Definitions


Antimicrobial prescription in hospitals is often characterised by high quantity but poor quality. There is evidence that antimicrobial resistance correlates with the total quantity of antimicrobials used, in that not only the number of individuals treated being important, but also the duration of each treatment course. Inappropriate antimicrobial use increases length of hospital stay, morbidity and mortality due to avoidable drug toxicity or side effects, suboptimal treatment of the initial infection, or (mostly avoidable) subsequent in-hospital acquired infection with multi drug-resistant pathogens, fungi or Clostridium difficile.

Inappropriate antibiotic therapy can be defined as one or more of the following:
  • ineffective empiric treatment of bacterial infection at the time of its identification
  • the wrong choice, dose or duration of therapy
  • use of an antibiotic to which the pathogen is resistant


Appropriate prescription demands consideration of several criteria, taken in the following order:

  • Bacteriology: the bacterium responsible for the infection must be sensitive to the antibiotic prescribed (as confirmed by disk, MIC, or automated tests)
  • Pharmacokinetics: doses may need to be adapted (intensive care unit, newborns, elderly people, renal or hepatic insufficiency,...), according to drug peculiarities and patient’s pathophysiological status
  • Pharmacodynamics: the antibiotic must enter the site of infection at an adequate concentration that warrants target concentration attainment
  • Tolerance and predisposition: any allergy, or particular susceptibility to its toxicity should be taken into account. Contraindication linked to pregnancy should be respected
  • Ecology: the clinician should choose the antibiotic with the least impact on the patient’s flora and environmental flora for the development of antimicrobial resistance
  • Economics: this is the last item to take into account, after all the above factors. If it is still possible to choose at this stage, opt for the cheapest.


Overview of the principles of antimicrobial therapy


The effort toward the most appropriate antimicrobial prescription within health care facilities require an established and shared antibiotic policy supported by administrators, and must focus on many different aspects of the antimicrobial usage. The most important issues, among others, can be summarised in:

a. Empiric therapy. Starting antibiotic treatment with the highest likelihood of being appropriate impact the morbidity and the mortality, especially in critically ill patients admitted to intensive care units. Local epidemiology of resistance, site and severity of infection, comorbidities and risk of colonisation with multidrug-resistant pathogens should all be taken into account. Collection, tabulation, analysis and feedback of information about antimicrobial resistance is essential before planning any intervention. To help drive appropriate antimicrobial prescription, the support of adequate microbiological reports, in the form of local antibiograms is mandatory. In an era of increased antimicrobial resistance, the updated description of an antibiotic’s spectrum should have two columns: the first sorting bacterial species into naturally “S”, “I”, or “R”; the second, for the “S” and “I” only, indicating the percentage of isolates with acquired resistance.

b. Targeted therapy/Streamlining. Once microbiological results and susceptibility testing become available, antimicrobial therapy should be reassessed accordingly, taking into account the opportunity of narrowing the spectrum of ongoing treatment and the patient’s clinical course. Measuring the antibiotic sensitivity of a strain isolated from a patient, to define its status as “S”, “I”, or “R”, is an individual point that help streamline antimicrobial treatment for each single patient. Defining the status of a bacterial species or genus is an epidemiological point, varying with locals and time, and requiring regular monitoring. This approach will help avoid useless antimicrobial overexposure.

c. PK/PD in clinical practice. Optimizing the potential for successful clinical outcomes with antimicrobial therapy requires consideration of pharmacokinetic properties and pharmacodynamic indices to maximize bacterial eradication while minimizing the potential for resistance. According to these characteristics, modifying the dosing interval, infusion time, or using the most potent drug within a class will enable the highest likelihood of achieving bactericidal exposures. When all of these requirements are met, economic benefits should also result, as the most expensive patient is the one that fails initial therapy and thus requires additional medical management and consequent prolonged hospital stay. Optimizing drug exposure via the application of currently available pharmacodynamic principles offers the opportunity to promote the use of highly potent therapies, thereby improving antimicrobial effectiveness and the quality of care.

d. Duration of therapy. In many cases, this is still a crucial point, since general consensus do not exist, nor an evidence-based approach provides really established rules. On the other hand, there is evidence suggesting that resistance increases with longer courses of antimicrobials. Duration of treatment often needs to be tailored to individual clinical response, especially considering delayed improvement in immunocompromised patients. Designing trials with more refined endpoint will probably help also define the shortest effective approach to many situations.

principles.jpg


e. Intravenous to oral route switch. Some antimicrobials display an excellent bioavailability (e.g., fluoroquinolones, rifampin, trimethoprim/ sulfamethoxazole) and the switch from intravenous to oral route of administration should be considered as soon as possible according to the clinical reassessment at bedside. When a scanty bioavailability does not allow a switch to the same drug in the different formulation (e.g., aminoglycosides, carbapenems), a shift to different antimicrobial class or to oral combination therapy should be considered to complete the treatment course. This approach will also improve patient safety, lessening the likelihood of infusion-related accidents, allergic reactions or errors in administration.

f. Surgical antimicrobial prophylaxis. Appropriate surgical prophylaxis is one of the most important issues to improve hospital antibiotic policy. In many cases, bundles or protocols of surgical prophylaxis are considered part of surgery quality and safety programs and are required for hospital quality accreditation. The three main steps of appropriate surgical antimicrobial prophylaxis can be summarised in:
  • selecting antimicrobial drugs that match local epidemiology and available guidelines (taking into consideration patient allergies)
  • timing the first dose within 30-60 minutes before skin incision
  • withdrawing antimicrobial administration within 24 hours after the first dose whenever possible

Routinely measuring compliance with these steps provides not only an indication of adherence to local surgical prophylaxis policy, but also data to be fed back to prescribers in the process of quality improvement.