The Infectious Disease Society of America (IDSA) recommends treating uncomplicated methicillin resistant staph aureus (MRSA) bacteremia with a 14-day course of intravenous vancomycin. Uncomplicated bacteremia is defined as having positive blood cultures for MRSA, but having no evidence of endocarditis, no implanted prostheses, negative blood cultures after 2–4 days of treatment, and signs of clinical improvement after 72 hrs.

The antibiotic treatment of choice for streptococcal and enteroccal infections differs by species. However, it is important to look at the antibiotic resistance pattern for each species from the blood culture to better treat infections caused by resistant organisms.

The presence of bacteria in the blood almost always requires treatment with antibiotics. This is because there are high mortality rates from progression to sepsis if antibiotics are delayed.

The treatment of bacteremia should begin with empiric antibiotic coverage. Any patient presenting with signs or symptoms of bacteremia or a positive blood culture should be started on intravenous antibiotics. The choice of antibiotic is determined by the most likely source of infection and by the characteristic organisms that typically cause that infection. Other important considerations include the patient's past history of antibiotic use, the severity of the presenting symptoms, and any allergies to antibiotics. Empiric antibiotics should be narrowed, preferably to a single antibiotic, once the blood culture returns with a particular bacteria that has been isolated.

General anaesthesia is recommended for people with sepsis who require surgical procedures to remove the infective source. Inhalational and intravenous anaesthetics are used. Requirements for anaesthetics may be reduced. Inhalational anaesthetics can reduce the level of proinflammatory cytokines, altering leukocyte adhesion and proliferation, inducing apoptosis (cell death) of the lymphocytes, possibly with a toxic effect on mitochondrial function. Although etomidate has a minimal effect on the cardiovascular system, it is often not recommended as a medication to help with intubation in this situation due to concerns it may lead to poor adrenal function and an increased risk of death. The small amount of evidence there is, however, has not found a change in the risk of death with etomidate.

It is recommended that the head of the bed be raised if possible to improve ventilation. Paralytic agents should be avoided unless ARDS is suspected.

Two sets of blood cultures (aerobic and anaerobic) should be taken without delaying the initiation of antibitoics. Cultures from other sites such as respiratory secretions, urine, wounds, cerebrospinal fluid, and catheter insertion sites (in-situ more than 48 hours) can be taken if infections from these sites are suspected. In severe sepsis and septic shock, broad-spectrum antibiotics (usually two, a β-lactam antibiotic with broad coverage, or broad-spectrum carbapenem combined with fluoroquinolones, macrolides, or aminoglycosides) are recommended. However, combination of antibiotics is not recommended for the treatment of sepsis but without shock and immuno-compromised persons unless the combination is used to broaden the anti-bacterial activity. The choice of antibiotics is important in determining the survival of the person. Some recommend they be given within one hour of making the diagnosis, stating that for every hour of delay in the administration of antibiotics, there is an associated 6% rise in mortality. Others did not find a benefit with early administration.

Several factors determine the most appropriate choice for the initial antibiotic regimen. These factors include local patterns of bacterial sensitivity to antibiotics, whether the infection is thought to be a hospital or community-acquired infection, and which organ systems are thought to be infected. Antibiotic regimens should be reassessed daily and narrowed if appropriate. Treatment duration is typically 7–10 days with the type of antibiotic used directed by the results of cultures. In case the culture result is negative, antibiotics should be de-escalated according to person's clinical response or stopped altogether if infection is not present to decrease the chances that the person is infected with multiple drug resistance organisms. In case of people having high risk of being infected with multiple drug resistance organisms such as "Pseudomonas aeruginosa", "Acinetobacter baumannii", addition of antibiotic specific to gram-negative organism is recommended. For Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin and teicoplanin is recommanded. For Legionella infection, addition of macrolide or fluoroquinolone is chosen. If fungal infection is suspected, echinocandin (caspofungin and micafungin) is chosen for people with severe sepsis, followed by triazole (fluconazole and itraconazole) for less ill people. Prolonged antibiotic prophylaxis is not recommended in people who has SIRS without any infectious origion such as acute pancreatitis and burns unless sepsis is suspected.

Once daily dosing of aminoglycoside is sufficient to achieve peak plasma concentration for clinical response without kidney toxicity. Meanwhile, for antibiotics with low volume distribution (vancomycin, teicoplanin, colistin), loading dose is required to achieve adequate therapeutic level to fight infections. Frequent infusions of beta-lactam antibiotics without exceeding total daily dose would help to keep the antibiotics level above minimum inhibitory concentration (MIC), thus providing better clinical response. Giving beta-lactam antibiotics continuously may be better than giving them intermittently. Access to therapeutic drug monitoring is important to ensure adequate drug therapeutic level while at the same time preventing the drug from reaching toxic level.

Lemierre's syndrome is primarily treated with antibiotics given intravenously. "Fusobacterium necrophorum" is generally highly susceptible to beta-lactam antibiotics, metronidazole, clindamycin and third generation cephalosporins while the other fusobacteria have varying degrees of resistance to beta-lactams and clindamycin. Additionally, there may exist a co-infection by another bacterium. For these reasons is often advised not to use monotherapy in treating Lemierre's syndrome. Penicillin and penicillin-derived antibiotics can thus be combined with a beta-lactamase inhibitor such as clavulanic acid or with metronidazole. Clindamycin can be given as monotherapy.

If antibiotic therapy does not improve the clinical picture, it may prove useful to drain any abscesses and/or perform ligation of the internal jugular vein where the antibiotic can not penetrate.

There is no evidence to opt for or against the use of anticoagulation therapy. The low incidence of Lemierre's syndrome has not made it possible to set up clinical trials to study the disease.

The disease can often be untreatable, especially if other negative factors occur, i.e. various diseases occurring at the same time, such as meningitis, pneumonia.

Antibiotics are the treatment of choice for bacterial pneumonia, with ventilation (oxygen supplement) as supportive therapy. The antibiotic choice depends on the nature of the pneumonia, the microorganisms most commonly causing pneumonia in the geographical region, and the immune status and underlying health of the individual. In the United Kingdom, amoxicillin is used as first-line therapy in the vast majority of patients acquiring pneumonia in the community, sometimes with added clarithromycin. In North America, where the "atypical" forms of community-acquired pneumonia are becoming more common, clarithromycin, azithromycin, or fluoroquinolones as single therapy have displaced the amoxicillin as first-line therapy.

Local patterns of antibiotic-resistance always need to be considered when initiating pharmacotherapy. In hospitalized individuals or those with immune deficiencies, local guidelines determine the selection of antibiotics.

"Streptococcus pneumoniae" — amoxicillin (or erythromycin in patients allergic to penicillin); cefuroxime and erythromycin in severe cases.

"Staphylococcus aureus" — flucloxacillin (to counteract the organism's β-lactamase).

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.

Treatment of CAP in children depends on the child's age and the severity of illness. Children under five are not usually treated for atypical bacteria. If hospitalization is not required, a seven-day course of amoxicillin is often prescribed, with co-trimaxazole an alternative when there is allergy to penicillins. Further studies are needed to confirm the efficacy of newer antibiotics. With the increase in drug-resistant Streptococcus pneumoniae, antibiotics such as cefpodoxime may become more popular. Hospitalized children receive intravenous ampicillin, ceftriaxone or cefotaxime, and a recent study found that a three-day course of antibiotics seems sufficient for most mild-to-moderate CAP in children.

Most newborn infants with CAP are hospitalized, receiving IV ampicillin and gentamicin for at least ten days to treat the common causative agents "streptococcus agalactiae", "listeria monocytogenes" and "escherichia coli". To treat the herpes simplex virus, IV acyclovir is administered for 21 days.

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.

Neuraminidase inhibitors may be used to treat viral pneumonia caused by influenza viruses (influenza A and influenza B). No specific antiviral medications are recommended for other types of community acquired viral pneumonias including SARS coronavirus, adenovirus, hantavirus, and parainfluenza virus. Influenza A may be treated with rimantadine or amantadine, while influenza A or B may be treated with oseltamivir, zanamivir or peramivir. These are of most benefit if they are started within 48 hours of the onset of symptoms. Many strains of H5N1 influenza A, also known as avian influenza or "bird flu", have shown resistance to rimantadine and amantadine. The use of antibiotics in viral pneumonia is recommended by some experts, as it is impossible to rule out a complicating bacterial infection. The British Thoracic Society recommends that antibiotics be withheld in those with mild disease. The use of corticosteroids is controversial.

Antibiotic treatment only has a marginal effect on the duration of symptoms, and its use is not recommended except in high-risk patients with clinical complications.

Erythromycin can be used in children, and tetracycline in adults. Some studies show, however, that erythromycin rapidly eliminates "Campylobacter" from the stool without affecting the duration of illness. Nevertheless, children with dysentery due to "C. jejuni" benefit from early treatment with erythromycin. Treatment with antibiotics, therefore, depends on the severity of symptoms. Quinolones are effective if the organism is sensitive, but high rates of quinolone use in livestock means that quinolones are now largely ineffective.

Antimotility agents, such as loperamide, can lead to prolonged illness or intestinal perforation in any invasive diarrhea, and should be avoided. Trimethoprim/sulfamethoxazole and ampicillin are ineffective against "Campylobacter".

It is extremely difficult to successfully treat BPF, mainly because of the difficulty obtaining a proper diagnosis. Since the disease starts out with what seems to be a common case of conjunctivitis, "H. aegyptius" is not susceptible to the antibiotic eye drops that are being used to treat it. This treatment is ineffective because it treats only the local ocular infection, whereas if it progresses to BPF, systemic antibiotic treatment is required. Although BPF is susceptible to many commonly used antibiotics, including ampicillin, cefuroxime, cefotaxime, rifampin, and chloramphenicol, by the time it is diagnosed the disease has progressed too much to be effectively treated. However, with the fast rate of progression of BPF it is unlikely that it will be successfully treated. With antibiotic therapy, the mortality rate of BPF is around 70%.

Antibiotics improve outcomes in those with bacterial pneumonia. Antibiotic choice depends initially on the characteristics of the person affected, such as age, underlying health, and the location the infection was acquired. In the UK, treatment before culture results with amoxicillin is recommended as the first line for community-acquired pneumonia, with doxycycline or clarithromycin as alternatives. In North America, where the "atypical" forms of community-acquired pneumonia are more common, macrolides (such as azithromycin or erythromycin), and doxycycline have displaced amoxicillin as first-line outpatient treatment in adults. In children with mild or moderate symptoms, amoxicillin remains the first line. The use of fluoroquinolones in uncomplicated cases is discouraged due to concerns about side-effects and generating resistance in light of there being no greater clinical benefit.

For those who require hospitalization and caught their pneumonia in the community the use of a β-lactam such as cephazolin plus macrolide such as azithromycin or a fluoroquinolones is recommended. The addition of corticosteroids also appears to improve outcomes.

The duration of treatment has traditionally been seven to ten days, but increasing evidence suggests that shorter courses (three to five days) are similarly effective. Recommendations for hospital-acquired pneumonia include third- and fourth-generation cephalosporins, carbapenems, fluoroquinolones, aminoglycosides, and vancomycin. These antibiotics are often given intravenously and used in combination. In those treated in hospital, more than 90% improve with the initial antibiotics.

Fulminant infection from meningococci bacteria in the bloodstream is a medical emergency and requires emergent treatment with adequate antibiotics. Benzylpenicillin was once the drug of choice with chloramphenicol as a good alternative in allergic patients. Ceftriaxone is an antibiotic commonly employed today. Hydrocortisone can sometimes reverse the adrenal insufficiency. Plastic surgery and tissue grafting are sometimes needed to treat tissue necrosis resulting from the infection.

The infection is usually self-limiting, and in most cases, symptomatic treatment by liquid and electrolyte replacement is enough in human infections.

Treatment consists of antibiotic therapy aimed at the typical bacterial pathogens in addition to supportive care for any complications which might result from the infection itself such as hypotension or respiratory failure. A typical regimen will include intravenous antibiotics such as from the penicillin-group which is active against "Staphylococcus aureus" and an aminoglycoside for activity against Gram-negative bacteria. For particularly invasive infections, antibiotics to cover anaerobic bacteria may be added (such as metronidazole). Treatment is typically for two weeks and often necessitates insertion of a central venous catheter or peripherally inserted central catheter.

"S. pneumonia" can be treated with a combination of penicillin and ampicillin.

In cases of herpes simplex virus-derived meningitis, antiviral therapy (acyclovir or vidarabine) must be started immediately for a favorable outcome. Acyclovir is a better antiviral because it shows a similar effect on the infection as vidarabine and is safer to use in the neonate. The recommended dosage is 20 mg/kg every six hours for 21 days.

The basic method for control of the conjunctivitis includes proper hygiene and care for the affected eye. If the conjunctivitis is found to be caused by "H. aegyptius" Biogroup III then prompt antibiotic treatment preferably with rifampin has been shown to prevent progression to BPF. If the infected person resides in Brazil, it is mandatory that the infection is reported to the health authority so that a proper investigation of the contacts can be completed. This investigation will help to determine the probable source of the infection.

While there is tentative evidence for β-Blocker therapy to help control heart rate, evidence is not significant enough for its routine use. There is tentative evidence that steroids may be useful in improving outcomes.

Tentative evidence exists that Polymyxin B-immobilized fiber column hemoperfusion may be beneficial in treatment of septic shock. Trials are ongoing and it is currently being used in Japan and Western Europe.

Recombinant activated protein C (drotrecogin alpha) in a 2011 Cochrane review was found not to decrease mortality and to increase bleeding, and thus, was not recommended for use. Drotrecogin alfa (Xigris), was withdrawn from the market in October 2011.

Among the choices for vasopressors, norepinephrine is superior to dopamine in septic shock. Norepinephrine is the preferred vasopressor, while epinephrine may be added to norepinephrine when needed. Low-dose vasopressin also may be used as an addition to norepinephrine, but is not recommended as a first-line treatment. Dopamine may cause rapid heart rate and arrhythmias, and is only recommended in combination with norepinephrine in those with slow heart rate and low risk of arrhythmia. In the initial treatment of low blood pressure in septic shock, the goal of vasopressor treatment is a mean arterial pressure (MAP) of 65 mm Hg. In 2017, the FDA approved angiotensin II injection for intravenous infusion to increase blood pressure in adults with septic or other distributive shock.

Note that, in neonates, sepsis is difficult to diagnose clinically. They may be relatively asymptomatic until hemodynamic and respiratory collapse is imminent, so, if there is even a remote suspicion of sepsis, they are frequently treated with antibiotics empirically until cultures are sufficiently proven to be negative. In addition to fluid resuscitation and supportive care, a common antibiotic regimen in infants with suspected sepsis is a beta-lactam antibiotic (usually ampicillin) in combination with an aminoglycoside (usually gentamicin) or a third-generation cephalosporin (usually cefotaxime—ceftriaxone is generally avoided in neonates due to the theoretical risk of kernicterus.) The organisms which are targeted are species that predominate in the female genitourinary tract and to which neonates are especially vulnerable to, specifically Group B Streptococcus, "Escherichia coli", and "Listeria monocytogenes" (This is the main rationale for using ampicillin versus other beta-lactams.) Of course, neonates are also vulnerable to other common pathogens that can cause meningitis and bacteremia such as "Streptococcus pneumoniae" and "Neisseria meningitidis". Although uncommon, if anaerobic species are suspected (such as in cases where necrotizing enterocolitis or intestinal perforation is a concern, clindamycin is often added.

Granulocyte-macrophage colony stimulating factor (GM-CSF) is sometimes used in neonatal sepsis. However, a 2009 study found that GM-CSF corrects neutropenia if present but it has no effect on reducing sepsis or improving survival.

Trials of probiotics for prevention of neonatal sepsis have generally been too small and statistically underpowered to detect any benefit, but a randomized controlled trial that enrolled 4,556 neonates in India reported that probiotics significantly reduced the risk of developing sepsis. The probiotic used in the trial was "Lactobacillus plantarum".

A very large meta-analysis investigated the effect of probiotics on preventing late-onset sepsis (LOS) in neonates. Probiotics were found to reduce the risk of LOS, but only in babies who were fed human milk exclusively. It is difficult to distinguish if the prevention was a result of the probiotic supplementation or if it was a result of the properties of human milk. It is also still unclear if probiotic administration reduces LOS risk in extremely low birth weight infants due to the limited number of studies that investigated it. Out of the 37 studies included in this systematic review, none indicated any safety problems related to the probiotics. It would be beneficial to clarify the relationship between probiotic supplementation and human milk for future studies in order to prevent late onset sepsis in neonates.

During the 1950s there were outbreaks of omphalitis that then led to anti-bacterial treatment of the umbilical cord stump as the new standard of care. It was later determined that in developed countries keeping the cord dry is sufficient, (known as "dry cord care") as recommended by the American Academy of Pediatrics. The umbilical cord dries more quickly and separates more readily when exposed to air However, each hospital/birthing center has its own recommendations for care of the umbilical cord after delivery. Some recommend not using any medicinal washes on the cord. Other popular recommendations include triple dye, betadine, bacitracin, or silver sulfadiazine. With regards to the medicinal treatments, there is little data to support any one treatment (or lack thereof) over another. However one recent review of many studies supported the use of chlorhexidine treatment as a way to reduce risk of death by 23% and risk of omphalitis by anywhere between 27-56% in community settings in underdeveloped countries. This study also found that this treatment increased the time that it would take for the umbilical stump to separate or fall off by 1.7 days. Lastly this large review also supported the notion that in hospital settings no medicinal type of cord care treatment was better at reducing infections compared to dry cord care.