Table 4

Guidelines for other clinical and non-clinical issuesa

Guidelines

References


1. Starting dose for ELBWbneonates: 1.5 × 109 cfu/dayc until reaching 50-60 ml/kg/day feeds

[84] and authors' opinion


2. Osmotic load: solution should be diluted to keep the osmolality below 600 mOsm/L

[86,87]


3. Diluent: sterile water or breast milk

Authors' opinion


4. Volume for administration: 1 to 1.5 ml per dose

[86] and authors' opinion


5. Clinical monitoring: patients should be monitored for intolerance (abdominal distension, diarrhea, vomiting), probiotic sepsis, and adverse effects (flatulence, loose stools) of additives such as prebiotic oligosaccharides.

[95-101] and manufacturer recommendation


6. Ongoing laboratory surveillance: Expertise in taxonomy confirmation (16S rRNA sequencing and PFGEd), ruling out contaminants, recovering probiotic strains at low inoculums from sterile sites, familiarity with the Gram stain and phenotypic appearance of probiotics, and monitoring for antibiotic susceptibility/resistance and cross-contamination are crucial.

[107]


7. Cold chain: maintenance of cold chain should be checked. Refrigerate at 4 to 10°C

Manufacturer recommendation


8. Product stability: stability should be checked by regular microbiological tests

[51,67,112,151]


9. Leftover solution should be discarded after giving small doses as it may get contaminated

Manufacturer recommendation


10. Regulatory issues: importing may be easier for research than for clinical use. National regulations on drugs and food supplements and customs quarantine guidelines should be checked

[131,132]


11. Data monitoring: high-quality data monitoring and collaboration between regional neonatal networks is crucial for monitoring outcomes at a population level

[145,146]


12. Information for parents: parents should be kept well informed about benefits and adverse effects, including the possibility of cross-contamination

[18,24]


13. Other potentially useful strategies: early preferential use of breast milk, strategies for prevention of sepsis, standardised feeding protocols, avoidance of undue prolonged exposure to antibiotic

[137-142]


aLevel of evidence was applicable to specific recommendations for clinical issues (Table 3) and not to other guideline components discussed in Table 4 above.

bExtremely low birth weight.

cCFU: Colony forming units.

dPulsed-field gel electrophoresis.

Deshpande et al. BMC Medicine 2011 9:92   doi:10.1186/1741-7015-9-92

Open Data