Health Care-Associated Infections
EVALUATION
Health care-associated infection (HCAI), also referred to as nosocomial or hospital acquired, is an infection that a patient acquires and (a) becomes evident 48 hours or more after admission, (b) was not present or incubating at the time of admission to the hospital, and (c) develops while the patient is receiving treatment of other conditions. Neonates admitted to the neonatal intensive care unit (NICU) frequently contract HCAIs1 and may present with a wide range of symptoms, including fulminant sepsis, particularly late-onset sepsis (LOS). A significant number of HCAIs are preventable, even in the high-risk and vulnerable NICU population. Therefore, any discussion of HCAI management must also emphasize the role of preventive measures (refer to chapter 53).
Risk Factors
Recognition of risk factors for HCAIs is important when evaluating an acutely ill/decompensating patient for a possible HCAI.
1. Patient related: These risk factors are strongly influenced by the gestational age or weight at birth.2 With decreasing gestational age and birth weight, the more likely it is that an HCAI can occur as there is an underdeveloped immune response, increased hospital length of stay, severity of illness, exposure to NICU-related risk factors (see next item), and development of chronic and exacerbating medical conditions such as chronic lung disease (CLD) or necrotizing enterocolitis (NEC).
2. NICU related: These risk factors include the following:
a. indwelling intravascular or transmucosal catheters,
b. mechanical ventilation,
c. total parenteral nutrition (TPN) and intralipids,
d. broad-spectrum antibiotic therapy,
e. treatment with histamine2 receptor antagonists (H2 blockers),
f. steroid administration, and
g. exposure to the endemic microbial flora of the NICU environment as well as its health care workers.3–5
Clinical Signs and Symptoms
The clinical presentation can range from nonspecific and subtle to severe, multisystem organ dysfunction. Common presenting findings are the following:
1. Neurological:
a. temperature instability (fever or hypothermia);
b. apnea (unrelated to/distinct from apnea of prematurity);
c. lethargy or irritability, hypotonia, poor suck; and
d. seizures.
2. Respiratory:
a. Tachypnea;
b. grunting, flaring, retracting, or decreased breath sounds;
c. worsening gas exchange by blood gas, increased oxygen requirement, pulse oximetry, etc;
d. change in chest x-ray findings, and
e. new onset or change in character of sputum and increased respiratory secretions and suctioning requirements (for ventilated patients).
3. Cardiovascular:
a. tachycardia or bradycardia;
b. arrhythmia;
c. cyanosis; and
d. hypotension, prolonged capillary refill time, mottled appearance, cool and clammy skin.
4. Hematological:
a. leukopenia or leukocytosis,
b. anemia, and
c. thrombocytopenia,
5. Skin:
a. jaundice,
b. petechiae,
c. purpura, and
d. pallor or cyanosis.
6. Gastrointestinal:
a. abdominal distension, feeding intolerance, emesis;
b. diarrhea or bloody stools; and
c. ileus or absent bowel sounds.
7. Renal:
a. oliguria or anuria and
b. pyuria or malodorous urine.
Diagnostic Tests/Laboratory Testing
Testing should always include consideration of the patient’s risk factors for HCAIs with the caveat that not all “positive” cultures signify the presence of an infection (warranting treatment). Clinicians should also follow available diagnostic guidelines where available (see chapter 53).
1. Blood cultures: At least 1 mL of blood is recommended for each culture.
a. Draw from all intravascular catheters and a peripheral source.
b. Fungal cultures should also be considered, particularly in extremely low birth weight (ELBW) infants who are at greater risk for invasive fungal infections.
c. Repeat cultures and expand to other potential sources (urine, CSF, etc.) if no clinical improvement is seen after initiating empiric antibiotic therapy.
d. If the blood culture is positive, blood cultures from all lines and a peripheral source should be repeated at least every 24 hours after antibiotics/antifungals are initiated until cultures become negative.
e. For persistently positive cultures caused by an intravascular or indwelling device, removal is necessary.
f. Sending additional cultures of a removed device (eg, catheter tip) rarely aids management in the setting of known positive blood cultures.6
2. Cerebrospinal fluid (CSF) culture/analysis: Meningitis in a sick NICU patient can be difficult to diagnose. In a 2004 study by Stoll et al, approximately one-third of patients with meningitis did not have evidence of sepsis.7 Further complicating the issue are those patients with posthemorrhagic hydrocephalus who have had placement of either a ventricular reservoir or a shunt because they are at increased risk for infection.8 A decision to evaluate CSF (via either lumbar puncture [LP] or sampling of a reservoir/shunt) should be made prior to initiating empiric antibiotic therapy. The treatment should not be postponed in an ill neonate who is too unstable for CSF evaluation. CSF studies to be obtained include Gram stain, cell count with differential, evaluation of protein and glucose concentrations, and CSF culture(s). However, only the CSF culture is the gold standard for diagnosis.9 Additional potentially useful diagnostic studies include the following:
a. CSF lactate: There are reference ranges available for CSF lactate in neonates10; however, we are unaware of studies specific to neonates suspected of CSF infection, so any results obtained should be interpreted with caution. Studies involving use of CSF lactate in pediatric patients are available.11,12
b. Polymerase chain reaction (PCR) analysis: This is an excellent test for rapid diagnosis, particularly when viral infection is strongly suspected.13 It is currently the standard for identification of herpes simplex virus (HSV) and enterovirus in CSF. PCR analysis has good sensitivity and specificity; however, if blood is present in the CSF, results should be cautiously interpreted.
3. Tracheal culture/analysis: Consideration for ventilator-associated pneumonia (VAP) is an important part of the evaluation for an HCAI. When presenting signs or symptoms are consistent with respiratory tract infection, culture and studies are recommended but should be interpreted with caution. Identifying an organism can indicate a pathogen but may just represent colonization. Tracheitis is a diagnostic possibility that may require treatment, but studies are limited in their ability to differentiate it from pneumonia. Gram stains demonstrating the presence of polymorphonuclear leukocytes (PMNs) with bacteria or fungi support the use of empiric therapy but cannot dictate targeted therapy or duration of treatment.14 Viral studies (respiratory syncytial virus (RSV), metapneumovirus, influenza, enterovirus, rhinovirus, etc) are important as viral nosocomial infections do occur.15 Testing (including PCR analysis) for pertussis, mycoplasma, and ureaplasma may also be considered.
4. Urine culture/studies: Compared to early-onset sepsis, the incidence of urinary tract infections (UTIs) is higher in neonates experiencing prolonged hospitalization.16,17 Premature neonates are particularly susceptible.18 The presence of an indwelling (Foley) catheter increases the likelihood of a UTI. For diagnosis, urinalysis plus bacterial cultures are recommended. Obtaining fungal cultures is encouraged as clinically indicated.
5. Viral cultures/studies: As previously mentioned, viral studies are important (CSF, blood, urine, nasopharyngeal and tracheal aspirates, skin swabs) because viruses can cause NICU-related HCAIs. PCR analysis is a valuable and rapid diagnostic tool for diagnosing viral infections and can aid in management decisions while awaiting culture results.
6. Complete blood cell count (CBC) with (manual) differential count: A CBC is readily available and frequently obtained from patients hospitalized in the NICU. Results can be trended and used to support or rule out a diagnosis of infection.
a. Platelets: In sick neonates, thrombocytopenia is frequently observed, but it has no consistent predictive value. Development of new-onset thrombocytopenia (>30% decline from prior baseline value), however, may signal progression to septic shock or invasive gram-negative bacterial or fungal infection.19
b. White blood cells: Either leukocytosis or leukocytopenia heightens a clinician’s concern for infection.
c. Immature/total (I:T) neutrophil ratio: This is calculated as a secondary data point from the differential of the CBC by dividing the total immature neutrophil forms by the total immature plus mature neutrophils. Values less than 0.2 are usually considered within normal limits and not indicative of the presence of an infection.20 Higher I:T ratios support a diagnosis of infection, especially in conjunction with other abnormal clinical signs and symptoms. An I:T ratio as an isolated index, however, lacks sensitivity and specificity for determining the presence of HCAIs.
d. Eosinophils: Eosinophilia is also associated with infection in sick infants,21,22 although there is still debate on the timing of its appearance and potential correlation with other inflammatory conditions (eg, CLD).23 For more information on the use of the CBC, please see chapter 128.
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