Antiinfectives Flashcards
Colonization
involves the presence of normal microbial flora or transient environmental organisms that do not harm the host.
Opportunistic micro organisms
are usually normal endogenous or environmental flora and nonpathogenic. However, they become pathogens in hosts whose defense mechanisms are impaired. Opportunistic infections are likely to occur in people with severe burns, cancer, human immunodeficiency virus (HIV) infection, indwelling intravenous (IV) or urinary catheters, and antibiotic or corticosteroid drug therapy. Oppor- tunistic bacterial infections, often caused by drug-resistant microorganisms, are usually serious and may be life threaten- ing. Fungi of the Candida genus, especially C. albicans, may cause life-threatening bloodstream or deep-tissue infections, such as abdominal abscesses. Viral infections may cause fatal pneumonia in people with renal or cardiac disorders, in those with HIV infection, and in those who have received bone mar- row transplants.
Mechanisms of resistance for bacterial
Production of enzymes that inactivate the drugs. For example, beta-lactamase enzymes change the chemical structure of penicillins and cephalosporins by opening the betalactam ring and preventing the antibiotic from binding with its target site (called penicillin-binding proteins) in the bacterial cell wall.
Modification of target sites for the antibiotic. This is a mechanism of resistance used by bacteria against fluoroquinolones.
Production of an alternative enzyme to bypass antibiotic activity (e.g., methicillin-resistant staphylococci)
Changing their cell wall structure to reduce permeability. An example is alteration in porin channels among P. aeruginosa to produce imipenem resistance.
Acquiring or increasing the ability to pump drug molecules out of the cell (efflux). Examples include some gram- positive cocci resistant to tetracyclines.
Modification of a binding target for the antibiotic (e.g., macrolides)
Major defense mechanisms of the human body are
intact skin and mucous membranes, various anti-infective secretions, mechanical movements, phagocytic cells, and the immune and inflammatory processes. The skin prevents penetration of for- eign particles, and its secretions and normal bacterial flora inhibit growth of pathogenic microorganisms. Secretions of the GI, respiratory, and genitourinary tracts (e.g., gastric acid, mucus) kill, trap, or inhibit growth of microorganisms. Cough- ing, swallowing, and peristalsis help remove foreign particles and pathogens trapped in mucus, as does the movement of cilia. Phagocytic cells in various organs and tissues engulf and digest pathogens and cellular debris. The immune system produces lymphocytes and antibodies (see Chap. 38). The inflammatory process is the body’s response to injury by microorganisms, foreign particles, chemical agents, or physical irritation of tissues. Inflammation localizes, destroys, dilutes, or removes the injurious agents so tissue healing can occur.
Many factors impair host defense mechanisms and predis- pose to infection by disease-producing microorganisms. These factors include the following:
Breaks in the skin and mucous membranes related to trauma, inflammation, open lesions, or insertion of prosthetic devices, tubes, and catheters for diagnostic or therapeutic purposes
Impaired blood supply
Neutropenia and other blood disorders
Malnutrition
Poor personal hygiene
Suppression of normal bacterial flora by antimicrobial drugs
Suppression of the immune system and the inflammatory response by immunosuppressive drugs, cytotoxic antineoplastic drugs, and adrenal corticosteroids
Diabetes mellitus and other chronic diseases
Advanced age
Specific mechanisms of action of antimi- crobial drugs include the following:
Inhibition of bacterial cell wall synthesis or activation of enzymes that disrupt bacterial cell walls (e.g., penicillins, cephalosporins, vancomycin)
Inhibition of protein synthesis by bacteria or production of abnormal bacterial proteins (e.g., aminoglycosides, clindamycin, macrolides, ketolides, tetracyclines). These drugs bind irreversibly to bacterial ribosomes, intracellular struc- tures that synthesize proteins. When antimicrobial drugs are bound to the ribosomes, bacteria cannot synthesize the proteins necessary for cell walls and other structures.
Disruption of microbial cell membranes (e.g., antifungals)
Inhibition of organism reproduction by interfering with nucleic acid synthesis (e.g., fluoroquinolones, rifampin, anti–acquired immunodeficiency syndrome antivirals)
Inhibition of cell metabolism and growth (e.g., sulfonamides, trimethoprim)
Guidelines to promote more appropriate use of anti microbial drugs:
Avoid the use of broad-spectrum antibacterial drugs to treat trivial or viral infections; use narrow-spectrum agents if they are likely to be effective. Give antibacterial drugs only when a significant bacterial infection is diagnosed or strongly suspected or when there is an established indication for prophylaxis. Antibacterial drugs are ineffective in viral infections and should not be used to treat them.
Collect specimens (e.g., sputum, urine) for culture and Gram’s stain before giving the first dose of an antibiotic. For best results, specimens must be collected accurately and taken directly to the laboratory. If analysis is delayed, contaminants may overgrow pathogenic microorganisms.
Minimize antimicrobial drug therapy for fever unless other clinical manifestations or laboratory data indicate infection.
Use antimicrobial drugs in combination with other interventions to decrease microbial proliferation, such as universal precautions, medical isolation techniques, frequent and thorough hand hygiene, and preoperative skin and bowel cleansing.
Because most laboratory tests used to definitively identify causative organisms and to determine susceptibility to antibi- otics require 48 to 72 hours,
the physician usually prescribes for immediate administration a drug that is likely to be effective. This empiric therapy is based on an informed estimate of the most likely pathogen(s) given the patient’s signs and symptoms and apparent site of infection. A single broad-spectrum antibi- otic or a combination of drugs is often chosen.
MRSA is commonly used but misleading because the organisms are
widely resistant to penicillins (including all of the antistaphylococcal penicillins, not just methicillin) and cephalosporins
Sulfonamide mechanism of action
Blocks synthesis of components necessary for cell metabolism and growth
Penicillin, cephalosporin, and vancomycin mechanism of action
inhibits formation of cell wall
Fluoroquinolones mechanism of action
inhibits DNA gyrase, an enzyme required for reproduction
Aminoglycosides, macrolides, ketolides, tetracyclines, linezolid, and quinupristin/dalfopristin mechanism of action
bind to ribosomes and inhibit production of essential proteins
Assessment for infection
Local signs include redness, heat, edema, and pain; systemic signs include fever and leukocytosis.
General interventions for infection treating drugs
Use measures to prevent and minimize the spread of infection
Wash hands thoroughly and often. This is probably the most effective method of preventing infection.
Support natural defense mechanisms by promoting general health measures (nutrition, fluid intake, rest, exercise)
Keep patient’s skin clean and dry, esp. the hands, underarms, groin, and perineum, because these areas harbor large numbers of microorganisms. Also, take care to prevent trauma to the skin and mucous membranes. Damaged tissues are susceptible to infection.
Treat all body fluids (blood, aspirates) and body substances (sputum, feces, urine, wound drainage) as infectious. Major elements of standard precautions to prevent transmission of hepatitis B, HIV, and other pathogens include wearing gloves when likely to be exposed to any of these materials and thorough hand hygiene when the gloves are removed. Where protective eyewear when a risk of spatter is present. Rigorous and consistent use of the recommended precautions helps to protect health care providers and patients.
Implement isolation procedures appropriately.
Intervention to prevent spread of respiratory infections
Have patients wash hands after coughing, sneezing, or contact with infected people; cover mouth and nose with tissues when sneezing or coughing and dispose of tissues by placing them in a paper bag and burning it; expectorate sputum (swallowing may cause reinfection); and avoid crowds when possible, especially during flu season (approximately November through February). Recommend an annual flu vaccine to high-risk populations (people with chronic diseases such as diabetes and heart, lung, or renal problems; older adults; HCP who are likely to be exposed). Pneumococcal vaccine is recommended for the same populations
Pulmonary hygiene measures
Ambulating, turning, coughing, and deep-breathing exercises; and incentive spirometry.
Fluid intake for patient’s receiving antimicrobial therapy
Maintain fluid intake of approximately 3000mL/24 hours. Adequate intake and avoidance of fluid volume deficit may help decrease drug toxicity; especially with aminoglycoside antibiotics.
Goal of therapy for infections
Eradicate the causative microorganism and return the host to full physiologic functioning
Guidelines to promote more appropriate use of antimicrobial drugs
Avoid the use of broad-spectrum antibacterial drugs to treat trivial or viral infections; use narrow-spectrum agents if they are likely to be effective. Give antibacterial drugs only when a significant bacterial infection is diagnosed or strongly suspected or when there is an established indication for prophylaxis. Antibacterial drugs are ineffective in viral infections and should not be used to treat them.
Collect specimens (sputum, urine) for culture and Gram’s stain before giving the first dose of an antibiotic. For best results, specimens must be collected accurately and taken directly to the laboratory. If analysis is delayed, contaminants may overgrow pathogenic microorganisms.
Minimize antimicrobial drug therapy for fever unless other clinical manifestations or laboratory data indicate infection.
Use antimicrobial drugs in combination with other interventions to decrease microbial proliferation, such as universal precautions, medical isolation techniques, frequent and thorough hand hygiene, and preoperative skin and bowel cleansing.
Indications for combination antimicrobial drug therapy
Infections caused by multiple organisms (abdominal and pelvic infections)
Nosocomial infections, which may be caused by many different organisms
Serious infections in which a combination is synergistic (an aminoglycoside and an antipseudomonal penicillin for pseudomonal infection)
Likely emergence of drug-resistant organisms if a single drug is used (in tuberculosis). Although drug combinations are widely used to prevent resistance, the only clearly effective use of combination therapy is for treatment of tuberculosis.
Fever or other signs of infection in patients whose immune system is suppressed.
Perioperative use of antimicrobial drugs
Single dose of antimicrobial medication is usually given within 1 hour of the first incision to provide effective tissue concentrations during the procedure.
Antimicrobial drug therapy for children
Penicillins and cephalosporins are considered safe for most age groups. However, they are eliminated more slowly in neonates because of immature renal function and must be used cautiously and dosed appropriately for age.
Erythromycin, azithromycin (Zithromax), and clarithromycin (Biaxin) are considered safe
Aminoglycosides (gentamicin) may cause nephrotoxicity and ototoxicity in any patient population. Neonates are at high risk because of immature renal function.
Tetracyclines are contraindicated in children younger than 8 because of the effects on teeth and bone
Clindamycin (Cleocin) warrants monitoring liver and kidney function when it is given to neonates and infants
Fluoroguinolones (ciprofloxacin [Ciprol]) are contraindicated for use in children (<18 years of age) because weight-bearing joints have been impaired in young animals given the drugs. However, if fluoroquinolones are the only therapeutic option for a resistant pathogen, the prescriber may decide to use a fluoroquinolone in children)
Linezolid (Zyvox) is considered safe for use in children.
Antimicrobial drug therapy for older adults
Penicillins are usually safe. However, hyperkalemia may occur with large IV doses of penicillin G potassium, and hypernatremia may occur with ticarcillin (Ticar).
Cephalosporins (cefazolin) are considered safe but may cause or aggravate renal impairment, especially when other nephrotoxic drugs are used concurrently. Dosage of most cephalosporins should be reduced in the presence of renal impairment.
Macrolides and ketolides (erthromycin, telithromycin) are usually safe. Dosage of clarithromycin should be reduced with severe renal impairment.
Aminoglycosides (gentamicin) are contraindicated in the presence of impaired renal function if less toxic drugs are effective against causative microorganisms. Older adults are at increased risk of nephrotoxicity and ototoxicity from these drugs.
Tetracyclines (except doxycycline) and nitrofurantoin (Microdantin) are contraindicated in the presence of impaired renal function if less toxic drugs are effective against causative organisms.
Clindamycin may cause diarrhea and should be used with caution in the presence of GI disease, especially colitis.
Trimethoprim-sulfamethoxazole (Bactrim, Septra) may be associated with an increased risk of severe adverse effects in older adults, especially those with impaired liver or kidney function. Severe skin reactions and bone marrow depression are the most frequently reported severe reactions.
Drugs requiring dosage reduction in severe renal impairment
Penicillin G, ampicillin, most cephalosporins, fluoroquinolones, and trimethoprim-sulfamethoxazole
Factor important in patients with acute or chronic renal failure who are receiving hemodialysis or peritoneal dialysis
Some drugs are removed by dialysis, and an extra dose may be needed during or after dialysis.
Strongest predisposing factor to infection in ICU
Mechanical ventilation, which bypasses airway defenses against movement of microorganisms from the upper to the lower respiratory tract.
Signs of superinfection
Recurrence of systemic signs and symptoms (fever, malaise)
New localized signs and symptoms–redness, heat, edema, pain, drainage, cough
Stomatitis or “thrush” – sore mouth, white patches on oral mucosa; black, furry tongue
Pseudomembranous colitis – severe diarrhea characterized by blood, pus, and mucus in stools
Monilial vaginitis – rash in perineal area, itching, vaginal discharge
Major mechanism by which microorganisms acquire resistance to beta-lactam antibiotics
They produce beta-lactamase enzymes that disrupt the beta-lactam ring and inactivate the drug
Indications for the use of penicillins
Bacterial infections caused by susceptible microorganisms. As a class, penicillins are usually more effective in infections caused by gram-positive bacteria than those caused by gram-negative bacteria.
Contraindications for the use of penicillins
Hypersensitivity or allergic reaction to any penicillin preparation.
Allergic reaction to one penicillin means the patient is allergic to all members of the penicillin class.
Administration of cephalosporins or carbapenems should be avoided in individuals with life-threatening allergic reactions to penicillin (anaphylaxis, laryngeal swelling angioedema, or hives)
Penicillin G and V used to treat:
Remains the drug of choice for the treatment of streptococcal pharyngitis, for prevention of recurrent attacks in patients who have had previous acute rheumatic fever due to group A streptococcus, and for treatment of neurosyphilis.
Penicillin G routes of administration information
Not effective orally because it is inactivated by gastric acid. IM and IV forms of penicillin G cannot be used interchangeably. Preparations containing benzathine or procaine can only be given IM.
Black Box Warning regarding penicillin G benzathine
IV administration may result in cardipulmonary arrest and death. Long-acting repository forms have additives that decrease their solubility in tissue fluids and delay their absorption.
Penicillin V compared to G
It has the same antibacterial spectrum, but it is not destroyed by gastric acid and is only given orally.
Penicillinase-resistant (antistaphylococcal) penicillins
Three drugs: dicloxacillin, nafcillin, and oxacillin. Drugs of choice for MRSA.
Aminopenicillins (Ampicillin [Principen])
Broad-spectrum, semisynthetic penicillin that is bactericidal for several types of gram-positive and gram-negative bacteria. It is excreted mainly by the kidneys; thus it is useful in some UTIs. It is used in the treatment of bronchitis, sinusitis, and otitis media.
Commonly combined with a penicillin to protect it from destruction by beta-lactamase enzymes
Beta-lactamase inhibitors
Cephalosporins
widely used group of drugs derived from a fungus. They are broad-spectrum agents with activity against both gram-positive and gram-negative bacteria. After absorption, they are widely distributed into most body fluids and tissues, with maximum concentrations in the liver and kidneys. Many cephalosporins do not reach therapeutic levels in CSF; exceptions are cefuroxime, a second-gen drug, and the third-gen agents. These drugs reach therapeuticl evels when meninges are inflamed. Most cephalosporins are excreted through the kidneys, except for ceftriaxone.
Indications for cephalosporins
Surgical prophylaxis and treatment of infections of the respiratory tract, skin and soft tissues, bones and joints, urinary tract, brain and spinal cord, and bloodstream (septicemia).
Penicillins are more effective and less expensive in most infections with strep and staph.
Cephalosporins are not clinically effective in MRSA infections.
Cefepime is indicated for use in sepsis; in severe infections of the lower respiratory and urinary tracts, skin and soft tissue, and female reproductive tract; and in febrile neutropenic patients.
Contraindications for cephalosporins
Previous severe anaphylactic reaction to a penicillin, because they are similar.
Cephalosporin allergy.
First-generation cephalosporin
Cephalothin (the first) no longer available for clinical use, but is used for determining susceptibility to first-gen cephalosporins. Effective against strep and staph (except MRSA).
Cefazolin is the drug of choice for surgical prophylaxis in most surgical procedures.
Second-generation cephalosporin
May be effective in infections resistant to other antibiotics, such as Haemophilus influenzae, Klebsiella, E. coli, and some strains of Proteus..
