Biologics, Volume 2, Issue 2 (June 2022) – 4 articles

Antimicrobial Resistance (AMR) has become a global threat to public health systems around the world in recent decades. In 2017, Italy was placed among the worst-performing nations in Europe by the European Centre for Disease Prevention and Control, due to worryingly high levels of AMR in Italian hospitals and regions. The aim of this systematic review was to investigate the state of the art of research on AMR in Italy over the last five years. The PubMed database was searched to identify studies presenting original data. Forty-three of the 9721 records identified were included. Overall, AMR rates ranged from 3% (in a group of sheep farmers) to 78% (in a hospital setting). The methods used to identify the microorganisms, to test their susceptibility and the criteria adopted for the breakpoint were deficient in 7, 7 and 11 studies, respectively. The main findings of our review were that most studies (79.1%) considered hospitalised patients only, 4 studies (9.3%) analysed non-hospitalised populations only. In addition, only 7 studies were multicentric and no scientific literature on the subject was produced in 7 Italian regions. In order to have a solid basis on the topic for the interventions of public health professionals and other stakeholders, studies analysing the phenomenon should be conducted in a methodologically standardised manner, should include all areas of the country and should also focus on out-of-hospital and community-based care and work settings. Full article

The minimum inhibitory concentration (MIC) is used to define the lowest concentration at which a substance can inhibit bacterial growth. This study aimed to evaluate the MIC of pyrogallol against Staphylococcus aureus and to propose a method for building growth inhibition curves of bacterial strains from MIC assays. S. aureus strains 1199B (NorA) and 1199 (wild type) were used for the assays. Pyrogallol MIC tests were performed by the broth microdilution method. The proposed method uses RGB images of the microdilution plate using the R (Red), G (Green), and B (Blue) channels to extract information for the construction of the bacterial growth inhibition curve (GIC). Pyrogallol demonstrated a MIC of 512 µg/mL against the two S. aureus strains tested. The GIC was calculated and the MIC point of pyrogallol was identified against the tested strains. The proposed method suggested the same MIC point for pyrogallol when using microplate images before and after the addition of resazurin. Through this methodology, the subjectivity of visual analysis in MIC tests can be eliminated. Full article

Abelmoschus esculentus (L.) Moench, commonly known as okra, is one of the most widely used vegetable crops currently used for diabetes treatment as well. It is thought that the large amount of soluble dietary fibers present in okra is responsible for the slowing of the absorption of glucose from the gut. However, its role in concomitant administration with commonly prescribed medications, including metformin (MET) and acarbose (ACR) for diabetes, is unclear. Therefore, this study assessed the effect of A. esculentus pod extract (AEE) administered concomitantly with MET and ACR in the glucose-induced hyperglycemic mice model. The AEE was prepared using green okra pods. In this experiment, each male Swiss Webster mouse was administered a 2.5 gm/kg/BW dose of glucose via gastric lavage to induce hyperglycemia. The experimental animals were divided into five groups: (i) negative control, (ii) positive control, (iii) MET only, (iv) MET and ACR, and (v) MET, ACR, and AEE. The orally administered doses of the MET, ACR, and the extract were 150 mg/kg/BW, 15 mg/kg/BW, and 0.2 mL/kg/BW, respectively. We found that MET only and a combination of MET and ACR reduced glucose levels significantly (p < 0.01) compared to the positive control. On the other hand, when MET, ACR, and AEE were administered simultaneously, the synergistic antihyperglycemic action of the MET and ACR was diminished. After 150 min, the blood glucose level was 4.50 ± 0.189 mmol/L (iv) and 6.58 ± 0.172 mmol/L (v). This study suggests that taking AEE concurrently with MET and ACR would reduce the effectiveness of antidiabetic drugs; thereby, concomitant administration of these antidiabetic agents is not recommended. This study provides an essential basis for decision-making about the consumption of AEE with conventional medicine. Further study is required to find the molecular insight of drug interactions in combination therapy of medicinal plants for diabetes. Full article

Biosimilars have come of age over the past 17 years, with 84 approvals in the EU and 35 in the US, representing almost 90% of the world market. While the acceptance of biosimilars in the US is catching up with that in the EU, the cost benefits remain elusive due to the high development barrier and complex distribution system involved, mainly in the US. In the EU, the cost of biosimilars has already dropped 70% or more, and interchangeability is a routine in some European jurisdictions, unlike in the US, where a separate regulatory approval is required. This paper projects significant changes coming in the US and EU’s biosimilars approval requirements that will impact the approval procedures in the rest of the world, leading to dramatic changes in the cost of biosimilars to patients. This perspective is based on the author’s first-hand experience to secure FDA approvals of biosimilars and an extensive analysis of the rationality of testing to demonstrate biosimilarity. Multiple citizen petitions by the author and meetings with the FDA may have prompted the recent announcement by the FDA to award a $5 million research grant to scientists to develop novel testing models to establish biosimilarity, including modifying the interchangeability protocols. Soon, demonstration of biosimilarity will not require animal testing and, in most cases, clinical efficacy testing; over time, the clinical pharmacology testing will be reduced as the regulatory agencies develop more confidence in the safety and efficacy of biosimilars. Biosimilars have come of age; now it is the turn of the developers to grow up, and one way to show this is to challenge the current regulatory guidelines but only on scientific grounds to seek more concessions, for which both FDA and EMA are ready. Full article