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CHAPTER

9
Surgical Infections and
Antibiotic Selection
Princess L. Venturina
DVM- 4A
Introduction
The golden age of modern antibiotic Widespread use of prophylactic
therapy began with the discovery antibiotics in surgical patients has
and mass production of penicillin in resulted in a de-emphasis on
1941. Since then many potentially surgical asepsis and development of
fatal infections have been antibiotic-resistant bacteria.
prevented through the use of
antibiotics; however, these drugs
are commonly misused.
Antibiotic therapy may be prophylactic or therapeutic. Prophylactic antibiotic
therapy should be used when there is a significant risk of infection or when
infection would be catastrophic; selection of prophylactic antibiotics should be
based on expected .bacterial flora in the targeted tissue. Selection of therapeutic
antibiotics ideally is based on culture and susceptibility results.

Inappropriate use may render antibiotics ineffective or cause morbidity and


mortality from toxicity or the development of resistant microbes.

Bacterial survival in a host depends on bacterial virulence and numbers, host


immunocompetence, and wound factors that deactivate host defenses (e.g.,
presence of blood clots, ischemic tissue, pockets of fluid, or foreign material).
Successful antibiotic therapy requires a reduction of bacterial numbers to the
point where host defenses are effective.
MECHANISMS
OF
ANTIBIOTIC ACTION
When antibiotics inhibit bacterial growth, they are termed bacteriostatic;
when they kill bacteria, they are termed bactericidal.

Antibiotics typically are classified according to their mechanism of action.


They may destroy or alter the bacterial cell wall or inhibit its synthesis, or
inhibit protein or deoxyribonucleic acid (DNA) synthesis.
Destruction of Bacterial Cell Walls
Destruction of Bacterial
Cell Walls
Antibiotics that inhibit synthesis or promote destruction of bacterial cell
walls include the β-lactam ring antibiotics (e.g., penicillins, cephalosporins,
carbapenems, and monobactams), vancomycin, bacitracin, polymyxin, and
the antifungal drugs nystatin, amphotericin B, and the imidazoles. β-Lactams
function by binding to penicillin-binding proteins (PBPs) in the cell wall,
thereby impairing cell wall synthesis.
Destruction of Bacterial
Cell Walls
Aminopenicillins (i.e., amoxicillin, ampicillin) are effective against many Gram-positive
aerobes and some Gram positive and Gram-negative anaerobes. The
carboxypenicillins (e.g., ticarcillin) have better Gram-negative and anaerobe spectrums
than the aminopenicillins, whereas the ureidopenicillins (e.g., piperacillin, mezlocillin) have
the best Gram negative spectrums of all the penicillins.

Cephalosporins are generally more effective than penicillins against Gram-negative


rods (e.g., Enterobacteriaceae), but they may be inactivated by cephalosporinases (a
type of β-lactamase). Most are poorly effective against anaerobes (cefoxitin is an
exception).
Destruction of Bacterial
Cell Walls
Imipenem and aztreonam are β-lactam antibiotics that are highly resistant to β-
lactamases. They are as effective against Gram-negative organisms as
aminoglycosides but are not nephrotoxic. Imipenem (a carbapenem) has the
broadest antibacterial spectrum of any systemic antimicrobial and is effective
against most clinically relevant bacterial species.

Aztreonam, a synthetic monobactam, is unaffected by bacterial β-lactamase. It


is highly effective against many Gram-negative aerobes but has little activity
against anaerobe
Inhibition
of
Protein Synthesis
Inhibition of Protein Synthesis
Chloramphenicol, tetracycline, erythromycin, and clindamycin bind to bacterial
ribosomes, causing reversible inhibition of protein synthesis.

Chloramphenicol has broad-spectrum activity against streptococci, staphylococci,


Salmonella spp., Brucella spp., Pasteurella spp., Ehrlichia spp., Rickettsia spp., and
anaerobes, but it has poor activity against Pseudomonas spp. It is highly lipophilic
and readily enters most tissues (e.g., CNS, prostate, eye). The drug may cause
idiosyncratic fatal anemia in humans; but, dogs and cats usually experience only a
mild, transient anemia. Although considered a bacteriostatic drug, chloramphenicol
can be bactericidal if present in adequate concentrations.
Inhibition of Protein Synthesis
The tetracyclines (e.g., tetracycline, oxytetracycline doxycycline, minocycline) are
effective against many Grampositive and Gram-negative bacteria, including
Chlamydia spp., rickettsiae, spirochetes, Mycoplasma spp., bacterial L-forms, and
some protozoa. They usually are ineffective against staphylococci, enterococci,
Pseudomonas spp., and Enterobacteriaceae.

Doxycycline is used more commonly than tetracycline or oxytetracycline because


it has fewer side effects, penetrates cells better, has less resistance developed
to it, is excreted across the intestinal wall (instead of the kidney or liver), and is
easier to administer. Minocycline is primarily used to treat Brucella infections.
Inhibition of Protein Synthesis
Inhibition of Protein Synthesis
Erythromycin is readily absorbed from the upper gastrointestinal system and
diffuses well throughout most tissues; however, it has a narrow spectrum of activity
and may be associated with nausea and vomiting because of its prokinetic activity.

Clindamycin, a semisynthetic derivative of lincomycin, has a limited spectrum of


activity compared with erythromycin. It is active against Gram-positive pathogens,
including staphylococci, streptococci, clostridia, several Actinomyces spp., and some
Nocardia spp. It is very effective against many anaerobic bacteria. Clindamycin
often is used to treat infections resistant to penicillins and erythromycin or patients
that cannot tolerate those drugs. It is effective
Inhibition of Protein Synthesis
The aminoglycosides (e.g., amikacin, gentamicin, kanamycin, neomycin, netilmicin,
tobramycin) disrupt protein synthesis. They bind irreversibly to bacterial
ribosomes and are bactericidal. They are effective against Gram-negative and
Gram-positive bacteria, including Enterobacteriaceae and pseudomonads, and
often have a synergistic effect with β-lactam antibiotics.
Inhibition of DNA Synthesis
Inhibition of DNA Synthesis
Fluoroquinolones (e.g., enrofloxacin, difloxacin, ciprofloxacin, ofloxacin,
marbofloxacin) (see and potentiated sulfas (e.g., trimethoprim-sulfa) inhibit DNA
synthesis. Fluoroquinolones inactivate DNA gyrase, preventing uncoiling of the DNA
molecule during DNA replication and transcription to messenger ribonucleic acid
(mRNA). They are rapidly bactericidal and historically have been effective for soft
tissue infections, pneumonia, osteomyelitis, and urinary tract infections caused by
Gram-negative organisms and staphylococci. They also are effective against
Rickettsia rickettsii and possibly L-form bacteria, but they are variably effective
against Gram-positive cocci, especially enterococci (except staphylococci) and
anaerobic bacteria.
Inhibition of DNA Synthesis
The dose of enrofloxacin varies depending on the target tissue (see Table 9-2).
Possible side effects of quinolones include vomiting, CNS effects in animals of all
ages, and cartilage and tendon lesions in developing animals.
Inhibition of DNA Synthesis
Oral ciprofloxacin is less expensive than enrofloxacin, but it is also less
bioavailable in dogs (approximately 30% to 40%) than in people (approximately
70% to 80%). Therefore, it is commonly underdosed when administered to dogs.

Marbofloxacin has a broad spectrum of activity against the major pathogens


encountered in surgical infections. It is safe in dogs, and a single IV injection of 2 to
4 mg/kg maintains plasma concentrations above the MIC for Enterobacteriaceae
and staphylococci for 12 to 24 hours.
Inhibition of DNA Synthesis
Trimethoprim-sulfonamide combinations are effective for the treatment of
osteomyelitis, prostatitis, pneumonia, tracheobronchitis, pyoderma, and urinary
tract infections.

Metronidazole is very effective against most anaerobic bacteria. It penetrates


most body tissues well. Dose dependent CNS toxicity is common if excessive doses
are administered.
“DRUGS OF LAST RESORT”
The number of antibiotics that are effective against multidrug-resistant
(MDR) infections is ever diminishing because of transmission of resistance between
bacteria, especially in hospital settings. Currently, there are some MDR bacteria for
which only one or two drugs are effective. These antibiotics are sometimes referred
to as “drugs of last resort.”

It is a moral and ethical imperative that veterinarians only use such drugs
when the bacteria have been isolated and determined to only respond to one of
these antibiotics.
CAUSES OF
ANTIBIOTIC FAILURE
AND MECHANISMS
OF
ANTIBIOTIC RESISTANCE
CAUSES OF ANTIBIOTIC FAILURE AND MECHANISMS OF
ANTIBIOTIC RESISTANCE

Successful antibiotic drug therapy requires attaining adequate


concentrations of the antibiotic at the site of infection so that
bacteria there are killed or suppressed sufficiently to allow host
defense mechanisms to control the infection.
CAUSES OF ANTIBIOTIC FAILURE AND MECHANISMS OF
ANTIBIOTIC RESISTANCE
Factors that contribute to antibiotic failure include inappropriate dose, frequency, or
route of administration; inadequate length of treatment; inappropriate antibiotic selection;
persistence of the cause of infection; inability of the antibiotic to reach the target tissue in
sufficient doses; antibiotic resistance by bacteria; depressed host immunity;
pharmacokinetics of the drug; drug reactions; antibiotic antagonism; and incorrect diagnoses.

Antibiotic resistance may be the result of enzymatic destruction of the antibiotic,


alteration of bacterial permeability to the antibiotic, alteration of the structural target for
the antibiotic, or development of alternative metabolic pathways that bypass the reaction
antagonized by the particular antibiotic.
SURGICAL INFECTIONS
Classification of Surgical Wounds
Classification of Surgical Wounds
Clean wounds have a published infection rate varying from zero to 6%. Clean
wounds associated with cruciate surgery have reported infection rates as high as
6%. In this category wounds associated with severe trauma with multiple
fractures, traumatic procedures, or fractures of the distal radius or tibia that
require plating are most likely to result in postoperative infection.

Clean-contaminated wounds are identified when nonsterile luminal organs are


entered without significant spillage of contents. Included in this category are
procedures in which a minor break in aseptic technique occurs, such as perforation
of a surgical glove
Classification of Surgical Wounds

Contaminated wounds have a published infection rate that varies from 5.8%
to 28.6%; contaminated fractures of long bones and the pelvis, and
contaminated urogenital procedures most frequently become infected.

Dirty wounds are those in which gross infection is present at the time of
surgical intervention (e.g., traumatic wounds with retained devitalized tissue,
foreign bodies, or fecal contamination).
SURGICAL INFECTIONS
Prevention of Surgical Infections
Prevention of Surgical Infections
Preventing infection of surgical wounds is the primary objective of aseptic
surgery. Factors that may determine if microbial contamination of a surgical
wound occurs include host factors, operating room practice, and characteristics
of bacterial contaminants.

Patients older than 10 years of age may be predisposed to infection because of


an inability to mount an appropriate immune response or the presence of
concurrent debilitating disorders. Patients younger than 1 year of age may be
predisposed because of an underdeveloped immune system.
Prevention of Surgical Infections
Patients with protein-calorie malnutrition are at increased risk, especially if
hypoproteinemic. Diagnostic procedures, long periods of hospitalization, previous
antibiotic therapy, remote infections, and wound or body cavity drains may also
predispose an animal to infection. Surgical duration is a risk factor for infection
with the risk for infection doubling approximately every 70 minutes during the
surgical procedure.
Prevention of Surgical Infections

Local conditions at the surgical site may influence the patient’s susceptibility to
infection because they allow bacterial proliferation and inhibit normal host
response.
Perioperative hypothermia should be minimized because it may reduce the
patient’s innate resistance to bacterial infections.
Operating room practices are important in preventing surgical wound infection.
Proper atraumatic tissue handling and instrument use are also important in
preventing infection.
Characteristics of bacterial contaminants may influence surgically acquired
infection.
PROPHYLACTIC AND
THERAPEUTIC
USE OF ANTIBIOTICS
Prophylactic Use
Prophylactic Use

Prophylactic antibiotics must be present at the surgical site during the time of
potential contamination to prevent growth of contaminating pathogens
Empiric selection of drugs is necessary for antimicrobial prophylaxis.
Prophylactic use of antibiotics should also be considered for surgical patients
predisposed to infections at sites other than the surgical incision. Specifically,
use of perioperative antibiotics may decrease the incidence of urinary tract
infections in dogs undergoing surgery for intervertebral disk disease.
PROPHYLACTIC AND
THERAPEUTIC
USE OF ANTIBIOTICS
Therapeutic Use
Therapeutic Use

Prophylactic antibiotics must be present at the surgical site during the time of
potential contamination to prevent growth of contaminating pathogens

Empiric selection of drugs is necessary for antimicrobial prophylaxis.

Prophylactic use of antibiotics should also be considered for surgical patients


predisposed to infections at sites other than the surgical incision. Specifically,
use of perioperative antibiotics may decrease the incidence of urinary tract
infections in dogs undergoing surgery for intervertebral disk disease.
Therapeutic Use

Therapeutic use of antibiotics is based on clinical judgment, knowledge of the


antibiotic’s mechanism of action, and microbiologic factors. The goal is to
choose a drug selectively active for the most likely infecting microorganism(s)
which has the least toxicity, kills bacteria at the site of infection, and does not
negatively influence the host immune system.
Therapeutic Use
THANK YOU!

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