A 16-month-old with cold symptoms

A previously healthy 16-month-old boy presented to the ED in December for evaluation of cold symptoms (nasal stuffiness, rhinorrhea, productive cough) for six days with high spiking fever for three days.

He had been febrile to 105°F and not responsive to alternating acetaminophen and ibuprofen. He had been eating well and had appropriate urine output. He had some loose, nonbloody stools but no emesis or rashes. His parent reported that he was fussy but consolable. The patient was seen in the ED on day one of his fever. A chest X-ray was done and reported as normal, and he was given ceftriaxone. He was seen a second time in the ED with X-ray, blood culture and complete blood count. He was once again assigned to ceftriaxone.

On day three of his fever, his blood culture grew gram-negative cocci. His family was contacted by the ED to return to the hospital for admission. By the time he returned to the ED, he had been afebrile for six hours with continued clinical symptoms of rhinorrhea, nasal congestion and productive cough.

The patient had no significant past medical history. Delivery was at term via normal spontaneous vaginal delivery. There was no history of serious illnesses, prior hospital admissions or surgeries. His vaccinations were up to date except for the seasonal influenza and influenza A (H1N1). He was not taking any medications other than acetaminophen, ibuprofen and the two doses of ceftriaxone that was assigned from the ED.

The patient and his parents had just flown to Texas from New York for vacation. The family had been staying at a local hotel since arriving in the San Antonio area. In New York, the patient lives with his parents and two pet dogs. No one in the family smokes. There were no known sick contacts, but he did have the recent airport and air travel exposures. He did not attend day care.

Vital signs on admission showed a temperature of 99.6°F with a heart rate of 157 beats per minute. Respiratory rate was 28 breaths per minute, and his oxygen saturation was 97% on room air. Blood pressure was 92 mm Hg/50 mm Hg. On exam, he was ill-appearing, quiet and fussy but consolable. His pupils were equal, round and reactive to light. Sclera were clear without erythema or icterus. Tympanic membranes were clear bilaterally with no erythema, a good light reflex and no bulging. He had no oropharyngeal erythema, strawberry tongue or lesions. Nasal discharge with crusting around the nostrils was present. No lymphadenopathy was noted. His cardiovascular exam was significant for tachycardia. No murmur was appreciated, and distal pulses were strong. His lungs were clear to auscultation without wheezes, crackles or rales. There was no increased work of breathing. His abdomen was soft and nontender. There was no hepatosplenomegaly or masses. Skin exam showed no rashes. There was no warmth, swelling or erythema of any joints.

What evaluation would you undertake at this time?

Labs were collected to include cbc, a repeat blood culture, rapid influenza A, rapid respiratory syncytial virus, chemistry, urinalysis and urine culture. His white blood cell count during his ED visit was 12,800 with a repeat value of 5,930. Testing for influenza A and RSV was negative. The urinalysis was negative for glucose, bili, blood, protein, nitrites and leukocyte esterase. It had a specific gravity of 1.026 and trace ketones. Urine culture ultimately was negative for bacterial growth.

He had two chest X-rays during his two ED visits. Both demonstrated normally aerated lungs without focal consolidation, mass, pleural effusion or pneumothorax. The cardiothymic silhouette and bilateral hila were within normal limits, and the visualized osseous structures were unremarkable for age. No focal pneumonia was ever seen.

What is the most likely diagnosis? How would you treat this patient?

This patient was admitted because of the concerning blood culture with growth of gram-negative cocci. When gram-negative cocci are grown out of a blood culture, physicians must consider disease due to Neisseria, specifically N. meningitidis and N. gonorrhoeae. He did not have the clinical presentation of a patient with N. meningitidis, meningitis or sepsis. He did not exhibit nuchal rigidity, vomiting, lethargy, petechial rash or hypotension, nor did he present with the clinical presentation or common age for N. gonorrhoeae to be high on the differential. Based on this patient’s respiratory symptoms and overall well appearance, we suspected his bacteremia was secondary to an often overlooked gram-negative coccus, Moraxella catarrhalis. This suspicion was later confirmed by final identification of the organism.

M. catarrhalis (formerly called Branamella catarrhalis or Neisseria catarrhalis) is a gram-negative, aerobic, oxidase-positive diplococcus. Because M. catarrhalis is a gram-negative diplococcus that produces nonhemolytic, round, opaque colonies on blood agar, it can be easily misidentified as Neisseria in culture. Microbiology labs commonly use commercially available kits utilizing various biochemical tests to determine identification and distinction from Neisseria. The features these biochemical tests use are production of oxidase, catalase and deoxyribonuclease; reduction of nitrate and nitrite; hydrolyzing of tributyrin; and fermentation of carbohydrates. After 48 hours of growth, M. catarrhalis colonies tend to be larger than those of Neisseria and take on a pink color. In addition, M. catarrhalis colonies can be slid along the agar surface without disruption that is termed the “hockey puck sign.”

M. catarrhalis is part of the normal respiratory flora with the rate of respiratory tract colonization dependent on age, living conditions, hygiene, environmental factors, genetics of the population and other factors. The rate of colonization among adults is low (1% to 5%); however, nasopharyngeal colonization is quite common through infancy (33% to 100%). A change in patterns of nasopharyngeal colonization is occurring in countries where pneumococcal conjugate vaccines are used widely. Colonization by vaccine serotypes of Streptococcus pneumoniae is decreasing, and colonization by nonvaccine serotypes is increasing.

M. catarrhalis is also known to cause sinusitis, bronchitis and pneumonia. M. catarrhalis causes bronchitis and pneumonia in children and adults with underlying chronic lung disease. This organism is an exclusively human pathogen. It is a significant human pathogen and is one of the top three bacterial causes of otitis media along with S. pneumoniae and Haemophilus influenzae. Bacteremia can be complicated by local infections such as osteomyelitis or septic arthritis. Immunocompromised patients appear to be at higher risk for more invasive disease and complications from infection with this organism.

M. catarrhalis bacteremia is rare in children. In a small case series spanning 10 years, M. catarrhalis bacteremia was found to be more common in children aged younger than 2 years; patients with respiratory tract symptoms; and those who are immunocompetent. Most cases were identified during the winter. In most patients, M. catarrhalis bacteremia has not been associated with significant fever or leukocytosis. The common presenting complaints are respiratory tract symptoms and fever. M. catarrhalis does not seem to be a particularly virulent pathogen, but bacteremia can be associated with community- associated pneumonia or sepsis and can result in prolonged hospitalization.

M. catarrhalis produces beta-lactamase and is thus resistant to penicillin. Empiric parenteral treatment of suspected M. catarrhalis infections should therefore be with a beta- lactamase–resistant antimicrobial, such as third-generation cephalosporins. Amoxicillin/clavulanate; oral second- or third-generation cephalosporins; or one of the newer oral macrolides can be used for treatment on an outpatient basis. Ultimate length of therapy is dependent on the site and type of infection as well as patient status, but overall these infections generally respond to standard courses of appropriate antibiotics.

Our patient’s ultimate course

While awaiting final organism identification, the patient was continued on empiric ceftriaxone therapy. He remained clinically well with his repeat blood culture on admission yielding no growth. After a two-day hospital stay, he was transitioned to oral cefdinir and discharged home. He finished 10 days of antibiotics without further complications. Following completion of treatment, he was seen at a follow-up visit with his primary care doctor in New York and at that time was without any further concerns.

Shannon M. Murphy, MD, is a Captain in the U.S. Air Force. She is currently a Pediatric Resident at the San Antonio Uniformed Services Health Education Consortium.

Ashley M. Maranich, MD, is a Major in the U.S Army. She is currently a Pediatric Infectious Disease Physician at the San Antonio Military Medical Center and an Assistant Professor of Pediatrics at the F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences in Bethesda, Md.

For more information:

• Abuhammour W. South Med J. 1999;93:1071-1074.
• Ahmed A. Pediatr Infect Dis J. 2008;27:459-461.
• Murphy T. Clin Infect Dis. 2009;49:124-131.

Disclaimer: The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of Defense.