Rolf SchlößerUniversity HospitalGoethe University

Department of Neonatology

NOSOCOMIAL INFECTIONS

Eucharius Rößlin 1528

Bremen

Berlin

Hamburg

Passau

Siegen

Mainz

Neonatal nosocomial infections arouse public interest in Germany

• Infection control at the unit

• Prevention and treatment of infections in the individual case

Two aspects of nosocomial infectionsin Neonatology

0102030405060708090

100

1983-90 1992-96

Doyle LW et al.: J Paediatr Child Health 1999

%

Berrington JE et al.: J Pediatr 2012

0102030405060708090

100

1988-1994 1995-2001 2002-2208

Respiratory failure

Infection/NEC

Nosocomial Infections as a increasing issue in Neonatology

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

Decreasing EOS, Increasing LOS

Van den Hoogen A et al. 2010

Late Onset Infections and late mortality of preterm infants1598 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

Iwashyna, T. J. et al. JAMA 2010;304:1787-1794.

Impact of sepsis on cognitive and motor functions in elderly

from Adams-Chapman I Seminars Perinat 2012 nach Stoll et al. 2004

Mo

rbid

ity

of

pre

term

infa

nts

A nosocomial infection (is defined) as a localized orsystemic condition 1) that results from adverse

reaction to the presence of an infectious agent(s) orits toxin(s) and 2) that was not present or incubating

at the time of admission to the hospital

Garner JS et al.: 1996

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

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

Changes in Neonatology – Family-centered care

www.neonatology.org

Bacterial Contamination of toys in incubators

Davies MW et al. Pediatrics 2000

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

Quelle Frosch-Shop.de

Harbarth S, et al.

Outbreak of Enterobacter cloacae related to understaffing, overcrowding, and poor hygiene practices.

Infect Control Hosp Epidemiol. 1999

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

Pooled Means of the Distribution of CVC-AssociatedBloodstream Infection Rates in Hospitals That Report to the

NNIS System, January 1992 to June 2001

O´Grady NP et al. Pediatrics 2002

100 µm

100 µmGeffers C et al. J Hosp Infect. 2008

Device-associated infections – not only central venous but also

peripheral venous catheter

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

Studie 2Studie 1

Spectrum of pathogens in nosocomial infections in NICU

Study 1: Nambiar S, Singh N; Pediatr Infect Dis J 2002Study 2: Robles Garcia MG et al.; Ann Esp Pediatr. 2002Study 3: Frankfurt experience during a 4 years period (71 positive blood cultures)

Study 1 Study 2 Study 3

Gram-neg Gram-pos Fungi

Pathogen Specific Mortality Organism Death Rate

1Death Rate

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 20022) 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)

Problem of Multiresistent Agents

• ESBLExtended-Spectrum-BetaLactamase

• MRSA

Methicillin-Resistant Staphylococcus aureus

„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

Duration of ESBL-colonization after discharge from hospital

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 %)

Transmission of MRSA

Gray JW, Suviste J J Hosp Infect 2013

• 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).

Human Cytomegalovirus (HCMV)

Importance of breast milk:

Police escorted transport!

29

(Kurath et al. Clin Microbiol Inf 2010;16:1172-8).

HCMV – short term consequences

30

Kurath et al. Clin Microbiol Inf 2010;16:1172-8

HCMV – short term consequences

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

Ranges for blood leukocyte count in preterm and term newborns, and in adults

Sharma AA et al. Clinical Immunology 2012

Sharma AA et al. Clinical Immunology 2012

Developmental changes occurring in the human immune system early in life

Classification of Nosocomial Infections

Infection Comment Prevention

Primary endogen Body´s own pathogens become source of infection through changed immunologic condition

partial

Secondary endogen Body´s own pathogens get into bloodstream or cavities through manipulation, devices, or instrumentation

partial

Exogen Pathogens are transmitted through either personal contact or the environment

Usually possible

mod. Gastmeier P et al. Dtsch Med Wochenschr 2010;

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

The „neonatal problem“ of extended length of stay in hospital

Benenson S et al. Neonatology 2013

Management

Infection control

• Hand desinfection• Gloves/aprons, gowns

• Patient isolation• Cohorting

Screening/Surveillance

Detection of nosocomial pathogens in hospital

Bomers MK et al. BMJ 2012;345:e7396

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).

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

Treatment

Time is Life!

Organism Number of Deaths

Time of Death in Relation to Blood Culture, 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-positive

46 19 (41%) 8 (17%) 19 (41%)

Fungi 48 23 (48%) 12 (25%) 13 (27%)

Stoll BJ et al.: Pediatrics 2002

Immediate treatment of gram-negative sepsis is essential

Clinical signs of late onset sepsis in preterm infants

Respiratory SymptomsApnoe/Bradykardie/cyanotic spells

Increased respiratory support

Increased oxygen requirement

Dyspnoea

Circulatory symptomsCapillary refill time > 2S

Pallor/grey skin

Tachykardia

General SymptomsTemperature instabilty

Lethargy

Hyperthermia

Feeding intolerance

Irritabilitity

Hypothermia

RiskfaktorsGestational age

Birth weight

Männl. Geschlecht

CVC in last 24 hrs

Weight at episode

Age at episode

Ventilation

Bekhof J et al. Eur J Pediatr 2012

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

Prophylaxis of neonatal sepsis?

Option Rating

G-CSF No significant increase of infection-free survival at 4 weeks after treat-mentKuhn P et al.: J Pediatr 2009

IVIG 3% reduction of sepis episodes, but no reduction of mortality from sepsisOhlssonA, Lacy JB Cochrane Database Syst Rev 2004

Fluconazole Most beneficial in NICUs with high incidence of invasive candidiasisShane 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 sepsisMihatsch W A et al.:Clin Nutr 2012 ; 31 : 6 – 15

Thank you for your attention!

Quelle Internet