Health Care Associated Infections on the NICU (aka Nosocomial

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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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