Efficacy/safety of amoxicillin/clavulanate in adults with bacterial rhinosinusitis

PURPOSE: Acute bacterial rhinosinusitis (ABRS) is a common and uncomfortable condition, frequently caused by Streptococcus pneumoniae or Haemophilus influenzae. Antibacterial resistance among these and other common respiratory pathogens is now widespread and of concern. Pharmacokinetically enhanced amoxicillin/clavulanate 2000/125 mg was developed to be effective against the common respiratory pathogens, including many resistant strains. MATERIALS AND METHODS: This open-label, noncomparative study assessed the bacteriologic and clinical efficacy of amoxicillin/clavulanate 2000/125 mg in adult patients with ABRS. Requirements for study entry included a clinical diagnosis of ABRS supported by radiologic findings. In addition, sinus puncture for bacteriologic assessment was required at study entry. RESULTS: Overall, bacteriologic success (eradication or clinical evidence of eradication) at the follow-up visit (days 17-28) was achieved in 87.8% (722/822) of patients with 1 or more pathogen isolated at screening, in 93.2% (246/264) of patients with S pneumoniae, in 96.7% (29/30) of those with penicillin-resistant S pneumoniae (penicillin minimum inhibitory concentrations >or=2 microg/mL), and in 88.7% (110/124) of patients with beta-lactamase-positive pathogens. Bacteriologic success was achieved against 6 of 7 S pneumoniae isolates with amoxicillin/clavulanic acid minimum inhibitory concentrations of 4/2 microg/mL or higher. CONCLUSIONS: Amoxicillin/clavulanate 2000/125 mg was generally well tolerated. This new amoxicillin/clavulanate formulation provides a suitable option for empiric therapy for ABRS in adults.     

Effect of telithromycin and azithromycin on nasopharyngeal bacterial flora in patients with acute maxillary sinusitis

OBJECTIVE: To explore the efficacy of the ketolide telithromycin compared with azithromycin in eradicating S pneumoniae from the nasopharynx of adults with acute maxillary sinusitis. The growing resistance of Streptococcus pneumoniae to penicillin and macrolides brought about the development of a new class of antibiotics-the ketolides-that are effective against resistant pneumococci. SETTING: Otolaryngology clinic. PATIENTS: One-hundred five patients with acute maxillary sinusitis. INTERVENTIONS: Nasopharyngeal cultures were obtained before therapy and 10 to 12 days after initiation of treatment. Fifty-nine patients were treated with 500 mg of azithromycin daily for 3 days and 46 were treated with 800 mg of telithromycin daily for 5 days. RESULTS: Sixty-seven potential pathogens were recovered prior to initiation of therapy in 57 patients, 32 treated with telithromycin and 25 treated with azithromycin: S pneumoniae (31 isolates), Haemophilus influenzae (non-type b) (13), Staphylococcus aureus (8), Streptococcus pyogenes (8), and Moraxella catarrhalis (7). The distribution of the pathogens was similar in both groups. The number of S pneumoniae isolates in the azithromycin group was reduced following treatment from 14 to 8 (43% reduction), and 5 of these 8 isolates were resistant to azithromycin. In contrast, the number of S pneumoniae isolates in the telithromycin group was reduced following treatment from 17 to 1 (94% reduction) (P < .01). This isolate was susceptible to azithromycin and telithromycin. No differences were noted in the eradication rate of all of the other potential pathogens, which were all susceptible to both azithromycin and telithromycin. Development of resistance to the antimicrobial agents used (defined as increase in the minimal inhibitory concentration by at least 2 tubes) was found only in 5 isolates (4 S pneumoniae and 1 H influenzae) recovered only from patients who received azithromycin (P < .05). CONCLUSION: These data illustrate the superiority of telithromycin to azithromycin in the eradication of S pneumoniae from the nasopharynx.     

Azidocillin and ampicillin concentrations in middle ear effusion

The penetration of azidocillin and ampicillin into the middle ear effusion after oral administration was studied and compared with blood levels of the drugs. In acute otitis media one hour after a single oral dose of azidocillin (15 mg/kg) 1.56 +/- 0.44 microgram/ml of the drug was found in the effusion fluid; after 2 hours the fluid contained 3.21 +/- 0.87 microgram/ml and after 12 hours,0.84 +/- 0.13 microgram/ml. The concentrations of ampicillin were 1.15 +/- 0.23 microgram/ml after one hour, 2.17 +/- 0.46 microgram/ml after 2 hours and 1.09 +/- 0.22 microgram/ml after 8 hours following a single oral dose of 10 mg/kg. Both drugs stay longer in the middle ear secretion than in the blood. This persistence supports the administration of azidocillin twice daily in acute otitis media. In contrast, the penetration of the drugs into the middle ear effusion fluid was poor in secretory otitis media, where the levels of the drugs were significantly lower.     

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.     

Bacterial etiology of acute otitis media and clinical efficacy of amoxicillin-clavulanate versus azithromycin

BACKGROUNDS: Acute otitis media (AOM) is one of the most common acute bacterial infection in childhood and also the most frequent reason for outpatient antibiotic therapy. Little recent information about susceptibility patterns of AOM bacterial pathogens in Turkish children has been reported. OBJECTIVE: To determine the bacterial etiology of acute otitis media in children and to compare the efficiency of 3 days course of azithromycin with a 10 days course of amoxicillin-clavulanate. METHODS: This prospective, single blind, randomised comparative study was carried out in 180 children with AOM. Paracentesis was performed for middle ear fluid culture before the first dose antibiotic therapy. Children with acute otitis media were randomised to receive either low dose amoxicillin-clavulanate (45/6.4 mg/kg/day in two divided doses for 10 days) or low dose azithromycin (10mg/kg/day for 3 days). Clinical response was assessed on days 2-4, 11-13, 26-28. RESULTS: Bacterial pathogens were isolated from 108 (60%) of 180 children. Streptococcus pneumoniae was the most common isolated pathogen (39.7%), followed by Haemophilus influenzae (20.7%), Moraxella catarrhalis (15.5%), Staphylococcus aureus (13.8%), Group A beta-hemolytic streptococcus (5.1%), Escherichia coli (3.4%) and Enterococcus faecalis (1.7%). This study demonstrated low resistance rates compared to studies of different countries. Although clinical response rates were better in patients treated with amoxicillin-clavulanate, this was not statistically significant [86.6% (78 of 90)] versus [95.2% (80 of 84)]. Success rates of amoxicillin-clavulanate were high for both S. pneumoniae and H. influenzae. Difference between success rates was not statistically significant (P=0.144 and 0.352). CONCLUSIONS: Bacteria were isolated in 60% of AOM cases. The clinical efficiency of amoxicillin-clavulanate was found to be equal compared to azithromycin in children with acute otitis media.     

Pharmacokinetically enhanced amoxicillin/clavulanate (2,000/125 mg) in acute bacterial rhinosinusitis caused by Streptococcus pneumoniae, including penicillin-resistant strains

We evaluated the efficacy of a new pharmacokinetically enhanced formulation of amoxicillin/clavulanate (2,000/125 mg) twice daily for the treatment of acute bacterial rhinosinusitis (ABRS) caused by Streptococcus pneumoniae, particularly penicillin-resistant S pneumoniae (PRSP; penicillin minimum inhibitory concentrations [MICs]: > or = 2 microg/ml. A total of 2,482 patients received study medication (safety population). Of these, 2,324 were clinically evaluable (efficacy population), and 1,156 of them had at least one pathogen isolated at screening (bacteriology population). S pneumoniae was isolated from 371 patients in the bacteriology population, including 37 with PRSP. Follow-up in the bacteriology population on days 17 through 28 revealed that amoxicillin/clavulanate therapy was successful in 345 of 371 patients with S pneumoniae infection (93.0%) and in 36 of 37patients with PRSP infection (97.3%), including 7 of 8 patients (87.5%) whose amoxicillin/clavulanic acid MICs were 4/2 microg/ml or higher. Pharmacokinetically enhanced amoxicillin/clavulanate was generally well tolerated, as only 2.2% of patients withdrew because of adverse events. This agent represents a valuable new therapeutic option for the empiric treatment of ABRS, particularly in areas where antimicrobial-resistant pathogens (including beta-lactamase-positive organisms) are prevalent, and for the treatment of patients who are at increased risk of infection with PRSP.     

慢性鼻-鼻窦炎患者窦腔的细菌分布及药敏观察研究

目的探究慢性鼻-鼻窦炎患者窦腔的细菌分布及药敏结果,旨意为相关人员的研究工作提供参考文献。方法本试验择取2018年10月26日-2019年10月26日我院内耳鼻喉头颈外科内收治的102例慢性鼻-鼻窦炎患者为研究样本。对其开展窦腔的细菌分布及药敏实验,分析结果。结果送检样本共计102例,阳性82例。其中诸如金黄色葡萄球菌等等菌株各2株;粪肠球菌、产气肠杆菌、铜绿假单胞菌、烟曲菌各4株;克氏库克菌6株;表皮葡萄球菌34株。就分离菌株针对于常用抗生素敏感度:青霉素为8.3%、头孢呋辛钠为30.4%、头孢曲松钠为39.4%、氨苄西林/舒巴坦为35.9%、克拉霉素为45.0%、阿奇霉素为47.6%、复方新诺明为67.7%、环丙沙星为81.6%、利福平为90.9%、左旋氧氟沙星为92.3%、莫西沙星以及万古霉素均为100.0%。结论慢性鼻鼻窦炎患者大都存在细菌感染的情况。此类患者在接受完毕内镜鼻窦手术之后,可以优先考虑使用喹诺酮类药物治疗疾病。     

The contribution of flexible endoscopy for diagnosis of acute bacterial rhinosinusitis

This prospective controlled study ascertained the contribution of flexible endoscopy (FE) for diagnosis of acute bacterial rhinosinusitis (ABRS) in a group of consecutive adult patients who had symptoms suggestive of ABRS and in whom sinus radiography (SRG) and FE were accomplished. We adopted for analysis the 2007 updated European guidelines on rhinosinusitis and computed the sensitivity and specificity of FE against SRG. Positive diagnosis was entertained when FE showed purulent material within sinus drainage area and/or SRG demonstrated air–fluid level, complete opacification, or at least 6 mm mucosal thickening. Of a total of 179 patients initially included in this study, 104 had clinical criteria compatible with guidelines for ABRS. Of them, 43 (41.3%) had positive FE and SRG, 17 (16.3%) had positive FE and negative SRG, and vice versa in 9 (8.7%); both modalities were negative in 35 (33.7%). FE yielded sensitivity of 82.7 ± 5.24% (95% CI: 72.41–92.97%) and specificity of 67.3 ± 6.50% (95% CI: 54.56–80.06%). Age, gender, symptom duration, pre-referral antibiotics, and treatment by primary/secondary physician were not associated with positive or negative diagnosis of ABRS. Of 75 patients who were excluded from the analysis, 33 (44%) had positive diagnosis of ABRS established by FE and/or SRG. The finding that clinical criteria had moderate predictive value (66.3%) highlights the need for objective measures for diagnosis of ABRS. In absence of feasible gold standard and considering that guidelines do not recommend SRG for routine diagnosis, FE serves as an indispensable ancillary tool for establishing ABRS.     

Penicillin resistance is not extrapolable to amoxicillin resistance in Streptococcus pneumoniae isolated from middle ear fluid in children with acute otitis media

OBJECTIVES: We evaluated the in vitro antibacterial activity of amoxicillin against penicillin-susceptible and -nonsusceptible Streptococcus pneumoniae strains isolated from children with acute otitis media (AOM). METHODS: Children more than 3 months of age with AOM who were seen in the Dr Sótero del Rio and Luis Calvo Mackenna Hospitals in Santiago, Chile, between July 1998 and December 2002 were subjected to tympanic puncture for middle ear fluid culture. The penicillin and amoxicillin susceptibilities of the S pneumoniae isolates were determined by epsilometer test (E test). RESULTS: A bacterial pathogen was isolated in 432 of 543 children (80%) as follows: S pneumoniae, 40%; Haemophilus influenzae, 29%; Moraxella catarrhalis, 7%; and Streptococcus pyogenes, 4%. Penicillin-susceptible S pneumoniae strains were less common than amoxicillin-susceptible strains (60% versus 95%; odds ratio [OR], 0.08; 95% confidence interval [CI], 0.04 to 0.18). Both intermediate- and high-resistance strains were more common for penicillin (22% versus 4.5%; OR, 5.6; 95% CI, 2.5 to 12.7) than for amoxicillin (18% versus 0.5%; OR, 41.3; 95% CI, 6.0 to 821). CONCLUSIONS: Penicillin resistance is not extrapolable to amoxicillin among S pneumoniae strains isolated from middle ear fluid of children with AOM. Our results support the recommendation to evaluate the minimal inhibitory concentrations of penicillin-nonsusceptible S pneumoniae for amoxicillin and to continue use of this antimicrobial as a first-line antimicrobial choice for children with AOM.     

The role of Chlamydia pneumoniae infection in children with chronic sinusitis

BACKGROUND: Chlamydia pneumoniae infection is a frequent cause of lower respiratory disease in both adults and children. However, its role in upper respiratory disease, including sinusitis, is less clear. OBJECTIVE: To determine the role of infection with C. pneumoniae in chronic sinusitis in children. DESIGN: Prospective collection of specimens. SETTING: Tertiary care academic medical center. PARTICIPANTS: Children with clinical and radiologic evidence of chronic sinusitis unresponsive to medical management undergoing adenoidectomy, maxillary sinus lavage, or endoscopic sinus surgery for treatment.Intervention Nasopharyngeal and middle meatal swabs and portions of surgical specimens were obtained and cultured for C. pneumoniae. RESULTS: Specimens were obtained from 20 children (14 boys and 6 girls) aged 3 through 16 years. Thirteen bilateral endoscopic ethmoidectomies with maxillary antrostomies, 10 adenoidectomies, and 3 bilateral maxillary sinus lavages were performed. Chlamydia pneumoniae was isolated from the nasopharyngeal swab and adenoid tissue of 1 child (aged 6 years); however, his middle meatal swabs and maxillary sinus aspirates were negative. After 10 days of treatment with clarithromycin, repeat nasopharyngeal cultures were negative for C. pneumoniae. CONCLUSIONS: With the use of sensitive culture methods, C. pneumoniae was not isolated from sinus specimens of children enrolled in this study. This preliminary study suggests that C. pneumoniae does not play a significant role in chronic sinusitis in children.     

Effect of proton pump inhibitor pantoprazole on growth and morphology of oral Lactobacillus strains

OBJECTIVES: Proton pump inhibitors (PPI) used to suppress acid secretion in the stomach are among the most widely prescribed medications. There is emerging evidence of proton secretion elsewhere in the aerodigestive tract, and acidic microenvironments are integral to oral flora such as Lactobacillus. The hypothesis of this study is that the growth rate and morphology of oral Lactobacillus strains are effected by PPIs. METHODS: Nineteen different strains of Lactobacilli were inoculated in microtiter plates at pH of 4.5 to 6.5 and exposed to twofold dilutions of pantoprazole at a range of 2.5 mg/mL to 2.5 microg/mL. Bacterial growth was monitored, and the minimum inhibitory concentration (MIC) of the drug was determined for the strains most sensitive to pantoprazole. RESULTS: In the unexposed (control) group, nine Lactobacilli strains were affected by pH changes from 6.5 to 4.5. In the group exposed to pantoprazole, 9 of the 19 Lactobacilli strains were found to have an MIC below 625 microg/mL, with L. plantarum 14917 being the most sensitive (MIC = 20 microg/mL). In some strains, such as L. s. salivarius 11741, Gram-staining revealed conformational changes in the bacteria when grown in the presence of pantoprazole. CONCLUSION: Growth rates and morphology of oral Lactobacillus are affected by the pH of the environment. Pantoprazole at supraphysiologic doses further affects growth rates and conformation in some strains. SIGNIFICANCE: The balance of oral flora and upper digestive tract homeostasis may be affected by unexpected targets of PPI pharmacotherapy, with possible unanticipated consequences.     

Endoscopy versus radiography for the diagnosis of acute bacterial rhinosinusitis

The aim of the study was to estimate the sensitivity and specificity of endoscopy and the diagnostic value of clinical criteria for acute bacterial rhinosinusitis (ABRS). The hospital records of 117 consecutive patients who had symptoms compatible with ABRS and who underwent sinus radiography and flexible nasendoscopy were retrieved. A positive diagnosis was entertained when radiography demonstrated air fluid level, complete opacification or at least 6 mm mucosal thickening and/or endoscopy revealed purulent material within the drainage area of the sinuses. Using a modified version of the Hui and Walter procedure, the sensitivity and specificity of nasendoscopy was calculated against sinus radiography, a standard reference test, with known estimated sensitivity (76%) and specificity (79%). The findings show that 40 patients (34%) had positive endoscopy and radiography. Twenty patients (17%) had positive endoscopy and negative radiography, and vice versa in 15 (13%). In 42 patients (36%) both modalities were negative. Endoscopy yielded a sensitivity of 80% (95% CI, 0.55–1.00) and a specificity of 94% (95% CI, 0.33–1.00). Although estimates seem better than those of radiography, the confidence intervals are quite wide and no firm conclusion is drawn. Neither single nor combination of symptoms, concurrent with two major and one minor factor advocated by the AAO-HNS Task Force on Rhinosinusitis, were associated with a positive diagnosis of ABRS. The data suggest that endoscopy is no less effective than radiography in predicting ABRS, also that clinical criteria are of rather limited diagnostic value, and thus should be supported by other diagnostic tests. Endoscopy is recommended as a first line diagnostic tool for the diagnosis of ABRS in routine ENT practice. If the outcome is negative, radiography may follow.     

Intranasal deposition of nebulized saline: a radionuclide distribution study

BACKGROUND: Despite the popularity of various nasal sprays and nebulizers, there are limited data regarding the anatomic distribution of particles generated by these devices. This pilot study sought to characterize distribution patterns of nebulized and sprayed saline particles in normal subjects and postsurgical sinus patients. METHODS: Fifteen subjects were studied in three trials: metered-dose nasal spray bottle versus vortex-propelled nebulizer in normal subjects, passive-diffusion nebulizer versus vortex nebulizer in normal subjects, and passive nebulizer versus vortex nebulizer in postsurgical sinus patients. Radiolabeled saline was administered, and nose, lungs, and stomach were imaged. Images were scored by four blinded reviewers for degree of penetration at nine anatomic subsites. RESULTS: Compared with spray bottle, the vortex nebulizer showed more focal intranasal distribution with reduced nasopharyngeal, pharyngeal, and gastric penetration in normal subjects. Three of five subjects showed probable frontal sinus penetration by vortex nebulizer, but no other sinus penetration was noted. No patients showed sinus penetration with the spray bottle. In a separate trial against the passive nebulizer, the vortex nebulizer again showed a greater tendency for sinus penetration in normal subjects, with three of five showing some degree of sphenoid penetration and one of five showing slight maxillary penetration. In contrast, no sinus penetration was observed with the passive nebulizer. In the postsurgical patient cohort, minimal sinus penetration was noted with either the vortex nebulizer or the passive nebulizer. Despite surgically patent sinuses, only one of five subjects showed any type of sinus penetration. CONCLUSION: The nebulizer and nasal spray devices tested in general showed limited penetration of the sinuses in both normal and postoperative patients. The device showing greatest promise for sinus penetration in normal patients was the vortex nebulizer, with an overall penetration rate in normal patients of 30% in the frontal, 30% in the sphenoid, and 10% in the maxillary. Understanding delivery patterns of topical therapies may be important in evaluating the efficacy of various topical treatment modalities.     

Failure of antibiotic therapy in acute otitis media

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.     

Concentration of penicillin in nasopharyngeal secretions

The penicillin concentration in the nasopharyngeal secretion after penicillin administration was studied in 33 patients undergoing tonsillectomy. Benzylpenicillin was either administrated by the intravenous or the intramuscular route in doses of 0.6-1.2 g. Phenoxymethylpenicillin was given perorally in doses of 0.5-1.0 g. The secretion from the nasopharynx was collected prior to the operation both in a disposable collector and on a filter paper disc. A serum sample was also drawn prior to and immediately after the operation. The serum penicillin concentration reached levels of 16.0 mg/l, 5.8 mg/l and 3.6 mg/l (mean values) when given by the intravenous, the intramuscular and the peroral route, respectively. The mean penicillin concentration in nasopharyngeal secretion was 1.6 mg/l, 0.3 mg/l and 0.3 mg/l for these three administration modes. In the majority of cases the concentration of penicillin in the nasopharyngeal secretion exceeded the minimum inhibitory concentration for Streptococcus pneumoniae (0.006-0.12 mg/l).     

Penetration of cefprozil to middle ear effusion in children with chronic otitis media with effusion

BACKGROUND: Because of chronic otitis media with effusion (COME) demonstrates pathogenic bacteria, treatment with appropriate antibiotic is reasonable. OBJECTIVE: We determined the penetration of cefprozil into the middle ear effusion (MEE) in children with COME. MATERIALS AND METHODS: 25 patients 2-13 years of age with COME were eligible for study. After the single dose of 15 mg/kg patients were assigned to have MEE, and serum samples were obtained during ventilation tube insertion at 0.5, 2, 3, 5, or 6 h after administration of the dose. The concentration of cefprozil was measured using validated high performance liquid chromatography method. RESULTS: The mean concentrations of cefprozil in the MEE ranged from 0.4 to 4.4 microg/ml. The penetration into MEE was rapid and effective. Cefprozil in the MEE was maintained at a greater level than MIC 90 in S. pneumoniae for at least 6 h after administration of 15 mg/kg. CONCLUSION: Cefprozil penetrated well into the MEE in children with COME.     

鼻窦炎口服液联合低剂量克拉霉素片治疗慢性鼻窦炎的临床疗效

目的 观察鼻窦炎口服液联合低剂量克拉霉素片治疗慢性鼻窦炎的临床疗效。方法 选择门诊慢性鼻窦炎患者86例, 采用随机对照分组试验的方法分为治疗组43例、对照组43例, 两组均口服克拉霉素片250 mg/d, 治疗组在此基础上加服鼻窦炎口服液10 mL/次, 每天3次, 连续3个月。比较两组用药前、用药3个月末主观、客观指标的变化。结果 治疗组患者视觉模拟量表评分、鼻内镜检查Lund-Kennedy评分及鼻窦CT扫描Lund-Mackay评分均明显下降(t=21.23, 30.23, 25.81, P均<0.05), 与对照组比较(t=10.21, 12.79, 9.58, P均<0.05)差异有统计学意义。治疗组有效率为83.72%, 对照组为65.12%, 差异有统计学意义(Mann-Whitney U=752.5 P<0.05), 两组均无严重不良反应。结论 鼻窦炎口服液联合低剂量克拉霉素片治疗慢性鼻窦炎疗效显著。     

Sinus tissue concentration of moxifloxacin after a single oral dose

Moxifloxacin is a new fluoroquinolone antimicrobial approved for the treatment of acute bacterial rhinosinusitis. In order to assess its distribution pattern into the paranasal sinuses, and specifically to evaluate how the histopathologic changes associated with chronic inflammation affect its tissue penetration, we conducted the present investigation, a randomized, open-label, single dose, sinus-tissue pharmacokinetic study with oral moxifloxacin. Twenty adult subjects, selected for surgery because of recalcitrant chronic rhinosinusitis, were preoperatively randomly allocated to receive a tablet of 400 mg moxifloxacin 3 or 4 hours before the procedure. During the operation, tissue samples were collected at specific sinonasal sites, and the concentration levels of the antimicrobial in the different parts of the paranasal sinuses were assayed. Simultaneously, the degree of inflammation at each site was evaluated. We found that moxifloxacin was distributed extensively throughout the sinuses, in both inflamed and noninflamed mucosae, but tended to be concentrated in maxillary sinus cysts. The tissue-to-blood ratios exceeded 4:1 at most sites, with mucosal concentration levels well above the MIC90 values of the drug against a wide range of microorganisms. We concluded that the oral moxifloxacin tissue kinetics provides an extremely potent antimicrobial activity in all parts of the sinuses, regardless of the inflammatory status of the mucosa.     

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.     

An evaluation of the penetration of cefuroxime axetil into human paranasal sinus tissue.

Nineteen patients presenting for sinus surgery were studied to evaluate the percentage penetration from serum to paranasal sinus tissue of a single orally administered dose of cefuroxime axetil. The methods and results are presented. Cefuroxime penetrates well into human sinus mucosa following oral administration and the concentrations obtained exceed minimum inhibitory concentrations of cefuroxime for the most common pathogens in sinusitis.