Ototoxicity in cystic fibrosis patients receiving intravenous tobramycin for acute pulmonary exacerbation: Ototoxicity following tobramycin treatment.

Aminoglycosides are commonly used to treat infections in CF patients and are highly ototoxic. The incidence of tobramycin-induced hearing loss, tinnitus, vertigo or dizziness (ototoxicity) varies widely from 0 to 56% secondary to variation in patient enrollment, dosing, audiometry, and ototoxic criteria. The aim of this study is to determine the incidence of ototoxicity after one course of once-daily IV tobramycin in CF patients. Adult CF patients with acute pulmonary exacerbations were enrolled on IV tobramycin (10 mg/kg/d, ≥10 days). Pure-tone audiometry was performed for standard and extended high frequencies in the sensitive range for ototoxicity (SRO). American-Speech-Language-Hearing-Association cochleotoxicity criteria were applied. Distortion product otoacoustic emissions (DPOAE) and the words-in-noise-test (WINT) were assessed. Tinnitus Functional Index (TFI) and Vertigo Symptoms Scale (VSS) were used. Eighteen CF patients, mean age 31.1 (18-59), were enrolled. The incidence of cochleotoxic change from baseline at 2 and 4 weeks post-treatment was 89% and 93%. For DPOAE, a measure of outer hair-cell function, the incidence of ≥5 dB decrease was 82% and 80%. For WINT, a measure of word recognition, the incidence of ≥10% decrease was 17% and 40%. For TFI, the incidence of ≥10pt increase was 12% and 8%, and for VSS, the incidence of ≥6pt increase was 0% and 8%. One course of IV tobramycin was sufficient to cause hearing loss and other ototoxic symptoms four weeks after treatment ended. Audiometric measures were more sensitive to ototoxic change than TFI & VSS. Age and duration of tobramycin treatment were not obvious factors for predicting ototoxicity.

Evaluation of clinically asymptomatic high risk infants with congenital cytomegalovirus infection.

OBJECTIVE: To determine the frequency of abnormal findings on evaluation of neonates with congenital CMV infection who have a normal physical examination STUDY DESIGN: Retrospective, 2-center study (1996-2017) that reviewed results of complete blood cell count and platelets, serum alanine aminotransferase (ALT) and bilirubin concentrations, eye examination, cranial ultrasonography or other neuroimaging, and brainstem evoked responses performed on neonates with congenital CMV infection and a normal physical examination RESULTS: Of 34 infants with congenital CMV infection and a normal physical examination, 56% (19/34) had ≥1 abnormality: 39%, elevated ALT concentration; 45%, abnormal neuroimaging (five, lenticulostriate vasculopathy; six, intraventricular hemorrhage; four, calcifications); 12%, anemia; 16%, thrombocytopenia; and 3%, chorioretinitis. Seven (21%) infants had sensorineural hearing loss, and 18 infants received antiviral therapy. CONCLUSION: Some infants with congenital CMV infection and a normal physical examination had abnormalities on laboratory or neuroimaging evaluation, which in some cases prompted antiviral treatment.

Blood genome expression profiles in infants with congenital cytomegalovirus infection.

Congenital CMV infection (cCMVi) affects 0.5-1% of all live births worldwide, making it the leading cause of sensorineural hearing loss (SNHL) in childhood. The majority of infants with cCMVi have normal hearing at birth, but are at risk of developing late-onset SNHL. Currently, we lack reliable biomarkers to predict the development of SNHL in these infants. Here, we evaluate blood transcriptional profiles in 80 infants with cCMVi (49 symptomatic, 31 asymptomatic), enrolled in the first 3 weeks of life, and followed for 3 years to assess emergence of late-onset SNHL. The biosignatures of symptomatic and asymptomatic cCMVi are indistinguishable, suggesting that immune responses of infants with asymptomatic and symptomatic cCMVi are not different. Random forest analyses of initial samples in infants with cCMVi, irrespective of their clinical classification, identify a 16-gene classifier signature associated with the development of SNHL with 92% accuracy, suggesting its potential value as a biomarker.

A Targeted Approach for Congenital Cytomegalovirus Screening Within Newborn Hearing Screening.

BACKGROUND AND OBJECTIVE: Congenital cytomegalovirus (cCMV) infection remains a leading cause of childhood hearing loss. Currently universal CMV screening at birth does not exist in the United States. An alternative approach could be testing infants who do not pass their newborn hearing screening (NHS) for cCMV. This study was undertaken to evaluate whether a targeted approach will identify infants with CMV-related sensorineural hearing loss (SNHL). METHODS: Infants born at 7 US medical centers received NHS and were also screened for cCMV while in the newborn nursery. Infants who tested positive for CMV received further diagnostic audiologic evaluations to identify or confirm hearing loss. RESULTS: Between 2007 and 2012, 99 945 newborns were screened for both hearing impairment and cCMV. Overall, 7.0% of CMV-positive infants did not pass NHS compared with 0.9% of CMV-negative infants (P < .0001). Among the cCMV infants who failed NHS, diagnostic testing confirmed that 65% had SNHL. In addition, 3.6% of CMV-infected infants who passed their NHS had SNHL confirmed by further evaluation during early infancy. NHS in this cohort identified 57% of all CMV-related SNHL that occurred in the neonatal period. CONCLUSIONS: A targeted CMV approach that tests newborns who fail their NHS identified the majority of infants with CMV-related SNHL at birth. However, 43% of the infants with CMV-related SNHL in the neonatal period and cCMV infants who are at risk for late onset SNHL were not identified by NHS.

Electrocochleography and intranasal allergen challenge as investigational tools in patients with inhalant allergy and Ménière's disease.

OBJECTIVES: To expand on a prior study investigating the relation between inhalant allergy and Ménière's disease using electrocochleography and to present data from five patients heretofore unmentioned in previous reports. STUDY DESIGN: Prospective study of five patients identified with Ménière's disease and inhalant allergy in the practices of two faculty otolaryngologists. METHODS: Patients were tested twice using electrocochleography: once as a baseline and again 20 minutes following intranasal challenge with the allergen to which they were most sensitive. RESULTS: Three patients had no prior history of immunotherapy, and all were found to have a >15% increase in summating potential (SP)/action potential (AP) ratio after antigen challenge. However, only one of these patients developed audiovestibular symptoms. Two patients had a history of immunotherapy. One of these patients was tested using three different antigens to which she was highly sensitive on skin testing, one of which provoked audiovestibular symptoms on environmental exposure. Postchallenge electrocochleography, however, demonstrated normal SP/AP ratios with only one antigen causing a >15% increase. The other patient had elevated SP/AP ratios both before and after challenge and developed no audiovestibular symptoms despite a >15% increase. CONCLUSIONS: Previous work using this investigational tool has identified that all patients with a normal electrocochleography were asymptomatic from an audiovestibular standpoint at the time of postchallenge testing. An elevated SP/AP was not reliably correlated with audiovestibular symptoms in this group of patients. Further investigation in this area will examine the utility of using the variability of the SP and AP to predict audiovestibular symptoms.

Newborn hearing screening and detection of congenital cytomegalovirus infection.

OBJECTIVES: The objectives were to determine the frequency of congenital cytomegalovirus infection among newborns who did not pass hearing screening tests or had confirmed hearing loss and to determine how often abnormal hearing screening results were the only manifestation of congenital cytomegalovirus infection. METHODS: Retrospective chart review was performed for newborns who had abnormal hearing screening results and positive urine cytomegalovirus culture results at Parkland Memorial Hospital between September 1, 1999, and August 31, 2004. RESULTS: During the 5-year study period, 572 of 79047 newborns (7 of 1000 live births) did not pass hearing screening tests. Cytomegalovirus infection was identified in 24 (5%) of 483 tested infants and 16 (6%) of the 256 infants with subsequently confirmed hearing impairment. Of those 16 infants, 12 (75%) were identified as having congenital cytomegalovirus infection only because of failure to pass newborn hearing screening tests. CONCLUSIONS: Congenital cytomegalovirus infection was present for 6% of newborns with confirmed hearing impairment, and the majority of those infants were identified on the basis of abnormal newborn hearing screening results.

The Parkland Memorial Hospital experience in ensuring compliance with Universal Newborn Hearing Screening follow-up.

OBJECTIVE: Reduce false-positive results and loss to follow-up through systematic modifications in Universal Newborn Hearing Screening at a large public hospital. STUDY DESIGN: During a pilot program, neonates who failed technician-performed automated auditory brain stem response were scheduled for diagnostic evaluation. In year 1, audiologists rescreened neonates who failed, and those who did not pass were screened as outpatients. For years 2 through 4, neonates who failed were rescreened by technicians before inpatient audiology rescreening. RESULTS: For the pilot, 3759 neonates were screened; 1% (n = 43) failed and 44% (n = 19) were lost to follow-up. In year 1, 15,297 neonates were screened and 2% (n = 365) failed; audiology rescreening reduced this to <1% (n = 129). Outpatient rescreening yielded 0.5% (n = 70) who failed; 17% (n = 12) were lost to follow-up. In year 2, 16,384 neonates were screened, 3% (n = 456) failed, and 1% (n = 167) failed after technician rescreen; audiology rescreening reduced inpatient fails to 0.6% (n = 108), and 0.4% (n = 61) failed outpatient rescreening; 11% (n = 7) were lost to follow-up. Results for years 3 and 4 were similar to year 2, with further reduction in loss to follow-up to 11% (n = 6) and 1.7% (n = 1). CONCLUSIONS: Successful Universal Newborn Hearing Screening with reduced false-positive results and loss to follow-up can be accomplished with a planned schedule of inpatient rescreens and outpatient rescreening at the birthing facility.