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Antibiotics

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Antibiotics
Antibiotics in ENT Surgery
Magdy M. Amin RIAD
Professor of Otolaryngology.
Ain shames University
Senior Lecturer in Otolaryngology
University of Dundee
Prophylactic antibiotics
• Prophylaxis with antibiotics has decreased the
high incidence of wound infection after head and
neck operations that involve incisions through oral
or pharyngeal mucosa.
• Prophylactic administration of antibiotics can
decrease postoperative morbidity, shorten
hospitalization, and reduce overall costs
attributable to infections.
Prophylactic antibiotics
• Many antibiotics require a single dose given
within 30 minutes of skin incision to provide
adequate tissue concentration throughout the
operation.
• Additional doses during the procedure are
advisable if surgery is prolonged (i. e, >4 h),
major blood loss occurs, or an antimicrobial with
a short half-life is used
The aim of prophylaxis
• The aim of prophylaxis is to augment host defense
mechanisms at the time of bacterial invasion,.
• Prophylaxis is an attempt to attack organisms
before they have a chance to induce infection.
• Previous surgery (i. e, scarring) and radiation
injury decrease host defenses.
• Likewise, certain medical conditions, such as
diabetes mellitus or HIV, predispose the patient to
infection because of diminished host response.
Choosing an antibiotic for prophylaxis
•
•
•
•
Choosing an antibiotic for prophylaxis is multifactorial and should be based on the following:
Type of operation
Kinetics and toxicity of the drugs
Microbiologic characteristics of the operative site
Antibiotic sensitivities specific to the particular
hospital environment
Choosing an antibiotic for
prophylaxis
• If a number of drugs appear equally acceptable
for prophylaxis, the agent least likely to be
used for definitive therapy in postoperative
wound infection should be chosen.
• This strategy should minimize the selection of
organisms resistant to valuable therapeutic
agents.
Choosing an antibiotic for
prophylaxis
• The regimen chosen should be compatible with
findings from the hospital's infection control
wound surveillance report.
• This regimen is particularly important in hospitals
with high incidence of infection with methicillinresistant organisms (eg, S aureus [MRSA], S
epidermidis [MRSE]) or with newly vancomycinresistant organisms.
CLASSIFICATION OF OPERATION
Class Definition
• Clean Operations
in which no inflammation is encountered .
The respiratory, alimentary or genitourinary tracts
are not entered.
There is no break in aseptic operating theatre
technique.
Non contaminated head and neck
surgery
• Non contaminated surgery refers to violation
of prepared skin only and no mucosal
exposure or incision (eg, neck dissection,
parotidectomy, thyroidectomy).
Non contaminated head and neck
surgery
• Clean surgical procedures are those in which no
infection exists prior to surgery.
• During surgery, sterility of the wound is
maintained.
• Following closure of the wound at completion of
surgery, the wound is never again exposed to
direct contact with bacteria.
• The risk of postoperative wound infection under
these circumstances is less than 5%.
CLASSIFICATION OF OPERATION
Class Definition
Clean-contaminated Operations
in which the respiratory, alimentary or
genitourinary tracts are entered
but without significant spillage.
CLASSIFICATION OF OPERATION
Class Definition
Contaminated Operations
where acute inflammation (without pus) is encountered.
or where there is visible contamination of the wound.
Examples include gross spillage from a hollow viscus during the
operation
or compound/open injuries operated on within four hours.
CLASSIFICATION OF OPERATION
Class Definition
Dirty Operations:
In the presence of pus.
where there is a previously perforated hollow
viscus,
or compound/open injuries more than four
hours old.
PROBABILITY OF WOUND INFECTION
BY TYPE OF WOUND AND RISK INDEX
Clean
Clean-contam.
Contaminated
0
1.0%
2.1%
3.4%
Risk Index
1
2
2.3%
5.4%
4.0%
9.5%
6.8%
13.2%
ENT SURGERY
•
Head and neck surgery - A Antibiotic prophylaxis is recommended
•
Head and neck surgery - clean C Antibiotic prophylaxis is not recommended
There is no evidence of effectiveness from RCTs
•
Ear surgery - clean A Antibiotic prophylaxis is not recommended There is no
evidence of effectiveness from RCTs
•
Nose or sinus surgery C Antibiotic prophylaxis is not recommended There is
evidence of no effectiveness from RCTs
•
Tonsillectomy C Antibiotic prophylaxis is not recommended There is no
evidence of effectiveness of prophylaxis from RCTs. The cited trials are of
treatment for seven days after tonsillectomy, not prophylaxis.
ADMINISTRATION OF INTRAVENOUS
PROPHYLACTIC ANTIBIOTICS
Prophylaxis should be started preoperatively in most
circumstances
ideally within 30 minutes of the induction of
anesthesia.
ADMINISTRATION OF INTRAVENOUS
PROPHYLACTIC ANTIBIOTICS
Antibiotic prophylaxis should be administered
immediately before or during a procedure.
Prophylactic antibiotics should be administered
intravenously.
The single dose of antibiotic for prophylactic use is,
in most circumstances, the same as would be used
therapeutically.
ADMINISTRATION OF INTRAVENOUS
PROPHYLACTIC ANTIBIOTICS
An additional dose of prophylactic agent is not
indicated in adults, unless there is blood loss of up
to 1500 ml during surgery or haemodilution of up
to 15 ml/kg.
Fluid replacement bags should not be primed with
prophylactic antibiotics because of the potential
risk of contamination and calculation errors.
Duration of Perioperative Antibiotic
Use
1. Prophylactic perioperative antibiotics
should be started prior to skin incision for
maximal benefit.
Duration of Perioperative Antibiotic
Use
2. There is no advantage to continuation of
perioperative antibiotics beyond 24 to 48
hours postoperatively has ever been
demonstrated.
Duration of Perioperative Antibiotic
Use
The possible exception to this is
metronidazole;
• because metronidazole may enter abscess
spaces better than other antibiotics.
• its prolonged use has been associated with
less severe postoperative infections in one
study.
Prophylactic Antibiotic Regimens
for Major Clean-Contaminated
1. Clindamycin: 600 mg IV within 1 hour of surgery, 4
additional doses Q6H following surgery.
The antibiotic may alternatively be given for a full 48
hours postoperatively.
there is no compelling evidence that the additional 24
hours confers any additional benefit.
Prophylactic Antibiotic Regimens
for Major Clean-Contaminated
2. Augmentine: 1.5 grams IV within 1 hour of
surgery .
and 8 additional doses at 6-hour intervals
following surgery.
Prophylactic Antibiotic Regimens
for Major Clean-Contaminated
3. Cefazolin: 2.0 grams IV within 1 hour of surgery.
and 3 postoperative doses at 8-hour intervals.
This regimen may be extended to a total of 48 hours
postoperatively.
Prophylactic Antibiotic Regimens
for Major Clean-Contaminated
4. Cefazolin/metronidazole: cefazolin 1 gm IV 1 hour
prior to surgery
then 1 gram IV every 8 hours postoperatively for a total
of 6 doses.
and metronidazole 900 mg IV 1 hour prior to surgery
then 900 mg IV every 8 hours postoperatively for a
total of 6 doses.
ENT SURGERY
Antibiotic prophylaxis is recommended
in:
• A – Head and neck surgery (cleancontaminated/contaminated)
•
•
•
•
•
Antibiotic prophylaxis is not recommended in:
A – Ear surgery (clean)
C – Head and neck surgery (clean)
C – Nose or sinus surgery
C – Tonsillectomy
Contaminated head and neck
surgery
• Contaminated surgery refers to transmucosal
operations (eg, composite resection,
glossectomy, maxillectomy).
• Saliva contains 108 bacteria per milliliter, 90%
of which are anaerobic. Ninety-six percent of
wound infections in the head and neck are
polymicrobial.
Contaminated head and neck
surgery
• Organisms involving oropharyngeal flora
included:
• anaerobic organisms (Bacteroides, 76%)
• gram-negative rods (eg, Escherichia coli and
Klebsiella, Serratia, and Proteus species)
• gram-positive organisms (ie, Staphylococcus,
Streptococcus).
Contaminated head and neck
surgery
• Clindamycin (600 mg PO/IV q8h for 4 doses) is the
recommended antibiotic to prevent anaerobic wound
contamination in extensive surgeries of the head and neck.
• Appropriate antibiotic choices also include a combination
of ampicillin and sulbactam (3 g IV followed by 1.5 g q8h
for 3 doses)
• combination Ancef and Flagyl.
• As an oral mouth rinse, use of clindamycin (75-mg caps
stirred in 8 oz of tap water) or chlorhexidine (Peridex)
provides rapid and sustained reductions in the
concentrations of aerobic and anaerobic oral flora.
Facial fractures
• Open fractures have an increased incidence
of infection in the absence of antibiotic
prophylaxis when compared to closed or
open fractures treated with prophylactic
antibiotics.
Facial fractures
• Antibiotic prophylaxis significantly reduce the
incidence of postoperative infections in facial
fractures, especially mandible fractures of the body.
• The infection rates in zygoma fractures, LeFort
fractures, and mandibular subcondylar fractures are
similar.
Disadvantages of antibiotics
• It promotes antibiotic resistance and contributes to
super infection.
• Antibiotic use is also costly and associated with
allergic reactions, toxic reactions, and adverse
effects
• The use of antibiotics may encourage laxity of
good surgical technique.
Oral, Dental, Respiratory Tract, or Esophageal Procedures
Situations
Agent
Adult Regimens
Standards general
prophylaxis
Amoxicillin
2 gm PO one hour before
procedure
Clindamycin
or
600 mg PO one hour before
procedure
Cephalexin or
Cefadroxil
or
2 gm PO one hour before
procedure
Azithromycin or
Clarithromycin
500 mg PO one hour before
procedure
Ampicillin
2 gm IV/IM 30 minutes before
procedure
Clindamycin
or
600 mg IV 30 minutes before
procedure
Cefazolin
1 gm IV/IM 30 minutes before
procedure
Allergic to Penicillin
If unable to take oral
medications
Allergic to penicillin and
unable to take oral
medications
Oral, Dental, Respiratory Tract, or Esophageal Procedures
Situations
Agent
Pediatric Regimen*
Standards general
prophylaxis
Amoxicillin
50 mg/kg PO one hour before
procedure
Clindamycin
or
20 mg/kg PO one hour before
procedure
Cephalexin or
Cefadroxil
or
50 mg/kg one hour before procedure
Azithromycin or
Clarithromycin
15 mg/kg PO one hour before
procedure
Ampicillin
50 mg/kg IM/IV 30 minutes before
procedure
Clindamycin
or
20 mg/kg IV 30 minutes before
procedure
Cefazolin
25 mg/kg IM/IV 30 minutes before
procedure
Allergic to Penicillin
If unable to take oral
medications
Allergic to penicillin and
unable to take oral
medications
Penicillin
• Mechanism of action
– Exerts action on actively dividing cells by
causing abnormal cell wall development
– Inhibits third stage of cell wall synthesis
• Resistance
– Alterations in penicillin-binding proteins
– Inability to penetrate bacterial cell walls
– Enzymatic hydrolysis of penicillin molecule
Penicillin
• Spectrum
–
–
–
–
–
Gram-positive cocci - Group A and group B Streptococcus
Gram-positive bacilli - Corynebacterium diphtheriae
Gram-negative cocci - Neisseria meningitidis
Gram-negative bacilli - Streptobacillus moniliformis
Anaerobes - Clostridium, Bacteroides, Fusobacterium, and
Peptostreptococcus species
– Miscellaneous - Treponema pallidum and Leptospira,
Enterobacter, and Acinetobacter species
Penicillin
• Adverse reactions
– Hypersensitivity (1-5%)
– Irritant properties that affect the peripheral
nervous system
– Nephropathy - Allergic reaction manifested by
interstitial nephritis and hypokalemia
Cephalosporin
• Mechanism of action
–
–
–
–
–
Inhibits third step of bacterial wall synthesis
Binds to specific proteins on cell membranes
Alters cell permeability
Inhibits protein synthesis
Releases autolysins
• Resistance - Decrease in bacterial cell wall
permeability to antibiotics and production of betalactamase
Cephalosporin
• Spectrum
– First generation (eg, Ancef, Keflin, Kefzol) - Have the greatest
degree of activity against gram-positive organisms, such as
Staphylococcus and Streptococcus (not MRSA); have the same
coverage against gram-positive, anaerobic, and aerobic bacilli as
penicillin
– Second generation (eg, Ceclor, Zinacef, Mefoxin) - Less active
against gram-positive bacteria, but have an advantage against
Haemophilus influenzae organisms and some gram-negative
bacilli, including Proteus and Enterobacter species
– Third generation (eg, Ceftazidime, Cefotaxime, Cefoperazone) Have the greatest activity against gram-negative aerobes, with
variable activity against Pseudomonas organisms
Cephalosporin
• Adverse reactions
– Hypersensitivity - Highest incidence in those
allergic to penicillin
– Hematologic - Neutropenia, leukopenia, and
thrombopenia
– GI disturbances - Nausea, vomiting, anorexia,
and diarrhea
– Reversible renal impairment
Erythromycin
• Mechanism of action - Inhibits bacterial
protein synthesis
• Resistance
– Alteration in protein component of 50s ribosomal
subunit
– Plasmid-mediated resistance
Erythromycin
• Spectrum
– Similar to that of penicillin G
– Effective against Mycoplasma, Legionella, and Actinomyces
species
– Combined with sulfisoxazole to make Pediazole, which is
used in the pediatric population
– Effective against H influenzae organisms
• Adverse reactions
– GI disturbances
– Hypersensitivity
– Cholestatic hepatitis
Clindamycin
• Mechanism of action: Binds to 50s
ribosomal subunit, thereby inhibiting
protein synthesis
• Resistance: Similar to that of erythromycin
Clindamycin
• Spectrum
– Active against most aerobic and anaerobic grampositive organisms
– Anaerobic gram-negative organisms
– although some staphylococcal organisms have
developed resistance
Clindamycin
• Adverse reactions
–
–
–
–
Pseudomembranous colitis
Mild nausea and diarrhea
Hypersensitivity
Leukopenia Transient increase
• Hepatotoxicity (rare)
Metronidazole (Flagyl)
• Mechanism of action
– Reduced intracellularly to its active metabolite that is
bactericidal
– May be administered orally, intravenously, or rectally
– Metabolized in the liver and excreted by the kidneys
Metronidazole (Flagyl)
• Adverse reactions (most of which are dose related
and are not seen with regular short-term use)
–
–
–
–
–
–
CNS toxicity
GI disturbance
Neutropenia
Drug fever
Synergistic alcohol effect
Prolonged activated partial thromboplastin time (aPTT)
Drug Name
Adult Dose
Pediatric
Dose
Contraindic
ations
Ceftazidime (Ceptaz, Fortaz, Tazicef, Tazidime) -Third-generation cephalosporin with broadspectrum gram-negative activity, lower efficacy
against gram-positive organisms, and higher
efficacy against resistant organisms. Arrests
bacterial growth by binding to one or more
penicillin binding proteins.
2 g IV q8h
Not established
Documented hypersensitivity
Interactions
Nephrotoxicity may increase with aminoglycosides,
furosemide, and ethacrynic acid; probenecid may
increase ceftazidime levels
Pregnancy
Precautions
B - Usually safe but benefits must outweigh the risks.
Adjust dose in renal impairment
Drug Name
Nafcillin (Nafcil, Unipen) -- Initial therapy
for suspected penicillin G–resistant
streptococcal or staphylococcal infections.
Use parenteral therapy initially in severe
infections. Change to oral therapy as
condition warrants. Due to thrombophlebitis,
particularly in elderly patients, administer
parenterally only for short term (1-2 d);
change to oral route as clinically indicated.
Adult Dose
2 g IV q4h
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity
Drug Name
Levofloxacin (Levaquin) -- For infections due to
multidrug-resistant gram-negative organisms.
Adult Dose
Pediatric
Dose
500 mg IV q24h
Not established
Contraindica
tions
Documented hypersensitivity
Interactions
Antacids, iron salts, and zinc salts may reduce serum levels; administer
antacids 2-4 h before or after taking fluoroquinolones; cimetidine may
interfere with metabolism of fluoroquinolones; levofloxacin reduces
therapeutic effects of phenytoin; probenecid may increase levofloxacin
serum concentrations; may increase toxicity of theophylline, caffeine,
cyclosporine, and digoxin (monitor digoxin levels); may increase effects of
anticoagulants (monitor PT)
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
In prolonged therapy, perform periodic evaluations of organ system
functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function
impairment; superinfections may occur with prolonged or repeated
antibiotic therapy
Drug Name
Clindamycin (Cleocin) -- Lincosamide for treatment of serious skin
and soft tissue staphylococcal infections. Also effective against
aerobic and anaerobic streptococci (except enterococci). Inhibits
bacterial growth, possibly by blocking dissociation of peptidyl
tRNA from ribosomes causing RNA-dependent protein synthesis to
arrest.
Adult Dose
600 mg IV q8h
Pediatric Dose
Not established
Contraindicatio
ns
Documented hypersensitivity; regional enteritis; ulcerative colitis;
hepatic impairment; antibiotic-associated colitis
Interactions
Increases duration of neuromuscular blockade induced by
tubocurarine and pancuronium; erythromycin may antagonize
effects of clindamycin; antidiarrheals may delay absorption of
clindamycin
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Adjust dose in severe hepatic dysfunction; no adjustment necessary
in renal insufficiency; associated with severe and possibly fatal
colitis
Drug Name
Ampicillin (Marcillin, Omnipen, Polycillin) -- Bactericidal activity
against susceptible organisms. Alternative to amoxicillin when
unable to take medication orally.
Adult Dose
2 g IV q4h
Pediatric Dose
Not established
Contraindicatio
ns
Documented hypersensitivity
Interactions
Probenecid and disulfiram elevate ampicillin levels; allopurinol
decreases ampicillin effects and has additive effects on ampicillin
rash; may decrease effects of oral contraceptives
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Adjust dose in renal failure; evaluate rash and differentiate from
hypersensitivity reaction
Drug Name
Gentamicin (Garamycin, Gentacidin) -- Aminoglycoside antibiotic for gram-negative
coverage. Used in combination with an agent against gram-positive organisms and
one that covers anaerobes.
Not the DOC. Consider if penicillins or other less toxic drugs are contraindicated,
when clinically indicated, and in mixed infections caused by susceptible
staphylococci and gram-negative organisms.
Dosing regimens are numerous; adjust dose based on CrCl and changes in volume of
distribution. May be administered IV/IM.
Adult Dose
2 mg/kg when using multiple daily dosing
5-7 mg/kg/d when once daily dosing used
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; non–dialysis-dependent renal insufficiency
Interactions
Coadministration with other aminoglycosides, cephalosporins, penicillins, and
amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of
neuromuscular blocking agents, thus prolonged respiratory depression may occur;
coadministration with loop diuretics may increase auditory toxicity of
aminoglycosides; possible irreversible hearing loss of varying degrees may occur
(monitor regularly)
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Narrow therapeutic index (not intended for long-term therapy); caution in renal
failure (not on dialysis), myasthenia gravis, hypocalcemia, and conditions that
depress neuromuscular transmission; adjust dose in renal impairment
Drug Name
Tobramycin (Nebcin) -- Indicated in the treatment of staphylococcal
infections when penicillin or potentially less toxic drugs are
contraindicated and when bacterial susceptibility and clinical
judgment justifies its use.
Adult Dose
2 mg/kg bid/qid or 5-7 mg/kg IV/IM qd; subsequent dosing is
individualized based on renal function
Pediatric Dose
Not established
Contraindicatio
ns
Documented hypersensitivity
Interactions
Increases effects of neuromuscular blockers and potentiates effect of
extended-spectrum penicillins; concurrent administration with
amphotericin B, cephalosporins, and loop diuretics increases risk of
nephrotoxicity
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Avoid use in renal impairment, preexisting auditory or vestibular
impairment, and in patients with neuromuscular disorders;
aminoglycosides are associated with nephrotoxicity and ototoxicity
Drug Name
Amikacin (Amikin) -- Irreversibly binds to 30S subunit of bacterial
ribosomes; blocks recognition step in protein synthesis; causes
growth inhibition. Use the patient's IBW for dosage calculation.
Adult Dose
7.5 mg/kg bid/qid or 15 mg/kg/d qd; individualize subsequent
dosing based on renal function
Pediatric Dose
Not established
Contraindicatio
ns
Documented hypersensitivity
Interactions
Coadministration with other aminoglycosides, penicillins,
cephalosporins, and amphotericin B increases nephrotoxicity;
enhances effects of neuromuscular blocking agents; causes
respiratory depression; irreversible hearing loss may occur with
coadministration of loop diuretics
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Not intended for long-term therapy; caution in patients with renal
failure (not on dialysis), hypocalcemia, myasthenia gravis, and
conditions that depress neuromuscular transmission
Drug Name
Erythromycin (Erythrocin, Eryc, E-Mycin) -- Inhibits bacterial growth,
possibly by blocking dissociation of peptidyl tRNA from ribosomes causing
RNA-dependent protein synthesis to arrest. For treatment of staphylococcal
and streptococcal infections.
In children, age, weight, and severity of infection determine proper dosage.
When bid dosing is desired, half-total daily dose may be taken q12h. For
more severe infections, double the dose.
Adult Dose
15 mg/kg IV q6h, up to 4 g/d
Pediatric Dose
Not established
Contraindications Documented hypersensitivity; hepatic impairment
Interactions
Coadministration may increase toxicity of theophylline, digoxin,
carbamazepine, and cyclosporine; may potentiate anticoagulant effects of
warfarin; coadministration with lovastatin and simvastatin increases risk of
rhabdomyolysis
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Caution in liver disease; estolate formulation may cause cholestatic
jaundice; GI adverse effects are common (administer doses pc); discontinue
use if nausea, vomiting, malaise, abdominal colic, or fever occur
Drug Name
Azithromycin (Zithromax) -- Treats mild-to-moderate microbial
infections
Adult Dose
500 mg IV qd
Pediatric Dose
Not established
Contraindicatio
ns
Documented hypersensitivity; hepatic impairment; do not
administer with pimozide
Interactions
May increase toxicity of theophylline, warfarin, and digoxin; effects
are reduced with coadministration of aluminum and/or magnesium
antacids; nephrotoxicity and neurotoxicity may occur when
coadministered with cyclosporine
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Site reactions can occur with IV route; bacterial or fungal
overgrowth may result with prolonged antibiotic use; may increase
hepatic enzymes and cholestatic jaundice; caution in patients with
impaired hepatic function, prolonged QT intervals, or pneumonia;
caution in hospitalized, geriatric, or debilitated patients
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