Trimethoprim with sulfamethoxazole

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. 

Co-trimoxazole (Septrin) is a well-known combination of a sulfonamide (sulfamethoxazole) with trimethoprim. This combination inhibits enzymes at two points of folic acid (32.2) utilisation - the sulfonamide inhibits incorporation of p-aminobenzoic acid during bacterial folic acid synthesis, and trimethoprim inhibits its conversion into tetrahydrofolate. The overall result is synergistic, i.e. there is a greater activity than the sum of the two components. 

Sulfonamides - The synergistic combination of sulfamethoxazole with trimethoprim has emerged as a first choice drug in the treatment of sal-monenosis , chronic pyelonephritis , non-specific and chronic urinary tract infections , and upper respiratory tract infections, especially chronic bronchitis . Favorable results were also achieved in the treatment of purulent angina, bacterial skin infections , staphylococcal osteomyelitis , and endocarditis due to E. coli as well as a variety... 

P-lactamases but can usually be treated with amoxidUin-clavulanic acid, a cephalosporin, or trimethoprim-sulfamethoxazole. Oral trimethoprim-sulfamethoxazole or minocycline may be used to treat S. maltophilia. 

DuPont HL, Reves R, Galindo R, Sullivan P, Wood L, Mendiola J Treatment of travelers diarrhea with trimethoprim/sulfamethoxazole and with trimethoprim alone. N Engl J Med 1982 307 841-844. 

A 2.5-year-old female with a sinus infection caused by Haemophilus influenzae is treated with trimethoprim-sulfamethoxazole. 

The answers are 484-k 485-j. (tlardman, pp 1061-1062, 1682-1685.) Sulfonamides can cause acute hemolytic anemia. In some patients it mayr be related to a sensitization phenomenon, and in other patients the hemolysis is due to a glucose-6-phosphate dehydrogenase deficiency Sulfamethoxazole alone or in combination with trimethoprim is used to treat UTls. The sulfonamide sulfasalazine is employed in the treatment of ulcerative colitis. Daps one, a drug that is used in the treatment of leprosy, and primaquine, an anti mala rial agent, can produce hemolysis, particularly in patients with a glucose-6-phosphate dehydrogenase deficiency. 

Treatment with trimethoprim-sulfamethoxazole or parenteral pentamidine is associated with a 60% to 100% response rate. Trimethoprim-sulfamethoxazole is the regimen of choice for treatment and subsequent prophylaxis of PCP in patients with and without HIV. 

The more common adverse reactions seen with trimethoprim-sulfamethoxazole are rash, fever, leukopenia, elevated serum transaminases, and... 

Initial therapy with trimethoprim-sulfamethoxazole appears to be effective for CA-MRSA and should be considered in geographic areas in which CA-MRSA are commonly encountered. Alternative agents for documented infections with resistant gram-positive bacteria such as methicil-lin-resistant staphylococci and vancomycin-resistant enterococci include linezolid, quinupristin/dalfopristin, daptomycin, and tigecycline. 

Short-course therapy (3-day therapy) with trimethoprim-sulfamethoxazole or a fluoroquinolone (e.g., ciprofloxacin, levofloxacin, or norfloxacin) is superior to single-dose therapy for uncomplicated infection and... 

Single-dose or short-course therapy with trimethoprim-sulfamethoxazole has been used effectively, and prolonged courses of therapy are not necessary for the majority of patients. 

In women who experience symptomatic reinfections in association with sexual activity, voiding after intercourse may help prevent infection. Also, self-administered, single-dose prophylactic therapy with trimethoprim-sulfamethoxazole taken after intercourse has been found to significantly reduce the incidence of recurrent infection in these patients. 

The majority of patients can be managed with oral antimicrobial agents, such as trimethoprim-sulfamethoxazole or the fluoroquinolones (ciprofloxacin, levofloxacin). When IV treatment is necessary, IV to oral sequential therapy with trimethoprim-sulfamethoxazole or a fluoroquinolone, such as ciprofloxacin or ofloxacin, would be appropriate. 

Tetracycline 500 mg every six hours or doxycycline 100 mg every twelve hours for five to seven days will shorten the duration of illness, and fever usually disappears within one to two days after treatment is begun. Ciprofloxacin and other quinolones are active in vitro and should be considered for victims unable to take tetracycline or doxycycline. Successful treatment of Q fever endocarditis is much more difficult. Tetracycline or doxycycline given in combination with trimethoprim-sulfamethoxazole (TMP-SMX) or rifampin for twelve months or longer has been successful in some cases. However, valve replacement is often required to achieve a cure. 

Trimethoprim has a broad spectrum of antimicrobial activity. It is 20-100 times more active than sulfamethoxazole with respect to most bacterial forms. Trimethoprim is active with respect to Gram-positive, aerobic bacteria such as Staphylococcus aureus, Staphylococcus epidermidis, and various types of Streptococcus and Listeria monocytogenes. Trimethoprim is inferior to sulfonamides against forms of Nocardia. It is active... 

Intermediate-acting sulfonamides include sulfadiazine and sulfamethoxazole. Sulfamethoxazole is combined with trimethoprim in co-trimoxazole. Sulfadiazine shows good penetration into the cerebrospinal fluid and is effective for cerebral Toxoplasmosis. It has an elimination half-life 10-17 hours which prolonged in renal impairment. 

Trimethoprim is well absorbed from the GI tract, and peak blood levels are achieved in about 2 hours. Tissue levels often exceed those of plasma, and the urine concentration of trimethoprim may be 100 times that of the plasma. Trimethoprim readily enters the CSF if inflammation is present. The half-life of the drug is approximately 11 hours. Sulfamethoxazole (ti,2 = 10 hours) is frequently coadministered with trimethoprim in a fixed dose ratio of 1 5 (trimethoprim to sulfamethoxazole). 

Serious adverse effects are rare except in AIDS patients. TMP-SMX can cause the same adverse effects as those associated with sulfonamide administration, including skin rashes, central nervous system (CNS) disturbances, and blood dyscrasias. Blood dyscrasias, hepatotoxicity, and skin rashes are particularly common in patients with AIDS. Most of the adverse effects of this combination are due to the sulfamethoxazole component. Trimethoprim may increase the hematological toxicity of sulfamethoxazole. Long-term use of trimethoprim in persons with borderline foUc acid deficiency, such as alcoholics and the malnourished, may result in megaloblastic anemia, thrombocytopenia, and granulocytopenia. 

As indicated earher, sulfonamides are effective in both gram-positive and gramnegative bacteria. Mostly prescribed for humans in the United States, in this class is sulfamethoxazole, mostly in combination with trimethoprim (SMZ-TMP) in a 5 1 ratio. Trimethoprim inhibits dihydropholic acid reductase and this, just like sulfonamides, also interferes with the synthesis of folic acid (Fig. 1.8). As a matter of fact, use of the combined SMZ-TMP has been steadily increasing recently as is displayed by the number of prescriptions (Fig. 1.7). Oral doses of sulfonamides are absorbed well and eliminated by the liver and kidney with 20-60% excreted as the parent compound (Queener and Gutierrez, 2003). 

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 ... 

Potential adverse effects are headache, dizziness, insomnia, fatigue, and gastrointestinal discomfort, although these are typically mild. Lamivudine s bioavailability increases when it is -administered with trimethoprim-sulfamethoxazole. Lamivudine and zalcitabine may inhibit the intracellular phosphorylation of one another therefore, their concurrent use should be avoided if possible. Short-term safety of lamivudine has been demonstrated for both mother and infant. 

Important specifications for the manufacture of all solutions include assay and microbial limits. Additional important specifications for suspensions include particle size of the suspended drug, viscosity, pH, and in some cases, dissolution. Viscosity can be important, from a processing aspect, to minimize segregation. In addition, viscosity has also been shown to be associated with bioequivalency. pH may also have some meaning regarding effectiveness of preservative systems and may even have an effect on the amount of drug in solution. With regard to dissolution, there are at least three products that have dissolution specifications. These products include pheny-toin suspension, carbamazepine suspension, and sulfamethoxazole and trimethoprim suspension. Particle size is also important, and at this point it would seem that any... 

Clinical Use. Atovaquone (Mepron) is used primarily to treat the protozoon that causes toxoplasmosis and the fungus that causes pneumocystis pneumonia in immunocompromised patients.6 This drug is not typically the primary treatment for pneumocystis, but is often reserved for patients who cannot tolerate more traditional treatments using sulfamethoxazole and trimethoprim (see Chapter 34) or pentamidine (see later). Atovaquone can also be used to prevent and treat resistant cases of malaria, and the antimalarial effects of this drug seem especially useful when combined with proguanil.48... 

The sulfas, including co-trimoxazole (sulfamethoxazole plus trimethoprim, see p. 293), are bacteriostatic. These drugs are active against selected enterobacteria, chlamydia, Pneumocystis, and nocardia. Typical clinical applications are shown in Figure 29.3. In addition, sulfadiazine [sul fa DYE a zeen] in combination with the dihydrofolate reductase inhibitor pyrimethamine [py ri METH a meen] is the only effective form of chemotherapy for toxoplasmosis (p. 353). 

CGD patients receive daily prophylaxis of bacterial infections with trimethoprim-sulfamethoxazole. In patients with active bacterial infections, initial... 

Doxycycline is commonly used for moderate to severe acne vulgaris. It is more effective and produces less resistance than tetracycline. The initial dose is 100 or 200 mg daily, followed by 50 mg daily as a maintenance dose after improvement is seen. Doxycycline maybe given with food, but it is more effective when taken 30 minutes before meals. / Minocycline is also commonly used for moderate to severe acne vulgaris. It is more effective than tetracycline. It is dosed similar to doxycycline (100 mg/day or 50 mg twice daily) and on an indefinite basis in selected patients. Minocycline has the most reported adverse effects of the tetracyclines, some of which may be serious. Trimethoprim-sulfamethoxazole (or trimethoprim alone) is a second-line oral agent that may be used for patients who do not tolerate tetracyclines and erythromycin or in cases of resistance to these antibiotics. The adult dose is usually 800 mg sulfamethoxazole and 160 mg trimethoprim twice daily. Clindamycin use is limited by diarrhea and the risk of pseudomembranous colitis. 

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