Therapeutic uses of Amoxicillin
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Therapeutic Uses of Amoxicillin
Amoxicillin is an aminopenicillin (extended-spectrum penicillin) with excellent oral bioavailability. It shares a similar antibacterial spectrum with ampicillin but is significantly better absorbed orally. It acts by inhibiting bacterial cell wall synthesis (binding to penicillin-binding proteins, PBPs). Below are its major therapeutic applications.
Mechanism & Spectrum
Amoxicillin covers a broad range of organisms:
- Gram-positive: Streptococcus spp., Enterococcus spp. (susceptible strains), Listeria monocytogenes, non-beta-lactamase-producing Staphylococci
- Gram-negative: H. influenzae (non-beta-lactamase producing), E. coli (susceptible), Salmonella spp., Helicobacter pylori
- Others: Treponema pallidum, Borrelia burgdorferi (Lyme disease agent)
It is NOT effective against beta-lactamase-producing organisms unless combined with clavulanate.
(Katzung's Basic and Clinical Pharmacology, 16th Ed.)
1. Upper Respiratory Tract Infections
| Infection | Role of Amoxicillin |
|---|---|
| Acute Otitis Media (AOM) | First-line agent per AAP 2013 guidelines: 80-90 mg/kg/day in 2 divided doses |
| Acute Bacterial Sinusitis | First-line antibiotic for mild-moderate community-acquired disease |
| Streptococcal Pharyngitis | Effective alternative to phenoxymethylpenicillin (penicillin V); once-daily dosing studied |
| Acute Epiglottitis | Used in susceptible H. influenzae infections |
(Cummings Otolaryngology, Murray & Nadel's Respiratory Medicine)
2. Lower Respiratory Tract Infections
- Community-Acquired Pneumonia (CAP): Oral amoxicillin is the mainstay for mild-moderate CAP caused by S. pneumoniae; used as part of combination regimens for moderate disease (with clarithromycin)
- Amoxicillin and ampicillin are the preferred beta-lactams for penicillin-resistant pneumococcal infections (elevated MICs) because of their enhanced activity vs. other oral beta-lactams
- Chronic Obstructive Pulmonary Disease (COPD) exacerbations: Used in susceptible non-beta-lactamase-producing strains
(Murray & Nadel's Textbook of Respiratory Medicine)
3. Helicobacter pylori Eradication (Peptic Ulcer Disease)
Amoxicillin is a core component of H. pylori eradication regimens:
- Classic Triple Therapy: PPI + Amoxicillin + Clarithromycin (7-14 days)
- PPI + Amoxicillin + Metronidazole: Used when clarithromycin resistance is suspected or as rescue therapy
- Quadruple/Rescue Therapy: PPI + Amoxicillin + Clarithromycin + Bismuth, or sequential regimens
Eradication is strongly indicated in H. pylori-positive peptic ulcer disease for sustained ulcer healing.
(Tintinalli's Emergency Medicine; Mulholland & Greenfield's Surgery; Red Book 2021)
4. Urinary Tract Infections (UTIs)
- Historically used for uncomplicated UTIs caused by susceptible E. coli and Enterococcus
- Caution: Due to widespread beta-lactamase production among gram-negative bacilli, amoxicillin alone is no longer recommended for empirical UTI therapy in many regions
- Amoxicillin-clavulanate (co-amoxiclav) is preferred when beta-lactamase-producers are suspected
5. Skin and Soft Tissue Infections
- Effective against streptococcal cellulitis and impetigo caused by non-beta-lactamase-producing organisms
- Typically given as 250-500 mg three times daily
6. Lyme Disease (Borrelia burgdorferi)
- Drug of choice (along with doxycycline and cefuroxime axetil) for early Lyme disease - both localized and disseminated
- Dosing: 14-21 days for early infection
- Doxycycline may be slightly more effective at preventing late manifestations, but amoxicillin is the preferred agent in children <8 years and in pregnant women (where doxycycline is contraindicated)
(Jawetz, Melnick & Adelberg's Medical Microbiology, 28th Ed.)
7. Infective Endocarditis Prophylaxis
Standard dental and respiratory procedure prophylaxis (for patients with high-risk cardiac conditions):
- Amoxicillin 2 g PO, 1 hour before the procedure (standard regimen)
- Indicated before dental extractions, periodontal/endodontic procedures, teeth cleaning, tonsillectomy, and surgery on respiratory mucosa
- Unable to take oral medication: Ampicillin 2 g IM/IV
- Penicillin-allergic patients: Use clindamycin, azithromycin, or clarithromycin
(Washington Manual of Medical Therapeutics; Harriet Lane Handbook, 23rd Ed.; Lippincott Illustrated Reviews: Pharmacology)
8. Typhoid Fever & Salmonellosis
- Oral amoxicillin is an alternative for typhoid fever caused by susceptible Salmonella typhi strains (though fluoroquinolones and third-generation cephalosporins have largely replaced it due to resistance)
9. Genitourinary & Other Infections
- Gonorrhea (Neisseria gonorrhoeae): Historically used; now largely replaced due to resistance
- Listeria monocytogenes meningitis: IV ampicillin preferred; oral amoxicillin used for continuation therapy
- Anthrax post-exposure prophylaxis: Oral amoxicillin is an alternative in pregnant women and children when ciprofloxacin is not preferred
10. Amoxicillin-Clavulanate (Co-amoxiclav / Augmentin) Extended Indications
When combined with clavulanic acid (a beta-lactamase inhibitor), the spectrum is significantly expanded:
| Infection | Notes |
|---|---|
| Bite wounds (animal/human) | Drug of choice |
| Acute sinusitis with risk factors | Beta-lactamase-producing H. influenzae / M. catarrhalis |
| Recurrent/complicated AOM | Especially after amoxicillin failure |
| Aspiration pneumonia | Covers oral anaerobes |
| Complicated UTIs | Covers beta-lactamase-producing E. coli |
| Diabetic foot infections (mild) | Covers polymicrobial flora |
(Harriet Lane Handbook; Katzung's Pharmacology)
Key Dosing Summary
| Indication | Adult Dose | Pediatric Dose |
|---|---|---|
| Mild-moderate infections | 250-500 mg TID | 25-50 mg/kg/day |
| Severe infections / AOM | 500-875 mg TID or BID | 80-90 mg/kg/day |
| H. pylori triple therapy | 1 g BID (with PPI + clarithromycin) | - |
| Endocarditis prophylaxis | 2 g PO 1 hr before procedure | 50 mg/kg |
| Lyme disease (early) | 500 mg TID x 14-21 days | 50 mg/kg/day TID |
Important Limitations
- Beta-lactamase-producing organisms (MRSA, many E. coli, Klebsiella, H. influenzae) are resistant - use amoxicillin-clavulanate or other agents
- Hypersensitivity: Penicillin allergy (5-8% report it; true anaphylaxis <0.01%); cross-reactivity with cephalosporins is low (~1-2%)
- Not effective against: Pseudomonas aeruginosa, Enterobacter spp., Klebsiella spp. (intrinsic beta-lactamase producers)
- Widespread use has driven resistance, particularly among H. influenzae, E. coli, and S. pneumoniae strains
Difference between therapeutic uses of benzyl penicliin and Amoxicillin
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Benzylpenicillin (Penicillin G) vs. Amoxicillin - Therapeutic Uses Compared
Both are beta-lactam antibiotics that inhibit bacterial cell wall synthesis, but they differ fundamentally in their spectrum, route of administration, bioavailability, and hence their clinical indications.
Key Pharmacological Differences (Foundation for Use Differences)
| Property | Benzylpenicillin (Penicillin G) | Amoxicillin |
|---|---|---|
| Class | Natural penicillin | Aminopenicillin (semi-synthetic, extended-spectrum) |
| Route | IV / IM only (acid-labile, destroyed by gastric acid) | Oral (acid-stable, excellent bioavailability ~80%) |
| Spectrum | Narrow - mainly Gram-positive + anaerobes | Broader - Gram-positive + selected Gram-negative |
| Gram-negative coverage | Very limited (no enteric GNRs) | Extended: H. influenzae, E. coli, Salmonella, H. pylori |
| Beta-lactamase stability | Destroyed by any beta-lactamase | Also destroyed - but can be combined with clavulanate |
| Oral alternative | Penicillin V (but narrow and poor bioavailability) | Amoxicillin itself IS the oral agent |
(Katzung's Basic and Clinical Pharmacology, 16th Ed.; Jawetz, Melnick & Adelberg's Medical Microbiology, 28th Ed.)
Therapeutic Uses - Side by Side
1. Streptococcal Infections
| Indication | Benzylpenicillin | Amoxicillin |
|---|---|---|
| Streptococcal pharyngitis | Drug of choice - Benzathine Pen G 1.2 MU IM single dose | Alternative (often preferred orally) |
| Rheumatic fever prophylaxis | Benzathine Pen G 1.2 MU IM every 3-4 weeks | Alternative if parenteral not feasible |
| Severe streptococcal sepsis | First choice - IV Pen G 4-24 MU/day | Not used (no IV form) |
| Streptococcal cellulitis (mild) | Not practical (requires IV) | Oral amoxicillin used |
Penicillin G remains the definitive drug of choice for serious streptococcal infections given its proven efficacy and narrow, targeted spectrum. Amoxicillin covers the same organisms orally.
2. Pneumococcal Infections
| Indication | Benzylpenicillin | Amoxicillin |
|---|---|---|
| Pneumococcal meningitis (susceptible strains) | Drug of choice - high-dose IV Pen G | Not used |
| Community-acquired pneumonia (mild-moderate) | Not practical orally | First-line oral agent (preferred over penicillin V) |
| Penicillin-resistant pneumococcal infections | Less effective (needs very high doses) | Preferred oral beta-lactam - higher MIC coverage than penicillin V |
Amoxicillin is the preferred oral beta-lactam for pneumococcal pneumonia, including strains with elevated MICs to penicillin, because it achieves higher serum concentrations than oral penicillin V.
3. Meningococcal Disease
| Benzylpenicillin | Amoxicillin |
|---|---|
| Drug of choice - IV high-dose for meningococcal meningitis and septicaemia | No role |
Benzylpenicillin is irreplaceable here - IV administration is mandatory and the narrow spectrum is ideal for susceptible N. meningitidis.
4. Syphilis (Treponema pallidum)
| Benzylpenicillin | Amoxicillin |
|---|---|
| Drug of choice - Benzathine Pen G 2.4 MU IM weekly x 1-3 doses | No standard role |
Treponema pallidum remains exquisitely sensitive to penicillin G. There is no proven oral substitute.
5. H. influenzae Infections (Otitis Media, Sinusitis, Pneumonia)
| Benzylpenicillin | Amoxicillin |
|---|---|
| No role - H. influenzae is not covered by benzylpenicillin | First-line for non-beta-lactamase-producing strains |
| Amoxicillin-clavulanate for beta-lactamase-producing strains |
This is a major advantage of amoxicillin. The extended Gram-negative spectrum picks up H. influenzae, the key pathogen in AOM, sinusitis, and CAP.
6. Helicobacter pylori Eradication
| Benzylpenicillin | Amoxicillin |
|---|---|
| No role | Core component of all standard regimens: PPI + Amoxicillin + Clarithromycin (triple therapy); also in quadruple/rescue regimens |
Completely exclusive to amoxicillin.
7. Lyme Disease (Borrelia burgdorferi)
| Benzylpenicillin | Amoxicillin |
|---|---|
| IV penicillin G used for late/severe Lyme (e.g., Lyme carditis, neuroborreliosis) | Drug of choice for early Lyme disease orally (14-21 days); preferred in children <8 yrs and pregnancy |
8. Clostridial Infections (Gas Gangrene, Tetanus, Botulism)
| Benzylpenicillin | Amoxicillin |
|---|---|
| Drug of choice - IV Pen G for gas gangrene (C. perfringens), tetanus (C. tetani) | No standard role |
High-dose IV benzylpenicillin is essential for life-threatening clostridial infections.
9. Actinomycosis (Actinomyces israelii)
| Benzylpenicillin | Amoxicillin |
|---|---|
| Drug of choice - high-dose IV Pen G for 4-6 weeks | Used orally as step-down/continuation therapy |
10. Enterococcal Endocarditis
| Benzylpenicillin | Amoxicillin |
|---|---|
| IV Pen G + aminoglycoside (synergistic combination) | IV ampicillin/amoxicillin + aminoglycoside preferred |
Both cover enterococci but require combination with an aminoglycoside for bactericidal effect. Ampicillin/amoxicillin are marginally preferred over Pen G for enterococcal endocarditis.
11. Endocarditis Prophylaxis (Dental / Respiratory Procedures)
| Benzylpenicillin | Amoxicillin |
|---|---|
| IM/IV form used if patient cannot take oral | Standard oral prophylaxis: Amoxicillin 2 g PO 1 hour before procedure |
Amoxicillin has largely replaced other penicillins for prophylaxis due to its superior oral bioavailability.
12. Urinary Tract Infections
| Benzylpenicillin | Amoxicillin |
|---|---|
| No role | Historically used for susceptible E. coli and Enterococcus; now limited by widespread resistance. Empirical use not recommended in most regions |
Summary Table: Exclusive & Shared Uses
| Indication | Benzylpenicillin Only | Amoxicillin Only | Shared/Either |
|---|---|---|---|
| Meningococcal meningitis/sepsis | ✓ | ||
| Syphilis | ✓ | ||
| Gas gangrene / Clostridial infections | ✓ | ||
| H. pylori eradication | ✓ | ||
| AOM, bacterial sinusitis | ✓ | ||
| H. influenzae infections | ✓ | ||
| Lyme disease (early, oral) | ✓ | ||
| Endocarditis prophylaxis (dental) | ✓ | ||
| Streptococcal pharyngitis (oral) | ✓ | ||
| Serious streptococcal sepsis (IV) | ✓ | ||
| Rheumatic fever prophylaxis (IM) | ✓ | ||
| Actinomycosis | ✓ (initial) | ✓ (step-down) | |
| Pneumococcal pneumonia | ✓ (IV, severe) | ✓ (oral, mild-mod) |
One-Line Summary
Benzylpenicillin (Pen G) is the gold standard for serious, parenteral treatment of narrow-spectrum Gram-positive and anaerobic infections (meningococcus, streptococcus, syphilis, clostridia) where IV/IM delivery is needed.
Amoxicillin extends this coverage orally and into the Gram-negative world (H. influenzae, H. pylori, E. coli) - making it the workhorse for community-acquired respiratory, GI, and dental infections managed in outpatient settings.
(Katzung's Basic and Clinical Pharmacology, 16th Ed.; Jawetz, Melnick & Adelberg's Medical Microbiology, 28th Ed.)
Compare amoxicillin-clavulanate vs. amoxicillin alone
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I now have excellent material from Goodman & Gilman's and the other sources. Let me compile the comprehensive comparison.
Amoxicillin-Clavulanate (Co-amoxiclav) vs. Amoxicillin Alone
The Core Concept: Why Add Clavulanate?
Many bacteria produce beta-lactamases - enzymes that hydrolyse the beta-lactam ring of amoxicillin, rendering it inactive. Clavulanic acid is a beta-lactamase inhibitor - it has minimal intrinsic antibacterial activity of its own, but it irreversibly binds and inactivates bacterial beta-lactamases, "shielding" amoxicillin and restoring its activity against resistant organisms.
Clavulanate specifically inhibits: Class A (Bush group 1) serine beta-lactamases, including TEM-type, SHV-type, and staphylococcal beta-lactamases. It does NOT inhibit AmpC (class C) or metallo-beta-lactamases (class B).
(Goodman & Gilman's Pharmacological Basis of Therapeutics; Tietz Laboratory Medicine, 7th Ed.)
Spectrum Comparison
| Organism | Amoxicillin Alone | Amoxicillin-Clavulanate |
|---|---|---|
| Streptococcus spp. | ✓ | ✓ |
| Penicillin-susceptible Pneumococci | ✓ | ✓ |
| Enterococci (E. faecalis) | ✓ | ✓ (clavulanate adds little here - resistance via PBP changes) |
| MSSA (non-beta-lactamase) | ✓ | ✓ |
| MSSA (beta-lactamase producing) | ✗ | ✓ |
| MRSA | ✗ | ✗ |
| H. influenzae (non-beta-lactamase) | ✓ | ✓ |
| H. influenzae (beta-lactamase producing, ~20-40%) | ✗ | ✓ |
| Moraxella catarrhalis (universally beta-lactamase producing) | ✗ | ✓ |
| E. coli (susceptible) | ✓ | ✓ |
| E. coli (beta-lactamase producing, 30-60%) | ✗ | ✓ |
| Klebsiella pneumoniae | ✗ | ✓ (many strains) |
| Proteus mirabilis (beta-lactamase producing) | ✗ | ✓ |
| Bacteroides fragilis (anaerobe) | ✗ | ✓ |
| Staphylococcus aureus (beta-lactamase producing) | ✗ | ✓ |
| Pseudomonas aeruginosa | ✗ | ✗ |
| ESBL-producing Enterobacterales | ✗ | ✗ |
| AmpC-producing organisms (Enterobacter, Serratia) | ✗ | ✗ |
(Goodman & Gilman's, 16th Ed.)
Therapeutic Uses - Detailed Comparison
1. Acute Otitis Media (AOM)
| Amoxicillin | Amoxicillin-Clavulanate | |
|---|---|---|
| First-line | Yes - 80-90 mg/kg/day (AAP guideline) | Second-line |
| When to switch to co-amoxiclav | - | Failure after 48-72 hrs on amoxicillin; recurrent AOM; recent antibiotic exposure; concurrent conjunctivitis (suggests beta-lactamase-producing H. influenzae or Moraxella) |
Rationale: Most AOM is caused by S. pneumoniae (covered by amoxicillin), but when H. influenzae or Moraxella catarrhalis (both beta-lactamase producers) are suspected, clavulanate is needed.
2. Acute Bacterial Sinusitis
| Amoxicillin | Amoxicillin-Clavulanate | |
|---|---|---|
| Mild, no risk factors | First-line | Alternative |
| Moderate/severe, prior antibiotics, day-care attendance | - | Preferred (covers beta-lactamase-producing H. influenzae and Moraxella) |
| Frontal/sphenoid sinusitis (risk of complications) | - | Preferred |
3. Community-Acquired Pneumonia (CAP)
| Amoxicillin | Amoxicillin-Clavulanate | |
|---|---|---|
| Mild CAP, low-risk, typical pathogens | First-line (1 g every 8 hrs) | Alternative |
| CAP with aspiration risk | No | Yes - adds anaerobic coverage (B. fragilis, oral anaerobes) |
| CAP post-influenza (S. aureus risk) | No (beta-lactamase-producing MSSA) | Yes |
4. Urinary Tract Infections (UTIs)
| Amoxicillin | Amoxicillin-Clavulanate | |
|---|---|---|
| Uncomplicated UTI (E. coli) | Limited - high resistance rates (30-60% E. coli); NOT recommended empirically | Broader coverage - preferred when aminopenicillin use is warranted |
| Enterococcal UTI | Yes (clavulanate adds little against Enterococcus) | Yes |
| Complicated UTI / pyelonephritis | Not preferred | Reasonable oral option with susceptibility data |
Note: For both agents, fluoroquinolones or trimethoprim-sulfamethoxazole generally achieve higher cure rates for cystitis. (Goodman & Gilman's)
5. Skin and Soft Tissue Infections (SSTIs)
| Amoxicillin | Amoxicillin-Clavulanate | |
|---|---|---|
| Streptococcal cellulitis | Yes | Yes (no added benefit over amoxicillin alone) |
| Animal bite wounds (dog, cat) | No | Drug of choice - covers Pasteurella multocida, oral anaerobes, Capnocytophaga, and skin flora |
| Human bite wounds | No | Drug of choice - covers Eikenella corrodens + oral flora |
| Diabetic foot infection (mild) | No | Yes - polymicrobial coverage |
| Impetigo / MSSA skin infection | No (beta-lactamase-producing staph) | Yes |
6. Intra-abdominal / Dental / Oropharyngeal Infections
| Amoxicillin | Amoxicillin-Clavulanate | |
|---|---|---|
| Dental abscess | Reasonable (oral streptococci) | Preferred - better anaerobic coverage of oral flora |
| Periodontitis | Adjunct | Preferred adjunct |
| Mild intra-abdominal infections (outpatient) | No | Yes - covers gut anaerobes including Bacteroides fragilis |
7. Respiratory Tract in Specific Contexts
| Amoxicillin | Amoxicillin-Clavulanate | |
|---|---|---|
| COPD exacerbation | Yes (mild) | Preferred when beta-lactamase-producing H. influenzae or Moraxella likely |
| Epiglottitis (H. influenzae) | Only if susceptible strain confirmed | Preferred empirically (Moraxella/beta-lactamase H. influenzae risk) |
8. H. pylori Eradication
| Amoxicillin | Amoxicillin-Clavulanate | |
|---|---|---|
| Triple therapy (PPI + amoxicillin + clarithromycin) | Yes - core component | Not used (clavulanate not needed; H. pylori susceptible to amoxicillin itself) |
9. Endocarditis Prophylaxis
| Amoxicillin | Amoxicillin-Clavulanate | |
|---|---|---|
| Standard dental prophylaxis | 2 g PO 1 hour before procedure | No advantage; amoxicillin alone is standard |
Shared Indications (Either Can Be Used)
- Streptococcal pharyngitis (amoxicillin preferred - narrower spectrum)
- Early Lyme disease (amoxicillin preferred)
- Mild community-acquired pneumonia
- Susceptible UTIs
Pharmacokinetic Properties Compared
| Property | Amoxicillin | Amoxicillin-Clavulanate |
|---|---|---|
| Oral bioavailability | ~80% | Broadly similar (pharmacokinetics of co-formulated agents similar to single agents) |
| Effect of food | Not significantly affected | Take WITH food (reduces GI side effects from clavulanate) |
| t½ (both components) | ~80 min | Amoxicillin ~80 min; Clavulanate ~60 min (broadly matched) |
| Protein binding | ~20% | Similar |
| Renal excretion | Primarily renal | Both primarily renal; dose adjust in renal impairment |
(Goodman & Gilman's Pharmacological Basis of Therapeutics)
Adverse Effects Compared
| Adverse Effect | Amoxicillin | Amoxicillin-Clavulanate |
|---|---|---|
| Diarrhoea / GI upset | Mild - less than ampicillin (better absorbed, less bowel residue) | More frequent - clavulanate disrupts gut flora and causes osmotic diarrhoea; major limiting factor |
| Cholestatic jaundice / hepatotoxicity | Rare | Higher risk - clavulanate-associated; reversible but can be severe; more common with prolonged/repeated courses in elderly |
| Nausea/vomiting | Mild | More frequent |
| Hypersensitivity (rash, urticaria, anaphylaxis) | Yes (class effect) | Yes (class effect; rash slightly more common than other penicillins) |
| Maculopapular rash with EBV/CMV | Yes (aminopenicillin class effect) | Yes |
| C. difficile colitis | Low risk | Higher risk with clavulanate due to broader spectrum disrupting normal flora |
Key clinical point: The GI side effects of clavulanate are dose-dependent. The 7:1 (amoxicillin:clavulanate) and 14:1 formulations were developed specifically to reduce clavulanate-related diarrhoea while maintaining efficacy.
(Goodman & Gilman's; Lippincott Illustrated Reviews: Pharmacology)
When NOT to Use Amoxicillin-Clavulanate
- When amoxicillin alone is sufficient (e.g., H. pylori, early Lyme, streptococcal pharyngitis, endocarditis prophylaxis) - avoid unnecessary clavulanate to reduce side effects and resist stewardship concerns
- MRSA infections - neither agent covers it
- Pseudomonas / AmpC-producing Enterobacter, Serratia - intrinsic resistance; clavulanate does not help
- ESBL-producing organisms - clavulanate at standard doses does not reliably cover these
Summary: Choose Amoxicillin When... vs. Co-amoxiclav When...
| Choose Amoxicillin Alone When... | Choose Amoxicillin-Clavulanate When... |
|---|---|
| Pathogen confirmed susceptible | Beta-lactamase-producing organism likely or confirmed |
| First-line AOM in children | AOM treatment failure / recurrence / conjunctivitis |
| H. pylori eradication (triple therapy) | Animal/human bite wounds |
| Early Lyme disease | Aspiration pneumonia or CAP with aspiration risk |
| Streptococcal pharyngitis | Diabetic foot infection (mild) |
| Endocarditis prophylaxis | Dental abscess / periodontal infection |
| Simple streptococcal cellulitis | Sinusitis after treatment failure / high-risk features |
| Stewardship-preferred narrow-spectrum | Polymicrobial or mixed aerobe-anaerobe infections |
(Goodman & Gilman's Pharmacological Basis of Therapeutics; Jawetz, Melnick & Adelberg's Medical Microbiology, 28th Ed.; Harrison's Principles of Internal Medicine, 22nd Ed.)
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