14.5 Drug resistance  (Page 4/9)

Vancomycin-resistant enterococci and Staphylococcus aureus

Vancomycin is only effective against gram-positive organisms, and it is used to treat wound infections, septic infections, endocarditis, and meningitis that are caused by pathogens resistant to other antibiotics. It is considered one of the last lines of defense against such resistant infections, including MRSA. With the rise of antibiotic resistance in the 1970s and 1980s, vancomycin use increased, and it is not surprising that we saw the emergence and spread of vancomycin-resistant enterococci (VRE) , vancomycin-resistant S. aureus (VRSA) , and vancomycin-intermediate S. aureus (VISA) . The mechanism of vancomycin resistance among enterococci is target modification involving a structural change to the peptide component of the peptidoglycan subunits, preventing vancomycin from binding. These strains are typically spread among patients in clinical settings by contact with health-care workers and contaminated surfaces and medical equipment.

VISA and VRSA strains differ from each other in the mechanism of resistance and the degree of resistance each mechanism confers. VISA strains exhibit intermediate resistance, with a minimum inhibitory concentration (MIC) of 4–8 μg/mL, and the mechanism involves an increase in vancomycin targets. VISA strains decrease the crosslinking of peptide chains in the cell wall, providing an increase in vancomycin targets that trap vancomycin in the outer cell wall. In contrast, VRSA strains acquire vancomycin resistance through horizontal transfer of resistance genes from VRE, an opportunity provided in individuals coinfected with both VRE and MRSA. VRSA exhibit a higher level of resistance, with MICs of 16 μg/mL or higher. Centers for Disease Control and Prevention. “Healthcare-Associated Infections (HIA): General Information about VISA/VRSA.” http://www.cdc.gov/HAI/organisms/visa_vrsa/visa_vrsa.html. Accessed June 2, 2016. In the case of all three types of vancomycin-resistant bacteria, rapid clinical identification is necessary so proper procedures to limit spread can be implemented. The oxazolidinones like linezolid are useful for the treatment of these vancomycin-resistant, opportunistic pathogens, as well as MRSA.

Extended-spectrum β-lactamase–producing gram-negative pathogens

Gram-negative pathogens that produce extended-spectrum β-lactamases (ESBLs) show resistance well beyond just penicillins. The spectrum of β-lactams inactivated by ESBLs provides for resistance to all penicillins , cephalosporins , monobactams , and the β-lactamase-inhibitor combinations, but not the carbapenems . An even greater concern is that the genes encoding for ESBLs are usually found on mobile plasmids that also contain genes for resistance to other drug classes (e.g., fluoroquinolones , aminoglycosides , tetracyclines ), and may be readily spread to other bacteria by horizontal gene transfer . These multidrug-resistant bacteria are members of the intestinal microbiota of some individuals, but they are also important causes of opportunistic infections in hospitalized patients, from whom they can be spread to other people.