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..
Third-generation cephalosporin
Further extend the spectrum of activity against gram-negative organisms. Active against several strains resistant to other antibiotics and to first- and second-generation cephalosporins. They may be useful in infections caused by unusual strains of enteric organisms such as Citrobacter, Serratia, and Providencia species.
They also penetrate inflamed meninges to reach therapeutic concentration in CSF. May be useful in meningeal infections caused by common pathogens.
Fourth-generation cephalosporin
Greater spectrum of antimicrobial activity and greater stability against breakdown by beta-lactamase enzymes compared with third-gen.
Carbapenems
Broad-spectrum, bactericidal beta-lactam antimicrobials. Inhibit synthesis of bacterial cell walls by binding with penicillin-binding proteins. Three drugs:
Imipenem-cilastatin (Primaxin) - given parenterally and distributed in most body fluids. Effective in infections caused by a wide range of bacteria. Main use is tx of infections caused by organisms resistant to other drugs. Risk for cross-sensitivity in pt’s with penicillin hypersensitivity. Lidocone + this drug solution for IM injection contraindicated for those allergic or who have severe shock or heart block.
Meropenem (Merrem) - may be used as a single drug for empiric therapy before causative microorganisms are identified. Indicated for use in intra-abdominal infections and bacterial meningitis caused by susceptible organisms.
Ertapenem (Invanz) - approved for complicated intra-abdominal, skin and skin structure, acute pelvic, and UT infections. Can be used to treat community-acquired pneumonia caused by penicillin-susceptible S. pneuomoniae.
Monobactam
Aztreonam (Azactam). Indicated for UTI, skin and skin structures, and lower respiratory tract, as well as intra-abdominal and gynecologic infections and septicemia.
Penicillin drug selection
Drug of choice for many infections. An antipseudomonal penicillin is indicated in Pseudomonas infections. Antistaph penicillin indicated in staph infections; antistaph drugs of choice are nafcillin for IV use and dicloxacillin for oral use.
Cephalosporin drug selection
First-gen often used for surgical prophylaxis, especially with prosthetic implants. May also be used alone for tx of infections caused by susceptible organisms in body sites where drug penetration and host defenses are adequate. Cefazolin (Kefzol) is frequently used parenterally.
Second-gen cephalosporins are also often used for surgical prophylaxis, especially for gynecologic and colorectal surgery. They are also used for tx of intra-abdominal infections such as pelvic inflammatory disease, diverticulitis, penetrating wounds of the abdomen, and other infections caused by organisms inhabiting pelvic and colorectal areas.
Third-gen cephalosporins are recommended for serious infections caused by susceptible organisms that are resistant to first- and second-gen cephalosporins. They are often used in the tx of infections caused by E. coli, Proteus, Klebsiella, and Serratia species. These drugs should not be used alone in treating pseudomonal infections because drug resistance develops.
Fourth-gen drugs are the most useful in serious gram-negative infections, especially those resistant to third-gen.
Preferred drug for IM administration
Cefazolin
Most common cause of drug-induced anaphylaxis
Penicillin
Use of penicillins with Probenecid (Benemid)
Can be given concurrently to increase serum drug levels. Probenecid blocks renal excretion of the penicillins.
Use of penicillins with aminoglycosides
Should not be admixed in a syringe or in an IV solution because penicillin inactivates the aminoglycoside
When to give cephalosporin for surgical prophylaxis
Within 2 hours before the first skin incision is made. Postop doses should generally not exceed 24 hours, if used.
Safety of penicillins and cephalosporins in children
Widely used and are generally safe. Use cautiously in neonates because immature kidney function slows their elimination.
Use of imipenem in renal impairment
It is contraindicated in pt’s with severe renal impairment unless hemodialysis is started within 48 hours. For pt’s already on hemodialysis, the drug may cause seizures and should be used very cautiously, if at all.
Aminoglycosides
Bactericidal agents with similar pharmacologic, antimicrobial, and toxicologic characteristics. Poorly absorbed from the GI tract. Thus, when given orally, they exert local effects in the GI tract. They are well absorbed from IM injection sites and reach peak effects in 30 to 90 minutes if circulatory status is good
After parenteral administration, aminoglycosides are widely distributed in ECF and reach therapeutic levels in blood, urine, bone, inflamed joints, and pleural and ascitic fluids. They accumulate in high concentrations in the proximal renal tubules of the kidney, leading to acute tubular necrosis.
They also accumulate in high concentrations in the inner ear, damaging sensory cells in the cochlea (disrupting hearing) and the vestibular apparatus (disturbing balance).
Poorly distributed to the CNS, intraocular fluids, and respiratory tract secretions.
Aminoglycoside mechanism of action
They penetrate the cell walls of susceptible bacteria and bind irreversibly to ribosomes. The bacteria cannot synthesize proteins necessary for their function and replication.
Aminoglycoside indications for use
Major clinical use of parenteral aminoglycosides is to treat serious systemic infections caused by susceptible aerobic gram-negative organisms. Many hospital-acquired infections are caused by gram-positive cocci and gram-negative organisms.
In pseudomonal infections, an aminoglycoside is often given concurrently with an antipseudomonal penicillin (e.g., piperacillin) for synergistic therapeutic effects.
Decreased mortality has been demonstrated from combination antibiotic therapy in tx of infections due to Pseudomonas aeruginosa and other multidrug-resistant gram-negative bacilli.
Second clinical use is for tx of tuberculosis. Streptomycin may be used as part of a four to six drug regimen for tx of multidrug-resistant tuberculosis.
Third clinical use is for synergistic action when combined with ampicillin, penicillin G, or vancomycin. Regimens for these infections, particularly meningitis or endocarditis, should include gentamicin in divided doses rather than one-daily dosing.
Final clinical use is oral administration to suppress intestinal bacteria. Neomycin and kanamycin may be given before bowel surgery and to treat hepatic coma. In hepatic coma, intestinal bacteria produce ammonia, which enters the bloodstream and causes encephalopathy. Drug therapy to suppress intestinal bacteria decreases ammonia production.
Aminoglycoside contraindications for use
Aminoglycosides are generally reserved for infections that have not responded to less toxic drugs. BLACK BOX WARNING alerts HCP that these drugs are nephrotoxic and ototoxic and must be used very cautiously in the presence of renal impairment.
Also must be used cautiously in patients with myasthenia gravis and other neuromuscular disorders because muscle weakness may be increased.
Fluoroquinolones
Synthetic bactericidal drugs with activity against gram-negative and gram-positive organisms. May allow oral, ambulatory tx of infections that previously required parenteral therapy and hospitalization. Most fluoroquinolones are given orally, after which they are well absorbed, achieve therapeutic concentrations in most body fluids, and are metabolized to some extent in the liver. The kidneys are the main route of elimination.
Fluoroquinolone mechanism of action
Interferes with enzymes required for synthesis of bacterial DNA and therefore are required for bacterial growth and replication.
Fluoroquinolone indications for use
Indicated for various infections caused by aerobic gram-negative and other microorganisms. May be used to treat infections of the respiratory, genitourinary, and GI tracts as well as infections of bones, joints, skin, and soft tissues. Currently, the CDC no longer recommends the use of fluoroquinolones for gonococcal (gonorrhea) disease, unless no other option exists and susceptibility can be confirmed.
Ciprofloxacin is currently recommended as the first-line tx for suspected Bacillus anthracis infections (anthrax) until C&S results are available.
Fluoroquinolone contraindications for use
Children younger than 18 years of age, if other alternative are available. rugs should not be used with pregnant or lactating women unless the benefits outweigh the potential risks.
Nursing assessment for fluoroquinolones
Assess for presence of factors that increase risks of adverse drug effects such as impaired renal function, inadequate fluid intake, concomitant use of multivitamins or antiacids, frequent or prolonged exposure to sunlight in usual activities of daily living
Aminoglycoside multiple daily dosing
Peak serum concentrations should be assessed 30 to 60 minutes after drug administration.
Contraindications for single daily dosing of aminoglycosides
Individuals aged 18 or less, those pregnant or in the postpartum period, and those with endocarditis
Guidelines for reducing toxicity of aminoglycosides
Identify patients at high risk for adverse effects (neonates, older adults, pts with renal impairment, pts with disease processes or drug therapies that impair blood circulation and renal function)
Keep pts well hydrated to decrease drug concentration in serum and body tissues.
Use caution with concurrent administration of diuretics. Diuretics may increase the risk of nephrotoxicity by decreasing fluid volume, thereby increasing drug concentration in the blood and tissues.
Give the drug for no longer than 10 days unless necessary for tx of certain infections.
Use of fluoroquinolones and aminoglycosides in children
Aminoglycosides must be used cautiously. Neonates may have increased risk of nephrotoxicity and ototoicity. Neomycin is not recommended for use in infants and children.
Fluoroquinolones are not recommended for use in children if other alternaties are avilable because they have been associated with permanent damage in cartilage and joints in some animal studies.
Fluoroquinolone/aminoglycoside use in older adults
BLACK BOX WARNING emphasizes increased risk of ototoxicity with kanamycin in older adults.
Avoid urinary alkalinizing agents because drug crystals form more readily in alkaline urine. BLACK BOX WARNING for fluoroquinolones about the increased risk of developing tendinitis and tendon rupture. The risk is greater for those over the age of 60, those with heart kidney and lung transplants, and those taking corticosteroidal medications and necessitates the discontinuation of the fluoroquinolone.
BLACK BOX WARNING for trovafloxacin
Reports that it is associated with severe liver injury leading to liver transplantation or death and should be reserved for serious infections only.
Fluoroquinolone use in diabetes mellitus pts
Associated with hyperglycemia and hypoglycemia. Older patients may be more at risk for these glucose disturbances. Severe hypoglycemia has occured in pts receiving concomitant glyburide and fluoroquinolones.
Gatifloxacin has been associated with hypoglycemic and hyperglycemic events more commonly than other fluoroquinolones.
S/S of nephrotoxicity
casts, albumin, red or white blood cells in urine; decreased creatinine clearance; increased serum creatinine; increased blood urea nitrogen
S/S ototoxicity
deafness or decreased hearing, tinnitus, dizziness, ataxia
Why observe for photosensitivity with fluoroquinolone use?
May occur with most fluoroquinolones with exposure to sunlight.
Tetracyclines
Effective against both gram-negative and gram-positive microorganisms, although they are usually not drugs of choice. Bacterial infections caused by Brucella and Vibrio cholerae are still treated by tetracyclines. The drugs also remain effective against rickettsiae, chlamydia, some protozoa, spirochetes, and others. Doxycycline (Vibramycin) is one of the drugs of choice for Bacillus anthracis (anthrax) and Chlamydia trachomatis and used in respiratory tract infections due to Mycoplasma pneumoniae.
They are widely distributed into most body tissues and fluids.
Sulfonamides
Bacteriostatic against a wide range of gram-positive and gram-negative bacteria, although increasing resistance is making them less useful. Combination of trimethoprim-sulfamethoxazole (Bactrim, Septra) is useful in bronchitis, UTIs due to Enterobacteriaceae, and Pneuomocystic juroveci infection (in high doses).
Urinary antiseptics
May be bactericidal for sensitive organisms in the urinary tract because these drugs are concentrated in renal tubules and reach high levels in urine. They are not used in systemic infections.
Tetracycline mechanism of action
Penetrates microbial cells by passive diffusion and an active transport system.
The presence of pus, serum, or necrotic tissue interferes with sulfonamide action because these materials contain PABA.
Tetracycline indications for use
It is the drug of choice for a few infections (brucellosis, chancroid, cholera, granuloma inguinale, psittacosis, Rocky Mountain spotted fever, syphilis, trachoma, typhus, gastroenteritis due to V. cholerae or Helicobacter pylori). Tetracyclines are also useful in treating some animal bites and Lyme disease.
Specific clinical indications include: tx of uncomplicated urethral, endocervical, or rectal infections caused by Chlamydia organisms,
adjunctive tx, with other antimicrobials, in the tx of pelvic inflammatory disease and sexually transmitted diseases,
posteposure prophylaxis and tx of anthrax. Doxycycline is the tetracycline of choice as part of a combination-drug regimen
Long-term tx of acne,
As a substitute for penicillin in penicillin-allergic patients. May be effective in treating syphilis when penicillin cannot be given. Does not prevent rheumatic fever.
Doxycycline may be used to prevent traveler’s diarrhea due to enterotoxic strains of E. coli.
Demeclocycline (Declomycin) may be used to inhibit antidiuretic hormone in the tx of chronic inappropriate antidiuretic hormone secretion.
Tetracycline contraindications for use
Renal failure.
Pregnant women and children up to 8 years of age. In the fetus and young child, tetracyclines are deposited in bones and teeth along with calcium. It can interfere with tooth enamel formation, cause permanent discoloration of tooh enamel, and depress bone growth.
Increased photosensitivity is a common adverse effect, and pts should be warned to take precautions against sunburn when taking these drugs.
Sulfonamide contraindications
Late pregnancy, lactation, children younger than 2 months of age (except for tx of congenital toxoplasmosis), and people who are sensitive.
Sulfasalazine (Azulfidine) contraindication
People who are allergic to salicylates and people with intestinal or urinary tract obstruction
Store tetracyclines correctly because:
they decompose with age, exposure to light, and extreme heat and humidity. The breakdown products may be toxic.
Pt teaching for sulfonamides and tetracyclines
They inhibit rather than kill bacteria. Take as prescribed around the clock.
They increase sensitivity to light and risks of sunburn. Avoid sunlamps, tanning beds, and intense or prolonged exposure to sunlight.
Do not take tetracyclines with or within 2 hours of dairy products, antacids, or iron supplements. Take on an empty stomach.
Use of sulfonamides and tetracyclines in older adults
Folic acid deficiency may occur because trimethoprim-sulfamethoxazole interferes with folic acid metabolism.
Must be used with caution in pts with hepatic impairment because it causes cholestatic jaundice
Sulfonamides
Use of tetracyclines in critical illness
Doxycycline is the drug of choice because it can be given to pts with renal impairment.
Use of sulfonamides in critical illness
Rarely used except for topical silver sulfadiazine (Silvadene) used to treat burn wounds and Bactrim/Septra used to treat P. jiroveci pneumonia.
S/S of superinfection
Sore mouth; white patches on oral mucosa; black, furry tongue; diarrhea; skin rash; itching in the perineal area; pseudomembranous colitis
Macrolides
Erythromycin, azithromycin (Zithromax), and clarithromycin (Biaxin).
Widely distributed in body tissues and fluids and may be bacteriostatic or bactericidal, depending on drug concentration in infected tissues. Azithromycin and clarithromycin are active against the atypical mycobacteria that cause Mycobacterium avium complex disease. MAC disease is an opportunistic infection that occurs mainly with advanced HIV infection. Helicobacter pylori, a pathogen implicated in peptic ulcer disease, is also treated by these.
Macrolide/ketolide mechanism of action
They enter microbial cells and reversibly bind to ribosomes, thereby inhibiting microbial protein synthesis. Ketolides have a greater affinity for ribosomal RNA, expanding their antimicrobial spectrum compared with macrolides.
Macrolide/ketolide indications for use
Macrolides are widely used for tx of respiratory tract and skin/soft tissue infections caused by streptococci and staphylococci. Erythromycin is also used as a penicillin substitute in pts who are allergic to penicillin; for prevention of rheumatic fever, gonorrhea, syphilis, pertussis, and chlamydial conjunctivitis in newborns; and to treat other infections (Legionnaire’s disease, genitourinary infections caused by Chlamydia, intestinal amebiasis caused by Entamoeba histolytica).
Azithromycin is approved for tx of urethritis and cervicitis caused by C. trachomatis organisms and is being used for the prevention and tx of MAC disease.
Macrolide/ketolide contraindications to use
Hypersensitivity. Telithromycin is contraindicated in people who have had hypersensitivity reactions to macrolides. All macrolides and telithromycin must be used with caution in patients with pre-existing liver disease.
BLACK BOX WARNING for erythromycin estolate and an FDA alert for telithromycin emphasize the liver toxicity associated with these drugs.
BLACK BOX WARNING - do not use telithromycin in patients with myasthenia gravis due to the potential for fatal and life-threatening respiratory failure.
BLACK BOX WARNING for clindamycin
Reports the development of severe colitis with its use that can be life threatening.
Linezolid (Zyvox)
Indicated for pneumonia, complicated and uncomplicated skin and skin structure infections, and VREF infections. Myelosuppresion is a serious adverse effect that may occur with prolonged therapy over 2 weeks. Pseudomembranous colitis may also occur.
Metronidazole (Flagyl)
Effective against anaerobic bacteria, such as Bacteroides and Clostridia. Also effective against protozoa t hat cause amebiasis, giardiasis, and trichomoniasis. Can be used to treat anaerobic brain abscesses. Clinical indications for use include prevention or tx of anaerobic bacterial infections (in colorectal surgery, intra-abdominal infections) and tx of C. difficile associated with pseudomembranous colitis.
Contraindicated during the first trimester of pregnancy and must be used with caution in pts with CNS or blood disorders
Quinupristin-dalfopristin (Synercid)
Indicated for skin and skin structure infections caused by S. aureus. Also for tx of pts with serious or life-threatening infections associated with VREF bactermia.
BLACK BOX WARNING reports that FDA approval for this use is based on the ability of the drug to clear bacteria from the bloodstream rather than its ability to cure the underlying infection.
Interferes with the metabolism of drugs such as cyclosporine, antiretrovirals, carbamazepine, and many others. Toxicity may occur with the inhibited drugs.
Vancomycin (Vancocin)
active only against gram-positive microorganisms. Inhibits cell wall synthesis. Parenteral vanco used extensively to treat infections caused by MRSA. Widely used for prophylaxis of infections in pts who are at high risk of developing MRSA, and who require placement of long-term IV catheters and other invasive tx or monitoring devices.
Avoid or minimize use in empiric tx of febrile pts with neutropenia, in initial tx for C. diff, and as prophylaxis for surgery, low birth weight infants, IV catheter colonization or infection, and peritoneal dialysis.
Very important to give IV infusions slowly, over 1 to 2 hours, to avoid an adverse reaction characterized by hypotension, flushing and skin rash known as “red man syndrome,” attributed to histamine release.
Effects of macrolides on other drugs
Erythromycin in combination with potent inhibitors of CYP3A4 (fluconazole, diltiazem) increases the risk of sudden cardiac death.
BLACK BOX WARNING regarding chloramphenicol
Blood dyscrasias (potentially serious and life threatning) have occurred in pts taking this drug.
BLACK BOX WARNING for clindamycin
If diarrhea develops in pt receiving clindamycin, stop the drug. There is a potential for severe and possible fatal colitis. Pseudomembranous colitis has often been associated with clindamycin therapy.
Erythromycin in pts with hepatic impairment
Should be used cautiously, if at all because it is metabolized in the liver to an active metabolite that is excreted in the bile. It has been associated with cholestatic hepatitis.
Clindamycin, chloramphenicol, and metronidazole should be used cautiously, if at all, in the presence of liver disease.
BLACK BOX WARNING for critical pts receiving clindamycin
They are at high risk for development of pseudomembranous colitis because they often receive aggresive antibiotic therapy with multiple or broad-spectrum antibacterial drugs that destroy normal bowel microorganisms.
Can chloramphenicol be administered IM?
No.
Daptomycin administration
It is incompatible with dextrose-containing IV solutions.
Administration of quinupristin-dalfopristin
Do NOT mix the drug or flush the IV line with saline or heparin containing solutions.
Antiinfectives for peri operative use
When used to prevent infections associated with surgery, a sin- gle dose of an antimicrobial medication is usually given within 1 hour of the first incision. This provides effective tissue con- centrations during the procedure. If intraoperative contamina- tion occurs, the patient should be treated for an infection. The choice of drug depends on the pathogens most likely to colo- nize the operative area. For most surgeries involving an inci- sion through the skin, a first-generation cephalosporin such as cefazolin (Kefzol) with activity against S. aureus or Streptococ- cus species is commonly used. Repeated doses may be given during surgery for procedures of long duration, procedures involving insertion of prosthetic materials, and contaminated or infected operative sites. Postoperative antimicrobials are indicated with intraoperative contamination, traumatic wounds, or ruptured viscera.
