Infectious mononucleosis with Staphylococcus aureus pharyngitis co-infection

Christopher P. Zipp, UMDNJ-SOM, Family Medicine, 42 E. Laurel Road, Ste. 2100, Stratford, NJ 08084-1354.

E-mail address: zippch@umdnj.edu.

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‌Case presentation

History of present illness

‌D.D., an 18-year-old female dance student in Philadel- phia presented with a three-day history of fever of 101 °F, night sweats, sore throat, upper respiratory congestion, swollen glands, abdominal pain, nausea, and fatigue. A rapid strep test was performed in the office and was nega- tive; however, a throat culture was sent out for analysis. In addition, blood work was ordered for a mono spot hetero- phile antibody test, Epstein-Barr Virus (EBV) panel, com- plete blood count, and complete metabolic profile.

Focused physical examination

The patient had posterior pharyngeal erythema and exu- dates with enlarged tonsils. Enlarged posterior and anterior cervical lymph nodes were also noted. The abdomen was soft with minor nonlocalized tenderness on palpation. The spleen and liver were examined for enlargement and ten- derness, both were unremarkable. The remainder of the physical examination was unremarkable.

Laboratory and cultures

Laboratory studies revealed an elevated white blood cell count of 13.8, absolute lymphocytes of 9.5, and absolute monocytes of 1.2. Neutrophils were 21% and lymphocytes were 69%, with 23% atpical lymphocytes. Liver function test revealed elevated total bilirubin of 2.1 mg/dL, alkaline phosphatase of 321, AST of 241, and ALT of 312.

Table 1 Symptoms and signs of infectious mononucleosis

Symptoms of infectious Signs of infectious mononucleosis mononucleosis

Sore throat (75%) Lymphadenopathy (95%)

Malaise (47%) Fever (93%)

Headache (38%) Pharyngitis and tonsillitis (82%) Abdominal pain, nausea, Splenomegaly (51%)

and vomiting (17%) Hepatomegaly (11%)

Chills (10%) Rash (10%)

Periorbital edema (13%)

Palatal exanthem (7%)

Jaundice (5%)

Percentages indicate the likelihood that a person with infectious mononucleosis will present with the described sign or symptom. Data taken from Ref. 16.

‌ination, her nasal mucosa and turbinates were found to be normal. Her posterior pharynx showed no signs of exudate. Her abdomen was soft and nontender with normal bowel sounds. Liver and spleen palpation showed no signs of enlargement or nodularity. Minor anterior cervical adenop- athy was present. The patient was instructed to return to the office six weeks later to recheck her laboratory values, particularly her liver function tests, and to receive permis- sion to return to school and resume dancing.‌

‌Treatment

At the conclusion of the office visit, the patient was instructed to complete a course of amoxicillin 875 mg twice daily for 10 days to treat suspected group A beta-hemolytic streptococci (GABHS). In addition, the patient was in- structed to use over-the-counter guaifenesin for congestion. A few days later, the lab results returned and a diagnosis of acute infectious mononucleosis with hepatitis was made. In addition, the throat culture results were positive for Staphy- lococcous aureus and yeast.

‌The patient was called and informed to refrain from physical activity, to drink plenty of fluids, and to rest. She was informed of danger signs that might prompt a visit to the emergency department (e.g., abdominal pain, odynopha- gia, dysphonia). The patient was instructed to return to the office in one month for a follow-up and to have her labo- ratory values rechecked. The patient was prescribed a one- day course of fluconazole (1 tablet, 150 mg) for the isolated yeast on the throat culture, and sulfamethoxazole and tri- methoprim double strength, one tablet by twice daily for 10 days to treat the Staphylococcus aureus pharyngitis.

Follow-up visit

At follow-up, the patient had completed the course of fluconazole and trimethoprim/sulfamethoxazole and stated that she felt much improved and was regaining her energy. She denied any abdominal pain, chest pain, shortness of breath, nausea, vomiting, or diarrhea. Upon physical exam-

Discussion

Infectious mononucleosis is usually caused by the Epstein- Barr virus (EBV; or human herpesvirus 4). More than 90% of adults worldwide are seropositive for EBV. Infectious mononucleosis may be seen at any age but usually occurs sporadically or epidemically in persons in the United States between the ages of 10 and 35 years. EBV is transmitted by close human contact, frequently with the saliva during kiss- ing. In certain instances it can be associated with certain lymphomas and nasopharyngeal carcinomas. Infectious mononucleosis is characterized by generalized lymphade- nopathy, splenomegaly, pharyngeal erythema and exudate, and the appearance of atypical activated T lymphocytes (CD8+ T cells) in the blood.2,3 Table 1 lists the symptoms and signs of infectious mononucleosis.

In this case report, the patient presented with signs and symptoms suggestive of GABHS pharyngitis or infectious mononucleosis. An EBV panel verified infectious mononu- cleosis and the results are shown in Tables 2 and 3. Hete- rophile antibodies are 40% positive in patients with infec- tious mononucleosis in the first week, and initial tests may be negative. In addition, throat culture swab results indi- cated a S. aureus pharyngitis infection (Table 4). The sig- nificance of this finding is that infectious mononucleosis with S. aureus pharyngitis co-infection is not commonly encountered in the clinical setting. In general, the studies we encountered showed that GABHS is the most common bacterial cause of pharyngitis.4,5 Three studies to date illus- trate a relationship between infectious mononucleosis and GABHS pharyngitis co-infection. In one study of 500 pa- tients with infectious mononucleosis, 30% had GABHS.6 Two other studies reported that rates were between 3% to 4% in more than 100 patients.7,8 As a result of these find- ings, the true rate most likely falls somewhere between 3% and 30%.

‌S. aureus infections, on the other hand, are better known for causing skin lesions and cellulitis, in addition to osteo- myelitis, pneumonia after an influenza infection, endocar- ditis, food poisining, and toxic shock syndrome.3 S. aureus pharnygitis infections are possible but are not nearly as prevalent as GABHS pharyngitis infections. Studies in the past have been documented to investigate the relationship and mechanism between oropharyngeal bacterial coloniza- tion during a viral illness. Two studies in the 1980s dem- onstrated that adherence of S. aureus to pharyngeal cells is increased during upper respiratory infections.9,10 In addi- tion, epidemiological studies have shown a prevalence of S. aureus in the Unites States. However, these studies moni- tored nasal colonization of S. aureus as opposed to pharyn- geal colonization.11,12 A recent study in 2006 by Nilsson and Ripa illustrated that S. aureus throat colonization is more frequent than nasal colonization. They concluded that S. aureus carriage in the anterior nares in most cases indi- cates the presence of the organism in the throat.13 Admit- tedly, in this study the individuals were healthy so it remains to be seen whether the frequency of infection would change when comparing throat colonization to anterior nares colonization in persons who are also concomitantly infected with a viral illness. Questions still remain as to what is the best source for detecting S. aureus. According to an article by Mertz et al., throat swabs are necessary to more accu- rately detect carriers of S. aureus.14 All carriers of S. aureus are not identified by nasal swabs alone. The study showed that 30% of persons in the population are carriers of S. aureus in the anterior nares and an additional 12.8% are pharyngeal carriers alone.14 With the rising occurrence of methicillin-resistant Staphylococcus aureus (MRSA) in the United States, determining which patients are pharyngeal asymptomatic carriers from patients who have an acute S. aureus pharnygitis infection may help to reduce the occur- rence of MRSA infections in the future. Current screening programs for MRSA do not call for pharyngeal swabs, but the standard of care my change during the upcoming years as we continue to see an increase in the prevalence of MRSA in the heath care setting.14,15

‌In conclusion, the patient was treated with antibiotics for infectious mononucleosis with S.aureus pharyngitis co-in- fection. We acknowledge that the patient may have been an asymptomatic carrier and more research should be directed towards investigating the percentage of the population who are pharyngeal-asymptomatic carriers of S. aureus versus those with an active S. aureus pharyngitis infection. We must be careful because treatment of asymptomatic carriers may promote antimicrobial resistance. It may not be neces- sary for physicians to treat patients who are previously found to be asymptomatic carriers with antibiotics, thus helping to prevent antimicrobial resistance, particularly that to MRSA.

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14. Mertz D, Frei R, Jaussi B, et al: Throat swabs are necessary to reliably detect carriers of Staph aureus. CID 45:475-477, 2007

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