Multiple drug resistance (MDR), multidrug resistance or multiresistance is antimicrobial resistance shown by a species of microorganism to multiple antimicrobial drugs. The types most threatening to public health are MDR bacteria that resist multiple antibiotics; other types include MDR viruses, fungi, and parasites (resistant to multiple antifungal, antiviral, and antiparasitic drugs of a wide chemical variety). Recognizing different degrees of MDR, the terms extensively drug resistant (XDR) and pandrug-resistant (PDR) have been introduced. The definitions were published in 2011 in the journal "Clinical Microbiology and Infection" and are openly accessible.

Antimicrobial resistance (AMR) is the ability of a microbe to resist the effects of medication previously used to treat them. The term includes the more specific "antibiotic resistance", which applies only to bacteria becoming resistant to antibiotics. Resistant microbes are more difficult to treat, requiring alternative medications or higher doses, both of which may be more expensive or more toxic. Microbes resistant to multiple antimicrobials are called multidrug resistant (MDR); or sometimes superbugs.

Resistance arises through one of three mechanisms: natural resistance in certain types of bacteria, genetic mutation, or by one species acquiring resistance from another. All classes of microbes can develop resistance: fungi develop antifungal resistance, viruses develop antiviral resistance, protozoa develop antiprotozoal resistance, and bacteria develop antibiotic resistance. Resistance can appear spontaneously because of random mutations; or more commonly following gradual buildup over time.

Preventive measures include only using antibiotics when needed, thereby stopping misuse of antibiotics or antimicrobials. Narrow-spectrum antibiotics are preferred over broad-spectrum antibiotics when possible, as effectively and accurately targeting specific organisms is less likely to cause resistance. For people who take these medications at home, education about proper use is essential. Health care providers can minimize spread of resistant infections by use of proper sanitation and hygiene, including handwashing and disinfecting between patients, and should encourage the same of the patient, visitors, and family members.

Rising drug resistance is caused mainly by use of antimicrobials in humans and other animals, and spread of resistant strains between the two. Antibiotics increase selective pressure in bacterial populations, causing vulnerable bacteria to die; this increases the percentage of resistant bacteria which continue growing. With resistance to antibiotics becoming more common there is greater need for alternative treatments. Calls for new antibiotic therapies have been issued, but new drug development is becoming rarer.

Antimicrobial resistance is on the rise. Estimates are that 700,000 to several million deaths result per year. Each year in the United States, at least 2 million people become infected with bacteria that are resistant to antibiotics and at least 23,000 people die as a result. There are public calls for global collective action to address the threat include proposals for international treaties on antimicrobial resistance. Worldwide antibiotic resistance is not fully mapped, but poorer countries with weak healthcare systems are more affected.

Carbapenem-resistant Enterobacteriaceae (CRE) or carbapenemase-producing Enterobacteriaceae (CPE) are Gram-negative bacteria that are resistant to the carbapenem class of antibiotics, considered the drugs of last resort for such infections. They are resistant because they produce an enzyme called a carbapenemase that disables the drug molecule. The resistance can vary from moderate to severe. Enterobacteriaceae are common commensals and infectious agents. Experts fear CRE as the new "superbug". The bacteria can kill up to half of patients who get bloodstream infections. Tom Frieden, former head of the Centers for Disease Control and Prevention has referred to CRE as "nightmare bacteria". Types of CRE are sometimes known as KPC (Klebsiella pneumoniae carbapenemase) and NDM (New Delhi Metallo-beta-lactamase). KPC and NDM are enzymes that break down carbapenems and make them ineffective. Both of these enzymes, as well as the enzyme VIM (Verona Integron-Mediated Metallo-β-lactamase) have also been reported in Pseudomonas.

Carbapenem-resistant Enterobacteriaceae (CRE) have been defined as carbapenem-nonsusceptible and extended-spectrum cephalosporin-resistant "Escherichia coli, Enterobacter aerogenes, Enterobacter cloacae" complex, "Klebsiella pneumoniae", or "Klebsiella oxytoca". Some exclude ertapenem resistance from the definition.

Drug resistance is the reduction in effectiveness of a medication such as an antimicrobial or an antineoplastic in curing a disease or condition. The term is used in the context of resistance that pathogens or cancers have "acquired", that is, resistance has evolved. Antimicrobial resistance and antineoplastic resistance challenge clinical care and drive research. When an organism is resistant to more than one drug, it is said to be multidrug-resistant. Even the immune system of an organism is in essence a drug delivery system, albeit endogenous, and faces the same arms race problems as external drug delivery.

The development of antibiotic resistance in particular stems from the drugs targeting only specific bacterial molecules (almost always proteins). Because the drug is "so" specific, any mutation in these molecules will interfere with or negate its destructive effect, resulting in antibiotic resistance. Furthermore there is mounting concern over the abuse of antibiotics in the farming of livestock, which in the European Union alone accounts for three times the volume dispensed to humans – leading to development of super-resistant bacteria.

Bacteria are capable of not only altering the enzyme targeted by antibiotics, but also by the use of enzymes to modify the antibiotic itself and thus neutralise it. Examples of target-altering pathogens are "Staphylococcus aureus", vancomycin-resistant enterococci and macrolide-resistant "Streptococcus", while examples of antibiotic-modifying microbes are "Pseudomonas aeruginosa" and aminoglycoside-resistant "Acinetobacter baumannii".

In short, the lack of concerted effort by governments and the pharmaceutical industry, together with the innate capacity of microbes to develop resistance at a rate that outpaces development of new drugs, suggests that existing strategies for developing viable, long-term anti-microbial therapies are ultimately doomed to failure. Without alternative strategies, the acquisition of drug resistance by pathogenic microorganisms looms as possibly one of the most significant public health threats facing humanity in the 21st century.

Resistance to chemicals is only one aspect of the problem, another being resistance to physical factors such as temperature, pressure, sound, radiation and magnetism, and not discussed in this article, but found at Physical factors affecting microbial life.

Antibiotic misuse, sometimes called antibiotic abuse or antibiotic overuse, refers to the misuse or overuse of antibiotics, with potentially serious effects on health. It is a contributing factor to the development of antibiotic resistance, including the creation of multidrug-resistant bacteria, informally called "super bugs": relatively harmless bacteria (such as staphylococcus, enterococcus and acinetobacter) can develop resistance to multiple antibiotics and cause life-threatening infections.

Strains of hVISA and VISA do not have resistant genes found in "Enterococcus" and the proposed mechanisms of resistance include the sequential mutations resulting in a thicker cell wall and the synthesis of excess amounts of D-ala-D-ala residues. VRSA strain acquired the vancomycin resistance gene cluster "vanA" from VRE.

The diagnosis of vancomycin-resistant Staphylococcus aureus can be done with disk diffusion(and VA screen plate)

Vancomycin-resistant "Enterococcus", or vancomycin-resistant enterococci (VRE), are bacterial strains of the genus "Enterococcus" that are resistant to the antibiotic vancomycin.

Once the individual has VRE, it is important to ascertain which "strain".

A quinolone antibiotic is any member of a large group of broad-spectrum bactericides that share a bicyclic core structure related to the compound 4-quinolone. They are used in human and veterinary medicine to treat bacterial infections, as well as in animal husbandry.

Nearly all quinolone antibiotics in modern use are fluoroquinolones, which contain a fluorine atom in their chemical structure and are effective against both Gram-negative and Gram-positive bacteria. One example is ciprofloxacin (Cipro), one of the most widely used antibiotics worldwide.

The WHO defines antimicrobial resistance as a microorganism's resistance to an antimicrobial drug that was once able to treat an infection by that microorganism.

A person cannot become resistant to antibiotics. Resistance is a property of the microbe, not a person or other organism infected by a microbe.

The Gonorrhea bacterium Neisseria gonorrhoeae has developed antibiotic resistance to many antibiotics.

The bacteria was first identified in 1879, although some Biblical scholars believe that references to the disease can be found as early as Parshat Metzora of the Old Testament.

In the 1940s effective treatment with penicillin became available, but by the 1970s resistant strains predominated. Resistance to penicillin has developed through two mechanisms: chromasomally mediated resistance (CMRNG) and penicillinase-mediated resistance (PPNG). CMRNG involves step wise mutation of penA, which codes for the penicillin-binding protein (PBP-2); mtr, which encodes an efflux pump that removes penicillin from the cell; and penB, which encodes the bacterial cell wall porins. PPNG involves the acquisition of a plasmid-borne beta-lactamase. "N. 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.

Fluoroquinolones were a useful next-line treatment until resistance was achieved through efflux pumps and mutations to the gyrA gene, which encodes DNA gyrase. Third-generation cephalosporins have been used to treat gonorrhoea since 2007, but resistant strains have emerged. As of 2010, the recommended treatment is a single 250 mg intramuscular injection of ceftriaxone, sometimes in combination with azithromycin or doxycycline. However, certain strains of "N. gonorrhoeae" can be resistant to antibiotics usually that are normally used to treat it. These include: cefixime (an oral cephalosporin), ceftriaxone (an injectable cephalosporin), azithromycin, aminoglycosides, and tetracycline.

Mycobacterium fortuitum is a nontuberculous species of the phylum actinobacteria (Gram-positive bacteria with high guanine and cytosine content, one of the dominant phyla of all bacteria), belonging to the genus mycobacterium.

Secondary peritonitis and intra-abdominal abscesses including splenic and hepatic abscesses generally occur because of the entry of enteric micro-organisms into the peritoneal cavity through a defect in the wall of the intestine or other viscus as a result of obstruction, infarction or direct trauma. Perforated appendicitis, diverticulitis, inflammatory bowel disease with perforation and gastrointestinal surgery are often associated with polymicrobial infections caused by aerobic and anaerobic bacteria, where the number of isolates can average 12 (two-thirds are generally anaerobes). The most common aerobic and facultative bacteria are "Escherichia coli", "Streptococcus" spp. (including Enterococcus spp.), and the most frequently isolated anaerobic bacteria are the "B. fragilis" group, "Peptostreptococcus" spp., and "Clostridium" spp.

Abdominal infections are characteristically biphasic: an initial stages of generalized peritonitis associated with "Escherichia coli" sepsis, and a later stages, in which intra abdominal abscesses harboring anaerobic bacteria ( including "B. fragilis" group ) emerge.

The clinical manifestations of secondary peritonitis are a reflection of the underlying disease process. Fever, diffuse abdominal pain, nausea and vomiting are common. Physical examination generally show signs of peritoneal inflammation, isuch as rebound tenderness, abdominal wall rigidity and decrease in bowel sounds. These early findings may be followed by signs and symptoms of shock.

Biliary tract infection is usually caused by "E. coli, Klebsiella" and "Enterococcus" spp. Anaerobes (mostly "B. fragilis" group, and rarely "C. perfringens") can be recovered in complicated infections associated with carcinoma, recurrent infection, obstruction, bile tract surgery or manipulation.

Laboratory studies show elevated blood leukocyte count and predominance of polymorphonuclear forms. Radiographs studies may show free air in the peritoneal cavity, evidence of ileus or obstruction and obliteration of the psoas shadow. Diagnostic ultrasound, gallium and CT scanning may detect appendiceal or other intra-abdominal abscesses. Polymicrobial postoperative wound infections can occur.

Treatment of mixed aerobic and anaerobic abdominal infections requires the utilization of antimicrobials effective against both components of the infection as well as surgical correction and drainage of pus. Single and easily accessible abscesses can be drained percutaneously.

Anaerobes are able to cause all types of intracranial infections. These often cause subdural empyema, and brain abscess, and rarely cause epidural abscess and meningitis. The origin of brain abscess is generally an adjacent chronic ear, mastoid, or sinus infection oropharynx, teeth or lungs. Mastoid and ear or infections generally progress to the temporal lobe or cerebellum, while facial sinusitis commonly causes frontal lobe abscess. Hematogenous spread of the infection into the CNS often occurs after oropharyngeal, dental, or pulmonary infection. Infrequently bacteremia originating of another location or endocarditis can also cause intracranial infection.

Meningitis due to anaerobic bacteria is infrequent and may follow respiratory tract infection or complicate a cerebrospinal fluid shunt. Nerological shunt infections are often caused by skin bacteria such as "Propionibacterium acnes", or in instances of ventriculoperitoneal shunts that perforate the gut, by anaerobes of enteric origin (i.e. "Bacteroides fragilis")."Clostridium perfringens" can cause of brain abscesses and meningitis following intracranial surgery or head trauma.

The anaerobes often isolated from brain abscesses complicating respiratory and dental infections are anaerobic Gram-negative bacilli (AGNB, including Prevotella, "Porphyromonas", Bacteroides), "Fusobacterium" and Peptostreptococcus spp. Microaerophilic and other streptococci are also often isolated. Actinomyces are rarely isolated.

At the stage of encephalitis, antimicrobial therapy and utilization of measures to lower the increase in the intracranial pressure can prevent the formation of an intracranial abscess However, after an abscess has emerged, surgical removal or drainage may be necessary, along with an extended course of antimicrobial therapy (4–8 weeks). Some advocate complete drainage of intracranial abscess, while others use repeated aspirations of the abscess., Repeated aspirations of an abscess are preferable in those with multiple abscesses or when the abscess is located in a predominate brain site. Administration of antimicrobials in a high-dose for an extended period of time can offer an alternative treatment strategy in this type of patients and may substitute for surgical evacuation of an abscess.

Because of the poor penetration of many antimicrobial agents through the blood–brain barrier, there are few agents available for the treatment of intracranial infections. The antimicrobials with good intracranial penetration are metronidazole, chloramphenicol, penicillins, and meropenem. Optimally, the selection of antimicrobial is done according to the recovered isolates and their antimicrobial susceptibilities. A substantial improvement in patients' survival rate has occurred after the introduction of computed tomography (CT) and other scans and utilization of metronidazole therapy.

Common multidrug-resistant organisms are usually bacteria:

- Vancomycin-Resistant Enterococci (VRE)

- Methicillin-Resistant "Staphylococcus" "aureus" (MRSA)

- Extended-spectrum β-lactamase (ESBLs) producing Gram-negative bacteria

- "Klebsiella" "pneumoniae" carbapenemase (KPC) producing Gram-negatives

- Multidrug-Resistant gram negative rods (MDR GNR) MDRGN bacteria such as "Enterobacter species", "E.coli", "Klebsiella pneumoniae", "Acinetobacter baumannii", "Pseudomonas aeruginosa"

A group of gram-positive and gram-negative bacteria of particular recent importance have been dubbed as the ESKAPE group ("Enterococcus faecium", "Staphylococcus aureus", "Klebsiella pneumoniae", "Acinetobacter baumannii", "Pseudomonas aeruginosa" and Enterobacter species).

- Multi-drug-resistant tuberculosis

Fluoroquinolones are often used for genitourinary infections and are widely used in the treatment of hospital-acquired infections associated with urinary catheters. In community-acquired infections, they are recommended only when risk factors for multidrug resistance are present or after other antibiotic regimens have failed. However, for serious acute cases of pyelonephritis or bacterial prostatitis where the patient may need to be hospitalised, fluoroquinolones are recommended as first-line therapy.

Due to sickle-cell disease patients' being at increased risk for developing osteomyelitis from the "Salmonella "genus, fluoroquinolones are the "drugs of choice" due to their ability to enter bone tissue without chelating it, as tetracyclines are known to do.

Fluoroquinolones are featured prominently in guidelines for the treatment of hospital-acquired pneumonia.

Totally drug-resistant tuberculosis (TDR-TB) is a generic term for tuberculosis strains that are resistant to a wider range of drugs than strains classified as extensively drug-resistant tuberculosis. TDR-TB has been identified in three countries; India, Iran, and Italy. The emergence of TDR-TB has been documented in four major publications. However, it is not yet recognised by the World Health Organization.

TDR-TB has resulted from further mutations within the bacterial genome to confer resistance, beyond those seen in XDR- and MDR-TB. Development of resistance is associated with poor management of cases. Drug resistance testing occurs in only 9% of TB cases worldwide. Without testing to determine drug resistance profiles, MDR- or XDR-TB patients may develop resistance to additional drugs. TDR-TB is relatively poorly documented, as many countries do not test patient samples against a broad enough range of drugs to diagnose such a comprehensive array of resistance. The United Nations' Special Programme for Research and Training in Tropical Diseases has set up a TDR Tuberculosis Specimen Bank to archive specimens of TDR-TB.

Gram-positive, nonmotile and acid-fast rods (1-3 µm x 0.2-0.4 µm). Sometimes long rods with occasional beaded or swollen cells having non-acid-fast ovoid bodies at one end.

Colony characteristics

- Smooth hemispheric colonies, usually off-white or cream colored. May be butyrous, waxy, multilobate and even rosette clustered (dilute inocula).

- On Malachite green containing media, such as Löwenstein-Jensen media, colonies can absorb the green dye.

Physiology

- Rapid growth on Löwenstein-Jensen media within 2–4 days.

- No growth at 45 °C, but grows on MacConkey agar.

Differential characteristics

- Differentiation from "M. fortuitum subsp. acetamidolyticum" by its ability to use L-glutamate and its inability to use acetamide as simultaneous nitrogen and carbon source. Both subspecies share an identical 5'-16S rDNA sequence. However, the ITS sequences are different.

Multi-drug-resistant tuberculosis (MDR-TB) is a form of tuberculosis (TB) infection caused by bacteria that are resistant to treatment with at least two of the most powerful first-line anti-TB medications (drugs), isoniazid and rifampin. Some forms of TB are also resistant to second-line medications, and are called extensively drug-resistant TB (XDR-TB).

Tuberculosis is caused by infection with the bacteria Mycobacterium tuberculosis. Almost one in four people in the world are infected with TB bacteria. Only when the bacteria become active do people become ill with TB. Bacteria become active as a result of anything that can reduce the person’s immunity, such as HIV, advancing age, diabetes or other immunocompromising illnesses. TB can usually be treated with a course of four standard, or first-line, anti-TB drugs (i.e., isoniazid, rifampin and any fluoroquinolone).

However, beginning with the first antibiotic treatment for TB in 1943, some strains of the TB bacteria developed resistance to the standard drugs through genetic changes (see mechanisms.) Currently the majority of multidrug-resistant cases of TB are due to one strain of TB bacteria called the Beijing lineage. This process accelerates if incorrect or inadequate treatments are used, leading to the development and spread of multidrug-resistant TB (MDR-TB). Incorrect or inadequate treatment may be due to use of the wrong medications, use of only one medication (standard treatment is at least two drugs), not taking medication consistently or for the full treatment period (treatment is required for several months). Treatment of MDR-TB requires second-line drugs (i.e., fluoroquinolones, aminoglycosides, and others), which in general are less effective, more toxic and much more expensive than first-line drugs. Treatment schedules for MDR-TB involving fluoroquinolones and aminoglycosides can run for 2 years, compared to the 6 months of first-line drug treatment, and cost over $100,000 USD.If these second-line drugs are prescribed or taken incorrectly, further resistance can develop leading to XDR-TB.

Resistant strains of TB are already present in the population, so MDR-TB can be directly transmitted from an infected person to an uninfected person. In this case a previously untreated person develops a new case of MDR-TB. This is known as primary MDR-TB, and is responsible for up to 75% of cases. Acquired MDR-TB develops when a person with a non-resistant strain of TB is treated inadequately, resulting in the development of antibiotic resistance in the TB bacteria infecting them. These people can in turn infect other people with MDR-TB.

MDR-TB caused an estimated 480,000 new TB cases and 250,000 deaths in 2015. MDR-TB accounts for 3.3% of all new TB cases worldwide. Resistant forms of TB bacteria, either MDR-TB or rifampin-resistant TB, cause 3.9% of new TB cases and 21% of previously treated TB cases. Globally, most MDR-TB cases occur in South America, Southern Africa, India, China, and the former Soviet Union.

Treatment of MDR-TB requires treatment with second-line drugs, usually four or more anti-TB drugs for a minimum of 6 months, and possibly extending for 18–24 months if rifampin resistance has been identified in the specific strain of TB with which the patient has been infected. Under ideal program conditions, MDR-TB cure rates can approach 70%.

An opportunistic infection is an infection caused by pathogens (bacteria, viruses, fungi, or protozoa) that take advantage of an opportunity not normally available, such as a host with a weakened immune system, an altered microbiota (such as a disrupted gut flora), or breached integumentary barriers. Many of these pathogens do not cause disease in a healthy host that has a normal immune system. However, a compromised immune system, a penetrating injury, or a lack of competition from normal commensals presents an opportunity for the pathogen to infect.

Drug, toxin, or chemical resistance is a consequence of evolution and is a response to pressures imposed on any living organism. Individual organisms vary in their sensitivity to the drug used and some with greater fitness may be capable of surviving drug treatment. Drug-resistant traits are accordingly inherited by subsequent offspring, resulting in a population that is more drug-resistant. Unless the drug used makes sexual reproduction or cell-division or horizontal gene transfer impossible in the entire target population, resistance to the drug will inevitably follow. This can be seen in cancerous tumors where some cells may develop resistance to the drugs used in chemotherapy. Chemotherapy causes fibroblasts near tumors to produce large amounts of the protein WNT16B. This protein stimulates the growth of cancer cells which are drug-resistant. Malaria in 2012 has become a resurgent threat in South East Asia and sub-Saharan Africa, and drug-resistant strains of "Plasmodium falciparum" are posing massive problems for health authorities. Leprosy has shown an increasing resistance to dapsone.

A rapid process of sharing resistance exists among single-celled organisms, and is termed horizontal gene transfer in which there is a direct exchange of genes, particularly in the biofilm state. A similar asexual method is used by fungi and is called "parasexuality". Examples of drug-resistant strains are to be found in microorganisms such as bacteria and viruses, parasites both endo- and ecto-, plants, fungi, arthropods, mammals, birds, reptiles, fish, and amphibians.

In the domestic environment, drug-resistant strains of organism may arise from seemingly safe activities such as the use of bleach, tooth-brushing and mouthwashing, the use of antibiotics, disinfectants and detergents, shampoos, and soaps, particularly antibacterial soaps, hand-washing, surface sprays, application of deodorants, sunblocks and any cosmetic or health-care product, insecticides, and dips. The chemicals contained in these preparations, besides harming beneficial organisms, may intentionally or inadvertently target organisms that have the potential to develop resistance.

"Drug resistance develops naturally, but careless practices in drug supply and use are hastening it unnecessarily." - Center for Global Development

"The overuse of antibacterial cleaning products in the home may be producing strains of multi-antibiotic-resistant bacteria." - Better Health Channel - Australian Government

"The use and misuse of antimicrobials in human medicine and animal husbandry over the past 70 years has led to a relentless rise in the number and types of microorganisms resistant to these medicines - leading to death, increased suffering and disability, and higher healthcare costs." - World Health Organisation 2010

"Deaths from acute respiratory infections, diarrhoeal diseases, measles, AIDS, malaria, and tuberculosis account for more than 85% of the mortality from infection worldwide. Resistance to first-line drugs in most of the pathogens causing these diseases ranges from zero to almost 100%. In some instances resistance to second- and thirdline agents is seriously compromising treatment outcome. Added to this is the significant global burden of resistant, hospital-acquired infections, the emerging problems of antiviral resistance and the increasing problems of drug resistance in the neglected parasitic diseases of poor and marginalized populations." - WHO Global Strategy for Containment of Antimicrobial Resistance 2010

HIV drug resistance occurs when microevolution causes virions to become tolerant to antiretroviral treatments.

Bacillary dysentery is a type of dysentery, and is a severe form of shigellosis.

Bacillary dysentery is associated with species of bacteria from the Enterobacteriaceae family. The term is usually restricted to "Shigella" infections.

Shigellosis is caused by one of several types of "Shigella" bacteria. Three species are associated with bacillary dysentery: "Shigella sonnei, Shigella flexneri" and "Shigella dysenteriae". A study in China indicated that "Shigella flexneri" 2a was the most common serotype.

Salmonellosis caused by "Salmonella enterica" (serovar "Typhimurium") has also been described as a cause of bacillary dysentery, though this definition is less common. It is sometimes listed as an explicit differential diagnosis of bacillary dysentery, as opposed to a cause.

Bacillary dysentery should not be confused with diarrhea caused by other bacterial infections. One characteristic of bacillary dysentery is blood in stool, which is the result of invasion of the mucosa by the pathogen.