Newer antibiotics potent weapons

Aruba - Newer antibiotics with novel mechanisms of action offer activity against drug-resistant gram-positive organisms and are important additions to the dermatologist's therapeutic arsenal for treating cutaneous infections, according to Bernardo Vainrub, M.D., consultant in internal medicine and infectious diseases, Hospital de Clinicas, Caracas, Venezuela.

"Staphylococci and streptococci are the most common causes of skin and soft tissue infections. However, there has been a shift in the antimicrobial susceptibility of those gram-positive pathogens, with increasing development of resistance to the usual first-line treatment options, even in community-acquired infections, as well as an alarming increase in vancomycin resistance," said Dr. Vainrub, who spoke at the Caribbean Dermatology Symposium here. "While initial treatment may be chosen empirically based on clinical and morphologic clues that suggest the etiologic cause of infection, culture and sensitivity may be important to determine the specific pathogen and the appropriate treatment for eradicating the infection and preventing further development of resistance."

Newer antibiotics The newer antibiotics are useful for treating infections caused by resistant, gram-positive organisms. These drugs include the streptogramins quinupristin and dalfopristin, which are available in a combination product (Synercid, Monarch Pharmaceuticals), the oxazolidinedione linezolid (Zyvox, Pfizer) and the newer-generation fluoroquinolones: moxifloxacin (Avelox, Bayer) and gatifloxacin (Tequin, Bristol-Myers Squibb).

Study results Results from in vitro studies indicate that quinupristin/dalfopristin also covers Streptococcus pneumoniae, including resistant strains, as well as some other important gram-positive, anaerobic and atypical organisms, including Bacteroides fragilis, Moraxella sp., meningococci, Mycoplasma pneumoniae, and Legionella sp. However, the combination is not effective against E. faecalis or gram-negative bacteria.

Both quinupristin and dalfopristin are converted in vivo to metabolites that also have antimicrobial activity. There is low urinary excretion (20 percent) of the parent drugs and their metabolites so that no dosing modification is needed for patients with renal impairment.

"However, adverse events are common with quinupristin/dalfopristin and it is associated with a number of drug interactions. Those features and prudent use to avoid promoting microbial resistance must be taken into account in decisions to use this potent antimicrobial agent," Dr. Vainrub says.

Side effects Administration-related side effects, including local pain, phlebitis and thrombophlebitis, are very common when treatment is administered via a peripheral vein.

"Diluting the antibiotic in a larger volume of fluid or administering treatment via a central line may be helpful for reducing the venous adverse events," he notes.

In addition, 30 percent of patients treated with quinupristin/dalfopristin have developed mild to moderate myalgias and/or arthralgias and 5 percent of patients have had an elevated direct bilirubin on laboratory testing.

Drug interactions with quinupristin/dalfopristin are a result of the antibiotic's inhibition of the cytochrome P450 3A4 isoenzyme. Careful therapeutic drug-level monitoring is needed with concomitantly administered protease inhibitors, midazolam, diazepam, nifedipine and cyclosporine. Amlodipine, statins, caffeine, ergotamine and macrolides should be avoided due to the risk for QTc interval prolongation.