Κυριακή 29 Μαΐου 2022

Carglumic acid in methylmalonic acidemia: Use of breast milk as an alternative vehicle to water

alexandrossfakianakis shared this article with you from Inoreader
Carglumic acid in methylmalonic acidemia: Use of breast milk as an alternative vehicle to water

We aim to report the use of breast milk (BM) as an alternative vehicle in a neonate with methylmalonic acidemia rejecting carglumic acid (NCG) diluted in water. The patient presented symptomatic acidemia and hyperammonemia and after refusal of oral NCG administration, the clinician consulted the Pharmacy Department for advice. Data sheet of NCG does not recommend administration in other vehicle than water. Consequently, a dissolution test was conducted in BM showing correct dissolution. The solution was well tolerated, and plasma ammonium concentrations remained within range in subsequent analytical controls.


Abstract

What Is Known and Objective

Carbaglu® or N-carbamylglutamate (NCG) is not recommended for administration in a vehicle other than water. We aim to report the use of breast milk (BM) as an alternative vehicle in a neonate rejecting NCG diluted in water.

Case Summary

A neonate diagnosed with methylmalonic acidemia presented symptomatology of acidemia and hyperammonemia. After the patient refused oral NCG administration, a dissolution test was conducted in BM showing correct dissolution. The NCG-BM solution was tolerated and plasma ammonium concentrations remained within range in subsequent analytical controls.

What Is New and Conclusion

BM as a vehicle for NCG is a safe and effective option for patients who refuse suspension in water and could lead to better treatment compliance in paediatric patients.

View on Web

Plasma trough concentration distribution and safety of high‐dose teicoplanin for patients with augmented renal clearance

alexandrossfakianakis shared this article with you from Inoreader
Plasma trough concentration distribution and safety of high-dose teicoplanin for patients with augmented renal clearance

Teicoplanin plasma trough concentration (C min) and probability rates of C min > 10 mg/L in the augmented renal clearance (ARC) and non-ARC groups on the third day of medication (day 3) and during the dose maintenance period. After the HD, plasma samples were collected before the third day of medication. The teicoplanin C min values in the ARC and non-ARC groups were 17.3 ± 9.2 mg/L and 15.5 ± 7.9 mg/L, respectively (p = 0.663) (Figure A). The probability rate of C min > 10 mg/L also did not differ significantly between the two groups (85.7% [6/7] vs. 60.0% [6/10], p = 0.338, Figure C). During the dose maintenance period (3 days after medication), the teicoplanin C min was significantly lower in ARC group than in the non-ARC group (18.3 ± 5.1 mg/L vs. 25.5 ± 11.9 mg/L, p = 0.016, Figure A), while there was no significant difference in the probability rate of C min > 10 mg/L between the two groups (90.0% [9/10] vs. 96.2% [25/26], p = 0.484, Figure C). After the LD, plasma samples were collected before the third day of medication. The teicoplanin C min values in the ARC and non-ARC groups were 6.8 ± 3.9 mg/L and 7.9 ± 3.1 mg/L, respectively (p = 0.585) (Figure B). The probability rate of C min > 10 mg/L did not differ significantly between the two groups (20.0% [1/5] vs. 11.1% [1/9], p = 1.000, Figure D). During the dose maintenance period, the teicoplanin C min values in the ARC and non-ARC groups were 12.2 ± 6.3 mg/L and 13.0 ± 4.6 mg/L, respectively (p = 0.713) (Figure B). The probability rate of C min > 10 mg/L was 61.5% (8/13) in both groups (Figure D). It should be noted that on the third day of medication, the HD group had a significantly higher teicoplanin C min than the LD group for ARC (17.3 ± 9.2 mg/L vs. 6.8 ± 3.9 mg/L, p = 0.039, Figure A and B), but there was no significant intergroup difference in the probability rates of C min > 10 mg/L (85.7% [6/7] vs. 20.0% [1/5], p = 0.072, Figures C and D). During the dose maintenance period, the teicoplanin C min was significantly higher in the HD group than in the LD group for ARC (18.3 ± 5.1 mg/L vs. 12.2 ± 6.3 mg/L, p = 0.022, Figures A and B), while there was no significant intergroup difference in their probability rates of C min > 10 mg/L (90.0% [9/10] vs. 61.5% [8/13], p = 0.179, Figures C and D). Notes: A, HD; B, LD; C, HD; D, LD; *p < 0.05.


Abstract

What Is Known and Objective

There are few reports on the distribution of the plasma trough concentration (C min) of teicoplanin in patients with augmented renal clearance (ARC) and on the safety of a high-dose regimen (HD; 800 mg loading dose for q12h three times followed by an 800 mg qd maintenance dose). The objective of this study was to determine the C min values of teicoplanin in ARC patients using HD teicoplanin to provide a reference for individualized medication.

Methods

Data on patients treated with teicoplanin from January 2019 to January 2021 were collected retrospectively and divided into ARC (creatinine clearance rate [CCr] >130 ml/min, n = 22) and non-ARC (60 ml/min ≤ CCr ≤130 ml/min, n = 24) groups. The C min values in the two patient groups were analysed during the HD and the low-dose regimen (LD; all other regimens) on the third day of medication and during the dose maintenance period. Liver and kidney function indexes were also analysed before and after medication.

Results and Discussions

On the third day of the HD, C min did not differ significantly between the ARC and non-ARC groups (17.3 ± 9.2 mg/L [mean ± SD] vs. 15.5 ± 7.9 mg/L, p = 0.663), while C min in the ARC group was significantly lower for the LD (6.8 ± 3.9 mg/L, p = 0.039). During the dose maintenance period, C min in the ARC group when receiving the HD (18.3 ± 5.1 mg/L) was significantly lower than that in the non-ARC group (25.5 ± 11.9 mg/L, p = 0.016) and significantly higher than that for the LD (12.2 ± 6.3 mg/L, p = 0.022). Nephrotoxicity and hepatotoxicity incidence rates did not differ significantly between these groups.

What Is New and Conclusion

These results suggest that it is necessary to apply a loading dose of 800 mg (but not higher) q12h three times for patients with ARC, with 800 mg needed as a maintenance dose during severe infection, and 600 mg or 400 mg for mild infection.

View on Web

Could the Audiometric Criteria for Sudden Sensorineural Hearing Loss Miss Vestibular Schwannomas?

alexandrossfakianakis shared this article with you from Inoreader
Could the Audiometric Criteria for Sudden Sensorineural Hearing Loss Miss Vestibular Schwannomas?

Patients with sudden hearing loss whose audiograms did not meet the formal audiometric criteria for sudden sensorineural hearing loss were found to have a similar rate of vestibular schwannoma as those who did. Therefore, we advocate a high index of suspicion of a concomitant vestibular schwannoma with sudden hearing loss of any severity, and urge our colleagues to consider referring those patients to an MRI scan regardless of the hearing loss severity.


Objective

To investigate the likelihood of missing a vestibular schwannoma (VS) diagnosis in patients who present with a sudden hearing loss (SHL) that does not meet the most accepted audiometric criteria for sudden sensorineural hearing loss (SSNHL) (a decrease of ≥30 dB at three consecutive frequencies).

Methods

All adult patients (>18 years) diagnosed with SHL of any severity in a tertiary care referral medical center between 2015 and 2020 and who underwent an MRI scan to rule out VS were included. Statistical analyses were conducted to evaluate the difference between the rate of VS among patients with an initial audiogram, which met the abovementioned criteria, and those who did not. Other audiometric criteria for SNHL were also evaluated (≥10 dB at ≥2 frequencies and ≥ 15 dB at one frequency).

Results

Of the 332 patients included in the study, 152 met the audiometric criteria for SSNHL, and 180 did not. Both groups had a similar VS rate (8.6% vs. 8.9%, p = 0.914). Similar results were found when other audiometric criteria for asymmetric SNHL were analyzed. In a subgroup analysis of patients with VS-associated SSNHL, neither the tumor size nor the Koos classification was associated with any of the audiometric criteria systems.

Conclusion

There should be a high index of suspicion for the presence of VS in patients with an SHL of any severity.

Level of Evidence

3 Laryngoscope, 2022

View on Web