Antibacterial & Antimycobacterial Therapy – Lecture Review

Administrative / Course Logistics

• Exam 2 (no comprehensive final) is Tuesday, 9:00 AM • Two testing rooms; both cohorts test simultaneously.
  • Students with accommodation also test at 09:00.

• Immediately after the pharmacology test students may proceed to Health-Assessment head-to-toe check-offs.

• Printable study aids:
  • Classification chart for anti-infectives is posted on Blackboard (hard copies available on request).
  • ATI modules contain a 1-page drug “print-out” at the bottom of each section (e.g.
  – Penicillins,
  – Cephalosporins,
  – Antimycobacterials). Students are encouraged to print/annotate these.

Big-Picture Framework for Drug Study

• Identify classification (antibacterial, antifungal, antiparasitic, antiviral, antimycobacterial).
• Decide if drug is bacteriCIDAL (kills / lyses) or bacterioSTATIC (inhibits growth → immune system finishes). Mechanisms:
– \text{Inhibit cell-wall synthesis}
– \text{Disrupt DNA/RNA replication}
– \text{Block folic-acid synthesis}
– \text{Inhibit protein synthesis at ribosome}
• Note spectrum:
– Narrow-spectrum → targets limited organisms (e.g. nitrofurantoin for UTIs only).
– Broad-spectrum → useful for many pathogens (e.g. penicillin).
• Determine causative organism (Gram +/− bacteria, mycobacteria, fungus, virus, parasite, aerobic vs. anaerobic).
• Pinpoint HIGH-YIELD side-effects versus “routine” N/V/D.
• Contra-indications & serious precautions (pregnancy, < 8 y o, renal failure, seizures, G-6-PD deficiency, etc.). • Nursing specifics: – Route restrictions (PO-only, IV-only, inhalation). – Dilution & infusion rate. – Required labs (peak/trough, \text{BUN}\,/\,\text{Cr}, \text{AST/ALT}, \text{PT/INR}). – Patient teaching (take w/ food? avoid Ca++? photosensitivity? backup contraception?). – Critical interventions hierarchy (airway > itching).

Sensitivity, Culture, and Resistance

• ALWAYS obtain culture & sensitivity (C&S) before first antibiotic dose.

• C&S identifies Gram +/− status and determines which antibiotics the organism is S (sensitive) or R (resistant) to.

• Resistance: natural or acquired; limit by:
  • Using the correct drug (narrow when possible).
  • Adequate dose & duration; emphasize finishing course.
  • Avoiding “antibiotic for every sniffle” (viral infections ≠ antibiotics).

Common Super-Infections & Adverse Events

• Candidiasis (oral thrush, vaginal yeast)
– Etiology: loss of normal flora.
– Treatment: nystatin “swish & swallow”, OTC azole creams, fluconazole.
• Clostridioides difficile (C-Diff)
– Profuse malodorous watery diarrhea ± blood, fever, distention.
– Stop culprit antibiotic; treat with \text{PO vancomycin} or fidaxomicin; add probiotics.
• Anaphylaxis
– Rapid airway swelling, wheeze, hives.
– PRIORITY:
1. Maintain airway / oxygen
2. STOP infusion
3. Administer epinephrine IM/IV & diphenhydramine
4. Start/maintain IV access & VS monitoring.

Key Laboratory Monitoring

• Renal: \text{BUN}, \text{Creatinine}, urine output, specific gravity.

• Hepatic: \text{AST}, \text{ALT}, \text{Bilirubin}, \text{Albumin}.

• Hematology / Bleeding: \text{Platelets}, \text{PT}, \text{PTT}, \text{INR}.

• Drug Levels (peak & trough): vancomycin, gentamicin, erythromycin, etc.
  • \text{Trough} drawn 30–60 min before next dose.
  • \text{Peak} drawn 30 min after completion of infusion.

Antibiotics That Inhibit Cell-Wall Synthesis

Penicillins

• Prototype = Amoxicillin. Broad-spectrum (ear, throat, UTI).

• PO tablets/caps, do NOT crush XR.

• Major issues: allergy/anaphylaxis, N/V/D, possible yeast.

• Teach: take all doses; take with food; back-up contraception; 30-min observation if IM/IV.

Cephalosporins

• Prototype = Cephalexin. Look for “cef/ceph-”.

• Generation concept (1st → 4th) shifts Gram + to Gram − coverage.

• PO most common; IV can cause thrombophlebitis → infuse slowly.

• Disulfiram-like reaction with alcohol (flushing, chest pain, vomiting).

• Watch for C-Diff, bleeding (↓ vit K); vitamin K is antidote for severe bleeding.

Monobactams

• Prototype = Aztreonam. Narrow: Gram − aerobes (LRTI, abd, GYN, UTI).

• IV/IM or inhaled for cystic fibrosis—not PO.

• Incompatible in same IV line with most drugs; rotate IM sites; monitor IV site.

Carbapenems

• Prototype = Imipenem-cilastatin. Very broad for severe infections; IV/IM only.

• Adverse: seizures, thrombophlebitis, nephro-/hepatotoxicity.

• Contra: severe PCN allergy, seizure hx, renal failure.

Vancomycin

• Drug & prototype. Uses: MRSA (IV), C-Diff (PO).

• Infuse over ≥ 60 min; separate line (non-compatible).

• Red-Man Syndrome if infused too fast (pruritus, rash, ↓BP, tachy).

• Ototoxic & nephrotoxic → check trough, \text{BUN/Cr}, strict I&O.

Protein-Synthesis Inhibitors

Tetracyclines

• Prototype = Tetracycline.

• Contra: pregnancy & < 8 y o (tooth discoloration, bone growth suppression).

• Hepatotoxic, photosensitivity; store in dark container (light-sensitive).

• Admin: empty stomach (1 h before / 2 h after) AND no dairy/Ca++, antacids, iron, zinc.

Macrolides

• Prototype = Erythromycin. Uses: pertussis, diphtheria.

• Adverse: QT prolongation → ventricular dysrhythmias; ototoxicity.

• Verify cardiac history; monitor EKG; serum drug level.

• Take with food if GI upset.

Aminoglycosides

• Prototype = Gentamicin. Serious Gram − (E. coli, Klebsiella), synergy with β-lactams.

• Routes: topical, ophthalmic, IM/IV, intrathecal — not PO.

• Major risks:
  • Ototoxicity (CN VIII) → baseline & periodic audiogram.
  • Nephrotoxicity → \text{I&O}, \text{BUN/Cr}, daily weights.

• Peaks/troughs essential (peak 30 min post-infusion, trough 1 h pre-dose).

Drugs Affecting DNA / Cell Division

Fluoroquinolones

• Prototype = Ciprofloxacin (Cipro). Severe UTIs, anthrax, etc.; PO or IV.

• Adverse: CNS effects, Achilles-tendon rupture (avoid if > 60 y o), photosensitivity, ↑ ICP, seizures.

• Avoid in < 18 y o (cartilage damage).

• Teaching: Limit caffeine; 1.5–2 L fluid/day; no dairy/antacids within 2 h; sun protection.

Folic-Acid Synthesis Inhibitors & Urinary Antiseptics

Sulfonamides

• Prototype = Trimethoprim-Sulfamethoxazole (TMP-SMX). UTIs, some MRSA skin infections.

• Serious possibilities:
  • Stevens–Johnson Syndrome (SJS)—flu-like → blistering rash.
  • Blood dyscrasias (agranulocytosis, aplastic anemia, thrombocytopenia).
  • Crystalluria → renal failure.

• Patient must drink ≥ 8 oz water per dose & 2–3 L/day total; avoid alcohol; watch bruising/fatigue.

Nitrofurantoin

• Highly specific urinary-tract antiseptic. Capsule (do NOT open) or suspension.

• Rare but notable: pulmonary fibrosis, peripheral neuropathy, blood dyscrasias, brown urine.

• Teaching: take w/ food or milk; report cough/SOB, numbness; rinse mouth after liquid.

Antimycobacterials (Tuberculosis Drugs)

Isoniazid (INH)

• First-line for active & latent TB; given daily for 6–9 months.

• Adverse: hepatotoxicity, peripheral neuropathy (give vit B₆), CNS issues, DRESS.

• No alcohol; caution phenytoin, antacids; emphasize adherence.

Rifampin

• Synergistic TB drug; also meningococcal prophylaxis.

• Turns sweat, urine, tears red-orange; may stain soft contacts.

• Hepatotoxicity, DRESS possible.

• Potent CYP-450 inducer → ↓ effectiveness of OCPs, warfarin, NNRTIs.

• Give 1 h before or 2 h after meals; alternative contraception advised.

Nursing Process Integration

1. Assessment – collect cues (culture result, allergies, VS, labs).

2. Analysis/Diagnosis – interpret cues (infection type, risk of toxicity).

3. Planning – set goals (eradicate infection, prevent ADRs).

4. Implementation – administer drug with correct route/rate; teaching.

5. Evaluation – reassess temp, WBC, culture, side-effects; restart cycle PRN.

Calculation Review (from lecture)

• Weight conversion: \text{kg} = \dfrac{\text{lb}}{2.2} (e.g. 44\,\text{lb} \to 20\,\text{kg}).
• Dose-per-kg example:
– Order: 20\,\tfrac{\text{mg}}{\text{kg}} BID
– Weight: 20\,\text{kg}
– Available: 200\,\text{mg}\,/\,5\,\text{mL}
– Daily amount =20\times20=400\,\text{mg} ⇒ \dfrac{400}{200}=10\,\text{mL/day} ⇒ 5\,\text{mL/dose}.
• IV-rate formula: \text{mL/hr}=\dfrac{\text{Total mL}}{\text{Infusion time (hr)}}
– Example: 50 mL over 30 min → 30\,\text{min}=0.5\,\text{hr} ⇒ \dfrac{50}{0.5}=100\,\text{mL/hr}.

Ethical & Practical Implications

• Antibiotic stewardship reduces resistance & preserves future efficacy.

• Teach completion of therapy even when asymptomatic.

• Document & verify allergies to prevent fatal anaphylaxis.

• Encourage probiotics to maintain gut flora & reduce C-Diff.

• Sun-safety education prevents severe burns with photosensitizing drugs.

• Multidisciplinary approach (pharmacy, provider, nurse) optimizes dosing, renal/hepatic adjustments, drug–drug checks.

Administrative / Course Logistics

• Exam 2 (no comprehensive final) is Tuesday, 9:00 AM • Two testing rooms; both cohorts test simultaneously. Students must ensure they know their assigned testing location to avoid delays.
  

  • Students with accommodation also test at 09:00; specific arrangements will be communicated via the disability services office.

• Immediately after the pharmacology test, students may proceed to Health-Assessment head-to-toe check-offs. Be prepared to transition promptly between tests and practical assessments.

• Printable study aids:
  

  • A comprehensive classification chart for anti-infectives is posted on Blackboard, providing a structured overview of drug categories. Hard copies are also available upon request in class.
  

  • ATI modules contain a 1-page drug “print-out” at the bottom of each section (e.g., Penicillins, Cephalosporins, Antimycobacterials). These print-outs offer concise summaries of key drug information. Students are strongly encouraged to print and annotate these for personalized study guides.

Big-Picture Framework for Drug Study

• Identify classification: Precisely categorize the anti-infective drug as antibacterial, antifungal, antiparasitic, antiviral, or antimycobacterial based on the type of pathogen it targets.

• Decide if drug is bacteriCIDAL or bacterioSTATIC:

• Bactericidal drugs actively kill or lyse bacteria, leading to their destruction.

• Bacteriostatic drugs inhibit bacterial growth, relying on the host's immune system to eliminate the weakened pathogens.
  Mechanisms often include:
  

  – \text{Inhibit cell-wall synthesis}: Prevents the formation of the rigid bacterial cell wall, leading to cell lysis (e.g., Penicillins, Cephalosporins).
  – \text{Disrupt DNA/RNA replication}: Interferes with the genetic material necessary for bacterial reproduction and function (e.g., Fluoroquinolones, Rifampin).
  – \text{Block folic-acid synthesis}: Prevents bacteria from synthesizing essential folate, which is crucial for their growth and DNA synthesis (e.g., Sulfonamides).
  – \text{Inhibit protein synthesis at ribosome}: Targets bacterial ribosomes, halting the production of essential proteins (e.g., Tetracyclines, Macrolides, Aminoglycosides).
  

  • Note spectrum:

• Narrow-spectrum: Targets a limited range of specific organisms, minimizing disruption to normal flora (e.g., nitrofurantoin for UTIs only, Isoniazid for M. tuberculosis).

• Broad-spectrum: Effective against a wide variety of pathogens, useful for empiric therapy when the causative organism is unknown (e.g., penicillin against many Gram-positive bacteria, Imipenem for very severe infections).
  

  • Determine causative organism: Identify whether the infection is caused by Gram-positive or Gram-negative bacteria, mycobacteria, fungus, virus, or parasite. Also consider if the organism is aerobic (requires oxygen) or anaerobic (grows without oxygen) as this affects drug choice.
  

  • Pinpoint HIGH-YIELD side-effects versus “routine” N/V/D: Differentiate between common, usually mild gastrointestinal side effects (nausea, vomiting, diarrhea) and critical adverse drug reactions (ADRs) that require immediate nursing intervention or patient education due to their severity (e.g., ototoxicity, nephrotoxicity, anaphylaxis, Stevens-Johnson Syndrome, Red-Man Syndrome, Achilles tendon rupture).
  

  • Contra-indications & serious precautions: Identify conditions or patient characteristics that prohibit or require extreme caution with drug administration (e.g., pregnancy, age under 8 years, pre-existing renal failure, history of seizures, G-6-PD deficiency, severe drug allergies).
  

  • Nursing specifics:

• Route restrictions: Understand if the drug is strictly PO-only, IV-only, inhalation, or if multiple routes are available, noting implications for administration and absorption.

• Dilution & infusion rate: Adhere to specific guidelines for diluting IV medications and the recommended rate of infusion to prevent adverse reactions (e.g., Red-Man Syndrome with rapid vancomycin infusion) or local complications (e.g., thrombophlebitis).

• Required labs: Identify essential laboratory tests for monitoring drug efficacy and potential organ damage (e.g., peak/trough levels for narrow therapeutic index drugs; \text{BUN}\,\text{/}\,\text{Cr} for renal function; \text{AST/ALT} for hepatic function; \text{PT/INR} for coagulation).

• Patient teaching: Educate patients thoroughly on how to take the medication (e.g., with food? avoid Ca++? photosensitivity? need for backup contraception?), potential side effects, and warning signs to report.

• Critical interventions hierarchy: Prioritize nursing actions based on urgency and risk to patient safety (e.g., maintaining airway and oxygenation is paramount over managing itching in anaphylaxis).

Sensitivity, Culture, and Resistance

• ALWAYS obtain culture & sensitivity (C&S) before administering the first antibiotic dose. This crucial step ensures appropriate drug selection and minimizes the risk of resistance.

• C&S identifies the Gram-positive or Gram-negative status of the invading organism and determines which specific antibiotics the organism is S (sensitive) or R (resistant) to. This lab information guides targeted therapy.

• Resistance: Can be natural (inherent to the organism) or acquired (developed over time through mutation or gene transfer). To limit resistance development:
  

  • Use the correct drug: Prescribe narrow-spectrum antibiotics when possible to specifically target the pathogen and preserve broad-spectrum agents.
  

  • Adequate dose & duration: Administer the optimal dose for the appropriate duration to ensure complete eradication of the pathogen and prevent regrowth of resistant strains; emphasize the critical importance of finishing the entire prescribed course, even if symptoms resolve.
  

  • Avoiding “antibiotic for every sniffle”: Educate patients and prescribers about the ineffectiveness of antibiotics against viral infections (e.g., common cold, flu) to prevent unnecessary use and reduce resistance.

Common Super-Infections & Adverse Events

• Candidiasis (oral thrush, vaginal yeast):
– Etiology: Results from the disruption of normal protective flora (e.g., in the mouth or vagina) by broad-spectrum antibiotics, allowing opportunistic fungi like Candida albicans to overgrow. Signs include white patches in the mouth or vaginal itching/discharge.
– Treatment: Oral nystatin “swish & swallow” for thrush; OTC azole creams (e.g., miconazole, clotrimazole) for vaginal yeast; systemic fluconazole may be used for more severe or persistent cases.

• Clostridioides difficile (C-Diff):
– Profuse, malodorous, watery diarrhea, often containing blood, accompanied by fever, abdominal cramping, and distention. This severe complication typically occurs after disruption of normal gut flora, allowing C. difficile to proliferate and produce toxins.
– Management: The first step is to stop the culprit antibiotic causing the disruption. Treatment involves specific oral antibiotics like \text{PO vancomycin} or fidaxomicin. Adjunctive probiotics may be recommended to help restore healthy gut flora, but their role in active C. difficile infection is controversial.

• Anaphylaxis:
– A life-threatening, rapid-onset allergic reaction characterized by widespread airway swelling (leading to stridor, dyspnea), wheezing (bronchospasm), diffuse hives (urticaria), pruritus, and often systemic hypotension and tachycardia.
– PRIORITY NURSING INTERVENTIONS:

1. Maintain airway / oxygen: Immediately provide supplemental oxygen and prepare for intubation if airway compromise worsens.

2. STOP infusion: Discontinue the offending medication infusion immediately to prevent further exposure.

3. Administer epinephrine IM/IV & diphenhydramine: Epinephrine is the primary treatment (typically IM in the thigh) to reverse bronchospasm and hypotension. Diphenhydramine (antihistamine) helps alleviate histamine-mediated symptoms like hives and itching.

4. Start/maintain IV access & VS monitoring: Secure or maintain IV access for fluid resuscitation and administration of other medications. Continuously monitor vital signs (blood pressure, heart rate, respiratory rate, oxygen saturation) to assess response to treatment.

Key Laboratory Monitoring

• Renal function: \text{BUN} (Blood Urea Nitrogen), \text{Creatinine} (most reliable indicator of kidney function), urine output, specific gravity. These labs assess kidney function and detect potential nephrotoxicity, which is a risk with many antibiotics (e.g., aminoglycosides, vancomycin).

• Hepatic function: \text{AST} (Aspartate Aminotransferase), \text{ALT} (Alanine Aminotransferase), \text{Bilirubin}, \text{Albumin}. These liver enzymes and proteins are monitored to detect drug-induced hepatotoxicity (e.g., with Isoniazid, Rifampin, Tetracyclines).

• Hematology / Bleeding: \text{Platelets} (for thrombocytopenia), \text{PT} (Prothrombin Time), \text{PTT} (Partial Thromboplastin Time), \text{INR} (International Normalized Ratio). These tests assess bone marrow suppression (e.g., sulfanomides) and clotting ability, especially with drugs affecting Vitamin K (e.g., certain Cephalosporins, Rifampin interactions with warfarin).

• Drug Levels (peak & trough): Essential for drugs with a narrow therapeutic index, such as vancomycin, gentamicin, and some macrolides (e.g., erythromycin). These levels ensure drug concentration remains within therapeutic range while minimizing toxicity.

  • \text{Trough} levels are drawn 30–60 minutes before the next scheduled dose to determine the lowest drug concentration in the patient's bloodstream and ensure adequate renal clearance, preventing accumulation and potential toxicity.
  • \text{Peak} levels are typically drawn 30 minutes after the completion of the infusion to determine the highest drug concentration in the bloodstream, confirming therapeutic effectiveness.

Antibiotics That Inhibit Cell-Wall Synthesis

Penicillins

• Prototype = Amoxicillin. Broad-spectrum, commonly used for a wide range of bacterial infections including ear infections (otitis media), throat infections (strep throat), and urinary tract infections (UTIs).

• Available as PO tablets/capsules; extended-release (XR) formulations must NOT be crushed as this can lead to rapid absorption and toxicity.

• Major issues: The most critical concern is allergy/anaphylaxis, which can be life-threatening. Other common side effects include gastrointestinal upset (N/V/D) and potential for superinfections like yeast infections (candidiasis).

• Patient teaching: Emphasize the importance of taking all prescribed doses to ensure complete eradication of the infection and prevent resistance; advise taking with food to reduce GI upset; warn about the need for back-up contraception as penicillins can reduce the effectiveness of oral contraceptives; observe patients for 30 minutes after IM/IV administration to monitor for immediate allergic reactions.

Cephalosporins

• Prototype = Cephalexin. Easily identifiable by the “cef/ceph-” prefix in their names (e.g., Cefazolin, Ceftriaxone, Cefepime).

• Generation concept: Cephalosporins are classified into generations (1st through 5th) based on their spectrum of activity. Generally, as you move from 1st to higher generations, the coverage shifts from predominantly Gram-positive bacteria to increased activity against Gram-negative bacteria and improved beta-lactamase stability.

• PO administration is most common for lighter infections; IV forms can cause thrombophlebitis, so they should be infused slowly and diluted properly to minimize irritation at the injection site.

• Disulfiram-like reaction with alcohol: Patients must be educated to avoid alcohol consumption while on certain cephalosporins (especially Cefotetan) due to the risk of severe reactions including flushing, chest pain, palpitations, vomiting, and headache.

• Watch for C-Diff infection due to alteration of gut flora, and bleeding tendencies (due to interference with vitamin K synthesis or platelet function). Vitamin K is the antidote for severe bleeding.

Monobactams

• Prototype = Aztreonam. It has a narrow spectrum, specifically targeting Gram-negative aerobes, making it useful for lower respiratory tract infections (LRTI), abdominal infections, gynecological infections, and UTIs.

• Administered via IV/IM or inhaled for specific conditions like cystic fibrosis; it is not available PO, as it's poorly absorbed orally.

• Nursing considerations: Often incompatible in the same IV line with most other drugs, requiring a dedicated line or careful flushing. Rotate IM injection sites to prevent tissue irritation. Monitor IV sites closely for signs of phlebitis or extravasation.

Carbapenems

• Prototype = Imipenem-cilastatin (cilastatin prevents imipenem breakdown). These are very broad-spectrum antibiotics reserved for severe, life-threatening infections, often multi-drug resistant strains. Administered strictly via IV/IM.

• Adverse effects: Can include seizures (especially at high doses or in patients with pre-existing seizure disorders), thrombophlebitis at the injection site, and potential for nephro- and hepatotoxicity.

• Contraindications: History of severe penicillin allergy (cross-reactivity is possible), history of seizures, and significant renal failure due to risk of increased drug levels and toxicity.

Vancomycin

• Drug & prototype. Primary uses include severe Gram-positive infections, notably Methicillin-Resistant Staphylococcus Aureus (MRSA) when administered IV, and Clostridioides difficile (C-Diff) when administered PO (as it acts locally in the gut).

• Administration: Must be infused over at least 60 minutes (or longer for higher doses) to prevent Red-Man Syndrome. Requires a separate IV line as it is non-compatible with many other IV solutions.

• Red-Man Syndrome: A common and distinct adverse reaction if infused too fast, characterized by intense pruritus (itching), a characteristic red rash on the face, neck, and upper torso, significant hypotension (low blood pressure), and tachycardia. It is a histamine-release reaction, not a true allergy, and can be managed by slowing the infusion rate and administering antihistamines.

• Toxicity: Highly ototoxic (damage to ear/hearing) and nephrotoxic (damage to kidneys) at high concentrations or with prolonged use. Strict monitoring is required: check trough levels regularly to ensure therapeutic but non-toxic levels, and closely monitor \text{BUN/Cr} and maintain strict fluid I&O (intake & output) to assess renal function.

Protein-Synthesis Inhibitors

Tetracyclines

• Prototype = Tetracycline.

• Contraindications: Absolutely contraindicated in pregnancy (can cause permanent tooth discoloration in the fetus and potentially inhibit fetal bone growth) and in children under 8 years old for the same reasons.

• Adverse effects: Can be hepatotoxic (liver damage), cause significant photosensitivity (severe sunburn reaction with minimal sun exposure), and are light-sensitive themselves, requiring storage in dark containers.

• Administration: Must be taken on an empty stomach (1 hour before or 2 hours after meals) as food interferes with absorption. Crucially, avoid taking with dairy products/calcium, antacids, iron supplements, or zinc supplements, as these chelate with tetracyclines and significantly reduce absorption. Patient education on these interactions is vital.

Macrolides

• Prototype = Erythromycin. Commonly used for respiratory tract infections, pertussis (whooping cough), diphtheria, and chlamydia.

• Adverse Effects: Can cause significant QTc prolongation, which increases the risk of serious ventricular dysrhythmias (e.g., Torsades de Pointes). Also ototoxic (hearing loss, tinnitus) at high doses, especially with impaired renal or hepatic function.

• Nursing considerations: Verify patient's cardiac history and monitor EKG for QTc interval prolongation, especially with concurrent use of other QTc-prolonging drugs. Serum drug levels may be monitored in severe cases of toxicity. Can cause significant GI upset, so advise patients to take with food if GI distress occurs, though this may slightly reduce absorption.

Aminoglycosides

• Prototype = Gentamicin. Primarily used for serious Gram-negative bacterial infections (e.g., E. coli, Klebsiella, Pseudomonas) and often used in synergy with beta-lactam antibiotics for severe Gram-positive infections (e.g., endocarditis).

• Routes: Administered via topical, ophthalmic, IM/IV, or intrathecal routes. They are not absorbed PO and therefore not effective orally for systemic infections.

• Major risks:
  

  • Ototoxicity (CN VIII): Irreversible damage to the auditory and vestibular branches of the 8th cranial nerve, leading to hearing loss, tinnitus, and balance issues. Baseline and periodic audiograms are essential, especially for long-term therapy.
  

  • Nephrotoxicity: Reversible damage to the kidneys. Closely monitor \text{I&O} (intake & output), \text{BUN/Cr} levels, and daily weights to assess renal function and early signs of kidney injury. Maintaining adequate hydration is important.

• Peaks/troughs essential: Due to their narrow therapeutic index and dose-dependent toxicity, precise peak and trough levels are critical for safe and effective dosing. Peak levels are drawn 30 minutes post-infusion completion to ensure adequate drug concentration, while trough levels are drawn 1 hour pre-dose to ensure adequate renal clearance and minimal accumulation between doses.

Drugs Affecting DNA / Cell Division

Fluoroquinolones

• Prototype = Ciprofloxacin (Cipro). Broad-spectrum antibiotics used for complicated UTIs, respiratory infections, skin infections, and even anthrax exposure. Available PO or IV.

• Adverse Effects: Can cause significant CNS effects (dizziness, headache, confusion, restlessness, rarely seizures). Black box warning for Achilles-tendon rupture, which is more common in patients over 60 years old, those on corticosteroids, or with a history of kidney, heart, or lung transplants; patients should report any tendon pain or swelling immediately. Also causes photosensitivity and can increase intracranial pressure (ICP) and lower the seizure threshold.

• Contraindication: Avoid in children under 18 years old due to the risk of irreversible cartilage damage in developing joints.

• Patient teaching: Limit caffeine intake as fluoroquinolones can increase caffeine levels. Encourage 1.5–2 liters of fluid per day to prevent crystalluria. Advise patients to avoid dairy products, antacids, iron, and zinc supplements within 2 hours of taking the drug as they interfere with absorption. Emphasize strict sun protection (clothing, sunscreen) due to severe photosensitivity.

Folic-Acid Synthesis Inhibitors & Urinary Antiseptics

Sulfonamides

• Prototype = Trimethoprim-Sulfamethoxazole (TMP-SMX), commonly known as Bactrim or Septra. Used primarily for UTIs, but also effective for some MRSA skin infections, PCP pneumonia, and bronchitis.

• Serious possibilities:
  

  • Stevens–Johnson Syndrome (SJS): A severe, life-threatening hypersensitivity reaction that begins with flu-like symptoms followed by a painful, blistering rash that spreads and causes the top layer of skin to die and shed. Prompt recognition and discontinuation of the drug are critical.
  

  • Blood dyscrasias: Can cause severe hematologic abnormalities including agranulocytosis (low white blood cells), aplastic anemia (bone marrow failure), and thrombocytopenia (low platelets), requiring regular blood count monitoring.
  

  • Crystalluria: Formation of crystals in the urine, which can lead to renal failure if not prevented.

• Patient education: Must drink at least 8 ounces of water with each dose and 2–3 liters total per day to prevent crystalluria. Avoid alcohol. Watch for signs of bleeding (bruising, petechiae), fatigue, or fever, and report immediately.

Nitrofurantoin

• Highly specific urinary-tract antiseptic primarily used for acute lower UTIs and prophylaxis. Available as a capsule (which should NOT be opened) or suspension.

• Rare but notable adverse effects: Can cause serious pulmonary fibrosis (especially with long-term use), peripheral neuropathy (numbness, tingling), and blood dyscrasias. It can also turn urine harmlessly brown.

• Teaching: Take with food or milk to enhance absorption and reduce GI upset. Report any signs of cough or shortness of breath (indicating pulmonary issues) or numbness/tingling (indicating neuropathy). Rinse mouth after taking liquid suspension to prevent staining of teeth.

Antimycobacterials (Tuberculosis Drugs)

Isoniazid (INH)

• First-line antitubercular drug used for both active and latent TB infections. Typically given daily for 6–9 months.

• Adverse effects: Significant hepatotoxicity (liver damage), requiring regular monitoring of liver function tests (AST/ALT). Can also cause peripheral neuropathy (numbness, tingling, pain in extremities), which can largely be prevented by co-administration of vitamin B₆ (Pyridoxine). Other CNS issues may include dizziness, ataxia. Can cause DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms), a severe hypersensitivity reaction.

• Nursing considerations: Advise against alcohol consumption due to increased risk of hepatotoxicity. Caution simultaneous use with phenytoin (can increase phenytoin levels) and antacids (reduce INH absorption). Emphasize strict adherence to the prolonged treatment regimen to prevent drug resistance and ensure successful eradication.

Rifampin

• A potent synergistic TB drug, often used in combination with INH due to its strong bactericidal action. Also used for meningococcal prophylaxis.

• Distinctive side effect: Causes sweat, urine, tears, and other body fluids to turn a red-orange color, which is harmless but can permanently stain soft contact lenses and clothing. Patients must be warned about this expected effect.

• Adverse effects: Hepatotoxicity and DRESS are possible, requiring liver function monitoring.

• Drug interactions: Rifampin is a potent CYP-450 enzyme inducer, significantly decreasing the effectiveness of many other drugs metabolized by this system, including oral contraceptives (OCPs), warfarin (requiring increased warfarin doses and close INR monitoring), and non-nucleoside reverse transcriptase inhibitors (NNRTIs) used in HIV treatment.
  

• Administration: Best given 1 hour before or 2 hours after meals for optimal absorption. Alternative contraception methods are strongly advised for women of childbearing potential due to interaction with OCPs.

Nursing Process Integration

1. Assessment: Systematically collect comprehensive patient cues relevant to drug therapy, including obtaining culture results, documenting known allergies, monitoring vital signs, and reviewing baseline and ongoing laboratory values (e.g., renal, hepatic, hematologic profiles). This initial phase provides critical data for safe and effective medication administration.

2. Analysis/Diagnosis: Interpret the collected cues to identify patient problems and risks. This includes determining the type of infection, assessing the risk of drug toxicity based on patient comorbidities and lab values, and identifying potential drug interactions.

3. Planning: Establish patient-centered goals and expected outcomes related to drug therapy. These goals typically involve eradicating the infection, preventing or minimizing adverse drug reactions (ADRs), and ensuring patient adherence to the regimen. Specify measurable outcomes and a timeframe.

4. Implementation: Administer the prescribed drug following the 5 rights of medication administration (right patient, right drug, right dose, right route, right time). Ensure correct dilution and infusion rates for IV medications. Perform essential patient teaching regarding the medication, potential side effects, and warning signs. Implement critical interventions as needed (e.g., managing anaphylaxis).

5. Evaluation: Continuously reassess the patient's response to therapy. Monitor objective indicators such as temperature (for fever resolution), WBC count (for return to normal levels), and follow-up culture results (for organism eradication). Also, vigilantly monitor for and document any side-effects or adverse reactions. This evaluation phase informs whether the cycle needs to be restarted with adjustments to the care plan.

Calculation Review (from lecture)

• Weight conversion: \text{kg} = \dfrac{\text{lb}}{2.2} (e.g. 44\,\text{lb} \to 20\,\text{kg}).

• Dose-per-kg example:

– Order: 20\,\tfrac{\text{mg}}{\text{kg}} BID (twice daily)

– Weight: 20\,\text{kg}

– Available: 200\,\text{mg}\,\text{/}\,5\,\text{mL}

– Daily amount (for 2 doses) =20\,\frac{\text{mg}}{\text{kg}} \times 20\,\text{kg} \times 2 \,\text{doses} = 800\,\text{mg}. So, per dose it would be 20\,\text{mg}\,\text{/}\,\text{kg} \times 20\,\text{kg} = 400\,\text{mg}. To calculate volume per dose: \dfrac{400\,\text{mg}}{200\,\text{mg}\,\text{/}\,5\,\text{mL}} = 2 \times 5\,\text{mL} = 10\,\text{mL/dose}.

• IV-rate formula: \text{mL/hr}=\dfrac{\text{Total mL}}{\text{Infusion time (hr)}}

– Example: 50 mL over 30 min → Convert minutes to hours: 30\,\text{min}=0.5\,\text{hr} ⇒ Calculate rate: \dfrac{50\,\text{mL}}{0.5\,\text{hr}}=100\,\text{mL/hr}. This ensures accurate and safe IV infusion.

Ethical & Practical Implications

• Antibiotic stewardship is crucial for reducing the development and spread of antibiotic resistance. This involves promoting the responsible use of antibiotics, prescribing them only when necessary, selecting the narrowest effective spectrum, and optimizing dosing and duration. This preserves the future efficacy of these vital medications.

• Teach completion of therapy even when asymptomatic: Emphasize to patients the critical importance of finishing the entire antibiotic course, even if their symptoms resolve early. Premature discontinuation can lead to recurrence of infection and the development of drug-resistant bacteria.

• Document & verify allergies to prevent fatal anaphylaxis: Thoroughly assess and document all patient allergies, especially drug allergies, and ensure these are communicated across the healthcare team. Verification involves confirming the type of reaction (e.g., rash vs. anaphylaxis) to guide safe medication choices and prevent life-threatening allergic reactions.

• Encourage probiotics to maintain gut flora & reduce C-Diff: While not a treatment for active C-Diff, probiotics can help maintain a healthy balance of gut microbiota during or after antibiotic therapy, potentially reducing the risk of antibiotic-associated diarrhea and Clostridioides difficile infection.

• Sun-safety education prevents severe burns with photosensitizing drugs: Educate patients on drugs that cause photosensitivity (e.g., tetracyclines, sulfonamides, fluoroquinolones) to use protective clothing, sunglasses, and high-SPF sunscreen, and to avoid prolonged sun exposure to prevent severe sunburns.

• Multidisciplinary approach (pharmacy, provider, nurse) optimizes dosing, renal/hepatic adjustments, drug–drug checks: Collaboration among the healthcare team (pharmacists reviewing orders, providers making prescribing decisions, nurses administering and monitoring) ensures