Case 10

6-MONTH-OLD WITH A FEVER - HOLLY

Author: Christopher White, M.D., Medical College of Georgia Case Objectives 1. Meningitis must be considered in the differential diagnosis of any febrile infant, regardless of the presence or absence of meningeal signs. 2. The only reliable way to rule out meningitis in a febrile infant less than 12 months of age is with a lumbar puncture. 3. Urinary tract infections should be considered in the differential diagnosis of any febrile infant with a non-focal History and Physical Examination. 4. The only reliable method of diagnosing a urinary tract infection in an infant is a urine culture from a catheterized specimen (urine cultures obtained from bag specimens are unreliable). 5. Empiric antibiotic therapy for an infant or young child with an uncomplicated urinary tract infection should cover predominantly enteric gram-negative bacilli, particularly E. coli. Infants with severe symptoms should receive parenteral antibiotics. 6. All infants with a urinary tract infection need to have an evaluation of their genitourinary tract. This consists of an abdominal and pelvic ultrasound, and a voiding cystourethrogram (VCUG). Summary of Clinical Scenario: 6 month old Holly has had a fever for 2 days, is fussy and not eating. Her review of symptoms is negative. There are no focal findings on physical exam, including negative Kernigs Brudzinkis signs. Elevated WBC with left shift suggests bacterial infection but normal chest X-ray rules out pneumonia and normal CSF rules out meningitis. Leukocytes and nitrite in the urine strongly suggests a bacterial UTI.

Fever for two days Fussy

Key Findings from History

Poor appetite Absence of coryza/cough Absence of vomiting/diarrhea

Non-focal PE

Key Findings from Physical Exam

(-) Kernigs and Brudzinskis signs Tachycardia Tachypnea

URI Gastroenteritis

Differential Diagnosis

Otitis media Meningitis UTI Pneumonia

Elevated WBC

Key Findings from Testing

Normal CSF Leukocytes/nitrite in urine, Normal CXR

Final Diagnosis

UTI with pyelonephritis

Case Highlights: Students learn to narrow the diagnosis for fever using targeted questions to the mother, and by using lab and imaging studies. They learn about the Yale Infant Observation Scale, and how to perform and interpret maneuvers to elicit Kernig's and Brudzinki's signs. The case teaches how to interpret Holly's CBC and dipstick urinalysis, leading to a diagnosis of UTI. Students then learn guidelines for admitting a child with a UTI, and which antibiotics to prescribe for treating the acute symptoms and providing later prophylaxis. Information on tests for renal scarring is also provided. Multimedia features include: image of dipstick and its interpretation, voiding cystourethrogram.

Key Teaching Points

Knowledge:
Definitions for Fever Conditions Fever - 100.5F, or 38.0C. Bacteremia - presence of viable bacteria in circulating blood. Septicemia - systemic disease caused by multiplication of microorganisms in the circulating blood. Fever Without Source (FWS) - fever with no apparent focus of infection after careful Hx and PE. Fever of Unknown Origin is a fever of at least two weeks duration with failure to reach a diagnosis after one week of evaluation. Occult bacteremia (OB) - pathogenic bacterial species in blood cx from child not suspected of having a bacterial infection based on history, physical examination, and screening laboratory tests, including chest X-ray, lumbar puncture, and urinalysis. OB occurs in febrile infants birth to 3 yo. Serious bacterial Illness (SBI) - bacteremia, bacterial meningitis, bacterial enteritis, pneumonia, sepatientic arthritis, osteomyelitis, and cellulitis.

Skills:
History and Physical Exam: Meningeal Signs ("meningismus") - physical findings after meningeal irritation from inflammation, tumor or hemorrhage. Basis for tests is to see if patient rejects any

movement that stretches spinal nerves, which pass through the irritated subarachnoid space. 1. Neck Stiffness ("nuchal rigidity") - involuntary resistance to neck flexion. Clinician flexes patient's neck forward. In severe cases, increased extensor tone of neck and spine leads to hyperextension of entire spine, or "opisthotonus." 2. Kernig's Sign - Flex patient's hips and extend knees, and see if patient resists knee extension from this position. (+) Kernig's sign when patient resists extension. 3. Brudzinski's Sign - flex supine patient's neck, and see if patient flexes both hips and knees. (+) Brudzinski's if patient retracts legs toward the chest. (Reference: McGee, S. Evidence-Based Physical Diagnosis. Philadelphia, Pennsylvania: W.B. Saunders Company. 2001: 303-304.) Differential Diagnosis: UTI - consider in patients two months two years with unexplained fever, non-focal Hx and PE. Consider degree of toxicity, dehydration, and ability to retain oral intake. In this case UTI likely since UA abnormal, elevated WBC, and absence of physical findings suggesting other causes. Based on high WBC and fever, she may have an upper UTI (pyelonephritis). Gastroenteritis - Viral or bacterial gastroenteritis may cause high fever, but would expect to see vomiting and/or diarrhea by 2nd day of illness. URI - Infants with viral URI may present with a high fever, but diagnosis unlikely because no cough, congestion or coryza. AOM - ruled out by PE. Meningitis - Must consider in any febrile infant, regardless of presence or absence of meningeal signs. The only reliable way to R/O meningitis in febrile infant <12 mos old is with LP. In this case, meningitis is possible, need to R/O by LP as normal CSF rules out this diagnosis. Pneumonia - Most infants with pneumonia have cough and/or tachypnea, but fever may be only presenting sx. Even though chest exam normal, still consider pneumonia. However, pneumonia very unlikely with normal CXR. URI - Viral URI unlikely due to the negative history and PE, and elevated WBC. Studies: Diagnostic Tests 1. CXR - Bacterial pneumonia is possible in any ill-appearing infant with a fever for several days, even in the absence of respiratory symptoms or abnormal pulmonary findings. Most clinicians would consider getting obtaining a CXR in this setting. 2. CBC A total WBC > 15,000 cells/mm3 with a "left shift" suggests a possible serious bacterial infection, although the predictive value of this finding is low. Most viral infections have normal WBC and differential. 3. UA Positive nitrate, leukocyte esterase, and blood strongly suggest bacterial UTI. Urine specimens obtained by bags have high rate of contamination. Therefore, get catheterized sample when need to R/O UTI in child who is not toilettrained. (+) Nitrite in UA highly specific for bacteruria (few false positives). A negative nitrite has very poor sensitivity (lots of false negatives) for bacteruria or infection. (+) leukocyte esterase detects esterases released from broken-down leukocytes. (+) test usually indicates presence of WBCs in urine (pyuria), but it can be seen in a variety of conditions besides UTI. Thus, (+) leukocyte insufficient to make UTI diagnosis.

4. Lumbar Puncture Indications - examine spinal fluid for suspected infection or malignancy, instill intrathecal chemo, measure opening pressure. Some perform LPs in any febrile young infant (<6 mos old) who has no obvious focus of infection. Others only perform when infant is toxicappearing, or laboratory studies suggesting serious bacterial infection (i.e., WBC > 15,000 with a "left shift," or temperature >40 with no obvious other focus for infection). General rule - if going to treat any febrile young infant with parenteral antibiotics for a "presumed" bacterial infection, LP should be done. Contraindications/Cautions 1. Increased intracranial pressure - before LP, look for evidence of high ICP (papilledema, retinal hemorrhage). 2. Bleeding diathesis - platelet count should be >50,000 before LP. 3. Overlying skin infection 4. Unstable patients (Reference: Harriet Lane, 16th Ed.) 5. Voiding cysturethrogram (VCUG). Recommended for all infants after their first UTI. "Backwash" of urine from bladder into ureter or kidney due to incompetent ureterovesical junction. Most VUR cases mild and resolve spontaneously. In up to 50% of patients < 1 yo with UTI. Patients with VUR have increased risk recurrent UTIs, so often placed on prophylactic abx until reflux has resolved or been surgically corrected. Potential complication - renal scarring due to high pressures during voiding and repeated episodes pyelonephritis. Diagnosis Vesicoureteral reflux (VUR) 6. Abdominal ultrasound Necessary to perform on all infants after their first UTI. Provides information about renal structure and dilations in the collecting system.

Management:
UTI Abx Tx If patient does not appear ill but has (+) urine cx, start IV or po abx. Empiric abx for an infant or young child with uncomplicated UTI should cover predominantly enteric gram-negative bacilli, particularly E. coli. Infants with severe symptoms should receive IV abx. If patient with suspected UTI is toxic, dehydrated, or unable to retain oral intake, initiate abx and consider hospitalization. If patient not responsive to abx after 2 days, reevaluate and repeat urine cx. All patients with UTI should complete a 7- to 14-day abx course orally. After 7- to 14-day course of abx, patients with UTI should be on abx until the imaging studies completed. Other Studies - all infants with UTI need eval of GU tract, which includes abdominal and pelvic U/S, and voiding cystourethrogram (VCUG). Indications for Inpatient Tx Toxic appearance, dehydration, or inability to retain oral intake. Evidence of: clinical urosepsis, bacteremia. Antibiotics for Pyelonephritis IV Antibiotics

In a child who has not been on prophylactic abx, most likely cause of an initial episode of pyelonephritis is E. coli, with the remainder of cases caused by other enteric gram-negative organisms or enterococci. Ampicillin and gentamicin are still the antibiotics of choice for IV treatment of UTI. Ceftriaxone has excellent coverage against most gram-negative bacilli (except Pseudomonas aeruginosa and enterococci), and has excellent safety profile in children. Ciprofloxacin can be used, but expensive and potential adverse reactions in children, particularly damage to articular cartilage, especially the knee (usually not permanent). Should not be routinely used in children <16 yo. PO Antibiotics after D/C for Pyelonephritis Trimethoprim/Sulfamethoxazole (TMP/SMZ) good choice because it's inexpensive, well tolerated, and requires only twice-daily dosing. Rare problems include serious skin reactions. Ampicillin/clavulanate (Augmentin) okay, but much more expensive than TMP/SMZ. Nitrofurantoin recommended for lower UTI, not pyelonephritis. Sulfisoxazole should not be used because of resistance. Followup for pyelonephritis 1. 2. 3. 4. Voiding Cystourethrogram (VCUG) Abdominal Ultrasound Urinalysis for any febrile incidents without clear focus Periodic radionuclide cystogram to follow vesicoureteral reflux (VUR)

Web links: CDC sites on the National Immunization Program and adverse event report system National Network for Immunization Information Web site (current info on vaccines) Immunization Action Coalition Web site CDC's The Pink Book (Epidemiology and Prevention of Vaccine-Preventable Diseases) The CDC's Vaccine Adverse Event Reporting System Article on using the Yale Infant Observation Scale Article on meningitis and how to use Kernig's and Brudzinski's maneuvers to diagnose the disease AAP practice guideline diagnosing and treating the initial UTI in febrile infants and young children A Web site that explains voiding cystourethrogram as you might describe it to a parent (Cincinnati Children's Hospital Medical Center) AAP parent handout on UTIs in children

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