Araştırmamızın amacı, Yenidoğan Yoğun Bakım Ünitesinde yatırılarak gentamisin ile tedavi edilen orta ve geç prematüre bebeklerde bebeklik döneminin erken dönemleri boyunca ototoksisite prevalansını belirlemekti. Çalışmamız hastanemiz Yenidoğan Yoğun Bakım Ünitesine 1 Mayıs 2015 ile 30 Nisan 2016 tarihleri arasında kabul edilen orta ve ileri evre prematüre bebekler ile yürütüldü. Hastalar gentamisin tedavisi alan ve almayan olarak iki gruba ayrıldı. Her gruptan bir hasta, ilk işitsel beyin sapı tepkisi (ABR) değerlendirmesini geçemedi. İki grup arasında belirgin bir ayrım yoktu. 8 hastanın TEOAE testini geçemediği belirlendi. Bu hastaların dördü gentamisin alan gruba, dördü ise kontrol grubuna atandı. Bu 8 hasta muayene için Kulak Burun Boğaz Kliniğine yönlendirildi. Altı olguda otitis media tanısı konularak tedavi başlandı, iki olguda ise değerlendirmede özellik saptanmadı. Terapilerin ardından bu sekiz kişiye bir kez daha ikinci işitsel beyin sapı tepkisi (ABR) testi uygulandı. Her hasta bu testi aştı. Yapılan değerlendirmede herhangi bir işitme bozukluğu tespit edilmiyor. İşitme sisteminde gentamisinin neden olduğu hasara (ototoksisite) ilişkin belgelenmiş bir olay yoktu.
Çalışmada elde ettiğimiz sonuçlara göre gentamisin gibi ototoksik ajanlara ve diğer işitme kaybı risk faktörlerine maruz kalan yenidoğan yoğun bakım hastalarının ve özellikle prematüre olanların uzun süreli takiplerinin bu açıdan önemli olduğunu düşünmekteyiz. Kullanım süresi ve doz gibi faktörler göz önüne alındığında çalışma grubumuzda gentamisine bağlı ototoksisite gelişmediğini gözlemledik.
1- Year 2007 Position statement: principles and guidelines for early hearing detection and intervention programs. Joint Committee on Infant Hearing. Pediatrics 2007; 120: 898-921.
2- Amin SB, Orlando MS, Dalzell LE, Merle KS, Guillet R.Morphological changes in serial auditory brain stem responses in 24 to 32 weeks’ gestational age infants during the first week of life. Ear Hear 1999; 20:410-418.
3- Moore JK, Perazzo LM, Braun A. Time course of axonal myelination in the human brainstem auditory pathway. Hear Res 1995; 87: 21-31.
4- Kuhl PK, Williams KA, Lacerda F, Stevens KN, Lindblom B. Linguistic experience alters phonetic perception in infants by 6 months of age. Science 1992; 255: 606-8.
5- Oudesluys-Murphy AM, Van Straaten HL, Bholasingh R, Van Zanten GA. Neonatal hearing screening. Eur J Pediatr 1996; 155; 429-35.
6- Yoshinaga-Itano C, Sedey AL, Coulter DK, Mehl AL. Language of early and later-identified children with hearing loss. Pediatrics 1998; 102; 1161-71.
7- Grant R. The case to fund universal newborn hearing screening in New York State Int J Pediatr Otolaryngol 2000;54:8-9.
8- P.E. Mohr, J.J. Feldman, J.L. Dunbar, A. McConkey-Robbins, J.K. Niparko, R.K. Rittenhouse, M.W. Skinner, The societal costs of severe to profound hearing loss in the United States, Int. J. Technol. Assess. Health Care 16 (2000) 1120e1135.
9- Cunningham M, Cox EO. Hearing assesment in infants and children: recommendations beyond neonatal screening Pediatrics 2003;111:436-439.
10- Marchant CD, Shurin PA, Turczyk VA, Wasikowski DE, Tutihasi MA, KinneySE. Course and outcome of otitis media in early infancy: A prospective study J Pediatr 1984;104:826-31.
11- Markides A. Age at fitting of hearing aids and speech intellgibility Br J Audiol 1986; 20: 165-7.
12- Mayne A, Yoshanaga-Itano C, Sedey AL, Carey A. Expressive vocabulary development of infants and toddlers who are deaf or hard of hearing.Volta Rev.. 1998;100 :1 –52.
13- Wrightson A. Universal newborn hearing screening. American Family Physician. 2007;75(9):1349-1352.
15- P.J. Yoon, M. Price, K. Gallagher, B.E. Fleisher, A.H. Messner, The need for longterm audiologic follow-up of neonatal intensive care unit (NICU) graduates, Int. J. Pediatr. Otorhinolaryngol. 67 (2003) 353-7.
16- Van Straaten HL, Hile Et, Kok JH, Verkerk PH, et al. Implementation of a nation- wide automated auditory brainstem response hearing screening programme in neonatal intensive care units. Acta Pediatr 2003;92(3):332-338.
17- Flynn M, Austin N, Flynn TS, Ford R, et al. Universal Newborn Hearing Screening introduced to NICU infants in Canterbury province, New Zealand. N Z Med J 2004;117(1206):U1183.
18- Uchôa NT, Procianoy RS, Lavinsky L, Sleifer P. [Prevalence of hearing loss in very low birth weight newborns]. [J Pediatr (Rio J). 2003]
19- Jiang ZD, Brosi DM, Wilkinson AR. Hearing impairment in preterm very low birth weight babies detected at term by brainstem auditory evoked responses Acta Paediatr. 2001 ;90 :1411-5.
20- Ari-Even Roth D, Hildesheimer M, Maayan-Metzger A, et al. Low prevalence of hearing impairment among very low birthweight infants as detected by universal neonatal hearing screening Arch Dis Child FNE 2006;91:F257–62.
21- Fernanda Alves Botelho, Maria Cândida Ferrarez Bouzada, Luciana Macedo de Resende, Cynthia Francisca Xavier Silva, Eduardo Araújo Oliveira, Prevalence of 52 hearing impairment in children at risk, Brazilian Journal of Otorhinolaryngology 2010;76(6):739-44.
22- J.E. Lawn, S. Cousens, J. Zupan, 4 million neonatal deaths: when? Where? Why, Lancet 365 (2005) 891–900.
23- E.S. Thingvoll, R. Guillet, M. Caserta, R. Dicenzo, Observational trial of a 48- hour gentamicin dosing regimen derived from Monte Carlo simulations in infants born at less than 28 weeks’ gestation, J. Pediatr. 153 (2008) 530–534.
24- B. Chattopadhyay, Newborns and gentamicin—how much and how often? J. Antimicrob. Chemother. 49 (2002) 13–16.
25- Rybak LP: Vestibüler ve İşitsel Toksisite. In Cummings CW, Fredrickson JM, Harker LA, Krause CJ, Richardson MA, Schuller DE, editors. Koç C, Çev. Editörü. Cummings Otolaringoloji Baş ve Boyun Cerrahisi, 4. baskı. Güneş Tıp Kitabevi, Ankara. 2007, s 2933–130.
26- Fausti SA, Henry JA, Schaffer HI, Olson DJ, Frey RH, McDonald WJ. Highfrequency audiometric monitoring for early detection of aminoglycoside ototoxicity. J. Infect. Dis. 1992;165: 1026.1032.
27- Janfaza P, Nadol JB: Temporal kemik. Janfaza P, Nadol JB, Gala R, Fabian RL, Montgomery WW, editors, Cansız H, çev. ed. Baş Boyun Cerrahi Anatomisi. Nobel Tıp Kitabevleri, İstanbul, 2002. s. 420–79.
28- Özturan O, Jerger J, Lew H, Lynch GR: Monitoring of Cisplatin Ototoxicity by Distortion Product Otoacoustic Emissions. Auris Nasus Larynx, 23: 147–51, 1996.
29- Hotz MA, Haris FP, Probst R. Otoacoustic Emissions: An approach for monitoring aminoglycoside induced ototoxicity. Laryngoscope1994;104:1130-1134.
30- De Groot JC, Meeuwsen F, Ruizendaal WE, Veldman JE. Ultrastructural localization of gentamicin in the cochlea. Hear Res 1990;50:35-42.
31- Finckh-kramer U, Gross M, Bartsch M, Kewitz G, et al. Hearing screening of high risk newborn infants. HNO 2000;48(3):215-220.
32- Robertson CMT, Tyebkhan JM, Peliowski A, et al. Ototoxic drugs and sensorineural hearing loss following severe neonatal respiratory failure. Acta Pediatr 2006;95:214–23.
33- Aust G. Vestibulotoxicity and ototoxicity of gentamicin in newborns at risk. Int Tinnitus J 2001;7:27–9.
34- S. Pourarian, B. Khademi, N. Pishva, A. Jamali, Prevalence of hearing loss in newborns admitted to neonatal intensive care unit, Iran. J. Otorhinolaryngol. 24 (68) (2012) 129–134.
35- D. Raveh, M. Kopyt, Y. Hite, B. Rudensky, M. Sonnenblick, A.M. Yinnon, Risk factors for nephrotoxicity in elderly patients receiving once-daily aminoglycosides, QJM 95 (5) (2002) 291–297.
36- J.E. Saunders, S. Vaz, J.H. Greinwald, J. Lai, K. Mojica, Prevalence and etiology of hearing loss in rural Nicaraguan children, Laryngoscope 117 (3) (2007) 387–398.
37- H. Li, P. Steyger, Synergistic ototoxicity due to noise exposure and aminoglycoside antibiotics, Noise Health 11 (42) (2009) 26–32.
38- E. Zimmerman, A. Lahav, Ototoxicity in preterm infants: effects of genetics, aminoglycosides, and loud environmental noise, J. Perinatol. 33 (1) (2013) 3–8.
40- M. Bitner-Glindzicz, S. Rahman, Ototoxicity caused by aminoglycosides, BMJ 335 (7624) (2007) 784–785.
41- C.M. Robertson, J.M. Tyebkhan, A. Peliowski, P.C. Etches, P.Y. Cheung, Ototoxic drugs and sensorineural hearing loss following severe neonatal respiratory failure, Acta Pediatr. 95 (2006) 214–223.
42- P.J. Yoon, M. Price, K. Gallagher, B.E. Fleisher, A.H. Messner, The need for long-term audiologic follow-up of neonatal intensive care unit (NICU) graduates, Int. J. Pediatr. Otorhinolaryngol. 67 (2003) 353–357.
43- K. Kawamoto, S.H. Sha, R. Minoda, M. Izumikawa, H. Kuriyama, J. Schacht, et al., Antioxidant gene therapy can protect hearing and hair cells from ototoxicity, Mol. Ther. 9 (2004) 173–181.
44- M. English, S. Mohammed, A. Ross, S. Ndirangu, G. Kokwaro, F. Shann, et al., A randomised controlled trial of once daily and multi-dose daily gentamicin in young Kenyan infants, Arch. Dis. Child. 89 (7) (2004) 665–669.
EVALUATION OF OTOTOXICITY IN GENTAMICIN TREATED MODERATELY AND LATE PREMATURE INFANTS
The objective of our research is to investigate the prevalence of ototoxicity throughout the early stages of infancy in middle and late preterm infants who were hospitalized and treated with gentamicin in the Neonatal Intensive Care Unit (NICU). Our study focused on premature babies admitted to the Neonatal Intensive Care Unit of our hospital between 1 May 2015 and 30 April 2016, in their middle and late stages. Patients were divided into two groups as receiving and not receiving gentamicin treatment. One patient from each group were unable to succeed the initial auditory brainstem response (ABR) assessment. There was no discernible distinction between the two groups. It was determined that 8 patients failed the TEOAE test. Four of these patients were assigned to the group receiving gentamicin, whereas four were assigned to the control group. These 8 patients were directed to the Ear Nose and Throat Clinic for examination. Otitis media was diagnosed in six cases and treatment was initiated, whereas the evaluation of two patients yielded unremarkable results. Following the therapies, the second auditory brainstem response (ABR) test was conducted once more on these eight individuals. Each patient exceeded this test. Upon evaluation, no auditory impairment is detected. There was no documented occurrence of gentamicin-induced damage to the auditory system (ototoxicity).
We think that neonatal intensive care patients who are exposed to ototoxic agents such as gentamicin and other hearing loss risk factors and long-term follow-up of especially premature ones are important in this respect. Considering factors such as duration of use and dose, we observed that gentamicin-induced ototoxicity did not develop in our study group.
1- Year 2007 Position statement: principles and guidelines for early hearing detection and intervention programs. Joint Committee on Infant Hearing. Pediatrics 2007; 120: 898-921.
2- Amin SB, Orlando MS, Dalzell LE, Merle KS, Guillet R.Morphological changes in serial auditory brain stem responses in 24 to 32 weeks’ gestational age infants during the first week of life. Ear Hear 1999; 20:410-418.
3- Moore JK, Perazzo LM, Braun A. Time course of axonal myelination in the human brainstem auditory pathway. Hear Res 1995; 87: 21-31.
4- Kuhl PK, Williams KA, Lacerda F, Stevens KN, Lindblom B. Linguistic experience alters phonetic perception in infants by 6 months of age. Science 1992; 255: 606-8.
5- Oudesluys-Murphy AM, Van Straaten HL, Bholasingh R, Van Zanten GA. Neonatal hearing screening. Eur J Pediatr 1996; 155; 429-35.
6- Yoshinaga-Itano C, Sedey AL, Coulter DK, Mehl AL. Language of early and later-identified children with hearing loss. Pediatrics 1998; 102; 1161-71.
7- Grant R. The case to fund universal newborn hearing screening in New York State Int J Pediatr Otolaryngol 2000;54:8-9.
8- P.E. Mohr, J.J. Feldman, J.L. Dunbar, A. McConkey-Robbins, J.K. Niparko, R.K. Rittenhouse, M.W. Skinner, The societal costs of severe to profound hearing loss in the United States, Int. J. Technol. Assess. Health Care 16 (2000) 1120e1135.
9- Cunningham M, Cox EO. Hearing assesment in infants and children: recommendations beyond neonatal screening Pediatrics 2003;111:436-439.
10- Marchant CD, Shurin PA, Turczyk VA, Wasikowski DE, Tutihasi MA, KinneySE. Course and outcome of otitis media in early infancy: A prospective study J Pediatr 1984;104:826-31.
11- Markides A. Age at fitting of hearing aids and speech intellgibility Br J Audiol 1986; 20: 165-7.
12- Mayne A, Yoshanaga-Itano C, Sedey AL, Carey A. Expressive vocabulary development of infants and toddlers who are deaf or hard of hearing.Volta Rev.. 1998;100 :1 –52.
13- Wrightson A. Universal newborn hearing screening. American Family Physician. 2007;75(9):1349-1352.
15- P.J. Yoon, M. Price, K. Gallagher, B.E. Fleisher, A.H. Messner, The need for longterm audiologic follow-up of neonatal intensive care unit (NICU) graduates, Int. J. Pediatr. Otorhinolaryngol. 67 (2003) 353-7.
16- Van Straaten HL, Hile Et, Kok JH, Verkerk PH, et al. Implementation of a nation- wide automated auditory brainstem response hearing screening programme in neonatal intensive care units. Acta Pediatr 2003;92(3):332-338.
17- Flynn M, Austin N, Flynn TS, Ford R, et al. Universal Newborn Hearing Screening introduced to NICU infants in Canterbury province, New Zealand. N Z Med J 2004;117(1206):U1183.
18- Uchôa NT, Procianoy RS, Lavinsky L, Sleifer P. [Prevalence of hearing loss in very low birth weight newborns]. [J Pediatr (Rio J). 2003]
19- Jiang ZD, Brosi DM, Wilkinson AR. Hearing impairment in preterm very low birth weight babies detected at term by brainstem auditory evoked responses Acta Paediatr. 2001 ;90 :1411-5.
20- Ari-Even Roth D, Hildesheimer M, Maayan-Metzger A, et al. Low prevalence of hearing impairment among very low birthweight infants as detected by universal neonatal hearing screening Arch Dis Child FNE 2006;91:F257–62.
21- Fernanda Alves Botelho, Maria Cândida Ferrarez Bouzada, Luciana Macedo de Resende, Cynthia Francisca Xavier Silva, Eduardo Araújo Oliveira, Prevalence of 52 hearing impairment in children at risk, Brazilian Journal of Otorhinolaryngology 2010;76(6):739-44.
22- J.E. Lawn, S. Cousens, J. Zupan, 4 million neonatal deaths: when? Where? Why, Lancet 365 (2005) 891–900.
23- E.S. Thingvoll, R. Guillet, M. Caserta, R. Dicenzo, Observational trial of a 48- hour gentamicin dosing regimen derived from Monte Carlo simulations in infants born at less than 28 weeks’ gestation, J. Pediatr. 153 (2008) 530–534.
24- B. Chattopadhyay, Newborns and gentamicin—how much and how often? J. Antimicrob. Chemother. 49 (2002) 13–16.
25- Rybak LP: Vestibüler ve İşitsel Toksisite. In Cummings CW, Fredrickson JM, Harker LA, Krause CJ, Richardson MA, Schuller DE, editors. Koç C, Çev. Editörü. Cummings Otolaringoloji Baş ve Boyun Cerrahisi, 4. baskı. Güneş Tıp Kitabevi, Ankara. 2007, s 2933–130.
26- Fausti SA, Henry JA, Schaffer HI, Olson DJ, Frey RH, McDonald WJ. Highfrequency audiometric monitoring for early detection of aminoglycoside ototoxicity. J. Infect. Dis. 1992;165: 1026.1032.
27- Janfaza P, Nadol JB: Temporal kemik. Janfaza P, Nadol JB, Gala R, Fabian RL, Montgomery WW, editors, Cansız H, çev. ed. Baş Boyun Cerrahi Anatomisi. Nobel Tıp Kitabevleri, İstanbul, 2002. s. 420–79.
28- Özturan O, Jerger J, Lew H, Lynch GR: Monitoring of Cisplatin Ototoxicity by Distortion Product Otoacoustic Emissions. Auris Nasus Larynx, 23: 147–51, 1996.
29- Hotz MA, Haris FP, Probst R. Otoacoustic Emissions: An approach for monitoring aminoglycoside induced ototoxicity. Laryngoscope1994;104:1130-1134.
30- De Groot JC, Meeuwsen F, Ruizendaal WE, Veldman JE. Ultrastructural localization of gentamicin in the cochlea. Hear Res 1990;50:35-42.
31- Finckh-kramer U, Gross M, Bartsch M, Kewitz G, et al. Hearing screening of high risk newborn infants. HNO 2000;48(3):215-220.
32- Robertson CMT, Tyebkhan JM, Peliowski A, et al. Ototoxic drugs and sensorineural hearing loss following severe neonatal respiratory failure. Acta Pediatr 2006;95:214–23.
33- Aust G. Vestibulotoxicity and ototoxicity of gentamicin in newborns at risk. Int Tinnitus J 2001;7:27–9.
34- S. Pourarian, B. Khademi, N. Pishva, A. Jamali, Prevalence of hearing loss in newborns admitted to neonatal intensive care unit, Iran. J. Otorhinolaryngol. 24 (68) (2012) 129–134.
35- D. Raveh, M. Kopyt, Y. Hite, B. Rudensky, M. Sonnenblick, A.M. Yinnon, Risk factors for nephrotoxicity in elderly patients receiving once-daily aminoglycosides, QJM 95 (5) (2002) 291–297.
36- J.E. Saunders, S. Vaz, J.H. Greinwald, J. Lai, K. Mojica, Prevalence and etiology of hearing loss in rural Nicaraguan children, Laryngoscope 117 (3) (2007) 387–398.
37- H. Li, P. Steyger, Synergistic ototoxicity due to noise exposure and aminoglycoside antibiotics, Noise Health 11 (42) (2009) 26–32.
38- E. Zimmerman, A. Lahav, Ototoxicity in preterm infants: effects of genetics, aminoglycosides, and loud environmental noise, J. Perinatol. 33 (1) (2013) 3–8.
40- M. Bitner-Glindzicz, S. Rahman, Ototoxicity caused by aminoglycosides, BMJ 335 (7624) (2007) 784–785.
41- C.M. Robertson, J.M. Tyebkhan, A. Peliowski, P.C. Etches, P.Y. Cheung, Ototoxic drugs and sensorineural hearing loss following severe neonatal respiratory failure, Acta Pediatr. 95 (2006) 214–223.
42- P.J. Yoon, M. Price, K. Gallagher, B.E. Fleisher, A.H. Messner, The need for long-term audiologic follow-up of neonatal intensive care unit (NICU) graduates, Int. J. Pediatr. Otorhinolaryngol. 67 (2003) 353–357.
43- K. Kawamoto, S.H. Sha, R. Minoda, M. Izumikawa, H. Kuriyama, J. Schacht, et al., Antioxidant gene therapy can protect hearing and hair cells from ototoxicity, Mol. Ther. 9 (2004) 173–181.
44- M. English, S. Mohammed, A. Ross, S. Ndirangu, G. Kokwaro, F. Shann, et al., A randomised controlled trial of once daily and multi-dose daily gentamicin in young Kenyan infants, Arch. Dis. Child. 89 (7) (2004) 665–669.
Uysal, B., Ceylan, S., & Erdoğan, H. (2023). EVALUATION OF OTOTOXICITY IN GENTAMICIN TREATED MODERATELY AND LATE PREMATURE INFANTS. International Anatolia Academic Online Journal Health Sciences, 9(3), 185-196.