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

Solithromycin (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-resistant Streptococcus pneumoniae and nontypeable Haemophilus 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 of S. pneumoniae or 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 in Cmax and AUC0-24 values 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, Cmax and AUC0-24 values 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. For S. pneumoniae EOM, 3 isolates with MIC/MBC ratios of 0.06/0.125 µg/ml (S. pneumoniae 331), 0.125/1 µg/ml (S. pneumoniae CP-645 [MLSB phenotype]), and 0.5/2 µg/ml (CP-712 [mefA subclass mefA resistance]) were selected. Solithromycin sterilized MEF in 100% of animals infected with S. pneumoniae 331 and S. pneumoniae CP-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 with S. pneumoniae with an MIC of ≤0.125 µg/ml.

In vitro Activity of Cefditoren against Middle Ear Fluid Isolates from Costa Rican Children with Otitis Media.

Otitis media (OM) is one of the most common infections in children, Streptococcus pneumoniae and nontypable Haemophilus influenzae being the two most common pathogens isolated in the middle ear fluid (MEF) of children with OM. Cefditoren is a third-generation cephalosporin with broad-spectrum antibacterial activity, including activity against those pathogens commonly causing OM, with enhanced stability against common ß-lactamases. The main objective of this study was to evaluate the in vitro activity of cefditoren against pathogens collected from the MEF of Costa Rican children with OM between 2006 and 2011. A total of 715 samples were analyzed. Among the 89 S. pneumoniae strains that were penicillin-nonsusceptible, only 7% were cefditoren-resistant according to Spanish Regulatory Agency criteria; among the H. influenza and M. catarrhalis isolates obtained, 100 and 90% of the isolates, respectively, were cefditoren-susceptible. MIC50/90 against the 207 PCV-13 S. pneumoniae serotyped strains and the 79 serotypes not covered by PCV-13 for cefditoren were 0.03/1 and 0.03/0.12 mg/l, respectively. For both amoxicillin-susceptible and resistant H. influenzae strains, the MIC range against cefditoren was from ≤0.015 to 0.06 mg/l as well. In conclusion, the confirmation of the wide spectrum of activity of cefditoren and its intrinsic strength against resistant strains allows us to suggest that cefditoren might be included as one of the best choices among antibiotics that are widely used in empiric therapy for OM in pediatric patients.

Bacteriology of chronic suppurative otitis media (CSOM) in children in Garissa district, Kenya: a point prevalence study.

OBJECTIVES: To identify by type and sensitivity to drugs the bacteria found in ears of school-going children with chronic otitis media in Garissa district. STUDY DESIGN: This was a descriptive prevalence study of CSOM bacterial flora in eligible ears conducted among a cohort of children attending public and private primary as well as Islamic religious schools, screened for chronic ear discharge in Garissa district, Kenya. Procedure and bacteriological techniques: We used sterile swab-sticks to collect a specimen of the discharge from eligible ears of consenting pupils at the induction stage of the zinc supplementation trial for treatment of chronic suppurative otitis media conducted between January and July 2010. All pupils below 18 years present on day of visit were eligible. Both aerobic and anaerobic bacterial cultures were done to identify clinically and epidemiologically important bacteria. Sensitivity tests were based on disc diffusion methods. Results are presented as frequencies and proportions. RESULTS: Of the pupils seen, 61% were still in pre- or lower primary school. Majority were aged 13 and 14 years. Of the 261 ear swab samples processed, 336 isolates - either in mixed or pure flora - were identified, being almost exclusively aerobes. Proteus spp., Enterococcus, Staphylococcus aureus and Pseudomonas spp. were isolated in 32.7%, 28.6%, 12.8% and 11.3% respectively. Proteus was susceptible to majority of the antibiotics tested for, while Enterococcus was poorly susceptible. CONCLUSIONS: Aerobic bacteria were most prevalent in this study. Several of the bacteria identified are known to require iron for their growth. This may be important for CSOM treatment if biofilm formation is involved in pathogenesis. Majority of the isolates were susceptible to basic antibiotics compared to Enterococcus bacteria. This portends an important consideration for clinical management and therapeutic decision-making. Additionally, given the prevalence of Enterococcus bacteria, which is an indicator of faecal contamination of the environment, there is need to consider relevant public health components in managing childhood CSOM besides the clinical ones alone.

Effect of tympanic cavity evacuation and flushing on microbial isolates during total ear canal ablation with lateral bulla osteotomy in dogs.

OBJECTIVE: To evaluate differences in bacterial numbers, identity, and susceptibility in samples obtained from the tympanic cavity on entry (preflush) and after evacuation and lavage (postflush) and assess perioperative and empiric antimicrobial selection in dogs that underwent total ear canal ablation (TECA) with lateral bulla osteotomy (LBO) or reoperation LBO. DESIGN: Prospective clinical study. ANIMALS: 34 dogs. PROCEDURE: TECA with LBO or reoperation LBO was performed on 47 ears. Pre- and postflush aerobic and anaerobic samples were obtained from the tympanic cavity. Isolates and antimicrobial susceptibility patterns were compared. RESULTS: Different isolates (31/44 [70%] ears) and susceptibility patterns of isolate pairs (6/44 [14%] ears) were detected in pre- and postflush samples from 84% of ears. Evacuation and lavage of the tympanic cavity decreased the number of bacterial isolates by 33%. In 26% of ears, bacteria were isolated from post-flush samples but not preflush samples. Only 26% of isolates tested were susceptible to cefazolin. At least 1 isolate from 53% of dogs that received empirically chosen antimicrobials postoperatively was resistant to the selected drugs. Anaerobic bacteria were recovered from 6 ears. CONCLUSIONS AND CLINICAL RELEVANCE: Accurate microbiologic assessment of the tympanic cavity should be the basis for selection of antimicrobials in dogs undergoing TECA with LBO. Bacteria remain in the tympanic cavity after evacuation and lavage. Cefazolin was a poor choice for dogs that underwent TECA with LBO, as judged on the basis of culture and susceptibility testing results.

Otitis media in dairy calves: a retrospective study of 15 cases (1987 to 2002).

Epidemiological data, clinical signs, complementary examination findings, antimicrobial treatments, and outcome were reviewed in 15 calves diagnosed with otitis media at the Centre hospitalier universitaire vétérinaire de l'Université de Montréal between 1987 and 2002. Age at presentation ranged from 2 to 18 weeks. A purulent ear discharge and epiphora were seen in 8/12 and 6/15 cases, respectively. Neurological signs observed were head tilt (13), eyelid ptosis (7), paresis/paralysis of the pinna (8), ataxia (2), strabismus (2), and convulsions (1). Concurrent pneumonia was frequently diagnosed (n = 11). A Mycoplasma sp. was the principal pathogen isolated from ear discharge; 6 out of 6 samples submitted were positive for mycoplasma. Tympanic bullae radiographs were considered abnormal in 12 out of 13 cases. Cerebrospinal fluid analysis was considered abnormal in 2 out of 5 cases. The antibiotic most commonly used was enrofloxacin (n = 7). Average treatment duration was 19.6 days. Four out of 8 treated animals for which follow-up information was available completely recovered. These results suggest that M. bovis is a major pathogen of otitis media in dairy calves and effective antimicrobial therapy should be of long duration.

High prevalence of antibiotic resistance in isolates from the middle meatus of children and adults with acute rhinosinusitis.

BACKGROUND: The pathogens in acute rhinosinusitis are similar worldwide. An increase in antibiotic resistance has been shown in a large number of studies in recent years. The prevalence of resistance varies greatly in different countries. This study was performed to determine the endemic prevalence of antibiotic resistance in pathogens of acute rhinosinusitis in Taiwan. METHODS: Middle meatus discharge was taken for aerobic culture in 133 outpatients with the diagnosis of acute rhinosinusitis. RESULTS: One hundred two isolates of pathogens were found, including three major bacteria: Haemophilus influenzae (37.3%), Streptococcus pneumoniae (28.4%), and Moraxella catarrhalis (11.8%). Polymicrobial infections and positive cultures occurred more frequently in pediatric patients, as did recovery of M. catarrhalis infection. An extremely high percentage of resistance to first-line antibiotics was noted, viz., penicillin-nonsusceptible S. pneumoniae (PNSSP) (72.4%), ampicillin-resistant H. influenzae (60.5%), and M. catarrhalis (58.3%). CONCLUSION: The high prevalence of drug resistance is a great threat to public health. Antibiotic use should be more prudent, especially in pediatric patients, who were found to be more susceptible to bacterial rhinosinusitis and multiple pathogenic infection.

Bacterial eradication in the treatment of otitis media.

Drugs differ in their ability to eradicate various pathogens from the middle-ear cavity during acute otitis media (AOM), and these differences clearly affect clinical outcome. Outcome is derived from differences in the association between concentrations of the drugs at the site of infection and the antimicrobial effect (termed pharmacodynamics). These differences are even more marked in the present era of antimicrobial resistance. However, since AOM is a self-limiting disease in most cases, difference in clinical outcome is more difficult to ascertain than that of bacteriological outcome, which is measured within 3-5 days. A favourable clinical outcome regardless of the bacteriological effect of the drug can result in false optimism when less-effective antibiotic drugs are used. Inappropriate study design and manipulation of clinical results add to this confusion. In this review we attempt to highlight the evidence regarding bacteriological response to antibiotics in AOM and to draw attention to potential flaws that may mislead clinicians.

[Effect of bioceramics on biological activity of microorganisms]. / Untersuchungen zum Einfluss von Biokeramiken auf biologische Leistungen von Mikroorganismen.

BACKGROUND AND OBJECTIVE: Biomaterials that come into contact with microorganisms in the middle ear or paranasal sinuses should be tested before clinical application. Thus, it is necessary to test the influence exerted on bacterial growth by biomaterials used as bone substitutes in head and neck surgery before implantation. PATIENTS AND METHODS: In this study, Bioverit, Al2O3 ceramic, and glass carbon were subjected to contamination with typical microorganisms in the middle ear and paranasal sinuses such as Staphylococcus aureus, Streptococcus pneumoniae and salivarius, Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis and Candida albicans. RESULTS: In the suspension test, all gram-negative species were inhibited, but gram-positive microorganisms and Candida albicans were not affected. The Al2O3 ceramic showed the largest inhibition effect while growth inhibition of glass carbon was low. Streptococcus pneumoniae and salivarius can use glass carbon as a nutrient. In contrast, Bioverit and Al2O3 ceramic could not improve the growth of all tested microorganisms. CONCLUSIONS: In conclusion, we think that Bioverit is suitable for implantation in bacterially contaminated regions of the head and neck, whereas glass carbon is unsuitable for this application in reconstructive surgery.

A novel method for isolation of Chlamydia pneumoniae by treatment with trypsin or EDTA.

To establish a novel method for the efficient isolation of Chlamydia pneumoniae, experiments were performed to determine the effects of EDTA or trypsin treatment of C. pneumoniae on its adsorption and inclusion body formation. Treatment of C. pneumoniae with 0.1% trypsin or 1 mM EDTA significantly increased inclusion body-forming activity from 8,000- to 10,000-fold higher than that of the control. C. pneumoniae was successfully isolated in cultured cells which were inoculated with clinical specimens after treatment with 0.1% trypsin.

Enhancement of respiratory immunity to Pasteurella multocida by cholera toxin in rabbits.

Cholera toxin (CT) is a potent adjuvant for the mucosal immune system. The purpose of this study was to determine if coadministration of CT with a potassium thiocyanate extract of Pasteurella multocida (PTE) leads to enhanced anti-PTE antibody activity and increased protection of rabbits against infection with P. multocida and associated disease. Groups of rabbits were immunized intranasally on days 0, 7, and 14, with phosphate buffered saline (PBS), 200 micrograms of CT, 1.0 mg of PTE, or 1.0 mg PTE with 200 micrograms CT. Nasal lavage and serum samples were collected over 28 days after initial immunization and evaluated by ELISA for specific antibody directed against PTE. Marked increases in serum (IgG) and nasal lavage (IgA) anti-PTE antibody activity were found beginning after day 14 in rabbits immunized with PTE. Rabbits immunized with PTE and CT demonstrated further increases in this activity. Tracheobronchial lavage samples collected at the time of necropsy demonstrated a significant level of anti-PTE IgA activity in animals immunized with PTE, and coadministration with CT stimulated a further significant increase in this activity. Groups of similarly immunized rabbits were challenged 16 days after initial immunization with 5 x 10(7) CFUs of P. multocida. Nasal lavage samples were cultured for P. multocida over the next 10 days. Rabbits were euthanized within 10 days after challenge, tissues cultured for P. multocida, and histopathologic lesion severity graded using a numeric scale. Rabbits immunized with PTE survived longer, had less severe lesions of the lungs, pleura, and liver, and fewer P. multocida CFUs cultured from samples than PBS or CT controls. Coadministration of CT led to further reductions in lesion severity of those tissues and numbers of P. multocida CFUs cultured from samples. Increased nasal turbinate atrophy of rabbits immunized with PTE with or without CT was associated with increased mean survival time. In summary, coadministration of CT with PTE enhanced protective immunity to P. multocida disease and infection in rabbits.

Inefficacy of enrofloxacin in the elimination of Pasteurella multocida in rabbits.

The administration of enrofloxacin (5 mg/kg subcutaneously every 12 h for 10 days) failed to eliminate Pasteurella multocida from all naturally and experimentally infected rabbits. Although the enrofloxacin concentrations in serum and in turbinate bones were greater than the determined minimal inhibitory concentrations, P. multocida could be detected in nasal cavities, turbinates, trachea, middle ear and outer ear of experimentally infected rabbits after treatment. It is to be supposed that P. multocida colonizes organs or tissues in which an effective enrofloxacin concentration cannot be achieved. Such sites could be the paranasal sinuses, the auditory tube and the middle ear. This finding underlines the indispensibility of in vivo testing of antibiotic effectiveness.