Appropriate antibiotic treatment should be started immediately when there is a suspicion of Rocky Mountain spotted fever on the basis of clinical and epidemiological findings. Treatment should not be delayed until laboratory confirmation is obtained. In fact, failure to respond to a tetracycline argues against a diagnosis of Rocky Mountain spotted fever. Severely ill patients may require longer periods before their fever resolves, especially if they have experienced damage to multiple organ systems. Preventive therapy in healthy patients who have had recent tick bites is not recommended and may, in fact, only delay the onset of disease.

Doxycycline (a tetracycline) (for adults at 100 milligrams every 12 hours, or for children under at 4 mg/kg of body weight per day in two divided doses) is the drug of choice for patients with Rocky Mountain spotted fever, being one of the only instances doxycycline is used in children. Treatment should be continued for at least three days after the fever subsides, and until there is unequivocal evidence of clinical improvement. This will be generally for a minimum time of five to ten days. Severe or complicated outbreaks may require longer treatment courses. Doxycycline/ tetracycline is also the preferred drug for patients with ehrlichiosis, another tick-transmitted infection with signs and symptoms that may resemble those of Rocky Mountain spotted fever.

Chloramphenicol is an alternative drug that can be used to treat Rocky Mountain spotted fever, specifically in pregnancy. However, this drug may be associated with a wide range of side effects, and careful monitoring of blood levels can be required.

Tetracycline-group antibiotics (doxycycline, tetracycline) are commonly used. Chloramphenicol is an alternative medication recommended under circumstances that render use of tetracycline derivates undesirable, such as severe liver malfunction, kidney deficiency, in children under nine years and in pregnant women. The drug is administered for seven to ten days.

The treatment for bacillary angiomatosis is erythromycin given for three to four months.

The disease can be fatal if left untreated, but endemic typhus is highly treatable with antibiotics. Most people recover fully, but death may occur in the elderly, severely disabled or patients with a depressed immune system. The most effective antibiotics include tetracycline and chloramphenicol. In United States, CDC recommends solely doxycycline.

The illness can be treated with tetracyclines (doxycycline is the preferred treatment), chloramphenicol, macrolides or fluoroquinolones.

Without treatment, the disease is often fatal. Since the use of antibiotics, case fatalities have decreased from 4–40% to less than 2%.

The drug most commonly used is doxycycline or tetracycline, but chloramphenicol is an alternative. Strains that are resistant to doxycycline and chloramphenicol have been reported in northern Thailand. Rifampicin and azithromycin are alternatives. Azithromycin is an alternative in children and pregnant women with scrub typhus, and when doxycycline resistance is suspected. Ciprofloxacin cannot be used safely in pregnancy and is associated with stillbirths and miscarriage.

Combination therapy with doxycycline and rifampicin is not recommended due to possible antagonism.

Doxycycline has been used in the treatment of rickettsial infection.

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.

The American Public Health Association recommends treatment based upon clinical findings and before culturing confirms the diagnosis. Without treatment, death may occur in 10 to 60 percent of patients with epidemic typhus, with patients over age 60 having the highest risk of death. In the antibiotic era, death is uncommon if doxycycline is given. In one study of 60 hospitalized patients with epidemic typhus, no patient died when given doxycycline or chloramphenicol. Some patients also may need oxygen and intravenous (IV) fluids.

Most healthy people clear the infection without treatment, but in 5 to 14 percent of individuals, the organisms disseminate and infect the liver, spleen, eye, or central nervous system. Although some experts recommend not treating typical CSD in immunocompetent patients with mild to moderate illness, treatment of all patients with antimicrobial agents (Grade 2B) is suggested due to the probability of disseminated disease. The preferred antibiotic for treatment is azithromycin since this agent is the only one studied in a randomized controlled study.

Azithromycin is preferentially used in pregnancy to avoid the teratogenic side effects of doxycycline. However, doxycycline is preferred to treat "B. henselae" infections with optic neuritis due to its ability to adequately penetrate the tissues of the eye and central nervous system.

Rocky Mountain spotted fever can be a very severe illness and patients often require hospitalization. Because "R. rickettsii" infects the cells lining blood vessels throughout the body, severe manifestations of this disease may involve the respiratory system, central nervous system, gastrointestinal system, or kidneys.

Long-term health problems following acute Rocky Mountain spotted fever infection include partial paralysis of the lower extremities, gangrene requiring amputation of fingers, toes, or arms or legs, hearing loss, loss of bowel or bladder control, movement disorders, and language disorders. These complications are most frequent in persons recovering from severe, life-threatening disease, often following lengthy hospitalizations

Treatment of infections caused by "Bartonella" species include:

Some authorities recommend the use of azithromycin.

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.

Cat-scratch disease can be primarily prevented by taking flea control measures and washing hands after handling a cat or cat feces; since cats are mostly exposed to fleas when they are outside, keeping cats inside can prevent infestation.

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.

As of 2017 there is no commercially available vaccine. A vaccine has been in development for scrub typhus known as the scrub typhus vaccine.

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.

It is caused by the bacteria "Rickettsia typhi", and is transmitted by the fleas that infest rats. While rat fleas are the most common vectors, cat fleas and mouse fleas are less common modes of transmission. These fleas are not affected by the infection. Human infection occurs because of flea-fecal contamination of the bites on human skin. Rats, cats, opossums maintain the rickettsia colonization by providing it with a host for its entire life cycle. Rats can develop the infection, and help spread the infection to other fleas that infect them, and help multiply the number of infected fleas that can then infect humans.

Less often, endemic typhus is caused by "Rickettsia felis" and transmitted by fleas carried by cats or opossums.

In the United States of America, murine typhus is found most commonly in southern California, Texas and Hawaii. In some studies, up to 13% of children were found to have serological evidence of infection.

No licensed vaccines are available.

An early attempt to create a scrub typhus vaccine occurred in the United Kingdom in 1937 (with the Wellcome Foundation infecting around 300,000 cotton rats in a classified project called "Operation Tyburn"), but the vaccine was not used. The first known batch of scrub typhus vaccine actually used to inoculate human subjects was dispatched to India for use by Allied Land Forces, South-East Asia Command in June 1945. By December 1945, 268,000 cc had been dispatched. The vaccine was produced at Wellcome′s laboratory at Ely Grange, Frant, Sussex. An attempt to verify the efficacy of the vaccine by using a placebo group for comparison was vetoed by the military commanders, who objected to the experiment.

Enormous antigenic variation in "Orientia tsutsugamushi" strains is now recognized, and immunity to one strain does not confer immunity to another. Any scrub typhus vaccine should give protection to all the strains present locally, to give an acceptable level of protection. A vaccine developed for one locality may not be protective in another, because of antigenic variation. This complexity continues to hamper efforts to produce a viable vaccine.

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)

A spotted fever is a type of tick-borne disease which presents on the skin. They are all caused by bacteria of the genus "Rickettsia". Typhus is a group of similar diseases also caused by "Rickettsia" bacteria, but spotted fevers and typhus are different clinical entities.

The phrase apparently originated in Spain in the seventeenth century and was ‘loosely applied in England to typhus or any fever involving petechial eruptions.’ During the seventeenth and eighteenth centuries, it was thought to be ‘“cousin-germane” to and herald of the bubonic plague’, a disease which periodically afflicted the city of London and its environs during the sixteenth and seventeenth centuries, most notably during the Great Plague of 1665.

Types of spotted fevers include:

- Mediterranean spotted fever

- Rocky Mountain spotted fever

- Queensland tick typhus

- Helvetica Spotted fever

The preventative measure of keeping cats inside in areas with high infection rates can prevent infection. Approved tick treatments for cats can be used but have been shown not to fully prevent tick bites.

The most often used treatments for cytauxzoonosis are imidocarb dipropionate and a combination of atovaquone and azithromycin. Although imidocarb has been used for years, it is not particularly effective. In a large study, only 25% of cats treated with this drug and supportive care survived. 60% of sick cats treated with supportive care and the combination of the anti-malarial drug atovaquone and the antibiotic azithromycin survived infection.

Quick referral to a veterinarian equipped to treat the disease may be beneficial. All infected cats require supportive care, including careful fluids, nutritional support, treatment for complications, and often blood transfusion.

Cats that survive the infection should be kept indoors as they can be persistent carriers after surviving infection and might indirectly infect other cats after being themselves bitten by a vector tick.

Investigational vaccines exist for Argentine hemorrhagic fever and RVF; however, neither is approved by FDA or commonly available in the United States.

The structure of the attachment glycoprotein has been determined by X-ray crystallography and this glycoprotein is likely to be an essential component of any successful vaccine.

In 1988, English "et al." isolated and cultured a bacterium that was named "Afipia felis" in 1992 after the team at the Armed Forces Institute of Pathology that discovered it. This agent was considered the cause of cat-scratch Disease (CSD) but further studies failed to support this conclusion. Serologic studies associated CSD with "Bartonella henselae", reported in 1992. In 1993, Dolan isolated "Rochalimae henselae" (now called "Bartonella henselae") from lymph nodes of patients with CSD.

"Bartonella" spp. are commonly treated with antibiotics including azithromycin, based on a single small randomized clinical trial. Treatment may take up to one year to completely eliminate the disease.

CSD often resolves spontaneously without treatment.

Boutonneuse fever (also called Mediterranean spotted fever, fièvre boutonneuse, Kenya tick typhus, Indian tick typhus, Marseilles fever, or African tick-bite fever) is a fever as a result of a rickettsial infection caused by the bacterium "Rickettsia conorii" and transmitted by the dog tick "Rhipicephalus sanguineus". Boutonneuse fever can be seen in many places around the world, although it is endemic in countries surrounding the Mediterranean Sea. This disease was first described in Tunisia in 1910 by Conor and Bruch and was named "boutonneuse" (French for "spotty") due to its papular skin rash characteristics.

Trench fever (also known as "five-day fever", "quintan fever" ("febris quintana" in Latin), and "urban trench fever") is a moderately serious disease transmitted by body lice. It infected armies in Flanders, France, Poland, Galicia, Italy, Salonika, Macedonia, Mesopotamia, Russia and Egypt in World War I. Three noted sufferers during WWI were the authors J.R.R. Tolkien, A. A. Milne, and C.S. Lewis. From 1915 to 1918 between one-fifth and one-third of all British troops reported ill had trench fever while about one-fifth of ill German and Austrian troops had the disease. The disease persists among the homeless. Outbreaks have been documented, for example, in Seattle and Baltimore in the United States among injection drug users and in Marseille, France, and Burundi.

Trench fever is also called Wolhynia fever, shin bone fever, Meuse fever, His disease and His–Werner disease (after Wilhelm His, Jr. and Heinrich Werner).

The disease is caused by the bacterium "Bartonella quintana" (older names: "Rochalimea quintana", "Rickettsia quintana"), found in the stomach walls of the body louse. "Bartonella quintana" is closely related to "Bartonella henselae", the agent of cat scratch fever and bacillary angiomatosis.