Organisms::Antimicrobial resistance


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Staphylococcus aureus


Staphylococcus aureus (colloquially known as "Staph aureus" or a "Staph infection") is one of the major resistant pathogens. Found on the mucous membranes and the human skin of around a third of the population, it is extremely adaptable to antibiotic pressure. It was one of the earlier bacteria in which penicillin resistance was found—in 1947, just four years after the drug started being mass-produced. Methicillin was then the antibiotic of choice, but has since been replaced by oxacillin due to significant kidney toxicity. Methicillin-resistant Staphylococcus aureus (MRSA) was first detected in Britain in 1961, and is now "quite common" in hospitals. MRSA was responsible for 37% of fatal cases of sepsis in the UK in 1999, up from 4% in 1991. Half of all S. aureus infections in the US are resistant to penicillin, methicillin, tetracycline and erythromycin.

This left vancomycin as the only effective agent available at the time. However, strains with intermediate (4–8 μg/ml) levels of resistance, termed glycopeptide-intermediate Staphylococcus aureus (GISA) or vancomycin-intermediate Staphylococcus aureus (VISA), began appearing in the late 1990s. The first identified case was in Japan in 1996, and strains have since been found in hospitals in England, France and the US. The first documented strain with complete (>16 μg/ml) resistance to vancomycin, termed vancomycin-resistant Staphylococcus aureus (VRSA) appeared in the United States in 2002.<ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> However, in 2011, a variant of vancomycin has been tested that binds to the lactate variation and also binds well to the original target, thus reinstating potent antimicrobial activity.<ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref>

A new class of antibiotics, oxazolidinones, became available in the 1990s, and the first commercially available oxazolidinone, linezolid, is comparable to vancomycin in effectiveness against MRSA. Linezolid-resistance in S. aureus was reported in 2001.<ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref>

Community-acquired MRSA (CA-MRSA) has now emerged as an epidemic that is responsible for rapidly progressive, fatal diseases, including necrotizing pneumonia, severe sepsis, and necrotizing fasciitis.<ref name="pmid17146447">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> MRSA is the most frequently identified antimicrobial drug-resistant pathogen in US hospitals. The epidemiology of infections caused by MRSA is rapidly changing. In the past 10 years,{{ safesubst:#invoke:Unsubst||$N=When |date=__DATE__ |$B= {{#invoke:Category handler|main}}[when?] }} infections caused by this organism have emerged in the community. The two MRSA clones in the United States most closely associated with community outbreaks, USA400 (MW2 strain, ST1 lineage) and USA300, often contain Panton-Valentine leukocidin (PVL) genes and, more frequently, have been associated with skin and soft tissue infections. Outbreaks of CA-MRSA infections have been reported in correctional facilities, among athletic teams, among military recruits, in newborn nurseries, and among men that have sex with men. CA-MRSA infections now appear endemic in many urban regions and cause most CA-S. aureus infections.<ref name="pmid17479885">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref>

Streptococcus and Enterococcus

Streptococcus pyogenes (Group A Streptococcus: GAS) infections can usually be treated with many different antibiotics. Early treatment may reduce the risk of death from invasive group A streptococcal disease. However, even the best medical care does not prevent death in every case. For those with very severe illness, supportive care in an intensive-care unit may be needed. For persons with necrotizing fasciitis, surgery often is needed to remove damaged tissue.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Strains of S. pyogenes resistant to macrolide antibiotics have emerged; however, all strains remain uniformly susceptible to penicillin.<ref name="pmid15109426">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref>

Resistance of Streptococcus pneumoniae to penicillin and other beta-lactams is increasing worldwide. The major mechanism of resistance involves the introduction of mutations in genes encoding penicillin-binding proteins. Selective pressure is thought to play an important role, and use of beta-lactam antibiotics has been implicated as a risk factor for infection and colonization. S. pneumoniae is responsible for pneumonia, bacteremia, otitis media, meningitis, sinusitis, peritonitis and arthritis.<ref name="pmid15109426"/>

Multidrug-resistant Enterococcus faecalis and Enterococcus faecium are associated with nosocomial infections.<ref name="pmid18947320">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> Among these strains, penicillin-resistant Enterococcus was seen in 1983, vancomycin-resistant Enterococcus in 1987, and linezolid-resistant Enterococcus in the late 1990s.{{ safesubst:#invoke:Unsubst||date=__DATE__ |$B= {{#invoke:Category handler|main}}{{#invoke:Category handler|main}}[citation needed] }}

Pseudomonas aeruginosa

Pseudomonas aeruginosa is a highly prevalent opportunistic pathogen. One of the most worrisome characteristics of P. aeruginosa is its low antibiotic susceptibility, which is attributable to a concerted action of multidrug efflux pumps with chromosomally encoded antibiotic resistance genes (e.g., mexAB-oprM, mexXY) and the low permeability of the bacterial cellular envelopes.<ref name="Poole2004">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> Pseudomonas aeruginosa has the ability to produce 4-hydroxy-2-alkylquinolines (HAQs) and it has been found that HAQs have prooxidant effects, and overexpressing modestly increased susceptibility to antibiotics. The study experimented with the Pseudomonas aeruginosa biofilms and found that a disruption of relA and spoT genes produced an inactivation of the Stringent response (SR) in cells with nutrient limitation, which provides cells be more susceptible to antibiotics.<ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref>

Clostridium difficile

Clostridium difficile is a nosocomial pathogen that causes diarrheal disease in hospitals world wide.<ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref><ref name=McDonald_2005>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref>

C. difficile colitis is most strongly associated with fluoroquinolones, cephalosporins, carbapenems, and clindamycin.<ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref><ref name="pmid17072575">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref><ref name="pmid16156323">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref>

Some research suggests the overuse of antibiotics in the raising of livestock is contributing to outbreaks of bacterial infections such as C. difficile.[16]

Antibiotics, especially those with a broad activity spectrum (such as clindamycin) disrupt normal intestinal flora. This can lead to an overgrowth of C. difficile, which flourishes under these conditions. Pseudomembranous colitis can follow, creating generalized inflammation of the colon and the development of "pseudomembrane", a viscous collection of inflammatory cells, fibrin, and necrotic cells.[4] Clindamycin-resistant C. difficile was reported as the causative agent of large outbreaks of diarrheal disease in hospitals in New York, Arizona, Florida and Massachusetts between 1989 and 1992.<ref name=Johnson1999>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> Geographically dispersed outbreaks of C. difficile strains resistant to fluoroquinolone antibiotics, such as ciprofloxacin and levofloxacin, were also reported in North America in 2005.<ref name=Loo_2005>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref>

Salmonella and E. coli

Infection with Escherichia coli and Salmonella can result from the consumption of contaminated food and water. Both of these bacteria are well known for causing nosocomial (hospital-linked) infections, and often, these strains found in hospitals are antibiotic resistant due to adaptations to wide spread antibiotic use.<ref name=Davies2010>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> When both bacteria are spread, serious health conditions arise. Many people are hospitalized each year after becoming infected, with some dying as a result. Since 1993, some strains of E. coli have become resistant to multiple types of fluoroquinolone antibiotics.{{ safesubst:#invoke:Unsubst||date=__DATE__ |$B= {{#invoke:Category handler|main}}{{#invoke:Category handler|main}}[citation needed] }}

Although mutation alone plays a huge role in the development of antibiotic resistance, a 2008 study found that high survival rates after exposure to antibiotics could not be accounted for by mutation alone.<ref name=Adam2008>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> This study focused on the development of resistance in E. coli to three antibiotic drugs: ampicillin, tetracycline, and nalidixic acid. The researchers found that some antibiotic resistance in E. coli developed due to epigenetic inheritance rather than by direct inheritance of a mutated gene. This was further supported by data showing that reversion to antibiotic sensitivity was relatively common as well. This could only be explained by epigenetics.<ref name="Adam2008"/> Epigenetics is a type of inheritance in which gene expression is altered rather than the genetic code itself. There are many modes by which this alteration of gene expression can occur, including methylation of DNA and histone modification; however, the important point is that both inheritance of random mutations and epigenetic markers can result in the expression of antibiotic resistance genes.<ref name="Adam2008"/>

Acinetobacter baumannii

On November 5, 2004, the Centers for Disease Control and Prevention (CDC) reported an increasing number of Acinetobacter baumannii bloodstream infections in patients at military medical facilities in which service members injured in the Iraq/Kuwait region during Operation Iraqi Freedom and in Afghanistan during Operation Enduring Freedom were treated. Most of these showed multidrug resistance (MRAB), with a few isolates resistant to all drugs tested.<ref name="pmid15549020">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Klebsiella pneumoniae

Klebsiella pneumoniae carbapenemase (KPC)-producing bacteria are a group of emerging highly drug-resistant Gram-negative bacilli causing infections associated with significant morbidity and mortality whose incidence is rapidly increasing in a variety of clinical settings around the world. Klebsiella pneumoniae includes numerous mechanisms for antibiotic resistance, many of which are located on highly mobile genetic elements.<ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> Carbapenem antibiotics (heretofore often the treatment of last resort for resistant infections) are generally not effective against KPC-producing organisms.<ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref>

Mycobacterium tuberculosis

Tuberculosis is increasing across the globe, especially in developing countries, over the past few years. TB resistant to antibiotics is called MDR TB (Multidrug Resistant TB). Globally, MDR TB causes 150,000 deaths annually.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The rise of the HIV/AIDS epidemic has contributed to this.<ref name="">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref>

TB was considered one of the most prevalent diseases, and did not have a cure until the discovery of Streptomycin by Selman Waksman in 1943.<ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> However, the bacteria soon developed resistance. Since then, drugs such as isoniazid and rifampin have been used. M. tuberculosis develops resistance to drugs by spontaneous mutations in its genomes. Resistance to one drug is common, and this is why treatment is usually done with more than one drug. Extensively Drug-Resistant TB (XDR TB) is TB that is also resistant to the second line of drugs.<ref name=""/><ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref>

Resistance of Mycobacterium tuberculosis to isoniazid, rifampin, and other common treatments has become an increasingly relevant clinical challenge. (For more on Drug-Resistant TB, visit the Multi-drug-resistant tuberculosis page.) Evidence is lacking for whether these bacteria have plasmids.<ref name=pmid2115217>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> Also M. tuberculosis lack the opportunity to interact with other bacteria in order to share plasmids.<ref name=pmid2115217/><ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref>

Neisseria gonorrhoeae

{{#invoke:main|main}} Neisseria gonorrhoeae is a sexually transmitted pathogen that can cause pelvic pain, pain on urination, penile and vaginal discharge, as well as systemic symptoms. The bacteria was first identified in 1879,<ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> although some Biblical scholars believe that references to the disease can be found as early as Parshat Metzora of the Old Testament.<ref>{{#invoke:citation/CS1|citation |CitationClass=book }}</ref>

In the 1940s effective treatment with penicillin became available, but by the 1970s resistant strains predominated. Resistance to penicillin has developed through two mechanisms: chomasomally mediated resistance (CMRNG) and penicillinase-mediated resistance (PPNG). CMRNG involves stepwise mutation of penA, which codes for the penicilin-binding protein (PBP-2); mtr, which encodes an efflux pump to remove penicilin from the cell; and penB, which encodes the bacterial cell wall porins. PPNG involves the acquisition of a plasmid-borne beta-lactamase.<ref name="Tapsall 2001">Tapsall (2001) Antimicrobial resistance in Niesseria gonorrhoeae. World Health Organization.</ref>

Fluoroquinolones were a useful next-line treatment until resistance was achieved through efflux pumps and mutations to the gyrA gene, which encodes DNA gyrase.<ref name="Tapsall 2001"/> Third-generation cephalosporins have been used to treat gonorrhoea since 2007, but resistant strains have emerged. Strains of Neisseria gonorrhoea have also been found to be resistant to tetracyclines and aminoglycosides. Neisseria gonorrheoea has a high affinity for horizontal gene transfer, and as a result, the existence of any strain resistant to a given drug could spread easily across strains.

As of 2010, the recommended treatment is a single 250 mg intramuscular injection of ceftriaxone, sometimes in combination with azithromycin or doxycycline.<ref name=Japan10>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref><ref name=MMWR2012>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref>


Specific antiviral drugs are used to treat some viral infections. These drugs prevent viruses from reproducing by inhibiting essential stages of the virus's replication cycle in infected cells. Antivirals are used to treat HIV, hepatitis B, hepatitis C, influenza, herpes viruses including varicella zoster virus, cytomegalovirus and Epstein-Barr virus. With each virus, some strains have become resistant to the administered drugs.<ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref>

Resistance to HIV antivirals is problematic, and even multi-drug resistant strains have evolved.<ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> Resistant strains of the HIV virus emerge rapidly if only one antiviral drug is used.<ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> Using three or more drugs together has helped to control this problem, but new drugs are needed because of the continuing emergence of drug-resistant HIV strains.<ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref>


Infections by fungi are a cause of high morbidity and mortality in immunocompromised persons, such as those with HIV/AIDS, tuberculosis or receiving chemotherapy.<ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> The fungi candida, Cryptococcus neoformans and Aspergillus fumigatus cause most of these infections and antifungal resistance occurs in all of them.<ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> Multidrug resistance in fungi is increasing because of the widespread use of antifungal drugs to treat infections in immunocompromised individuals.<ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref>


The protozoan parasites that cause the diseases malaria, trypanosomiasis, toxoplasmosis, cryptosporidiosis and leishmaniasis are important human pathogens.<ref name="pmid25057459">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref>

Malarial parasites that are resistant to the drugs that are currently available to infections are common and this has led to increased efforts to develop new drugs.<ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> Resistance to recently developed drugs such as artemisinin has also been reported. The problem of drug resistance in malaria has driven efforts to develop vaccines.<ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref>

Trypanosomes are parasitic protozoa that cause African trypanosomiasis and Chagas disease (American trypanosomiasis).<ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref><ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> There are no vaccines to prevent these infections so drugs such as pentamidine and suramin, benznidazole and nifurtimox and used to treat infections. These drugs are effective but infections caused by resistant parasites have been reported.<ref name="pmid25057459"/>

Leishmaniasis is caused by protozoa and is an important public health problem worldwide, especially in sub-tropical and tropical countries. Drug resistance has "become a major concern".<ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref>

Antimicrobial resistance sections
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