Background

Omphalitis is an infection of the umbilical stump.[1] Omphalitis typically presents as a superficial cellulitis that may spread to involve the entire abdominal wall and may progress to necrotizing fasciitis, myonecrosis, or systemic disease. Omphalitis is uncommon in industrialized countries; however, it remains a common cause of neonatal mortality in less developed areas. Omphalitis is predominantly a disease of the neonate. Only a few cases have been reported in adults. Approximately three fourths of omphalitis cases are polymicrobial in origin. Aerobic bacteria are present in approximately 85% of infections, predominated byStaphylococcus aureus, group A Streptococcus, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis.[2, 3] In the past, studies emphasized the importance of gram-positive organisms (eg, S aureus and group A Streptococcus) in the etiology of omphalitis. This was followed by a series of reports that highlighted the role of gramnegative organisms in the etiology of omphalitis. These studies suggested that the change in etiology may have been caused by the introduction of prophylactic umbilical cord care using antistaphylococcal agents, such as hexachlorophene and triple dye (a widely adopted practice in the 1960s), with a subsequent increase in gram-negative colonization of the umbilical stump. Monitoring the microbial etiology of omphalitis is important, as recent trends have moved back to dry cord care without routine application of topical antiseptic agents. This trend has been widely accepted and is supported by the American Academy of Pediatrics (AAP), which supports dry cord care of the umbilicus after birth. Dry cord care leads to earlier separation of the cord after birth. It also leads to reports of wetter, odoriferous cords (described by some parents as nasty, smelly, or yucky) and higher, sometimes dramatic, colonization rates with S aureus and other bacteria. Whether this increased colonization rate is, or will be, associated with higher rates of omphalitis or other neonatal infection is controversial. Some studies have suggested that higher colonization rates are associated with increased infection, whereas others have not. Discontinuation of routine application of topical agents may not be prudent in certain populations. A study from Nepal demonstrated that early chlorhexidine application reduced omphalitis and overall neonatal mortality;[4]a study from Germany had similar results,[5] and a study of infants in Bangladesh is underway.[6] When techniques adequate for the recovery of anaerobic bacteria are used in studying newborns with omphalitis, anaerobes are recovered from one to two thirds of patients.[7, 8] [9] The predominant anaerobic isolates include Bacteroides fragilis,Peptostreptococcus species, and Clostridium perfringens. Several mothers whose newborns had omphalitis caused by B fragilis also had amnionitis caused by this organism. Isolated cases due to other anaerobic organisms, including Clostridium sordellii, also are reported. Neonatal tetanus (with or without omphalitis) caused byClostridium tetani usually results from contamination of the umbilical cord during improperly managed deliveries outside of a medical facility or the cultural practice of placing cow dung on the umbilical stump after delivery. Neonatal tetanus is rare in the United States but is common in developing countries.

Pathophysiology
The umbilical stump represents a unique but universally acquired wound, in which devitalized tissue provides a medium that supports bacterial growth. Normally, the cord area is colonized with potential bacterial pathogens during or soon after birth. These bacteria have the potential to invade the umbilical stump, leading to omphalitis. If this occurs, the infection may progress beyond the subcutaneous tissues to involve fascial planes (necrotizing fasciitis), abdominal wall musculature (myonecrosis), and the umbilical and portal veins (phlebitis). The factors that cause colonization to progress to infection are not well understood. The image below shows the anatomic relationship between the umbilicus and its embryologic attachments.

Anatomic relationship between the umbilicus and its embryologic attachments.

Epidemiology
Frequency
International Overall incidence varies from 0.2-0.7% in industrialized countries.[10] Incidence is higher in hospitalized preterm infants than in full-term infants. Episodes of omphalitis are reported and are usually sporadic, but, rarely, epidemics occur (eg, due to S aureus or group A Streptococcus).[11, 12, 13]

Mortality/Morbidity
Outcome is usually favorable in infants with uncomplicated omphalitis associated with cellulitis of the anterior abdominal wall. In a study by Sawin and colleagues, no deaths occurred among 32 infants with omphalitis in the absence of necrotizing fasciitis and myonecrosis.[14] The mortality rate among all infants with omphalitis, including those who develop complications, is estimated at 7-15%. The mortality rate is significantly higher (38-87%) after the development of necrotizing fasciitis or myonecrosis. Suggested risk factors for poor prognosis include male sex, prematurity or being small for gestational age, and septic delivery (including unplanned home delivery); however, data are limited and conclusions cannot be drawn regarding the role of these factors in the mortality rate.

Sequelae of omphalitis may be associated with significant morbidity and mortality, including necrotizing fasciitis, myonecrosis, sepsis, septic embolization, intra-abdominal complications, and death (see Complications).

Sex
No sex predilection has been reported, although males may have a worse prognosis than females.

Age
In full-term infants, the mean age at onset is 5-9 days. In preterm infants, the mean age at onset is 3-5 days. Proceed to Clinical Presentation

History
A detailed review of the pregnancy, labor, delivery, and the neonatal course is important when assessing omphalitis.

A history of poor feeding or feeding intolerance may be an early indication of infection. A history of change in mental status, such as irritability, lethargy, and somnolence, or a history of a decreased level of activity may be an important indicator of systemic dissemination of the infection. Anaerobic bacteria are part of the normal flora of the female genital tract and are commonly involved in ascending infections of the uterus and in septic complications of pregnancy; therefore, the higher incidence of omphalitis caused by anaerobes (especially B fragilis) in infants with adverse perinatal histories, such as premature or prolonged rupture of membranes and amnionitis, may relate to exposure to maternal infection. History of urine or stool discharge from the umbilicus suggests an underlying anatomic abnormality.

Physical
The following may be associated with omphalitis:

Local disease: Physical signs vary with the extent of disease. Signs of localized infection include the following: o Purulent or malodorous discharge from the umbilical stump o Periumbilical erythema (Recently, algorithms that attempt to standardize the clinical diagnosis of omphalitis have been developed, emphasizing extent of periumbilical erythema and absence or presence of pus.) o Edema o Tenderness The image below shows a case of omphalitis associated with bullous impetigo due to Staphylococcus aureus.

A case of omphalitis associated with bullous impetigo due to Staphylococcus aureus.

Extensive local disease, with extension: The following signs indicate more extensive local disease, such as necrotizing fasciitis or myonecrosis, which are typically found in a periumbilical location but may spread across the abdominal wall, onto the flanks and back, and into the scrotum. These signs may also suggest infection by both aerobic and anaerobic organisms and include the following: o Ecchymoses, violaceous discoloration o Bullae o Peau d'orange appearance o Crepitus o Petechiae o Progression of cellulitis despite antimicrobial therapy The images below demonstrate findings in a case of omphalitis (left) associated with extensive myonecrosis (right).

A case of omphalitis (left) associated with extensive myonecrosis (right).

Systemic disease: Signs of sepsis or other systemic disease are nonspecific and include disturbances of thermoregulation or evidence of dysfunction of multiple organ systems. Examples include the following: o Disturbances of thermoregulation - Fever (temperature >38C), hypothermia (temperature < 36C), or temperature instability o Cardiovascular disturbances - Tachycardia (pulse >180 beats per minute [bpm]), hypotension (systolic blood pressure < 60 mm Hg in full-term infants), or delayed capillary refill (< 2-3 s) o Respiratory disturbances - Apnea, tachypnea (respirations >60/min), grunting, flaring of the alae nasi, intercostal or subcostal retractions, or hypoxemia o GI tract disturbances - Rigid or distended abdomen or absent bowel sounds o Cutaneous abnormalities - Jaundice, petechiae, or cyanosis o Neurologic abnormalities - Irritability, lethargy, weak sucking, hypotonia, or hypertonia

Causes

Omphalitis is a polymicrobial infection typically caused by a mixture of aerobic and anaerobic organisms.

Associated risk factors include the following: Low birth weight (< 2500 g) Prior umbilical catheterization Septic delivery (as suggested by premature rupture of membranes, nonsterile delivery, or maternal infection) o Prolonged rupture of membranes Omphalitis occasionally manifests from an underlying immunologic disorder.[15] Leukocyte adhesion deficiency (LAD) is most prominent among the immunodeficiency syndromes.[16, 17, 18, 19, 20] Numerous infants with acute or chronic omphalitis have been diagnosed with LAD, a rare immunologic disorder with an autosomal recessive pattern of inheritance. These infants typically present with the following: o Leukocytosis o Delayed separation of the umbilical cord, with or without omphalitis o Recurrent infections Omphalitis may also be the initial manifestation of neutropenia in the neonate. [21, 22, 23, 24, 25, 26] Infants with neonatal alloimmune neutropenia or congenital neutropenia have presented with omphalitis. Neonatal alloimmune neutropenia is a disease analogous to Rh-hemolytic disease and results from maternal sensitization to fetal neutrophils bearing antigens that differ from the mother's. Maternal immunoglobulin G antibodies cross the placenta and result in an immune-mediated neutropenia that can be severe and last for several weeks to 6 months. Affected infants may present with other cutaneous infections, pneumonia, sepsis, and meningitis. Because omphalitis complicated by sepsis can also be associated with neutropenia, the underlying immune-mediated neutrophil destruction may not be immediately appreciated in affected newborns. The congenital neutropenias are a disease group of heterogenous disorders that range from intermittent to persistent manifestations of varying severity. Omphalitis may complicate congenital neutropenia. Rarely, an anatomic abnormality such as a patent urachus, patent omphalomesenteric duct, or urachal cyst may be present.[27, 28, 29, 30, 31]
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Laboratory Studies
The following studies are indicated in omphalitis:

Routinely obtain specimens from umbilical infection and submit specimens for Gram stain and culture for aerobic and anaerobic organisms. If myonecrosis is suspected, obtain specimens from the involved muscle rather than the wound surface. Obtain blood cultures for aerobic and anaerobic organisms. Obtain a CBC count with manual differential. o Neutrophilia or neutropenia may be present in acute infection. An immature-to-total neutrophil ratio greater than 0.2 may be a useful indicator of systemic bacterial infection in the first few days of life. o Thrombocytopenia may be present.

Other nonspecific laboratory tests, either alone or in combination with a defined scoring system, have been evaluated for their usefulness in rapid detection of bacterial infection in neonates, although none has demonstrated sensitivity or specificity sufficiently high to dictate clinical care. The tests include the following: o C-reactive protein levels o Procalcitonin o Erythrocyte sedimentation rate o Neutrophil CD64 o Limulus lysate test, which detects endotoxin The following laboratory studies are suggested in neonates in whom sepsis and disseminated intravascular coagulation (DIC) are suspected: o Peripheral blood smear o Prothrombin time o Activated partial thromboplastin time o Fibrinogen o Fibrinogen split products or D-dimer Other abnormalities associated with serious systemic infection include the following: o Hypoglycemia o Hypocalcemia (often related to saponification with fatty acids released by bacterial lipases in subcutaneous tissue) o Metabolic acidosis

Imaging Studies
The following imaging studies may be indicated:

Abdominal radiography may reveal intra-abdominal wall gas. Ultrasonography may reveal fascial thickening and fluid accumulation between subcutaneous fat and muscle in cases with fascial involvement. It may also be useful in the detection of anatomic abnormalities. CT scanning of the abdomen may determine the presence and extent of muscle and/or fascial involvement and potentially aid in detection of anatomic abnormalities.

Procedures
Lumbar puncture may be warranted in infants in whom sepsis is suspected.

Histologic Findings
Analysis of biopsy specimens may reveal necrotizing fasciitis, which is an acute inflammatory infiltrate found in subcutaneous fat and connective tissue, or myonecrosis, which is an acute inflammatory process surrounding muscle bundles, many of which are no longer viable.

Medical Care
Treatment of omphalitis (periumbilical edema, erythema, and tenderness) in the newborn includes antimicrobial therapy and supportive care.

Antimicrobial therapy

Include parenteral antimicrobial coverage for gram-positive and gram-negative organisms. A combination of an antistaphylococcal penicillin vancomycin and an aminoglycoside antibiotic is recommended. o Some believe that anaerobic coverage is important in all patients. Omphalitis complicated by necrotizing fasciitis or myonecrosis requires a more aggressive approach, with antimicrobial therapy directed at anaerobic organisms as well as gram-positive and gram-negative organisms. Metronidazole or clindamycin may provide anaerobic coverage. o Pseudomonas species have been implicated in particularly rapid or invasive disease. o As with antimicrobial therapy for other infections, consider local antibiotic susceptibility patterns, particularly patterns of S aureus and enterococcal susceptibility. o Additional topical therapy with triple dye, bacitracin, and other antimicrobials has been suggested in addition to parenteral antibiotic therapy, but such treatment is unproven. Supportive care: In addition to antimicrobial therapy, supportive care is essential to survival. These measures include the following: o Provide ventilatory assistance and supplementary oxygen for hypoxemia or apnea unresponsive to stimulation. o Administer fluid, vasoactive agents, or both (as indicated) for hypotension. o Administration of platelets, fresh frozen plasma, or cryoprecipitate for disseminated intravascular coagulation (DIC) and clinical bleeding is suggested. o Treat infants at centers capable of supporting cardiopulmonary function. Other treatment considerations o Monitor patients for progression of disease. Early surgical intervention may be lifesaving. o In uncomplicated cases, expect erythema of the umbilical stump to improve within 12-24 hours after the initiation of antimicrobial therapy. Failure to respond may suggest disease progression, presence of an anatomic defect, or an immunodeficiency state. o The role of hyperbaric oxygen in treatment of patients with anaerobic necrotizing fasciitis and myonecrosis is controversial because no prospective controlled data are available and pediatric data are scarce. In the treatment chambers, tissue levels of oxygen are maximized when the patient breathes 100% oxygen at 2-3 atm. The delivery of high concentrations of oxygen to marginally perfused tissues may have a detrimental effect on the growth of anaerobic organisms and improve phagocyte function. However, surgical therapy has the highest priority, and initiation of hyperbaric oxygen therapy should not delay transport to a facility with staff capable of performing surgical debridement.
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Surgical Care
Management of necrotizing fasciitis and myonecrosis involves early and complete surgical debridement of the affected tissue and muscle.[32, 33]

Although the extent of debridement depends on the viability of tissue and muscle, which is determined at the time of surgery, excision of preperitoneal tissue (including

the umbilicus, umbilical vessels, and urachal remnant) is critically important in the eradication of the infection. These tissues can harbor invasive bacteria and provide a route for progressive spread of infection after less extensive debridement. Delay in diagnosis or surgery allows progression and spread of necrosis, leading to extensive tissue loss and worsening systemic toxicity. Several surgical procedures may be required before all nonviable tissue is removed.

Consultations
The following consultations may be indicated:

Infectious disease specialist - For appropriate antimicrobial selection, particularly if necrotizing fasciitis or myonecrosis occurs Surgeon - If necrotizing fasciitis or myonecrosis is suspected (consult early in the disease course)

Diet
Once omphalitis is suspected, do not feed the infant enterally. Enteral feedings may be resumed once the acute infection resolves. Parenteral nutrition is required in infants with omphalitis.

Medication Summary
A combination of parenterally administered antistaphylococcal penicillin and an aminoglycoside antibiotic is recommended for uncomplicated omphalitis. Some believe that anaerobic coverage also should be considered in all infants with omphalitis. Omphalitis complicated by necrotizing fasciitis or myonecrosis requires a more aggressive approach, and antimicrobial therapy directed at anaerobic organisms, as well as gram-positive and gram-negative organisms, is suggested. Metronidazole may be added to the combination of antistaphylococcal penicillin and aminoglycoside to provide anaerobic coverage, or clindamycin may be substituted for antistaphylococcal penicillin. As with antimicrobial therapy for other infections, consider local antibiotic susceptibility patterns and results of blood and biopsy specimen culturing. Blood products (eg, packed RBCs, platelets, fresh frozen plasma) and other medications (eg, inotropic agents, sodium bicarbonate) may be required for supportive care.

Antibiotics
Class Summary
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.[34]
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Gentamicin (Garamycin)
Aminoglycoside antibiotic for gram-negative coverage. Used in combination both with an agent against gram-positive organisms and with an agent that covers anaerobes.

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Oxacillin (Bactocill)
Antistaphylococcal penicillin. Bactericidal antibiotic that inhibits cell wall synthesis. Used in the treatment of infections caused by penicillinase-producing staphylococci. May be used to initiate therapy when staphylococcal infection is suspected.
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Clindamycin (Cleocin)
Used to treat infections caused by anaerobic bacteria. Lincosamide for treatment of serious skin and soft tissue staphylococcal infections. Also effective against aerobic and anaerobic streptococci (except enterococci). Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes causing RNA-dependent protein synthesis to arrest.
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Metronidazole IV (Flagyl)
Anaerobic antibiotic that also has amebicide and antiprotozoal actions.
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Ampicillin
Broad-spectrum penicillin. Interferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms. Bactericidal for organisms, such as GBS, Listeria, nonpenicillinase-producing staphylococci, some strains of Haemophilus influenzae, and meningococci.
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Vancomycin (Vancocin, Vancoled)

Bacteriocidal agent against most aerobic and anaerobic gram-positive cocci and bacilli. Especially important in the treatment of MRSA. Recommended therapy when coagulase-negative staphylococcal sepsis is suspected.

Further Inpatient Care

Examine the patient with omphalitis frequently, and immediately debride any tissue that shows signs of advancing infection or necrosis.

Postoperatively, inspect the gross appearance of the tissue on the perimeter of the debrided area several times a day or more frequently if the infant has any unresolved signs of systemic infection. Monitor aminoglycoside levels, and adjust dose accordingly. Monitor and manage metabolic abnormalities, which are common in any ill neonate.

Further Outpatient Care

Routine postsurgical follow-up care is indicated. Infants developing portal vein thrombosis require follow-up care for complications associated with portal hypertension.

Inpatient & Outpatient Medications

Intravenous antimicrobial therapy with an antistaphylococcal penicillin, aminoglycoside, and clindamycin or metronidazole if indicated, are administered during hospitalization.

Transfer
Critically ill infants, including those who may require surgical intervention, may require transfer to an ICU equipped to treat infants. Transport the patient with advanced life support technology in place and qualified personnel in attendance. Options for further treatment or intervention must be immediately available. (SeeTransport of the Critically Ill Newborn.)

Deterrence/Prevention
Antimicrobial agents have been applied to the umbilicus to decrease bacterial colonization and to prevent omphalitis and associated complications.
o o o o o o o o o

Several effective umbilical cord care regimens are available, including the following: Triple dye applied once daily until cord separation Triple dye applied once, then alcohol applied daily until cord separation Triple dye applied once, then no further antimicrobial treatment Povidone-iodine applied daily until cord separation Silver sulfadiazine applied daily until cord separation Bacitracin ointment applied daily until cord separation Chlorhexidine 4% applied once, with no further antimicrobial treatment Chlorhexidine 4% applied daily until cord separation Salicylic sugar powder (97% powdered sugar, 3% salicylic acid) applied daily until cord separation Routine topical therapy may be indicated in developing countries where omphalitis is more common. Topical therapy is also commonly used in attempts to control outbreaks of omphalitis.

Complications
The sequelae of omphalitis may be associated with significant morbidity and mortality. These include necrotizing fasciitis; myonecrosis; sepsis; septic embolization; and, particularly, endocarditis and liver abscess formation, abdominal complications (eg, spontaneous evisceration, peritonitis, bowel obstruction, abdominal or retroperitoneal abscess), and death.[35, 36, 37]

Necrotizing fasciitis: This is a florid bacterial infection of the skin, subcutaneous fat, and superficial and deep fascia that complicates 8-16% of cases of neonatal omphalitis.[38, 39, 40, 41, 42, 33, 43] It is characterized by rapidly spreading infection and severe systemic toxicity. Necrotizing fasciitis typically involves the abdominal wall but may also involve the scrotum or penis. o Necrotizing soft tissue infections are caused by production of factors (by single or multiple organisms) that lead directly to tissue cell death, enzymatic destruction of supporting connective tissue, and destruction of host humoral and cellular immune responses to infecting organisms.

Certain organisms are well known to invade tissue and proliferate in necrotic areas. Group A Streptococcus, S aureus, and Clostridiumspecies may elaborate extracellular enzymes and toxins that can damage tissue, may facilitate movement of organisms through soft tissue planes, and may limit host defenses and penetration of systemic antimicrobial agents.[3] Myonecrosis: This refers to infectious involvement of muscle. o In infants with omphalitis, development of myonecrosis usually depends on conditions that facilitate the growth of anaerobic organisms. These conditions include the presence of necrotic tissue, poor blood supply, foreign material, and established infection by aerobic bacteria such as staphylococci or streptococci. C perfringens, in particular, does not replicate under conditions of an oxidationreduction potential (Eh) greater than -80 mV; the Eh of healthy muscle is 120-160 mV. In infections with mixtures of facultative aerobes and anaerobes, the aerobic organisms use oxygen available in tissue, thereby further reducing the Eh in tissues inoculated by Clostridium species or other anaerobic bacteria, often to less than 150 mV, allowing anaerobic bacterial growth. o The toxins produced in the anaerobic environment of necrotic tissue allow rapid spread of organisms through tissue planes. Local spread of toxins extends the area of tissue necrosis, allowing continued growth of organisms and increasing elaboration of toxins. Because of progressive deep tissue destruction and subsequent systemic spread of toxins, anaerobic infections, in particular, may be fatal if not treated promptly. In addition, rapid development of edema, which constricts the muscle within its fascia, may lead to ischemic myonecrosis. Sepsis: This is the most common complication of omphalitis. In a study by Mason and colleagues, bacteremia was a complication in 13% of infants with omphalitis. In these infants, disseminated intravascular coagulation (DIC) and multiple organ failure may occur.[44] Septic embolization: If septic embolization arises from infected umbilical vessels, it may lead to metastatic foci in various organs, including the heart, liver, lungs, pancreas, kidneys, and skin. Abdominal complications: Abdominal complications include spontaneous evisceration, peritonitis, bowel obstruction, abdominal abscess, retroperitoneal abscess, or liver abscess. Long-term or late complications of omphalitis: These may include nonneoplastic cavernous transformation of the portal vein, portal vein thrombosis, extrahepatic portal hypertension, and biliary obstruction.[45, 46, 47]
o

Prognosis
The prognosis for infants with omphalitis varies.

Patient Education
Referral for psychosocial counseling may assist the family in coping with a critically ill infant. For excellent patient education resources, visit eMedicineHealth's Children's Health Center. Also, see eMedicineHealth's patient education article Umbilical Cord Care.