Daptomycin: A Novel Cyclic Lipopeptide Antimicrobial
Gerard R. Barber, B.S.Pharm., M.P.H.
The infectious process consists of an epidemiologic triad of agent, host, and environment. Clinicians should always be mindful that the interaction among these three variables is never static. A scant three generations ago, the discovery of penicillin heralded the modern era of antibiotics. In recent decades, increasingly aggressive therapies and technical diagnostic procedures have yielded impressive benefits for patients. But what is their current influence on the epidemiologic triad?
This issue features a review of daptomycin, the first of a new class of antimicrobial agents, the cyclic lipopeptides. Since 2000, the only other novel antibacterial drug has been linezolid (an oxazolidenone). By the time this issue goes to press, telithromycin, of the new ketolides (derivatives of macrolides), will have been approved. Other than quinupristin-dalfopristin and cephalosporin derivatives of the penicillins, novel antibacterial classes have not been developed since the 1960s. Pharmaceutical companies cite such factors as overall cost, the inability to establish market dominance, and the lack of a sizable economic margin for the sluggishness of antimicrobial development.[1] Meanwhile, antimicrobial resistance, virulence, and other routes to pathogenesis (e.g., novel portals of entry for infectious agents through central venous access and shunts) continue to increase. Clearly, the microbes themselves have been anything but sluggish.
Intensive development of antimicrobials after World War II so effectively battled the great nemeses of the time, streptococci and staphylococci, that gram-negative infections grew dramatically. Most new agents brought to market since the 1960s combated those gram-negative pathogens, including the dreaded Pseudomonas aeruginosa. Many institutions have been witnessing a shift in infections from gram-negative to gram-positive, and many of the pathogens are increasingly resistant to our armamentarium. Another disturbing shift is the growing frequency of non- albicans Candida isolates. Patients coming to hospitals from long-term-care facilities in need of acute care are often colonized with or infected by drug-resistant organisms. The recent emergence of truly community-acquired drug-resistant isolates, such as methicillin-resistant Staphylococcus aureus causing infection among never-institutionalized, healthy hosts, is also troubling.
Given host risk factors and antimicrobial resistance patterns, it is impossible to avoid some negative selection pressure on microflora when choosing an antibiotic regimen. The widespread use of antimicrobials to control infection and promote growth in livestock and pets further complicates the epidemio-logic triad's variables and is a topic of increasing scientific and political debate. The last two years saw the continued spread of the West Nile virus, the emergence of severe acute respiratory syndrome, an outbreak of avian influenza, cases of monkeypox, and the first U.S. case of mad cow disease. These infections challenge our reactive stance in treating disease, especially since our antiviral war chest is less full than our antibacterial one. Strong epidemiologic efforts to identify and understand causative agents, reservoirs, modes of transmission, and host susceptibility are needed to break the "chain of infection," as are proactive infection control and public health education.
It is curious how many clinicians aggressively pursue proper infection-control measures only under the pressures of an exotic infection or an epidemic. For example, clinicians in various disciplines consistently violate hand-washing guidelines.[2] Ignaz Semmelweis proved that hand washing reduced the risk of puerperal sepsis 150 years ago, before the antibiotic age and even before the discovery of microorganisms.
The release of a novel compound always brings with it hope and excitement. It should also stimulate, among pharmacists and other clinicians, a sense of profound professional responsibility. They should constantly ask questions. Is the drug being used for an appropriate indication? Is it appropriate for the patient? Is the dosage correct? Is the drug working or failing, and why? Are there any adverse effects beyond those listed in the package insert? Do culture and susceptibility test results and clinical findings dictate the use of another agent?
Pharmacists should keep abreast of relevant data on antimicrobial susceptibility and know the unique trends at their institution. They should initiate, maintain, and broaden communication among the departments of microbiology, epidemiology, infection control, and infectious diseases and other relevant specialties. The triad's variables -- agent, host, and environment -- are forces relevant to any health care discipline.
We'll keep making more antibiotics, but microbes will keep making more of themselves -- and adapting. So please wash your hands, vigorously and often.
References
- Wenzel RP. The antibiotic pipeline -- challenges, costs, and values. N Engl J Med. 2004; 351:523, 525.
- Pittet D, Simon A, Huggonnet S et al. Hand hygiene among physicians: performance, beliefs, and perceptions. Ann Intern Med. 2004; 141:1-8.