3.0 - Principles of Antibiotic Prescribing

INTRODUCTION

Antimicrobial drugs are different from other drugs in that their use in one patient can influence their future effects in other patients by altering the human and environmental microbiome.

Choice of antibiotics may be influenced by many factors including local susceptibility trends of current isolates, cost of the drugs, as well as traditional preference or familiarity. 

Prescribers should always be keep in mind that the body's innate defense mechanisms is able to eliminate most viral and minor bacterial infections successfully without antimicrobial therapy. These infections are usually self-limiting and do not require antibiotics.  This guideline outlines acceptable approaches to the use of antimicrobials in our hospital.  The antibiotic recommendation in this guideline is based on the UMMC antibiogram from January 2013- June 2013 and the consensus of representatives from the various departments.

This guideline will be reviewed and updated yearly based on the hospital antibiogram and current clinical evidence in the literature.


ANTIMICROBIAL RESISTANCE

Resistance to the commonly used antibiotics are increasing in many organisms including penicillin resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase resistance (ESBL) Klebsiella and Escherichia coli ,  vancomycin-resistant enterococci (VRE) and with and multiresistant Pseudomonas aeruginosa and extremely drug resistant Acinetobacter (sensitive only to colistin). And recently the emergence of resistance to our so called "last defense antibiotics”, carbapenem is of great concern. The risk of mortality in those infected with multi drug resistant organism (MDROs) is approximately 50% higher than those infected with a sensitive organism.

What causes the emergence of antimicrobial resistant organisms?

1. Selection pressure: Over use and misuse of antibiotics leads to inhibition of susceptible organisms and overgrowth of multi-resistant bacteria which will eventually replace the susceptible bacteria that is colonized within us and in our environment. Colonized MDROs may become pathogenic and cause infections.

2.  Mutation of the bacterial genome after exposure to antibiotics and transfer of these resistant genes from one organism to another also contributes to antimicrobial resistance.

This ecological adverse effect of antibiotic therapy is referred to “Collateral damage”. The use of any class of antibiotic can lead to development of resistance. However, broad spectrum antibiotics such as those from the fluoroquinolone, cephalosporin and carbapenem classes are more prone to cause collateral damage and should be reserved for specific indications only. It is also important to note that that the perpetuation of resistance is greater when more antibiotics are used.

What causes the spread of antimicrobial resistant organisms?

Poor infection control measures facilitate the transfer of resistant organism form healthcare workers to patients.

The emergence and the spread of bacterial resistance to antimicrobials is not only a major problem worldwide but also in Malaysia and in our hospital. Though it is primarily associated with hospital acquired infections, there have been increasing reports of these organisms arising in the community. Coupled with the decline in the development of new antimicrobial, we are heading towards the post antibiotic era whereby patients will succumb to even minor infections due to the lack of effective antibiotics.


STRATEGIES TO PREVENT ANTIMICROBIAL RESISTANCE AND SPREAD

Rational use of antibiotics and strict infection control measures are imperative to combat antimicrobial resistance. Appropriate antimicrobial use will delay the emergence of resistance and minimize resistance prevalence after it has emerged. In view of this, sensible antibiotic prescribing and adherence to the general principles of antibiotic use outlined below is crucial to ensure that antimicrobials remain effective in treating critical or major infections.


GENERAL PRINCIPLES OF ANTIBIOTIC USE

Antimicrobial use can be empirical, directed or prophylactic.

Empirical (Initial) Therapy

Empirical antimicrobials are initiated at the time of diagnosis of infection prior to confirmation of the causative organism. Avoid use in minor or self-limited illness as unnecessary use is a significant driver of antimicrobial resistance. Before commencing therapy, where appropriate, obtain specimens for blood culture (at least two sets from clinically septic patients) and other appropriate cultures.

Factors to consider when determining appropriate empiric antibiotic therapy:

1. Host: Severity of illness, immune status, likelihood of infection by with MDROs.

2. Bug: Localize the site of infection and reasonably consider the likely organisms arising from that site. Obtain appropriate sample for culture before commencing antibiotic is important. Once the first dose of antibiotic is given, it would be difficult to isolate the causative organism. Adequate source control is paramount.

3. Drugchoose antimicrobial agents with the narrowest spectrum of activity required to treat the most likely potential organism(s) based on the site of infection. Consider the local antibiogram. Avoid the classes of antibiotic that cause collateral damage as first line antibiotics (unless indicated).

Document indication for antibiotic clearly in the patient folder or prescription.



Ensure adequate dose is given to:

1. Maximize efficacy of drug.

2. Minimize the risk of resistance selection.

3. Minimize the dose related toxicity.

Empiric broad spectrum antibiotics should be considered in the following groups of patients:

  • Septic shock or sepsis with multiorgan impairment
  • Health-Care Associated Infection, especially hospital onset, recent ICU admission or immunocompromised
  • Exposures to multiple broad spectrum antibiotics in the last 90 days
  • Recent procedures or patient has devices insitu
  • Colonized with MDROs

When to start empiric antibiotics:

Start antibiotics immediately (within 1 hour of diagnosis) in the following conditions:

1. Meningitis, patient in septic shock or sepsis with multiorgan dysfunction, febrile neutropenia and necrotizing fasciitis.

2. For all other infective conditions, start antibiotics after appropriate cultures have been obtained based on diagnosis.

Clear documentation of clinical indication of antibiotic is a MUST.

"Antibiotic Time Out at 48-72 hr"

At 48-72 hr, review clinical decision, check microbiology results and make decision to either:

  • Stop antibiotic (if no evidence of bacterial infection)
  • De-escalate based on culture results or clinical improvement (if no culture available)
  • Diminish the number of antibiotics
  • Continue
  • IV to oral conversion

De-escalation:

    This is the practice of changing antibiotics from initial broad spectrum agent to a narrower, more focused spectrum at 72 hours based on pathogen identified or clinical presentationDe-escalation is one of the most important strategies in reducing antibiotic resistance and has shown to improve patient outcome.  General principles of de-escalation include assessing the need for antibiotics everyday based on:

    • Clinical and biochemical improvement
    • Adequate source control
    • Appropriate culture and sensitivity results

    In the absence of a proven causative organism at 72 hours, evaluate the clinical and microbiological justification for continuing therapy.

    Directed Therapy

    Directed use of antibiotics occurs when culture susceptibility results are available. Culture and other microbiological results along with clinical presentation should be evaluated critically to differentiate infection from colonization or contamination that does not require specific antimicrobial treatment. If unsure, obtain advice from an infectious diseases physician or a clinical microbiologist.

    Based on the indentified pathogen and its antimicrobial susceptibility, select an antibiotic in accordance with recommendations using the most effective, narrowest spectrum and least toxic drug available. Use a single drug unless it has been proven that combination therapy is required to ensure efficacy (eg a proven mixed infection), for synergy, or to reduce the selection of clinically significant resistance (eg treatment of tuberculosis, HIV infection).

    Switching from intravenous (IV) to oral (PO) therapy:

    Critically ill patients who were started on IV antibiotic therapy should be switched to equivalent oral therapy when possible. Advantages of early IV to PO switch programs include reduced IV line infections, early hospital discharge and reduced cost.

    Consider switching from IV to oral when: 

    • Clinically and biochemically improving
    • Afebrile > 24 hr
    • Taking orally, GI absorption OK
    Longer duration may be required for certain conditions (staphylococcus aureus bacteremia, fungemia etc).

    Change to an oral antibiotic based on sensitivity pattern. (i.e. Co-amoxiclav, Amoxicillin, Doxycycline, Cefuroxime, Ampicillin-sulbactam, Co-trimoxazole etc)

    Duration:

    Duration of treatment varies depending on the site of infections and causative organism. Assess response to therapy clinically and microbiologically. Keep duration of the therapy as short as possible. Avoid using antibiotics for more than 5-7 days without a proven indication for a longer duration (eg for endocarditis, staphylococcus aureus bacteremia, candidemia).

    Not all antibiotics are made equal:

    Certain antibiotics are more prone to developing resistance and causing collateral damage. 
    Use these antibiotics only if absolutely necessary and with caution.




    Causes of apparent antibiotic failure:

    This include drug fever, antibiotic unresponsive infections and febrile non-infectious diseases.

    It is inappropriate to manage apparent antibiotic failure by changing or adding additional antibiotics instead of determining the causes:


     Microbiologic factors:
    • In vitro susceptibility but ineffective in vivo
    • Antibiotic tolerance with gram positive cocci
    • Treating colonization (not infection)

    Antibiotic factors:
    • Inadequate coverage / spectrum
    • Inadequate antibiotic blood levels
    • Inadequate antibiotic tissue levels
    • Decreased antibiotic activity in tissue
    • Drug-drug interaction
       
    Antibiotic penetration problems:
    • Undrained abscess
    • Foreign body related infection
    • Protected focus
    • Organ hypoperfusion / diminished blood supply

    Non infectious diseases:
    • Medical disorders mimicking infection
    • Drug fever

     Antibiotic unresponsive infectious disease:
    • Viral or fungal infection

    Prophylactic Therapy

    Prophylactic antimicrobial(s):

    • Aimed to prevent an infection in clinical situations where there is significant risk of an infection occurring.
    • Should be restricted to situations in which prophylaxis has been shown to be effective or where the consequences of infection would be detrimental/terrible.
    Three principles of prophylactic antibiotic:
    • Depending on the type of procedure.
    • The individual patient having high risk of infection.
    • The antibiotics selected for prophylaxis must cover the known or expected pathogen(s) for that operative site.

    Intravenous antibiotics should be given within 60 minutes surgical incision (Vancomycin infusion 90 minutes prior to skin incision). The duration of prophylactic antibiotic therapy should be single dose except in special circumstances (illustrated in Chapter on Prophylaxis).