1. An outbreak in a neonatal unit
Sani Aliyu
Cambridge University Hospitals

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

3. 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.

4. Case
Abdominal examination was unremarkable. A venous blood gas showed a metabolic acidosis with a glucose level of 2.8 mmol/L ( ).
Q1. What additional history do you wish to elicit?

5. Answer to Q1 Note – discuss NICE CG149 red flags here)
Circumstances surrounding delivery
intrapartum maternal pyrexia >38⁰C
prelabour rupture of membrane
prolonged rupture of membrane >18h
maternal Group B strep status
use of parenteral antibiotics in mother at anytime during labour, or in the 24-hour period before and after the birth

6. Answer to Q1 Baby’s clinical state at the time of birth
evidence of fetal distress at or before birth
meconium aspiration
Apgar score ≤ 6

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

8. Answer to Q2
Blood culture
CRP
Lumbar puncture

9. Answer to Q2
Do not routinely perform urine microscopy/culture or skin swab microscopy or culture as part of investigations for early onset neonatal sepsis in the absence of local signs of infection.

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

11. Case
Full blood count showed a white cell count of 3.2 X 109/L with a neutrophil count of 1.2 X 109/L . CRP was elevated at 100mg/L. Lumbar puncture showed an acellular CSF with normal biochemistry.

12. Case
On day 2 blood cultures signalled positive with Gram positive bacilli

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

14. Answer to Q3 Baby’s current status ventilation status
presence of central venous catheters
method of feeding (NG or parenteral nutrition)
clinical progress on current antibiotics
Risk factors for listeriosis
history of non-specific flu-like illness in mother during third trimester of pregnancy
history of maternal ingestion of soft cheese or other high risk food
maternal history of immunosuppression

15. 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.

16. 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.

17. Q4. What is your advice at this stage?

18. Answer to Q4
Send blood cultures
Manage as usual for neonatal sepsis

19. Answer to Q4
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.

20. Q5. What is your next line of action?

21. Answer to Q5
Management
treatment changed to vancomycin plus gentamicin
all intravascular lines changed
infection control informed

22. Answer to Q5 Infection control cohort patients
barrier nurse with gloves and aprons
enforce scrupulous hand hygiene
change all cot linen
enhanced environmental cleaning with chlorine-based agents
replace all blood culture bottles on unit
restrict admissions and discharges from unit

23. Answer to Q5 Inform local health protection unit
Institute screening of all babies on the unit
surveillance swabs from axillary, groin, umbilical and rectal sites
blood cultures if sepsis is suspected

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

25. Answer to Q6 Linen issues check frequency of cot linen change
take contact swabs from environmental surfaces and linen imprints
review unit procedure for washing of personal items

26. Answer to Q6 Equipment issues any new equipment being used?
shared equipment between babies
similar interventions carried out on both babies
check infusions including TPN

27. 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.

28. 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.

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

30. 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.

31. Discussion point 1 Identification of B. cereus MALDI-TOF vs. API
Selective (PEMBA) media

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

33. Discussion point 2 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

34. Discussion point 2 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

35. Discussion point 3
Meningo-encephalitis associated with B. cereus septicaemia
lumbar puncture recommended in neonates with septicaemia

36. References
Public Health England. Guidance for the Management of cases of Bacillus cereus in view of the current neonatal outbreak in England, June 2014
National Institute of Clinical Excellence. Antibiotics for early-onset neonatal infection: antibiotics for the prevention and treatment of early-onset neonatal infection. Clinical Guideline 149. August 2012.
Ramarao N, Belotti L, Deboscker S, Ennahar-Vuillemin M, de Launay J, Lavigne T, Koebel C, Escande B, Guinebretière MH. Two unrelated episodes of Bacillus cereus bacteremia in a neonatal intensive care unit. Am J Infect Control. 2014; 42:
Bottone EJ. Bacillus cereus, a volatile human pathogen. Clin Microbiol Rev 2010;23:
Sasahara T1, Hayashi S, Morisawa Y, Sakihama T, Yoshimura A, Hirai Y. Eur J Clin Microbiol Infect Dis. Bacillus cereus bacteremia outbreak due to contaminated hospital linens 2011 Feb;30(2):
Van Der Zwet WC1, Parlevliet GA, Savelkoul PH, Stoof J, Kaiser AM, Van Furth AM, Vandenbroucke-Grauls CM. Outbreak of Bacillus cereus infections in a neonatal intensive care unit traced to balloons used in manual ventilation. J Clin Microbiol Nov;38(11):
Gaur AH, Patrick CC, McCullers JA, Flynn PM, Pearson TA, Razzouk BI, Thompson SJ, Shenep JL. Bacillus cereus bacteremia and meningitis in immunocompromised children. Clin Infect Dis. 2001; 32: