Anne Filleron

Group B streptococci in milk and late neonatal infections: an analysis of cases in the literature

Background The source for late-onset neonatal infections (LONI) due to group B Streptococcus (GBS) has not been fully explored. We reviewed GBS LONI cases associated with contaminated breast milk to determine whether breast milk was a possible route for neonatal infection. Data sources A PubMed search from January 1977 to March 2013 was performed with MeSH words “Streptococcus agalactiae”, “group B Streptococcus”, “infection”, “milk”, “human”, “late-onset infection” and/or “neonate”; relevant cross references were also reviewed. Results Forty-eight documented cases of GBS LONI matched our search criteria and were retrieved from the literature. When performed, molecular typing identified clonal isolates in the neonate and milk samples taken after LONI in all cases, with the hypervirulent sequence type 17 (ST-17) clone identified in two of these cases. Caesarean delivery combined with the absence of GBS recovery from maternal samples other than milk was noted for four cases. The rate of recurrent infections was high (35%) and, together with the data reviewed, points to a potential role of breast milk in GBS LONI. Conclusions The cases reviewed here, together with the evidence of breast milk transmission for other pathogens, suggest that breast milk, which would account for repeated GBS transmission to the neonate, may favour gut translocation and subsequent LONI. Further investigations are nevertheless needed to study the relative importance of this contamination route compared with persistent postnatal gut colonisation and the dynamics of milk and neonatal gut colonisation.

Current insights in invasive group A streptococcal infections in pediatrics

A rising incidence of invasive group A Streptococcus infections (IGASI) has been noted in children in the past three decades. The relative frequency of the infection types showed marked differences to IGASI in adults, and severity of the disease resulted in a mortality rate usually comprising between 3.6% and 8.3%. The emm1-type group A Streptococcus (GAS) subclone displaying a particular pattern of virulence factors was widely disseminated and prevalent in children with IGASI while the emm3-type GAS subclone appeared as a recent emerging genotype. However, the implication of these hypervirulent clones in the increase of IGASI in children is still controversial. Recent advances in our knowledge on pathogenesis of IGASI underlined that deregulation of virulence factor production, individual susceptibility, as well as exuberant cytokine response are important factors that may account for the severity of the disease in children. Future changes in IGASI epidemiology are awaited from current prospects for a safe and effective vaccine against GAS. IGASI are complex infections associating septic, toxic, and immunological disorders. Treatment has to be effective on both the etiologic agent and its toxins, due to the severity of the disease associated to the spread of highly virulent bacterial clones. More generally, emergence of virulent clones responsible for septic and toxic disease is a matter of concern in pediatric infectiology in the absence of vaccination strategy.

Streptococcus agalactiae late-onset neonatal infections: should breast milk be more systematically tested for bacterial contamination?

Dear Sir, Neonatal late-onset infections (NLOI) are defined as infections occurring between seven days and three months of life. Their incidence in industrialized countries is stable (1). A recent review reported an average incidence of NLOI owing to Streptococcus agalactiae, socalled Group B Streptococcus (GBS), of 0.24 ⁄1000 live births and a case fatality ratio of 6.8% (2). The pathophysiology of GBS NLOI is still not fully understood despite recent advances in the pathogenesis knowledge of invasive infections because of serotype III GBS (S3GBS) and the identification of the hypervirulent clone of sequence type-17 (S3GBS ST-17) (3). Digestive translocation consecutive to prolonged intestinal carriage after neonate colonization occurring at birth is the more usually suspected route for infection (4). Here, we report four cases of late-onset or recurrent S3GBS infection that may be related to contaminated breast milk feeding. Case 1: A full-term male neonate was born by noninstrumental vaginal delivery, from a mother whose vaginal smear at 32 weeks of gestation was negative. On day 27, the newborn presented vomiting and fever. The initial sepsis severity imposed a transfer in the intensive care unit (ICU); S3GBS ST-17 was isolated from cerebrospinal fluid (CSF), urine and blood. Intravenous treatment, including cefotaxime, vancomycin and amikacin, was given immediately. The breast milk cultures performed at days 4, 22 and 26 after the onset of infection were positive for S3GBS ST-17 although the mother was asymptomatic. Despite the communicant hydrocephalus one month after infection, follow-up at six months showed normal neurological status. Case 2: A full-term male infant was born by non-instrumental vaginal delivery. Although the mother’s vaginal smears were negative for GBS, the newborn’s systematic gastric fluid aspirate was positive for GBS. At day 2, he presented fever, grunting and a C-reactive protein (CRP) level of 157 mg ⁄ L. Blood culture was positive for S3GBS ST-17. Intravenous amoxicillin and amikacin were started, infant left the hospital on day 12. On day 29, clinical deterioration with fever and mottling led to rehospitalization and the diagnosis of S3GBS ST-17 NLOI with positive blood, CSF and urinary samples. The mother’s milk culture at day 30 after first infection was positive for GBS, although the mother was asymptomatic. The clinical examination was normal at his hospital release at day 50, and there was no further recurrence of infection. Case 3: A female infant was born at 30 weeks of gestation in a context of premature rupture of membranes and foetal bradycardia. Cultures of gastric fluid aspirate and placenta were negative. At day 35, clinical deterioration and biological inflammatory syndrome (CRP, 67 mg ⁄ L) led to the diagnosis of NLOI with one blood culture positive for S3GBS. The mother’s milk analysed seven days after the onset of the infection was positive for S3GBS. The newborn went home at day 57 after a normal clinical examination. Case 4: A full-term female was born after a normal pregnancy and delivery. The mother’s vaginal smears were negative in the third quarter. On day 21, the infant was admitted to ICU after a ‘missed sudden death’. Blood, CSF and respiratory secretions were positive for S3GBS ST-17. Despite the intravenous antibiotic therapy, the course of septic shock was unfavourable. The mother’s milk analysed on day 23 revealed S3GBS ST-17. As the newborn’s mucosal surface and immunity are not fully mature, gut translocation is thought to precede neonatal septicaemia (5). For GBS, prolonged intestinal carriage – lasting up to one year – has been observed in about 10% of infants whose mother is carrier (4) and may favour translocation. However, beside neonatal colonization at birth, several cases documenting GBS transmission via breastfeeding were reported, suggesting that an alternative route for infection should be also considered (6). Recent advances in our knowledge on S3GBS pathogenesis support the high invasive potential of ST-17 isolates, showing a high propensity for both persistence in the gut at a high load for a prolonged period, that is, at least 14 days, and translocation that may be related to an improved adhesion to intestinal and blood–brain barrier cells (3). The hypervirulent ST-17 clone was present in three of the cases reported here including a recurrent infection at day 29 after early-onset infection (EOI) at day 2 (case 2) while molecular characterization of GBS isolated in the remaining case was not performed. In cases 1 and 4, we documented for the first time the presence of this hypervirulent clone in both breast milk and neonate samples. GBS vaginal carriage investigated for three of the reported cases was negative and although carriage may be intermittent, no other maternal samples were positive for GBS, suggesting that breastfeeding was the most probable route for S3GBS transmission to the neonates. Incidence of GBS NLOI remained stable in the past years and contrasted with the decrease observed for EOI (1,2), suggesting that prevention of NLOI may require specific screening procedures to track bacterial colonization. Transmission of bacterial pathogen including GBS through breast milk is a poorly understood route of NLOI. Future studies are necessary to establish the prevalence of GBS in breast milk and to elucidate the importance of breast milk-mediated infections. These questions need to be resolved before implementation of any routine GBS screening policy in mother milk. In the meanwhile, we recommend that bacteriological analysis be performed more systematically to search for GBS excretion, particularly in asymptomatic mothers, because recurrent infection after effective Acta Pædiatrica ISSN 0803–5253

Staphylococcus aureus in a neonatal care center: methicillin-susceptible strains should be a main concern

BackgroundIn the context of a methicillin-susceptible Staphylococcus aureus (MSSA) outbreak, we aimed to improve our knowledge of S. aureus (SA) epidemiology in the neonatal care center (NCC) of a tertiary care teaching hospital.MethodsWe performed a complete one-year review of SA carrier, colonized or infected patients. Monthly prevalence and incidence of SA intestinal carriage, colonization and infection were calculated and the types of infection analysed. During the MSSA outbreak, strains were studied for antimicrobial resistance, content of virulence genes and comparative fingerprint in Pulsed-Field Gel Electrophoresis. Hand hygiene and catheter-related practices were assessed by direct observational audits. Environmental investigation was performed in search of a SA reservoir.ResultsEpidemiological analyses showed 2 or 3 prevalence peaks on a background of SA endemicity. In the NCC, during 2009, overall MSSA prevalence did not decrease below 5.5%, while mean MRSA prevalence was about 1.53%. Analysis of infection cases revealed that the outbreak corresponded to the emergence of catheter-related infections and was probably related to the relaxation in infection control practices in a context of high colonization pressure. Health care workers’ white coats appeared as a potential environmental reservoir that could perpetuate SA circulation in the ward.ConclusionThis report emphasizes the importance of integrating MSSA along with methicillin-resistant SA in a program of epidemiological surveillance in the NCC.

Validation of nosocomial infection in neonatology: A new method for standardized surveillance

BACKGROUND Nosocomial infections (NIs) are a leading cause of mortality and morbidity in premature infants. We present a new method for detecting and confirming NIs in a neonatal intensive care unit. METHODS Newborns with birth weight < 1,500 g or gestational age (GA) < 33 weeks were included prospectively over 2 years in a single-center tertiary neonatal intensive care unit. The computerized physician order entry system (CPOE) generated alerts when antibiotics were prescribed for at least 5 consecutive days and these cases were reviewed by an expert group following international recommendations. RESULTS Four hundred sixty-one neonates were included, with a mean GA of 30 weeks (range, 26-32 weeks) and mean birth weight 1,270 g (range, 950-1600 g). The CPOE flagged 158 cases of potential NI, 85.1% of which were classified as true NI and 14.9% of which were false positive. Incidence and device-associated nosocomial bloodstream infection rates were 21.9% and 10.8 per 1,000 central venous catheter days, respectively. GA ≤ 28 weeks (odds ratio, 2.18; 95% confidence interval, 1.2-4) and > 7 central venous catheter days (odds ratio, 1.47; 95% confidence interval, 1.3-1.7) were independently associated with the risk of nosocomial bloodstream infection. CONCLUSION Combining CPOE and interdisciplinary review may improve the accuracy of NI recording in a neonatal intensive care unit.

tuf-PCR-temporal temperature gradient gel electrophoresis for molecular detection and identification of staphylococci: application to breast milk and neonate gut microbiota.

Coagulase negative staphylococci (CoNS) are a leading cause of infections in preterm infants, mostly involved in late-onset infection in low birth weight neonates. The epidemiology and pathophysiology of these infections remain unclear, notably because the causing agents are gathered in the artificial CoNS group. The aim of this work was to optimize the study of Staphylococcus species diversity in human breast milk and neonate stool, two sample types with bacterial communities dominated by CoNS, using PCR-temporal temperature gel electrophoresis based on the tuf gene. The optimized protocol identified 18 Staphylococcus species involved in neonate gut microbiota and infections and was applied to cultivation-independent study of breast milk and neonate stool. The efficiency, sensitivity, specificity and species discrimination of the proposed protocol appears suitable for patient follow-up in order to link microbiological data at the community level in milk and stool and interpret them from epidemiological and pathophysiological points of view.

Atypical Pneumonia Linked to Community-Acquired Staphylococcus aureus Cross-Transmission in the Nursery

We report the observation of a necrotizing pneumonia due to methicillin-resistant Staphylococcus aureus harboring the Panton-Valentine leukocidin-encoding gene in a previously healthy neonate, with favorable clinical outcome in spite of extensive radiologic lesions. The case was linked to a cluster of 3 neonates colonized by Panton-Valentine leukocidin-producing, methicillin-resistant S. aureus through cross-transmission in the nursery, underlining the need to comply with standard infection control precautions in the maternity ward.

Reentry Tachycardia in Children: Adenosine Can Make It Worse.

Objectives We report on a rare but severe complication of adenosine use in a child with reentry tachycardia. Methods and Results Treatment with adenosine, which is the standard medical therapy of atrioventricular reentry tachycardia, led to the development of an irregular wide complex tachycardia, caused by rapid ventricular response to atrial fibrillation. The girl was finally stabilized with electrical cardioversion. We analyze the pathomechanism and discuss possible treatment options. Conclusions Atrial fibrillation, as well as its conduction to the ventricles, can be caused by adenosine. Rapid ventricular response in children with Wolff-Parkinson-White syndrome is more frequent than previously believed. A patient history of atrial fibrillation is a contraindication for cardioversion with adenosine and needs to be assessed in children with reentry tachycardia. High-risk patients may potentially profit from prophylactic comedication with antiarrhythmic agents, such as flecainide, ibutilide, or vernakalant, before adenosine administration.

Torticollis in Children: A Challenging Diagnosis of C1-C2 Septic Arthritis

The causes of torticollis are highly varied. In most cases, benign causes are found. However, other serious causes that require rapid diagnosis and treatment may be involved. We report here 4 cases of septic atlanto-axial arthritis in infants with torticollis. A search on PubMed using the keywords “atlanto-axial septic arthritis” or “C1-C2 septic arthritis” associated to “torticollis” could not find any pediatric case. We found only cases of “osteomyelitis of the odontoid” with torticollis. The aim of this study is to report this cause of cervical arthritis in children. We first describe in detail 4 observations of torticollis in children secondary to C1-C2 septic arthritis then discuss this issue.

Complications in the Subacute Phase of Invasive Streptococcus pyogenes Infections in Pediatrics Two Case Reports and Review of the Literature

Streptococcus pyogenes, so-called group A streptococcus (GAS), is classically responsible for a number of suppurative infections and nonsuppurative sequelae. Epidemiology of GAS infections has greatly evolved in the past decade with an increase in both incidence and severity of invasive infections. Modification in the pattern of post-streptococcal diseases was also observed. Acute rheumatic fever (ARF) disappeared in the industrialized countries, whereas other complex diseases such as pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections and multifocal postinfectious inflammation were recognized. Here, we report 2 cases of nonsuppurative complications occurring in the subacute phase (6-28 days after initial antibiotic treatment) of invasive group A streptococcus infections (IGASI) in children and review the literature.