The Safety Profile of Single Daily Dose of Aminoglycosides in Comparison with Multiple Daily Dose

To review the feasibility and effectiveness of single daily dosing of lithium in patients with affective disorder and to discuss advantages and disadvantages of this schedule of administration. A comprehensive search of the literature was conducted using a combination of electronic databases and a search of reference lists and relevant journals. English-language articles were selected for the review if they discussed the issues comparing multiple and single daily dosing schedules of lithium. We found 9 comparative studies. Single daily dosing of lithium causes transient higher peak lithium concentrations; however, no comparative study revealed a significant difference in side effects between multiple and single daily dosing groups. Numerous reports concluded that taking lithium in a single dose prevents, or at least limits, the increase in urine output (and the reduction of osmolality) and subsequent thirst. There is no evidence that a single lithium dosing schedule preserves glomerular function. According to the presented data, it could be reasonable to use lithium as a single evening dose in patients who can tolerate this schedule because no studies have suggested any benefit from administration of multiple daily doses. Possible advantages of single daily dosing, especially in improved compliance, could not be veiled by disadvantages of transient and mild postabsorptive side effects.

Despite several decades of research, there is still uncertainty regarding the optimal lithium dosage regimen associated with a decreased risk of renal effects, such as polyuria, in patients with bipolar affective disorder. We present an updated review of the literature to provide an informed dosing regimen recommendation for prescribers. Major databases MEDLINE and Embase were searched using terms, such as lithium, drug administration schedule, dose-response relationship, once daily, twice daily, and sustained release. In addition, the bibliographies of related publications were manually searched. A total of 20 trials were included. Some trials showed a reduction in urine volume with single daily dosing (SDD), while others showed no change. The only trial evaluating patients newly started on lithium found a reduction in urinary frequency with SDD after 21 days. Trials examining renal biopsy results found that multiple daily doses were associated with more pathologic damage to the kidneys. SDD regimens were generally well tolerated, and no reduction in efficacy was noted in any of the trials. The available evidence is contradictory as to whether SDD of lithium reduces polyuria; however, no trial has demonstrated any downfall of SDD in terms of prophylactic efficacy or adverse effects. Given the added benefits of SDD, such as improved compliance, we recommend patients newly started on lithium should be converted to a SDD of lithium at bedtime once an appropriate daily dose is determined.

Administration of antidepressants: Single versus split dosing: a meta-analysis

To review insights gained from a 21-year experience with gentamicin-induced vestibulotoxicity including differences in vestibulotoxicity between single daily dosing (SDD) and multiple daily dosing (MDD) regimens. Retrospective case series. Tertiary care center. Patients with gentamicin vestibulotoxicity referred to the Hertz Multidisciplinary Neurotology Clinic between January 1993 and September 2014. None. Spectrum of vestibular dysfunction measured using videonystagmography, vestibular evoked myogenic potentials, video head impulse testing, and magnetic scleral search coil testing. Of 53 patients with gentamicin-induced vestibulotoxicity, 24 received SDD and 29 received MDD treatment. The most common indications for treatment were sepsis, endocarditis, and osteomyelitis. Angular acceleration receptor function (semicircular canals) was more commonly affected than linear acceleration receptor function (otolithic organ of the saccule; 100% vs. 62%). A significant proportion of patients (53%) developed vestibulotoxicity in the absence of nephrotoxicity and 40% experienced vestibulotoxicity in a delayed fashion up to 10 days posttreatment cessation (mean 3.9 ± 0.7). Therapeutic monitoring did not necessarily prevent delayed vestibulotoxicity. Nephrotoxicity was less common for SDD compared with MDD (60% vs. 35%, p = 0.01). However, the SDD group experienced vestibulotoxicity at a lower cumulative dose (6.3 vs. 7.0 g, p = 0.04) and shorter duration of therapy (20.7 vs 29.4 d, p = 0.02). Our study further highlights important insights regarding gentamicin-induced vestibulotoxicity. While SDD is associated with decreased risk for nephrotoxicity compared with MDD, it confers a higher risk for vestibulotoxicity.

β-lactam antibiotic versus combined β-lactam antibiotics and single daily dosing regimens of aminoglycosides for treating serious infections: A meta-analysis

Lithium has been reported to induce polyuria in up to 35% of patients receiving it. It has been suggested that polyuria may be reduced by using single rather than multiple daily dosing. However, this information is based on non-randomized studies, which used higher serum lithium levels than are currently used. In fact, the incidence of polyuria may be lower at currently used lithium levels, and the benefits of a single daily dose regimen on urine volume at these levels have not been assessed. We conducted a prospective randomized study to test the hypothesis that switching patients from multiple daily dose lithium to single daily dose lithium would significantly lower urine volume. Twenty-four patients previously stabilized on multiple daily dosing were randomly allocated to either single or multiple daily dose lithium. Twenty-four-hour urine volume, serum creatinine, creatinine clearance and serum lithium were measured at study entry and completion. Switching to single daily dose lithium did not significantly reduce the 24-h urine volume.

Background/Aim. High adherence to angiotensin- converting-enzyme inhibitors in newly diagnosed hypertensive patients reduces the risk of cardiovascular complications. The aim of this pilot study was to assess the adherence level in patients by Morisky-8 item scale and to determine whether it is different if the medicine is taken in single or multiple daily doses. Methods. In this study 51 hypertensive patient (60.8% women) on monotherapy with angiotensin- converting-enzyme (ACE) inhibitor was included, categorized into two groups (A and B) based on the number of daily doses that were used in therapy. On the basis of the results of Morisky-8 scale, the patients were categorized in 3 subgroups. The patients that had a score on the Morisky-8 item scale > 2 were categorized as low adherent, those with a score of 1 or 2 were medium adherent and those with Morisky score zero were categorized as highly adherent. Results. According to the Morisky-8 scale, from the total number of respondents 51% were categorized as low adherent, 31.4% as medium adherent and 17.6% were categorized as highly adherent; the average value of the Morisky-8 score was 2.8±2.3 points. Group A (patients who were taking medication divided into multiple daily doses) consisted of 83.3% low adherent, 12.5% medium adherent and 4.2% highly adherent patients, and the average score was 4.42±1.9 points. In the group B (patients who were taking their medication in a single daily dose) 22.2% were low adherent, 48.1% medium adherent and 29.7% highly adherent patients; the average score was 1.37±1.4 points. The average Morisky-8 scale scores of the examined groups were significantly different (p-value<0.0001). Conclusion. The results show that more than half of the patients have low levels of adherence. Comparing groups A and B, we found that adherence was lower in group A, which may indicate that the level of adherence is higher if the drug is used in a single daily dose.

BACKGROUNDThe Centers for Disease Control and Prevention estimate that Clostridioides difficile (C. difficile) causes half a million infections (CDI) annually and is a major cause of total infectious disease death in the United States, causing inflammation of the colon and potentially deadly diarrhea. We recently reported the isolation of ADS024, a Bacillus velezensis (B. velezensis) strain, which demonstrated direct in vitro bactericidal activity against C. difficile, with minimal collateral impact on other members of the gut microbiota. In this study, we hypothesized that in vitro activities of ADS024 will translate in vivo to protect against CDI challenge in mouse models.AIMTo investigate the in vivo efficacy of B. velezensis ADS024 in protecting against CDI challenge in mouse models.METHODSTo mimic disruption of the gut microbiota, the mice were exposed to vancomycin prior to dosing with ADS024. For the mouse single-dose study, the recovery of ADS024 was assessed via microbiological analysis of intestinal and fecal samples at 4 h, 8 h, and 24 h after a single oral dose of 5 × 108 colony-forming units (CFU)/mouse of freshly grown ADS024. The single-dose study in miniature swine included groups that had been pre-dosed with vancomycin and that had been exposed to a dose range of ADS024, and a group that was not pre-dosed with vancomycin and received a single dose of ADS024. The ADS024 colonies [assessed by quantitative polymerase chain reaction (qPCR) using ADS024-specific primers] were counted on agar plates. For the 28-d miniature swine study, qPCR was used to measure ADS024 levels from fecal samples after oral administration of ADS024 capsules containing 5 × 109 CFU for 28 consecutive days, followed by MiSeq compositional sequencing and bioinformatic analyses to measure the impact of ADS024 on microbiota. Two studies were performed to determine the efficacy of ADS024 in a mouse model of CDI: Study 1 to determine the effects of fresh ADS024 culture and ADS024 spore preparations on the clinical manifestations of CDI in mice, and Study 2 to compare the efficacy of single daily doses vs dosing 3 times per day with fresh ADS024. C. difficile challenge was performed 24 h after the start of ADS024 exposure. To model the human distal colon, an anerobic fecal fermentation system was used. MiSeq compositional sequencing and bioinformatic analyses were performed to measure microbiota diversity changes following ADS024 treatment. To assess the potential of ADS024 to be a source of antibiotic resistance, its susceptibility to 18 different antibiotics was tested.RESULTSIn a mouse model of CDI challenge, single daily doses of ADS024 were as efficacious as multiple daily doses in protecting against subsequent challenge by C. difficile pathogen-induced disease. ADS024 showed no evidence of colonization based on the observation that the ADS024 colonies were not recovered 24 h after single doses in mice or 72 h after single doses in miniature swine. In a 28-d repeat-dose study in miniature swine, ADS024 was not detected in fecal samples using plating and qPCR methods. Phylogenetic analysis performed in the human distal colon model showed that ADS024 had a selective impact on the healthy human colonic microbiota, similarly to the in vivo studies performed in miniature swine. Safety assessments indicated that ADS024 was susceptible to all the antibiotics tested, while in silico testing revealed a low potential for off-target activity or virulence and antibiotic-resistance mechanisms.CONCLUSIONOur findings, demonstrating in vivo efficacy of ADS024 in protecting against CDI challenge in mouse models, support the use of ADS024 in preventing recurrent CDI following standard antibiotic treatment.

Background: Bacterial sepsis is highly prevalent among premature infants. Amikacin is an antibiotic widely recommended for the treatment of neonatal sepsis, one of the consequences of which might be nephrotoxicity. The present study aimed to compare the efficacy and nephrotoxicity of multiple daily dosing (MDD) and once-daily dosing (ODD) of amikacin in preterm infants suspected of sepsis. Methods: This triple-blind, randomized, controlled clinical trial was conducted on 40 premature infants suspected of sepsis, who were randomly divided into two groups. In addition to ampicillin, one group was administered with the standard daily dose, and the other group received an ODD of intravenous amikacin. Maximum and minimum serum levels of amikacin and urine neutrophil gelatinase-associated lipocalin (NGAL) were measured in both groups. Data were extracted and analyzed based on the research hypothesis and literature review. Results: No significant differences were observed between the study groups in terms of gender, gestational age, mode of delivery, birth weight, and Apgar score. After the intervention, mean plasma creatinine reduced in both groups, while the mean reduction was significantly higher in the group administered with the ODD of amikacin (P=0.0001). However, mean changes in the urine NGAL had no significant difference between the groups (P=0.635). Minimum and maximum serum levels of amikacin in the study groups indicated a more significant reduction in mean level of the infants administered with the ODD of amikacin compared to the MDD group (P=0.0001). Conclusion: Considering the higher maximum and lower minimum levels of amikacin in the neonates receiving the daily dosage regimen, it seems that this regimen is more effective in the treatment of sepsis in preterm infants. Moreover, no significant difference was observed in the efficacy and nephrotoxicity of the daily amikacin dosing in the premature infants suspected of sepsis compared to those treated by multiple doses of amikacin.

A double-blind study of the efficacy and safety of multiple daily doses of amikacin versus one daily dose for children with perforated appendicitis in Costa Rica

Investigators conducting clinical trials may have trouble replicating in ill patients results obtained in tightly controlled models of efficacy and toxicity that use healthy animals [1]. Trials of single daily dosing (SDD) of aminoglycosides (also known as once-daily aminoglycoside therapy) vs. multiple daily dosing (MDD) are a good example. The rationale for SDD therapy is clear [1]: SDD of aminoglycosides results in high peak serum concentrations that enhance the concentrationdependent bactericidal activity of these drugs against susceptible aerobic gram-negative bacilli. Aminoglycosides have a postantibiotic effect (PAE) that is longer when the peak drug level is higher. SDD results in the absence of detectable drug in serum for several hours at the end of a dosage interval, whereas the drug remains detectable with MDD. Because of the PAE, this drug-free period does not appear to compromise antibacterial efficacy (although it may be compromised in cases of infective endocarditis). The clearance of aminoglycosides from serum has two advantages, including a lower risk of nephrotoxicity and ototoxicity and a reduced likelihood that adaptive resistance to the drug might occur [2-5]. Hence, the clinical assessment of SDD vs. MDD of aminoglycosides requires documentation that the patients randomized to SDD have high peak levels and low (<1 ag/mL) or undectable drug levels for several hours at the end of the 24-hour dosage interval.

Man has been fighting diseases for centuries. One of the major battles is against microorganisms and diseases they cause. A health education course was organized on prescribing aminoglycoside antibiotics and postantibiotic effect. The aim of the course was to change the prescription habits in our colleagues. The postantibiotic effect of aminoglycoside antibiotics as well as impact of subinhibiting doses on duration of postantibiotic effect requires modification of previous therapeutic protocols. Single daily dose has the same or even greater effect than multiple daily doses. The toxicity of aminoglycosides is not increased and remains the same or smaller in single daily regimens. The single daily dose regimen of aminoglycosides has been used in 63.6% of cases in Clinic for Infectious Diseases of the Clinical Center of Novi Sad, 41.2% in Outpatient Health Care Center of Novi Sad "Liman" and this regimen has not been used in General Practice Department, Children's Health Care Department and Ear, Nose and Throat Clinic at all. The twice daily regimen has been used instead. Doctors are aware of the postantibiotic effect, but vast majority are still bound to their old habits in regard to prescribing antibiotics. Our educational course failed to achieve its goal.

TherapeuticsJuly 1, 1996Meta-analysis: A single daily dose of aminoglycosides is as effective as multiple daily dosing with less nephrotoxicityPeter S. Millard, MD, PhDPeter S. Millard, MD, PhDFamily Practice Residency Program, Bangor, Maine, USA (P.S.M.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-1996-125-1-010 SectionsAboutFull Text ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinkedInRedditEmail Source CitationBarza M, Ioannidis JP, Cappelleri JC, Lau J. Single or multiple daily doses of aminoglycosides: a meta-analysis. BMJ. 1996 Feb 10;312:338-45. https://pubmed.ncbi.nlm.nih.gov/8611830References1 Levison ME. New dosing regimens for aminoglycoside antibiotics. Ann Intern Med. 1992;117:693-4. Google Scholar2 Hatala R, Dinh TT, Cook DJ. Single daily dosing of aminoglycosides in immunocompromised adults: a systematic review. Clin Infect Dis. 1997;24:810-5. Google Scholar3 Tan K, Bunn H. Once daily versus multiple daily dosing with intravenous aminoglycosides for cystic fibrosis. Cochrane Database Syst Rev. 201(2):CD002009 (latest version 18 Aug 2000.) Google Scholar Author, Article, and Disclosure InformationAffiliations: Family Practice Residency Program, Bangor, Maine, USA (P.S.M.) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails July 1, 1996Volume 125, Issue 1Page: 10KeywordsAntibioticsClinical trialsCreatinineDatabasesDrugsEpidemiologyInformation storage and retrievalProphylaxisPseudomonas infectionsSystematic reviewsToxicity ePublished: 9 March 2020 Issue Published: July 1, 1996 Copyright & PermissionsCopyright © 1996 by American College of Physicians. All Rights Reserved.Loading ...

SummaryTwo open studies were carried out on hypertensive patients to assess the effectiveness of treatment with pindolol on a single daily dose regimen. In a multi-centre trial, 57 patients whose blood pressures were being adequately controlled by multiple daily doses of a beta-blocker were changed over to a single daily dose of pindolol (mean 13 mg, range 10 mg to 20 mg) and treated over a 9-month period. Satisfactory control could not be maintained in 4 patients. In the 44 patients completing the study, however, no significant differences from baseline values were noted in systolic and diastolic pressures or heart rate on once daily pindolol.In the second trial lasting 4 months, 16 previously untreated patients started therapy on 5 mg pindolol as a single daily dose and this was increased in stages up to a maximum of 20 mg, as necessary, to achieve adequate blood pressure control. Only 2 patients failed to respond satisfactorily on this dosage regimen, and these did so when a diuretic was subsequently added to their treatment. Few side-effects were reported ineither study.

For many years it has been standard practice to give aminoglycosides in divided daily doses monitored by serum aminoglycoside assays. Recent experience indicates that aminoglycosides can be given as a single daily dose with equal or better efficacy and equal or less toxicity. The single-daily dose regimen is both cheaper and more convenient. Recommended serum aminoglycoside concentrations immediately before the next dose, or 8 h later, vary according to whether a single daily dose or divided dose schedule is used. This is seldom realized in practice. Estimated creatinine clearance enables better prediction of the daily dose than was formerly recognized, and is to be preferred. Earlier fears of giving aminoglycosides as a bolus intravenous injection have not been substantiated. After more than 40 years of use, we are beginning to learn how to monitor these potentially toxic drugs.