Walid Abuhammour

Newer antifungal agents

Invasive fungal infections have evolved into significant causes of morbidity and mortality in premature infants, immunocompromised children, and patients receiving immunosuppressive agents. Since the discovery in 1955, amphotericin B has been the cornerstone of antifungal treatment. The past 10 years, however, have witnessed a major expansion in the antifungal armamentarium through the development of less toxic formulations of Amphotericin B, the introduction of improved triazoles, and the advent of the echinocandin lipopeptides. In this article we discuss the Lipid-based amphotericin B, Voriconazole (a new azole), and Caspofungin (an echinocandin).

Kawasaki Disease Hospitalizations in a Predominantly African-American Population

This is a descriptive study of the occurrence of Kawasaki disease (KD) in an urban population that was a majority of African Americans. Records of 189 children (mean age, 2.9 ± 2.2 years [range: 2 months to 11.1 years]) hospitalized for KD over 8 years (January 1, 1992 to December 31, 1999) were reviewed and data analyzed. One hundred thirty-six (72%) were African American (AA), 43 (23%) were white, and 9 (5%) children were “others.” The annual frequency was 15 for AA and 7.7 for white per 100,000 5-year-old children. Coronary artery abnormalities (CAA) were reported in 21 (11%) children (18 [13.2%] of 136 AA, and 3 [4.7%] of 43 whites [p=0.095]). AA children with CAA were older than their white counterparts (26 to 24 vs. 5 to 2.8 months, p=0.03). There was a higher occurrence in winter and spring (110 cases [58%] vs. 79 cases [42%]) compared to summer and fall. KD occurrence was positively associated with average monthly snowfall (r=0.35, p=0.004) and inversely associated with average monthly temperature (r= - 0.2, p=0.048). African-American children were more likely to be hospitalized for KD compared to white children. The association of KD with temperature and precipitation suggest that it is influenced by environmental factors.

Group A Β-Hemolytic streptococcal bacteremia

Objective. The aim of this study was to review the clinical features, laboratory findings and the risk factors associated with invasive group A streptococcal infections in children admitted to our institution over a 9-year period (January 1, 1990 through December 31, 1999).Methods: Medical records of children who had a positive blood culture for group A betahemolytic streptococci and children who had this organism isolated from any other sterile site were identified and retrospectively reviewed.Results: Forty-one children with invasive GAS were identified, of whom 15 (36%) were diagnosed between 1990 and 1994, while the balance (26 patients, 63%) were diagnosed between 1995 and 1999 (p< 0.05). The mean age was 4.3 ± 2.5 years (age range: 2 months to 16 years). Thirteen (32%) patients were infants. Sixteen patients had only bacteremia, while 25 patients had in addition to bacteremia the following: cellulitis (n: 13), osteomyelitis (n: 6), pneumonia (n: 3), meningitis (n: 1), pharyngitis (n:3) and Toxic Shock Syndrome (n: 2). Primary varicella infection constituted the most common predisposing factor for invasive GAS infections and occurred in 11 (27%) patients. Leukocytosis (A white blood cell count > 15,000/ mm3) occurred in 21 (51 %) patients, while leukopenia (A white blood cell count < 5000/ mm3) occurred in 2 patients. Parenteral crystalline penicillin G followed by oral penicillin or amoxicillin were the most common antibiotics administered. The mean hospital length of stay was 8 days (range: 6–32 days). All, but one patient survived. The one patient who died had malnutrition and died from streptococcal toxic shock syndrome.Conclusion: More cases of invasive GAS were diagnosed during the second half of the study period, however, the overall rate of occurrence of bacteremia during the study period was consistent with previous reports. Primary varicella infection was the most common predisposing factor for invasive GAS infections. The low occurrence of toxic shock syndrome and fatalities among children with invasive GAS infections are consistent with other pediatric but not with adult series.

Invasive Aspergillosis in Children with Hematologic Malignancies

The respiratory tract is the most common system affected by aspergillosis in children with hematologic malignancies. However, Aspergillus spp. tend to invade blood vessels, resulting in systemic dissemination to multiple organs including, but not limited to, the brain, bones, liver, kidneys, and skin.Because early diagnosis and treatment are critical to the patient’s outcome, a high index of suspicion should be maintained in children with hematologic malignancies who are neutropenic and have prolonged fever that is unresponsive to systemic antibacterials. Several diagnostic modalities should be used simultaneously in order to establish the diagnosis in an expeditious manner. Detailed radiographic evaluations with plain radiographs, and CT scans of the chest, sinuses, brain, and other organs should be performed as soon as clinical suspicion is raised. Detection of circulating antigens, such as galactomannan and 1,3-β-glucan, and polymerase chain reaction appear promising in aiding in the diagnosis. A definitive diagnosis requires both a positive culture from a sterile site and evidence of tissue damage demonstrated by imaging studies or microscopic evaluations of sites of infection.Because the mortality rate is very high, empiric systemic antifungal therapy with amphotericin B, or one of its lipid formulations, should be initiated while laboratory investigations to substantiate or refute the diagnosis are continued. Surgical intervention is associated with a high mortality rate but may be of benefit in children with localized disease.

Bilateral optic neuritis in a patient with Kawasaki disease

We describe a 7-year-old male with a history of fever, headache, bilateral non-purulent conjunctivitis, and photophobia. Patient was initially treated for suspected bacterial meningitis with intravenous antibiotics. Due to lack of clinical response, negative cultures, and evolving signs of Kawasaki disease, he was treated with one dose of intravenous immunoglobulin. Patient improved except for the persistence of photophobia and bilateral conjunctival injection. Eye examination showed bilateral optic neuritis and a visual acuity of 20/80 in both eyes. Follow up eye examination after 6 weeks showed normal visual acuity, resolution of conjuctival injection, photophobia, and optic neuritis. This case highlights the posterior segment involvement in Kawasaki disease and the need for careful eye examination in patients with Kawasaki disease who have prolonged photophobia and conjunctival injection.

Systemic Antifungal Agents

Anti-fungal agents are classified under two major headings, systematic and topical agents. Only systematic anti-fungal agents will be discussed in this chapter. Since the discovery in 1955, amphotericin B has been the cornerstone of anti-fungal treatment. It is active against most species of fungl. However,Candida lusitaniae, Pseudallescheria boydii, and fusarium spp have primary resistance to amphotericin B. Recently, new liposomal preparations of amphotericin B have been developed. They are less nephrotoxic. The azole family of anti-fungal includes two broad classes: the imidazoles (clotrimazote, ketoconazote, miconazole) and the triazoles (flucouazole and itracouazole). Imidazoles are still widely used for the treatment of superficial mycoses and vaginal candidiasis. The systematic triazoles are more slowly metabolized and have less effect on human synthesis than imidazoles, hence they are preferred for systemic therapy. Flucytosine is a fluorinated pyrimidine. Clinically, the principal use of flucytosine is as adjunctive therapy with amphotericin B in the treatment of candidial or cryptococcal diseases. Griseofuluin is derived from penicillium. It is fungistaticin vitro for species of dermatophytes. It is useful for the treatment of tinea capitis and tinea unginum.

Bacille Calmette-Guerin Lymphadenitis: A single center experience

To describe the clinical presentation, course and management of infants that presented with the diagnosis of lymphadenitis after Bacille Calmette-Guerin (BCG) vaccination. This is a descriptive study of 89 patients that were referred to the pediatric infectious disease clinic at King Hussein Medical Center in Jordan with regional lymphadenitis after BCG vaccination. The presentation, course and treatment options of these cases were discussed. The study was conducted between September 2006 and September 2007. Eighty-nine patients (47 males (53%) and 42 females (47%) were studied. All infants received the same type of vaccine used by our Ministry of Health, which is the Danish strain. Unilateral axillary lymph node enlargement was the most commonly seen (47%). Cervical lymph nodes were noted in 22 patients (25%) and supraclavicular lymphadenopathy was seen in 16 (18%). Sinus formation was seen in 16 (18%) patients. 27 cases (30%) had fluctuating lymph nodes. Four infants had disseminated infection. The majority (65%) of patients had their symptoms starting within the first 2 months after BCG vaccination. Forty-two (47%) infants had conservative observational management. Anti-tuberculosis medications were commenced in 27 (30%). Surgical excision was performed in 10 (11.5%) cases. All infants but one had complete recovery by the end of the study period. BCG lymphadenitis is a potential complication that necessitates an early recognition and implementing appropriate treatment protocols. Complete healing of suppurative lymphadenitis after BCG vaccine can be achieved using different treatment protocols.

Treatment of invasive aspergillosis in children with hematologic malignancies

The respiratory tract is the most common organ involved with Aspergillosis in children with hematologic malignancies. AlsoAspergillus species tend to invade blood vessels resulting in systemic dissemination to multiple organs. Early diagnosis and treatment are pivotal to the patient’s outcome. A high index of suspicion should be maintained in children who have profound neutropenia and present with prolonged fever that is unresponsive to systemic antibiotics. Several diagnostic modalities should be used simultaneously in order to confirm the diagnosis in an expedited manner. Combination and sequential antifungal therapy have been shown to be of added benefit. Surgical intervention is associated with a high mortality rate, but may be indicated in children with a localized disease. In this article the authors review the epidemiology, microbiology, pathology, and clinical manifestations of invasive aspergillosis in children with hematologic malignancies. Current diagnostic approach, medical, and surgical treatment options are discussed.

Pulmonary Tuberculosis Outbreak in a Pediatric Population

Community-based outbreaks of Mycobacterium tuberculosis are uncommon in the United States but represent a dramatic type of epidemic that can lead to considerable investigations. Most of our knowledge regarding spread of tuberculosis (TB) has accumulated from the study of outbreaks. We describe the most recent outbreak of TB in Genesee County, Michigan. In February 2007, isoniazid-sensitive infectious pulmonary TB was identified in a 45-year-old African American grandmother who frequently provided care for her grandchildren and other children. The source case was reported to the Genesee County Health Department, which started an investigation to identify family and social contacts. We reviewed past medical records of contacts and prioritized them for evaluation based on the period of exposure to the index case. Health department staff screened contacts using clinical evaluation, tuberculin skin test, and chest radiography when indicated. Results were reviewed, and data were analyzed using descriptive inferential and epidemiological statistics.

Fulminant Hemorrhagic Pneumonitis

A7-day-old female infant was admitted to the pediatric intensive care unit (PICU) because of fever, rapid breathing, poor feeding, and lethargy. She was born by spontaneous vaginal delivery at 41 weeks of gestation to a 34-year-old mother after an uneventful pregnancy. There was no history of prolonged rupture of amniotic membranes or maternal fever during labor. There was no history of sexually transmitted diseases or of oral or genital lesions in the parents or siblings. The mother’s prenatal serologic tests for syphilis and group B beta-hemolytic streptococci were negative. On initial physical examination the infant was in moderate respiratory distress with intercostal retractions and a respiratory rate of 65 bpm, but the oxyhemoglobin saturation (SpO2) was 95% without oxygen supplementation. She was mildly dehydrated and lethargic. Temperature was 96.8°F and pulse 160/min. Blood pressure in the right upper and right lower extremities were 80/58 and 84/60 mm Hg, respectively. Upon auscultation of the chest bilateral f ine rales and rhonchi were noted. There were no cutaneous or mucous membrane lesions. The initial chest radiograph disclosed bilateral interstitial infiltrates with a normal cardiothoracic ratio. There was no evidence of pnenemothorax or pleural effusion. Initial laboratory studies revealed a white blood cell (WBC) count of 13,600/mm3 with 80% polymorphonuclear leucocytes, 6% band cells, 11% lymphocytes, 3% monocytes; hemoglobin, 14.5 g/dL, and hematocrit, 43%. The cerebrospinal fluid (CSF) showed 6 WBC/mm3, 9 red blood cells (RBC)/mm3, a protein level of 67 mg/dL, and a glucose level of 68 mg/dL. CSF Gram stain and tests for bacterial antigens, by latex agglutination particles, were negative. Serum transaminases and coagulation profile were within normal limits. Intravenous ampicillin sodium, 400 mg/kg/day, and cefotaxime, 200 mg/kg/day, were initiated. The infant’s respiratory status worsened with progressively increasing respiratory rate and hypoxemia. Arterial blood gases (on 100% oxygen) at this time showed the following values: pH, 7.3; partial pressure of carbon dioxide (PaCO2) 47 mm Hg; and partial pressure of arterial oxygen (PaO2) 45 mm Hg. Tracheal intubation and ventilatory support were necessary 8 hours after hospitalization. Following an atraumatic tracheal intubation, fresh blood and serosanguineous tracheal effluent were retrieved. The bloody tracheal effluent resolved following application of 10 cm H2O of positive end-expirator y pressure (PEEP). The repeat chest radiograph showed worsening of the bilateral interstitial infiltrates (Figure 1). The Gram stain of the pulmonary aspirates did not reveal any bacteria. The possibility of a viral etiology for the pneumonia was entertained and respiratory aspirates obtained via the endotracheal tube were submitted for viral cultures including the following: respiratory syncytial virus, parainfluenza, influenza, adenovirus, and HSV type 1 and 2. Oral swabs, urine, stool and CSF were submitted for herpes simplex virus (HSV) types 1 and 2