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#1
28.08.2009, 19:19
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Инъекционные антибиотики пер ос
Уважаемый коллеги!
Как Вы относитесь к таким назначениям. Откуда "растут уши" :Из аннотации к флакону ванкомицина,который КАК ПРАВИЛО вводится парентерально "Ванкомицин может применяться перорально для лечения псевдомембранозного колита, вызванного Clostridium difficile, вследствие применения антибиотиков, а также для лечения стафилококкового энтероколита. В/в введение препарата не имеет преимуществ для лечения данных заболеваний. Препарат следует применять в следующих дозах: взрослым по 0.5 - 2 г 3-4 , детям по 0.04 г/кг 3-4 Соответствующую дозу приготовить в 30 мл воды и дать пациенту выпить или ввести через зонд. Для улучшения вкуса раствора к нему можно добавлять обычные пищевые сиропы. Продолжительность лечения от 7 до 10 дней. Ванкомицин неэффективен при приеме внутрь в случае других типов инфекций." То же коллеги педиатры говорят и про гентамицин ... Ваше мнение коллеги? Ссылки есть какие-нибудь? 
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#2
28.08.2009, 19:55
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Есть такое. Даже не "В/в введение препарата не имеет преимуществ для лечения данных заболеваний.", а "парентеральное введение не должно использоваться при лечении данных заболеваний". Помимо капсул ванкомицина, существуют рекомендации по введению через рот парентерального раствора (правда, ссылки старые).
Из Микромедекса: DRUGDEX® Evaluations VANCOMYCIN 2) Dosing Information a) Vancomycin Hydrochloride 1) Adult a) Antibiotic induced pseudomembranous enterocolitis - Clostridium difficile infection 1) 500 mg to 2 g ORALLY daily divided every 6 to 8 hours for 7 to 10 days (Prod Info VANCOCIN(R) PULVULES(R) oral capsules, 2005) d) Staphylococcal enterocolitis 1) 500 mg to 2 g ORALLY daily divided every 6 to 8 hours for 7 to 10 days (Prod Info VANCOCIN(R) PULVULES(R) oral capsules, 2005) 2) Pediatric a) Antibiotic induced pseudomembranous enterocolitis - Clostridium difficile infection 1) 40 mg/kg/day ORALLY divided every 6 to 8 hours for 7 to 10 days; maximum is 2 g daily (Prod Info VANCOCIN(R) PULVULES(R) oral capsules, 2005) d) Staphylococcal enterocolitis 1) 40 mg/kg/day ORALLY divided every 6 to 8 hours for 7 to 10 days; maximum is 2 g daily (Prod Info VANCOCIN(R) PULVULES(R) oral capsules, 2005) 1.2 Storage and Stability A) Vancomycin Hydrochloride 1) Preparation a) Intravenous route 1) Oral a) Vancomycin may be administered as capsules and oral solution, or the reconstituted intravenous formulation may be administered orally if desired. If the intravenous formulation is used for oral administration, dilute in 1 ounce of water (Prod Info vancomycin hcl IV injection, 2003; Kucers & Bennett, 1987b; Cheung & DiPiro, 1986; Tedesco et al, 1978; Marrie et al, 1978; Keighley et al, 1978; Batts et al, 1980; Fekety et al, 1989). C) Oral route 1) Capsule a) Vancomycin oral capsules should be stored at controlled room temperature, 59 to 86 degrees F (15 degrees to 30 degrees C) (Prod Info Vancocin(R) capsules and pavules, 2000a). 2) Solution a) Reconstituted oral solutions of intravenous vancomycin are stable for at least 90 days at 0 degrees Celsius and 4 degrees Celsius without appreciable loss of potency. Although a reconstituted solution was stable for 58 days at room temperature (45 degrees Celsius), a precipitate was observed on the 6th day in the storage vials and storage at room temperature is not recommended (Mallet et al, 1982). b) The reconstituted oral solution provided by the manufacturer is stable for 2 weeks in the refrigerator (Prod Info Vancocin(R) capsules and pavules, 2000a).
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#3
28.08.2009, 19:56
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Даже пишут, что парентеральный путь не должен использоваться при псевдомембранозном или стафилококковом колите, так как не обеспечивает нужных концентраций в кишке:
1.3.1.B.8.a Antibiotic induced pseudomembranous enterocolitis - Clostridium difficile infection 1) The recommended oral dose of vancomycin is 500 to 2000 milligrams/day in 3 to 4 divided doses for 7 to 10 days (Prod Info VANCOCIN(R) PULVULES(R) oral capsules, 2005). 2) Vancomycin 125 milligrams every 6 hours is as effective as 500 milligrams every 6 hours (Ramsey, 1996). See Drug Consult reference: ANTIBIOTIC-ASSOCIATED PSEUDOMEMBRANOUS COLITIS 1.3.1.B.8.b Staphylococcal enterocolitis 1) The recommended dose is 500 to 2000 milligrams/day orally in 3 to 4 divided doses for 7 to 10 days (Prod Info VANCOCIN(R) PULVULES(R) oral capsules, 2005). 1.3.1.B.8.c Important Note 1) Parenteral administration of vancomycin DOES NOT achieve therapeutically effective fecal levels and should not be used to treat Clostridium difficile colitis or enterocolitis associated with Staphylococcus aureus (Prod Info Vancocin(R), 2001; Wilhel & Estes et al, 1999). 2) Oral vancomycin is indicated ONLY for the treatment of pseudomembranous colitis or enterocolitis associated with Staphylococcus aureus; it is not effective in other types of infection (Prod Info Vancocin(R), 2001).
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#4
28.08.2009, 20:27
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По гентамицину (сорри, многа букф)
1.4.1.A.4 Oral route 1.4.1.A.4.a Necrotizing enterocolitis in fetus OR newborn 1) Gentamicin 2.5 milligrams/kilogram orally every 6 hours has been used for the prevention of necrotizing enterocolitis in low birth weight infants (Bury & Tudehope, 02; Grylack & Scanlon, 1978). In infants receiving oral GENTAMICIN (10 to 200 mg/kg/day) for either the treatment of diarrhea or to prevent necrotizing enterocolitis, the serum concentrations of GENTAMICIN were considered negligible usually in the range of 0.3 to 0.4 micrograms/milliliter (mcg/mL) (Bhat & Meny, 1984; Miranda et al, 1984; Berkovitch et al, 1993; Gemer et al, 1983) A study evaluated the efficacy of gentamicin in 215 infants and children for the treatment of severe infections. In 76 patients, 15 to 100 milligrams/kilogram/day (mg/kg/day) was administered orally and in 137 patients doses of less than 1 mg/kg/day to greater than 6 mg/kg/day was administered twice daily to 4 times daily intramuscularly. Duration of therapy was 1 to 57 days. Highest response rate was observed in 76 patients with bacterial gastroenteritis who received oral GENTAMICIN, resulting in a 91% cure rate. In 54 patients with urinary tract infections, satisfactory results were obtained in 82%. In 30 infants and children with pneumonia and respiratory infections, satisfactory results were obtained in 66%. In the remaining patients with meningitis, septicemia, osteomyelitis, skin and soft tissue infections, satisfactory results were obtained in 60% to 71% of patients treated (Riley et al, 1971a). Oral gentamicin was used successfully to prevent cholestasis in a small group of infants receiving hyperalimentation. In a retrospective chart review, 24 very low birth weight infants were evaluated. Twelve infants received gentamicin 2.5 milligrams/kilogram orally every 12 hours for 1 week then every 6 hours for 2 weeks; another 12 infants were evaluated that did not receive gentamicin. The incidence of cholestasis (defined as a direct bilirubin of 1.5 milligrams/deciliter or greater) was significantly greater in the group that received no treatment than in the gentamicin group (42% versus 8%, respectively). Authors hypothesized that the cause of cholestasis in these infants may be due to overgrowth of bacteria which results in the production of endotoxins which are hepatotoxic (Spurr et al, 1989). Oral GENTAMICIN combined with oral CHOLESTYRAMINE was effective in treating 8 pediatric patients, aged 3.5 to 5 months, with persistent diarrhea that required hospitalization. GENTAMICIN 50 milligrams/kilogram/day in 6 divided doses over 3 days was given with CHOLESTYRAMINE 1 gram every 6 hours, and the CHOLESTYRAMINE was continued for a total of 5 days. None of the patients had a recognized bacterial pathogen in the stools. All patients began to respond within 24 hours and by 9 to 11 days after initiation of therapy the clinical results were highly significant (Hill et al, 1986). 2) In a double-blind, randomized trial 68 children with persistent diarrhea were randomized to placebo or GENTAMICIN 50 milligrams/kilogram/day orally divided into 4 doses for 6 days. At the end of the trial there were no differences between groups for rate of recovery from diarrhea, weight gain, or need for unscheduled intravenous fluids. No adverse effects were noted with GENTAMICIN therapy (Bhatnagar et al, 1992). Similar results have been reported (Bartlett et al, 1992). 3) Metronidazole in combination with GENTAMICIN and CHOLESTYRAMINE has been demonstrated effective in the treatment of persistent, dehydrating diarrhea in infants. Ten infants with persistent diarrhea were administered combination therapy of GENTAMICIN 50 milligrams/kilogram/day (in 6 divided oral doses for 3 days), METRONIDAZOLE 100 milligrams orally every 8 hours for 5 days and CHOLESTYRAMINE 1 g for 6 days. A marked decrease in stool weight was observed during the first 24 hours of therapy with a more gradual but progressive decline thereafter. Infants also received IV fluids (half-strength Darrows solution in 5% dextrose); a decrease in the requirement of IV fluids was observed, with discontinuation of fluids after 48 hours. The authors speculate the mechanism of action of combination therapy is related to bacterial overgrowth causing damage to the intestinal mucosa and subsequent diarrhea, for which antimicrobial agents should be effective. In addition, bacterial overgrowth may cause diarrhea by causing deconjugation and dehydroxylation of bile salts, and thus CHOLESTYRAMINE in combination would be effective by binding bile salts and also binding endotoxins. The study was uncontrolled and further studies are required with the combination therapy to evaluate its role in the management of persistent diarrhea in infants (Hill et al, 1980). In a study of neonates who developed NEC, the use of oral gentamicin in combination with parenteral antibiotics did not offer any advantage over the use of parenteral antibiotics alone c) Pediatric: 1) A review (Cochrane Review) of the literature regarding the use of oral antibiotics, including gentamicin, for the prevention of necrotizing enterocolitis (NEC) concluded that oral antibiotics (gentamicin, kanamycin, vancomycin) reduce the incidence of NEC in low birth weight infants, but concerns of adverse outcomes including the development of resistant organisms have not been adequately addressed. The review included 5 randomized studies with a total of 456 infants. The relative risk for reduction in NEC was 0.47 (0.28, 0.78) and the relative risk for the reduction in NEC-related deaths was 0.32 (0.10, 0.96). The relative risk for an increase in colonization with resistant bacteria was reported as 1.73 (1.00, 2.97). Dose and duration of therapy for gentamicin in 2 of the studies reviewed was 2.5 milligrams/kilogram every 6 hours for 7 days (Bury & Tudehope, 02). 2) The addition of orally administered gentamicin to parenteral antibiotics did not appear to speed recovery, reduce mortality, or reduce the incidence of complications in neonates with necrotizing enterocolitis. The dose of oral gentamicin used was 15 milligrams/kilogram/day given every 4 hours (Hansen et al, 1980). Bartlett AV, Torun B, Morales C, et al: Oral gentamicin is not effective treatment for persistent diarrhea. Acta Paediatr 1992; 381(suppl):149-154. Bhatnagar S, Ghan MK, Sazawal S, et al: Efficacy of massive dose oral gentamicin therapy in nonbloody persistent diarrhea with associated malnutrition. J Pediatr Gastroenterol Nutr 1992; 15:117-124. Grylack LJ & Scanlon JW: Oral gentamicin therapy in the prevention of neonatal necrotizing enterocolitis. A controlled double-blind trial. Am J Dis Child 1978; 132(12):1192-1194. Hansen TN, Ritter DA, Speer ME, et al: A randomized, controlled study of oral gentamicin in the treatment of neonatal necrotizing enterocolitis. J Pediatr 1980; 97(5):836-839. Hasfurther DL & Bailey PL: Failure of neuromuscular blockade reversal after rocuronium in a patient who received oral neomycin. Can J Anaesth 1996; 43:617-620. Hill ID, Mann MD, Househam KC, et al: Use of oral gentamicin, metronidazole, and cholestyramine in the treatment of severe persistent diarrhea in infants. Pediatrics 1986; 77:477-481. Spurr SG, Grylack LJ, & Mehta NR: Hyperalimentation-associated neonatal cholestasis: effect of oral gentamicin. J Parenter Enteral Nutr 1989; 13:633-636.
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#5
28.08.2009, 22:11
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Цитата:
Но ежели производитель ванкомицина смог провести РКИ, приведшие к одобрению оного в пероральной форме для лечения псевдомембранозного колита и стафилококкового энтероколита, то для гентамицина кроме перечисленных крошечных исследований таких данных нет и лично я бы поостерегся бы его давать перорально.
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#6
29.08.2009, 08:58
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Цитата:
Однако можно представить ситуацию, в которой введение гентамицина парентерально является КРАЙНЕ нежелательным (предшествующая ототоксичность, почечная недостаточность), а терапевтический мониторинг недоступен. Может ли тогда клинический фармаколог при наличии соответствующих показаний, оценив риск и пользу каждого из путей введения, рекомендовать именно пероральный путь как менее потенциально опасный в связи с более низкими сывороточными концентрациями, пусть и не обеспечивающий преимущества в эффективности?
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#7
29.08.2009, 13:12
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Цитата:
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#8
29.08.2009, 19:15
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Цитата:
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#9
29.08.2009, 19:24
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Цитата:
... We do not recommend the use of oral aminoglycosides because this treatment has significant toxicity, and can result in the development of resistant bacterial strains, and has not been shown to be more beneficial than standard care. 
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#10
30.08.2009, 01:31
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Цитата:
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#11
30.08.2009, 04:09
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Цитата:
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#12
30.08.2009, 07:30
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Цитата:
"Противопоказания: детский возраст (до 18 лет - до завершения процесса формирования скелета, кроме терапии осложнений, вызванных Pseudomonas aeruginosa у детей с муковисцидозом легких от 5 до 17 лет; профилактики и лечения легочной формы сибирской язвы)" Цитата:
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#13
30.08.2009, 10:36
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Цитата:
Цитата:
И по поводу биодоступности парентеральных аминогликозидов не совсем понял - почему при парентеральном введении биодоступность плохая? Она хорошая, а при в/в - так и вовсе 100% .
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#15
01.09.2009, 22:06
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Цитата:
Цитата:
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Линейный вид
