Antibiotic Resistance

Methicillin-Resistant Staphylococcus Aureus

MRSA was first identified five decades ago.Since then, MRSA infections have spread worldwide, appearing at a high incidence in several countries in Europe, the Americas, and the Asia-Pacific region.MRSA infections can be very serious and are among the most frequently occurring of all antibiotic-resistant threats. In the U.S., 11,285 deaths per year have been attributed to MRSA alone.

MRSA is resistant to penicillin-like beta-lactam antibiotics. However, a number of drugs still retain activity against MRSA, including glycopeptides (e.g., vancomycin and teicoplanin), linezolid, tigecycline, daptomycin, and even some new beta-lactams, such as ceftaroline and ceftobiprole. However, MRSA has shown outstanding versatility at emerging and spreading in different epidemiological settings over time (in hospitals, the community, and, more recently, in animals). This compounds the epidemiology of MRSA infections and creates a challenge for infection-control systems that focus only on health care–associated infections (HAIs). Moreover, although resistance to anti-MRSA agents usually occurs through bacterial mutation, there have been reports of the transfer of resistance to linezolid and glycopeptide antibiotics, which is cause for major concern.

Fortunately, the incidence of HAI MRSA infections seems to be declining, since aggressive preventive hygiene measures in hospitals in some areas (i.e., the Netherlands and United Kingdom) have had a positive effect.Between 2005 and 2011, overall rates of invasive MRSA dropped 31%; the largest declines (around 54%) were observed in HAIs. This outcome provides evidence that infection control can be highly effective at limiting the spread of MRSA. However, during the past decade, rates of community-acquired MRSA infections have increased rapidly among the general population. While there is some evidence that these increases are slowing, they are not following the same downward trends that have been observed for hospital-acquired MRSA infections.

Vancomycin-Resistant Enterococci

VRE presents a major therapeutic challenge. Enterococci cause a wide range of illnesses, mostly among patients in hospitals or other health care settings, including bloodstream, surgical-site, and urinary tract infections. VRE infections, often caused by Enterococcus faecium and less frequently by Enterococcus faecalis, have a lower prevalence and epidemiological impact than MRSA does worldwide, except for the U.S. and some European countries.An estimated 66,000 HAI Enterococci infections occur in the U.S. each year.The proportion of infections that are vancomycin-resistant depends on the species.Overall, 20,000 (30%) of hospital-acquired enterococcal infections per year are vancomycin-resistant, leading to 1,300 deaths.

Few antimicrobial options are available to treat VRE.Antibiotics used against VRE include linezolid and quinupristin/dalfopristin, while the role of daptomycin and tigecycline needs to be further defined. VRE remains a major threat; consequently there is tremendous interest in developing novel drugs that could have bactericidal activity against VRE, such as oritavancin.

Drug-Resistant Streptococcus pneumoniae

1. pneumoniaecan cause serious and sometimes life- threatening infections.It is a major cause of bacterial pneumonia and meningitis, as well as bloodstream, ear, and sinus infections. Resistant S. pneumoniaeinfections complicate medical treatment, resulting in nearly 1.2 million illnesses and 7,000 deaths per year. The majority of these cases and deaths occur among adults 50 years of age or older, with the highest rates among those 65 years of age or older.S. pneumoniae has developed resistance to drugs in the penicillin class and erythromycins, such as amoxicillin and azithromycin, respectively. It has also developed resistance to less commonly used drugs.In 30% of severe S. pneumoniae cases, the bacteria are fully resistant to one or more clinically relevant antibiotics.

Fortunately, a new version of pneumococcal conjugate vaccine (PCV13), introduced in 2010, protects against infections caused by the most resistant pneumococcus strains, so rates of resistant S. pneumoniae infections are declining.From 2000 to 2009, an earlier pneumococcal conjugate vaccine, PCV7, provided protection against seven pneumococcal strains, but PCV13 expanded this protection to 13 strains. Use of this vaccine has not only prevented pneumococcal disease, it has also reduced antibiotic resistance by blocking the transmission of resistant S. pneumoniae strains.

Drug-Resistant Mycobacterium Tuberculosis

Drug-resistant M. tuberculosis infections are a serious threat in the U.S., and an even more urgent threat worldwide. The WHO reported that in 2012, 170,000 people died from drug-resistant tuberculosis (TB) infections. M. tuberculosis is most commonly spread through the air. Infections caused by this bacterium can occur anywhere in the body but most often appear in the lungs. Of a total of 10,528 TB cases reported in the U.S. in 2011, antibiotic resistance was identified in 1,042, or 9.9%. The major factors driving TB drug resistance are incomplete, incorrect, or unavailable treatment and a lack of new drugs.

In most instances, TB infections are treatable and curable with available first-line drugs, such as isoniazid or rifampicin; however, in some cases, M. tuberculosis can be resistant to one or more of these first-line drugs. Treatment of drug-resistant TB can be complex, requiring longer treatment periods and more expensive drugs that often have more side effects. Extensively drug-resistant TB (XDR-TB) is resistant to most TB drugs, including isoniazid and rifampicin, any fluoroquinolones, and any of the three second-line injectable drugs (i.e., amikacin, kanamycin, and capreomycin); therefore, fewer treatment options are available for patients with XDR-TB, and the drugs that are available are much less effective. Although drug-resistant TB and XDR-TB infections are an increasing threat worldwide, these infections are uncommon in the U.S. because of the implementation of a robust TB infection prevention and management program.

Carbapenem-Resistant Enterobacteriaceae (CRE)

Carbapenem-resistant Enterobacteriaceae (CRE) are a group of bacteria that have become resistant to “all or nearly all” available antibiotics, including carbapenems, which are typically reserved as the “treatment of last resort” against drug-resistant pathogens. An enzyme called New Delhi metallo-beta-lactamase (NDM-1) is present in some gram-negative Enterobacteriaceae bacteria (notably Escherichia coli and K. pneumoniae) that makes them resistant to virtually all beta-lactams, including carbapenems.

Untreatable or difficult-to-treat infections due to CRE bacteria are on the rise among patients in medical facilities. An estimated 140,000 health care–associated Enterobacteriaceae infections occur in the U.S. each year; 9,300 of these are caused by CRE.Each year, approximately 600 deaths result from infections caused by the two most common types of CRE, carbapenem-resistant Klebsiella species and carbapenem-resistant E. coli.

MDR Pseudomonas Aeruginosa

1. aeruginosais a common cause of HAIs, including pneumonia and bloodstream, urinary tract, and surgical-site infections. More than 6,000 (13%) of the 51,000 health care–associated P. aeruginosainfections that occur in the U.S. each year are MDR. Roughly 400 deaths per year are attributed to these infections.Some strains of MDR P. aeruginosa have been found to be resistant to nearly all antibiotics, including aminoglycosides, cephalosporins, fluoroquinolones, and carbapenems.

MDR Acinetobacter

Acinetobacter is a gram-negative bacterium that causes pneumonia or bloodstream infections, especially in critically ill patients on mechanical ventilation. Some Acinetobacter species have become resistant to all or nearly all antibiotics, including carbapenems, which are often considered to be the drug of last resort. About 12,000 health care–acquired Acinetobacter infections occur in the U.S. each year, and 7,300 (63%) of these are MDR (resistant to at least three different classes of antibiotics), causing 500 deaths per year.

ESBL-Producing Enterobacteriaceae

Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae carry a broad-spectrum beta-lactamase enzyme that enables them to become resistant to a wide variety of penicillin and cephalosporin antibiotics. ESBL-producing Enterobacteriaceae cause 26,000 HAIs and 1,700 deaths per year. Some ESBL-producing Enterobacteriaceae are resistant to nearly all antibiotics in the penicillin and cephalosporin classes.In such cases, the remaining treatment option is an antibiotic from the carbapenem family. However, these drugs should be used with caution, since use contributes to resistance.

Drug-resistant Neisseria gonorrhoeae

In recent years, drug-resistant forms of N. gonorrhoeae, the causative agent for the sexually transmitted disease gonorrhea, have begun to emerge in the U.S.¹ Gonorrhea is characterized by discharge and inflammation of the urethra, cervix, pharynx, or rectum. While not normally fatal, gonorrhea spreads easily and can cause severe complications in reproductive functions. The CDC estimates that more than 800,000 cases of gonorrhea occur annually, making it the second-most-frequently reported infectious disease in the U.S. Should drug-resistant N. gonorrhoeae become more widespread, it has been estimated that it would cause 75,000 additional cases of pelvic inflammatory disease, 15,000 cases of epididymitis, and 222 additional human immunodeficiency virus infections over a projected 10-year period.

Cephalosporin-resistant N. gonorrhoeae is often resistant to other types of antibiotics, such as fluoroquinolones, tetracyclines, and penicillins. Infections caused by these bacteria will therefore likely fail empiric treatment regimens. In response to this challenge, the CDC has updated its treatment guidelines to recommend ceftriaxone, plus either azithromycin or doxycycline, as the first-line treatment for gonorrhea.