Fluoroquinolones for Infectious Diseases Treatment

Fluoroquinolones for Infectious Diseases Treatment 1.10 Pharmaceuticals 1.10.2 Fluoroquinolones Fluoroquinolones are extensively used for treatment of various infectious diseases. [[1]]. Because of their extensive Gram negative treatment, quinolone antibiotics were initially used for the treatment urinary tract related diseases. Higher drug concentrations promote their effectiveness in the treatment of urinary infections. lomefloxacin, levofloxacin ciprofloxacin, ofloxacin, enrofloxacin, and gatifloxacin have higher renal clearance to analyze the activity of the kidney and urine concentration test measures the ability of the kidneys to excrete water. Fluoroquinolones enter the environment by different routes including municipal and industrial wastewater effluent. The recent studies show that from many parts of the world reported the presence of fluoroquinolones in surface water bodies at concentrations ranging from non-detectable to around 50 ng dm-3 [[2]]. The existence and addition of fluoroquinolone antibiotics in aquatic environments, at very low concentrations, may cause affect to the ecosystem and human health. They require development of the different oxidation methods for the transformation of fluoroquinolones in water during water treatment. Disinfection processes (e.g., chlorination, oxidation, and UV irradiation) appear to result in considerable addition of fluoroquinolone and their transformation during municipal treatment of waste before to release into water stream [[3]]. An added disinfectant may undergo transformation reactions with antibacterial agents during water treatment. Sodium hypochlorite is a commonly intended for chlorination of water during disinfection process, and also potassium permanganate may be also used for disinfection processes[[4][5]]. Considering the occurrence of chlorine in municipal wastewater and drinking water disinfection processes, reactions with aqueous chlorine species likely play a particularly important role in the environmental fate of fluoroquinolones. Levofloxacin Levofloxacin is in a class of antibacterial agent called fluoroquinolones. It is used for the treatment of certain bacterial infections. Levofloxacin is used to treat certain infections such as urinary tract, chronic pneumonia, bronchitis, kidney and skin infections. Levofloxacin may used to prevent anthrax in people who may have been open to anthrax germs in the air. It works by destroying bacteria that causes infections. Antibiotics will not work for viral infections, flu, colds, or other diseases. Lomefloxacin Structure of Lomefloxacin (LMF) Lomefloxacin is also class of fluoroquinolones antibacterial agent.This used to treat a wide range of bacterial infections. It is used to treat bacterial infections including bronchitis and urinary tract infections. Lomefloxacin is associated with photo toxicity and central nervous system adverse effects [[6]]. 1.10.3 Oxazolidinones The oxazolidinones, a new class of synthetic antibacterial agents have a distinctive mechanism of to contorol bacterial protein synthesis. The oxazolidinone to be approved for clinical use, show in-vitro activity against many important resistant harmful organisms. Clinical trials verified the action in the setting of pneumonia soft-tissue, and skin infections, and infections due to vancomycin-resistant. [[7]]. Linezolid Linezolid is an antibacterial agent used to treat certain serious bacterial infections that have not taken action from other antibacterial agents. Linezolid is not only used to treats bacterial infections, but also for viral infections. Unnecessary use or over use of any antibiotic can lead to its reduces effectiveness. Linezolid is a relatively safe drug; it can be used in patients of all ages and in people with poor kidney function or liver disease [[8]]. The current study was undertaken to elucidate reaction products, kinetics, and mechanism between free available chlorine (FAC) or permanganate with fluoroquinolones class of antibacterial agents such as levofloxacin (LFC) Lomefloxacin (LMF) and oxazolidinone class of antibacterial agent linezolid (LNZ). Which are the most popular for disease control and prevention in the recently are used. 1.10.1. Routes of pharmaceuticals entering into the environment The figures 1.4.a. and 1.4.b. and figure 1.5 shows that a large fraction of clinically prescribed antibiotic dose is discharged into municipal waste water systems due to incomplete metabolism of antibiotics within the human body. (Rain) runoff water carries the hospital wastes to rivers and contaminates the river water. In recent years, there has been growing concern about the presence of pharmaceuticals in the aquatic environment. Continuous exposure of antibiotics to bacterial communities, promotes the bacteria to develop antibiotic resistance. Possible induction of antibiotic resistance in bacteria is directly related to human health. The action of antibiotics during water treatment process clearly plays a significant role in this regard. Antibacterials and other pharmaceutical are having the tendency to persist contaminants in the water supply is of increasing concern in the field of environmental toxicology. Several national and international bodies have reported the presence of antibacterials in surface water, ground water, drinking water, and waste water [[9]]. Antibacterials were primarily observed as â€Å"wonder medicines† mainly because they were introduced from surgical drains or spontaneous cure were available to treat serious bacterial diseases. Many classes of these antibacterial agents were discovered in the last five to six decades. These include penicillins, sulfonamides, trimethoprim, chloramphenicol, cephalosporins, colimycins, tetracyclines, lincosamides etc, [[10]]. Understanding the fate and transportation of antibacterial agents in the aquatic environment is vital to properly assess the risk associated with these emerging contaminants [[11]]. What happens to these antibacterial agents during municipal water treatment? Municipal water treatment essentially involve following processes; The steps involved in conventional water treatment method are shown in the above flow diagram. The aeration process is carried out to remove the odor from the water. The filtration is the removal of the solids, specially suspended matter, by passing the water through a granular media (sand, coal, diatomaceous earth, granular activated carbon). The colloidal particles pass through the filtration process and removed using coagulants in the flocculation process. The micro contaminants, which are dissolved in water, can easily pass through aeration, filtration and flocculation processes but they may react with the disinfectants in the last process. What are the commonly used disinfectants? Chlorine: Chlorine gas, NaOCl, Bleaching powder, Conventional water treatment Chloramines: Weak disinfectant and low rate of reaction Ozone: Costly UV/H2O2: Costly Not suitable for Municipal water treatment KMnO4: Potassium permanganate is usually applied for waste water treatment 1.11 Disinfection Disinfection is the process of killing pathogenic organisms like bacteria and viruses in the drinking water supply. It is the last step in the treatment and is necessary to supply a â€Å"bacteriologically free† drinking water for the general public usage. Disinfection is the necessary step before the public water supplies. Chlorination is the treatment technique of killing harmful microorganisms in water supplies. 1.11.1 Chlorination An added layer of complexity in this problem lies in the potential bio-transformation antibacterial agents can undergo during drinking water chlorination. Chlorination, in the form of sodium hypochlorite, is a common mechanism of drinking water disinfection. [[12]]. Chlorination has been shown degradation of certain parent drugs in drinking water [[13]]. The effect of chlorination has been studied for several non antibacterials. However, these studies are few in comparison to the variety of pharmaceutical contaminants our environment faces [[14]]. A long-term objective of this research work is to know the fate of antibacterial in the water supply when they are exposed to chlorination and oxidation in the drinking water treatment process. Microorganisms can be found in raw water like rivers, lakes and groundwater. Some microorganisms may cause diseases in human and are called pathogens. These pathogens existing in water can be transmitted through a drinking water distribution system, causes water related diseases. The use of chlorine in the water treatment process was originally directed to the primary function of disinfection. Chlorination is one of the methods that can be used to make germ-free water. This method was first used over a hundred years ago, and is still it is continued. It is a chemical disinfection method that uses various types of chlorine or chlorine-containing substances for the oxidation and disinfection of what will be the potable water source. 1.11.2 Importance and benefits of chlorination of water Many investigations and studies have been carried out to make sure success in new treatment plants using chlorine as a cleaning agent. An important benefit of chlorination is that it has effective against viruses and bacteria. The three most common types of chlorinating agents used in water treatment are: Ca (OCl)2 (calcium hypochlorite), NaOCl (sodium hypochlorite), and Cl2 (chlorine) gas, Any type of chlorinating agent is added to water during the water treatment process will lead to form of hypochlorous acid (HOCl) and hypochlorite ion (OCl), which are the main disinfecting species. Of the two disinfecting species, hypochlorous acid is the most effective. The amount of each compound present in the water is dependent on the pH level of the water. At lower pH levels, the hypochlorous acid will dominant. The quantity of chlorine that is required to disinfect water is depends on the impurities in the water. The amount of chlorine that is required to satisfy all the impurities is termed the ‘chlorine demand. Once the chlorine demand has been reached is called breakpoint chlorination i.e., the addition of chlorine to water until the chlorine demand has been fulfilled. After the breakpoint, any extra chlorine added will result in free chlorine residual, residual chlorine can react with a number of different contaminants present in raw water The main purpose of chlorination is to disinfect water, but it also has many other benefits. Unlike some of the other disinfection methods like ozonation and ultraviolet radiation, chlorination is able to provide a residual to reduce the chance of growing pathogens in water storage tanks or the water distribution system. 1.11.3 Types of chlorinating agents 1.11.3 .1 Chlorine Gas Chlorine gas is good disinfectant, but it is toxic to more than just waterborne pathogens; it is also toxic to humans. When chlorine gas (Cl2) is added to the water (H2O), it hydrolyzes rapidly to produce hypochlorous acid (HOCl) and the hypochlorous acid will then dissociate into hypochlorite ions (OCl) and hydrogen ions (H+). Because hydrogen ions are produced, the water will become more acidic (the pH of the water will decrease). The amount of dissociation depends on the original pH of the water. If the pH of the water is below a 6.5, nearly no dissociation will occur and the hypochlorous acid will dominate. A pH above 8.5 will see a complete dissociation of chlorine, and hypochlorite ions will dominate. A pH between 6.5 and 8.5 will see both hypochlorous acid and hypochlorite ions present in the water. Together, the hypochlorous acid and the hypochlorite ions are referred to as free chlorine. Hypchlorous acid is the more effective disinfectant, and therefore, a lower pH is preferred for disinfection. 1.11.3.2 Calcium hypochlorite Calcium hypochlorite Ca (OCl) 2 is made up of the calcium salts of hypochlorous acid. When treating water, a lesser amount of calcium hypochlorite is needed than if using chlorine gas. When calcium hypochlorite is added to water, hypochlorite and calcium ions are produced. Instead of decreasing the pH like chlorine gas does, calcium hypochlorite increases the pH of the water. However, hypochlorous acid and hypochlorite concentrations are still dependent on the pH of the water; therefore by decreasing the pH of the water, hypochlorous acid will still be present in the water. As a result, calcium hypochlorite and chlorine gas both produce the same type of residuals. 1.11.3 .3 Sodium hypochlorite Sodium hypochlorite (NaOCl) is made up of the sodium salts of hypochlorous acid and is a chlorine-containing compound that can be used as a disinfectant. It is produced when chlorine gas is dissolved into a sodium hydroxide solution. It is in liquid form, clear with a light yellow color, and has a strong chlorine smell. Sodium hypochlorite is extremely corrosive and must be stored in a cool, dark, and dry place. Sodium hypochlorite will naturally decompose; therefore it cannot be stored for more than one month at a time. Of all the different types of chlorine available for use, this is the easiest to handle. Like calcium hypochlorite, sodium hypochlorite will also produce a hypochlorite ion, but instead of calcium ions, sodium ions are produced. NaOCl will also increase the pH of the water through the formation of hypochlorite ions. To obtain hypochlorous acid, which is a more effective disinfectant, the pH of the water should be decreased. In drinking water, the concentration of chlorine is usually very low and is thus not a concern in acute exposure. More of a concern is the long term risk of cancer due to chronic exposure to chlorinated water. Chlorination is a very conventional method of water disinfection that has been used from several years. It is efficient for destroying viruses and bacteria. 1.12 Aqueous chlorination chemistry In water treatment, gaseous chlorine Cl2 or hypochlorite are commonly used for chlorination processes. Chlorine gas (Cl2) hydrolyzes in water according to the following reaction: Fig.1.5. Relative distribution of main aqueous chlorine species as a function of pH at 25 ËÅ ¡C and for a chloride concentration Where k1 and k-1 values, calculated at  µ=0 M and 25ËÅ ¡C from Wang and Margerum, are 22.3 s-1 and 4.3Ãâ€"104 M-2 s-1, respectively. For temperatures between 0 and 25 1ËÅ ¡C, KCl2 ranges from 1.3Ãâ€"10-4 to 5.1Ãâ€"10-4 [[15]]. Hypochlorous acid resulting from reaction (1), is a weak acid which dissociates in aqueous solution: With KHOCl reported in literature between 1.5Ãâ€"10-8 (pKaHOCl,0ËÅ ¡C = 7.82) and 2.9Ãâ€"10-8 (pKaHOCl,25ËÅ ¡C= 7.54) for temperatures between 0 and 25 ËÅ ¡C [[16]]. Under typical water treatment conditions in the pH range 6–9, hypochlorous acid and hypochlorite are the main chlorine species. Depending on the temperature and pH level, different distributions of aqueous chlorine species are observed. Fig. 1.6. Shows the distribution of HOCl and ClO as a function of the pH at 25ËÅ ¡C and for a chloride concentration of 5Ãâ€"10-3 M (177.5mgL-1). For these high chloride concentrations, Fig. 1 6. shows that Cl2 hydrolysis is almost complete at pH >4. Therefore, Cl2 can usually be neglected under typical drinking water treatment conditions [[17]]. References 1 [1]. P.C.Sharma, A. Jain and S. Jain, Fluoroquinolone antibacterial: a review on chemistry, Microbiology and therapeutic prospects, Acta Poloniae Pharmaceutica-Drug Res, Vol. 66 , 2009, pp. 587-604. [2]. P.Wang, Y.L. He and C.H. Huang, Oxidation of fluoroquinolone antibiotics and structurally related amines by chlorine dioxide: Reaction kinetics, product and pathway, Eval. Water res. vol.4 4, 2010, pp.5989-5998. [3]. M.C. Dodd , A.Shah ,U. V.Gunten and C. H.Huang, â€Å" Interactions of Fluoroquinolone Antibacterial Agents with Aqueous Chlorine: Reaction -Kinetics, Mechanisms, and Transformation Pathways† Environ. Sci. Technol. Vol.39, 2005, pp. 7065-7076. [4]. S. D. Richardson and T. A. Ternes, Emerging contaminants and current issues,† â€Å"Water analysis, Analytical Chemistry, vol. 77(12), 2005, pp. 3807–3838. [5] .J. Gibs, P. E. Stackelberg, E. T. Furlong, M. Meyer, S. D. Zaugg, and R. L. Lippincott, â€Å"Persistence of pharmaceuticals and other organic compounds in chlorinated drinking water as a function of time,† Science of the Total Environment, vol. 373(1), 2007 ,pp. 240–249. [6]. E.Rubinstein, History of quinolones and their side effects.† Chemotherapy 2001,47 (Suppl 3): 3 [7]. D.J. Diekema and R.N Jones. Oxazolidinone antibiotics. Lancet. 2001, 358 (9297):1975-82. Review. Pub Med PMID: 11747939. [8]. A.E. Barnhill, M.T. Brewer and S.A. Carlson. Adverse effects of antimicrobials via predictable or idiosyncratic inhibition of host mitochondrial components. Antimicrob. Agent. Chemother., 2012,Vol.56 (8):pp. 4046–4051. [9]. T C. Melton and S. D. Brown, Hindawi Publishing Corporation International Journal of Medicinal Chemistry, Vol. 2012, pp.1-6. [10] .S. H. Zinner, Antibiotic use: present and future, New microbiologica, Vol.30, 2007, pp. 321-325. [11] .H.C. Zhang, W. R. Chen and C.H. Huang Kinetic Modeling of Oxidation of Antibacterial Agents by Manganese Oxide, Environ. Sci. Tech., Vol. 42(15), 2008, pp. 5548–5554. [12]. S. D. Richardson and T. A. Ternes, â€Å"Water analysis: emerging contaminants and current issues,† Anal. Chem., Vol.77 (12), 2005, pp. 3807–3838. [13]. J. Gibs, P. E. Stackelberg, E. T. Furlong, M. Meyer, S. D. Zaugg, and R. L. Lippincott, â€Å"Persistence of pharmaceuticals and other organic compounds in chlorinated drinking water as a function of time,† Sci. Tot. Environ. Vol. 373(1), 2007, pp. 240–249. [14]. Z. Li, H. Fenet, E. Gomez, and S. Chiron, â€Å"Transformation of the antiepileptic drug oxcarbazepine upon different water disinfection processes,† Water Res., Vol. 45(4), 2011, pp. 1587– 1596. [15]. T.X. Wang and D.W.Margerum,. Kinetics of reversible chlorine hydrolysis: temperature dependence and general-acid/ base-assisted mechanisms. Inorg. Chem. Vol.33, 1994, pp.1050–1055. [16]. J.C.Morris, The acid ionization constant of HOCl from 5 to 351. J. Phys. Chem. Vol.70, 1966, pp.3798–3805. [17]. M. Deborde, U.V. Gunten, Reactions of chlorine with inorganic and organic compounds during water treatment—Kinetics and mechanisms: A critical review, water res., Vol. 42, 2008, pp.13 – 51.