What are ampicillin and cloxacillin used for?

Ampicillin and Cloxacillin: Clinical Uses

Ampicillin and cloxacillin are used together to provide broad-spectrum coverage against both Gram-positive organisms (particularly staphylococci) and Gram-negative bacteria, making this combination particularly valuable for mixed infections where both pathogen types are suspected.

Primary Clinical Indications

Skin and Soft Tissue Infections

Cloxacillin is a first-choice agent for mild skin and soft tissue infections caused by staphylococci, including methicillin-susceptible Staphylococcus aureus. 1 The WHO Essential Medicines List designates cloxacillin as an Access group antibiotic for these infections, noting that any intravenous anti-staphylococcal penicillin is appropriate, though oral formulations like dicloxacillin and flucloxacillin have better bioavailability. 1

• For diabetic wound infections (mild): Dicloxacillin (a cloxacillin analog) is recommended as a first-line option. 1
• For incisional surgical site infections: Oxacillin or nafcillin (cloxacillin equivalents) are recommended first-line agents. 1
• Clinical data demonstrates that S. aureus shows 93% sensitivity to cloxacillin but 89.5% resistance to ampicillin alone, supporting the rationale for combination therapy in mixed infections. 2

Neonatal and Pediatric Sepsis

Ampicillin combined with gentamicin (not cloxacillin) is the standard first-choice regimen for neonatal sepsis. 1 However, amikacin plus cloxacillin represents a second-choice combination when first-line therapy fails or resistance is suspected. 1

• Ampicillin provides coverage against Group B Streptococcus and Listeria monocytogenes, critical neonatal pathogens. 1
• Cloxacillin in this context targets staphylococcal infections. 1

Moderate to Severe Diabetic Wound Infections

Ampicillin-sulbactam (which combines ampicillin with a beta-lactamase inhibitor) is recommended for moderate to severe diabetic wound infections, suggesting that ampicillin's Gram-negative coverage is valuable when combined with anti-staphylococcal protection. 1

Ampicillin-Specific Indications

FDA-Approved Uses

Ampicillin alone is indicated for infections of the genitourinary tract (including gonorrhea), respiratory tract, gastrointestinal tract, and meningitis caused by susceptible organisms. 3

• Genitourinary infections: E. coli, Proteus mirabilis, enterococci, Shigella, Salmonella, and non-penicillinase-producing N. gonorrhoeae. 3
• Respiratory infections: Non-penicillinase-producing H. influenzae, staphylococci, and streptococci including S. pneumoniae. 3
• Gastrointestinal infections: Shigella, Salmonella, E. coli, P. mirabilis, and enterococci. 3
• Meningitis: N. meningitidis. 3

Enterococcal Infections

Ampicillin is the drug of choice for ampicillin-susceptible enterococcal catheter-related bloodstream infections. 1 Vancomycin should only be used if the pathogen is ampicillin-resistant. 1

Combination Therapy Rationale

Synergistic Activity

The combination of ampicillin and cloxacillin demonstrates in vitro synergism against certain ampicillin-resistant Gram-negative bacteria at concentrations where neither agent alone is effective. 4

• Studies show that 7 of 23 ampicillin-resistant E. coli strains (MBC 128 μg/mL) were killed by combinations containing 4-32 μg/mL ampicillin plus 16-32 μg/mL cloxacillin. 4
• Synergism was also demonstrated in Enterobacter, Serratia, Klebsiella, and Pseudomonas species. 4
• Peak serum levels after standard IV dosing (ampicillin 56 mg/kg, cloxacillin 14 mg/kg) achieve concentrations of 235 μg/mL and 85 μg/mL respectively, well above synergistic thresholds. 4

Clinical Applications of Combination

The ampicillin-cloxacillin combination has limited routine use except for cellulitis and infected eczemas where both Gram-positive and Gram-negative coverage is needed. 2

• In primary pyodermas (impetigo, folliculitis, furuncles), cloxacillin alone should be first-line. 2
• Secondary pyodermas (infected ulcers, infected eczema) have higher rates of Gram-negative organisms and mixed infections, justifying combination therapy. 2
• A cephalosporin may be preferred if single-drug therapy is desired for these mixed infections. 2

Important Clinical Considerations

Resistance Patterns

• S. aureus demonstrates 89.5% resistance to penicillin and ampicillin but maintains 93% sensitivity to cloxacillin. 2
• Methicillin-resistant S. aureus (MRSA) strains are resistant to cloxacillin and require vancomycin, linezolid, or daptomycin. 1
• Erythromycin resistance in S. aureus is 18.7%, making it a less reliable alternative. 2

Surgical Prophylaxis

Dicloxacillin (a cloxacillin analog) demonstrated superior outcomes compared to ampicillin in total hip replacement prophylaxis, with zero infections versus three staphylococcal infections in the ampicillin group. 5 This supports using anti-staphylococcal penicillins over ampicillin for surgical prophylaxis where staphylococci are the primary concern.

Adverse Effects

• Ampicillin causes more side effects than cloxacillin: 12 cases versus 1 case in comparative studies. 6
• Ampicillin commonly causes gastrointestinal disturbances and has a high incidence of rash, particularly when combined with allopurinol. 3
• Both agents are excreted in breast milk and should be used cautiously in nursing mothers. 3

Administration Considerations

• Ampicillin should be taken with a full glass of water, one-half hour before or two hours after meals for optimal absorption. 3
• False-positive glucose tests may occur with copper sulfate methods (Benedict's, Fehling's, Clinitest) but not enzyme-based tests. 3