Pediatric Examination and Board Review (175 page)

6.
(C)
Amantadine and rimantadine are only active against influenza A. Interferon-alpha is not recommended for treatment of influenza. Zanamivir is approved for prophylaxis of influenza A or B in children 5 years of age and older and for treatment of children 7 years of age and older.

7.
(B)
Based on placebo-controlled studies in both adults and children, patients who receive oseltamivir within 2 days of onset of symptoms of influenza had a shorter illness duration, more rapid return to normal health and activity, and decreased frequency of secondary complications such as sinusitis and otitis media that required antibiotic prescriptions. Therapy should be considered for children at increased risk of severe or complicated influenza, healthy children with severe illness, and for children in special environmental, family, or social situations in which ongoing illness would be detrimental.

8.
(A)
Patients with the first episode of genital herpes may initially have mild symptoms but develop more severe or prolonged symptoms. Both acyclovir and valacyclovir decrease the duration of symptoms and viral shedding in genital herpes. If oral acyclovir is initiated within 6 days of the onset of disease, the duration of illness and viral shedding are shortened by 3-5 days.

9.
(A)
Acyclovir is a dioxygenase analog that is monophosphorylated by virus-encoded thymidine kinase and then diphosphorylated and triphosphorylated by host cell enzymes. Acyclovir triphosphate prevents viral DNA synthesis by inhibiting viral DNA polymerase. Acyclovir also results in DNA chain termination.

10.
(C)
The most frequent neurologic manifestations are tremors, myoclonus, lethargy, agitation, and hallucinations. These side effects occur in patients with compromised renal function who achieve high concentrations of acyclovir. Neutropenia has been observed in neonates receiving high doses of IV acyclovir (60 mg/kg per day) for treatment as well as infants receiving oral acyclovir for suppressive therapy.

11.
(D)
Foscarnet is a noncompetitive inhibitor of viral DNA polymerase. Foscarnet can be used for treatment of CMV retinitis in patients with AIDS. Foscarnet also is an option for a patient with severe CMV infection that is unresponsive to ganciclovir. Foscarnet also is the antiviral agent of choice for treatment of acyclovir-resistant herpes simplex and varicella zoster infections. Parainfluenza virus is an RNA virus, and foscarnet is not active against RNA viruses.

12.
(E)
Azotemia, proteinuria, acute tubular necrosis, crystalluria, and interstitial nephritis can occur. Risk factors for renal dysfunction include preexisting renal disease, use of other nephrotoxic drugs, dehydration, rapid injection of large doses, and continuous IV infusion. Hypocalcemia can occur because of chelation of ionized calcium by foscarnet. Seizures are one CNS complication that can occur as a manifestation of hypocalcemia.

13.
(B)
Interferons are a family of immunoregulatory proteins associated with a variety of antiviral, antiproliferative, and immunomodulatory activities. Interferon-alpha is approved for treatment of chronic hepatitis B and hepatitis C infection as well as papillomavirus-induced anogenital disease.

14.
(A)
The symptoms of an influenza-like illness usually remit with continued therapy. These symptoms rarely require discontinuing therapy or changing the dose. The two major therapy-limited toxicities of interferon are neuropsychiatric complications (somnolence, confusion, behavioral disturbances, depression, seizures) and bone marrow suppression. Neutropenia and thrombocytopenia commonly occur.

15.
(D)
Either choice A or B are preferred regimens for initial antiretroviral therapy and would be considered highly active antiretroviral therapy (HAART). This includes at least three drugs for the initial treatment of infants, children, and adolescents with HIV infection. This triple drug regimen should include at least two different classes of antiretroviral medications. Choice C, which is triple NRTI therapy, should only be used in special circumstances. The regimen should be considered only when there is concern regarding drug interactions or adherence (
Table 99-1
). In infants exposed to nevirapine as a result of maternal-infant prophylaxis, nevirapine is not recommended for initial therapy. Choice D, which is monotherapy, should never be used as therapy for children with HIV infection. Dual therapy with two NRTIs also should never be recommended for initial therapy. If there are significant concerns regarding adherence with antiretroviral medications, these should be addressed first before starting therapy.

16.
(B)
Monotherapy as initial therapy for HIV infection in children is only recommended for chemoprophylaxis administered to HIV-exposed infants during the first 6 weeks of life to prevent perinatal HIV transmission.

17.
(A)
The most common toxicities in children with zidovudine treatment are anemia and neutropenia, both of which usually resolve with temporary cessation of drug or dose modification. The NRTI drugs didanosine (ddI) and stavudine (d4T) have peripheral neuropathy as their primary toxicity. Abacavir (ABC) has been associated with a hypersensitivity reaction consisting of fever, rash, nausea, vomiting, or abdominal pain. This reaction should result in permanent discontinuation of the drug.

18.
(E)
With the protease class inhibitors, resistance requires multiple mutations. The protease inhibitors target HIV during maturation of the virion by inhibiting the viral protease.

TABLE 99-1
Recommended Antiviral Drugs for Initial Therapy of Children with Human Immunodeficiency Virus Infection

Abbreviations: PI, protease inhibitor; NNRTI, nonnucleoside analog reverse transcriptase inhibitor; NRTI, nucleoside analog reverse transcriptase inhibitor.

S
UGGESTED
R
EADING

Guidelines for the use of antiretroviral agents in pediatric HIV infection. USDHHS AIDSinfo Web site.
http://AIDSinfo.nih.gov
. Accessed July 28, 2009.

Kimberlin DW. Antiviral agents. In: Long SS, Pickering LK, Prober CG, eds.
Principles and Practices of Infectious Diseases.
3rd ed. Philadelphia, PA: Churchill Livingstone; 2008: 1470.

CASE 100: A 12-YEAR-OLD GIRL WITH LEUKEMIA AND PERSISTENT FEVER

A 12-year-old girl, whom you have followed in your practice since birth, was recently diagnosed with AML after developing fever, fatigue, and epistaxis. Your patient had begun chemotherapy under the guidance of your pediatric oncology consultant. After induction chemotherapy was completed, you receive a phone call on a Saturday evening that your patient has developed fever at home. You direct your patient’s parents to bring her to the children’s hospital emergency department.

On physical examination at the emergency department, the adolescent girl was nontoxic in appearance. The temperature was 102.2°F (39°C). There was mild erythema of the posterior pharynx. Examination of both lungs and the heart were normal. A WBC count revealed an absolute neutrophil count of 200/mm
³
, hemoglobin of 9.0 g/dL, and platelet count of 130,000/mm
³
. Ceftazidime empirical therapy was begun. However, fever persisted, and after 4 days a repeat WBC count revealed an absolute neutrophil count of 0/mm
³
.

SELECT THE ONE BEST ANSWER

1.
The most appropriate course of action to follow with the persistence of fever includes

(A) addition of vancomycin to antibiotic regimen

(B) change of ceftazidime to imipenem

(C) addition of ketoconazole

(D) addition of liposomal amphotericin B

(E) addition of acyclovir

2.
One of the common adverse events to monitor now in the 12-year-old patient after the change in management just described is

(A) hypercalcemia

(B) hypokalemia

(C) hypermagnesemia

(D) hyperuricemia

(E) hyponatremia

3.
An 850 g very low birthweight infant now 24 days old has a central venous catheter and has completed a 10-day course of broad-spectrum antibiotic therapy with cefotaxime and gentamicin for a bacteremia caused by
E coli
. The infant develops apnea along with poor feeding and hypothermia. A blood culture sent to the microbiology laboratory is reported in 24 hours to be growing a yeast. Appropriate initial therapy would now include

(A) amphotericin B deoxycholate

(B) fluconazole

(C) liposomal amphotericin B

(D) flucytosine

(E) caspofungin

4.
You prescribe griseofulvin for a 6-year-old child with
Tinea capitis
. Which of the following is not true about griseofulvin?

(A) treatment for 4-6 weeks is the usual regimen

(B) the drug is applied topically to the lesions

(C) prolonged therapy is associated with hepatotoxicity

(D) the drug is given once daily

(E) the drug should be given after a meal containing fat

5.
You are asked about the appropriate indications for use of the triazole antifungal agent fluconazole. For which of the following infections would fluconazole be appropriate for first-time therapy?

(A) treatment of esophageal candidiasis caused by
Candida albicans
in a 6-year-old child with HIV infection