Sulphonamides antimicrobial

Sulphonamide antimicrobial agents (Figure 8.22) such as sulphamethoxazole [21] are oxidized to protein-reactive cytotoxic metabolites in the liver and also other tissues. These include hydroxylamines and further products such as nitroso-deriva-tives. Sulphonamide drugs are linked with agranulocytosis, aplastic anaemia and... 

Gobel A, McArdell CS, Suter MJ-C, Giger W, Trace determinations of macrolide and sulphonamide antimicrobials, a human sulphonamide metabolite, and trimethoprim in wastewater using liquid chromatography coupled to electrospray tandem mass spectrometry. Anal. Chem. 2004 76 4756-4764. 

In this chapter, the latest applications published in the literature from 1994 to 1998 are reviewed. The following groups of antimicrobial agents are discussed tetracyclines, penicillins, poiyethers, aminoglycosides, macrolides, amphenicols, nitrofurans, sulphonamides, quinolones and other antimicrobials. 

The HPLC-receptorgram assay combined the advantages of HPLC separation with the multiresidue detection of the Charm II tests. The procedure was tested for identification and quantitation of the most common veterinary drugs at regulatory levels or lower. It was validated for 40 individual drugs from seven antibiotic families 10 /3-lactams, 13 sulphonamides, 8 tetracyclines, 4 macrolides, 3 amphenicols, and other miscellaneous antimicrobials. This procedure combined a simple aqueous extraction and SPE with HPLC fractionation of individual drugs. Final identification and quantitation was achieved with the Charm II test. A drug contaminant could be identified in less then 3 hours (50). 

Cribb AE, Lee BL, Trepanier LA, et al. Adverse reactions to sulphonamide and sulphonamide-trimethoprim antimicrobials clinical syndromes and pathogenesis. Adverse Drug React Toxicol Rev 1996 15 9-50. 

Humans cannot synthesise folic acid. Many bacteria, however, synthesise it from PABA this bacteria-specific pathway provides a target for synthetic antimicrobial agents like the sulphonamides and trimethoprim (Figure 20.4). Sulphonamides inhibit dihydropteroate syn-... 

Antimicrobials. Metronidazole is present in milk in moderate amounts avoid prolonged exposure. Nalidixic acid and nitrofurantoin should be avoided where glucose-6-phosphate dehydrogenase deficiency is prevalent. Avoid clindamycin, dapsone, Uncomycin, sulphonamides. Regard chloramphenicol as unsafe. 

Drugs that carry a definite risk of haemolysis in most G6PD deficient subjects include dapsone (and other sulphones), methylene blue, niridazole, nitrofurantoin, pamaquin, primaquine, quinolone antimicrobials, some sulphonamides. 

Systemically taken drugs that can induce photosensitivity are many. Of the drug groups given below, those most commonly reported are antimitotics dacarbazine, vinblastine antimicrobials demeclocycline, doxycycline, nalidixic acid, sulphonamides antipsychotics chlorpromazine, prochlorperazine cardiac arrhythmic amiodarone diuretics frusemide (furosemide), chlorothiazide, hydrochlorothiazide fibric acid derivatives, e.g. fenofibrate hypoglycaemic tolbutamide... 

Exanthematic/maculopapular reactions are the most frequent unlike a viral exanthem the eruption typically starts on the trunk the face is relatively spared. Continued use of the drug may lead to erythroderma. They commonly occur at about the ninth day of treatment (or day 2-3 in previously exposed patients), although onset may be delayed until after treatment is completed causes include antimicrobials, especially ampicillin, sulphonamides and derivatives (sulphonylureas, frusemide (furosemide) and thiazide diuretics). Morbilliform (measles-like) eruptions typically recur on rechallenge. 

Dermatitis herpetiformis Dapsone is typically effective in 24 h, or sulfapyrldine. Prolonged therapy necessary, a gluten-free diet can help, Antipruritics locally as required. Not other sulphonamides benef dal effect not due to antimicrobial action. Methaemoglobinaemia may complicate dapsone therapy. 

Antimicrobials. Aztreonam, cefamandole, chloramphenicol, ciprofloxacin, co-trimoxazole, erythromycin, fluconazole, itraconazole, ketoconazole, metronidazole, miconazole, ofloxacin and sulphonamides (including co-trimoxazole) increase anticoagulant effect by mechanisms that include interference with warfarin or vitamin K metabolism. Rifampicin and griseofulvin accelerate warfarin metabolism (enzyme induction) and reduce its effect. Intensive broad-spectrum antimicrobials, e.g. eradication regimens for Helicobacter pylori (see p. 630), may increase sensitivity to warfarin by reducing the intestinal flora that produce vitamin K. 

Acute hepatocellular necrosis. This reaction varies from a transient disturbance of liver function tests to acute hepatitis. It can be induced by several drugs including general anaesthetics (halothane), antiepileptics (carbamazepine, phenytoin, sodium valproate, phenobarbital), antidepressants (MAO inhibitors), antiinflammatory drugs (indomethacin, ibuprofen), antimicrobials (isoniazid, sulphonamides, nitrofurantoin) and cardiovascular drugs (methyldopa, hydralazine). 

Antimicrobial agents such as sulphonamides (section 13.1) and the 4-quinolones (section 13.7), produced solely by synthetic means, are often referred to as antibiotics. 

Antimicrobial agents most likely to be affected by the first-pass effect include trimethoprim, sulphonamides, fluoroquinolones, chloramphenicol, metronidazole and rifampin. The metabolites of trimethoprim, sulphonamides, most fluoroquinolones and chloramphenicol are inactive, while ciprofloxacin and sarafloxacin formed by N-dealkylation of enrofloxacin and difloxacin, respectively, and desacetylrifampin have antimicrobial activity similar to or greater than (ciprofloxacin) the parent drug. Certain antimicrobial agents (chloramphenicol and erythromycin) inhibit hepatic microsomal enzyme activity, whereas rifampin is a potent inducer of hepatic microsomal enzymes. 

The effect of experimentally induced bacterial infections, all of which have in common the presence of fever, on the disposition of various antimicrobial agents in pigs is presented in Table 3.1. In the infected pigs, the apparent volume of distribution of penicillin G, ampicillin and, to a lesser extent, trimethoprim is increased, of enrofloxacin and sulphonamides remains unchanged, and of oxytetracycline is decreased. The systemic clearance of penicillin G, ampicillin and trimethoprim is increased, of sulphamethoxazole and sulphadimethoxine remains unchanged, and of sulphadimidine,... 

The chemical nature and related physicochemical properties largely govern the distribution and elimination, which refers to biotransformation (metabolism) and excretion, of antimicrobial agents. The majority of antimicrobial agents are weak organic electrolytes, either weak acids (penicillins, cephalosporins, sulphonamides) or weak bases (aminoglycosides, lincosamides, macrolides, diaminopyrimidines, metronidazole), while fluoroquinolones, tetracyclines and rifampin are amphoteric compounds, and chloramphenicol and its... 

The role of enterococci in nosocomial infections is probably due to a variety of factors of which antimicrobial resistance appears to be a primary cause. Enterococci possess a broad spectrum of both natural (intrinsic) resistance and acquired (transferable) resistance (Franz et al. 2003). Examples of antibiotics to which the enterococci present an intrinsic resistance include the P-lactam antibiotics (third generation cephalosporins), sulphonamides and clindamycin and aminoglycosides in low levels (Eranz et al. 2003). Acquired resistance based on plasmids or transpo-sons acquisition has relevance for chloramphenicol, erythromycin, high levels of clindamycin, aminoglycosides, tetracycline, high levels of P-lactam antibiotics, fluoroquinolones and glycopeptides like vancomycin (Murray 1990 Leclercq 1997). In particular, vancomycin-resistant enterococci (VRE) pose a major problem... 

Lindsey ME, Meyer M, Thurman EM, Analysis of trace levels of sulphonamide and tetracycline antimicrobials in groundwater and surface water using solid-phase extraction and liquid chromatography/mass spectrometry. Anal. Chem. 1998 73 4640-4646. 

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