Many bacteria are capable of producing ß-lactamase, an enzyme which breaks the ß-lactam ring, rendering the antibiotic ineffective

Simplified diagram to show break in ß-lactam ring

ß-lactamase producing bacteria are widely prevalent and include

- Staphyloccus aureus (especially notorious)
- Haemophilus influenzae
- Escherichia coli
- Proteus spp.
- Salmonella spp.
- Bacteroides
- Neisseria spp.
- And others

Hence ß-lactamase induced resistance is an important problem

Ampicillin

- a penicillin - one of the greatest drugs ever, with time tested efficacy and safety
- broad spectrum coverage of bacteria causing day-to-day infections

But…...

inactivated by ß-lactamase

The Need...

- An antibiotic which covers both
ß-lactamase- producing and
non-ß-lactamase-producing bacteria

- With time tested efficacy and safety of penicillins

 

Ampicillin + Cloxacillinmeets the need!

- 2 time-tested penicillins known for their efficacy and safety

-ß-lactamase stability of cloxacillin makes it an appropriate companion to ampicillin

- coverage against both ß-lactamase-producing and non-ß-lactamase-producing bacteria

Ampicillin + Cloxacillin

Broad spectrum combination for day-to-day infections, particularly situations where Staph. aureus may be involved, and in mixed infections

Ampicillin

- Aminopenicillin, possesses broad spectrum coverage against gram +ve and gram -ve bacteria

- Acts by inhibition of bacterial cell wall synthesis

- Bactericidal effect

- Covers streptococci, H.influenzae, E. coli, Salmonella, Shigella, Proteus mirabilis, Neisseria

- Inactivated by bacterial ß-lactamase

 

Cloxacillin

- Isoxazolyl penicillin, possesses narrow spectrum coverage chiefly against gram +ve bacteria, especially staphylococci (drug of choice against Staph. aureus)

- Stable against many bacterial ß-lactamases

- Acts by inhibition of bacterial cell wall synthesis

- Bactericidal effect

- Covers staphylococci (inhibits ß-lactamase and also bactericidal against staphylococci), some streptococci and Neisseria

Ampicillin + cloxacillin suited for combination because

- They act synergistically in combination

- Similar pharmacokinetic profile (both administered 6 hourly)

- Chemically compatible for combination - No drug interactions

Benefits of combination

Synergism
* antibacterial effect against organisms not covered by either drug alone (lower MIC makes same tissue concentration more effective)
* wider spectrum
* efficacy in lower doses
* greater efficacy

ß-lactamase inhibition
* Cloxacillin is resistant to staphylococcal beta-lactamase and also inhibits ß-lactamases produced by other bacteria, thus permitting ampicillin to act

Indications

Ampicillin + Cloxacillin is indicated when broad spectrum coverage involving these two antibiotics is required:

- Empiric therapy when the causative organism is unknown
- When Staph. aureus is a likely causative orrganism- Mixed infections

Indications

- Respiratory Tract infections
pharyngitis, tonsillitis, sinusitis, otitis media, bronchitis, pneumonia
- Skin & Soft Tissue infections
furunculosis, carbuncle, abscesses, paronychia, pyoderma, traumatic/surgical wound infection
- Bone & Joint Infections
osteomyelitis, septic arthritis, surgical infections

Dosage & Administration

Adults
Amp 250+Clox250 capsules / injections 1-2 capsules 3-4 times daily

Children
15-50 mg of each ingredient/kg body weight/day

Tolerability

Possesses the well-known safety of penicillins.Relatively commoner adverse effects, if any, include skin rash, G.I. effects such as diarrhoea and drug hypersensitivity. Safe in children, pregnancy & lactation

Contraindications

Hypersensitivity to penicillins

Salient Features of Amp+Clox

- Combination of 2 time tested, effective and safe penicillins
- Synergistic combination
- Broad spectrum coverage of ß-lactamase producing and non ß-lactamase producing bacteria
- Pharmacokinetically and chemically compatible combination
- Oral and parenteral use
- Suitable for day-to-day infections
- For empiric therapy and mixed infections
- ENT/RTI, Skin & Soft Tissue infection, Bone & Joint Infection

 

 

Advantages over Fluoroquinolones
(Ciprofloxacin, Norfloxacin, Sparfloxacin, Pefloxacin)

- Norfloxacin poorly distributed in the body; chiefly used for GI and urogenital infections
- Ciprofloxacin mainly effective against gram -ve bacteria; poor efficacy in staphylococcal and streptococcal infections in day-to-day practice
- Sparfloxacin is needlessly expensive for common infections
- Pefloxacin associated with adverse effects

 

Advantages over Macrolides
(Erythromycin, Roxithromycin, Azithromycin)

- Macrolides are chiefly effective against gram positive organisms, Amp+Clox has broad spectrum coverage involving gm +ve and gm -ve organisms
- Even against gm +ve bacteria, cloxacillin is a drug of choice
- Antibacterial spectrum of macrolides is similar to
each other; pharmacokinetics differ

Advantages over Oral Cephalosporins
(Cephalexin, Cefadroxil, Cefaclor)

- Oral cephalosporins are generally not the drugs of first choice for most infections; ampicillin and cloxacillin have been first line drugs in many infections
- Oral cephalosporins are costly for day-to-day infections

Advantages over Tetracyclines
(Tetracycline, Doxycycline)

- Bacterial resistance is common to tetracyclines
- Tolerability profile is poorer than penicillins
- Cannot be administered to children and pregnant women due to adverse effects on developing bones and teeth

Advantages over SMX-TMP
(Sulfamethoxazole-Trimethoprim)

- Resistance to sulphonamides is widespread; often only one ingredient is actually working
- Optimum tissue concentration ratio of 1:20 is not obtained hence loss of synergistic activity
- Sulphonamides are associated with serious adverse effects including blood dyscrasias