Methicillin toxicity

Linezolid Prevents bacterial protein synthesis by binding to the 23S ribosomal RNA of 50S subunit Bacteriostatic activity against susceptible bacteria Infections caused by methicillin-resistant staphylococci and vancomycin-resistant enterococci Oral, IV hepatic clearance (half-life 6 h) dosed twice-daily Toxicity Duration-dependent bone marrow suppression, neuropathy, and optic neuritis serotonin-syndrome may occur when coadministered with other serotonergic drugs (eg, selective serotonin reuptake inhibitors)... 

Along this line Matsue et al. [37,45,78,79] have developed a number of biochips. Among them are multi-analyte assays for human placental lactogen (HPL) and human chorionic gonadotropin (HCG) [45] and leukocidin, a toxic protein produced by methicillin-resistant Staphylococcus aureus [79]. Figure 37.8 shows an example of a dual immunoassay with SECM detection. The analyte is defined by the position on the chip and the amount of analyte is quantified via the collection current at the UME. The current originates from the reduction of ferrocinium methanol (Fc+) at the UME. Fc+ is produced locally at the chip surface by the enzyme HRP under consumption of H202. 

Antistaphylococcal penicillins Methicillin [meth i SILL in], naf-cillin [naf SILL in], oxacillin [ox a SILL in], cloxacillin [klox a SILL in], and dicloxacillin [dye klox a SILL in] are penicillinase-resistant penicillins. Their use is restricted to the treatment of infections caused by penicillinase-producing staphylococci. Because of its toxicity, methicillin is rarely used. Methicillin-resistarft strains of Staphylococcus aureus (MRSA), currently a serious source of nosocomial (hospital-acquired) infections, are usually susceptible to vancomycin, and rarely to ciprofloxacin or rifampin. 

As this category of penicillins was used for treatment, S. aureus and S. epidermidis became resistant to them through the production of altered penicillin-binding proteins. These strains of staphylococci are called methicillin resistant, which denotes resistance not only to all penicillinase-resistant penicillins but to all penicillin drugs. Methicillin-resistant staphylococci have become a major problem in treatment because they are also resistant to the cephalosporins, aminoglycosides, and macrolides. For this reason vancomycin, a more toxic antibiotic, is the drug of choice for these organisms. 

Because of its potential toxicity, vancomycin is reserved for serious infections in which less toxic antibiotics are ineffective or not tolerated. Generally, vancomycin is administered intravenously because of poor intestinal absorption. It is the drug of choice for treating infections caused by methicillin-resistant staphylococci and penicillin-resistant Streptococcus pneumoniae. Vancomycin has been used to treat enterococcal infections because of their resistance to the P-lactam antibiotics, but most enterococci are now also resistant to vancomycin. Oral administration of rancomycin is important for treatment of some gastrointestinal infections such as pseudomembranous colitis caused by C. difficile. 

In vitro, methicillin and ceftazidime in high concentrations produced toxic effects on comeal and endothelial cells of the eye (58,59). 

The combination of cephalothin wifh an aminoglycoside was more nephrotoxic than methicillin plus aminoglycoside [143]. There is good evidence that concurrent administration of cephalothin and gentamicin are additive nephrotoxins in humans, especially in patients over 60 years of age as wells as in rabbits [144], and renal injuries are intensified in the presence of mild renal ischemia or endotoxemia [108]. The results of prospective randomized comparative studies of the combination mezlocillin/cefotaxime versus gentamicin/cefoxitin showed that the concurrent administration of mezlocillin/cefotaxime has low renal toxicity and can be recommended for the rational and empirical treatment of serious systemic infections [145]. 

Penicillin-induced renal toxicity is most commonly seen as allergic acute interstitial nephritis (AIN). Methicillin is the most common penicillin to induce AIN, but the use of penicillin G, ampicillin, am-oxacillin, oxacillin, and carbenicillin also can lead to the development of AIN. Typically, acute renal failure follows 1 or 2 weeks of treatment with fever or rashes sometimes occurring before overt renal dysfunction. Removal of the penicillin generally allows renal function to return to normal within a few days or weeks. AIN can also be induced by certain cephalosporins (e.g., cephalothin, cephalexin, cephradine, cefoxitin, cefotaxime) and non-/i-lactam antimicrobials (e.g., sulfonamides, rifampicin, tetracyclines, erythromycin). 

It Is easier to demonstrate synergy in vitro than in vivo, and concerns about the toxic contribution of the sulfonamide (and, doubtless, commercial considerations as well) have led to a recent vogue for the use of trimethoprim alone. Trimethoprim has a broad spectrum in vitro, so it Is potentially useful against many microorganisms. Combined with sulfamethoxazole, it Is used for oral treatment of urinary tract infections, shigellosis, otitis media, traveler s diarrhea, methicillin-resistant Staphylococcus aureus (MRSA), Legionella infection, and bronchitis. 

Fitzgerald, J. R., Sturdevant, D. E., Mackie, S. M., Gill, S. R., and Musser, J. M. (2001) Evolutionary genomics of Staphylococcus aureus insights into the origin of methicillin-resistant strains and the toxic shock syndrome epidemic. Proc. Natl. Acad. Sci. USA 98, 8821-8826. 

Evolutionary genomics of Staphylococcus aureus insights into the origin of methicillin-resistant strains and the toxic shock syndrome epidemic. Proc. Natl. Acad. Sci. U.S.A. 98, 8821-8826. 

Documented effects Similar to Ferula foetida. Compounds isolated from the fruits were toxic against gram-positive bacteria, including methicilhn-sensitive and methicillin-resistant Staphylococcus aureus (Tamemoto et al. 2001). 

Fosfomycin is one of a few natural products containing a carbon-phosphorus (C— P) bond isolated from Streptomyces fradiae, Streptomyces viridochromogenes, and Streptomyces wedmorensis [73]. It was also isolated from Pseudomonas syringae and Pseudomonas viridiflava [74, 75], Fosfomycin is a highly effective antibiotic of low toxicity clinically utilized for the treatment of lower urinary tract infections [76] as well as methicillin-resistant [77] and vancomycin-resistant [78] strains of S. aureus. Moreover, fosfomycin is effective for the treatment of cephalosporin- and penicillin-resistant Streptococcus pneumonia [79] and ciprofloxacin-resistant E. coli [80], The antimicrobial activity of fosfomycin has been ascribed to the inactivation of UDP-GlcAAc-3-O-enolpyruvyltransferase (MurA), an essential enzyme that catalyzes the first committed step in the biosynthesis of peptidoglycan, the main component of the cell wall, by covalent alkylation of an active site cysteine [81]. 

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