Useful Tools
Antibiotic Stewardship

Antibiotic Stewardship

Note

The overall use of antibiotics needs to be reduced in hospital. There needs to be evidence for infection to start the initiation of antibiotic treatment. Antibiotic courses should not be prolonged if the infection is treated or if infection is subsequently excluded.

Clinical Considerations

  • Antibiotic dosing should be based on the patient’s weight, renal/hepatic functioning/metabolism, and source of the infection to make sure that the antibiotic concentration achieved in the infected tissue is above the mean inhibitor concentration (MIC)
  • The frequency of dosing is important to maintain since certain antibiotics are time dependent killing, which requires that the levels are maintained for a prolonged period over the MIC (beta-lactams)
  • Other antibiotics (aminoglycosides, quinolones) are concentration dependent killing, which are at their best with high peak levels
  • Inadequate dosing leads to low levels and development of resistance
  • Since dosing can be difficult with vancomycin and aminoglycosides, levels need to be obtained to make sure they achieve therapeutic as well as non-toxic concentrations in the blood
  • Dosing of the antibiotic should be adjusted to optimize achievable levels in the targeted tissues for the specific infection/organism
    • This may require increased total dose as well as the interval timing of the dose
  • Interactions with other medications need to be considered to make sure no interference with the metabolism of the antibiotics as well as the other medications that the patient may be taking
  • Certain organisms will require higher dosing or increased frequency such as the use of Zosyn or cefepime when treating Pseudomonas
  • In contrast, unnecessary overutilization of antibiotics can lead to toxicity, increased damage to the microflora leading to increased side effects such as C. difficile as well as increased costs
  • Certain organisms may require choice of specific antibiotic to optimize therapy
  • Although reported as sensitive by the lab, certain organisms are better treated certain classes of antibiotics
    • For example, Enterobacter resistance can develop to a single mutation of one of its porin proteins (channels that allow passage of molecules through the cell membrane)
    • Carbapenems, Bactrim, quinolones are less affected by these mutations and will be more effective when treating severe infections
  • Patient needs to receive antibiotics which are active against potential pathogens
  • Choice of antibiotics should be based on:
    • Location where the patient resides (home, adult home, and nursing facility)
    • Recent hospitalizations
    • Review of past cultures available in the laboratory system or on transfer records
    • Recent antibiotic usage
    • Antibiogram of the hospital
  • Recent hospitalizations, and prior antibiotic use may require the use of broader/more toxic agents such as carbapenems, aminoglycosides and polymyxin B/colistin
  • With the increase incidence of resistance, and low genetic barriers to resistance in certain organisms, there may be a role for multiple antibiotic combinations to treat as well as prevent further emergence of resistance
    • For example, the addition of tygacil or minocycline to meropenem/polymyxin to treat MDR (multiple drug resistant) Acinetobacter is used to reduce further development of resistance
  • Although best to try to always narrow the spectrum of activity, in serious illnesses, such as severe sepsis/septic shock/immunosuppressive state, initial broad-spectrum antibiotic coverage against potential resistance should be used empirically since outcome is poor if there is no effective antibiotic coverage
  • Within 48 to 72 hours, antibiotic need to be re-adjusted based on the results of available cultures, documented sources of infection and clinical response
  • Spectrum should be narrowed as much as possible to reduce the development of resistance
  • If no resistant gram-positive organisms, Vancomycin should be discontinued
  • Carbapenems should discontinued and change to cephalosporins or penicillins if there are no ESBL or specific resistance present
  • Proper infection control practices to prevent the spread of resistant organisms is paramount
  • Need to maintain proper hand washing between patients as well as contact precautions in all patients with resistant organisms (for example: ESBL (extended-spectrum beta-lactamase), CRE/CRO (carbapenem resistant Enterobacteriaceae/organisms)
  • In addition, any unusual sensitivity pattern or cluster of patients should be immediately reported to Infection Control for investigation/monitoring
  • Prior to start of antibiotics, cultures should be obtained
  • Before initiation of IV antibiotics, minimal of two sets of blood cultures with 10 ml of blood in each bottle (total of 4 bottles) should be obtained
  • Urine cultures, sputum cultures, wound cultures should be obtained based on the evaluation of the potential sources
  • The results of these cultures are to be used to guide changes in antibiotic therapy
  • There should be monitoring for side effects of antibiotic therapy
  • CBC and CMP should be followed since cytopenia, renal toxicities and hepatic toxicities can occur with many antibiotics
  • These toxicities can be overlapping with other medications, making it difficult to determine which medication could be causing the toxicity
  • If toxicity is present, antibiotics need to be changed to an agent in a different antibiotic class
  • Specific antibiotics have unique side effects:
    • Fluoroquinolones - neuropathy, tendinitis, hepatic toxicity, and occasionally hypoglycemia
    • Daptomycin - myositis - need to follow CPKs and muscle tenderness especially in patients on statins
    • Aminoglycosides - ototoxicity (hearing and/or vestibular), renal toxicity
    • Vancomycin - red man’s syndrome (histamine release potentiated by narcotics), renal failure, neutropenia, thrombocytopenia
    • Polymyxin B - renal failure, neuromuscular blockage, perioral paresthesia
  • Levels need to be for certain antibiotics to make sure their blood concentration is therapeutic and not toxic
    • Vancomycin - trough levels should be obtained before the fourth dose if given every 12 hours or sooner if being given daily (48 hours)
      • Severe disease such as pneumonia, and/or bacteremia - trough levels should be between 15 to 20 while cellulitis, urine infections troughs between 10 to 15 are acceptable
    • Aminoglycosides - both peak and trough levels should be done
      • Since aminoglycoside have prolonged antibiotic effects/concentration dependent killing, high peak levels with low trough levels (prevent toxicities) are important
      • Once daily dosing can be done with aminoglycosides for these reasons
  • Empirical antifungal therapy may be needed in severely ill patients with recurrent hospitalizations and antibiotic therapy
  • Echinocandins would be consider the empirical antifungal of choice for Candida infections due to the emergence of multiple drug resistant Candida auris
  • Length of treatment should be the minimal required based on the specific organism(s), the source of the infection, clinical response and clinical guidelines
  • Prolonged antibiotics can lead to changes to the patient’s bacterial flora with development of resistance as well as loss of “protective” flora allowing infection with C. difficile or other resistant organisms including fungus/VRE (vancomycin resistant enterococci)
  • Transition to oral therapy to complete a course of therapy should be considered once there is adequate therapeutic response as well as based on the source/extent of the infection
  • When using antibiotics for prophylaxis, the choice is limited to cover the most likely or common organisms instead of trying to cover all possible organisms
  • Use of broad-spectrum antibiotics for prophylaxis can lead to development of highly resistant organisms if infection does develop, leading to difficulties/limited options for treatment
  • Surgical prophylaxis should not extend past 24 hours and should be shorter in most situations - see Surgical Prophylaxis guideline