Infectious diseases remain the second leading cause of death worldwide. Despite numerous advances in the diagnosis, treatment, and prevention of infectious diseases, threats of antimicrobial resistance, and emerging/reemerging infectious diseases continue to pose challenges.
Multidrug resistance has been increasing in prevalence in recent years and differs among different geographical regions and among institutions in the same area. The overall prevalence of antimicrobial resistance is affected by reservoirs in the pt population, use of antimicrobial drugs that favor resistant strains, and transmission of resistant strains to pts from their environment or other persons (e.g., health care workers with poor hand hygiene).
The Centers for Disease Control and Prevention (CDC) has estimated that >2 million resistant bacterial infections occur in the United States each year, with 23,000 deaths, and has identified particular resistant pathogens that are of greatest concern, given their impact on public health (Table 80-1).
Bacteria circumvent the activity of antibacterial agents by mechanisms that generally fall into three categories: (1) alteration or bypassing of targets that exhibit reduced binding of the drug, (2) altered access of the drug to its target by reductions in uptake or increases in active efflux, and (3) a modification of the drug that reduces its activity (Table 80-2).
The CDC has emphasized four actions to address the growing problem of antimicrobial resistance: (1) prevent infections, (2) track resistance patterns, (3) improve use of existing antimicrobial agents, and (4) develop new antimicrobial drugs and diagnostic tests.
TABLE 80-1Antibiotic Resistance Threats in the United States, 2013 ||Download (.pdf) TABLE 80-1 Antibiotic Resistance Threats in the United States, 2013
|THREAT CATEGORY ||ORGANISMS |
|Urgent || |
Drug-resistant Neisseria gonorrhoeae
|Serious || |
Extended-spectrum β-lactamase–producing Enterobacteriaceae
Multidrug-resistant Pseudomonas aeruginosa
Drug-resistant nontyphoidal Salmonella
Drug-resistant Salmonella typhi
Methicillin-resistant Staphylococcus aureus
Drug-resistant Streptococcus pneumoniae
Drug-resistant Mycobacterium tuberculosis
|Concerning || |
Vancomycin-resistant S. aureus
Erythromycin-resistant group A Streptococcus
Clindamycin-resistant group B Streptococcus
TABLE 80-2The Most Common Mechanisms of Resistance to Antibacterial Agents ||Download (.pdf) TABLE 80-2 The Most Common Mechanisms of Resistance to Antibacterial Agents
|ANTIBACTERIAL AGENT(S) ||MAJOR TARGET ||MECHANISM(S) OF ACTION ||MECHANISM(S) OF RESISTANCE |
|β-Lactams (penicillins, cephalosporins, monobactams, carbapenems) ||Cell wall synthesis ||Bind cell-wall cross-linking enzymes (PBPs, transpeptidases) || |
Drug inactivation by β-lactamases
Altered PBP targets
Reduced diffusion through porin channels
|Glycopeptides and lipoglyco-peptides (vancomycin, teicoplanin, telavancin, dalbavancin, oritavancin) ||Cell wall synthesis || |
Block cell wall glycosyltransferases by binding D-Ala-D-Ala stem-peptide terminus
Teicoplanin, telavancin, dalbavancin, and oritavancin: affect membrane function
Altered D-Ala-D-Ala target (D-Ala-D-Lac)
Increased D-Ala-D-Ala target binding at sites distant from cell wall synthesis enzymes
|Bacitracin ||Cell wall synthesis ||Blocks lipid carrier of cell wall precursors ||Active drug efflux |
|Fosfomycin ||Cell ...|