Evolving antibiotic resistance in Group B Streptococci causing invasive infant disease: 1970-2021.

BACKGROUND: We sought to define the frequency of antibiotic resistance over time in a collection of invasive GBS isolates derived from infant early-onset disease (EOD), late-onset disease (LOD), and late-late onset disease (LLOD). METHODS: A multicenter retrospective review of infants born from 1970 to 2021 with GBS isolated from blood, cerebrospinal fluid, synovial fluid, cellulitis, or bone. All isolates were serotyped and antimicrobial susceptibility testing performed using disk diffusion. RESULTS: The most common serotypes in our 2017 isolates were III (n = 1112, 55.1%), Ia (n = 445, 22%), Ib (n = 182, 9%) and II (n = 146, 7.2%). A total of 945 (46.8%) isolates were from infants with EOD, 976 (48.3%) from LOD, and 96 (4.75%) from LLOD. All isolates were penicillin-susceptible. Compared to strains isolated <2000, strains isolated ≥2000 showed significantly greater frequency of erythromycin (4.0% to 32.3%, P < 0.0001) and clindamycin (1.5% to 17.5%, P < 0.0001) resistance. Year of isolation (≥2000) and serotype V were significantly associated with erythromycin and/or clindamycin resistance. CONCLUSIONS: We document a rapid and significant increase in clindamycin and erythromycin resistance. As clindamycin may be considered in severely penicillin-allergic women needing GBS intrapartum prophylaxis, obstetricians, pediatricians, and neonatologist should be aware of this disturbing trend. IMPACT: Group B streptococcal strains isolated from infants with invasive infection have become more resistant to second-line antibiotics over time. In this epidemiologic study of 2017 group B streptococci isolated from 1970 to 2021, penicillin susceptibility remained uniform; however, resistance to erythromycin and clindamycin increased significantly over time across all capsular serotypes. Clindamycin resistance exceeded 20% by 2010 in most serotypes. While penicillin remains the treatment of choice for group B streptococcal infant disease, pediatricians and neonatologists should be aware of the high prevalence of resistance to clindamycin, a recommended alternative drug used for intrapartum-antibiotic prophylaxis in penicillin-allergic women.

Invasive Group B Streptococcal Disease In Childhood.

Invasive group B streptococcal disease in childhood is uncommon and occupies a unique clinical niche. We present 10 children, 1-17 years of age, with invasive group B streptococcal disease from 2010 to 2020. Seven had conditions predisposing to infection and 3 had no identifiable risk factors. With appropriate consideration of pathogenesis, source control, and treatment, all children recovered.

Group B Streptococcal Cellulitis-Adenitis Syndrome in Infants: Insights From 24 Years of Experience.

This series of 28 infants with group B streptococcal (GBS) cellulitis-adenitis from a single institution over 24 years offers insights important to the early recognition, spectrum of findings, and optimal management of this rare manifestation of invasive GBS disease.

Recommendations for Screening and Diagnosis of Chagas Disease in the United States.

BACKGROUND: Chagas disease affects an estimated 326 000-347 000 people in the United States and is severely underdiagnosed. Lack of awareness and clarity regarding screening and diagnosis is a key barrier. This article provides straightforward recommendations, with the goal of simplifying identification and testing of people at risk for US healthcare providers. METHODS: A multidisciplinary working group of clinicians and researchers with expertise in Chagas disease agreed on 6 main questions, and developed recommendations based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, after reviewing the relevant literature on Chagas disease in the United States. RESULTS: Individuals who were born or resided for prolonged time periods in endemic countries of Mexico and Central and South America should be tested for Trypanosoma cruzi infection, and family members of people who test positive should be screened. Women of childbearing age with risk factors and infants born to seropositive mothers deserve special consideration due to the risk of vertical transmission. Diagnostic testing for chronic T. cruzi infection should be conducted using 2 distinct assays. CONCLUSIONS: Increasing provider-directed screening for T. cruzi infection is key to addressing this neglected public health challenge in the United States.

Congenital Chagas disease: progress toward implementation of pregnancy-based screening.

PURPOSE OF REVIEW: Lack of recognition of congenital Chagas disease in infants of mothers from endemic regions who are living in countries nonendemic for Trypanosoma cruzi infection suggests a high rate of underdiagnosis. Pregnancy is the optimal access point for identifying Chagas disease in at-risk mothers and their infants. In this review, we update progress toward implementation of pregnancy-based screening for congenital Chagas disease in nonendemic settings. RECENT FINDINGS: International organizations have updated recommendations for diagnosis, treatment and prevention of congenital Chagas disease. Reports of successful implementation of pregnancy-based screening at some centers provide a model for optimizing diagnosis of congenital Chagas disease. Screening family members of index patients may identify additional T. cruzi-infected persons. Promising tests to augment current diagnostic modalities for maternal and congenital Chagas disease are in development. Universal or risk-based screening would be cost-effective. More healthcare providers are now aware that treatment of congenital Chagas disease is curative and are promoting efforts to make pregnancy-based screening for congenital Chagas disease a standard of care. SUMMARY: Ongoing efforts to implement routine pregnancy-based screening for congenital Chagas disease in nonendemic regions will mutually benefit infants, their mothers and family members and can prevent potentially fatal Chagas cardiomyopathy.

Chagas Disease: Implementation of Screening to Benefit Mother and Infant.

Pregnancy-based screening would identify women with Chagas disease, allowing for treatment of Trypanosoma cruzi-infected women and infants to prevent potentially fatal Chagas cardiomyopathy.

Two Cases of Cronobacter Sakazakii Meningitis in Infants: The Importance Of Early Advanced Brain Imaging and Public Health Reporting.

We report 2 infants hospitalized with Cronobacter sakazakii meningitis. Each infant had exposure to powdered infant formula at home. Both infants survived, but 1 infant had a subdural empyema drained and developed left sensorineural hearing loss. Early advanced brain imaging is recommended in infants with C. sakazakii meningitis. Reporting to state and federal public health officials may help identify outbreaks.

Evaluation and Management of Congenital Chagas Disease in the United States.

Chagas disease is underappreciated as a health concern in the United States. Approximately 40 000 women of childbearing age living in the United States have chronic Chagas disease. Most of them are unaware that they have an infection that is transmissible to their offspring. The estimated US maternal-to-infant transmission rate of Trypanosoma cruzi is 1% to 5%. Ten percent to 40% of neonates with congenital T cruzi infection have clinical signs consistent with a congenital infection but no findings are unique to Chagas disease. If left untreated, 20% to 40% of infants with Chagas disease will later develop potentially fatal cardiac manifestations. Molecular testing can confirm the diagnosis in neonates. Treatment is well tolerated in infancy and usually results in cure. Screening of at-risk women during pregnancy can identify maternal infection and allow early assessment and treatment for congenital T cruzi infection.

Serocorrelates of protection against infant group B streptococcus disease.

Group B streptococcus (GBS) is a leading cause of young infant mortality and morbidity globally, with vaccines being developed for over four decades but none licensed to date. A serocorrelate of protection against invasive disease in young infants is being considered to facilitate vaccine early licensure, followed by demonstration of efficacy assessed postlicensure. In this Review, we synthesise the available scientific evidence to define an immune correlate associated with GBS disease risk reduction on the basis of studies of natural infection. We summarise studies that have investigated GBS serum anticapsular or anti-protein antibodies, and studies measuring the association between antibody function and disease risk reduction. We highlight how knowledge on the development of correlates of protection from existing vaccines could be harnessed to facilitate GBS vaccine development. These lessons include aggregation of serocorrelates of protection for individual serotypes, understanding the relationship between immunity derived from natural exposure of adults and vaccine-induced immunity, or using extrapolation of protection from in-vitro immunoassay results. We also highlight key considerations for the assessment of the role of antibodies to derive a serocorrelate of risk reduction in future seroepidemiological studies of GBS disease.

A Phase 2, Randomized, Control Trial of Group B Streptococcus (GBS) Type III Capsular Polysaccharide-tetanus Toxoid (GBS III-TT) Vaccine to Prevent Vaginal Colonization With GBS III.

BACKGROUND: Group B Streptococcus (GBS) frequently colonizes pregnant women and can cause sepsis and meningitis in young infants. If colonization was prevented through maternal immunization, a reduction in perinatal GBS disease might be possible. A GBS type III capsular polysaccharide (CPS)-tetanus toxoid conjugate (III-TT) vaccine was evaluated for safety and efficacy in preventing acquisition of GBS colonization. METHODS: Healthy, nonpregnant women aged 18-40 years and screened to be GBS III vaginal and rectal culture negative were randomized to receive III-TT conjugate or tetanus diphtheria toxoid vaccine in a multicenter, observer-blinded trial. GBS vaginal and rectal cultures and blood were obtained bimonthly over 18 months. Serum concentrations of GBS III CPS-specific antibodies were determined using enzyme-linked immunosorbent assay. RESULTS: Among 1525 women screened, 650 were eligible for the intent-to-treat analysis. For time to first acquisition of vaginal GBS III, vaccine efficacy was 36% (95% confidence interval [CI], 1%-58%; P = .044), and for first rectal acquisition efficacy was 43% (95% CI, 11% to 63%; P = .014). Two months post-immunization, geometric mean concentrations of serum GBS type III CPS-specific immunoglobulin G were 12.6 µg/mL (95% CI, 9.95 to 15.81) in GBS III-TT recipients, representing a 4-fold increase from baseline in 95% of women, which persisted. Both vaccines were well tolerated. CONCLUSIONS: GBS CPS III-TT conjugate vaccine significantly delayed acquisition of vaginal and rectal GBS III colonization. In addition to its use for maternal immunization to passively protect infants with maternally derived antibodies, a multivalent vaccine might also serve to reduce fetal and neonatal exposure to GBS. CLINICAL TRIALS REGISTRATION: NCT00128219.

Survey of Pediatric Infectious Diseases Society Members About Congenital Chagas Disease.

Participants in a survey about congenital Chagas disease, distributed electronically to Pediatric Infectious Diseases Society members, perceived having limited knowledge about congenital Trypanosoma cruzi infection. Most rarely or never consider the diagnosis in infants born to parents from Latin America. Improved awareness of congenital Chagas disease and assessment of at-risk infants is needed.

Trichosporonosis in Pediatric Patients With a Hematologic Disorder.

BACKGROUND: Trichosporonosis is an emerging and often fatal opportunistic fungal infection in immunocompromised patients, particularly those with hematologic malignancy, but data in children are lacking. METHODS: We report here 3 cases of invasive infection caused by Trichosporon asahii in pediatric patients with acute lymphoblastic leukemia at Texas Children's Hospital in Houston, Texas. We also conducted a literature review and identified 16 additional reports of pediatric patients with invasive T asahii infection and an underlying malignant or nonmalignant hematologic disorder. RESULTS: Of the 19 cases of invasive T asahii infection, the most commonly reported underlying hematologic disorder was acute lymphoblastic leukenia (47%), followed by acute myelogenous leukemia (21%). Most of the patients (94%) had neutropenia, defined as an absolute neutrophil count of <500 cells/mm3. Antifungal prophylaxis information was available in 6 of the 19 cases, and micafungin use was reported in 5 cases. Treatment regimens frequently included voriconazole monotherapy (47%) or the combination of an azole antifungal with amphotericin B (35%). The mortality rate was 58%. CONCLUSIONS: Recognizing that echinocandins, which are increasingly used for prophylaxis in patients with a hematologic malignancy, are not active against Trichosporon species is of critical importance. The recommended first-line therapy for trichosporonosis is voriconazole, but successful outcome depends largely on the underlying immune status of the host.

Prevalence and Capsular Types of Group B Streptococci Colonizing Indian Women Living in the United States.

Group B streptococcal rectovaginal colonization prevalence in women of Indian descent living in the United States was 24.7% comparable with US rates but higher than rates reported from India. The capsular polysaccharide types were distinct in that type V was most common and 33% of group B streptococcal strains were nontypeable.

Addressing the Challenges of Chagas Disease: An Emerging Health Concern in the United States.

Chagas disease is an emerging health concern in the United States. US health care providers have an unparalleled opportunity to respond to the challenges this infection poses and to provide state-of-the-art care for patients with Chagas disease. Most of the approximately 300,000 persons with Trypanosoma cruzi infection living in the United States have chronic, asymptomatic infection acquired in endemic regions in Latin America. Congenital infection is often asymptomatic and, even when symptomatic, has no features that distinguish it from other congenitally transmitted infections. Health care providers and the public have limited awareness of this infection. Recognizing risk groups and performing targeted diagnostic testing for at-risk infants, children, and adults are a health priority because early treatment can effect cure and avert the life-threatening cardiac manifestations of Chagas disease. Two medications for treatment, benznidazole and nifurtimox, are available through the Centers for Disease Control and Prevention. Although challenges exist, informed health care providers can greatly reduce the effects of Chagas disease in the United States.

Group B Streptococcal Colonization Among Pregnant Women in Delhi, India.

BACKGROUND: Little is known regarding maternal group B streptococcal (GBS) colonization prevalence and capsular (CPS) serotype distribution among pregnant women in India. The objective of this prospective cohort study was to determine GBS recto-vaginal colonization prevalence in pregnant women at Dr. Ram Manohar Lohia Hospital in Delhi, India. METHODS: Literature review identified reports from India assessing GBS colonization prevalence in pregnant women. Rectal and vaginal swabs were inoculated into Strep B Carrot Broth (Hardy Diagnostics, Santa Maria, CA) and subcultured onto GBS Detect plates (Hardy Diagnostics, Santa Maria, CA). Isolates were serotyped using ImmuLex Strep-B latex kits (Statens Serum Institut, Copenhagen, Denmark). RESULTS: Thirteen studies were identified citing GBS colonization prevalence during pregnancy as 0.47%-16%. Among 300 pregnant women (mean age: 26.9 years; mean gestation: 34 weeks) enrolled (August 2015 to April 2016), GBS colonization prevalence was 15%. Fifteen percent of women had vaginal only, 29% had rectal only and 56% had both sites colonized. CPS types were Ia (13.3%), Ib (4.4%), II (20%), III (22.2%), V (20%) and VII (6.7%); 13.3% were nontypable. Fetal loss in a prior pregnancy at ≥20-weeks gestation was more common in colonized than noncolonized women (15.6% vs. 3.5%; P = 0.004). Employing recent census data for the birth cohort and estimating that 1%-2% of neonates born to colonized women develop early-onset disease, at least 39,000 cases of early-onset disease may occur yearly in India. CONCLUSIONS: Using optimal methods, 15% of third trimester pregnant women in India are GBS colonized. A multivalent vaccine containing 6 CPS types (Ia, Ib, II, III, V and VII) would encompass ~87% of GBS carried by pregnant women in India.

Immune Responses to Invasive Group B Streptococcal Disease in Adults.

Immunization of nonpregnant adults could help prevent invasive group B Streptococcus (GBS) infections, but adult immune responses have not been investigated. We defined capsular polysaccharide (CPS) and pilus island (PI) surface antigen distribution and expression and immune responses to GBS infection in nonpregnant adults. Prospective surveillance from 7 hospitals in Houston, Texas, USA, identified 102 adults with GBS bacteremia; 43% had skin/soft tissue infection, 16% bacteremia without focus, and 12% osteomyelitis. CPS-specific IgG was determined by ELISA and pilus-specific IgG by multiplex immunoassay. CPS types were Ia (24.5%), Ib (12.7%), II (9.8%), III (16.7%), IV (13.7%), and V (12.7%); 9.8% were nontypeable by serologic methods. Pili, expressed by 89%, were most often PI-2a. CPS and pilus-specific IgG increased during convalescence among patients with strains expressing CPS or PI. All GBS expressed CPS or PI; 79% expressed both. Increased antibodies to CPS and PI during recovery suggests that GBS bacteremia in adults is potentially vaccine preventable.