Safety of intravenous tobramycin in combination with a variety of anti-pseudomonal antibiotics in children with cystic fibrosis

Animal studies report equal or greater clinical efficacy with once daily versus multiple daily aminoglycoside dosing; however, results are inconsistent. Extrapolation of these animal data to human data is difficult, since marked variability exists in terms of pharmacokinetic disposition of aminoglycosides. Human data suggest that once daily aminoglycoside dosing regimens are as effective as multiple dosing regimens. However, studies need to be performed assessing the efficacy of once daily aminoglycoside dosing for infectious sites other than intra-abdominal and the urinary tract. In addition, the results of these studies should not be extrapolated to those with renal dysfunction, the immunocompromised, or in patients with aminoglycoside treatment durations of greater than 8 days, as the efficacy of once daily dosing in these patient populations has not been proven. Animal studies assessing nephrotoxicity suggest that multiple daily aminoglycoside dosing results in more frequent or more severe nephrotoxicity compared to once daily dosing. Nine human studies have been published comparing the nephrotoxicity of once daily versus multiple daily aminoglycoside dosing. The majority of investigators have studied nonimmunocompromised patients with urinary tract infections. Netilmicin has been the most frequently used aminoglycoside, although other agents such as gentamicin, amikacin, and sisomicin have been studied. The most common netilmicin dosage regimen has ranged from approximately 4 to 6 mg/kg administered once daily. Eight of the nine trials performed have documented no significant differences in serial serum creatinine concentrations between once daily and multiple daily aminoglycoside dosing regimens, by the end of the study period. In conclusion, preliminary data suggest that once daily aminoglycoside dosing in nonimmunocompromised patients is equally efficacious and nephrotoxic compared to multiple daily dosing regimens.

Extended-interval aminoglycoside administration for children: a meta-analysis.

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.

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.

Since their introduction one or more decades ago, aminoglycosides have generally been administered in multiple daily (i.e. twice- or thrice-daily) dosing regimens. However, nephrotoxicity can be reduced in animal models by administering the same total daily dose as one large dose instead of as multiple small doses. In addition, in vitro and in vivo studies that considered the impact of dosing regimens on efficacy suggest that once-daily dosing is equally or more effective compared to multiple daily dosing. Once-daily versus multiple daily dosing regimens have been compared for amikacin, netilmicin, and gentamicin in 24 randomized, clinical trials including a total of 3,181 patients. An analysis of these studies revealed superior results for once-daily regimens with respect to clinical efficacy (89.5% vs. 84.7%, p < 0.001) as well as bacteriological efficacy (88.6% vs. 83.4%, p < 0.01). No statistically significant differences were noted for toxicity. Nevertheless, both nephrotoxicity and ototoxicity occurred less frequently during once-daily dosing (4.5% vs. 5.5% and 4.2% vs. 5.8%, respectively). Finally, once-daily dosing is more economical, since less nursing time and infusion material are required and the efforts for drug monitoring can be reduced. In conclusion, amikacin, netilmicin, and gentamicin can be administered once a day.

BackgroundParkinson’s disease (PD) is a progressive neurological disorder for which, at present, there is no cure. Current therapy is largely based on the use of dopamine agonists and dopamine replacement therapy, designed to control the signs and symptoms of the disease. The majority of current treatments are administered in tablet form and can involve multiple daily doses, which may contribute to sub-optimal compliance. Previous studies with small groups of patients suggest that non-compliance with treatment can result in poor response to therapy and may ultimately increase direct and indirect healthcare costs.ObjectiveTo determine the extent of non-compliance within the general PD population in the USA as well as the patient characteristics and healthcare costs associated with compliance and non-compliance.MethodsA retrospective analysis from a managed care perspective was conducted using data from the USA PharMetrics patient-centric claims database. PharMetrics claims data were complete from 31 December 2005 to 31 December 2009. Patients were included if they had at least two diagnoses for PD between 31 December 2005 and 31 December 2008, were older than 18 years of age, were continuously enrolled for at least 12 months after the date of the most recent PD diagnosis, and had no missing or invalid data. The follow-up period was the most recent 12-month block of continuous enrollment that occurred between 2006 and 2009. Patients were required to have at least one PD-related prescription within the follow-up period. The medication possession ratio (MPR) was used to categorise patients as compliant or non-compliant. Direct all-cause annual healthcare costs for patients with PD were estimated for each patient, and regression analyses were conducted to determine predictors for non-compliance.ResultsA total of 15,846 patients were included, of whom 46 % were considered to be non-compliant with their prescribed medication (MPR <0.8). Predictors of non-compliance included prescription of a medication administered in multiple daily doses (p < 0.0001), a period of <2 years since the initial PD diagnosis (p = 0.0002), a diagnosis of gastrointestinal disorder (p < 0.0001), and a diagnosis of depression (p < 0.0001). Non-compliance was also found to be related to age, with a lower odds of non-compliance in patients aged 41–80 years than in patients aged ≥81 years (p < 0.05). Although total drug mean costs were higher for compliant patients than non-compliant patients (driven mainly by the cost of PD-related medications), the mean costs associated with emergency room and inpatient visits were higher for patients non-compliant with their prescribed medication. Overall, the total all-cause annual healthcare mean cost was lower for compliant ($77,499) than for non-compliant patients ($84,949; p < 0.0001).ConclusionNon-compliance is prevalent within the general USA PD population and is associated with a recent PD diagnosis, certain comorbidities, and multiple daily treatment dosing. Non-compliance may increase the burden on the healthcare system because of greater resource usage compared with the compliant population. Treatments that require fewer daily doses may have the potential to improve compliance, which in turn could reduce the economic burden associated with PD.

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 ...

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

The purpose of the study is to explore the efficacy of mefloquine administered orally at single, multiple doses, or in combination with artesuante, artemether, or praziquantel in mouse--Schistosoma japonicum model. A total of 205 mice were divided into 4 batches and each batch of mice was infected percutaneously with 40 S. japonicum cercariae for 35 days. The infected mice were treated orally with mefloquine at single doses, multiple daily doses, or combined with artesunate, artemether, or praziquantel, while infected but untreated mice served as control. All treated animals were killed 4 weeks post-treatment for assessment of effect. When infected mice were treated orally with mefloquine at single or multiple daily doses under the same total dose levels, the tendency to decrease the efficacy was seen. Particularly, when a lower single dose of 100 mg/kg was divided equally into five daily doses of 20 mg/kg, the efficacy decreased statistically significant (P<0.05), i.e., the total worm and female worm reductions of 67.9% and 73.4% decreased to 31.3% and 30.3%, respectively. In infected mice treated with mefloquine or artesuante at a single dose of 100 mg/kg, a moderate effect against schistosomes was observed. No further significant reduction of total and female worm burdens was seen, when the two drugs combined together at the same dose level. On the other hand, administration of mefloquine combined with artesunate at single dose of 50 mg/kg, which exhibited no effect against schistosomes, resulted in significant reduction of total and female worm burdens in comparison with the groups treated with mefloquine and artesunate alone at the same dose level. Similar results were observed in treatment of infected mice with mefloquine in combination with artemether at the smaller dose of 50 mg/kg. The total worm burden was significantly lower than that of control and the female worm burden was also significant lower than that of groups treated with mefloquine and artemether alone. Interestingly, in administration of mefloquine 100 mg/kg combined with artemether 100 mg/kg to the infected mice, all female worms were killed and the total worm burden was also statistically significant lower than that of groups treated with either drug alone. Finally, when infected mice were treated with mefloquine combined with prazqiuatel at single dose of 50 mg/kg, no apparent improvement in efficacy was seen. Administration of mefloquine 100 mg/kg combined with praziquantel 100 mg/kg, only the difference of female worm burdens between praziquantel group and combined treatment group was statistically significant. The results indicate that under the same dose level of mefloquine, the efficacy of single dose is superior to that of multiple daily doses; mefloquine combined with artesunate or artemether at an invalid or moderate effective dose may show synergistic effect, especially the effect against female worms; no prominent synergistic effect is observed, when the similar dose level of mefloquine in combination with praziquantel.

Our objective was to evaluate urinary cytokine excretion after daily cranberry or placebo exposure in pregnant women. Four-hour urine samples were collected from 27 pregnant women subjects who were randomized to cranberry juice cocktail or placebo in three treatment arms: A: Cranberry (C) two times daily (C, C; n = 10 pregnant); B: cranberry in the AM, then placebo (P) in the PM (C, P; n = 9 pregnant); and C: placebo two times daily (P, P; n = 8 pregnant). Urinary cytokines were measured using commercially available kits. There was a statistically significant difference in interleukin (IL)-6 of the urinary cytokines between the multiple daily cranberry dosing group (group A [C, C]): median, 3.16 (range, 0.01 to 7.34) and the placebo group (group C [P, P]): 9.32 (0.53 to 29.61 pg/mL; p = 0.038, Kruskal-Wallis test). We concluded that a difference in IL-6 was found in the multiple daily cranberry dosing groups compared with placebo. Lack of differences based on treatment allocation in the other cytokines may be due to beta error. Further studies are planned to evaluate these assays for the assessment of clinical effect.

Objectives: 1) Analyze the recurrence rate of vertigo and the need for repeated injections of two different regimens of intratympanic gentamicin (ITG) (low dose and multiple daily dose). 2) Evaluate the efficacy of retreatment after long-term recurrence of vertigo attacks. Methods: We retrospectively analyzed 2 series of patients suffering from unilateral Ménière’s disease treated with low dose ITG (42) and multiple daily dose ITG (35) in a tertiary referral center. The mean period of follow-up was 4.8 years, and the outcome measurements were a) control of vertigo attacks, b) need of repeated treatment for recurrent vertigo evaluated using the Kaplan-Meyer method, and c) incidence of side effects (post-treatment dizziness, hearing loss). Results: At 2-year follow-up, complete control of vertigo was obtained with only 1 round of treatment in 30 (71%) low dose patients and 28 (80%) multiple daily dose patients. Side effects of ITG were significantly higher in the multiple daily dose group. At long-term follow-up (&gt; 4 years), the complete control vertigo rate decreased significantly, especially in the low dose group. 13 (31%) patients in the low dose group and 9 (25%) in the multiple daily dose group needed multiple rounds of treatment. Conclusions: Both regimen of ITG offered an excellent rate of vertigo control at 2-year follow-up. At long-term follow-up, the probability of recurrent vertigo attacks progressively increases, especially in the low dose group. The patients who experienced late recurrences of vertigo had less chance of achieving good results with additional rounds of ITG.

Once versus individualized multiple daily dosing of aminoglycosides in critically ill patients

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

To overcome the problems which associated with the standard multiple daily doses (MDD)&#x0D; of aminoglycosides (AGs) like high incidence of toxicity(nephrotoxicity, ototoxicity)(5-25%) and high cost, an alternative approach was developed which was single daily dose (SDD).This new regimen was designed to maximize bacterial killing by optimizing the peak concentration/minimum inhibitory concentration(MIC)ratio and to reduce the potential for toxicity. The study includes 75 patients selected randomly, 50 of them received SDD regimen of age range of 17-79 years and the remaining received MDD regimen of age range of 13-71 years. The study was designed to evaluate the safety of SDD regimen in comparison with MDD regimen. All the patients in SDD group received a constant dose of 5-mg/kg/day of gentamicin and 20mg/kg/day of amikacin with a drug administration interval based on estimated creatinine clearance(CLcr): if ≥60 ml//min every 24 hours (q24h), 59- 40 ml/ min every 36hours and 39- 30 ml/min every 48 hours.The calculated dose was diluted with 0.9% normal saline or 5% dextrose to 50-100 ml and given as intravenous infusion over 30-60 minutes. In SDD group , the mean length of therapy was 6.4±1.73 days .Gentamicin accounted for 96% of the aminoglycoside use, and the majority(58%) of patients received the drug every 24 hours.The 36- and -48 hours intervals were used for 34 and 8% of the population, respectively.While in MDD group , the mean length of therapy was 5.0±0.91 days. Gentamicin accounted for all (100%) of aminoglycoside use, and all of the patients received the drug every 8 hours. No clinically apparent ototoxicity and nephrotoxicity were observed in the patients in the SDD group, in contrast to the patients in MDD group, in whom 4 patients (16%) were developed nephrotoxicity and 1 patient (4%) was developed ototoxicity. The obtained results indicate that SDD regimen was safer through decreasing the incidence of both nephrotoxicity and ototoxicity.For statistical analysis, ANOVA test was used with P&lt;0.01.Each mean was expressed as mean±SEM(Standard Error of Mean).&#x0D; Key words: Aminoglycosides, Single Daily Dose, Nephrotoxicity and Ototoxicity.

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