How Do We Combat Bogus Medicines in the Age of the COVID-19 Pandemic?

The COVID-19 pandemic has brought concurrent challenges. The increased incidence of fake and falsified product distribution is one of these problems with tremendous impact, especially in low- and middle-income countries. Up to a tenth of medicines including antibiotics and antimalarial drugs in the African market are considered falsified. Pandemics make this worse by creating an ecosystem of confusion, distraction, and vulnerability stemming from the pandemic as health systems become more stressed and the workload of individuals increased. These environments create opportunities for substandard and falsified medicines to be more easily introduced into the marketplace by unscrupulous operators. In this work, we discussed some of the challenges with fake or falsified product distribution in the context of COVID-19 and proposed strategies to best manage this problem

Using pharmacokinetics and pharmacodynamics to optimise dosing of antifungal agents in critically ill patients: a systematic review

The prevalence of invasive fungal infections (IFIs) caused by Candida spp. is increasing in critically ill patients. Recent development of new antifungal agents has significantly contributed to the successful treatment of IFIs. However, the pharmacokinetics of antifungal agents can be altered in a number of disease states, including critical illness. Therefore, doses established in healthy volunteers and other patient groups may not be appropriate for the critically ill. Moreover, inadequate dosing may contribute to treatment failure and the emergence of resistance. This systematic review provides a critical analysis of the pharmacokinetics of antifungal agents in the critically ill and their relevance to dosing requirements in clinical practice. Based on the limited data available, dosing of some antifungal agents may have to be adjusted in critically ill patients with conserved renal function as well as in those requiring renal replacement therapy. Further research to confirm the appropriateness of current dosing strategies to attain the appropriate pharmacodynamic targets is recommended.Mahipal Sinnollareddy, Sandra L. Peake, Michael S. Roberts, Jeffrey Lipman, Jason A. Robert

Influence of sustained low-efficiency diafiltration (SLED-f) on interstitial fluid concentrations of fluconazole in a critically ill patient: use of microdialysis

Abstract not availableMahipal G. Sinnollareddy, Michael S. Roberts, b, Jeffrey Lipman, Sandra L. Peake, Jason A. Robert

Plasma and interstitial fluid population pharmacokinetics of vancomycin in critically ill patients with sepsis

Abstract not availableJacob Abraham, Mahipal G. Sinnollareddy, Michael S. Roberts, Patricia Williams, Sandra L. Peake, Jeffrey Lipman, Jason A. Robert

In vivo microdialysis to determine subcutaneous interstitial fluid penetration and pharmacokinetics of fluconazole in intensive care unit patients with sepsis

The objective of the study was to describe the subcutaneous interstitial fluid (ISF) pharmacokinetics of fluconazole in critically ill patients with sepsis. This prospective observational study was conducted at two tertiary intensive care units in Australia. Serial fluconazole concentrations were measured over 24 h in plasma and subcutaneous ISF using microdialysis. The concentrations in plasma and microdialysate were measured using a validated high-performance liquid chromatography system with electrospray mass spectrometer detector method. Noncompartmental pharmacokinetic analysis was performed. Twelve critically ill patients with sepsis were enrolled. The mean in vivo fluconazole recovery rates ± standard deviation (SD) for microdialysis were 51.4% ± 16.1% with a mean (±SD) fluconazole ISF penetration ratio of 0.52 ± 0.30 (coefficient of variation, 58%). The median free plasma area under the concentration-time curve from 0 to 24 h (AUC0-24) was significantly higher than the median ISF AUC0-24 (340.4 versus 141.1 mg · h/liter; P = 0.004). There was no statistical difference in median fluconazole ISF penetration between patients receiving and not receiving vasopressors (median, 0.28 versus 0.78; P = 0.106). Both minimum and the maximum concentrations of drug in serum (Cmax and Cmin) showed a significant correlation with the fluconazole plasma exposure (Cmax, R(2) = 0.86, P < 0.0001; Cmin, R(2) = 0.75, P < 0.001). Our data suggest that fluconazole was distributed variably, but incompletely, from plasma into subcutaneous interstitial fluid in this cohort of critically ill patients with sepsis. Given the variability of fluconazole interstitial fluid exposures and lack of clinically identifiable factors by which to recognize patients with reduced distribution/exposure, we suggest higher than standard doses to ensure that drug exposure is adequate at the site of infection.Mahipal G. Sinnollareddy, Michael S. Roberts, Jeffrey Lipman, Melissa Lassig-Smith, Therese Starr, Thomas Robertson, Sandra L. Peake, Jason A. Robert

Emerging Treatment Strategies for Impetigo in Endemic and Nonendemic Settings:A Systematic Review

Purpose:Impetigo affects approximately 162 million children worldwide at any given time. Lack of consensus on the most effective treatment strategy for impetigo and increasing antibiotic resistance continue to drive research into newer and alternative treatment options. We conducted a systematic review to assess the effectiveness of new treatments for impetigo in endemic and nonendemic settings.Methods:We searched PubMed, MEDLINE, CINAHL, Web of Science, and Embase via Scopus for studies that explored treatments for bullous, nonbullous, primary, and secondary impetigo published between August 1, 2011, and February 29, 2020. We also searched online trial registries and hand-searched the reference lists of the included studies. We used the revised Cochrane risk of bias (version 2.0) tool for randomized trials and the National Heart, Lung, and Blood Institute for nonrandomized uncontrolled studies to assess the risk of bias.Findings:We included 10 studies that involved 6651 participants and reported on 9 treatments in the final analysis. Most clinical trials targeted nonbullous impetigo or did not specify this. The risk of bias varied among the studies. In nonendemic settings, ozenoxacin 1% cream appeared to have the strongest evidence base compared with retapamulin and a new minocycline formulation. In endemic settings, oral co-trimoxazole and benzathine benzylpenicillin G injection were equally effective in the treatment of severe impetigo. Mass drug administration intervention emerged as a promising public health strategy to reduce the prevalence of impetigo in endemic settings.Implications:This review highlights the limited research into new drugs used for the treatment of impetigo in endemic and nonendemic settings. Limited recent evidence supports the use of topical ozenoxacin or retapamulin for impetigo treatment in nonendemic settings, whereas systemic antibiotics and the mass drug administration strategy have evidence for use in endemic settings. Given the troubling increase in resistance to existing treatments, there is a clear need to ensure the judicious use of antibiotics and to develop new treatments and alternative strategies; this is particularly important in endemic settings. PROSPERO identifier: CRD42020173042

DALI: Defining Antibiotic Levels in Intensive care unit patients: a multi-centre point of prevalence study to determine whether contemporary antibiotic dosing for critically ill patients is therapeutic

Background: The clinical effects of varying pharmacokinetic exposures of antibiotics (antibacterials and antifungals) on outcome in infected critically ill patients are poorly described. A large-scale multi-centre study (DALI Study) is currently underway describing the clinical outcomes of patients achieving pre-defined antibiotic exposures. This report describes the protocol