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IMPORTANCE OF KINGELLA KINGAE AS A PEDIATRIC PATHOGEN IN THE UNITED STATES

2000; Lippincott Williams & Wilkins; Volume: 19; Issue: 3 Linguagem: Inglês

10.1097/00006454-200003000-00023

1532-0987

Edina Moylett, Susan Rossmann, Howard R. Epps, Gail J. Demmler,

Infectious Diseases and Tuberculosis

Reports of Kingella kingae as a pediatric pathogen have been noted since the early 1980s. Since the introduction of immunization against Haemophilus influenza type b, coupled with improved laboratory isolation techniques, there has been a shift in the etiology of osteoarticular infections in infants and children with K. kingae as one of the primary Gram-negative bacteria isolated.1, 2 Countries outside of the United States have reported the recent emergence of K. kingae3, 4 but only isolated case reports concerning K. kingae in pediatric patients in the US have been published.5 An apparent increase in the number of pediatric infections caused by K. kingae was recently noted at Texas Children's Hospital. We reviewed the hospital microbiology records and report here four children with invasive K. kingae infection in the 6-month period from January, 1999, to June, 1999. Further review of the microbiology database during the previous 10 years revealed only a single instance of K. kingae isolation from a normally sterile site. At our laboratory routine processing of clinical specimens including blood, synovial fluid and exudates involves direct inoculation onto a blood/chocolate agar biplate, a MacConkey agar plate and thioglycolate broth. In addition osteoarticular fluid specimens are directly inoculated into a blood culture bottle (Bac-Tec blood culturing system; Becton Dickinson Microbiology Systems, Cockeysville MD). All cultures are monitored for 5 days. Case 1. A 16-month-old African-American male child was admitted with a 2-week history of subjective fever and a 1-day history of right knee swelling and refusal to bear weight. His mother reported some slight reduction in oral intake but he was otherwise well. On examination he was noted to be febrile to 101.6°F, his right knee was moderately swollen and erythematous, and apart from some bilateral middle ear effusions, the rest of the physical examination was unremarkable. Laboratory studies revealed a normal total white blood cell count (WBC) and differential. The erythrocyte sedimentation rate (ESR) was 36 mm/h. A blood culture grew K. kingae, susceptible to all antibiotics tested, but the knee joint fluid was sterile. Roentgenograms of his right knee revealed soft tissue swelling with associated suprapatellar effusion. A 99Tc bone scan demonstrated right knee synovitis. Nafcillin was initiated intravenously, and clinical recovery was apparent by the second hospital day. The patient received 14 days of parenteral therapy and cefotaxime once the organism was identified; he was discharged to receive amoxicillin orally for another 7 days. Case 2. A 17-month-old African-American male child was admitted with a 1-week history of progressive swelling affecting the right ankle and refusal to bear weight. The patient recently had nasal congestion but no fever. On examination he was afebrile and irritable, he had crusted rhinorrhea and his right foot was markedly swollen over the lateral distal fibula with associated point tenderness and increased skin temperature. Laboratory studies revealed a normal WBC count and differential. The ESR was 69 mm/h. Roentgenograms of the right ankle showed marked soft tissue swelling and joint effusion. Magnetic resonance imaging studies were consistent with a soft tissue inflammatory process. Fluid aspirated from the soft tissue grew K. kingae, susceptible to all antibiotics tested. Blood culture was sterile. Clinical findings resolved promptly once treatment with intravenous nafcillin for 7 days was initiated. Cephalexin was administered orally for an additional 7 days after hospital discharge. Case 3. A 15-month-old African-American male child was admitted with a 4-day history of a limp. His mother reported increased fussiness as well as reduced oral intake over the preceding 7 days; there was also a history of a recent upper respiratory tract infection. Physical examination revealed a temperature of 103.6°F. The left hip was held in the frog leg position with pain induced by hip flexion or adduction. Laboratory findings were significant for an ESR of 112 mm/h and WBC count of 12 800/mm3 with 55% polymorphonuclear cells, 4% band forms and 33% lymphocytes. The child underwent left hip arthrotomy, and 5 ml of purulent material were aspirated that grew K. kingae, susceptible to all antibiotics tested. Cultures of blood and urine were sterile. The child received a 3-week course of intravenous nafcillin with clinical improvement apparent by Hospital Day 2. Case 4. A 12-month-old male Hispanic child with a history of a myelomeningocele was admitted a 1-week history of cough. On the day of admission he had reduced urine output and temperature to 102.5°F. Physical examination at presentation was unremarkable apart from fussiness and minimal bibasilar inspiratory rales. Laboratory studies revealed a WBC count of 11 400/mm3, with 51% polymorphonuclear cells, 2% band forms and 39% lymphocytes. Urinalysis showed 51 to 100 WBC per high power field and 4+ bacteria. Blood culture grew K. kingae, susceptible to all antibiotics tested, and the urine grew Klebsiella oxytoca, 105 colony-forming units/ml. Treatment included intravenous ampicillin and gentamicin for 5 days followed by oral cephalexin for 10 days. Recovery was complete. Discussion. Review of the microbiology laboratory records at Texas Children's Hospital in Houston demonstrated an apparent increase in the isolation of K. kingae from normally sterile sites during a 6-month period. Our four pediatric patients with K. kingae invasive disease had isolates that were susceptible by the disc diffusion method to ampicillin, first and third generation cephalosporins, aminoglycosides and semisynthetic penicillins. Rapid and complete clinical recovery was noted for each child without complications. Initially named for Dr. Elizabeth King in the 1960s, K. kingae is a small Gram-negative nonencapsulated coccobacillus that appears morphologically either as pairs or short chains. Kingella organisms are fastidious aerobes that grow in both nutrient and blood agar, but many strains will not grow on MacConkey agar. Colonies on agar plates may be small, smooth and translucent or appear as larger spreading colonies which look pitted because of corrosion of the solid media surface. Biochemically this organism is catalase-, indole- and urease-negative and oxidase-positive. K. kingae is the only species in the genus to produce beta-hemolysis, but not all strains are beta-hemolytic. Identification of this organism by clinical laboratories is frequently delayed because of the slow rate of growth. Both the speed of growth and the isolation rate may be improved by the direct inoculation of clinical specimens into an automated culture system.6 Yagupsky et al.6 compared the use of the Bac-Tec blood culturing system to direct inoculation onto solid media for isolation of K. kingae. Of 100 samples processed 11 grew K. kingae; 10 of the 11 isolates were detected by the Bac-Tec system alone. Rapid isolation from the BacT/Alert automated system (Organon Teknika Corp., Durham, NC) has also been reported for blood isolates. It is unclear whether one automated system is superior to another; however, the improved recovery from such a system may be related to a dilutional effect of the liquid media on possible inhibitory substances in synovial fluid or to the fact that a higher inoculum is being cultured. To enhance isolation of K. kingae and other fastidious organisms, direct inoculation of osteoarticular aspirates into blood culture bottles is becoming the standard in many clinical laboratories. Epidemiologic studies have revealed that K. kingae frequently colonizes the respiratory tract of infants and young children.7 Of 624 consecutive tonsillar and nasopharyngeal cultures performed on day-care attendees, 17.5% of the tonsillar but none of the nasopharyngeal specimens grew K. kingae. In a striking 73% of the infants K. kingae grew from specimens at some time during the 11-month period.7 In addition 2 distinct strains of K. kingae identified by 3 different typing methods represented >70% of isolates from these day-care attendees, suggesting that person-to-person spread occurred.8 None of the cultures performed on the adult day-care personnel was positive. These studies support the hypothesis that children are a reservoir for this pathogen, with frequent colonization of the respiratory tract. K. kingae infection results in a variety of clinical manifestations, primarily bacteremia and osteoarticular infections, as are illustrated in our case series. Classically invasive infection appears to be preceded by upper respiratory tract disease, dental procedures or stomatitis.3, 9, 10 Each of our four patients had had a prior upper respiratory tract infection. A recent review from Israel of 25 cases of invasive K. kingae infections noted that 96% of cases occurred in children <2 years of age, the age of our patients. Typically osteoarticular infection with K. kingae is associated with minimal systemic symptoms, mild to moderate inflammatory response at the affected site and minimal bony destruction,10 features also observed in our patients. The change in bacterial etiology of childhood osteoarticular infection has been documented in recent reviews.1, 2 Lundy at al1 reviewed the records of 60 children in Atlanta with culture-proved osteoarticular infections in a 5-year period. K. kingae was responsible for 23% of septic arthritis cases in children younger than 36 months of age and for 10% of acute/subacute osteomyelitis cases in this same age group. Luhmann and Luhmann2 reported 64 patients with septic arthritis, 38 of whom had a pathogen identified. Of 7 patients <2 years of age, K. kingae and Streptococcus pneumoniae were the most frequently isolated pathogens. In summary the prevalence of K. kingae appears to have increased and may be responsible for up to 50% of previously undiagnosed suppurative bone and joint infections in children <2 years of age. Inoculation of blood culture bottles with aspirates from soft tissue, joint fluid or bone specimens should enhance the recovery rate for this organism. Optimal therapy is not known, but K. kingae is susceptible to many antibiotics. However, resistance to some antibiotics was noted in a recent review of clinical isolates.4 Therefore the choice of therapy should be guided by the susceptibility profile. Prompt and complete resolution of disease occurs after initiation of appropriate antimicrobial therapy.