scholarly journals Efficacy of Solithromycin (CEM-101) for Experimental Otitis Media Caused by Nontypeable Haemophilus influenzae and Streptococcus pneumoniae

2016 ◽  
Vol 60 (9) ◽  
pp. 5533-5538 ◽  
Author(s):  
M. Figueira ◽  
P. Fernandes ◽  
S. I. Pelton
Keyword(s):  
Streptococcus Pneumoniae ◽  
Haemophilus Influenzae ◽  
Otitis Media ◽  
Middle Ear ◽  
Fourth Generation ◽  
Minimal Bactericidal Concentration ◽  
Nontypeable Haemophilus Influenzae ◽  
Time Curve ◽  
Content Type ◽  
Middle Ear Fluid

ABSTRACTSolithromycin (CEM-101) is a “fourth-generation” macrolide, as it has three binding site and is acid stable. The three binding sites confer activity against bacteria resistant to the older macrolides and ketolides, including multidrug-resistantStreptococcus pneumoniaeand nontypeableHaemophilus influenzae(NTHi). The objective of this study was to evaluate solithromycin pharmacokinetics (PK), middle ear fluid (MEF) concentrations, and microbiologic efficacy in a chinchilla model of experimental otitis media (EOM) due to strains ofS. pneumoniaeor NTHi. Plasma PK (maximum concentration of drug in serum [Cmax] and area under the concentration-time curve from 0 to 24 h [AUC0–24]) and middle ear fluid (MEF) concentrations were determined. Isolates with specified antimicrobial susceptibility patterns were inoculated directly into the middle ear (ME). Plasma and MEF were collected for PK and MEF cultures performed to determine efficacy. Solithromycin administered at 150 mg/kg of body weight/day resulted inCmaxand AUC0–24values of 2.2 μg/ml and 27.4 μg · h/ml in plasma and 1.7 μg/ml and 28.2 μg · h/ml in extracellular MEF on day 1. By day 3,Cmaxand AUC0–24values had increased to 4.5 μg/ml and 54 μg · h/ml in plasma and 4.8 μg/ml and 98.6 μg · h/ml in extracellular MEF. For NTHi EOM, three isolates with MIC/minimal bactericidal concentration (MBC) ratios of 0.5/1 μg/ml (isolate BCH1), 2/2 μg/ml (isolate BMC1247C), and 4/4 μg/ml (isolate BMC1213C) were selected. The MEF of >85% of animals infected with BCH1 and BMC1247C was sterilized. For NTHi BMC1213, >85% of MEF cultures remained positive. ForS. pneumoniaeEOM, 3 isolates with MIC/MBC ratios of 0.06/0.125 μg/ml (S. pneumoniae331), 0.125/1 μg/ml (S. pneumoniaeCP-645 [MLSBphenotype]), and 0.5/2 μg/ml (CP-712 [mefAsubclassmefAresistance]) were selected. Solithromycin sterilized MEF in 100% of animals infected withS. pneumoniae331 andS. pneumoniaeCP-645. ME infection persisted in 60% of animals infected with CP-712. In a model of EOM, solithromycin sterilized MEF in >85% of animals challenged with NTHi with an MIC of ≤2 μg/ml and 100% of ME infected withS. pneumoniaewith an MIC of ≤0.125 μg/ml.

scholarly journals Activity of Faropenem against Middle Ear Fluid Pathogens from Children with Acute Otitis Media in Costa Rica and Israel

2007 ◽  
Vol 51 (6) ◽  
pp. 2230-2235 ◽  
Author(s):  
Kimberley Clawson Stone ◽  
Ron Dagan ◽  
Adriano Arguedas ◽  
Eugene Leibovitz ◽  
Elaine Wang ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Costa Rica ◽  
Haemophilus Influenzae ◽  
Otitis Media ◽  
Streptococcus Pyogenes ◽  
Middle Ear ◽  
Moraxella Catarrhalis ◽  
Acute Otitis Media ◽  
The Other ◽  
Middle Ear Fluid

ABSTRACT Faropenem was tested against 1,188 middle ear fluid pathogens from children in Israel and Costa Rica. Against Streptococcus pneumoniae and Haemophilus influenzae, faropenem was the most active β-lactam, with activity that was similar to or greater than of the other oral antimicrobial classes studied. Faropenem was also active against Moraxella catarrhalis and Streptococcus pyogenes.

Failure of antibiotic therapy in acute otitis media

2003 ◽  
Vol 117 (3) ◽  
pp. 173-176 ◽  
Author(s):  
Emmanuel Babin ◽  
Vincent Lemarchand ◽  
Sylvain Moreau ◽  
Marc Goullet de Rugy ◽  
André Valdazo ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Haemophilus Influenzae ◽  
Antibiotic Therapy ◽  
Otitis Media ◽  
Middle Ear ◽  
Acute Otitis Media ◽  
Bacterial Strains ◽  
Middle Ear Fluid ◽  
Two Samples ◽  
Microbiological Techniques

The aim of this retrospective study was to determine the possible causes of failure of antibiotic therapy in children with acute otitis media (AOM). Thirty-nine samples of middle-ear fluid were obtained by myringotomy from 31 children suffering from AOM, unrelieved by antibiotic therapy administered for over 48 hours. The samples were analysed by the usual microbiological techniques, including cultures, tests for beta-lactamase producing strains and the determination of the minimal inhibitory concentration of penicillin for Streptococcus pneumoniae. In 14 samples, no bacterial strains were detected in the cultures of middle-ear fluid; and in two samples the cultures revealed two strains of bacteria. The bacteria most frequently identified were Haemophilus influenzae, found in 11 samples, and Streptococcus pneumoniae, found in seven samples, of which four produced strains with reduced susceptibility to penicillin. The failure of antibiotic therapy in AOM appears to be related to the increased resistance of Haemophilus influenzae and to the reduced susceptibility of Streptococcus pneumoniae to penicillin. Other factors contributing to the failure of antibiotic therapy in AOM may be the viruses or the bacteria that produce multiple pathogens in the middle ear.

Immune Response to Acute Otitis Media: Association Between Middle Ear Fluid Antibody and the Clearing of Clinical Infection

1976 ◽  
Vol 4 (3) ◽  
pp. 306-308
Author(s):  
John L. Sloyer ◽  
Virgil M. Howie ◽  
John H. Ploussard ◽  
Gerald Schiffman ◽  
Richard B. Johnston
Keyword(s):  
Immune Response ◽  
Streptococcus Pneumoniae ◽  
Haemophilus Influenzae ◽  
Otitis Media ◽  
Middle Ear ◽  
Specific Antibody ◽  
Acute Otitis Media ◽  
Clinical Infection ◽  
Middle Ear Fluid

Clearing of the middle ear fluid in patients with acute otitis media due to Streptococcus pneumoniae or Haemophilus influenzae was significantly associated with the presence and concentration of specific antibody in the middle ear fluid at the time of diagnosis.

scholarly journals Acute Mastoiditis in the Pneumococcal Conjugate Vaccine Era

2014 ◽  
Vol 21 (8) ◽  
pp. 1189-1191 ◽  
Author(s):  
Sharon Ovnat Tamir ◽  
Yehudah Roth ◽  
Ilan Dalal ◽  
Abraham Goldfarb ◽  
Tal Marom
Keyword(s):  
Streptococcus Pneumoniae ◽  
Middle Ear ◽  
Pneumococcal Conjugate Vaccine ◽  
Inverse Relationship ◽  
Acute Otitis Media ◽  
Acute Mastoiditis ◽  
Conjugate Vaccines ◽  
Content Type ◽  
Bacterial Cultures ◽  
Middle Ear Fluid

ABSTRACTFollowing the introduction of the 7- and 13-valent pneumococcal conjugate vaccines, we observed an inverse relationship between the increasing rate of immunized children and the proportion of middle ear fluid cultures collected during acute mastoiditis episodes that tested positive forStreptococcus pneumoniaeamong a subset of children 0 to 6 years old who had initially presented with severe acute otitis media and had bacterial cultures collected during tympanocentesis or from spontaneous otorrhea.

scholarly journals Biofilm Biology and Vaccine Strategies for Otitis Media Due to Nontypeable Haemophilus influenzae

2018 ◽  
Vol 14 (02) ◽  
pp. 069-078 ◽  
Author(s):  
Laura Novotny ◽  
Kenneth Brockman ◽  
Elaine Mokrzan ◽  
Joseph Jurcisek ◽  
Lauren Bakaletz
Keyword(s):  
Haemophilus Influenzae ◽  
Otitis Media ◽  
Middle Ear ◽  
Causative Agent ◽  
Upper Respiratory Tract ◽  
Nontypeable Haemophilus Influenzae ◽  
Physical Defenses ◽  
Upper Respiratory ◽  
Recurrent Nature ◽  
Gain Access

AbstractOtitis media (OM) is one of the most common diseases of childhood, and nontypeable Haemophilus influenzae (NTHI) is the predominant causative agent of chronic and recurrent OM, as well as OM for which treatment has failed. Moreover, NTHI is now as important a causative agent of acute OM as the pneumococcus. NTHI colonizes the human nasopharynx asymptomatically. However, upon perturbation of the innate and physical defenses of the airway by upper respiratory tract viral infection, NTHI can replicate, ascend the Eustachian tube, gain access to the normally sterile middle ear space, and cause disease. Bacterial biofilms within the middle ear, including those formed by NTHI, contribute to the chronic and recurrent nature of this disease. These multicomponent structures are highly resistant to clearance by host defenses and elimination by traditional antimicrobial therapies. Herein, we review several strategies utilized by NTHI to persist within the human host and interventions currently under investigation to prevent and/or resolve NTHI-induced diseases of the middle ear and uppermost airway.

Bacteriology of chronic otitis media with effusion

1989 ◽  
Vol 103 (4) ◽  
pp. 369-371 ◽  
Author(s):  
C. Diamond ◽  
P. R. Sisson ◽  
A. M. Kearns ◽  
H. R. Ingham
Keyword(s):  
Streptococcus Pneumoniae ◽  
Haemophilus Influenzae ◽  
Otitis Media ◽  
Middle Ear ◽  
Otitis Media With Effusion ◽  
Anaerobic Bacteria ◽  
Chronic Otitis Media

AbstractSamples of middle ear effusions from 102 children with serous and mucoid otitis media were cultured for mycoplasmas and bacteria. No sample yielded mycoplasmas but bacteria were cultured from 48 (47 per cent). Organisms commonly regarded as pathogens were present in 25 samples (Haemophilus influenzae 17, Streptococcus pneumoniae four, other streptococci four). The only sample from which anaerobic bacteria were isolated was from a patient with cholesteatoma.

MIDDLE-EAR FLUID STREPTOCOCCUS PNEUMONIAE SUSCEPTIBILITY AND SEROTYPE AND DISTRIBUTION IN MEXICAN CHILDREN WITH ACUTE OTITIS MEDIA

PEDIATRICS ◽  
2008 ◽  
Vol 121 (Supplement 2) ◽  
pp. S129.2-S129 ◽  
Author(s):  
Claudia Lopez-Enriquez ◽  
A. Blanco-Montero ◽  
L. E. Espinosa-Monteros ◽  
R. Rodriguez ◽  
C. De La Torre ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Otitis Media ◽  
Middle Ear ◽  
Acute Otitis Media ◽  
Mexican Children ◽  
Middle Ear Fluid
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