Appendix III - Annual Review proforma

This is the antibiotic protocol designed for all newborn screened babies who are enrolled into the above study. To avoid confusion we will treat all NBS babies the same way using this protocol.

NOTE: choice of antibiotic may vary from the protocol depending on culture sensitivities

1. Cough swabs

All infants in the study to have cough swabs done at all clinic visits, and as a minimum of 2-3 monthly using a standard protocol for collection, storage and analysis of samples.

2. Oral flucloxacillin prophylaxis dose

3 to < 5 kg                   125 mg bd       

5 to < 9 kg                   175 mg bd       

9-15 kg (~1-2 y)          250 mg bd       

Based on therapeutic dose given twice daily to achieve MIC for Staphylococcus Aureus with each dose.

3. Pseudomonas aeruginosa (PsA)

3a. First growth

Cough swabs to be done at monthly intervals while on treatment.

Well child (clinical judgment), home therapy:(Frederiksen, Koch, and Hoiby 330-35)

• Oral Ciprofloxacin 15mg/kg bd for 3 weeks, PLUS

• Nebulised Colistin 1 mu bd for 3 months

Unwell child (clinical judgment), hospital therapy –

The choice of the initial IV antibiotics will be independent of sensitivities and if necessary tailored once sensitivities are known.

• IV tobramycin 10 mg/kg once daily for 2 weeks (trough level 23 hours after 1^st dose, must be < 1 mg/l), PLUS

• IV ceftazidime 50 mg/kg three times a day

• Also start nebulised Colistin 1 mu bd for 3 months, (initiated in hospital as appropriate).

3b. Re-growth during the initial 3 month treatment period (whilst still on colistin)

Well child

• Give a further 3 weeks Ciprofloxacin 15mg/kg bd for 3 weeks

Unwell child

• IV Tobramycin and Ceftazidime for 2 weeks then further 3 months nebulised colistin (doses as above).

• OR If IV antibiotics already given at 1^st isolation, can give 3 weeks ciprofloxacin and further 3 months nebulised colistin (if 2^nd IVAB            course inappropriate).

3c. Regrowth at end of 3 weeks ciprofloxacin / 3 months nebulised colistin course

• Admit for 2 weeks of IV antibiotics (tobramycin and ceftazidime) 

• And either:

  • 3 further months nebulised Colomycin (1 mu bd)
    or

  • 3 further months of alternating nebulised Colomycin (1mu bd) / Tobramycin (300mg bd) / Colomycin (1mu bd) or Tobramycin (300mg bd) / Colomycin (1mu/bd) / Tobramycin (300mg bd)

N.B. If Tobramycin is used, either TOBI or Bramitob is acceptable

3d. Regrowth after IVs and at least 6 months of nebulised colistin

• Try 28 days nebulised TOBI ™ (Gibson et al. 841-49) and then continuous nebulised colistin 1 mu bd for a further six months. In practice this is unlikely to arise during the study

3e. Regrowth > 6 months from first growth

• Treat as for 3a ie first growth.

3f. Chronic Pseudomonas Infection

Defined for analysis purposes by the Leeds criteria:(Lee et al. 29-34)

            Never               never cultured

            Free                 cultured previously but not in last year

            Intermittent      cultured in < 50% of samples in past year

            Chronic            cultured in > 50% of samples in past year

4. Staphylococcus aureus

4a. First growth

Well child (clinical judgment), home therapy:

• Oral Augmentin Duo (400/57) 0.3 mls/kg bd for 2 (minimum) to 4 weeks (clinical judgment)

• or equivalent dose of co-amoxiclav syrup tds
      0.25ml/kg TDS co-amoxiclav 250/62
      for 2 (minimum) to 4 weeks (clinical judgment)

Unwell child (clinical judgement), hospital therapy: 

Tobramycin 10 mg/kg once daily (trough level 23 hours after 1^st dose, must be < 1 mg/l), for 2 weeks, PLUS

• Teicoplanin 10 mg/kg 12 hrly for 3 doses then 10 mg/kg once daily for 2 weeks total

4b. Re-growth after more than 6 months from first growth

• Treat as for 4a ie first growth.

4c. Re-growth less than 6 months from first growth

• Oral flucloxacillin 50mg/kg bd for 28 days 

4d. Further re-growth within 6 months

• Two oral anti-staphylococcal antibiotics (clinical judgment) for 28 days.

5. Haemophilus influenzae

5a. First growth

Well child (clinical judgement), home therapy:

• Oral Augmentin Duo (400/57) 0.3 mls/kg bd for 2 (minimum) to 4 weeks (clinical judgment)

• or equivalent dose of co-amoxiclav syrup tds
       0.25ml/kg TDS co-amoxiclav 250/62
       for 2 (minimum) to 4 weeks (clinical judgment)

Unwell child (clinical judgement), hospital therapy:

• IV tobramycin 10 mg/kg once daily for 2 weeks (trough level 23 hours after 1^st dose, must be < 1 mg/l), PLUS

• IV ceftazidime 50 mg/kg three times a day

5b. Re-growth after more than 6 months from first growth

• Treat as for 5a ie first growth

5c. Re-growth less than 6 months from first growth

• Oral Augmentin Duo (400/57) 0.3 mls/kg bd for 2 (minimum) to 4 weeks (clinical judgment)

• or equivalent dose of co-amoxiclav syrup tds
      0.25ml/kg TDS co-amoxiclav 250/62
      for 2 (minimum) to 4 weeks (clinical judgment)

5d. Further re-growth within 6 months

• Clarithromycin for 14-28 days.
  < 8kg: 7.5mg/kg bd
  8-11 kg: 62.5mg bd
  12-15kg 125 mg bd

In practice this is unlikely to arise during the study

6. Other growths

• Well child (clinical judgment), home therapy: Oral antibiotic (clinical judgment) for 2 (minimum) to 4 weeks

• Unwell child (clinical judgment), hospital therapy: 2 IV antibiotics (clinical judgment) for 2 weeks

7. Viral URTI (otherwise well child)

• Oral augmentin duo (400/57) 0.3 mls/kg bd for 2 (minimum) to 4 weeks (clinical judgment)

• or equivalent dose of co-amoxiclav syrup tds
        0.25ml/kg TDS co-amoxiclav 250/62
        for 2 (minimum) to 4 weeks (clinical judgment)

Cough swab, treat as per protocol for any organism cultured.

8. Respiratory exacerbation with unknown organism, unwell child (clinical judgment)

Depending on severity of exacerbation:

• Oral augmentin duo (400/57) 0.3 mls/kg bd for 2 (minimum) to 4 weeks (clinical judgment)

• or equivalent dose of co-amoxiclav syrup tds
      0.25ml/kg TDS co-amoxiclav 250/62
      for 2 (minimum) to 4 weeks (clinical judgment)

OR

• IV tobramycin 10 mg/kg once daily for 2 weeks (trough level 23 hours after 1^st dose, must be < 1 mg/l), PLUS

• IV ceftazidime 50 mg/kg three times a day