Amoxycillin and clavulanic acid in the treatment of urinary tract infections in children

The efficacy of amoxycillin-clavulanic acid combination in the treatment of urinary tract infections resistant, in vitro, to amoxycillin was studied in 42 children. Of the 24 children with urinary tract infection for the first time, combination therapy, dosing twice daily for 5 days (40 mg/kg.day), cleared the infection in 23 (96%) cases. Relapse occurred in four (17%) cases within 30 days. Of the 18 children who presented with recurrent urinary tract infections therapy, as above, cleared the infection in 16 (89%) cases. In these cases, long-term therapy was performed at a dosage of 20 mg/kg once daily. Tolerance was good; gastro-intestinal disorders in five (12%) cases which regressed by dosing at 8 h rather than 12 h intervals. In conclusion, amoxycillin-clavulanic acid can be considered a first choice treatment of urinary tract infections in children.     

Amoxycillin/clavulanic acid combinations increase transmigration of leucocytes through endothelial cell monolayers: endothelial cells play a key role

Postoperative inflammation is still viewed as an unresolved problem. During inflammation, leucocytes play a tremendous role and migrate from intravascular spaces into the tissue to attack microorganisms. Different agents, e.g. anaesthetic drugs, are able to influence leucocyte recruitment. Previous studies have investigated the influence of amoxycillin on chemotaxis of leucocytes alone. The aim of our study was to examine the effect of amoxycillin/clavulanic acid (co-amoxiclav) on leucocyte migration through endothelial cell monolayers (ECMs). Human umbilical endothelial cells were cultured on microporous membranes, achieving a monolayer. Polymorphonuclear neutrophil leucocytes (PMNLs) were used in a migration assay. The numbers of untreated PMNLs migrating through untreated ECMs were used as control and set as 100%. PMNLs and/or ECMs were pretreated with co-amoxiclav using clinically relevant as well as higher and lower concentrations. Co-amoxiclav was able to increase PMNL migration through ECMs significantly (P<0.05) when both cell types were treated (291+/-18.7%). When PMNLs or ECMs were treated alone, it could be shown that ECMs were more affected than PMNLs. The greatest effect was shown when both cell types, PMNLs and ECMs, were treated. In conclusion, co-amoxiclav was identified as a potent drug to increase leucocyte transmigration through ECMs. ECMs were also critically involved. Co-amoxiclav also affects endothelial cells.     

下呼吸道分泌物中糠秕马拉色菌的分离与鉴定

目的 对痰涂片镜检可疑为马拉色菌的标本进行马拉色菌的分离培养,并对分离菌株进行系统鉴定.方法 收集2010年3月至201 1年9月卫生部北京医院经派克墨水染色镜检可疑为马拉色菌的下呼吸道分泌物标本133份,接种于含1％吐温60的科玛嘉琼脂培养基(即改良念珠菌显色培养基),于35℃大气环境中培养.挑取疑似菌落在含0.5％吐温40和0.5％吐温60的沙保弱平板上进行纯培养.采用传统的表型鉴定方法对分离菌株进行鉴定,包括染色镜检观察菌体形态及染色性、沙保弱培养基生长试验、吐温试验、七叶苷分解试验、过氧化氢试验、吐温沉淀试验和蓖麻油试验,可疑菌株采用18s rRNA基因序列分析方法对分离菌株进行菌种鉴定.结果 镜检可疑的下呼吸道分泌物中马拉色菌分离率为47.4％ (63/133),63株分离菌经传统的表型鉴定方法结合l8srRNA基因序列分析方法均鉴定为糠秕马拉色菌.标本直接涂片,用派克墨水染色镜下可明显区分马拉色菌和念珠菌.结论 糠秕马拉色菌在改良念珠菌显色培养基上的菌落呈粉红色,可明显区别于其他念珠菌菌落,用改良念珠菌显色培养基可提高下呼吸道分泌物中糠秕马拉色菌的分离率.传统的表型鉴定结合基因序列分析可提高马拉色菌鉴定的准确性.     

Factors determining the appearance of glucose in upper and lower respiratory tract secretions

Objectives (a) To describe the glucose content of normal human airways secretions; (b) to observe the effects of hyperglycemia and airways inflammation on airways glucose.Design Observational studies.Settings (a) St George's Hospital Medical School; (b) diabetes mellitus outpatient clinics; (c) adult general intensive care unit.Patients Nineteen healthy volunteers, 24 volunteers with acute rhinitis, 20 patients with diabetes mellitus, and 60 patients admitted to a general adult intensive care unit.Measurements (a) Non-ventilated patients: simultaneous measurement of blood and nasal glucose concentrations; (b) ICU patients: simultaneous blood, nasal, and endotracheal (ET) glucose concentrations.Results Nasal glucose was undetectable in all healthy volunteers. Glucose was detected in 12/24 volunteers with acute viral rhinitis [1 (1–2) mmol l^–1] and 18/20 people with diabetes [4 (2–7) mmol l^–1]. Glucose was detected in the ET secretions of 31/60 ventilated patients on ICU. Patients with ET glucose had significantly higher blood glucose (9.8±0.4 mmol l^–1) than patients without ET glucose (7.2±0.3 mmol l^–1, P<0.001), and all patients with blood glucose >10.1 mmol l^–1 had glucose in ET secretions. Enteral nutrition did not affect the presence or concentration of glucose in ET secretions.Conclusions Glucose is not normally present in airways secretions, but appears where hyperglycaemia or epithelial inflammation occur. The detection of glucose cannot reliably be used to detect enteral feed aspiration.Abbreviations CSF Cerebrospinal fluid - HbA₁C Glycosylated haemoglobin - ICU Intensive care unit - SEM Standard error of mean     

In-vitro bacterial killing kinetics of ticarcillin/clavulanic acid

An in-vitro model was developed to study the rates of killing by ticarcillin/clavulanic acid combinations of various beta-lactamase producing, ticarcillin resistant, logarithmic phase clinical isolates. Killing, defined as a 3 log reduction, was dependent on the organism, the concentration of clavulanic acid and the duration of exposure. For most isolates studied an optimum period of exposure to and concentration of clavulanic acid could be defined. Certain test strains showed optimum response to readily attainable in-vivo concentrations of clavulanic acid while other strains, although sensitive by MIC data showed a poor response. The clinical implications of this are discussed.     

Intraperitoneal penetration of ticarcillin/clavulanic acid (Timentin)

Thirty-eight patients undergoing elective abdominal surgery were given 3.0 g ticarcillin plus 0.2 g clavulanic acid as a single intravenous injection at varying times prior to the operation. Sterile assay discs were placed on the peritoneal surface in order to measure peritoneal fluid levels of each agent. Simultaneous serum levels were also measured. A total of 38 serum and peritoneal samples were analysed. There was rapid penetration of both agents into peritoneal fluid. The mean peritoneal fluid levels of ticarcillin were 70% (S.D. 13) of the serum level and 67% (S.D. 4) for clavulanic acid. The peritoneal levels of both agents declined in parallel to the serum levels (the half-lives being about 1 h) and the ratio of ticarcillin-clavulanic acid in serum and peritoneal fluid did not vary significantly with time.     

Bactericidal effects of amoxycillin/clavulanic acid against Legionella pneumophila

The antibacterial activities of amoxycillin, clavulanic acid and the combination of both agents against Legionella spp. were compared in serial-dilution tests, time-kill curve studies and in turbidimetric studies in a continuous recording biophotometer. Both beta-lactam compounds showed high levels of activity against L. pneumophila in serial dilution tests, clavulanic acid (MIC 0.1-0.25 mg/l) being two-fold more active than amoxycillin. The combination of amoxycillin and clavulanic acid was more effective than either of the constituents and was two to four times more active than erythromycin. Clavulanic acid was shown to reduce the extent of inactivation of amoxycillin by L. pneumophila and amoxycillin/clavulanic acid was rapidly bactericidal against the organism in tests in which amoxycillin was ineffective. Microscopical examination showed distinctive morphological effects produced by amoxycillin and by clavulanic acid and synergy between the compounds could be attributed to beta-lactamase inhibition, or by binding to different penicillin binding proteins, or both. These results warrant further studies in vitro and in vivo to elaborate the bactericidal effects demonstrated by amoxycillin and clavulanic acid against Legionella spp.     

Comparison of non-protected lower respiratory tract secretions and protected specimen brush samples in the diagnosis of pneumonia

The aim of this prospective study was to compare the results obtained with the non-protected lower respiratory tract secretions samples (LRS) with the protected specimen brushes (PSB) performed through a fiberoptic bronchoscope in mechanically ventilated patients, when pneumonia was suspected. The diagnosis of pneumonia was ultimately made at the end of the hospitalisation, in a double-blind manner by 2 members of the medical staff not aware of the bacteriologic results of LRS and PSB. LRS and PSB were performed in 24 patients. PSB culture was considered as positive at a level of 10³ colony-forming units per milliliter (cfu/ml) microorganisms. Twentyfive samples from 24 patients were divided as follows: (1) LRS (-) and PSB (-) 5 samples: the clinical diagnosis of pneumonia was never established. (2) LRS (+) and PSB (+) 10 samples: the clinical diagnosis of pneumonia was always established, 2 microorganisms were involved 4 times and 1 microorganism 6 times. (3) LRS (+) and PSB (-) 10 samples: the clinical diagnosis of pneumonia was retained in 3 with the possibility of false negative PSB. We conclude that (1) a negative LRS eliminated the diagnosis of pneumonia without PSB; (2) a positive LRS was not sufficient to diagnose pneumonia since PSB was negative in 50% of all LRS (+) cases; (3) the possibility of a false negative PSB must be kept in mind particularly in patients previously treated with antibiotics; (4) 2 microorganisms may be responsible for the pneumonia if the previously determined, as significant, bacteriological count (>-10³ cfu/ml) appears to be accurate.     

Efficacy of amoxycillin/clavulanic acid in experimental Bacteroides fragilis/Escherichia coli mixed infections

The efficacy of amoxycillin/clavulanic acid was compared with those of metronidazole, cefuroxime, metronidazole/ampicillin, metronidazole/gentamicin and metronidazole/cefuroxime, in experimental mixed infections produced in mice by subcutaneous inoculation of amoxycillin-resistant strains of Bacteroides fragilis and Escherichia coli. The combination of metronidazole/ampicillin failed to inhibit the growth of E. coli, and exerted only a transient effect on the numbers of Bact. fragilis in the groin abscesses. In contrast, amoxycillin/clavulanic acid prevented the development of the infection, eliminating both organisms. Metronidazole and cefuroxime, alone and in combination, were less effective than amoxycillin/clavulanic acid in inhibiting the growth of the infecting organisms. These results demonstrate the clinical potential of amoxycillin/clavulanic acid in prophylaxis, or in the therapy of mixed aerobe/anaerobe infections.     

A comparative study of Miraxid (pivmecillinam plus pivampicillin) and Augmentin (amoxycillin plus clavulanic acid) in the treatment of lower respiratory tract infections in general practice

Two treatments, pivmecillinam 200 mg plus pivampicillin 250 mg (Miraxid) given twice-daily and amoxycillin 250 mg plus clavulanic acid 125 mg (Augmentin) given three times daily were compared in two parallel groups of 388 general practice patients with acute bronchitis or acute exacerbations of chronic bronchitis. Patients with acute bronchitis (140 on Miraxid, 144 on Augmentin) received a 7-day course of treatment and those with acute exacerbations of chronic bronchitis (55 on Miraxid, 49 on Augmentin) a 10-day course of treatment. Both treatments were equally effective, with 99 (71%) patients with acute bronchitis being successfully treated with Miraxid and 107 (74%) with Augmentin. In acute exacerbations of chronic bronchitis, Miraxid was successful in 29 (53%) patients and Augmentin in 24 (49%) patients. Side-effects were reported by 26 (12%) of patients in both treatment groups. This single blind multicentre general practice study comparing twice-daily Miraxid with 3 times daily Augmentin demonstrated that both treatments were equally effective clinically and equally well tolerated.     

Efficacy of amoxycillin/clavulanic acid in experimental Staphylococcus aureus endocarditis in the rat

The efficacy of amoxycillin/clavulanic acid was compared with that of flucloxacillin, vancomycin and amoxycillin in an experimental model of Staphylococcus aureus endocarditis. Doses of the antibiotics were selected to produce peak concentrations in rat serum similar to those achievable in man after administration of parenteral therapeutic doses. Amoxycillin clavulanic acid was more effective than amoxycillin alone against endocarditis caused by beta-lactamase producing strains of Staph. aureus, illustrating the beta-lactamase inhibitory activity of clavulanic acid in vivo. Amoxycillin/clavulanic acid was as effective as flucloxacillin in these infections whereas vancomycin was generally less active. These results illustrate the clinical potential of amoxycillin/clavulanic acid in the prophylaxis, or in the therapy of severe staphylococcal infections.     

Treatment of respiratory tract infections in children: a study of a combination of amoxycillin and clavulanic acid

In an open study, 70 in-patients and 23 out-patients aged between 1 and 14 years with sinusitis (n = 1), perforated otitis media (n = 4), pharyngotonsillitis (n = 25), tracheobronchitis (n = 30) or broncho-pneumonia (n = 33) were treated daily with a combination of 40 mg/kg amoxycillin and 10 mg/kg clavulanic acid in three equal doses for between 6 and 15 days. Purulent specimens were cultured when obtainable and pathogenic organisms identified were Staphylococcus aureus, beta-haemolytic streptococcal group A, Pseudomonas aeruginosa, Pseudococcus species and Klebsiella pneumoniae infections, of which 45.7% were beta-lactamase-producing and 54.3% were ampicillin-susceptible. After treatment, only one beta-lactamase-producing Streptococcus and one Staphylococcus infection persisted. Side-effects (vomiting, nausea, diarrhoea, maculopapular exanthema, rash) occurred in 16 patients and treatment was withdrawn in eight. It is concluded that the amoxycillin--clavulanic acid combination is a suitable first choice for the treatment of respiratory tract infections in children in whom the pathogenic organism may not have been established.     

The pharmacokinetics of orally absorbed cefuroxime compared with amoxycillin/clavulanic acid

The pharmacokinetics of a new orally absorbed pro-drug of cefuroxime were compared with those of co-administered amoxycillin and clavulanic acid in six healthy male volunteers. Doses of 600 mg of acetoxyethyl cefuroxime and 500 mg amoxycillin plus 250 mg clavulanic acid were each administered for ten doses 8 hourly. Tissue penetration after the first dose of the antibiotic was estimated by a cantharides blister method. The faecal flora of the volunteers was studied throughout the study. The pharmacokinetics of cefuroxime and amoxycillin were very similar, peak levels of about 6.4 mg/l being found between 2 and 2.5 h after administration. The peak serum level of clavulanic acid was 4.3 mg/l at 1.25 h after administration. The serum half-lives were about 1.1 h for all three agents. No drug accumulation occurred over the four days of the study. The 0-8 h urinary recovery of cefuroxime was 30%. All three agents penetrated the blister fluid rapidly, the main peak levels being 64% of the peak serum level for cefuroxime, 72% for amoxycillin and 55% for clavulanic acid. The incidence of side effects was similar for each regimen. Three volunteers having diarrhoea after cefuroxime showed significant alterations in their bowel flora.     

Should yeasts in respiratory secretions be identified?

Four hundred forty samples of sputa and bronchial washings were examined microscopically for evidence of pulmonary and oropharyngeal secretions. Most (88%) sputa showed definite evidence of oropharyngeal contamination, whereas bronchial washings showed much less frequent (21%) contamination. Culture results of the same specimens showed that yeasts (excluding dimorphic fungi) were recovered from 74% of the sputa and 25% of the bronchial washings. It seems that microscopic evidence of oropharyngeal contamination is a reliable index for predicting the presence of yeasts in respiratory secretions. Their presence in cultures of respiratory secretions probably represents "normal flora" except for Cryptococcus neoformans, and their routine identification is not warranted.     

Penetration of cefotaxime into respiratory secretions.

The objective of this study was to quantitate cefotaxime and its active metabolite, desacetyl cefotaxime, in the distal airways and to compare these levels to concentrations in plasma. Respiratory secretions were obtained from the subsegmental level in 17 adult patients undergoing fiber-optic bronchoscopy within 2 h after receiving four doses of cefotaxime (2 g intravenously every 6 h). In 11 patients, cefotaxime levels measured by high-pressure liquid chromatography in bronchial secretions were below detectable limits (less than 0.5 mg/liter); however, levels of desacetyl cefotaxime exceeded 1.5 mg/liter in 9 of these 11 patients (range, 1.6 to 10 mg/liter). Concentrations of desacetyl cefotaxime in lung secretions (6.9 +/- 0.85 [standard error] mg/liter) was 77% of mean levels of desacetyl cefotaxime in plasma (8.9 +/- 1.26 mg/liter). In summary, concentrations of desacetyl cefotaxime in bronchial secretions are markedly higher than those of cefotaxime.