ArticleAntimicrobial agents and chemotherapy2015
Amikacin Concentrations Predictive of Ototoxicity in Multidrug-Resistant Tuberculosis Patients.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 5 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
47 citing papers in PubMed, 5 syntheses or guidelines pooled it, 85 citations in OpenAlex.
- Hearing-Functioning Problems Across High-Burden Adult Health Conditions in Africa.International journal of environmental research and public health · 2026Pooled it
- Bibliometric analysis of global research on the clinical applications of aminoglycoside antibiotics: improving efficacy and decreasing risk.Frontiers in microbiology · 2025Pooled it
- Lesion Penetration and Activity Limit the Utility of Second-Line Injectable Agents in Pulmonary Tuberculosis.Antimicrobial agents and chemotherapy · 2021Pooled it
- Pooled it
- Increased risk of aminoglycoside-induced hearing loss in MDR-TB patients with HIV coinfection.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2018Pooled it
- Amikacin Liposome Inhalation Suspension forAnnals of the American Thoracic Society · 2021Trial
- Effect of Coadministration of Lidocaine on the Pain and Pharmacokinetics of Intramuscular Amikacin in Children With Multidrug-Resistant Tuberculosis: A Randomized Crossover Trial.The Pediatric infectious disease journal · 2018Trial
- Fractal Geometry-Based Decrease in Trimethoprim-Sulfamethoxazole Concentrations in Overweight and Obese People.CPT: pharmacometrics & systems pharmacology · 2016Trial
- Tobramycin pharmacokinetic and pharmacodynamic targets in people with cystic fibrosis.British journal of clinical pharmacology · 2026Review
- Amikacin exposure in MDR-TB patients in Uganda: Revisiting old drugs in a new era of resistance - A pharmacokinetic assessment.New microbes and new infections · 2026Article
- Preclinical evaluation of epetraborole in the hollow fibre system model of Mycobacterium abscessus lung disease.The Journal of antimicrobial chemotherapy · 2026Article
- Mechanisms, prevention, and management of aminoglycoside-induced hearing loss in neonates and children: a translational review.Frontiers in pharmacology · 2026Review
- High-dose amikacin in the first week of all-oral rifampicin-resistant TB treatment is safe: a single-arm trial.IJTLD open · 2025Article
- Article
- Case report of peritoneal dialysis-associated peritonitis caused byASM case reports · 2025Article
- Imipenem Pharmacokinetics/Pharmacodynamics in Preclinical Hollow Fiber Model, Dose Finding in Virtual Patients, and Clinical Evidence of Efficacy for Mycobacterium abscessus Lung Disease.The Journal of infectious diseases · 2025Article
- An Update on the Clinical Management of HIV and Tuberculosis Co-Infection in Pregnancy: TB Preventative Therapy, Long-Acting ARVs, and Bedaquiline-Based Regimens.Current HIV/AIDS reports · 2025Review
- A modified BPaL regimen for tuberculosis treatment replaces linezolid with inhaled spectinamides.eLife · 2024Article
- Omadacycline pharmacokinetics/pharmacodynamics and efficacy against multidrug-resistantAntimicrobial agents and chemotherapy · 2024Article
- Time-dependent pharmacodynamics of amikacin onMicrobiology spectrum · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 5 institutions in 4 countries.
Funding
Abstract
Aminoglycosides, such as amikacin, are used to treat multidrug-resistant tuberculosis. However, ototoxicity is a common problem and is monitored using peak and trough amikacin concentrations based on World Health Organization recommendations. Our objective was to identify clinical factors predictive of ototoxicity using an agnostic machine learning method. We used classification and regression tree (CART) analyses to identify clinical factors, including amikacin concentration thresholds that predicted audiometry-confirmed ototoxicity among 28 multidrug-resistant pulmonary tuberculosis patients in Botswana. Amikacin concentrations were measured for all patients. The quantitative relationship between predictive factors and the probability of ototoxicity were then identified using probit analyses. The primary predictors of ototoxicity on CART analyses were cumulative days of therapy, followed by cumulative area under the concentration-time curve (AUC), which improved on the primary predictor by 87%. The area under the receiver operating curve was 0.97 on the test set. Peak and trough were not predictors in any tree. When algorithms were forced to pick peak and trough as primary predictors, the area under the receiver operating curve fell to 0.46. Probit analysis revealed that the probability of ototoxicity increased sharply starting after 6 months of therapy to near maximum at 9 months. A 10% probability of ototoxicity occurred with a threshold cumulative AUC of 87,232 days · mg · h/liter, while that of 20% occurred at 120,000 days · mg · h/liter. Thus, cumulative amikacin AUC and duration of therapy, and not peak and trough concentrations, should be used as the primary decision-making parameters to minimize the likelihood of ototoxicity in multidrug-resistant tuberculosis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.