The EC-COMPASS: Long-term, multi-centre surveillance of Enterobacter cloacae complex - a clinical perspective.

BACKGROUND: Enterobacter cloacae complex (ECCO) comprises closely related Enterobacterales, causing a variety of infections ranging from mild urinary tract infections to severe bloodstream infections. ECCO has emerged as a significant cause of healthcare-associated infections, particularly in neonatal and adult intensive care. AIM: The Enterobacter Cloacae COMplex PASsive Surveillance (EC-COMPASS) aims to provide a detailed multi-centre overview of ECCO epidemiology and resistance patterns detected in routine microbiological diagnostics in four German tertiary-care hospitals. METHODS: In a sentinel cluster of four German tertiary-care hospitals, all culture-positive ECCO results between 1st January 2020 and 31st December 2022, were analysed based on Hybase® laboratory data. FINDINGS: Analysis of 31,193 ECCO datasets from 14,311 patients revealed a higher incidence in male patients (P<0.05), although no significant differences were observed in ECCO infection phenotypes. The most common sources of ECCO were swabs (42.7%), urine (17.5%), respiratory secretions (16.1%), blood cultures (8.9%) and tissue samples (5.6%). The annual bacteraemia rate remained steady at approximately 33 cases per hospital. Invasive ECCO infections were predominantly found in oncology and intensive care units. Incidences of nosocomial outbreaks were infrequent and limited in scope. Notably, resistance to carbapenems was consistently low. CONCLUSION: EC-COMPASS offers a profound clinical perspective on ECCO infections in German tertiary-healthcare settings, highlighting elderly men in oncology and intensive care units as especially vulnerable to ECCO infections. Early detection strategies targeting at-risk patients could improve ECCO infection management.

Natural and hybrid immunity after SARS-CoV-2 infection in children and adolescents.

PURPOSE: In contrast to adults, immune protection against SARS-CoV-2 in children and adolescents with natural or hybrid immunity is still poorly understood. The aim of this study was to analyze different immune compartments in different age groups and whether humoral immune reactions correlate with a cellular immune response. METHODS: 72 children and adolescents with a preceding SARS-CoV-2 infection were recruited. 37 were vaccinated with an RNA vaccine (BNT162b2). Humoral immunity was analyzed 3-26 months (median 10 months) after infection by measuring Spike protein (S), nucleocapsid (NCP), and neutralizing antibodies (nAB). Cellular immunity was analyzed using a SARS-CoV-2-specific interferon-γ release assay (IGRA). RESULTS: All children and adolescents had S antibodies; titers were higher in those with hybrid immunity (14,900 BAU/ml vs. 2118 BAU/ml). NCP antibodies were detectable in > 90%. Neutralizing antibodies (nAB) were more frequently detected (90%) with higher titers (1914 RLU) in adolescents with hybrid immunity than in children with natural immunity (62.5%, 476 RLU). Children with natural immunity were less likely to have reactive IGRAs (43.8%) than adolescents with hybrid immunity (85%). The amount of interferon-γ released by T cells was comparable in natural and hybrid immunity. CONCLUSION: Spike antibodies are the most reliable markers to monitor an immune reaction against SARS-CoV-2. High antibody titers of spike antibodies and nAB correlated with cellular immunity, a phenomenon found only in adolescents with hybrid immunity. Hybrid immunity is associated with markedly higher antibody titers and a higher probability of a cellular immune response than a natural immunity.

Prevalence and molecular diversity of invasive Streptococcus dysgalactiae and Streptococcus pyogenes in a German tertiary care medical centre.

Prevalence of invasive ß-haemolytic streptococci (BHS) at a tertiary care hospital and molecular diversity of S. pyogenes and S. dysgalactiae was studied. Between 2012 and 2016, all blood culture sets (n = 55,839), CSF (n = 8413) and soft tissue (n = 20,926) samples were analysed for BHS positivity using HYBASE software. Molecular profiles of 99 S. pyogenes and S. dysgalactiae were identified by sequencing of M protein genes (emm types) and multiplex PCR typing of 20 other virulence determinants. Streptococci contributed to 6.2% of blood, 10.7% of CSF and 14.5% of soft tissue isolates, being among the most common invasive isolates. The overall rates of invasive S. pyogenes, S. agalactiae, S. dysgalactiae and S. pneumoniae were 2.4, 4.4, 2.1, and 5.3%. Whereas S. pneumoniae was 1.5% more common in CSF samples, BHS isolates were 2-fold and 11-fold higher in bacteraemia and invasive soft tissue infections. Genetic BHS typing revealed wide molecular diversity of invasive and noninvasive group A and group G BHS, whereas one emm-type (stG62647.0) and no other virulence determinants except scpA were detected in invasive group C BHS. BHS were important invasive pathogens, outpacing S. pneumoniae in bacteraemia and invasive soft tissue infections. The incidence of S. dysgalactiae infections was comparable to that of S. pyogenes even with less diversity of molecular virulence. The results of this study emphasise the need for awareness of BHS invasiveness in humans and the need to develop BHS prevention strategies.

Molecular epidemiology of Staphylococcus aureus from Lambaréné, Gabon.

While there is an abundance of data on the epidemiology and molecular typing of Staphylococcus aureus, especially those carrying Panton-Valentine leucocidin (PVL) genes or mecA from Western Europe, Northern America and Australia, comparably few studies target African strains. In this study, we characterised genes associated with virulence and resistance, as well the phylogenetic background of S. aureus from healthy carriers and outpatients in Gabon. In total, 103 isolates from 96 study participants were characterised. Seventy-nine isolates originated from throat swabs and 24 isolates from skin lesions. Three isolates carried mecA, although only one, belonging to CC8-MRSA-IV [PVL+] 'USA300', was found to be phenotypically oxacillin-resistant; two CC88-MRSA-IV isolates appeared to be oxacillin-susceptible. PVL genes were common, with a total of 44 isolates (43 %) found to be PVL-positive. CC15-MSSA [PVL+] (n = 29) and CC152-MSSA [PVL+] (n = 9) were the predominant clones among the PVL-positive isolates. Among PVL-negative isolates, CC5-MSSA (n = 12), CC101-MSSA (n = 10) and CC15 (n = 9) were the most frequent. A hitherto undescribed multilocus sequence type of S. schweitzeri was detected twice in unrelated patients. The data emphasise a need for further studies on the role of PVL in African populations and the clinical significance of S. schweitzeri.

Impact of technical training on rapid antigen detection tests (RADT) in group A streptococcal tonsillopharyngitis.

Rapid antigen detection tests (RADT) are widely used for the rapid diagnosis of group A streptococcal (GAS) tonsillopharyngitis. In a prospective 3-year study, the reliability of two different RADT methods was compared, as performed by lab technicians versus physicians. Sensitivity and specificity, as well as positive and negative predictive values, were calculated. When performed by physicians, the results (44.4 %, 8.3 %, 26.7 % and 16.7 %) of a latex agglutination test (LAT) were unacceptably low. However, after switching to a lateral-flow immunoassay (LFIT) and implementing additional hands-on training, the performance improved dramatically (100 %, 92.6 %, 84.6 % and 100 %). In conclusion, technical errors, along with a lack of experience and expertise, negatively impact RADT accuracy.

Accidental clozapine intoxication in a toddler: clinical and pharmacokinetic lessons learnt.

WHAT IS KNOWN AND OBJECTIVE: Clozapine, a second generation antipsychotic which is relatively safe in overdose, has been used as an effective treatment alternative to traditional antipsychotics. The therapeutic use in children remains controversial. However, in accordance with the increasing prescription in adults, the accidental ingestion in childhood becomes more frequent. We report the youngest case of accidental clozapine ingestion. CASE SUMMARY: A 13-month-old girl presented with acute respiratory insufficiency and coma of unknown origin. The medical history, laboratory and radiological assessment did not link to aetiology until an almost spontaneous arousal after 22 h pointed towards intoxication. The initial standard drug screening using immunoassay had been negative. Hence, liquid chromatography mass spectrometry/mass spectrometry (LC-MS/MS) was performed, and clozapine was detected with a serum concentration of 736 ng/mL. WHAT IS NEW AND CONCLUSION: This case illustrates the diagnostic and forensic pitfalls in a coma of unknown origin due to the limits of toxicological screening immunoassays. LC-MS/MS analysis by an established method showed clozapine metabolites (norclozapine and clozapine-N-oxide) are detectable for longer period, especially in urine, when compared with clozapine. The clinical course is presented in unique correlation with plasma and urine concentrations of clozapine and its metabolites. The elimination pattern of clozapine in toddlers is similar to adults, and the toxic dose was found to be lower when compared with school-age children and adults.