Dear Editor:

We read with interest the paper by Olver et al[1] describing triplets with group B streptococcal (GBS) infections acquired from breast milk. We have recently seen a case of GBS meningitis in a 34 week gestation infant and suspect that the source of infection was the maternal breast milk.

At delivery there were no risk factors for sepsis. In particular, the baby was delivered by elective Caesarian section for growth retardation, without any prior rupture of membranes. No organisms were grown from routine admission blood culture and surface swabs. During the first week of life, our infant remained asymptomatic. The white cell count and C reactive protein levels remained within the normal range. On day 7, a full septic screen was performed for recurrent bradycardias. The white cell count was 3.9 x 10⁹/l (neutrophils 0.3 x 10⁹/l) and the C reactive protein was less than 7mg/l. GBS (serotype III) was isolated from both the blood and CSF cultures. The C reactive protein started to rise after twelve hours, and reached a peak of 353mg/l. As the source of the infection was not clear, a sample of maternal breast milk was cultured and the same serotype of GBS was isolated. There was no clinical evidence of mastitis.

Following the development of meningitis, cranial ultrasonography demonstrated periventricular vasculitis and increased echogenicity of the caudothalamic nucleus. No haemorrhagic lesions or structural abnormalities were detected either before or after the onset of this illness. On day 12 our infant became polyuric with dilute urine (osmolarity 70mOsm/kg) in the face of a high serum osmolarity (314mOsm/kg). A diagnosis of diabetes insipidus was therefore made and treatment with ddAVP was commenced. Subsequent investigations revealed evidence of hypopituitarism requiring replacement therapy. Cortisol was undetectable. Free thyroxine was low with a TSH level of 3.52mIU/l.

We agree that GBS transmission in breast milk may have been underestimated as a cause of late-onset sepsis and agree that breast milk should be screened in all such cases. Larger studies would be required to determine the true incidence of the problem. This case also underlines the need to actively look for the known-but-uncommon complications following neonatal meningitis such as diabetes insipidus and hypopituitarism.[2]

Anjum Deorukhkar
Robin Miralles

Jessop Hospital for Women
Sheffield, South Yorkshire, UK

References

(1) Olver WJ, Bond DW, Boswell TC, Watkin SL. Neonatal group B streptococcal disease associated with infected breast milk. Arch Dis Child Fetal Neonatal Ed 2000;83:F48-9.

(2) Cohen C, Rice EN, Thomas DE, Carpenter TO. Diabetes insipidus as a hallmark neuroendocrine complication of neonatal meningitis. Current Opinion in Pediatrics 1998;10:449-52.

Katz-Salamon et al[1] make the important point that children with chronic lung disease (CLD) need careful neurodevelopmental follow up irrespective of whether or not they suffered from intraventricular haemmorhage or periventricular leucomalacia.

Visual dysfunction due to retinopathy of prematurity (ROP) could contribute to defects in control of hand and eye coordination.

It would be interesting to know if they found a greater incidence of ROP in the preterm infants with CLD as compared to the control group.

Reference

(1) Katz-Salamon M, Gerner E M, Jonsson B, Lagercrantz H. Early motor and mental development in very preterm infants with chronic lung disease. Arch Dis Child Fetal Neonatal Ed 2000;83:F1-6.

Dear Editor:

A recent advance in premedicating infants requiring intubation has gained wide acceptance for humanitarian and physiological reasons.[1] The use of muscle relaxation to facilitate intubation is quite separate from sedation providing analgesia, amnesia and lack of awareness.

Practice is variable with little evidence-based guidance to suitable drugs. Clinical Governance dictates continuing audit of any such practice supported with written guidelines. We advocate a minimum monitoring policy (Saturation, Pulse, Non-Invasive Blood Pressure and Respiratory rate) and the presence of at least two skilled operators, one of which should be an experienced specialist registrar or consultant, when using neuromuscular blockade. This exercise is reserved for elective intubations and tube changes but not for use in resuscitation on the labour suite.

Recent reports to the CSM (Committee for the Safety of Medicines) via the UK Yellow Card Scheme of mortality associated with premedication using atracurium (dose 500 mcg/kg) and diamorphine (dose 50 mcg/kg) in three premature infants (24, 26 and 26 weeks' gestation) have attributed the problem mainly to using atracurium, which we consider debatable (Nicholas Rutter, Nottingham; Personal Communication). In addition, neuromuscular blockade should be unnecessary in pre-term infants.

Diamorphine is a prodrug that is metabolised to active 6-0-acetylmorphine and then to morphine. It has faster CNS penetration than morphine due to increased lipid solubility but its side effects are similar. Bradycardia of vagal origin (in combination with laryngoscopy) and decreased sympathetic response can cause a fall in cardiac output. Both morphine and atracurium cause histamine release that can precipitate bronchospasm and a fall in systemic vascular resistance (SVR).

Atracurium is a non-depolarising muscle relaxant that is slow onset and long acting. It provides intubating conditions within 90 seconds (dose 300-600 mcg/kg) and has a recovery index of 16 minutes (adult data). Premature infants have a small functional residual capacity (FRC) particularly when paralysed. A rapid fall in alveolar oxygen in an already under-ventilated infant may lead to pulmonary hypertension and increase V/Q mismatch. Consequently, mask ventilation or tube placement becomes necessary before the 90 seconds, which may not be long enough to reach therapeutic levels. Patients receiving a long acting muscle relaxant that cannot be ventilated for whatever reason will not start any independent respiratory effort for at least 16 minutes!

Our guidelines propose using fentanyl (dose 2 mcg/kg), which does not cause histamine release, so there is no bronchospasm. Cardiac output, systemic vascular resistance, pulmonary vascular resistance, and pulmonary artery occlusion pressure are preserved. High doses (10-15 mcg/kg) can lead to vagal bradycardias or chest wall rigidity. Where a muscle relaxant is indicated, we suggest suxamethonium (dose 1 mg/kg) which is to be preceded with atropine.

References
(1) Whyte S, Birrell G, Wyllie J. Premedication before intubation in UK neonatal units. Arch Dis Child Fetal Neonatal Ed 2000;82:F38-F41.

Dear Editor

We read the article by Kumar et al[1] with interest especially in light of the changing profiles of NICU practices as applicable to a developing nation with limited resources and lack of uniform parameters for antibiotic usage, resulting in the emergence of drug resistant strains. However, the utility of a rapid diagnostic system has to be viewed in the light of its universal applicability. The cost of setup and subsequent maintenance of a rapid culture system like BacT/Alert needs to be looked into vis a vis the traditional culture methodologies, which still are high yield relative to their low cost and results are available within 48-72 hours. Appearance of a growth itself can be taken as a decision tool for continuation of antibiotics pending the subculturing process in an appropriate clinical scenario. Automation has its advantages but need for calibration and standardization should not be ignored. Possibilities of false positive signals do remain and in a scenario of frequent power failures the performance of such a system may be far from ideal and can lead to potentially disastrous decisions.

Authors emphasise that the clinical status of the neonate still remains the most important factor in deciding the management of neonatal sepsis and therefore, a symptomatic neonate will continue to get antibiotics even in the absence of laboratory support, for a duration, if the clinical condition so demands. In asymptomatic neonates, there is need to have more clear guidelines about the duration of therapy once the antibiotics were started initially, may be based upon either symptomatology or high perinatal risk scores. In this study, the authors have not spelt out the clinical or laboratory criteria utilized after negative blood culture results at 36 hours, so as to consider presence or absence of sepsis and to justify continuation or discontinuation of antibiotics beyond 36 hours, awaiting the final culture report at 72 hours. It will be pertinent for the practice that between 36 and 72 hours period, the decisions about antibiotic therapy should not be based on negative culture test at 36 hours alone but must additionally utilize the rapid diagnostic tests (RDT), like use of IL-6 and C-reactive protein or TNF alpha. These RDTs have good cumulative accuracies for the diagnosis and exclusion of sepsis. [2,3] RDTs negativity after 36 hours, in culture negatives will give additional strength to decision of stopping of antibiotics. If these RDTs remain positive at 36 hours in culture negatives, then it will be justified to continue antibiotics till the final blood culture report becomes available at 72 hours and decision about antibiotic continuation taken accordingly. Therefore, it will be interesting to have information from the current study, on clinical condition and RDTs status of neonates, after obtaining 36 hours report of culture till 72 hours of life and final decisions about use of antibiotics. A rapid diagnostic blood culture system is likely to be most relevant in a clinical scenario of high perinatal sepsis risk score dictating use of antibiotics [4], asymptomatic neonate and with early negative RDT. An early negative blood culture result at 36 hours then could be the gold standard proof for absence of sepsis and mandating discontinuation of antibiotics in this subset of neonates.

Lastly the study in its retrospective design has limitations of applicability. There appears to be a bias towards LBW/prematures in the study, as data regarding term/AGA babies is not available in this study. The definitive pathogens in term babies are likely to be different and there may not be predominance of coagulase negative staphylococcus in them.

References:
(1) Kumar Y, Qunibi M, Neal TJ, Yoxall CW Time to positivity of neonatal blood cultures. Arch Dis Child Fetal Neonatal Ed 2001 Nov;85(3):F182-6
(2) Ng PC, Cheng SH, Chui KM, Fok TF, Wong MY, Wong W, Wong RP, Cheung KL.Diagnosis of late onset neonatal sepsis with cytokines, adhesion molecule, and C-reactive protein in preterm very low birthweight infants. Arch Dis Child Fetal Neonatal Ed 1997 Nov;77(3):F221-7)
(3) Philip AG, Mills PC Use of C-reactive protein in minimizing antibiotic exposure: experience with infants initially admitted to a well-baby nursery. Pediatrics 2000 Jul;106(1):E4
(4) Singh M, Narang A, Bhakoo ON Predictive perinatal score in the diagnosis of neonatal sepsis J Trop Pediatr 1994 Dec;40(6):365-8