CLINICAL USE OF AMINOGLYCOSIDES AND FLUOROQUINOLONES

Transcription

1 CLINICAL USE OF AMINOGLYCOSIDES AND FLUOROQUINOLONES Douglas Black, Pharm.D. Associate Professor School of Pharmacy University of Washington THE AMINOGLYCOSIDES: Drug Streptomycin Neomycin Kanamycin Paromomycin Spectinomycin Gentamicin Tobramycin Sisomicin Amikacin Netilmicin Year Source organism Streptomyces griseus Streptomyces fradiae Streptomyces kanamyceticus Streptomyces rimosus Streptomyces spectabilis Micromonospora purpurea Streptomyces tenebrarius Micromonospora inyoensis Semisynth deriv of kanamycin Semisynth deriv of sisomicin

2 THE AMINOGLYCOSIDES: QUICK SUMMARY Generally used only when necessary (less toxic drugs are preferred) IV/IM, occasionally intrathecal; PO for certain GI infections Bactericidal Usually combined with a β-lactam for serious Gram-negative infections including Pseudomonas Also used (in lower doses) to help drugs for Gram-positive infections work better Occasionally used for mycobacterial infections Resistance is a significant issue TOXIC!!! WHICH IS WORSE: NEPHROTOXICITY OR OTOTOXICITY? KIDNEY Reversible Well-defined risk factors* Well-defined time course (see next slide) Monitor serum creatinine Serum concentrations correlate EAR Irreversible Poorly-defined risk factors Poorly-defined time course No simple lab values to monitor Poor correlation with serum concentrations *advanced age, duration of therapy, hypotension, concomitant liver disease, use of other nephrotoxins

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4 MEASUREMENT OF GENTAMICIN AND TOBRAMYCIN SERUM CONCENTRATIONS Infection Gram-positive Gram-negative (except pneumonia) Gram-negative pneumonia Peak conc (µg/ml) Trough conc (µg/ml) < 1 < 1 < 1 CRITICAL: the peak is measured one hour after an infusion begins; the trough is measured immediately prior to the next dose (all done at steady state) EXTENDED-INTERVAL AMINOGLYCOSIDE THERAPY

5 AMINOGLYCOSIDE THERAPY THAT WENT TERRIBLY WRONG 67 yo male, retired, very active. Chief complaint: 3 month history of dizziness Treatment: mitral valve replacement, 4- week course of nafcillin/gentamicin Patient stayed in the hospital for a week, discharged on home IV antibiotics Immediately complained of dizziness to the home care nurse and consulting pharmacist FLUOROQUINOLONES BY GENERATION FIRST* SECOND** THIRD FOURTH All obsolete Ciprofloxacin Gatifloxacin Trovafloxacin*** Levofloxacin Moxifloxacin Gemifloxacin *nalidixic acid, cinoxacin, oxolinic acid **obsolete: norfloxacin, enoxacin, lomefloxacin, ofloxacin ***generally avoided (hepatotoxicity)

6 FLUOROQUINOLONE ACTIVITY AGAINST STREPTOCOCCUS PNEUMONIAE (MIC 90 in mcg/ml) CIPRO LEVO GATI MOXI 0.03 GEMI CIPRO LEVO GATI MOXI GEMI PSSP (550) PISP, PRSP (210) AUC/MIC: THE BEST WAY TO DESCRIBE FQ ACTIVITY

7 AUC/MIC RATIOS FOR S. PNEUMONIAE CIPRO LEVO GATI MOXI GEMI TOXICITY ASSOCIATED WITH FLUOROQUINOLONES GI: nausea, vomiting, diarrhea, abdominal pain CNS: HA, dizziness, sleep disturbance, confusion, seizure Liver: increased LFTs, hepatitis, liver failure Kidney: hematuria, crystalluria, nephritis, renal failure Musculoskeletal: tendinitis, arthropathy, tendon rupture Cardiovascular: hypotension, tachycardia with QTc changes Skin: rash, pruritis, photosensitivity Endocrine: disturbance in glucose homeostasis

8 A NEW INDICATION FOR CIPROFLOXACIN It happened in April of 2004 Ciprofloxacin is now approved for complicated UTIs and pyelonephritis due to E. coli in pediatric patients (1-17 years of age) Dose: 6-10 mg/kg IV q8h, or mg/kg po q12h A higher incidence of musculoskeletal adverse effects was observed in pediatric patients receiving ciprofloxacin compared to cephalosporin-treated controls (9.3% vs. 6.0%) so certainly not the drug of choice Will this new indication open the floodgates and encourage inappropriate fluoroquinolone use, leading to increased resistance?

9 NEW INDICATION FOR MOXIFLOXACIN Approved on Nov for complicated intraabdominal infections (ciai), e.g. bowel perforations, abscess formation Organisms: E. coli, B. fragilis, S. anginosus, S. constellatus, E. faecalis, P. mirabilis, C. perfringens, B. thetaiotaomicron, Peptostreptococcus spp. Two studies demonstrate clinical equivalence moxifloxacin vs piperacillin/tazobactam followed by PO amoxicillin/clavulanate moxifloxaxin vs ceftriaxone/metronidazole followed by PO amoxicillin/clavulanate Dose: 400 mg IV/PO qd x5-14 days Now the big question: when to use?