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Group A Streptococcus infections in children: from virulence to clinical management. Curr Opin Infect Dis 2019; 31:224-230. [PMID: 29601325 DOI: 10.1097/qco.0000000000000452] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
PURPOSE OF REVIEW Recent findings have open new perspectives on group A Streptococcus (GAS) virulence understanding with special focus on the carrier stage and new hopes for an efficient vaccine against this important pathogen. RECENT FINDINGS Understanding of carriage state, transmission and role of virulence factors in invasive infections have been recently active research fields questioning the link between carriage and infections and highlighting the potential to prevent invasive diseases. New roles for already well known virulence factors, such as Streptolysin O, M protein or NAD(+)-glycohydrolase have been discovered. Immunological studies have also shown diversity in both clinical and immunological responses toward various GAS antigens raising questions, and hopes, for the development of an efficient global vaccine candidate. SUMMARY A greater understanding of GAS virulence strategies, and their associated clinical manifestations, may be obtained by shifting our research scope toward virulence determinant interactions and cooperation rather than focusing on individual virulence factor or specific strain characterization only.
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Wozniak A, Scioscia N, Geoffroy E, Ponce I, García P. Importance of adhesins in the recurrence of pharyngeal infections caused by Streptococcus pyogenes. J Med Microbiol 2017; 66:517-525. [DOI: 10.1099/jmm.0.000464] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Affiliation(s)
- Aniela Wozniak
- Laboratorio de Microbiología, Departamento de Laboratorios Clínicos, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Natalia Scioscia
- Laboratorio de Microbiología, Departamento de Laboratorios Clínicos, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Enrique Geoffroy
- Laboratorio de Microbiología, Departamento de Laboratorios Clínicos, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Iván Ponce
- Laboratorio de Microbiología, Departamento de Laboratorios Clínicos, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Patricia García
- Laboratorio de Microbiología, Departamento de Laboratorios Clínicos, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
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Soriano F, Giménez MJ, Aguilar L. Pharmacodynamics for predicting therapeutic outcome and countering resistance spread: The cefditoren case. World J Clin Infect Dis 2012; 2:28-38. [DOI: 10.5495/wjcid.v2.i3.28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The relationship between pharmacokinetics and pharmacodynamics is a key instrument to improve antimicrobial stewardship and should be aimed to identification of the drug exposure measure that is closely associated not only with the ability to kill organisms but also to suppress the emergence of resistant subpopulations. This article reviews published studies for efficacy prediction with cefditoren and those aimed to explore its potential for countering resistance spread, focusing on the three most prevalent community-acquired isolates from respiratory infections: Streptococcus pneumoniae (S. pneumoniae), Haemophilus influenzae (H. influenzae) and Streptococcus pyogenes (S. pyogenes). Studies for efficacy prediction include in vitro pharmacodynamic simulations (using physiological concentrations of human albumin) and mice models (taking advantage of the same protein binding rate in mice and humans) to determine the value of the pharmacodynamic indices predicting efficacy, and Monte Carlo simulations to explore population pharmacodynamic coverage, as weapons for establishing breakpoints. Studies exploring the potential of cefditoren (free concentrations obtained with 400 mg cefditoren bid administration) for countering spread of resistance showed its capability for countering (1) intra-strain spread of resistance linked to ftsI gene mutations in H. influenzae; (2) the spread of H. influenzae resistant strains (with ftsI gene mutations) in multi-strain H. influenzae niches or of S. pneumoniae strains with multiple resistance traits in multi-strain S. pneumoniae niches; and (3) for overcoming indirect pathogenicity linked to β-lactamase production by H. influenzae that protects S. pyogenes in multibacterial niches. This revision evidences the ecological potential for cefditoren (countering resistance spread among human-adapted commensals) and its adequate pharmacodynamic coverage of respiratory pathogens (including those resistant to previous oral compounds) producing community-acquired infections.
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Brook I. Anaerobic bacteria in upper respiratory tract and head and neck infections: microbiology and treatment. Anaerobe 2011; 18:214-20. [PMID: 22197951 DOI: 10.1016/j.anaerobe.2011.12.014] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2011] [Revised: 12/09/2011] [Accepted: 12/11/2011] [Indexed: 11/26/2022]
Abstract
Anaerobes are the predominant components of oropharyngeal mucous membranes bacterial flora, and are therefore a common cause of bacterial infections of endogenous origin of upper respiratory tract and head and neck. This review summarizes the aerobic and anaerobic microbiology and antimicrobials therapy of these infections. These include acute and chronic otitis media, mastoiditis and sinusitis, pharyngo-tonsillitis, peritonsillar, retropharyngeal and parapharyngeal abscesses, suppurative thyroiditis, cervical lymphadenitis, parotitis, siliadenitis, and deep neck infections including Lemierre Syndrome. The recovery from these infections depends on prompt and proper medical and when indicated also surgical management.
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Affiliation(s)
- Itzhak Brook
- Departments of Pediatrics and Medicine, Georgetown University School of Medicine, Washington, DC 20016, USA.
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Mouratidou A, Karbach J, d'Hoedt B, Al-Nawas B. Antibiotic Susceptibility of Cocultures in Polymicrobial Infections Such as Peri-Implantitis or Periodontitis: An In Vitro Model. J Periodontol 2011; 82:1360-6. [DOI: 10.1902/jop.2011.100657] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
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Schwaab M, Gurr A, Hansen S, Minovi AM, Thomas JP, Sudhoff H, Dazert S. Human β-Defensins in different states of diseases of the tonsilla palatina. Eur Arch Otorhinolaryngol 2009; 267:821-30. [DOI: 10.1007/s00405-009-1086-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2009] [Accepted: 08/24/2009] [Indexed: 10/20/2022]
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Role of methicillin-resistant Staphylococcus aureus in head and neck infections. The Journal of Laryngology & Otology 2009; 123:1301-7. [DOI: 10.1017/s0022215109990624] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
AbstractThe prevalence of infection with methicillin-resistant Staphylococcus aureus is increasing. Methicillin-resistant Staphylococcus aureus is also being recognised as an important pathogen in head and neck infections. This review summarises studies published over the past two decades which illustrate the growing prevalence of methicillin-resistant Staphylococcus aureus, and the current therapeutic approaches to head and neck infections caused by this bacterium. These infections include sinusitis, otitis, periorbital cellulitis, cervical lymphadenitis, tonsillitis, thyroiditis, retropharyngeal abscess, and abscesses and wounds of the neck. Treatment of head and neck infections associated with methicillin-resistant Staphylococcus aureus includes drainage and debridement, as well as administration of local and systemic antimicrobials that provide coverage against these organisms and against potential aerobic and anaerobic pathogens that may be present if the infection is polymicrobial.
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Sevillano D, Aguilar L, Alou L, Giménez MJ, González N, Torrico M, Cafini F, Coronel P, Prieto J. Beta-lactam effects on mixed cultures of common respiratory isolates as an approach to treatment effects on nasopharyngeal bacterial population dynamics. PLoS One 2008; 3:e3846. [PMID: 19052648 PMCID: PMC2587697 DOI: 10.1371/journal.pone.0003846] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2008] [Accepted: 11/10/2008] [Indexed: 11/19/2022] Open
Abstract
Background Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae are bacteria present in the nasopharynx as part of normal flora. The ecological equilibrium in the nasopharynx can be disrupted by the presence of antibiotics. Methodology/Principal Findings A computerized two-compartment pharmacodynamic model was used to explore β-lactam effects on the evolution over time of a bacterial load containing common pharyngeal isolates by simulating free serum concentrations obtained with amoxicillin (AMX) 875 mg tid, amoxicillin/clavulanic acid (AMC) 875/125 mg tid and cefditoren (CDN) 400 mg bid regimens over 24 h. Strains and MICs (µg/ml) of AMX, AMC and CDN were: S. pyogenes (0.03, 0.03 and 0.015), S. pneumoniae (2, 2 and 0.25), a β-lactamase positive H. influenzae (BL+; >16, 2 and 0.06) and a β-lactamase positive AMC-resistant H. influenzae (BLPACR, >16, 8 and 0.06). Mixture of identical 1∶1∶1∶1 volumes of each bacterial suspension were prepared yielding an inocula of ≈4×106 cfu/ml. Antibiotic concentrations were measured both in bacterial and in bacteria-free antibiotic simulations. β-lactamase production decreased AMX concentrations and fT>MIC against S. pneumoniae (from 43.2% to 17.7%) or S. pyogenes (from 99.9% to 24.9%), and eradication was precluded. The presence of clavulanic acid countered this effect of co-pathogenicity, and S. pyogenes (but not BL+ and S. pneumoniae) was eradicated. Resistance of CDN to TEM β-lactamase avoided this co-pathogenicity effect, and CDN eradicated S. pyogenes and H. influenzae strains (fT>MIC >58%), and reduced in 94% S. pneumoniae counts (fT>MIC ≈25%). Conclusions/Significance Co-pathogenicity seems to be gradual since clavulanic acid countered this effect for strains very susceptible to AMX as S. pyogenes but not for strains with AMX MIC values in the limit of susceptibility as S. pneumoniae. There is a potential therapeutic advantage for β-lactamase resistant cephalosporins with high activity against streptococci.
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Affiliation(s)
- David Sevillano
- Microbiology Department., School of Medicine, University Complutense, Madrid, Spain
| | - Lorenzo Aguilar
- Microbiology Department., School of Medicine, University Complutense, Madrid, Spain
- * E-mail:
| | - Luis Alou
- Microbiology Department., School of Medicine, University Complutense, Madrid, Spain
| | - María-José Giménez
- Microbiology Department., School of Medicine, University Complutense, Madrid, Spain
| | - Natalia González
- Microbiology Department., School of Medicine, University Complutense, Madrid, Spain
| | - Martha Torrico
- Microbiology Department., School of Medicine, University Complutense, Madrid, Spain
| | - Fabio Cafini
- Microbiology Department., School of Medicine, University Complutense, Madrid, Spain
| | - Pilar Coronel
- Scientific Department, Tedec-Meiji Farma S. A., Madrid, Spain
| | - José Prieto
- Microbiology Department., School of Medicine, University Complutense, Madrid, Spain
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Brook I. Current management of upper respiratory tract and head and neck infections. Eur Arch Otorhinolaryngol 2008; 266:315-23. [PMID: 18985371 DOI: 10.1007/s00405-008-0849-8] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2008] [Accepted: 10/13/2008] [Indexed: 11/25/2022]
Abstract
The objective of this study is to present the antimicrobial management modalities of treating upper respiratory tract (URT) and head and neck infections. This article discusses the current antimicrobial treatment strategies of URT and head and neck infections. The increasing antimicrobial resistance of many bacterial pathogens has made the treatment of URT and head and neck infections more difficult. This review summarizes the aerobic and anaerobic microbiology and antimicrobials therapy of acute and chronic URT and head and neck infections. These infections include dental (gingivitis, periodontitis, necrotizing ulcerative gingivitis, and periodontal abscess), acute and chronic otitis media, mastoiditis and sinusitis, pharyngo-tonsillitis, peritonsillar, retropharyngeal and parapharyngeal abscesses, suppurative thyroiditis, cervical lymphadenitis, parotitis, siliadenitis, and deep neck infections including Lemierre syndrome. In conclusion, the proper management of these infections requires an accurate clinical and bacteriological diagnosis.
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Affiliation(s)
- Itzhak Brook
- Departments of Pediatrics and Medicine, Georgetown University School of Medicine, Washington, DC 20016, USA.
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Affiliation(s)
- Itzhak Brook
- Department of Pediatrics, Georgetown University School of Medicine, 4431 Albemarle Street, NW, Washington, DC 20016, USA.
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Isaacson G, Parikh T. Developmental anatomy of the tonsil and its implications for intracapsular tonsillectomy. Int J Pediatr Otorhinolaryngol 2008; 72:89-96. [PMID: 17996953 DOI: 10.1016/j.ijporl.2007.09.021] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2007] [Accepted: 09/28/2007] [Indexed: 10/22/2022]
Abstract
OBJECTIVE To describe the developmental anatomy of the human tonsil from the embryonic period through adulthood and to use this information to define the applicability of intracapsular tonsillectomy in the management of disease. DESIGN Descriptive-anatomic. SUBJECTS (1) Normal embryos and fetuses from two archival collections, (2) children with adenotonsillar hypertrophy and (3) adult autopsy material. RESULTS The second branchial pouch is visible in the 4th post-conceptional week and demonstrates canalization and branching in the 8th week. Lymphoid infiltration of the lamina propria occurs in the seventh month of intrauterine life. Primary follicles form late in gestation, but germinal center stimulation does not occur until shortly after birth. During the first year of life, there is rapid proliferation of lymphoid elements and formation of active germinal centers. During the phase of maximum tonsillar hyperplasia, the lymphoid elements proliferate rapidly, increasing tonsillar bulk. In senescence, there is involution of the lymphoid elements and proliferation of fibrous tissue in the capsule and trabeculae. The overall bulk of the tonsil is much decreased. CONCLUSIONS There is an intimate relationship between the epithelial and lymphoid components of the tonsil which continues through life. To adequately control upper airway obstruction of tonsillar origin and recurrent tonsillar infection in childhood, total or near total intracapsular tonsillectomy likely will prove the minimum acceptable surgical intervention. Changes in tonsillar anatomy after the first decade may alter operative choice in older patients.
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Affiliation(s)
- Glenn Isaacson
- Department of Otolaryngology - Head & Neck Surgery and Pediatrics, Temple University School of Medicine, Temple University Children's Medical Center, Philadelphia, PA 19140, USA.
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Brook I. Microbiology and Principles of Antimicrobial Therapy for Head and Neck Infections. Infect Dis Clin North Am 2007; 21:355-91, vi. [PMID: 17561074 DOI: 10.1016/j.idc.2007.03.014] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
The principles of antimicrobial management for head and neck infections include establishing an accurate clinical and microbiologic diagnosis and treating the patient initially with an empiric antimicrobial regimen based on predicted likelihood of success and reduced potential for resistance. Subsequent adjustments may be required based on clinical response and available culture results. This article summarizes the aerobic and anaerobic microbiology of selected acute and chronic infections of the head and neck and the approaches to antimicrobial therapy.
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Affiliation(s)
- Itzhak Brook
- Department of Pediatrics and Medicine, Georgetown University School of Medicine, 4431 Albemarle St. NW, Washington, DC 20016, USA.
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Brook I, Gober AE. Recovery of interfering and β-lactamase-producing bacteria from group A β-haemolytic streptococci carriers and non-carriers. J Med Microbiol 2006; 55:1741-1744. [PMID: 17108280 DOI: 10.1099/jmm.0.46796-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
The purpose of this study was to compare the frequency of recovery of aerobic and anaerobic organisms with interfering capability against group A β-haemolytic streptococci (GABHS) and β-lactamase-producing bacteria (BLPB) from the tonsils of GABHS carriers and non-carriers. The presence of aerobic and anaerobic bacteria capable of such interference in vitro was evaluated in cultures obtained from the tonsils of 20 healthy children who were non-GABHS carriers and 20 who were GABHS carriers, and also from 20 children who were asymptomatic after completing a course of penicillin for acute GABHS pharyngo-tonsillitis (PT) and were non-GABHS carriers and 20 who were GABHS carriers. In healthy children, 32 interfering isolates were recovered from 16 non-GABHS carriers (1.6 per child) and 13 were isolated from 7 GABHS carriers (0.65 per child) (P<0.001). In children who had suffered acute GABHS PT, 26 interfering organisms were recovered from 15 non-GABHS carriers (1.3 per child) and 8 were isolated from 5 GABHS carriers (0.4 per child) (P<0.005). In healthy children, 13 BLPB were recovered from 5 non-GABHS carriers and 13 were isolated from 6 GABHS carriers. In children who had suffered acute GABHS PT, 14 BLPB were recovered from 5 (25 %) non-GABHS carriers and 32 were isolated from 17 (85 %) GABHS carriers (P<0.05). It was demonstrated in this study that there was a higher rate of recovery of aerobic and anaerobic organisms capable of interfering with GABHS in non-GABHS carriers than in GABHS carriers. This was observed in all GABHS non-carriers and included healthy children as well as those recently treated for symptomatic GABHS PT with penicillin that failed to eradicate GABHS. A higher rate of recovery of BLPB was observed only in GABHS carriers who were treated with penicillin for GABHS PT.
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Affiliation(s)
- Itzhak Brook
- Department of Pediatrics, Georgetown University School of Medicine, Washington DC, USA
| | - Alan E Gober
- Department of Pediatrics, Georgetown University School of Medicine, Washington DC, USA
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Brook I, Foote PA. Isolation of methicillin resistant Staphylococcus aureus from the surface and core of tonsils in children. Int J Pediatr Otorhinolaryngol 2006; 70:2099-102. [PMID: 16962178 DOI: 10.1016/j.ijporl.2006.08.004] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2006] [Accepted: 08/09/2006] [Indexed: 11/28/2022]
Abstract
BACKGROUND The rate of recovery methicillin resistant Staphylococcus aureus (MRSA) in tonsils that were removed because of recurrent Group A-beta-hemolytic streptococci (GABHS) tonsillitis was not previously reported. MRSA may serve as a potential source for the spread of these organisms to other body sites as well to other individuals. This study investigated the rate of recovery of MRSA as well as other aerobic organisms from tonsils that were removed because of recurrent GABHS infection. PATIENTS AND METHODS Core and surface tonsillar cultures for aerobic bacteria were obtained from 44 children who had tonsillectomy because of recurrent GABHS tonsillitis. RESULTS A total of 167 aerobic isolates were recovered from the core of the tonsils (3.8/specimen) and 151 (3.4/specimen) were isolated from the surface. The predominant isolates were alpha-hemolytic streptococci, GABHS, S. aureus, gamma-hemolytic streptococci, Haemophilus influenzae and Moraxella catarrhalis. Concordance in the recovery of all organisms was noted in 117 instances. Certain organisms (i.e. GABHS, S. aureus) were recovered more often from the tonsillar cores, where other (i.e. alpha-hemolytic streptococci, gamma-hemolytic streptococci) were recovered more often from the tonsillar surface. Forty-four beta-lactamase-producing bacteria (BLPB) were recovered from 32 (75%) of the tonsillar cores, and 28 were isolated from 23 (52%) of the tonsillar surfaces. The predominant BLPB were S. aureus, H. influenzae and M. catarrhalis. Seven isolates of MRSA were recovered from the cores and two were isolated from the surface. Five of the core isolates and the two surface isolates were also BLPB. All of the MRSA isolates were resistant to oxacillin, penicillin and erythromycin and were susceptible to clindamycin, trimethoprim-sulfamethoxazole and vancomycin. CONCLUSIONS These data demonstrated that in recurrently GABHS infected tonsils, BLPB was recovered from over 75% of the tonsillar cores, core tonsillar cultures yielded more GABHS and S. aureus, and MRSA was isolated from 16% of the tonsils.
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Affiliation(s)
- Itzhak Brook
- Department of Pediatrics, Georgetown University School of Medicine, Washington, DC, USA.
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Brook I, Hausfeld JN. Recovery of interfering bacteria in the nasopharynx following antimicrobial therapy of acute maxillary sinusitis with telithromycin or amoxicillin-clavulanate. Antimicrob Agents Chemother 2006; 49:4793-4. [PMID: 16251334 PMCID: PMC1280152 DOI: 10.1128/aac.49.11.4793-4794.2005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
The effect on the nasopharyngeal flora of 7 days of amoxicillin-clavulanate or 5 days of 800 mg once a day was studied in 50 adults with acute sinusitis. The numbers of potential pathogens and interfering alpha-hemolytic streptococci were equally reduced after both therapies. However, the number of interfering Prevotella spp. declined more significantly after amoxicillin-clavulanate treatment.
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Affiliation(s)
- Itzhak Brook
- Georgetown University School of Medicine, Washington, DC 20016, USA.
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Brook I. A pooled comparison of cefdinir and penicillin in the treatment of group a β-hemolytic streptococcal pharyngotonsillitis. Clin Ther 2005; 27:1266-73. [PMID: 16199251 DOI: 10.1016/j.clinthera.2005.08.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/07/2005] [Indexed: 10/25/2022]
Abstract
OBJECTIVE This pooled analysis compared the clinical cure and bacterial eradication rates achieved by cefdinir and penicillin in the treatment of group A beta-hemolytic streptococcal (GABHS) pharngotonsillitis. METHODS Data from 4 multicenter, randomized, controlled, investigator-blinded trials, 2 in children receiving oral suspensions and 2 in adults receiving capsules/tablets, were pooled and analyzed in terms of clinical cure rates, microbiologic eradication rates, and adverse events. RESULTS A total of 2751 patients were enrolled (age <13 years, n = 1274; age > or =13 years, n = 1477). Patients were randomized to receive cefdinir once daily (n = 569) or twice daily (n = 1086) for 5 or 10 days, or penicillin 4 times daily (n = 1096) for 10 days. Of the 2751 patients enrolled, 2198 were evaluable for clinical and microbiologic outcomes. Compared with the 10-day penicillin regimens, the cefdinir regimens for 5 or 10 days produced higher clinical cure and microbiologic eradication rates. Combined clinical cure rates were significantly higher for cefdinir compared with penicillin (94% vs 83%, respectively; P < 0.001). Combined microbiologic eradication rates were also significantly higher for cefdinir compared with penicillin (92% vs 77%; P < 0.001). Both cefdinir and penicillin were well tolerated, as >98% of patients completed the course of therapy. CONCLUSION In this pooled analysis of data from 4 multicenter, randomized, controlled, investigator-blinded trials in children and adults, 5- and 10-day regimens of cefdinir achieved significantly higher clinical cure and microbiologic eradication rates compared with 10-day penicillin regimens in the treatment of GABHS pharyngotonsillitis.
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Affiliation(s)
- Itzhak Brook
- Department of Pediatrics, Georgetown University School of Medicine, Washington, DC, USA.
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17
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Brook I, Gober AE. Long-term effects on the nasopharyngeal flora of children following antimicrobial therapy of acute otitis media with cefdinir or amoxycillin-clavulanate. J Med Microbiol 2005; 54:553-556. [PMID: 15888464 DOI: 10.1099/jmm.0.45837-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
The effect on the nasopharyngeal bacterial flora of 10 days of amoxycillin-clavulanate or cefdinir antimicrobial therapy was studied in 50 children with acute otitis media. Before therapy, 17 potential pathogens (Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis) were isolated from the nasopharynx of 14 (56%) of those treated with amoxycillin-clavulanate, and 20 potential pathogens were recovered from 15 (60%) of those treated with cefdinir. Following therapy, at days 12-15, the number of potential pathogens was reduced to a similar extent with both therapies, to three in those treated with amoxycillin-clavulanate and two in those treated with cefdinir. However, the number of potential pathogens rebounded faster in those treated with amoxycillin-clavulanate as compared with cefdinir in the two subsequent specimens taken at days 30-35 and 60-65 (12 and 18 in the amoxycillin-clavulanate group, and six and nine in the cefdinir group, P < 0.01 and P < 0.001, respectively). Differences between the groups were also noted in the recovery of organisms with interfering capability. Immediately following amoxycillin-clavulanate therapy, the number of interfering organisms declined from 54 to 13, while following cefdinir treatment their number was reduced from 59 to 39 (P < 0.001). The differences between the two therapy groups persisted in the two later specimens taken at days 30-35 and 60-65 (25 and 38 in the amoxycillin-clavulanate group, and 52 and 51 in the cefdinir group, P < 0.001 and P < 0.05, respectively). This study illustrates the potential beneficial effect of using a narrow-spectrum antimicrobial that selectively spares the interfering organisms while eliminating pathogens. The benefit of such therapy is the prevention of reacquisition of pathogenic bacteria in the nasopharynx. In contrast, utilization of a broad-spectrum antimicrobial is associated with prolonged absence of inhibitory organisms and rapid recolonization with pathogens.
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Affiliation(s)
- Itzhak Brook
- Departments of Pediatrics, Georgetown University School of Medicine, 4431 Albemarle St NW, Washington DC 20016, USA
| | - Alan E Gober
- Departments of Pediatrics, Georgetown University School of Medicine, 4431 Albemarle St NW, Washington DC 20016, USA
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Eradication of Streptococcus pneumoniae in the Nasopharyngeal Flora of. Curr Infect Dis Rep 2004. [DOI: 10.1007/s11908-004-0004-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Cenjor C, García-Rodríguez JA, Ramos A, Cervera J, Tomás M, Asensi F, Cañada JL, Gobernado M, Isasiá T, López-Madroñero C, Martínez M, Pérez-Escanilla F, Picazo J, Prieto J, Sampelayo T. [Patient consent to "antimicrobial treatment of tonsillitis"]. ACTA OTORRINOLARINGOLOGICA ESPANOLA 2003; 54:369-83. [PMID: 12916480 PMCID: PMC7111178 DOI: 10.1016/s0001-6519(03)78425-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- C Cenjor
- Servicio de Otorrinolaringología, Fundación Jiménez Díaz, Avda. Reyes Católicos 2, 28040 Madrid
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Brook I, Gober AE. Effect of amoxicillin and co-amoxiclav on the aerobic and anaerobic nasopharyngeal flora. J Antimicrob Chemother 2002; 49:689-92. [PMID: 11909846 DOI: 10.1093/jac/49.4.689] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
The effects of co-amoxiclav (AMC) and amoxicillin (AMX) therapy on the nasopharyngeal flora of children with acute otitis media (AOM) were compared. Nasopharyngeal culture for aerobic and anaerobic bacteria were obtained before therapy and 2-4 days after completion of antimicrobial therapy in 25 patients treated with either antibiotic. After therapy, 16 (64%) of the 25 patients treated with AMX and 23 (92%) of the 25 patients treated with AMC were considered clinically cured. Polymicrobial aerobic-anaerobic flora were present in all instances. A significant reduction in the number of both aerobic and anaerobic isolates occurred after therapy in those treated with AMX (177 isolates versus 133, P< 0.005) and AMC (172 isolates versus 60, P< 0.001). However, the number of all isolates recovered after therapy in those treated with AMC was significantly lower (60 isolates) than in those treated with AMX (133 isolates, P < 0.001). The recovery of known aerobic pathogens (e.g. Streptococcus pneumoniae, Staphylococcus aureus, beta-haemolytic streptococci, Haemophilus species and Moraxella catarrhalis) and penicillin-resistant bacteria after therapy was lower in the AMC group than in the AMX group (P < 0.005). This study illustrates the greater ability of AMC, compared with AMX, to reduce the number of potential nasopharyngeal pathogens and penicillin-resistant bacteria in children with AOM.
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Affiliation(s)
- Itzhak Brook
- Department of Pediatrics, Georgetown University School of Medicine, Washington, DC, USA.
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Brook I, Aronovitz GH, Pichichero ME. Open-Label, parallel-group, multicenter, randomized study of cefprozil versus erythromycin in children with group A streptococcal pharyngitis/tonsillitis. Clin Ther 2001; 23:1889-900. [PMID: 11768840 DOI: 10.1016/s0149-2918(00)89084-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
BACKGROUND Cefprozil and erythromycin are acceptable alternatives to penicillin in the treatment of pharyngitis/tonsillitis due to group A beta-hemolytic streptococcus (GABHS). OBJECTIVE The purpose of this trial was to determine the relative efficacy and tolerability of cefprozil and erythromycin in the treatment of pediatric pharyngitis/tonsillitis due to GABHS. METHODS This trial compared the bacteriologic and clinical efficacy of erythromycin and cefprozil in children 2 to 12 years of age with culture-documented GABHS pharyngitis/ tonsillitis. Children who were allergic to penicillin, cefprozil, or erythromycin were excluded. Patients were prospectively randomly assigned to receive 10 days of oral therapy with either cefprozil suspension 15 mg/kg per day in 2 divided doses or erythromycin ethylsuccinate suspension 30 mg/kg per day in 3 divided doses. Primary efficacy end points were bacteriologic and clinical response 2 to 8 days after treatment ended. The frequency and severity of adverse events and their relationship to treatment were also assessed. RESULTS A total of 199 patients were enrolled and treated (cefprozil, 99; erythromycin, 100); 12 patients in the cefprozil group and 15 in the erythromycin group were not evaluable. The GABHS eradication rate was significantly higher with cefprozil (95%) than with erythromycin (74%) (P = 0.001). The posttreatment carrier rate was lower in the cefprozil group (5%) than in the erythromycin group (18%) (95% CI, -22.3 to -3.8). Clinical cure rate was 90% (78/87) with cefprozil and 91% (77/85) with erythromycin (P = 0.95) (treatment group difference, -0.93; 95% CI, -9.9% to 8.0%). The overall incidence of drug-related adverse events was not significantly different in the 2 groups (11% with cef- prozil, 18% with erythromycin). The most common adverse events were diarrhea and vomiting. Two patients in the erythromycin group discontinued therapy because of adverse events. CONCLUSIONS The bacteriologic eradication rate was significantly greater with cefprozil compared with erythromycin in children with pharyngitis/tonsillitis. Both cefprozil and erythromycin produced a clinical cure in >90% of patients.
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Affiliation(s)
- I Brook
- Department of Pediatrics, Georgetown University School of Medicine, Washington, DC 20016, USA
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