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The current incidence in the United States is somewhere around 0.5% per year; overall, the incidence rate for developed world falls between 0.2–0.7%. In developing countries, the incidence of omphalitis varies from 2 to 7 for 100 live births. There does not appear to be any racial or ethnic predilection.
Like many bacterial infections, omphalitis is more common in those patients who have a weakened or deficient immune system or who are hospitalized and subject to invasive procedures. Therefore, infants who are premature, sick with other infections such as blood infection (sepsis) or pneumonia, or who have immune deficiencies are at greater risk. Infants with normal immune systems are at risk if they have had a prolonged birth, birth complicated by infection of the placenta (chorioamnionitis), or have had umbilical catheters.
Late-onset meningitis is most likely infection from the community. Late onset meningitis may be caused by other Gram-negative bacteria and "staphylococcal" species. In developing countries "Streptococcus pneumoniae" accounts for most cases of late onset.
In early-onset neonatal meningitis, acquisition of the bacteria is from the mother before the baby is born or during birth. The most common bacteria found in early-onset are group B "Streptococcus" (GBS), "Escherichia coli", and "Listeria monocytogenes". In developing countries, Gram-negative enteric (gut) bacteria are responsible for the majority of early onset meningitis.
Fungi and parasites may also cause the disease. Fungi and parasites are especially associated with immunocompromised patients. Other causes include: "Nocardia asteroides", "Mycobacterium", Fungi (e.g. "Aspergillus", "Candida", "Cryptococcus", "Mucorales", "Coccidioides", "Histoplasma capsulatum", "Blastomyces dermatitidis", "Bipolaris", "Exophiala dermatitidis", "Curvularia pallescens", "Ochroconis gallopava", "Ramichloridium mackenziei", "Pseudallescheria boydii"), Protozoa (e.g. "Toxoplasma gondii", "Entamoeba histolytica", "Trypanosoma cruzi", "Schistosoma", "Paragonimus"), and Helminths (e.g. "Taenia solium"). Organisms that are most frequently associated with brain abscess in patients with AIDS are poliovirus, "Toxoplasma gondii", and "Cryptococcus neoformans", though in infection with the latter organism, symptoms of meningitis generally predominate.
These organisms are associated with certain predisposing conditions:
- Sinus and dental infections—Aerobic and anaerobic streptococci, anaerobic gram-negative bacilli (e.g. "Prevotella", "Porphyromonas", "Bacteroides"), "Fusobacterium", "S. aureus", and Enterobacteriaceae
- Penetrating trauma—"S. aureus", aerobic streptococci, Enterobacteriaceae, and "Clostridium" spp.
- Pulmonary infections—Aerobic and anaerobic streptococci, anaerobic gram-negative bacilli (e.g. "Prevotella", "Porphyromonas", "Bacteroides"), "Fusobacterium", "Actinomyces", and "Nocardia"
- Congenital heart disease—Aerobic and microaerophilic streptococci, and "S. aureus"
- HIV infection—"T. gondii", "Mycobacterium", "Nocardia", "Cryptococcus", and "Listeria monocytogenes"
- Transplantation—"Aspergillus", "Candida", "Cryptococcus", "Mucorales", "Nocardia", and "T. gondii"
- Neutropenia—Aerobic gram-negative bacilli, "Aspergillus", "Candida", and "Mucorales"
Approximately 20–35% of people with severe sepsis and 30–70% of people with septic shock die. Lactate is a useful method of determining prognosis with those who have a level greater than 4 mmol/L having a mortality of 40% and those with a level of less than 2 mmol/L have a mortality of less than 15%.
There are a number of prognostic stratification systems such as APACHE II and Mortality in Emergency Department Sepsis. APACHE II factors in the person's age, underlying condition, and various physiologic variables to yield estimates of the risk of dying of severe sepsis. Of the individual covariates, the severity of underlying disease most strongly influences the risk of death. Septic shock is also a strong predictor of short- and long-term mortality. Case-fatality rates are similar for culture-positive and culture-negative severe sepsis. The Mortality in Emergency Department Sepsis (MEDS) score is simpler and useful in the emergency department environment.
Some people may experience severe long-term cognitive decline following an episode of severe sepsis, but the absence of baseline neuropsychological data in most people with sepsis makes the incidence of this difficult to quantify or to study.
Death occurs in about 10% of cases and people do well about 70% of the time. This is a large improvement from the 1960s due to improved ability to image the head, better neurosurgery and better antibiotics.
Sixty percent of mothers of preterm infants are infected with cytomegalovirus (CMV). Infection is asymptomatic in most instances but 9% to 12% of postnatally infected low birth weight, preterm infants have severe, sepsis-like infection. CMV infection duration can be long and result in pneumonitis in association with fibrosis. CMV infection in infants has an unexpected effect on the white blood cells of the immune system causing them to prematurely age. This leads to a reduced immune response similar to that found in the elderly.
Congential rubella is still a risk with higher risk among immigrant women from countries without adequate vaccination programs.
Sepsis causes millions of deaths globally each year and is the most common cause of death in people who have been hospitalized. The worldwide incidence of sepsis is estimated to be 18 million cases per year. In the United States sepsis affects approximately 3 in 1,000 people, and severe sepsis contributes to more than 200,000 deaths per year.
Sepsis occurs in 1–2% of all hospitalizations and accounts for as much as 25% of ICU bed utilization. Due to it rarely being reported as a primary diagnosis (often being a complication of cancer or other illness), the incidence, mortality, and morbidity rates of sepsis are likely underestimated. A study by the Agency for Healthcare Research and Quality (AHRQ) of selected States found that there were approximately 651 hospital stays per 100,000 population with a sepsis diagnosis in 2010. It is the second-leading cause of death in non-coronary intensive care unit (ICU) and the tenth-most-common cause of death overall (the first being heart disease). Children under 12 months of age and elderly people have the highest incidence of severe sepsis. Among U.S. patients who had multiple sepsis hospital admissions in 2010, those who were discharged to a skilled nursing facility or long term care following the initial hospitalization were more likely to be readmitted than those discharged to another form of care. A study of 18 U.S. States found that, amongst Medicare patients in 2011, sepsis was the second most common principal reason for readmission within 30 days.
Several medical conditions increase a person's susceptibility to infection and developing sepsis. Common sepsis risk factors include age (especially the very young and old); conditions that weaken the immune system such as cancer, diabetes, or the absence of a spleen; and major trauma and burns.
Patients with the following conditions, treatments or situations are at increased risk for invasive candidiasis.
- Critical illness
- Long-term intensive care unit stay
- Abdominal surgery (aggravated by anastomotic leakage or repeat laparotomies)
- Immunosuppressive diseases
- Acute necrotizing pancreatitis
- Malignant hematologic disease
- Solid-organ transplantation
- Hematopoietic stem cell transplantation
- Solid-organ tumors
- Neonates (especially low birth weight and preterm infants)
- Broad-spectrum antibiotic treatment
- Central venous catheter
- Internal prosthetic device
- Total parenteral nutrition
- Hemodialysis
- Glucocorticoid use
- Chemotherapy
- Noninvasive "Candida" colonization (particularly if multifocal)
Omphalitis is most commonly caused by bacteria. The culprits usually are "Staphylococcus aureus", "Streptococcus", and "Escherichia coli". The infection is typically caused by a combination of these organisms and is a mixed Gram-positive and Gram-negative infection. Anaerobic bacteria can also be involved.
Since its first description in the 1960s, only seven people worldwide have been reported to have survived PAM as of 2015, with three in the United States and one in Mexico; one of the US survivors had brain damage that is probably permanent. Less than 1% of people with naegleriasis survive.
Invasive candidiasis is a nosocomial infection with the majority of cases associated with hospital stays.
The disease is rare and highly lethal: there have only been 300 cases as of 2008. Drug treatment research at Aga Khan University in Pakistan has shown that "in-vitro" drug susceptibility tests with some FDA approved drugs used for non-infectious diseases have proved to kill "Naegleria" "fowleri" with an amoebicidal rate greater than 95%. The same source has also proposed a device for drug delivery via the transcranial route to the brain.
The number of cases of infection could increase due to climate change, and was posited as the reason for 3 cases in Minnesota in 2010, 2012, and 2015. In 2016, an infection was contracted in Maryland, four miles south of the Pennsylvania border;
As of 2013, numbers of reported cases were expected to increase, simply because of better informed diagnoses being made both in ongoing cases and in autopsy findings.
The types of bacteria that cause bacterial meningitis vary according to the infected individual's age group.
- In premature babies and newborns up to three months old, common causes are "group B streptococci" (subtypes III which normally inhabit the vagina and are mainly a cause during the first week of life) and bacteria that normally inhabit the digestive tract such as "Escherichia coli" (carrying the K1 antigen). "Listeria monocytogenes" (serotype IVb) is transmitted by the mother before birth and may cause meningitis in the newborn.
- Older children are more commonly affected by "Neisseria meningitidis" (meningococcus) and "Streptococcus pneumoniae" (serotypes 6, 9, 14, 18 and 23) and those under five by "Haemophilus influenzae" type B (in countries that do not offer vaccination).
- In adults, "Neisseria meningitidis" and "Streptococcus pneumoniae" together cause 80% of bacterial meningitis cases. Risk of infection with "Listeria monocytogenes" is increased in persons over 50 years old. The introduction of pneumococcal vaccine has lowered rates of pneumococcal meningitis in both children and adults.
Recent skull trauma potentially allows nasal cavity bacteria to enter the meningeal space. Similarly, devices in the brain and meninges, such as cerebral shunts, extraventricular drains or Ommaya reservoirs, carry an increased risk of meningitis. In these cases, the persons are more likely to be infected with Staphylococci, Pseudomonas, and other Gram-negative bacteria. These pathogens are also associated with meningitis in people with an impaired immune system. An infection in the head and neck area, such as otitis media or mastoiditis, can lead to meningitis in a small proportion of people. Recipients of cochlear implants for hearing loss are more at risk for pneumococcal meningitis.
Tuberculous meningitis, which is meningitis caused by "Mycobacterium tuberculosis", is more common in people from countries in which tuberculosis is endemic, but is also encountered in persons with immune problems, such as AIDS.
Recurrent bacterial meningitis may be caused by persisting anatomical defects, either congenital or acquired, or by disorders of the immune system. Anatomical defects allow continuity between the external environment and the nervous system. The most common cause of recurrent meningitis is a skull fracture, particularly fractures that affect the base of the skull or extend towards the sinuses and petrous pyramids. Approximately 59% of recurrent meningitis cases are due to such anatomical abnormalities, 36% are due to immune deficiencies (such as complement deficiency, which predisposes especially to recurrent meningococcal meningitis), and 5% are due to ongoing infections in areas adjacent to the meninges.
Meningitis is typically caused by an infection with microorganisms. Most infections are due to viruses, with bacteria, fungi, and protozoa being the next most common causes. It may also result from various non-infectious causes. The term "aseptic meningitis" refers to cases of meningitis in which no bacterial infection can be demonstrated. This type of meningitis is usually caused by viruses but it may be due to bacterial infection that has already been partially treated, when bacteria disappear from the meninges, or pathogens infect a space adjacent to the meninges (e.g. sinusitis). Endocarditis (an infection of the heart valves which spreads small clusters of bacteria through the bloodstream) may cause aseptic meningitis. Aseptic meningitis may also result from infection with spirochetes, a type of bacteria that includes "Treponema pallidum" (the cause of syphilis) and "Borrelia burgdorferi" (known for causing Lyme disease). Meningitis may be encountered in cerebral malaria (malaria infecting the brain) or amoebic meningitis, meningitis due to infection with amoebae such as "Naegleria fowleri", contracted from freshwater sources.
A recent retrospective study of all cases of Ecthyma gangrenosum from 2004-2010 in a university hospital in Mexico shows that neutropenia in immunocompromised patients is the most common risk factor for ecthyma gangrenosum.
"Listeria monocytogenes" is ubiquitous in the environment. The main route of acquisition of "Listeria" is through the ingestion of contaminated food products. "Listeria" has been isolated from raw meat, dairy products, vegetables, fruit and seafood. Soft cheeses, unpasteurized milk and unpasteurised pâté are potential dangers; however, some outbreaks involving post-pasteurized milk have been reported.
Rarely listeriosis may present as cutaneous listeriosis. This infection occurs after direct exposure to "L. monocytogenes" by intact skin and is largely confined to veterinarians who are handling diseased animals, most often after a listerial abortion.
Incidence in 2004–2005 was 2.5–3 cases per million population a year in the United States, where pregnant women accounted for 30% of all cases. Of all nonperinatal infections, 70% occur in immunocompromised patients. Incidence in the U.S. has been falling since the 1990s, in contrast to Europe where changes in eating habits have led to an increase during the same time. In the EU, it has stabilized at around 5 cases per annum per million population, although the rate in each country contributing data to EFSA/ECDC varies greatly.
There are four distinct clinical syndromes:
- Infection in pregnancy: "Listeria" can proliferate asymptomatically in the vagina and uterus. If the mother becomes symptomatic, it is usually in the third trimester. Symptoms include fever, myalgias, arthralgias and headache. Miscarriage, stillbirth and preterm labor are complications of this infection. Symptoms last 7–10 days.
- Neonatal infection (granulomatosis infantiseptica): There are two forms. One, an early-onset sepsis, with "Listeria" acquired in utero, results in premature birth. "Listeria" can be isolated in the placenta, blood, meconium, nose, ears, and throat. Another, late-onset meningitis is acquired through vaginal transmission, although it also has been reported with caesarean deliveries.
- Central nervous system (CNS) infection: "Listeria" has a predilection for the brain parenchyma, especially the brain stem, and the meninges. It can cause cranial nerve palsies, encephalitis, meningitis, meningoencephalitis and abscesses. Mental status changes are common. Seizures occur in at least 25% of patients.
- Gastroenteritis: "L. monocytogenes" can produce food-borne diarrheal disease, which typically is noninvasive. The median incubation period is 21 days, with diarrhea lasting anywhere from 1–3 days. Patients present with fever, muscle aches, gastrointestinal nausea or diarrhea, headache, stiff neck, confusion, loss of balance, or convulsions.
"Listeria" has also been reported to colonize the hearts of some patients. The overall incidence of cardiac infections caused by "Listeria" is relatively low, with 7-10% of case reports indicating some form of heart involvement. There is some evidence that small subpopulations of clinical isolates are more capable of colonizing the heart throughout the course of infection, but cardiac manifestations are usually sporadic and may rely on a combination of bacterial factors and host predispositions, as they do with other strains of cardiotropic bacteria.
It has been hypothesized that biofilm bacterial infections may account for many cases of antibiotic-refractory chronic sinusitis. Biofilms are complex aggregates of extracellular matrix and inter-dependent microorganisms from multiple species, many of which may be difficult or impossible to isolate using standard clinical laboratory techniques. Bacteria found in biofilms have their antibiotic resistance increased up to 1000 times when compared to free-living bacteria of the same species. A recent study found that biofilms were present on the mucosa of 75% of people undergoing surgery for chronic sinusitis.
Acute sinusitis is usually precipitated by an earlier upper respiratory tract infection, generally of viral origin, mostly caused by rhinoviruses, coronaviruses, and influenza viruses, others caused by adenoviruses, human parainfluenza viruses, human respiratory syncytial virus, enteroviruses other than rhinoviruses, and metapneumovirus. If the infection is of bacterial origin, the most common three causative agents are "Streptococcus pneumoniae", "Haemophilus influenzae", and "Moraxella catarrhalis". Until recently, "Haemophilus influenzae" was the most common bacterial agent to cause sinus infections. However, introduction of the "H. influenza" type B (Hib) vaccine has dramatically decreased "H. influenza" type B infections and now non-typable "H. influenza" (NTHI) are predominantly seen in clinics. Other sinusitis-causing bacterial pathogens include "Staphylococcus aureus" and other streptococci species, anaerobic bacteria and, less commonly, gram negative bacteria. Viral sinusitis typically lasts for 7 to 10 days, whereas bacterial sinusitis is more persistent. Approximately 0.5% to 2% of viral sinusitis results in subsequent bacterial sinusitis. It is thought that nasal irritation from nose blowing leads to the secondary bacterial infection.
Acute episodes of sinusitis can also result from fungal invasion. These infections are typically seen in patients with diabetes or other immune deficiencies (such as AIDS or transplant patients on immunosuppressive anti-rejection medications) and can be life-threatening. In type I diabetics, ketoacidosis can be associated with sinusitis due to mucormycosis.
Chemical irritation can also trigger sinusitis, commonly from cigarette smoke and chlorine fumes. Rarely, it may be caused by a tooth infection.
There are five main causes of infections of the central nervous system (CNS): bacterial, viral, fungal, protozoal, and prionic.
Persons with component deficiencies in the final common complement pathway (C3,C5-C9) are more susceptible to "N. meningitidis" infection than complement-satisfactory persons, and it was estimated that the risk of infection is 7000 times higher in such individuals. In addition, complement component-deficient populations frequently experience frequent meningococcal disease since their immune response to natural infection may be less complete than that of complement non-deficient persons.
Inherited properdin deficiency also is related, with an increased risk of contracting meningococcal disease. Persons with functional or anatomic asplenia may not efficiently clear encapsulated "Neisseria meningitidis" from the bloodstream Persons with other conditions associated with immunosuppression also may be at increased risk of developing meningococcal disease.
While typical drug side effects reactions are mild to moderate; sometimes serious adverse effects occur.
As of 2016, the U.S. FDA recommended that "serious side effects associated with fluoroquinolone antibacterial drugs generally outweigh the benefits for patients with acute sinusitis, acute bronchitis, and uncomplicated urinary tract infections who have other treatment options. For patients with these conditions, fluoroquinolones should be reserved for those who do not have alternative treatment options."
Partly as a result of the efforts of Public Citizen, in 2008 the U.S. FDA ordered boxed warnings on all fluoroquinolones, advising consumers of an enhanced risk of tendon damage.
Prominent among these are side effects that became the subject of a black box warning by the U.S. FDA in 2016. The FDA wrote: "An FDA safety review has shown that fluoroquinolones when used systemically (i.e. tablets, capsules, and injectable) are associated with disabling and potentially permanent serious side effects that can occur together. These side effects can involve the tendons, muscles, joints, nerves, and central nervous system."
Quinolones are associated with a small risk of tendonitis and tendon rupture; a 2013 review found the incidence of tendon injury among those taking fluoroquinolones to be between 0.08 and 0.2%. The risk appears to be higher among people older than 60 and those also taking corticosteroids; there may also be higher risk among people who are male, have a pre-existing joint or tendon issue, have kidney disease, and are highly active. Some experts have advised avoidance of fluoroquinolones in athletes. If tendonitis occurs, it generally appears within one month, and the most common tendon that is injured appears to be the Achilles tendon. The cause is not well understood.
Nervous system effects include insomnia, restlessness, and rarely, seizure, convulsions, and psychosis. Other rare and serious adverse events have been observed with varying degrees of evidence for causation.
More generally, fluoroquinolones are tolerated, with typical drug side effects being mild to moderate. Common side effects include gastrointestinal effects such as nausea, vomiting, and diarrhea, as well as headache and insomnia. Postmarketing surveillance has revealed a variety of relatively rare but serious adverse effects that are associated with all members of the fluoroquinolone antibacterial class. Among these, tendon problems and exacerbation of the symptoms of the neurological disorder myasthenia gravis are the subject of "black box" warnings in the United States.
The overall rate of adverse events in patients treated with fluoroquinolones is roughly similar to that seen in patients treated with other antibiotic classes. A U.S. Centers for Disease Control and Prevention study found patients treated with fluoroquinolones experienced adverse events severe enough to lead to an emergency department visit more frequently than those treated with cephalosporins or macrolides, but less frequently than those treated with penicillins, clindamycin, sulfonamides, or vancomycin.
Fluoroquinolones prolong the heart's QT interval by blocking voltage-gated potassium channels. Prolongation of the QT interval can lead to torsades de pointes, a life-threatening arrhythmia, but in practice this appears relatively uncommon in part because the most widely prescribed fluoroquinolones (ciprofloxacin and levofloxacin) only minimally prolong the QT interval.
"Clostridium difficile" colitis may occur in connection with the use of any antibacterial drug, especially those with a broad spectrum of activity such as clindamycin, cephalosporins, and fluoroquinolones. Fluoroquinoline treatment is associated with risk that is similar to or less than that associated with broad spectrum cephalosporins. Fluoroquinoline administration may be associated with the acquisition and outgrowth of a particularly virulent "Clostridium" strain.
Events that may occur in acute overdose are rare, and include renal failure and seizure. Susceptible groups of patients, such as children and the elderly, are at greater risk of adverse reactions during therapeutic use.
In 2017 the FDA included the following important warning:
"The U.S. Food and Drug Administration (FDA) has required the drug labels and Medication Guides for all fluoroquinolone antibacterial drugs be updated to better describe the serious side effect of peripheral neuropathy. This serious nerve damage potentially caused by fluoroquinolones (see Table for a list) may occur soon after these drugs are taken and may be permanent.
The risk of peripheral neuropathy occurs only with fluoroquinolones that are taken by mouth or by injection. Approved fluoroquinolone drugs include levofloxacin (Levaquin), ciprofloxacin (Cipro), moxifloxacin (Avelox), norfloxacin (Noroxin), ofloxacin (Floxin), and gemifloxacin (Factive). The topical formulations of fluoroquinolones, applied to the ears or eyes, are not known to be associated with this risk.
If a patient develops symptoms of peripheral neuropathy, the fluoroquinolone should be stopped, and the patient should be switched to another, non-fluoroquinolone antibacterial drug, unless the benefit of continued treatment with a fluoroquinolone outweighs the risk. Peripheral neuropathy is a nerve disorder occurring in the arms or legs. Symptoms include pain, burning, tingling, numbness, weakness, or a change in sensation to light touch, pain or temperature, or the sense of body position. It can occur at any time during treatment with fluoroquinolones and can last for months to years after the drug is stopped or be permanent. Patients using fluoroquinolones who develop any symptoms of peripheral neuropathy should tell their health care professionals right away.
FDA will continue to evaluate the safety of drugs in the fluoroquinolone class and will communicate with the public again if additional information becomes available. "
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.