Sulfonamides combination therapy

It warrants mention that resistance to a particular antimicrobial agent in vitro may not preclude successful treatment with the drug as long as high concentrations are achieved in urine. Similarly, demonstrable susceptibility in vitro does not always guarantee a successful response to treatment. For example. Enterococcus spp. is often found to be susceptible to the potentiated sulfonamide combinations in vitro however, this pathogen is inherently resistant to these combinations in vivo (Jose-Cunilleras Hinchcliff 1999, Schott 1998). Antimicrobial therapy should be continued for at least 1 week for the treatment of lower UTIs and for 2-6 weeks for upper UTls in horses. Ideally, a voided, midstream urine sample should be submitted for bacterial culture 2-4 days after the initiation of therapy and again 1-2 weeks after treatment has been discontinued. 

On the positive side, it should be recalled that the CQ s gametocidal action in the other three malarial species is still useful in reducing the human reservoir of those organisms. Combination therapy of CQ with sulfonamides and/or dihydrofolate reductase inhibitors can overcome resistance in some cases (see later). 

S u ifa met hoxaro ie (C) Sulfonamide Orally administered bacteriostatic agent used primarily for urinary tract infections often used in combination therapy with trimethoprim. 

The nephrotoxicity associated with the use of amphotericin B was found to vary with individual susceptibility, not dose.9o jjjg adverse effects of amphotericin B on renal function have been summarized.97 The inhibition of p-amino-hippuric acid (PAH) transport in rat kidney by amphotericin B may reflect on the significance of renal blood measurements.9 Amphotericin B is cleared from cerebrospinal fluid by simple diffusion and not an active transport mechanism.99 Combination therapy of amphotericin B and sulfonamides resulted in a high frequency of patient intolerance. Close attention to fungal pathogen inhibitory values and peak serum levels permitted less amphotericin B to be used with less toxicity. ... 

Other Infections. The slowly excreted sulfonamides (eg, sulfamethoxypyrida2ine, sulfadimethoxine) are used for treatment of minor infections such as sinusitis or otitis, or for prolonged maintenance therapy. Soluble sulfonamides are sometimes used for proto2oal infections in combination with other agents. Pyrimethamine, combined with sulfonamides, has been used for toxoplasmosis or leishmaniasis, and trimethoprim with sulfonamides has been used in some types of malaria. In nocardiosis, sulfonamides have been used with cycloserine [68-41-7] (17). 

The type of antibacterial therapy used is important. No effect need be expected from the use of a single chemotherapeutic agent. Successful use has been made of a triple combination of sulfonamide, chloramphenicol, and chlortetracycline (A8). It would seem advisable to avoid neomycin (FI, J2), since this can itself cause a malabsorption syndrome. 

Several drugs closely related to the sulfonamides have been used effectively in the long-term treatment of leprosy. The most widely used is dapsone (diaminodiphenylsulfone). Like the sulfonamides, it inhibits folate synthesis. Resistance can emerge in large populations of M leprae, eg, in lepromatous leprosy, if very low doses are given. Therefore, the combination of dapsone, rifampin, and clofazimine is recommended for initial therapy. Dapsone may also be used to prevent and treat Pneumocystis jiroveci pneumonia in AIDS patients. 

Administration of streptomycin intramuscularly is the method of choice for treating systemic infections. Oral forms of streptomycin or dihydrostreptomycin, frequently combined with sulfonamide drugs and other compounds, are also used in animals for treatment of enteric infections. In addition, streptomycin is used as a feed additive for growth promotion purposes. In some countries, the combination of streptomycin with procaine penicillin is used as an initial nonspecific therapy in farm animals, and in intramammary applications for treatment of mastitis. Intramuscular dosages are in the range 5-10 mg/kg bw, while oral dosages are 20 mg/kg bw. Dihydrostreptomycin is also used in veterinary medicine in intramammary and topical treatments. 

The sulfonamide antibiotics were the first synthetic antibiotics to have general utility in human therapy (B-79MI10806). Of the numerous compounds thus developed, comparatively few are presently used in veterinary practice. They include sulfapyridine (40), sulfamethazine (41) and sulfadimethoxine (42). They are much less potent than the /3-lactams (dose 100-200 mg kg-1), and have a bacteriostatic effect. They are commonly used in combination with trimethoprim (43), when a synergistic effect is observed, i.e. the combination is more potent than either drug alone, and species of bacteria which are unaffected by the drugs individually are susceptible to the combination. 

Pharmacokinetics When a chloroquine-resistant organism is encountered, therapy usually consists of a combination of quinine, pyrimethamine, and a sulfonamide. All are administered orally. [Note fansidar, a combination of pyrimethamine and sulfa-doxime is used.] Taken orally, quinine is well distributed throughout the body and can reach the fetus across the placenta. Alkalinization of the urine decreases its excretion. 

AIDS." A primary infection that is treated with the combination is PCP. The sulfonamide-trimethoprim combination can be used fur treatment and prophylaxis. Additionally, cerebral toxoplasmosis con be treated in active infection or prophyluctically. Urinary tract infections and bum therapy" " " round out the list of therapeutic applications. The sulfonamides arc drugs of choice for a few other types of infections, but their u.sc is quite limited in modem antimicrobial chemotherapy." " "... 

Amlnocyclitols in general, and spectinomycin in particular, are effective in no more than half the patients with NGU, an observation that correlates with the fact that U. urealyticum is susceptible but C. trachomatis is not. Conversely, sulfonamide therapy is successful in chlamydial NGU, but not in NGU associated with U. urealyticum. The differential response to sulfisoxazole or spectinomycin has been used to differentiate chlamydial from ureaplasmal NGU, and a combination of these two agents deserves a clincial trial as an alternative to the tetracyclines. C. trachomatis and U. urealyticum are individually susceptible to several other antimicrobial agents,but all are clinically ineffective or have not been subjected to controlled studies. 

Oral Therapy Sulfonamides Trimethoprim-sulfamethoxazole (TMP-SMX) These agents generally have been replaced by more agents due to resistance. This combination is highly effective against most aerobic enteric bacteria except Pseudomonas aeruginosa. High urinary tract tissue levels and urine levels are achieved, which may be important in complicated infection treatment. Also effective as prophylaxis for recurrent infections. 

An even more extreme situation is found with carbonic anhydrase inhibitors such as ac-etazolamide, ethoxyzolamide, and methazol-amide, which are useful for the treatment cf glaucoma. Because of their limited aqueous solubility or unfavorable lipophilicity,they are not active when given topically to the eye and must be given orally or parenterally. Systemic side effects severely limit this mode of therapy and, consequently, numerous investigations are presently under way to find a new carbonic anhydrase inhibitor that readily penetrates the cornea or to prepare a prodrug with adequate water solubility and lipophilicity combined with the ability to be reconverted to the parent sulfonamide after corneal passage (255-257). 

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