James W. Bass

Practice guideline for the management of infants and children 0 to 36 months of age with fever without source

STUDY OBJECTIVE To develop guidelines for the care of infants and children from birth to 36 months of age with fever without source. PARTICIPANTS AND SETTING An expert panel of senior academic faculty with expertise in pediatrics and infectious diseases or emergency medicine. DESIGN AND INTERVENTION A comprehensive literature search was used to identify all publications pertinent to the management of the febrile child. When appropriate, meta-analysis was used to combine the results of multiple studies. One or more specific management strategies were proposed for each of the decision nodes in draft management algorithms. The draft algorithms, selected publications, and the meta-analyses were provided to the panel, which determined the final guidelines using the modified Delphi technique. RESULTS All toxic-appearing infants and children and all febrile infants less than 28 days of age should be hospitalized for parenteral antibiotic therapy. Febrile infants 28 to 90 days of age defined at low risk by specific clinical and laboratory criteria may be managed as outpatients if close follow-up is assured. Older children with fever less than 39.0 C without source need no laboratory tests or antibiotics. Children 3 to 36 months of age with fever of 39.0 C or more and whose WBC count is 15,000/mm3 or more should have a blood culture and be treated with antibiotics pending culture results. Urine cultures should be obtained from all boys 6 months of age or less and all girls 2 years of age or less who are treated with antibiotics. CONCLUSION These guidelines do not eliminate all risk or strictly confine antibiotic treatment to children likely to have occult bacteremia. Physicians may individualize therapy based on clinical circumstances or adopt a variation of these guidelines based on a different interpretation of the evidence.

Prospective randomized double blind placebo-controlled evaluation of azithromycin for treatment of cat-scratch disease

OBJECTIVE To determine the efficacy of azithromycin in the treatment of patients with typical cat-scratch disease. DESIGN Prospective, randomized, double blind, placebo-controlled clinical trial. SETTING Large military medical center and its referring clinics. PATIENTS Active duty military members and their dependents with laboratory-confirmed, clinically typical cat-scratch disease. INTERVENTION Study participants assigned by randomization to treatment with oral azithromycin or placebo for 5 days. OUTCOME MEASURES Lymph node volume was calculated using three dimensional ultrasonography at entry and at weekly intervals. The ultrasonographer was blinded to the treatment groups. Endpoint evaluations were predetermined as time in days to 80% resolution of the initial total lymph node volume. RESULTS Demographic and clinical data showed that the azithromycin and placebo treatment groups were comparable at entry although the placebo group tended to be older. Eighty percent decrease of initial lymph node volume was documented in 7 of 14 azithromycin-treated patients compared with 1 of 15 placebo-treated controls during the first 30 days of observation (P = 0.026). After 30 days there was no significant difference in rate or degree of resolution between the two groups. CONCLUSIONS Treatment of patients with typical cat-scratch disease with oral azithromycin for five days affords significant clinical benefit as measured by total decrease in lymph node volume within the first month of treatment.

The expanding spectrum of Bartonella infections : II. Cat-scratch disease

Recent advancements and developments in molecular biotechnology have allowed more precise reclassification of many microorganisms. With the use of these new taxonomy tools, several organisms previously thought to belong to other genera have been recently described as bartonellae. Of the 11 organisms now described as Bartonella spp., only four have been shown to be pathogenic for humans. Table 1 lists the four Bartonella human pathogens along with the their known epidemiology and the scope and range of disease associated with each. All are now considered to be bacteria and can be grown on blood-enriched agar although primary isolation in some may best be achieved in cell tissue culture. B. bacilliformis infection is limited to certain geographic regions in South America where the only human reservoir and the sandfly vector(s) that spreads the disease reside together. Specific antibiotic treatment is dramatically effective in treating the highly fatal, acute intraerythrocytic hemolytic form of the disease, but their effectiveness in treating the vascular proliferative forms (verruga peruana) or the chronic asymptomatic, bacteremic, carrier state of the disease has not been effective. This disease should remain confined to its present endemic geographic areas in South American unless asymptomatic bacteremic persons from these areas migrate to areas where sandflies and humans exist that are capable of establishing this infection in new endemic areas. B. quintana and B. henselae cause a wide range of clinical diseases in humans, the type and extent of which varies significantly with the immune status of the host. In immunocompetent hosts the pathologic response is granulomatous, suppurative, extracellular and intracellular, generally self-limited and usually unresponsive to antibiotic treatment, even to those drugs to which the organism is shown to be sensitive in vitro. In contrast, in immunocompromised hosts the pathologic response is vasculoproliferative, organisms may be seen intracellularly but they are often seen in abundance in extracellular clumps and infection is usually progressive and fatal unless treated. In these patients clinical response to treatment with drugs that are effective in vitro against these organisms has usually been dramatic. Of these agents those that penetrate cells and are found in high concentrations intracellularly, such as erythromycin, clarithromycin, azithromycin, rifampin, doxycycline and gentamicin, appear to be most effective. These agents not only appear to provide the most dramatic treatment response in patients with BA, BP and PRFB and other manifestations of B. henselae (and B. quintana as well) in immunocompromised persons, they appear to be the most promising agents for treatment of persons with both typical and atypical CSD. Further studies will be necessary to more clearly elucidated the mechanisms responsible for the diverse clinical presentations of infection with these organisms in human hosts relative to their immune status. In addition clarification of the epidemiology of B. elizabethae infections in humans may be helpful in understanding the nature of infection with Bartonella organisms.

Cat-scratch disease in Hawaii: Etiology and seroepidemiology

OBJECTIVE To study the etiology and seroepidemiology of cat-scratch disease (CSD) in Hawaii. METHODS Blood and fine-needle aspirate (FNA) from the lymph nodes of 39 consecutive patients with clinical CSD were cultured for Bartonella henselae, and blood samples from index cats, stray cats, and dogs were cultured and their sera were tested by indirect fluorescence antibody test for antibodies to B. henselae and Afipia felis. Sera from age- and sex-matched human subjects without cat exposure served as controls. RESULTS Warthin-Starry staining showed positive results in only 4 of 32 FNAs, and B. henselae was isolated from only one FNA specimen. All of 38 patients who had two or more sera tested had elevated titers of antibody to B. henselae. Only 1 of 48 human control sera had antibody to B. henselae. Of 31 kittens, 21 had positive blood culture results and elevated antibody titers to B. henselae. Of three adult cats, all had negative blood culture results, but they had serologic evidence of past infection. Of 23 adult stray cats, 18 had elevated titers of antibody to B. henselae, but in only one was the blood culture result positive. Results of IFA tests were marginally positive for A. felis in 1 of 29 patients with CSD and in one adult stray cat and one dog. CONCLUSIONS This study shows that the B. henselae IFA test is both highly sensitive and specific for the detection of infection caused by B. henselae and for the laboratory diagnosis of CSD, and that FNA is seldom helpful in confirming the diagnosis. We further demonstrated that CSD in Hawaii is due to B. henselae and that infection is directly linked to the scratch or bite of a kitten. Older cats seldom have bacteremia but often have serologic evidence of past infection. Our study fails to implicate dogs in the epidemiology of CSD in Hawaii, and A. felis was not etiologically implicated in CSD in the human subjects and animals we studied.

Antimicrobial treatment of occult bacteremia: A multicenter cooperative study

This prospective multicenter study was conducted to define more clearly clinical and laboratory criteria that predict a strong probability of occult bacteremia and to evaluate the effect of empiric broad spectrum antimicrobial treatment of these children. Children 3 to 36 months old with fever ≥40°C (104°F) or, ≥39.5°C (103°F) with white blood cells (WBC) ≥15 × 109/liter, and no focus of infection had blood cultures obtained and were randomized to treatment with oral amoxicillin/potassium clavulanate or intramuscular ceftriaxone. Sixty of 519 (11.6%) study patients had positive blood cultures: Streptococcus pneumoniae, 51; Haemophilus influenzae b, 6; Neisseria meningitidis, 2; and Group B Streptococcus, 1. Subgroups of high risk were identified as fever ≥39.5°C and WBC ≥15 × 109/liter, 55 of 331 or 16.6% positive with increasing incidence of positive culture with increasing increments of degrees of leukocytosis to WBC ≥30 × 109/liter where 9 of 21 or 42.9% were positive. Subgroups of significantly lower risk were identified as fever ≥39.5°C and WBC <15 × 109/liter, 5 of 182 or 2.7% positive and those with WBC <10 × 109/liter, 0 of 99 or 0.0% positive. Children with positive cultures who received ceftriaxone were nearly all afebrile after 24 hours whereas a significant number who received amoxicillin/potassium clavulanate remained febrile. In the 459 culture-negative children more amoxicillin/potassium clavulanate-treated children developed diarrhea and had less improvement in clinical scores after 24 hours than ceftriaxone-treated children. Children 3 to 36 months old with fever ≥39.5°C and WBC ≥15 × 109/liter and no focus of infection are at high risk (≥16%) for having occult bacteremia. Antimicrobial treatment of febrile children with these high risk criteria appears prudent whereas routine treatment of those with low risk criteria does not. Both treatment regimens evaluated are rational and all patients did well.

A survey about management of febrile children without source by primary care physicians

BACKGROUND The management of young children with fever without source is controversial, and differences between physician specialties have been noted previously. The emergence of penicillin-resistant Streptococcus pneumoniae, the sharp decline in invasive Haemophilus influenzae infections in immunized populations and publication of practice guidelines have potentially altered physician practices. OBJECTIVE To determine the present practice preferences of pediatricians, family medicine physicians (FP) and emergency medicine physicians (EP). METHODS We mailed a checklist survey to 1600 randomly selected pediatricians, family medicine practitioners (FP) and emergency medicine physicians (EP) in the United States and replicated the methodology of a 1991/1992 survey. Physicians were asked about their evaluation and management of children of various ages (3 weeks, 7 weeks, 4 months and 16 months) with fever without source. RESULTS Most primary care physicians would admit the 3- and 7-week-old infants. For the 4-month-old infant 59% of EP, 45% of pediatricians and 28% of FP would give empiric antibiotic(s) as an outpatient (P=0.005 for FP compared with pediatricians and P=0.02 for EP compared with pediatricians). The majority of physicians would manage the 16-month-old child as an outpatient without antibiotic therapy. Ceftriaxone was the preferred antibiotic for outpatient empiric therapy. There was a 3-fold increase (28% vs. 9%) for pediatricians in the use of empiric outpatient antibiotics for the 7-week-old infant in the present survey compared with the 1991/1992 survey. CONCLUSIONS Physicians in the United States generally agree in their management of the young febrile infant, but with increasing patient age there is considerable variation. FP were the least aggressive in their evaluation and EP were the most aggressive.

Sedation of Children for Technical Procedures Current Standard of Practice

We sought to define the current standard of care for children undergoing sedation for painless diagnostic procedures by sending questionnaires to 284 pediatric residency program directors in North America. From the 89 responses, we determined that departments of pediatrics set sedation policies for children in most institutions, often with formal written guidelines for these procedures. Most require that children have some form of cardiorespiratory monitoring while under sedation and that they are attended by individuals trained in cardiorespiratory resuscitation until the child is fully recovered. The use of parents to transport and monitor the sedated child is uncommon, and total lack of monitoring is rare. Chloral hydrate in dosages of 25 mg/kg to 100 mg/kg is the most common drug used for sedation; DPT, a combination of parenteral Demerol(meperidine), Phenergan (promethazine), and Thorazine (chlorpromazine), at a maximum dose of 2 mg/lmg/lmg/kg is the second; and pentobarbital in a dosage of 5 mg/kg to 7 mg/kg is the third. These sedation regimens were associated with few serious side effects, except that two deaths were reported in infants with congenital heart disease who were sedated with DPT. We believe this survey may reflect the current standard of practice for sedation in North American infants and children undergoing diagnostic procedures.

Antimicrobial drug suspensions: a blind comparison of taste of fourteen common pediatric drugs.

Children of preschool age most often receive medications in liquid form, and smell and taste are major determinants in achieving compliance. We compared smell, taste and other characteristics of 14 commonly prescribed antimicrobial suspensions in a blind test in 30 adult volunteers to determine whether there was a difference in their acceptability. A significant difference was observed with cephalosporins ranking highest and penicillins ranking lowest. Our findings support anecdotal observations and claims often made by parents that cephalosporin antimicrobial suspensions taste good and are readily accepted by children and that penicillin suspensions have an unpleasant taste and aftertaste and are poorly accepted. Other drugs had intermediate scores. Of the two erythromycin suspensions evaluated, Ilosone tested superior to Erythromycin ES.

Antimicrobial drug suspensions: a blinded comparison of taste of twelve common pediatric drugs including cefixime, cefpodoxime, cefprozil and loracarbef

We conducted a blinded taste test evaluating 12 antimicrobial suspensions by smell, texture, taste, aftertaste and overall acceptance. Drugs received cumulative scores in each category as well as a total score ranking. Overall Lorabid® scored highest but not significantly higher than Keflex®, Suprax® and Ceclor®, all of which scored higher than the other test drugs. Cefzil® and Augmentin® scored just below this group of drugs and higher than all other test drugs. Vantin® was inferior to these drugs primarily because of its low score in aftertaste. It was ranked along with V-Cillin-K®, Veetids®, Sulfatrim® and Pediazole®, the lowest scoring group of drugs other than Dynapen® which scored lower than all other test drugs. No difference overall was detected between the two penicillin VK suspensions evaluated, V-Cillin-K® and Veetids®.

Febrile children with no focus of infection : a survey of their management by primary care physicians

We mailed a checklist survey to 1600 randomly selected pediatricians, family practice physicians (FPPs) and emergency medicine physicians (EMPs) in the United States regarding their management of children with high fever and no focus of infection at various ages: 3 weeks; 7 weeks; 4 months; and 16 months. Completed questionnaires were returned by 211 of 600 (35.2%) pediatricians, 145 of 500 (29%) FPPs and 141 of 500 (28.2%) EMPs. Most pediatricians, FPPs and EMPs would hospitalize a 3- or 7-week-old infant with fever and most pediatricians and FPPs would treat infants of this age group empirically with antibiotics. Most pediatricians, FPPs and EMPs would not hospitalize a 4-month-old or a 16-month-old with high fever with no focus of infection but 44 and 25% of pediatricians, 38 and 24% of FPPs and 41 and 34% of EMPs, respectively, would treat a 4- and 16-month-old child with high fever and no focus of infection with antibiotics. The preferred antibiotic treatment for hospitalized 3- and 7-week-old infants was ampicillin plus gentamicin or ampicillin plus cefotaxime; for older outpatients preferred treatment was amoxicillin or ceftriaxone. We conclude that hospitalization and empiric antibiotic treatment of very young infants (< 2 months of age) with high fever and no focus of infection are preferred by most of the pediatricians, FPPs and EMPs surveyed. Nearly one-half of these physicians would treat 4-month-olds and a fourth would treat 16-month-olds with high fever and no focus of infection with antibiotics as outpatients.