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The Journal of Antimicrobial... Oct 2016The objectives of this study were to identify the amikacin dosage regimens and drug concentrations consistent with good outcomes and to determine the drug exposures... (Review)
Review
OBJECTIVES
The objectives of this study were to identify the amikacin dosage regimens and drug concentrations consistent with good outcomes and to determine the drug exposures related to nephrotoxicity and ototoxicity.
METHODS
A literature review was conducted in Medline, EMBASE and the Cochrane Central Register of Controlled Trials. Full journal articles reporting randomized controlled trials, controlled clinical trials, interrupted time series trials, and controlled before and after studies involving amikacin therapeutic drug monitoring (TDM) and dose adjustment were considered for inclusion.
RESULTS
Seventeen studies for inclusion were identified, comprising 1677 participants. Amikacin doses ranged from 11 to 15 mg/kg/day with 13 studies using 15 mg/kg/day. Studies were generally designed to compare different aminoglycosides rather than to assess concentration-effect relationships. Only 11 papers presented data on target concentrations, rate of clinical cure and toxicity. Target peak concentrations ranged from 15 to 40 mg/L and target troughs were typically <10 or <5 mg/L. It was not clear whether these targets were achieved. Measured peaks averaged 28 mg/L for twice-daily dosing and 40-45 mg/L for once-daily dosing; troughs averaged 5 and 1-2 mg/L, respectively. Fifteen of the included studies reported rates of nephrotoxicity; auditory and vestibular toxicities were reported in 12 and 8 studies.
CONCLUSIONS
This systematic review found little published evidence to support an optimal dosage regimen or TDM targets for amikacin therapy. The use of alternative approaches, such as consensus opinion and a review of current practice, will be required to develop guidelines to maximize therapeutic outcomes and minimize toxicity with amikacin.
Topics: Adult; Amikacin; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Humans; Interrupted Time Series Analysis; Treatment Outcome
PubMed: 27494904
DOI: 10.1093/jac/dkw250 -
International Archives of... Jan 2022Chloroquine and hydroxychloroquine are antimalarial drugs widely used in the treatment of rheumatic diseases. With the global pandemic caused by the new coronavirus,... (Review)
Review
Chloroquine and hydroxychloroquine are antimalarial drugs widely used in the treatment of rheumatic diseases. With the global pandemic caused by the new coronavirus, there was an increase in the prescription of these drugs, which led to a major concern regarding their ototoxic effects. The objective of the present study was to assess existing scientific evidence about the toxic effects of chloroquine and hydroxychloroquine on the peripheral and/or central auditory system. A systematic literature review was performed by searching the PubMed (Medline), Scopus, Web of Science, LILACS, and SciELO electronic databases, in a search of articles that fullfiled the predefined inclusion and exclusion criteria. The review was conducted in three phases and, in all of them, analyses were performed by two independent researchers. Disagreements were discussed with a third researcher until a consensus was reached. A total of 437 articles were found and 8 were included in this review. Seven of the included studies reported hearing loss in their samples and presented a diagnostic hypothesis of ototoxicity induced by chloroquine or hydroxychloroquine. The most common type of hearing loss was sensorineural, with varying laterality and degrees of severity. The most frequently used audiological test was pure tone audiometry, and only two studies assessed brainstem evoked responses. The scientific evidence compiled in this research showed that chloroquine and hydroxychloroquine have an ototoxic effect in the peripheral auditory system. These drugs can cause cochlear damage, including changes in the stria vascularis and lesions in sensory hair cells.
PubMed: 35096175
DOI: 10.1055/s-0041-1740986 -
The Cochrane Database of Systematic... May 2021Neonatal sepsis is a major cause of morbidity and mortality. It is the third leading cause of neonatal mortality globally constituting 13% of overall neonatal mortality....
BACKGROUND
Neonatal sepsis is a major cause of morbidity and mortality. It is the third leading cause of neonatal mortality globally constituting 13% of overall neonatal mortality. Despite the high burden of neonatal sepsis, high-quality evidence in diagnosis and treatment is scarce. Possibly due to the diagnostic challenges of sepsis and the relative immunosuppression of the newborn, many neonates receive antibiotics for suspected sepsis. Antibiotics have become the most used therapeutics in neonatal intensive care units. The last Cochrane Review was updated in 2004. Given the clinical importance, an updated systematic review assessing the effects of different antibiotic regimens for early-onset neonatal sepsis is needed.
OBJECTIVES
To assess the beneficial and harmful effects of different antibiotic regimens for early-onset neonatal sepsis.
SEARCH METHODS
We searched the following electronic databases: CENTRAL (2020, Issue 8); Ovid MEDLINE; Embase Ovid; CINAHL; LILACS; Science Citation Index EXPANDED and Conference Proceedings Citation Index - Science on 12 March 2021. We searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs.
SELECTION CRITERIA
We included RCTs comparing different antibiotic regimens for early-onset neonatal sepsis. We included participants from birth to 72 hours of life at randomisation.
DATA COLLECTION AND ANALYSIS
Three review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. We used the GRADE approach to assess the certainty of evidence. Our primary outcome was all-cause mortality, and our secondary outcomes were: serious adverse events, respiratory support, circulatory support, nephrotoxicity, neurological developmental impairment, necrotising enterocolitis, and ototoxicity. Our primary time point of interest was at maximum follow-up.
MAIN RESULTS
We included five RCTs (865 participants). All trials were at high risk of bias. The certainty of the evidence according to GRADE was very low. The included trials assessed five different comparisons of antibiotics. We did not conduct any meta-analyses due to lack of relevant data. Of the five included trials one trial compared ampicillin plus gentamicin with benzylpenicillin plus gentamicin; one trial compared piperacillin plus tazobactam with amikacin; one trial compared ticarcillin plus clavulanic acid with piperacillin plus gentamicin; one trial compared piperacillin with ampicillin plus amikacin; and one trial compared ceftazidime with benzylpenicillin plus gentamicin. None of the five comparisons found any evidence of a difference when assessing all-cause mortality, serious adverse events, circulatory support, nephrotoxicity, neurological developmental impairment, or necrotising enterocolitis; however, none of the trials were near an information size that could contribute significantly to the evidence of the comparative benefits and risks of any particular antibiotic regimen. None of the trials assessed respiratory support or ototoxicity. The benefits and harms of different antibiotic regimens remain unclear due to the lack of well-powered trials and the high risk of systematic errors.
AUTHORS' CONCLUSIONS
Current evidence is insufficient to support any antibiotic regimen being superior to another. Large RCTs assessing different antibiotic regimens in early-onset neonatal sepsis with low risk of bias are warranted.
Topics: Anti-Bacterial Agents; Bias; Cause of Death; Humans; Infant, Newborn; Neonatal Sepsis; Randomized Controlled Trials as Topic
PubMed: 33998666
DOI: 10.1002/14651858.CD013837.pub2 -
The Cochrane Database of Systematic... May 2021Neonatal sepsis is a major cause of morbidity and mortality. It is the third leading cause of neonatal mortality globally constituting 13% of overall neonatal mortality....
BACKGROUND
Neonatal sepsis is a major cause of morbidity and mortality. It is the third leading cause of neonatal mortality globally constituting 13% of overall neonatal mortality. Despite the high burden of neonatal sepsis, high-quality evidence in diagnosis and treatment is scarce. Due to the diagnostic challenges of sepsis and the relative immunosuppression of the newborn, many neonates receive antibiotics for suspected sepsis. Antibiotics have become the most used therapeutics in neonatal intensive care units, and observational studies in high-income countries suggest that 83% to 94% of newborns treated with antibiotics for suspected sepsis have negative blood cultures. The last Cochrane Review was updated in 2005. There is a need for an updated systematic review assessing the effects of different antibiotic regimens for late-onset neonatal sepsis.
OBJECTIVES
To assess the beneficial and harmful effects of different antibiotic regimens for late-onset neonatal sepsis.
SEARCH METHODS
We searched the following electronic databases: CENTRAL (2021, Issue 3); Ovid MEDLINE; Embase Ovid; CINAHL; LILACS; Science Citation Index EXPANDED and Conference Proceedings Citation Index - Science on 12 March 2021. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs.
SELECTION CRITERIA
We included RCTs comparing different antibiotic regimens for late-onset neonatal sepsis. We included participants older than 72 hours of life at randomisation, suspected or diagnosed with neonatal sepsis, meningitis, osteomyelitis, endocarditis, or necrotising enterocolitis. We excluded trials that assessed treatment of fungal infections.
DATA COLLECTION AND ANALYSIS
Three review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. We used the GRADE approach to assess the certainty of evidence. Our primary outcome was all-cause mortality, and our secondary outcomes were: serious adverse events, respiratory support, circulatory support, nephrotoxicity, neurological developmental impairment, necrotising enterocolitis, and ototoxicity. Our primary time point of interest was at maximum follow-up.
MAIN RESULTS
We included five RCTs (580 participants). All trials were at high risk of bias, and had very low-certainty evidence. The five included trials assessed five different comparisons of antibiotics. We did not conduct a meta-analysis due to lack of relevant data. Of the five included trials one trial compared cefazolin plus amikacin with vancomycin plus amikacin; one trial compared ticarcillin plus clavulanic acid with flucloxacillin plus gentamicin; one trial compared cloxacillin plus amikacin with cefotaxime plus gentamicin; one trial compared meropenem with standard care (ampicillin plus gentamicin or cefotaxime plus gentamicin); and one trial compared vancomycin plus gentamicin with vancomycin plus aztreonam. None of the five comparisons found any evidence of a difference when assessing all-cause mortality, serious adverse events, circulatory support, nephrotoxicity, neurological developmental impairment, or necrotising enterocolitis; however, none of the trials were near an information size that could contribute significantly to the evidence of the comparative benefits and risks of any particular antibiotic regimen. None of the trials assessed respiratory support or ototoxicity. The benefits and harms of different antibiotic regimens remain unclear due to the lack of well-powered trials and the high risk of systematic errors.
AUTHORS' CONCLUSIONS
Current evidence is insufficient to support any antibiotic regimen being superior to another. RCTs assessing different antibiotic regimens in late-onset neonatal sepsis with low risks of bias are warranted.
Topics: Amikacin; Ampicillin; Anti-Bacterial Agents; Aztreonam; Bias; Cefazolin; Clavulanic Acid; Drug Therapy, Combination; Floxacillin; Gentamicins; Humans; Infant, Newborn; Neonatal Sepsis; Randomized Controlled Trials as Topic; Ticarcillin; Vancomycin
PubMed: 33998665
DOI: 10.1002/14651858.CD013836.pub2 -
JAC-antimicrobial Resistance Dec 2021Ototoxicity has been reported after administration of aminoglycosides and glycopeptides. (Review)
Review
BACKGROUND
Ototoxicity has been reported after administration of aminoglycosides and glycopeptides.
OBJECTIVES
To identify available evidence for the occurrence and determinants of aminoglycoside- and glycopeptide-related ototoxicity in children.
MATERIALS AND METHODS
Systematic electronic literature searches that combined ototoxicity (hearing loss, tinnitus and/or vertigo) with intravenous aminoglycoside and/or glycopeptide administration in children were performed in PubMed, EMBASE and Cochrane Library databases. Studies with sample sizes of ≥50 children were included. The QUIPS tool and Cochrane criteria were used to assess the quality and risk of bias of included studies.
RESULTS
Twenty-nine aminoglycoside-ototoxicity studies met the selection criteria (including 7 randomized controlled trials). Overall study quality was medium/low. The frequency of hearing loss within these studies ranged from 0%-57%, whereas the frequency of tinnitus and vertigo ranged between 0%-53% and 0%-79%, respectively. Two studies met the criteria on glycopeptide-induced ototoxicity and reported hearing loss frequencies of 54% and 55%. Hearing loss frequencies were higher in gentamicin-treated children compared to those treated with other aminoglycosides. In available studies aminoglycosides had most often been administered concomitantly with platinum agents, diuretics and other co-medication.
CONCLUSIONS
In children the reported occurrence of aminoglycoside/glycopeptide ototoxicity highly varies and seems to depend on the diagnosis, aminoglycoside subtype and use of co-administered medication. More research is needed to investigate the prevalence and determinants of aminoglycoside/glycopeptide ototoxicity. Our results indicate that age-dependent audiological examination may be considered for children frequently treated with aminoglycosides/glycopeptides especially if combined with other ototoxic medication.
PubMed: 34917943
DOI: 10.1093/jacamr/dlab184 -
Otolaryngology--head and Neck Surgery :... Jun 2023The objective of this meta-analysis is to evaluate the impact of genetic polymorphisms on platinum-based chemotherapy (PBC)-induced ototoxicity. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The objective of this meta-analysis is to evaluate the impact of genetic polymorphisms on platinum-based chemotherapy (PBC)-induced ototoxicity.
DATA SOURCES
Systematic searches of PubMed, Embase, Cochrane, and Web of Science were conducted from the inception of the databases to May 31, 2022. Abstracts and presentations from conferences were also reviewed.
REVIEW METHODS
Four investigators independently extracted data in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Differences in the prevalence of PBC-induced ototoxicity between reference and variant (i) genotypes and (ii) alleles were analyzed. The overall effect size was presented using the random-effects model as an odds ratio (OR) with a 95% confidence interval (CI).
RESULTS
From 32 included articles, 59 single nucleotide polymorphisms on 28 genes were identified, with 4406 total unique participants. For allele frequency analysis, the A allele in ACYP2 rs1872328 was positively associated with ototoxicity (OR: 2.61; 95% CI: 1.06-6.43; n = 2518). Upon limiting to cisplatin use only, the T allele of COMT rs4646316 and COMT rs9332377 revealed significant results. For genotype frequency analysis, the CT/TT genotype in ERCC2 rs1799793 demonstrated an otoprotective effect (OR: 0.50; 95% CI: 0.27-0.94; n = 176). Excluding studies using carboplatin or concomitant radiotherapy revealed significant effects with COMT rs4646316, GSTP1 rs1965, and XPC rs2228001. Major sources of variations between studies include differences in patient demographics, ototoxicity grading systems, and treatment protocols.
CONCLUSION
Our meta-analysis presents polymorphisms that exert ototoxic or otoprotective effects in patients undergoing PBC. Importantly, several of these alleles are observed at high frequencies globally, highlighting the potential for polygenic screening and cumulative risk evaluation for personalized care.
Topics: Humans; Antineoplastic Agents; Ototoxicity; Platinum; Cisplatin; Polymorphism, Single Nucleotide; Xeroderma Pigmentosum Group D Protein; Acid Anhydride Hydrolases
PubMed: 36802061
DOI: 10.1002/ohn.222 -
Otology & Neurotology : Official... Mar 2019This study explores the current literature regarding associations between phosphodiesterase-5 (PDE-5) inhibitors and ototoxicity and provides a detailed summary and...
OBJECTIVE
This study explores the current literature regarding associations between phosphodiesterase-5 (PDE-5) inhibitors and ototoxicity and provides a detailed summary and discussion of the findings.
DATA SOURCES
A comprehensive electronic search of PubMed/MEDLINE, Scopus, and Cochrane Library for studies published from database inception through March 21, 2018.
STUDY SELECTION
Basic science articles, epidemiological studies, randomized controlled trials, cohort studies, case reports, reviews, meta-analyses, press releases, and newsletters were included. The PRISMA search strategy was used to select papers. Search terms are included in the appendix (http://links.lww.com/MAO/A733).
RESULTS
Twenty-two articles met the inclusion criteria. Among case reports, there were a total of nine patients, all male, with an average age of 57.4 years (37-79 years, SD = 13.87 years). Of the cases of hearing loss, 25% (2/8 cases) were bilateral and 75% (6/8) were unilateral; 22% (2/9) were associated with tinnitus; and 33% (3/9) had accompanying vestibular symptoms (including vertigo and dizziness). Among multipatient studies, all prospective studies failed to find a significant association between ototoxicity and PDE-5 inhibitor use. Results of the retrospective studies were also heterogeneous. Many key molecules in the PDE-5 inhibition pathway have been demonstrated to exist in the cochlea. However, mirroring the clinical studies, the basic science mechanisms have suggested both ototoxic and otoprotective effects.
CONCLUSIONS
Currently, the literature is inconclusive regarding the interaction between PDE-5 inhibitor use and ototoxicity. Future study such as a double-blinded placebo controlled randomized trial with audiometric assessment would provide more sound evidence. Similarly, a unified molecular model is necessary.
Topics: Adult; Aged; Hearing Disorders; Humans; Male; Middle Aged; Phosphodiesterase 5 Inhibitors
PubMed: 30741888
DOI: 10.1097/MAO.0000000000002148 -
Supportive Care in Cancer : Official... Oct 2023Immune checkpoint inhibitors (ICIs) are related to various immune-related adverse events (irAEs). However, the knowledge is limited with rare irAEs like hearing loss.... (Review)
Review
PURPOSE
Immune checkpoint inhibitors (ICIs) are related to various immune-related adverse events (irAEs). However, the knowledge is limited with rare irAEs like hearing loss. Therefore, we evaluated the characteristics, presentation, and treatment of ICI-related hearing loss by reviewing the individual patient data from the previous studies.
METHODS
We conducted a systematic search of the Web of Science, PubMed, and Embase databases for studies published until 17 November 2022. The selected MeSH search terms were "hearing loss" OR "hearing impairment" OR "ototoxicity" OR "vestibular toxicity" OR "audiovestibular toxicity" AND "immune checkpoint inhibitor" OR "immunotherapy."
RESULTS
A total of 38 patients were included. Melanoma was the most frequent diagnosis (73.7%). The median time from ICI initiation to hearing loss development was 3 months. The hearing impairment was secondary to bilateral sensorineural hearing loss (SNHL) in 24 (68.6%) patients, and at least one other irAE accompanied the hearing loss in 24 patients. Hearing loss significantly improved in 45.7% of the patients. The overall response rate and disease control rate were 67.6% and 85.3%, respectively.
CONCLUSION
We observed that most cases of ICI-related hearing loss were reversible, observed in patients with melanoma, accompanied by other irAEs, and associated with a high response rate to ICIs. With the expanded use of ICIs in the earlier treatment lines and adjuvant settings, the number of survivors with ICI-related hearing loss is expected to increase. Further research is needed to define the true prevalence of ICI-related hearing loss, optimal diagnosis, and management.
Topics: Humans; Immune Checkpoint Inhibitors; Antineoplastic Agents, Immunological; Melanoma; Hearing Loss; Retrospective Studies
PubMed: 37819422
DOI: 10.1007/s00520-023-08083-w -
Clinical Otolaryngology : Official... Jan 2024Ototoxicity is a common disabling side effect of platinum-based chemotherapy. This study aimed to assess the evidence on the management of platinum-induced ototoxicity... (Review)
Review
OBJECTIVES
Ototoxicity is a common disabling side effect of platinum-based chemotherapy. This study aimed to assess the evidence on the management of platinum-induced ototoxicity in adult cancer patients.
METHODS
Four databases were searched up to 1 November 2022. Original studies were included if they reported on a pharmacologic or non-pharmacologic intervention to prevent or treat platinum ototoxicity in adults. The articles' quality was assessed via two grading scales.
RESULTS
Nineteen randomised controlled trials and five quasi-experimental studies with 1673 patients were analysed. Eleven interventions were identified, nine pharmacological and two non-pharmacological. Six of the interventions (sodium thiosulphate, corticoids, sertraline, statins, multivitamins and D-methionine) showed mild benefits in preventing cisplatin-induced ototoxicity. Only one trial assessed corticoids as a potential treatment. Overall, only six trials were deemed with a low risk of bias. The majority of studies inadequately documented intervention-related adverse effects, thereby limiting safety conclusions.
CONCLUSIONS
Current interventions have mild benefits in preventing cisplatin-induced ototoxicity in adult cancer patients. Sodium thiosulphate is the most promising intervention as a preventive strategy. Rigorous, high-quality research is warranted, encompassing an evaluation of all potential symptoms and innovative treatment modalities.
Topics: Adult; Humans; Cisplatin; Antineoplastic Agents; Carboplatin; Ototoxicity; Hearing Loss; Neoplasms; Adrenal Cortex Hormones; Randomized Controlled Trials as Topic
PubMed: 37818931
DOI: 10.1111/coa.14106 -
Audiology Research Jul 2022This systematic review investigates ear cooling and cryotherapy in the prevention and treatment of inner ear damage and disease, within the context of animal models and... (Review)
Review
This systematic review investigates ear cooling and cryotherapy in the prevention and treatment of inner ear damage and disease, within the context of animal models and clinical studies. A literature search was carried out in the databases Pubmed and Cochrane Library. Ten studies were identified concerning the otoprotective properties of cryotherapy. Nine of these were rodent in vivo studies (mice, rats, gerbils, guinea pigs). One study involved human subjects and investigated cryotherapy in idiopathic sensorineural hearing loss. The studies were heterogeneous in their goals, methods, and the models used. Disorder models included ischemia and noise damage, ototoxicity (cisplatin and aminoglycoside), and CI-electrode insertion. All ten studies demonstrated significant cryotherapeutic otoprotection for their respective endpoints. No study revealed or expressly investigated otodestructive effects. While limited in number, all of the studies within the scope of the review demonstrated some degree of cryotherapeutic, otoprotective effect. These promising results support the conducting of further work to explore and refine the clinical applicability and impact of cryotherpeutics in otolaryngology.
PubMed: 35892664
DOI: 10.3390/audiolres12040038