Omphalitis refers to a soft tissue infection involving the navel and surrounding tissues.
It is characterized by erythema and induration around the stump of the umbilicus and may be associated with purulent discharge.1 Omphalitis is rare in high-income countries, with an estimated incidence of <1%.1 Advances in cord care have led to dramatic decreases in the prevalence, mortality, and complication rate of omphalitis.2 However, the incidence in lower-middle-income countries is estimated to be as high as 6%, and omphalitis still causes significant morbidity. mortality.3,4
In general, mortality from omphalitis is estimated between 7% and 15%.5 In addition to inadequate cord hygiene, risk factors for omphalitis include premature or prolonged rupture of membranes, maternal infection, low birth weight, history of catheterization umbilical, and home delivery.4,6 The most commonly reported pathogens are Staphylococcus aureus , Streptococcus pyogenes, and Gram-negative bacteria.5,7 Anaerobic pathogens have also been reported.8 There is no information available on the prevalence of resistant S. aureus to methicillin.
The most reported complication of omphalitis is sepsis.6 Other reported complications include necrotizing fasciitis, peritonitis, intestinal necrosis, small intestinal evisceration, liver abscess, and portal vein thrombosis.9,10
When evaluating infants with omphalitis, the clinician should consider whether they have a concomitant serious bacterial infection (SBI) or are at risk for serious outcomes. There is little current evidence available to guide the optimal approach to diagnosis and management of infants with omphalitis in high-income countries. There is no literature on the incidence of meningitis or concurrent urinary tract infection (UTI).
To address these knowledge gaps, a multicenter study was conducted to describe the clinical presentation and prevalence of SBI and adverse outcomes in infants ≤90 days of age with clinical omphalitis.
| Methods |
> Study design and population
Using the framework of the American Academy of Pediatrics Pediatric Emergency Medicine Collaborative Research Committee, a retrospective, cross-sectional study was conducted of children clinically diagnosed with omphalitis in the emergency department (ED) of 28 sites. Participating sites included 26 pediatric EDs in the United States, 1 in Canada, and 1 in Spain.
The study was approved by the steering committee of the Pediatric Emergency Medicine Collaborative Research Committee and the research ethics committees of all participating hospitals with a waiver of informed consent. Data sharing agreements were obtained between the main site, all participating institutions, and the centralized data center at Baylor College of Medicine.
We included infants ≤90 days old, diagnosed with omphalitis, who presented to a participating ED between January 1, 2008 and December 31, 2017. Potentially eligible infants were identified by searching the electronic health record for codes diagnoses for omphalitis from the International Classification of Diseases, 9th or 10th Revision, Clinical Modification.
To ensure accuracy, once potential subjects were identified, medical records were reviewed to confirm a clinical diagnosis consistent with omphalitis, with required evidence of at least 1 of the following at the umbilicus: surrounding erythema, induration, fluctuation, or purulent drainage. . Patients were excluded if chart review suggested diagnoses such as umbilical granuloma or nonspecific noninfectious cord problems.
> Study protocol
The study variables were defined and described a priori in a shared operations manual. A standardized data collection form was used for all sites, and all investigators reviewed these forms for clarity and consistency prior to the start of the study. Researchers entered de-identified data electronically into the web-based Electronic Research Data Capture database (Vanderbilt University; Nashville, TN).
Data collected included demographic information, medical history, presenting symptoms, vital signs and physical examination findings in the ED, laboratory values, and patient management in the ED and on admission (if required). A history of fever at home was defined as any temperature measurement ≥ 38°C or use of terms such as “it felt hot,” “touch temperature,” or any other subjective fever term. These variables were classified as “yes.” , “no” or “unclear/not documented”.
For potentially more subjective descriptions in the electronic medical record, restrictive keywords were provided to define general appearance on examination, clinical diagnoses of sepsis or shock, and the presence of extensive infection or soft tissue necrosis.
Infants were classified as “well” if the documentation included the terms “good general condition,” “no apparent distress,” “alert,” “normal mental status,” “interactive,” “playful,” or other similar terms, and as "poor" if the documentation included the terms “sick,” “toxic,” “decreased mental status,” “lethargic,” “unresponsive,” “irritable,” “fussy,” “inconsolable,” “unseen.” well”, “poor or decreased pulses” or other similar terms.
Overall appearance was categorized as good, poor, or unclear/undocumented. A clinical diagnosis of sepsis or shock was assumed if the term "shock" was clearly indicated in the ED or ICU team care note, if parenteral vasopressor agents (dopamine, dobutamine, epinephrine, norepinephrine, vasopressin) were administered, if there was evidence of low blood pressure (<60 mmHg systolic), or if the terms “hypotension” or “sepsis” were clearly indicated in the medical record and the patient had been treated with isotonic fluid boluses at ≥ 40 ml/kg. The presence of severe or necrotizing soft tissue infection was determined by documentation of those specific terms, the terms “extensive” or “significant,” or other similar terms describing severe local infection.
> Outcome measures
The primary outcomes were the presence of SBI and adverse events. SBI was defined as bacteremia, bacterial meningitis, or UTI. Bacteremia and meningitis were defined by the growth of a pathogen in blood cultures or cerebrospinal fluid (CSF), respectively, and UTI by the growth of ≥ 50,000 colony-forming units/mL of a single pathogen or ≥ 10,000 colony-forming units/mL. mL in association with a positive urinalysis11 from a catheterization sample.
The authors defined adverse events as a clinical diagnosis of sepsis or shock, severe or necrotizing soft tissue infection, endotracheal intubation, administration of vasopressors, or death. The presence of adverse outcomes was classified as yes, no, or unclear/not documented. Additionally, surgical treatment of infection was defined as bedside incision and drainage, intraoperative debridement, or another surgical procedure. For infants discharged from the ED, medical records were reviewed to identify readmission to the ED within 7 days.
> Statistical analysis
Age and laboratory values are presented with medians and interquartile ranges (IQR), and categorical variables (demographics, historical and clinical findings, use of cultures, prevalence of SBI, and adverse events) with proportions and 95 binomial confidence intervals. % (CI). Statistical analyzes were performed using Microsoft Excel (Excel version 16.0, 2019).
| Results |
> Patient characteristics
566 infants diagnosed with omphalitis in the ED who met the study criteria were analyzed. The median age was 16 (IQR 8-22) days. 90% were born at term and 81% had no significant medical history. Fever was reported before or during the ED visit in 11%; This data was available for all subjects.
Caregivers reported agitation or poor feeding in 25% of cases ; these data were available for 84% of the subjects.
The professionals described that 95% of the babies looked well at the time of the consultation; these data were available for 97% of the children. A complete blood count was obtained in 478 (84%) patients, with a median white blood cell count of 13.0 × 103/µL (IQR 10.5–16.0), and a median absolute neutrophil count ( ANC) of 3.8 × 103/µL (IQR 1.2–6.1).
Among infants with any adverse event (defined as bacteremia, UTI, meningitis, clinical diagnosis of sepsis or shock, necrotizing soft tissue infection, endotracheal intubation, vasopressor use, or death), the median white blood cell count was 12.5 × 103/µL (IQR 11.6–18.1), and the median ANC was 5.7 × 103/µL (IQR 3.9–8.4). C-reactive protein was obtained in 163 (29%) patients, with a median of 0.6 mg/dL (IQR 0.5-1.3).
> IBG frequency and results
Of the 566 subjects, 472 (83%) had blood cultures performed, with bacteremia identified in 5 infants (1.1% [95% CI, 0.3%–2.5%]), representing 0.9% [CI 95%, 0.3%–2.1%] of all patients: 3 with Staphylococcus aureus : 2 methicillin-susceptible and 1 indeterminate; 1 with group B Streptococcus and 1 with Streptococcus pyogenes . Growth of a contaminant was observed in 16 (3.4% [95% CI, 2.0%–5.5%]) blood cultures.
Urinary studies were obtained in 326 (58%) patients, of which 3 were consistent with a UTI (0.9% [95% CI, 0.1%-2.7%]), representing 0.5%. (95% CI, 0.1%–1.5%) of all patients. CSF culture was obtained in 222 (39%) patients, of which 2 were positive (0.9% [95% CI, 0.1%–3.2%]), representing 0.4% (95% CI %, 0.0%–1.3%) of all patients. In both positive CSF cultures, atypical organisms grew: in one Clostridium tertium and in the other Moraxella osloensis .
Ten infants had SBI: each had a single positive blood, urine, or CSF culture. All positive cultures occurred in full-term neonates with no significant past medical history. Cultures were obtained from the site of infection in 320 (57%) patients, with growth of a pathogen in 271 (85% [95% CI, 80%–88%]).
The most common organism isolated from the infection site was methicillin-susceptible Staphylococcus aureus (62%), followed by methicillin-resistant Staphylococcus aureus (MRSA) (11%), and Escherichia coli (10%). The majority of children (498, 88%) were admitted to hospitalization; 81 (16%) of them were admitted to the ICU. Bedside incision and drainage, intraoperative debridement, or another surgical procedure was performed in 33 (6%) infants.
Of all patients, 12 (2.1% [95% CI, 1.1%–3.7%]) had a clinical diagnosis of sepsis or shock; however, only 6 (1.1% [95% CI, 0.4%–2.3%]) of these infants were admitted to an ICU. Two infants (0.4% [95% CI, 0.0%–1.3%]) had severe cellulitis or documented necrotizing soft tissue infection.
Ultrasound was performed in 156 (28%) children; of these, 40 (26% [95% CI, 19%–33%]) had findings suggestive of a urachal anomaly, such as urachal remnant, sinus, cyst, or fistula. Four infants (0.7% [95% CI, 0.2%–1.8%]) received vasopressors, and 4 (0.7% [95% CI, 0.2–1.8]) required endotracheal intubation .
Of the 68 patients discharged at the initial ED visit, 7 (10% [95% CI, 4%–20%]) returned to the ED within 7 days. None of these babies were admitted on their return visit. A total of 21 infants (3.7% [95% CI, 2.3%–5.6%]) experienced at least 1 adverse event, defined as positive blood, urine, or CSF culture; clinical diagnosis of sepsis or shock; necrotizing soft tissue infection; endotracheal intubation; use of vasopressors; Or death.
Only 1 infant with IBG (a 17-day-old infant with Clostridium tertium in the CSF) also had a diagnosis of sepsis or shock. There was 1 death: a 12-day-old infant with fever, severe cellulitis on initial examination, and leukocytosis, who developed septic shock and abdominal compartment syndrome and died on day 11 in the hospital. Cultures from the site grew Enterobacter , Enterococcus , and Serratia , but blood, urine, and CSF cultures were negative.
| Discussion |
Although all febrile infants ≤21 days require evaluation with blood, urine, and CSF cultures,12 we sought to evaluate the utility of cultures and determine rates of IBG in all infants presenting with omphalitis. In this large multicenter cohort of children with omphalitis, IBG and adverse events were uncommon, with bacteremia occurring in 1%, and sepsis or shock requiring ICU care in another 1%.
Although adverse outcomes were rare, the single fatality in this cohort emphasizes the fact that omphalitis can lead to serious injuries and potentially devastating outcomes.
Although almost all babies (95%) were described as in good general condition and only a tenth were febrile, 83% had blood cultures performed and more than a third underwent lumbar puncture. Growth of a contaminant in blood cultures occurred 3 times more frequently than growth of a true pathogen, which has important implications in terms of additional testing, medical interventions, and funding costs.13,14
Although 8 of the 10 infants with SBI were <24 days old, only 3 had fever and none were described as being in poor general condition. The 2 infants with positive CSF cultures had unusual organisms. Clostridium tertium has been previously reported as a pathogen associated with omphalitis.7
The clinical significance of Moraxella osloensis is unclear, but it has been reported in several cases of meningitis in children.15 The infant with Moraxella osloensis in the CSF was a 3-day-old boy in good general condition and without fever or pleocytosis in the CSF. and was treated with intravenous antibiotics for 14 days without complications. The 3 positive urine cultures occurred in infants with urachal abnormalities on ultrasound. The frequency of UTIs in this cohort was lower than that seen in infants with bronchiolitis.16 Furthermore, the frequency of UTIs was lower than that seen in febrile infants without an obvious focus.17
The 12 babies with sepsis or shock were ≤21 days old. Only 1 of these had a positive culture result, the 17-day-old child with Clostridium tertium in CSF. Given this very low rate of IBG, this study suggests that routinely obtaining CSF cultures may not be indicated in infants ≤21 days with omphalitis if they are afebrile and in good performance condition.
Blood cultures in this age group may be prudent given the small risk of bacteremia. Routine blood and CSF cultures may not be necessary in well-appearing, afebrile infants >21 days of age. Urine cultures should be considered at all ages given the association with urachal abnormalities.
These findings are similar to those previously reported by the authors in infants with neonatal mastitis.18 Although both neonatal mastitis and omphalitis represent soft tissue infections with similar bacteriology, they are associated with different anatomic risk factors and are not necessarily analogous.
There are very few cohort studies of omphalitis in high-income countries. The most recent series from the United States included patients from 1967 to 1985.6 In this series of 84 patients, the incidence of positive blood cultures was 13%, and mortality was 7%. This large multicenter cohort suggests a significantly lower incidence of concurrent SBI and lower mortality rate.
In this cohort, very few children were diagnosed with sepsis or shock, and only 2 had a severe or necrotizing soft tissue infection. Although specific definitions were provided for the classification of sepsis and shock, it is possible that these diagnoses were under or overestimated. Additionally, ICU utilization may reflect local practice patterns; As a note, only 6 babies had a diagnosis of sepsis or shock and were also admitted to an ICU.
Given the low frequency of adverse events and the retrospective nature of the study, risk factors for the presence of SBI and other adverse outcomes could not be evaluated and identified. Similarly, the diagnostic utility of inflammatory markers could not be evaluated . Although infants with any adverse event appeared to have greater ANC, there was not enough power to statistically test this result.
Antibiotic treatment generally targets the most commonly reported pathogens.6 There is no clear guideline as to the optimal empiric antibiotic regimen for omphalitis. Given the isolation of MRSA in at least 10% of positive site cultures in this cohort, empirical antibiotic coverage for MRSA should be considered depending on local resistance patterns. The majority of patients in this cohort were admitted to the hospital, and 6% had surgical treatment of their infection.
Among the 12% of patients discharged from the ED at their initial visit, 10% returned within 7 days of discharge, but none required admission to their new visit, and there were no adverse outcomes among this group. Although there may be a lower risk population that may not require hospitalization or surgical intervention, the authors’ data did not allow for such risk stratification. Future studies focused on identifying lower risk patients may lead to opportunities for quality improvement in reducing unnecessary admissions.
Urachal anomalies were found in 26% of the ultrasounds performed, representing 7% of the cohort. Anomalies of the urachus may present with umbilical drainage or abnormal appearance of the umbilicus,19,20 so they should be considered in the differential diagnosis of the baby with suspected omphalitis. Ultrasound should be considered in infants who present with omphalitis, especially in the setting of a UTI, and a urine culture should be obtained in infants with these abnormalities.
This study has several limitations . Although the frequency of concurrent SBI was very low, the 5 patients with bacteremia were described as in good general condition and were afebrile in the ED, so clinical appearance at presentation cannot be relied upon alone to help guide the approach. management. Because case determination was made based on International Classification of Diseases diagnostic codes, potential cases could be missed if the recorded diagnosis was something other than omphalitis, such as abscess or nonspecific cellulitis, or a complication such as meningitis.
Given the retrospective nature of the study, the accuracy and completeness of the extracted data could not be fully confirmed. Although restrictive guidelines were used to ensure diagnostic adequacy, it was not possible to ensure that all patients actually had confirmed omphalitis. Patients with urachal anomalies without true omphalitis may have been inadvertently included.
Interrater reliability was not considered. If infants with noninfectious conditions such as umbilical granuloma or other noninfectious cord issues were inadvertently included, it could falsely decrease the prevalence of SBI and other adverse outcomes. Additionally, a sensitivity analysis was not performed to find cases of omphalitis that may have occurred in infants with primary diagnosis codes of IBG that may not have been coded as omphalitis, again potentially underestimating the incidence of concurrent IBG.
There was 1 death in this cohort. Although it is possible that other fatal cases of omphalitis could be missed if they never presented to the hospital, or if they presented to a different hospital in the same geographic area, the probability of this seems quite low.
Since this study was conducted primarily in pediatric hospitals or pediatric ED hospitals, these data may not accurately reflect the signs or symptoms present or the treatment of infants with omphalitis seen in general hospitals, office-based primary care or clinics. Additionally, given the retrospective nature of the study, there is no way to determine why some babies had cultures performed and others did not, and whether this was idiosyncratic and practitioner-driven or if there were other reasons.
| Conclusion |
In this large multicenter cohort of mostly full-term, previously healthy infants with omphalitis, the prevalence of concurrent SBI and adverse outcomes was very low. Routine evaluation for meningitis in most afebrile, unwell infants with omphalitis is probably unnecessary, and routine blood cultures may not be necessary in patients > 21 days. Ultrasound evaluation for urachal abnormalities should be considered, and a urine culture should be obtained in those who have them.
| Comment |
Omphalitis refers to a soft tissue infection involving the umbilicus and surrounding tissues, and is characterized by erythema and induration around the stump of the umbilicus, sometimes with purulent discharge.
Advances in cord care have led to dramatic decreases in the prevalence, mortality, and complication rate of omphalitis, although in lower-middle-income countries it can still cause significant morbidity and mortality.
Although the rate of adverse events secondary to omphalitis is relatively low, the possibility of fatal outcomes emphasizes the fact that this condition can lead to serious injuries and potentially devastating outcomes.
Adequate cord care and alarm guidelines at the time of neonatal discharge, together with appropriate diagnostic and therapeutic measures when consulting for symptoms compatible with omphalitis, will help reduce the complications associated with this clinical condition.
