Urinary tract infections trimethoprim-sulfamethoxazole

Q3.1 Co-trimoxazole tablets contain sulfamethoxazole and trimethoprim and are used in the treatment of chest and urinary tract infections. Classify sulfamethoxazole and trimethoprim as acidic, basic or neutral and hence describe how you could separate a mixture of the two drugs in the laboratory using simple glassware and reagents. See Figure 3.24. 

Urinary Tract Infections. The sulfa drugs have maintained an important place in treatment of urinary tract infections, where short acting, highly soluble drugs are requited (19). Those most used in the United States ate sulfts ox azole, sulfamethizole, sulfisomidine, and sulfacytine. For chronic urinary tract infection, the sulfamethoxazole—trimethoprim combination is ftequendy employed. 

The sulfa dmgs are stiH important as antimicrobials, although they have been replaced in many systemic infections by the natural and semisynthetic antibiotics. They are of great value in third world countries where problems of storage and lack of medical personnel make appropriate use of antibiotics difficult. They are especially useful in urinary tract infections, particularly the combination of sulfamethoxazole with trimethoprim. Their effectiveness has been enhanced by co-adniinistration with dihydrofolate reductase inhibitors, and the combination of sulfamethoxazole with trimethoprim is of value in treatment of a number of specific microbial infections. The introduction of this combination (cotrimoxazole) in the late 1960s (1973 in the United States) resulted in increased use of sulfonamides. 

Sulfa drugs Mild rash occurred 2 hours after taking a double-strength trimethoprim-sulfamethoxazole tablet prescribed for a urinary tract infection. 

Septra DS Septra SS Antibiotic Tab Sulfamethoxazole 800 mg, trimethoprim 160 rrg Tab Sulfamethoxazole 400 mg, trimethoprim 80 mg Urinary tract infections 1 tab bid x 7-10 days Shigellosis 1 lab bid x 3-5 days Bronchitis 1 tab bid x 2 weeks Travelers diarrhea 1 tab bid x 5 days Rash common Stevens Johnson Syndrome (erythema multiforme) rarely UTI Prophylaxis 1 tabqhs... 

Septra IV Antibiotic Inj per 5 mL Sulfamethoxazole 400 mg, trimethoprim 80 mg P carinii pneumonia 15 mg/l day (based on TMP) IV in 3 doses x 21 days (each dose in 250 mL of D5Wover 2 hours). Urinary tract infections and shigellosis 8-10 mg/kg daily based on trimethoprim in 3 equal doses (q8h by IV infusion) for 7 days. 

A 59-year-old woman presents to an urgent care clinic with a 4-day history of frequent and painful urination. She has had fevers, chills, and flank pain for the last 2 days. Her physician advised her to immediately come to the clinic for evaluation. In the clinic she is febrile (38.5°C [101.3°F]) but otherwise stable and states she is not experiencing any nausea or vomiting. Her urine dipstick test is positive for leukocyte esterase. Urinalysis and urine culture are also ordered. Her past medical history is significant for three urinary tract infections in the past year. Each of these episodes was uncomplicated, treated with trimethoprim-sulfamethoxazole, and promptly resolved. She also has osteoporosis for which she takes a daily calcium supplement. The decision is made to treat her with oral antibiotics for a complicated urinary tract infection with close follow-up. Given her history what would be a reasonable empiric antibiotic choice Depending on the antibiotic choice are there potential drug interactions she should be counseled on ... 

A combination of trimethoprim-sulfamethoxazole is effective treatment for a wide variety of infections including P jiroveci pneumonia, shigellosis, systemic salmonella infections, urinary tract infections, prostatitis, and some nontuberculous mycobacterial infections. It is active against most Staphylococcus aureus strains, both methicillin-susceptible and methicillin-resistant, and against respiratory tract pathogens such as the pneumococcus, Haemophilus sp, Moraxella catarrhalis, and Klebsiella pneumoniae (but not Mycoplasma pneumoniae). However, the increasing prevalence of strains of E coli (up to 30% or more) and pneumococci that are resistant to trimethoprim-sulfamethoxazole must be considered before using this combination for empirical therapy of upper urinary tract infections or pneumonia. 

Trimethoprim- sulfamethoxazole Synergistic combination of folate antagonists blocks purine production and nucleic acid synthesis Bactericidal activity against susceptible bacteria Urinary tract infections Pneumocystis jiroveci pneumonia toxoplasmosis nocardiosis Oral, IV renal clearance (half-life 8 h) dosed every 8-12 h t formulated in a 5 1 ratio of sulfamethoxazole to trimethoprim Toxicity Rash, fever, bone marrow suppression, hyperkalemia... 

Nitrofurantoin is bacteriostatic and bactericidal for many gram-positive and gram-negative bacteria but P aeruginosa and many strains of proteus are resistant. There is no cross-resistance between nitrofurantoin and other antimicrobial agents and resistance emerges slowly. As Escherichia coli resistant to trimethoprim-sulfamethoxazole and fluoroquinolones has become more common, nitrofurantoin has become an important alternative oral agent for treatment of uncomplicated urinary tract infection. 

Klebsiella pneumoniae Pneumonia urinary tract infection 3rd-generation cephalosporin an aminoglycoside Cefuroxime ciprofloxacin ofloxacin ampicillin/ sulbactam amoxicillin/ clavulanate imipenem meropenem trimethoprim-sulfamethoxazole... 

Petri WA. Sulfonamides, trimethoprim-sulfamethoxazole, quinolones, and agents for urinary tract infections. In Brunton LL, et al, eds. The Pharmacological... 

In acute and chronic urinary tract infection, the combination of trimethoprim and sulfamethoxazole (Bactrim, Septra) exerts a truly synergistic effect on bacteria. The sulfonamide inhibits the utilization of p-amino-benzoic acid in the synthesis of folic acid (Figure 2.3), whereas trimethoprim, by inhibiting dihydrofolic acid reductase, blocks the conversion of dihydrofolic acid to tetrahydrofolic acid, which is essential to bacteria in the denovo synthesis of purines, pyrimidines, and certain amino acids. Because mammalian organisms do not synthesize folic acid and therefore need it as a vitamin in their daily diets, trimethoprim-sulfamethoxazole does not interfere with the metabolism of mammalian cells. 

Urinary tract infections (UTI) Recurrent infection Trimethoprim- sulfamethoxazole Excellent... 

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). 

Aminoglycosides are NOT indicated for the treatment of uncomplicated urinary tract infections these Infections respond to less toxic antimicrobial agents, such as trimethoprim-sulfamethoxazole. 

Mandell, G.L. Sande, M.A. Antimicrobial agents sulfonamides, trimethoprim, sulfamethoxazole, quinolones, and agents for urinary tract infections. In Pharmacological Basis of Therapeutics, 8th Ed. Gilman, A.G., Rail, T.W., Nies, A.S., Taylor, P., Eds. Pergamon Press New York, 1991 1047-1064. 

Hoigne R, Klein U, Muller U. Results of four-week course of therapy of urinary tract infections a comparative study using trimethoprim with sulfamethoxazole (Bactrim Roche) and trimethoprim alone In Hejzlar M, Semonsky M, Masak S, editors. Advances in Antimicrobial and Antineoplastic Chemotherapy. Munchen-Berhu-Wien Urban and Schwatzenberg, 1972 1283. 

Bennett WM, Craven R. Urinary tract infections in patients with severe renal disease.Treatment with ampicillin and trimethoprim-sulfamethoxazole. Jama. 1976 Aug 23 236(8) 946-8. 

Uncomplicated urinary tract infections can be managed most effectively with short-course (3 days) therapy with either trimethoprim-sulfamethoxazole or a fluoroquinolone. Complicated infections require longer treatment periods (2 weeks) usually with one of these agents. 

McCarty JM, Richard G, Huck W, et al. A randomized trial of short-course ciprofloxacin, ofloxacin, or trimethoprim-sulfamethoxazole for treatment of acute urinary tract infections in women. Am J Med 1999 106 292-299. 

A patient presents with a urinary tract infection and is prescribed a combination drug containing trimethoprim and sulfamethoxazole. These drugs are effective because they do which of the following ... 

The synergistic combination of trimethoprim (TMP), and sulfamethoxazole (SMZ), both folic acid antagonist antibacterial agents, was introduced over 25 years ago for its effect against a variety of infective organisms, including Pneumocystis carinii (PC). Prior to the AIDS era, TMP-SMZ, also referred to as cotrimoxazole, was used predominantly for the treatment of respiratory and urinary tract infections, including PC pneumonia (PCP) [40-45]. 

Nanra RS, Anderton JL, Evans M, Fairley KF, Kincaid-Smith P. The use of trimethoprim and sulfamethoxazole in the management of chronic and recurrent upper and lower urinary tract infection. Med J Aust 1971 1 25-26. 

Urinary tract infection—Acnte nncomplicated cystitis in women can be effectively and inexpensively treated, before the infecting organism is known, with a three-day course of oral trimethoprim-sulfamethoxazole in areas where the prevalence of E. coli resistant to trimethoprim-sulfamethoxazole exceeds 15 to 20%, a fluoroquinolone can be substituted. 

As a signihcant percentage of urinary tract infections in many parts of the world are caused by sulfonamide-resistant microorganisms, snlfonamides are no longer a therapy of first choice. Trimethoprim-sulfamethoxazole, a quinolone, trimethoprim, fosfomycin, or ampicillin are the preferred agents. 

Orally admiifistered trimethoprim is used in the treatment of chroific recurring urinary tract infection. Oral forms of trimethoprim-sulfamethoxazole are used in Shigella and some Salmonella infections, particularly when they are... 

Orally administered trimethoprim is used in the treatment of chronic recurring urinary tract infection. Oral forms of trimethoprim-sulfamethoxazole are used in Shigella and some Salmonella infections, particularly when they are resistant to ampicillin and chloramphenicol. High doses of oral trimethoprim-sulfamethoxazole are used in Pneumocystis pneumonia. This combination, along with polymyxin, has been shown to be effective in treating sepsis caused by Serratia or Pseudomonas organisms. 

Prophylaxis may be used to protect healthy persons from acquisition of or invasion by specific microorganisms to which they are exposed. Successful examples of this practice include rifampin administration to prevent meningococcal meningitis in close contacts of a known case, prevention of gonorrhea or syphUis after contact with an infected person, and the intermittent use of trimethoprim-sulfamethoxazole to prevent recurrent urinary tract infections. 

CHAPTER 43 Sulfonamides, Trimethoprim-Sulfamethoxazole, Quinolones, and Agents for Urinary Tract Infections... 

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