Master ABX

Wound Classification

• Class I/Clean: Uninfected operative wounds with no inflammation, no entry into respiratory, alimentary, genital, or urinary tracts, primarily closed, and drained with closed drainage if necessary.

Clean Wounds Criteria

• No penetrating trauma
• Meet Class I criteria

Class II/Clean-Contaminated

• Operative wounds entering respiratory, alimentary, genital, or urinary tracts under controlled conditions with no unusual contamination
• Includes operations on:
  • Biliary tract
  • Appendix
  • Vagina
  • Oropharynx
• No evidence of infection or major break in sterile technique

Class III/Contaminated

• Open, fresh, accidental wounds
• Operations with:
  • Major breaks in sterile technique (e.g., open cardiac massage)
  • Gross spillage from gastrointestinal tract
  • Incisions with acute or no purulent inflammation

Class IV/Dirty-Infected

• Old traumatic wounds with retained devitalized tissue
• Existing clinical infections or perforated viscera
• Organisms causing postoperative infection were present in the operative field before the operation

Classification of Operative Wounds

• Class I/Clean: Uninfected operative wounds with no inflammation, no entry into respiratory, alimentary, genital, or urinary tracts, primarily closed, and drained with closed drainage if necessary.
• Class II/Clean-Contaminated: Operative wounds where respiratory, alimentary, genital, or urinary tracts are entered under controlled conditions, no unusual contamination, and no evidence of infection or major breaks in sterile technique.

Contamination and Infection

• Class III/Contaminated: Open, fresh, accidental wounds, major breaks in sterile technique, gross spillage from gastrointestinal tract, and incisions with acute or no purulent inflammation.
• Class IV/Dirty-Infected: Old traumatic wounds with devitalized tissue, existing clinical infections, or perforated viscera, implying pre-operative infection in the operative field.

Anesthetic Complications

Bronchospasm

• Decreased ETCO2 and SaO2
• Increased PIP
• Symptoms: Hypotension, Tachycardia, Arrhythmia, and Cardiac arrest

Anaphylaxis Presentation

• Skin symptoms: Flushing, Urticaria, Erythema
• Severe reaction: Stevens-Johnson Syndrome

Insulin Management

• Insulin administration is necessary to maintain glucose levels below 200 mg/dl.
• The IV route is preferred in perioperative settings due to unreliable absorption through the subcutaneous (SQ) route in cases of hypothermia, vasoconstriction, and other conditions.
• Insulin administration may not be necessary for minor procedures.

Blood Glucose Control

• Maintain control of blood glucose levels.
• Keep blood glucose levels below 200 mg/dl.
• Some sources recommend maintaining blood glucose levels between 140-180 mg/dl for specific procedures, such as CT scans and colorectal surgery.

Adverse Reactions

• Stevens-Johnson Syndrome is a potential complication associated with insulin management.

Antibacterial Properties

• Thiazolidine ring connected to a Beta-lactam ring, which inhibits cell wall synthesis through transpeptidation reaction.

Pre-Operative Treatment

• Used as pre-operative prophylaxis for patients with congenital heart disease or implants (e.g., TKA, THA, heart valves).

Transient Bacteremia

• Transient bacteremia often occurs with dental and surgical procedures.

Drug of Choice

• Treatment of choice for infections caused by:
  • Pneumococcal
  • Streptococcal
  • Meningococcal

1st Generation Penicillins

• Effective against Gram-positive bacteria, but not Gram-negative bacteria due to inability to cross the inner cytoplasmic bilayer.
• Examples of 1st generation penicillins include Penicillin G (Pen G), nafcillin, and methicillin.
• Penicillin G is unable to cross the inner cytoplasmic bilayer in Gram-negative cells, making it ineffective against these bacteria.
• Excretion of 1st generation penicillins occurs primarily through the kidneys, with 90% being excreted through tubular secretion (except for nafcillin).
• Caution is advised when using 1st generation penicillins in patients with renal disease, especially those with low urine output.

Penicillin G

• Susceptible to Beta-lactamases
• High dose of 10 million units equivalent to 16 mEq of potassium (K+)
• Use with caution in patients with:
  • Renal disease due to nephrotoxicity
  • Hyperkalemia

Nafcillin

• Resistant to Beta-lactamases
• Unpredictable oral absorption, not used orally
• Highly protein bound in the bloodstream
• Primarily cleared by biliary excretion, no dose adjustment needed in:
  • Renal disease

2nd Generation Penicillins

• Include ampicillin and amoxicillin, which are bacteriocidal against both gram-positive and gram-negative bacteria
• Amoxicillin is absorbed better from the GI tract and has a longer duration of action compared to ampicillin
• Ampicillin has high renal excretion
• Ampicillin has the highest incidence of rash, often due to the commercial preparation rather than an allergic reaction

Carbenicillin

• Effective against organisms resistant to ampicillin
• Must be administered intravenously (IV) as it is not absorbed by the gastrointestinal (GI) tract
• Combination with probenecid increases plasma concentration by 50%
• High sodium content, use with caution in patients with congestive heart failure (CHF)
• Interferes with platelet aggregation, leading to increased bleeding time
• Platelet count remains normal despite increased bleeding time

Probenecid Mechanism of Action

• Inhibits the renal tubular excretion of penicillins
• Increases plasma levels of penicillins when paired with them

Interactions with Other Drugs

• Inhibits the excretion of acetaminophen
• Inhibits the excretion of lorazepam
• Inhibits the excretion of ketoprofen
• Inhibits the excretion of naproxen
• Inhibits the excretion of rifampin

Cephalosporins

• Effective against both Gram-negative and Gram-positive bacteria
• Mechanism of Action (MOA): inhibit bacterial cell wall synthesis
• Inhibited by cephalosporinases, a type of beta-lactamase
• Cross-reactivity with penicillins (PCN) due to shared beta-lactam ring structure (rare)
• Rare incidence of anaphylaxis reaction: approximately 0.02%
• Can cause thrombophlebitis as a side effect
• May produce a positive Coombs' test, but hemolysis is rare
• Inexpensive and suitable for various procedures:
  • Cardiovascular (CV)
  • Orthopedic (ortho)
  • Biliary
  • Pelvic
  • Intraabdominal

1st Generation Cephalosporins

• Cefazolin (Ancef) is the most widely used antibiotic in surgery.
• Dosage for Cefazolin:
  • Adults: 1-2 gm IV for 50-120 kg, 3 gm IV if > 120 kg.
  • Pediatrics: 15-30 mg/kg IV.
• Re-dosing guidelines for Cefazolin:
  • Re-dose after 3-4 hours.
  • Re-dose after significant blood loss (1500 cc).
  • Maximum dose: 6gmin24hours.
• Important note: Do not use Cefazolin if allergic to Cephalexin (Keflex).
• Cephalexin (Keflex) is an oral antibiotic.

2nd Generation Cephalosporins

• Cefuroxime (Ceftin) is effective in treating meningitis and can cross into cerebrospinal fluid (CSF).
• Cefuroxime is effective against Haemophilus influenzae.
• Cefoxitin is resistant to cephalosporinases produced by gram-negative bacteria.
• Cefoxitin is useful for treating gram-negative bacterial infections.

Carbapenems

• Examples: Ertapenem, Imipenem, Meropenem
• High levels of Imipenem can cause seizures, especially in patients with renal failure
• Effective against Enterobacter infections due to resistance to beta-lactamases
• Excretion occurs through the kidneys, requiring dosage adjustment in renal failure cases

Aztreonam

• Monocyclic beta-lactam ring structure
• Penetrates the Central Spinal Fluid (CSF)
• Suitable alternative for patients allergic to Penicillin (PCN) for pneumonia, meningitis, and sepsis caused by Gram-negative bacteria
• Disadvantage: Can cause Enterococcal superinfections
• Relatively expensive antibiotic

Aminoglycosides

• Aminoglycosides provide gram negative coverage and exhibit a synergistic effect when used in combination with other antimicrobials.
• Examples of aminoglycosides include gentamicin, streptomycin (limited use today), amikacin, and neomycin.

Precautions and Interactions

• Amikacin should not be used with PCNs as it may antagonize PCN against enterococcus faecalis.

Neomycin

• Neomycin is used topically and orally, but does not undergo systemic absorption.
• It is useful orally to decrease bacterial flora prior to GI surgery.
• Neomycin is extremely nephrotoxic and should not be given IV.
• It may prolong NMB (neuromuscular blockade).

Adverse Effects

Renal Disease

• Renal disease can increase the elimination half-life of aminoglycosides by 20-40 fold.

Ototoxicity

• Aminoglycosides can cause ototoxicity, which is accentuated by furosemide and mannitol.

Nephrotoxicity

• Aminoglycosides can cause renal tubular necrosis, which is usually reversible when discontinued.

Skeletal Muscle Weakness

• Aminoglycosides can decrease the prejunctional release and sensitivity to ACh at the postsynaptic junction.
• Calcium administration can decrease this effect.
• Use with caution in patients with myasthenia gravis, as aminoglycosides can potentiate NMB.

Gentamycin

• Penetrates pleural, ascitic, and synovial fluids, but only when they are inflamed
• Plasma levels must be monitored to guide dosage adjustments
• Side effects are directly related to plasma concentration levels, so dosage should be decreased in patients with renal disease

Side Effects

• Ototoxicity can cause nystagmus, vertigo, nausea, tinnitus, and pressure in the ears
• Deafness can develop suddenly, highlighting the importance of monitoring plasma levels

Glycopeptides: Vancomycin

• Inhibits cell wall synthesis, effective against Gram-positive bacteria
• Treatment of choice for:
  • MRSA
  • Severe staphylococcal infections
  • Streptococcal or enterococcal endocarditis (if penicillin or cephalosporin allergy)

Pharmacology

• Dosage: 10-15 mg/kg IV over 60-120 minutes
• Dosing frequency: every 12 hours
• Renal considerations: dose reduction necessary in renal disease
• Excretion: 90% unchanged in urine via kidneys

Monitoring and Interactions

• Lab monitoring necessary to prevent:
  • Ototoxicity
  • Nephrotoxicity (especially with concurrent aminoglycosides)
• Interaction: may potentiate succinylcholine NMB

Vancomycin Contraindications

• Arterial hypoxemia is a possible complication, characterized by an unexpected decrease in SpO2
• Drug-induced ventilation/perfusion mismatch can occur
• Rapid infusion can lead to "Red Man Syndrome", which requires decreasing the infusion rate if flushing or other symptoms occur

Red Man Syndrome

• Caused by massive histamine release
• Symptoms include:
  • Hypotension
  • Facial and truncal flushing
  • Cardiac Arrest
• May be treated with diphenhydramine (1mg/kg) or cimetidine (4mg/kg) 1 hour preoperatively

Oxazolidinones

• Linezolid is a type of oxazolidinone that inhibits bacterial protein synthesis by binding to the 50S ribosomal unit
• Has similar coverage to vancomycin
• 100% bioavailable, making it suitable for oral use
• Has a lower incidence of Red Man syndrome compared to vancomycin

Side Effects of Linezolid

• Short-term effects:
  • Nausea
  • Hypoglycemia
• Long-term effects:
  • Bone marrow suppression
  • Peripheral and ocular neuropathy
  • Serotonin syndrome (if used with SSRIs)

Macrolides

• Macrolides include erythromycin and azithromycin (Z-pack)
• Effective against Gram-positive bacteria, including strep, staph, H. influenzae, and chlamydia

Azithromycin

• Long half-life: active 4-7 days after last dose
• Oral dosing: once/day for 5 days

Erythromycin

• Advantage: useful alternative to penicillins (PCN) and cephalosporins
• Disadvantages:
  • Gastrointestinal (GI) upset (severe nausea and vomiting)
  • Thrombophlebitis and tinnitus with IV form
  • Prolonged QT interval (torsades de pointes)
• Metabolism: via CYP3A4 and CYP1A2
• Interactions:
  • Increased levels with ketoconazole (CYP3A4 inhibitor)
  • Increased ventricular irritability with increased concentrations
  • Inhibits P450 enzyme, prolonging metabolism of concurrently used drugs

Macrolides

• Erythromycin and azithromycin (Z-pack) are used to treat Gram-positive bacteria such as strep, staph, H. influenzae, and chlamydia
• Azithromycin has a long half-life, remaining active for 4-7 days after the last dose
• Oral dosing for azithromycin involves taking the medication once a day for 5 days

Lincosamides

• Clindamycin and lincomycin inhibit protein synthesis of the 50S ribosomal subunit
• These antibiotics are metabolized to inactive compounds
• The dose of clindamycin and lincomycin should be decreased in severe liver disease

Clindamycin

• Clindamycin is similar to erythromycin but covers more anaerobes
• It can cause skeletal muscle weakness due to prejunctional and postjunctional effects on the neuromuscular junction (NMJ)
• Large doses of clindamycin can cause significant and prolonged neuromuscular blockade (NMB)
• Clindamycin-induced NMB is not readily antagonized by calcium and anticholinesterase drugs
• Clindamycin has several disadvantages, including toxicity, and should only be used if other agents have failed
• It can cause severe pseudomembranous colitis, and should be discontinued if the patient experiences significant diarrhea

Fluoroquinolones

• Effective against Gram-negative and Gram-positive bacteria
• Effective for treatment of Gastrointestinal (GI) and Genitourinary (GU) infections
• Mechanism of Action (MOA): inhibits DNA synthesis by targeting topoisomerase II and IV, preventing bacterial replication
• Excreted by the kidneys
• FDA warning: use only when alternative treatments are not available

Side Effects

• Peripheral neuropathy
• Psychosis
• Gastrointestinal symptoms: nausea, vomiting, and diarrhea
• Dizziness and insomnia
• Increased risk of tendonitis and tendon rupture
• Muscle weakness in myasthenia gravis (MG)

Important Contraindications

• Not recommended for routine use in patients under 18 years old due to risk of cartilage damage and arthropathy

Specific Fluoroquinolones

Ciprofloxacin

• Useful for many systemic infections
• Treatment of choice for anthrax exposure
• Can be used to treat tuberculosis (TB)

Levofloxacin

• Used in genitourinary (GU) procedures

Moxifloxacin

• Use only when no other options are available
• Additional side effects: SIADH (Syndrome of Inappropriate Antidiuretic Hormone), liver failure, QT prolongation, and psychotic reactions

Antimycobacterials

• Used to treat tuberculosis

Isoniazid

• Inhibits CYP2D6 enzyme
• Can cause:
  • Drug-induced lupus
  • Hepatitis
  • CNS toxicity

Rifampin

• Induces CYP3A4 enzyme (and others)
• Interacts with medications, such as:
  • Methadone
  • Anticoagulants
  • Anticonvulsants
  • Benzodiazepines
• Causes harmless orange coloration of:
  • Urine
  • Sweat
  • Tears
• Adverse effects:
  • Rash
  • Thrombocytopenia
  • Nephritis
• Teratogenicity

Nitroimidazole Antimicrobials

• Effective against anaerobic gram-negative bacilli and Clostridium
• Metronidazole is a key antimicrobial in this class

Metronidazole

• Inhibits bacterial DNA
• Dosage:
  • IV: 500mg-1gm (30 mg/kg/d)
  • Can also be used orally
• Indications:
  • Colorectal, GYN, and ENT procedures
• Metabolism and excretion:
  • Metabolized in the liver
  • Excreted in urine
• Uses:
  • Treats non-severe C. diff cases (alternative to vancomycin)
  • Can be combined with vancomycin to treat severe C. diff cases

Metronidazole Side Effects and Interactions

• Common side effects:
  • Dry mouth
  • Headache
  • Metallic taste
  • Nausea
• Rare but serious adverse effects:
  • Pancreatitis
  • CNS effects (ataxia, encephalopathy, seizures)
• Drug interactions:
  • Potentiates coumadin-like anticoagulants
  • Phenytoin and phenobarbital accelerate clearance
  • Cimetidine may prolong clearance
  • Increases risk of Lithium toxicity
  • EtOH may cause adverse reactions

Tetracyclines

• Mechanism of action: prevents bacterial protein synthesis by binding to 30S ribosomal subunit
• Doxycycline: notable exception in terms of excretion, not renally excreted

Adverse Effects

• Gastrointestinal: nausea, vomiting, diarrhea
• Dermatological: photosensitivity
• Obstetric: contraindicated in pregnancy due to ability to cross placenta
• Teratogenic effects: can cause tooth discoloration, dysplasia, and impaired bone growth in the fetus
• Hepatotoxic and nephrotoxic: can cause liver and renal toxicity

Sulfonamides

• Inhibit folate synthesis in bacterial cells, which is why they're often combined with trimethoprim or pyrimethamine for a synergistic effect.
• Metabolized in the liver and excreted in the urine.
• Can precipitate in acid pH urine.

Adverse Reactions

• Fever
• Rash
• Stevens-Johnson syndrome
• Nausea and vomiting
• Diarrhea
• Photosensitivity
• Hematopoietic disturbances

Sulfonamides in Clinical Use

• Sulfamethoxazole/trimethoprim is used to treat:
  • Genitourinary (GU) infections
  • Respiratory infections
• Increasing resistance to E. coli
• Trimethoprim:
  • Inhibits creatinine secretion without affecting GFR (can be distinguished from sulfonamide nephrotoxicity)

Topical Sulfonamides

• Silver sulfadiazine:
  • Used to prevent infection in burns
  • May slow wound healing

Other Sulfur-Containing Drugs

• Diuretics
• Diazoxide
• Sulfonylurea hypoglycemic agents
• Low risk of cross-sensitivity with allergic reactions

Drug Interactions with Antimicrobials

• Methotrexate accumulation is seen with penicillins, except amoxicillin, which does not cause accumulation.

Interactions with Specific Medications

• Allopurinol can cause hypersensitivity syndrome when taken with amoxicillin, especially in individuals with renal impairment.

Warfarin Interactions

• Warfarin's effects are potentiated by certain antimicrobials, including macrolides, metronidazole, trimethoprim-sulfa, and ciprofloxacin.

Fluoroquinolone Interactions

• Fluoroquinolone absorption is decreased by Ca++, Fe++, and Mg++, as well as by carafate, which reduces their concentration.

Enzyme Inducers

• Phenytoin and phenobarbital are P450 enzyme inducers.

Wound Classifications

• Class I/Clean: uninfected operative wounds with no inflammation, respiratory, alimentary, genital, or urinary tract entry, and primarily closed and drained with closed drainage.
• Class II/Clean-Contaminated: operative wounds with entry into respiratory, alimentary, genital, or urinary tracts under controlled conditions with no unusual contamination.
• Class III/Contaminated: open, fresh, accidental wounds, or operations with major breaks in sterile technique, gross spillage, or acute inflammation.
• Class IV/Dirty-Infected: old traumatic wounds with retained devitalized tissue, existing clinical infection, or perforated viscera.

Anaphylaxis Presentation

• Flushing
• Urticaria
• Erythema
• Stevens-Johnson Syndrome

Insulin

• Maintain glucose levels below 200 mg/dl
• IV route is best in perioperative period
• Not always necessary for minor procedures

Beta-Lactams

• Inhibit cell wall synthesis (transpeptidation reaction)
• Preoperative treatment for patients with congenital heart disease or implants
• 1st Generation Penicillins:
• Pen G: unable to cross inner cytoplasmic bilayer in gram-negative cells, destroys gram-positive cells
• Nafcillin: resistant to beta-lactamases, high protein binding, cleared by biliary excretion
• 2nd Generation Penicillins:
• Ampicillin and amoxicillin: bacteriocidal against gram-positive and negative bacteria
• Amoxicillin: better absorbed from the GI tract, longer acting than ampicillin
• Carbenicillin: useful for organisms resistant to ampicillin

Cephalosporins

• Inhibit bacterial cell wall synthesis
• Inhibited by cephalosporinases (beta-lactamases)
• Cross-reactivity with PCN due to shared beta-lactam ring (rare)
• Anaphylaxis reaction very low (-0.02%)
• 1st Generation Cephalosporins:
• Cefazolin (Ancef): most widely used antibiotic in surgery
• Cephalexin (Keflex): oral, do not use cefazolin if allergic to cephalexin
• 2nd Generation Cephalosporins:
• Cefuroxime (Ceftin): effective in meningitis treatment, crosses into CSF
• Cefoxitin: resistant to cephalosporinases produced by gram-negative bacteria

Other Beta-Lactams

• Carbapenems: ertapenem, imipenem, meropenem
• Aztreonam: monocyclic beta-lactam ring, penetrates CSF, used for pneumonia, meningitis, and sepsis from gram-negative bacteria

Aminoglycosides

• Gram-negative coverage
• Synergistic effect when used in combination with other antimicrobials
• Gentamicin, streptomycin, amikacin, neomycin

Glycopeptides

• Vancomycin: inhibits cell wall synthesis, gram-positive bacteria, treatment of choice for MRSA

Oxazolidinones

• Linezolid: inhibits bacterial protein synthesis, similar coverage as vancomycin, short-term effects: nausea and hypoglycemia

Macrolides

• Erythromycin and azithromycin (Z-pack): gram-positive bacteria, strep, staph, H.influenzae, chlamydia
• Azithromycin: long half-life, active 4-7 days after last dose

Lincosamides

• Clindamycin and lincomycin: inhibit protein synthesis of the 50S ribosomal subunit

Fluoroquinolones

• Gram-negative and positive bacteria
• Effective for GI and GU infections
• MOA: inhibit DNA synthesis of topoisomerase II and IV
• Excreted by kidneys

Antimycobacterials

• Isoniazid: CYP2D6 enzyme inhibitor, can cause drug-induced lupus and hepatitis
• Rifampin: CYP3A4 enzyme inducer, harmless orange color to urine, sweat, and tears

Nitroimidazole Antimicrobials

• Metronidazole: inhibits bacterial DNA, useful for colorectal, GYN, and ENT procedures

Tetracyclines

• Prevents bacterial protein synthesis by binding to 30s ribosomal subunit
• Doxycycline: not renally excreted, adverse effects: N/V, diarrhea, photosensitive