Antibiotic agents polymyxin

Nystatin (100,000 lU) is also available in combination with neomycin sulfate [1405-10-3] (35,000 lU), polymyxin B sulfate [1405-20-5] (35,000 lU), acetarsol [97-44-9] (150 mg), and dimethicone [8050-81-5] (2,500 mg). One or two ovules per day are inserted vaginaHy for at least 6—12 days. This combination has an antibacterial, antimycotic, and antitrichomonas action (see also Antibiotics, oligosaccharides Antiparasitic agents, antiprotozoals). 

Systemic therapy with a variety of (3-lactams, macro-lides and lincosamides (clindamycin) has been the cornerstone of skin infection therapy for many years [17]. However, topical antibiotics can play an important role in both treatment and prevention of many primary cutaneous bacterial infections commonly seen in the dermatological practice [18], Indeed, while systemic antimicrobials are needed in the complicated infections of skin and skin structure, the milder forms can be successfully treated with topical therapy alone [18], The topical agents used most often in the treatment of superficial cutaneous bacterial infections are tetracyclines, mupirocin, bacitracin, polymyxin B, and neomycin. 

On the other hand, the negatively charged Kdo-lipid A domain constitutes a target for binding of certain antibiotics, such as polymyxin B (125) and basic peptides derived from host cells such as the bactericidal/perme-ability-increasing protein (BPI) (261). In this respect the Kdo-lipid A domain constitutes a weak site of the outer membrane, rendering bacteria vulnerable to the action of cationic agents. 

With the advent of potent broad-spectrum antibiotics, such as the quinolones and third-generation cephalosporins, the indications for the use of the polymyxins, with their serious potential for toxicity, are few. Their only justifiable use may be as topical agents. 

Polymyxin B is effective against many gramnegative bacteria, including E. coli, Klebsiella, and Salmonella. Systemic administration of this drug, however, is often associated with extreme nephrotoxicity. Hence, this agent is used primarily for the treatment of local, superficial infections of the skin, eyes, and mucous membranes. When applied topically for these conditions, adverse reactions are relatively rare. Polymyxin B is often combined with other antibiotics such as bacitracin and neomycin in commercial topical preparations. 

Antibiotics such as neomycin, streptomycin, kanamycin, gentamycin, polymyxin A, polymyxin B, colistin, lincomycin, and tetracycline have all been implicated as augmenting the action of the nondepolarizing agents. 

Microbes also have a plasma membrane that resides adjacent to their cell wall. Polymyxins are amphipathic agents (containing both nonpolar, lipophilic and polar, lipophobic groups) that interact with phospholipids in microbial cell membranes. The result is disruption of the membrane and increased permeability. However, because microbial and mammalian cell membranes are not exceedingly dissimilar, polymixins can produce significant toxicity in humans (i.e., they have low selective toxicity). This is also true for the related drug nystatin. This is why these particular antibiotics are not generally used systemically and are usually restricted to topical application. 

Although topical antibiotics are used frequently in the management of ocular rosacea, no firm evidence demonstrates their efficacy as a sole therapeutic agent. Topical steroids, however, are effective for treating the inflammatory aspects and frequently are used four times daily in conjimction with antibiotics in combination products such asTobraDex (tobramycin-dexamethasone), Pred-G (gentamicin-prednisone), or Maxitrol (neomycin-polymyxin B-dexamethasone). Because of potential steroid-induced side effects, chronic use of these agents should be avoided. 

Unlike dendritic keratitis, indolent ulcers are typically very difficult to treat. Instillation of a prophylactic antibiotic, such as polymyxin B-bacitracin ointment two to four times a day, and a cycloplegic agent, such as 5% homatropine two to three times a day, is indicated. Therapeutic soft contact lens use with appropriate antibiotic therapy can also be considered as alternatives. These patients must be monitored carefully to ensure that no secondary infection develops. If the ulcer deepens, a new infiltrate forms, or if there is an increase in the anterior chamber reaction while the patient is being treated, cultures should be performed to rule out bacterial or fungal infection. Cyanoacrylate glue, conjunctival flap surgery, or tarsorrhaphy may be required if healing does not occur. 

If it is suspected that an antibiotic is contributing to prolonged neuromuscular blockade, the patient should be monitored and the effect of calcium (up to 1 g of calcium chloride slowly) should be observed. If this is unsuccessful, neostigmine (maximum dose 5 mg for an adult) or edrophonium (0.5 mg/kg) can be tried, but these agents may intensify a block due to cohstin, lincomycin, or polymyxin B. If the other remedies fail, 4-aminopjTidine (maximum dose 0.3 mg/kg) can be successful. Artificial ventilation should be continued until adequate spontaneous efforts are achieved and other possible factors, such as acidosis or electrolyte disturbances, are corrected. 

Neomycin is not usually administered parenter-ally to animals because of nephrotoxicity and ototoxicity. Only 3% of a dose of neomycin is absorbed following p.o. administration it is, therefore, used in the therapy of coliform enteritis in small and large animals. It is available as tablets, boluses and water additives, in many different combinations with antibiotics, corticosteroids and anticholinergic agents. It can also be used to decrease nitrogenous waste production by the normal gastrointestinal flora in animals with hepatic encephalopathy. Neomycin is not absorbed through the skin, so it is frequently utilized as the antibacterial constituent in ophthalmic formulations (especially in combination with bacitracin and polymyxin B) and in preparations for the treatment of otitis externa in small animals. 

By early 2004, 15 million doses of smallpox vaccine, Dryvax, were available in the United States. Dryvax, a Wyeth product, is a live virus preparation of vaccinia. The vaccine comes as a lyophilized (freeze-dried) powder in 100 dose vials containing the antibiotics polymyxin B, streptomycin, tetracycline, and neomycin. Fifty percent glycerin, containing a small amount of phenol as a preservative, serves as the diluent for reconstitution (25). Studies have shown that diluting the vaccine in a 1 5 ratio could expand the supply without reducing vaccine efficacy (25). In addition, 200 million antibiotic-free doses are in production. The CDC Web site has detailed directions on how to reconstitute and administer the vaccine at http //www.bt.cdc.gov/agent/smallpox/vaccination/ administration.asp. 

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