Pink and black capsule a45

demonstrated that continuous infusion of amoxicillin provides fewer low concentrations than intermittent administration, they reported highly inconstant amoxicillin plasma concentrations using this administration mode, despite adapted doses [34]. Moreover, despite continuous administration of high-doses amoxicillin (12 g/day), Arensdorff et al.

observed, very low amoxicillin plasma concentrations (0.9 and 2.4 mg/mL) in two out of the nine patients enrolled [23].

In both these studies, amoxicillin unstability may have resulted in inaccurate dose administration, leading to suboptimal or ineffective concentrations in treated patients, with respect to the MIC of the bacteria involved in the infection. Clearly, while the great variability in amoxicillin plasma levels is due to many factors, unstability issue should not be ruled out as a causal factor.

Last but not least, drug degradation may lead to toxic byproducts [17]. Regarding amoxicillin we have identified four degradation products, Among them, amoxicilloic acid and diketopiperazine amoxicillin have been identified as the two major degradation products of amoxicillin. Hydroxyphenylglycyl amoxicillin acid and amoxicillin penilloic acid have also been described by others [35,36]. None of these degradation products have antimicrobial activity, but amoxicilloic acid and diketopiperazine amoxicillin are at risk of allergic reaction, of the same order of magnitude as those observed with amoxicillin [37,38]. In addition, it has been demonstrated that the amoxicilloic acid concentrations measured in pig kidney after intravenous administration are higher than amoxicillin concentrations and decrease more slowly, meaning that this degradation product may accumulate in the patient [39,40]. This issue could partly explain the side effects reported in patients treated with high-dose amoxicillin. In conclusion, according to the experiments carried out in this work, the optimal conditions for the administration of continuous infusion of high-dose amoxicillin using portable elastomeric pumps have been defined. First of all, amoxicillin has to be diluted in order to obtain a final concentration of 25 mg/ml, allowing for complete dissolution and long-term stability. Dilution should be performed in sterile water for injection combined with 0.9% sodium choride for injection (50:50, v:v) in order to maintain osmolarity at a level (approximately 280 mOsm/L, data no shown) suitable for intravenous infusion using peripheral access [16].

Dilution in dextrose should be avoided since lower stability using this solvent has been demonstrated [20]. Then, under these optimized conditions, the elastomeric pump may be stored at ambient temperature (22 ± 4°C) for 12 hours, requiring filling an elastomeric pump every 12 hours for continuous infusion.

In addition, it is important to store the elastomeric pump at a temperature below 26°C, which implies not holding the device near the body or under clothing during the day, and keeping it beside the head, outside of the blankets when the patient is bedridden.

Finally, amoxicillin may remain stable over the entire day under the same conditions, provided that the elastomeric pump is stored between +4°C and +8°C throughout the administration, using for instance a refrigerated bag; however this can lead to potential intolerance due to infusion of cold solution. We wish to thank Jeffrey Arsham, an American medical translator, for his highly helpful reading of our original text.

Changes and new listings for four antibiotics on the PBS. On 1 April 2020, four antibiotics listed on the PBS General Schedule (Section 85) had changes made to their listings and new listings added for the treatment of a range of infections, such as acute cystitis, streptococcal pharyngitis or tonsillitis and periorbital cellulitis. amoxicillin amoxicillin + clavulanic acid cefalexin roxithromycin.

See the PBS website for complete details for each item, including the specific infections.

These are also listed in Table 1 at the end of this article.

The listing changes and new listings aim to promote antimicrobial stewardship, by reducing inappropriate, inadvertent repeat prescribing when initiating a course of antibiotics.

Antibiotics are overprescribed for many conditions in Australia. For example, prescribing of antibiotics may be recommended for 19%–40% of patients with acute tonsillitis, but NPS MedicineWise’s MedicineInsight program found that 94% of patients with acute tonsillitis were prescribed antibiotic treatment. Antimicrobial stewardship promotes optimal prescribing of antibiotic, antifungal, antiviral and antiparasitic agents. It helps to improve safe and appropriate use of antimicrobials, reduce patient harm and decrease the incidence of antimicrobial resistance in the Australian healthcare system.

In 2017, the General Practice National Antimicrobial Prescribing Survey (GP NAPS) identified several interventions to

promote

Inappropriate repeat prescriptions typically occur inadvertently because many clinical software prescribing tools used by GPs have repeats ticked as a default setting for frequently prescribed antibiotics.

The proportion of prescriptions issued with a repeat varies between different antibiotics, which is expected as some indications may appropriately require repeats.

For example, using doxycycline for the treatment of acne requires longer time frames. However, many common infections do not require repeat prescriptions and there is evidence supporting shorter antibiotic courses.

More than 26 million antibiotic prescriptions were dispensed through the PBS in Australia in 2017. In 2018, the Department of Health reviewed PBS listings of frequently used antibiotics that allowed repeat prescriptions to be issued as the default setting for computer-generated prescriptions.

The aim of this review was to reduce antibiotic prescribing without impacting clinical decision making, by ensuring health professionals could actively decide to prescribe repeats for antibiotics where clinically indicated.

The antibiotics selected for the review

were

2 These antibiotics – amoxicillin, amoxicillin + clavulanic acid, cefalexin, doxycycline and roxithromycin – represented over 70% of all dispensed antibiotics under the PBS in 2017. The Pharmaceutical Benefits Advisory Committee (PBAC) noted that one in five repeat prescriptions of these antibiotics supplied through the PBS were dispensed more than 30 days after the dispensing date of the original prescription.

Alignment with Therapeutic Guidelines: Antibiotic (version 16) In April 2019, version 16 of the Therapeutic Guidelines: Antibiotic was published. The Therapeutic Guidelines: Antibiotic are a collection of guidelines published by an independent not-for-profit Australian organisation to provide clear, practical, evidence-based and up-to-date information to prescribers.

They are endorsed by reputable organisations and peak bodies, and used commonly in public teaching hospitals and community medical and pharmacy practices across Australia.

The Department of Health review used version 16 of the guidelines to ensure changes and additions to PBS listings were in alignment. At its August 2019 meeting, the PBAC considered the changes proposed in the PBS

review