Sulfonamides, Trimethoprim, Fluoroquinolones

Antimetabolite A drug that through chemical similarity is able to interfere with the role of an endogenous compound in cellular metabolism. The term includes antibacterial agents that inhibit bacterial folic acid metabolism 

Sequential blockade The combined action of two drugs that inhibit sequential steps in a pathway of bacterial metabolism 

Resistance Bacterial resistance to sulfonamides is common and may be plasmid-mediated. It can result from decreased intracellular accumulation of the dmgs, increased production of PABA by bacteria, or a decrease in the sensitivity of dihydropteroate synthase to the sulfonamides. Clinical resistance to trimethoprim most commonly results from the production of dihydrofolate reductase that has a reduced affinity for the dmg. 

Trimethoprim and sulfamethoxazole (TMP-SMZ) This important drug combination is currently accepted treatment for complicated urinary tract infections and for respiratory, ear, and sinus infections due to H influenzae and Moraxella catarrhalis. In the immunocompromised patient, TMP-SMZ is used for infections due to Aeromonas hydrophila and is the drug of choice for prevention and treatment of pneumocystis pneumonia. TMP-SMZ is a possible backup drug for typhoid fever and shigellosis and has been used in the treatment of infections caused by methicillin-resistant staphylococci and Listeria monocytogenes. 

Hypersensitivity Allergic reactions, including skin rashes and fever, occur commonly. Cross-allergenicity between the individual sulfonamides should be assumed and may also occur with chemically related dmgs (eg, oral hypoglycemics, thiazides). Exfoliative dermatitis, polyarteritis nodosa, and Stevens-Johnson syndrome have occurred rarely. 

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The antibacterial spectrum of trimethoprim is similar to that of sulfamethoxazole (see p. 290) however, trimethoprim is 20 to 50 times more potent than the sulfonamide. Trimethoprim may be used alone in acute urinary tract infections and in the treatment of bacterial prostatitis (though fluoroquinolones are preferred). 

The highest sales in humans and animals were f)-lactams and tetracyclines, respectively. Tetracyclines alone, in veterinary medicine, represented approximately 50.4% of all sales, while tetracyclines, sulfonamides/trimethoprim, P-lactams, and aminoglycosides combined accounted for more than 80% of AMDs used. During the 7-year period, sales of cephalosporins and fluoroquinolones in veterinary medicine increased by 38.4% and 31.6%, respectively. Nevertheless, as percentages of total veterinary sales, their use remained relatively small cephalosporins 0.64% and fluoroquinolones 0.33% in 2005. In animals, oral administration accounted for 88% of sales, and estimated sales for parenteral products were 10.5%. Moreover, while 92% of total tonnage was intended for food-producing animals, 64% of cephalosporins were intended for pets. 

The results showed that the compounds studied with more frequency in the aquatic environment, and of which, logically, there is more information, are the antibiotics, analgesics and anti-inflammatories (like diclofenac, ibuprofen, naproxen, acetylsalicylic acid, and paracetamol), as well as the p-blocker atenolol. In the category of antibiotics, several families are included, like the macrolides (erythromycin), the fluoroquinolones (ofloxacin and ciprofloxacin), sulfonamides (sulfamethoxazole), penicillins (amoxicillin), the metronidazol, and trimethoprim. Other therapeutic groups also widely studied and frequently found in the environmental waters are the lipid regulators (gemfibrozil and bezafibrat), antiepileptic carbamaze-pine, and antidepressants (diazepam, fluoxetine, paroxetine) (see Table 3). 

Aminoglycosides Chloramphenicol Clindamycin Fluoroquinolones p-Lactams Macrolldes Rifampin Sulfonamides Tetracycline Trimethoprim Vancomycin... 

Trimethoprim is the only weak base listed (fluoroquinolones and sulfonamides are acidic compounds), and its high lipid solubility at blood pH allows penetration of the drug into prostatic and vaginal fluid to reach levels similar to those in plasma. Leukopenia and thrombocytopenia may occur in folate deficiency when the drug is used alone or in combination with sulfamethoxazole. Fluoroquinolones do not exacerbate symptoms of folic acid deficiency. The answer is (D). 

A family of antibiotics called sulfonamides, that stops the growth of bacteria, is used to treat UTI. These include trimethoprim-sulfamethoxazole (TMP-SMX) and cephalasporins. Aztreonam and fluoroquinolones are used as urinary tract antiseptics. Phenazopyridine (Pyridium) is used to treat pain from a UTI. 

Notation-. A = aminoglycosides AMP = amphenicols fj-L = P-lactams d-SPE, dispersive SPE FQ = fluoroquinolones IP = ionophores L = lincosamides M = macrolides NMZ = nitroimidazoles P = penicillins PLE = pressurized liquid extraction Q = quinolones S = sulfonamides T = tetracyclines TMP = trimethoprim. This table is adapted from QuEChERS = quick, easy, cheap, effective, rugged, and safe ... 

Renew, J.E. and Huang, C.-H. (2004) Simultaneous determination of fluoroquinolone, sulfonamide, and trimethoprim antibiotics in wastewater using tandem solid phase extraction and liquid chromatography-electrospray mass spectrometry. Journal of Chromatography A 1042, 113-121. 

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