4 Antimicrobials & Pharmacotherapy Flashcards
Describe the key factors that influence antibiotic choice.
- An antimicrobial active against the organism causing the infection should be used. If this is not known, then the typical organisms known to cause the infection should be considered and treatment directed toward these organisms.
- The anticipated resistance pattern of the organism must be considered. If the organism has been cultured, resistance testing should be done. If susceptibility testing is not possible, local resistance patterns should be taken into consideration when choosing antibiotics.
- The location of the infection, and delivery and penetration of the antibiotic must be considered.
- The mechanism of action of the antibiotic is important. If the patient does not have an intact immune system, a bacteriocidal antibiotic should be chosen over a bacteriostatic one if possible.
- Host factors such as age, history of drug allergy, renal or liver dysfunction, pregnancy, drug–drug interactions due to other medications the patient is taking, and the immune status must be taken into consideration. Drug dosage adjustment is required for many antibiotics in the setting of renal or hepatic dysfunction.
What facts must the clinician consider when deciding between oral and intravenous antibiotic therapy?
What facts must the clinician consider when deciding between oral and intravenous antibiotic therapy?
Severity of infection: Oral antibiotics are typically used in mild infections whereas intravenous (IV) antibiotics are chosen for moderate to severe infections. Intravenous antibiotics should be given to patients who are in shock, because oral absorption can be erratic.
Degree of systemic absorption: If an oral antibiotic is given, the absorption of the antibiotic must be considered. For example, some antibiotics such as aminoglycosides are not given orally due to poor absorption. On the other hand, some antibiotics have excellent oral bioavailability and can be used nearly interchangeably with IV antibiotics. Examples of antibiotics with excellent oral bioavailability include fluoroquinolones, clindamycin and linezolid.
What are some advantages of topical antibiotics?
What are some advantages of topical antibiotics?
Optimal delivery to the site, ability to deliver higher concentration, ability to overcome resistance mechanisms, minimized systemic side effects
Describe the mechanism of action and spectrum of activity of the penicillin class of antibiotics.
Describe the mechanism of action and spectrum of activity of the penicillin class of antibiotics.
Penicillins are β-lactam antibiotics and are bactericidal. They kill bacteria by inhibiting cell wall synthesis
Explain the spectrum of activity of the different classes of cephalosporin antibiotics.
Explain the spectrum of activity of the different classes of cephalosporin antibiotics.
First generation cephalosporins (intravenous cefazolin, oral cephalexin) primarily have activity against gram-positive cocci, such as Staphylococcus sp. and Streptococcussp.
Second generation cephalosporins (cefuroxime) have increased activity against gram-negative respiratory pathogens, including Haemophilus influenza and Moraxella catarrhalis. However, the second generation cephalosporins have limited activity against many Enterobacteriaceae. Cefuroxime is active against penicillin-sensitive strains of Streptococcus pneumoniae.
Third generation cephalosporins (intravenous ceftriaxone and ceftazidime, oral cefixime and cefditorin) demonstrate increased activity against gram-negative organisms. Some of the drugs in this class, such as ceftriaxone, also have activity against penicillin-resistant S. pneumoniae.
Fourth generation cephalosporins (cefepime is the only drug in this class available in the United States) have the broadest activity against gram-negative organisms, including P. aeruginosa.
Fifth generation or methicillin-resistant Staphylococcus aureus (MRSA) active cephalosporins (only approved agent in this class is ceftaroline) have excellent activity against MRSA and other gram-positive organisms including S. pneumoniae. The gram-negative activity of this drug is similar to ceftriaxone. Currently, ceftaroline is FDA approved only for treatment of pneumonia and skin and soft tissue infections, but likely will be approved for other indications in the future.
Like the penicillin class of antibiotics, the cephalosporin antibiotic class possesses a β-lactam ring. Can the cephalosporins be safely used in patients who report a history of penicillin allergy?
Can the cephalosporins be safely used in patients who report a history of penicillin allergy?
Penicillin skin testing is recommended if available. Many patients who report a history of penicillin allergy (assumed to be an allergy to any antibiotic in the penicillin class) in fact have negative penicillin skin tests. If the penicillin skin test is negative, then there is no increased risk for cross-reactivity to cephalosporins. However, if penicillin skin testing is positive, then the patient is at increased risk for cephalosporin reaction and antibiotics should be administered via graded challenge, rapid desensitization or should be avoided all together.
Penicillin skin testing is frequently not available. Of patients with a history of penicillin allergy, only 10% have positive penicillin skin tests and studies have shown that 3.4% of patients with a positive skin test to penicillin have allergy to cephalosporins. Therefore, the risk is low, but risk is still present. In this case, the nature of the penicillin allergy should be considered. If the reaction is severe (anaphylaxis), options are to avoid cephalosporins or to administer antibiotics via a graded challenge.
In addition to the penicillin and cephalosporin class of antibiotics, the carbapenems are also β-lactam antibiotics. What is their range of antimicrobial activity?
What is their range of antimicrobial activity?
There are four carbapenems available for use in the United States—ertapenem, imipenem, doripenem, and meropenem. All have a very broad range of antimicrobial activity, including gram-positive organisms, gram-negative organisms (including drug-resistant gram-negatives) and anaerobic organisms. Ertapenem is the least broad of the carbapenems due to its lack of activity against Enterococcus sp. and P. aeruginosa.
There are differences in antimicrobial coverage between the various agents of the fluoroquinolone class of antibiotics. Describe the mechanism of action of the fluoroquinolones and the differences in coverage between the drugs in this class.
There are differences in antimicrobial coverage between the various agents of the fluoroquinolone class of antibiotics. Describe the mechanism of action of the fluoroquinolones and the differences in coverage between the drugs in this class.
Fluoroquinolones are bactericidal antibiotics that work by inhibiting bacterial DNA synthesis.
The macrolides are used frequently for infections of the head and neck. How do they work and what is their antimicrobial activity?
The macrolides are used frequently for infections of the head and neck. How do they work and what is their antimicrobial activity?
There are three members of the macrolide class of antibiotics—erythromycin, azithromycin, and clarithromycin. They are bacteriostatic antibiotics which inhibit RNA protein synthesis. Erythromycin has fairly broad antimicrobial activity, with activity against gram-positive and gram-negative organisms. Azithromycin and clarithromycin are the newest agents in the class and were developed with an even broader range of antimicrobial activity. Azithromycin and clarithromycin are more easily absorbed than erythromycin with fewer gastrointestinal side effects.
Describe the spectrum of activity of clindamycin.
Describe the spectrum of activity of clindamycin.
Clindamycin has good activity against gram-positive organisms, including Staphylococcus aureus (including MRSA) and Streptococcus sp. including S. pyogenes, S. pneumonia, and members of the viridans streptococcus group. The special quality of clindamycin is the anaerobic coverage it provides. The adage is to use clindamycin for “anaerobic infections above the diaphragm” because clindamycin has activity against the anaerobes found in the oral cavity including Peptostreptococcus sp. and Veillonella sp.
Describe the signs and symptoms of Clostridium difficile colitis.
Describe the signs and symptoms of Clostridium difficile colitis.
Patients with Clostridium difficile colitis typically complain of diffuse watery diarrhea, up to several times daily. Leukocytosis is a very common manifestation and can present prior to development of symptoms of diarrhea. Fever, bloody diarrhea, and abdominal pain can be present in severe disease. Prior antibiotic use is the primary risk factor for development of disease. The antibiotics associated with increased risk are clindamycin, fluoroquinolones, cephalosporins, and carbapenems. Macrolides, penicillins, and sulfonamides are less frequently associated.
Trimethaprim-sulfamethoxazole (TMP-SMX) is a bactericidal antibiotic that works by inhibiting bacterial production of folic acid. Describe the antimicrobial spectrum of action of the drug and its major side effects.
Describe the antimicrobial spectrum of action of the drug and its major side effects.
TMP-SMZ is a fairly broad spectrum antibiotic, with activity against a wide range of aerobic gram-positive and gram-negative bacteria. Examples include Staphylococcus aureus (both methicillin sensitive and methicillin resistant), S. pneumoniae, M. catarrhalis, and H. influenza and enteric aerobic gram-negative bacilli.
The most common side effects of TMP-SMX are gastrointestinal upset and dermatologic reactions such as rash. More severe dermatologic reactions can occur including Stevens-Johnson syndrome and toxic epidermal necrolysis. Nephrotoxicity can also occur.
Describe the mechanism of action of the tetracyclines and their spectrum of activity.
Describe the mechanism of action of the tetracyclines and their spectrum of activity.
Tetracyclines (doxycycline, minocycline, tetracycline) are bacteriostatic antibiotics which work by inhibiting bacterial protein synthesis. Tetracyclines are active against a wide range of gram-positive and gram-negative organisms, including respiratory pathogens such as S. pneumonia, H. influenza, and Mycoplasma pneumoniae. Tigecycline, a new IV tetracycline, also has activity against drug-resistant gram-negative organisms. The tetracyclines should not be used in children or pregnant women due to the effect on developing teeth and bones.
Name the antibiotics with activity against MRSA.
Name the antibiotics with activity against MRSA.
The most commonly used IV agent is vancomycin, which is an inhibitor of bacterial cell wall synthesis. Other intravenous agents with MRSA activity include daptomycin, linezolid, and ceftaroline.
There are also a number of oral agents with activity against MRSA. These include TMP-SMX, clindamycin, tetracyclines, and oral linezolid. The fluoroquinolones do have activity against Staphylococcus aureus including MRSA, but should not be used as monotherapy for Staphylococcal infections as resistance can rapidly develop on therapy.
Fungal infections of the head and neck are uncommon, but can be devastating. What are the classes of antifungal medications and what infections do they treat?
What are the classes of antifungal medications and what infections do they treat?
The azoles are the most commonly used antifungal medications. Examples of medications in this class include fluconazole, itraconazole, posaconazole, and voriconazole. Fluconazole is commonly used for infections due to Candida sp., whereas voriconazole is first line therapy for aspergillosis.
Micafungin, caspofungin, and anidulafungin are all echinocandins. These are used for invasive candidiasis due to certain species of Candida, including Candida krusei andCandida glabrata.
The polyene amphotericin B is typically reserved for serious fungal infections, including invasive rhinosinusitis due to mucormycosis. The different formulations of the medication are conventional amphotericin B and liposomal amphotericin B. The liposomal form of the drug has less nephrotoxicity, so it is more commonly used.
Overview of the activity and MOA of each major abx class.\
PCN, Ceph, Carb, Fluoro,Macrol, Clinda, Bactrim, Vanc, Tetra, Amino
