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The efficacy of an antimicrobial agent in the therapy of infection depends upon the interaction of bacteria, antibiotic and phagocytes. The influence of both ticarcillin/clavulanic acid and amoxycillin/clavulanic acid on the phagocytic and bactericidal activity of human PMNs in vitro was investigated. The results show that clavulanic acid, with its beta-lactamase inhibitory properties, potentiated the efficacy of both ticarcillin and amoxycillin, resulting in a significantly increased susceptibility of a beta-lactamase producing strain of Klebsiella pneumoniae to phagocytic and microbicidal activities of human PMNs. Overall, amoxycillin/clavulanic acid showed greater enhancement of the killing of K. pneumoniae by human PMNs. [ABSTRACT FROM AUTHOR]

Background. Chronic haemodialysis patients and renal transplant recipients are highly susceptible to infection characterized by high morbidity and mortality and related to an impairment of the phagocytic response. [ABSTRACT FROM PUBLISHER]

Background and Aims: Statin utilization and lipid goal achievement were estimated in a large sample of Italian patients at high/very-high cardiovascular (CV) risk., Methods: Patients aged ≥18 years with a valid low-density lipoprotein cholesterol (LDL-C) measurement in 2015 were selected from the IMS Health Real World Data database; non-high-density lipoprotein cholesterol (non-HDL-C) was assessed in those with available total cholesterol measurements. Index dates were defined as the last valid lipid measurement in 2015. Patients were hierarchically classified into mutually exclusive risk categories: heterozygous familial hypercholesterolemia (primary and secondary prevention), atherosclerotic CV disease (including recent acute coronary syndrome [ACS], chronic coronary heart disease, stroke, and peripheral arterial disease), and diabetes mellitus (DM) alone. Statin and non-statin lipid-modifying therapy (LMT) use, and European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guideline-recommended goal attainment, were assessed., Results: Among 66,158 patients meeting selection criteria, the overall rate of LMT prescriptions was 53.3%, including 7.7% on high-intensity statin therapy. Statin use was highest for recent ACS and lowest for DM alone. LDL-C goal attainment was 16.0% for <1.8 mmol/l and 45.0% for <2.5 mmol/l; 24.3% reached non-HDL-C <2.6 mmol/l and 52.2% were at <3.3 mmol/l. Goal achievement was greatest with high-intensity statin use., Conclusions: Statin use in this cohort was consistent with previous reports in Italian patients at high/very-high CV risk, and low relative to statin use in other European countries. The low rate of ESC/EAS lipid goal attainment observed was consistent with outcomes of other European studies., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Angiotensin II (ANG II) has profibrotic actions in the heart and kidney, whereas blockade of the renin angiotensin system (RAS) attenuates injury. This study examines whether the RAS is present in the liver and examines its regulation in the bile duct-ligation model of hepatic fibrogenesis., Methods: Sham-operated and bile duct-ligated (BDL) Sprague-Dawley rats were studied. Gene and protein expression of hepatic renin, angiotensinogen, angiotensin-converting enzyme (ACE), and the angiotensin receptors AT1 and AT2 were assessed using real-time reverse-transcription polymerase chain reaction, in vitro autoradiography, and immunohistochemistry., Results: Angiotensinogen and renin messenger RNA were detected in sham liver but were not increased following BDL. Angiotensinogen protein was widely distributed in hepatocytes in both normal and injured livers, but in BDL livers, it was also expressed within areas of active fibrogenesis. Both ACE and AT1 receptor genes were up-regulated following BDL. The low level of ACE activity in sham animals was significantly increased in areas of active fibrogenesis in BDL livers. The AT1 receptor was present in both normal and diseased liver parenchyma, with increased AT1 receptor binding seen in fibrotic areas in the diseased liver. The AT2 receptor gene was not detected in normal or diseased liver., Conclusions: Key elements of the RAS are present in normal liver tissue, and there is major up-regulation of the system in the bile duct-ligated liver. These findings are in keeping with recent experimental studies that have demonstrated antifibrotic effects of RAS blockade in the bile duct-ligated liver.

The recent increase in the incidence of infections due to Streptococcus pneumoniae resistant to penicillin and other antibiotics, often associated with considerable morbidity and mortality, has been recognized as an alarming problem. From the recent medical literature data it emerges that among beta-lactam antibiotics used as an empiric treatment for infections caused by S. pneumoniae, amoxycillin and amoxycillin/clavulanic acid are the most active oral antibiotics and may be considered as a first-line therapeutic agent for the treatment of these infections. Since the therapeutic result of the treatment of an infection is determined by the combined effect of the antimicrobials and host defenses, we investigated the effect of amoxycillin, with and without clavulanic acid, upon the in vitro interaction between human polymorphonuclear leukocytes (PMNs) and a penicillin-resistant strain of S. pneumoniae. Amoxycillin significantly inhibited the streptococcal uptake by PMNs referred to the control system. Clavulanic acid did not have any significant effect upon the interaction PMNs-S. pneumoniae. The addition of amoxycillin/clavulanic acid to phagocytes and streptococci resulted in a synergystic potentiation of the activity of both drugs upon the PMN functions towards S. pneumoniae in such a manner that the bacteria became more susceptible to either the phagocytosis or the microbicidal activities of phagocytes. These effects came in addition to the intrinsic, excellent antimicrobial properties of this drug combination. Although the clinical significance of the observed enhanced effects of amoxycillin/clavulanate are far from elucidated, the possibility exists that they may play a contributory role, especially in patients with impaired host defense.

Patients with community acquired pneumonia (CAP) previously treated with other oral antibiotics (Cephalosporins 35,3%, Macrolides 26,9%, Tetracyclines 14,1%, Quinolones 12,8%, other 10,9%) for at least 72 hours at home were considered for this national multicentre study. 43 hospitalized patients (17 males and 26 females) ranging between the ages of 19 and 79 were treated with Amoxicillin/Clavulanic acid (AMC) 1,2 g e.v., T.l.D. for at least 3 days. I.V. Treatments were switched to AMC p.o. after apyrexial status. Average treatment duration was 10,8 + 3.6. Sputum/B.A.L. samples were obtained from all patients submitted for microbiological exams in order to determine microbiological aetiology of CAP in patients who have failed on previous antibiotics. At the end of treatment, 30 patients (96,8%) were considered cured, while treatment failed in 1 patient (3,2%). 12 patients were considered not evaluable because serology was positive for M.pneumoniae (5 pts); for C.pneumoniae (3 pts.); 1 patients was positive for Mycobacterium tuberculosis; 1 patient was positive for HIV and Mycobacterium spp.; 2 patients were non-evaluable for lung or bronchial tumor. Not reported adverse events.

The use of broad spectrum beta-lactamase inhibitors in association with beta-lactam agents provides one strategy to overcome the enzymatic resistance. Clavulanic acid is a potent inhibitor of a wide range of bacterial beta-lactamases and its potentiating effect on amoxycillin has been established both in vitro and in clinical trials. Since the efficacy of an antimicrobial agent in the therapy of infections depends on the interaction of bacteria, antibiotic and phagocytes, we investigated the effect of amoxycillin/clavulanic acid on the in vitro interaction between human polymorphonuclear cells (PMNs) and beta-lactamase producing strains of Klebsiella pneumoniae and Staphylococcus aureus. Clavulanic acid did not have any significant influence upon the PMN phagocytosis and killing against intracellular bacteria. Interestingly, the presence of the suicide inhibitor, with its beta-lactamase inhibitory properties, potentiated the activity of amoxycillin against the beta-lactamase producing strains of K. pneumoniae and S. aureus in such a manner that bacteria became significantly more susceptible to either phagocytosis or microbicidal activities of human phagocytes, compared to both the control and amoxycillin systems.

The effect of amoxycillin, and amoxycillin/clavulanic acid on the in vitro interaction between human polymorphonuclear cells and a beta-lactamase producing strain of Staphylococcus aureus was investigated. Amoxycillin alone, at half the MIC, significantly inhibited the bacterial uptake by polymorphonuclear (PMN) cells compared with the control; as a consequence the killing of intracellular staphylococci was higher. Clavulanic acid did not have any significant effect upon the activities of phagocytes. The combination amoxycillin/clavulanic acid possesses beneficial properties which result in enhancement of both phagocytosis and microbicidal activity of PMN cells against the beta-lactamase producing strain of S. aureus. A synergic effect between drugs and serum activity was noted.

Clavulanic acid is an effective inhibitor of a broad range of clinically important beta-lactamases and its combination with some beta-lactam antibiotics such as ticarcillin has been shown to extend the inhibition spectrum of the beta-lactams. The activity of ticarcillin, both alone and in combination with clavulanic acid, upon PMN phagocytosis and bactericidal activity towards Klebsiella pneumoniae was investigated. The results indicate that a combination of ticarcillin with clavulanic acid is more active than ticarcillin alone against a beta-lactamase-producing strain of K. pneumoniae, and hence may significantly increase the bacterial vulnerability to phagocyte functions.

Recently it has been recognized that steady-state serum digoxin concentrations may increase or fall to ineffective levels when the glycoside is administered together with several antibiotics. Our study was designed to assess if serum digoxin levels may be modified by the concomitant use of a ticarcillin and clavulanic acid. The study was carried out in 15 hospitalized patients suffering from exacerbation of their chronic bronchitis without liver disease and renal failure. Serum digoxin levels were not significantly modified by the concomitant use of a ticarcillin and clavulanic acid, although peak digoxin serum concentrations were slightly lower. However, the average time to achieve the maximum concentration and area under the curve over 24 h did not change.

Unlabelled: EFFICACY, renal effects and nephrotoxicity of the cephalosporin cefonicid (CEF) were evaluated in 11 adult patients with urinary tract infection and varying renal function (creatinine cl 19-161 ml/min, mean 75). CEF was administered i.m. for 7 days at a daily dose adjusted to renal function of the patients., Efficacy: At the 4th day and at the end of the treatment urine cultures were negative in all cases; a recurrence of the infection was observed in 4 patients 10 days after completion of therapy. Renal effects and nephrotoxicity: CEF neither modified plasma creatinine, urea, uric acid and their renal clearances nor glomerular filtration rate. Only the urinary enzyme activity of alanine aminopeptidase increased slightly at the end of the therapy. It returned to basal values in the post-treatment period. Urinary enzyme activities of gamma-glutamyltransferase, alkaline phosphatase, N-acetyl-beta-D-glucosaminidase and lysozyme were unmodified during and after treatment with CEF. These results indicate that CEF is an effective antimicrobial agent which does not influence renal function, nor cause nephrotoxic effects.

The present study was undertaken in order to investigate the penetration of cefonicid, a long-acting parenteral cephalosporin, with enhanced activity against most gram-positive and gram-negative pathogens, into human lung tissue and lymph nodes in patients undergoing open thoracotomy. Samples of lung tissue, lymph nodes and serum were obtained at various times after a single intramuscular dose of 1 g. The concentration of cefonicid was assayed by an agar diffusion method with Bacillus subtilis used as the test organism. The mean concentrations of cefonicid in serum at 2, 4, 8, 12 and 24 h after the injection were 91.5, 66.1, 35.7, 21.8 and 2.9 micrograms/ml, respectively. The mean levels of cefonicid into the hilar lymph nodes at the same times were 22.3, 18.7, 12.0, 6.9 and 1.5 micrograms/ml, respectively, while its concentrations in lung tissue were lower than those in lung lymph nodes up to the 12th hour (12.1, 14.6, 7.8, 5.4 and 1.9 micrograms/ml, respectively). Our results show that cefonicid was well distributed in interstitial fluid from which pulmonary lymph is formed and that its concentrations in lung tissue and lymph nodes were sufficient to inhibit most pathogens involved in respiratory tract infections. This finding was considered important, because it demonstrated that the high binding by plasma protein of cefonicid did not prevent it from entering lung tissue and fluids in useful quantities.

The ultrastructural study carried out in a case of tonsillar malakoplakia confirmed that granulomatous lesions consisted mainly of macrophages containing peculiar calcified inclusions (Michaelis-Gutmann bodies) considered pathognomonic for the disease. Moreover macrophages frequently contained ingested Gram-negative bacilli and presented aspects of mitochondrial degeneration and autophagy. These latter features were probably the consequence of bacterial infection rather than the expression of primary cellular defects, as the clinical evolution of this case of malakoplakia did not support the existence of generalized macrophage alterations.