The disease may remain manageable, but in more severe cases, lymph nodes in the neck may swell, and breathing and swallowing are more difficult. People in this stage should seek immediate medical attention, as obstruction in the throat may require intubation or a tracheotomy. Abnormal cardiac rhythms can occur early in the course of the illness or weeks later, and can lead to heart failure. Diphtheria can also cause paralysis in the eye, neck, throat, or respiratory muscles. Patients with severe cases are put in a hospital intensive care unit and given a diphtheria antitoxin. Since antitoxin does not neutralize toxin that is already bound to tissues, delaying its administration is associated with an increase in mortality risk. Therefore, the decision to administer diphtheria antitoxin is based on clinical diagnosis, and should not await laboratory confirmation.

Antibiotics have not been demonstrated to affect healing of local infection in diphtheria patients treated with antitoxin. Antibiotics are used in patients or carriers to eradicate "C. diphtheriae" and prevent its transmission to others. The Centers for Disease Control and Prevention recommends either:

- Metronidazole

- Erythromycin is given (orally or by injection) for 14 days (40 mg/kg per day with a maximum of 2 g/d), or

- Procaine penicillin G is given intramuscularly for 14 days (300,000 U/d for patients weighing 10 kg); patients with allergies to penicillin G or erythromycin can use rifampin or clindamycin.

In cases that progress beyond a throat infection, diphtheria toxin spreads through the blood and can lead to potentially life-threatening complications that affect other organs, such as the heart and kidneys. Damage to the heart caused by the toxin affects the heart's ability to pump blood or the kidneys' ability to clear wastes. It can also cause nerve damage, eventually leading to paralysis. About 40% to 50% of those left untreated can die.

Quinvaxem is a widely administered pentavalent vaccine, which is a combination of five vaccines in one that protect babies from diphtheria, among other common childhood diseases. Diphtheria vaccine is usually combined at least with tetanus vaccine (Td) and often with pertussis (DTP, DTaP, TdaP) vaccines, as well.

The antibiotics erythromycin, clarithromycin, or azithromycin are typically the recommended treatment. Newer macrolides are frequently recommended due to lower rates of side effects. Trimethoprim-sulfamethoxazole (TMP/SMX) may be used in those with allergies to first-line agents or in infants who have a risk of pyloric stenosis from macrolides.

A reasonable guideline is to treat people age >1 year within 3 weeks of cough onset and infants age <1 year and pregnant women within 6 weeks of cough onset. If the person is diagnosed late, antibiotics will not alter the course of the illness, and even without antibiotics, they should no longer be spreading pertussis. Antibiotics when used early decrease the duration of infectiousness, and thus prevent spread. Short-term antibiotics (azithromycin for 3–5 days) are as effective as long-term treatment (erythromycin 10–14 days) in eliminating "B. pertussis" with fewer and less severe side effects.

People with pertussis are infectious from the beginning of the catarrhal stage (a runny nose, sneezing, low-grade fever, symptoms of the common cold) through the third week after the onset of paroxysms (multiple, rapid coughs) or until 5 days after the start of effective antimicrobial treatment.

Effective treatments of the cough associated with this condition have not been developed.

Corticosteroids, such as dexamethasone and budesonide, have been shown to improve outcomes in children with all severities of croup. Significant relief is obtained as early as six hours after administration. While effective when given by injection, or by inhalation, giving the medication by mouth is preferred. A single dose is usually all that is required, and is generally considered to be quite safe. Dexamethasone at doses of 0.15, 0.3 and 0.6 mg/kg appear to be all equally effective.

The primary method of prevention for pertussis is vaccination. Evidence is insufficient to determine the effectiveness of antibiotics in those who have been exposed, but are without symptoms. Preventive antibiotics, however, are still frequently used in those who have been exposed and are at high risk of severe disease (such as infants).

Moderate to severe croup may be improved temporarily with nebulized epinephrine. While epinephrine typically produces a reduction in croup severity within 10–30 minutes, the benefits last for only about 2 hours. If the condition remains improved for 2–4 hours after treatment and no other complications arise, the child is typically discharged from the hospital.

Main article: COVID-19 drug repurposing research

At least 29 phase II–IV efficacy trials in COVID-19 were concluded in March 2020 or scheduled to provide results in April from hospitals in China. There are more than 300 active clinical trials underway as of April 2020. Seven trials were evaluating already approved treatments for malaria, including four studies on hydroxychloroquine or chloroquine. Repurposed antiviral drugs make up most of the Chinese research, with nine phase III trials on remdesivir across several countries due to report by the end of April. Other potential candidates in trials include vasodilators, corticosteroids, immune therapies, lipoic acid, bevacizumab, and recombinant angiotensin-converting enzyme 2.

The COVID-19 Clinical Research Coalition has goals to 1) facilitate rapid reviews of clinical trial proposals by ethics committees and national regulatory agencies, 2) fast-track approvals for the candidate therapeutic compounds, 3) ensure standardised and rapid analysis of emerging efficacy and safety data and 4) facilitate sharing of clinical trial outcomes before publication. A dynamic review of clinical development for COVID-19 vaccine and drug candidates was in place, as of April 2020.

Several existing antiviral medications are being evaluated for treatment of COVID-19, including remdesivir, chloroquine and hydroxychloroquine, lopinavir/ritonavir and lopinavir/ritonavir combined with interferon beta. There is tentative evidence for efficacy by remdesivir, as of March 2020. Clinical improvement was observed in patients treated with compassionate-use remdesivir. Remdesivir inhibits SARS-CoV-2 in vitro. Phase III clinical trials are being conducted in the US, China and Italy.

Chloroquine, previously used to treat malaria, was studied in China in February 2020, with preliminary results. However, there are calls for peer review of the research. The Guangdong Provincial Department of Science and Technology and the Guangdong Provincial Health and Health Commission issued a report stating that chloroquine phosphate "improves the success rate of treatment and shortens the length of person's hospital stay" and recommended it for people diagnosed with mild, moderate and severe cases of novel coronavirus pneumonia.

On 17 March, the Italian Pharmaceutical Agency included chloroquine and hydroxychloroquine in the list of drugs with positive preliminary results for treatment of COVID-19. Korean and Chinese Health Authorities recommend the use of chloroquine. However, the Wuhan Institute of Virology, while recommending a daily dose of one gram, notes that twice that dose is highly dangerous and could be lethal. On 28 March 2020, the FDA issued an emergency use authorisation for hydroxychloroquine and chloroquine at the discretion of physicians treating people with COVID-19.

The Chinese 7th edition guidelines also include interferon, ribavirin or umifenovir for use against COVID-19. Preliminary data indicate that high doses of ribavirin are necessary to inhibit SARS-CoV-2 in vitro. Since studies have been inconsistent with respect to ribavirin's efficacy against other novel coronaviruses (e.g., SARS, MERS) and its significant toxicity, this suggests its role in treating COVID-19 is limited and its best chance of being effective is being a part of combination therapy.

In 2020, a trial found that lopinavir/ritonavir was ineffective in the treatment of severe illness. Nitazoxanide has been recommended for further in vivo study after demonstrating low concentration inhibition of SARS-CoV-2.

Studies have demonstrated that initial spike protein priming by transmembrane protease serine 2 (TMPRSS2) is essential for entry of SARS-CoV-2 via interaction with the ACE2 receptor. These findings suggest the TMPRSS2 inhibitor camostat approved for use in Japan for inhibiting fibrosis in liver and kidney disease might constitute an effective off-label treatment.

In February 2020, favipiravir was being studied in China for experimental treatment of the emergent COVID-19 disease.

In April 2020 ivermectin is being studied in Australia for a possible treatment for COVID-19 and has been shown to stop viral growth within 48 hours in vitro.

There are mixed results as of 3 April 2020 as to the effectiveness of hydroxychloroquine as a treatment for COVID-19, with some studies showing little or no improvement. The studies of chloroquine and hydroxychloroquine with or without azithromycin have major limitations that have prevented the medical community from embracing these therapies without further study.

Oseltamivir does not inhibit SARS-CoV-2 in vitro and has no known role in COVID-19 treatment.

Severe cases will require admission to intensive care. In addition to the measures listed above for mild tetanus:

- Human tetanus immunoglobulin injected intrathecally (increases clinical improvement from 4% to 35%)

- Tracheotomy and mechanical ventilation for 3 to 4 weeks. Tracheotomy is recommended for securing the airway because the presence of an endotracheal tube is a stimulus for spasm

- Magnesium, as an intravenous (IV) infusion, to prevent muscle spasm

- Diazepam as a continuous IV infusion

- The autonomic effects of tetanus can be difficult to manage (alternating hyper- and hypotension hyperpyrexia/hypothermia) and may require IV labetalol, magnesium, clonidine, or nifedipine

Drugs such as diazepam or other muscle relaxants can be given to control the muscle spasms. In extreme cases it may be necessary to paralyze the patient with curare-like drugs and use a mechanical ventilator.

In order to survive a tetanus infection, the maintenance of an airway and proper nutrition are required. An intake of 3,500 to 4,000 calories and at least 150 g of protein per day is often given in liquid form through a tube directly into the stomach (percutaneous endoscopic gastrostomy), or through a drip into a vein (parenteral nutrition). This high-caloric diet maintenance is required because of the increased metabolic strain brought on by the increased muscle activity. Full recovery takes 4 to 6 weeks because the body must regenerate destroyed nerve axon terminals.

The serious complications of HiB are brain damage, hearing loss, and even death.

"Haemophilus influenzae" produces beta-lactamases, and it is also able to modify its penicillin-binding proteins, so it has gained resistance to the penicillin family of antibiotics.

In severe cases, cefotaxime and ceftriaxone delivered directly into the bloodstream are the elected antibiotics, and, for the less severe cases, an association of ampicillin and sulbactam, cephalosporins of the second and third generation, or fluoroquinolones are preferred. (Fluoroquinolone-resistant "Haemophilus influenzae" have been observed.)

Macrolide antibiotics (e.g., clarithromycin) may be used in patients with a history of allergy to beta-lactam antibiotics. Macrolide resistance has also been observed.

Mild cases of tetanus can be treated with:

- tetanus immunoglobulin (TIG), also called "tetanus antibodies" or "tetanus antitoxin." It can be given as intravenous therapy or by intramuscular injection.

- metronidazole IV for 10 days

- diazepam oral or IV

As of April 2020, there is no specific treatment for COVID-19. Research is, however, ongoing. For symptoms, some medical professionals recommend paracetamol (acetaminophen) over ibuprofen for first-line use. The WHO does not oppose the use of non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen for symptoms, and the FDA says currently there is no evidence that NSAIDs worsen COVID-19 symptoms.

While theoretical concerns have been raised about ACE inhibitors and angiotensin receptor blockers, as of 19 March 2020, these are not sufficient to justify stopping these medications. Steroids, such as methylprednisolone, are not recommended unless the disease is complicated by acute respiratory distress syndrome.

Medications to prevent blood clotting have been suggested for treatment, and anticoagulant therapy with low molecular weight heparin appears to be associated with better outcomes in severe COVID‐19 showing signs of coagulopathy (elevated D-dimer).

Throughout history treatment relied primarily on β-lactam antibiotics. In the 1960s nearly all strains of "S. pneumoniae" were susceptible to penicillin, but more recently there has been an increasing prevalence of penicillin resistance especially in areas of high antibiotic use. A varying proportion of strains may also be resistant to cephalosporins, macrolides (such as erythromycin), tetracycline, clindamycin and the quinolones. Penicillin-resistant strains are more likely to be resistant to other antibiotics. Most isolates remain susceptible to vancomycin, though its use in a β-lactam-susceptible isolate is less desirable because of tissue distribution of the drug and concerns of development of vancomycin resistance. More advanced beta-lactam antibiotics (cephalosporins) are commonly used in combination with other drugs to treat meningitis and community-acquired pneumonia. In adults recently developed fluoroquinolones such as levofloxacin and moxifloxacin are often used to provide empiric coverage for patients with pneumonia, but in parts of the world where these drugs are used to treat tuberculosis resistance has been described.

Susceptibility testing should be routine with empiric antibiotic treatment guided by resistance patterns in the community in which the organism was acquired. There is currently debate as to how relevant the results of susceptibility testing are to clinical outcome. There is slight clinical evidence that penicillins may act synergistically with macrolides to improve outcomes.

Antibiotics to combat the streptococcal infection are the mainstay of treatment for scarlet fever. Prompt administration of appropriate antibiotics decreases the length of illness. Peeling of the outer layer of skin however will happen despite treatment. One of the main goals of treatment is to prevent the child from developing one of the suppurative or nonsuppurative complications, especially acute rheumatic fever. As long as antibiotics are started within 9 days, it is very unlikely for the child to develop acute rheumatic fever. Antibiotic therapy has not been shown to prevent the development of poststreptococcal glomerulonephritis. Another important reason for prompt treatment with antibiotics is the ability to prevent transmission of the infection between children. An infected individual is most likely to pass on the infection to another person during the first 2 weeks. A child is no longer contagious (able to pass the infection to another child) after 24 hours of antibiotics.

The antibiotic of choice is penicillin V which is taken by mouth in pill form. Children who are not able to take pills can be given amoxicillin which comes in a liquid form and is equally effective. Duration of treatment is 10 days. Benzathine Penicillin G can be given as a one time intramuscular injection as another alternative if swallowing pills is not possible. If the patient is allergic to the family of antibiotics which both penicillin and amoxicillin are a part of (beta-lactam antibiotics), a first generation cephalosporin is used. Cephalosporin antibiotics however can still cause adverse reactions in patients whose allergic reaction to penicillin is a Type 1 Hypersensitivity reaction. In those cases it is appropriate to choose clindamycin or erythromycin instead.

Tonsillectomy, although once a reasonable treatment for recurrent streptococcal pharyngitis, is not indicated. This is due to the fact that a person can still be infected with group A streptococcus without their tonsils.

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.

The live attenuated BCG vaccine developed against tuberculosis has been shown to have strong beneficial effects on the ability to combat non-tuberculosis infections.

Several studies have suggested that BCG vaccination may reduce atopy, particularly when given early in life. Furthermore, in multiple observational studies BCG vaccination has been shown to provide beneficial effects on overall mortality. These observations encouraged randomised controlled trials to examine BCG vaccination's beneficial non-specific effects on overall health. Since BCG vaccination is recommended to be given at birth in countries that have a high incidence of tuberculosis it would have been unethical to randomize children into 'BCG' vs. 'no BCG' groups. However, many low-income countries delay BCG vaccination for low-birth-weight (LBW) infants; this offered the opportunity to directly test the effect of BCG on overall mortality.

In the first two randomised controlled trials receipt of BCG+OPV at birth vs. OPV only ('delayed BCG') was associated with strong reductions in neonatal mortality; these effects were seen as early as 3 days after vaccination. BCG protected against sepsis as well as respiratory infections.

Among BCG vaccinated children, those who develop a BCG scar or a positive skin test (TST) are less likely to develop sepsis and exhibit an overall reduction in child mortality of around 50%.

In a recent WHO-commissioned review based on five clinical trials and nine observational studies, it was concluded that "the results indicated a beneficial effect of BCG on overall mortality in the first 6–12 months of life. Relevant follow-up in some of the trials was short, and all of the observational studies were regarded as being at risk of bias, so the confidence in the findings was rated as very low according to the GRADE criteria and "There was a suggestion that BCG vaccination may be more beneficial the earlier it is given". Furthermore, "estimated effects are in the region of a halving of mortality risk" and "any effect of BCG vaccine on all-cause mortality is not likely to be attributable to any great extent to fewer deaths from tuberculosis (i.e. to a specific effect of BCG vaccine against tuberculosis)". Based on the evidence, the WHO's Strategic Group of Experts on Immunization concluded that "the non-specific effects on all-cause mortality warrant further research".

Neither the combination of antivirals and interferons (ribavirin + interferon alfa-2a or interferon alfa-2b) nor corticosteroids improved outcomes.

When rhesus macaques were given interferon-α2b and ribavirin and exposed to MERS, they developed less pneumonia than control animals. Five critically ill people with MERS in Saudi Arabia with ARDS and on ventilators were given interferon-α2b and ribavirin but all ended up dying of the disease. The treatment was started late in their disease (a mean of 19 days after hospital admission) and they had already failed trials of steroids so it remains to be seen whether it may have benefit earlier in the course of disease. Another proposed therapy is inhibition of viral protease or kinase enzymes. Researchers are investigating a number of ways to combat the outbreak of Middle East respiratory syndrome coronavirus, including using interferon, chloroquine, chlorpromazine, loperamide, and lopinavir, as well as other agents such as mycophenolic acid and camostat.

Numerous observational studies and randomised trials (RCTs) have found that the impact on mortality of live and inactivated vaccines differ markedly. All live vaccines studied so far (BCG, measles vaccine, oral polio vaccine (OPV) and smallpox vaccine) have been shown to reduce mortality more than can be explained by prevention of the targeted infection(s). In contrast, inactivated vaccines (diphtheria-tetanus-pertussis (DTP), hepatitis B, inactivated polio vaccine) may have deleterious effects in spite of providing target disease protection.

One method is long term use of antibiotics to prevent future group A streptococcal infections. This method is only indicated for people who have had complications like recurrent attacks of acute rheumatic fever or rheumatic heart disease. Antibiotics are limited in their ability to prevent these infections since there are a variety of subtypes of group A streptococci that can cause the infection.

The vaccine approach has a greater likelihood of effectively preventing group A streptococcal infections because vaccine formulations can target multiple subtypes of the bacteria. A vaccine developed by George and Gladys Dick in 1924 was discontinued due to poor efficacy and the introduction of antibiotics. Difficulties in vaccine development include the considerable strain variety of group A streptococci present in the environment and the amount of time and number of people needed for appropriate trials for safety and efficacy of any potential vaccine. There have been several attempts to create a vaccine in the past few decades. These vaccines, which are still in the development phase, expose to the person to proteins present on the surface of the group A streptococci to activate an immune response that will prepare the person to fight and prevent future infections.

There used to be a diphtheria scarlet fever vaccine. It was, however, found not to be effective. This product was discontinued by the end of World War II.

Medications are usually not needed as hand, foot, and mouth disease is a viral disease that typically resolves on its own. Currently, there is no specific curative treatment for hand, foot and mouth disease. Disease management typically focuses on achieving symptomatic relief. Pain from the sores may be eased with the use of analgesic medications. Infection in older children, adolescents, and adults is typically mild and lasts approximately 1 week, but may occasionally run a longer course. Fever reducers and lukewarm baths can help decrease body temperature.

A minority of individuals with hand, foot and mouth disease may require hospital admission due to complications such as inflammation of the brain, inflammation of the meninges, or acute flaccid paralysis. Non-neurologic complications such as inflammation of the heart, fluid in the lungs, or bleeding into the lungs may also occur.

Prescribing antibiotics for laryngitis is not suggested practice. The antibiotics penicillin V and erythromycin are not effective for treating acute laryngitis. Erythromycin may improve voice disturbances after one week and cough after two weeks, however any modest subjective benefit is not greater than the adverse effects, cost, and the risk of bacteria developing resistance to the antibiotics. Health authorities have been strongly encouraging physicians to decrease the prescribing of antibiotics to treat common upper respiratory tract infections because antibiotic usage does not significantly reduce recovery time for these viral illnesses. Decreased antibiotic usage could also have prevented drug resistant bacteria. Some have advocated a delayed antibiotic approach to treating URIs which seeks to reduce the consumption of antibiotics while attempting to maintain patient satisfaction. Most studies show no difference in improvement of symptoms between those treated with antibiotics right away and those with delayed prescriptions. Most studies also show no difference in patient satisfaction, patient complications, symptoms between delayed and no antibiotics. A strategy of "no antibiotics" results in even less antibiotic use than a strategy of "delayed antibiotics".

Paracetamol (acetaminophen) and NSAIDs, such as ibuprofen, may be used to reduce fever and pain. Prednisone, a corticosteroid, while used to try to reduce throat pain or enlarged tonsils, remains controversial due to the lack of evidence that it is effective and the potential for side effects. Intravenous corticosteroids, usually hydrocortisone or dexamethasone, are not recommended for routine use but may be useful if there is a risk of airway obstruction, a very low platelet count, or hemolytic anemia.

There is little evidence to support the use of antivirals such as aciclovir and valacyclovir although they may reduce initial viral shedding. Although antivirals are not recommended for people with simple infectious mononucleosis, they may be useful (in conjunction with steroids) in the management of severe EBV manifestations, such as EBV meningitis, peripheral neuritis, hepatitis, or hematologic complications.

Although antibiotics exert no antiviral action they may be indicated to treat bacterial secondary infections of the throat, such as with streptococcus (strep throat). However, ampicillin and amoxicillin are not recommended during acute Epstein–Barr virus infection as a diffuse rash may develop.

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.

Infectious mononucleosis is generally self-limiting, so only symptomatic or supportive treatments are used. The need for rest and return to usual activities after the acute phase of the infection may reasonably be based on the person's general energy levels. Nevertheless, in an effort to decrease the risk of splenic rupture experts advise avoidance of contact sports and other heavy physical activity, especially when involving increased abdominal pressure or the Valsalva maneuver (as in rowing or weight training), for at least the first 3–4 weeks of illness or until enlargement of the spleen has resolved, as determined by a treating physician.

The Centers for Disease Control describe protocol for treating sinusitis while at the same time discouraging overuse of antibiotics:

- Target likely organisms with first-line drugs: Amoxicillin, Amoxicillin/Clavulanate

- Use shortest effective course: Should see improvement in 2–3 days. Continue treatment for 7 days after symptoms improve or resolve (usually a 10–14 day course).

- Consider imaging studies in recurrent or unclear cases: some sinus involvement is frequent early in the course of uncomplicated viral URI

Treatment comprises symptomatic support usually via analgesics for headache, sore throat and muscle aches. Moderate exercise in sedentary subjects with naturally acquired URTI probably does not alter the overall severity and duration of the illness. No randomized trials have been conducted to ascertain benefits of increasing fluid intake.