Module 8 pp. Surgical Site Infections (SSI) and Antimicrobials

• Antimicrobials are discussed, particularly in the context of surgical site infections (SSIs) and prophylactic use.

Surgical Site Infections (SSI) Epidemiology

• SSI prevalence is 2-4%, accounting for 20% of healthcare-associated infections (HAIs).
• SSIs increase the length of stay (LOS) by 7-10 days.
• SSIs result in a 5x higher readmission rate.
• Mortality is 2-11x higher with SSIs.
• The cost of SSIs is greater than $20,000 per admission.
• 60% of SSIs are preventable.

Surgical Site Infections (SSI) Characteristics

• SSIs are infections occurring within 30 days postoperatively or within 90 days post-implant.
• Involvement can be incisional (superficial or deep) or within an opened/manipulated anatomical space.

SSI Pathogenesis

• SSIs can arise from intraoperative contamination and foreign bodies.
• SSIs are caused by endogenous and exogenous risk factors.

SSI Pathogenesis - Contamination

• Endogenous contamination involves open wounds and the location of flora.
• Hair follicles and glands (e.g., sweat, sebaceous) are sources of flora.
• Exogenous contamination involves environmental risks, like colonized surfaces.

Surgical Site Infection - Signs and Symptoms

• Signs and symptoms include purulent drainage, pain, localized swelling, erythema, heat, abscess, and fever.
• SSIs are diagnosed by a surgeon.

Endogenous Risk Factors

• Endogenous risk factors include extremes of age, poor nutritional status, obesity, and diabetes.
• Also included are poor perioperative glycemic control, peripheral vascular disease, current infection, corticosteroid use, pre-op skin prep and prolonged hospital stays.

Exogenous Risk Factors

• Exogenous factors include sterile technique, surgical scrub, maintenance of sterility, foreign bodies and implants.
• Additional exogenous factors are placement of drains, OR environment (ventilation, traffic) and decontamination of surfaces.

Wound Classification - Class I (Clean)

• No infection or inflammation is present.
• The wound is primarily closed.
• There is no entry into the respiratory, GI, or GU tracts.
• There is no tissue other than skin carrying indigenous flora.
• Skin flora and staphylococci are common pathogens.

Wound Classification - Class II (Clean-Contaminated)

• There are controlled conditions without unusual contamination.
• There is entry into the respiratory, GI, or GU tracts.
• Skin flora, gram-negative rods, and enterococci are common pathogens.

Wound Classification - Class III (Contaminated)

• The wound is open and fresh.
• There is a major break in sterile technique or major spillage from the GI tract.
• There is entry into the respiratory, GI, or GU tracts.
• Skin flora, gram-negative rods, and enterococci are common pathogens.

Wound Classification - Class IV (Dirty/Infected)

• There is an existing clinical infection and/or old traumatic wounds with perforated viscera.
• Any site is possible.
• There are many potential pathogens.

SSI Performance Improvement Programs

• Initiatives from the CDC, CMS, and SCIP aim to improve SSI rates.
• CMS requires reporting SSI outcome data, tracking rates for various procedures.
• Facility-specific protocols, guidelines, and antimicrobial stewardship are essential.

SCIP-1 Measure Details

• Prophylactic antibiotic should be administered prior to the surgical incision.
• Goal is to achieve bactericidal serum and tissue levels at the time of incision.
• The risk of infection progressively increases after 1 hour.
• Vancomycin or fluoroquinolone is initiated within 2 hours before incision due to longer infusion times.

SCIP-2 Measure

• Prophylactic antibiotic selection should be safe, cost-effective, and target common surgical contaminants.
• Cephalosporins are generally favored.
• Vancomycin is not recommended routinely due to resistance risk and beta-lactam allergy.

SCIP-2 Measure Details

• Prophylactic antibiotics should be discontinued within 24 hours after surgery end time.
• It's important to maintain appropriate serum/tissue levels during surgery.
• Extending antibiotic use beyond 24-48 hours increases risk.

Preoperative Antibiotic Prophylaxis

• Antibiotics given before surgery, incision, and procedure decrease chances of postoperative infections.
• Evidence supports use with foreign body implantation, bone grafting, large dissections and surgeries with expected large blood loss.

Preoperative Antibiotic Prophylaxis Considerations - Timing

• Antibiotics is optimal to administer prior to skin incision.
• It's less effective after limb tourniquet application.

Preoperative Antibiotic Prophylaxis Considerations - Organisms

• Common target organisms: Staphylococcus aureus, Staphylococcus epidermidis, aerobic streptococci and anaerobic cocci.

Preoperative Antibiotic Prophylaxis Considerations - Selection

• Selection based on surgical site and targeted to narrowest spectrum of activity, but to the most common organisms
• This also varies by drugs, cost, safety, administration and hospital resistance patterns.

Prehospital Interventions

• Preoperative bathing with chlorhexidine decreases skin surface pathogen concentrations, but with no reduction in SSI.
• Smoking cessation is recommended 4 to 6 weeks before surgery.
• Recommends good glucose control to minimize SSI.
• Mechanical and antibiotic bowel preparation is recommended for all elective colectomies.

Hospital Interventions

• Target perioperative blood glucose between 110-150 mg/dL, with a higher target (<180 mg/dL) for cardiac surgery patients.
• Avoid hair removal unless it interferes with surgery, and if needed, use clippers, not a razor.
• Clean skin around the incision site, using an alcohol-containing preparation if there is no contraindication.
• Administer prophylactic antibiotics only when indicated and 1 hr before incision (2 hrs for vancomycin or fluoroquinolone).

Beta-Lactam Antibiotics

• Beta-lactams include penicillin derivatives (penams), cephalosporins, carbapenems, monobactams, and carbacephems.

Beta-Lactam Action

• They work by interfering with peptidoglycan and inhibiting penicillin-binding proteins to affect cell wall cross-linking.
• They also interfere with murein hydrolase inhibitor.
• These drugs are bactericidal/bacteriolytic.

Bacterial Resistance to Beta-Lactams

• Bacteria resist beta-lactams by limiting access to the site of action and producing beta-lactamases for hydrolysis.
• Altered PCN-binding proteins or efflux pumps also confer resistance.
• Gram-negative bacteria have decreased porins and carry a beta-lactamase gene.

Penicillins (PCNs)

• Penicillin G is effective against G+/G- cocci, G+ rods, and anaerobes.
• Anti-staphylococcal PCNs like nafcillin target penicillinase-producing staphylococci.
• Broad-spectrum PCNs include ampicillin, amoxicillin (2nd gen), carbenicillin, ticarcillin (3rd gen) and piperacillin (4th gen), effective against G+/G- bacilli.

PCNs - Uses and Considerations

• PCNs are used for prophylaxis in dental, oral, GI, and GU/vaginal surgeries.
• Rapid renal excretion is a key pharmacokinetic feature; ampicillin and piperacillin require dose adjustment in renal disease.
• Beta-lactamase inhibitors bind enzymes, allowing bacteria to become sensitive to antimicrobial action.

PCN Allergy Details

• PCN allergy is the most common drug allergy.
• Hives, angioedema, anaphylaxis are the symptoms.
• It's important to take a good history to check for organ involvement, timing, treatment, and other tolerated antibiotics.

PCN Allergy Specifics

• A family history of PCN allergy isn't heritable.
• Those with serious delayed reactions to PCN should avoid other beta-lactams.
• Mild or IgE-mediated reaction is treated with 3rd-5th gen cephalosporin or PCN with test dose.
• Those without known allergies may receive PCN.

Cephalosporins Classes

• 1st generation: Effective primarily against Gram (+) bacteria
• 2nd generation: Have broader coverage, including some Gram (-) bacteria.
• 3rd generation: Extended Gram (-) coverage with some activity against Gram (+) bacteria.
• 4th generation: Broad-spectrum activity against both Gram (+) and Gram (-) bacteria.

Cephalosporins Mode of Action

• They have a bactericidal effect by inhibiting peptidoglycan synthesis and preventing cross-linking to stop transpeptidase/PBP.

Cephalosporins Uses

• Cephalosporins are used for E. coli, K. pneumoniae, Pseudomonas a., and H. influenzae.
• Additional uses include surgical antimicrobial prophylaxis and meningitis treatment.
• They can reach therapeutic levels in pleural, pericardial, peritoneal, synovial fluids, urine, and bile.

Cephalosporins Actions

• They can be administered PO, IM, or IV.
• Resistance is developed due to cephalosporinases.
• Dose adjustments are needed in renal failure.

Cefazolin (Ancef, Kefzol)

• Cefazolin is the drug of choice for surgical prophylaxis.
• Effective against s. aureus and PCNase staphylococci.
• Relatively resistant to G-.
• It has higher blood levels than other first-generation drugs, but poor ability to cross BBB and poor CSF penetration.

Cefazolin Details

• It does cross the placenta, and is given with metronidazole for colorectal surgery.
• It should be given subconjunctival for ophthalmic surgery. Surgical prophylaxis dosing is IV, and 3 g should be given if the patient is over 120 kg).
• Dosing intervals must be adjusted in renal failure (creatinine clearance).

Cefazolin - Adverse Effects

• Adverse effects include N/V, hypersensitivity, phlebitis, transient elevation of hepatic enzymes and Stevens-Johnson syndrome.
• Additional adverse effects are superinfection, seizure, increases effects of anticoagulants, increase risk with lasix and pregnancy category B.

Other Cephalosporins

• Cefoxitin and cefuroxime treat meningitis and pneumonia.
• Ceftriaxone and cefotaxime (3rd gen) treat meningitis and have resistance to beta-lactamase.

Cefepime (Maxipime)

• It is effective against G+ and G- organisms as well as beta-lactamase.
• The dose is 2 g IV every 12 hrs.
• Adverse effects include superinfection, hypersensitivity, increased INR, and neurotoxicity.

Beta-Lactam Cross-Reactivity

• Allergy to PCNs increases the likelihood of allergies to other PCNs.
• Potential cross-reactivity across beta-lactams is rare.

Beta-Lactam Cross-Reactivity - Prevalence and Strategies

• In the 60s-80s, reported prevalence was 8-18%.
• Today, the risk is around 1-2%.
• The most important determinant is Risk-benefit analysis
• It's negligible in 2nd/3rd gen when there are different side chains.
• Alternatives are Quinolones and macrolides

Beta-Lactam Hypersensitivity Assessment

• Immediate hypersensitivity results in laryngeal edema, bronchospasm, and cardiovascular collapse.
• Sensitization may be lost over time.
• Late-onset reactions include maculopapular rash and fever.
• Cefazolin is most common to cause anaphylaxis.

Aminoglycosides

• Types of aminoglycosides are Gentamicin, Tobramycin, Amikacin, Streptomycin, and Neomycin. They work by interfering with protein (peptide) synthesis during mRNA translation.

Aminoglycosides

• Effective with other antibacterial agents for G+ infections.
• Treats N. gonorrhoeae, mycobacterial infections and protozoa.
• Bacterial resistance involves inability to penetrate cell, inactivation through microbial enzymes and ribosomes.

Aminoglycosides Pharmacokinetics

• They have poor lipid solubility and bioavailability.
• Half-life is increased by 20-40x in renal failure.
• Bactericidal activity can continue after serum concentrations decline (post-antibiotic effect).

Gentamicin Details

• Gentamicin is used off-label as a surgical prophylaxis.
• 1.5-5 mg/kg IV single dose is given within 60 min of procedure start, infused.
• The does should be decreased in renal failure
• It increases the effects of neuromuscular blockers
• Loop diuretics increase toxicity risk with loop diuretics.

Aminoglycosides Adverse Effects

• Can cause ototoxicity.
• Can cause accumulation in renal cortex = an acute tubular necrosis,
• It cause an inability to concentrate urine as well as resulting in the presence of protein.

Aminoglycosides Adverse Effects

• Can cause skeletal muscle weakness
• Can affect prejunctional release of ACh
• Myasthenia gravis patients at high risk
• Administer IV calcium

Aminoglycosides Hypersensitivity

• Allergy reactions are uncommon, most are allergic contact dermatitis, and reactions are well-tolerated.

Macrolides

• Types of macrolides are Erythromycin, Azithromycin and ClarithromycinMacrolides interfere with protein (peptide) synthesis during mRNA translation.

Macrolides Characteristics

• Good broad, uses as they are bacteriostatic (can be -cidal in high doses)
• Active against some Gram-Negative Bacteria
• Used to treat lung and throat infections; pharyngitis, bronchitis, PNA
• Used to treat Severe infections given IV.

Macrolides Pharmacokinetics

• PO usage is most common way to administer, but IV route runs various risks.
• Erythromycin is metabolized in liver, which gets excreted through through biliary means.
• Azithromycin averages half time of ~68 hrs.

Macrolides Adverse Effects

• Risk for cardiac arrest with repolarization
• Diarrhea, nausea, abdominal pain are common.
• Can increase anticoagulants effectiveness.

Clindamycin (Cleocin) Specifics

• It is a lincosamide class
• It binds the 50s ribosome to inhibit peptide-chain synthesisIt is bacteriostatic with some exceptions
• It is effective for anaerobes and certain respiratory-related infections.

Clindamycin (Cleocin)

• Fast oral availability
• Great concentration capacity for urine samples and the placenta
• Hepatic metabolism and renal excretion

Clindamycin (Cleocin) Details

• It has several components
• Must dilute with a solution
• Administer solution in 10-60 minute window, 1 hour post incision
• High interaction potential with IV, calcium gluconate and much more

Clindamycin Adverse Effects

• Neuromuscular blockade
• Gastrointestinal effects are diarrhea and,
• Abdominal pain N/VThrombophlebitis

Clindamycin Hypersensitivity

• Uncommon allergic reactions
• Can commonly cause a maculopapular eruption
• Reports on reactions that are on the higher end of the allergic scale

Vancomycin (Vancocin) Type

• Mechanism of type involves tight binding to block glycopeptide

Vancomycin

• It is bactericidal to G+ bateria, and Treats C. difficile.Sepsis.and PCN- resistant strains
• Should always monitor kidney function to see how body transports it
• Is found in IV with 60-120 min infusion window.

Vancomycin (Vancocin) Warnings

• There are varied side effects with all factors
• There are allergic reactions, always assess for allergic elements and reactions
• Discontinue infusion

Metronidazole (Flagyl) - Action

• Metronidazole diffuses across cell membranes to produce cytotoxic particles.
• The particles break down which then destabilize cell

Metronidazole Uses.

• Can be used Bactericidal
• TreatsAnaerobic, G- bacteria, protozoa, Clostridium, H. pylori
• Works well in cololrectal, urologic, head/neck locations
• Can be used as surgical prophylaxix at 60 mintues to incidsion marks
• Has about 100% bioavaliability through methods oral administration

Metronidazole Sideffects

• Comes with general side effects plus more
• Bacterial infections possible
• Neurologic disturbances are possible
• Stay safe with doses
• Avoid ETOH

Fluoroquinolones Elements

• There are many parts related to it
• Mode of action: inhibits dna synthesis and promotes dna breakage
• Comes alongside a few other things
• Comes in waves

Fluoroquinolones Uses

• Broad spectrum and bactericidal
• Good wwith Entric, Gr- and Gr+ types
• Respiratory pathogens; H. influenzae

Fluoroquinolones Specifics

• It may come with other elements, pay attention to administration times, needs large IV.

Fluoroquinolones Side Effects

• There is gastritis.
• Involves heart
• Can mutate genes
• Check for risks for bacteria resistance with mutation

Other Points

• Antimicrobial selection should match adult guidelines
• Always reference the notes and dosages for children

Topical Antiseptics - Chlorhexidine

• Surgical wash, good at washing the skin
• Good and persistent affect

Chlorhexidine Uses

• disrupt's bacterial cell membranes
• Very toxic
• Can potentially affects your brain if you have a neuro issue

Betadine and lodine

• Rapid-acting as an antiseptic
• Can kill every virus/batteria known to man
• Can cause fever