Characterization of third-generation cephalosporin-resistant Escherichia coli from slaughter calves and fattening pigs: A pilot study for monitoring antimicrobial resistance by whole genome sequencing in Switzerland.

INTRODUCTION: Whole genome sequencing (WGS) was introduced into Swiss antimicrobial resistance monitoring in 2022 as an additional method to phenotypic antimicrobial susceptibility testing by broth microdilution to characterize presumptive third-generation cephalosporin-resistant (3GC-R) Escherichia coli. Caecal samples from Swiss slaughter calves and fattening pigs, as well as beef and pork meat from Swiss retail taken in 2021, were analyzed for the presence of 3GC-R E. coli according to European harmonized protocols. In 2021, 3GC-R E. coli was detected in 23,8 % of slaughter calves, 5,9 % of fattening pigs, and 0 % of meat. Comparative analysis of the antimicrobial resistance results obtained by phenotypic measurement and those obtained by the detection of corresponding underlying molecular mechanisms by WGS showed very high agreement (99 %). Resistance to third-generation cephalosporins (3GCs) was mainly associated with the presence of blaCTX-M-15 in E. coli isolates from calves and blaCTX-M-1 in E. coli isolates from pigs and mutations in the ampC-promoter (g.-42 C>T) in E. coli isolates from both animal species. Moreover, WGS data were used for phylogenetic analysis based on multi locus sequence types (MLST) and core genome MLST(cgMLST) revealing that 3GC-R E. coli isolated from Swiss slaughter calves and fattening pigs were genetically diverse. In this study, it was shown that using WGS alone to monitor antimicrobial resistance could detect trends in known molecular antimicrobial resistance mechanisms while also providing other valuable information about the isolates, such as genetic relatedness. However, only by combining phenotypic susceptibility testing and WGS early detection of previously unknown resistance mechanisms will be possible.

INTRODUCTION: Le séquençage du génome entier (Whole Genome Sequencing, WGS) a été introduit dans la surveillance suisse de la résistance aux antibiotiques en 2022 en tant que méthode supplémentaire aux tests phénotypiques de sensibilité aux antibiotiques pour caractériser les Escherichia coli résistants aux céphalosporines de troisième génération (3GC-R). Des échantillons de cæcum pris en 2021 à l'abattoir de veaux et de porcs suisses, ainsi que de viande de bœuf et de porc provenant de détaillants suisses ont été analysés pour détecter la présence d'E. coli 3GC-R conformément aux protocoles européens harmonisés. En 2021, les E. coli 3GC-R ont été détectés dans 23,8 % des veaux d'abattage, 5,9 % des porcs d'engraissement et 0 % dans la viande. Les résultats de résistance aux antibiotiques obtenus par mesure phénotypique et ceux obtenus par la détection des mécanismes moléculaires sous-jacents concordaient à 99 %. La résistance aux céphalosporines de troisième génération était principalement associée à la pré-sence de blaCTX-M-15 dans les isolats d'E. coli provenant de veaux et de blaCTX-M-1 dans les isolats d'E. coli provenant de porcs et à des mutations dans le promoteur ampC (g.-42 C>T) dans les isolats d'E. coli provenant des deux espèces animales. Les données WGS ont également été utilisées pour une analyse phylogénétique basée sur les types de séquences multilocus (MLST) et MLST du génome de base (cgMLST) révélant que les E. coli 3GC-R isolés des veaux et des porcs suisses étaient génétiquement divers. Dans cette étude, il a été démontré que l'utilisation du WGS seul pour surveiller la résistance aux antibiotiques pouvait détecter des tendances dans les mécanismes moléculaires connus de la résistance aux antibiotiques tout en fournissant d'autres informations précieuses sur les isolats, comme la parenté génétique. Cependant, ce n'est qu'en combinant les tests de sensibilité phénotypique avec le WGS que la détection pré-coce de mécanismes de résistance inconnus sera possible.

Impaired antibody memory to varicella zoster virus in HIV-infected children: low antibody levels and avidity*.

OBJECTIVE: HIV-infected children have impaired antibody responses after exposure to certain antigens. Our aim was to determine whether HIV-infected children had lower varicella zoster virus (VZV) antibody levels compared with HIV-infected adults or healthy children and, if so, whether this was attributable to an impaired primary response, accelerated antibody loss, or failure to reactivate the memory VZV response. METHODS: In a prospective, cross-sectional and retrospective longitudinal study, we compared antibody responses, measured by enzyme-linked immunosorbent assay (ELISA), elicited by VZV infection in 97 HIV-infected children and 78 HIV-infected adults treated with antiretroviral therapy, followed over 10 years, and 97 age-matched healthy children. We also tested antibody avidity in HIV-infected and healthy children. RESULTS: Median anti-VZV immunoglobulin G (IgG) levels were lower in HIV-infected children than in adults (264 vs. 1535 IU/L; P<0.001) and levels became more frequently unprotective over time in the children [odds ratio (OR) 17.74; 95% confidence interval (CI) 4.36-72.25; P<0.001]. High HIV viral load was predictive of VZV antibody waning in HIV-infected children. Anti-VZV antibodies did not decline more rapidly in HIV-infected children than in adults. Antibody levels increased with age in healthy (P=0.004) but not in HIV-infected children. Thus, antibody levels were lower in HIV-infected than in healthy children (median 1151 IU/L; P<0.001). Antibody avidity was lower in HIV-infected than healthy children (P<0.001). A direct correlation between anti-VZV IgG level and avidity was present in HIV-infected children (P=0.001), but not in healthy children. CONCLUSION: Failure to maintain anti-VZV IgG levels in HIV-infected children results from failure to reactivate memory responses. Further studies are required to investigate long-term protection and the potential benefits of immunization.

Acute transverse myelitis in Lyme neuroborreliosis.

INTRODUCTION: Acute transverse myelitis (ATM) is a rare disorder (1-8 new cases per million of population per year), with 20% of all cases occurring in patients younger than 18 years of age. Diagnosis requires clinical symptoms and evidence of inflammation within the spinal cord (cerebrospinal fluid and/or magnetic resonance imaging). ATM due to neuroborreliosis typically presents with impressive clinical manifestations. CASE PRESENTATION: Here we present a case of Lyme neuroborreliosis-associated ATM with severe MRI and CSF findings, but surprisingly few clinical manifestations and late conversion of the immunoglobulin G CSF/blood index of Borrelia burgdorferi sensu lato. CONCLUSION: Clinical symptoms and signs of neuroborrelial ATM may be minimal, even in cases with severe involvement of the spine, as shown by imaging studies. The CSF/blood index can be negative in the early stages and does not exclude Lyme neuroborreliosis; if there is strong clinical suspicion of Lyme neuroborreliosis, appropriate treatment should be started and the CSF/blood index repeated to confirm the diagnosis.

Molecular epidemiology of the nasal colonization by methicillin-susceptible Staphylococcus aureus in Swiss children.

Nasal carriage of Staphylococcus aureus contributes to an increased risk of developing an infection with the same bacterial strain. Genetic regulatory elements and toxin-expressing genes are virulence factors associated with the pathogenic potential of S. aureus. We undertook an extensive molecular characterization of methicillin-susceptible S. aureus (MSSA) carried by children. MSSA were recovered from the nostrils of children. The presence of Panton-Valentine leukocidin (PVL), exfoliatins A and B (exfoA and exfoB), and the toxic-shock staphylococcal toxin (TSST-1) and agr group typing were determined by quantitative PCR. A multiple-locus variable-number of tandem repeat analysis (MLVA) assay was also performed for genotyping. Five hundred and seventy-two strains of MSSA were analysed. Overall, 30% were positive for toxin-expressing genes: 29% contained one toxin and 1.6% two toxins. The most commonly detected toxin gene was tst, which was present in 145 (25%) strains. The TSST-1 gene was significantly associated with the agr group 3 (OR 56.8, 95% CI 32.0-100.8). MLVA analysis revealed a large diversity of genetic content and no clonal relationship was demonstrated among the analysed MSSA strains. Multilocus sequence typing confirmed this observation of diversity and identified ST45 as a frequent colonizer. This broad diversity in MSSA carriage strains suggests a limited selection pressure in our geographical area.

H-ficolin serum concentration and susceptibility to fever and neutropenia in paediatric cancer patients.

H-ficolin (Hakata antigen, ficolin-3) activates the lectin pathway of complement similar to mannose-binding lectin. However, its impact on susceptibility to infection is currently unknown. This study investigated whether the serum concentration of H-ficolin at diagnosis is associated with fever and neutropenia (FN) in paediatric cancer patients. H-ficolin was measured by time-resolved immunofluorometric assay in serum taken at cancer diagnosis from 94 children treated with chemotherapy. The association of FN episodes with H-ficolin serum concentration was analysed by multivariate Poisson regression. Median concentration of H-ficolin in serum was 26 mg/l (range 6-83). Seven (7%) children had low H-ficolin (< 14 mg/l). During a cumulative chemotherapy exposure time of 82 years, 177 FN episodes were recorded, 35 (20%) of them with bacteraemia. Children with low H-ficolin had a significantly increased risk to develop FN [relative risk (RR) 2.24; 95% confidence interval (CI) 1.38-3.65; P = 0.004], resulting in prolonged duration of hospitalization and of intravenous anti-microbial therapy. Bacteraemia occurred more frequently in children with low H-ficolin (RR 2.82; CI 1.02-7.76; P = 0.045). In conclusion, low concentration of H-ficolin was associated with an increased risk of FN, particularly FN with bacteraemia, in children treated with chemotherapy for cancer. Low H-ficolin thus represents a novel risk factor for chemotherapy-related infections.

Prospective population-based study of RSV-related intermediate care and intensive care unit admissions in Switzerland over a 4-year period (2001-2005).

OBJECTIVES: Respiratory syncytial virus (RSV) infections are a leading cause of hospital admissions in small children. A substantial proportion of these patients require medical and nursing care, which can only be provided in intermediate (IMC) or intensive care units (ICU). This article reports on all children aged < 3 years who required admission to IMC and/or ICU between October 1, 2001 and September 30, 2005 in Switzerland. PATIENTS AND METHODS: We prospectively collected data on all children aged < 3 years who were admitted to an IMC or ICU for an RSV-related illness. Using a detailed questionnaire, we collected information on risk factors, therapy requirements, length of stay in the IMC/ICU and hospital, and outcome. RESULTS: Of the 577 cases reported during the study period, 90 were excluded because the patients did not fulfill the inclusion criteria; data were incomplete in another 25 cases (5%). Therefore, a total of 462 verified cases were eligible for analysis. At the time of hospital admission, only 31 patients (11%) were older than 12 months. Since RSV infection was not the main reason for IMC/ICU admission in 52% of these patients, we chose to exclude this subgroup from further analyses. Among the 431 infants aged < 12 months, the majority (77%) were former near term or full term (NT/FT) infants with a gestational age > or = 35 weeks without additional risk factors who were hospitalized at a median age of 1.5 months. Gestational age (GA) < 32 weeks, moderate to severe bronchopulmonary dysplasia (BPD), and congenital heart disease (CHD) were all associated with a significant risk increase for IMC/ICU admission (relative risk 14, 56, and 10, for GA < or = 32 weeks, BPD, and CHD, respectively). Compared with NT/FT infants, high-risk infants were hospitalized at an older age (except for infants with CHD), required more invasive and longer respiratory support, and had longer stays in the IMC/ICU and hospital. CONCLUSIONS: In Switzerland, RSV infections lead to the IMC/ICU admission of approximately 1%-2% of each annual birth cohort. Although prematurity, BPD, and CHD are significant risk factors, non-pharmacological preventive strategies should not be restricted to these high-risk patients but also target young NT/FT infants since they constitute 77% of infants requiring IMC/ICU admission.

Establishing glycaemic control with continuous subcutaneous insulin infusion in children and adolescents with type 1 diabetes: experience of the PedPump Study in 17 countries.

AIMS/HYPOTHESIS: To assess the use of paediatric continuous subcutaneous infusion (CSII) under real-life conditions by analysing data recorded for up to 90 days and relating them to outcome. METHODS: Pump programming data from patients aged 0-18 years treated with CSII in 30 centres from 16 European countries and Israel were recorded during routine clinical visits. HbA(1c) was measured centrally. RESULTS: A total of 1,041 patients (age: 11.8 +/- 4.2 years; diabetes duration: 6.0 +/- 3.6 years; average CSII duration: 2.0 +/- 1.3 years; HbA(1c): 8.0 +/- 1.3% [means +/- SD]) participated. Glycaemic control was better in preschool (n = 142; 7.5 +/- 0.9%) and pre-adolescent (6-11 years, n = 321; 7.7 +/- 1.0%) children than in adolescent patients (12-18 years, n = 578; 8.3 +/- 1.4%). There was a significant negative correlation between HbA(1c) and daily bolus number, but not between HbA(1c) and total daily insulin dose. The use of <6.7 daily boluses was a significant predictor of an HbA(1c) level >7.5%. The incidence of severe hypoglycaemia and ketoacidosis was 6.63 and 6.26 events per 100 patient-years, respectively. CONCLUSIONS/INTERPRETATION: This large paediatric survey of CSII shows that glycaemic targets can be frequently achieved, particularly in young children, and the incidence of acute complications is low. Adequate substitution of basal and prandial insulin is associated with a better HbA(1c).

[Lymphadenopathy and absences]. / Lymphadenopathie und Absenzen.

A 6-year-old boy presented with deterioration of general well-being during several weeks, headache and swelling of lymph nodes in the neck. In addition, the parents reported brief episodes resembling typical absence seizures. Serological tests and the examination of cerebrospinal fluid revealed neuroborreliosis. At the same time, electroencephalography showed characteristic patterns of absence epilepsy. The boy's condition improved rapidly during a 2-week course of intravenous ceftriaxone and after initiation of antiepileptic therapy. To our knowledge, absence epilepsy has not previously been reported in association with neuroborreliosis. We consider the two conditions to be coincidental.

Swiss recommendations for the management of varicella zoster virus infections.

Infections with varicella zoster virus (VZV) are common viral infections associated with significant morbidity. Diagnosis and management are complex, particularly in immunocompromised patients and during pregnancy. The present recommendations have been established by a multidisciplinary panel of specialists and endorsed by numerous Swiss medical societies involved in the medical care of such patients (Appendix). The aim was to improve the care of affected patients and to reduce complications.

Serum levels of mannose-binding lectin and the risk of fever in neutropenia pediatric cancer patients.

BACKGROUND: Fever in neutropenia (FN) is a frequent complication in pediatric oncology. Deficiency of mannose-binding lectin (MBL), an important component of innate immunity, is common due to genetic polymorphisms, but its impact on infections in oncologic patients is controversial. This study investigated whether MBL serum levels at cancer diagnosis are associated with the development of FN in pediatric cancer patients. PROCEDURE: Serum MBL was measured using ELISA. Frequency, duration, and cause of FN were assessed retrospectively. Association with MBL level was analyzed using uni- and multivariate Poisson regression taking into account both intensity and duration of chemotherapy. RESULTS: In 94 children, with a cumulative follow-up time of 81.7 years, 177 FN episodes were recorded. Patients with both very low MBL levels (<100 microg/L; risk ratio (RR), 1.93; 95% CI, 1.14-3.28; P = 0.014) and normal MBL levels (>or=1,000 microg/L; RR, P = 0.011) had significantly more frequent FN episodes than patients with low MBL levels (100-999 microg/L). Patients with very low MBL levels had significantly more episodes of FN with severe bacterial infection (bacteremia or pneumonia; RR, 4.49; 1.69 = 11.8; P = 0.003), while those with normal MBL levels had more FN episodes with no microbial etiology identified (RR, 1.85; 1.14 = 3.03; P = 0.014). CONCLUSIONS: Very low MBL levels are associated with more frequent FN episodes, mainly due to severe bacterial infections. The surprising finding that children with normal MBL levels had more frequent FN episodes than those with low MBL levels needs testing in prospective studies.

The prevalence of penicillin-non-susceptible Streptococcus pneumoniae among children aged < 5 years correlates with the biannual epidemic activity of respiratory syncytial virus.

This study investigated whether the epidemiology of penicillin-non-susceptible pneumococci (PNSP) colonising small children correlated with the biannual epidemic activity of respiratory syncytial virus (RSV). Colonisation rates and the prevalence of PNSP among paediatric outpatients aged < 5 years was analysed between January 1998 and September 2003 using an established national surveillance network. Resistance trends were investigated using time-series analysis to assess the correlation with the biannual pattern of RSV infections and national sales of oral paediatric formulations of antibiotics and antibiotic prescriptions to children aged < 5 years for acute respiratory tract infections. PNSP rates exhibited a biannual cycle in phase with the biannual seasonal RSV epidemics (p < 0.05). Resistance rates were higher during the winter seasons of 1998-1999 (20.1%), 2000-2001 (16.0%) and 2002-2003 (19.1%), compared with the winter seasons of 1997-1998 (8.2%), 1999-2000 (11.6%) and 2001-2002 (9.5%). Antibiotic sales and prescriptions showed regular peaks during each winter, with no significant correlation with the biannual pattern of RSV activity and seasonal trends of PNSP. RSV is an important determinant of the spread of PNSP and must be considered in strategies aimed at antimicrobial resistance control.

[Orbital complications of acute pediatric rhinosinusitis: medical treatment versus surgery and analysis of the computer tomogram]. / Orbitale Komplikationen der pädiatrischen Rhinosinusitis: Konservative versus chirurgische Therapie und Analyse der Computertomografie.

BACKGROUND: One of the most common complications of acute pediatric rhinosinusitis is orbital complication. For subperiosteal abscess, in particular, there are no generally accepted therapy recommendations. PATIENTS: A retrospective study of 45 children with acute orbital rhinosinusitis complications, treated on an in-patient basis at the Department of ENT, Inselspital, University of Bern (1999-2004) is presented. The aim was to analyze conservative medical versus surgical treatment with regard to the individual stages of complications (according to the classification of Moloney, 1987) and, subsequently, to arrive at a therapy recommendation. RESULTS: All children with preseptal cellulitis (stage I), 80 % of children with radiological a subperiosteal phlegmona (Stage IIA) and 67 % of the children with radiological a subperiosteal abscess (Stage IIB) could be treated conservatively. The child with the orbital cellulitis (Stage III) was treated surgically. CONCLUSION: The preseptal cellulitis can be treated conservatively. We recommend an initial conservative therapy of 24 - 48 hours for subperiosteal phlegmona and subperiosteal abscess in the presence of normal vision. Surgical intervention should take place only if there is no improvement after this time interval. The orbital cellulitis should be treated primary surgically.

[Prevention of tick-borne encephalitis (TBE)]. / Prävention der Früh- sommer-Meningoenzephalitis (FSME).

Active immunization is the only reliable means of preventing TBE. Evidence suggests that effectiveness is greater than 95%. Breakthrough infections in fully immunized individuals, however, do occur. Recent data indicate that the duration of protection following basic immunization is substantially longer than previously appreciated. The vast majority of vaccinees are still seropositive > or = 8 years after the last dose. Thus, the current practice of administering booster doses every 3 years is a topic of intense debate. Until it is resolved, patients can be offered the determination of a serum anti-TBE IgG titre as an alternative to "blind" administration of a booster dose. It has recently been shown that seropositivity determined by some commonly used commercial ELISA tests correlates closely with the presence of protective antibody. In Switzerland, TBE vaccination is currently recommended for individuals older than 6 years of age who frequently dwell in endemic areas. Since 2005, health care insurances are required to cover for costs incurred by immunization according to these recommendations.

[Exanthema as a main symptom in the febrile child]. / Exanthem als Leit--symptom beim febrilen Kind.

Distinguishing in febrile children between harmless rashes and those, which require specific action, is a common problem in pediatric primary care. Major exanthematous diseases necessitating emergency hospitalization include invasive meningococcal disease and rarely gram-negative septicaemia caused by other pathogens, staphylococcal and streptococcal toxic shock syndrome, endocarditis, fever and rash in travellers returning from tropical countries and drug hypersensitivity syndrome. Therapeutic intervention is also necessary in patients with scarlet fever, rheumatic fever, varicella in postpuberal and immunocompromised individuals, in Kawasaki's disease, in Still's disease and in other non-infectious, inflammatory diseases (e.g., familial mediterranean fever). Finally, various specific measures need to be taken in reportable diseases, erythema infectiosum (parvovirus B19), primary HIV infection and in Henoch-Schölein purpura.

Frontotemporal dementia, semantic dementia, and Alzheimer's disease: the contribution of standard neuropsychological tests to differential diagnosis.

CERAD-NAB (Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological Assessment Battery) data were compared between 51 patients with frontotemporal dementia, 13 with semantic dementia, and 69 with Alzheimer's disease. There were statistically significant differences between the 3 groups. Compared with patients with Alzheimer's disease, patients with frontotemporal dementia were more impaired on Animal Fluency but not on any other CERAD-NAB subtest. Patients with semantic dementia performed worse in Animal Fluency and Boston Naming Test compared with frontotemporal dementia and Alzheimer's disease. Multiple logistic regression analysis revealed that in the differentiation between frontotemporal dementia and Alzheimer's disease, the combination of Animal Fluency and Boston Naming Test correctly classified 90.5% of patients. In segregating semantic dementia and Alzheimer's disease, the combination of Boston Naming Test and Mini Mental State Examination resulted in a correct classification of 96.3%. These findings demonstrate that the Mini Mental State Examination and the language subtests of the CERAD-NAB are valuable clinical instruments for the differential diagnosis between early frontotemporal dementia, semantic dementia, and Alzheimer's disease.