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Infectious Disorders
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Background
Elevation in body temperature as a result of cytokine-induced displacement of the hypothalamic set point.
Regulated through the hypothalamus.
Pyrogens can be exogenous or endogenous substances.
Endogenous pyrogens: interleukin 1 (IL-1), interleukin 6 (IL-6), tumor necrosis factor á (TNF-á).
Exogenous cytokines: derived from bacterial toxins, bacterial products, or microorganisms.
Results in elevated core temperature, shivering, and core vasoconstriction.
Definitions (Rectal)
Neonate (0-28 days): ≥38.0°F/100.4°C.
Young infant (29-90 days): ≥38.0°F/100.4°C.
Older infant and toddler: ≥39.0°F/102.2°C.
Fever in Neonate
Andrea M. Kline-Tilford
Temperature ≥38.0°C (100.4°F); rectal.
Neonates, birth to 28 days, are at greater risk for significant bacterial infection (SBI).
At birth, presence of maternal IgG cells; however, absence of immunologic memory and adaptive immunity.
B and T cells are at normal levels, but are less efficient than adult cells.
Complete evaluation required when a neonate develops fever (e.g., full septic workup/evaluation).
Complete blood count (CBC) with differential, blood culture, urinalysis (UA), and urine culture (specimen obtained through catheterization).
Lumbar puncture.
Immune system rapidly develops in the first 3 months of life.
Neonates often lack focal examination findings in the presence of an SBI.
Most commonly, SBI in neonates results from bacteremia, meningitis, pneumonia, or urinary tract infection (UTI).
Common SBI pathogens in neonates:
Group B streptococcus.
Listeria monocytogenes.
Salmonella.
Escherichia coli.
Neisseria meningitides.
Streptococcus pneumoniae.
Haemophilus influenzae type B.
Staphylococcus aureus.
Other common pathogens resulting in serious infection/illness in the neonate:
Respiratory syncytial virus (RSV).
Varicella-zoster virus.
Candida species.
If nasal congestion, evaluation is needed for RSV, parainfluenza, and influenza.
Plan is individualized; however, admission indicated in negative evaluation.
If nontoxic, empiric antibiotics may be delayed until laboratory evaluation is collected and results are available.
Recommended empiric antibiotic coverage in neonates includes ampicillin and gentamicin or ampicillin and cefotaxime.
Acyclovir, in addition to empiric antibiotics, if one of the following: seizures, cerebrospinal fluid (CSF) pleocytosis, primary maternal herpes simplex virus (HSV) infection, prolonged maternal rupture of membranes, mucocutaneous lesion, or fetal scalp electrode use.
Continue until CSF HSV polymerase chain reaction (PCR) results are available.
Recent evidence suggests acyclovir therapy for any infant <4 weeks of age with fever.
If laboratory evaluation is suggestive of UTI, full laboratory evaluation is still warranted. Admission and initiation of ampicillin and gentamicin are indicated.
Discharge if cultures are negative at 48 to 72 hours and the neonate is stable and afebrile. Close with primary care provider is needed, typically 48 hours after discharge.
PEARLS
Normal white blood cell (WBC) count does not exclude infection.
If CSF pleocytosis, send CSF sample for HSV PCR.
If RSV positive, risk for SBI does not change and full evaluation for SBI is indicated.
An identifiable source is not found in most neonates with fever.
Fever without a Source
Andrea M. Kline-Tilford
Definition
Presence of fever when history and physical examination are unable to identify a specific etiology/cause in an acutely ill nontoxic-appearing infant/child <3 years of age.
Also called “fever without localizing signs” or “fever without a focus.”
Risk of SBI is higher in younger infants/children.
Most infants/children with fever without a source (FWS) will have an underlying self-limiting viral infection.
Etiology has changed significantly since the advancement in vaccination (e.g., use of H. influenzae [Hib] vaccine has reduced the incidence of invasive infection by 90% in developed countries).
Bacteremia, UTIs, and pneumonia may not be associated with clinical symptoms.
If toxic-appearing, hospital admission, empiric antibiotics, and full diagnostic evaluation are indicated. If well-appearing, hospital admission and empiric antibiotic therapy are determined based on patient age and laboratory evaluation results.
Physical examination in young infants cannot be relied on, solely, and a more detailed diagnostic evaluation is needed.
Higher fever in older infants/toddlers is associated with increased incidence of occult bacteremia.
If toxic in appearance (any age infant/child), evaluation includes CBC, UA, urine culture, and lumbar puncture. Chest radiography if respiratory signs/symptoms, temperature >40°C, or pulse oximetry value <95% on room air; stool evaluation for WBCs if presence of diarrhea.
Common bacterial infection in older infants and children:
Staph. aureus and Mycoplasma pneumoniae
N. meningitides.
Salmonella.
Empiric antibiotic coverage in young infants often includes ampicillin, ceftriaxone, or cefotaxime and vancomycin. In older toxic-appearing infants and children, ceftriaxone or cefotaxime and vancomycin are often selected.
Tailor antibiotics when organism and sensitivities are available.
If an older infant is well-appearing and able to tolerate oral medications, consider a dose of intramuscular ceftriaxone, followed by oral antibiotics and with primary health care provider in 1 to 2 days.
Three most common approaches with FWS are summarized by Rochester, Milwaukee, Boston, and Philadelphia Criteria (see Table 11.1).
PEARLS
Approach to FWS is greatly impacted by infant/child’s immunization status.
Fever >38.5°C is not typically associated with teething.
In older toddlers and children, incidence of occult bacteremia increases with height of temperature.
Normal CBC and physical examination do not exclude meningitis.
UTI is the most common cause of SBI in febrile infants.
Fever of Unknown Origin
Meghan Shackelford
Definition
Fever >101°F or >38.3°C lasting for at least 8 days and up to 3 weeks with no apparent clinical diagnosis.
Etiology
Most common causes of fever of unknown origin (FUO) are infectious disease and connective tissue disorders.
Neoplastic disorders are less common and typically have manifestations other than fever.
Generally caused by a common disorder with an unusual presentation.
Sepsis, meningitis, urosepsis, toxic shock syndrome (TSS), and pneumonia should be considered during investigation of fever.
Meningitis should always be considered when evaluating an infant/child with FUO. See Table 11.2 for common pathogens in meningitis.
Pathophysiology
Variable, depending on fever source.
Evaluation
History.
Fever identification: touch, thermometry device, and site of temperature measurement.
Fever history is an important consideration.
Presentation of fever with sweating could indicate heat intolerance or hyperthyroid disease.
Lack of response to nonsteroidal anti-inflammatory drugs (NSAIDs) can indicate a noninflammatory condition causing the FUO (e.g., dysautonomia, ectodermal dysplasia).
TABLE 11.1 Examples of Criteria Approaches to FWS
Boston
Milwaukee
Philadelphia
Rochester
Age
28-89 d
28-56 d
29-60 d
≤60 d
Temperature
≥38.0°C
≥38.0°C
≥38.2°C
≥38.0°C
History
No immunizations or antibiotics in prior 48 hr.
No evidence of dehydration.
Not defined.
Not defined.
Term infant.
No perinatal antibiotic administration.
Absence of underlying disease.
Not hospitalized longer than mother.
Appearance/Physical Examination
Well-appearing.
No signs of focal infection (e.g., otitis media, soft tissue).
Well-appearing.
No evidence of dehydration.
No signs of focal infection (e.g., otitis media, soft tissue).
Well-appearing.
Unremarkable physical examination.
Well-appearing.
No signs of focal infection (e.g., otitis media, soft tissue).
Laboratory Results
Serum WBC <20,000/mm3.
CSF <10 WBC/mm3.
UA <10 WBC/hpf.
Chest radiograph: no focal infiltrate (if obtained).
Serum WBC <15,000/mm3.
CSF <10 WBC/mm3.
UA <5-10 WBC/hpf; no bacteria, leukocyte, and nitrite negative.
Chest radiograph: no focal infiltrate (if obtained).
Serum WBC <15,000/mm3.
Band to neutrophil ratio <0.2.
CSF <8 WBC/mm3.
CSF Gram stain negative. UA <10 WBC/hpf.
Urine Gram stain negative.
Chest radiograph: no focal infiltrate. Stool: no blood, few or no WBCs on smear (if obtained).
Serum WBC <5,000/mm3 >15,000/mm3.
Band neutrophils <1,500/mm3.
CSF: not applicable; no lumbar puncture indicated.
UA <10 WBC/hpf Stool WBC ≤5/hpf (if obtained).
Low-Risk Management Strategy
Home/outpatient.
Empiric antibiotics.
Follow-up evaluation required.
Home with reliable caretaker.
Follow-up evaluation required.
Ceftriaxone 50 mg/kg IM with reevaluation in 24 hr.
Home/outpatient.
No antibiotics.
Follow-up evaluation required.
Home/outpatient.
No antibiotics.
Follow-up evaluation required.
High-Risk Management Strategy
Hospitalize.
Antibiotic therapy.
Not defined.
Hospitalize.
Antibiotic therapy.
Hospitalize.
Antibiotic therapy.
hpf, high-powered field; WBC, white blood cell; IM, intramuscular
TABLE 11.2 Most Common Pathogens in Meningitis by Age Group
Age
Pathogens
Symptoms
Neonates-28 d of life
Group B streptococcus E. coli.
L. monocytogenes
Strep. pneumoniae
H. influenzae type b
Staph. aureus
Herpes simplex virus (HSV)
Also consider viral etiology.
Lethargy
Poor feeding
Fever or hypothermia
Vomiting
Apnea
1-3 mo of age
C. trachomatis
Strep. pneumoniae
N. meningitidis
Group B streptococcus (late-onset GBS infection)
Pertussis
Consider viral etiology.
Fever
Nuchal rigidity
Change in mental status
Change in LOC
+ Kernig sign
+ Brudzinski sign
3 mo-2 y of age
N. meningitidis
Strep. pneumoniae
Moraxella catarrhalis
Group A streptococcus
Salmonella
Mycoplasma pneumoniae
M. tuberculosis
Mostly bacterial; low incidence of viral.
Fever
Headache
Nuchal rigidity
Change in LOC
+ Kernig sign
+ Brudzinski sign
Erythematous
rash, if toxic shock syndrome present.
2-18 y of age
N. meningitidis
Strep. pneumoniae Chlamydia
M. tuberculosis
Mostly bacterial; low incidence of H. influenzae.
Fever
Headache
Nuchal rigidity
Change in LOC
+ Kernig sign
+ Brudzinski sign
Erythematous rash if toxic shock syndrome present.
LOC, loss of consciousness
Evaluate other clinical manifestations that accompany the fever, such as urine output, feeding intolerance, vomiting, pain, headache.
Diagnostic evaluation.
CBC, blood culture, UA and urine culture, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complete metabolic panel (CMP); consider lactate if the child appears septic.
Consider chest radiography.
Tuberculosis testing, human immunodeficiency virus (HIV) evaluation, or immune evaluation.
Management
Based on age and presentation at time of fever.
If a child is ill-appearing or in septic shock, the evaluation is more comprehensive.
Neonates to 28 days with temperature >38.0°C rectal (see “Fever in Neonate” for more detail).
Infants 1 to 3 months of age:
The most common differential for this age group includes bacteremia, meningitis, and UTI.
In the ill-appearing infant, cultures should be obtained, including blood, urine, and CSF culture. A WBC count with differential should also be obtained. IV antibiotics should be started and the child is admitted to the hospital. A chest radiography is optional in this age group.
If meningitis is suspected, ampicillin and cefotaxime are indicated with acyclovir.
Infant >3 months of age:
Vancomycin and ceftriaxone are antibiotics of choice.
If treating pneumonia, cefotaxime and ampicillin or clindamycin are recommended.
Children 3 months to 2 years of age:
This age group has fever typically related to a bacterial etiology.
Differential diagnosis: meningitis, pneumonia, toxic shock, and urosepsis. Toxic shock typically presents with an erythematous rash.
In the ill-appearing child, cultures should be sent in addition to WBC count with differential and hospital admission is warranted.
Antibiotic choices for meningitis include vancomycin and ceftriaxone.
If treating pneumonia, ampicillin, cefuroxime, or ceftriaxone can be used with clindamycin or vancomycin for empiric treatment.
If the child is well-appearing, discharge home with outpatient follow-up.
Children 2 to 18 years of age:
Toxic shock, meningitis, and pneumonia are common etiologies.
If the child is ill-appearing and hemodynamically unstable, blood, urine, and CSF cultures should be obtained, along with CBC count and differential. IV antibiotics should be started and hospital admission is warranted.
If treating pneumonia, azithromycin with cefuroxime or ceftriaxone, and clindamycin or vancomycin are antibiotics of choice.
If meningitis is suspected, ceftriaxone and vancomycin are initiated.
See Table 11.3 for common infectious diseases by body system.
See Table 11.4 for examples of cephalosporin coverage.
See Box 11.1 for helpful cephalosporin mnemonics.
TABLE 11.3 Common Infectious Organisms and Disease/System Involved
Organism
Disease/System Process
Gram-positive cocci (aerobic):
Staph. aureus
Staph. epidermis
Other Staphylococcus species
Nosocomial: wound, ventilator
Neonatal
UTI
(typically hospital-associated infections)
Gram-positive enterococcus (aerobic):
Strep. gordoni
Strep. pneumoniae
Strep. mutans
Strep. viridans
Endocarditis
Sepsis
Meningitis
Urinary tract infection
Gram-positive enterococcus (aerobic):
Staph. pyogenes
Toxic shock syndrome
Necrotizing fasciitis
Gram-positive cocci (anaerobic):
Peptostreptococcus
Peritonitis; can occur anywhere (e.g., soft tissue, CNS, chest, bone)
Gram-negative cocci:
N. meningiditis
M. cattarhalis
Meningitis
Myocarditis
Otitis media
Sinusitis
Gram-positive bacilli:
L. monocytogenes
C. difficile
C. botulinum
Sepsis (L. monocytogenes); primarily <2 mo of age
Meningitis (L. monocytogenes); primarily <2 mo of age
Antibiotic or hospital-acquired diarrhea (C. difficile)
Flaccid paralysis
(C. botulinum)
Gram-negative bacilli:
E. coli
Enterobacter
P. mirabilis
K. pneumoniae
Wound infection
UTI
Meningitis
Bacteremia
Health care-associated infections (especially
Klebsiella; increasing resistance also)
Gram-negative bacilli:
P. aeruginosa
Bacteremia
Sepsis
Health care-associated infections
Encephalitis
Meningitis
Pneumonia
See Box 11.2 for examples of organisms requiring double antibiotic coverage.
Refer to an antimicrobial reference (e.g., Sanford Guide) for additional information on appropriate antibiotic coverage for pathogens (Tables 11.5 and 11.6).
Box 11.1 First- and Second-Generation Cephalosporin Coverage Mnemonic
First-Generation Cephalosporin Coverage:
“PEcK”
Proteus
E. coli
Klebsiella.
In addition, first-generation cephalosporins cover grampositive cocci, including methicillin-sensitive Staph. aureus, Staph. epidermis, Strep. agalactiae, Strep. pneumoniae, and Strep. pyogenes.
Second-Generation Cephalosporin Coverage:
“HENPEcKS”
H. influenzae
Enterobacter aerogenes
N. meningitidis
Proteus
E. coli
Klebsiella
Serratia marcescens
In addition, second-generation cephalosporins are active against gram-positive cocci, including methicillin-sensitive Staph. aureus, Staph. epidermidis, Strep. species (excluding Strep. faecalis). Activity against gram-positive cocci is not as strong as first-generation cephalosporins.
Box 11.2 Pathogens Requiring “Double” Antimicrobial Coverage*
“SPACE” Mnemonic
S—Serratia
P—Pseudomonas
A—Acinetobacter
C—Citrobacter
E—Enterobacter
TABLE 11.4 Examples of Cephalosporin Generations | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ||||||||||||||||||||||||
PEARLS
For suspected meningitis, the gold standard is to administer antibiotics based on suspected organism within 1 hour of evaluation.
Temperature >38.0°C in neonates and infants ≤3 months of age can indicate a serious infection requiring immediate evaluation.
Noninfectious etiologies of fever must also be considered (e.g., connective tissue disease, malignancies, drug fever, factitious fever, diabetes insipidus, central nervous system (CNS) dysfunction).
Fever and Neutropenia
Meghan Shackelford
Definition
Fever with neutropenia can present in a patient with cancer diagnosis secondary to chemotherapy or secondary to hematologic disease.
One third of children treated with chemotherapy or stem cell transplant develop fever.
Fever in a neutropenic patient is defined as a single temperature >38.3°C or >38.0°C for >1 hour with an absolute neutrophil count (ANC) <500 cells/µL or an ANC that is expected to decrease <500 cells/µL within the next 48 hours.
Etiology
Bacteremia is the most common etiology.
Common sites of infection include the gastrointestinal (GI) tract (e.g., oral and intestinal mucositis, diarrhea), upper and lower respiratory tracts, urinary tract, skin, and soft tissues.
Diarrhea is most commonly caused by Clostridium difficile and Salmonella.
Gram-positive and gram-negative organisms must be considered.
Gram-positive pathogens are coagulase-negative staphylococci, viridans streptococci, and Staph. aureus (including MRSA).
Gram-negative organisms are gram-negative bacilli, E. coli, Klebsiella, Pseudomonas, Acinetobacter, and Enterobacter.
Candida and other fungal species can develop after prolonged use of broad-spectrum antibiotic therapy.
Other opportunistic fungi include Aspergillus, Phycomycetes, and Cryptococcus.
Viral etiologies in these children include HSV, varicella-zoster virus, as well as respiratory viruses.
Pathophysiology
Neutropenia is defined as a decrease in neutrophils with a circulating count of < 1,500 cells/µL.
Occurs secondary to the damage of the precursor cells and depression of bone marrow function or can be linked to an autoimmune reaction.
Clinical Presentation
A complete history is essential in determining whether neutropenia and fever are linked to chemotherapy and an infectious process or are of a hemolytic etiology.
Important history includes antimicrobial prophylaxis, infectious exposures, chronic steroid therapy, history of infections or bacterial colonization, fever-causing medications, type of chemotherapeutic agents received, recent blood product transfusion, presence of invasive lines/devices, previous chemotherapy.
Skin breakdown is a portal of infection for an immunocompromised patient.
Monitoring for pancreatitis and pneumonia and evaluation of subtle vital sign changes such as tachycardia assist in diagnosis and prompt, accurate treatment.
Diagnostic Evaluation
Laboratory evaluation: CBC with differential and platelet count, CMP, including BUN (blood urea nitrogen)/creatinine, AST (aspartate aminotransferase)/ALT (alanine transaminase), and total bilirubin; blood, urine, body fluid, and, sometimes, CSF cultures.
Imaging may be indicated: computed tomography (CT) or ultrasound if concern for fluid collections, effusions, or acute changes; chest radiography if respiratory symptoms.
If a central venous catheter is present, a blood culture should be obtained and sent from each lumen.
Removal of the central line may be indicated.
In the absence of a central venous catheter, a peripheral culture should be obtained using sterile technique.
Lumbar puncture if altered mental status.
C. difficile toxin assay if diarrhea is present.
Management
Broad-spectrum antibiotics are administered quickly to the neutropenic patient with fever. Treatment varies according to individual patient according to specific guidelines.
Two categories: high-risk and low-risk.
High-risk patients have neutropenia expected to last >7 days, are clinically unstable, and have comorbidities.
Low-risk patients have neutropenia expected to last <7 days and are clinically stable with no comorbidities.
Low-risk outpatient: Ciprofloxacin and amoxicillin-clavulanate PO are recommendations for treatment, followed by observation for 4 to 24 hours after initiation of antibiotics.
Low-risk inpatient: Zosyn, carbapenem, ceftazidime, or cefepime based on suspected organism, severity of infection, and preference.
High-risk patient: hospital admission and antibiotic therapy with Zosyn, carbapenem, ceftazidime, or cefepime. For patients with minimal response or signs of decline, therapy should be adjusted for clinical, radiographic, and/or culture data. Vancomycin or linezolid should be used for cellulitis or pneumonia. An aminoglycoside and carbapenem should be used for pneumonia or a gram-negative bacteremia. Flagyl should be used if the patient has abdominal symptoms or suspected C. difficile infection.
Infectious disease consult is warranted for the high-risk patient, especially if not responsive to therapy.
Antifungal therapy is reserved for neutropenic patients with fever persisting for 4 to 7 days after starting broad-spectrum antibiotics.
Amphotericin B is often the initial recommendation; however, should be considered with caution because of significant toxicity risk.
PEARLS
Prompt treatment in the neutropenic patient with a fever is essential to decreasing mortality.
High-risk and low-risk patient classifications guide therapy.
The gold standard is to treat with a broad-spectrum antibiotic as quickly as possible and to obtain cultures prior to the start of antibiotic therapy.
Health Care Associated Infections
Jill S. Thomas
Central Line-Associated Bloodstream Infections
Background
A health care-associated infection is an infection that is not present upon hospital admission but develops within 48 hours of admission in an acute care setting.
Infections not present at discharge but apparent within 10 days after discharge are also considered to be of nosocomial origin.
Definition
Central line-associated bloodstream infection: a primary bloodstream infection (BSI) in a patient who had a central line infection within the 48-hour period before the development of a BSI and the BSI is not related to another infected site.
Etiology/Types
Migration of skin organisms at the insertion site, leading to colonization of the catheter tip.
Direct catheter or catheter hub contamination; infusate contamination.
Hematogenous seeding of catheters by other sites of infection.
Common causative organisms include coagulase-negative staphylococci, gram-negative bacteria, Staph. aureus, and Candida species.
Clinical Presentation
Fever, chills, hypotension: neonates/infants may present with hypothermia, apnea, and bradycardia.
See http://www.cdc.gov/nhsn/PDFs/pscManual/17pscNosInfDef_current.pdf for delineation of Center for Disease Control and Prevention (CDC) CLABSI criteria.
Diagnostic Evaluation
Two quantitative blood cultures, with at least one drawn peripherally.
Qualitative blood cultures can be used with continuously monitored differential time to positivity.
Catheter tip cultures, CBC with differential, CRP, ESR.
Urine, sputum, respiratory viral cultures as indicated to evaluate for other infectious sources.
Management
Empiric antibiotic coverage with broad-spectrum gram-positive and gram-negative bacterial coverage with adjustment of coverage on determination of isolate’s sensitivities.
Consideration of central line removal with subsequent replacement of intravenous access.
Ventilator-Associated Events, Including Pneumonia
Definitions
Ventilator-associated events: include a surveillance algorithm to identify a broad range of conditions and complications occurring during mechanical ventilation.
Ventilator-associated condition: period of baseline stability or improvement on mechanical ventilation; ≥2 calendar days of stable or decreasing Fio2 or positive end-expiratory pressure (PEEP) values, followed by at least one of the following indicators of deteriorating status.
Increase in Fio2 ≥0.20 from baseline period, sustained for ≥2 calendar days.
Increase in PEEP level of ≥3 cm H2O from baseline period, sustained for ≥2 calendar days.
PEEP values of 0 to 5 cm H2O are considered equivalent in ventilator-associated pneumonia (VAP) surveillance.
Infection-related ventilator-associated complication (IVAC).
≥Calendar day 3 of mechanical ventilation and within 2 days before or after the deterioration in oxygenation, both of the following criteria are met.
Temperature >38°C or <36°C, or WBC count ≥12,000 cells/mm3 or ≤4,000 cells/mm3.
New antimicrobial(s) initiated and continued for ≥4 calendar days.
VAP.
Pediatric VAP surveillance guidelines were published by the CDC in January 2015. Specific guidelines for diagnosis of pediatric VAP are not yet available. Refer to CDC website: http://www.cdc.gov/HAI/vap/vap.html
Guidelines for surveillance and diagnosis are based on changes in ventilation requirements, presence of purulent or increased secretions, fever, and results of laboratory testing to include culture of bronchial aspiration.
Typical organisms responsible for VAP in children include coagulase-negative staphylococcus, enterococcus, Pseudomonas aeruginosa, E. coli, Klebsiella pneumoniae, Staph. aureus, Staph. epidermidis.
Typical viral causes: influenza virus, RSV, adenovirus, parainfluenza virus, rhinovirus, human metapneumovirus, coronavirus.
Clinical Presentation
Fever, leukopenia, or leukocytosis.
Increased respiratory secretions or change in sputum character.
New-onset or worsening apnea, tachypnea, dyspnea, wheezing, rales, rhonchi, cough, bradycardia, oxygenation.
Two or more serial chest radiographs with new or progressive and persistent infiltrate, consolidation, cavitation, or pneumatoceles (in infants <1 year of age).
See http://www.cdc.gov/nhsn/PDFs/pscManual/17pscNosInfDef_current.pdf and http://www.cdc.gov/nhsn/PDFs/pscManual/10-VAE_FINAL.pdf for delineation of CDC VAE and VAE criteria.
Diagnostic Evaluation
Chest radiography.
CBC with differential, CRP, ESR.
Blood and bacterial cultures, and Gram staining from endotracheal aspirate.
Bronchoalveolar lavage, using protected-specimen brush collection specimen.
Pleural fluid or lung biopsy.
Evaluation for viral etiology with respiratory viral culture/viral panel.
Management
Increase oxygen and other ventilator settings.
Hemodynamic support, as indicated support.
Broad-spectrum antibiotic administration.
Catheter-Associated Urinary Tract Infection
Definition
A UTI in which an indwelling urinary catheter was in place for >2 calendar days when all elements of the CDC UTI infection criteria were present.
The indwelling urinary catheter must be in place on the day of, or the day prior to, diagnosis.
Etiology/Types
Symptomatic UTI; asymptomatic bacteriuria.
Common Causative Organisms
E. coli, P. aeruginosa, Candida species, Enterococcus species, K. pneumoniae.
Clinical Presentation
Fever.
Urinary urgency, frequency, dysuria.
Costovertebral pain or suprapubic tenderness.
Associated with a positive urine culture, pyuria, positive dipstick for leukocyte esterase and/or nitrate.
Infants may present with hypothermia, apnea, bradycardia, lethargy, vomiting.
See http://www.cdc.gov/nhsn/PDFs/pscManual/17pscNosInfDef_current.pdf for delineation of CDC catheter-associated urinary tract infection criteria.
Diagnostic Evaluation
UA and urine culture with Gram stain.
CBC with differential, CRP.
Management
Antibiotic administration.
Analgesia and higher-level support if urosepsis.
Nosocomial Respiratory Syncytial Virus
Definition
Symptoms of lower respiratory tract infection and RSV antigen >72 hours after hospital admission.
Background
RSV is one of the most common etiologies of pediatric nosocomial respiratory tract infections in the pediatric intensive care unit (PICU) and is the most common nosocomial infection overall on pediatric wards.
Incubation period ranges from 2 to 8 days; median hospitalization for RSV disease is approximately 5 days; 10 days for nosocomial RSV disease.
Children with underlying morbidities and risk for severe disease, increased risk for prolonged hospitalization, and risk for mortality.
Hand washing and barrier devices are greatest tools in disease transmission prevention.
For more information, see RSV bronchiolitis in Section 3.
Surgical Site Infection
Definition
An infection occurring within 30 or 90 days after an operative procedure involving the skin, subcutaneous tissue, or deep soft tissues of the incision; associated with clinical signs of infection or associated positive wound culture.
Organ/space SSI: An infection that occurs 30 or 90 days after an operative procedure involving any part of the body, excluding the skin incision, fascia, or muscle layers, which was opened or manipulated during an operation.
Etiology/Types
Superficial incisional primary or secondary SSI.
Deep incisional primary or secondary SSI.
Organ/space SSI.
Common Causative Organisms (Pediatrics)
Staph. aureus, coagulase-negative staphylococci, P. aeruginosa.
Clinical Presentation
Diagnostic Evaluation
Wound culture or tissue biopsy.
CBC with differential, ESR, CRP.
Radiography, magnetic resonance imaging (MRI), CT, as indicated.
Management
Antibiotic administration.
Surgical drainage (include cultures).
Implant removal, as indicated.
Invasive Fungal Infections in Pediatric Patients: Aspergillus, Mucor, and Pneumocystis
Daniel K. Choi
Background/Definition
Nonacute fungal infections, such as tinea infections (e.g., tinea capitis, tinea pedis), are quite common.
Invasive fungal infections are overall rare, usually seen in patients who are immunocompromised, such as children with malignancies, on chronic immunosuppression after a solid organ transplant, patients in the PICU/NICU setting, and children with primary immunodeficiencies (including children with HIV).
Overall incidence of invasive fungal disease in children is hard to determine, but mortality is quite high, with estimates for mortality by Aspergillus alone to be 68% to 77%.
Etiology/Types
Three major groups of fungus.
Yeasts: round/oval, unicellular, and reproduce via budding. Examples include the Candida species.
Molds: long, floppy, fluffy colonies that have long tubular structures called hyphae. Reproduce by forming spore-forming structures called conidia. Examples include Aspergillus and Mucor species.
Dimorphs: change from yeast to mold and back, and grow in environment as molds.
Fungus is ubiquitous in the environment, preferring warm/damp environments to grow/reproduce (e.g., respiratory tract, endotracheal tubes, plastic in central venous catheters).
Pathophysiology
Inhalation of fungal spores is the most common route of infection.
Fungi then disseminate in the bloodstream to various organs.
Although fungal infection can occur anywhere, most common organs involved are respiratory tract (sinuses, lungs in particular), skin, kidney/bladder, and CNS.
Clinical Presentation
Skin rashes.
Persistent fever in an immunocompromised patient.
In the oncology population, fever for >4 days in a neutropenic patient is suggestive of fungal infection.
Persistent cough and/or other sinopulmonary symptoms.
Purulent sinusitis/sinus pain is suggestive of Mucor infection.
Persistent tachypnea and lower oxygen saturations are suggestive of Pneumocystis jirovecii pneumonia (formerly known as Pneumocystis carinii pneumonia [PCP]) infection.
Patients often appear asymptomatic.
Diagnostic Evaluation
Blood culture, urine culture; specify the specimen for fungal culture as well, as it is not universal across institutions.
Note that fungal cultures often take days to start growing.
Samples should have calcofluor white testing (formerly ordered as KOH) to test for yeast elements.
Suspicion for Pneumocystis jirovecii/P. carinii pneumonia can be tested via silver staining, confirmed by PCR testing.
Biopsy-proven infection is the gold standard, but is often difficult to obtain (except for skin biopsies).
Respiratory tract biopsies can be done via bronchoalveolar lavage, surgical biopsy, induced sputum culture, endotracheal tube culture.
Candida species will grow from urine and blood cultures.
Chest radiograph with diffuse “fluffy” infiltrates is suggestive of Pneumocystis jirovecii/P. carinii pneumonia.
CT of the sinuses/chest/abdomen/pelvis with contrast often indicated.
Fungal imaging varies widely, from single nodules to diffuse/necrotic tissue.
In some instances, MRI of the soft tissue is indicated.
Galactomannan antigen testing is helpful for Aspergillus species, but has variable sensitivity and specificity; must be interpreted with caution.
Management
Consultation with a pediatric infectious disease specialist is indicated.
Broad-spectrum coverage for invasive fungal infections is usually with an IV formulation of an echinocandin (e.g., micafungin) or polyene class (e.g., amphotericin B).
Azoles (e.g., voriconazole) do have activity against invasive species, although often have multiple drug interactions.
In localized Mucor infection, aggressive debridement (particularly in the sinuses) is indicated to prevent CNS extension.
For confirmed PCP infection, treatment with IV trimethoprim-sulfamethoxazole (i.e., Bactrim). For patients who cannot tolerate trimemethoprim-sulfamethoxazole, IV pentamidine is another option.
Treatments are often for a minimum of 6 to 8 weeks, and longer as needed under the supervision of pediatric infectious disease specialist.
Trimethoprim-sulfamethoxazole prophylaxis should strongly be considered for patients who are at risk for continued immunosuppression.
Viral and Bacterial Infections
Jill S. Thomas
Multidrug-Resistant Organisms
Increased prevalence of microorganisms resistant to one or more antimicrobial agents in the acute care setting leads to increased length of stay, mortality, and hospital costs.
Have created management challenges due to limited antibiotic selection and limited new antibiotic development.
Requires commitment to antibiotic stewardship by health care providers (Table 11.5).
Meningococcemia
Elizabeth Rosner
Definition
Bacteremia and sepsis caused by the bacteria N. meningitidis, also referred to as meningococcus.
Etiology
N. meningitidis is an encapsulated, gram-negative, oxidase-positive diplococcus.
Five clinically important serotypes are A, B, C, W-135, and Y.
W-135 accounts for approximately 75% of invasive disease in the United States.
Serotype B accounts for the majority of disease in infants <1 year of age.
TABLE 11.5 Multiresistant Organisms | ||||||||||||||||||||||||||||||
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Pathophysiology
Acquired primarily through respiratory tract.
The bacteria attach to epithelial cells and gain access to the bloodstream.
Survival of meningococcus is enhanced by its polysaccharide capsule and acquisition of iron from human transferrin.
Growth and lysis of the bacteria lead to release of endotoxin.
The endotoxin has an important role in stimulating cytokine release through activation of toll-like receptors, especially TLR4.
The inflammation produced by the cytokines, TNFα, IL-β, IL-6, and IL-8, causes capillary leak, shock, and multiorgan failure.
Endotoxin also causes activation of the clotting cascade, which can lead to disseminated intravascular coagulopathy (DIC).
Clinical Presentation
Initially may present with nonspecific symptoms of fever, malaise, vomiting, diarrhea, headache, and myalgias.
Later symptoms include limb pain, difficulty walking, maculopapular rash, signs of meningitis, including photophobia, nuchal rigidity, lethargy, and seizures.
In fulminant meningococcemia, purpura, limb ischemia, shock, coma, and death can occur in as little as a few hours (Figure 11.1).
Diagnostic Evaluation
Blood and CSF cultures identifying N. meningitidis are the definitive diagnosis.
May not be able to obtain CSF in unstable patients.
PCR from the blood and CSF can also be used to detect the organism.
CBC, coagulation studies, and blood gas analysis should also be obtained.
 FIGURE 11.1 • Meningococcemia. Gangrene in a child with sepsis from acute meningococcemia. |
Management
Intravenous ceftriaxone at meningitic doses (100 mg/kg/day) as soon as possible for 5 to 7 days.
Cefotaxime is also acceptable.
Once the organism has been identified, it may be acceptable to switch to penicillin G.
In a penicillin-allergic patient, use either chloramphenicol or meropenem.
Fluid resuscitation up to and beyond 60 mL/kg as fast as possible until perfusion improves.
Hemodynamic support with agents such as dopamine, epinephrine, and/or norepinephrine may be necessary for fluid-refractory shock.
Correct for metabolic and electrolyte derangements.
Intubation and mechanical ventilation for severe shock, sepsis, and subsequent multiple organ dysfunction, especially acute respiratory distress syndrome (ARDS).
Treatment of seizures with antiepileptics, as indicated.
Prevention
Patients should be placed on droplet precautions for the first 24 hours of antibiotic therapy.
Close contacts should be given prophylactic antibiotics within 24 hours.
Ciprofloxacin 500 mg by mouth × 1 dose.
Ceftriaxone and rifampin are other options.
All adolescents and those at risk for invasive disease should receive a meningococcal conjugate vaccine, (e.g. Menactra, MenHibrix, Menveo).
Serotype B is not covered by the vaccine.
Find latest immunization recommendations on the CDC website http://www.cdc.gov/vaccines/schedules/hcp/child-adolescent.html
Sexually Transmitted Infections
Jill S. Thomas
Sexually Transmitted Infections
Sexually transmitted infections (STIs) refer to a variety of clinical syndromes caused by pathogens that can be acquired and transmitted through sexual activity.
Part of the management of any patient with an STI is counseling about prevention and referral of partner.
Human Papillomavirus Definition
A double-stranded DNA virus belonging to the family Papovaviridae.
STIs are most prevalent in individuals <24 years of age.
Etiology/Types
Clinical Presentation
Typically asymptomatic, may present with genital warts occurring on the vulva, perianal area, vaginal walls, or cervix.
Recurrent respiratory papillomatosis presents with warts occurring in the throat.
Diagnostic Evaluation
Visual inspection.
Pap test with HPV test detecting viral nucleic acid or capsid protein.
Management
No pharmacologic treatment recommended in the absence of genital warts.
For external warts, antibiotic therapy includes podofilox 0.5% solution or imiquimod 5% cream, podophyllin resin, or trichloroacetic acid.
Cryotherapy and/or surgical removal.
Intralesional interferon, laser surgery.
PEARLS
Two vaccines are available for vaccination against HPV with a 9-valent vaccine; routine vaccination has been recommended for males and females beginning at approximately 11 years of age.
Follow the latest immunization recommendations on the CDC website http://www.cdc.gov/vaccines/schedules/hcp/child-adolescent.html
Herpes Simplex Virus (HSV)
Definition
An enveloped, double-stranded DNA virus belonging to the family Herpesviridae.
Genital herpes is a chronic, lifelong viral infection caused by the HSV.
Etiology/Types
HSV-1.
HSV-2: believed to cause the majority of genital HSV infections.
Clinical Presentation
Asymptomatic or may have vesicular lesions, ulcers, leucorrhea, dysuria, inguinal adenopathy.
Diagnostic Evaluation
Viral cell culture.
PCR (greater sensitivity than viral cultures).
HSV type-specific serological assay.
Management
Antiviral therapy with acyclovir, famciclovir, or valacyclovir.
Length of therapy dependent on initial presentation or recurrence of infection.
Gonorrhea
Definition
The second most common STI in the United States.
Caused by N. gonorrhoeae, gram-negative, oxidase-positive diplococcus.
Clinical Presentation
General: urinary frequency, urgency, and burning with urination.
Females: may have inflammation of the Bartholin and Skene glands, cervical mucoid discharge, or may remain asymptomatic until complications occur.
Males: penile discharge.
Diagnostic Evaluation
Test endocervical, vaginal, urethral (male only), and urine specimens.
Bacterial culture with Gram stain, nucleic acid hybridization tests, and nucleic acid amplification tests (NAATs) detect N. gonorrhoeae.
Culture and antimicrobial susceptibility testing if treatment failure is suspected.
Evaluate for other STIs, including chlamydia, syphilis, and HIV.
Management
Intramuscular ceftriaxone plus azithromycin or doxycycline.
PEARL
Major cause of cervicitis, pelvic inflammatory disease (PID), ectopic pregnancy, and infertility.
Chlamydia
Definition
The most common reportable STI in the United States.
Obligate intracellular bacteria.
Etiology/Types
Chlamydia trachomatis.
Clinical Presentation
Asymptomatic infection common among men and women.
Women may present with vaginitis, urethritis, cervicitis, endometriosis, salpingitis, PID. May experience vaginal discharge or dysuria.
Diagnostic Evaluation
Urine, endocervical, vaginal, urethral (men), rectal, and oropharyngeal swabs.
NAATs are the test of choice.
Cell culture, direct immunofluorescence, enzyme immunoassay (EIA), and nucleic acid hybridization tests available for endocervical specimens.
Urethral swab specimens from men.
U.S. Preventive Services Task Force recommends routine chlamydia screening for all women ≤25 years of age who are sexually active.
Management
Azithromycin or doxycycline as per CDC recommendations.
PEARL
Leading cause of PID, which can lead to infertility and chronic pelvic pain, often associated with gonorrhea.
Syphilis
Definition
A systemic STI caused by the spirochete Treponema pallidum.
Etiology/Types
Primary: develops 10 to 90 days after exposure.
Secondary: develops 4 to 10 weeks after primary infection.
Tertiary: develops 2 to 19 years after primary infection in untreated individuals.
Clinical Presentation
Primary: presents with an ulcer or painless chancre at the infected site.
Secondary: myalgias, mucocutaneous lesions, lymphadenopathy, influenza-like symptoms, cranial nerve dysfunction, altered mental status, or skin rash involving soles of the feet and palms of the hands.
Tertiary: cardiac or gummatous lesions.
Latent infections lack clinical symptoms.
Diagnostic Evaluation
Darkfield examinations and direct fluorescent antibody (DFA) detection of T. pallidum in lesion exudate or tissue are the definitive methods for diagnosing early syphilis.
Dual serological testing using a nontreponemal test (Venereal Disease Research Laboratory and rapid plasma reagin tests) and treponemal test (fluorescent treponemal antibody absorption tests, the Treponema pallidum passive particle agglutination assay, EIA), study of choice for latent, secondary, and tertiary syphilis.
