Comprehensive Antibiotic Reference Table for Primary Care & AANP Board Exam
Use this table as your primary reference for outpatient antibiotic selection—penicillins and amoxicillin remain first-line for most respiratory infections, while narrow-spectrum agents should always be prioritized over broad-spectrum alternatives when appropriate.
PENICILLINS
Natural Penicillins
| Agent | Primary Care Indications | First-Line For | Dosing | Duration | Alternatives (Allergy/Intolerance) | Key Adverse Effects | Black Box Warnings | Drug Interactions | Contraindications | Special Considerations |
|---|---|---|---|---|---|---|---|---|---|---|
| Penicillin V (Phenoxymethylpenicillin) | Group A Strep pharyngitis | GAS pharyngitis | Adults: 250 mg QID or 500 mg BID PO Children: 250 mg BID-TID PO |
10 days [1] | Cephalexin, cefadroxil (avoid in immediate hypersensitivity), clindamycin, azithromycin, clarithromycin [1] | GI upset, hypersensitivity reactions (rash, anaphylaxis), drug fever [2] | Serious hypersensitivity reactions including anaphylaxis | Probenecid (↑ penicillin levels), oral contraceptives (↓ efficacy), warfarin (↑ INR) | Penicillin allergy (especially immediate-type) | Preferred over amoxicillin for GAS pharyngitis due to narrower spectrum [1]; resistance rare in GAS |
| Benzathine Penicillin G | GAS pharyngitis (compliance concerns) | GAS pharyngitis when adherence uncertain | <27 kg: 600,000 U IM ≥27 kg: 1,200,000 U IM |
Single dose [1] | Same as Penicillin V | Injection site pain, hypersensitivity, Jarisch-Herxheimer reaction | Same as Penicillin V | Same as Penicillin V | Same as Penicillin V | Use when oral compliance is questionable; ensures complete treatment [1] |
Aminopenicillins
| Agent | Primary Care Indications | First-Line For | Dosing | Duration | Alternatives | Key Adverse Effects | Black Box Warnings | Drug Interactions | Contraindications | Special Considerations |
|---|---|---|---|---|---|---|---|---|---|---|
| Amoxicillin | GAS pharyngitis, acute bacterial rhinosinusitis (ABRS), community-acquired pneumonia (CAP) in children, acute otitis media | GAS pharyngitis, uncomplicated ABRS (no risk factors), mild-moderate CAP in children | Adults: 500 mg BID or 250 mg TID PO Children: 50 mg/kg/day once daily (max 1000 mg) or 25 mg/kg BID (max 500 mg) [1] High-dose ABRS: 1 g TID or 2 g BID [3] |
10 days (GAS) [1] 5-7 days (ABRS) [3] 5 days (CAP children) [4] |
Macrolides (azithromycin, clarithromycin), doxycycline, respiratory fluoroquinolones [5] | Diarrhea (10-25%), rash (especially with EBV), hypersensitivity, C. difficile | Serious hypersensitivity reactions | Same as Penicillin V; allopurinol (↑ rash risk) | Penicillin allergy, mononucleosis (high rash risk) | Preferred over penicillin V for GAS due to once-daily dosing option [1]; preferred over amoxicillin-clavulanate for uncomplicated infections [3]; British guidelines prefer for CAP [5] |
Beta-Lactamase Inhibitor Combinations
| Agent | Primary Care Indications | First-Line For | Dosing | Duration | Alternatives | Key Adverse Effects | Black Box Warnings | Drug Interactions | Contraindications | Special Considerations |
|---|---|---|---|---|---|---|---|---|---|---|
| Amoxicillin-Clavulanate (Augmentin) | ABRS with risk factors, animal/human bites, non-severe CAP, COPD exacerbations, skin/soft tissue infections | ABRS with: recent antibiotic use (<1 month), daycare contact, smoking, moderate-severe symptoms, comorbidities, age >65, frontal/sphenoid sinusitis [3] | Adults: 875/125 mg BID or 500/125 mg TID PO High-dose: 2000/125 mg (extended-release) BID [3] Children: 25 mg/kg BID (of amoxicillin component) [6] |
5-10 days (ABRS) [3] 10 days (impetigo) [6] |
Respiratory fluoroquinolones (levofloxacin, moxifloxacin), doxycycline [7] | Diarrhea (25-30%), nausea, hepatotoxicity (rare but serious), C. difficile | Hepatotoxicity (cholestatic jaundice) | Same as amoxicillin | Penicillin allergy, history of amoxicillin-clavulanate-associated hepatic dysfunction | Use high-dose formulation for resistant S. pneumoniae risk [3]; GI side effects more common than amoxicillin alone; preferred for non-severe pneumonia in hospital [7] |
CEPHALOSPORINS
First-Generation
| Agent | Primary Care Indications | First-Line For | Dosing | Duration | Alternatives | Key Adverse Effects | Black Box Warnings | Drug Interactions | Contraindications | Special Considerations |
|---|---|---|---|---|---|---|---|---|---|---|
| Cephalexin (Keflex) | GAS pharyngitis (penicillin allergy—non-immediate), skin/soft tissue infections (MSSA), impetigo | MSSA skin infections | Adults: 500 mg QID or 250 mg QID PO Children: 25 mg/kg/day in 4 divided doses (max 500 mg/dose) [1,6] |
10 days (GAS) [1] 7 days (SSTI) [6] |
Dicloxacillin, clindamycin, TMP-SMX, doxycycline [6] | Diarrhea, hypersensitivity (5-10% cross-reactivity with penicillin allergy), C. difficile | Hypersensitivity reactions | Probenecid (↑ levels), warfarin (↑ INR) | Immediate-type penicillin allergy (anaphylaxis, urticaria), cephalosporin allergy | Avoid in immediate penicillin hypersensitivity [1]; 5-10% cross-reactivity with penicillin allergy; good oral bioavailability |
| Cefadroxil | GAS pharyngitis (penicillin allergy—non-immediate) | GAS pharyngitis (alternative) | Adults/Children: 30 mg/kg once daily PO (max 1 g) [1] | 10 days [1] | Same as cephalexin | Same as cephalexin | Same as cephalexin | Same as cephalexin | Same as cephalexin | Once-daily dosing advantage [1]; similar spectrum to cephalexin |
Second-Generation
| Agent | Primary Care Indications | First-Line For | Dosing | Duration | Alternatives | Key Adverse Effects | Black Box Warnings | Drug Interactions | Contraindications | Special Considerations |
|---|---|---|---|---|---|---|---|---|---|---|
| Cefuroxime (Ceftin) | CAP (hospitalized, non-severe), COPD exacerbations (moderate-severe) | Hospitalized non-severe pneumonia (parenteral) | Oral: 250-500 mg BID IV: 1.5 g TID [7] |
Variable by indication | Amoxicillin-clavulanate, respiratory fluoroquinolones [7] | Diarrhea, hypersensitivity, C. difficile | Hypersensitivity reactions | Same as cephalexin | Cephalosporin allergy, immediate penicillin allergy | Better H. influenzae coverage than 1st-gen; oral bioavailability reduced with food (take with food to ↑ absorption); switch to oral amoxicillin-clavulanate preferred over oral cephalosporin [7] |
Third-Generation
| Agent | Primary Care Indications | First-Line For | Dosing | Duration | Alternatives | Key Adverse Effects | Black Box Warnings | Drug Interactions | Contraindications | Special Considerations |
|---|---|---|---|---|---|---|---|---|---|---|
| Cefotaxime (Claforan) | Severe CAP (hospitalized), neonatal sepsis/ophthalmia neonatorum | Severe CAP (parenteral), neonatal gonococcal infection | Adults: 1 g TID IV [7] Neonates: 100 mg/kg IV/IM single dose [8] |
Variable | Ceftriaxone, fluoroquinolone + macrolide [7] | Diarrhea, hypersensitivity, C. difficile, thrombophlebitis | Hypersensitivity reactions | Probenecid (↑ levels) | Cephalosporin allergy | Parenteral only; no biliary excretion issues (safer than ceftriaxone in neonates with hyperbilirubinemia); used for severe pneumonia + macrolide [7] |
| Ceftriaxone (Rocephin) | Severe CAP, gonococcal conjunctivitis, pelvic inflammatory disease | Gonococcal infections, severe CAP | Adults: 1-2 g IV/IM daily Gonorrhea: 250 mg IM single dose Children: 25-50 mg/kg IV/IM (max 250 mg for gonorrhea) [8] |
Single dose (gonorrhea) Variable (pneumonia) |
Cefotaxime, fluoroquinolones [8] | Diarrhea, hypersensitivity, biliary sludging, C. difficile | Hypersensitivity reactions; do not mix with calcium-containing solutions (precipitation) | Calcium-containing IV solutions (contraindicated in neonates) | Hyperbilirubinemia in neonates (displaces bilirubin), cephalosporin allergy | Once-daily dosing; avoid in neonates with jaundice (kernicterus risk); preferred for gonorrhea [8]; used for severe CAP + macrolide [7] |
MACROLIDES
| Agent | Primary Care Indications | First-Line For | Dosing | Duration | Alternatives | Key Adverse Effects | Black Box Warnings | Drug Interactions | Contraindications | Special Considerations |
|---|---|---|---|---|---|---|---|---|---|---|
| Azithromycin (Z-Pak) | GAS pharyngitis (penicillin allergy), CAP (atypical coverage), chlamydial conjunctivitis, pertussis | Chlamydia (genital/conjunctivitis), CAP with atypical pathogens (North American guidelines) [5] | Adults: 500 mg day 1, then 250 mg days 2-5 PO Children (GAS): 12 mg/kg once daily (max 500 mg) [1] Chlamydia: 1 g PO single dose [8] |
5 days (GAS, CAP) [1] Single dose (chlamydia) [8] |
Doxycycline, fluoroquinolones, clindamycin [1,8] | QT prolongation, GI upset (less than erythromycin), hepatotoxicity, ototoxicity (high doses), C. difficile | QT prolongation and torsades de pointes (especially with other QT drugs) | CYP3A4 substrate (less interaction than erythromycin/clarithromycin); warfarin (↑ INR), digoxin (↑ levels); avoid with QT-prolonging drugs | Long QT syndrome, history of torsades, concurrent QT-prolonging drugs | Geographic resistance in GAS varies [1]; single-dose for chlamydia [8]; less GI upset than erythromycin; poor H. influenzae coverage [7]; North American guidelines favor for CAP [5] |
| Clarithromycin (Biaxin) | GAS pharyngitis (penicillin allergy), CAP, H. pylori, COPD exacerbations | CAP with atypical coverage, COPD exacerbations | Adults: 250-500 mg BID PO Children (GAS): 7.5 mg/kg BID (max 250 mg/dose) [1] COPD: 500 mg BID [7] |
10 days (GAS) [1] 5-7 days (CAP) |
Azithromycin, doxycycline, fluoroquinolones [1] | QT prolongation, GI upset, hepatotoxicity, metallic taste, C. difficile | QT prolongation | Strong CYP3A4 inhibitor: statins (↑ rhabdomyolysis), warfarin (↑ INR), theophylline (↑ toxicity), carbamazepine, digoxin; avoid with QT drugs | Long QT, concurrent CYP3A4-metabolized statins (simvastatin, lovastatin), pimozide | Better H. influenzae coverage than azithromycin [7]; twice-daily dosing; more drug interactions than azithromycin; resistance varies geographically [1] |
| Erythromycin | GAS pharyngitis (penicillin allergy), pertussis, chlamydial conjunctivitis (neonates), impetigo | Neonatal chlamydial conjunctivitis/pneumonia, pertussis | Adults: 250-500 mg QID PO or 500 mg QID IV [7,6] Neonates: 50 mg/kg/day divided QID × 14 days [8] Impetigo: 250 mg QID [6] |
10 days (GAS) [1] 14 days (neonatal chlamydia) [8] |
Azithromycin, clarithromycin [1,8] | Severe GI upset (most common), QT prolongation, hepatotoxicity, ototoxicity, pyloric stenosis (neonates <6 weeks), C. difficile | QT prolongation; pyloric stenosis in neonates <6 weeks | Strong CYP3A4 inhibitor: same as clarithromycin; prokinetic effect (↑ GI motility) | Long QT, concurrent CYP3A4 drugs, neonates <6 weeks (pyloric stenosis risk) | Highest GI side effects of macrolides (30-50%); clarithromycin preferred if GI intolerance [7]; pyloric stenosis risk in young infants [8]; resistance varies [1] |
TETRACYCLINES
| Agent | Primary Care Indications | First-Line For | Dosing | Duration | Alternatives | Key Adverse Effects | Black Box Warnings | Drug Interactions | Contraindications | Special Considerations |
|---|---|---|---|---|---|---|---|---|---|---|
| Doxycycline | CAP, COPD exacerbations, ABRS, Lyme disease, chlamydia, MRSA skin infections, acne | Chlamydia (alternative to azithromycin), CAP (alternative), tick-borne illnesses, MRSA SSTI | Adults: 100 mg BID PO (200 mg loading dose) [7,6] Children ≥8 years: 100 mg BID [8] |
7 days (chlamydia, CAP) [8] 10-21 days (Lyme) |
Azithromycin, amoxicillin-clavulanate, fluoroquinolones [7] | Photosensitivity, GI upset, esophagitis (take with water, remain upright 30 min), tooth discoloration (<8 years), C. difficile | Tooth discoloration and enamel hypoplasia in children <8 years; photosensitivity | Chelation: antacids, calcium, iron, magnesium (↓ absorption—separate by 2-3 hours); warfarin (↑ INR); may ↓ oral contraceptive efficacy | Age <8 years (tooth staining), pregnancy (tooth/bone effects), severe hepatic impairment | Preferred tetracycline (better absorption, BID dosing); take with food to ↓ GI upset (unlike tetracycline); excellent tissue penetration; British guidelines favor for COPD/pneumonia [7] |
| Minocycline | Acne, MRSA skin infections (alternative) | Acne (chronic therapy) | Adults: 100 mg BID PO | Variable (acne: months) | Doxycycline, TMP-SMX [6] | Dizziness, vertigo, photosensitivity (less than doxycycline), autoimmune syndromes (lupus-like, hepatitis), tooth discoloration | Same as doxycycline | Same as doxycycline | Same as doxycycline | Vestibular side effects more common than doxycycline; less photosensitivity; autoimmune reactions (rare but serious); limited use in acute infections [6] |
FLUOROQUINOLONES (RESPIRATORY)
| Agent | Primary Care Indications | First-Line For | Dosing | Duration | Alternatives | Key Adverse Effects | Black Box Warnings | Drug Interactions | Contraindications | Special Considerations |
|---|---|---|---|---|---|---|---|---|---|---|
| Levofloxacin (Levaquin) | CAP (with comorbidities/recent antibiotics), COPD exacerbations (recent antibiotics/steroids), complicated UTI, ABRS (alternative) | CAP with modifying factors (COPD, recent antibiotics, age >65, comorbidities) [5], severe CAP [7] | Adults: 500-750 mg once daily PO/IV [7] Severe CAP: 500 mg BID IV [7] |
5-7 days (CAP, ABRS) [3] | Amoxicillin-clavulanate, doxycycline, azithromycin [7] | Tendon rupture (Achilles), peripheral neuropathy, QT prolongation, CNS effects (seizures, confusion), hyperglycemia/hypoglycemia, C. difficile, photosensitivity | Tendon rupture, peripheral neuropathy, CNS effects, exacerbation of myasthenia gravis, QT prolongation, aortic dissection/rupture | Chelation: antacids, calcium, iron, magnesium (separate by 2 hours before, 6 hours after); warfarin (↑ INR); NSAIDs (↑ seizure risk); QT-prolonging drugs | Myasthenia gravis, history of tendon disorders with fluoroquinolones, long QT, concurrent QT drugs | Reserve for resistant pathogens or penicillin allergy [7]; excellent S. pneumoniae and atypical coverage; risk ↑ with age >60, steroids, transplant; avoid in ABRS unless high resistance [3]; Canadian/ATS guidelines reserve for modifying factors [5] |
| Moxifloxacin (Avelox) | CAP (with comorbidities), ABRS (alternative), COPD exacerbations | CAP with modifying factors (alternative to levofloxacin) [5] | Adults: 400 mg once daily PO [7] | 5-7 days (CAP, ABRS) [3] | Levofloxacin, amoxicillin-clavulanate [7] | Same as levofloxacin; hepatotoxicity more common | Same as levofloxacin | Same as levofloxacin | Same as levofloxacin | Oral formulation only in UK [7]; not licensed for severe pneumonia in UK [7]; enhanced anaerobic coverage vs. levofloxacin; same black box warnings; reserve for resistant infections [3] |
| Ciprofloxacin (Cipro) | Complicated UTI, pseudomonal infections (COPD with P. aeruginosa risk, bronchiectasis), traveler's diarrhea | Pseudomonal respiratory infections (COPD with risk factors) [9] | Adults: 500-750 mg BID PO or 400 mg BID-TID IV [9] | Variable by indication | Antipseudomonal beta-lactams (piperacillin-tazobactam, ceftazidime, meropenem) [9] | Same as levofloxacin; poor S. pneumoniae coverage | Same as levofloxacin | Same as levofloxacin; theophylline (↑ toxicity) | Same as levofloxacin | Do NOT use for CAP or strep pharyngitis (inadequate S. pneumoniae/GAS coverage); reserve for Pseudomonas [9]; avoid in ABRS [3]; higher tendon rupture risk than other fluoroquinolones |
LINCOSAMIDES
| Agent | Primary Care Indications | First-Line For | Dosing | Duration | Alternatives | Key Adverse Effects | Black Box Warnings | Drug Interactions | Contraindications | Special Considerations |
|---|---|---|---|---|---|---|---|---|---|---|
| Clindamycin (Cleocin) | GAS pharyngitis (penicillin allergy), MSSA/MRSA skin infections, anaerobic infections, dental infections | MRSA skin infections (community-acquired), anaerobic infections, dental abscesses | Adults: 300-450 mg TID-QID PO or 600 mg TID IV [1,6] Children (GAS): 7 mg/kg TID (max 300 mg/dose) [1] SSTI: 300-450 mg TID PO [6] |
10 days (GAS) [1] 7-10 days (SSTI) [6] |
TMP-SMX, doxycycline, linezolid [6] | C. difficile colitis (highest risk among oral antibiotics, 10-20%), diarrhea (20%), rash, hepatotoxicity | C. difficile-associated diarrhea and colitis | Erythromycin (antagonism—don't combine); neuromuscular blockers (↑ blockade) | Severe C. difficile history, inflammatory bowel disease (relative) | Excellent anaerobic and MRSA coverage; inducible resistance in erythromycin-resistant MRSA (D-test needed) [6]; bacteriostatic; high C. diff risk limits use [6]; good bone penetration |
SULFONAMIDES & COMBINATIONS
| Agent | Primary Care Indications | First-Line For | Dosing | Duration | Alternatives | Key Adverse Effects | Black Box Warnings | Drug Interactions | Contraindications | Special Considerations |
|---|---|---|---|---|---|---|---|---|---|---|
| Trimethoprim-Sulfamethoxazole (TMP-SMX, Bactrim, Septra) | Uncomplicated UTI (cystitis), MRSA skin infections, PCP prophylaxis | Uncomplicated cystitis (first-line despite ~20% E. coli resistance) [10], MRSA SSTI | Adults: 1-2 double-strength (DS) tablets (160/800 mg) BID PO [6] Children: 8-12 mg/kg/day (TMP component) divided BID [6] |
3 days (cystitis) 7-10 days (SSTI) [6] |
Nitrofurantoin (cystitis), fluoroquinolones (reserve), doxycycline, clindamycin [6,10] | Stevens-Johnson syndrome/TEN, hyperkalemia, bone marrow suppression, rash, GI upset, photosensitivity, hepatotoxicity, C. difficile | Fatal hypersensitivity reactions (Stevens-Johnson, TEN, toxic epidermal necrolysis), blood dyscrasias | Warfarin (↑ INR significantly), methotrexate (↑ toxicity), ACE-I/ARBs (↑ hyperkalemia), sulfonylureas (↑ hypoglycemia), phenytoin (↑ levels) | Sulfa allergy, G6PD deficiency, severe renal/hepatic impairment, pregnancy (3rd trimester—kernicterus), infants <2 months, megaloblastic anemia | Preferred over fluoroquinolones for cystitis despite resistance [10]; check potassium in elderly/renal impairment; bactericidal; no Streptococcus coverage (don't use for pharyngitis/pneumonia); efficacy for MRSA poorly documented [6] |
NITROFURANS
| Agent | Primary Care Indications | First-Line For | Dosing | Duration | Alternatives | Key Adverse Effects | Black Box Warnings | Drug Interactions | Contraindications | Special Considerations |
|---|---|---|---|---|---|---|---|---|---|---|
| Nitrofurantoin (Macrobid, Macrodantin) | Uncomplicated UTI (cystitis), UTI prophylaxis | Uncomplicated cystitis (alternative to TMP-SMX) | Adults: 100 mg BID (macrocrystal/monohydrate) PO | 5 days (cystitis) | TMP-SMX, fosfomycin (single dose) | Pulmonary fibrosis (chronic use, irreversible), peripheral neuropathy (irreversible), GI upset (take with food), hepatotoxicity, hemolytic anemia (G6PD deficiency) | Pulmonary toxicity (acute, subacute, chronic fibrosis), hepatotoxicity, peripheral neuropathy | Antacids (↓ absorption); probenecid (↓ renal excretion—avoid) | CrCl <30 mL/min (ineffective and ↑ toxicity), G6PD deficiency, pregnancy at term (hemolysis in newborn), pulmonary fibrosis history | Do NOT use for pyelonephritis (inadequate tissue levels); only for cystitis; take with food to ↓ GI upset and ↑ absorption; avoid chronic use (pulmonary fibrosis risk) [2]; irreversible toxicities [2] |
OXAZOLIDINONES
| Agent | Primary Care Indications | First-Line For | Dosing | Duration | Alternatives | Key Adverse Effects | Black Box Warnings | Drug Interactions | Contraindications | Special Considerations |
|---|---|---|---|---|---|---|---|---|---|---|
| Linezolid (Zyvox) | MRSA skin infections (complicated or failed therapy), VRE | MRSA SSTI (second-line, oral option for complicated cases) [6] | Adults: 600 mg BID PO/IV [6] Children: 10 mg/kg BID [6] |
10-14 days (SSTI) [6] | Vancomycin (IV), daptomycin (IV), clindamycin, TMP-SMX [6] | Bone marrow suppression (thrombocytopenia, anemia—monitor CBC weekly if >2 weeks), peripheral/optic neuropathy, serotonin syndrome (with SSRIs), lactic acidosis, hypertension | Myelosuppression (thrombocytopenia, anemia) | MAO inhibitor: avoid SSRIs, SNRIs, TCAs, meperidine, tramadol, sympathomimetics (serotonin syndrome, hypertensive crisis); tyramine-rich foods (↑ BP) | Concurrent MAOIs or <2 weeks after MAOI, uncontrolled hypertension, pheochromocytoma, carcinoid | Bacteriostatic; expensive (~$100-150/day) [6]; no cross-resistance with other classes [6]; monitor CBC if >2 weeks; avoid tyramine-rich foods (cheese, wine, cured meats); reserve for documented MRSA or failed therapy [6] |
GLYCOPEPTIDES
| Agent | Primary Care Indications | First-Line For | Dosing | Duration | Alternatives | Key Adverse Effects | Black Box Warnings | Drug Interactions | Contraindications | Special Considerations |
|---|---|---|---|---|---|---|---|---|---|---|
| Vancomycin (Vancocin) | MRSA infections (parenteral), C. difficile colitis (oral) | MRSA SSTI (parenteral, severe cases) [6], C. difficile (oral only) | Adults: 30 mg/kg/day IV divided BID (target trough 10-20 mcg/mL) [6] C. diff: 125 mg QID PO Children: 40 mg/kg/day IV divided QID [6] |
Variable by indication | Linezolid (oral MRSA), daptomycin (IV MRSA) [6] | Nephrotoxicity, ototoxicity (irreversible), Red Man Syndrome (infusion reaction—histamine release), thrombophlebitis | Nephrotoxicity, ototoxicity | Aminoglycosides (↑ nephro/ototoxicity); loop diuretics (↑ ototoxicity) | Vancomycin allergy | Parenteral drug of choice for MRSA [6]; oral NOT absorbed (only for C. diff colitis); monitor trough levels and renal function; infuse over ≥60 min to prevent Red Man Syndrome; adjust for renal function; not for outpatient MRSA SSTI (IV only) |
LIPOPEPTIDES
| Agent | Primary Care Indications | First-Line For | Dosing | Duration | Alternatives | Key Adverse Effects | Black Box Warnings | Drug Interactions | Contraindications | Special Considerations |
|---|---|---|---|---|---|---|---|---|---|---|
| Daptomycin (Cubicin) | MRSA skin infections (complicated), bacteremia, endocarditis | MRSA SSTI (parenteral, alternative) [6] | Adults: 4 mg/kg IV once daily (SSTI) [6] 6 mg/kg (bacteremia/endocarditis) |
Variable by indication | Vancomycin, linezolid [6] | Myopathy (↑ CPK—monitor weekly), rhabdomyolysis, eosinophilic pneumonia, peripheral neuropathy | Myopathy and rhabdomyolysis | Statins (↑ myopathy risk—consider holding); warfarin (monitor INR) | Daptomycin allergy | Bactericidal; inactivated by pulmonary surfactant—do NOT use for pneumonia [6]; monitor CPK weekly; once-daily dosing; expensive; reserve for severe MRSA or vancomycin failure [6] |
KEY CLINICAL PEARLS & PITFALLS
Antibiotic Selection Principles
- Narrow-spectrum first: Amoxicillin and penicillin V remain preferred for GAS pharyngitis and uncomplicated infections 1, 3
- Avoid fluoroquinolones for routine respiratory infections: Reserve for resistant pathogens or specific indications (COPD with recent antibiotics, Pseudomonas risk) 7, 5, 3, 7, 5
- Amoxicillin-clavulanate is NOT always better: Use plain amoxicillin for uncomplicated ABRS; reserve combination for risk factors 3
- Recent antibiotic use (<1 month) = risk factor: Consider broader coverage or different class 3
Allergy Considerations
- Immediate vs. delayed penicillin allergy: Cephalosporins contraindicated in immediate-type (anaphylaxis, urticaria); safe in delayed rash 1
- Cross-reactivity: Penicillin-cephalosporin ~5-10%; penicillin-carbapenem ~1% 1
- Penicillin allergy alternatives: Macrolides (resistance concerns), doxycycline, fluoroquinolones (reserve), clindamycin (C. diff risk) 1
Duration of Therapy
- Shorter is often better: 5-7 days for ABRS and CAP equally effective as 10 days with fewer side effects 3, 4
- GAS pharyngitis requires 10 days (except benzathine PCN single dose) to prevent rheumatic fever 1
- Cystitis: 3 days TMP-SMX or 5 days nitrofurantoin sufficient
Age-Specific Considerations
- Children <3 years: Don't test/treat for GAS pharyngitis (rheumatic fever rare) 1
- Children <8 years: Avoid tetracyclines (tooth staining) 6, 8
- Neonates <6 weeks: Avoid erythromycin (pyloric stenosis risk) 8
- Age >60: ↑ fluoroquinolone tendon rupture risk, especially with steroids 7
Black Box Warning Priorities
- Fluoroquinolones: Tendon rupture, peripheral neuropathy, aortic dissection, myasthenia exacerbation—reserve for serious infections 7
- TMP-SMX: Stevens-Johnson syndrome/TEN—monitor for rash 6
- Clindamycin: C. difficile colitis (highest oral risk) 6
- Linezolid: Myelosuppression—monitor CBC weekly if >2 weeks 6
- Nitrofurantoin: Pulmonary fibrosis (chronic use), peripheral neuropathy—both irreversible 2
Common Pitfalls
- Don't use ciprofloxacin for CAP or pharyngitis: Inadequate S. pneumoniae/GAS coverage
- Don't use nitrofurantoin for pyelonephritis: Inadequate tissue levels (cystitis only)
- Don't use oral cephalosporins for step-down from IV: Prefer amoxicillin-clavulanate 7
- Don't use daptomycin for pneumonia: Inactivated by surfactant 6
- Don't combine clindamycin + erythromycin: Antagonism 6
- Macrolide resistance in GAS varies geographically: Check local patterns 1
Drug Interaction Priorities
- Warfarin: ↑ INR with most antibiotics (especially TMP-SMX, macrolides, fluoroquinolones)—monitor INR closely
- Statins + macrolides/fluoroquinolones: ↑ rhabdomyolysis risk—consider holding statin
- Oral contraceptives: May ↓ efficacy with rifampin (significant), possibly tetracyclines—use backup method
- Chelation (fluoroquinolones, tetracyclines): Separate from antacids, calcium, iron, magnesium by 2-6 hours
- QT prolongation: Macrolides + fluoroquinolones + other QT drugs = torsades risk
Resistance Considerations
- S. pneumoniae: High-dose amoxicillin (1 g TID or 2 g BID) overcomes resistance 3
- E. coli (cystitis): ~20% TMP-SMX resistance, but still preferred over fluoroquinolones 10
- MRSA: Community-acquired strains usually susceptible to TMP-SMX, doxycycline, clindamycin (check D-test) 6
- GAS macrolide resistance: Varies by region—penicillin remains 100% susceptible 1
Cost-Effectiveness
- Generic penicillins/amoxicillin: <$10 for 10-day course 11
- Amoxicillin-clavulanate: ~$15-30 11
- Azithromycin Z-Pak: ~$10-20 (generic)
- Fluoroquinolones: ~$10-50 (generic)
- Linezolid: ~$2,000-3,000 for 10-day course (reserve for documented need) 6
Documentation Requirements
- Always document: Allergy type (immediate vs. delayed), recent antibiotic use (<1 month), comorbidities, symptom duration
- Justify broad-spectrum use: Document risk factors (recent antibiotics, comorbidities, treatment failure, resistance concerns)
- No clinical justification in ~30% of prescriptions: Ensure diagnosis supports antibiotic use 12
This table synthesizes current IDSA, BTS, ATS, Canadian, and WHO guidelines 1, 7, 5, 3, 7, 5, 6, 8, 9, 4 with emphasis on outpatient primary care management. Always consider local resistance patterns, patient-specific factors, and guideline updates when prescribing.