Stoelting Chapters 41 ANTIMICROBIALS, ANTISEPTICS, DISINFECTANTS

Question 1

Macrolides
- Erythromycin
- Erythromycin has a spectrum of activity, which includes most _______(1) bacteria, Streptococcus pneumoniae, S aureus, Moraxella catarrhalis, H influenzae, Mycoplasma, Chlamydia pneumoniae, and Corynebacterium diphtheriae.
- In patients who cannot tolerate penicillins or cephalosporins, erythromycin or clindamycin is an effective alternative for the treatment of streptococcal pharyngitis, bronchitis, and pneumonia.
- _____ (2) intolerance is the most common side effect, which severely limits its use
- Oral erythromycin prolongs cardiac repolarization and is associated with reports of _______(3). → Effects on QTc

• Azithromycin
  
  • Azithromycin resembles erythromycin in its antimicrobial spectrum, but an extraordinarily prolonged elimination half-time (68 hours) permits once-a-day dosing for 5 days (500 mg on day 1 and 250 mg on days 2-5).
  • Tissue levels of azithromycin can be expected to remain at therapeutic levels for _______(4) days after a 5- day treatment course.

Clindamycin

• Clindamycin resembles erythromycin in antimicrobial activity, but it is

more active against many anaerobes.
- Because severe _______(1) can be a complication of clindamycin therapy, this drug should be used only to treat infections that cannot be adequately treated by less toxic antimicrobials.
- Significant _______(2) in patients treated with clindamycin is an indication to discontinue this drug and initiate evaluation for pseudomembranous colitis.
- However, clindamycin is indicated in the treatment of or prophylaxis for serious infections caused by susceptible anaerobes,

particularly those originating in the gastrointestinal tract and female genital tract.
- Side Effects:
- Clindamycin produces prejunctional and postjunctional effects at the neuromuscular junction, and these effects cannot be readily antagonized with _______(3) or anticholinesterase drugs.
- Large doses of clindamycin can induce profound and long-lasting _______(4) in the absence of nondepolarizing muscle relaxants and after full recovery from the effects of succinylcholine has occurred.
- Skin rashes occur in about 10% of patients treated with clindamycin.

Answer 1

Answers: Macrolides
1. gram-positive
2. Gastrointestinal
3. orsades de pointes
4. 4 to 7

Answers: clindamycin
1. pseudomembranous colitis
2. diarrhea
3. calcium
4. neuromuscular blockade

Question 2

Vancomycin
- Vancomycin is a bactericidal glycopeptide antimicrobial that impairs cell wall synthesis of gram-_______(1) bacteria.
- The oral route of administration is used only for the treatment of staphylococcal enterocolitis and antimicrobial-associated pseudomembranous enterocolitis, taking advantage of the fact that vancomycin is poorly absorbed from the gastrointestinal tract.
- Vancomycin is administered IV for the treatment of severe staphylococcal infections or streptococcal or enterococcal _______(2) in patients who are allergic to penicillins or cephalosporins.
- Vancomycin is the drug of choice in the treatment of infections caused by _______(3).
- When vancomycin is administered IV, the recommendation is to infuse the calculated dose (10-15 mg/kg) over 60 minutes to minimize the occurrence of drug-induced histamine release and hypotension

Side Effects:
- Rapid infusion (<30 minutes) of vancomycin has been associated with profound _______(1) and even cardiac arrest.
- Hypotension is often accompanied by signs of histamine release characterized by intense facial and truncal erythema (“_______(2) syndrome”).
- The red man syndrome may occur even with slow infusion of vancomycin and is not always associated with hypotension.
- Cardiovascular side effects most likely reflect nonimmunologic histamine release induced by vancomycin
- Vancomycin may also produce allergic reactions characterized as anaphylactoid with associated hypotension, erythema, and occasionally bronchospasm.
- _______(3) manifesting as an unexpected decrease in the oxygen saturation (SpO2) may occur in association with vancomycin administration, perhaps reflecting drug-induced vasodilation in the lungs leading to an increase in ventilation to perfusion mismatching
- The administration of vancomycin to a patient recovering from _______(4)-induced neuromuscular blockade has resulted in a return of neuromuscular blockade.

Answer 2

Answers: Vancomycin
1. positive
2. endocarditis
3. MRSA

Answers: S/Es
1. hypotension
2. red man
3. Arterial hypoxemia
4. succinylcholine

Question 3

Bacitracins
- Bacitracins are a group of polypeptide antibiotics effective against a variety of gram-positive bacteria.
- Use of these antimicrobials is limited to _______(1) application in ophthalmologic and dermatologic ointment

• Topical uses of bacitracin include treatment of furunculosis, carbuncle, impetigo, suppurative conjunctivitis, and infected corneal ulcer.

Metronidazole
- Metronidazole is bactericidal against most anaerobic gram _______(2) bacilli and Clostridium species
- This antimicrobial has been useful in treating a variety of CNS, bone and joint infections, abdominal and pelvic sepsis, and endocarditis
- An IV metronidazole is still a useful part of preoperative prophylactic regimens for elective colorectal surgery.
- Side effects of metronidazole include _______(3), _______(4), and nausea.

Fluoroquinolones
- The fluoroquinolones are _______(1)-spectrum antimicrobials that are bactericidal against most enteric gram-negative bacilli and some gram-positive bacteria
- The dose of the fluoroquinolones should be _______(2) in the presence of renal dysfunction.
- Side effects are minimal, with mild gastrointestinal disturbances (nausea, vomiting) and CNS disturbances (dizziness, insomnia) occurring in less than 10% of treated patients.
- Fluoroquinolones are associated with an increased risk of _______(3) and tendon rupture that is enhanced in patients older than 60 years of age, taking corticosteroid drugs, and in patients with kidney, heart, or lung transplants.

• Ciprofloxacin
  
  • Ciprofloxacin is highly effective in the treatment of _______(4) and genital tract infections, including prostatitis, and gastrointestinal infections
  • The major advantage of ciprofloxacin is its greatly enhanced serum concentration and its availability as an IV preparation.
• Moxifloxacin
  
  • Moxifloxacin is _______(5) acting for the treatment of acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, community-acquired pneumonia, skin infections, and complicated intra-abdominal infections.

Answer 3

Answers: Bacitracins
1. topical
2. negative
3. dry mouth
4. metallic taste

Answers: Fluoroquinolones
1. broad
2. decreased
3. tendinitis
4. urinary
5. long

Question 4

Methods for Sterilization of Instruments” section

Formaldehyde
- Formaldehyde is a volatile, wide-spectrum disinfectant that kills bacteria, fungi, and viruses by precipitating protein
- A 2% to 8% concentration is used to disinfect inanimate objects such as _______(1).
- Known carcinogen

Glutaraldehyde
- Glutaraldehyde is _______(2) to formaldehyde as a disinfectant because it is rapidly effective against all microorganisms, including viruses and spores.
- This disinfectant also possesses tuberculocidal activity.
- As a sterilizing solution for endoscopes, glutaraldehyde is _______(3) to iodophors and hexachlorophene

Pasteurization
- Pasteurization (hot water disinfection) is a process that destroys microorganisms in a liquid medium by application of heat.
- Pasteurizing water temperatures in the range of 55°C to 75°C will destroy all vegetative bacteria of significance in human disease as well as many fungi and viruses.
- Equipment (respiratory therapy breathing circuits, anesthesia breathing circuits) should be submerged in water at 68°C for a minimum of 30 minutes.
- With respect to breathing circuits, pasteurization is effective against gram-_______(4) rods, M tuberculosis, and most fungi and viruses.

Cresol
- Cresol is bactericidal against common pathogenic organisms including M tuberculosis.
- It is widely used for disinfecting inanimate objects.

Silver Nitrate
- Silver sulfadiazine or _______(5) is used in the treatment of burns.

Ethylene Oxide
- Ethylene oxide is a readily diffusible gas that is noncorrosive and antimicrobial to all organisms at room temperature.
- This gaseous alkylating material is widely used as an alternative to heat sterilization.
- Adequate airing of sterilized materials, such as tracheal tubes, is essential to ensure removal of residual ethylene oxide and thus minimize tissue irritation.
- Ethylene oxide sensitization has been described in children with spina _______(6) experiencing preoperative anaphylactic reactions, always in association with _______(7) sensitization.

Answer 4

1. surgical instruments
2. superior
3. superior
4. negative
5. nitrate
6. bifida
7. latex

Question 5

Antiseptic and Disinfectant Prophylaxis for Surgical Procedures:

• Decontamination of the skin with antiseptic preparations reduces the burden of skin flora and, in more recent randomized prospective studies, reduces the incidence of surgical site infection
• Centers for Disease Control and Prevention guidelines recommend showering or bathing with an _______(1) solution before surgery and the clinical practice guidelines from the National Institute for Health and Care Excellence recommend bathing or showering with soap, use of an _______(2)-impregnated drape, and immediate preparation with an antiseptic solution.
  
  • The main types of disinfectants are alcohols, chlorhexidine, and _______(3)-containing preparations, which can be used alone or in combination.

Topical Antiseptics

• Iodine
  
  • Iodine is a rapid-acting antiseptic that, in the absence of organic material, kills bacteria, viruses, and spores.
  • An allergic reaction usually manifests as fever and generalized skin eruption.
  • The most important use of iodine is disinfection of the _______(1). For this use, it is best used in the form of a tincture of iodine because the alcohol vehicle facilitates spreading and skin penetration.
  • Iodine may also be used in the treatment of wounds and abrasions.
• Hexachlorophene
  
  • Hexachlorophene (pHisoHex) is a polychlorinated bisphenol that exhibits bacteriostatic activity against gram-_______(2) but not gram-negative organisms.
  • Immediately after a hand scrub with hexachlorophene, the cutaneous bacterial population may be decreased by only 30% to 50% compared with greater than 90% following use of an iodophor.
  • Because most of the potentially pathogenic bacteria on the skin are gram-_______(3), 3% hexachlorophene is commonly used by physicians and nurses to decrease the spread of contaminants from caregivers’ hands.
  • This antiseptic is also used to cleanse the skin of patients scheduled for certain surgical procedures.
  • Hexachlorophene may be absorbed through intact skin in sufficient amounts to produce neurotoxic effects, including cerebral irritability.

Answer 5

Answers: Antiseptic and Disinfectant Prophylaxis for Surgical Procedures:
1. antiseptic
2. iodine
3. iodine

Answers: Topical Antiseptics
1. skin
2. positive
3. positive

Question 6

Aminoglycoside Antimicrobials
* Aminoglycosides are poorly lipid-soluble antimicrobials that are rapidly bactericidal for aerobic gram-_______(1) bacteria.
* As would be predicted with the poor lipid solubility of these drugs, less than 1% of an orally administered aminoglycoside is absorbed into the systemic circulation.
* _______(2) was the first parenterally administered antimicrobial that was active against many gram-negative bacilli and Mycobacterium tuberculosis.
* _______(3) is active against P aeruginosa as well as the gram-negative bacilli.
◦ _______(3) penetrates pleural, ascitic, and synovial fluids in the presence of inflammation.
* _______(4) is a semisynthetic derivative of kanamycin that has the advantage of not being associated with the development of resistance.
◦ The principal use of _______(4) is in the treatment of infections caused by gentamicin- or tobramycin-resistant gram-negative bacilli.
* _______(5) is commonly used for _______(6) application to treat infections of the skin (as after burn injury), cornea, and mucous membranes.

◦ The side effects of aminoglycosides that limit their clinical usefulness include:
▪ Ototoxicity
* Manifests as vestibular dysfunction, auditory dysfunction, or both and parallels the accumulation of aminoglycosides in the perilymph of the inner ear.
* Vestibular toxicity manifests as nystagmus, vertigo, nausea, and the acute onset of _______(1) syndrome
* Auditory dysfunction manifests as tinnitus or a sensation of pressure or fullness in the ears.
* Deafness may develop suddenly.
▪ Nephrotoxicity
* _______(2) is the most nephrotoxic of the aminoglycosides and therefore is not administered by the parenteral route.
▪ Skeletal muscle weakness
* An IV administration of _______(3) overcomes the effect of aminoglycosides at the neuromuscular junction.
* Patients with _______(4) are uniquely susceptible to skeletal muscle weakness if treated with an aminoglycoside.
* Administration of a single dose of an _______(5) is unlikely to produce skeletal muscle weakness in an otherwise healthy patient.
▪ Potentiation of nondepolarizing neuromuscular blocking drugs.

Answer 6

Answers: Aminoglycosides
1. negative
2. Streptomycin
3. Gentamicin
4. Amikacin
5. Neomycin
6. topical

Answers: Side Effects of Aminoglycosides

1. Ménière
2. Neomycin
3. calcium
4. myasthenia gravis
5. aminoglycoside

Question 7

Cephalosporins

• Cephalosporins, like the penicillins, are bactericidal antimicrobials that inhibit bacterial cell wall synthesis and have a low intrinsic toxicity.
• These antimicrobials are derived from 7-aminocaphalosporanic acid.
• The IV administration of any of the cephalosporins can cause _______(1)
• A _______(2) reaction frequently occurs in patients who receive large doses of cephalosporins.
• The incidence of allergic reactions in patients being treated with cephalosporins ranges from 1% to 10%.
  ◦ The majority of the allergic reactions consist of cutaneous manifestations, which occur 24 hours after drug exposure.
  ◦ Life-threatening anaphylaxis is estimated to occur in 0.02% of treated patients.
  ◦ Because the cephalosporins share immunologic cross-reactivity, patients who are allergic to one cephalosporin are likely to be allergic to others.
• Cephalosporins and Allergy to Penicillins
  ◦ _______(1) is the most common adverse reaction to β-lactam antimicrobials.
  ◦ Allergic reactions were previously noted in 1% to 10% of patients treated with penicillins, making these antimicrobials the most allergenic of all drugs.
  ▪ Most often, the allergic response is a delayed reaction characterized by a maculopapular rash and/or fever
  ▪ Manifestations of immediate hypersensitivity may include laryngeal edema, bronchospasm, and cardiovascular collapse.
• Cross-Reactivity
  ◦ There would seem to be the potential for cross-reactivity between penicillins and cephalosporins as they both share a common β-lactam ring.
  ◦ However, actual cross reactivity is rare.
• Classification
  ◦ Cephalosporins are classified as first-, second-, and third generation because of their antimicrobial spectrum
  ◦ First-generation cephalosporins are inexpensive, exhibit low toxicity
  ◦ active as second and third-generation cephalosporins against staphylococci and nonenterococcal _______(2).
  ▪ For these reasons, first-generation cephalosporins have been commonly selected for antimicrobial prophylaxis in patients undergoing cardiovascular, orthopedic, biliary, pelvic, and intra-abdominal surgery
  ▪ All cephalosporins can penetrate into _______(3) and can readily cross the placenta.

Answer 7

Answers:
1. thrombophlebitis
2. positive Coombs

Answers:
1. Hypersensitivity
2. streptococci
3. joints

Question 8

Penicillinase-Susceptible Broad Spectrum Penicillins (2nd Generation)
* Broad-spectrum penicillins, such as ampicillin, amoxicillin, and carbenicillin, have a wider range of activity than other penicillins, being bactericidal against gram-positive and gram-negative bacteria.
* These drugs are not effective against most staphylococcal infections.
* Ampicillin
◦ Ampicillin (α-aminobenzylpenicillin) has a broader range of activity than penicillin G.
◦ Its spectrum encompasses not only pneumococci, meningococci, gonococci, and various streptococci but also a number of gram-negative bacilli, such as Haemophilus influenzae and Escherichia coli.
◦ Among the penicillins, ampicillin is associated with the highest incidence of _______(1) (9%), which typically appears 7 to 10 days after initiation of therapy.
▪ Many of these rashes are due to protein impurities in the commercial preparation of the drug and do not represent true allergic reactions.
* Amoxicillin
◦ Amoxicillin is chemically identical to ampicillin except for an –OH substituent instead of an –H on the side chain.
◦ Its spectrum of activity is identical to that of ampicillin, but it is more efficiently absorbed from the _______(2) tract than ampicillin, and effective concentrations are present in the circulation for twice as long.

Carboxypenicillins (3rd Generation)
* Carbenicillin
◦ Carbenicillin (α-carboxybenzylpenicillin) results from the change from an amino to carboxyl substituent on the side chain of ampicillin.
◦ The principal advantage of carbenicillin is its effectiveness in the treatment of infections caused by _______(1) aeruginosa and certain Proteus strains that are resistant to ampicillin.
◦ _______(2) may develop in susceptible patients in response to the acute drug-produced sodium load ( > 10% of carbenicillin is sodium)
◦ _______(3) and metabolic alkalosis may occur because of obligatory excretion of potassium with the large amount of nonabsorbable carbenicillin.
◦ Carbenicillin interferes with normal platelet aggregation such that bleeding time is prolonged but platelet count remains normal.

Answer 8

Answers: 2nd Generation
1. skin rash
2. gastrointestinal
Extended Spectrum

Answers: 3rd Generation
1. Pseudomonas
2. Congestive heart failure
3. Hypokalemia

Question 9

Antimicrobial prophylaxis for surgical procedure
* Ideally, tissue concentration of the antibiotic should exceed the minimum inhibitory concentration associated with the procedure and/or patient characteristics from the time of incision to the completion of surgery
◦ For short-acting antibiotics, this may require redosing especially when blood loss is greater than 1,500 mL.
◦ Antibiotic treatment is not recommended for longer than 24 hours.
* The antibiotic chosen should be appropriate for the most likely microorganism related to the procedure and patient characteristics.
◦ For clean elective surgical procedures such as mastectomy and thyroidectomy in which no tissue (other than the skin) carrying an indigenous flora is penetrated, the risks of routine antimicrobial prophylaxis outweigh the possible benefits.
◦ The predominant organisms causing surgical site infections after clean procedures are skin flora (_______(1) and Staphylococcus epidermidis)
◦ In clean-contaminated procedures, including abdominal procedures and solid organ transplantation, the most common organisms include gram-negative rods and enterococci in addition to skin flora
◦ Because of their wide therapeutic index and low incidence of side effects, _______(2) (most often a cost-effective first generation cephalosporin such as cefazolin) are the antimicrobials of choice for surgical procedures in which skin flora and normal flora of the gastrointestinal and genitourinary tracts are the most likely pathogens.
▪ Cephalosporins can safely be used in patients with an allergic reaction to penicillins that is not an IgE-mediated reaction (eg, anaphylaxis, urticaria, bronchospasm) or _______(3) (Stevens-Johnson syndrome, toxic epidermal necrolysis).

◦ Vancomycin may also be considered when methicillin-resistant S aureus (MRSA) is considered likely, for example, in children or elderly patients known to be colonized with MRSA.
▪ The recommendation against routine prophylaxis with vancomycin is due to concerns about selection of resistant organisms, its risk of inducing hemodynamic instability due to histamine release (_______(1)) if given rapidly, and evidence that vancomycin is less effective than cefazolin in methicillin-susceptible S aureus.

◦ Clean-contaminated procedures such as colorectal and abdominal surgeries require additional coverage for gram negative rods and anaerobes in addition to skin flora.
▪ _______(2) can be added to cefazolin or cefoxitin, cefotetan, ampicillin-sulbactam, ertapenem, or ceftriaxone.

• _______(3) is the most frequent complication of prophylactic antimicrobials, including the IV cephalosporins.

Antimicrobial Selection:
Prompt identification of the causative organism is essential for the selection of appropriate antimicrobial drugs to treat ongoing infection.

Antimicrobial therapy is more likely to be effective if infected material (foreign body, prosthesis) is removed.

Infections behind obstructing lesions such as pneumonia behind a blocked bronchus will not respond to antimicrobials until the obstruction is relieved
Transport across the blood–brain barrier varies greatly among antimicrobials and is important to consider when prescribing an antibiotic for a neuraxial infection.

Answer 9

Answers: Prophylaxis
1. Staphylococcus aureus
2. cephalosporins
3. exfoliative dermatitis

Answers:
1. red man syndrome
2. Metronidazole
3. Pseudomembranous colitis

Question 10

• Penicillins
  ◦ The basic structure of penicillins is a dicyclic nucleus (aminopenicillanic acid) that consists of a thiazolidine ring connected to a β-lactam ring.
  ◦ The bactericidal action of penicillins reflects the ability of these antimicrobials to interfere with the synthesis of peptidoglycan, which is an essential component of cell walls of susceptible bacteria.
  ◦ Clinical Indications:
  ▪ Penicillin is the drug of choice for treatment of _______(1), _______(2), and _______(3) infections
  ▪ Treatment of _______(4) with penicillin is highly effective.
  ▪ Penicillin is the drug of choice for treating all forms of actinomycosis and clostridial infections causing _______(5).
  ▪ Prophylactic administration of penicillin is highly effective against streptococcal infections, accounting for its value in patients with _______(6) fever.
  ▪ Administration of high doses of penicillin G IV to patients with renal dysfunction may result in _______(7) and hyperkalemia (10 million units of penicillin G contains 16 mEq of potassium).
  ▪ Intrathecal administration of penicillins is not recommended because these drugs are potent convulsants when administered by this route.
  * Furthermore, arachnoiditis and _______(8) may follow intrathecal penicillin administration.
• Penicillinase-Resistant Penicillins
  ◦ The major mechanism of resistance to the penicillins is bacterial production of β-lactamase enzymes that hydrolyze the β-lactam ring, rendering the antimicrobial molecule inactive.
  ▪ Methicillin, oxacillin, nafcillin, cloxacillin, and dicloxacillin are not susceptible to hydrolysis by staphylococcal penicillinases that would otherwise hydrolyze the cyclic amide bond of the β-lactam ring and render the antimicrobial inactive.▪ Specific indications for these drugs are infections caused by staphylococci known to produce this enzyme.
  * Penetration of _______(1) into the central nervous system (CNS) is sufficient to treat staphylococcal meningitis.
  * Hemorrhagic cystitis and an allergic interstitial nephritis (hematuria, proteinuria) may accompany administration of _______(2).
  * Hepatitis has been associated with high-dose _______(3) therapy
  * _______(4) and dicloxacillin are available only as oral preparations and may be preferable because they produce higher blood levels than do oxacillin and nafcillin.

Answer 10

Answers: Penicillins
1. pneumococcal
2. streptococcal
3. meningococcal
4. syphilis
5. gas gangrene
6. rheumatic
7. neurotoxicity
8. encephalopathy

Answers: Penicillinase-Resistant Penicillins
1. nafcillin
2. methicillin
3. oxacillin
4. Cloxacillin