Antibiotic Desensitization Protocols

Marquette General Health System
Pharmacy and Therapeutics Committee

Medication Guideline
Desensitization Protocols for Commonly Used Antibiotics
Oral Penicillin (Penicillin VK) Desensitization Protocol
IV Penicillin (Ampicillin) Desensitization Protocol
Dose Concentration Volume
Dose
Cumulative Dose
Dose Concentration
Volume
Dose
Cumulative
No.
(mg/ml)
(ml)
(mg)
(mg)
No.
(mg/ml)
(ml)
(mg)
Dose (mg)
1
0.0005
1
0.0005
0.0005
1
0.0625
1
0.0625
0.0625
2
0.005
1
0.005
0.0055
2
0.0625
2
0.125
0.188
3
0.25
1
0.25
0.44
3
0.1
0.4
0.04
0.0455
4
0.25
2
0.5
0.94
4
0.1
0.8
0.08
0.1255
5
0.25
4
1
1.94
5
1
0.15
0.15
0.2755
6
0.25
8
2
4
6
1
0.3
0.3
0.5755
7
4
1
4
8
7
1
0.6
0.6
1.1755
8
4
2
8
16
8
1
1
1
2.1755
9
4
4
16
32
9
1
2
2
4.1755
10
50
0.6
30
62
10
1
4
4
8.1755
11
50
1
50
112
11
1
8
8
16.1755
12
50
2
100
212
12
100
0.15
15
31.1755
13
50
4
200
412
13
100
0.3
30
61.1755
50
14
8
400
812
14
100
0.6
60
121.1755
Adapted from N Eng J Med. 1985;312(19):1229-32.
15
100
1
100
221
Preparation
16
100
2
200
421
Dilute penicillin (i.e., penicillin VK) 250 mg/5ml (50 mg/ml or 80,000 units/mL) as
17
100
4
400
821
directed to make a stock solution. Take 2.5 mL of penicillin VK solution and add
18*
to 28.75 mL sterile water for irrigation and label this solution 4 mg/ml (6,400
100
8
800
1621
Adapted from DiPiro JT, Ownby DR, Schlesselman LS. Allergic and Pseudoallergic
Drug Reactions. In: DiPiro JT (ed) Pharmacotherapy, a Pathophysiologic Approach
(5th ed). New York, New York: Mcgraw-Hill; 2002:1585-97.
Preparation
Dilute 1 gram of penicillin (i.e., ampicillin) to 1,000 ml of 0.9% sodium chloride
(normal saline or NS) to achieve the 1 mg/ml solution (expiration = 12 hours)
Dose 1: Take 0.1 ml of the 1mg/ml solution and add to 200 ml of NS (0.0005
mg/mL)
Dose 2: Take 1 ml of the 1 mg/ml solution and add to 200 ml of NS (0.005 m/mL)
Dose 3 & 4: Take 1 ml of the 1 mg/ml solution and QS with NS to 10 ml (0.1
mg/ml)
Doses 5 thru 11: Withdraw appropriate volume from 1mg/ml solution to make
doses.
For Doses 12 thru 18*: Dispense a sufficient number of 1 gram vials (not
reconstituted).
Administer doses every 15 minutes.
Following final dose, observe patient for 15 to 30 minutes; administer full
therapeutic dose intravenously.
*Due to the short stability (1 hour) of the 100 mg/ml concentration, each vial must
be reconstituted prior to administration. Each vial should be diluted with 9.4 ml of
sterile water to provide a 10 ml volume (100 mg/ml). Sufficient volume should be
withdrawn from each vial to make the respective dose.
Document created: 07/12.

Revised: None.
Cross Reference: August 2012 P&T Committee Newsletter.
units/mL).
Dilute drug volumes in 30 mL water prior to ingestion
Administer doses every 15 minutes
Doses 1-2: Take 1 mL of 4 mg/ml solution and add to 63 mL sterile water for
irrigation to obtain a 0.0625 mg/ml (100 units/mL); Withdraw appropriate
volumes to make doses.
Doses 3-6: Take 2 mL of 4 mg/ml solution and add to 30 mL sterile water for
irrigation to obtain a 0.25 mg/ml (400 units/mL). Withdraw appropriate volumes
to make doses.
Doses 7-9: Withdraw appropriate volumes from 4 mg/ml solution to make
doses 7-9.
Doses 10-14: Withdraw appropriate volumes from the stock solution (50 mg/ml
or 80,000 units/mL) solution to make doses 10-14.

Marquette General Hospital
Marquette, MI 49855
This is a confidential professional/peer review and quality assessment document of Marquette General Health System of Marquette, MI. It is protected from disclosure pursuant to the
provisions of MCL 333.20175, MCL 333.21513, MCL 21515, MCL 331.531, MCL 331.533, MCL 330.1143a, and other state and federal laws. Unauthorized disclosure or duplication is
absolutely prohibited.

IV Cephalosporin Desensitization Protocol
Dose Concentration
Volume
Dose
No.
(mg/ml)
(ml)
(mg)
1
0.01
1.5
0.015
2
0.01
3
0.03
3
0.01
6
0.06
4
0.1
1.25
0.125
5
0.1
2.5
0.25
6
0.1
5
0.5
7
0.1
10
1
8
0.1
20
2
9
0.1
40
4
10
10
0.75
7.5
11
10
1.5
15
12
10
3
30
13
10
6.25
62.5
14
10
12.5
125
15
100
2.5
250
16
100
5
500
17
100
10
1000
Cumulative
Dose (mg)
0.015
0.045
0.105
0.23
0.48
1
2
4
8
15
30
60
123
250
500
1000
2000
Adapted from Immunol Allergy Clin N Am. 2004;24:425-443.

Preparation
Dilute 1 gram of cephalosporin (i.e., ceftriaxone) in 9.6 ml of 0.9% sodium
chloride (normal saline or NS) to achieve the 100 mg/ml solution, repeat for a
total of 2 vials. Withdraw 2.5 mL from 100mg/mL solution and add to 22.5 mL
NS (10 mg/mL).
Doses 1-3: Take 0.1 mL of 10 mg/mL solution and add to 99.9 mL NS (0.01
mg/mL).
Doses 4-9: Take 0.8 mL of 10 mg/mL solution and add to 79.2 mL NS (0.1
mg/mL).
Doses 10-14: Withdraw 24 mL of 10 mg/mL solution. Use appropriate
volume to make doses.
Dose 15-16: Withdraw 7.5 mL of 100 mg/mL solution. Use appropriate
volume to make doses.
Dose 17: Take 10 mL of 100 mg/mL solution to make dose.
*This protocol requires an infusion pump for administration. The interval
between doses is 15 minutes. Following final dose, observe patient for 15 to 30
minutes; administer full therapeutic dose intravenously.

Revised: None.

Marquette, MI 49855

IV Sulfamethoxazole/trimethoprim (SMX/TMP)
Desensitization Protocol**
Dose
Volume
Dose
No.
Time (minutes)
(ml)
(mg)
1
0
0.2*
0.8/0.16
2
20
2
8/1.6
3
40
10
40/8
4
60
20
80/16
5
80
100
400/80
6
100
170
680/136
7
120
300
1200/240
Adapted from Hospital Pharm. 1997;32(10):1362-9.
Cumulative
Dose (mg)
0.8/0.16
8.8/1.76
48.8/9.76
128.9/92
528.9/172
1208.9/308
2408/548
Preparation
Dilute 30 ml of SMX/TMP (80 mg/16mg per ml) injection in 600 ml of diluent to
obtain a concentration of 4mg/0.8 mg per ml. Administer each dose over 15
minutes.** The IV line should be flushed following each dose to ensure
complete delivery of medication.
*Further dilute the first dose to 10 ml for ease of administration.
**This protocol requires an infusion pump for administration. The interval
between doses is 20 minutes. Following final dose, therapeutic doses of
SMX/TMP may be scheduled at normal intervals.

Revised: None.
Oral (Slow) Sulfamethoxazole/trimethoprim (SMX/TMP)

Desensitization Protocol
Day
Dose
Cumulative Dose (mg)
Dosage Form: Suspension containing SMX 40 mg + TMP 8 mg per ml
1
1.25 ml once daily
SMX 2 mg + TMP 0.4 mg
2
1.25 ml twice daily
3
1.25 ml three times daily
4
2.5 ml twice daily
5
2.5 ml three times daily
Dosage Form: Single strength tablet (SMX 400 mg/TMP 80 mg)
6
1 tablet
SMX 1152 mg + TMP 230.4mg
Adapted from J Infect Dis. 2001 Oct 15;184:992-7.
Preparation
Use the commercially available SMX/TMP pediatric suspension (SMX 200
mg/TMP 40 mg per 5 ml) and dilute as directed. Following dose #6, therapeutic
doses of SMX/TMP may be scheduled at normal intervals.
Oral (Rapid) Sulfamethoxazole/trimethoprim (SMX/TMP)

Desensitization Protocol
Day
Dose
Cumulative Dose (mg)
Dosage Form (doses 1-4): Suspension (1:20 dilution) containing SMX 2
mg + TMP 0.4 mg per ml
1
1 ml
2
2 ml
3
4 ml
4
8 ml
SMX 30 mg + TMP 6 mg
Dosage Form (doses 5-8): Suspension containing SMX 40 mg + TMP 8
mg per ml
5
0.6 ml
6
1.25 ml
7
2.5 ml
8
5 ml
Dosage Form (doses 9-19+): Double strength tablets containing SMX
800 mg + TMP 160 mg
9
0.5 tablet
10
1 tablet
SMX 1600 mg + TMP 320.8 mg
111 tablet twice daily
SMX 3200 mg + TMP 640 mg
18
SMX 1600-3200 mg + TMP 32019+
1-2 tablet(s) twice daily
640 mg
Adapted from Ann Int Med. 1987;106:335.
Marquette, MI 49855

IV Imipenem/cilastatin (Rapid) Desensitization Protocol
Imipenem
Infusion
Concentration
Rate
(mg/ml)
(ml/min)
Infusion
Rate
(mg/min)
Dose/
30 min
Cumulative
Dose (mg)
0.0001
0.003
0.003
0.0001
0.0002
0.006
0.009
0.001
0.001
0.03
0.039
0.001
0.002
0.06
0.099
0.01
0.01
0.3
0.399
150
0.01
0.02
0.6
0.999
180
0.1
0.1
3.999
190
0.1
0.2
9.999
200
0.1
0.3
18.999
210
60
69.999
240
10
120
189.999
Time
(min)
Dose
#
Bag
#
0.0001
30
60
90
120
250
11
5
2
3
6
180*
500
Developed from similar protocols in Ann Pharmacother. 2003 Apr;37:513-6. &
Allergy. 1997;52:683-4.
Oral Linezolid Desensitization Protocol (using IV formulation)

Final
Preparation
Volume
Doses 1-12 were compounded from a
(ml)
premixed intravenous solution of linezolid 600
mg/300 ml. For each dose, sterile water for
1
0.366
2
injection was added in sufficient quantity ot
2
0.732
2
attain a final volume of at least 2 ml.
3
0.146
2
4
0.293
2
Following dose #14, the full therapeutic
5
0.586
2
dosage was administered as linezolid 600 mg
6
1.17
2
(one tablet) every 12 hours.
7
2.34
3
8
4.69
5
*For palatability, 1 ml of simple syrup was
9
9.38
10
added to doses 10-12.
10*
18.8
15
11*
37.5
25
12*
75
50
13
200
1/3 tablet
14
400
2/3 tablet
Adapted from Pharmacother. 2006;26(4)563-8.
Dose #
Dose
(mg)
Preparation
1. Bag #5 is prepared first. Remove the overfill from a 250 ml bag of 0.9% sodium chloride
(NS) and add 500 mg of imipenem to obtain a 2 mg/ml concentration. Label Bag #5 (2
mg/ml).
2. Bag#4: Remove 10 ml of the 2 mg/ml solution from Bag#5 and add it to 200 ml of NS.
Label Bag #4 (0.1 mg/ml)
3. Bag#3: Remove 10 ml of the 0.1 mg/ml solution from Bag#4 and add it to 100 ml of NS.
Label Bag #3 (0.01 mg/ml).
4. Bag#2: Remove 10 ml of the 0.01 mg/ml solution from Bag#3 and add it to 100 ml of NS.
Label Bag #2 (0.001 mg/ml).
5. Bag#1: Remove 10 ml of the 0.001 mg/ml solution from Bag#2 and add it to 100 ml of
NS. Label Bag #1 (0.0001 mg/ml).
Administration
Bags #1 - #3 (doses #1-6) are administered over a one hour period. The rate of each bag
should be doubled after 30 minutes.
Bag #4 (doses7-9) is administered over 1.5 hours. The rate of infusion should increase
every 30 minutes.
Bag #5 (doses 9-11) is administered over ~2 hours. The rate of infusion is increased every
30 minutes.
*Dose #11 should infuse until the bag is empty to obtain a cumulative dose of 500 mg.
Following successful desensitization, standard doses of imipenem may be administered at
the normal interval.

Revised: None.

Marquette, MI 49855

IV Vancomycin (Rapid) Desensitization Protocol
Dose
Concentration
Vancomycin
Dilution
#
(mg/ml)
Dose (mg)
1
1:10,000
0.0002
0.02
2
1:1000
0.002
0.2
3
1:100
0.02
2
4
1:10
0.2
20
5
Standard
2
500
Adapted from Ann Intern Med.1984;100:157 & Ann
Pharmacother. 2001 Nov;35:1458-64.
Premedication
Diphenhydramine 50 mg IV and hydrocortisone 100 mg IV 15 minutes
prior to initiation of protocol, then every 6 hours throughout protocol.
Preparation
1. Prepare a standard bag of 500 mg vancomycin in 250 ml of normal
saline [0.9% sodium chloride (NS)] or dextrose 5% in water (D5W);
label as infusion #5, vancomycin 2 mg/ml.
2. Draw up 10 ml of the 2 mg/ml vancomycin preparation and place in
100 ml bag of NS or D5W; label as infusion #4, vancomycin 0.2
mg/ml.
3. Draw up 10 ml of the 0.2 mg/ml vancomycin preparation and place in
100 ml bag of NS or D5W; label as infusion #3, vancomycin 0.02
mg/ml.
4. Draw up 10 ml of the 0.02 mg/ml vancomycin preparation and place
in 100 ml bag of NS or D5W; label as infusion #2, vancomycin 0.002
mg/ml.
5. Draw up 10 ml of the 0.002 mg/ml vancomycin preparation and place
in 100 ml bag of NS or D5W; label as infusion #1, vancomycin 0.0002
mg/ml.
IV Vancomycin (Slow) Desensitization Protocol (Lin)

Concentration
Vancomycin
How Provided
(mg/ml)
Dose (mg)
1
1
0.001
0.5
0.5 mg in 500 ml
2
2
0.01
5
5 mg in 500 ml
3
3
0.02
10
10 mg in 500 ml
4
4
0.10
50
50 mg in 500 ml
5
4
0.10
50
50 mg in 500 ml
6
5
0.2
100
100 mg in 500 ml
7*
6
0.4
200
100 mg in 250 ml x 2
8
7
0.6
300
150 mg in 250 ml x 2
9
8
1
500
250 mg in 250 ml x 2
10
9
2
1000
500 mg in 250 ml x 2
11
9
2
1000
500 mg in 250 ml x 2
12
9
2
1000
500 mg in 250 ml x 2
13
10
4
1000
1000 mg in 250 ml x 2
Adapted from Ann Pharmacother. 2001 Nov;35:1458-64.
Day
Dose #
*Beginning on day 7, the doses are infused consecutively.

Infusion Directions
Infuse each dose over 5 hours. If pruritus, hypotension, rash, or difficulty breathing occurs,
stop the infusion and reinfuse the previously tolerated infusion.
On day 14, administer the required dose of vancomycin in the usual dilution of NS or D5W
(e.g., 1000 mg in 250 ml ) at a rate of 100 ml/hour. Decrease the rate if the patient becomes
symptomatic or, alternatively, increase the rate if the patient tolerates the dose. Consider
premedicating with oral antihistamines prior to each dose.
Infusion Directions
Initiate infusion at 0.5 ml/min (30 ml/hour) and increase by 0.5 ml/min (30
ml/hour) as tolerated every 5 minutes to a maximum rate of 5 ml/min (300
ml/hour). If pruritus, hypotension, rash, or difficulty breathing occurs, stop
infusion and reinfuse the previously tolerated infusion at the highest
tolerated rate. This step may be repeated up to three times for any given
concentration.
Upon completion of infusion #5, immediately administer the required dose
of vancomycin in the usual dilution of NS or D5W over 2 hours. Decrease
the rate if the patient becomes symptomatic or, alternatively, increase the
rate if the patient tolerates the dose. Administer diphenhydramine 50 mg
by mouth 1 hour prior to each standard dose.

Revised: None.

Marquette, MI 49855

IV Tobramycin Desensitization Protocol
Dose
Elapsed Time
Dose (mg)
#
(hours)
1
0
0.001
2
0.5
0.002
3
1
0.004
4
1.5
0.008
5
2
0.016
6
2.5
0.032
7
3
0.364
8
3.5
0.128
9
4
0.256
10
4.5
0.512
11
5
1
12
5.5
2
13
6
4
14
6.5
8
15
7
16
16
7.5
32
17
8
16
Cumulative
(Dose)
0.001
0.003
0.007
0.015
0.031
0.063
0.127
0.255
0.511
1.023
2.023
4.023
8.023
16.023
32.023
64.023
80.023
TOBI (Tobramycin Preservative-free Solution for

Nebulization) Desensitization Protocol
Doses were administered every 2
Dose #
Dose (mg)
hours with continuous pulse oximetry
1
0.3
and vital signs being followed every 2
2
0.6
hours.
3
0.9
4
1.2
Dilutions were made from TOBI
5
1.5
using preservative-free diluent to
make up a 5 ml nebulized mist
6
3
treatment solution.
7
6
8
12
Anaphylaxis emergency treatment kits
9
24
and intubation supplies were present
10
48
at bedside throughout the entire
11
96
protocol and beyond.
12
150
13
200
14
250
15
300
Adapted from Pediatr Pulmonol. 2002;33:311-4.
Adapted from J Allergy Clin Immunol. 1987;79:477-83.

No premedications were administered
Each dose is diluted in 10 ml of normal saline (0.9% sodium
chloride) and delivered in 20 minute intervals with a delay of 10
minutes between doses.
The final dose is decreased to 16 mg to ensure that a total of 80
mg is received.
Heart rate, blood pressure and oxygen saturations should be
monitored throughout. Persistent tachycardia (>120 bpm) or a
fall in blood pressure (>20 mmHg) should halt further dose
escalation.
After dose #17, a regimen of 80 mg every 6 hours was
instituted.

Revised: None.

Marquette, MI 49855

IV Meropenem Desensitization Protocol
Dose
#
1
2
3
4
5
6
7
8
9
Meropenem
Concentration
(mg)
0.004
0.02
0.1
0.6
3
15
30
62
125
10
250
11
500
12
1000
Preparation Instructions
Add 2 ml from bag 3
Add 1.67 ml from bag 4
Add 0.313 ml of stock solution to minibag
Remove 15 ml of NS from minibag (5 ml for
amount being added and 10 ml overfill). Add
5 ml of stock solution to minibag.
Remove 20 ml of NS from minibag (10 ml
for amount being added and 10 ml overfill).
Add 10 ml of stock solution to minibag
Remove 30 ml from of NS from minibag (20
ml for amount being added and 10 ml
overfill). Add 20 ml of stock solution to
minibag.
Final
Concentration
(mg/ml)
0.00008
0.0004
0.002
0.012
0.06
0.3
0.625
1.25
2.5
5
10
20
Adapted from Ann Pharmacother. 2003 Oct;37:1424-8.

Preparation
A stock solution was prepared from two 1 gram vials of meropenem by adding
20 ml of sterile water for injection into each vial with the resulting concentration
of 50 mg/ml.
Each dose was prepared in a 50 ml minibag of 0.9% sodium chloride (NS) and
infused over 20 minutes. The IV line should be flushed between doses. The
overfill volume should be removed from each minibag prior to adding
medication. In addition, if greater than 2 ml of drug are added to the minibag
(doses #9-12), that amount of volume should also be removed from the minibag
prior to adding medication.
Doses 1-5 were made from previously prepared doses.
Doses 6-11 are made from the second stock solution vial (1 gram vial).
One of the stock solutions is used completely to make dose 12.

Revised: None.

Marquette, MI 49855

Antibiotic Desensitization Protocols

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Marquette General Health System

Pharmacy and Therapeutics Committee

Document created: 07/12.

Marquette General Health System

Marquette General Health System

Adapted from Immunol Allergy Clin N Am. 2004;24:425-443.

Document created: 07/12.

Marquette General Health System

Marquette General Health System

Document created: 07/12.

Oral (Slow) Sulfamethoxazole/trimethoprim (SMX/TMP)

Oral (Rapid) Sulfamethoxazole/trimethoprim (SMX/TMP)

Marquette General Health System

Oral Linezolid Desensitization Protocol (using IV formulation)

Document created: 07/12.

Marquette General Health System

Marquette General Health System

IV Vancomycin (Slow) Desensitization Protocol (Lin)

*Beginning on day 7, the doses are infused consecutively.

Document created: 07/12.

Marquette General Health System

Marquette General Health System

TOBI (Tobramycin Preservative-free Solution for

Adapted from J Allergy Clin Immunol. 1987;79:477-83.

Document created: 07/12.

Marquette General Health System

Marquette General Health System

Adapted from Ann Pharmacother. 2003 Oct;37:1424-8.

Document created: 07/12.

Marquette General Health System

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