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Biomedical subjects

Michael E Pichichero

Publications and source records attributed to Michael E Pichichero.

At least 19 recordsLinked to original sources
PubMed2003

White blood cell count can aid judicious antibiotic prescribing in acute upper respiratory infections in children.

Fifty percent or more of children with upper respiratory infections (URIs) and nonspecific febrile illnesses (e.g., children febrile, anorexic, decreased activity, irritable) receive unnecessary antibiotics from community-based physicians. This study was undertaken to show that white blood cell (WBC) count testing can aid physicians in avoiding antibiotic prescribing when managing children with URIs, and nonspecific febrile illnesses. A prospective, 3-year study was conducted in a community-based pediatric practice. A weekly convenience sample (Tuesdays) of acute URI and febrile patients ages 3 months to 21 years was studied. Data collected on enrollment included: age, gender, duration of illness, recent/current antibiotic use, temperature, symptoms, signs, laboratory testing (WBC count, cultures), diagnosis and treatment. Similar data on any illness visits in the previous 2 weeks and the subsequent 2 weeks after enrollment were collected. Viral culture specimens were obtained on a subset. The use of the WBC count was assessed, including obviating antibiotic prescription, frequency of related follow-up visits, and the occurrence of subsequent bacterial infections. Of 1,956 patients with respiratory or febrile illness enrolled, 1,219 (62%) had a diagnosis established by history and examination (e.g., acute otitis media) and 737 (38%) did not. Of the 737 patients without an established diagnosis, 386 (52%) did not receive an antibiotic because they did not appear particularly ill, their temperature was less than 101 degrees F, and parents were not demanding antibiotics, leaving 351 (48%) patients who appeared ill, had a temperature greater than 101 degrees F, and parents were demanding an antibiotic or physicians were inclined to give an antibiotic. A WBC count was performed on these 351 children; 337 children (96%) had a WBC count less than 15,000/mm3, and 14 (4%) had a WBC 15,000/mm3 or greater. An antibiotic was prescribed for 13 of the 14 children with a WBC count greater than 15,000/mms. With this approach, return office visits in the following 2 weeks were infrequent (13% of 737 patients), and no child had significant bacterial illness that was missed. With selective use of WBC count testing

Acute Disease↗
PubMed2003

Efficacy of penicillin vs. amoxicillin in children with group A beta hemolytic streptococcal tonsillopharyngitis.

The purpose of this study was to compare the bacteriologic and clinical efficacy of oral penicillin versus amoxicillin as first-line therapy for group A beta-hemolytic streptococcal (GABHS) tonsillopharyngitis. The prospective observational study was conducted over 18 months (January 2000-June 2001). Children enrolled had acute onset of symptoms and signs and a laboratory-documented GABHS tonsillopharyngitis illness. Follow-up examination and laboratory testing occurred 10 +/- 4 days following completion of treatment. In total, 389 patients were enrolled (intent-to-treat group): 195 received penicillin V and 194 received amoxicillin. Fifty-six of the penicillin-treated and 57 amoxicillin-treated patients refused to take the drug, or were noncompliant, or did not return for the follow-up visit, leaving 276 patients in the per-protocol group: 139 penicillin-treated and 137 amoxicillin-treated. Bacteriologic cure for amoxicillin-treated children occurred in 76% versus 64% in the penicillin-treated children (p = 0.04). The clinical cure rate for amoxicillin-treated children was 84% compared to 73% in the penicillin-treated children (p = 0.03). Since treatment allocation was not randomized, logistic regression analysis was used to adjust for treatment group differences. The odds ratio (OR) estimate for cure for patients in the amoxicillin versus penicillin V treatment group remained significant (OR = 1.84, 95% confidence interval 1.02-3.29); the same was true for dinical cure (OR = 1.99, 95% CI = 1.02-3.87). Amoxicillin may be superior to penicillin for bacteriologic and clinical cure of GABHS tonsillopharyngitis.

Adolescent↗
PubMed2002

Mercury concentrations and metabolism in infants receiving vaccines containing thiomersal: a descriptive study.

BACKGROUND: Thiomersal is a preservative containing small amounts of ethylmercury that is used in routine vaccines for infants and children. The effect of vaccines containing thiomersal on concentrations of mercury in infants' blood has not been extensively assessed, and the metabolism of ethylmercury in infants is unknown. We aimed to measure concentrations of mercury in blood, urine, and stools of infants who received such vaccines. METHODS: 40 full-term infants aged 6 months and younger were given vaccines that contained thiomersal (diptheria-tetanus-acellular pertussis vaccine, hepatitis B vaccine, and in some children Haemophilus influenzae type b vaccine). 21 control infants received thiomersal-free vaccines. We obtained samples of blood, urine, and stools 3-28 days after vaccination. Total mercury (organic and inorganic) in the samples was measured by cold vapour atomic absorption. FINDINGS: Mean mercury doses in infants exposed to thiomersal were 45.6 microg (range 37.5-62.5) for 2-month-olds and 111.3 microg (range 87.5-175.0) for 6-month-olds. Blood mercury in thiomersal-exposed 2-month-olds ranged from less than 3.75 to 20.55 nmol/L (parts per billion); in 6-month-olds all values were lower than 7.50 nmol/L. Only one of 15 blood samples from controls contained quantifiable mercury. Concentrations of mercury were low in urine after vaccination but were high in stools of thiomersal-exposed 2-month-olds (mean 82 ng/g dry weight) and in 6-month-olds (mean 58 ng/g dry weight). Estimated blood half-life of ethylmercury was 7 days (95% CI 4-10 days). INTERPRETATION: Administration of vaccines containing thiomersal does not seem to raise blood concentrations of mercury above safe values in infants. Ethylmercury seems to be eliminated from blood rapidly via the stools after parenteral administration of thiomersal in vaccines.

Case-Control Studies↗
PubMed2002

Zanamivir prophylaxis: an effective strategy for the prevention of influenza types A and B within households.

A double-blind, randomized study of inhaled zanamivir for the prevention of influenza in families was conducted. Once a person with a suspected case of influenza was identified (index patient), treatment of all other household members (contacts) > or =5 years old was initiated. Contacts received either 10 mg zanamivir or placebo inhaled once daily for 10 days. Index patients received relief medication only. In total, 487 households (242 placebo and 245 zanamivir) were enrolled, with 1291 contacts randomly assigned to receive prophylaxis. Four percent of zanamivir versus 19% of placebo households (P<.001) had at least 1 contact who developed symptomatic, laboratory-confirmed influenza, representing 81% protective efficacy (95% confidence interval, 64%-90%). Protective efficacy was similarly high for individuals (82%) and against both influenza types A and B (78% and 85%, respectively, for households). Zanamivir was well tolerated and was effective in preventing influenza types A and B within households where the index patient was not treated.

Adolescent↗
PubMed2002

Detection and characterization of pediatric serum antibody to the OMP P5-homologous adhesin of nontypeable Haemophilus influenzae during acute otitis media.

We reported earlier that antibody in sera collected from seven children with acute otitis media (AOM) due to nontypeable Haemophilus influenzae (NTHI) recognized immunodominant regions of P5-fimbrin just as we had observed in a chinchilla model of experimental NTHI-induced AOM. To expand upon those preliminary findings, we further characterized pediatric serum antibodies directed against this adhesin during AOM. Collectively, the data show that children respond immunologically to P5-fimbrin and they do so in a manner that allows for the distinction of sequence diversity within short linear peptides representing a focused region of this surface-exposed protein. The immune recognition we observed encourages us to further develop a P5-fimbrin based vaccine component.

Acute Disease↗
PubMed2002

Lack of consistent relationship between quantity of aluminum in diphtheria-tetanus-acellular pertussis vaccines and rates of extensive swelling reactions.

The precise role that aluminum plays in local reactogenicity is not clear. We explored the relationship between rates of severe local reactions following the fourth and fifth booster doses of several diphtheria-tetanus-acellular pertussis vaccines (DTaP) and the quantity of aluminum contained in the different vaccines. Although there was a significant relationship between higher aluminum contents and swelling reactions >50 mm after dose 5, no relationship was seen with entire thigh swelling or with swelling >50 mm after dose 4. Because of the inconsistency of the data, a dose response between local reactogenicity and aluminum is questionable.

Adjuvants, Immunologic↗
PubMed2002

Prospective identification and treatment of children with pediatric autoimmune neuropsychiatric disorder associated with group A streptococcal infection (PANDAS).

BACKGROUND: The current diagnostic criteria for pediatric autoimmune neuropsychiatric disorder associated with group A streptococcal infection (PANDAS) are pediatric onset, neuropsychiatric disorder (obsessive-compulsive disorder [OCD]) and/or tic disorder; abrupt onset and/or episodic course of symptoms; association with group A beta-hemolytic streptococcal (GABHS) infection; and association with neurological abnormalities (motoric hyperactivity or adventitious movements, including choreiform movements or tics). OBJECTIVE: To assess new-onset PANDAS cases in relation to acute GABHS tonsillopharyngitis. DESIGN: Prospective PANDAS case identification and follow-up. RESULTS: Over a 3-year period (1998-2000), we identified 12 school-aged children with new-onset PANDAS. Each patient had the abrupt appearance of severe OCD behaviors, accompanied by mild symptoms and signs of acute GABHS tonsillopharyngitis. Throat swabs tested positive for GABHS by rapid antigen detection and/or were culture positive. The GABHS serologic tests, when performed (n = 3), showed very high antideoxyribonuclease antibody titers. Mean age at presentation was 7 years (age range, 5-11 years). In children treated with antibiotics effective in eradicating GABHS infection at the sentinel episode, OCD symptoms promptly disappeared. Follow-up throat cultures negative for GABHS were obtained prospectively after the first PANDAS episode. Recurrence of OCD symptoms was seen in 6 patients; each recurrence was associated with evidence of acute GABHS infection and responded to antibiotic therapy, supporting the premise that these patients were not GABHS carriers. The OCD behaviors exhibited included hand washing and preoccupation with germs, but daytime urinary urgency and frequency without dysuria, fever, or incontinence were the most notable symptoms in our series (58% of patients). Symptoms disappeared at night, and urinalysis and urine cultures were negative. CONCLUSION: To our knowledge, this is the first prospective study to confirm that PANDAS is associated with acute GABHS tonsillopharyngitis and responds to appropriate antibiotic therapy at the sentinel episode.

Age Factors↗
PubMed2002

Impact of a birth dose of hepatitis B vaccine on the reactogenicity and immunogenicity of diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b combination vaccination.

OBJECTIVES: To assess the impact of a birth dose of hepatitis B vaccine (HepB) on the reactogenicity and immunogenicity of a novel diphtheria-tetanus-acellular pertussis (DTaP)- HepB-inactivated poliovirus (IPV)/ type b (Hib) combination vaccine administered subsequently at 2, 4 and 6 months of age. METHODS: Neonates ( = 550) were randomized into two groups with regard to receipt of HepB at birth. All subjects in both groups received DTaP-HepB-IPV/Hib at 2, 4 and 6 months of age. Solicited local and general adverse events were recorded for 8 days after each dose. Antibodies to hepatitis B surface antigen were measured 1 month after the third dose of DTaP-HepB-IPV/Hib in a subset of 170 infants; titers of at least 10 mIU/ml were considered protective. RESULTS: The DTaP-HepB-IPV/Hib combination vaccine was well-tolerated in both groups. Of the infants who received a birth dose of HepB, 22.6% had severe (Grade 3) reactions after any of the three doses of DTaP-HepB-IPV/Hib combination vaccine compared with 23.2% of subjects who did not receive a birth dose of HepB (difference, -0.5%; 90% confidence interval, -7.4 to 6.1). Antibody to hepatitis B surface antigen titers were > or =10 mIU/ml for all tested infants. Geometric mean titers were 2996.2 and 1240.1 mIU/ml with and without a birth dose of HepB, respectively. CONCLUSIONS: A HepB birth dose does not increase the reactogenicity of a combination DTaP-HepB-IPV/Hib vaccine administered at 2, 4 and 6 months of age, and all tested subjects achieved protective anti-HBs titers (> or =10 mIU/ml), although geometric mean titers were higher when a birth dose of HepB was given.

Bacterial Capsules↗
PubMed2002

Otitis media.

Bacterial pathogens are isolated from middle ear fluid in up to 90% of children with acute otitis media (OM). Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis predominate. Acute OM can be classified as uncomplicated, persistent, recurrent or chronic. Patient age, symptom severity, prior treatment history and exposure through day-care attendance in children influences pathogen distribution, antimicrobial susceptibility and anticipated clinical and microbiological responses to empirical and pathogen-directed therapies. The natural history of acute OM without intervention is favourable. However, meta-analysis of clinical trials shows an improvement in symptom and middle ear effusion resolution with antimicrobials. Aminopenicillins, cephalosporins and macrolides are often selected as therapy for acute OM. The various agents have differing activity against acute OM pathogens, particularly organisms with resistance mechanisms and they differ in dosing schedule, side effects and compliance enhancing factors. Consideration should be given to pharmacokinetic and pharmacodynamic principles in antibiotic selection. Selection criteria include antibiotic activity against drug-resistant S. pneumoniae and efficacy against beta-lactamase-producing Gram-negative organisms. The necessary duration of treatment for acute OM varies according to multiple factors, including local preferences, but there is growing, compelling data to support short-course therapy. Tympanocentesis has been endorsed in various guidelines as a diagnostic and therapeutic procedure. Best-practice for management of acute OM continues to advocate antibiotic therapy with careful, accurate diagnosis and consideration of the major pathogens and their mechanisms of resistance.

Acute Disease↗
PubMed2002

Seven-year follow-up of vaccine response in extremely premature infants.

OBJECTIVE: To assess the immune response of 7-year-old former extremely preterm (PT) infants to routine childhood immunizations. METHODS: Sixteen PT (<29 weeks and <1000 g) infants, followed since their primary immunizations at the recommended chronological ages, and 16 age-matched full-term (FT) control subjects were evaluated at 7 years of age. Antibodies to Haemophilus influenzae type b polyribosylribitol phosphate (Hib-PRP), tetanus, pertussis, diphtheria, polio, and hepatitis B (HBsAb) were measured. RESULTS: The FT group had higher antidiphtheria geometric mean titers (GMT) than the PT group (1.07 vs 0.36 IU/mL). All FT and 13 of 16 PT had protective diphtheria antibody titers (>0.1 IU/mL). The tetanus GMT were 4.22 IU/mL (FT) and 1.99 IU/mL (PT). All children had protective tetanus titers (>0.01 IU/mL). Pertussis titers did not differ between FT and PT. Hib-PRP GMT were higher in FT than in PT (3.21 vs 1.41 microg/mL). All children had anti-PRP > or = 0.15 microg/mL; 12 of 16 FT and 10 of 16 PT had levels > or = 1.0 microg/mL. Polio serotype 1 and 2 GMT were similar between groups, and all children had protective titers (> or = 8). Polio serotype 3 GMT were 59 (FT) and 24 (PT) Karber units; all FT and 12 of 16 PT had protective titers. Among children who had received hepatitis B vaccine, GMT were similar in FT and PT children (120 vs 186 mIU/mL, and similar proportions of children (11 of 16 FT and 12 of 14 PT) had protective HBsAb titers (>10 mIU/mL). CONCLUSIONS: At 7 years of age, PT children had lower antibody titers to many vaccine antigens than FT children. However, most PT children maintained antibody titers in the protective range.

Antibodies, Viral↗
PubMed2002

Interchangeability of 2 diphtheria-tetanus-acellular pertussis vaccines in infancy.

OBJECTIVE: Currently, 4 diphtheria-tetanus-acellular pertussis (DTaP) vaccines are licensed for pediatric use in the United States, and 2 are commercially available. Although a single manufacturer's DTaP vaccine should be used for all 3 doses of the primary immunization series, some circumstances result in infants receiving DTaP vaccines from more than 1 manufacturer. The purpose of this study was to evaluate the safety and immunogenicity of a mixed sequence of 2 different DTaP vaccines. METHODS: In this multicenter, observer-blinded, controlled study, 449 infants were randomized into 1 of 3 groups (1:1:1 ratio) to receive Tripedia at 2, 4, and 6 months of age (control group); Tripedia at 2 and 4 months of age and Infanrix at 6 months of age; or Tripedia at 2 months and Infanrix at 4 and 6 months of age. Other vaccines were administered concurrently as separate injections according to the recommended childhood immunization schedule. Safety was monitored closely, and standard enzyme immunoassays were used to measure antibody concentrations to each antigen of the DTaP vaccines. RESULTS: The rates of injection-site and systemic adverse events were similar in each study group, and there were no clinically significant differences among groups after any dose. Infants in all 3 groups responded well to each antigen contained in both vaccines, with 97% to 100% seroprotection or vaccine response rates after the 3-dose primary series. Postvaccination geometric mean antibody concentrations and seroprotection or vaccine response rates to nearly all vaccine antigens were as high or higher in the mixed-sequence groups as in the control group. CONCLUSION: Initiating the primary immunization series with 1 or 2 doses of Tripedia and completing the 3-dose series with Infanrix is as safe and at least as immunogenic as administering Tripedia for all 3 doses.

Antibodies↗
PubMed2002

Diagnostic accuracy, tympanocentesis training performance, and antibiotic selection by pediatric residents in management of otitis media.

OBJECTIVE: To assess the accuracy of pediatric residents in recognizing the physical examination findings of acute otitis media (AOM) and otitis media with effusion (OME), technical competence to perform tympanocentesis, and knowledge of guideline-recommended antibiotic management of AOM. METHODS: A total of 383 pediatric residents from various programs in the United States viewed 9 different video-recorded pneumatic otoscopic examinations of tympanic membranes during a continuing medical education course. The ability to differentiate AOM, OME, and normal was ascertained. A mannequin of a child was used to assess technical proficiency of performing tympanocentesis on artificial tympanic membranes. A series of questions was posed regarding appropriate, pathogen-directed, second-line antibiotic selection for AOM. RESULTS: The average +/- standard deviation correct diagnosis on the otoscopic video examination was 41% +/- 16% (range: 19%-70%; median: 38%) by pediatric residents, tympanocentesis was optimally performed by 89%, and appropriate antibiotic therapy for drug-resistant Streptococcus pneumoniae was selected by 78% and appropriate therapy for beta-lactamase-producing Haemophilus influenzae was selected by 74%. CONCLUSIONS: According to this video-based examination, pediatric residents misdiagnose OME frequently. Pediatric residents have the skills to be trained to perform tympanocentesis. Approximately 75% of pediatric residents have knowledge of the appropriate antibiotics to select for treatment of resistant AOM pathogens. Interactive instruction with simulation technology may enhance skills and lead to improved diagnostic accuracy and treatment paradigms.

Anti-Bacterial Agents↗