## 1 Introduction  
The accessibility to effective treatment alternatives of infectious diseases depends on the availability of appropriate antibiotic compounds in the market. Efficient antibiotic production is crucial for health systems worldwide, especially in outbreaks, epidemics, and health emergencies, in which the antibiotic supply chain can be put under pressure. Additionally, the acquired antibiotic resistance phenomenon became a global concern as it may increase the vulnerability of health systems [1]. The antibiotic resistance phenomenon emerged along with the antibiotic era [2, 3]. Years before penicillin was used at global scale, a penicillinase enzyme able to inactivate penicillin was discovered in bacteria extracts [4]. Antibiotic resistance has forced humanity to maintain an endless search for new and more powerful antibiotics. In this regard, the pharmaceutical industry plays a key role in the development of effective treatments against such multidrug-resistant bacteria [1]. Since the discovery of benzylpenicillin in the 1920s, the class of compounds referred to as \(\beta\)-lactam antibiotics has been the most extensively used antibiotics. Nevertheless, a significant number of different antibiotic compounds (such as carbapenems, cephemymcins, cephalospor, and monobactams) has been developed and implemented in the clinical practice as a strategy to evade the acquired resistance [5]. The new combinations of antibiotics are aimed to increase their spectrum of activity and overcome the resistance barriers developed by the bacteria. In order to mitigate the bacterial resistance to \(\beta\)-lactam antibiotics, several compounds have been identified as \(\beta\)-lactamase inhibitors. Those compounds can irreversibly inactivate the \(\beta\)-lactamases allowing the \(\beta\)-lactam antibiotics to act against the infection. The main \(\beta\)-lactamase inhibitors are Sulbactam, Tazobactam, and clavulanic acid (CA) as clavulanate salt. CA is a \(\beta\)-lactam compound with modest antibiotic activity but high inhibition capacity of \(\beta\)-lactamase enzymes. The CA molecule is an analog of the penicillin nucleus, in which the characteristic sulfur atom has been substituted by an oxygen atom. CA is one of the so-called \"clavam metabolites\" produced by the filamentous bacterium _Streptomyces clavuligerus_ (_S. clavuligerus_); most of those metabolites have the characteristic fused bicyclic \(\beta\)-lactam/oxazolidine ring. Nevertheless, the CA molecule (Figure 1) has 3R, 5R stereochemistry, opposite to the 3S, 5S configuration present in other clavam metabolites, which do not exhibit \(\beta\)-lactamase inhibition activity, although some of them have antibacterial or antifungal properties [6]. In addition to the stereochemistry, the inhibitory effect of CA has been explained by the presence of the \(\beta\)-lactam/oxazolidine ring that bonds irreversibly with a serine residue in the catalytic center of the \(\beta\)-lactamase enzyme, thus rendering it inactive [7]. Currently, CA is used in combination with other \(\beta\)-lactam antibiotics as an effective treatment against several clinical syndromes including pneumonia and exacerbations of chronic obstructive pulmonary disease, complicated intra-abdominal infections, acute infectious diarrhea, urinary tract infections, pharyngitis, surgical, wound, and skin infections [8]. Some of them are caused by resistant pathogenic bacteria already included in the World Health Organization priority list: _Escherichia coli_, _Staphylococcus aureus_, _Neisseria gonorrhoeae_, _Streptococcus pneumonia_, and all _Enterobacteriaceae_ and _Klebsiella_ species [1]. CA is produced worldwide at large scale by several pharmaceutical companies, and it is also prescribed in more than 150 countries [9]. CA has a relatively limited market availability and a middle-high cost for the health system, especially in the developing countries when compared with the income level, being quite inaccessible for people without health insurance.