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No change No change No change Not known No change Not known4 Not known4
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Table 30 11 Use of antimicrobials in patients with renal failure1 and hepatic failure (continued)
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Proposed Dosage Regimen in End-Stage Renal Failure (all doses IV unless stated otherwise) Initial Dose3 200 mg PO 1g 05 g IV 150 mg 15 g 1 2 million units 4 mg/kg 3g 200 400 mg 600 mg PO 800 mg PO 3g 100 mg 320 mg TMP + 1600 mg SMZ 45 mg/m2 1g 200 mg orally; avoid IV in renal failure Maintenance Dose 200 400 mg q24h PO 05 1 g q24h 05 g q8h 150 mg q24h 15 g q4h 1 million units q8h 4 mg/kg q24h 2 g q6 8h 200 mg q6 8h PO 400 mg q12h PO 600 mg q24h PO 800 mg q24h PO 2 g q6 8h 50 mg q12h 80 mg TMP + 400 mg SMZ q12h 40 mg/m2 q24h 1 g q6 10d based on serum levels8 200 mg orally twice daily; avoid IV in renal failure
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Drug Ketoconazole Meropenem Metronidazole Micafungin Nafcillin Penicillin G Pentamidine Piperacillin and piperacillin + tazobactam Posaconazole Rifampin Telithromycin Ticarcillin Tigecycline Trimethoprim-sulfamethoxazole Trimetrexate Vancomycin Voriconazole
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Principal Mode of Excretion or Detoxification Hepatic Renal Liver Bilary/hepatic Liver 80%; kidney 20% Tubular secretion Not known Renal 50 70%; biliary 20 30% Hepatic Hepatic Hepatic Tubular secretion Hepatic Some liver
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Approximate Half-Life in Serum Normal 8 hours 1 hour 6 10 hours 15 hours 075 hour 05 hour 6 9 hours 1 hour 20 66 hours 2 3 hours 7 10 hours 11 hours 25 40 hours TMP 10 12 hours; SMZ 8 10 hours 15 hours 6 hours 6 24 hours; dosedependent Renal Failure2 8 hours 5 10 hours 6 10 hours 15 hours 15 hours 7 10 hours 6 9 hours 3 6 hours 20 66 hours 3 5 hours 7 10 hours 15 20 hours 25 40 hours TMP 24 48 hours; SMZ 18 24 hours Not known 6 10 days 6 24 hours
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Removal of Drug by Hemodialysis No Yes Yes No No Yes No Yes No No Not known Yes No Yes
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Dose after Hemodialysis None 05 g 025 g None None 500,000 units None needed 1g
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Dosage in Hepatic Failure Not known4 No change 025 g q12h No change 2 3 g q12h No change
CMDT 2008 CHAPTER 30
No change 1 2 g q8h
None Not known 1g None 80 mg TMP + 400 mg SMZ None None None
Not known4 Not known No change No change No change
Hepatic Glomerular filtration Hepatic
No No No
Not known No change 100 mg twice daily
For cephalosporins, see text and Tables 30 5 and 30 6; for aminoglycosides, see Table 30 7 Considered here to be marked by creatinine clearance of 10 mL/min or less 3 For a 70-kg adult with a serious systemic infection 4 Dose adjustment in hepatic failure has not been studied, but because clearance of the drug is principally hepatic, dose reduction may be required 5 Pharmacokinetics and dosing are in reference to the active agent, penciclovir 6 When creatinine clearance is 30 mL/min, a dose of 60 mg/kg is given once daily For clearances less than 30 mL/min, the dose has not been established 7 Oral valganciclovir is same as IV ganciclovir except that the initial dose is 900 mg, maintenance dose is 450 mg twice weekly in patients with creatinine clearance 10 40 mL/min Post doses not known 8 When serum levels reach 10 15 mcg/mL, another dose should be given
Common Problems in Infectious Diseases & Antimicrobial Therapy
nephritis with primary tubular lesions associated with antibasement membrane antibodies If the intradermal test described below is negative, desensitization is not necessary, and a full dose of the material may be given If the test is positive, alternative drugs should be strongly considered If that is not feasible, desensitization is necessary Patients with a history of allergy to penicillin are also at an increased risk for having a reaction to cephalosporins Since the specific immunogens responsible for anaphylaxis are not known for drugs other than penicillin, skin testing with cephalosporins is not recommended A common approach to these patients is to assess the severity of the reaction If an IgE-mediated reaction to penicillin can be excluded by history, a cephalosporin can be administered When the history justifies concern about an immediate-type reaction, penicillin skin testing should be performed If the test is negative, a cephalosporin can be given If the test is positive, there is a 5 10% chance of cross reactivity, and cephalosporin desensitization should be performed
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