MT-RNR1 gene (A1555G, C1494T, T1095C, T1291C, A827G and 961 indel C) in a cohort of MDR-TB patients; To determine whether HIV positive MDR-TB patients are more likely to develop aminoglycoside-induced hearing loss than HIV negative MDR-TB patients; To provide clinical guidelines to the medical fraternity on the use of aminoglycoside antibiotics with regard to the side-effect of ototoxicity

Aminoglycoside-induced hearing loss: South Africans at risk

South Africa is currently experiencing a TB epidemic with an estimated incidence of 940/100 000 population/year, and the country has been ranked 4th among the 22 high-burden TB countries worldwide by the World Health Organization (WHO). A potentially devastating threat to TB control is the emergence of multidrug-resistant TB (MDR-TB) and, more recently, extensively drug-resistant TB (XDR-TB), mainly as a result of poor drug adherence by TB patients and incorrect management or treatment regimens by health providers; however, direct transmission of drug-resistant strains also plays an important role. The MDR/XDR-TB strains necessitate prolonged chemotherapy for up to 2 years or more, and the use of more toxic second-line drugs including the aminoglycoside (streptomycin, kanamycin and amikacin) and polypeptide (capreomycin) antibiotics. In South Africa, in accordance with WHO guidelines, streptomycin is used for retreatment of TB while kanamycin, amikacin and capreomycin are used to treat MDR/XDR-TB

Aminoglycoside-induced hearing loss in HIV-positive and HIV-negative multidrug-resistant tuberculosis patients

Background. Ototoxicity following aminoglycoside treatment for multidrug-resistant tuberculosis (MDR-TB) is a significant problem. This study documents the incidence of ototoxicity in HIV-positive and HIV-negative patients with MDR-TB and presents clinical guidelines relating to ototoxicity. Methods. A prospective cohort study of 153 MDR-TB patients with normal hearing and middle ear status at baseline controlling for 6 mitochondrial mutations associated with aminoglycoside-related ototoxicity, at Brooklyn Chest Hospital in Cape Town. Pure tone audiometry was performed monthly for 3 months to determine hearing loss. HIV status was recorded, as was the presence of 6 mutations in the MT-RNR1 gene. Results. Fifty-seven per cent developed high-frequency hearing loss. HIV-positive patients (70%) were more likely to develop hearing loss than HIV-negative patients (42%). Of 115 patients who were genetically screened, none had MT-RNR1 mutations. Conclusion. Ototoxic hearing loss is common in MDR-TB patients treated with aminoglycosides. HIV-positive patients are at increased risk of ototoxicity. Auditory monitoring and auditory rehabilitation should be an integral part of the package of care of MDR-TB patients

A rapid method for detection of five known mutations associated with aminoglycoside-induced deafness

<p>Abstract</p> <p>Background</p> <p>South Africa has one of the highest incidences of multidrug-resistant tuberculosis (MDR-TB) in the world. Concomitantly, aminoglycosides are commonly used in this country as a treatment against MDR-TB. To date, at least five mutations are known to confer susceptibility to aminoglycoside-induced hearing loss. The aim of the present study was to develop a rapid screening method to determine whether these mutations are present in the South African population.</p> <p>Methods</p> <p>A multiplex method using the SNaPshot technique was used to screen for five mutations in the <it>MT-RNR1 </it>gene: A1555G, C1494T, T1095C, 961delT+C(n) and A827G. A total of 204 South African control samples, comprising 98 Mixed ancestry and 106 Black individuals were screened for the presence of the five mutations.</p> <p>Results</p> <p>A robust, cost-effective method was developed that detected the presence of all five sequence variants simultaneously. In this pilot study, the A1555G mutation was identified at a frequency of 0.9% in the Black control samples. The 961delT+C(n) variant was present in 6.6% of the Black controls and 2% of the Mixed ancestry controls. The T1095C, C1494T and A827G variants were not identified in any of the study participants.</p> <p>Conclusion</p> <p>The frequency of 0.9% for the A1555G mutation in the Black population in South Africa is of concern given the high incidence of MDR-TB in this particular ethnic group. Future larger studies are warranted to determine the true frequencies of the aminoglycoside deafness mutations in the general South African population. The high frequencies of the 961delT+C(n) variant observed in the controls suggest that this change is a common non-pathogenic polymorphism. This genetic method facilitates the identification of individuals at high risk of developing hearing loss prior to the start of aminoglycoside therapy. This is important in a low-resource country like South Africa where, despite their adverse side-effects, aminoglycosides will continue to be used routinely and are accompanied with very limited or no audiological monitoring.</p

Fatal Lemierre’s syndrome as a complication of chronic otitis media with cholesteatoma

Background. Lemierre’s syndrome is septic thrombophlebitis of the internal jugular vein, initiated by an infection of the head and neck region. This septic thrombophlebitis gives rise to septic microemboli that can disseminate throughout the body to form septic infarctions and abscesses, with the most frequent site being pulmonary. Methods. We discuss the case of a 14-year-old male with Lemierre’s syndrome as a complication of chronic middle ear infection. Results. The patient developed septic shock and microemboli, and subsequently died. Conclusion. This case report illustrates that untreated chronic middle ear infection can lead to potentially fatal complications such as Lemierre’s syndrome, and emphasises the importance of timeous treatment of chronic middle ear pathology

Aminoglycoside-induced hearing loss : South Africans at risk

EditorialThe original publication is available at http://www.samj.org.zaBibliographyPublishers' versionEditorial

Aminoglycoside-induced hearing loss in HIV-positive and HIV-negtive multidrug-resistant tuberculosis patients

The original publication is available at http://www.samj.org.zaBackground. Ototoxicity following aminoglycoside treatment for multidrug-resistant tuberculosis (MDR-TB), is a significant problem. This study documents the incidence of ototoxicity in HIVpositive and HIV-negative patients with MDR-TB and presents clinical guidelines relating to ototoxicity. Methods. A prospective cohort study of 153 MDR-TB patients with normal hearing and middle ear status at baseline controlling for 6 mitochondrial mutations associated with aminoglycosiderelated ototoxicity, at Brooklyn Chest Hospital in Cape Town. Pure tone audiometry was performed monthly for 3 months to determine hearing loss. HIV status was recorded, as was the presence of 6 mutations in the MT-RNR1 gene. Results. Fifty-seven per cent developed high-frequency hearing loss. HIV-positive patients (70%) were more likely to develop hearing loss than HIV-negative patients (42%). Of 115 patients who were genetically screened, none had MT-RNR1 mutations. Conclusion. Ototoxic hearing loss is common in MDR-TB patients treated with aminoglycosides. HIV-positive patients are at increased risk of ototoxicity. Auditory monitoring and auditory rehabilitation should be an integral part of the package of care of MDR-TB patients.Medical Research CouncilStellenbosch UniversitySouth African Society of Otorhinolarynogolog

Investigation of mitochondrial sequence variants associated with aminoglycoside-induced ototoxicity in South African TB patients on aminoglycosides

A known side effect of aminoglycoside antibiotics is the development of permanent hearing loss. As South Africa is currently facing a tuberculosis (TB) epidemic, with an increasing number of multi-drug resistant tuberculosis (MDR-TB) infections, the use of aminoglycosides is on the increase. It is therefore important to determine whether the mitochondrial mutations associated with aminoglycoside-induced hearing loss occur at high frequencies in particular ethnic groups in our population. A total of 115 mainly MDR-TB patients all on aminoglycosides and 439 controls representative of the main ethnic groups in South Africa were screened for six mutations using the SNaPshot technique. Furthermore, the mitochondrial genomes of eight patients with ototoxicity were sequenced. Homoplasmic mutations were found in controls (A1555G in 0.9% of Black controls and A827G in 1.1% of Afrikaner controls) which reveal that a significant proportion of the South African population is genetically predisposed to developing aminoglycoside-induced hearing loss. The 961delT+insC (n) and T961G variants were found at frequencies of >1% indicating that both are probably non-pathogenic polymorphisms. Sequencing of the entire mitochondrial genome in eight patients did not reveal any mutations in the MT-RNR1 gene. However, two potentially pathogenic variants, T10114C (I19T in MT-ND3) and T15312C (I189T in MT-CYB) were found that may impact on the oxidative phosphorylation capacity and warrant further investigation for their possible role in this disorder. It is imperative that the genetic basis of this potentially preventable condition be investigated, particularly in countries where aminoglycosides are still commonly used, in order to identify individuals and/or ethnic groups who are at risk for this type of hearing loss