NURS 251 Module 6

Module 6 6.1: Introduction to Infectious Diseases Infectious diseases are caused by pathogenic (disease-causing) organisms such as bacteria, fungi, and parasites as well as by viruses. Bacteria are defined as single-celled microorganisms. They can be found virtually everywhere and can either be harmless or very dangerous. This module will focus on the role of antibiotics to eliminate the pathogenic effects brought on by bacteria within a human host. Antibiotics are drugs that have the ability to destroy or interfere with the development of a living organism, typically bacteria. Bacteria Bacteria can be classified as either Gram-positive or Gram-negative. This classification refers to how they respond to the Gram stain procedure. Gram-positive bacteria stain purple, and Gram-negative stain pink. Interestingly, the results of a Gram stain actually play a significant role in selecting an appropriate antibiotic therapy. Due to differences in the composition of the cell membrane, some drugs cannot effectively penetrate the membrane which is often required to elicit the desired effects. Generally, Gram-negative bacterial infections are harder to treat because Gram-negative bacteria have a more complex cell wall structure. Another way bacteria are classified is by whether they are an aerobe or anaerobe. An aerobe is defined as a bacterium that grows in the presence of air or requires oxygen for growth. An anaerobe is defined as a bacterium that does not require oxygen in order to grow. Anaerobes, for instance, are most commonly found in the GI tract. Although there are many different kinds of bacteria and strategies for classifying them, this goes beyond the scope of this introductory module. Instead, it is important to understand generally that bacteria do not simply cause a single disease: rather, multiple disorders are possible depending on where in the body the bacteria accumulate. For example, the bacteria streptococcus pyogenes is the specific bacteria responsible for the common throat infection known as strep throat. This bacterium is spread through airborne droplets when someone with the bacteria coughs or sneezes. It can also be spread by sharing food or drinks. When the bacteria spread through the air or even food, the throat is one of the first contact points in the body, which makes strep throat a common result. However, if it happened to be transferred via contact with a contaminated surface and the person had an open sore, the very same bacteria could cause an entirely different infection, in this case, a skin infection. There are also common infections associated with certain bacteria based on where they are found naturally or how the pathogen is acquired. Take for instance, the bacteria E.coli. Although typically found within the intestines of a healthy individual, when someone becomes exposed to a pathogenic strain of E.coli, often via contaminated food, it often presents as diarrhea because of where the bacteria naturally end up by way of the digestive tract. One last factor is related to where the person contracts the infection—different types of bacteria are found in the environmental community compared to a healthcare setting. Generally, healthcare-associated infections are much more difficult to treat because the microorganisms have been exposed to strong antibiotics in the past; therefore, they are resistant to many treatments. Healthcare-associated infections are defined as an infection acquired during the course of receiving treatment for another condition in a health care institution. Examples of common Gram-positive bacteria and Gram-negative bacteria can be found in Table 5.1 below. This study source was downloaded by from CourseH on :55:57 GMT -06:00 Important terminology to be familiar with regarding antibiotics and bacteria: Antibiotic spectrum- bacteria that are susceptible to the antibacterial actions of a particular drug. Broad Spectrum is defined as an antibiotic that is effective against a wide variety of both Gram-positive and Gramnegative bacteria. Bacteria Resistance is defined as the ability of some bacteria to resist the actions of antibiotics. MRSA stands for methicillin-resistance Staphylococcus aureus. Methicillin is a penicillin-related antibiotic that was previously effective against resistant staph infections. However, over time, an even more drug-resistant strain developed and was termed MRSA. MRSA infections have become a major problem because none of the penicillin-class drugs are effective against it. In fact, only a few antibiotics, such as Vancomycin, have demonstrated effectiveness. 6.2: Antibiotics Similar to other types of medications, antibiotics are classified into broad categories or classes. These classifications are most often based on their chemical structure; however, these classes vary in more ways than just their chemical structure. Distinguishing characteristics include antibacterial spectrum, mechanism of action, potency, toxicity, and pharmacokinetic properties. Antibiotics are different than most other drugs in that their targeted site of action is not a part of the body but is actually the foreign bacteria that is causing an infection. The ultimate goal of the drug treatment is to kill or destroy the bacteria causing harm. There are four common mechanisms of action associated with antibiotics: 1. Interference with bacterial cell wall synthesis. This causes the formation of defective cell walls within the bacteria that are unstable and easily broken down. This generally causes the bacteria cell to rupture and ultimately die. 2. Interference with protein synthesis. Without the ability to make proteins, the bacteria can no longer function. 3. Interference with replication of DNA and RNA. DNA and RNA replication are how bacteria cells multiply. If they are not able to multiply, then the infection cannot survive. 4. Antimetabolite action that disrupts important metabolic reactions within the bacterial cell. By inhibiting important metabolic activities, the bacteria are no longer able to grow and function properly. Antibiotics are either considered bactericidal or bacteriostatic. Bactericidal antibiotics work by killing the bacteria. This study source was downloaded by from CourseH on :55:57 GMT -06:00 Bacteriostatic antibiotics do not actually kill bacteria but instead only inhibit their growth. Antibiotic Classes covered in this module include (1) Sulfonamides, (2) Penicillins, (3) Cephalosporins, (4) Macrolides, (5) Tetracyclines, (6) Aminoglycosides, and (7) Fluoroquinolones Sulfonamides are one of the first group of drugs to be used as antibiotics. Mechanism of Action- Sulfonamides are bacteriostatic and work by preventing the bacteria from making folic acid. Folic acid is a vitamin that is necessary for DNA and RNA synthesis. Spectrum of Activity - broad spectrum with activity against both Gram-positive and Gram-negative bacteria. Adverse Events/Toxicity- Nausea, vomiting, and diarrhea. A more serious adverse effect is that should dehydration occur, the sulfonamide can crystalize in the kidney and cause damage. Sulfonamides should not be used when there is a known allergy, which is relatively common. Allergic reaction includes rash, itching, and sensitivity to the sun. There is also risk of Stevens-Johnson Syndrome a serious, sometimes fatal skin reaction. They should also not be used in pregnant women at term or in infants younger than 2 months. Drug Interactions- Most common are the interactions with warfarin, increasing the risk of bleeding and sulfonylureas, and increasing the risk of hypoglycemia. Example Drug- Sulfamethoxazole- trimethoprim (SMZ-TMP) or Bactrim. This is a combination drug and the Trimethoprim component is not a sulfonamide: however, it works by similar mechanism of action. Common Uses- Urinary Tract Infections (UTIs) Beta Lactam antibiotics include both penicillin and cephalosporins. Beta Lactam antibiotics are named as such due to the presence of a beta-lactam ring as a part of their chemical structure. They share a common structure and mechanism of action. Penicillin are a large group of antibiotics that were first derived from a mold often seen on bread or fruit. There are four subgroups of penicillin: natural penicillin, penicillinase resistant penicillin, aminopenicillins, and extended spectrum penicillin. Mechanism of Action- Penicillin are bactericidal, specifically working to inhibit the synthesis of the bacterial peptidoglycan cell wall. Some bacteria have acquired the ability to produce an enzyme that is able to destroy the penicillin called beta-lactamase. Beta-lactamase inhibitors have been developed that can be added to the original chemical structure of penicillin to prevent this from happening. One very common example of this is Augmentin (amoxicillin combined with clavulanic acid which is the beta-lactamase inhibitor). Spectrum of Activity- The spectrum of activity is dependent on the subgroup. Natural penicillin- Gram-positive infections Penicillinase resistant penicillin- Resistant Staphylococcal infections Aminopenicillins- Gram-positive infection/ common Gram-negative Extended spectrum penicillin- Serious Gram-negative infections Adverse Events/Toxicity- As a group, penicillin are relatively nontoxic. Common adverse events include nausea and rashes. Diarrhea is common with oral administration. Most serious events are patients that develop an allergy to This study source was downloaded by from CourseH on :55:57 GMT -06:00 penicillin. Notably, penicillin is the drug class with the highest incidence of drug allergy. Signs of an allergic reaction include rash and fever. However, anaphylaxis is life-threatening and is also possible. Drug Interactions- Examples include increasing the risk of bleeding when taken with warfarin, decreasing the effectiveness of oral contraceptives, increasing the antibacterial effect when used in combination with aminoglycosides. Example Drug Natural penicillin- Penicillin Penicillinase resistant penicillin- Cloxacillin Aminopenicillins- Amoxicillin Extended spectrum penicillin- Piperacillin/tazobactam* (Zosyn) *tazobactam is a beta lactamase inhibitor. Common Uses Natural penicillin- Strep throat Penicillinase resistant penicillin- Used to treat resistant staph infections (*not MRSA) Aminopenicillins- Ear infections, sinusitis, respiratory and skin infections, urinary tract infections Extended spectrum penicillin- Reserved for resistant Gram-negative infections for example pneumonia, intraabdominal infections and sepsis (infection in the blood). Cephalosporins are also within the beta lactam family. They are structurally and pharmacologically related to penicillin. Mechanism of Action- Cephalosporins are bactericidal and work by interfering with bacteria cell wall synthesis. Spectrum of Activity- Cephalosporins can destroy a wide range of bacteria related to the generation that they fall into. Scientists have modified the original chemical structure over time to develop five generations of cephalosporins all with varied spectrums of activity. In general, the amount of Gram-negative coverage increases with each generation. The first generation has the most Gram-positive coverage, and the last generation has the most Gram-negative coverage. The only generation with any anaerobic coverage is the second generation. The fifth generation has the broadest covering Grampositive (including MRSA) and Gram-negative. Adverse Events/Toxicity- The most common adverse events are mild diarrhea, abdominal cramps, rash, itching, redness, and edema. Due to the similar chemical structure, a person who is allergic to penicillin may also be allergic to cephalosporins. This is called a cross-sensitivity and occurs in about 1-4% of patients. Drug Interactions - Examples include increasing the risk of bleeding when taken with warfarin, decreasing the effectiveness of oral contraceptives, and increasing the antibacterial effect when used in combination with aminoglycosides. See Table 6.2 for specific drug examples of the cephalosporins and common infections each generation is used to treat. Table 6.2 Example Drug and Common Uses of the CephalosporinsGeneration Drug Example Example Use First Cephalexin (Kelflex) Simple staphylococcal infections Second Cefoxitin (Mefoxin) Prophylaxis for patients undergoing abdominal surgery because it can kill intestinal bacteria including anaerobes. Third Ceftazidime (Fortaz) Meningitis caused by pseudomonas (gram-negative) Resistance is beginning to limit its usefulness. This study source was downloaded by from CourseH on :55:57 GMT -06:00 Fourth Cefepime (Maxipime) Uncomplicated and complicated UTIs, pneumonia specifically those caused by the Enterobacter species (gramnegative) Fifth Ceftaroline (Teflaro) Pneumonia and skin and skin structure infections including those caused by MRSA. Macrolides are another large group of antibiotics that first became available in the 1950s with erythromycin. The bettertolerated azithromycin and clarithromycin are now more commonly used. Mechanism of Action- Macrolides are generally considered bacteriostatic, although at high enough concentrations, can be bactericidal against some bacteria. They work by inhibiting protein synthesis within the bacteria cell. Spectrum of Activity- Primarily Gram-positive. Azithromycin and clarithromycin have increased Gram-negative coverage than erythromycin. Adverse Events/Toxicity- Common adverse events include nausea, vomiting, diarrhea, and minor skin rashes. Drug Interactions- As macrolides are metabolized in the liver, there is a possibility of competition with other drugs for metabolic enzymes. Examples of this include theophylline and warfarin, both of which increase in concentration when given in combination with macrolides. Macrolides are also known to decrease the effect of oral contraceptives. Clarithromycin specifically should not be used with simvastatin and lovastatin due to increasing the risk of myopathy (muscle pain, see Module 3). Azithromycin has the least effect on the metabolic enzymes within the liver and therefore is not as prone to these drug interactions. Example Drug(s)- Erythromycin, Azithromycin, Clarithromycin Common Uses- Upper and lower respiratory tract infections, skin, and soft tissue infections. Often used in place of penicillin when there is a penicillin allergy. Tetracyclines Mechanism of Action- Tetracyclines work by inhibiting protein synthesis in susceptible bacteria Spectrum of Activity- Tetracyclines have activity against a variety of Gram-negative and Gram-positive bacteria. Adverse Events/Toxicity- Tetracyclines are a pregnancy category D based on the possibility that they can slow fetal skeletal development. They are also known to cause increased sensitivity to the sun. A unique adverse event is their ability to cause discoloration of tooth enamel. Drug Interactions- The absorption of tetracyclines is reduced when taken in combination with antacids, dairy products, and calcium. They are also known to decrease the effectiveness of oral contraceptives. Warfarin effects may be increased requiring more frequent monitoring. Example Drug(s)- Doxycycline, minocycline, and tigecycline Common Uses- Traditionally, tetracyclines have been used to treat acne, skin infections respiratory, and GI tract infections. The most recent tetracycline, Tigecycline is indicated for skin and skin structure infections including MRSA and intraabdominal infections. Aminoglycosides are a class of antibiotics with very poor absorption from the GI tract. Therefore, the usual route of administration for systemic effects is either IM or IV. This study source was downloaded by from CourseH on :55:57 GMT -06:00 Mechanism of Action- Aminoglycosides are bactericidal antibiotics that work by binding to the bacterial ribosome causing the inhibition of protein synthesis. Spectrum of Activity- These drugs are effective against most Gram-negative bacteria and are typically used only in hospitalized patients with serious Gram-negative infections. Adverse Events/Toxicity- When taken orally prior to abdominal surgery (in an effort to sterilize the bowel), they can cause nausea, vomiting, and diarrhea. When given parenterally for their systemic effects, they can cause both nephrotoxicity (kidney damage) and ototoxicity (ear damage). Signs of nephrotoxicity include reduced urine output and protein in the urine. The earliest symptoms of ototoxicity include ringing in the ears. Generally, any hearing loss is temporary and only in cases where aminoglycosides were given for long periods of time is it sometimes permanent. Aminoglycosides are also pregnancy category D and have been shown to cause hearing loss and deafness in the fetus. Drug Interactions- They can interact with general anesthesia by producing excessive muscular blockade that could lead to respiratory arrest or paralysis of the diaphragm. The ototoxic effect can be increased when used with other drugs such as furosemide. Similarly, the nephrotoxic effect can be increased when used in combination with cephalosporins. Example Drug- Amikacin and Tobramycin Common Uses- Amikacin is reserved for the treatment of serious Gram-negative infections resistant to other aminoglycosides. Tobramycin is reserved for the treatment of serious Gram-negative infections particularly pseudomonas aeruginosa. Fluoroquinolones have the advantage over other broad-spectrum antibiotics in that they have good oral absorption. Mechanism of Action- Fluoroquinolones work by inhibiting bacterial enzymes, DNA gyrase and topoisomerase IV which are necessary for DNA synthesis and bacterial replication. Spectrum of Activity- They have a broad spectrum of activity especially against Gram-negative bacteria. Fluoroquinolones are also effective against some Gram-positive bacteria but not MRSA. Moxifloxacin has the most Grampositive coverage. Adverse Events/Toxicity- Most commonly experienced adverse events are headache, dizziness, GI issues, and rash. They are not recommended in pregnant women and children. There is evidence of cartilage defects including ruptured tendons. Drug Interactions- Antacids should be avoided several hours before and after dosing because they can decrease the absorption of the fluoroquinolones. Ciprofloxacin specifically inhibits theophylline metabolism and can increase the stimulation of the CNS leading to seizure. Example Drug(s)- ciprofloxacin, levofloxacin, and moxifloxacin Common Uses- They are indicated for urinary tract infections, respiratory, abdominal, bone, and soft tissue infections. Antibiotic Selection While knowing the specific coverage of antibiotics against its respective bacteria is certainly useful, in clinical practice, the signs and symptoms of infection often appear long before the causative organism can be identified. Generally, an antibiotic need to be selected prior to knowing the specific bacteria being targeted. Such an approach is called empiric therapy and is defined as the administration of antibiotics based on the practitioner’s judgment of pathogens most likely to be causing an apparent infection in order to avoid treatment delay before specific culture information has been obtained. In the case of a serious or life-threatening infection, practitioners will empirically select a broad-spectrum This study source was downloaded by from CourseH on :55:57 GMT -06:00 antibiotic that has the greatest chance of targeting the causative organism. Cultures will be grown in the lab and then can be tested for susceptibility to different antibiotics through a process called sensitivity analysis. Based on the results of sensitivity testing, which can take 48-72 hours, the antibiotic treatment regimen can then be tailored to the narrowestspectrum, least toxic drug that best targets the causative organism. Such an approach is done in an effort to decrease antibiotic resistance and expose the patient to the least toxic drug possible. Overuse of broad-spectrum antibiotics contributes to the emergence of drug-resistant bacteria. With repeated exposure to antibiotics, bacteria can, over time, undergo structural or metabolic changes or even adopt mutations all of which can allow the bacteria to withstand the actions of the antibiotic. For example, some bacteria become resistant to antibiotics by changing the composition of the outer cell wall so that antibiotics can no longer penetrate. In addition, some bacteria start producing enzymes that inactivate the antibiotics. A common example of this is the enzyme beta lactamase that is able to inactivate penicillins and cephalosporins (see above). Because of bacteria’s ability to resist antibiotics, it is critical that we minimize the use of broad-spectrum antibiotics to periods of actual necessity so that they still work when needed for life-threatening infections. Problem Set 1 Question 1 Define key terms: antibiotic, bacterial resistance, bactericidal, bacteriostatic, empiric therapy, gram negative, gram positive. Antibiotics are drugs that have the ability to destroy or interfere with the development of a Bacteria Resistance is defined as the ability of some bacteria to resist the actions of antibiotics. living organism, typically bacteria. Bactericidal – antibiotics that work by killing the bacteria Bacteriostatic antibiotics do not actually kill bacteria, but only inhibit their growth. Empiric therapy - the administration of antibiotics based on the practitioner’s judgment of pathogens most likely to be causing an apparent infection to avoid treatment delay before specific culture information has been obtained Question 2 List the four-general mechanism by which antibiotics generally work to rid the body of infection. Your Answer: The four-general mechanism by which antibiotics work to get rid of the body infection  Interference with bacterial cell wall synthesis  Interference with protein synthesis  Interference with replication of DNA and RNA  Antimetabolite action that disrupts important metabolic reactions within the bacterial cell Question 3 Describe the different types of bacteria classification i.e. gram positive vs. gram negative, anaerobic and aerobic. Gram-positive- bacteria that stain purple on a gram stain. Gram-negative- bacteria that stain pink on a gram stain. Aerobe- a bacterium that grows in the presence of air or requires oxygen for growth. Anaerobe - a bacterium that does not live or grow when oxygen is present. Question 4 List examples of common Gram- positive and Gram-negative bacteria. This study source was downloaded by from CourseH on :55:57 GMT -06:00 Gram-positive: staphylococcus aureus, streptococcus pyogenes, enterococcus faecalis Gram-negative- Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia Coli, and Enterobacter spp. Question 5 What does MRSA stand for? methicillin-resistance Staphylococcus aureus Question 6 Provide one example drug for each of the following antibiotic classes: sulfonamides, penicillins, cephalosporins, macrolides, aminoglycosides, fluoroquinolones, and tetracyclines. sulfonamides- sulfamethoxazole-trimethoprim Penicillin- penicillin, cloxacillin, amoxicillin, or piperacillin/tazobactam Cephalosporin- cephalexin, cefoxitin, ceftazidime, cefepime, or ceftaroline Macrolide- erythromycin, azithromycin, or clarithromycin Tetracycline- doxycycline, minocycline, or tigecycline Aminoglycoside- Amikacin, tobramycin Fluoroquinolone- ciprofloxacin, levofloxacin, moxifloxacin. Question 7 Define Beta Lactam antibiotics. Beta Lactam antibiotics include penicillins and cephalosporins. Beta Lactam Antibiotics are named such because of the presence of a beta-lactam ring as a part of their chemical structure. They share a common structure and mechanism of action. Question 8 Explain the spectrum of activity of cephalosporins specifically as it relates to the different generations. They can destroy a wide range of bacteria related to the generation that they fall into. Scientists have modified the original chemical structure over time to develop five generations of cephalosporins all with varied spectrums of activity. In general, the amount of gram-negative coverage increases with each generation. The first generation have the most gram-positive coverage and the last generation has the most gram-negative coverage. The only generation with any anaerobic coverage is the second generation. The fifth generation has the broadest covering gram positive (including MRSA) and gram negative. Question 9 List common adverse effects and toxic effects of each antibiotic class. Sulfonamides: Adverse Events/Toxicity- Nausea, vomiting, diarrhea. A more serious adverse effects is in the presence of dehydration the sulfonamide can crystalize in the kidney and cause damage. Allergic reactions are relatively common. Allergic reaction includes rash, itching, sensitivity to the sun. There is also risk of Stevens-Johnson Syndrome a serious, sometimes fatal skin reaction. They should also not be used in pregnant women at term or infants younger than 2 months. This study source was downloaded by from CourseH on :55:57 GMT -06:00 Penicillins: As a group penicillins are relatively nontoxic. Common adverse events include nausea and rashes. Diarrhea is common with oral administration. Most serious is patients that develop an allergy to penicillins. This is the drug class with the highest incidence of drug allergy. Signs of an allergic reaction include rash and fever. Anaphylaxis is life threatening and is also possible. Cephalosporins- The most common adverse events are mild diarrhea, abdominal cramps, rash, itching, redness, and edema. Because of their similar chemical structure there is a chance that a person who is allergic to penicillins may also be allergic to cephalosporins. This is call a cross-sensitivity and is about 1-4% of patients. Macrolides- Common adverse events include nausea, vomiting, and diarrhea and minor skin rashes. Tetracyclines: They are a pregnancy category D based on the possibility that they can slow fetal skeletal development. They are also known to cause increased sensitivity to the sun. A unique adverse event is their ability to cause discoloration of tooth enamel Aminoglycosides: When taken orally they can cause nausea, vomiting, and diarrhea. When given parenterally for their systemic effects they can cause both nephrotoxicity (kidney damage) and ototoxicity (ear damage). Aminoglycosides are also pregnancy category D and have been shown to cause hearing loss and deafness in the fetus. Fluoroquinolones: Most commonly experienced adverse events are headache, dizziness, GI issues and rash. They are not recommended in pregnant women and children. There is evidence of cartilage defects including ruptured tendons. Question 10 What is a common use for the following antibiotics: Bactrim, amoxicillin, ceftazidime, azithromycin, doxycycline, tobramycin, ciprofloxacin. Bactrim- UTI Amoxicillin- Ear infections, sinusitis, respiratory and skin infections, urinary tract infections Ceftazidime- Meningitis caused by pseudomonas (gram-negative) Azithromycin- Upper respiratory tract infection Doxycycline- Acne Tobramycin- Serious gram-negative infections Ciprofloxacin- They are indicated for urinary tract infections, respiratory, abdominal, bone and soft tissue infections. Question 11 Define what a health care associated infection is. Health care-associated infections are defined as an infection acquired during the course of receiving treatment for another condition in a health care institution. This study source was downloaded by from CourseH on :55:57 GMT -06:00 Powered by TCPDF ()