Trimethoprim+sulfamethoxazole desensitisation protocols for adults

Consider whether trimethoprim+sulfamethoxazole desensitisation is appropriate; see Patient appropriateness for antimicrobial desensitisation. For most patients who report sulfonamide hypersensitivity, allergy assessment and allergy testing is all that is required.

If trimethoprim+sulfamethoxazole desensitisation is required, organisational oversight to ensure patient safety is necessary. Key requirements for antimicrobial desensitisation programs are listed in Key requirements for antimicrobial desensitisation programs.

Various protocols for trimethoprim+sulfamethoxazole desensitisation existPryor, 2019Urbancic, 2018. A pragmatic protocol for rapid oral desensitisation is included in this topic; see Rapid oral trimethoprim+sulfamethoxazole desensitisation protocol for adults. Seek expert advice if rapid desensitisation using this protocol is unsuccessful.

Desensitisation with oral trimethoprim+sulfamethoxazole is recommended even if subsequent therapy will be parenteral. Intravenous desensitisation is more likely to cause anaphylaxis than oral desensitisation.

There are limited data on antimicrobial desensitisation in children. In many cases, the protocols are extrapolated from protocols used in adult patientsNorton, 2018Cernadas, 2013Diaferio, 2020Caimmi, 2019. If antimicrobial desensitisation is necessary, seek expert advice from a paediatric allergist.

Table 1. Rapid oral trimethoprim+sulfamethoxazole desensitisation protocol for adultsRial Prado, 2018Pyle, 2014

Step 1 (at 0 hours)

Step 2 (at 1 hour)

Step 3 (at 2 hours)

Step 4 (at 3 hours)

Step 5 (at 4 hours)

Step 6 (at 5 hours)

Step 7 (at 6 hours)

Step 1 (at 0 hours)

Solution C [NB1]

volume

0.2 mL

sulfamethoxazole dose (mg)

0.02 mg

cumulative dose (mg)

0.02 mg

Step 2 (at 1 hour)

Solution C [NB1]

volume

2 mL

sulfamethoxazole dose

0.2 mg

cumulative dose

0.22 mg

Step 3 (at 2 hours)

Solution C [NB1]

volume

20 mL

sulfamethoxazole dose

2 mg

cumulative dose

2.22 mg

Step 4 (at 3 hours)

Solution A [NB2]

volume

0.5 mL

sulfamethoxazole dose

20 mg

cumulative dose

22.22 mg

Step 5 (at 4 hours)

Solution A [NB2]

volume

5 mL

sulfamethoxazole dose

200 mg

cumulative dose

222.22 mg

Step 6 (at 5 hours) [NB3]

Tablet (160+800 mg)

number of tablets

1

sulfamethoxazole dose

800 mg

cumulative dose

1022.22 mg

Step 7 (at 6 hours) [NB4]

Tablet (160+800 mg)

number of tablets

2

sulfamethoxazole dose

1600 mg

cumulative dose

2622.22 mg

Note:

NB1: To make Solution C (0.1 mg/mL sulfamethoxazole solution), first dilute 25 mL of the proprietary trimethoprim+sulfamethoxazole suspension (40+200 mg/5 mL) to 100 mL with water for irrigation and mix well (label ‘Solution B 10 mg/mL’, this will not be used for administration, but is needed for dilution). Take 1 mL of Solution B and dilute to 100 mL with water for irrigation. Mix well. Pour into a 100 mL amber glass bottle and label ‘Solution C 0.1 mg/mL’.

NB2: Solution A is the proprietary trimethoprim+sulfamethoxazole 40+200 mg/5 mL product that comes prediluted.

NB3: If the therapeutic dose will be 160+800 mg (1 tablet), stop at step 6. Consider the desensitisation protocol as the first dose and start therapy at the standard frequency required for the indication. For prophylaxis of Pneumocystis jirovecii pneumonia or Toxoplasma gondii encephalitis in immunocompromised patients, use one of the daily treatment regimens rather than the 3-times-weekly regimen (see Opportunistic and co-infections in adults with HIV infection and Primary prophylaxis in immunocompromised adults without HIV infection).

NB4: If the therapeutic dose will be 320+1600 mg (2 tablets), consider the desensitisation protocol as the first dose and start therapy at the standard frequency required for the indication.