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Kingella Kingae Emerging and Gram-Negative Ocular Pathogens

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Kingella Kingae Emerging and Gram-Negative Ocular Pathogens 22 Infectious Diseases P EDIATRIC N EWS • September 2005 ID CONSULT BRIEF SUMMARY DESCRIPTION QUIXIN® (levofloxacin ophthalmic solution) 0.5% is a sterile topical ophthalmic solution. Levofloxacin is a fluoroquinolone antibacterial active against a broad spectrum of Gram-positive Kingella kingae Emerging and Gram-negative ocular pathogens. Levofloxacin is the pure (-)-(S)-enantiomer of the racemic drug substance, ofloxacin. It is more soluble in water at neutral pH than ofloxacin. keletal in- tic arthritis, keeping in mind that it is a positive hematogenous septic arthritis and QUIXIN® solution is isotonic and formulated at pH 6.5 with an osmolality of approximately 300 mOsm/kg. Levofloxacin is a fection medical and surgical emergency. In the acute or subacute osteomyelitis, while fluorinated 4-quinolone containing a six-member (pyridoben- has al- febrile limping toddler with presumed gram-negative organisms were identified zoxazine) ring from positions 1 to 8 of the basic ring structure. S Clinical Studies: In randomized, double-masked, multicenter ways been septic arthritis, immediate evaluation by in 13 (22%). Of those, K. kingae was cul- controlled clinical trials where patients were dosed for 5 days, QUIXIN® demonstrated clinical cures in 79% of patients treated among the top an orthopedic surgeon is necessary. Joint tured in 10 (17%); all such cases occurred for bacterial conjunctivitis on the final study visit day (day 6-10). Microbial outcomes for the same clinical trials demonstrated an five reasons for drainage is promptly performed. in children between the ages of 10.5 and eradication rate for presumed pathogens of 90%. BY MARY ANNE inpatient pedi- What tip-offs might suggest to you that 23.5 months. (J. Pediatr. Orthop. INDICATIONS AND USAGE JACKSON, M.D. QUIXIN® solution is indicated for the treatment of bacterial atric infectious K. kingae should be 1998;18:262-7). conjunctivitis caused by susceptible strains of the following organisms: disease consul- considered as a po- Now comes infor- AEROBIC GRAM-POSITIVE AEROBIC GRAM-NEGATIVE Kingella kingae has MICROORGANISMS MICROORGANISMS tations in our institution. Early diagnosis, tential pathogen, and mation that impli- Corynebacterium species* Acinetobacter Iwoffii* emerged as potentially Staphylococcus aureus Haemophilus influenzae prompt surgical drainage, and appropriate how might this im- cates K. kingae in a Staphylococcus epidermidis Serratia marcescens* antimicrobial therapy remain the keys to pact your therapeutic cluster of skeletal in- Streptococcus pneumoniae the No. 1 cause of Streptococcus (Groups C/F) good outcome. While the clinical mani- decision making? fection in one day Streptococcus (Group G) Viridans group streptococci festations of these infections haven’t For the most part, septic arthritis in care center in Min- *Efficacy for this organism was studied in fewer than 10 infections. changed over the years, the microbiolog- this organism is an nesota. Three cases CONTRAINDICATIONS the child younger than QUIXIN® solution is contraindicated in patients with a history of ic etiologies have, and this has impacted important cause of occurred among hypersensitivity to levofloxacin, to other quinolones, or to any of the components in this medication. therapeutic decision making. skeletal infection only 24 months of age. children aged 17-21 WARNINGS NOT FOR INJECTION. Staphylococcal infection remains the in those less than 2 months attending QUIXIN® solution should not be injected subconjunctivally, nor most common cause of skeletal infection years of age. Other information that may the same toddler classroom. Within the should it be introduced directly into the anterior chamber of the eye. overall. In recent years, as methicillin-re- be helpful includes the fact that concomi- same week, all affected children had on- In patients receiving systemic quinolones, serious and occa- sionally fatal hypersensitivity (anaphylactic) reactions have been sistant Staphylococcus aureus (MRSA) has tant URI or stomatitis occurs frequently in set of fever, and antalgic gait. They all reported, some following the first dose. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, emerged, clindamycin has become a com- such patients (over half in one study), had preceding or concurrent upper res- angioedema (including laryngeal, pharyngeal or facial edema), mon empiric antimicrobial choice for such suggesting a respiratory or buccal source piratory illness. K. kingae was isolated airway obstruction, dyspnea, urticaria, and itching. If an allergic reaction to levofloxacin occurs, discontinue the drug. Serious cases. However, this may not be a good for the infection. And this organism has a from clinical specimens. acute hypersensitivity reactions may require immediate emer- gency treatment. Oxygen and airway management should be choice for therapy for some children with predilection for ankle involvement in cas- For physicians who have been practicing administered as clinically indicated. PRECAUTIONS skeletal infection. es of arthritis and calcaneal involvement long enough to remember the General: As with other anti-infectives, prolonged use may result Once considered an unusual cause of in bone infection. Haemophilus influenzae type b era, this may in overgrowth of non-susceptible organisms, including fungi. If superinfection occurs, discontinue use and institute alternative pediatric infection, Kingella kingae has Keeping this in mind, since K. kingae is seem familiar. therapy. Whenever clinical judgment dictates, the patient should be examined with the aid of magnification, such as slit-lamp extremely hard to Before the Hib vaccine became widely biomicroscopy, and, where appropriate, fluorescein staining. Patients should be advised not to wear contact lenses if they grow on culture, used, H. influenzae type b was recognized have signs and symptoms of bacterial conjunctivitis. you should alert as the etiologic agent in 80% of septic Information for Patients: Avoid contaminating the applicator tip with material from the eye, fingers or other source. your surgeon and arthritis cases in children less than 2 years Systemic quinolones have been associated with hypersensitivity reactions, even following a single dose. Discontinue use imme- microbiology labo- of age, and day care center outbreaks diately and contact your physician at the first sign of a rash or allergic reaction. ratory. In addition were notable. Drug Interactions: Specific drug interaction studies have not to routine cultures, A colonization study was performed in been conducted with QUIXIN®. However, the systemic adminis- tration of some quinolones has been shown to elevate plasma ask your orthope- response to the Minnesota outbreak. Pub- concentrations of theophylline, interfere with the metabolism of caffeine, and enhance the effects of the oral anticoagulant war- dic surgeon to lished in Pediatrics in August 2005, the in- farin and its derivatives, and has been associated with transient elevations in serum creatinine in patients receiving systemic place some of the vestigators demonstrated that 13% of chil- cyclosporine concomitantly. Carcinogenesis, Mutagenesis, Impairment of Fertility: In a purulent fluid into dren at the index day care center (and 45% long term carcinogenicity study in rats, levofloxacin exhibited a blood culture in the room where the cluster occurred) no carcinogenic or tumorigenic potential following daily dietary administration for 2 years; the highest dose (100 mg/kg/day) bottle, in addition were colonized in the nasopharynx with K. was 875 times the highest recommended human ophthalmic dose. to plating for rou- kingae. Interestingly, no day care center Levofloxacin was not mutagenic in the following assays: Ames AGUPSKY tine culture. Over a staff or children less than 16 months old bacterial mutation assay (S. typhimurium and E. coli), CHO/ Y HGPRT forward mutation assay, mouse micronucleus test, mouse dominant lethal test, rat unscheduled DNA synthesis decade ago, physi- were colonized. They compared the na- assay, and the in vivo mouse sister chromatid exchange assay. ABLO cians were alerted sopharyngeal colonization results with a It was positive in the in vitro chromosomal aberration (CHL cell . P line) and in vitro sister chromatid exchange (CHL/IU cell line) R D to the importance control day care center. Similarly, 16% of assays. Levofloxacin caused no impairment of fertility or reproduction in of using BACTEC toddler age children were colonized. (Pe- rats at oral doses as high as 360 mg/kg/day, corresponding to 3,150 times the highest recommended human ophthalmic dose. blood culture bot- diatrics 2005;116:e206-13). Pregnancy: Teratogenic Effects. Pregnancy Category C: OURTESY C In the pre-Hib vaccine era, we routine- Levofloxacin at oral doses of 810 mg/kg/day in rats, which corre- tles to isolate K. sponds to approximately 7,000 times the highest recommended An example of a typical Gram stain of organisms from a kingae in toddlers ly used to use rifampin to eradicate Hib human ophthalmic dose, caused decreased fetal body weight and increased fetal mortality. Kingella kingae colony is shown. with skeletal infec- carriage among children in day care. Ri- No teratogenic effect was observed when rabbits were dosed orally as high as 50 mg/kg/day, which corresponds to tion (J. Clin. Mi- fampin was used to attempt decoloniza- approximately 400 times the highest recommended maximum human ophthalmic dose, or when dosed intravenously as high emerged as
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