commentary
MULTIPLE, EXTREMELY RESISTANT ORGANISMS: WHAT YOU NEED TO KNOW
BY OLADAPO A. ABODUNDE, MD; PAUL SOUTHERN, MD; AND JAMES P. LUBY, MD Defining the optimal approach to microbial drug resistance may be the Holy Grail. The global impact of drug resistance on morbidity, mortality, and related health care costs have all been well elucidated. Within the frame- work of the extensively studied mech- anisms of target modification, enzy- matic neutralization, entry channel modulation, and efflux mechanisms, human pathogenic bacteria, viruses, and fungi continue to evolve novel resistance mutations to available an- timicrobials. Important examples are the recently described MCR-1 gene in Escherichia coli and NDM-1 gene in Enterobacteriaceae. Multiple drug- resistant (MDR) and extensively drug- resistant pathogens are now among the most significant threats to human health, according to a study published in Clinical Infectious Diseases in 2010. Accepted approaches to the epi-
demic of multidrug-resistant patho- gens include direct (pharmacologic) and indirect (stewardship, etc.) meth- ods. For instance, a study published
in Clinical Infectious Diseases in 2011 suggested empirical combination therapy, pharmacokinetic/pharma- codynamic optimization, limiting du- ration of antimicrobial exposure, and active surveillance as core strategies for combating MDR infections in criti- cally ill patients. Use of alternative or second-line antibiotics, combination therapy, and development of new pharmacothera- peutic agents are the most important pharmacologic options available. With the need for alternative agents, sev- eral studies point to a resurgence in the use of older and often more tox- ic antimicrobials, including but not limited to the aminoglycosides and polymyxins. Synergistic antimicrobial (antibiotic-antibiotic or antibiotic-ad- juvant) prescribing, on the other hand, is predicated on targeting multiple steps in a single pathway, inhibiting multiple pathways, or using multiple agents to neutralize a single target, ac- cording to a 2013 study published in Trends in Biotechnology. Several novel alternatives to conventional microbial inhibition are currently experimental
and may not be ready for clinical use for several years, perhaps decades, as noted in a 2013 study published by F1000Prime Reports. Currently used methods are gener- ally effective but have limitations. Em- pirical therapy, especially in severe in- fections, is more challenging, leading many practitioners to resort to broad- spectrum antibiotics initially, promot- ing further drug resistance. Newer diagnostics, including mo-
lecular techniques, matrix-assisted laser desorption/ionization time-of- flight (MALDI-TOF), and others are promising for rapid identification and resistance testing and will likely miti- gate the widespread polypharmacy for empirical therapy besides aiding focused therapy, optimizing drug dos- ing and duration of treatment. Insti- tuting second-line agents after failed treatments is often associated with prolonged antibiotic exposure, there- by increasing risk of toxicity and de- velopment of opportunistic infections, especially Clostridium difficile, accord- ing to a study published in Clinical In- fectious Diseases in 2011.
The one thing we all can and should excel at is antimicrobial stewardship.
February 2017 TEXAS MEDICINE 17
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