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.

A study performed at Strong Memorial Hospital in Rochester, New York, showed that infants ≤ 60 days old meeting the following criteria were at low-risk for having a serious bacterial illness:

- generally well-appearing

- previously healthy

- full term (at ≥37 weeks gestation)

- no antibiotics perinatally

- no unexplained hyperbilirubinemia that required treatment

- no antibiotics since discharge

- no hospitalizations

- no chronic illness

- discharged at the same time or before the mother

- no evidence of skin, soft tissue, bone, joint, or ear infection

- White blood cells (WBCs) count 5,000-15,000/mm

- absolute band count ≤ 1,500/mm

- urine WBC count ≤ 10 per high power field (hpf)

- stool WBC count ≤ 5 per high power field (hpf) "only in infants with diarrhea"

Those meeting these criteria likely do not require a lumbar puncture, and are felt to be safe for discharge home without antibiotic treatment, or with a single dose of intramuscular antibiotics, but will still require close outpatient follow-up.

One risk for Group B streptococcal infection (GBS) is Preterm rupture of membranes. Screening women for GBS (via vaginal and rectal swabbing) and treating culture positive women with intrapartum chemoprophylaxis is reducing the number of neonatal sepsis caused by GBS.

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.

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.

Treating fever in people with sepsis does not affect outcomes.

Monoclonal and polyclonal preparations of intravenous immunoglobulin (IVIG) do not lower the rate of death in newborns and adults with sepsis. Evidence for the use of IgM-enriched polyclonal preparations of IVIG is inconsistent. A 2012 Cochrane review concluded that N-acetylcysteine does not reduce mortality in those with SIRS or sepsis and may even be harmful.

Recombinant activated protein C (drotrecogin alpha) was originally introduced for severe sepsis (as identified by a high APACHE II score), where it was thought to confer a survival benefit. However, subsequent studies showed that it increased adverse events—bleeding risk in particular—and did not decrease mortality. It was removed from sale in 2011. Another medication known as eritoran also has not shown benefit.

Early recognition and focused management may improve the outcomes in sepsis. Current professional recommendations include a number of actions ("bundles") to be followed as soon as possible after diagnosis. Within the first three hours someone with sepsis should have received antibiotics and, intravenous fluids if there is evidence of either low blood pressure or other evidence for inadequate blood supply to organs (as evidenced by a raised level of lactate); blood cultures also should be obtained within this time period. After six hours the blood pressure should be adequate, close monitoring of blood pressure and blood supply to organs should be in place, and the lactate should be measured again if initially, it was raised. A related bundle, the "Sepsis Six", is in widespread use in the United Kingdom; this requires the administration of antibiotics within an hour of recognition, blood cultures, lactate and hemoglobin determination, urine output monitoring, high-flow oxygen, and intravenous fluids.

Apart from the timely administration of fluids and antibiotics, the management of sepsis also involves surgical drainage of infected fluid collections and appropriate support for organ dysfunction. This may include hemodialysis in kidney failure, mechanical ventilation in lung dysfunction, transfusion of blood products, and drug and fluid therapy for circulatory failure. Ensuring adequate nutrition—preferably by enteral feeding, but if necessary, by parenteral nutrition—is important during prolonged illness. In those with high blood sugar levels, insulin to bring it down to 7.8–10 mmol/L (140–180 mg/dL) is recommended with lower levels potentially worsening outcomes. Medication to prevent deep vein thrombosis and gastric ulcers also may be used.

Early onset sepsis can occur in the first week of life. It usually is apparent on the first day after birth. This type of infection is usually acquired before the birth of the infant. Premature rupture of membranes and other obstetrical complications can add to the risk of early-onset sepsis. If the amniotic membrane has been ruptured greater than 18 hours before delivery the infant may be at more risk for this complication. Prematurity, low birth weight, chorioamnionitis, maternal urinary tract infection and/or maternal fever are complications that increase the risk for early-onset sepsis. Early onset sepsis is indicated by serious respiratory symptoms. The infant usually suffers from pneumonia, hypothermia, or shock. The mortality rate is 30 to 50%.

the only form of prevention from viral infection of the neonate is a caesarean section form of delivery if the mother is showing symptoms of infection.

Infections that occur after the first week of life but before the age of 30 days are considered late onset infections. Obstetrical and maternal complications are not typically the cause of these late onset infections; they are usually acquired by the infant in the hospital neonatal intensive care unit. The widespread use of broad-spectrum antibiotics in the nursery intensive care unit can cause a higher prevalence of invasive antibiotic resistant bacteria. Meconium aspiration syndrome has a mortality rate just over 4%. This accounts for 2% for all neonatal deaths.

When properly diagnosed, the mortality of Lemierre's syndrome is about 4.6%. Since this disease is not well known and often remains undiagnosed, mortality might be much higher.

Neuroimaging (X-ray imaging of the brain) is recommended to detect the complications of meningitis. Complications should be suspected when the clinical course is characterized by shock, respiratory failure, focal neurological deficits, a positive CSF culture after 48–72 hours of appropriate antibiotic therapy, or infection with certain organisms, such as "Citrobacter koseri" and "Cronobacter sakazakii" for example. Ultrasounds are useful for early imaging to determine ventricular size and hemorrhaging. CT scans later in the therapy should be used to dictate prolonged treatment.

If intracranial abscesses (collection of pus in the brain) are found, treatment consisting of a combination of surgical drainage of the abscess and antimicrobial therapy for 4–6 weeks is recommended. More imaging should be completed after the end of antibiotic treatment because abscesses have been found after weeks from start of treatment.

Relapses have also occurred after appropriate treatment when infected by Gram-negative enteric bacilli, so follow ups are needed in cases of Gram-negative derived meningitis.

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.

For healthcare-associated bacteremia due to intravenous catheters, the IDSA has published guidelines for catheter removal. Short term catheters (in place 14 days) should be removed if the patient is developing signs or symptoms of sepsis or endocarditis, or if blood cultures remain positive for more than 72 hours.

The main means of prevention is through the promotion of safe handling, cooking and consumption of food. This includes washing raw vegetables and cooking raw food thoroughly, as well as reheating leftover or ready-to-eat foods like hot dogs until steaming hot.

Another aspect of prevention is advising high-risk groups such as pregnant women and immunocompromised patients to avoid unpasteurized pâtés and foods such as soft cheeses like feta, Brie, Camembert cheese, and bleu. Cream cheeses, yogurt, and cottage cheese are considered safe. In the United Kingdom, advice along these lines from the Chief Medical Officer posted in maternity clinics led to a sharp decline in cases of listeriosis in pregnancy in the late 1980s.

The treatment of gram negative bacteremia is also highly dependent on the causative organism. Empiric antibiotic therapy should be guided by the most likely source of infection and the patient's past exposure to healthcare facilities. In particular, a recent history of exposure to a healthcare setting may necessitate the need for antibiotics with "pseudomonas aeruginosa" coverage or broader coverage for resistant organisms. Extended generation cephalosporins such as ceftriaxone or beta lactam/beta lactam inhibitor antibiotics such as piperacillin-tazobactam are frequently used for the treatment of gram negative bacteremia.

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.

Bacteremia should be treated for 2 weeks, meningitis for 3 weeks, and brain abscess for at least 6 weeks. Ampicillin generally is considered antibiotic of choice; gentamicin is added frequently for its synergistic effects. Overall mortality rate is 20–30%; of all pregnancy-related cases, 22% resulted in fetal loss or neonatal death, but mothers usually survive.

An overwhelming post-splenectomy infection (OPSI) or Overwhelming post-splenectomy sepsis (OPSS) is a rare but rapidly fatal infection occurring in individuals following removal of the spleen. The infections are typically characterized by either meningitis or sepsis, and are caused by encapsulated organisms including "Streptococcus pneumoniae".

The risk of OPSI is 0.23–0.42 percent per year, with a lifetime risk of 5 percent. Most infections occur in the first few years following splenectomy, but the risk of OPSI is lifelong. OPSI is almost always fatal without treatment, and modern treatment has decreased the mortality to approximately 40–70 percent. Individuals with OPSI are most commonly treated with antibiotics and supportive care. Measures to prevent OPSI include vaccination and prophylactic antibiotics.

Sepsis has a worldwide incidence of more than 20 million cases a year, with mortality due to septic shock reaching up to 50 percent even in industrialized countries.

According to the U.S. Centers for Disease Control, septic shock is the thirteenth leading cause of death in the United States and the most frequent cause of deaths in intensive care units. There has been an increase in the rate of septic shock deaths in recent decades, which is attributed to an increase in invasive medical devices and procedures, increases in immunocompromised patients, and an overall increase in elderly patients.

Tertiary care centers (such as hospice care facilities) have 2-4 times the rate of bacteremia than primary care centers, 75% of which are hospital-acquired infections.

The process of infection by bacteria or fungi may result in systemic signs and symptoms that are variously described. Approximately 70% of septic shock cases were once traceable to gram-negative bacteria that produce endotoxins, however, with the emergence of MRSA and the increased use of arterial and venous catheters, gram-positive bacteria are implicated approximately as commonly as bacilli. In rough order of increasing severity these are, bacteremia or fungemia; sepsis, severe sepsis or sepsis syndrome; septic shock, refractory septic shock, multiple organ dysfunction syndrome, and death.

35% of septic shock cases derive from urinary tract infections, 15% from the respiratory tract, 15% from skin catheters (such as IVs), and more than 30% of all cases are idiopathic in origin.

The mortality rate from sepsis is approximately 40% in adults and 25% in children. It is significantly greater when sepsis is left untreated for more than seven days.

Recombinant granulocyte-colony stimulating factor preparations, such as filgrastim can be effective in patients with congenital forms of neutropenia including severe congenital neutropenia and cyclic neutropenia, the amount needed (dosage) varies considerably (depending on the individual's condition) to stabilize the neutrophil count. Guidelines for neutropenia regarding diet are currently being studied.

Most cases of neonatal neutropenia are temporary. Antibiotic prophylaxis is not recommended because of the possibility of encouraging the development of multidrug-resistant bacterial strains.

Neutropenia can be treated with hematopoietic Growth Factors, granulocyte-colony stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF). These are cytokines (inflammation-inducing chemicals) that are present naturally in the body. These factors are used regularly in cancer treatment with adults and children. The factors promote neutrophil recovery following anticancer therapy.

The administration of intravenous immunoglobulins (IVIGs) has had some success in treating neutropenias of alloimmune and autoimmune origins with a response rate of about 50%. Blood transfusions have not been effective.

The spleen contains many macrophages (part of the reticuloendothelial system), which are immune cells that phagocytose (eat) and destroy bacteria. In particular, these macrophages are activated when bacteria are bound by IgG antibodies (IgG1 or IgG3) or the complement component C3b. These types of antibodies and complement are immune substances called opsonizers, molecules that bind to the surface of bacteria to facilitate phagocytosis.

When the spleen is no longer present (asplenia), IgG and C3b are still bound to bacteria, but they cannot be removed from the blood circulation due to the loss of the splenic macrophages. Hence the bacteria are free to cause infection.

Patients without spleens often need immunizations against pathogens that normally require opsonization and phagocytosis by macrophages in the spleen. These include common human pathogens with bacterial capsules ("Streptococcus pneumoniae, Salmonella typhi, Neisseria meningitidis, E. coli, Hemophilus influenzae, Streptococcus agalactiae, Klebsiella pneumoniae"). Capsules made of polysaccharides (sugars) permit bacteria to evade phagocytosis by macrophages alone, since only proteins are directly recognized by macrophages in phagocytosis. So humoral immunity in forms of IgG and complement proteins is the human immune system's response against bacterial capsules.

If left untreated, patients with fever and absolute neutrophil count <500 have a mortality of up to 70% within 24 hours. The prognosis of neutropenia depends on the cause. Antibiotic agents have improved the prognosis for individuals with severe neutropenia. Neutropenic fever in individuals treated for cancer has a mortality of 4-30%.

Currently, the only reliable way to prevent GBS-EOD is intrapartum antibiotic prophylaxis (IAP) - administration of antibiotics during delivery. Intravenous penicillin or ampicillin given at the onset of labour and then again every four hours until delivery to GBS colonized women have been proven to be very effective at preventing vertical transmission of GBS from mother to baby and GBS-EOD

(penicillin G, 5 million units IV initial dose, then 2.5–3.0 million units every 4 hours until delivery or ampicillin, 2 g IV initial dose, then 1 g IV every 4 hours until delivery).

Penicillin-allergic women without a history of anaphylaxis (angioedema, respiratory distress, or urticaria) following administration of a penicillin or a cephalosporin (low risk of anaphylaxis) could receive cefazolin (2 g IV initial dose, then 1 g IV every 8 hours until delivery) instead of penicillin or ampicillin. Clindamycin (900 mg IV every 8 hours until delivery), and vancomycin (1 g IV every 12 hours until delivery) are used to prevent GBS-EOD in infants born to penicillin-allergic mothers. Erythromycin is not recommended under any circumstances today.

Antibiotic susceptibility testing of GBS isolates is crucial for appropriate antibiotic selection for IAP in penicillin-allergic women, because resistance to clindamycin, the most common agent used (in penicillin-allergic women), is increasing among GBS isolates. Appropriate methodologies for testing are important, because resistance to clyndamicin (antimicrobial resistance) can occur in some GBS strains that appear susceptible (antibiotic sensitivity) in certain susceptibility tests.

If appropriate IAP in GBS colonized women starts at least 2 hours before the delivery, the risk of neonatal infection is also somehow reduced.

True penicillin allergy is rare with an estimated frequency of anaphylaxis of one to five episodes per 10,000 cases of penicillin therapy. Penicillin administered to a woman with no history of β-lactam allergy has a risk of anaphylaxis of 0.04 to 4 per 100,000. Maternal anaphylaxis associated with GBS IAP occurs, but any morbidity associated with anaphylaxis is offset greatly by reductions in the incidence of GBS-EOD.

Home births are becoming increasingly popular in the UK. Recommendations for preventing GBS infections in newborns are the same for home births as for hospital births. Around 25% of women having home births probably carry GBS in their vaginas at delivery without knowing, and it could be difficult to follow correctly the recommendations of IAP and to deal with the risk of a severe allergic reaction to the antibiotics outside of a hospital setting.

IAPs have been considered to be associated with the emergence of resistant bacterial strains and with an increase in the incidence of early-onset infections caused by other pathogens, mainly Gram-negative bacteria such as "Escherichia coli". Nevertheless, most studies have not found an increased rate of non-GBS early-onset sepsis related to the widespread use of IAP.

Other strategies to prevent GBS-EOD have been studied, and chlorhexidine intrapartum vaginal cleansing has been proposed to help preventing GBS-EOD, nevertheless no evidence has been shown for the effectiveness of this approach.

Mycoplasmas have a triple-layered membrane and lack a cell wall. Commonly used antibiotics are generally ineffective because their efficacy is due to their ability to inhibit cell wall synthesis. Micoplasmas are not affected by penicillins and other antibiotics that act on the cell wall. The growth of micoplasmas in their host is inhibited by other broad-spectrum antibiotics. These broad-spectrum antibiotics inhibit the multiplication of the mycoplasma but does not kill them. Tetracyclines, macrolides, erythromycin, macrolides, ketolides, quinolones are used to treat mycoplasma infections. In addition to the penicillins, mycoplasmas are resistant to rifampicin. Mycoplasmas may be difficult to eradicate from human or animal hosts or from cell cultures by antibiotic treatment because of resistance to the antibiotic, or because it does not kill the mycoplasma cell. Mycoplasma cells are able to invade the cells of their hosts.

In 2001 the American Thoracic Society, drawing on the work of the British and Canadian Thoracic Societies, established guidelines for the management of adult CAP dividing patients into four categories based on common organisms:

- Healthy outpatients without risk factors: This group (the largest) is composed of otherwise-healthy patients without risk factors for DRSP, enteric gram-negative bacteria, "pseudomonas" or other, less-common, causes of CAP. Primary microoganisms are viruses, atypical bacteria, penicillin-sensitive "streptococcus pneumoniae" and "haemophilus influenzae". Recommended drugs are macrolide antibiotics, such as azithromycin or clarithromycin, for seven to ten days.

- Outpatients with underlying illness or risk factors: Although this group does not require hospitalization, patients have underlying health problems (such as emphysema or heart failure) or are at risk for DRSP or enteric gram-negative bacteria. They are treated with a quinolone active against "streptococcus pneumoniae" (such as levofloxacin) or a β-lactam antibiotic (such as cefpodoxime, cefuroxime, amoxicillin or amoxicillin/clavulanic acid) and a macrolide antibiotic, such as azithromycin or clarithromycin, for seven to ten days.

- Hospitalized patients without risk for "pseudomonas": This group requires intravenous antibiotics, with a quinolone active against "streptococcus pneumoniae" (such as levofloxacin), a β-lactam antibiotic (such as cefotaxime, ceftriaxone, ampicillin/sulbactam or high-dose ampicillin plus a macrolide antibiotic (such as azithromycin or clarithromycin) for seven to ten days.

- Intensive-care patients at risk for "pseudomonas aeruginosa": These patients require antibiotics targeting this difficult-to-eradicate bacterium. One regimen is an intravenous antipseudomonal beta-lactam such as cefepime, imipenem, meropenem or piperacillin/tazobactam, plus an IV antipseudomonal fluoroquinolone such as levofloxacin. Another is an IV antipseudomonal beta-lactam such as cefepime, imipenem, meropenem or piperacillin/tazobactam, plus an aminoglycoside such as gentamicin or tobramycin, plus a macrolide (such as azithromycin) or a nonpseudomonal fluoroquinolone such as ciprofloxacin.

For mild-to-moderate CAP, shorter courses of antibiotics (3–7 days) seem to be sufficient.

Some patients with CAP will be at increased risk of death despite antimicrobial treatment. A key reason for this is the host's exaggerated inflammatory response. On one hand it is required to control the infection but on the other, it leads to bystander tissue damage. As a consequence of this recent research focuses on immunomodulatory therapy that can modulate the immune response to reduce injury to the lung and other affected organs such as the heart. Although the evidence for these agents has not resulted in their routine use, there potential benefits are highly promising.