Commentary on “The Impact of Anti-Infective Drug Shortages on Hospitals in the United States: Trends and Causes”

Clinical Infectious Diseases, Mar 2012

Ira Leviton

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Commentary on “The Impact of Anti-Infective Drug Shortages on Hospitals in the United States: Trends and Causes”

Ira Leviton () 0 1 0 Received 2 November 2011; accepted 8 November 2011; electronically published 19 January 2012. Diseases, Montefiore Hospital , 111 E 210th St, Bronx, NY 10467 1 Division of Infectious Diseases, Montefiore Hospital , Bronx , New York Griffith et al [1] comprehensively review the problem of drug shortages as they pertain to antimicrobial agents and the treatment of infectious diseases, and they highlight an extremely important problem in the everyday clinical practice of infectious disease specialists and many other types of physicians, from surgeons to internists, and critical care specialists to dermatologists. By doing a simple analysis of antimicrobial shortages, obtained from the Web site of the American Society of Health-System Pharmacists, they have brought to attention the frequent widespread lack of availability of antibiotics, and that this problem reflects trends in other pharmaceutical agents. They evaluate the variety of reasons for antibiotic shortages, provide examples, and, most importantly, point out how they can affect patient care, sometimes with serious consequences. Their analysis was little more than a listing of antimicrobial agents, reasons for each shortage, and the time periods - that the drugs were unavailable, but their investigation covered 20052010, a long enough time frame to evaluate trends and draw some conclusions. As they noted, while drug shortages in any pharmacologic area can be an inconvenience for pharmacists, clinicians, and others; lead to increased costs for patients, hospitals, and insurance companies; and have an easily discerned anecdotal impact on individual patients, it is difficult to systematically measure the resulting clinical problem or draw quantitative conclusions about differences in outcomes. Many broad clinical syndromes, such as pneumonia or various types of skin infections, can be treated with several antibiotics or combinations that are equally good. Guidelines published by the Infectious Diseases Society of America and other professional groups generally do not specify a single best antibiotic treatment for most diseases. Nearly all large prospective antimicrobial studies are done as noninferiority trials, in which the superiority of one antibiotic over another cannot be established. Sometimes a new antibiotic fails the test of noninferiority, so we know about some antibiotics to avoid in certain situations, such as daptomycin for pneumonia, because of its inactivation by pulmonary surfactant. Other antibiotics are not expected to work in certain clinical situations, such as bacteriostatic agents for endocarditis, and are also generally avoided. However, when clinicians are used to using a particular antibiotic for a commonly encountered clinical situation, and are then no longer able to use it because of a shortage, they may not select an equally good alternative. This may be due to lack of knowledge of the local antibiogram data, or even the lack of a recent local antibiogram, or for other reasons, and may be a particular problem for clinicians who do not use antimicrobials on a frequent, regular basis. As Griffith et al [1] point out, studies of several clinical syndromes have shown higher mortality when inadequate empiric treatment is used, so the choice of an empiric antibiotic with antimicrobial activity against the infecting bacteria is not merely an academic exercise. However, for diseases such as pneumonia or cellulitis, the infecting bacteria and their antimicrobial susceptibilities are usually not identified, so concluding with certainty that clinical failure was because of the selection of an incorrect antibiotic can be done only in a small subset of patients from whom a culture from a normally sterile site grows the causative bacteria. The initial antibiotic is frequently the only antibiotic unless a change is needed because of deterioration, lack of improvement, or other clinical reasons. On the other hand, for some infections, such as Lyme disease and syphilis, there is often a best antibiotic to use, which may depend on the stage of the illness or whether a patient needs an intravenous or an oral agent. In 2007, the lack of availability of penicillin G for neurosyphilis, with only anecdotal data for other antibiotics, forced the use of second-line agents such as ceftriaxone, which probably would have been used only if patients could not tolerate penicillin G had it been available. Differences in syphilis outcome as a rate of failure or lack of cure, or how many patients needed retreatment, were not studied, but there may have been some impact. Shortages of antimicrobials are different from those of pharmacologic agents that are used for the treatment of chronic diseases. For example, whereas statins or angiotensin-converting enzyme inhibitors may have slight differences in indications, many physicians consider them to be equivalent in common clinical situations such as the treatment of hypercholesterolemia or hypertension, respectively, and a substitution can be made for several weeks or months without an expected difference in clinical outcome, such as development of coronary plaques, strokes, or heart attacks due to high cholesterol or high blood pressure. With an acute bacterial infection, the effect of the selected pharmacologic agent over a short time frame has a much more direct and measurable effect on clinical outcome, and when bacteria grow from a culture, the accompanying susceptibility information can point to whether the right antibiotic was chosen. Drug shortages always seem to occur at a bad time, and the current problems bear this out. If it were the 1970s, one firstgeneration cephalosporin could simply be substituted for another that was not available, but most of the current shortages are not in the area of me too drugs, and the rising rates and types of bacterial resistance have additionally severely curtailed the available substitutions. Furthermore, the number of new antibiotics and classes with broad-spectrum antimicrobial activity have not kept up with the new breeds of multiresistant bacteria. Griffiths et al [1] did not comment on teaching of infectious diseases. This is also something that is difficult or perhaps impossible to quantify, but there is almost certainly an effect. The impact of antibiotic and other drug shortages go beyond the straightforward care of patients and influence the next generation of physicians and pharmacists. House staff at teaching hospitals learn both by being taught and by doingthe latter reinforcing the former. However, when house staff members are taught about 1 set of principles, facts, or drugs, and then have to do something else because the antibiotic they want to use is not available, such as amikacin for multidrug-resistant Gram-negative rod infections or streptomycin for gentamicinresistant enterococcal endocarditis, they are not getting the education and experience that they should be receiving. In some instances, they may be using a second-best treatment not because of a serious allergy but because of a drug shortage. Until there are significant changes in areas ranging from drug manufacturing regulations to the allocation of pharmaceutical resources, shortages of antimicrobials will persist and be unpredictable. For the benefit of our patients, all physicians should be prepared with alternative plans to treat without the full armamentarium of antimicrobials. Note Potential conflicts of interest. I. L. has been a consultant for Pfizer, and is on the speakers bureaus of Cubist, Forest, and Pfizer. The author has submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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Ira Leviton. Commentary on “The Impact of Anti-Infective Drug Shortages on Hospitals in the United States: Trends and Causes”, Clinical Infectious Diseases, 2012, 692-693, DOI: 10.1093/cid/cir942