Aminoglycosides procedures

The success of dibekacin prompted worldwide attention to the removal of selected OH groups in aminoglycoside antibiotics susceptible to modification by resistant bacteria, and the chemical deoxygenation procedure of D. H. R. Barton was found particularly useful. 

Although most CF patients have shorter half-lives and larger volumes of distribution than non-CF patients, some patients exhibit decreased clearance. Possible causes include concomitant use of nephrotoxic medications, presence of diabetic nephropathy, history of transplantation (with immunosuppressant use and/or procedural hypoxic injury), and age-related decline in renal function in older adult patients. Additionally, CF patients are repeatedly exposed to multiple courses of IV aminoglycosides, which can result in decreased renal function. Evaluation of previous pharmacokinetic parameters and trends, along with incorporation of new health information, is key to providing appropriate dosage recommendations. 

Neomycin has been separated from mixtures of other aminoglycoside antibiotics containing the 2-deoxystreptamine moiety as both the pertrimethylsilyl derivative and the N-trifluoro-acetyl pertrimethylsilyl derivative using a column of 0.75% 0V-1 on Gas Chrom q240. The procedure may be used to estimate the number of sugar moieties bound in the antibiotic as a close relationship exists between the number of rings and the retention time. 

The medically useful products demethyltetracycline and doxorubicin (adriamycin) were discovered by simple mutation of the cultures producing tetracycline and daunorubicin (daunomycin), respectively. The tectmique of mutational biosynthesis (mutasynthesis) has been used for the discovery of many new aminoglycoside, macrolide, and anthracycline antibiotics. In this tectmique, a non-producing mutant ( idiotroph ) is isolated and then fed various analogs of the missing moiety. When such a procedure leads to a return of antibiotic activity, it usually is due to the... 

Although a number of chromatographic methods have been reported for determinations of aminoglycoside antibiotics in blood serum and urine, the application of chromatographic methods to residue analysis has been very limited. Shaikh et al (93) recently described an HPLC method for neomycin in animal tissue, and Lachatre et al (94) described a method for nine aminoglycosides in plasma, urine, and renal cortex tissue. Both procedures use post column derivatization with a-pthalaldehyde and fluorescence detection. 

Topical use Aminoglycosides are quickly and almost totally absorbed when applied topically in association with surgical procedures, except to the urinary bladder. 

Clindamycin is indicated for the treatment of skin and soft-tissue infections caused by streptococci and staphylococci. It is often active against community-acquired strains of methicillin-resistant S aureus, an increasingly common cause of skin and soft tissue infections. Clindamycin is also indicated for treatment of anaerobic infection caused by bacteroides and other anaerobes that often participate in mixed infections. Clindamycin, sometimes in combination with an aminoglycoside or cephalosporin, is used to treat penetrating wounds of the abdomen and the gut infections originating in the female genital tract, eg, septic abortion and pelvic abscesses and aspiration pneumonia. Clindamycin is now recommended rather than erythromycin for prophylaxis of endocarditis in patients with valvular heart disease who are undergoing certain dental procedures. Clindamycin plus primaquine is an effective alternative to trimethoprim-sulfamethoxazole for moderate to moderately severe Pneumocystis jiroveci pneumonia in AIDS patients. It is also used in combination with pyrimethamine for AIDS-related toxoplasmosis of the brain. 

Selective oxidation of alcohols. The procedure of David and Thieffry has been employed for selective oxidation of the 4-hydroxyl group in the tetrad 1, a key intermediate in the synthesis of the aminoglycoside antibiotic spectinomycin (3). 

Factors 4 and 4 are 6"-0-carbamoylkanamycin B aad kanamycin B. respectively factors 5 and 6 arc 6"-0-ar-bamoyltobramycin and tobramycin and factor 2 is upni-mycin, a tetracyclic aminoglycoside with an unu.sual bicyclic central ring structure. Kanamycin B and tobramycin probably do not occur in fermentation broths per sc but are fonned by hydrolysis of the 6-0"-carbamoy I derivatives in the isolation procedure. 

During tliis synthetic work, Umezawa developed several tecluiiques for the selective protection of hydroxy 1 and amino groups in aminoglycosides. These include the carbamate - and zinc-chelate protection of kanamycins, developed in collaboration with Tsucliiya and Takagi. The latter procedure became crucial for the industrial production of amikacin from kanamycin A and arbekacin (habekacin) from dibekacin. 

---