Ampicillin/sulbactam

Ampicillin/sulbactam is a combination of the common concentrations in the body remain above the minimum
penicillin-derived antibiotic ampicillin and sulbactam, inhibitory concentration (MIC). The duration of expo-
an inhibitor of bacterial beta-lactamase. Two dierent sure will thus correspond to how much bacterial killing
forms of the drug exist. The rst, developed in 1987 will occur. Various studies have shown that, for maxi-
and marketed in the United States under the tradename mum bacterial killing, drug concentrations must be above
Unasyn, generic only outside of the United States, is an the MIC for 50-60% of the time for the penicillin group
intravenous antibiotic. The second, an oral form called of antibiotics. This means that longer durations of ade-
sultamicillin, is marketed under the trade name Ampic- quate concentrations are more likely to produce therapeu-
tam outside of the United States. And generic only in tic success. However, when ampicillin is given in com-
the United States, ampicillin/sulbactam is used to treat bination with sulbactam, regrowth of bacteria has been
infections caused by bacteria resistant to beta-lactam an- seen when sulbactam levels fall below certain concentra-
tibiotics. Sulbactam blocks the enzyme which breaks tions. As with many other antibiotics, under-dosing of
down ampicillin and thereby allows ampicillin to attack ampicillin/sulbactam may lead to resistance.[3]
and kill the bacteria. Ampicillin/sulbactam has poor absorption when given
orally.[2] The two drugs have similar pharmacokinetic
proles that appear unchanged when given together.
1 Chemistry Ampicillin and sulbactam are both hydrophilic antibiotics
and have a volume of distribution (Vd) similar to the vol-
Ampicillin sodium is derived from the basic peni- ume of extra-cellular body water. The volume that the
cillin nucleus, 6-aminopenicillanic acid. Its chemical drug distributes throughout in healthy patients is approxi-
name is monosodium (2S, 5R, 6R)6-[(R)2-amino- mately 0.2 liters per kilogram of body weight. Patients on
2-phenylacetamido]3,3-dimethyl-7-oxo-4-thia-1- hemodialysis, elderly patients, and pediatric patients have
azabicyclo[3.2.0]heptane-2-carboxylate. It has a shown a slightly increased volume of distribution. Us-
molecular weight of 371.39 grams and its chemical ing typical doses, ampicillin/sulbactam has been shown
formula is C16H18N3NaO4S.[1] Sulbactam sodium is to reach desired levels to treat infections in the brain,
[3]
also a derivative of 6-aminopenicillanic acid. Chemi- lungs, and abdominal tissues. Both agents have mod-
cally, it is known as either sodium penicillinate sulfone erate protein binding, reported at 38% for sulbactam and
or sodium (2S, 5R)3,3-dimethyl-7-oxo-4-thia-1- 28% for ampicillin.15,16 The half-life of ampicillin is
azabicyclo[3.2.0]heptane-2-carboxylate 4,4-dioxide. It approximately 1 hour, when used alone or in combina-
has a molecular weight of 255.22 grams and its chemical tion with sulbactam; therefore it will be completely elim-
formula is C8H10NNaO5S.[1] inated from a healthy person in around 5 hours. It is
eliminated primarily by the urinary system, with 75% ex-
Ampicillin/sulbactam is also used when the cause of
creted unchanged in the urine. Only small amounts of
an infection is not known (empiric therapy), such as
each drug were found to be excreted in the bile.[3] Ampi-
intra-abdominal infections, skin infections, pneumonia,
cillin/sulbactam should be given with caution in infants
and gynecologic infections. It is active against a wide
less than a week old and premature neonates. This is
range of bacterial groups, including Staphylococcus au-
due to the underdeveloped urinary system in these pa-
reus, Enterobacteriaceae, and anaerobic bacteria. Impor-
tients, which can cause a signicantly increased half-
tantly, it is not active against Pseudomonas aeruginosa
life for both drugs.16 Based on its elimination, ampi-
and should not be used alone when infection with this or-
cillin/sulbactam is typically given every 6 to 8 hours.
ganism is suspected or known.
Slowed clearance of both drugs has been seen in the el-
derly, renal disease patients, and critically ill patients on
renal replacement therapy. Reduced clearance has been
2 Pharmacodynamics/Pharmacokinetics seen in both pediatric and post-operative patients. Ad-
justments in dosing frequency may be required in these
[3]
The addition of sulbactam to ampicillin enhances the patients due to these changes.
eects of ampicillin. This increases the antimicrobial
activity by 4- to 32-fold when compared to ampicillin
alone.[2] Ampicillin is a time-dependent antibiotic. Its
bacterial killing is largely related to the time that drug

1
2 6 FORMULATION

3 Mechanism of Action (all known species are beta-lactamase producing),

Proteus mirabilis (beta-lactamase and non-beta-
Ampicillin/sulbactam is a combination of a -lactam an- lactamase producing), Proteus vulgaris, Providencia
tibiotic and a -lactamase inhibitor. Ampicillin works rettgeri, Providencia stuartii, Morganella morganii,
by binding to penicillin-binding proteins (PBPs) to in- and Neisseria gonorrhoeae (beta-lactamase and
hibit bacterial cell wall synthesis.[2][3] This causes dis- non-beta-lactamase producing).[1][6]
ruption of the bacterial cell wall and leads to bacte-
Anaerobes: Clostridium species, Peptococcus
rial cell death. However, resistant pathogens may pro-
species, Peptostreptococcus species, Bacteroides
duce -lactamase enzymes that can inactivate ampicillin
species including B. fragilis.[1][6]
through hydrolysis.[3] This is prevented by the addition
of sulbactam, which binds and inhibits the -lactamase
enzymes.[2][3] It is also capable of binding to the PBP of Gynecological Infections Ampicillin/sulbactam can be
Bacteroides fragilis and Acinetobacter spp., even when it used to treat gynecological infections caused by beta-
is given alone. The activity of sulbactam against Acine- lactamase producing strains of Escherichia coli, and Bac-
tobacter spp. seen in in-vitro studies makes it distinc- teroides (including B. fragilis).[1][7]
tive compared to other -lactamase inhibitors, such as Bone and Joint infections Ampicillin/sulbactam can
tazobactam and clavulanic acid.[3] be used in the treatment of bone and joint infec-
tions caused by susceptible beta-lactamase producing
bacteria.[8][9][10][11]
4 History Intra-abdominal infections Ampicillin/sulbactam can
be used to treat intra-abdominal infections caused by
The introduction and use of ampicillin alone started beta-lactamase producing strains of Escherichia coli,
in 1961.[4] The development and introduction of this Klebsiella (including K. pneumonia), Bacteroides fragilis,
drug allowed the use of targeted therapies against gram- and Enterobacter.[1][7]
negative bacteria. With the rise of beta-lactamase pro-
Skin & skin structure Infections This medication can
ducing bacteria, ampicillin and the other penicillin-
be used to treat skin and skin structure infections caused
derivatives became ineective to these resistant organ-
from beta-lactamase-producing strains of Staphylococcus
isms. With the introduction of beta-lactamase inhibitors
Aureus, Enterobacter, Escherichia coli, Klebsiella (in-
such as sulbactam, combined with ampicillin made beta-
[5] cluding K. pneumonia), Proteus mirabilis, Bacteroides
lactamase producing bacteria susceptible.
fragilis, and Acinetobacter calcoaceticus.[1][7] Examples
of skin conditions treated with ampicillin-sulbactam are
moderate to severe diabetic foot infections and type 1
5 Medical Uses Necrotizing fasciitis, commonly referred to as esh-
eating bacteria.[12]
Ampicillin/sulbactam has a wide array of medical use for
many dierent types of infectious disease. It is usually
reserved as a second-line therapy in cases where bacte- 6 Formulation
ria have become beta-lactamase resistant, rendering tra-
ditional penicillin-derived antibiotics ineective. It is
eective against certain gram positive bacteria, gram- Ampicillin-sulbactam only comes in a parenteral for-
negative bacteria, and anaerobe.[1] mulation to be either used as intravenous or intra-
muscular injections, and can be formulated for intra-
venous infusion.[1][13] It is formulated in a 2:1 ratio
Gram-positive bacteria: Staphylococcus Aureus of ampicillin:sulbactam. The commercial preparations
(beta-lactamase and non-beta-lactamase produc- available include:[13]
ing), Staphylococcus epidermis (beta-lactamase
and non-beta-lactamase producing), Staphylococ-
cus saprophyticus (beta-lactamase and non-beta- 1.5 grams (1 gram ampicillin and 0.5 gram sulbac-
lactamase producing), Streptococcus faecalis (Ente- tam)
rococcus), Streptococcus pneumonia, Streptococcus
pyogenes, and Streptococcus viridians.[1][6] Brand names: Unasyn, Unasyn ADD-Vantage, Unasyn
Piggyback
Gram-negative bacteria: Hemophilus inuenzae
(beta-lactamase and non-beta-lactamase pro-
ducing), Moraxella (Branhamella) catarrhalis 3 grams (2 grams ampicillin and 1 gram sulbactam)
(beta-lactamase and non-beta-lactamase pro-
ducing), Escherichia coli (beta-lactamase and Brand names: Unasyn, Unasyn ADD-Vantage, Unasyn
non-beta-lactamase producing), Klebsiella species Piggyback

15 grams (10 grams ampicillin and 5 grams sulbac-
tam)
Brand name: Unasyn
7 Dosing
The recommended adult dose of ampicillin/sulbactam is
1.5 grams (1g ampicillin sodium plus 0.5g sulbactam
sodium) to 3.0 grams (2g ampicillin sodium plus 1g sul-
bactam sodium) every six hours. In pediatric patients, the
dose is based on body weight and is recommended at 300
mg per kilogram of body weight per day. This total daily
dose is to be divided into equal amounts to be given every
six hours. In patients with decreased kidney function, the
dosing frequency may need to be reduced.[1]
8 Adverse drug eects
Reported adverse events include both local and systemic
reactions. Local adverse reactions are characterized by
redness, tenderness, and soreness of the skin at the in-
jection site. The most common local reaction is injection
site pain. It has been reported to occur in 16% of patients
receiving intramuscular injections, and 3% of patients re-
ceiving intravenous injections. Less frequently reported
side eects include inammation of veins (1.2%), some-
times associated with a blood clot (3%). The most
commonly reported systemic reactions are diarrhea (3%)
and rash (2%).[14][15] Less frequent systemic reactions to
ampicillin/sulbactam include chest pain, fatigue, seizure,
headache, painful urination, urinary retention, intestinal
gas, nausea, vomiting, itching, hairy tongue, tightness in
throat, reddening of the skin, nose bleeding, and facial
swelling. These are reported to occur in less than 1% of
patients.[14][15][16]
9 Contraindications
Ampicillin/sulbactam is contraindicated in individuals
who have a history of a penicillin allergy. Symptoms
of allergic reactions may range from rash to potentially
life-threatening conditions, such as anaphylaxis. Pa-
tients who have asthma, eczema, hives, or hay fever are
more likely to develop undesirable reactions to any of the
penicillins.[14]
10 Synonyms
Unasyn (USA)
Subacillin (Taiwan)
3
Sultamicillin
unictam(egypt)
ultracillin ( egypt)
fortibiotic
sulbin(egypt)
11 References
[1] Pamphlet Pzer. Unasyn (ampicillin sodium/sulbactam
sodium) prescribing information. New York, NY; Up-
dated May 2014.
[2] Rafailidis PI, Ioannidou EN, Falagas ME (2007).
Ampicillin/Sulbactam Current Status in Severe
Bacterial Infections. Drugs. 67 (13): 18291849.
doi:10.2165/00003495-200767130-00003. PMID
17722953.
[3] Adnan S, Paterson DL, Lipman J, Roberts JA (Novem-
ber 2013). Ampicillin/sulbactam: its potential use in
treating infections in critically ill patients. Interna-
tional Journal of Antimicrobial Agents. 42 (5): 384
389. doi:10.1016/j.ijantimicag.2013.07.012. PMID
24041466.
[4] Acred P, Brown DM, Turner DH, et al. (April
1962). Pharmacology and chemotherapy of ampicillin-
-a new broad-spectrum penicillin. Br J Pharmacol
Chemother. 18 (2): 356369. doi:10.1111/j.1476-
5381.1962.tb01416.x. PMC 1482127 . PMID
13859205.
[5] Arono SC, Jacobs MR, Johenning S, et al. (Octo-
ber 1984). Comparative activities of the beta-lactamase
inhibitors YTR 830, sodium clavulanante, and sulbac-
tam combined with amoxicillin or ampicillin. Antimicro
Agents Chemother. This is also called Ampicillin Sodium
that also carries dierent strength in medical status. 26
(4): 528582. PMID 6097169.
[6] Clinical and Laboratory Standard Institute (CLSI). Per-
formance Standards for Antimicrobial Disk Diusion
Susceptibility Tests; Approved Standard 11th ed. CLSI
document M02-A11. CLSI, 950 West Valley Rd., Suite
2500, Wayne, PA 19087, 2012.
[7] Clinical and Laboratory Standards Institute (CLSI). Per-
formance Standards for Antimicrobial Susceptibility Test-
ing; 22nd Supplement. CLSI document M100-S22,
2012.>
[8] Campoli-Richards DM, Brogden RN (1987). ". Sul-
bactam/ampicillin: a review of its antibacterial activity,
pharmacokinetic properties, and therapeutic use. Drugs.
33 (6): 577609. doi:10.2165/00003495-198733060-
00003. PMID 3038500.
4 11 REFERENCES

[9] Ler L, Bauernfeind A, Keyl W, et al. (1986). An

open, comparative study of sulbactam plus ampicillin vs.
cefotaxime as initial therapy for serious soft tissue and
bone and joint infections. Rev Infect Dis. 8 (suppl5):
S593S598. PMID 3026009.

[10] Arono SC, Scoles PV, Makley JT, et al. (1986). E-

cacy and safety of sequential treatment of parenteral sul-
bactam/ampicillin and oral sultamicillin for skeletal infec-
tions in children. Rev Infect Dis. 8 (suppl5): S639S642.
PMID 3026018.

[11] Ler L, Bauernfeind A, Keyl W (1988). Sulbac-

tam/ampicillin versus cefotaxime as initial therapy in se-
rious soft tissue, joint and bone infections. Drugs. 35
(suppl7): 4652. PMID 3265378.

[12] Fish DN, Pendland SL. Chapter 88. Skin and Soft-Tissue
Infections. In: DiPiro JT, Talbert RL, Yee GC, Matzke
GR, Wells BG, Posey L. eds. Pharmacotherapy: A Patho-
physiologic Approach, 9e. New York, NY: McGraw-Hill;
2014.

[13] Unasyn. DynaMed Web Site. Updated

April 11, 2011. Available at: http://web.
a.ebscohost.com/dynamed/detail?vid=2&sid=
f98a4297-1217-4e15-82c2-d3dd03e17ed0@
sessionmgr4001&hid=4214&bdata=
JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU=
#db=dme&AN=233436. Accessed November 19, 2014.

[14] Clinical Pharmacology Web site. http://www.

clinicalpharmacologyip.com/Forms/Monograph/
monograph.aspx?cpnum=35&sec=moncontr&t=0.
Accessed November 21, 2014.

[15] UNASYN [package insert]. Pifzer Inc., New York, NY;

April 2007.http://labeling.pfizer.com/ShowLabeling.
aspx?id=617. Accessed November 21, 2014.

[16] Unasyn. Lexi-Drugs Online. LexiComp Web Site.

http://online.lexi.com/lco/action/doc/retrieve/docid/
patch_f/6354#f_adverse-reactions. Accessed November
21, 2014.
 5

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