**1. Introduction**

Pharmaceutical traces, and their metabolites and degradation products have been found in both surface and ground water across the globe [1]. Antibiotics contribute a higher proportion to this in pharmaceutical wastewater [2] due to their significant use [3]. They are used to treat different diseases and bacterial infections in human beings and other animals [4–6]. Wastewater containing such complex components becomes difficult to treat [7,8]. Their high solubility in aqueous systems, longer half-life [9], and low biodegradability [10] makes them accumulate over time. Ceftriaxone (refer Figure 1) is a type of antibiotic used to treat a variety of bacterial illnesses. It is a 3rd generation cephalosporin that inhibits the formation of mucopeptide in bacterial cell walls [11]. Its systematic chemical name is [6R-[6a,7b,(Z)]]-5-thia-1-azabicclo-[4.2.0]-oct-2-ene-2-carboxylicacid,7-[[(2-amino-4 thiazolyl)(methoxyimino)-acetyl]amino]-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1- 2,4–triazin-3-yl)-thio]methyl]]-, disodium salt [12]. It is widely used in clinical settings due to its strong antibacterial effect, good lactamase tolerance, good clinical effect, low toxicity, and low allergic reaction [13].

Like other 3rd generation cephalosporins, this antibiotic is less effective against Grampositive bacteria compared to first-generation medicines, but it has a far larger spectrum of activity against Gram-negative bacteria [14]. Ceftriaxone has been useful for the treatment of infections caused by susceptible organisms in the lower respiratory tract, abdomen, skin and soft tissue, pelvic area, bone and joint, meninges, and urinary tract [15]. Based on intramuscular injections, ceftriaxone is 100% bioavailable and it is removed by biliary and renal excretion [16].

**Citation:** Karungamye, P.; Rugaika, A.; Mtei, K.; Machunda, R. A Review of Methods for Removal of Ceftriaxone from Wastewater. *J. Xenobiot.* **2022**, *12*, 223–235. https://doi.org/10.3390/ jox12030017

Academic Editors: François Gagné, Stefano Magni and Valerio Matozzo

Received: 3 June 2022 Accepted: 27 July 2022 Published: 2 August 2022

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**Figure 1.** Chemical structure of ceftriaxone [17].

The antibiotics used for animals and humans' treatment enter the environment via urine and feces, thus optimizing and/or limiting antibiotic use, which is essential to minimize contamination of the environment [18]. It is believed that around 40–90% of the prescribed antibiotic dose (depending on the class of pharmaceutical) is excreted as a parent compound in the active form in the feces and urine, and when it finally reaches the environment it causes soil, water, and plant contamination [19–21]. The use of excessive doses of antibiotics in livestock farming can pollute agro-ecosystems through either the application of contaminated manure as fertilizer in agriculture, or the irrigation of farms with wastewater [22,23]. Another source of concern comprises the improper disposal of leftover, expired, or unused pharmaceuticals which are released into sewage systems [24]. Due to the incomplete removal of pharmaceutical compounds and their metabolites by conventional treatment technologies, several pharmaceutical residues have been detected in wastewater effluents. This makes antibiotics present in wastewater treatment plants sludge and, finally, effluent [25–27]. Hospital effluents also comprise a significant source of antibiotics and antibiotic-resistant microorganisms in the environment [28].

Although antibiotic residue quantities in aquatic environments range from ng/L to μg/L, their continual discharge and persistence may have unexpected consequences for non-target aquatic organisms [11]. Antibiotics in water resources can generate a wide range of issues, including toxicity on aquatic organisms such as bacteria, algae, crabs, and fish, and increased antibiotic resistance in bacteria [5,29]. According to the WHO [23], antibiotic resistance is one of the three biggest dangers to human health. As a result, developing effective and environmentally friendly methods to break down those antibiotics in the aquatic environment is critical [2,4,30]. Being an antibiotic, ceftriaxone has similar effects. Due to its widespread usage in medicine and veterinary medicine, ceftriaxone contributes significantly to environmental pollution [9].

Several studies show that ceftriaxone aqueous solution is unstable, with a stability that is pH and temperature-dependent. The ideal pH for ceftriaxone stability in aqueous solution is 7.5, and when maintaining this pH for more than 6 h at 37 ◦C, only around 10% of ceftriaxone can be degraded. However, degradation occurs more quickly at lower or higher pH levels. The aqueous solution of ceftriaxone is stable for 4 days at room temperature in the presence and absence of light, and that ceftriaxone is stable for a longer amount of time at lower temperatures, but it decomposes after a specific period of time [31]. More characteristics of ceftriaxone are presented in Table 1.

**Table 1.** Characteristics of ceftriaxone sodium [16].


Ceftriaxone in wastewater has been reported by various researchers. For instance, research was conducted in India to examine the effluent of selected health care establishments and municipal wastewater treatment plants. The study findings indicated that the results for ceftriaxone ranged from 1.25–29.15 μg/mL [32]. The antibiotics have been proven in several publications as emergent contaminants in the aquatic environments around the world. However, the majority of the findings are from outside Africa [33]. Therefore, the purpose of this literature review was to analyze the information available in relation to the techniques for the removal of ceftriaxone from wastewater systems. The reviewed literature employed electronic databases, manual searches of reference lists from chosen electronic publications, and internet search engines to find relevant literature on the occurrence, concentrations, and techniques used to examine ceftriaxone in wastewater. The expressions ceftriaxone in wastewater, ceftriaxone analysis, and ceftriaxone removal or degradation were searched in Google Scholar, PubMed, Science Direct, Scopus, Taylor & Francis online, Web of Science, and Wiley Online Library. The search was limited to articles written in the English language.
