New trends, aminoglycoside toxicity and multidrug resistance

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New trends, aminoglycoside toxicity and multidrug
resistance

• Kim Wan (NICU pharmacist)
• Dept of Pharmacy Services
• LLUMC
• May, 2007

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Aminoglycoside

• Includes Streptomycin, Gentamicin, Tobramycin,
  Neomycin, Kanamycin, Amikacin
• Auditory changes are irreversible
• Has inherent potential for causing
  nephrotoxicity and ototoxicity

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Nephrotoxicity

• Accumulation of drugs in the proximal renal
  tubular epithelia cells.
• Saturated at relative low concentration
• Higher peak level do not associate with greater
  toxicity

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Ototoxicity

• Aminoglycoside induced high frequency hearing
  loss results from progressive loss of function
  from the outer hair cells to the inner hair cells
• Can occur with normal levels ( prolonged use)
• Tends to accumulate within the inner ear

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Aminoglycoside

• Dosing should be based on indication, dosing
  weight, and renal function
• Blood urea nitrogen, serum creatinine, creatinine
  clearance
• Drug level monitoring, avoiding troughgt2mcg/ml
  (gent and tobramycin) lt5 mcg/ml for
  streptomycin
• Peak level to stay within therapeutics
  (4-8mcg/ml)gentamicin/tobramycin Streptomycin
  15-40mcg/ml

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Aminoglycoside

• Dosing adjustment based upon result of serum drug
  concentration monitoring
• Dosing for neonates should also based on age
• Peak level drawn at 1 hr post IM injection ( iv
  30 minutes after end of 30 min. infusion)
• Trough with 30 minutes before next dose

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Prevention

• Use non-ototoxic antibiotics
• Avoid potentiating agents ( e.g. loop diuretics)

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Multiple drug resistance (MDRO)

• Defined as microorganisms (bacteria) are
  resistant to one or more classes of antimicrobial
  agents
• e.g. MRSA, VRE resistant to most antimicrobial
  agents

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Clinical importance

• Options for treating patients for susceptible
  pathogens are limited
• e.g. VRE during 1990virtually no antimicrobial
  agents to treat VRE
• Increase length of stay, cost and mortality

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Epidemiology of MDROs

• Prevalence varies temporally, geographically and
  by healthcare setting
• Level of care of especially tertiary care
  facilities
• Antimicrobial resistance rates are strongly
  corrected with hospital size, tertiary-level care
  and facility type
• Gram negative bacilli ( GNB) resistant to
  extended spectrum beta lactamases ( ESBLS),
  fluroquinolones, carbapenems and aminoglycoside
  also increased in prevalence

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Concepts in transmission

• Once MDROs is introduced to a healthcare setting,
  transmission and persistence of resistant strain
  to vulnerable patients, selective pressure by
  antimicrobial use.
• Increase potential transmission from colonized
• or infected patients

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Community associated MRSA

• CA MRSA infection commonly presents as relative
  minor skin and soft tissues, but severe invasive
  disease, including necrotizing pneumonia,
  necrotizing faciitis, severe osteomyelitis, and a
  sepsis syndrome with increased

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MDRO prevention

• Optimal management of vascular and urinary
  catheters
• Prevention of lower respiratory tract infection
  in intubated patients
• Accurate diagnosis of infectious etiologies
• Judicious antimicrobial selection and utilization

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MDRO prevention and control

• Improvements in hand hygiene
• Use Contact precautions until patients are
  culture negative for a target MDRO
• Active surveillance cultures , education
• Enhanced environmental cleaning
• Improvement in communication about patients with
  MDROs with and between healthcare facilities

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New challenge

• More elderly
• More patients from long term care facilities
• Sicker patients
• Increased treatment on an outpatient basis
• More ICU beds

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New challenge

• New infectious diseases
• More resistant pathogens
• Availability of new antibiotics
• New diagnosis
• New vaccine development

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Reference

• Siegl, Jane D. Management of Multidrug-Resistant
  Organisms in Healthcare Settings, 2006, CDC.
• Kimble, Kodah. Applied Therapeutics, the Clinical
  use of Drugs, 4th editions, 1989
• www.infectionacademy.org/meetings/berlin_presentat
  ions/Suttorp_Berlin.ppt -