Conversion from acute to subacute care beds.
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Biomedical subjects
Publications and source records attributed to D W Joubert.
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Mechanism of action, antimicrobial spectrum, pharmacology, adverse reactions and therapeutic uses of nitrofurantoin, a broad-spectrum antimicrobial agent, are discussed. The frequency and potential severity of reactions attributed to nitrofurantoin, plus its inability to achieve therapeutic blood concentrations, relegate this drug to a position of secondary importance. Nitrofurantoin compares favorably with other standard agents for the therapy of acute and recurrent urinary tract infections in women which may be caused by susceptible organisms, and it is an effective chemoprophylactic agent for patients with recurrent urinary tract infections. The compound has no apparent adverse effects on the developing fetus and can be used in pregnant women. This is not sanctioned by the package insert, however. Nitrofurantoin should not be administered when the possibility of bacteremia exists, as the drug does not achieve therapeutic serum levels when administered orally. Nitrofurantoin is contraindicated for patients with renal insufficiency. The value of this compound for men with acute urinary tract infection, recurrent urinary tract infection, acute bacterial prostatitis or chronic bacterial prostatitis has not been established. There are no indications for prescribing parenteral nitrofurantoin.
The mechanism of action, antimicrobial spectrum, pharmacokinetic properties, drug interactions, adverse reactions and therapeutic uses of trimethoprim-sulfamethoxazole, a combination enzyme-specific inhibitor of bacterial folate synthesis, are reviewed. Trimethoprim-sulfamethoxazole currently is approved by the FDA for the therapy of established recurrent bacterial urinary tract infections, pneumocystosis, otitis media in children and shigellosis. Claimed advantages of the drug are synergistic activity, bactericidal activity and ability to decrease the rate of emergence of resistance to the individual components. Trimethoprim-sulfamethoxazole is the drug of choice for treatment of pneumocystosis and an acceptable oral therapy for recurrent urinary tract infections caused by susceptible bacteria. In children with otitis media, it is used as an alternative to ampicillin and amoxicillin and is preferred when these patients are penicillin-sensitive or when the infection is caused by beta-lactamase-producing Haemophilus influenzae. Hematologic reactions (anemia, thrombocytopenia, granulocytopenia, agranulocytosis) to trimethoprim-sulfamethoxazole occur rarely. Gastrointestinal intolerance and skin eruptions are the most prevalent adverse reactions. Most untoward reactions to trimethoprim-sulfamethoxazole develop within two weeks of onset of therapy, and their incidence compares favorably with that of standard agents administered for the same indications.
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The mechanism of action, spectrum of antimicrobial activity, pharmacokinetics, adverse effects, therapeutic use, and dosage of methenamine hippurate and methenamine mandelate are reviewed. The antimicrobial activity of methenamine depends on its conversion in the urine to formaldehyde. Formaldehyde's spectrum of antibacterial activity encompasses all urinary tract pathogens. Urinary concentrations of formaldehyde vary with pH and urine volume; however, there is no documentation that acdification of the urine enhances methenamine's therapeutic activity. Adverse reactions to methenamine, including gastrointestinal intolerance and skin reactions, are mild and reversible and occur infrequently. Methenamine mandelate and hippurate are effective in the prevention of recurrent urinary tract infections except in patients with Foley catheters or who require intermittent catheterization.
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Biogenesis of tetrahydrofolate cofactors essential for bacterial growth and survival is blocked by sulfamethoxazole-trimethoprim. An intravenous form of the antimicrobial combination has recently been approved for the treatment of acute, symptomatic, bacterial pyelonephritis, recurrent urinary tract infections, shigellosis, and Pneumocystis carinii pneumonia. Intravenous sulfamethoxazole-trimethoprim has emerged as an invaluable agent for the management of selected infections, including bacterial meningitis and Salmonella bacteremia, where limited therapeutic alternatives exist. In addition, co-administration of intravenous sulfamethoxazole-trimethoprim with a carboxypenicillin provides an empiric treatment for the infected granulocytopenic patient that compares favorably with standard combinations. Adverse events unique to the intravenous form of the drug consist of phlebitis and fluid imbalances. Fluid overload results from the relatively large volumes of 5% dextrose solution required as diluent.
Trimethoprim has recently been marketed as a single-entity product for the treatment of initial episodes of uncomplicated symptomatic urinary tract infections; it was previously available only in combination with sulfamethoxazole. Trimethoprim exerts antimicrobial activity by blocking the reduction of dihydrofolate to tetrahydrofolate, the active form of folic acid, by susceptible organisms. It has inhibitory activity for most gram-positive aerobic cocci and some gram-negative aerobic bacilli. Resistance to trimethoprim may be either intrinsic or acquired. Acquired resistance most commonly stems from a chromosomal mutation that results in the production of a dihydrofolate reductase enzyme which is less vulnerable to trimethoprim inhibition. Gastrointestinal intolerance and skin eruptions are the most common untoward reactions resulting from the administration of trimethoprim. Trimethoprim constitutes very effective therapy for women with acute symptomatic urinary tract infections caused by E. coli, and the compound compares favorably with alternative standard agents, such as ampicillin and cephalexin. The safety of trimethoprim in the pregnant woman has not been established. Since indiscriminate use of trimethoprim could foster the emergence of trimethoprim resistance, thereby negating the value of both trimethoprim and trimethoprim-sulfamethoxazole, trimethoprim should only be prescribed for well defined indications. Trimethoprim is currently being investigated as definitive therapy for a wide range of infections, including bacterial exacerbations of chronic bronchitis, bacterial pneumonia, and typhoid fever. Initial reports are encouraging.
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