Antibiotics/infections

Question 1

1) Define MBC vs MIC
2) what’s the importance of MBC/MIC ratio? At what ratio is an Abx considered bacteriostatic Vs bactericidal?

Answer 1

1)MIC (minimum inhibitory concentration) - The minimum concentration of a certain antibiotic (ug/ML) to inhibit visible bacterial growth after incubation for 24 hours
MBC (minimum bacterial concentration) - The minimal concentration of a certain antibiotic (ug/ML) necessary to kill 99.9% of bacteria after incubation for 24 hours

2) The MBC/MIC ratio determines whether antibiotic is bactericidal or bacteriostatic. This ratio is a relative sense factors such as penetration/wound factors (presence of necrotic tissue, clots, fluid, foreign body) also affect antibiotic effect. A factor of 4 or less indicate that the antibiotic is bactericidal.

Question 2

Antibiotics are typically classified according to their mechanism of action. Those are…(6)

Answer 2

1)Destruction or alteration of the bacterial cell wall;
2) inhibition of protein synthesis. 
3) inhibition of DNA synthesis
4) inhibition of RNA synthesis
5) Mycolic acid synthesis inhibition
6) Folic Acid Synthesis inhibition

Question 3

Mechanism of action and five examples of beta-lactam ring antibiotics

Answer 3

Disruption of the bacterial cell wall, leading to increased permeability and lysis. Time dependent, bactericidal, eliminated via kidneys
Penicillins, cephalosporins, carbapenens, monobactams, vancomycin, bacitracin; anti-fungal drugs nystatin and polymyxin B

Question 4

Aminopenicillins - two examples, spectrum,  mechanism of bacterial resistance, compounds added to decrease resistance

Answer 4

Amoxicillin, ampicillin; most gram-positive aerobes, certain gram-positive and gram-negative anaerobes; resistance through penicillinases which prevent antibiotic adherence to the cell wall; Clavulanic acid and sulfabactam added for anti-penicillinase effect

Question 5

Cephalosporins - mechanism of action, spectrum per generation

Answer 5

Disruption of the bacterial cell wall leading to altered permeability and cell lysis; more effective than penicillins against Gram-negatives (Enterobacteriaceae); resistance also through penicillinases;

First generation (cefazolin, cephalexin) - effective against most gram-positive and some gram-negative organisms, but not anaerobes

Second generation (cefoxitin, cefovecin)
greater activity against gram-negative bacteria and anaerobes but no additional efficacy against gram-positive organisms

Third generation (cefotaxime, cefpodoxime) - highly effective against more than 90% of gram-negative bacteria, but they often are less active against gram-positive organisms than first-generation cephalosporins * this is not consistent among third generation cephalosporins* - cefpodoxime, for instant, offers good activity against most streptococci and staphylococci and Enterobacteriaceae

Question 6

Carbapenems - class, mechanism of action, spectrum, known resistance

Answer 6

Beta-lactam ring antibiotic; disruption of the bacterial cell wall; broad gram-negative and gram-positive spectra and are highly resistant to most β-lactamases ; excessive use has already produced resistant bacteria, especially Enterobacteriaceae (i.e., Klebsiella and E. coli). 

Question 7

Antibiotics that inhibit bacterial proteins synthesis - 4 examples, mechanism of action;

Answer 7

Chloramphenicol, tetracycline, erythromycin, and clindamycin bind to bacterial ribosomes, causing reversible inhibition of protein synthesis

Question 8

Chloramphenicol - mechanism of action, spectrum, excretion, potential adverse effects

Answer 8

Mechanism of action - Inhibition of bacterial proteins synthesis; considered bacteriostatic but achieves high enough tissue concentration to be bactericidal; highly lipophilic, penetrates eye and CNS;

Spectrum - most anaerobic and aerobic bacteria, as well as Ehrlichia spp. and Rickettsia spp., but poor activity against Pseudomonas spp;

Excretion - hepatic metabolism and urine excretion

Potential adverse effect - mild, transient anemia (severe in people). Suppresses cytochrome P450, affecting hepatic metabolism of certain drugs

Question 9

Tetracyclines - mechanism of action, preferred drug choice, spectrum of activity; metabolism; precautions/adverse effects

Answer 9

Mechanism of action - inhibits bacterial protein synthesis; well distributed in most tissues but does not penetrate CNS

Preferred drug choice - doxycycline (Fewer side effects, last resistance)

Specrum - effective against many gram-positive and gram-negative bacteria, including Chlamydia spp., rickettsia, spirochetes, Mycoplasma spp., bacterial L-forms, and some protozoa. They are usually ineffective against staphylococci, enterococci, Pseudomonas spp., and Enterobacteriaceae; typically used against tickborne diseases and for prostatic infections.

Metabolism - intestinal excretion

Precautions/adverse effects - binds to calcium. Should not be administered with milk products. Will bind to dental calcium in young patients leading to staining. potential for hepatic toxicity and esophagitis.

Question 10

Macrolides - mechanism of action, metabolism, preferred drug choice, spectrum of activity

Answer 10

Mechanism of action - inhibition of bacterial protein synthesis

Metabolism - easily diffuses through tissues and accumulates in phagocytic cells; eliminated in the bile

Preferred drug choice - Azithromycin (active against aerobic bacteria, such as staphylococci and streptococci, and anaerobes. It also has good activity against Mycoplasma spp. and intracellular organisms, such as Bartonella spp., Toxoplasma spp., and atypical mycobacteria).

Question 11

Clindamycin - mechanism of action, metabolism, spectrum of activity; adverse affect

Answer 11

Mechanism of action - inhibition of bacterial proteins synthesis

Metabolism -  excellent concentrations in the skin and bones, as well as high concentrations in white blood cells. Excreted in the bile

Spectrum of activity - effective against most anaerobic bacteria, plus it is active against many gram-positive pathogens. Effective against toxoplasma and Neospora. Typical indications include intra-abdominal infections, osteomyelitis, discospondylitis, and oral/dental disease. Can be used as part of therapy against Pseudomonas because it inhibits bacterial adherence to epithelial cells, making it more susceptible to other antibiotics.

Adverse effects - can cause esophagitis in cats

Question 12

Aminoglycosides - mechanism of action, metabolism, preferred drug choices, spectrum of action, adverse effects, common combinations

Answer 12

Mechanism of action: inhibition of bacterial proteins synthesis

Metabolism: Poor oral absorption; concentration dependent (given QD); Limited distribution in the extra cellular and cerebrospinal fluid; good distribution into the pleural fluid, bone, joints, and peritoneal cavity is good

Preferred drug choices: amikacin, gentamicin, neomycin, tobramycin

Adverse effects: nephrotoxicity, particularly if dehydrated, used with potentially nephrotoxic drugs (I.e. NSAID’s) or if patient already has renal disease; neuromuscular blockade and ototoxicity possible but infrequently observed

Spectrum of activity: effective against gram-negative and gram-positive bacteria, including Enterobacteriaceae and pseudomonads, but not anaerobes. Their activity is reduced in necrotic tissue because of free nucleic acid material.

Common combo: combination of a β-lactam and an aminoglycoside is often synergistic, plus it helps prevent bacteria from becoming resistant to these drugs.

Question 13

Antibiotics that inhibit DNA synthesis - two major classes,

Answer 13

Classes - Fluoroquinolones and potentiated sulfas

Question 14

Fluoroquinolones: 3 examples;  mechanism of action/metabolism; spectrum; adverse effects

Answer 14

Examples: enrofloxacin; marbofloxacin; orbifloxacin

Mechanism of action/Metabolism: inhibit DNA synthesis, bactericidal, concentration dependent, concentrates in phagocytic cells, primarily excreted to the kidneys.

Spectrum of Activity: principally gram-negative spectrum but is also effective against Rickettsia rickettsii, Mycobacteria, and possibly L-form bacteria. Enrofloxacin is poorly effective against most gram-positive cocci and anaerobic bacteria except for newer fluoroquinolones (e.g., pradofloxacin) have enhanced anaerobic activity.

Marbofloxacin - very good activity against all major pathogens associated with surgical infections; single IV injection of 2 to 4 mg/kg maintains plasma concentrations above the MIC for Enterobacteriaceae and staphylococci for 12 to 24 hours.

Ciprofloxacin - poor bioavailability in the dog (40%) in comparison to people (80%), so frequently underdosed

Adverse Effects: blindness in cats, CNS effects, cartilage lesions in rapidly growing large breed dogs, and vomiting. Rapid IV injection of undiluted enrofloxacin can be fatal.

Question 15

Trimethoprim-Sulfonamide; mechanism of action; metabolism; common uses; spectrum; adverse effects

Answer 15

Mechanism of action: inhibits bacterial Folate synthesis; Time-dependent bactericidal - difficult for bacteria to develop resistance. Tissue concentration depends on the type of sulfonamide

Metabolism: hepatic metabolism, Renal excretion.

Common uses: osteomyelitis, prostatitis, pneumonia, tracheobronchitis, pyoderma, and UTI.

Spectrum: broad spectrum of activity against gram-positive and gram-negative bacteria, as well as Nocardia spp. and anaerobic bacteria. They are usually not effective against pseudomonads

Adverse effects: keratoconjunctivitis sicca, thrombocytopenia, anemia, neutropenia, bone marrow suppression, fever, vomiting, hypersensitivity (i.e., vasculitis or arthritis), and hepatic disease. Some breeds (e.g., miniature Schnauzers, Samoyeds, Doberman pinschers) and some families of dogs seem more likely to suffer side effects, probably because of altered hepatic metabolism.

Question 16

Metronidazole - spectrum; penetration

Answer 16

Spectrum - effective against most anaerobes

Penetration - good in most body tissues

Adverse effects - CNS toxicity in higher doses



Question 17

Factors that contribute to antibiotic therapy failure

Answer 17

Factors contributing to therapeutic failure include inappropriate dose, frequency, or route of administration; inadequate duration of treatment; inappropriate antibiotic selection; presence of foreign material (i.e., foreign body or implant); inability of sufficient antibiotic to reach the target tissue (e.g., cross the blood-brain barrier); bacterial resistance (see later discussion); depressed host immunity (e.g., concurrent debilitating illness, immunosuppressive drug therapy); pharmacokinetics of the drug; drug reactions; antibiotic antagonism; and incorrect diagnoses (i.e., viral diseases or foreign bodies misdiagnosed as primary bacterial infections)

Question 18

What are the two mechanisms of bacterial resistance to antibiotics

Answer 18

There are two main ways that bacteria develop resistance; they can alter the site that the antibiotic targets (i.e., receptors in/on the bacteria), or they can alter the concentration of the antibiotic in the bacteria. Intracellular concentrations may be altered by enzymatic destruction of the antibiotic (e.g., β-lactamases), decreasing bacterial permeability to the antibiotic (e.g., altering porin size such that antibiotics can no longer access intracellular targets), or developing efflux proteins (i.e., these are closely associated with porins, and they pump specific chemicals out of the bacteria).

Question 19

SSI categories according to the CDC; criteria

Answer 19

Superficial incisional - within 30 days of Sx, only skin/SQ +
- purulent exudate with or without pos. culture OR
- pos. culture OR
- signs of infection (unless culture negative)

Deep incisional - within 30 days of Sx w/o implants or 1 year with implants AND involves deep soft tissue (muscle/fascia) +
- Purulent exudate from deep incision but not from organ/space OR
- Deep incision dehisces or is opened by surgeon with fever or localized pain (unless culture negative)
- Abscess is identified
- Diagnosis of deep incision infection made by surgeon or clinician

Organ/space - within 30 days of Sx w/o implants or 1 year with implants AND involves organ or cavity other than the incision manipulated during the operation +
- purulent exudate from a drain placed into organ/cavity
- positive bacterial culture of fluid or tissue
- abscess identified
- Diagnosis of deep incision infection made by surgeon or clinician

Question 20

Incidence of SSI in veterinary patients, divided by superficial, deep and organ/space; most common pathogen; time frame for diagnosis

Answer 20

The incidence of SSI in this study was 3% overall with 42% classified as superficial, 50% classified as deep, and 8% as organ/space. The most prominent bacterial species cultured in this study was methicillin-resistant Staphylococcus pseudintermedius (MRSP) at 47%. The majority of SSIs are recognized within 30 days of surgery

Question 21

Wound Classification System - Clean wound, examples

Answer 21

Nontraumatic, noninflamed operative wounds in which the respiratory, gastrointestinal, genitourinary, and oropharyngeal tracts are not entered
Elective celiotomy (for spay, for example), TPLO, THR, PDA

Question 22

Wound Classification System - Clean-contaminated wound, examples

Answer 22

Operative wounds in which the respiratory, gastrointestinal, or genitourinary tract is entered under controlled conditions without unusual contamination; an otherwise clean wound in which a drain is placed
Enterotomy, small intestinal resection/anastomosis, bronchoscopy
* includes perforation of surgical glove

Question 23

Wound Classification System - Contaminated wound, examples

Answer 23

Open, fresh, accidental wounds; procedures in which gastrointestinal contents or infected urine is spilled or a major break in aseptic technique occurs
Cystotomy with spillage of urine; cholecystectomy with spillage of bile

Question 24

Wound Classification System - dirty, examples

Answer 24

Old traumatic wounds with purulent discharge, devitalized tissue, or foreign bodies; procedures in which a viscus is perforated or fecal contamination occurs
Abscess, peritonitis, TECA

Question 25

Patient related factors that contribute to surgery site infection

Answer 25

Hypotension, endocrinopathies, gender (androgens increase risk of infection), potential factors (obesity, hypothermia, blood loss, immune-suppressive drugs)

Question 26

Procedure related factors that contribute to surgery site infections

Answer 26

Surgery site clipping, surgical time, tissue handling, anesthesia time, operating room conditions, implants,

Question 27

Increased risk of SSI with Vs. without surgical implants in small animal patients

Answer 27

5.6 times (Turk, 2015)

Question 28

Most common pathogens associated with SSI in Small Animals

Answer 28

Staphylococcus spp. (Particularly pseudintermedius), E.coli and Pasteurella spp. (Particularly cats).

Question 29

Situations in which multifilament suture should be avoided

Answer 29

Infected surgical sites or anywhere wicking of bacteria is considered undesirable (i.e. G.I. tract)

Question 30

Mechanism of action of Triclosan used to coat sutures

Answer 30

Inhibits bacterial fatty acid synthesis

Question 31

What do fluoroquinolones and metronidazole have in common (regarding mechanism of action)

Answer 31

The act by inhibition of bacterial DNA synthesis

Question 32

Describe the mechanism of UMN bladder - site of injury, innervation, clinical features

Answer 32

Lesions cranial to the L7 spinal cord segment result in preservation of the sacral spinal cord segments but disruption of the ascending and descending pathways to and from the brain. This loss of supraspinal input results in impaired control over detrusor muscle activation and relaxation and loss of bladder fullness sensation and voluntary micturition. The pelvic and pudendal nerves remain functional; therefore, the external urethral sphincter remains closed. This condition is often referred to as “upper motor neuron” bladder, and clinically, the manifestation is urine retention with a large distended bladder, often felt as tensed or firm on palpation, that is difficult to express. Some neurologists have suggested presence of “small unsynchronized” bladder contractions (5). Therefore, there is incontinence either due to bladder overflow or intermittent emission of urine from involuntary bladder contractions. These animals are at risk for bladder rupture either through excess filling against a closed sphincter or as a complication during manual bladder expression, although this is rare.

Question 33

Describe the mechanism of LMN bladder dysfunction. Site of injury, innervation, clinical presentation

Answer 33

Sacral lesions result in loss of bladder innervation from the pelvic and pudendal nerves which causes loss of detrusor muscle function and urethral sphincter tone. It results in excessive bladder distension that feels flaccid on manual palpation and there is typically constant leakage of urine due to poor sphincter function. This is often referred as “lower motor neuron” bladder. The incontinence can occur because of overflow or simply when the pressure in the bladder exceeds that of the weakened urethral sphincter but clinically, the bladder is often quite large. The animal is frequently soiled with urine and this causes major difficulties in nursing care of these patients in hospital and also at home.

Question 34

Explain cat “tail pull“ injury - site of injury, nerves involved, clinical presentation

Answer 34

In some instances of focal sacral lesions, sphincter tone can be preserved resulting in a combination of flaccid detrusor muscle with sphincter tone that is difficult to overcome and resulting bladder distension. While this is most commonly seen in cats with “tail pull” injuries that damage the pelvic and pudendal nerve roots, it can occur with dogs that have suffered a focal sacral lesion due to acute non-compressive nucleus pulposus extrusions or fibrocartilaginous emboli (17). The exact mechanisms causing this type of dysfunction remain unclear, although there is a suggestion that this could be mediated by the preserved hypogastric structures and internal urethral function.

Question 35

Most common bacterial isolates from a septic joint in a dog

Answer 35

Staphylococcus intermedius, staphylococcus aureus and beta hemolytic streptococci

Question 36

b) Briefly describe the cytological features of septic joint fluid

Answer 36

Polymorphonuclear leukocytosis (primarily neutrophils) with degenerative and toxic changes such as pyknotic nuclei, degranulation and cell rupture. Intracellular bacteria may be present and is pathognomonic for septic arthritis, but only observe in the minority of cases. High protein concentration

Question 37

List six risk factors known to increase the chance of surgical infections

Answer 37

Increasing American Society of Anesthesiologists’ preoperative assessment score ~3 •Increasing duration of anesthesia (~30% increase for each hour) •Increasing duration of surgery (doubles every 70–90 minutes) •Increasing number of persons in operating room (1.3 times higher/person) •Dirty classification of wound site •No preoperative or intraoperative antimicrobial prophylaxis (6–7 times more likely) •Increasing duration of postoperative intensive care stay (1.16 times for each additional day) •Wound drain (foreign materials reduce number of microorganisms required for infection by 104) •Increasing patient weight

Question 38

Antibiotic choice to be administered before surgery on the upper and middle small intestines versus the distal small intestine and large intestine

Answer 38

“First-generation cephalosporins (e.g., cefazolin; Box 18.37) should be administered before surgery on the upper and middle small intestine, second-generation cephalosporins (e.g., cefoxitin) or a penicillin plus a beta-lactamase inhibitor (e.g., ampicillin plus sulbactam) should be considered for procedures involving the distal small intestine and large intestine. ” Excerpt From Small Animal Surgery E-Book Theresa Welch Fossum DVM, MS, PhD, Dipl ACVS https://books.apple.com/us/book/small-animal-surgery-e-book/id1367916984 This material may be protected by copyright.

Question 39

Metronidazole is effective against anaerobic bacteria, and can be used prior to colonic surgery. How should be administered in what should I be combined with?

Answer 39

Begin oral treatment 24 hours before surgery. Combine with second generation cephalosporin (cefoxitin) IV at induction. Combination aminoglycoside (neomycin, kanamycin) and metronidazole can also be used together begin in 24 hours before surgery

Question 40

Should antibiotics be used prior to/during liver surgery? Why? What antibiotics are recommended and which should be avoided?

Answer 40

“Aerobic and anaerobic bacteria normally reside in the liver but may proliferate with hepatic ischemia or hypoxia. Therefore prophylactic antibiotics are warranted in patients with severe hepatic disease that are undergoing hepatic surgery (other than simple biopsy).” “Broad-spectrum antibiotics effective against anaerobes (e.g., penicillin derivatives, metronidazole, clindamycin) are appropriate and relatively safe in patients with hepatocellular compromise (Box 20.1). Potentially hepatotoxic antibiotics (e.g., doxycycline, chlortetracycline, erythromycin) should be avoided if possible.” Excerpt From Small Animal Surgery E-Book Theresa Welch Fossum DVM, MS, PhD, Dipl ACVS https://books.apple.com/us/book/small-animal-surgery-e-book/id1367916984 This material may be protected by copyright.

Question 41

What is the reported rate of infection associated with active closed drains?

Answer 41

A retrospective study reported a 15.6% infection rate with active drains used in clean canine surgeries.4 The majority of infections occurred in patients that had axial pattern flap reconstructions. As indicated by the authors, it is difficult to determine whether the relatively high infection rate was associated with the surgical procedure, complications of the procedure (high rate of partial flap dehiscence), or other factors (eg, length of procedure) caused by the drain itself. Aseptic placement and meticulous postoperative management minimize the risk for drain-associated surgical site infection.