Aminoglycosides antibacterial activity

There is an in vitro interaction between aminoglycoside antibiotics and carbenicUhn or ticarciUin, leading to a significant loss of aminoglycoside antibacterial activity if these antibiotics are mixed in the same infusion bottle (184). The extent of inactivation depends on the penicUhn concentration, the contact time, and the temperature. Azlocillin and mezlocUhn inactivate aminoglycosides in a similar manner to that described for carbenicUhn (185,186). Aminoglycosides should not be mixed with penicillins or cephalosporins in the same infusion bottle. 

The in vivo protective activity of rifaximin was studied in mice, infected experimentally by intraperitoneal inoculation of S. aureus Colliva and compared to that of rifampicin (a systemic rifamycin) and gentamicin (a poorly absorbed aminoglycoside) [74]. After oral administration, only rifampicin was effective whereas the other two compounds were inactive at doses up to 10 mg/kg. However, when injected subcutaneously, rifaximin displayed a good therapeutic efficacy (table 2). While confirming its antibacterial activity, these results clearly indicate that rifaximin, like gentamycin, is poorly absorbed after oral administration. 

AND ANTIBACTERIAL ACTIVITY OF KANAMYCIN AND NEOMYCIN CLASS AMINOGLYCOSIDE ANTIBIOTICS... 

It has been shown that the stereochemistry of the glycosidic bond to which the carbohydrate component is attached at the neamine core is essential for antibacterial activity. The neomycin class aminoglycoside consists of a neamine core and a P-linked carbohydrate component attached at the 0-5 position, while the kanamycin class aminoglycoside consists of a neamine core with a-linked carbohydrate component attached at the 0-6 position. Since neamine is the pivotal component of both neomycin and kanamycin, a readily accessible library of nnnsnal sugars will provide opportunity for the facile construction of both classes of aminoglycosides via glycosylation approach. 

By employing a 27-nucleotide RNA that represents the binding site of aminoglycoside toward the 16S rRNA, it has been found that neamine binds to such an rRNA sequence in a 2 1 ratio. Several neamine dimers were then constructed to investigate their antibacterial activity and their capability to resist or inhibit the action of AME (Scheme 4.25). These neamine dimers displayed modest to excellent antibacterial activity (Table 4.16). In addition, these dimers have also been noted for their inhibitory effect against AAC(6 )-APH(2"). 

Aminoglycosides have a very broad spectrum of antibacterial activity and are effective against many aerobic... 

Neomycin is a topical aminoglycoside widely nsed for skin wounds and in otolaryngology. Its antibacterial activity resembles that of gentamicin and tobramycin, except that P aeruginosa, S. pneumoniae, and the a-hemolytic streptococci are generally resistant. Neomycin s usefnl-ness for treating acnte bacterial conjunctivitis is limited... 

Table 7.13. ANTIBACTERIAL ACTIVITY OF A NUMBER OF AMINOGLYCOSIDE ANTIBIOTICS AGAINST STRAINS OF PS. AERUGINOSA...

For gentamycin derivatives, the introduction of an axial hydroxymethyl substituent at C-1 in the 2-deoxystreptamine moiety reportedly ameliorates nephrotoxicity and confers protection against inactivation by bacterial enzymes. The Belgium team investigated a similar modification in the kanamycin B series [265]. As expected, l-C-(hydroxymethyl)kanamycin B (212) proved equipotent with the parent aminoglycoside (208) against kanamycin B-sensitive bacteria and the introduction of a 6"-azido, 6"-chloro, or 6"-acetamido group (213)-(215), did not reduce antibacterial activity Table 3.19). However, the introduction of a l-C-(hydroxymethyl)... 

In the purposeful search that followed the demonstration of the clinical efficacy of penicillin, streptomycin was obtained from Streptomyces griseus in 1944, cultured from a heavily manured field, and also from a chicken s throat. Aminoglycosides resemble each other in their mode of action, and their pharmacokinetic, therapeutic and toxic properties. The main differences in usage reflect variation in their range of antibacterial activity crossresistance is variable. 

It may also have ANTIPSYCHOTIC activity, dapiprazole hydrochloride dapiprazole. dapitant [inn] (RPR 100893) is a substituted isoindole, a TACHYKININ RECEPTOR ANTAGONIST, selective for the NK,-receptor subtype. It has potential as an ANTIMIGRAINE AGENT, dapsone [ban, inn, usan] is a sulphone with actions similar to SULPHONAMIDES and with ANTIBACTERIAL activity. It can be used as an antileprotic and for infective dermatitis herpetiformis. and is being investigated for the treatment and prevention of Pneumocystis carinii pneumonia (e.g. in AIDS), daptomycin [ban, inn, usan] is an (aminoglycoside) antibiotic. It has antibacterial properties. 

Matt T, Ng CL, Lang K, Sha SH, Akbergenov R, Shcherbakov D, Meyer M, Duscha S, Xie J, Dubbaka SR, Perez-Fernandez D, Vasella A, Ramakrishnan V, Schacht J, Bottger EC (2012) Dissociation of antibacterial activity and aminoglycoside ototoxicity in the 4-monosubstituted 2-deoxystreptamine apra-mycin. Proc Natl Acad Sci U S A 109(27) 10984-10989... 

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