Antibiotics clinical relevance

The clinical relevance of biocide resistance of antibiotic-resistant staphylococci is, however, unclear. It has been claimed that the resistance of these organisms to cationic-type biocides confers a selective advantage, i.e. survival, when such disinfectants are employed clinically. However, the in-use concentrations are several times higher than those to which the organisms are resistant. 

After oral administration of 400 mg of rifaximin to fasted healthy volunteers blood drug concentration was found to be lower than the detection limit of the analytical method (i.e. 2.5 ng/ml) in half of them [102]. In the remaining subjects very low amounts were detected at some of the time intervals during the first 4 h after intake. Along the same lines, the urinary concentrations of the drug were very low and often undetectable. The effect of food on the absorption of the antibiotic was also evaluated [34] and a significant, albeit not clinically relevant, increase of bioavailabity was observed after a high-fat breakfast (table 5). 

Chloramphenicol [20 CAP D-(—)-ft reo-l-(p-nitrophenyl)-2-(dichloroacetamido)-l,3-propanediol] is an important antibiotic due to its broad activity against a number of clinically relevant microbial pathogens and its ability to penetrate easily the blood-brain barrier. Besides human application, CAP became widely and routinely used in veterinary practice and is used in Europe in most animal productions including fish128. 

Adelowo O, Fagade OE, Oke AJ (2008) Prevalence of co-resistance to disinfectants and clinically relevant antibiotics in bacterial isolates from three hospital laboratory wastewaters in South-western Nigeria. World J Microbiol Biotechnol 24 1993-1997... 

Essentially, three major lines of evidence contribute to demonstrate the gradual increase of antibiotic resistance - (1) annual reports on antibiotic resistance prevalence values of clinically relevant antibiotics for human pathogens [27, 28] (2) the comparison of antibiotic resistance prevalence values in samples or bacterial cultures of our days with others archived from the pre-antibiotic era (e.g. [29, 30]) and (3) the establishment of significant correlations between antibiotics consumption and resistance increase [28, 31]. 

Over the last years, a renewed interest on the antibiotic resistance phenotypes in municipal waste water treatment plants became apparent in the scientific literature. The underlying hypothesis of these smdies is that urban sewage treatment plants are potential reservoirs of antibiotic resistance, and, in general, it is aimed at contributing to assess the risks of dissemination, posed by the treated effluents discharged into natural water courses. As a general trend, these studies focus on human/animal commensal and environmental bacteria, frequently disseminated via faecal contamination, and which can survive in waters. The relevance of these bacteria, which may exhibit clinically relevant resistance phenotypes, as possible nosocomial agents seems also to be a motivation behind these smdies. 

Table 3 Examples of antibiotic resistance genes of clinical relevance distributed worldwide in aquatic environments and illustration of some methodological approaches commonly used to detect resistance determinants in the environment... 

Szczepanowski R, Linke B, Krahn I et al (2009) Detection of 140 clinically relevant antibiotic-resistance genes in the plasmid metagenome of waste water treatment plant bacteria showing reduced susceptibility to selected antibiotics. Microbiology 155 (Pt 7) 2306-2319... 

Volkmann H, Schwartz T, Bischoff P et al (2004) Detection of clinically relevant antibiotic-resistance genes in municipal waste water using real-time PCR (TaqMan). J Microbiol Methods 56(2) 277-286... 

A novel cyclic lipopeptide antibiotic was isolated from cultures of Strep-tomyces roseosporus grown in the presence of decanioc acid. Daptomycin interacts with the bacterial cell membrane and interferes with membrane potential.Unlike polymyxin B, daptomycin can target majority of clinically relevant Gram-positive pathogens. 

Maximal plasma concentrations occur 2 to 3 hours after oral administration of reboxetine (178). Reboxetine has linear pharmacokinetics over its clinically relevant dosing range and a half-life of approximately 12 hours. For this latter reason, a twice a day, equally divided dosing schedule was used during clinical trial development. Its clearance is reduced and half-life becomes longer as a function of advanced age (mean = 81 years of age) and renal and hepatic impairment ( 178, 322, 323). Reboxetine is principally metabolized by CYP 3A3/4 such that its dose should be reduced when used in combination with drugs that are substantial inhibitors of CYP (e.g., certain azole antifungals, certain macrolide antibiotics). Reboxetine itself, however, does not cause detectable inhibition of CYP 3A3/4 based on formal in vivo pharmacokinetic interaction studies as well as its own linear pharmacokinetics. 

Prins, J.M., Van Deventer, S.J.H., Kuijper, E.J., Speelman, P. Clinical relevance of antibiotic-induced endotoxin release. Antimicrob Agents Chemother 38 (1994) 1211-1218. 

TOREMIFENE ANTIBIOTICS -MACROLIDES T plasma concentrations of toremifene with clarithromycin and erythromycin Due to inhibition of metabolism of toremifene by the CYP3A4 isoenzymes by clarithromycin Clinical relevance is uncertain. Necessaiy to monitor for clinical toxicities... 

GRAPEFRUIT JUICE ANTIBIOTICS - CLARITHROMYCIN, ERYTHROMYCIN Significant delay in onset of action of clarithromycin (t from 82 to 148 minutes), t plasma concentrations of erythromycin (maximum concentration t, AUC 11,5-fbld) Due to inhibition of absorption attributed to effect on P-gp The interaction is unlikely to cause clinically relevant 1 antimicrobial activity of clarithromycin Telithromycin is unlikely to be affected by grapefruit juice. Be aware... 

Aminoglycoside-induced neuromuscular blockade can be clinically relevant in patients with respiratory acidosis, in myasthenia gravis, and in other neuromuscular diseases. Severe illness, the simultaneous use of anesthetics, for example in the immediate postoperative phase, and apphcation of the antibiotic to serosal surfaces are predisposing factors (10). 

There are various conflicting reports about acute interactions of beta-lactam antibiotics, especially acylaminope-nicillins (apalcillin, azlocUhn, mezlocilhn, piperacUhn), with vecuronium, leading to prolongation of muscle blockade. Reports of clinically relevant effects (356-358) conflict with reports of no effect (359). 

Both antibiotic-specific and MDR pumps are known to confer clinically relevant resistance [22, 53]. The former are carried on plasmids and transposons. While they can be rapidly spread between various strains, they are at hand only in a proportion of a total population of a given species. Tet and Mef pumps, which confer resistance to tetracycline and macrolides, respectively, in both Gram-positive and Gram-negative bacteria, are clinically important and highly prevalent antibiotic-specific transporters. 

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