Using antibiotics responsibly.
The though process presented in this section can be applied to all infectious diseases! It’s composed for four simple questions that need to be asked by pharmacists when faced with a patient dealing with an confirmed or possible infection. The information collected from these four questions will help create a complete picture to guide appropriate antibiotic therapy. Keep in mind, these questions are only the beginning. Over time, continual application of this framework will develop into a comprehensive infectious disease assessment that no bug can match!
1. Is there an infection?
Confirming an infection can involve using microbiology techniques (i.e. culturing), molecular tools (i.e. sequencing), and/or symptomatic assessment (i.e. vital signs). However, many institutions allow a majority of these processes to be assessed without actually seeing the patient! It’s important to involve the patient in his or her own care as much as possible. Although the majority of infections will be confirmed through objective measures, these clinical values need to be put in context with patient presentation and common sense. See below for a case scenario to illustrate the importance of involving the patient to confirm an infection.
Case scenario: You're assigned to follow a patient a positive Clostridium Difficile result. Take a look at the microbiology results and medication history. Does this patient actually have a C. Difficile infection?
Patient: Male 54 years old.
Chief Complaint: Recent onset of diarrhea
Past Medical History: Liver cirrhosis
Current Medications: Lactulose (dose recently increased)
Vital Signs: Blood Pressure 130/80; Heart Rate 70 beats per minute, regular; Temperature 37.5°C
Blood work: White Blood Cell Count 5.0 x 10^9 per liter
Microbiology: C. Difficile Positive
Considerations: Although this patient has a positive C. Difficile result, take a look at his medications. Lactulose can cause diarrhea! What if the the dose of lactulose was increased around the time of the C. Difficile test? How does this change your interpretation of the C. Difficile result? In this situation, it's important to talk to the patient! The patient can help you clarify the temporal relationship between the lactulose dose increase and onset of symptoms. Remember, always make rational decisions based on clinical measures, professional assessment, and patient involvement!
Case scenario: You're assigned to follow a patient a positive Clostridium Difficile result. Take a look at the microbiology results and medication history. Does this patient actually have a C. Difficile infection?
Patient: Male 54 years old.
Chief Complaint: Recent onset of diarrhea
Past Medical History: Liver cirrhosis
Current Medications: Lactulose (dose recently increased)
Vital Signs: Blood Pressure 130/80; Heart Rate 70 beats per minute, regular; Temperature 37.5°C
Blood work: White Blood Cell Count 5.0 x 10^9 per liter
Microbiology: C. Difficile Positive
Considerations: Although this patient has a positive C. Difficile result, take a look at his medications. Lactulose can cause diarrhea! What if the the dose of lactulose was increased around the time of the C. Difficile test? How does this change your interpretation of the C. Difficile result? In this situation, it's important to talk to the patient! The patient can help you clarify the temporal relationship between the lactulose dose increase and onset of symptoms. Remember, always make rational decisions based on clinical measures, professional assessment, and patient involvement!
2. What are the 'usual' bugs?
This represents one of the most important questions within this framework. Unfortunately, this particular question scares many new pharmacists because of the extensive number of bacteria that cause different types of infectious disease. Pharmacists can master this question over time with experience and diligent studying. In the meantime, new pharmacists can appropriately answer this question by using reliable infectious disease resources (see Resources). Also, new pharmacists are encouraged to get familiar with the normal microbial flora in the human body. There are many bacteria that naturally colonize various places in our body <1>. Understanding the normal microbial flora can help rationalize why some bugs cause certain diseases. More importantly, knowing where the bugs come from can guide empiric treatment for certain infectious diseases. See Embedded Document below for bacteria that are part of the normal microbial flora in humans.
To complicate matters, it's important to realize that the 'usual' bugs that cause infectious diseases are changing! Multiple factors are facilitating this change, including selection pressures from misguided antibiotic use <2>. Thus, it's imperative to think about the bug before we think about the drug!
To complicate matters, it's important to realize that the 'usual' bugs that cause infectious diseases are changing! Multiple factors are facilitating this change, including selection pressures from misguided antibiotic use <2>. Thus, it's imperative to think about the bug before we think about the drug!
3. What's the source of the infection?
The term 'source of infection' (or 'source') is a novel concept to many new pharmacists. The 'source' simply refers to the starting point of the infection. As example, many hospitalized patients are catheterized to optimize medical treatment <3>. Unfortunately, catheters are frequently contaminated causing infection <3>. In this situation, the catheter represents the source. To ensure that patients are not persistently re-infected, the source must be removed. Infectious disease practitioners refer to this process as 'source control' <4>. This sounds like a relatively easy course of action to prevent re-infection and optimize antibiotic treatment. However, finding the source proves to be a difficult task in some situations <4>. Nevertheless, new pharmacists should have a general understanding about ways to achieve source control.
Source control can be achieved through drainage, debridement (or device removal), decompression, and restoration of anatomy/function <4>. Drainage refers clearing abscesses to limit the progression of an infection <4>. Debridement refers to removing tissue or foreign objects that may contribute to a persistent infection, despite adequate antibiotic therapy <4>. Decompression refers to removing any obstructions, particularly in the bowel, that may cause displacement of normal microbial flora that can cause colonizing bacteria to become pathogenic. Restoration of anatomy refers to appropriate wound care to eliminate portals of entry for bacteria <4>.
Source control can be achieved through drainage, debridement (or device removal), decompression, and restoration of anatomy/function <4>. Drainage refers clearing abscesses to limit the progression of an infection <4>. Debridement refers to removing tissue or foreign objects that may contribute to a persistent infection, despite adequate antibiotic therapy <4>. Decompression refers to removing any obstructions, particularly in the bowel, that may cause displacement of normal microbial flora that can cause colonizing bacteria to become pathogenic. Restoration of anatomy refers to appropriate wound care to eliminate portals of entry for bacteria <4>.
4. What drugs can be used to treat the bugs?
This can be a daunting question for new pharmacists. However, a systematic approach can make this question less intimidating and facilitate good antibiotic practices! See below for a systemic approach to picking the right drug for the right bug.
Know your options! Based on either suspected or confirmed bacterial infection, an antibiotic can be empirically selected to treat the infection (refer to the Antibiotic section to view the spectrum of activity for commonly used antibiotics). However, antibiotics act in different ways to treat the infection. Antibiotic mechanisms are defined by their in vitro activity, pharmacokinetic and pharmacodynamics properties.
In vitro activity: In vitro activity represents a natural starting point for picking an antibiotic for empiric therapy. If an antibiotic shows that it can eradicate particular bacteria on a Petri Dish, it can be assumed it would do the same in vivo. However, in vitro activity does not directly translate to clinical efficacy. Based on in vitro assays, antibiotics can be classified as either bactericidal or bacteriostatic. These designations are based on in vitro parameters called minimal bactericidal concentration (MBC; concentration required to kill bacteria) and minimal inhibitory concentration (MIC; concentration required to inhibit visible growth) <5>. Although bactericidal or bacteriostatic distinctions for antibiotics are determined in vitro, infectious disease practitioners commonly use these properties to guide antibiotic therapy, especially for serious gram-positive infections <5>. However, in vitro data should always be used in conjunction with appropriate pharmacokinetic and pharmacodynamic properties to guide antibiotic therapy.
Pharmacokinetics: Antibiotic activity depends on its absorption, distribution, metabolism, and elimination. Pharmacokinetic properties determine where the antibiotic goes, and how much of it gets there <6>. If the antibiotic doesn't where it needs to go, it won't treat the infection!
Pharmacodynamics: Pharmacodynamic principles describe the relationship between the antibiotic and the bacteria. In clinical terms, this can be described as either a concentration-dependent or time-dependent mechanism of activity <6>. Based on its chemical structure, antibiotics work in different ways. It's important to understand these principles to make sure the antibiotic is dosed correctly to kill the bacteria.
Review your resources! There are many primary, secondary, and tertiary resources to guide your antibiotic selection process. Please refer to the Resources section for some examples.
Know your options! Based on either suspected or confirmed bacterial infection, an antibiotic can be empirically selected to treat the infection (refer to the Antibiotic section to view the spectrum of activity for commonly used antibiotics). However, antibiotics act in different ways to treat the infection. Antibiotic mechanisms are defined by their in vitro activity, pharmacokinetic and pharmacodynamics properties.
In vitro activity: In vitro activity represents a natural starting point for picking an antibiotic for empiric therapy. If an antibiotic shows that it can eradicate particular bacteria on a Petri Dish, it can be assumed it would do the same in vivo. However, in vitro activity does not directly translate to clinical efficacy. Based on in vitro assays, antibiotics can be classified as either bactericidal or bacteriostatic. These designations are based on in vitro parameters called minimal bactericidal concentration (MBC; concentration required to kill bacteria) and minimal inhibitory concentration (MIC; concentration required to inhibit visible growth) <5>. Although bactericidal or bacteriostatic distinctions for antibiotics are determined in vitro, infectious disease practitioners commonly use these properties to guide antibiotic therapy, especially for serious gram-positive infections <5>. However, in vitro data should always be used in conjunction with appropriate pharmacokinetic and pharmacodynamic properties to guide antibiotic therapy.
Pharmacokinetics: Antibiotic activity depends on its absorption, distribution, metabolism, and elimination. Pharmacokinetic properties determine where the antibiotic goes, and how much of it gets there <6>. If the antibiotic doesn't where it needs to go, it won't treat the infection!
Pharmacodynamics: Pharmacodynamic principles describe the relationship between the antibiotic and the bacteria. In clinical terms, this can be described as either a concentration-dependent or time-dependent mechanism of activity <6>. Based on its chemical structure, antibiotics work in different ways. It's important to understand these principles to make sure the antibiotic is dosed correctly to kill the bacteria.
Review your resources! There are many primary, secondary, and tertiary resources to guide your antibiotic selection process. Please refer to the Resources section for some examples.
References:
1. Brooks GF, Carroll KC, Butel JS, et al. Jawetz, Melnick, & Adelberg's Medical Microbiology, 25th ed. Columbus: McGraw-Hill Education; 2010.
2. McGowan JE. The impact of changing pathogens of serious infections in hospitalized patients. Clin Infect Dis 2000; 31 (Supplement 4):S124-30.
3. Mermel LA, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Disease Society of America. Clin Infect Dis 2009; 49:1-45.
4. De Waele JJ. Early source control in sepsis. Langenbecks Arch Surg 2010; 395:489-94.
5. Pankey GA, Sabath LD. Clinical relevance of bacteriostatic versus bactericidal mechanisms of action in the treatment of gram-positive bacterial infections. Clin Infect Dis 2004; 38:864-70.
6. Van Bambeke F, Barcia-Macay M, Lemaire S, et al. Cellular pharmacodynamics and pharmacokinetics of antibiotics: current views and perspectives. Curr Opin Drug Discov Devel 2006; 9(2):218-30.
1. Brooks GF, Carroll KC, Butel JS, et al. Jawetz, Melnick, & Adelberg's Medical Microbiology, 25th ed. Columbus: McGraw-Hill Education; 2010.
2. McGowan JE. The impact of changing pathogens of serious infections in hospitalized patients. Clin Infect Dis 2000; 31 (Supplement 4):S124-30.
3. Mermel LA, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Disease Society of America. Clin Infect Dis 2009; 49:1-45.
4. De Waele JJ. Early source control in sepsis. Langenbecks Arch Surg 2010; 395:489-94.
5. Pankey GA, Sabath LD. Clinical relevance of bacteriostatic versus bactericidal mechanisms of action in the treatment of gram-positive bacterial infections. Clin Infect Dis 2004; 38:864-70.
6. Van Bambeke F, Barcia-Macay M, Lemaire S, et al. Cellular pharmacodynamics and pharmacokinetics of antibiotics: current views and perspectives. Curr Opin Drug Discov Devel 2006; 9(2):218-30.