Pseudomonas pyocyanea INFECTION TREATED WITH COLISTIN METHANE SULPHONATE

McMillan, Mary; Price, Thomas M; Maclaren, D. M.; Scott, G.W.

doi:10.1016/s0140-6736(62)90568-8

Cited by 27 publications

(14 citation statements)

References 8 publications

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“…For complete eradication of a urinary infection, adequate concentrations of an active drug within the infected tissues of the urinary tract is probably more important than a high urinary concentration, so it is not surprising that relapses occur when the drug used is in a form that produces low activity in the blood. The relatively poor responses in systemic infections can also be attributed to circulation of the drug mainly in the inactive form and to loss of the antibiotic through the kidneys in an inactive form; the results in systemic infections with this relatively nontoxic form of the sulphomethyl derivative (Colymycin) have been so disappointing that McMillan et al (1962) recommend that the large daily dose of 720 mg (9 megaunits) should be used; Fekety, Norman & Cluff (1962) reached similar conclusions.…”

Section: Discussionmentioning

confidence: 99%

Sodium Sulphomethyl Derivatives of Polymyxins

Barnett

Bushby

Wilkinson

1964

British Journal of Pharmacology and Chemotherapy

111

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Variations in the treatment of polymyxin B and polymyxin E (colistin) with formaldehyde and sodium bisulphite produce sulphomethyl derivatives which differ quantitatively in acute toxicity and in antibacterial activities in vitro and in vivo. The acute intravenous LD50 values of some sixty samples of these derivatives range from six-to more than eighty-fold those of the parent antibiotics; the in vitro antibacterial activities range from 2 to 12% and the in vivo activities from 20 to 50% of those of the parent antibiotics, with the most toxic derivatives showing the highest activities. When short and prolonged incubation methods are used, assays of the derivatives in solutions of different ages and of blood collected from man and dog after intramuscular injection, show that the antibacterial activities of these sulphomethyl derivatives depend on reversion to the unsubstituted form, and that the differences in the activities are due to variations in stability. These conclusions are supported by comparison of these sulphomethyl derivatives with stable acetyl derivatives. The lower in vivo activity is due, at least partly, to the high renal excretion of the substituted form. Electrophoresis shows that the derivatives are composite, the components corresponding to mono-to pentasulphomethyl polymyxin. Pain at the injection site is the most troublesome side-effect of polymyxin therapy, and this is avoided with these derivatives. In rats injected with quantities some twenty-times the usual human dose, the derivatives cause transitory decrease in urinary output and transitory proteinuria. After intramuscular injection of these derivatives into dogs, no antibiotic is detectable in the cerebrospinal fluid and concentrations present in the bile are not significantly different from those after injection of the parent antibiotic. When injected intracisternally into these animals, derivatives are less toxic than the parent compounds. These studies show that acute intravenous toxicity is a useful index of therapeutic efficiency and that derivatives with intravenous LD50 values of about 100 mg/kg are the most satisfactory ones. Because activity depends on reversion to the parent antibiotic, the use of these derivatives for topical application is contraindicated.

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Section: Discussionmentioning

confidence: 99%

Sodium Sulphomethyl Derivatives of Polymyxins

Barnett

Bushby

Wilkinson

1964

British Journal of Pharmacology and Chemotherapy

111

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“…The serum half-life has been estimated to be ϳ3 to 4.5 h with normal renal function and increases with declining renal function (64,112,144). The data regarding Colomycin are similar: single doses of 2 to 4 mg/kg of colistimethate produced serum levels of 11 to 25 g/ml and urinary concentrations of 200 g/ml of bioactive colistin (119).…”

Section: Serum Concentrationsmentioning

confidence: 99%

“…Virtually all patients received other antimicrobial agents, and their impact on outcomes at- (35,40,119), with particularly high success rates (ϳ85% to 95%) in treating urinary tract infections. In the late 1990s, colistimethate used in the treatment of respiratory exacerbations in patients with cystic fibrosis was reported (33,34,95).…”

Section: Clinical and Microbiological Outcomesmentioning

confidence: 99%

“…However, the more prominent side effects involve neurotoxicity and nephrotoxicity, perhaps attributed to high binding to brain and renal tissue (91). Neurological side effects, occurring in 7% to 27% of patients, typically manifested as paresthesias (often perioral) and ataxia (35,40,49,75,85,119,184). These symptoms usually quickly resolved once the dose was reduced or discontinued.…”

Section: Initial Toxicity Reportsmentioning

confidence: 99%

“…Polymyxins fell out of favor due to reports of nephrotoxicity and neurotoxicity (35,40,85,119). Case series examining the efficacy of polymyxins against multidrug-resistant pathogens have provided some reassurance regarding the toxicity rates of these agents (Table 8), and even prolonged courses have been well tolerated (48,162).…”

Section: Toxicity In Contemporary Studiesmentioning

confidence: 99%

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Polymyxins Revisited

et al. 2008

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SUMMARY The global emergence of multidrug-resistant gram-negative bacilli has spurred a renewed interest in polymyxins. Once discarded due to concerns regarding nephrotoxicity and neurotoxicity, polymyxins now hold an important role in the antibiotic armamentarium. However, more reliable information is needed to determine the optimal dosing of these agents. Also, unanswered questions regarding in vitro testing remain, including questions regarding the reliability of automated systems and the establishment of appropriate breakpoints for defining susceptibility. Most contemporary clinical studies examining the use of these agents have involved patients with infections due to multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii strains. It has been reassuring that polymyxin therapy for resistant bacteria has resulted in clinical responses and toxicity rates similar to those for carbapenem therapy for susceptible isolates. While most surveillance studies demonstrated high rates of susceptibility, several reports noted the emergence of polymyxin-resistant nosocomial pathogens. Polymyxins have assumed an important antibiotic niche for therapy for hospital-acquired infections; further studies defining the optimal use of these agents will likely extend the duration of their clinical usefulness.

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Colistin Therapy in Infants and Children

Walker¹,

Patron²

1965

Arch Pediatr Adolesc Med

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COLISTIN, a polypeptide antibiotic derived from Aerobacillus colistinus, was introduced by Koyama in Japan in the year 1950.2 Gastrointestinal absorption is limited so that intramuscular injection is required for systemic effect and for this purpose sodium colistimethate (sodium colistin methanesulfonate) has been in use in the United States. This drug has been shown to produce serum levels in proportion to the administered dose 3 which are in excess of those required for inhibition and for bactericidal effect upon many Gram-negative organisms in vitro.4 Most strains of Pseudomonas, Escherichia coli, paracolon, and Klebsiella organisms have been demonstrated to be sensitive by tube dilution studies.5 The toxicity of colistin in older children and adults, though variably reported, has been slight with no residual damage or death.6The study reported herein was devised in an attempt to determine whether colistin methane sulfonate was an effective and safe agent in the prevention and management of common lifethreatening bacterial infections of infancy. The clinical effectiveness, toxicity, both immediate and long-term residual, and the incidence of sig¬ nificant alteration in mucous membrane flora were determined in a large number of infants treated with this drug (in conjunction with oxacillin or bacitracin) on the Mercy Hospital Pediatrie Service. These factors have been evaluated in relation to a high and to a moderate dosage schedule and in relation to the serum levels achieved by the dosage utilized.

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Pseudomonas pyocyanea INFECTION TREATED WITH COLISTIN METHANE SULPHONATE

Cited by 27 publications

References 8 publications

Sodium Sulphomethyl Derivatives of Polymyxins

Sodium Sulphomethyl Derivatives of Polymyxins

Polymyxins Revisited

Colistin Therapy in Infants and Children

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