Ampicillin sulbactam microbiology
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Microbiology
Ampicillin is similar to benzyl penicillin in its bactericidal action against susceptible organisms during the stage of active multiplication. It acts through the inhibition of cell wall mucopeptide biosynthesis. Ampicillin has a broad spectrum of bactericidal activity against many gram-positive and gram-negative aerobic andanaerobic bacteria. (Ampicillin is, however, degraded by beta-lactamases, and therefore the spectrum of activity does not normally include organisms which produce these enzymes.) A wide range of beta-lactamases found in microorganisms resistant to penicillins and cephalosporins have been shown in biochemical studies with cell-free bacterial systems to be irreversibly inhibited by sulbactam. Although sulbactam alone possesses little useful antibacterial activity except against the Neisseriaceae, whole organism studies have shown that sulbactam restores ampicillin activity against beta-lactamase producing strains. In particular, sulbactam has good inhibitory activity against the clinically important plasmid mediated beta-lactamases most frequently responsible for transferred drug resistance. Sulbactam has no effect on the activity of ampicillin against ampicillin susceptible strains. The presence of sulbactam in the ampicillin/sulbactam formulation effectively extends the antibiotic spectrum of ampicillin to include many bacteria normally resistant to it and to other beta-lactam antibiotics. Thus, ampicillin/sulbactam possesses the properties of a broad-spectrum antibiotic and a beta-lactamase inhibitor.[1]
Susceptible Microorganisms
Gram-Positive Bacteria
- Staphylococcus aureus (beta-lactamase and non-beta-lactamase producing)
- Staphylococcus epidermidis (beta-lactamase and non-beta-lactamase producing)
- Staphylococcus saprophyticus (beta-lactamase and non-beta-lactamase producing)
- Streptococcus faecalis† (Enterococcus)
- Streptococcus pneumoniae† (formerly D. pneumoniae)
- Streptococcus pyogenes†
- Streptococcus viridans†
Gram-Negative Bacteria
- Escherichia coli (beta-lactamase and non-beta-lactamase producing)
- Hemophilus influenzae (beta-lactamase and non-beta-lactamase producing)
- Klebsiella species (all known strains are beta-lactamase producing)
- Moraxella catarrhalis (beta-lactamase and non-beta-lactamase producing)
- Morganella morganii
- Neisseria gonorrhoeae (beta-lactamase and non-beta-lactamase producing)
- Proteus mirabilis (beta-lactamase and non-beta-lactamase producing)
- Proteus vulgaris
- Providencia rettgeri
- Providencia stuartii
Anaerobes
- Bacteroides species, including B. fragilis
- Clostridium species†
- Peptococcus species†
- Peptostreptococcus species
† These are not beta-lactamase producing strains and, therefore, are susceptible to ampicillin alone.
Susceptibility Testing
Diffusion Technique
For the disk diffusion method of susceptibility testing, a 20 mcg (10 mcg ampicillin + 10 mcg sulbactam) disk should be used. The standardized procedure requires the use of a standardized inoculum concentration. With this procedure, a report from the laboratory of "Susceptible" indicates that the infecting organism is likely to respond to UNASYN therapy and a report of "Resistant" indicates that the infecting organism is not likely to respond to therapy. An "Intermediate" susceptibility report suggests that the infecting organism would be susceptible to UNASYN if a higher dosage is used or if the infection is confined to tissues or fluids (e.g., urine) in which high antibiotic levels are attained.
Dilution Techniques
Broth, agar, microdilution or equivalent methods may be used to determine the minimal inhibitory concentration (MIC) value for susceptibility of bacterial isolates using standardized methods, inoculums and concentrations of ampicillin/sulbactam.
The recommended dilution method employs a constant ampicillin/sulbactam ratio of 2:1 in all tubes with increasing concentrations of ampicillin. MIC's are reported in terms of ampicillin concentration in the presence of sulbactam at a constant 2 parts ampicillin to 1 part sulbactam.
| Ranges | Resistant | Intermediate | Susceptible |
| Gram(-) and Staphylococcus | |||
| Bauer/Kirby Zone Sizes (mm) | ≤11 | 12–13 | ≥14 |
| MIC (mcg of ampicillin/mL) | ≥32 | 16 | ≤ 8 |
| Haemophilus influenzae | |||
| Bauer/Kirby Zone Sizes (mm) | ≤19 | — | ≥20 |
| MIC (mcg of ampicillin/mL) | ≥ 4 | — | ≤ 2 |
* The non-beta-lactamase producing organisms which are normally susceptible to ampicillin, such as Streptococci, will have similar zone sizes as for ampicillin disks.
† Staphylococci resistant to methicillin, oxacillin, or nafcillin must be considered resistant to UNASYN.
‡ The quality control cultures should have the following assigned daily ranges for ampicillin/sulbactam.
| Micro-organism | Strain | Disk Diffusion (mm) | MIC of Ampicillin/Sulbactam (mcg/mL) |
| Escherichia coli | ATCC 25922 | 20–25 | 2/1–8/4 |
| Staphylococcus aureus | ATCC 25923 | 29–37 | Not applicable |
| Escherichia coli | ATCC 35218 | 13–19 | 8/4–32/16 |
| Haemophilus influenzae | ATCC 49247 | 14–22 | 2/1–8/4 |
References
- ↑ "http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/050608s040lbl.pdf" (PDF). External link in
|title=(help)
Adapted from the FDA Package Insert.