Antimicrobial Stewardship in Neonates with Necrotizing Enterocolitis: A Quality Improvement Initiative.

BACKGROUND: Antibiotic overutilization in the neonatal intensive care unit (NICU) has many adverse effects, and necrotizing enterocolitis (NEC) is one of the most common indications for antibiotics in premature infants. Evidence for a preferred antibiotic regimen for NEC is lacking. This project aims to reduce piperacillin-tazobactam use and overall antibiotic duration in neonates with NEC through the implementation of an antibiotic stewardship pathway based on the modified Bell stage classification system. METHODS: A multidisciplinary team consisting of neonatology, pharmacy, infectious disease, and surgery developed an antibiotic protocol for the management of NEC based on Bell stage. Recommendations included 48 h of ampicillin/gentamicin (AG) for stage I, 5-10 days of AG for stage II, the addition of metronidazole for stage IIIA, and 7-14 days of piperacillin-tazobactam (PT) for stage IIIB. We evaluated overall antibiotic and PT exposure, progression to surgical NEC, NEC recurrence, antibiotic resistance, bacteremia/fungemia, and mortality 1 year pre- and post-protocol implementation. RESULTS: 27 patients pre-intervention and 44 post-intervention were analyzed. Antibiotic exposure was reduced from a median 119.19 to 80.65 days of therapy (DOT) per 1000 patient days (p = 0.11). PT exposure decreased after protocol implementation (median 68.78 vs. 7.97 DOT per 1000 patient days, p = 0.002). There were no significant differences in morbidity or mortality outcomes. CONCLUSIONS: Antibiotic stewardship strategies can be implemented in the NICU without compromising outcomes in patients with NEC. Bell stage stratification appears to be an effective method for antibiotic selection. Further studies are needed in a larger population to optimize regimens and ensure safety. TYPE OF STUDY: Retrospective comparative study. LEVEL OF EVIDENCE: Level III.

Genomic surveillance of SARS-CoV-2 in the state of Delaware reveals tremendous genomic diversity.

The use of next generation sequencing is critical for the surveillance of severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, transmission, as single base mutations have been identified with differences in infectivity. A total of 1,459 high quality samples were collected, sequenced, and analyzed in the state of Delaware, a location that offers a unique perspective on transmission given its proximity to large international airports on the east coast. Pangolin and Nextclade were used to classify these sequences into 16 unique clades and 88 lineages. A total of 411 samples belonging to the Alpha 20I/501Y.V1 (B.1.1.7) strain of concern were identified, as well as one sample belonging to Beta 20H/501.V2 (B.1.351), thirteen belonging to Epsilon 20C/S:452R (B.1.427/B.1.429), two belonging to Delta 20A/S:478K (B.1.617.2), and 15 belonging to Gamma 20J/501Y.V3 (p.1). A total of 2217 unique coding mutations were observed with an average of 17.7 coding mutations per genome. These data paired with continued sample collection and sequencing will give a deeper understanding of the spread of SARS-CoV-2 strains within Delaware and its surrounding areas.

COVID-19 vaccination coverage among hospital-based healthcare personnel reported through the Department of Health and Human Services Unified Hospital Data Surveillance System, United States, January 20, 2021-September 15, 2021.

To protect both patients and staff, healthcare personnel (HCP) were among the first groups in the United States recommended to receive the COVID-19 vaccine. We analyzed data reported to the U.S. Department of Health and Human Services (HHS) Unified Hospital Data Surveillance System on COVID-19 vaccination coverage among hospital-based HCP. After vaccine introduction in December 2020, COVID-19 vaccine coverage rose steadily through April 2021, but the rate of uptake has since slowed; as of September 15, 2021, among 3,357,348 HCP in 2,086 hospitals included in this analysis, 70.0% were fully vaccinated. Additional efforts are needed to improve COVID-19 vaccine coverage among HCP.

Trends in COVID-19 Cases, Emergency Department Visits, and Hospital Admissions Among Children and Adolescents Aged 0-17 Years - United States, August 2020-August 2021.

Although COVID-19 generally results in milder disease in children and adolescents than in adults, severe illness from COVID-19 can occur in children and adolescents and might require hospitalization and intensive care unit (ICU) support (1-3). It is not known whether the B.1.617.2 (Delta) variant,* which has been the predominant variant of SARS-CoV-2 (the virus that causes COVID-19) in the United States since late June 2021,† causes different clinical outcomes in children and adolescents compared with variants that circulated earlier. To assess trends among children and adolescents, CDC analyzed new COVID-19 cases, emergency department (ED) visits with a COVID-19 diagnosis code, and hospital admissions of patients with confirmed COVID-19 among persons aged 0-17 years during August 1, 2020-August 27, 2021. Since July 2021, after Delta had become the predominant circulating variant, the rate of new COVID-19 cases and COVID-19-related ED visits increased for persons aged 0-4, 5-11, and 12-17 years, and hospital admissions of patients with confirmed COVID-19 increased for persons aged 0-17 years. Among persons aged 0-17 years during the most recent 2-week period (August 14-27, 2021), COVID-19-related ED visits and hospital admissions in the states with the lowest vaccination coverage were 3.4 and 3.7 times that in the states with the highest vaccination coverage, respectively. At selected hospitals, the proportion of COVID-19 patients aged 0-17 years who were admitted to an ICU ranged from 10% to 25% during August 2020-June 2021 and was 20% and 18% during July and August 2021, respectively. Broad, community-wide vaccination of all eligible persons is a critical component of mitigation strategies to protect pediatric populations from SARS-CoV-2 infection and severe COVID-19 illness.

Restoring Immunization Services Provided by the Vaccines for Children Program in Puerto Rico After Hurricanes Irma and Maria, 2017-2019.

CONTEXT: In September 2017, Hurricanes Irma and Maria impacted Puerto Rico, causing significant disruption of immunization services and vaccine losses due to widespread infrastructure and electrical grid damage and resulting cold chain failures. OBJECTIVE: To describe posthurricane efforts undertaken to restore and strengthen immunization services provided by Puerto Rico's federally funded Vaccines for Children (VFC) Program, a network of clinics that provide vaccines to eligible children. DESIGN: Historical records were reviewed to characterize Puerto Rico's prehurricane immunization system. Site visits to assess VFC clinic posthurricane operational status were conducted by the Puerto Rico Department of Health, working with the Centers for Disease Control and Prevention and other partners. Infrastructure repair and acquisition of backup generators, temperature data loggers, and replacement vaccines were carried out to restore operations. RESULTS: Prior to the hurricanes, 224 VFC clinics throughout the island provided immunizations. An initial assessment 10 days after Hurricane Maria showed that only 11 (5%) of the clinics were operational. Reasons included ongoing power outages; difficulties in obtaining generator fuel; equipment or facility damage; and damaged vaccines. The VFC clinics were restored incrementally; 123 (55%) were operational by December 2017, 193 (86%) by May 2018, and 204 (91%) by May 2019. Long-term recovery activities are underway and focus on strengthening Puerto Rico's immunization system to withstand future disasters, including improving backup power systems. CONCLUSION: Through coordinated efforts of the Puerto Rico Department of Health, the Centers for Disease Control and Prevention, and other partners, the operational status of VFC clinics posthurricanes was assessed and operations restored. Emergency plans for vaccine storage and handling, which called for alternative vaccine storage locations and backup generators, were inadequate to address disasters of the magnitude of Hurricanes Irma and Maria; such plans need to consider the possibility of large-scale disasters that result in long-term power outages.

Lessons from the reestablishment of Public Health Laboratory activities in Puerto Rico after Hurricane Maria.

Public Health Laboratories (PHLs) in Puerto Rico did not escape the devastation caused by Hurricane Maria. We implemented a quality management system (QMS) approach to systematically reestablish laboratory testing, after evaluating structural and functional damage. PHLs were inoperable immediately after the storm. Our QMS-based approach began in October 2017, ended in May 2018, and resulted in the reestablishment of 92% of baseline laboratory testing capacity. Here, we share lessons learned from the historic recovery of the largest United States' jurisdiction to lose its PHL capacity, and provide broadly applicable tools for other jurisdictions to enhance preparedness for public health emergencies.

Initial Public Health Laboratory Response After Hurricane Maria - Puerto Rico, 2017.

Hurricane Maria made landfall in Puerto Rico on September 20, 2017, causing major damage to infrastructure and severely limiting access to potable water, electric power, transportation, and communications. Public services that were affected included operations of the Puerto Rico Department of Health (PRDOH), which provides critical laboratory testing and surveillance for diseases and other health hazards. PRDOH requested assistance from CDC for the restoration of laboratory infrastructure, surveillance capacity, and diagnostic testing for selected priority diseases, including influenza, rabies, leptospirosis, salmonellosis, and tuberculosis. PRDOH, CDC, and the Association of Public Health Laboratories (APHL) collaborated to conduct rapid needs assessments and, with assistance from the CDC Foundation, implement a temporary transport system for shipping samples from Puerto Rico to the continental United States for surveillance and diagnostic and confirmatory testing. This report describes the initial laboratory emergency response and engagement efforts among federal, state, and nongovernmental partners to reestablish public health laboratory services severely affected by Hurricane Maria. The implementation of a sample transport system allowed Puerto Rico to reinitiate priority infectious disease surveillance and laboratory testing for patient and public health interventions, while awaiting the rebuilding and reinstatement of PRDOH laboratory services.

Pediatric Dental Clinic-Associated Outbreak of Mycobacterium abscessus Infection.

BACKGROUND: Mycobacterium abscessus is an uncommon cause of invasive odontogenic infection. METHODS: M abscessus-associated odontogenic infections occurred in a group of children after they each underwent a pulpotomy. A probable case-child was defined as a child with facial or neck swelling and biopsy-confirmed granulomatous inflammation after a pulpotomy between October 1, 2013, and September 30, 2015. M abscessus was isolated by culture in confirmed case-children. Clinical presentation, management, and outcomes were determined by medical record abstraction. RESULTS: Among 24 children, 14 (58%) were confirmed case-children. Their median age was 7.3 years (interquartile range, 5.8-8.2 years), and the median time from pulpotomy to symptom onset was 74 days (range, 14-262 days). Clinical diagnoses included cervical lymphadenitis (24 [100%] of 24), mandibular or maxillary osteomyelitis (11 [48%] of 23), and pulmonary nodules (7 [37%] of 19). Each child had ≥1 hospitalization and a median of 2 surgeries (range, 1-6). Of the 24 children, 12 (50%) had surgery alone and 11 (46%) received intravenous (IV) antibiotics. Nineteen of the 24 (79%) children experienced complications, including vascular access malfunction (7 [64%] of 11), high-frequency hearing loss (5 [56%] of 9), permanent tooth loss (11 [48%] of 23), facial nerve palsy (7 [29%] of 24), urticarial rash (3 [25%] of 12), elevated liver enzyme levels (1 [20%] of 5), acute kidney injury (2 [18%] of 11), incision dehiscence/fibrosis (3 [13%] of 24), and neutropenia (1 [9%] of 11). CONCLUSIONS: M abscessus infection was associated with significant medical morbidity and treatment complications. Unique manifestations included extranodal mandibular or maxillary osteomyelitis and pulmonary nodules. Challenges in the identification of case-children resulted from an extended incubation period and various clinical manifestations. Clinicians should consider the association between M abscessus infection and pulpotomy in children who present with subacute cervical lymphadenitis. The use of treated/sterile water during pulpotomy might prevent further outbreaks.

Assessment of U.S. Pediatrician Knowledge of Toxocariasis.

Toxocariasis, one of a group of parasitic diseases known as neglected parasitic infections, is a disease caused by the larvae of two species of Toxocara roundworms, Toxocara canis, from dogs, and less commonly Toxocara cati, from cats. Although most infected individuals are asymptomatic, clinical manifestations may include fever, fatigue, coughing, wheezing, or abdominal pain (visceral toxocariasis) or vision loss, retina damage, or eye inflammation (ocular toxocariasis). To assess U.S. pediatrician knowledge of toxocariasis, we conducted an electronic survey of American Academy of Pediatrics members. Of the 2,684 respondents, 1,120 (47%) pediatricians correctly selected toxocariasis as the diagnosis in an unknown case presentation with findings typical for toxocariasis; overall 1,695 (85%) stated they were not confident that their knowledge of toxocariasis was current. This knowledge gap suggests a need for improved toxocariasis awareness and education for U.S. pediatricians, especially those caring for children at risk for infection.

Etiology and Laboratory Abnormalities in Bacterial Meningitis in Neonates and Young Infants.

We conducted a retrospective review of electronic medical records of all cases of bacterial meningitis in neonates and young infants at our institution from 2004 to 2014. Fifty-six cases were identified. The most common causative organism was group B streptococcus, followed by Escherichia coli and then Listeria monocytogenes. Forty-four of the 56 patients in the study had abnormalities of the blood white blood cell (WBC) count. The most common WBC count abnormalities were leukopenia and elevation of the immature to total (I:T) neutrophil ratio. Six patients in the case series lacked cerebrospinal fluid (CSF) pleocytosis. Overall, just 3 of the 56 patients had normal WBC count with differential, CSF WBC count, and urinalysis. Only 1 of the 56 patients was well appearing with all normal lab studies. Our study indicates that bacterial meningitis may occur without CSF pleocytosis but very infrequently occurs with all normal lab studies and well appearance.

Zika Virus Transmission - Region of the Americas, May 15, 2015-December 15, 2016.

Zika virus, a mosquito-borne flavivirus that can cause rash with fever, emerged in the Region of the Americas on Easter Island, Chile, in 2014 and in northeast Brazil in 2015 (1). In response, in May 2015, the Pan American Health Organization (PAHO), which serves as the Regional Office of the Americas for the World Health Organization (WHO), issued recommendations to enhance surveillance for Zika virus. Subsequently, Brazilian investigators reported Guillain-Barré syndrome (GBS), which had been previously recognized among some patients with Zika virus disease, and identified an association between Zika virus infection during pregnancy and congenital microcephaly (2). On February 1, 2016, WHO declared Zika virus-related microcephaly clusters and other neurologic disorders a Public Health Emergency of International Concern.* In March 2016, PAHO developed case definitions and surveillance guidance for Zika virus disease and associated complications (3). Analysis of reports submitted to PAHO by countries in the region or published in national epidemiologic bulletins revealed that Zika virus transmission had extended to 48 countries and territories in the Region of the Americas by late 2016. Reported Zika virus disease cases peaked at different times in different areas during 2016. Because of ongoing transmission and the risk for recurrence of large outbreaks, response efforts, including surveillance for Zika virus disease and its complications, and vector control and other prevention activities, need to be maintained.

Origins, design and implementation of the China GAVI project.

China received GAVI support for hepatitis B vaccination in 2001 because of high disease burden and strong government will to protect infants at risk. The China/GAVI project, implemented since 2002, was funded 50% by GAVI and 50% by the Government of China. The purpose of the project was to increase coverage of hepatitis B vaccine through a pro-poor approach targeting all counties of the 12 Western provinces and poverty counties of the 10 Central provinces, to accelerate integration of hepatitis B vaccine into routine immunization, and assure immunization injection safety. The mechanism of internal coordination among multiple government entities and international cooperation was established and comprehensive strategies were used to improve vaccine coverage and injection safety. After 8 years of implementation, 193,000 health care workers in 118,316 health care facilities participated in the project, mostly at the township hospitals level (55,051) and in community centres (104,547). Through the China GAVI project, the 85% HepB3 coverage goal was reached in 98% of GAVI China project counties, the 75% timely birth dose (TBD) coverage goal was reached in 80% of GAVI project counties, and AD syringes were introduced into 100% of GAVI-supported areas. Additionally, the GAVI project was instrumental in convincing the Chinese Government to sustainably introduce and fully fund HepB vaccine for all newborns in China. The impact of hepB vaccination on HBsAg prevalence was observed throughout China, as HBsAg prevalence (previously ~10%) is now less than 1% among children under 5 years of age.

Effect of risedronate on bone in renal transplant recipients.

Bisphosphonates may prevent or treat the bone loss promoted by the immunosuppressive regimens used in renal transplantation. Risedronate is a commonly used third-generation amino-bisphosphonate, but little is known about its effects on the bone health of renal transplant recipients. We randomly assigned 42 new living-donor kidney recipients to either 35 mg of risedronate weekly or placebo for 12 months. We obtained bone biopsies at the time of renal transplant and after 12 months of protocol treatment. Treatment with risedronate did not affect bone mineral density (BMD) in the overall cohort. In subgroup analyses, it tended to preserve BMD in female participants but did not significantly affect the BMD of male participants. Risedronate did associate with increased osteoid volume and trabecular thickness in male participants, however. There was no evidence for the development of adynamic bone disease. In summary, further study is needed before the use of prophylactic bisphosphonates to attenuate bone loss can be recommended in renal transplant recipients.

Sixteen-Year-Old Boy From Nigeria With a Rash.

DATE: Thursday, October 20, 2011. SESSION TITLE: Pediatric Fellows' Day Workshop Hosting Organization: Infectious Diseases Society of America. HOSTING EVENT: 49th Annual Meeting of the Infectious Diseases Society of America. LOCATION: Boston, Massachusetts.

Hepatitis B vaccination of newborn infants in rural China: evaluation of a village-based, out-of-cold-chain delivery strategy.

OBJECTIVE: To prevent perinatal transmission of hepatitis B virus (HBV), WHO recommends that the first dose of hepatitis B (HepB) vaccine be given within 24 hours after birth. This presents a challenge in remote areas with limited cold-chain infrastructure and where many children are born at home. METHODS: Rural townships in three counties in China's Hunan Province were randomized into three groups with different strategies for delivery of the first dose of HepB vaccine. In group 1, vaccine was stored within the cold chain and administered in township hospitals. In group 2, vaccine was stored out of the cold chain in villages and administered by village-based health workers to infants at home. Group 3 used the same strategy as group 2, but vaccine was packaged in a prefilled injection device. Training of immunization providers and public communication conveying the importance of the birth dose was performed for all groups. FINDINGS: Among children born at home, timely administration (within 24 hours after birth) of the first dose of HepB vaccine increased in all groups after the study: group 1, from 2.4% to 25.2%; group 2, from 2.6% to 51.8%; and group 3, from 0.6% to 66.7%; P < 0.001 in each case. No significant difference in antibody response to vaccine was observed between the groups. CONCLUSION: Timely administration of the first dose of HepB vaccine was improved by communication and training activities, and by out-of-cold-chain storage of vaccine and administration at the village level, especially among children born at home.

Evidence for a novel cryoprotective protein from freeze-tolerant larvae of the goldenrod gall fly Eurosta solidaginis.

Third-instar larvae of the goldenrod gall fly Eurosta solidaginis (Diptera: Tephritidae) from populations in northern North America transition from freeze-susceptible to freeze-tolerant just prior to the onset of winter. While studies have documented the accumulation of carbohydrate cryoprotectants during this transition, protein cryoprotectants common to other freeze-tolerant species have not been reported in the gall fly. Using larvae collected from a population in Madison County, NY, which changes from freeze-susceptible to freeze-tolerant in early October, we assayed for the presence of factors that could preserve the catalytic activity of the cold-labile enzyme, rabbit muscle lactate dehydrogenase. Freezing this enzyme with a heat-stable, hydrophilic fraction derived from homogenates of both freeze-tolerant larvae and those in the process of becoming freeze-tolerant preserved between 70% and 80% of this enzyme's activity. Neither a comparable solution of bovine serum albumin nor the naturally-occurring carbohydrates (glycerol, sorbitol, or trehalose) conferred this level of cryoprotection. The putative cryoprotective protein from gall fly larvae did not bind to a weak anion exchanger, implying that its character may be cationic.

Immunogenicity of an inactivated hepatitis A vaccine in infants and young children.

BACKGROUND: Infants with passively transferred maternal antibody, born to mothers immune to hepatitis A virus (HAV), have a blunted response to hepatitis A (HA) vaccine. We compared HA vaccine immunogenicity among infants born to immune and susceptible mothers, vaccinated on different schedules. METHODS: Infants were randomized into 3 groups, each receiving 2 doses of 720 EL.U. of HA vaccine (HAVRIX; Glaxo SmithKline): group 1 at ages 6 and 12 months, group 2 at ages 12 and 18 months and group 3 at ages 15 and 21 months. We determined mothers' antibody to HAV (anti-HAV) status and infants' anti-HAV concentrations at the first vaccine dose (baseline) and at 1, 7 and 12 months thereafter. All were tested at age 13 months for responses to recommended routine vaccinations administered during infancy. RESULTS: Of 248 participants, 140 were born to HA-susceptible mothers and 108 to immune mothers. At baseline, 34 of 36 (94%) group 1, 5 of 34 (15%) group 2 and one of 38 (3%) group 3 infants born to immune mothers were seropositive. By month 7, all participants in all groups were seropositive except group 1 infants born to immune mothers (34 of 36 [94%], seropositive). In group 1, peak geometric mean concentrations between infants born to immune (794 mIU/mL) and susceptible (2083 mIU/mL) mothers were significantly different. Across groups, peak geometric mean concentrations were similar among infants born to susceptible mothers (3166 mIU/mL, group 2; 3153 mIU/mL, group 3). Among infants born to immune mothers, the difference between groups 1 and 3 (2715 mIU/mL) was significant. There were no differences in responses to routine vaccinations. CONCLUSIONS: HA vaccine is immunogenic among infants born to HA-susceptible mothers and those born to immune mothers and vaccinated beginning > or =12 months old. Passively transferred maternal antibody persists for at least 6 months and results in a blunted response to HA vaccination.

Prevalence of coronary artery lesions on the initial echocardiogram in Kawasaki syndrome.

OBJECTIVES: To determine whether coronary artery lesions (ectasia and aneurysm) are commonly observed on the initial echocardiogram of patients with acute Kawasaki syndrome, whether coronary artery ectasia and/or aneurysms occur more frequently in patients with incomplete Kawasaki syndrome than in those patients with complete findings, and whether earlier diagnosis and treatment of Kawasaki syndrome are associated with less frequent occurrence of coronary artery ectasia and/or aneurysm. DESIGN: A retrospective medical record review. SETTING: A tertiary care pediatric hospital. PARTICIPANTS: One hundred patients treated for Kawasaki syndrome between July 1, 1998, and June 30, 2003, who were identified by a medical record search. MAIN OUTCOME MEASURE: Prevalence of coronary artery lesions (ectasia and aneurysm) on the initial and subsequent echocardiograms. RESULTS: Forty-four percent of patients had a coronary artery lesion (31% with ectasia, 13% with aneurysm) on the initial echocardiogram. Patients with incomplete Kawasaki syndrome were treated significantly later (median, 10 days) and had a significantly higher occurrence of coronary artery aneurysms over the course of their illness (37%) than those with complete Kawasaki syndrome, who were treated at a median of 7 days (P<.001) and had a 12% aneurysm occurrence (P = .009). Patients treated by day 7 of illness had a less frequent occurrence of aneurysm (6%) compared with those patients treated between days 8 and 10 of illness (27%) (P = .03). CONCLUSIONS: Coronary artery lesions are frequently detected on the initial echocardiogram of children with Kawasaki syndrome. If future studies show ectasia to have a relatively high degree of specificity for Kawasaki syndrome, the initial echocardiography may be a useful adjunctive diagnostic test.