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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
PubMed2006

The use of tympanocentesis in the diagnosis and management of acute otitis media.

Acute otitis media (AOM), when associated with a bulging or full tympanic membrane, has a bacterial etiology in more than 90% of cases. Not infrequently, the organisms present express resistance mechanisms to commonly prescribed antibiotic therapy. Tympanocentesis is a procedure advocated by several national guidelines for use in selected patients not clinically responding to antimicrobial treatment. In this paper we discuss the use of tympanocentesis as a tool to track pathogen shifts and to guide antibiotic selection. We detail the indications for tympanocentesis, compare guidelines endorsing the procedure, and describe how to implement a technique for use in the primary care setting. The pros and cons of using tympanocentesis in clinical trial designs are also presented.

Journal Article↗
PubMed2006

Acellular pertussis vaccine boosters combined with diphtheria and tetanus toxoid boosters for adolescents: safety and immunogenicity assessment when preceded by different 5-dose DTaP/DTwP schedules.

A sixth dose of tetanus, diphtheria, acellular pertussis (Tdap) vaccine in adolescents might produce a differing reactogenicity and/or immunogenicity response depending on the composition of the 5 prior doses of DTaP or DT-whole cell pertussis (DTwP) vaccine. Reactions and immune responses following receipt of the Sanofi Pasteur (Adacel) and GlaxoSmithKline (Boostrix) Tdap vaccines were assessed in 229 adolescents. No differences were observed for reactions to either Tdap vaccine regardless of the prior DTaP/DTwP vaccination history. Seroprotective levels and antibody concentrations were comparable regardless of prior DTaP/DTwP vaccine history. A sixth sequential dose of Tdap after 5 doses of DTaP appears safe and immunogenic.

Adolescent↗
PubMed2006

Pathogen shifts and changing cure rates for otitis media and tonsillopharyngitis.

Pneumococcal conjugate vaccine use has caused a decrease in the incidence of recurrent and refractory acute otitis media in the United States and a shift in the predominant pathogens. Now Haemophilus influenzae is the most commonly isolated organism (about 60% of the total), and more than half the strains make beta-lactamase, rendering them resistant to amoxicillin. Penicillin nonsusceptible pneumococci, the main target of antibiotic therapy in the 1990s, has become a much less common isolate (10%- 25% of the total). These changes impact antibiotic selection for acute otitis media. Penicillin treatment of group A streptococcal tonsillopharyngitis does not meet the minimum United States Food and Drug Administration standards for first-line treatment, which is 85% or greater eradication at the end of therapy. Recent results with amoxicillin suggest its efficacy is also waning. Cephalosporins have the highest bacteriologic and clinical efficacy. This has implications for optimal antibiotic therapy.

Anti-Bacterial Agents↗
PubMed2006

Acellular pertussis vaccine booster combined with diphtheria and tetanus toxoids for adolescents.

BACKGROUND: The incidence of pertussis is increasing, especially in adolescents, attributed in part to waning of immunity after childhood immunization. Recently licensed in the United States for use in adolescents, acellular pertussis vaccines will provide an immunogenic and safe option for booster immunization against pertussis. METHODS: This prospective, randomized, observer-blinded, multicenter, comparative study evaluated the safety and immunogenicity of a vaccine formulated with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis antigens (Tdap) compared with tetanus and diphtheria toxoids vaccine (Td) for booster immunization in adolescents. There were 4114 healthy adolescents aged 10 to 18 years who completed childhood vaccination against diphtheria, tetanus, and pertussis who were enrolled, randomized, and received study vaccine. RESULTS: Local and general symptoms were comparable between the Tdap and Td groups. The immune response of Tdap was comparable with Td vaccine for tetanus and diphtheria seroprotection and booster responses. In addition, geometric mean concentrations of antibody to pertussis antigens, pertussis toxoid, filamentous hemagglutinin, and pertactin exceeded the antibody response elicited after infant immunization with diphtheria and tetanus toxoids and acellular pertussis antigens (DTaP) that had proven efficacy against pertussis. CONCLUSIONS: In adolescents, the studied Tdap was safe and immunogenic and induced pertussis antibodies that were higher than those associated with efficacy in infants.

Adolescent↗
PubMed2006

An adolescent and adult formulation combined tetanus, diphtheria and five-component pertussis vaccine.

Pertussis causes substantial morbidity among adolescents and adults, as well as other persons in contact with affected individuals. In the context of widespread childhood immunization, vaccination of adolescents and adults is a relatively new strategy for reducing the disease in all age groups. ADACEL is a tetanus-diphtheria-acellular pertussis combination vaccine (incorporating pertussis toxoid, filamentous hemagglutinin, pertactin and fimbriae type 2 and 3 antigens) formulated for use in adolescents and adults based on similar products designed for infants and children. ADACEL vaccine is approved for use in Australia, Canada, Germany and the USA, and has been demonstrated to induce robust immune responses and acceptable levels of reactogenicity in clinical trials. Surveillance data from Canada, where ADACEL vaccine has been used in adolescents and adults in conjunction with ongoing childhood vaccination for several years, indicate an enhanced overall reduction in pertussis disease.

Adolescent↗
PubMed2006

Cephalosporins can be prescribed safely for penicillin-allergic patients.

The widely quoted cross-allergy risk of 10% between penicillin and cephalosporins is a myth. Cephalothin, cephalexin, cefadroxil, and cefazolin confer an increased risk of allergic reaction among patients with penicillin allergy. Cefprozil, cefuroxime, cefpodoxime, ceftazidime, and ceftriaxone do not increase risk of an allergic reaction.

Anti-Bacterial Agents↗
PubMed2005

N-fragment of edema factor as a candidate antigen for immunization against anthrax.

The nontoxic N-terminal fragment of Bacillus anthracis edema factor (EF) was evaluated as a candidate antigen in an anthrax vaccine using a replication-incompetent adenoviral vector. An E1/E3 deleted adenovirus (Ad/EFn) encoding the N-terminal region 1-254 amino acids of the edema factor (EFn) was constructed using the native DNA sequence of EFn. Intramuscular immunization three times with 10(8) plaque forming units (pfu)/dose of Ad/EFn in A/J mice resulted in 37% and 57% protection against a subcutaneous challenge with B. anthracis Sterne strain spores at a dosage of 200 x LD50 and 100 x LD50, respectively. EF-specific serum IgG responses (including total IgG, IgG1, and IgG2a isotype titers) were robust in the Ad/EFn immunized animals. Interestingly, anti-EF antibodies cross-reacted with anthrax lethal factor (LF), and had a neutralizing capability against both anthrax lethal toxin (Letx) and edema toxin (Edtx), as demonstrated by in vitro toxin neutralization assays using J774A.1 mouse macrophage and Chinese hamster ovary cell (CHO), respectively. Our data suggest that EF plays a role in eliciting protective immunity against anthrax, and that it should be included in a new generation multi-component subunit vaccine.

Adenoviridae↗
PubMed2005

Safety and efficacy of gatifloxacin therapy for children with recurrent acute otitis media (AOM) and/or AOM treatment failure.

BACKGROUND: Because of concerns about arthrotoxicity, fluoroquinolones are restricted for use in children. This study describes the safety and efficacy of gatifloxacin when used for treatment of children with recurrent acute otitis media (ROM) or acute otitis media (AOM) treatment failure (AOMTF). METHODS: We performed an analysis of 867 children included in 4 clinical trials who had ROM and/or AOMTF and were treated with gatifloxacin (10 mg/kg once daily for 10 days). RESULTS: Gatifloxacin had adverse event rates that were similar overall to those of a comparator antibiotic (amoxicillin-clavulanate), except for increased diarrhea in children <2 years old receiving amoxicillin-clavulanate. There was no evidence of arthrotoxicity, hepatotoxicity, alteration of glucose homeostasis, or central nervous system toxicity acutely or during 1 year follow-up in any child. Regarding efficacy, in 2 noncomparative trials, the gatifloxacin cure rate of AOM was 89% (95% confidence interval [CI], 83%-95%) at the test of cure (TOC) visit, 3-10 days after completion of therapy. In 2 comparative trials of gatifloxacin versus amoxicillin-clavulanate, the efficacy of gatifloxacin was 88% (95% CI, 82%-94%). Gatifloxacin led to better clinical outcomes than amoxicillin-clavulanate for AOMTF (91% vs. 81%; P=.029), for AOMTF and age <2 years old (89% vs. 69%; P=.009), and for severe AOM in children <2 years old (90% vs. 75%; P=.012). Among children with AOMTF previously treated with amoxicillin-clavulanate or ceftriaxone injections, gatifloxacin cure rates were high (88% and 75%, respectively). CONCLUSIONS: Gatifloxacin appears to be safe for children, with no evidence of producing arthrotoxicity in 867 children exposed to the antibiotic when used as treatment for ROM and AOMTF.

Anti-Infective Agents↗
PubMed2005

Combined tetanus, diphtheria, and 5-component pertussis vaccine for use in adolescents and adults.

CONTEXT: Increasing reports of pertussis among US adolescents, adults, and their infant contacts have stimulated vaccine development for older age groups. OBJECTIVE: To assess the immunogenicity and reactogenicity of a tetanus-diphtheria 5-component (pertussis toxoid, filamentous hemagglutinin, pertactin, and fimbriae types 2 and 3) acellular pertussis vaccine (Tdap) in adolescents and adults. DESIGN, SETTING, AND PARTICIPANTS: A prospective, randomized, modified double-blind, comparative trial was conducted in healthy adolescents and adults aged 11 through 64 years from August 2001 to August 2002 at 39 US clinical centers. INTERVENTIONS: A single 0.5-mL intramuscular dose of either Tdap or tetanus-diphtheria vaccine (Td). MAIN OUTCOME MEASURES: Antibody titers to diphtheria and tetanus toxoids for Tdap and Td were measured in sera collected from subsets of adolescents and adults, before and 28 days after vaccination. For pertussis antigens, titers in sera from Tdap vaccinees were assessed vs those from infants who received analogous pediatric diphtheria-tetanus-acellular pertussis vaccine (DTaP) in a previous efficacy trial. Safety was assessed via solicited local and systemic reactions for 14 days and adverse events for 6 months following vaccination. RESULTS: A total of 4480 participants were enrolled. For both Tdap and Td, more than 94% and nearly 100% of vaccinees had protective antibody concentrations of at least 0.1 IU/mL for diphtheria and tetanus, respectively. Geometric mean antibody titers to pertussis toxoid, filamentous hemagglutinin, pertactin, and fimbriae types 2 and 3 exceeded (by 2.1 to 5.4 times) levels in infants following immunization at 2, 4, and 6 months with DTaP. The incidence of solicited local and systemic reactions and adverse events was generally similar between the Tdap and Td groups. CONCLUSIONS: This Tdap vaccine elicited robust immune responses in adolescents and adults to pertussis, tetanus, and diphtheria antigens, while exhibiting an overall safety profile similar to that of a licensed Td vaccine. These data support the potential routine use of this Tdap vaccine in adolescents and adults.

Adolescent↗
PubMed2005

Higher dosages of azithromycin are more effective in treatment of group A streptococcal tonsillopharyngitis.

BACKGROUND: Azithromycin has become a frequent choice for the treatment of group A streptococcal (GAS) tonsillopharyngitis. In this study, our objective was to determine the optimal dose of azithromycin for treatment of GAS tonsillopharyngitis in children and adults by analyzing trials that used different dose regimens. METHODS: We performed a meta-analysis of randomized, controlled trials that involved bacteriological confirmation of GAS tonsillopharyngitis, random assignment to receive either azithromycin or a 10-day comparator antibiotic, and assessment of bacteriological eradication by throat culture after therapy. The primary outcomes of interest were bacteriological and clinical cure rates. RESULTS: Nineteen trials involving 4626 patients were included in the analysis. One trial used 10-day course of 2 different comparator antibiotics, and 2 trials compared 2 dose regimens of azithromycin with a 10-day course of comparator antibiotic; all other trials compared 1 dose regimen of azithromycin with a single 10-day course of comparator antibiotic. In children, azithromycin administered at 60 mg/kg per course was superior to the 10-day courses of comparators (P < .00001), with bacterial failure occurring 5 times more often in patients receiving the 10-day courses of antibiotics. Azithromycin administered at 30 mg/kg per course was inferior to the 10-day courses of comparators (P = .02), with bacterial failure occurring 3 times more frequently in patients receiving azithromycin. Three-day regimens were inferior to 5-day regimens (P = .002). In adults, no studies compared dosages by weight. Three-day regimens of 500 mg/day showed a trend favoring azithromycin over the 10-day courses of comparators (P = .14); 5-day regimens were inferior to 3-day regimens (P = .006). Clinical cure rates were significantly different for the different azithromycin regimens, with differences that resembled those for bacterial cure rate. CONCLUSION: This analysis suggests that azithromycin administered at a dosage of 60 mg/kg in children or administered for 3 days at a dosage of 500 mg/day in adults is more effective than other treatment regimens in producing eradication and clinical cure of GAS tonsillopharyngitis.

Adult↗
PubMed2005

Acellular pertussis vaccines for adolescents.

BACKGROUND: The epidemiology of pertussis is changing, with a clear increase in the number of cases diagnosed in adolescents and adults. This development has spurred studies and anticipated licensure of safer diphtheria, tetanus, acellular pertussis combined (Tdap) vaccines for this older population. METHODS: Literature review. RESULTS: Tdap vaccines are safe and immunogenic when administered to adolescents and adults. Correlates of immunity to pertussis after Tdap vaccination have not been established, but various combinations of antibody to pertussis antigens (pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae) provide protection. The importance of the number of antigens in Tdap vaccines for protection against mild pertussis disease is unclear. Pertussis vaccination establishes herd immunity after sufficient uptake within communities and countries. As experience with TdaP vaccines has accumulated, a 1-2% occurrence of large, local injection-site reactions with all TdaP vaccine products have been observed for booster doses in children 4-6 years of age. The frequency of large local reactions appears lower in adolescents and adults. The pathophysiologic mechanisms for the local reactions are not established, but a majority appears to be immunoglobulin E-mediated-reactive edema, and a minority appears to be immunoglobulin G-mediated Arthus-type reactions. CONCLUSIONS: Tdap vaccines appear safe and immunogenic. The economic impact of pertussis provides a cost-benefit justification for widespread use of Tdap vaccine boosting in adolescents.

Adolescent↗
PubMed2005

Metaanalysis of short course antibiotic treatment for group a streptococcal tonsillopharyngitis.

OBJECTIVE: To compare bacterial and clinical cure rates in patients with group A streptococcal (GAS) tonsillopharyngitis treated with oral beta-lactam or macrolide antibiotics for 4-5 days versus 10-day comparators. METHODS: Medline, Embase, reference lists and abstract searches were used to identify available publications. Trials were included if there was bacteriologic confirmation of GAS tonsillopharyngitis, random assignment to antibiotic therapy for a beta-lactam or macrolide antibiotic of a shortened course versus a 10-day comparator and assessment of bacteriologic outcome using a throat culture. RESULTS: Twenty-two trials involving 7470 patients were included in 4 separate analyses. Trials were grouped by a short course of cephalosporins (n = 14), macrolides (other than azithromycin) (n = 6) and penicillin (n = 2). Cephalosporin trials were further grouped by the comparator, penicillin or the same cephalosporin. Short course cephalosporin treatment was superior for bacterial cure rate compared with 10 days of penicillin [odds ratio (OR), 1.47; 95% confidence interval (CI), 1.06-2.03]. For trials with short course macrolide therapy, OR = 0.79 (95% CI 0.59-1.06) neither the macrolides nor the 10-day comparators. Short course penicillin therapy was inferior in achieving bacterial cure versus 10 days of penicillin, OR = 0.29 (95% CI 0.13-0.63). Clinical cure rates mirrored bacteriologic cure rates. CONCLUSION: Superior cure rates can be achieved with shortened courses of cephalosporin therapy, but 5 days is inferior to 10 days of penicillin treatment.

Anti-Bacterial Agents↗
PubMed2005

Preferred antibiotics for treatment of acute otitis media: comparison of practicing pediatricians, general practitioners, and otolaryngologists.

The antibiotic preferences of 2,190 pediatricians (peds) 360 general practitioners (GPs), and 273 otolaryngologists (ENTs) in the United States and concurrence with treatment guideline recommendations for acute otitis media (AOM) for suspected drug-resistant Streptococcus pneumoniae (DRSP) and beta-lactamase-producing Haemophilus influenzae before and after an educational workshop were compared. Peds and GPs preferred amoxicillin/clavulanate high-dose, whereas ENTs preferred higher generation cephalosporins. Before the workshop, endorsement of guideline-recommended antibiotics for treatment of AOM caused by DRSP by Peds, GPs, and ENTs was 80%, 75%, and 78%, respectively, and for Haemophilus influenzae was 73%, 63%, and 84%, respectively. After the workshop concurrence with AOM guideline recommendations for DRSP increased to 96%, 95%, and 97% and for H. influenzae increased to 93%, 94%, and 96% for Peds, GPs, and ENTs, respectively (p<0.0001 for all comparisons). Peds, GPs, and ENTs select appropriate antibiotics for AOM 63-84% of the time. After instruction that provides the rationale for guideline-recommended agents based on pharmacokinetics/pharmacodynamics and double tympanocentesis trials, endorsement of recommended antibiotics significantly improved to >90%.

Drug Resistance, Bacterial↗