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Purpose: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death in the world. Current treatment options provide relief from symptoms rather than stop disease progress. Results from various preclinical experiments suggest a causal benefit of acetylic salicylic acid (ASA) in the treatment of COPD. Hence, this study set out to examine the clinical benefit of ASA in the treatment of COPD. COPD patients (Global Initiative for Chronic Obstructive Lung Disease II-III) received either once daily 500 mg of ASA or a matching placebo for 12 weeks in addition to their preexisting medication. Clinical response in terms of pulmonary function testing, symptomatic response and adverse events were assessed. After 40 subjects were included, the study was stopped and an interim analysis was performed. The addition of ASA to the treatment of subjects with COPD had no effect on clinical features or spirometry (forced expiratory volume in 1 s: F = 0.49, d.f.1 = 1, d.f.2 = 74, p = 0.486) and non-pulmonary markers. COPD represents a complex of different diseases, although currently classified mainly by markers of lung function. If future trials test the effects of anti-inflammatory therapies, COPD subpopulations should be predefined based on inflammatory features., (© 2016 S. Karger AG, Basel.)

Background: In vitro studies suggest that antimicrobial activity of antibiotics meant to treat central nervous system infections such as meningitis or ventriculitis may be altered by cerebrospinal fluid (CSF). This could explain the reason behind the often observed discrepancies between the activity of antibiotics determined in artificial growth media in vitro, and their sometimes reduced clinical efficacy in CSF in vivo. If conducted in CSF, in vitro microbiological investigations might predict the ability of antibiotic drugs to treat CSF infections better than experiments in artificial growth media. In addition, they are less expensive, critical and time consuming than animal studies, and might potentially be appreciated in drug development as a rapid and cost-effective means to gain valuable information on drugs meant to treat infections residing in CSF., Summary: Data from microbiological in vitro experiments performed in CSF were compiled for fosfomycin, rifampicin, cefepime, cefotaxime, ceftriaxone, ciprofloxacin, gentamicin and vancomycin. Where possible, correlations between in vitro data and evidence from in vivo studies were established., Key Messages: As discussed in the text, no clear correlations between in vitro studies in CSF and clinical outcomes could be identified. Methodological recommendations derived from the collected studies are summarized in order to optimize future research on the topic., (© 2016 S. Karger AG, Basel.)

Abscesses are often treated with antibiotics in addition to incision or when incision is unfeasible, but accurate information about antibiotic abscess penetration in humans is missing. This study aimed at evaluating the penetration of moxifloxacin into human abscesses. After administration of a single dose of 400 mg moxifloxacin, drug concentrations were measured in 10 differently located abscesses at incision, and in plasma over 8 h. At incision performed 0.9-4.8 h after administration, moxifloxacin concentrations in abscesses ranged from ≤0.01 to 9.2 mg/l (1.9 ± 3.4 mg/l), indicating pronounced drug accumulation in some abscesses. The degree of abscess penetration could not be explained by covariates like the ratio of surface area to volume or pH of abscesses, or by moxifloxacin plasma concentrations. Concluding, moxifloxacin was detectable in most abscesses and may be a useful antibiotic for this indication. However, antibiotic abscess penetration was highly variable and unpredictable, suggesting surgical abscess incision whenever possible., (Copyright © 2012 S. Karger AG, Basel.)

Objective: The present study aimed at testing the effect of S- and R-ibuprofen on thromboxane B(2) (TXB(2)), collagen-epinephrine closure time (CEPI-CT) and collagen-adenosine 5'-diphosphate closure time (CADP-CT) in lipopolysaccharide (LPS)-stimulated and non-stimulated human whole blood., Materials and Methods: Whole blood was incubated with S- or R-ibuprofen with and without prior stimulation with LPS. To verify ibuprofen's potential effects on TXB(2), varying ratios of concentrations of S- and R-ibuprofen ranging from 0 to 100% were used. TXB(2) levels were measured by ELISA. The effects of S- and R-ibuprofen enantiomers on platelet aggregability were tested utilizing a PFA-100 apparatus., Results: In non-stimulated and LPS-stimulated whole blood, S-ibuprofen markedly decreased TXB(2) levels at concentrations ranging from 10 to 200 microg/ml. R-ibuprofen showed its inhibiting effect at concentrations >100 microg/ml. In inflammatory and non-inflammatory conditions, CEPI-CT was prolonged at concentrations of 12.5 and 75 microg/ml for S-ibuprofen and at a concentration of 150 microg/ml of combined R- and S-ibuprofen. S-ibuprofen was significantly more effective than R-ibuprofen (p < 0.05). The combined use of S- and R-ibuprofen did not additively or synergistically prolong CEPI-CTs. CADP-CTs remained unaffected by both enantiomers., Conclusions: S-ibuprofen was more effective than the R-ibuprofen enantiomer in inhibiting TXB(2) plasma levels and aggregability of thrombocytes in non-inflammatory and inflammatory conditions., ((c) 2008 S. Karger AG, Basel.)

Daptomycin is the first approved member of a new class of antibiotics, namely the cyclic lipopeptides. Daptomycin has rapid bactericidal activity against Gram-positive pathogens. It acts by penetrating into the bacterial cell wall with consecutive formation of pores, loss of electrical membrane potential and inhibition of peptidoglycan synthesis. As the mode of action of daptomycin is 'concentration-dependent', the pharmacokinetic/pharmacodynamic indices that correlate best with its activity are the ratios of the peak concentration (C(max)) to minimum inhibitory concentration (MIC) or the area under the curve (24-hour AUC) to MIC. Daptomycin should be administered intravenously once daily, because adverse effects on skeletal muscle associated with an increase in plasma levels of creatine phosphokinase and myopathy were observed more frequently at shorter dosing intervals. Overall, the rate of adverse events during daptomycin therapy is comparable to that of other standard regimens. Daptomycin was shown to be not inferior to antimicrobial standard therapy and therefore was approved for complicated skin and skin structure infections at a dose of 4 mg/kg, for Staphylococcus aureus bacteremia and right-sided endocarditis at a dose of 6 mg/kg. Dosage regimens remain a matter of discussion, and an increase in the currently approved doses from 4-6 to 6-8 mg/kg per day for severe infections seems promising. Though not approved up to now, daptomycin appears to be a treatment alternative for Gram-positive bone and joint infections based on clinical observations. Large international studies showed high susceptibility of relevant Gram-positive pathogens to daptomycin, even in multidrug-resistant strains. Thus, treatment of infections caused by Gram-positive cocci resistant to other antimicrobial drugs is a potential indication of daptomycin. Since glycopeptides and daptomycin have the same target site, there appears to be a risk of reduced susceptibility to both drugs after consecutive use. Therefore, daptomycin should be used with caution for treatment of vancomycin-resistant isolates or after prior vancomycin (glycopeptide) therapy. This review describes the history, mechanism of action, susceptibility, recent discoveries and clinical experience regarding daptomycin, discussing its current role in the field of infectious diseases., ((c) 2008 S. Karger AG, Basel.)

The present study was carried out to test bioequivalence between two different oral desmopressin formulations. Sixty healthy volunteers were enrolled in the study and were randomly assigned to receive the test (T) and reference (R) drug in a two-period two-sequence, crossover, analyst-blinded study design. Subjects received an oral dose of 400 mug of desmopressin acetate separated by a wash-out period of at least 7 days. The area under the concentration-time curve (AUC) over 12 h in plasma and the maximum concentration (C(max)) were compared by analysis of variance (ANOVA) after log transformation. The mean ratios of the T to R drug were within the bioequivalence boundaries with mean values of 1.00 (90% CI: 0.87-1.14) and 1.03 (90% CI: 0.92-1.15) for AUC(0-t) and AUC(0-inf), respectively. For the C(max), the mean ratio of the T to R drug was 0.97 (90% CI: 0.87-1.08). The rate and the extent of oral desmopressin absorption were identical for both formulations. Hence, the desmopressin test tablet met all bioequivalence criteria of the marketed reference desmopressin tablet., (Copyright 2006 S. Karger AG, Basel)

Although drainage is considered the gold standard in abscess treatment, abscesses of different sizes and locations have been successfully cured by means of antibiotic treatment alone. The penetration of an antibiotic into an encapsulated purulent lesion is limited and highly dependent on the degree of abscess maturation. In fact, in vivo pharmacokinetic data demonstrate that substantial antibiotic concentrations can be reached within abscesses in humans and animals, provided the choice of an appropriate agent and an optimal dosing regimen. However, the efficacy of antibiotics in pus may be hampered by various factors like low pH, protein binding and degradation by bacterial enzymes. This article provides a comprehensive review on conservative abscess treatment, presenting clinical data on success rates of antibiotic therapy. Antibiotic concentrations measured in abscesses of humans and animals are outlined, and theoretical considerations on the understanding of pharmacokinetics and efficacy of antibiotics in abscesses are discussed., (Copyright 2006 S. Karger AG, Basel.)