Notes for Core Concepts in Pharmacology Chapter 27: Drugs for Bacterial Infections

Core Concept 27.1: Pathogens

• Pathogens are organisms that cause disease by invading tissues or secreting toxins.
• Types of pathogenic organisms include:
  • Bacteria
  • Virus
  • Protozoan pathogens
  • Multicellular parasites
  • Fungi
• Visual reference: Figure 27.1 shows types of pathogenic organisms (a) bacterium, (b) virus, (c) protozoan pathogens, (d) multicellular parasites, (e) fungi.

Core Concept 27.2: Classification of Bacteria (by Method of Description)

• Methods of describing and classifying bacteria (Table 27.2):
  • Staining: Gram-positive or Gram-negative
  • Shape: Bacilli (rods), cocci (spheres), and spirilla (spirals)
  • Oxygen usage: Aerobic (uses O2) or anaerobic (without O2)

Core Concept 27.3: Mechanisms of Action of Anti-infective Drugs

• Anti-infective drugs act by selectively targeting a pathogen’s metabolism or life cycle.

Core Concept 27.4: Acquired Resistance

• Acquired resistance is a major clinical problem worsened by improper use of anti-infectives.
• Mechanism of acquired resistance (Figure 27.3):
  1. Infection with organism
  2. Antibiotic kills susceptible organisms, leaving resistant one(s)
  3. Resistant organism rapidly divides and infects; antibiotic is no longer effective
• Additional details:
  • Errors during DNA replication cause random mutations; some mutations confer antibiotic resistance.
  • Therapy kills affected bacteria; resistant ones multiply and spread within the patient.

Core Concept 27.5: Prevention Principles (From CDC) (1 of 4)

• Prevent infections when possible; easier to prevent than to treat.
• Emphasize immunizations against diseases such as influenza, tetanus, measles, and hepatitis B.

Core Concept 27.5: Prevention Principles (From CDC) (2 of 4)

• Restrict antibiotic use to medically necessary conditions; prescribe antibiotics only with a clear rationale.

Core Concept 27.5: Prevention Principles (From CDC) (3 of 4)

• Advise patients to take anti-infectives for the full length of therapy, even if symptoms disappear before regimen completion.
• Premature stopping promotes survival and spread of resistant strains.

Core Concept 27.5: Prevention Principles (From CDC) (4 of 4)

• Prevent transmission of pathogens using standard infection control procedures.
• Teach patients hygiene practices for home and community settings to prevent transmission.

Core Concept 27.6: Penicillins

• Penicillins are among the oldest and safest anti-infectives.
• Mechanism: Kill bacteria by disrupting cell walls.
• Key structural feature: The beta-lactam ring is responsible for antibacterial activity.
• Resistance: Some bacteria produce beta-lactamase (penicillinase) that splits the beta-lactam ring, conferring resistance.
• See Figure 27.4: Penicillinase action; beta-lactam ring broken → loss of activity.
• Modifications (Modifications yield different classes):
  • Penicillinase-resistant penicillins
  • Broad-spectrum penicillins
  • Extended-spectrum penicillins

Table 27.3: Penicillins (1 of 2) – Key Drugs, Route, Dose, Remarks

• amoxicillin (Amoxil, Trimox): Route: PO; Dose: 250-500 ext{ mg} ext{ tid}; Remarks: Broad-spectrum penicillin
• amoxicillin–clavulanate (Augmentin): Route: PO; Dose: 250-500 ext{ mg} ext{ every } 8 ext{–}12 ext{ hours}; Remarks: Broad-spectrum with beta-lactamase inhibitor
• ampicillin (Principen): Route: PO; Dose: 250-500 ext{ mg} ext{ qid}; Remarks: Broad-spectrum
• ampicillin–sulbactam (Unasyn): Route: IV/IM; Dose: 1.5 ext{–}3 ext{ g} ext{ qid}; Remarks: Broad-spectrum
• dicloxacillin: Route: PO; Dose: 125 ext{–}500 ext{ mg} ext{ qid}; Remarks: Penicillinase resistant
• nafcillin: Route: IV/IM; Dose: 500 ext{ mg} ext{–}1 ext{ g} ext{ qid}; Remarks: Penicillinase resistant (max: 12 ext{ g/day})
• oxacillin: Route: IV; Dose: 250 ext{–}500 ext{ mg} ext{–}1 ext{ g} ext{ every } 4 ext{–}6 ext{ h}; Remarks: Penicillinase resistant (max: 12 ext{ g/day}); IM form available
• penicillin G benzathine (Bicillin): Route: IM; Dose: 1.2 ext{ million U} ext{ single dose}; Remarks: Prolonged duration of action
• penicillin G potassium: Route: IV/IM; Dose: 2 ext{–}24 ext{ million U} ext{ divided every } 4 ext{–}6 ext{ h}; Remarks: Ineffective against most forms of S. aureus
• penicillin G procaine (Wycillin): Route: IM; Dose: 0.6 ext{–}1.2 ext{ million U/day}; Remarks: Prolonged duration of action
• penicillin V (Pen-Vee K, Veetids, others): Route: PO; Dose: 125 ext{–}500 ext{ mg} ext{ qid}; Remarks: Acid-stable
• piperacillin: Route: IM; Dose: 2 ext{–}4 ext{ g} ext{ tid–qid} (max: 24 ext{ g/day}); Remarks: Extended-spectrum
• piperacillin–tazobactam (Zosyn): Route: IV; Dose: 3.375 ext{–}4.5 ext{ g} ext{ qid over 30 min}; Remarks: Extended-spectrum with beta-lactamase inhibitor
• ticarcillin–clavulanate (Timentin): Route: IV; Dose: 3.1 ext{ g} ext{ qid}; Remarks: Extended-spectrum with beta-lactamase inhibitor

Table 27.3: Penicillins (2 of 2) – Key Drugs, Route, Dose, Remarks

• penicillin G potassium (IV/IM): 2 ext{–}24 ext{ million U divided every } 4 ext{–}6 ext{ h}; Remarks: Ineffective against most forms of S. aureus
• penicillin G procaine (Wycillin): 0.6 ext{–}1.2 ext{ million U/day}; Remarks: Prolonged duration of action
• penicillin V: 125 ext{–}500 ext{ mg qid}; Remarks: Acid-stable
• piperacillin: 2 ext{–}4 ext{ g tid–qid}; Remarks: Extended-spectrum
• piperacillin–tazobactam (Zosyn): 3.375 ext{–}4.5 ext{ g qid over 30 min}; Remarks: Extended-spectrum with inhibitor
• ticarcillin–clavulanate (Timentin): 3.1 ext{ g} ext{ qid}; Remarks: Extended-spectrum with inhibitor

Core Concept 27.7: Cephalosporins

• Cephalosporins are structurally related to penicillins and share a beta-lactam ring; they are bactericidal and inhibit cell wall synthesis.
• Primary use: Gram-negative infections; for patients who cannot tolerate penicillins; cross-allergy with penicillins.
• Generations reflect spectrum and beta-lactamase resistance:
  • First generation: more active on Gram-positive; limited beta-lactamase resistance; generally less activity on Gram-negatives.
  • Second generation: broader spectrum; more resistant to beta-lactamase; broader activity than first generation.
  • Third generation: preferred for Pseudomonas, Klebsiella, Neisseria, Salmonella, Proteus, Haemophilus influenzae; broader Gram-negative activity; often IV/IM; better CNS penetration for some infections.
  • Fourth generation: enhanced activity against beta-lactamase-producing organisms; broader spectrum including Pseudomonas.
  • Fifth generation: effective against MRSA; broad spectrum; activity retained against resistant organisms.

Table 27.4: Selected Cephalosporins (1 of 2) – First and Second Generations

• First generation:
  • cefadroxil (Duricef): Route: PO; Dose: 500 ext{ mg} ext{–}1 ext{ g} ext{ once or twice daily}; Remarks: Bactericidal
  • cefazolin (Ancef, Kefzol): Route: IM; Dose: 250 ext{ mg} ext{–}2 ext{ g} ext{ tid} (IV form available); Remarks: Bactericidal
  • cephalexin (Keflex): Route: PO; Dose: 250 ext{–}500 ext{ mg qid}; Remarks: Bactericidal; broad spectrum
• Second generation:
  • cefaclor (Ceclor): Route: PO; Dose: 250 ext{–}500 ext{ mg} ext{ tid}; Remarks: Extended-release form available; bactericidal
  • cefotetan (Cefotan): Route: IM; Dose: 1 ext{–}2 ext{ g every 12 h}; IV form available
  • cefprozil (Cefzil): Route: PO; Dose: 250 ext{–}500 ext{ mg} ext{ once or twice daily}; Remarks: Bactericidal
  • cefuroxime (Ceftin, Zinacef): Route: PO; Dose: 250 ext{–}500 ext{ mg bid}; Remarks: IV/IM forms available; bactericidal

Table 27.4: Selected Cephalosporins (2 of 2) – Third to Fifth Generations

• Third to Fifth Generations
  • cefdinir (Omnicef): Route: PO; Dose: 300 ext{ mg bid}; Remarks: Third generation; broad spectrum
  • cefditoren (Spectracef): Route: PO; Dose: 400 ext{ mg bid for 10 days}; Remarks: Third generation
  • cefepime (Maxipime): Route: IV; Dose: 0.5 ext{–}1 ext{ g bid} (max: 3 ext{ g/day}); Remarks: Fourth generation; IV form available
  • cefixime (Suprax): Route: PO; Dose: 400 ext{ mg daily or }200 ext{ mg bid}; Remarks: Third generation; bactericidal
  • cefotaxime (Claforan): Route: IM; Dose: 1 ext{–}2 ext{ g bid–tid} (max: 12 ext{ g/day}); Remarks: Third generation; bactericidal; IV form available
  • ceftaroline (Teflaro): Route: IV; Dose: 600 ext{ mg every 12 h}; Remarks: Fifth generation; broad spectrum, effective against MRSA
  • ceftriaxone (Rocephin): Route: IM; Dose: 1 ext{–}2 ext{ g once or twice daily} (max: 4 ext{ g/day}); Remarks: Third generation; IV form also available; bactericidal

Core Concept 27.8: Tetracyclines

• Tetracyclines have broad spectra and are only in selected indications; primarily bacteriostatic.
• Mechanism: inhibit bacterial protein synthesis.
• Spectrum: wide range of Gram-negative and Gram-positive organisms.
• Important patient teaching:
  • Do not take with milk or calcium/aluminum-containing medicines (interferes with absorption).
  • Avoid direct sun exposure (photosensitivity).
  • Not given to patients younger than 9 ext{ years} due to risk of permanent tooth discoloration.

Table 27.5: Tetracyclines – Drugs, Route/Dose, Remarks

• demeclocycline (Declomycin): Route: PO; Dose: 150 ext{ mg every 6 h} ext{ or }300 ext{ mg bid}; Remarks: Intermediate duration; broad spectrum
• doxycycline (Vibramycin, others): Route: PO; Dose: 100 ext{ mg bid on day 1, then }100 ext{ mg daily}; Remarks: Long duration; IV form available; subgingival form available for periodontitis
• minocycline (Minocin, others): Route: PO; Dose: 200 ext{ mg as one dose followed by }100 ext{ mg bid}; Remarks: Long duration; IV form available; periodontitis/Acne uses
• tetracycline (Sumycin): Route: PO; Dose: 250 ext{–}500 ext{ mg bid–qid}; Remarks: Short acting; inhibits protein synthesis; bacteriostatic; IM/topical forms available
• tigecycline (Tygacil): Route: IV; Dose: 100 ext{ mg} ext{ loading}, then }50 ext{ mg every 12 h}; Remarks: Newest tetracycline; very limited indications

Core Concept 27.9: Macrolides

• Macrolides are safe alternatives to penicillin for many infections.
• Mechanism: inhibit bacterial protein synthesis; may be bactericidal or bacteriostatic depending on organism and concentration.
• Typical use: Safe alternatives to penicillin; often chosen for patients with penicillin allergy.

Table 27.6: Macrolides – Drugs, Route/Dose, Remarks

• azithromycin (Zithromax, Zmax): Route: PO; Dosing: Zithromax: 500 ext{ mg for one dose, then }250 ext{ mg daily for 4 days}; PO (Zmax): 1 ext{–}2 ext{ g single dose}; Remarks: Inhibits protein synthesis; bacteriostatic; IV form available
• clarithromycin (Biaxin): Route: PO; Dose: 250 ext{–}500 ext{ mg bid}; Remarks: Inhibits protein synthesis; bacteriostatic; part of regimen for H. pylori infections
• erythromycin (E Mycin, Erythrocin): Route: PO; Dose: 250 ext{–}500 ext{ mg qid or }333 ext{ mg tid}; Remarks: Bacteriostatic or bactericidal depending on organism and drug concentration; IV form available
• fidaxomicin (Dificid): Route: PO; Dose: 200 ext{ mg bid}; Remarks: Newer macrolide for treatment of pseudomembranous colitis or Clostridium difficile–associated diarrhea

Core Concept 27.10: Aminoglycosides

• Aminoglycosides are narrow-spectrum drugs with potential for serious toxicity.
• Use: Treatment of various aerobic Gram-negative bacteria, mycobacteria, and some protozoa.
• Mechanism: Bactericidal; inhibit bacterial protein synthesis.
• Major toxicities:
  • Ototoxicity: damage to inner ear; hearing loss, dizziness, balance issues, tinnitus.
  • Nephrotoxicity: kidney damage; abnormal urinary tests; elevated serum creatinine or BUN.

Table 27.7: Aminoglycosides – Drugs, Route/Dose, Remarks

• amikacin (Amikin): Route: IM; Dose: 5 ext{–}7.5 ext{ mg/kg as a loading dose, then }7.5 ext{ mg/kg bid}; Remarks: Broader spectrum; usually bactericidal; IV form available
• gentamicin (Garamycin): Route: IM; Dose: 1.5 ext{–}2 ext{ mg/kg as a loading dose, then }1 ext{–}2 ext{ mg/kg bid–tid}; Remarks: IV/ topical/ ophthalmic forms available
• kanamycin: Route: IM; Dose: 5 ext{–}7.5 ext{ mg/kg bid–tid}; Remarks: Also used to sterilize the bowel prior to colon surgery; oral, inhalation, and IV forms available
• neomycin: Route: PO; Dose: 4 ext{–}12 ext{ g/day} in divided doses; Remarks: Oral, topical, and IV forms available
• paromomycin (Humatin): Route: PO; Dose: 7.5 ext{–}12.5 ext{ mg/kg tid}; Remarks: For parasitic infections of the intestine; also used to treat hepatic coma
• streptomycin: Route: IM; Dose: 15 ext{ mg/kg} ext{ up to }1 ext{ g} as a single dose; Remarks: For TB, tularemia, and plague
• tobramycin: Route: IM/IV; Dose: 3 ext{ mg/kg tid} (max: 5 ext{ mg/kg/day}); Remarks: Most effective against Pseudomonas aeruginosa

Core Concept 27.11: Fluoroquinolones

• Fluoroquinolones have broad clinical applications due to broad spectrum and relative safety.
• Activity: Primarily against Gram-negative pathogens; newer agents are more active against Gram-positive microbes.
• Mechanism: Bactericidal; inhibit bacterial DNA synthesis.

Table 27.8: Fluoroquinolones – Drugs, Route/Dose, Remarks

• besifloxacin (Besivance): Route: Ophthalmic; Dose: One drop in each affected eye q8h; Remarks: For bacterial conjunctivitis
• ciprofloxacin (Cipro): Route: PO; Dose: 250 ext{–}750 ext{ mg bid}; Remarks: Broad spectrum; for lung, skin, bone, joint infections, and anthrax; IV form available
• finafloxacin (Xtoro): Route: Eardrops; Dose: 4 drops in affected ear bid for 1 week; Remarks: For otitis media
• gatifloxacin (Zymar, Zymaxid): Route: Ophthalmic; Dose: One drop in affected eye q2–6h; Remarks: For bacterial conjunctivitis
• gemifloxacin (Factive): Route: PO; Dose: 320 ext{ mg daily}; Remarks: For respiratory infections
• levofloxacin (Levaquin): Route: PO; Dose: 250 ext{–}500 ext{ mg daily}; Remarks: For respiratory tract and skin infections; IV form available
• moxifloxacin (Avelox, Moxeza, Vigamox): Route: PO/IV (Avelox): 400 ext{ mg daily}; Ophthalmic: one drop in affected eye tid (Vigamox) or bid (Moxeza);
  Dose: PO: for sinus, skin, intraabdominal, and respiratory infections; Ophthalmic: for conjunctivitis
• nalidixic acid (NegGram): Route: PO; Dose: 500 ext{–}1000 ext{ mg qid}; Remarks: For UTI
• norfloxacin (Norflox): Route: PO; Dose: 400 ext{ mg bid}; Remarks: For UTI; ophthalmic form available
• ofloxacin (Floxin): Route: PO; Dose: 200 ext{–}400 ext{ mg bid}; Remarks: For UTI, RT infections, gonorrhea; otic drops available

Core Concept 27.12: Sulfonamides and Urinary Antiseptics

• Traditional drugs for urinary tract infections (UTIs).

Table 27.9: Sulfonamides and Urinary Antiseptics (1 of 2) – Drugs, Route/Dose, Remarks

• silver sulfadiazine: Route: Topical; Dose: Apply cream 1–2 times per day; Remarks: Prevention of sepsis in patients with serious burns
• sulfadiazine: Route: PO; Dose: 2 ext{–}4 ext{ g daily} in 4–6 divided doses; Remarks: Also for malaria, toxoplasmosis, rheumatic fever prophylaxis
• sulfadoxine–pyrimethamine (Fansidar): Route: PO; Dose: 1 ext{ tablet weekly}; Remarks: Also for prevention and treatment of malaria
• sulfasalazine (Azulfidine): Route: PO; Dose: 1 ext{–}2 ext{ g/day in four divided doses}; Remarks: Also for ulcerative colitis and rheumatoid arthritis
• sulfisoxazole (Gantrisin): Route: PO; Dose: 2 ext{–}4 ext{ g initially, then }1 ext{–}2 ext{ g qid}; Remarks: For UTI; vaginal form available
• TMP–SMX (Bactrim, Septra): Route: PO; Dose: 1 ext{ double-strength tablet} (160 ext{ mg TMP}/800 ext{ mg SMZ) }bid; Remarks: Combination drug; for UTI, Pneumocystis, and ear infections; IV form available

Table 27.9: Sulfonamides and Urinary Antiseptics (2 of 2) – Urinary Antiseptics

• fosfomycin (Monurol): Route: PO; Dose: 3 ext{ g} single dose dissolvable in water; Remarks: Bactericidal; for UTI
• methenamine hippurate (Hiprex) / methenamine mandelate: Route: PO; Dose: Hippurate 1 ext{ g bid}; mandelate 1 ext{ g qid}; Remarks: For chronic UTI; broad spectrum
• nitrofurantoin (Furadantin, Macrobid, Macrodantin): Route: PO; Dose: 50 ext{–}100 ext{ mg qid}; Remarks: For UTI; extended-release form available; interferes with bacterial enzymes

Core Concept 27.13 Miscellaneous Anti-infectives

• A range of additional anti-infectives with distinct mechanisms and specific indications.

Table 27.10: Miscellaneous Anti-infectives (1 of 4) – Carbapenems

• doripenem (Doribax): Route: IV; Dose: 500 ext{ mg every 8 h} (max: 500 ext{ mg every 8 h}); Remarks: Very broad spectrum; for serious intra-abdominopelvic, skin infections, pneumonia, complicated UTI, meningitis
• ertapenem (Invanz): Route: IV/IM; Dose: 1 ext{ g/day}; Remarks: Blank
• imipenem-cilastatin (Primaxin): Route: IV; Dose: 250 ext{–}500 ext{ mg tid–qid} (max: 4 ext{ g/day}); Remarks: Blank
• meropenem (Merrem): Route: IV; Dose: 0.5 ext{–}1 ext{ g tid}; Remarks: Blank

Table 27.10: Miscellaneous Anti-infectives (2 of 4) – Other Antibiotics

• aztreonam (Azactam): Route: IM/IV; Dose: 0.5 ext{–}2 ext{ g bid–qid} (max: 8 ext{ g/day}); Remarks: Monobactam; for Gram-negative aerobic bacteria
• chloramphenicol: Route: PO; Dose: 50 ext{ mg/kg qid}; Remarks: Broad spectrum; for typhoid fever and meningitis; IV form available
• clindamycin (Cleocin): Route: PO; Dose: 150 ext{–}450 ext{ mg qid}; Remarks: Bacteriostatic; effective against anaerobes; topical, IM, IV forms available
• dalbavancin (Dalvance): Route: IV; Dose: 1000 ext{ mg} followed 1 week later by 500 ext{ mg}; Remarks: Newer; bactericidal for serious skin infections

Table 27.10: Miscellaneous Anti-infectives (3 of 4) – Other Antibiotics

• daptomycin (Cubicin): Route: IV; Dose: 4 ext{ mg/kg} once every 24 hours for 7 ext{–}14 ext{ days}; Remarks: Bactericidal; for serious skin infections
• lincomycin (Lincocin): Route: PO; Dose: 500 ext{ mg tid–qid}; Remarks: Bacteriostatic; effective against anaerobes; IM form available
• linezolid (Zyvox): Route: PO; Dose: 600 ext{ mg bid} (max: 1{,}200 ext{ mg/day}); Remarks: For vancomycin-resistant Enterococcus; IV form available
• metronidazole (Flagyl): Route: PO; Dose: 7.5 ext{ mg/kg qid}; Remarks: For serious anaerobic infections; also for protozoan infections; IV form available
• oritavancin (Orbactiv): Route: IV; Dose: Single dose of 1200 ext{ mg} infused over 3 hours; Remarks: Newer drug; bactericidal for serious skin infections

Table 27.10: Miscellaneous Anti-infectives (4 of 4) – Other antibiotics

• quinupristin-dalfopristin (Synercid): Route: IV; Dose: 7.5 ext{ mg/kg} infused over 50 minutes every 8 h; Remarks: Streptogramins class; for serious infections resistant to vancomycin
• spectinomycin (Trobicin): Route: IM; Dose: 2 ext{ g} as a single dose; Remarks: Bacteriostatic; for gonorrhea
• tedizolid (Sivextro): Route: PO/IV; Dose: 200 ext{ mg once daily} for 6 days; Remarks: Newer drug for serious skin infections
• telavancin (Vibativ): Route: IV; Dose: 10 ext{ mg/kg} over 60 minutes for 24 hours; Remarks: For hospital-acquired pneumonia
• telithromycin (Ketek): Route: PO; Dose: 800 ext{ mg daily}; Remarks: Ketolide class; for community-acquired respiratory tract infections
• vancomycin (Vancocin): Route: IV; Dose: 500 ext{ mg qid}–1 ext{ g bid}; Remarks: For MRSA infections; PO form available

Core Concept 27.14 Tuberculosis (TB) – Special Pharmacotherapy

• TB therapy requires special dosing regimens and schedules.

Table 27.11: First-Line Antitubercular Drugs

• ethambutol (Myambutol): Route: PO; Dose: 15 ext{–}25 ext{ mg/kg daily}; Remarks: Used in combination with other anti-tuberculars
• isoniazid (INH, Nydrazid): Route: PO; Dose: 300 ext{ mg/day} or 900 ext{ mg twice weekly} for latent TB or 15 ext{ mg/kg/day} for active TB; Remarks: Used in combination with other anti-tuberculars; IM form available
• pyrazinamide (PZA): Route: PO; Dose: 15 ext{–}30 ext{ mg/kg daily} (max: 3 ext{ g/day})
• rifabutin (Mycobutin): Route: PO; Dose: 300 ext{ mg once daily} or 5 ext{ mg/kg/day} (max: 300 ext{ mg/day}); Remarks: Very similar to rifampin and rifapentine
• rifampin (Rifadin, Rimactane): Route: PO; Dose: 600 ext{ mg daily} as a single dose or 900 ext{ mg twice weekly} for 4 ext{ months}; Remarks: IV form available; also for H. influenzae, meningococcus infections
• rifapentine (Priftin): Route: PO; Dose: 600 ext{ mg twice a week for 2 months}, then once a week for 4 months; Remarks: Used in combination with other anti-tuberculars

TB Therapy Concepts (1 of 2)

• TB therapy differs from conventional anti-infective chemotherapy; treatment duration is typically 6 ext{ to }12 ext{ months}.
• Mycobacteria have a cell wall that is resistant to penetration by many anti-infectives, requiring at least two, sometimes four or more, antibiotics concurrently.

TB Therapy Concepts (2 of 2)

• Mycobacteria grow slowly; resistance is common; drugs are used extensively to prevent disease in addition to treating it.

Typical Treatment Regimen (1 of 2)

• Initial phase: 2 ext{ months} of daily therapy with isoniazid (INH), rifampin, pyrazinamide, and ethambutol.
• If lab results show strain is sensitive to the first three drugs, ethambutol is dropped from the regimen.

Typical Treatment Regimen (2 of 2)

• Continuation phase: 4 ext{ months} of therapy with isoniazid and rifampin, two to three times per week.

Concept Review 27.3

• Question: How does drug therapy of TB differ from that of conventional anti-infective chemotherapy? What are the rationales for these differences?

Summary: Practical and Ethical Considerations

• Proper antibiotic selection requires balancing efficacy with safety and the risk of resistance.
• Culture and sensitivity testing guide therapy when possible (see Culture and Sensitivity Testing).
• Narrow-spectrum agents are preferred when the organism is identified; broad-spectrum agents are used when cover is needed or when organism is unknown.
• Compliance and education are critical to prevent resistance (full course, avoid unnecessary use).

Culture and Sensitivity Testing (Recap)

• Culture and sensitivity testing demonstrated in two parts:
  • Part 1: The organism is grown and effective antibiotics identified; should identify organism before anti-infective therapy is begun, though treatment often starts sooner.
  • Part 2: Definitions:
  • Broad-spectrum antibiotic: effective against a wide variety of microbial species; ext{broad spectrum}
  • Narrow-spectrum antibiotic: effective against a smaller group of microbes or only the isolated species; ext{narrow spectrum}

Connections to Foundational Principles and Real-World Relevance

• Understanding bacterial pathogens and antibiotic mechanisms underpins rational antibiotic selection in clinical practice.
• Antibiotic resistance is a dynamic clinical challenge; proper stewardship reduces emergence and spread of resistance.
• TB requires structured regimens and adherence due to slow-growing bacteria and high resistance risk; public health implications are significant.
• Ethical implications include preventing harm through adverse drug effects, avoiding unnecessary antibiotics, and ensuring equitable access to essential medicines.

Key Formulas and Notation (LaTeX)

• TB treatment duration: 6 ext{ to }12 ext{ months}
• Dosing ranges (examples):
  • Amoxicillin: 250 ext{–}500 ext{ mg} ext{ PO, tid}
  • Piperacillin–tazobactam: 3.375 ext{–}4.5 ext{ g} ext{ qid over 30 min}
  • Isoniazid: 300 ext{ mg/day} or 900 ext{ mg twice weekly} for latent TB
• Drug generation descriptors (qualitative, not numeric): First, Second, Third, Fourth, Fifth generation cephalosporins; MRSA coverage noted for certain agents.

Quick Reference: Common Drug Highlights (Reminders)

• Penicillins: beta-lactam ring; beta-lactamase resistance achievable via modifications.
• Cephalosporins: cross-allergy with penicillins; generational spectrum differences.
• Tetracyclines: avoid in children < 9 ext{ years}; interactions with dairy and sunlight sensitivity.
• Macrolides: alternative to penicillin; variable bactericidal/static depending on context.
• Aminoglycosides: toxicity monitoring essential (oto/nephrotoxicity risk).
• Fluoroquinolones: broad Gram-negative coverage; caution due to resistance and safety profiles in some populations.
• Sulfonamides and urinary antiseptics: key in UTI management; combination therapies common (TMP-SMX).
• TB drugs require adherence, combination therapy, and phased regimens to prevent resistance.