Infective endocarditis may also be classified as "culture-positive" or "culture-negative". By far the most common cause of a "culture-negative" endocarditis is prior administration of antibiotics.

Sometimes microorganisms can take a longer period of time to grow in the culture media, such organisms are said to be "fastidious" because they have demanding growth requirements. Some examples include pathogens like "Aspergillus" species, "Brucella" species, "Coxiella burnetii", "Chlamydia" species, and HACEK bacteria. Due to delay in growth and identification in these cases, patients may be erroneously classified as "culture-negative" endocarditis.

Historically, infective endocarditis has been clinically divided into "acute" and "subacute" presentations (because untreated patients tended to live longer with the subacute as opposed to the acute form). This classifies both the rate of progression and severity of disease.

- "Subacute bacterial endocarditis" (SBE) is often due to streptococci of low virulence (mainly viridans streptococci) and mild to moderate illness which progresses slowly over weeks and months (>2 weeks) and has low propensity to hematogenously seed extracardiac sites.

- "Acute bacterial endocarditis" (ABE) is a fulminant illness over days to weeks (<2 weeks), and is more likely due to "Staphylococcus aureus" which has much greater virulence, or disease-producing capacity and frequently causes metastatic infection.

This classification is now discouraged, because the ascribed associations (in terms of organism and prognosis) were not strong enough to be relied upon clinically. The terms "short incubation" (meaning less than about six weeks), and "long incubation" (greater than about six weeks) are preferred.

Among the signs of subacute bacterial endocarditis are:

- Malaise

- Weakness

- Excessive sweat

- Fever

The several forms of the infection are:

- Skin/subcutaneous tissue disease is a septic phlegmon that develops classically in the hand and forearm after a cat bite. Inflammatory signs are very rapid to develop; in 1 or 2 hours, edema, severe pain, and serosanguineous exudate appear. Fever, moderate or very high, can be seen, along with vomiting, headache, and diarrhea. Lymphangitis is common. Complications are possible, in the form of septic arthritis, osteitis, or evolution to chronicity.

- Sepsis is very rare, but can be as fulminant as septicaemic plague, with high fever, rigors, and vomiting, followed by shock and coagulopathy.

- Pneumonia disease is also rare and appears in patients with some chronic pulmonary pathology. It usually presents as bilateral consolidating pneumonia, sometimes very severe.

- Zoonosis, pasteurellosis can be transmitted to humans through cats.

Other locations are possible, such as septic arthritis, meningitis, and acute endocarditis, but are very rare.

Diagnosis is made with isolation of "Pasteurella multocida" in a normally sterile site (blood, pus, or cerebrospinal fluid).

Subacute bacterial endocarditis (also called endocarditis lenta) is a type of endocarditis (more specifically, infective endocarditis). Subacute bacterial endocarditis can be considered a form of type III hypersensitivity.

Bacteremia is the presence of bacteria in the bloodstream that are alive and capable of reproducing. It is a type of bloodstream infection. Bacteremia is defined as either a primary or secondary process. In primary bacteremia, bacteria have been directly introduced into the bloodstream. Injection drug use may lead to primary bacteremia. In the hospital setting, use of blood vessel catheters contaminated with bacteria may also lead to primary bacteremia. Secondary bacteremia occurs when bacteria have entered the body at another site, such as the cuts in the skin, or the mucous membranes of the lungs (respiratory tract), mouth or intestines (gastrointestinal tract), bladder (urinary tract), or genitals. Bacteria that have infected the body at these sites may then spread into the lymphatic system and gain access to the bloodstream, where further spread can occur.

Bacteremia may also be defined by the timing of bacteria presence in the bloodstream: transient, intermittent, or persistent. In transient bacteremia, bacteria are present in the bloodstream for minutes to a few hours before being cleared from the body, and the result is typically harmless in healthy people. This can occur after manipulation of parts of the body normally colonized by bacteria, such as the mucosal surfaces of the mouth during teeth brushing, flossing, or dental procedures, or instrumentation of the bladder or colon. Intermittent bacteremia is characterized by periodic seeding of the same bacteria into the bloodstream by an existing infection elsewhere in the body, such as an abscess, pneumonia, or bone infection, followed by clearing of that bacteria from the bloodstream. This cycle will often repeat until the existing infection is successfully treated. Persistent bacteremia is characterized by the continuous presence of bacteria in the bloodstream. It is usually the result of an infected heart valve, a central line-associated bloodstream infection (CLABSI), an infected blood clot (suppurative thrombophlebitis), or an infected blood vessel graft. Persistent bacteremia can also occur as part of the infection process of typhoid fever, brucellosis, and bacterial meningitis. Left untreated, conditions causing persistent bacteremia can be potentially fatal.

Bacteremia is clinically distinct from sepsis, which is a condition where the blood stream infection is associated with an inflammatory response from the body, often causing abnormalities in body temperature, heart rate, breathing rate, blood pressure, and white blood cell count.

Post-mortem findings include friable internal organs, abdominal effusion and evidence of sepsis in the joints, heart valves and brain.

Bacteria can usually be cultured from tissues collected at necropsy or identified by microscope examination.

Bacteremia (also bacteraemia) is the presence of bacteria in the blood. Blood is normally a sterile environment, so the detection of bacteria in the blood (most commonly accomplished by blood cultures) is always abnormal. It is distinct from sepsis, which is the host response to the bacteria.

Bacteria can enter the bloodstream as a severe complication of infections (like pneumonia or meningitis), during surgery (especially when involving mucous membranes such as the gastrointestinal tract), or due to catheters and other foreign bodies entering the arteries or veins (including during intravenous drug abuse). Transient bacteremia can result after dental procedures or brushing of teeth.

Bacteremia can have several important health consequences. The immune response to the bacteria can cause sepsis and septic shock, which has a high mortality rate. Bacteria can also spread via the blood to other parts of the body (which is called hematogenous spread), causing infections away from the original site of infection, such as endocarditis or osteomyelitis. Treatment for bacteremia is with antibiotics, and prevention with antibiotic prophylaxis can be given in high risk situations.

"C. psittaci" in birds is often systemic and infections can be inapparent, severe, acute or chronic with intermittent shedding. Signs in birds include "inflamed eyes, difficulty in breathing, watery droppings and green urates."

Streptococcus species are the cause of opportunistic infections in poultry leading to acute and chronic conditions in affected birds. Disease varies according to the Streptococcal species but common presentations include septicaemia, peritonitis, salpingitis and endocarditis.

Common species affecting poultry include:

- "S. gallinaceus" in broiler chickens

- "S. gallolyticus" which is a pathogen of racing pigeons and turkey poults

- "S. dysgalactiae" in broiler chickens

- "S. mutans" in geese

- "S. pluranimalium" in broiler chickens

- "S. equi subsp. zooepidemicus" in chickens and turkeys

- "S. suis" in psittacine birds

Trench fever, also known as five-day fever or quintan fever, is the initial manifestation of "B. quintana" infection. Clinical manifestations range from asymptomatic infection to severe illness. Classical presentations include a febrile illness of acute onset, headache, dizziness, and shin pain. Chronic infection manifestations include attacks of fever and aching in some cases and persistent bacteremia in soldiers and homeless people.

Patients can develop two clinical phases: an acute septic phase and a chronic eruptive phase associated with skin lesions. In the acute phase (also known as Oroya fever or "fiebre de la Oroya"), "B. bacilliformis" infection is a sudden, potentially life-threatening infection associated with high fever and decreased levels of circulating red blood cells (i.e., hemolytic anemia)and transient immunosuppression. "B. bacilliformis" is considered the most deadly species to date, with a death rate of up to 90% during the acute phase, which typically lasts two to four weeks. Peripheral blood smears show anisomacrocytosis with many bacilli adherent to red blood cells. Thrombocytopenia is also seen and can be very severe. Neurologic manifestations (neurobartonellosis) are altered mental status, agitation, or even coma, ataxia, spinal meningitis, or paralysis. It is seen in 20% of patients with acute infection, in which the prognosis is very guarded with an about 50% mortality. The most feared complication is overwhelming infection mainly by Enterobacteriaceae, particularly "Salmonella" (both "S. typhi" and " S. "non-"typhi", as well as reactivation of toxoplasmosis and other opportunistic infections .

The chronic manifestation consists of a benign skin eruption with raised, reddish-purple nodules (angiomatous tumours). The bacterium can be seen microscopically, if a skin biopsy is silver stained (the Warthin–Starry method).

Nonbacterial thrombotic endocarditis (NBTE) is most commonly found on previously undamaged valves. As opposed to infective endocarditis, the vegetations in NBTE are small, sterile, and tend to aggregate along the edges of the valve or the cusps. Also unlike infective endocarditis, NBTE does not cause an inflammation response from the body. NBTE usually occurs during a hypercoagulable state such as system-wide bacterial infection, or pregnancy, though it is also sometimes seen in patients with venous catheters. NBTE may also occur in patients with cancers, particularly mucinous adenocarcinoma where Trousseau syndrome can be encountered. Typically NBTE does not cause many problems on its own, but parts of the vegetations may break off and embolize to the heart or brain, or they may serve as a focus where bacteria can lodge, thus causing infective endocarditis.

Another form of sterile endocarditis is termed Libman–Sacks endocarditis; this form occurs more often in patients with lupus erythematosus and is thought to be due to the deposition of immune complexes. Like NBTE, Libman-Sacks endocarditis involves small vegetations, while infective endocarditis is composed of large vegetations. These immune complexes precipitate an inflammation reaction, which helps to differentiate it from NBTE. Also unlike NBTE, Libman-Sacks endocarditis does not seem to have a preferred location of deposition and may form on the undersurfaces of the valves or even on the endocardium.

In humans, after an incubation period of 5–19 days, the symptoms of the disease range from inapparent illness to systemic illness with severe pneumonia. It presents chiefly as an atypical pneumonia. In the first week of psittacosis the symptoms mimic typhoid fever: prostrating high fevers, joint pains, diarrhea, conjunctivitis, nose bleeds and low level of white blood cells in the blood. Rose spots can appear and these are called Horder's spots. Spleen enlargement is common towards the end of the first week. It may become a serious lung infection. Diagnosis can be suspected in case of respiratory infection associated with splenomegaly and/or epistaxis. Headache can be so severe that it suggests meningitis and some nuchal rigidity is not unusual. Towards the end of the first week stupor or even coma can result in severe cases.

The second week is more akin to acute bacteremic pneumococcal pneumonia with continuous high fevers, headaches, cough, and dyspnea. X-rays show patchy infiltrates or a diffuse whiteout of lung fields.

Complications in the form of endocarditis, liver inflammation, inflammation of the heart's muscle, joint inflammation, keratoconjunctivitis (occasionally extranodal marginal zone lymphoma of the lacrimal gland/orbit), and neurologic complications (brain inflammation) may occasionally occur. Severe pneumonia requiring intensive-care support may also occur. Fatal cases have been reported (less than 1% of cases).

In humans, "Erysipelothrix rhusiopathiae" infections most commonly present in a mild cutaneous form known as erysipeloid or fish poisoning. "E. rhusiopathiae" can cause an indolent cellulitis, more commonly in individuals who handle fish and raw meat. It gains entry typically by abrasions in the hand. Bacteremia and endocarditis are uncommon but serious sequelae. Due to the rarity of reported human cases, "E. rhusiopathiae" infections are frequently misidentified at presentation.

Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves. Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, or the surfaces of intracardiac devices. Endocarditis is characterized by lesions, known as "vegetations", which is a mass of platelets, fibrin, microcolonies of microorganisms, and scant inflammatory cells. In the subacute form of infective endocarditis, the vegetation may also include a center of granulomatous tissue, which may fibrose or calcify.

There are several ways to classify endocarditis. The simplest classification is based on cause: either "infective" or "non-infective", depending on whether a microorganism is the source of the inflammation or not. Regardless, the diagnosis of endocarditis is based on clinical features, investigations such as an echocardiogram, and blood cultures demonstrating the presence of endocarditis-causing microorganisms. Signs and symptoms include fever, chills, sweating, malaise, weakness, anorexia, weight loss, splenomegaly, flu-like feeling, cardiac murmur, heart failure, petechia of anterior trunk, Janeway's lesions, etc.

Cat-scratch disease commonly presents as tender, swollen lymph nodes near the site of the inoculating bite or scratch or on the neck, and is usually limited to one side. This condition is referred to as regional lymphadenopathy and occurs 1–3 weeks after inoculation. Lymphadenopathy in CSD most commonly occurs in the arms, neck, or jaw, but may also occur near the groin or around the ear. A vesicle or an erythematous papule may form at the site of initial infection. Most patients also develop systemic symptoms such as malaise, decreased appetite, and aches. Other associated complaints include headache, chills, muscular pains, joint pains, arthritis, backache, and abdominal pain. It may take 7 to 14 days, or as long as two months, for symptoms to appear. Most cases are benign and self-limiting, but lymphadenopathy may persist for several months after other symptoms disappear. The disease usually resolves spontaneously, with or without treatment, in one month.

In rare situations, CSD can lead to the development of serious neurologic or cardiac sequelae such as meningoencephalitis, encephalopathy, seizures, or endocarditis. Endocarditis associated with "Bartonella" infection has a particularly high mortality. Parinaud's oculoglandular syndrome is the most common ocular manifestation of CSD, and is a granulomatous conjunctivitis with concurrent swelling of the lymph node near the ear. Optic neuritis or neuroretinitis is one of the atypical presentations.

Immunocompromised patients are susceptible to other conditions associated with "B. henselae" and "B. quintana", such as bacillary angiomatosis or bacillary peliosis. Bacillary angiomatosis is primarily a vascular skin lesion that may extend to bone or be present in other areas of the body. In the typical scenario, the patient has HIV or another cause of severe immune dysfunction. Bacillary peliosis is caused by "B. henselae" that most often affects patients with HIV and other conditions causing severe immune compromise. The liver and spleen are primarily affected, with findings of blood-filled cystic spaces on pathology. In 2015 a Toledo, Ohio woman lost eyesight in an eye after a cat licked it.

The streptobacillosis form of rat-bite fever is known by the alternative names Haverhill fever and epidemic arthritic erythema. It is a severe disease caused by "Streptobacillus moniliformis", transmitted either by rat bite or ingestion of contaminated products (Haverhill fever). After an incubation period of 2–10 days, Haverhill fever begins with high prostrating fevers, rigors (shivering), headache, and polyarthralgia (joint pain). Soon, an exanthem (widespread rash) appears, either maculopapular (flat red with bumps) or petechial (red or purple spots) and arthritis of large joints can be seen. The organism can be cultivated in blood or articular fluid. The disease can be fatal if untreated in 20% of cases due to malignant endocarditis, meningoencephalitis, or septic shock. Treatment is with penicillin, tetracycline, or doxycycline.

Symptoms are different for every person depending on the type of rat-bite fever with which the person is infected. Both spirillary and streptobacillary rat-bite fever have a few individual symptoms, although most symptoms are shared. Streptobacillosis is most commonly found in the United States and spirillary rat-bite fever is generally diagnosed in patients in Africa. Rat-bite symptoms are visually seen in most cases and include inflammation around the open sore. A rash can also spread around the area and appear red or purple. Other symptoms associated with streptobacillary rat-bite fever include chills, fever, vomiting, headaches, and muscle aches. Joints can also become painfully swollen and pain can be experienced in the back. Skin irritations such as ulcers or inflammation can develop on the hands and feet. Wounds heal slowly, so symptoms possibly come and go over the course of a few months.

Symptoms associated with spirillary rat-bite fever include issues with the lymph nodes, which often swell or become inflamed as a reaction to the infection. The most common locations of lymph node swelling are in the neck, groin, and underarm. Symptoms generally appear within 2 to 10 days of exposure to the infected animal. It begins with the fever and progresses to the rash on the hands and feet within 2 to 4 days. Rash appears all over the body with this form, but rarely causes joint pain.

An infected aneurysm (also known as mycotic aneurysm or microbial arteritis) is an aneurysm arising from bacterial infection of the arterial wall. It can be a common complication of the hematogenous spread of bacterial infection.

William Osler first used the term "mycotic aneurysm" in 1885 to describe a mushroom-shaped aneurysm in a patient with subacute bacterial endocarditis. This may create considerable confusion, since "mycotic" is typically used to define fungal infections. However, mycotic aneurysm is still used for all extracardiac or intracardiac aneurysms caused by infections, except for syphilitic aortitis.

The term "infected aneurysm," proposed by Jarrett and associates is more appropriate, since few infections involve fungi. According to some authors, a more accurate term might have been endovascular infection or infective vasculitis, because mycotic aneurysms are not due to a fungal organism.

Mycotic aneurysms account for 2.6% of aortic aneurysms. For the clinician, early diagnosis is the cornerstone of effective treatment. Without medical or surgical management, catastrophic hemorrhage or uncontrolled sepsis may occur. However, symptomatology is frequently nonspecific during the early stages, so a high index of suspicion is required to make the diagnosis.

Intracranial mycotic aneurysms (ICMAs) complicate about 2% to 3% of infective endocarditis (IE) cases, although as many as 15% to 29% of patients with IE have neurologic symptoms.

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.

The symptoms are like those associated with many other febrile diseases, but with emphasis on muscular pain and night sweats. The duration of the disease can vary from a few weeks to many months or even years.

In the first stage of the disease, sepsis occurs and leads to the classic triad of undulant fevers, sweating (often with characteristic foul moldy smell sometimes likened to wet hay), and migratory arthralgia and myalgia (joint and muscle pain). Blood tests characteristically reveal a low number of white blood cells and red blood cells, show some elevation of liver enzymes such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and demonstrate positive Bengal Rose and Huddleston reactions. Gastrointestinal symptoms occur in 70% of cases and include nausea, vomiting, decreased appetite, unintentional weight loss, abdominal pain, constipation, diarrhea, an enlarged liver, liver inflammation, liver abscess, and an enlarged spleen.

This complex is, at least in Portugal, Israel, and Jordan, known as Malta fever. During episodes of Malta fever, melitococcemia (presence of brucellae in blood) can usually be demonstrated by means of blood culture in tryptose medium or Albini medium. If untreated, the disease can give origin to focalizations or become chronic. The focalizations of brucellosis occur usually in bones and joints and spondylodiscitis of the lumbar spine accompanied by sacroiliitis is very characteristic of this disease. Orchitis is also common in men.

Diagnosis of brucellosis relies on:

1. Demonstration of the agent: blood cultures in tryptose broth, bone marrow cultures. The growth of brucellae is extremely slow (they can take up to two months to grow) and the culture poses a risk to laboratory personnel due to high infectivity of brucellae.

2. Demonstration of antibodies against the agent either with the classic Huddleson, Wright, and/or Bengal Rose reactions, either with ELISA or the 2-mercaptoethanol assay for IgM antibodies associated with chronic disease

3. Histologic evidence of granulomatous hepatitis on hepatic biopsy

4. Radiologic alterations in infected vertebrae: the Pedro Pons sign (preferential erosion of the anterosuperior corner of lumbar vertebrae) and marked osteophytosis are suspicious of brucellic spondylitis.

The consequences of "Brucella" infection are highly variable and may include arthritis, spondylitis, thrombocytopenia, meningitis, uveitis, optic neuritis, endocarditis, and various neurological disorders collectively known as neurobrucellosis.

Incubation period is usually two to three weeks. The most common manifestation is flu-like symptoms with abrupt onset of fever, malaise, profuse perspiration, severe headache, muscle pain, joint pain, loss of appetite, upper respiratory problems, dry cough, pleuritic pain, chills, confusion, and gastrointestinal symptoms, such as nausea, vomiting, and diarrhea. About half of infected individuals exhibit no symptoms.

During its course, the disease can progress to an atypical pneumonia, which can result in a life-threatening acute respiratory distress syndrome, whereby such symptoms usually occur during the first four to five days of infection.

Less often, Q fever causes (granulomatous) hepatitis, which may be asymptomatic or becomes symptomatic with malaise, fever, liver enlargement, and pain in the right upper quadrant of the abdomen. Whereas transaminase values are often elevated, jaundice is uncommon. Retinal vasculitis is a rare manifestation of Q fever.

The chronic form of Q fever is virtually identical to inflammation of the inner lining of the heart (endocarditis), which can occur months or decades following the infection. It is usually fatal if untreated. However, with appropriate treatment, the mortality falls to around 10%.

"Bartonella henselae" is a fastidious, intracellular, Gram-negative bacteria.