The World Health Organization concluded that inappropriate use of antibiotics in animal husbandry is an underlying contributor to the emergence and spread of antibiotic-resistant germs, and that the use of antibiotics as growth promoters in animal feeds should be restricted. The World Organisation for Animal Health has added to the Terrestrial Animal Health Code a series of guidelines with recommendations to its members for the creation and harmonization of national antimicrobial resistance surveillance and monitoring programs, monitoring of the quantities of antibiotics used in animal husbandry, and recommendations to ensure the proper and prudent use of antibiotic substances. Another guideline is to implement methodologies that help to establish associated risk factors and assess the risk of antibiotic resistance.

Bacteria with resistance to antibiotics predate medical use of antibiotics by humans. However, widespread antibiotic use has made more bacteria resistant through the process of evolutionary pressure.

Reasons for the widespread use of antibiotics in human medicine include:

- increasing global availability over time since the 1950s

- uncontrolled sale in many low or middle income countries, where they can be obtained over the counter without a prescription, potentially resulting in antibiotics being used when not indicated. This may result in emergence of resistance in any remaining bacteria.

Other causes include:

- Antibiotic use in livestock feed at low doses for growth promotion is an accepted practice in many industrialized countries and is known to lead to increased levels of resistance.

- Releasing large quantities of antibiotics into the environment during pharmaceutical manufacturing through inadequate wastewater treatment increases the risk that antibiotic-resistant strains will develop and spread.

- It is uncertain whether antibacterials in soaps and other products contribute to antibiotic resistance, but antibacterial soaps are discouraged for other reasons.

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.

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

Vancomycin-resistant "Staphylococcus aureus" are strains of "Staphylococcus aureus" that have become resistant to the glycopeptide antibiotic vancomycin.

There are several risk factors that increase the likelihood of developing bacteremia from any type of bacteria. These include:

- HIV infection

- Diabetes Mellitus

- Chronic hemodialysis

- Solid organ transplant

- Stem cell transplant

- Treatment with glucocorticoids

- Liver failure

Six different types of vancomycin resistance are shown by enterococcus: Van-A, Van-B, Van-C, Van-D, Van-E and Van-G. The significance is that Van-A VRE is resistant to both vancomycin and teicoplanin, Van-B VRE is resistant to vancomycin but susceptible to teicoplanin, and Van-C is only partly resistant to vancomycin

The mechanism of resistance to vancomycin found in enterococcus involves the alteration of the peptidoglycan synthesis pathway. The D-alanyl-D-lactate variation results in the loss of one hydrogen-bonding interaction (four, as opposed to five for D-alanyl-D-alanine) being possible between vancomycin and the peptide. The D-alanyl-D-serine variation causes a six-fold loss of affinity between vancomycin and the peptide, likely due to steric hindrance.

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

Gram negative bacterial species are responsible for approximately 24% of all cases of healthcare-associated bacteremia and 45% of all cases of community-acquired bacteremia. In general, gram negative bacteria enter the bloodstream from infections in the respiratory tract, genitourinary tract, gastrointestinal tract, or hepatobiliary system. Gram-negative bacteremia occurs more frequently in elderly populations (65 years or older) and is associated with higher morbidity and mortality in this population.

"E.coli" is the most common cause of community-acquired bacteremia accounting for approximately 75% of cases. E.coli bacteremia is usually the result of a urinary tract infection. Other organisms that can cause community-acquired bacteremia include "pseudomonas aeruginosa", "klebsiella pneumoniae", and "proteus mirabilis". "Salmonella" infection, despite mainly only resulting in gastroenteritis in the developed world, is a common cause of bacteremia in Africa. It principally affects children who lack antibodies to Salmonella and HIV+ patients of all ages.

Among healthcare-associated cases of bacteremia, gram negative organisms are an important cause of bacteremia in the ICU. Catheters in the veins, arteries, or urinary tract can all create a way for gram negative bacteria to enter the bloodstream. Surgical procedures of the genitourinary tract, intestinal tract, or hepatobiliary tract can also lead to gram negative bacteremia. "Pseudomonas" and "enterobacter" species are the most important causes of gram negative bacteremia in the ICU.

The prime example for MDR against antiparasitic drugs is malaria. "Plasmodium vivax" has become chloroquine and sulfadoxine-pyrimethamine resistant a few decades ago, and as of 2012 artemisinin-resistant Plasmodium falciparum has emerged in western Cambodia and western Thailand.

"Toxoplasma gondii" can also become resistant to artemisinin, as well as atovaquone and sulfadiazine, but is not usually MDR

Antihelminthic resistance is mainly reported in the veterinary literature, for example in connection with the practice of livestock drenching and has been recent focus of FDA regulation.

The Centers for Disease Control and Prevention (CDC) estimated roughly 1.7 million hospital-associated infections, from all types of bacteria combined, cause or contribute to 99,000 deaths each year. Other estimates indicate 10%, or 2 million, patients a year become infected, with the annual cost ranging from $4.5 billion to $11 billion. In the USA, the most frequent type of infection hospitalwide is urinary tract infection (36%), followed by surgical site infection (20%), and bloodstream infection and pneumonia (both 11%).

HCAP is a condition in patients who can come from the community, but have frequent contact with the healthcare environment. Historically, the etiology and prognosis of nursing home pneumonia appeared to differ from other types of community acquired pneumonia, with studies reporting a worse prognosis and higher incidence of multi drug resistant organisms as etiology agents. The definition criteria which has been used is the same as the one which has been previously used to identify bloodstream healthcare associated infections.

HCAP is no longer recognized as a clinically independent entity. This is due to increasing evidence from a growing number of studies that many patients defined as having HCAP are not at high risk for MDR pathogens. As a result, 2016 IDSA guidelines removed consideration of HCAP as a separate clinical entity.

In 2012 the Health Protection Agency reported the prevalence rate of HAIs in England was 6.4% in 2011, against a rate of 8.2% in 2006. With respiratory tract, urinary tract and surgical site infections the most common types of HAI reported.

Healthcare-associated pneumonia can be defined as pneumonia in a patient with at least one of the following risk factors:

- hospitalization in an acute care hospital for two or more days in the last 90 days;

- residence in a nursing home or long-term care facility in the last 30 days

- receiving outpatient intravenous therapy (like antibiotics or chemotherapy) within the past 30 days

- receiving home wound care within the past 30 days

- attending a hospital clinic or dialysis center in the last 30 days

- having a family member with known multi-drug resistant pathogens

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

While the number of penicillin-resistant bacteria is increasing, penicillin can still be used to treat a wide range of infections caused by certain susceptible bacteria, including Streptococci, Staphylococci, Clostridium, and Listeria genera. The following list illustrates minimum inhibitory concentration susceptibility data for a few medically significant bacteria:

- "Listeria monocytogenes": from less than or equal to 0.06 μg/ml to 0.25 μg/ml

- "Neisseria meningitidis": from less than or equal to 0.03 μg/ml to 0.5 μg/ml

- "Staphylococcus aureus": from less than or equal to 0.015 μg/ml to more than 32 μg/ml

"S. pneumoniae" is normally found in the nose and throat of 5–10% of healthy adults and 20–40% of healthy children. It can be found in higher amounts in certain environments, especially those where people are spending a great deal of time in close proximity to each other (day-care centers, military barracks). It attaches to nasopharyngeal cells through interaction of bacterial surface adhesins. This normal colonization can become infectious if the organisms are carried into areas such as the Eustachian tube or nasal sinuses where it can cause otitis media and sinusitis, respectively. Pneumonia occurs if the organisms are inhaled into the lungs and not cleared (again, viral infection, or smoking-induced ciliary paralysis might be contributing factors). The organism's polysaccharide capsule makes it resistant to phagocytosis and if there is no pre-existing anticapsular antibody alveolar macrophages cannot adequately kill the pneumococci. The organism spreads to the blood stream (where it can cause bacteremia) and is carried to the meninges, joint spaces, bones, and peritoneal cavity, and may result in meningitis, brain abscess, septic arthritis, or osteomyelitis.

"S. pneumoniae" has several virulence factors, including the polysaccharide capsule mentioned earlier, that help it evade a host's immune system. It has pneumococcal surface proteins that inhibit complement-mediated opsonization, and it secretes IgA1 protease that will destroy secretory IgA produced by the body and mediates its attachment to respiratory mucosa.

The risk of pneumococcal infection is much increased in persons with impaired IgG synthesis, impaired phagocytosis, or defective clearance of pneumococci. In particular, the absence of a functional spleen, through congenital asplenia, surgical removal of the spleen, or sickle-cell disease predisposes one to a more severe course of infection (overwhelming post-splenectomy infection) and prevention measures are indicated (see asplenia).

People with a compromised immune system, such as those living with HIV, are also at higher risk of pneumococcal disease. In HIV patients with access to treatment, the risk of invasive pneumoccal disease is 0.2–1% per year and has a fatality rate of 8%.

There is an association between pneumococcal pneumonia and influenza. Damage to the lining of the airways (respiratory epithelium) and upper respiratory system caused by influenza may facilitate pneumococcal entry and infection.

Other risk factors include smoking, injection drug use, Hepatitis C, and COPD.

"Biological cost" or "metabolic price" is a measure of the increased energy metabolism required to achieve a function.

Drug resistance has a high metabolic price in pathogens for which this concept is relevant (bacteria, endoparasites, and tumor cells.) In viruses, an equivalent "cost" is genomic complexity.

Due to the importance of disease caused by "S. pneumoniae" several vaccines have been developed to protect against invasive infection. The World Health Organization recommend routine childhood pneumococcal vaccination; it is incorporated into the childhood immunization schedule in a number of countries including the United Kingdom, United States, and South Africa.

Common (≥ 1% of people) adverse drug reactions associated with use of the penicillins include diarrhoea, hypersensitivity, nausea, rash, neurotoxicity, urticaria, and superinfection (including candidiasis). Infrequent adverse effects (0.1–1% of people) include fever, vomiting, erythema, dermatitis, angioedema, seizures (especially in people with epilepsy), and pseudomembranous colitis. Penicillin can also induce serum sickness or a serum sickness-like reaction in some individuals. Serum sickness is a type III hypersensitivity reaction that occurs one to three weeks after exposure to drugs including penicillin. It is not a true drug allergy, because allergies are type I hypersensitivity reactions, but repeated exposure to the offending agent can result in an anaphylactic reaction. Anaphylaxis will occur in approximately 0.01% of patients.

Pain and inflammation at the injection site is also common for parenterally administered benzathine benzylpenicillin, benzylpenicillin, and, to a lesser extent, procaine benzylpenicillin.

People with recurrent boils are as well more likely to have a positive family history, take antibiotics, and to have been hospitalised, anemic, or diabetic; they are also more likely to have associated skin diseases and multiple lesions.

"Candida albicans", a yeast, is associated with endocarditis in IV drug users and immunocompromised patients. Other fungi demonstrated to cause endocarditis are "Histoplasma capsulatum" and Aspergillus. Endocarditis with "Tricosporon asahii" has also been reported in a case report.

Other causes include poor immune system function such as from HIV/AIDS, diabetes, malnutrition, or alcoholism. Poor hygiene and obesity have also been linked. It may occur following antibiotic use due to the development of resistance to the antibiotics used. An associated skin disease favors recurrence. This may be attributed to the persistent colonization of abnormal skin with "S. aureus" strains, such as is the case in persons with atopic dermatitis.

Boils which recur under the arm, breast or in the groin area may be associated with hidradenitis suppurativa (HS).

The treatment of choice is a single dose of benzathine benzylpenicillin given by intramuscular injection, or a five-day to one-week course of either oral penicillin or intramuscular procaine benzylpenicillin. Erythromycin or doxycycline may be given instead to people who are allergic to penicillin. "E. rhusiopathiae" is intrinsically resistant to vancomycin.

"Staphylococcus aureus" followed by "Streptococci" of the viridans group and coagulase negative Staphylococci are the three most common organisms responsible for infective endocarditis. Other "Streptococci" and "Enterococci" are also a frequent cause of infective endocarditis. HACEK group of microorganisms and fungi are seen less frequently in North America.

Viridans Alpha-hemolytic "streptococci", that are present in the mouth are the most frequently isolated microorganisms when the infection is acquired in a community setting. In contrast, "Staphylococcus" blood stream infections are frequently acquired in a health care setting where they can enter the blood stream through procedures that cause break in the integrity of skin like surgery, catheterisation or during access of long term indwelling catheters or secondary to intravenous injection of recreational drugs.

"Enterococcus" can enter the bloodstream as a consequence of abnormalities in the gastrointestinal or genitourinary tracts.

Some organisms, when isolated, give valuable clues to the cause, as they tend to be specific.

- "Pseudomonas" species, which are very resilient organisms that thrive in water, may contaminate street drugs that have been contaminated with drinking water. "P. aeruginosa" can infect a child through foot punctures, and can cause both endocarditis and septic arthritis.

- "S. bovis" and "Clostridium septicum", which are part of the natural flora of the bowel, are associated with colonic malignancies. When they present as the causative agent in endocarditis, it usually calls for a colonoscopy to be done immediately due to concerns regarding hematogenous spread of bacteria from the colon due to the neoplasm breaking down the barrier between the gut lumen and the blood vessels which drain the bowel.

- HACEK organisms are a group of bacteria that live on the dental gums, and can be seen with IV drug users who contaminate their needles with saliva. Patients may also have a history of poor dental hygiene, or pre-existing valvular disease.

- Less commonly reported bacteria responsible for so called "culture negative endocarditis" include "Bartonella", "Chlamydia psittaci", and "Coxiella". Such bacteria can be identified by serology, culture of the excised valve tissue, sputum, pleural fluid, and emboli; and by polymerase chain reaction or and sequencing of bacterial 16S ribosomal RNA.

Multiple case reports of infective endocarditis caused by unusual organisms have been published. Few examples include: "Propionibacterium" sp., which are normal skin flora, have been responsible for infective endocarditis sometimes leading to deaths due to the indolent course of this abscess producing infection."Tropheryma whipplei" has caused endocarditis without gastrointestinal involvement. "Citrobacter koseri" was found in an immunocompetent adult. "Neisseria bacilliformis" was found in a patient with a bicuspid aortic valve.