CASE 4 Dr Sani Aliyu Consultant in Microbiology & Infectious Diseases Cambridge University Hospitals

Case A 2-day-old baby born at 32 weeks via spontaneous vaginal delivery was noted to be more floppy, lethargic and refusing feeds.

Case On examination he was slightly icteric and his body temperature was 35.7 ⁰C. He had nasal flaring with grunting respiration. Chest examination revealed tachypnoea with normal breath sounds.

Case Abdominal examination was unremarkable. Venous blood gas analysis showed: metabolic acidosis lactate level 4.6 mmol/L (<2.5) glucose level 2.8 mmol/L (3.3-6.1).

Q1. What additional history do you wish to elicit?

Q2. What additional investigations would you perform before starting antibiotics in the baby?

Case Blood cultures were taken and the baby was started on intravenous benzylpenicillin and gentamicin.

Case Full blood count - white cell count of 3.2 X 109/L neutrophil count of 1.2 X 109/L CRP 100mg/L CSF – polys 0, lymph 0, RBC 12 no organisms seen biochemistry normal

Case 48h later - blood cultures positive 1/1 bottle large Gram positive bacilli

Q3. What additional history would you request for at this stage?

Case The organism was subsequently identified as Bacillus cereus from MALDI-TOF after 4h incubation. The baby was changed to vancomycin plus gentamicin at this stage.

Case On the same day, the neonatal consultant reports two more babies showing signs of sepsis on the unit (desaturation with episodes of bradycardia). All 3 babies are nursed in the same room.

Q4. What is your advice at this stage?

Case The two babies were commenced on intravenous benzylpenicillin and gentamicin. The next day blood cultures signalled positive with Gram positive bacilli in both babies, identified as Bacillus cereus with MALDI-TOF 4h later.

Q5. What is your next line of action?

Q6. How would you investigate the source of this outbreak?

Clinical progress The next day, new cases of B. cereus bacteraemia were reported from 3 London units and a national alert was sent out to all units. Initial investigation suggested a possible link with contaminated total parenteral nutrition (TPN infusions); MHRA investigations are still on going.

Clinical progress A total of 23 babies from at least 11 neonatal units in England were affected with 3 deaths. Strain typing is pending but antibiograms of London isolates suggest no significant difference between them.

Clinical progress The 3 babies in this particular centre made an excellent recovery with vancomycin plus gentamicin. All intravascular lines were changed.

Clinical progress Surveillance blood cultures taken from asymptomatic babies who had received the same batch of TPN infusion fluids were negative. Linen imprints were also culture negative but a single environmental swab grew B. cereus of questionable significance.

Discussion point 1 Clinical features of neonatal sepsis these are subtle and frequently non-specific suspect sepsis if there is any change in activity or feeding

Discussion point 1 Clinical features of neonatal sepsis Include: temperature instability – hyper or hypothermia respiratory distress – tachypnoea, grunting or nasal flaring refusing feeds reduced activity vomiting

Discussion point 1 Clinical features of neonatal sepsis Less frequent: apnoeic episodes irritability diarrhoea abdominal distension

Discussion point 2 Identification of B. cereus MALDI-TOF vs. API Selective (PEMBA) media

Discussion point 3 Antibiotic susceptibility tests no specific breakpoints, generic breakpoints used produces chromosomally-mediated metallo-beta lactamase (MBL) conferring resistance to beta lactams including carbapenems interpret in vitro beta lactam susceptibility with caution as clinical failure following treatment seen due to MBL production

Discussion point 3 Antibiotic susceptibility tests outbreak isolates were susceptible to glycopeptides, aminoglycosides, linezolid, quinolones initially reported locally as susceptible to penicillin and cefotaxime, subsequently confirmed by reference lab to be resistant to these agents

Discussion point 4 Meningo-encephalitis associated with B. cereus septicaemia lumbar puncture recommended in neonates with septicaemia

Discussion point 5 Importance of notifying Health Protection teams early recognition of outbreaks unusual infections or presentations