Exploration of the relationship between cumulative exposure to tobramycin and ototoxicity in patients with cystic fibrosis.

BACKGROUND: Aminoglycosides (AGs), such as tobramycin, are essential antibiotics in the management of pulmonary infections in patients with cystic fibrosis (CF). They induce ototoxicity without the relationship being clearly described in the literature. Our aim is to propose a mathematical and statistical model describing the relationship between the estimated cumulative exposure (Area Under the Curve, AUC) to tobramycin and ototoxicity with audiogram interpretation in young patients with CF. METHODS: Cumulative AUCs were estimated for each course of tobramycin, for the 106 individuals with CF (between 4 and 22 years of age) enrolled in this retrospective study (35 who had received IV tobramycin, 71 controls). Mean hearing loss was calculated for each audiogram and a statistical model was developed to predict hearing loss. RESULTS: The model confirms a significant relationship between cumulative tobramycin exposure and changes in hearing acuity: Meanhearingloss=2.7+(3×10-5)×AUC_tobramycin+individual_susceptibility However, the ototoxic effect is not clinically perceptible (mean hearing loss: 3.8 dB). The impact of AUC on hearing loss is minor in these subjects who received a limited number of courses of tobramycin (median: 5 courses). CONCLUSION: A significant relationship between cumulative exposure to tobramycin and ototoxicity was demonstrated. Individual treatment susceptibility should not be overlooked. As ototoxicity is not clinically perceptible in the study subjects, hearing tests should be continued during adulthood to provide individualized medical guidance and to obtain a lifetime analysis of the relationship between exposure and hearing loss.

Main outcomes from the first 2 years of France's screening programme for neonatal permanent hearing loss through a descriptive study.

AIM: This study aimed to evaluate the implementation of France's neonatal hearing loss screening programme years after its launch, and to estimate permanent bilateral neonatal hearing loss (PBNHL) prevalence and distribution by severity. METHODS: This descriptive study used aggregated regional data on all births in France in 2015-2016. Screening coverage, refusal rate, positive predictive value (PPV), proportion of children with suspected PBNHL, PBNHL prevalence and distribution by severity were calculated. RESULTS: Eight hundred thousand neonates were eligible for the screening programme per year. Between 2015 and 2016, screening coverage increased (83.3% vs. 93.8%; p < 0.001), and the refusal rate remained stable (0.1%). In 2016, when considering the additional tests performed several weeks after birth, the proportion of suspected PBNHL neonates decreased (1.4% vs. 0.9%) while the PPV increased (4.7% vs. 7.6%). In 2015, the estimated prevalence of PBNHL (moderate to profound) was 0.09% (95% CI 0.08-0.10). Among neonates with >= 41 decibels deficit, 56.8%, 16.6%, and 26.6% had moderate, severe and profound hearing loss, respectively. CONCLUSION: The national target of 90% screening coverage was exceeded. The additional test could be useful to avoid overcrowding in diagnostic structures. Diagnostic data quality must be improved to confirm PBNHL prevalence and distribution by severity.

Nontuberculous lymphadenitis in children: What management strategy?

OBJECTIVES: Nontuberculous mycobacterial (NTM) lymphadenitis is a rare disease of children under 5 years. Its treatment is not standardized, even a "wait-and-see" approach is shown to be effective in the literature. Here, we discuss the diagnostic and therapeutic strategies employed in our departments. METHODS: Records of pediatric patients treated for NTM cervical lymphadenitis from 2010 to 2015 in our tertiary center were retrospectively reviewed. Patients underwent cervical echotomography and/or CT scan. Every patient but one had microbiological explorations (NTM polymerase chain reaction [PCR] and culture) on fine needle aspiration of pus and/or adenitis biopsy. Differential diagnoses (tuberculosis, cat scratch disease) were excluded with serologies, chest X-Ray, and PCR on adenitis samples. Patients were classified as "proven diagnosis" (NTM detected), "highly probable" (suggestive clinical and anatomopathological aspect) or "possible" infection (suggestive adenitis alone). Treatments, follow-up and adverse events were reviewed. RESULTS: Thirty-one patients were treated for NTM, median age 2.40 years (Interquartile Range IQR = [1.85-3.16]). Twenty-nine patients (96.77%) had an isolated cervico-facial localization. Median follow-up was 8.00 months (IQR = [4.20-13.43]). We found 17 "proven diagnosis" (58.62%), 5 "highly probable" (17.24%) and 7 "possible" infections (24.14%). "Proven" infections were due to: Mycobacterium avium (n = 12, 66.67%) and M. intracellulare (n = 5, 27.78%). All 29 patients received antibiotics, which were effective for 10 (34.48%, group 1); 10 underwent surgical excision for a poor outcome with antibiotics (34.48%, group 2); spontaneous or surgical drainage occurred in 9 on antibiotics (31.03%, group 3). The median times to resolution for group 1, 2 and 3 were respectively 6.33 months, 6.22 months and 9.53 months. Antibiotics treatment was mostly clarithromycin (n = 27, 93.10%) and/or rifampicin (n = 19, 65.52%); 18 patients (62.07%) received both. Median antibiotics duration was 6.23 months (IQR = [5.17-7.46]), with good compliance (79.31%). The observed adverse effects were 3 (13.04%) isolated transient transaminase elevations, 1 case (4.35%) of minor creatinine elevation, and 1 case (4.35%) of transient diarrhea. Surgical drainage caused 1 transient marginal mandibular nerve palsy, resolutive after 1 month. CONCLUSION: Antibiotics in NTM adenitis lead to resolution in 7 months, with good tolerance and compliance. The efficacy of "wait-and-see" attitude in the literature make excision surgery a second line treatment.

Association of the Duration of Antibiotic Therapy With Major Surgical Site Infection in Cochlear Implantation.

Importance: Infection after cochlear implantation is a rare but serious event that can lead to meningitis. There is no consensus on prevention of infection in these patients, and each center applies its own strategy. Objective: To describe the rates of major surgical site infection for patients undergoing cochlear implantation who receive prolonged antibiotic treatment compared with those who receive a single perioperative dose of antibiotic prophylaxis. Design, Setting, and Participants: Retrospective cohort study of patients who underwent cochlear implantation between January 1, 2011, and July 8, 2015, with a postoperative follow-up of 1 to 3 years. In this multicenter study at 8 French university centers, 1180 patients (509 children and 671 adults) who underwent cochlear implantation during this period were included. Interventions: Prolonged antibiotic treatment vs single-dose antibiotic prophylaxis. Main Outcomes and Measures: Major infection and explantation. Results: Among 1180 patients (509 children [51.7% female] with a mean [SD] age of 4.6 [3.8] years and 671 adults [54.9% female] with a mean [SD] age of 54.8 [17.0] years), 12 patients (1.0%) developed a major infection, with 4 infections occurring in the prolonged antibiotic treatment group and 8 infections occurring in the antibiotic prophylaxis group (odds ratio, 2.45; 95% CI, 0.73-8.17). Children (9 of 509 [1.8%]) were more likely to develop infection than adults (3 of 671 [0.4%]). Among children, 4 infections occurred in the prolonged antibiotic group (n = 344), and 5 infections occurred in the antibiotic prophylaxis group (n = 158) (odds ratio, 2.78; 95% CI, 0.74-10.49). Among adults, 3 infections occurred in the antibiotic prophylaxis group (n = 365), whereas no infections occurred in the prolonged antibiotic treatment group (n = 290). Conclusions and Relevance: After cochlear implantation, infection was rare, was less common among those who received prolonged antibiotic treatment, and was less likely to occur in adults than in children.