International conference «Actual approaches to the extremely preterm babies: International experience and Ukrainian realities» (Kyiv, Ukraine, March 5-6, 2013)

1. NOSOCOMIAL INFECTIONS
Eucharius Rößlin 1528
Rolf Schlößer
University Hospital
Goethe University
Department of Neonatology

2. Neonatal nosocomial infections arouse public interest in Germany
Bremen
Siegen
Berlin
Passau
Hamburg
Mainz

3. Two aspects of nosocomial infections
in Neonatology
• Infection control at
the unit
• Prevention and
treatment of
infections in the
individual case

4. Nosocomial Infections as a increasing issue in Neonatology
Doyle LW et al.: J Paediatr Child Health 1999 Berrington JE et al.: J Pediatr 2012
% 100
100 90
90
80
80
70
70
60
60
50
50
40
40
30
30
20
20
10
10
0
0
1988-1994 1995-2001 2002-2208
1983-90 1992-96
Respiratory failure
Infection/NEC

5. Major contributors to hospital mortality in very-low-birth-weight infants
-Data of the birth year 2010 cohort of the German Neonatal Network-
Stichtenoth G et al. Klin Päd.2012

6. Decreasing EOS, Increasing LOS
Van den Hoogen A et al. 2010

7. Late Onset Infections and late mortality of preterm infants
1598 cases of death out of 7861 VLBW (<1500g) during 32 mts; 12 NICU (US)
Age at death (d) Number Number of death %
caused by infection
1-3 950 40 4,2
4-7 137 20 14,6
8-14 130 20 14,6
15-28 143 74 51,8
>29 220 88 40
Stoll BJ et al. J Pediatr. 1996

8. Impact of sepsis on cognitive and motor functions in elderly
Iwashyna, T. J. et al. JAMA 2010;304:1787-1794.

9. Morbidity of preterm infants
from Adams-Chapman I Seminars Perinat 2012 nach Stoll et al. 2004

10. A nosocomial infection (is defined) as a localized or
systemic condition 1) that results from adverse
reaction to the presence of an infectious agent(s) or
its toxin(s) and 2) that was not present or incubating
at the time of admission to the hospital
Garner JS et al.: 1996

11. Approximately 25% of VLBW have at least one nosocomial
infection during their stay in hospital (Geffers et al. 2008)

12. Risk Factors of LOS in Neonates
• Poor hygiene
• Invasive monitoring and invasive procedures
• Specific pathogens
• Specific immunologic situation of newborns
• Extended length of stay in hospital

13. Changes in Neonatology – Family-centered care
www.neonatology.org

14. Bacterial Contamination of toys in incubators
Quelle Frosch-Shop.de
19 Infants
34 Toys
86 Swabs:
All toys were contaminated with
bacteria during a 4 week period
8 Infants had infections
5 of them with the same
pathogen on their toy
Davies MW et al. Pediatrics 2000

15. Harbarth S, et al.
Outbreak of Enterobacter cloacae related to
understaffing, overcrowding, and
poor hygiene practices.
Infect Control Hosp Epidemiol. 1999

16. Risk Factors for LOS in Neonates
• Poor hygiene
• Invasive monitoring and invasive procedures
• Specific pathogens
• Specific immunologic situation of newborns
• Extended length of stay in hospital

17. Pooled Means of the Distribution of CVC-Associated
Bloodstream Infection Rates in Hospitals That Report to the
NNIS System, January 1992 to June 2001
O´Grady NP et al. Pediatrics 2002

18. Device-associated infections – not only central venous but also
peripheral venous catheter
100 µm
Geffers C et al. J Hosp Infect. 2008
100 µm

19. Risk Factors for LOS in Neonates
• Poor hygiene
• Invasive monitoring and invasive procedures
• Specific pathogens
• Specific immunologic situation of newborns
• Extended length of stay in hospital

20. Spectrum of pathogens in
nosocomial infections in NICU
Study 1
Studie 1
Study 2
Studie 2 Study 3
Gram-neg Gram-pos Fungi
Study 1: Nambiar S, Singh N; Pediatr Infect Dis J 2002
Study 2: Robles Garcia MG et al.; Ann Esp Pediatr. 2002
Study 3: Frankfurt experience during a 4 years period (71 positive blood cultures)

21. Pathogen Specific Mortality
Organism Death Rate Death Rate
1 2
All Gram-positive 11.2 % 10.6%
All Gram-negative 36.2 % 21.3 %
All Fungal 31.8 % 28.8 %
1) Stoll BJ et al.: Pediatrics 2002
2) Smith PB et al. Early Human Develop 2012
• Enterobacter cloacae
(10%; Chen2009)
• Acinetobacter spp.
(30% Touati 2009/37,5% Al Jarousha 2009)
• Serratia marcescens
(14%; Arslan 2009)
• Cronobacter (Enterobacter sakazakii)
(27%: Friedemann 2009)

22. Problem of Multiresistent Agents
• ESBL
Extended-Spectrum-BetaLactamase
• MRSA
Methicillin-Resistant Staphylococcus aureus

23. „ESBL-Bacteria are probably both imported into, and
spread within the NICU“ (Benenson S et al. Neonatology 2012)
Dubois V et al.J Antimicrob Chemother 2010

24. Duration of ESBL-colonization after
discharge from hospital

25. Methicillin Resistant Staphylococcus aureus
-MRSA-
 LOS with Staphylococcus aureus is rare (3.7%)
 LOS with MRSA is even rare (1 %)
But
Mortality for both is high (≈ 25 %)

26. Transmission of MRSA
Gray JW, Suviste J J Hosp Infect 2013

27. Human Cytomegalovirus (HCMV)
• HCMV-infected preterms are mainly asymptomatic
(Hamprecht et al. Lancet 2001).
• Up to 14 % of the nosocomial HCMV-infected preterms
develop severe clinical, sepsis-like symptoms (Kurath et al.
Clin Microbiol Inf 2010).
• One baby died (Hamele et al. Pediatr Infect Dis J 2010).
• Rate of transmission through breast milk is high.
(Wakabayashi et al. Am J Perinatol 2012).

28. Importance of breast milk:
Police escorted transport!

29. HCMV – short term consequences
(Kurath et al. Clin Microbiol Inf 2010;16:1172-8).
29

30. HCMV – short term consequences
Kurath et al. Clin Microbiol Inf 2010;16:1172-8
30

31. Risk Factors for LOS in Neonates
• Poor hygiene
• Invasive monitoring and invasive procedures
• Specific pathogens
• Specific immunologic situation of newborns
• Extended length of stay in hospital

32. Ranges for blood leukocyte count in preterm and term newborns, and in adults
Sharma AA et al. Clinical Immunology 2012

33. Developmental changes occurring in the human immune system early in life
Sharma AA et al. Clinical Immunology 2012

34. Classification of Nosocomial Infections
Infection Comment Prevention
Primary endogen Body´s own pathogens become source of partial
infection through changed immunologic
condition
Secondary endogen Body´s own pathogens get into bloodstream or partial
cavities through manipulation, devices, or
instrumentation
Exogen Pathogens are transmitted through either Usually possible
personal contact or the environment
mod. Gastmeier P et al. Dtsch Med Wochenschr 2010;

35. Risk Factors for LOS in Neonates
• Poor hygiene
• Invasive monitoring and invasive procedures
• Specific pathogens
• Specific immunologic situation of newborns
• Extended length of stay in hospital

36. The „neonatal problem“ of extended
length of stay in hospital
Benenson S et al. Neonatology 2013

37. Management

38. Infection control
• Hand desinfection
• Gloves/aprons, gowns
• Patient isolation
• Cohorting
Screening/Surveillance

39. Detection of nosocomial pathogens in hospital
Bomers MK et al. BMJ 2012;345:e7396

40. The purpose of Screening
• Knowledge of Pathogens in the own unit
– Isolation of patients
– Cohorting
– Detection of source of infection
• In case of clinical sepsis knowledge of associated
pathogen will help to choice antibiotics
– Poor predictive value of pharyngeal colonization (Evans ME et al.:
JAMA 1988),
but
– Concordance of gastrointestinal tract colonization with
subsequent sepsis (Smith A et al.: Pediatr Infect Dis 2010).

41. Potential sources for nosocomial infections in NICU
-A collection-
Powdered milk Simmons et al. Infect Control Hosp Epidemiol 1989
Glucose infusion Lalitha et al. J Hosp Infect 1999
Breastpump Donowitz et Rev Infect Dis 1981
IV infusion MMWR MMWR 1998
Bathwater Vochem et al. EJM 2001
Clinical thermometer Donkers et al. Ned Tijdschr Geneeskd 2001
Transducer Bloodpressure Ransjo et al. Acta Anaestesiol Scand 1992
Waterbath for FFP Muyldermanns et al. J Hosp Infect 1998
Ventilator circuits Gray et al. J Hosp Infect 1999
Air humidifiers Schlösser et al. Infection 1990
Desinfection Reiss et al. Lancet 2000
Almond oil Gras-Le Guen C J Perinatol. 2007

42. Treatment
Time is Life!

43. Immediate treatment of gram-negative sepsis is essential
Organism Number of Time of Death in Relation to Blood Culture,
Deaths n (%)
Days 1–3 Days 4–7 >7 Days
Gram-negative 93 66 (71%) 5 (5%) 22 (24%)
Gram-positive
CONS 55 10 (18%) 4 (7%) 41 (75%)
Other Gram- 46 19 (41%) 8 (17%) 19 (41%)
positive
Fungi 48 23 (48%) 12 (25%) 13 (27%)
Stoll BJ et al.: Pediatrics 2002

44. Clinical signs of late onset sepsis in preterm infants
Respiratory Symptoms Circulatory symptoms
Apnoe/Bradykardie/cyanotic spells Capillary refill time > 2S
Increased respiratory support Pallor/grey skin
Tachykardia
Increased oxygen requirement
Dyspnoea
General Symptoms Riskfaktors
Temperature instabilty Gestational age
Lethargy Birth weight
Hyperthermia Männl. Geschlecht
Feeding intolerance CVC in last 24 hrs
Irritabilitity Weight at episode
Hypothermia Age at episode
Ventilation
Bekhof J et al. Eur J Pediatr 2012

45. Brierley J et al.: Crit Care Med. 2009 Feb;37(2):666-88

46. Prophylaxis of neonatal sepsis?
Option Rating
G-CSF No significant increase of infection-
free survival at 4 weeks after treat-
ment
Kuhn P et al.: J Pediatr 2009
IVIG 3% reduction of sepis episodes, but no
reduction of mortality from sepsis
OhlssonA, Lacy JB Cochrane Database Syst Rev 2004
Fluconazole Most beneficial in NICUs with high
incidence of invasive candidiasis
Shane AL, Stoll BJ: Amer J Perinatol 2013
Vancomycin Reduction of nosocomial sepsis and
catheter related infection; risk of
resistance
Craft AP et al.: The Cochrane Library, Issue 3, 2002
Probiotics Reduction of NEC, no effect on sepsis
Mihatsch W A et al.:Clin Nutr 2012 ; 31 : 6 – 15

47. Thank you for your attention!
Quelle Internet