Health Care Associated Infections on the NICU (aka Nosocomial
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Health Care Associated Infections on the NICU (aka: Nosocomial infections) Catherine M. Bendel, MD Associate Professor of Pediatrics Director, Neonatal-Perinatal Medicine Fellowship Program
Objectives • Define and differentiate between early-onset, late-onset and health-care associated (nosocomial) infections on the NICU. • List the major micro-organisms responsible for each of these types of infection. • Understand the risk factors for NICU nosocomial infections. • Understand what laboratory tests are important in making the diagnosis of each of these infections. • Understand the primary prevention strategies
“Prematurity is an infectious disease.” - James Todd, M.D.
Definitions • Early Onset Neonatal Sepsis (EONS) • Late Onset Neonatal Sepsis (LONS) • Nosocomial or Health Care Associated Neonatal Infections (HCANI)
circulating pool • Neonates only 2-fold
Manroe et al, J Pediatr, 1979
7500
3600
ANC = absolute neutrophil count
Mouzinho et al, Pediatr 94:76, 1994
“Normal” VLBW neonates
Mouzinho et al, Pediatr 94:76, 1994
6000 1200
30 days
“Normal” VLBW neonates ( perc A-line
• Transient bacteremia results in tip infection (GI) • Increased incidence of infection with time UVC > UAC > PICC / Broviac • Minimally at 7 days • Significantly at 10-14 days or if clot present
Catheters • Micro-organisms love to stick to plastic • ANY CATHETER IS AT RISK!! • ETT, Foley, CT, Peritoneal drains, etc
Hyperalimentation / Intralipids • Associated with increased risk of CoNS, Candida spp and Malassezia spp • Exact etiology unclear – Inhibition of IL-2 and lymphocytes – Hyperglycemia – Sugar and fat source that promotes growth of select microbes – Affects of delayed enteral nutrition on GI flora/anatomy
Medications • Broad spectrum antibiotics – Alter normal flora (>5 days increases risk of candidemia) – Select for resistant microbes -- super bugs! • Third generation cephalosporins (Cefotaxime) – Emergence of beta-lactamase producing Klebseilla
pneumoniae
• Vancomycin - VRE
Antibiotic-resistant microbes • Vancomycin- resistant enterococcus (VRE) – Theoretic risk on NICU – risk with multiple course of vanco – Strict contact isolation
• Methicillin-resistant Staphylococcus aureus (MRSA) – Real risk on NICU – Community / maternal acquired – Vanco use required – Strict contact isolation
Medications • H2- blockers (ranitidine/Zantac) associated with increased bacterial and fungal infections • Steroids • • • •
Immunosuppression Hyperglycemia Skin compromise fragility Poor healing
• Topical petrolatum ointment (aquaphor) associated with increased fungal infections
Incidence of Systemic Candidiasis associated with TPO in infants with BW ≤ 1500 grams
Campbell JR, Zaccaria E, & Baker CJ, Pediatrics 2000;105:1041-1045.
Understaffing and Overcrowding • Understaffing / increase in census associated with – Decreased handwashing – Epidemics of • • • • •
Staphylococcus aureus MRSA Multi-drug resistant Enterobacter cloacae Multi-drug resistant K. pneumoniae Candida albicans
Care-giver to patient transmission of flora/pathogens • Hands of healthcare workers (HCW) a reservoir for pathogens - controlled with adequate hand washing • Persistent organisms on HCW hands due to: – – – –
Omitting or inadequate handwashing Contaminated antimicrobial washes Persistent organisms not addressed with antiseptic: Candida Artificial, painted and long natural nails, hand jewelry associated with infectious outbreaks
Health care associated infections on the NICU: Presentation and Diagnosis
Neonatal Infections Sepsis Meningitis Pneumonia NEC/perforation candidemia
EONS
NEC UTI Osteomyelitis Suppurative Arthritis Conjunctivitis Orbital Cellulitis Cellulitis - - Omphalitis Otitis Media Diarrheal Disease
Bacterial / Viral / Fungal
HCANI -Any & All Multi-organ
Signs/Symptoms
?
Laboratory Evaluation • Cultures • Complete Blood Cell Count • CSF glu, protein, WBC • Glucose • Bilirubin • Liver Function Tests • Coagulation studies • C-reactive Protein (CRP)
• • • • •
Chest Radiograph Abdominal X-ray Cardiac ultrasound Catheter ultrasound Renal ultrasound (fungal balls) • Ophthalmologic exam • Head ultrasound/ CT
New order-set in FCIS!
Cultures -- Who and Which? • Blood culture -- indicated in ALL infants with suspected sepsis. Repeat cultures indicated if initial culture positive.
• ETT culture (with gram stain)-- indicated in all intubated patients • Urine culture -- more helpful in LONS/HCANI – + in 1.6% EONS compared to 7.47% LONS Klein, Sem in Perinat, 5:3-8
Cultures -- Who and Which? • CSF culture -- should always be considered Meningitis frequently accompanies sepsis - Infants do not localize infections well - 50-85% meningitis cases have + blood culture - Specific signs & symptoms occur in less than 50% of infants with meningitis - Using “selective criteria” for obtaining CSF may result in missed or delayed diagnosis in up to 37% of infants with meningitis Wiswell et al, Pediatrics, 1995
Laboratory Diagnosis of Neonatal Meningitis CSF
--
> 32 WBC/mm3 > 60% PMN
glucose < 50% - 75% of serum protein > 150 mg/dl
organisms on gram stain
Complete Blood Cell Counts • Is the CBC helpful as an indicator of nosocomial neonatal sepsis? – Thrombocytopenia frequently associated with sepsis
– WBC may be high, low or “normal” – Persistent low WBC more predictive of sepsis than elevated WBC (ANC < 1200) – I:T quotient unreliable
C-Reactive Protein • Elevated CRP, > 10 mg/L (>1 mg/dl), highly associated with sepsis --- but NOT diagnostic • Limited by lack of “normal” reference values for preterm infants • Normal CRP in “rule-out NEC” evaluation correlates with absence of infection • Trend with multiple samplings correlates with persistence (CRP) or resolution (CRP) of infection
• May be useful tool in determining the endpoint for antibiotics
C-Reactive Protein
Pediatrics, 1997, 99:216-221
C-Reactive Protein • CRP levels 24 hours after beginning therapy correctly identified 99% of infants not needing further therapy. • CRP-guided determination of length of therapy, shortened the treatment course for most infected infants without increasing the rate of relapse. • Limitations: no studies evaluating meningitis or infections other than bacterial sepsis.
Specific Signs/Symptoms • NEC - risk of CoNS • GI perforation - risk of Candida /GI organisms/ anaerobes • Liver Dysfunction - risk of virus • Respiratory decompensation - risk GI bugs or respiratory virus (influenza, RSV-especially with apnea) • Renal insufficiency - risk of Candida • CNS involvement - anything • Thrombocytopenia - risk of Candida / HSV/ CMV
Empiric Therapy • Vancomycin IV - gram positive coverage treats CoNS, MRSA, GBS, Group D enterococcus • Cefotaxime IV - gram negative coverage treats Klebsiella spp, E.coli • Tailor therapy when culture results known
Additional Empiric Therapy • Add – Clindamycin when risk of anaerobes (GI perforation) – Acyclovir when risk of HSV – Amphotericin when risk of Candida
Yeast Susceptibilities Fairview-University Medical Center – 2006 C a ndi da
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9 9%
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9 9%
9 8%
0%
9 3%
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9 8%
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9 6%
9 7%
5 1%
6 7%
8 0%
1 00 %
a zo le Itra co na zo le
1 00 % 1 00 % 1 00 %
Health care associated infections on the NICU: Prevention!!!!!
Strategies for prevention: Eliminate/reduce risk factors - intrinsic – Prematurity - not likely/beyond our control – Low IgG - IVIG not successful – Low ANC - Granulocyte stimulating factor (GCSF) moderate success – Immature skin - Aquaphor not successful, use extreme care with adhesives/handling – Severity of illness - ????
Strategies for prevention: Eliminate/reduce risk factors - extrinsic Catheters • Insert only when indicated/remove promptly when no longer required • Utilize protocols for sterile insertion and maintenance (chlorhexidine, transparent dressings, etc) • Minimize manipulations • Remove if evidence of infection or clot formation • Replace UVC/UAC when required > 10-14 days – PICC / broviac / percutaneous a-line
Strategies for prevention: Eliminate/reduce risk factors - extrinsic Antibiotics • Judicious use • Avoid prolonged courses of BSA • Avoid prolonged and frequent courses of 3rd generation cephalosporins or vancomycin • Nystatin prophylaxis - prevents fungal overgrowth
Strategies for prevention: Eliminate/reduce risk factors - extrinsic Hyperalimentation • Advance enteral feeds as rapidly as possible • Minimize handling/breaks in line
Medications • Avoid rantidine (zantac) • Avoid/shorten courses of steroids • Avoid topical petrolatum
Strategies for prevention: Eliminate/reduce risk factors - extrinsic
#1 Preventative Measure: GOOD HAND-WASHING!!!!!
Miscellaneous
Human papillomavirus (HPV) • • • •
•
HPV causes both common skin warts (benign) and cervical/vaginal warts in the female (precursor to cervical dysplasia/cancer) Generally asymptomatic Infection can be passed to the infant during vaginal delivery Symptoms usually occur between 2-5 years of age – Respiratory tract – Mouth – Eye Difficult to treat -- vaccine might prevent
Respiratory Syncytial Virus (RSV) • Causes an acute respiratory illness • Infants prone to severe bronchiolitis and apnea, often requiring hospitalization with ventilation • Preterm infants at high risk for complications • May be associated with the development of asthma as an older child • Transmission is by direct or close contact with contaminated secretions • Good handwashing best prevention • Virus can live on environmental surfaces for hours
Respiratory Syncytial Virus (RSV) • Diagnosis – Classic symptoms - respiratory with apnea – Culture or rapid test on nasopharyngeal swab
• Treatment – Symptomatic – Supplemental oxygen or respiratory support
• Prevention – Palivizumab (Synagis) - monoclonal antibody – Passive immunization - monthly injections during RSV season (roughly Nov - March)
Indications for Synagis • Infants
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