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chemoprophylaxis surgical site infection principles examples
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artemisinin-based combination therapy ACT malaria
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penicillin classification extended spectrum penicillin
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tetracyclines uses adverse effects
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Here are comprehensive answers to all four questions:
Formative Assessment — Chemotherapy
Batch B | Date: 19/03/26
Q1. Chemoprophylaxis for Surgical Site Infection — Principles and Examples (5 marks)
Definition
Surgical chemoprophylaxis refers to the administration of antimicrobial agents to prevent infection at the surgical site (SSI), not to treat an established infection.
Principles
- Correct timing: Antibiotic should be given 30–60 minutes before skin incision (within 120 min for vancomycin/fluoroquinolones) to ensure adequate tissue levels at the time of bacterial contamination.
- Narrow spectrum: The agent should cover the most likely organisms for that specific surgery — not broad-spectrum agents (to avoid resistance and C. difficile).
- Short duration: A single preoperative dose is sufficient for most clean/clean-contaminated surgeries. Extending beyond 24 hours post-op adds no benefit and increases resistance.
- Re-dosing for long procedures: If surgery lasts >2× the half-life of the drug, an intraoperative redose is needed (e.g., cefazolin every 4 hours).
- Weight-based dosing: Obese patients require higher doses (e.g., cefazolin 3 g if weight >120 kg).
- Allergy assessment: Patients with penicillin allergy may receive clindamycin or vancomycin as alternatives.
Classification of Surgical Wounds
| Wound Class | Description | Infection Risk |
|---|---|---|
| Clean | No infection, no hollow viscus entered | 1–2% |
| Clean-contaminated | GI/GU/respiratory tract entered under controlled conditions | 5–15% |
| Contaminated | Acute inflammation, gross spillage | 15–30% |
| Dirty | Established infection, perforated viscus | >30% |
Prophylaxis is indicated for Clean-contaminated and selected Clean surgeries (especially those involving implants).
Examples by Surgery Type
| Surgery | Common Organisms | Drug of Choice |
|---|---|---|
| Cardiac / Orthopedic (implant) | S. aureus, CoNS | Cefazolin 1–2 g IV |
| Colorectal | Gram-negatives, anaerobes | Cefazolin + Metronidazole |
| Appendectomy | Enterobacteriaceae, anaerobes | Cefoxitin or Cefazolin + Metro |
| Hysterectomy | Gram-negatives, anaerobes, streptococci | Cefazolin |
| Head & Neck (entering oropharynx) | Oral flora, anaerobes | Ampicillin-sulbactam |
| C-section | Mixed flora | Cefazolin (before skin incision) |
| Urologic (clean) | E. coli | Trimethoprim-sulfamethoxazole or Ciprofloxacin |
Q2. Short Note on Artemisinin-Based Combination Therapy (ACT) (5 marks)
Background
Artemisinin is derived from the plant Artemisia annua (sweet wormwood). Due to its very short half-life (~1 hour), it must be combined with a longer-acting partner drug — forming ACT.
Rationale for Combination
- Artemisinins act rapidly but are eliminated quickly → used for 3 days to reduce parasite biomass
- The partner drug eliminates residual parasites over a longer duration
- Combination prevents resistance to either drug
WHO Recommendation
The WHO recommends ACT as first-line treatment for uncomplicated P. falciparum malaria in endemic areas, and also for P. knowlesi infections (Harrison's, p. 6443).
Approved ACT Regimens
| ACT | Artemisinin Component | Partner Drug | Duration |
|---|---|---|---|
| AL (most widely used) | Artemether | Lumefantrine | 3 days |
| AS+AQ | Artesunate | Amodiaquine | 3 days |
| AS+SP | Artesunate | Sulfadoxine-pyrimethamine | 3 days |
| DHA-PPQ | Dihydroartemisinin | Piperaquine | 3 days |
| AS+MQ | Artesunate | Mefloquine | 3 days |
Mechanism of Action
Artemisinins are endoperoxide sesquiterpene lactones — they generate free radicals via iron-catalyzed cleavage that alkylate and damage parasite proteins and membranes, rapidly reducing parasite biomass.
Advantages
- Rapid parasite clearance
- Active against all Plasmodium species and all asexual stages
- Reduces gametocytemia → lowers transmission
- Well tolerated
Resistance
Artemisinin partial resistance (marked by Kelch13 mutations) has emerged in Southeast Asia (Greater Mekong Subregion), leading to delayed parasite clearance. Combination with effective partner drugs remains essential.
Contraindications / Cautions
- Avoid artesunate in 1st trimester of pregnancy (use quinine + clindamycin instead)
- ACT is safe in 2nd and 3rd trimesters
Q3. Classification of Penicillin and Extended-Spectrum Penicillins (5 marks)
Classification of Penicillins
1. Natural Penicillins
- Penicillin G (benzylpenicillin) — IV/IM
- Penicillin V (phenoxymethylpenicillin) — oral
- Spectrum: Narrow — streptococci, N. meningitidis, treponemes, clostridia
2. Penicillinase-Resistant Penicillins (Anti-staphylococcal)
- Methicillin, Nafcillin, Oxacillin (parenteral)
- Cloxacillin, Dicloxacillin, Flucloxacillin (oral)
- Spectrum: S. aureus (MSSA); resistant to β-lactamase
3. Aminopenicillins (Broad-spectrum)
- Ampicillin, Amoxicillin
- Spectrum: Gram-positives + some Gram-negatives (E. coli, H. influenzae, Salmonella)
- Destroyed by β-lactamases
4. Extended-Spectrum Penicillins (Anti-pseudomonal)
- Carboxypenicillins: Carbenicillin, Ticarcillin
- Ureidopenicillins: Piperacillin, Mezlocillin, Azlocillin
- Spectrum: Broader Gram-negative coverage including Pseudomonas aeruginosa
5. β-Lactamase Inhibitor Combinations
- Amoxicillin-Clavulanate (Co-amoxiclav)
- Ampicillin-Sulbactam
- Ticarcillin-Clavulanate
- Piperacillin-Tazobactam (broadest spectrum)
Extended-Spectrum Penicillins — Detail
Drugs: Piperacillin, Ticarcillin, Carbenicillin (± β-lactamase inhibitors)
Mechanism: Inhibit transpeptidase (PBP) enzymes, preventing bacterial cell wall (peptidoglycan) cross-linking → cell lysis.
Spectrum:
- Gram-positive cocci (including enterococci — piperacillin)
- Most Gram-negative bacilli
- Pseudomonas aeruginosa (key feature)
- Anaerobes (especially when combined with tazobactam)
- B. fragilis may be covered by piperacillin-tazobactam (Harrison's, p. 5100)
Key Uses:
| Drug | Main Indication |
|---|---|
| Piperacillin-tazobactam | Hospital-acquired infections, febrile neutropenia, intra-abdominal infections, pseudomonal infections |
| Ticarcillin-clavulanate | Polymicrobial infections, Pseudomonas |
| Carbenicillin | UTI due to Pseudomonas (now rarely used) |
Adverse Effects:
- Hypersensitivity (rash, anaphylaxis)
- Hypokalemia (high sodium load — carbenicillin, ticarcillin)
- Platelet dysfunction (ticarcillin)
- CNS toxicity (seizures) at high doses
- Cross-reactivity with other β-lactams (~1–2%)
Q4. Short Note on Tetracyclines — Uses and Adverse Effects (5 marks)
Classification
- Older generation: Tetracycline, Doxycycline, Minocycline
- Newer generation: Tigecycline (glycylcycline), Eravacycline, Omadacycline
Mechanism of Action
Tetracyclines inhibit 30S ribosomal subunit → block binding of aminoacyl-tRNA to the acceptor (A) site → bacteriostatic inhibition of protein synthesis.
They enter bacteria via active transport (facilitated by the proton gradient).
Clinical Uses (Harrison's, p. 4347)
| Category | Examples |
|---|---|
| Intracellular / atypical organisms | Rickettsial infections (Rocky Mountain spotted fever, scrub typhus, Q fever), Chlamydia (PID, LGV, non-gonococcal urethritis), Mycoplasma (atypical pneumonia) |
| Sexually transmitted infections | Chlamydia trachomatis, granuloma inguinale, LGV, syphilis (penicillin-allergic) |
| Spirochetal infections | Lyme disease, leptospirosis, relapsing fever |
| Skin infections | Acne vulgaris (doxycycline/minocycline), MRSA soft tissue infections |
| Respiratory | Atypical pneumonia, CAP (doxycycline) |
| Others | Brucellosis, tularemia, plague, cholera, Whipple's disease, malaria (doxycycline — prophylaxis + treatment) |
| MRSA | Tigecycline, doxycycline |
| Complicated intra-abdominal/skin infections | Tigecycline, eravacycline |
Adverse Effects
Gastrointestinal
- Nausea, vomiting, diarrhea (most common)
- Esophageal ulceration (if tablet taken without adequate water / lying down)
- Hepatotoxicity (high doses, especially in pregnancy — avoid)
Dental and Skeletal
- Teeth discoloration (yellow-grey-brown staining) and enamel hypoplasia — occurs with use in children <8 years and in utero exposure
- Inhibit bone growth in developing children — contraindicated in children <8 years
Photosensitivity
- Especially with doxycycline — patients must avoid sun exposure
CNS (Minocycline)
- Vestibular toxicity: dizziness, vertigo, ataxia
- Pseudotumor cerebri (benign intracranial hypertension) — headache, visual disturbances
Renal
- Avoid tetracycline (not doxycycline) in renal failure — can worsen azotemia (anti-anabolic effect)
- Doxycycline is safe in renal failure (hepatically excreted)
Superinfection
- Broad-spectrum activity → disrupts normal flora → Candida overgrowth (oral/vaginal thrush), C. difficile
Outdated tetracyclines
- Degradation products → Fanconi syndrome (proximal renal tubular dysfunction)
Contraindications
- Pregnancy (Pregnancy category D)
- Children <8 years
- Hepatic failure (use with caution)
Drug Interactions
- Dairy products, antacids, iron salts, calcium chelate tetracyclines → reduced absorption
- Should be taken on an empty stomach (except doxycycline — can be taken with food)
Sources: Harrison's Principles of Internal Medicine, 21st Edition; Bailey and Love's Short Practice of Surgery, 28th Edition.
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