Several classes of antibiotics are effective in treating bubonic plague. These include aminoglycosides such as streptomycin and gentamicin, tetracyclines (especially doxycycline), and the fluoroquinolone ciprofloxacin. Mortality associated with treated cases of bubonic plague is about 1–15%, compared to a mortality of 40–60% in untreated cases.

People potentially infected with the plague need immediate treatment and should be given antibiotics within 24 hours of the first symptoms to prevent death. Other treatments include oxygen, intravenous fluids, and respiratory support. People who have had contact with anyone infected by pneumonic plague are given prophylactic antibiotics. Using the broad-based antibiotic streptomycin has proven to be dramatically successful against the bubonic plague within 12 hours of infection.

Starting antibiotics early is a first step in treating septicemic plague in humans. One of the following antibiotics may be used:

- Streptomycin

- Gentamicin

- Tetracycline or doxycycline

- Chloramphenicol

- Ciprofloxacin

Lymph nodes may require draining and the patient will need close monitoring.

In animals, antibiotics such as tetracyline or doxycycline can be used. Intravenous drip may be used to assist in dehydration scenarios. Flea treatment can also be used. In some cases euthanasia may be the best option for treatment and to prevent further spreading.

If diagnosed in time, the various forms of plague are usually highly responsive to antibiotic therapy. The antibiotics often used are streptomycin, chloramphenicol and tetracycline. Amongst the newer generation of antibiotics, gentamicin and doxycycline have proven effective in monotherapeutic treatment of plague.

The plague bacterium could develop drug-resistance and again become a major health threat. One case of a drug-resistant form of the bacterium was found in Madagascar in 1995. Further outbreaks in Madagascar were reported in November 2014 and October 2017.

Pneumonic plague is a very aggressive infection requiring early treatment. Antibiotics must be given within 24 hours of first symptoms to reduce the risk of death. Streptomycin, gentamicin, tetracyclines and chloramphenicol are all effective against pneumonic plague.

Antibiotic treatment for seven days will protect people who have had direct, close contact with infected patients. Wearing a close-fitting surgical mask also protects against infection.

The mortality rate from untreated pneumonic plague approaches 100%.

If infection occurs or is suspected, treatment is generally with the antibiotics streptomycin or gentamicin. Doxycycline was previously used. Gentamicin may be easier to obtain than streptomycin. There is also tentative evidence to support the use of fluoroquinolones.

The following steps and precautions should be used to avoid infection of the septicemic plague:

- Caregivers of infected patients should wear masks, gloves, goggles and gowns

- Take antibiotics if close contact with infected patient has occurred

- Use insecticides throughout house

- Avoid contact with dead rodents or sick cats

- Set traps if mice or rats are present around the house

- Do not allow family pets to roam in areas where plague is common

- Flea control and treatment for animals (especially rodents)

There are no safe, available, approved vaccines against tularemia. However, vaccination research and development continues, with live attenuated vaccines being the most thoroughly researched and most likely candidate for approval. Sub-unit vaccine candidates, such as killed-whole cell vaccines, are also under investigation, however research has not reached a state of public use.

Optimal preventative practices include limiting direct exposure when handling potentially infected animals, such as wearing gloves and face masks while handling potentially infected animals (importantly when skinning deceased animals).

Early antibiotic treatment of anthrax is essential; delay significantly lessens chances for survival.

Treatment for anthrax infection and other bacterial infections includes large doses of intravenous and oral antibiotics, such as fluoroquinolones (ciprofloxacin), doxycycline, erythromycin, vancomycin, or penicillin. FDA-approved agents include ciprofloxacin, doxycycline, and penicillin.

In possible cases of pulmonary anthrax, early antibiotic prophylaxis treatment is crucial to prevent possible death.

In recent years, many attempts have been made to develop new drugs against anthrax, but existing drugs are effective if treatment is started soon enough.

In May 2009, Human Genome Sciences submitted a biologic license application (BLA, permission to market) for its new drug, raxibacumab (brand name ABthrax) intended for emergency treatment of inhaled anthrax. On 14 December 2012, the US Food and Drug Administration approved raxibacumab injection to treat inhalational anthrax. Raxibacumab is a monoclonal antibody that neutralizes toxins produced by "B. anthracis". On March, 2016, FDA approved a second anthrax treatment using a monoclonal antibody which neutralizes the toxins produced by "B. anthracis". Obiltoxaximab is approved to treat inhalational anthrax in conjunction with appropriate antibacterial drugs, and for prevention when alternative therapies are not available or appropriate.

Smallpox vaccination within three days of exposure will prevent or significantly lessen the severity of smallpox symptoms in the vast majority of people. Vaccination four to seven days after exposure can offer some protection from disease or may modify the severity of disease. Other than vaccination, treatment of smallpox is primarily supportive, such as wound care and infection control, fluid therapy, and possible ventilator assistance. Flat and hemorrhagic types of smallpox are treated with the same therapies used to treat shock, such as fluid resuscitation. People with semi-confluent and confluent types of smallpox may have therapeutic issues similar to patients with extensive skin burns.

No drug is currently approved for the treatment of smallpox. Antiviral treatments have improved since the last large smallpox epidemics, and studies suggest that the antiviral drug cidofovir might be useful as a therapeutic agent. The drug must be administered intravenously, and may cause serious kidney toxicity.

The infection is treated with antibiotics. Intravenous fluids and oxygen may be needed to stabilize the patient. There is a significant disparity between the untreated mortality and treated mortality rates: 10-60% untreated versus close to 0% treated with antibiotics within 8 days of initial infection. Tetracycline, Chloramphenicol, and doxycycline are commonly used. Infection can also be prevented by vaccination.

Some of the simplest methods of prevention and treatment focus on preventing infestation of body lice. Complete change of clothing, washing the infested clothing in hot water, and in some cases also treating recently used bedsheets all help to prevent typhus by removing potentially infected lice. Clothes also left unworn and unwashed for 7 days also cause both lice and their eggs to die, as they have no access to their human host. Another form of lice prevention requires dusting infested clothing with a powder consisting of 10% DDT, 1% malathion, or 1% permethrin, which kill lice and their eggs.

Since human plague is rare in most parts of the world, routine vaccination is not needed other than for those at particularly high risk of exposure, nor for people living in areas with enzootic plague, meaning it occurs at regular, predictable rates in populations and specific areas, such as the western United States. It is not even indicated for most travellers to countries with known recent reported cases, particularly if their travel is limited to urban areas with modern hotels. The CDC thus only recommends vaccination for: (1) all laboratory and field personnel who are working with "Y. pestis" organisms resistant to antimicrobials; (2) people engaged in aerosol experiments with "Y. pestis"; and (3) people engaged in field operations in areas with enzootic plague where preventing exposure is not possible (such as some disaster areas).

A systematic review by the Cochrane Collaboration found no studies of sufficient quality to make any statement on the efficacy of the vaccine.

The first recorded epidemic affected the Eastern Roman Empire (Byzantine Empire) and was named the Plague of Justinian after emperor Justinian I, who was infected but survived through extensive treatment.

Effective antibiotics include penicillin G, ampicillin, amoxicillin and doxycycline. In more severe cases cefotaxime or ceftriaxone should be preferred.

Glucose and salt solution infusions may be administered; dialysis is used in serious cases. Elevations of serum potassium are common and if the potassium level gets too high special measures must be taken. Serum phosphorus levels may likewise increase to unacceptable levels due to kidney failure.

Treatment for hyperphosphatemia consists of treating the underlying disease, dialysis where appropriate, or oral administration of calcium carbonate, but not without first checking the serum calcium levels (these two levels are related). Administration of corticosteroids in gradually reduced doses (e.g., prednisolone) for 7–10 days is recommended by some specialists in cases of severe hemorrhagic effects. Organ-specific care and treatment are essential in cases of kidney, liver, or heart involvement.

Treatment is primarily supportive in nature. Early supportive care with rehydration and symptomatic treatment improves survival. Rehydration may be via the oral or by intravenous route. These measures may include management of pain, nausea, fever and anxiety. The World Health Organization recommends avoiding the use of aspirin or ibuprofen for pain due to the bleeding risk associated with use of these medications.

Blood products such as packed red blood cells, platelets or fresh frozen plasma may also be used. Other regulators of coagulation have also been tried including heparin in an effort to prevent disseminated intravascular coagulation and clotting factors to decrease bleeding. Antimalarial medications and antibiotics are often used before the diagnosis is confirmed, though there is no evidence to suggest such treatment helps. A number of experimental treatments are being studied.

If hospital care is not possible, the World Health Organization has guidelines for care at home that have been relatively successful. In such situations, recommendations include using towels soaked in bleach solutions when moving infected people or bodies and applying bleach on stains. It is also recommended that the caregivers wash hands with bleach solutions and cover their mouth and nose with a cloth.

The rediscovery of oral rehydration therapy in the 1960s provided a simple way to prevent many of the deaths of diarrheal diseases in general.

Where resistance is uncommon, the treatment of choice is a fluoroquinolone such as ciprofloxacin. Otherwise, a third-generation cephalosporin such as ceftriaxone or cefotaxime is the first choice. Cefixime is a suitable oral alternative.

Typhoid fever, when properly treated, is not fatal in most cases. Antibiotics, such as ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, amoxicillin, and ciprofloxacin, have been commonly used to treat typhoid fever in microbiology. Treatment of the disease with antibiotics reduces the case-fatality rate to about 1%.

Without treatment, some patients develop sustained fever, bradycardia, hepatosplenomegaly, abdominal symptoms and, occasionally, pneumonia. In white-skinned patients, pink spots, which fade on pressure, appear on the skin of the trunk in up to 20% of cases. In the third week, untreated cases may develop gastrointestinal and cerebral complications, which may prove fatal in up to 10–20% of cases. The highest case fatality rates are reported in children under 4 years. Around 2–5% of those who contract typhoid fever become chronic carriers, as bacteria persist in the biliary tract after symptoms have resolved.

No specific treatment is currently approved. The Food and Drug Administration (FDA) advises people to be careful of advertisements making unverified or fraudulent claims of benefits supposedly gained from various anti-Ebola products.

As the infection is usually transmitted into humans through animal bites, antibiotics usually treat the infection, but medical attention should be sought if the wound is severely swelling. Pasteurellosis is usually treated with high-dose penicillin if severe. Either tetracycline or chloramphenicol provides an alternative in beta-lactam-intolerant patients. However, it is most important to treat the wound.

Surgery is usually indicated in cases of intestinal perforation. Most surgeons prefer simple closure of the perforation with drainage of the peritoneum. Small-bowel resection is indicated for patients with multiple perforations.

If antibiotic treatment fails to eradicate the hepatobiliary carriage, the gallbladder should be resected. Cholecystectomy is not always successful in eradicating the carrier state because of persisting hepatic infection.

There is currently no effective marburgvirus-specific therapy for MVD. Treatment is primarily supportive in nature and includes minimizing invasive procedures, balancing fluids and electrolytes to counter dehydration, administration of anticoagulants early in infection to prevent or control disseminated intravascular coagulation, administration of procoagulants late in infection to control hemorrhaging, maintaining oxygen levels, pain management, and administration of antibiotics or antimycotics to treat secondary infections. Experimentally, recombinant vesicular stomatitis Indiana virus (VSIV) expressing the glycoprotein of MARV has been used successfully in nonhuman primate models as post-exposure prophylaxis. Novel, very promising, experimental therapeutic regimens rely on antisense technology: phosphorodiamidate morpholino oligomers (PMOs) targeting the MARV genome could prevent disease in nonhuman primates. Leading medications from Sarepta and Tekmira both have been successfully used in European humans as well as primates.

When infection attacks the body, "anti-infective" drugs can suppress the infection. Several broad types of anti-infective drugs exist, depending on the type of organism targeted; they include antibacterial (antibiotic; including antitubercular), antiviral, antifungal and antiparasitic (including antiprotozoal and antihelminthic) agents. Depending on the severity and the type of infection, the antibiotic may be given by mouth or by injection, or may be applied topically. Severe infections of the brain are usually treated with intravenous antibiotics. Sometimes, multiple antibiotics are used in case there is resistance to one antibiotic. Antibiotics only work for bacteria and do not affect viruses. Antibiotics work by slowing down the multiplication of bacteria or killing the bacteria. The most common classes of antibiotics used in medicine include penicillin, cephalosporins, aminoglycosides, macrolides, quinolones and tetracyclines.

Not all infections require treatment, and for many self-limiting infections the treatment may cause more side-effects than benefits. Antimicrobial stewardship is the concept that healthcare providers should treat an infection with an antimicrobial that specifically works well for the target pathogen for the shortest amount of time and to only treat when there is a known or highly suspected pathogen that will respond to the medication.

Pneumonic plague can be caused in two ways: primary, which results from the inhalation of aerosolised plague bacteria, or secondary, when septicaemic plague spreads into lung tissue from the bloodstream. Pneumonic plague is "not" exclusively vector-borne like bubonic plague; instead it can be spread from person to person. There have been cases of pneumonic plague resulting from the dissection or handling of contaminated animal tissue. This is one type of the plague formerly known as the Black Death.

The recommended treatment of new-onset pulmonary tuberculosis, as of 2010, is six months of a combination of antibiotics containing rifampicin, isoniazid, pyrazinamide, and ethambutol for the first two months, and only rifampicin and isoniazid for the last four months. Where resistance to isoniazid is high, ethambutol may be added for the last four months as an alternative.

If tuberculosis recurs, testing to determine which antibiotics it is sensitive to is important before determining treatment. If multiple drug-resistant TB (MDR-TB) is detected, treatment with at least four effective antibiotics for 18 to 24 months is recommended.

The earliest procedure used to prevent smallpox was inoculation (known as variolation after the introduction of smallpox vaccine to avoid possible confusion), which likely occurred in India, Africa, and China well before the practice arrived in Europe. The idea that inoculation originated in India has been challenged, as few of the ancient Sanskrit medical texts described the process of inoculation. Accounts of inoculation against smallpox in China can be found as early as the late 10th century, and the procedure was widely practiced by the 16th century, during the Ming dynasty. If successful, inoculation produced lasting immunity to smallpox. Because the person was infected with variola virus, a severe infection could result, and the person could transmit smallpox to others. Variolation had a 0.5–2 percent mortality rate, considerably less than the 20–30 percent mortality rate of the disease. Two reports on the Chinese practice of inoculation were received by the Royal Society in London in 1700; one by Dr. Martin Lister who received a report by an employee of the East India Company stationed in China and another by Clopton Havers.

Lady Mary Wortley Montagu observed smallpox inoculation during her stay in the Ottoman Empire, writing detailed accounts of the practice in her letters, and enthusiastically promoted the procedure in England upon her return in 1718. In 1721, Cotton Mather and colleagues provoked controversy in Boston by inoculating hundreds. In 1796, Edward Jenner, a doctor in Berkeley, Gloucestershire, rural England, discovered that immunity to smallpox could be produced by inoculating a person with material from a cowpox lesion. Cowpox is a poxvirus in the same family as variola. Jenner called the material used for inoculation vaccine, from the root word "vacca", which is Latin for cow. The procedure was much safer than variolation, and did not involve a risk of smallpox transmission. Vaccination to prevent smallpox was soon practiced all over the world. During the 19th century, the cowpox virus used for smallpox vaccination was replaced by vaccinia virus. Vaccinia is in the same family as cowpox and variola, but is genetically distinct from both. The origin of vaccinia virus and how it came to be in the vaccine are not known. According to Voltaire (1742), the Turks derived their use of inoculation to neighbouring Circassia. Voltaire does not speculate on where the Circassians derived their technique from, though he reports that the Chinese have practiced it "these hundred years".

The current formulation of smallpox vaccine is a live virus preparation of infectious vaccinia virus. The vaccine is given using a bifurcated (two-pronged) needle that is dipped into the vaccine solution. The needle is used to prick the skin (usually the upper arm) a number of times in a few seconds. If successful, a red and itchy bump develops at the vaccine site in three or four days. In the first week, the bump becomes a large blister (called a "Jennerian vesicle") which fills with pus, and begins to drain. During the second week, the blister begins to dry up and a scab forms. The scab falls off in the third week, leaving a small scar.

The antibodies induced by vaccinia vaccine are cross-protective for other orthopoxviruses, such as monkeypox, cowpox, and variola (smallpox) viruses. Neutralizing antibodies are detectable 10 days after first-time vaccination, and seven days after revaccination. Historically, the vaccine has been effective in preventing smallpox infection in 95 percent of those vaccinated. Smallpox vaccination provides a high level of immunity for three to five years and decreasing immunity thereafter. If a person is vaccinated again later, immunity lasts even longer. Studies of smallpox cases in Europe in the 1950s and 1960s demonstrated that the fatality rate among persons vaccinated less than 10 years before exposure was 1.3 percent; it was 7 percent among those vaccinated 11 to 20 years prior, and 11 percent among those vaccinated 20 or more years prior to infection. By contrast, 52 percent of unvaccinated persons died.

There are side effects and risks associated with the smallpox vaccine. In the past, about 1 out of 1,000 people vaccinated for the first time experienced serious, but non-life-threatening, reactions, including toxic or allergic reaction at the site of the vaccination (erythema multiforme), spread of the vaccinia virus to other parts of the body, and to other individuals. Potentially life-threatening reactions occurred in 14 to 500 people out of every 1 million people vaccinated for the first time. Based on past experience, it is estimated that 1 or 2 people in 1 million (0.000198 percent) who receive the vaccine may die as a result, most often the result of postvaccinial encephalitis or severe necrosis in the area of vaccination (called progressive vaccinia).

Given these risks, as smallpox became effectively eradicated and the number of naturally occurring cases fell below the number of vaccine-induced illnesses and deaths, routine childhood vaccination was discontinued in the United States in 1972, and was abandoned in most European countries in the early 1970s. Routine vaccination of health care workers was discontinued in the U.S. in 1976, and among military recruits in 1990 (although military personnel deploying to the Middle East and Korea still receive the vaccination). By 1986, routine vaccination had ceased in all countries. It is now primarily recommended for laboratory workers at risk for occupational exposure.