EFFECTS OF ACUTE AND CHRONIC ADMINISTRATION OF TWO ANTIBIOTICS, AZTREONAM AND GENTAMICIN, ALONE OR IN COMBINATION, ON "OPEN-FIELD TEST" IN MICE

A study aimed at investigating the behavioural effects of aztreonam and gentamicin, given separately or in combination, was carried out in mice. Animals were randomly assigned to two test conditions: acute and chronic treatment. Those receiving acute treatment had a single IP injection 60 min before the test. Those receiving chronic treatment had IP injections once daily for 5 successive days prior to the test. Behavioural patterns (ambulation, rearing, grooming and defecation) were assessed using the "open-field" test. The results indicate that, both after single and multiple dosing, aztreonam (10, 40 and 80 mg/kg IP) and/or gentamicin (10 mg/kg IP) do produce changes in the behaviour of animals. A rate increasing effect for certain behaviours (rearing, grooming and defecation) and a reduction in other behaviours (ambulation) seems to occur.     

Optimal airway antimicrobial therapy for cystic fibrosis: the role of inhaled aztreonam lysine

Importance of the field: Chronic endobronchial infection in cystic fibrosis (CF) leads to progressive lung function loss and respiratory failure. Most adult CF patients are infected with Pseudomonas aeruginosa, an important predictor of mortality. Suppressing chronic P. aeruginosa infection with inhaled antibiotics is standard of care for CF patients.

Areas covered in this review: This review describes the development (2003 – 2010) of aztreonam lysine 75 mg powder and solvent for nebulizer solution (AZLI; Cayston^®), an aerosolized formulation of the monobactam antibiotic aztreonam.

What the reader will gain: AZLI was studied in patients with CF and chronic P. aeruginosa airway infection. In placebo-controlled trials, AZLI improved respiratory symptoms, increased forced expiratory volume in 1 sec (FEV₁), decreased sputum P. aeruginosa density, and was well tolerated. An open-label follow-on trial of nine ‘on/off’ courses showed that AZLI was safe and the effect durable with repeated administration. AZLI was recently approved for use in CF patients in Australia and the USA, and conditionally approved in Canada and the European Union. AZLI is given three times daily for 28 days (2 – 3 min/dose), followed by 28 days off-drug. AZLI is used only with the Altera Nebulizer System?, which provides appropriate particle size and small airway deposition, and has excellent portability.

Take home message: AZLI is a new therapy that is safe and effectively improves respiratory symptoms and FEV₁ in patients with CF.     

Single-Dose Pharmacokinetics of Aztreonam in Healthy Volunteers and Renal Failure Patients

Summary

The pharmacokinetics of aztreonam were studied in 6 healthy male volunteers and 12 male patients with various degrees of chronic renal failure after intravenous bolus injection of 1g of the drug. Serum pharmacokinetics of aztreonam were described by an open, two-compartment kinetic model. The serum levels of aztreonam exceeded the reported minimum inhibitory concentration (MIC)₉₀ for Enterobacteriaceae for 8 hours and up to 24 hours, in healthy volunteers and renal failure patients, respectively. However, the serum levels of the drug exceeded the MIC₅₀ for Pseudomonas aeruginosa for only 4 hours and 12 hours in healthy volunteers and patients, respectively. The half-life of elimination (t 1/2/β) increased significantly (P < 0.001) from 1.8 ± 0.14 h in healthy volunteers and to 4.9 ± 1.1 h in patients with renal failure. The total serum clearance of aztreonam decreased significantly (P< 0.001) from 84.2 ± 7.8 ml/h/kg in healthy volunteers to 30.2 + 9.2 ml/h/kg in patients with renal failure. Á linear correlation (r = 0.971, P< 0.001) was found between creatinine clearance and the total serum clearance of aztreonam. The AUC_0–∞ increased significantly (P< 0.001) from 137.5 ± 12.2 μg/h/ml in healthy volunteers to 464 ± 114.5 μg/h/ml in patients with renal failure.     

干预前后氨曲南的临床应用及安全性评价

目的 通过分析干预前后氨曲南的使用情况,为临床合理用药提供依据。方法 采用回顾性调查方法,对2012年和2013年第2季度笔者所在医院氨曲南的使用情况和不良反应进行分析。结果 干预前有无适应证选药、用法用量错误及联合用药不合理等现象,干预后氨曲南使用基本合理,不良反应发生率为0.67%。结论 氨曲南临床应用干预效果明显,干预后氨曲南应用不合理情况明显降低。     

氨曲南治疗慢性肾功能不全患者肺部及尿路感染疗效

目的探讨使用氨曲南治疗慢性肾功能不全患者肺部感染和尿路感染临床疗效。方法68例患者用氨曲南2.0g,加入氯化钠注射液100mL中,静脉滴注,每12h1次,疗程7～14d。检测血常规、尿常规、肝功能、肾功能,并作细菌学检查和药物敏感性测定。结果68例患者治疗后痊愈39例,显效17例,进步9例,无效3例,临床总有效率82.35%（56/68）;耐药率为14.76%;肾功能指标治疗前后无变化;不良反应仅2例。结论氨曲南作为结构独特的单环类β-内酰胺类抗生素,对肾脏毒副作用轻,用于慢性肾功能不全的抗菌治疗,具有疗效显著、不良反应少和使用方便等优点,值得临床应用。     

Comparison of drug susceptibility between Escherichia coli detected in stool cultures of patients undergoing transrectal prostate needle biopsy and Escherichia coli in hospital-wide urine antibiograms

A prostate biopsy is essential for prostate cancer diagnosis. However, infections are one of the biopsy-associated complications, and post-biopsy fever is estimated to occur in approximately 1% of all cases. It may thus be beneficial to perform a rectal swab culture before a transrectal prostate biopsy to confirm the presence of resistant bacteria and select preventive antibacterial agents according to the drug susceptibility results. This study aimed to determine whether there is a difference between the drug susceptibility of bacteria detected in the stool of patients who were scheduled to undergo prostate biopsy and the hospital-wide urine antibiogram. Patients suspected of having prostate cancer who underwent transrectal prostate biopsy via transrectal ultrasonography between August 1, 2016, and June 30, 2020, were included in this study. Stool samples were collected and cultured before biopsy. Overall, 99 patients underwent prostate biopsy, and of these, culture results were available for 81 patients (81.8%). Escherichia coli was detected in 74.0% (60 samples) of the stool culture samples, of which 4 samples were extended-spectrum β-lactamase-producing types. We found greater susceptibility of Escherichia coli to ampicillin, fluoroquinolones, sulfamethoxazole/trimethoprim, and cefixime in the stool culture antibiogram than in the hospital-wide urine antibiogram. We also found a significantly low incidence of ESBL-positive Escherichia coli in the stool culture antibiogram with p-values of 0.009, 0.007, and 0.03 compared to the hospital-wide urine antibiograms for 2017, 2018, and 2019, respectively. Stool culture of prostate cancer patients undergoing biopsy may provide useful information for selecting prophylactic antimicrobial agents.     

Aztreonam inhalation solution for suppressive treatment of chronic Pseudomonas aeruginosa lung infection in cystic fibrosis

An aerosol form of aztreonam lysinate has recently been developed as a treatment for cystic fibrosis patients suffering from chronic Pseudomonas aeruginosa lung colonization. Local administration means the drug can reach mucus concentrations in the order of hundreds of times the MIC₅₀ of Pseudomonas associated with severe lung disease in cystic fibrosis, resulting in a significant reduction in airway bacterial density and a parallel improvement in lung function. These advantages are maintained over prolonged periods of treatments. Administration of the drug is optimized by the use of a specific eFlow^® system, resulting in considerable reductions in treatment times when compared with conventional nebulizers. The drug has been proven safe and no concomitant induction of resistance to Pseudomonas was found during the clinical trial period of 18 months. Aztreonam lysinate has been shown to ameliorate pulmonary function in cystic fibrosis patients with chronic airway Pseudomonas infection and this is paralleled by a reduction in bacterial density in the lungs. The increased availability of new aerosolized antibiotics for cystic fibrosis will lead to new scenarios in the treatment of the disease.     

氨曲南和亚胺培南对β－内酰胺酶稳定性和抑酶效应的研究

用紫外分光光度法．以其它青霉素类、头孢菌素类抗生素为对照．研究氨曲南（Ａｚｔｒｅｏｎａｍ．ＡＺ）和亚胺培南（Ｉｍｉｐｅｎｅｍ．ＩＭＰ）对１１种标准β－内酰胺酶的稳定性及抑酶作用。结果表明．ＡＺ．ＩＭＰ与第三代头孢菌素头孢噻甲羧肟．头孢氨噻类似，对１１种标准β－内酰胺酶均高度稳定。除酶Ｋ１对头孢氨噻相对水解率达２５％外．其余均不超过１５％．其余的青霉素类及第一、二代头孢菌素类，除头孢西丁酶稳定性较好外．均对β－内酰胺酶不稳定．大多数相对水解率１００％以上。抑酶结果表明．ＡＺ或ＩＭＰ对β－内酰胺酶抑制，除与β－内酰胺酶类型有关外．还与ＡＺ或ＩＭＰ本身浓度密切关联。     

Prediction of aztreonam pharmacokinetics in humans based on data from animals

Interspecies correlations of pharmacokinetic parameters obtained in animals were used to predict human pharmacokinetics in order to design the first clinical study of an investigational drug. The serum pharmacokinetics of aztreonam, a novel monocyclic beta-lactam antibiotic, were described for mice, rats, rabbits, and monkeys, using serum clearance and apparent volume of distribution. A one-compartment pharmacokinetic model yielded predictions for aztreonam clinical pharmacokinetics that were very helpful in choosing doses and serum sampling times for the first kinetic study in healthy male volunteers. Predicted serum aztreonam concentrations agreed well with subsequently measured values in man.