The term "penicillin" is often used generically to refer to benzylpenicillin (penicillin G, the original penicillin found in 1928), procaine benzylpenicillin (procaine penicillin), benzathine benzylpenicillin (benzathine penicillin), and phenoxymethylpenicillin (penicillin V). Procaine penicillin and benzathine penicillin have the same antibacterial activity as benzylpenicillin but act for a longer period of time. Phenoxymethylpenicillin is less active against gram-negative bacteria than benzylpenicillin. Benzylpenicillin, procaine penicillin and benzathine penicillin can be given by intravenous or intramuscular injections, but phenoxymethylpenicillin can be given by mouth because of its acidic stability.

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.

The side effects of penicillin are bodily responses to penicillin and closely related antibiotics that do not relate directly to its effect on bacteria. A side effect is an effect that is not intended with normal dosaging. Some of these reactions are visible and some occur in the body's organs or blood. Penicillins are a widely-used group of medications that are effective for the treatment of a wide variety of bacterial infections in human adults and children as well as other species. Some side effects are predictable, of which some are common but not serious, some are uncommon and serious and others are rare. The route of administration of penicillin can have an effect on the development of side effects. An example of this is irritation and inflammation that develops at a peripheral infusion site when penicillin is administered intravenously. In addition, penicillin is available in different forms. There are different penicillin medications (penicillin G benzathine, penicillin G potassium, penicillin G procaine, and penicillin V) as well as a number of β-lactam antibiotics derived from penicillin (e.g. amoxicillin) generally also referred to as "penicillin".

Side effects may only last for a short time and then go away. Side effects can be relieved in some cases with non pharmacological treatment. Some side effects require treatment to correct potentially serious and sometimes fatal reactions to penicillin. Penicillin has not been found to cause birth defects.

Many people have indicated that they have a side effect related to an allergic reaction to penicillin. It has been proposed that as many as 90% of those claiming to have an allergy to penicillin are able to take it. Identifying an allergy to penicillin requires a hypersensitivity skin test which diagnoses IgE-mediated immune responses caused by penicillin. This test is typically performed by an allergist who uses a skin-prick and intradermal injection of penicilloyl-polylysine, a negative control (normal saline), and a positive control (histamine).

There is a common side effect that can develop when other medications are used. This is the development of cross sensitivities to other antibiotics. If someone has developed side effects when taking penicillin, these side effects may develop with a new medication even though the person has not taken the new medication before. Those medications that may cause a cross sensitivity reaction are: carbapenems, ampicillin, cefazolin, cephalosporins and cloxacillin.

Pneumonia occurs when the lungs become infected, causing inflammation (swelling). Symptoms of pneumonia usually include:

- Fever (but older people may have lower than normal body temperature)

- Cough

- Shortness of breath

- Chills

- Sweating

- Chest pain that comes and goes with breathing

- Headache

- Muscle pain

- Excessive tiredness

- Nails may turn blue from lack of oxygen

A subset of children with acute, rapid-onset of tic disorders and obsessive compulsive disorder (OCD) are hypothesized to be due to an autoimmune response to group A beta-hemolytic streptococcal infection (PANDAS).

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.

Post-streptococcal glomerulonephritis (PSGN) is an uncommon complication of either a strep throat or a streptococcal skin infection. It is classified as a type III hypersensitivity reaction. Symptoms of PSGN develop within 10 days following a strep throat or 3 weeks following a GAS skin infection. PSGN involves inflammation of the kidney. Symptoms include pale skin, lethargy, loss of appetite, headache, and dull back pain. Clinical findings may include dark-colored urine, swelling of different parts of the body (edema), and high blood pressure. Treatment of PSGN consists of supportive care.

GBS is found in the gastrointestinal and genitourinary tract of humans. In different studies, GBS vaginal colonization rate ranges from 4 to 36%, with most studies reporting rates over 20%. These variations in the reported prevalence of asymptomatic (presenting no symptoms of disease) colonization could be related to the different detection methods used, and differences in populations studied.

Though GBS is an asymptomatic colonizer of the gastrointestinal human tract in up to 30% of otherwise healthy adults, including pregnant women,

this opportunistic harmless bacterium can, in some circumstances, cause severe invasive infections.

Among the signs of subacute bacterial endocarditis are:

- Malaise

- Weakness

- Excessive sweat

- Fever

Though GBS colonization is asymptomatic and, in general, does not cause problems, it can sometimes cause serious illness for the mother and the baby during gestation and after delivery. GBS infections in the mother can cause chorioamnionitis (intra-amniotic infection or severe infection of the placental tissues) infrequently, and postpartum infections (after birth). GBS urinary tract infections may induce labour and cause premature delivery (preterm birth) and miscarriage.

Clinical features may include initial symptoms of an upper respiratory tract infection mimicking a viral infection, usually associated with fevers, often low-grade. This may progress to the lower respiratory tract in a few days, with features often resembling those of a wheezy bronchitis. Sputum may be difficult to expectorate and is often grey or creamy in color. The cough may persist for weeks without appropriate treatment. Many cases are diagnosed after presenting chest infections do not respond to penicillins or first-generation cephalosporins.

Clinical diagnosis of "H. influenzae" is typically performed by bacterial culture or latex particle agglutinations. Diagnosis is considered confirmed when the organism is isolated from a sterile body site. In this respect, "H. influenzae" cultured from the nasopharyngeal cavity or sputum would not indicate "H. influenzae" disease, because these sites are colonized in disease-free individuals. However, "H. influenzae" isolated from cerebrospinal fluid or blood would indicate "H. influenzae" infection.

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.

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.

Infective endocarditis is an infection of the inner surface of the heart, usually the valves. Symptoms may include fever, small areas of bleeding into the skin, heart murmur, feeling tired, and low red blood cells. Complications may include valvular insufficiency, heart failure, stroke, and kidney failure.

The cause is typically a bacterial infection and less commonly a fungal infection. Risk factors include valvular heart disease including rheumatic disease, congenital heart disease, artificial valves, hemodialysis, intravenous drug use, and electronic pacemakers. The bacterial most commonly involved are streptococci or staphylococci. Diagnosis is suspected based on symptoms and supported by blood cultures or ultrasound. There is also a noninfective form of endocarditis.

The usefulness of antibiotics following dental procedures for prevention is unclear. Some recommend them in those at high risk. Treatment is generally with intravenous antibiotics. The choice of antibiotics is based on the blood cultures. Occasionally heart surgery is required.

The number of people affected is about 5 per 100,000 per year. Rates, however, vary between regions of the world. Males are affected more often than females. The risk of death among those infected is about 25%. Without treatment it is almost universally fatal.

Many microorganisms can cause infective endocarditis. These are generally isolated by blood culture, where the patient's blood is removed, and any growth is noted and identified. The term bacterial endocarditis (BE) commonly is used, reflecting the fact that most cases of IE are due to bacteria; however, infective endocarditis (IE) has become the preferred term.

Common signs and symptoms include:

- sore throat

- red, swollen tonsils

- pain when swallowing

- high temperature (fever)

- headache

- tiredness

- chills

- a general sense of feeling unwell (malaise)

- white pus-filled spots on the tonsils

- swollen lymph nodes (glands) in the neck

- pain in the ears or neck

- weight loss

- difficulty ingesting and swallowing meal/liquid intake

- difficulty sleeping

Less common symptoms include:

- nausea

- fatigue

- stomach ache

- vomiting

- furry tongue

- bad breath (halitosis)

- voice changes

- difficulty opening the mouth (trismus)

- loss of appetite

- Anxiety/fear of choking

In cases of acute tonsillitis, the surface of the tonsil may be bright red and with visible white areas or streaks of pus.

Tonsilloliths occur in up to 10% of the population frequently due to episodes of tonsillitis.

In most cases AIT is characterized by onset of pain, firmness, tenderness, redness or swelling in the anterior aspect of the neck. Patients will also present with a sudden fever, dysphagia and dysphonia. Symptoms may be present from 1 to 180 days, with most symptoms lasting an average of about 18 days. The main issue associated with the diagnosis of AIT is differentiating it from other more commonly seen forms of thyroid conditions. Pain, fever and swelling are often much more severe and continue to get worse in patients who have AIT compared to those with other thyroid conditions. Patients who are suspected of having AIT often undergo tests to detect for elevated levels of white blood cells as well as an ultrasound to reveal unilobular swelling. Depending on the age and immune status of the patient more invasive procedures may be performed such as fine needle aspiration of the neck mass to facilitate a diagnosis.

In cases where the infection is thought to be associated with a sinus fistula it is often necessary to confirm the presence of the fistula through surgery or laryngoscopic examination. While invasive procedures can often tell definitively whether or not a fistula is present, new studies are working on the use of computed tomography as a useful method to visualize and detect the presence of a sinus fistula.

Epiglottitis is associated with fever, difficulty in swallowing, drooling, hoarseness of voice, and typically stridor. Stridor is a sign of upper airways obstruction and is a surgical emergency. The child often appears acutely ill, anxious, and has very quiet shallow breathing with the head held forward, insisting on sitting up in bed. The early symptoms are insidious but rapidly progressive, and swelling of the throat may lead to cyanosis and asphyxiation.

Since the introduction of the "Hemophilus influenzae" (Hib) vaccination in many Western countries, childhood incidence has decreased while adult incidence has remained the same; the disease is thus becoming "relatively" more common in adults than children.

The disease typically develops two to four weeks after a throat infection. Symptoms include: fever, painful joints with those joints affected changing with time, involuntary muscle movements, and occasionally a characteristic non-itchy rash known as erythema marginatum. The heart is involved in about half of cases. Damage to the heart valves usually occurs only after multiple attacks but may occasionally occur after a single case of RF. The damaged valves may result in heart failure and also increase the risk of atrial fibrillation and infection of the valves.

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.

Rheumatic fever (RF) is an inflammatory disease that can involve the heart, joints, skin, and brain. The disease typically develops two to four weeks after a streptococcal throat infection. Signs and symptoms include fever, multiple painful joints, involuntary muscle movements, and occasionally a characteristic non-itchy rash known as erythema marginatum. The heart is involved in about half of cases. Damage to the heart valves, known as rheumatic heart disease (RHD), usually occurs after repeated attacks but can sometimes occur after one. The damaged valves may result in heart failure, atrial fibrillation and infection of the valves.

Rheumatic fever may occur following an infection of the throat by the bacterium "Streptococcus pyogenes". If the infection is untreated rheumatic fever can occur in up to three percent of people. The underlying mechanism is believed to involve the production of antibodies against a person's own tissues. Due to their genetics, some people are more likely to get the disease when exposed to the bacteria than others. Other risk factors include malnutrition and poverty. Diagnosis of RF is often based on the presence of signs and symptoms in combination with evidence of a recent streptococcal infection.

Treating people who have strep throat with antibiotics, such as penicillin, decreases the risk of developing rheumatic fever. In order to avoid antibiotic misuse this often involves testing people with sore throats for the infection, which may not be available in the developing world. Other preventive measures include improved sanitation. In those with rheumatic fever and rheumatic heart disease, prolonged periods of antibiotics are sometimes recommended. Gradual return to normal activities may occur following an attack. Once RHD develops, treatment is more difficult. Occasionally valve replacement surgery or valve repair is required. Otherwise complications are treated as per normal.

Rheumatic fever occurs in about 325,000 children each year and about 33.4 million people currently have rheumatic heart disease. Those who develop RF are most often between the ages of 5 and 14, with 20% of first-time attacks occurring in adults. The disease is most common in the developing world and among indigenous peoples in the developed world. In 2015 it resulted in 319,400 deaths down from 374,000 deaths in 1990. Most deaths occur in the developing world where as many as 12.5% of people affected may die each year. Descriptions of the condition are believed to date back to at least the 5th century BCE in the writings of Hippocrates. The disease is so named because its symptoms are similar to those of some rheumatic disorders.

The disease is characterised by the formation of painful abscesses in the mouth, lungs, breast, or gastrointestinal tract. Actinomycosis abscesses grow larger as the disease progresses, often over months. In severe cases, they may penetrate the surrounding bone and muscle to the skin, where they break open and leak large amounts of pus, which often contains characteristic granules (sulfur granules) filled with progeny bacteria. These granules are named due to their appearance, but are not actually composed of sulfur.

Despite the thyroid gland being extremely resistant to infection, it is still susceptible to infection by various bacteria. The cause can be almost any bacterium. "Staphylococcus aureus", "Streptococcus pyogenes", "Staphylococcus epidermidis", and "Streptococcus pneumoniae" in descending order are the organisms most commonly isolated from acute thyroiditis cases in children. Other aerobic organisms are "Klebsiella sp", "Haemophilus influenza", "Streptococcus viridans", "Eikenella corrodens", "Enterobacteriaceae", and "salmonella sp".

Occurrences of AIT are most common in patients with prior thyroid disease such as Hashimoto's thyroiditis or thyroid cancer. The most common cause of infection in children is a congenital abnormality such as pyriform sinus fistula. In most cases, the infection originates in the piriform sinus and spreads to the thyroid via the fistula. In many reported cases of AIT the infection occurs following an upper respiratory tract infection. One study found that of the reported cases of AIT, 66% occurred after an acute illness involving the upper respiratory tract. Although the rates of infection are still very low, cases of AIT have been on the rise in recent years due to the higher occurrence of immune-compromised patients.

Other causes of AIT are commonly due to contamination from an outside source and are included below.

- Repeated fine needle aspirates

- Perforation of esophagus

- Regional infection

"Actinomycosis" is a rare infectious bacterial disease caused by "Actinomyces" species. About 70% of infections are due to either "Actinomyces israelii" or "A. gerencseriae". Infection can also be caused by other "Actinomyces" species, as well as "Propionibacterium propionicus", which presents similar symptoms. The condition is likely to be polymicrobial aerobic anaerobic infection.