Sinus tissue pharmacokinetics after oral administration of amoxicillin/clavulanic acid.

OBJECTIVES: The in vitro synergy of the amoxicillin/clavulanic acid combination has not always translated in vivo into clinical superiority compared with amoxicillin alone. Specifically, conflicting reports have disputed the superiority of the combination in the treatment of both acute otitis media and acute sinusitis. One possible reason for this may have to do with inadequate target tissue pharmacokinetics. To explore this possibility in the sinuses, we undertook the present investigation. STUDY DESIGN: A randomized, open, single-dose, sinus tissue pharmacokinetic study with oral amoxicillin/clavulanic acid. METHODS: Twenty-three adult patients with chronic rhinosinusitis who had been selected for surgery were randomly allocated to receive a tablet of 875/125 mg amoxicillin/clavulanate 2 to 4 hours before surgery began. During the operation tissue samples were collected at specific sinonasal sites for determination of both amoxicillin and clavulanic acid concentration levels. RESULTS: Amoxicillin displayed adequate tissue levels throughout the sinuses, high enough to cover common susceptible pathogens. However, the presence of clavulanate was detected in only half of the sinonasal tissue samples. CONCLUSIONS: The kinetics of oral clavulanic acid apparently fails to provide a widespread anti-beta-lactamase activity capable of enhancing the activity of amoxicillin in all parts of the sinuses. Despite this, amoxicillin/clavulanic acid maintains a central role in the treatment of acute rhinosinusitis, because amoxicillin is still the most effective oral beta-lactam against Streptococcus pneumoniae, a particularly virulent and increasingly resistant upper respiratory tract pathogen. Also, as our data show, a concomitant anti-beta-lactamase activity can be expected to occur, although in an unpredictable fashion.

The effects of adenoid hypertrophy and subsequent adenoidectomy on pediatric nasal airway resistance.

To investigate how adenoid hypertrophy and subsequent adenoidectomy affect pediatric airway resistance, we developed a prospective controlled study. Fifty children, aged 3 to 12 years, diagnosed with adenoid hypertrophy and selected for adenoidectomy, preoperatively had their nasal airway resistance assessed by active anterior rhinomanometry. Twenty-five of these children were subsequently followed up postoperatively, undergoing nasal resistance evaluations at 1 month, 3 months, 6 months, and 12 months. Another 25 children, without chronic upper airway obstruction symptoms, were enrolled as a control group, and their airway resistance was assessed in the same fashion. We concluded that the children selected for adenoidectomy, compared to the control group and before surgery, had mean resistance values up to two- to threefold higher, in both untreated and decongested nose states. Surgery was found to dramatically reduce airway resistance, but only in children under the age of seven. However, the postoperative values still tended to remain higher than the control subjects results. If in a significant number of children the operation failed in completely resolving their complaints, no pre-operative rhinomanometric pattern could be found to specifically relate to a complete surgical success.

Penetration of cefuroxime into chronically inflamed sinus mucosa.

OBJECTIVES: Despite its seeming relevance, limited information exists about antibiotic sinus tissue penetration and how it is affected by inflammation. Thus the reason for the present investigation. STUDY DESIGN: A randomized, open, multiple-dose, pharmacological study, employing cefuroxime axetil, an approved oral antimicrobial for the treatment of acute bacterial rhinosinusitis, was developed. METHODS: Twenty subjects, selected for surgery because of chronic rhinosinusitis, were randomly allocated to receive either a short (3-8 d) or a long (9-14 d) preoperative treatment regime with 500 mg cefuroxime axetil BID, the last dosage being taken 3 to 4 hours before surgery. At the operation, tissue samples were collected at specific sinonasal sites for both pharmacological determination of antibiotic levels and histopathological assessment of the degree of inflammation. The blood levels of the drug were simultaneously assayed. RESULTS: Cefuroxime kinetic behavior on chronically inflamed mucosa was shown to be, for the most part, dependent on the blood levels, regardless of the inflammatory state. Distribution was even throughout the different sinus cavities, and the tissue levels were still, 3 to 4 hours after dosing, above the reported minimum inhibitory concentration (MIC) values for some of the most prevalent sinus pathogens. The extended treatment course did not seem to add any extra histopathological or pharmacological benefit. CONCLUSIONS: Cefuroxime penetrates adequately and uniformly into chronically inflamed sinus mucosa, apparently unaffected by the degree of inflammation, in a way not dissimilar to its pharmacokinetic behavior in the normal state. Persistent MIC levels for common pathogens still warrant antimicrobial efficacy for a significant period of time after dosing.

Psychosocial consequences of nasal aesthetic and functional surgery: a controlled prospective study in an ENT setting.

Much still needs to be known about what motivates and goes through patients' minds when undergoing nasal aesthetic surgery. Little is also known on how the aesthetic change affects the way other people see those patients after surgery, and if the improved appearance significantly benefits the patients' psychosocial functioning. So far, research has largely focused on subjects in Plastic Surgery settings, neglecting to investigate the specificities of rhinoplasty as performed by otolaryngologists. In order to elucidate these, a prospective controlled-study design was developed. Twenty-five consecutive patients, selected from an ENT practice for septorhinoplasty, were enrolled. They were submitted to pre-operative psychiatric interviews and psychological tests. Two control groups were simultaneously enlisted, and were submitted also to the same tests. Four to seven months after surgery, the septorhinoplasty patients were again evaluated by psychiatric interviews and psychological tests as well as asked to fill out a questionnaire addressing subjective satisfaction with the surgical results. They also underwent, at that time, a rhinomanometric examination assessing the objective success of surgery on nasal function. It was concluded that the study population was basically a psychologically well balanced group of patients, and that a successful surgical result could indeed, in some, improve pre-operative psychological "suffering" related to the nasal deformity, and give these patients a new social identity. Ultimately, it was found that the meeting of aesthetic requirements, frequently not put forward by the patient preoperatively, was the single most important factor required for a final complete satisfaction with the overall surgical results in this population.

Rhinomanometry, sinus CT-scan and allergy testing in the diagnostic assessment of chronic nasal obstruction.

In order to assess how effective a combination of diagnostic methods, each addressing specific aetiopathogenic aspects, would be in uncovering the cause of common chronic nasal obstruction, we evaluated 45 consecutive adult subjects. They were submitted to rhinomanometry testing, sinus CT-scans and RASTs to prevalent allergens. Most, but not all, patients ended up showing abnormal results in at least one of the diagnostic procedures. Sinus pathology was, by far, the most frequent diagnosis, while allergy took second place, with a number of atopic subjects displaying sinusitis as well. On the other hand, septal deviations with a significant effect on nasal resistance were only seldom found to be the cause of chronic nasal obstruction.

Sinusitis and asthma: how do they interrelate in sinus surgery?

Sinusitis has been suspected to be etiopathogenically linked to bronchial asthma. Asthma, on the other hand, has been reported to affect negatively the outcome of sinus surgery. The purpose of this study is to elucidate how sinusitis and asthma clinically interrelate, in a group of asthmatic subjects undergoing surgical interventions on the sinuses. A total of 43 asthmatic patients, selected for functional endoscopic sinus surgery, preoperatively had their sinus disease staged and their lung function tested, and were evaluated for allergy and aspirin sensitivity. One year after surgery the surgical results were analyzed, lung function was re-assessed, and patients' clinical status addressed through a questionnaire; and 93 nonasthmatic patients, whose functional endoscopic sinus surgery was contemporaneous, were used as a control group for the surgical results. Asthma was a critical factor negatively affecting the outcome of sinus surgery. On the other hand, sinus disease extension did not correlate with asthma severity at any stage. Sinus surgery, despite being capable of improving asthma, ultimately failed to produce significant change in lung function scores. Furthermore, consistent good surgical results on the nose did not come across as a critical issue for postoperative asthma improvement. We concluded that, if the surgical intervention on the sinuses was found to be able clinically to benefit asthma evolution, other evidence does not seem to support a causative relationship between sinusitis and asthma. Instead, since asthma was shown to affect sinus disease severity significantly, their association apparently reflects a systemic inflammatory process of the respiratory mucosa.

Immunologic mechanisms in secretory otitis media--recent concepts. Part I.

Increasing evidence has been accumulated in the last few years associating immunological mechanisms in the pathogenesis of secretory otitis media. If immunological processes were found to be involved in both of the previously accepted experimental pathogenic models (Eustachian tube obstruction: microbiologically induced) of the disease, recently published data has provided evidence for a third, not Eustachian tube--or microbiological-dependent, exclusively immunological, experimental model. This suggests that immunological mechanisms are probably always involved in the pathogenesis of a disease that is known to be multifactorial in origin, and thus eventually make Immunology the single most important factor in secretory otitis media. In the present article these recent concepts are extensively reviewed by the authors.