Penetration of Amoxicillin, Cefaclor, Erythromycin-Sulfisoxazole, and Trimethoprim-Sulfamethoxazole into the Middle Ear Fluid of Patients with Chronic Serous Otitis Media

Krause, Peter J.; Owens, Niamh; Nightingale, Charles H.; Klimek, Joseph J.; Lehmann, William B.; Quintiliani, Richard

doi:10.1093/infdis/145.6.815

Cited by 85 publications

(27 citation statements)

References 28 publications

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“…Of interest, however, was that cefuroxime MICs were .l1.0 jxg/ml for 201 (93%) of the 217 H. influenzae strains tested, while cefaclor MICs were .1.0 ,ug/ml for less than 1% of the isolates; .1.0 jig/ml is the concentration of these cephalosporin agents usually attained in middle ear fluid (7,21,23,24,26). Our findings regarding cefaclor are compatible with those of other investigators.…”

Section: Discussionsupporting

confidence: 88%

“…The antimicrobial combination trimethoprim-sulfamethoxazole was highly active in vitro against our H. influenzae study strains at concentrations achievable in middle ear fluid, .0.5/9.5 jig/ml (20,21). Antibiotic synergy was demonstrated against 54% of the study isolates tested against this combination.…”

Section: Discussionmentioning

confidence: 81%

“…However, for only 56% of these isolates tested against this combination were amoxicillin MICs reduced to the levels seen for P-lactamase negative strains or to levels readily achieved in middle ear fluid (.1.0 ,ug/ml) (10,15,21,26).…”

Section: Discussionmentioning

confidence: 88%

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In vitro activity of orally administered antimicrobial agents against Haemophilus influenzae recovered from children monitored longitudinally in a group day-care center

George

Henderson

et al. 1991

Antimicrob Agents Chemother

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To determine whether the prevalence of resistance to commonly used oral antimicrobial agents varied over time, we compared the in vitro susceptibilities of 217 strains of Haemophilus influenzae recovered from nasopharyngeal secretions of children in a day-care Oenter studied longitudinally between 1979 and 1987. The overall rate of 13-lactamase production in these strains was 18%, with rates of 57% in type b isolates (n = 21) and 14% in non-type b isolates (n = 196). The percentages of isolates for which MICs were '1.0 ,ug/ml for amoxicillin alone, amoxicillin in combination with clavulanic acid, and cefuroxime alone were 82, 92, and 93%, respectively. The percentage of strains for which cefaclor MICs were s1.0 ,ug/ml was only 0.5%. Isolates for which chloramphenicol MICs were >2.0 ,ug/ml or for which trimethoprim-sulfamethoxazole MICs were >0.5/9.5 pg/ml were uncommon: 1 and <1%, respectively. High concentrations of erythromycin alone and in combination with sulfisoxazole were required to inhibit the majority of test strains; there was no evidence of erythromycin-sulfisoxazole synergy. In vitro susceptibility to commonlly used oral antimicrobial agents remained at a constant level when H. influenzae isolates collected from children in a day'catae center during 1979 through 1983 were compared with strains collected during 1984 through 1987.Haemophilus influenzae is an important bacterial pathogen of the upper respiratory tract during childhood (2). Nonencapsulated (nontypeable) strains are common causes of conjunctivitis, otitis media, and maxillary sinusitis (9,16,36). Although these localized mucosal infections are rarely life-threatening, they are associated with significant morbidity; otitis media alone accounts for up to 40% of all pediatric office visits (17,34).The prevalence of otitis media appears to be two to four times higher in children attending group day-care,centers than it is in children cared for at home or in smaller day-care environments in homes (22,27,32,35). The clinical diagnosis of middle ear infection in children in group day-care centers typically results in empiric therapy with orally administered antimicrobial agents. The frequent use of these antimicrobial agents could contribute to the emergence of antibiotic-resistant pathogens within pediatric populations (13, 31). We recently reported a high rate of nasopharyngeal carriage of antibiotic-resistant pneumococci by children in a day-care center environment (14). In that report, we documented an increasing rate of pneumococcal resistance to trimethoprim-sulfamethoxazole during the 5 years of its use in that setting. Because colonizing H. influenzae strains were exposed to the same antibiotic pressures as the previously studied pneumococci, we were concerned that similar resistance trends could be occurring in H. influenzae carried by children in this day-care center population. The present investigation was undertaken to determine, in a longitudinal fashion, the prevalence of resistance to commonly used antimicrobial agents in H. infl...

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 81%

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In vitro activity of orally administered antimicrobial agents against Haemophilus influenzae recovered from children monitored longitudinally in a group day-care center

George

Henderson

et al. 1991

Antimicrob Agents Chemother

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“…The concentrations of loracarbef achieved in MEF compare favorably with those of other antibiotics studied in similar patients with chronic middle ear effusions (1,2). Two hours after a 15-mg/kg dose of cefaclor, the concentration in MEF was 1.06 mg/liter (2), as compared with the 3.9-mg/liter concentration found for loracarbef in this study.…”

supporting

confidence: 69%

Loracarbef concentrations in middle ear fluid

Kusmiesz

Shelton

Brown

et al. 1990

Antimicrob Agents Chemother

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Loracarbef concentrations in plasma and middle ear fluid (MEF) were measured in specimens obtained approximately 2 h after doses of 7.5 or 15 mg/kg. The mean + standard deviation concentrations in MEF were 2.0 + 2.6 mg/liter (48% of the concentration in plasma) after the smaller dose and 3.9 2.6 mg/liter (42% of the concentration in plasma) after the larger dose. With the larger dose, the concentrations in MEF were greater than the MIC for 90% of strains of the usual pathogens of acute otitis media tested in 16 of 17 specimens.Loracarbef (LY163892), a synthetic carbacephem antibiotic, has good in vitro activity against common respiratory pathogens (4). It is currently being tested in clinical trials for the treatment of acute otitis media and other respiratory infections. In this study, we assessed the penetration of loracarbef into middle ear fluid (MEF).Infants bacterial growth inhibition after 18 h of incubation were measured and read against a standard curve to calculate the concentration of drug. The lower limit of sensitivity of the assay was 0.25 mg/liter. The intra-assay variability of the standard curve was 3.4%, and the interassay variability was 2.1%. The concentrations at which variabilities were determined were 5.0, 3.0, 1.5, and 0.7 mg/liter.As controls, three specimens of MEF from children who were not receiving antibiotics were tested similarly and shown to cause no inhibition of the assay organism. In addition, a known quantity (4 mg/liter) of loracarbef was added to six similar MEF specimens; the assayed amounts ranged from 3.7 to 5.2 mg/liter.Twelve children taking the 7.5-mg/kg dose had a mean age of 32 months (range, 10 to 75 months). Nine were males and three were females. (Results from an additional child were discarded because the samples were grossly bloody.) Twenty MEF samples were obtained. Samples were obtained a mean of 135 min (range, 80 to 195 min) after the dose of loracarbef was given. The time between MEF sampling in cases of bilateral myringotomy was 6 min (range, 4 to 10 min). The time between plasma and MEF sampling was 9 min (range, 3 to 17 min). The mean ± standard deviation concentration of loracarbef in MEF was 2.0 ± 2.6 mg/liter (range, 0.2 to 5.6 mg/liter), and that in plasma was 4.2 ± 2.0 mg/liter (range, 1.4 to 6.8 mg/liter). The mean concentration in MEF was 48% of the mean concentration in plasma.The mean age of the 10 children taking the 15-mg/kg dose was 52 months (range, 21 to 82 months). Seven were males and three were females. (Results from an additional two patients were discarded because of grossly bloody samples in one and technical problems in the other.) Seventeen MEF samples were assayed. Samples were obtained a mean of 129 min (range, 60 to 165 min) after the dose of loracarbef was given. In cases of bilateral myringotomy, the time between sampling was 5 min (range, 3 to 8 min). The time between plasma and MEF sampling was 9 min (range, 5 to 15 min). The mean ± standard deviation concentration of loracarbef in MEF was 3.9 ± 2.6 mg/liter (range, 0.9 to 9....

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“…An additional consideration in the case of biofilms of otitis media is that there is very low penetration of antibiotics into the middle ear fluid. Krause et al (107) compared concentrations of amoxicillin, cefaclor, erythromycin-sulfisoxazole, and trimethoprim-sulfamethoxazole in middle ear fluid and serum of children with serous OM. For samples collected 15 to 240 min after administration of a single oral dose, levels of antibiotic in the middle ear fluid were always significantly lower than those in the serum.…”

Section: Otitis Mediamentioning

confidence: 99%

Biofilms: Survival Mechanisms of Clinically Relevant Microorganisms

2002

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Though biofilms were first described by Antonie van Leeuwenhoek, the theory describing the biofilm process was not developed until 1978. We now understand that biofilms are universal, occurring in aquatic and industrial water systems as well as a large number of environments and medical devices relevant for public health. Using tools such as the scanning electron microscope and, more recently, the confocal laser scanning microscope, biofilm researchers now understand that biofilms are not unstructured, homogeneous deposits of cells and accumulated slime, but complex communities of surface-associated cells enclosed in a polymer matrix containing open water channels. Further studies have shown that the biofilm phenotype can be described in terms of the genes expressed by biofilm-associated cells. Microorganisms growing in a biofilm are highly resistant to antimicrobial agents by one or more mechanisms. Biofilm-associated microorganisms have been shown to be associated with several human diseases, such as native valve endocarditis and cystic fibrosis, and to colonize a wide variety of medical devices. Though epidemiologic evidence points to biofilms as a source of several infectious diseases, the exact mechanisms by which biofilm-associated microorganisms elicit disease are poorly understood. Detachment of cells or cell aggregates, production of endotoxin, increased resistance to the host immune system, and provision of a niche for the generation of resistant organisms are all biofilm processes which could initiate the disease process. Effective strategies to prevent or control biofilms on medical devices must take into consideration the unique and tenacious nature of biofilms. Current intervention strategies are designed to prevent initial device colonization, minimize microbial cell attachment to the device, penetrate the biofilm matrix and kill the associated cells, or remove the device from the patient. In the future, treatments may be based on inhibition of genes involved in cell attachment and biofilm formation

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Penetration of Amoxicillin, Cefaclor, Erythromycin-Sulfisoxazole, and Trimethoprim-Sulfamethoxazole into the Middle Ear Fluid of Patients with Chronic Serous Otitis Media

Cited by 85 publications

References 28 publications

In vitro activity of orally administered antimicrobial agents against Haemophilus influenzae recovered from children monitored longitudinally in a group day-care center

In vitro activity of orally administered antimicrobial agents against Haemophilus influenzae recovered from children monitored longitudinally in a group day-care center

Loracarbef concentrations in middle ear fluid

Biofilms: Survival Mechanisms of Clinically Relevant Microorganisms

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