Submitted Successfully!
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1 -- 3383 2022-05-24 14:13:17 |
2 format -111 word(s) 3272 2022-05-25 03:32:27 |

Video Upload Options

Do you have a full video?


Are you sure to Delete?
If you have any further questions, please contact Encyclopedia Editorial Office.
Rahman, M.H.; Cavalu, S.; Rahman, M.M.; , .; Zehravi, M.; Sarker, M.; Yamin, M.; Rashid, M.; Ramproshad, S.; Dey, A.; et al. Antimicrobial Stewardship Optimization. Encyclopedia. Available online: (accessed on 24 February 2024).
Rahman MH, Cavalu S, Rahman MM,  , Zehravi M, Sarker M, et al. Antimicrobial Stewardship Optimization. Encyclopedia. Available at: Accessed February 24, 2024.
Rahman, Md. Habibur, Simona Cavalu, Md. Mominur Rahman,  , Mehrukh Zehravi, Md. Sarker, Md. Yamin, Md.harun Rashid, Sarker Ramproshad, Abhijit Dey, et al. "Antimicrobial Stewardship Optimization" Encyclopedia, (accessed February 24, 2024).
Rahman, M.H., Cavalu, S., Rahman, M.M., , ., Zehravi, M., Sarker, M., Yamin, M., Rashid, M., Ramproshad, S., Dey, A., Damiri, F., & Berrada, M. (2022, May 24). Antimicrobial Stewardship Optimization. In Encyclopedia.
Rahman, Md. Habibur, et al. "Antimicrobial Stewardship Optimization." Encyclopedia. Web. 24 May, 2022.
Antimicrobial Stewardship Optimization

Antimicrobials are a type of agent widely used to prevent various microbial infections in humans and animals. Antimicrobial resistance is a major cause of clinical antimicrobial therapy failure, and it has become a major public health concern around the world. Increasing the development of multiple antimicrobials has become available for humans and animals with no appropriate guidance. As a result, inappropriate use of antimicrobials has significantly produced antimicrobial resistance. However, an increasing number of infections such as sepsis are untreatable due to this antimicrobial resistance. In either case, life-saving drugs are rendered ineffective in most cases. The actual causes of antimicrobial resistance are complex and versatile. A lack of adequate health services, unoptimized use of antimicrobials in humans and animals, poor water and sanitation systems, wide gaps in access and research and development in healthcare technologies, and environmental pollution have vital impacts on antimicrobial resistance.

antimicrobial resistance human infection sanitation

1. The Natural History of Antibiotics

In 1947, S.A. Waksman characterized the expression “antibiotic” as follows: “A chemical material, which is produced by microorganisms, is an antibiotic that keeps back bacteria and other microorganisms, and even kills them” [1]. In a real sense, antibiotics signify “against life”; for this situation, against organisms. There are numerous anti-infection agents: anti-bacterial, anti-viral, anti-fungal, and anti-parasitic [2]. Nowadays, “antibiotic” has innumerable implications: (I) an organic compound of synthetic or natural source that restrains or kills pathogenic microscopic organisms; (II) any antimicrobial compound, or (III) restricted to microbial substances of microbial origin in the Waksman convention [3].
1928: Alexander Fleming found the main anti-microbial, penicillin. In any regard, penicillin was controlled for more than 10 years before it was introduced as a microbial illness therapy [4]. The 1930s: The first widely used antimicrobial was Prontosil, a sulfonamide synthesized by German organic biochemist Gerhard Domagk [5]. 1945: Penicillin was initially used to treat bacterial infections on a large scale. Florey and Chain’s attempts to refine the antibiotic and scale-up manufacturing made this feasible. 1940–1962: The golden era of antibiotics.

2. Resistance to Antibiotics

Antibiotic resistance is now becoming a more serious concern around the world. In addition to phenotypically resistant bacteria, isolates with silent but intact antibiotic resistance genes may constitute a great concern. Antimicrobial resistance (AR) can be transferred across bacteria via genetic elements, resulting in the rapid creation of multidrug resistance (MDR) in germs from animals, posing a risk to human health [6]. Antibiotic resistance occurs as germs such as bacteria and fungi can destroy antibiotic ingredients. This means that the germs are not killed and are still rising. Contaminations caused by antibiotic-resistant bacteria are difficult to handle and, at times, nonsensical. Antibiotic-resistant infections often necessitate more extended hospital stays, more doctor appointments, and expensive and risky alternative treatments. Resistance to antibiotics does not indicate a body’s resistance to antibiotics because bacteria are immune to the antibiotics meant to kill them [7]. Anti-microbials are medications used to prevent and treat bacterial contaminations. Antimicrobial tolerance occurs as microscopic species become resistant to antibiotics because of their application. Antibiotic resistance develops in microbes, not humans or animals. These microbes can infect people or livestock, and the infections they cause are more difficult to cure than those caused by bacteria that are not immune [8].

3. Mechanisms of Antimicrobial Resistance

Antimicrobials are specialists who execute or hinder microorganisms’ development and envelop anti-infection agents, antifungals, and antivirals [9]. Antimicrobial resistance (AMR) is created when microorganisms adjust and fill within sight of antimicrobials, when delivering therapy with an antimicrobial medication [9][10]. The elements prompting AMR are complex and multifactorial. Resistance happens because of a characteristic developmental cycle that outfits the microorganisms with mechanisms to balance the antimicrobials’ impacts. Antimicrobial resistance can occur, for instance, when an organism develops an enzyme that wrecks the medication in a straightforward manner (for example, β-lactamases, which corrupt β-lactam antimicrobials) [11]. Antibiotics that follow up on the cell wall by restraining peptidoglycan synthesis incorporate β-lactams and glycopeptides. β-Lactams include penicillin, cephalosporin, monobactams, and carbapenems [12]. Antimicrobial resistance mechanisms are classed into four main categories: (1) limiting uptake of a drug; (2) altering a drug target; (3) inactivating a drug; (4) active drug efflux [13].

4. Relationship between Antibiotic Use in Animals and Antibiotic Use in Humans

Antibiotics are primarily used in animals for three purposes: surgical treatment of sick animals, prophylactic infection prevention, and growth promoters to increase feed use and development. However, preventive therapy entails treating human animals with antibiotic doses that surpass the pathogen’s minimum inhibitory concentration for a limited period. In addition, therapeutic medication is often given to intensively farmed livestock in the form of feed or drinking water; however, because sick animals may not drink or eat, this procedure can be unsuccessful in some situations. Furthermore, prophylactic therapy includes giving a group of animals low to heavy doses of antibiotics in their feed or drink for a set amount of time. Antibiotics used as growth promoters are often fed to whole herds and flocks at sub-therapeutic doses for long periods and are available over the counter from feed producers and growers [14][15].

5. Development of Antimicrobial Resistance in Human and Animal Healthcare

Antimicrobial resistance poses severe threats to human and animal healthcare. The speedy elevation and expansion of resistant microbes and ARGs in populations, animals, and the climate is regarded as a severe global issue [16]. Fundamentally, resistance emerges from a natural evolving phase that assists microorganisms with pathways to combat the antimicrobials impact [11]. Antimicrobial resistance tries to intimidate to overturn the progress of antimicrobials with modern medications [17]. Antibiotic resistance is caused by excessive usage and improper usage (inappropriate selections, insufficient dosing, and unclear obedience to medication guidance). However, human medication in the population and clinics, in animal farming and agricultural sectors, and in the environment are the four major sectors that influence the emergence of antibiotic resistance, according to research findings [18][19]. AMR may lead to increases in-patient death rates and the duration of hospitalized stay and has numerous social and financial consequences. Any drug-resistant microbes necessitate physical separation from the community to prevent infection, resulting in lost work and family periods for patients. Additionally, the patient could be charged with further physician visits and hospitalization, as well as potential second-line therapies, laboratory examinations, and other diagnostic expenses [20][21].

5.1. New Antibiotics

Plazomicin is a chemically synthesized aminoglycoside [22] that inhibits bacterial protein synthesis and has dose-dependent bactericidal efficacy in vitro [23]. Plazomicin was certified by the FDA in 2018 for the treatment of cUTI and pyelonephritis at a dosage of 15 mg/kg IV, QD. The FDA package insert for plazomicin mentions nephrotoxicity and ototoxicity as potential adverse effects.
Plazomicin is more effective than other aminoglycosides against colistin-resistant Enterobacterales (including those with MCR-1 genes), with 89.5% of isolates susceptible (compared to amikacin, gentamicin, and tobramycin, which are effective against 16.8%, 47.4%, and 63.2 percent of isolates, respectively) [24]. In two clinical studies, plazomicin 15 mg/kg IV, QD was compared to meropenem 1 g IV, TID [25], and levofloxacin 750 mg IV, QD in patients with complicated urinary tract infections (UTI) for up to 10 days [26].
Eravacycline is a tetracycline-class fluorocycline. It suppresses bacterial protein production, just like other tetracyclines. Eravacycline was authorized by the FDA in 2018 for the treatment of cIAI at a dosage of 1 mg/kg IV, BD for a total of 4 to 14 days. According to surveillance studies [27], eravacycline is active against E. coli (MIC50/90: 0.12/0.5), including ESBL E. coli (0.25/0.5), and K. pneumonia (0.25/0.5), including ESBL K. pneumoniae (0.06/0.5) [27].
Temocillin is a derivative of ticarcillin, a penicillin antibiotic that primarily targets PBP3 and was developed and marketed in the United Kingdom in the 1980s, but was quickly abandoned due to its lack of activity against Gram-positive bacteria, non-fermenters (such as A. baumannii and P. aeruginosa), and anaerobes [28]. Given the increasing prevalence of infections caused by Enterobacterales that are resistant to third-generation cephalosporins, there has been increased interest in this antibacterial drug in recent decades as a carbapenem-sparing alternative. ESBL and AmpC do not affect temocillin, whereas OXA-48 and MBL do [28][29][30][31].
Cefiderocol is a catechol-substituted siderophore that has recently been discovered [32]. In 2019, the FDA authorized it at a dosage of 2 g IV. Cefiderocol has a MIC50/90 of 2/8 mg/L for Enterobacterales with ESBL and AmpC [33]. It is active against >90% of Enterobacterales isolates. It also kills over 90% of Acinetobacter spp. and Pseudomonas aeruginosa isolates [34], including carbapenem-resistant strains [35]. E. coli and Klebsiella spp. were the most frequent pathogens in this investigation (There was no information supplied on their sensitivity to third-generation cephalosporins), with P. aeruginosa accounting for 7%. A recently published RCT compared cefiderocol 2 g IV, TID in 145 patients with meropenem 2 g IV, and TID in 146 nosocomial pneumonia patients and found similar mortality at day 14, 12.4% vs. 11.6% [36].

5.2. Beta-Lactam/Beta-Lactamase Inhibitor

Antibiotics that combine a cephalosporin or carbapenem antibiotic with a beta-lactamase inhibitor are listed below (BLI). The companion beta-lactam antibiotic can reach its objective, penicillin-binding proteins, via inhibiting beta-lactamases (PBPs). Tazobactam (partner to ceftolozane), avibactam (to ceftazidime), vaborbactam (to meropenem), and sulbactam are the BLIs that are coupled with the novel beta-lactam antibiotics described here (to imipenem-cilastatin). Another example is the use of sulbactam, which boosts imipenem’s action against most Enterobacterales (lowering the MIC by 2- to 128-fold) and P. aeruginosa (lowering the MIC by 8-fold) [37]. The addition of vaborbactam decreases the MIC 2- to > 1024-fold and increases meropenem’s effectiveness against most Enterobacteria species [37].
Ceftazidime/avibactam was authorized by the FDA in 2015 for the treatment of cIAI (in combination with metronidazole) and cUTI at a dosage of 2.5 g IV, TD, and was later extended to HAP/VAP in 2018. Ceftazidime/avibactam had similar potential adverse effects to ceftazidime alone, according to the FDA package insert. Ceftazidime/avibactam has the most clinical evidence among the “novel” antibiotics. It was proven to be non-inferior to the best-available medication (mainly carbapenem) in treating cUTI caused by ceftazidime-resistant Enterobacterales and Pseudomonas aeruginosa [22].
Ceftolozane/tazobactam is a combination of antipseudomonal cephalosporins and BLI tazobactam. In 2014, the FDA authorized this antibiotic combination (brand name Zerbaxa) for cUTI and cIAI indications at a dosage of 1.5 g IV, TD. In 2019, the indication was expanded to include HAP/VAP. Ceftolozane has already been shown to be effective against ESBL Enterobacterales and carbapenem-resistant P. aeruginosa [38]. Its effectiveness against carbapenem-resistant Acinetobacter spp. [39] and Enterobacterales [40] is modest.
Meropenem/vaborbactam (Vabomere) was authorized by the FDA to treat cUTI at a dosage of 4 g (meropenem 2 g and vaborbactam 2 g) IV, TD. Carbapenem-resistant Enterobacterales, especially those that contain KPCs, benefit from the addition of vaborbactam. However, as previously stated, it has little activity against MBL and OXA-positive isolates [41]. Meropenem’s action against A. baumannii and P. aeruginosa is unaffected by the addition of vaborbactam [37].

6. Alternatives to Antibiotics

Antibiotic overuse in people and animals has contributed significantly to the rise of AMR and has also resulted in the buildup of these substances in the environment by selecting resistant bacteria and transforming the environment into a vast reservoir for AMR genes [42]. Furthermore, the abuse of antibiotics in animal production, as well as the EU restriction on their use in feed (Regulation EC/1831/2003), has resulted in a rise in the incidence of livestock disease and economic loss.
Antimicrobial peptides are among the most effective antibiotic substitutes. Due to their capability to heal bacterial infections, especially those induced by multidrug-resistant diseases, many antimicrobial peptides have been reported, with varied activity spectra and mechanisms of action. Hundreds of AMPs have been found to exhibit antibacterial action in vivo against bacteria that are resistant to antibiotics [43]. A new piscidin-like peptide from black sea bass fish was recently revealed to have broad-spectrum antibacterial action against many bacteria, particularly Gram-positive infections [44]. Similarly, jelling-I, a tiny AMP made up of eight amino acids, kills Gram-negative and Gram-positive bacteria by compromising the cell membrane’s integrity [45]. Furthermore, another new defensin-like peptide with an antibacterial action against Gram-positive bacteria such as Staphylococcus aureus, Staphylococcus carnosus, Nocardia asteroides, and one Gram-negative bacterium, Psychrobacter faecalis, was recently reported [46].
Antimicrobial lipids, such as medium-chain fatty acids (MCFAs) and monoglycerides, might be used instead of antibiotics. MCFAs are a key component of the innate immune system in mammalian breast milk, skin, and mucosa, and they can trigger the development of host defense peptides in humans and animals [47]. The antibacterial activity of lauric acid (LA) and its monoglyceride derivative, monolaurin (glycerol monolaurate, GML), is the greatest among MCFAs. Although the positive effects of MCFAs and LA are progressively becoming acknowledged, nothing is known about their content in insects. Because of their outstanding nutritional characteristics and possible impacts on animal health, insects have recently received a lot of interest as new alternative feed additives.

7. Regulate the Sale and Use of Antibiotics through Prescription

In 1997, the worldwide interest in anti-toxins was USD 17 billion (GBP 10.6 billion), with around 818 billion remedies for respiratory plot contaminations. While the market is increasing in size (it was USD 15 billion in 1993), the quantity of treatments remains the same. Nonetheless, in the period 1980–1991, the all-out ascent in anti-microbial solutions in England was 46%, which was still lower than the pace of development in France [48][49]. The rise in anti-microbial costs could be impacted by various factors [49][50][51]. Two attributes of anti-toxin recommendation have appeared to raise the danger of obstruction choice, specifically the utilization of too few dosages or too long treatments [52]. The terrible implementation of the utilization of profoundly specific specialists presently cannot seem to be resolved as far as their natural impacts. Seventy-five percent of populace remedies are for respiratory infections [50][51]. The most widely recognized explanation for these is tonsillopharyngitis, along with bronchitis. Anti-microbials are given to around 90% of tonsillopharyngitis patients in both France and the United Kingdom. This creates 9 million solutions in France each year. The conference rate in France is several times that of the United Kingdom [49][50]. A quick indicative test for bunch A streptococci with 90% affectability is available [53]. However, it is not generally utilized and is not covered by the French medical care framework. For this reason, 35% of patients have been polluted with bunch A streptococci [54]; a fast test may save around 6 million anti-toxin solutions.

8. Global Action Plan on Antimicrobial Resistance

Procedures that are crucial for healthcare services would be inaccessible or dangerous without antibiotics, as detailed by the WHO [55]. Critical operations, cancer care, and prophylaxis during cesarean are examples of facilities that can no longer be administered efficiently without appropriate antibiotics. The foundation for improving WHO health programs recognize the building blocks of a healthcare system relating to administration, funding processes, medications and technology, health information programs, human resources, and the provision of health services [56]. With the scale and intensity of the antimicrobial resistance challenge, there has been some improvement in developing national initiative plans by member countries of the WHO [57]. The overarching aim of the action strategy is to assure the potential to cure and avoid contagious diseases by reliable and secure, quality-assured drugs, which are used sensibly and are available to anyone that needs them, and this should be continued as long as possible [58]. Antibiotics can be used in favor of better animal breeding methods to develop growth and prevent disease progressively. For each human and animal medication, it is necessary to gain even more knowledge of the extent of resistant strains and the usage of antibiotics. Public health services must optimize their use of antibiotics to decrease the impact of the disease. In line with the objectives for sustainable improvement, the focus should be put on improving sanitation and the availability of safe water, promoting handwashing habits, and better protection and treatment of infection in clinics [59].

9. Role of Pharmacists in Combating Resistance to Antimicrobials

Pharmacists are critical participants of the healthcare system and play a vital role in using medications and the delivery of medical guidance [60]. They are in an excellent position to recognize antibiotics better and educate their intelligent use in society and hospitals through direct communication with the patient [61][62]. The utilization of antibiotics among medical practitioners, patients in the various areas of the care community, and the general consumers is one of the significant results of improved pharmacists’ responsibilities [63]. Hospital pharmacists can supervise the clinical setting by controlling compliance with common treatment protocols, including the appropriate antibiotics prescribed by physicians through their formulation and testing [64][65]. In the context of antimicrobial stewardship, pharmacists and nurses can cooperate successfully to minimize antimicrobial usage and fight antimicrobial resistance [65]. Community pharmacists could convince patients that antibiotics are ineffective for viral infections, and they could suggest people consult with a registered physician for alternative therapy for a mild infection. They should be diligent in compliance with legislation and not allow antibiotics to be sold over the counter [64]. Academic pharmacists play an important part in teaching pharmacists and other medical professionals about the appropriate use of drugs and the concept of antimicrobial stewardship [66]. Pharmacists could also develop national legislation, regulations, and directives that encourage the proper use and application of antimicrobials, where available [67]. They could, in turn, cooperate in the development and facilitation of training and behavioral actions that help the appropriate use of antimicrobials with the support of society and health professional groups.

10. Types of Intervention

Interventions usually fall into six different categories: norms and standards (acknowledgment, directives, public scrutiny, limit OTC sales, control of prescription); information interventions (observation, response); support for decision-making (algorithm, etiology); sequence of distribution (decentralized supply, delivery of medications); economy (financial support, strategic pricing, wellbeing insurance); and management processes (necessary policy on medicine, programs for stewardship) [68]. The more successful they are when they plan the interventions, compared to a national facility or level, the closer they are geared towards the supplier/prescriber of antibiotics. It is also necessary to realize how one intervention can affect other circumstances.
Persuasive intervention: Persuasive intervention is used to disseminate education services, to remember, audit, and discussion or educational provision. The ongoing training of medical professionals will help keep workers up-to-date, educate them about policies and improvements to pharmacotherapy, and encourage them to express perspectives and learn from discussions with their peers [69]. Passive education should preferably be paired with active interventions; passive education yields only modest results as an independent program [70][71].
Restrictive intervention: Restrictive interventions are initiatives that restrict the prescriber’s freedom to select such antibiotics. For example, targeted antibiotics may require approval by a specialist in infectious diseases and may be replaced by a pharmacist or be fully limited in the treatment [72][73][74].

11. Prescribing and Intervention Context

A few investigations depicted the context of interventions to deal with the availability of antibiotics in medical clinics, primary care, and pharmacies, including public, private, and casual suppliers. Some studies concentrated on drug stores, local-area drug specialists, and informal doctors in villages [68]. A better and faster decision by medical professionals associated with drug prescription may lead to substantial patient outcome changes and better use of healthcare costs. While there have been recent changes in the spread of evidence in practice, the prescription practice of medical professionals tends to differ.

12. Knowledge of Antimicrobial Resistance and Appropriate Antibiotics Use

Antibiotics have become a productive and proactive tool against many pathogens over the last four or five decades. The growth of antibiotic-resistant and propagated pathogens in the community is a significant problem globally that poses an important public health danger, particularly in developing areas, in the current era [75][76]. Concepts as to why and what should be done with antibiotic resistance are not the most significant basis for developing interventions to change prescriber execution in antibiotic prescriptions. A conceptual approach is required to choose and execute the procedures to change the medication [77]. The leading causes of antimicrobial resistance increase and spread may be self-medication, illegal prescription, improper use, and unnecessary use of such antimicrobial drugs [78][79][80]. This rise in antibiotic resistance gradually decreases their therapeutic efficacy and leads to more severe diseases with higher death rates. It will place a heavy strain on the global economy and various healthcare organizations [81].
Many studies accurately found that antibiotics had been appropriately administered to treat bladder or urinary tract infections (72% where n = 93), skin or wound infections (67% where n = 87), and gonorrhea (39% where n = 51) [82].


  1. Waksman, S.A. What Is an Antibiotic or an Antibiotic Substance? Mycologia 1947, 39, 565–569.
  2. American Academy of Pediatrics. The History of Antibiotics—HealthyChildren.Org. Available online: (accessed on 29 March 2022).
  3. Laskin, A.I.; Bennett, J.W.; Gadd, G.M. Advances in Applied Microbiology; Elsevier: Amsterdam, Netherlands, 2003; Volume 52.
  4. History of Antibiotic Development. Available online: (accessed on 29 March 2022).
  5. Sneader, W. History of Sulfonamides. Encycl. Life Sci. 2001, 1.
  6. McMillan, E.A.; Gupta, S.K.; Williams, L.E.; Jové, T.; Hiott, L.M.; Woodley, T.A.; Barrett, J.B.; Jackson, C.R.; Wasilenko, J.L.; Simmons, M.; et al. Antimicrobial Resistance Genes, Cassettes, and Plasmids Present in Salmonella Enterica Associated with United States Food Animals. Front. Microbiol. 2019, 10, 832.
  7. About Antibiotic Resistance|Antibiotic/Antimicrobial Resistance. Available online: (accessed on 29 March 2022).
  8. World Health Organization Antibiotic Resistance. Available online: (accessed on 29 March 2022).
  9. World Health Organization. The Evolving Threat of Antimicrobial Resistance Options for Action; World Health Organization: Geneva, Switzerland, 2012; ISBN 9789241503181.
  10. Laxminarayan, R.; Matsoso, P.; Pant, S.; Brower, C.; Røttingen, J.A.; Klugman, K.; Davies, S. Access to Effective Antimicrobials: A Worldwide Challenge. Lancet 2016, 387, 168–175.
  11. Holmes, A.H.; Moore, L.S.P.; Sundsfjord, A.; Steinbakk, M.; Regmi, S.; Karkey, A.; Guerin, P.J.; Piddock, L.J.V. Understanding the Mechanisms and Drivers of Antimicrobial Resistance. Lancet 2016, 387, 176–187.
  12. Sefton, A.M. Mechanisms of Antimicrobial Resistance: Their Clinical Relevance in the New Millennium. Drugs 2002, 62, 557–566.
  13. Reygaert, W.C. An Overview of the Antimicrobial Resistance Mechanisms of Bacteria. AIMS Microbiol. 2018, 4, 482.
  14. Van Den Bogaard, A.E.; Stobberingh, E.E. Antibiotic Usage in Animals. Impact on Bacterial Resistance and Public Health. Drugs 1999, 58, 589–607.
  15. Rahman, M.M.; Rahaman, M.S.; Islam, M.R.; Hossain, M.E.; Mithi, F.M.; Ahmed, M.; Saldías, M.; Akkol, E.K.; Sobarzo-Sánchez, E. Multifunctional Therapeutic Potential of Phytocomplexes and Natural Extracts for Antimicrobial Properties. Antibiotics 2021, 10, 1076.
  16. Rousham, E.K.; Unicomb, L.; Islam, M.A. Human, Animal and Environmental Contributors to Antibiotic Resistance in Low-Resource Settings: Integrating Behavioural, Epidemiological and One Health Approaches. Proc. R. Soc. B Biol. Sci. 2018, 285, 20180332.
  17. Eagar, H.; Swan, G.; Van Vuuren, M. A Survey of Antimicrobial Usage in Animals in South Africa with Specific Reference to Food Animals. J. S. Afr. Vet. Assoc. 2012, 83, 8.
  18. Prestinaci, F.; Pezzotti, P.; Pantosti, A. Antimicrobial Resistance: A Global Multifaceted Phenomenon. Pathog. Glob. Health 2015, 109, 309–318.
  19. Cavalu, S.; Simon, V. Microstructure and bioactivity of acrylic bone cements for prosthetic surgery. J. Optoelectron. Adv. Mater. 2006, 8, 1520–1523.
  20. World Health Organization. Antimicrobial Resistance: Global Report on Surveillance; World Health Organization: Geneva, Switzerland, 2014.
  21. South African National Aids Council. National Strategic Plan on HIV, STIs and TB 2012–2016; South African National Aids Council: Pretoria, South Africa, 2011.
  22. Shaeer, K.M.; Zmarlicka, M.T.; Chahine, E.B.; Piccicacco, N.; Cho, J.C. Plazomicin: A Next-Generation Aminoglycoside. Pharmacother. J. Hum. Pharmacol. Drug Ther. 2019, 39, 77–93.
  23. Eljaaly, K.; Alharbi, A.; Alshehri, S.; Ortwine, J.K.; Pogue, J.M. Plazomicin: A Novel Aminoglycoside for the Treatment of Resistant Gram-Negative Bacterial Infections. Drugs 2019, 79, 243–269.
  24. Denervaud-Tendon, V.; Poirel, L.; Connolly, L.E.; Krause, K.M.; Nordmann, P. Plazomicin Activity against Polymyxin-Resistant Enterobacteriaceae, Including MCR-1-Producing Isolates. J. Antimicrob. Chemother. 2017, 72, 2787–2791.
  25. Wagenlehner, F.M.E.; Cloutier, D.J.; Komirenko, A.S.; Cebrik, D.S.; Krause, K.M.; Keepers, T.R.; Connolly, L.E.; Miller, L.G.; Friedland, I.; Dwyer, J.P. Once-Daily Plazomicin for Complicated Urinary Tract Infections. J. Urol. 2019, 202, 641–642.
  26. Connolly, L.E.; Riddle, V.; Cebrik, D.; Armstrong, E.S.; Miller, L.G. A Multicenter, Randomized, Double-Blind, Phase 2 Study of the Efficacy and Safety of Plazomicin Compared with Levofloxacin in the Treatment of Complicated Urinary Tract Infection and Acute Pyelonephritis. Antimicrob. Agents Chemother. 2018, 62, e01989-17.
  27. Zhanel, G.G.; Baxter, M.R.; Adam, H.J.; Sutcliffe, J.; Karlowsky, J.A. In Vitro Activity of Eravacycline against 2213 Gram-Negative and 2424 Gram-Positive Bacterial Pathogens Isolated in Canadian Hospital Laboratories: CANWARD Surveillance Study 2014–2015. Diagn. Microbiol. Infect. Dis. 2018, 91, 55–62.
  28. Livermore, D.M.; Tulkens, P.M. Temocillin Revived. J. Antimicrob. Chemother. 2009, 63, 243–245.
  29. Balakrishnan, I.; Awad-El-Kariem, F.M.; Aali, A.; Kumari, P.; Mulla, R.; Tan, B.; Brudney, D.; Ladenheim, D.; Ghazy, A.; Khan, I.; et al. Temocillin Use in England: Clinical and Microbiological Efficacies in Infections Caused by Extended-Spectrum and/or Derepressed AmpC β-Lactamase-Producing Enterobacteriaceae. J. Antimicrob. Chemother. 2011, 66, 2628–2631.
  30. Adams-Haduch, J.M.; Potoski, B.A.; Sidjabat, H.E.; Paterson, D.L.; Doi, Y. Activity of Temocillin against KPC-Producing Klebsiella pneumoniae and Escherichia coli. Antimicrob. Agents Chemother. 2009, 53, 2700–2701.
  31. Tsakris, A.; Koumaki, V.; Politi, L.; Balakrishnan, I. Activity of Temocillin against KPC-Producing Enterobacteriaceae Clinical Isolates. Int. J. Antimicrob. Agents 2019, 55, 105843.
  32. Zhanel, G.G.; Golden, A.R.; Zelenitsky, S.; Wiebe, K.; Lawrence, C.K.; Adam, H.J.; Idowu, T.; Domalaon, R.; Schweizer, F.; Zhanel, M.A.; et al. Cefiderocol: A Siderophore Cephalosporin with Activity Against Carbapenem-Resistant and Multidrug-Resistant Gram-Negative Bacilli. Drugs 2019, 79, 271–289.
  33. Jacobs, M.R.; Abdelhamed, A.M.; Good, C.E.; Rhoads, D.D.; Hujer, K.M.; Hujer, A.M.; Domitrovic, T.N.; Rudin, S.D.; Richter, S.S.; van Duin, D.; et al. ARGONAUT-I: Activity of Cefiderocol (s-649266), a Siderophore Cephalosporin, against Gram-Negative Bacteria, Including Carbapenem-Resistant Nonfermenters and Enterobacteriaceae with Defined Extended-Spectrum β-Lactamases and Carbapenemases. Antimicrob. Agents Chemother. 2019, 63, e01801-18.
  34. Kresken, M.; Korte-Berwanger, M.; Gatermann, S.G.; Pfeifer, Y.; Pfennigwerth, N.; Seifert, H.; Werner, G. In Vitro Activity of Cefiderocol against Aerobic Gram-Negative Bacterial Pathogens from Germany. Int. J. Antimicrob. Agents 2020, 56, 106128.
  35. Kresken, M.; Körber-Irrgang, B.; Pfeifer, Y.; Werner, G. Activity of Temocillin against CTX-M-Producing Escherichia coli and Klebsiella pneumoniae from Germany. Int. J. Antimicrob. Agents 2018, 51, 159–160.
  36. Wunderink, R.G.; Matsunaga, Y.; Ariyasu, M.; Clevenbergh, P.; Echols, R.; Kaye, K.S.; Kollef, M.; Menon, A.; Pogue, J.M.; Shorr, A.F.; et al. Cefiderocol versus High-Dose, Extended-Infusion Meropenem for the Treatment of Gram-Negative Nosocomial Pneumonia (APEKS-NP): A Randomised, Double-Blind, Phase 3, Non-Inferiority Trial. Lancet Infect. Dis. 2021, 21, 213–225.
  37. Zhanel, G.G.; Lawrence, C.K.; Adam, H.; Schweizer, F.; Zelenitsky, S.; Zhanel, M.; Lagacé-Wiens, P.R.S.; Walkty, A.; Denisuik, A.; Golden, A.; et al. Imipenem–Relebactam and Meropenem–Vaborbactam: Two Novel Carbapenem-β-Lactamase Inhibitor Combinations. Drugs 2017, 78, 65–98.
  38. Shortridge, D.; Castanheira, M.; Pfaller, M.A.; Flamm, R.K. Ceftolozane-Tazobactam Activity against Pseudomonas aeruginosa Clinical Isolates from U.S. Hospitals: Report from the PACTS Antimicrobial Surveillance Program, 2012 to 2015. Antimicrob. Agents Chemother. 2017, 61, e00465-17.
  39. Kuo, S.C.; Liu, C.E.; Lu, P.L.; Chen, Y.S.; Lu, M.C.; Ko, W.C.; Hsueh, P.R.; Chuang, Y.C.; Wang, F. Der Activity of Ceftolozane-Tazobactam against Gram-Negative Pathogens Isolated from Lower Respiratory Tract Infections in the Asia-Pacific Region: SMART 2015–2016. Int. J. Antimicrob. Agents 2020, 55, 105883.
  40. Karlowsky, J.A.; Hackel, M.A.; Bouchillon, S.K.; Sahm, D.F. In Vitro Activity of WCK 5222 (Cefepime-Zidebactam) against Worldwide Collected Gram-Negative Bacilli Not Susceptible to Carbapenems. Antimicrob. Agents Chemother. 2020, 64, e01432-20.
  41. Lapuebla, A.; Abdallah, M.; Olafisoye, O.; Cortes, C.; Urban, C.; Landman, D.; Quale, J. Activity of Imipenem with Relebactam against Gram-Negative Pathogens from New York City. Antimicrob. Agents Chemother. 2015, 59, 5029–5031.
  42. Roca, I.; Akova, M.; Baquero, F.; Carlet, J.; Cavaleri, M.; Coenen, S.; Cohen, J.; Findlay, D.; Gyssens, I.; Heure, O.E.; et al. The Global Threat of Antimicrobial Resistance: Science for Intervention. N. Microbes N. Infect. 2015, 6, 22–29.
  43. Sheard, D.E.; O’Brien-Simpson, N.M.; Wade, J.D.; Separovic, F. Combating Bacterial Resistance by Combination of Antibiotics with Antimicrobial Peptides. Pure Appl. Chem. 2019, 91, 199–209.
  44. Qiao, Y.; Ma, X.; Zhang, M.; Zhong, S. Cerocin, a Novel Piscidin-like Antimicrobial Peptide from Black Seabass, Centropristis Striata. Fish Shellfish Immunol. 2021, 110, 86–90.
  45. Jia, F.; Wang, J.; Zhang, L.; Zhou, J.; He, Y.; Lu, Y.; Liu, K.; Yan, W.; Wang, K. Multiple Action Mechanism and in Vivo Antimicrobial Efficacy of Antimicrobial Peptide Jelleine-I. J. Pept. Sci. 2021, 27, e3294.
  46. Li, F.; Gao, Z.; Wang, K.; Zhao, Y.; Wang, H.; Zhao, M.; Zhao, Y.; Bai, L.; Yu, Z.; Yang, X. A Novel Defensin-like Peptide Contributing to Antimicrobial and Antioxidant Capacity of the Tick Dermacentor silvarum (Acari: Ixodidae). Exp. Appl. Acarol. 2021, 83, 271–283.
  47. Zhou, Z.; Huang, J.; Hao, H.; Wei, H.; Zhou, Y.; Peng, J. Applications of New Functions for Inducing Host Defense Peptides and Synergy Sterilization of Medium Chain Fatty Acids in Substituting In-Feed Antibiotics. J. Funct. Foods 2019, 52, 348–359.
  48. Davey, P.G.; Bax, R.P.; Newey, J.; Reeves, D.; Rutherford, D.; Slack, R.; Warren, R.E.; Watt, B.; Wilson, J. Growth in the Use of Antibiotics in the Community in England and Scotland in 1980–1993. Br. Med. J. 1996, 312, 613.
  49. Guillemot, D.; Carbon, C.; Vauzelle-Kervroëdan, F.; Balkau, B.; Maison, P.; Bouvenot, G.; Eschwège, E. Inappropriateness and Variability of Antibiotic Prescription among French Office-Based Physicians. J. Clin. Epidemiol. 1998, 51, 61–68.
  50. Carbon, C.; Bax, R.P. Regulating the Use of Antibiotics in the Community. Br. Med. J. 1998, 317, 663–665.
  51. Guillemot, D.; Maison, P.; Carbon, C.; Balkau, B.; Vauzelle-Kervroëdan, F.; Sermet, C.; Bouvenot, G.; Eschwège, E. Trends in Antimicrobial Drug Use in the Community-France, 1981-1992. J. Infect. Dis. 1998, 177, 492–497.
  52. Guillemot, D.; Carbon, C.; Balkau, B.; Geslin, P.; Lecoeur, H.; Vauzelle-Kervroedan, F.; Bouvenot, G.; Eschwege, E. Low Dosage and Long Treatment Duration of β-Lactam: Risk Factors for Carriage of Penicillin-Resistant Streptococcus Pneumoniae. J. Am. Med. Assoc. 1998, 279, 365–370.
  53. Pichichero, M.E. Group A Streptococcal Tonsillopharyngitis: Cost-Effective Diagnosis and Treatment. Ann. Emerg. Med. 1995, 25, 390–403.
  54. Kaplan, E.L.; Top, F.H.; Dudding, B.A.; Wannamaker, L.W. Diagnosis of Streptococcal Pharyngitis: Differentiation of Active Infection from the Carrier State in the Symptomatic Child. J. Infect. Dis. 1971, 123, 490–501.
  55. Kaplan, W.; Laing, R. Priority Medicines for Europe and the World. 2004. Available online: (accessed on 29 March 2022).
  56. Tomson, G.; Vlad, I. The Need to Look at Antibiotic Resistance from a Health Systems Perspective. Upsala J. Med. Sci. 2014, 119, 117–124.
  57. Dadgostar, P. Antimicrobial Resistance: Implications and Costs. Infect. Drug Resist. 2019, 12, 3903–3910.
  58. World Health Organization. WHO Western Pacific. Available online: (accessed on 29 March 2022).
  59. Jinks, T.; Lee, N.; Sharland, M.; Rex, J.; Gertler, N.; Diver, M.; Jones, I.; Jones, K.; Mathewson, S.; Chiara, F.; et al. A Time for Action: Antimicrobial Resistance Needs Global Response. Bull. World Health Organ. 2016, 94, 558.
  60. Williford, S.L.; Johnson, D.F. Impact of Pharmacist Counseling on Medication Knowledge and Compliance. Mil. Med. 1995, 160, 561–564.
  61. Booth, J.L.; Mullen, A.B.; Thomson, D.A.M.; Johnstone, C.; Galbraith, S.J.; Bryson, S.M.; McGovern, E.M. Antibiotic Treatment of Urinary Tract Infection by Community Pharmacists: A Cross-Sectional Study. Br. J. Gen. Pract. 2013, 63, e244–e249.
  62. Farley, T.M.; Shelsky, C.; Powell, S.; Farris, K.B.; Carter, B.L. Effect of Clinical Pharmacist Intervention on Medication Discrepancies Following Hospital Discharge. Int. J. Clin. Pharm. 2014, 36, 430–437.
  63. Sakeena, M.H.F.; Bennett, A.A.; McLachlan, A.J. Enhancing Pharmacists’ Role in Developing Countries to Overcome the Challenge of Antimicrobial Resistance: A Narrative Review. Antimicrob. Resist. Infect. Control 2018, 7, 63.
  64. Roiu, G.; Cavalu, S.; Teusdea, A.; Petricas-Heredea, D.A.; Fratila, O. Assessment of Antibiotic Influence on Structural Modifications of Amniotic Membrane by FTIR Spectroscopy. Mater. Plast. 2020, 57, 191–198.
  65. Schellack, N.; Pretorius, R.; Messina, A.P. ‘Esprit de Corps’: Towards Collaborative Integration of Pharmacists and Nurses into Antimicrobial Stewardship Programmes in South Africa. S. Afr. Med. J. 2016, 106, 973–974.
  66. Burger, M.; Fourie, J.; Loots, D.; Mnisi, T.; Schellack, N.; Bezuidenhout, S.; Meyer, J.C. Knowledge and Perceptions of Antimicrobial Stewardship Concepts among Final Year Pharmacy Students in Pharmacy Schools across South Africa. S. Afr. J. Infect. Dis. 2016, 31, 84–90.
  67. FIDSSA South African Antibiotic Stewardship Programme (SAASP). Available online: (accessed on 29 March 2022).
  68. Wilkinson, A.; Ebata, A.; MacGregor, H. Interventions to Reduce Antibiotic Prescribing in LMICs: A Scoping Review of Evidence from Human and Animal Health Systems. Antibiotics 2018, 8, 2.
  69. World Health Organization. Using Indicators to Measure Country Pharmaceutical Situations Fact Book on WHO Level I and Level II Monitoring Indicators. 2006. Available online: (accessed on 29 March 2022).
  70. Dellit, T.H.; Owens, R.C.; McGowan, J.E.; Gerding, D.N.; Weinstein, R.A.; Burke, J.P.; Huskins, W.C.; Paterson, D.L.; Fishman, N.O.; Carpenter, C.F.; et al. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America Guidelines for Developing an Institutional Program to Enhance Antimicrobial Stewardship. Clin. Infect. Dis. 2007, 44, 159–177.
  71. Pulcini, C.; Gyssens, I.C. How to Educate Prescribers in Antimicrobial Stewardship Practices. Virulence 2013, 4, 192–202.
  72. Rahal, J.J.; Urban, C.; Horn, D.; Freeman, K.; Segal-Maurer, S.; Maurer, J.; Mariano, N.; Marks, S.; Burns, J.M.; Dominick, D.; et al. Class Restriction of Cephalosporin Use to Control Total Cephalosporin Resistance in Nosocomial Klebsiella. JAMA 1998, 280, 1233–1237.
  73. Lautenbach, E.; LaRosa, L.A.; Marr, A.M.; Nachamkin, I.; Bilker, W.B.; Fishman, N.O. Changes in the Prevalence of Vancomycin-Resistant Enterococci in Response to Antimicrobial Formulary Interventions: Impact of Progressive Restrictions on Use of Vancomycin and Third-Generation Cephalosporins. Clin. Infect. Dis. 2003, 36, 440–446.
  74. Bradley, S.J.; Wilson, A.L.T.; Allen, M.C.; Sher, H.A.; Goldstone, A.H.; Scott, G.M. The Control of Hyperendemic Glycopeptide-Resistant Enterococcus Spp. on ahaematology Unit by Changing Antibiotic Usage. J. Antimicrob. Chemother. 1999, 43, 261–266.
  75. Organisation mondiale de la Santé. Plan D’ Action Mondial Pour Combattre la Résistance aux Antimicrobiens. 2016. Available online: (accessed on 29 March 2022).
  76. Vadivoo, N.S.; Usha, B.; Padmavathi, B.K. Assessment of Clinicians Knowledge and Perception on Antimicrobial Resistance a Primary Strategy for Antimicrobial Resistance Control. Glob. J. Med. Res. 2015, 15, 9–14.
  77. Eccles, M.P.; Grimshaw, J.M.; Johnston, M.; Steen, N.; Pitts, N.B.; Thomas, R.; Glidewell, E.; Maclennan, G.; Bonetti, D.; Walker, A. Applying Psychological Theories to Evidence-Based Clinical Practice: Identifying Factors Predictive of Managing Upper Respiratory Tract Infections without Antibiotics. Implement. Sci. 2007, 2, 26.
  78. Shehadeh, M.; Suaifan, G.; Darwish, R.M.; Wazaify, M.; Zaru, L.; Alja’fari, S. Knowledge, Attitudes and Behavior Regarding Antibiotics Use and Misuse among Adults in the Community of Jordan. A Pilot Study. Saudi Pharm. J. 2012, 20, 125–133.
  79. Gitzinger, M. Antibiotic Resistance Response—GARDP. Available online: (accessed on 29 March 2022).
  80. De Sosa, A.J.; Byarugaba, D.K.; Amabile-Cuevas, C.F.; Hsueh, P.R.; Kariuki, S.; Okeke, I.N. Antimicrobial Resistance in Developing Countries. In Antimicrobial Resistance in Developing Countries; Springer: New York, NY, USA, 2010; pp. 1–554.
  81. Jairoun, A.; Hassan, N.; Ali, A.; Jairoun, O.; Shahwan, M. Knowledge, Attitude and Practice of Antibiotic Use among University Students: A Cross Sectional Study in UAE. BMC Public Health 2019, 19, 518.
  82. Shahpawee, N.S.; Chaw, L.L.; Muharram, S.H.; Goh, H.P.; Hussain, Z.; Ming, L.C. University Students’ Antibiotic Use and Knowledge of Antimicrobial Resistance: What Are the Common Myths? Antibiotics 2020, 9, 349.
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to : , , , , , , , , , , ,
View Times: 256
Revisions: 2 times (View History)
Update Date: 25 May 2022