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Purpose Resistance of Staphylococcus aureus to vancomycin includes a general increase of minimal inhibitory concentrations (MIC) within the susceptible range over time (Vancomycin MIC Creep) and the presence of a subset of the bacterial population that expresses resistance (heterogeneous glycopeptide-intermediate S. aureus; hGISA). Increased MICs have been associated with adverse clinical outcomes. However, the vancomycin MIC creep is not a uniform trend suggesting the importance of regional surveys. Methods We performed a retrospective analysis at a German pediatric tertiary care hospital. Isolates from 2002 to 2017 were selected which were newly identified methicillin-resistant S. aureus (MRSA) or samples from invasive methicillin-susceptible S. aureus (MSSA) or MRSA infections. Vancomycin and oxacillin MICs as well as GISA/hGISA were measured using MIC test strips and resistance was evaluated over time. Results A total of 540 samples were tested, 200 from the early (2002–2009) and 340 from the later period (2010–2017). All samples were vancomycin susceptible, but the MIC was higher for the earlier samples as compared to the later ones (1.11 vs 0.99; p p Conclusion This study shows a decreasing trend for both MIC values and presence of hGISA strains highlighting the importance of monitoring local susceptibilities. Vancomycin remains a first-line treatment option for suspected severe infection with Gram-positive cocci and proven infection with MRSA.

Theodor Escherich (1857–1911) was one of the key players in early paediatric infectious diseases (PID). In fact, he can be regarded as the first paediatric infectious diseases physician and the founder of this subspecialty. During his long years in service for children, he spent 6 years at the Dr von Hauner children’s hospital (1884–1890), laying the foundations for PID clinical care and research in Munich. Walter Marget, founder of this journal and co-founder of the German Society for Infectious Diseases (DGI) graduated from medical school in 1946 and practised in Munich since 1967. His tireless efforts went into establishing close links between clinical paediatrics and microbiological diagnostics culminating in the foundation of the Department of Antimicrobial Therapy and Infection Epidemiology at the Dr von Hauner children’s hospital. Walter Marget was a key figure for PID in Germany having trained and supported many clinician scientists who followed in his footsteps. This article gives a brief overview of the history of PID in Munich while commemorating Walter Marget and his achievements in this field and for INFECTION.

Background The Borna disease virus (BoDV-1) is an emerging zoonotic virus causing severe and mostly fatal encephalitis in humans. Methods and Results A local cluster of fatal BoDV-1 encephalitis cases was detected in the same village three years apart affecting two children. While the first case was diagnosed late in the course of disease, a very early diagnosis and treatment attempt facilitated by heightened awareness was achieved in the second case. Therapy started as early as day 12 of disease. Antiviral therapy encompassed favipiravir and ribavirin, and, after bioinformatic modelling, also remdesivir. As the disease is immunopathogenetically mediated, an intensified anti-inflammatory therapy was administered. Following initial impressive clinical improvement, the course was also fatal, although clearly prolonged. Viral RNA was detected by qPCR in tear fluid and saliva, constituting a possible transmission risk for health care professionals. Highest viral loads were found post mortem in the olfactory nerve and the limbic system, possibly reflecting the portal of entry for BoDV-1. Whole exome sequencing in both patients yielded no hint for underlying immunodeficiency. Full virus genomes belonging to the same cluster were obtained in both cases by next-generation sequencing. Sequences were not identical, indicating viral diversity in natural reservoirs. Specific transmission events or a common source of infection were not found by structured interviews. Patients lived 750m apart from each other and on the fringe of the settlement, a recently shown relevant risk factor. Conclusion Our report highlights the urgent necessity of effective treatment strategies, heightened awareness and early diagnosis. Gaps of knowledge regarding risk factors, transmission events, and tailored prevention methods become apparent. Whether this case cluster reflects endemicity or a geographical hot spot needs further investigation.

Antimicrobial resistance (AMR) represents an ever increasing threat to the health care system. Even recently licensed drugs are often not efficient for the treatment of infections caused by Gram-negative bacteria, like Pseudomonas aeruginosa , a causative agent of lung infections. To address this unmet medical need, innovative antibiotics, which possess a new mode of action, need to be developed. Here, the antibiogram of clinical isolates derived from cystic fibrosis patients was generated and new bicyclic heptapeptides, which inhibit the outer membrane protein BamA, exhibited strong activity, also against multidrug-resistant isolates.

Purpose SARS-CoV-2 infections cause COVID-19 and have a wide spectrum of morbidity. Severe disease courses among children are rare. To date, data on the variability of morbidity in relation to variant of concern (VOC) in children has been sparse and inconclusive. We compare the clinical severity of SARS-CoV-2 infection among children and adolescents in Germany during the Wildtype and Alpha combined, Delta and Omicron phases of the COVID-19 pandemic. Methods Comparing risk of COVID-19-related hospitalization, intensive care unit (ICU) admission and death due to COVID-19 in children and adolescents, we used: (1) a multi-center seroprevalence study (SARS-CoV-2-KIDS study); (2) a nationwide registry of pediatric patients hospitalized with SARS-CoV-2 infections; and (3) compulsory national reporting for RT-PCR-confirmed SARS-CoV-2 infections in Germany. Results During the Delta predominant phase, risk of COVID-19-related hospitalization among all SARS-CoV-2 seropositive children was 3.35, ICU admission 1.19 and fatality 0.09 per 10,000; hence about halved for hospitalization and ICU admission and unchanged for deaths as compared to the Wildtype- and Alpha-dominant period. The relative risk for COVID-19-related hospitalization and ICU admission compared to the alpha period decreased during Delta [0.60 (95% CI 0.54; 0.67) and 0.51 (95% CI 0.42; 0.61)] and Omicron [0.27 (95% CI 0.24; 0.30) and 0.06 (95% CI 0.05; 0.08)] period except for the Conclusion Morbidity caused by SARS-CoV-2 infections among children and adolescents in Germany decreased over the course of the COVID-19 pandemic, as different VOCs) emerged.

Russia’s military incursion into Ukraine triggered the mass displacement of two-thirds of Ukrainian children and adolescents, creating a cascade of population health consequences and producing extraordinary challenges for monitoring and controlling preventable pediatric infectious diseases. From the onset of the war, infectious disease surveillance and healthcare systems were severely disrupted. Prior to the reestablishment of dependable infectious disease surveillance systems, and during the early months of the conflict, our international team of pediatricians, infectious disease specialists, and population health scientists assessed the health implications for child and adolescent populations. The invasion occurred just as the COVID-19 Omicron surge was peaking throughout Europe and Ukrainian children had not received COVID-19 vaccines. In addition, vaccine coverage for multiple vaccine-preventable diseases, most notably measles, was alarmingly low as Ukrainian children and adolescents were forced to migrate from their home communities, living precariously as internally displaced persons inside Ukraine or streaming into European border nations as refugees. The incursion created immediate impediments in accessing HIV treatment services, aimed at preventing serial transmission from HIV-positive persons to adolescent sexual or drug-injection partners and to prevent vertical transmission from HIV-positive pregnant women to their newborns. The war also led to new-onset, conflict-associated, preventable infectious diseases in children and adolescents. First, children and adolescents were at risk of wound infections from medical trauma sustained during bombardment and other acts of war. Second, young people were at risk of sexually transmitted infections resulting from sexual assault perpetrated by invading Russian military personnel on youth trapped in occupied territories or from sexual assault perpetrated on vulnerable youth attempting to migrate to safety. Given the cascading risks that Ukrainian children and adolescents faced in the early months of the war—and will likely continue to face—infectious disease specialists and pediatricians are using their international networks to assist refugee-receiving host nations to improve infectious disease screening and interventions.

BackgroundRefugee children and young people have complex healthcare needs. However, issues related to acute healthcare provision for refugee children across Europe remain unexplored. This study aimed to describe the urgent and emergency healthcare needs of refugee children in Europe, and to identify obstacles to providing this care.MethodsAn online cross-sectional survey was distributed to European healthcare professionals via research networks between 1 February and 1 October 2017 addressing health issues of children and young people aged ResultsOne hundred and forty-eight respondents from 23 European countries completed the survey, and most worked in academic institutions (n=118, 80%). Guidance on immunisations was available for 30% of respondents, and on safeguarding issues (31%), screening for infection (32%) or mental health (14%). Thirteen per cent reported regular teaching sessions related to refugee child health. Language barriers (60%), unknown medical history (54%), post-traumatic stress disorder (52%) and mental health issues (50%) were perceived obstacles to providing care; severity of presenting illness, rare or drug-resistant pathogens and funding were not.ConclusionsMany hospitals are not adequately prepared for providing urgent and emergency care to refugee children and young people. Although clinicians are generally well equipped to deal with most types and severity of presenting illnesses, we identified specific obstacles such as language barriers, mental health issues, safeguarding issues and lack of information on previous medical history. There was a clear need for more guidelines and targeted education on refugee child health.

Exclusive breastfeeding is recommended for women living with HIV (WLWH) in low-income-but not in high-income-countries, where milk substitutes are preferred. Some guidelines for high-income countries opted for a shared decision-making process regarding breastfeeding in optimal scenarios with adherence to antiretroviral therapy (cART), suppressed maternal viral load (mVL), and clinical monitoring. Although vertical transmission (VT) risk under cART is estimated below 1% in low-income settings, data from high-income countries are rare.We retrospectively analyzed all 181 live births from WLWH at the LMU Munich university hospital perinatal center in Germany between January 2016 and December 2020. We focused on VT, suppressed mVL and optimal scenario rates, breastfeeding frequency, cART regimens, and infant prophylaxis. All women were counseled according to current guidelines, foremost recommending avoidance of breastfeeding.In the 5-year cohort, no VT was observed. One hundred fifty-one WLWH (83.4%) decided not to breastfeed, even in optimal scenarios. Thrity infants (16.6%) were nursed, of which 25 were within an optimal scenario, whereas in 5 cases, breastfeeding was performed with a detectable VL in pregnancy or the postpartum period. All WLWH were treated with cART at delivery, and 91.7% sustained suppressed mVL. Zidovudine infant prophylaxis was given between 2 and 8 weeks but not necessarily over the whole breastfeeding duration and was declined from 5 breastfeeding WLWH.Although the cohort is too small to assess VT risk through breastfeeding with cART-suppressed mVL, breastfeeding might be an alternative even in high-income countries, but further studies are needed.

Here we report our results of a multi-center, open cohort study (“COVID-Kids-Bavaria”) investigating the distribution of SARS-CoV-2 among children and staff in 99 daycare facilities and 48 elementary schools in Bavaria, Germany. Overall, 2568 children (1337 school children, 1231 preschool children) and 1288 adults (466 teachers, 822 daycare staff) consented to participate in the study and were randomly tested in three consecutive phases (September/October 2020, November/December 2020, March 2021). In total, 7062 throat swabs were analyzed for SARS-CoV-2 by RT-PCR. In phase I, only one daycare worker tested positive. In phase II, SARS-CoV-2 was detected in three daycare workers, two preschool children, and seven school children. In phase III, no sample tested positive. This corresponds to a positive test rate of 0.05% in phase I, 0.4% in phase II and 0% in phase III. After phase III, antibody testing was offered to 713 study participants in elementary schools. A seroprevalence rate of 7.7% (students) and 4.5% (teachers) was determined. We conclude that during the initial waves of the SARS-CoV-2 pandemic, the risk of a positive SARS-CoV-2 result correlated positively with the local 7-day incidence. Thus, an increased risk of SARS-CoV-2 transmission in the setting of daycare and elementary schooling was unlikely.

Ein 17 Monate alter Junge wird mit seit 5 Tagen bestehendem Fieber in der Notaufnahme vorgestellt. Am Tag vor der Aufnahme war eine antibiotische Therapie vom Kinderarzt initiiert worden. Vor einer Woche hatte der Junge Symptome einer oberen Atemwegsinfektion gezeigt. Im Verlauf ist das Fieber immer weiter gestiegen. Der Mutter hatte er einen zunehmend unleidlichen Eindruck gemacht. Am Morgen der Vorstellung war nun auch ein Ausschlag an den Beinen zu sehen. Klinisch prasentiert sich das Kind weinerlich und irritabel. Bei deutlich erhohten Entzundungswerten erfolgt die stationare Aufnahme. Nach Stellung der korrekten Diagnose wird umgehend eine Therapie eingeleitet. Zuvor erfolgt noch eine bildgebende Diagnostik.

Objective (1) To derive reference values for the Shock Index (heart rate/systolic blood pressure) based on a large emergency department (ED) population of febrile children and (2) to determine the diagnostic value of the Shock Index for serious illness in febrile children. Design/setting Observational study in 11 European EDs (2017–2018). Patients Febrile children with measured blood pressure. Main outcome measures Serious bacterial infection (SBI), invasive bacterial infection (IBI), immediate life-saving interventions (ILSIs) and intensive care unit (ICU) admission. The association between high Shock Index (>95th centile) and each outcome was determined by logistic regression adjusted for age, sex, referral, comorbidity and temperature. Additionally, we calculated sensitivity, specificity and negative/positive likelihood ratios (LRs). Results Of 5622 children, 461 (8.2%) had SBI, 46 (0.8%) had IBI, 203 (3.6%) were treated with ILSI and 69 (1.2%) were ICU admitted. High Shock Index was associated with SBI (adjusted OR (aOR) 1.6 (95% CI 1.3 to 1.9)), ILSI (aOR 2.5 (95% CI 2.0 to 2.9)), ICU admission (aOR 2.2 (95% CI 1.4 to 2.9)) but not with IBI (aOR: 1.5 (95% CI 0.6 to 2.4)). For the different outcomes, sensitivity for high Shock Index ranged from 0.10 to 0.15, specificity ranged from 0.95 to 0.95, negative LRs ranged from 0.90 to 0.95 and positive LRs ranged from 1.8 to 2.8. Conclusions High Shock Index is associated with serious illness in febrile children. However, its rule-out value is insufficient which suggests that the Shock Index is not valuable as a screening tool for all febrile children at the ED., EU multicentre ED study of presenting vital signs in >5000 febrile children with an association between "shock index" and serious illness, but low sensitivity limits utility in screening.

Purpose Antibiotic exposure among hospitalized children is very high. With inappropriate antimicrobial use resulting in increased rates of antimicrobial resistance, the implementation of antibiotic stewardship programs is critically needed. This survey study aimed to identify current practice and knowledge about antibiotic stewardship and infection control among paediatricians in tertiary care paediatric hospitals in and around Munich, Germany. Methods A prospective cross-sectional study based on an anonymous questionnaire, structured into different sub-sections regarding antibiotic use, antimicrobial resistance, antibiotic stewardship and infection control, was conducted between 1st of May and 30th of June 2016 in five paediatric hospitals. Results In total, 111 paediatricians across all grades were eligible for participation. The overall proportion of correct answers for all sub-sections of the survey ranged from 54.1% correct answers in the antibiotic handling and bacterial resistance section to 72.9% correct answers in the hospital hygiene/infection control section. In general, knowledge across all categories was similar for junior doctors, middle-grade doctors or consultants. Advocating empiric use of narrow-spectrum instead of broad-spectrum antibiotics was considered to be the most difficult measure to implement in daily practice (36.9%). De-escalation from broad-spectrum empirical therapy to targeted treatment was considered the easiest measure to achieve (43.2%). Conclusion Our results demonstrate that principles of antimicrobial stewardship and aspects of hospital hygiene/infection control are not satisfactorily known among hospital-based paediatricians in and around Munich. We identified four important target areas for future educational interventions that should play a more prominent role in both pre- and postgraduate medical training.

BACKGROUND Because infections are a major driver of morbidity and mortality in children with hematologic or oncologic diseases, antimicrobials are frequently prescribed in pediatric oncology practice. However, excess or inappropriate use of antimicrobials is directly linked to the emergence of antimicrobial resistance. Although point-prevalence studies have examined the extent of antimicrobial use, a comprehensive qualitative evaluation of individual antimicrobial prescriptions remains lacking. OBJECTIVE The aim of this study is to identify appropriate versus inappropriate antimicrobial use among pediatric cancer patients in a point-prevalence study, followed by an expert panel adjudication process and a subsequent report of these findings to participating centers. This study also aims to improve the quality of patient care by informing centers about discrepancies between internal standards of care and national guidelines. METHODS Our point-prevalence study is performed at pediatric cancer centers in Germany and Austria. All patients under 18 years old who are hospitalized at the time of the study are included. As a supplement to the point-prevalence study, an expert panel is qualitatively assessing each of the antimicrobial prescriptions at the participating centers to review local guidelines and compare them with national guidelines. RESULTS As of December 2021, the point-prevalence survey has been conducted at 30 sites and expert panel adjudication for qualitative assessment of each antimicrobial use is ongoing. Results of the study are expected in 2022. CONCLUSIONS This is the first point-prevalence study conducted among pediatric cancer centers with an integrated, multistep, qualitative approach that assesses each antimicrobial prescription. The results of this study will inform possible interventions for internal guidelines and antimicrobial stewardship programs implemented at pediatric cancer centers. In addition, local guidelines will be compared with national guidelines. Furthermore, this study will contribute to the overall integration of antimicrobial stewardship principles and initiatives in pediatric oncology and hematology, thereby improving safety and quality of care for children and adolescents with cancer and blood disorders. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/35774

Background Vancomycin-resistant Enterococcus faecium (VREfm) strains are one of the most important pathogens causing nosocomial infections in Germany. Due to limited treatment options and an increased risk for acquisition in immunocompromised children, surveillance to monitor occurrence of VREfm in paediatric clinical facilities is of critical importance. Following an unusual accumulation of VREfm positive patients between April 2019 and August 2020 at Dr. von Hauner Children’s Hospital in Munich, Germany, our study aimed to identify dynamics and routes of transmission, and analyse the affected population in view of previously described host risk factors for VREfm colonisation or infection. Methods The hospital database was used to collect epidemiological and clinical data of VREfm cases. Descriptive statistical analyses were conducted to outline patient characteristics and depict possible differences between VREfm-colonised and -infected children. An outbreak investigation determining genetic relatedness among VREfm isolates was performed by core genome multilocus sequence typing (cgMLST). To examine potential transmission pathways, results of genome analysis were compared with epidemiological and clinical data of VREfm positive patients. Results VREfm acquisition was documented in a total of 33 children (p = 0.011), showed signs of clinical infection. cgMLST analysis revealed seven distinct clusters, demonstrating a possible connection within each clonal lineage. Additional eight singletons were identified. Comparison with epidemiological and clinical data provided strong evidence for a link between several VREfm positive patients within the hospital. Conclusions A nosocomial spread—at least in part—was the most likely reason for the unusual accumulation of VREfm cases. The study highlights that there is a constant need to increase efforts in hygiene measures, infection control and antibiotic stewardship to combat VREfm transmission events within German paediatric hospitals. Continuous monitoring of adherence to respective policies might reduce the occurrence of clustered cases and prevent future outbreaks.

Background During COVID-19-related public health non-pharmaceutical prevention measures, such as social distancing, lockdown periods and use of face masks, a decrease in viral respiratory and gastroenterological infections was observed worldwide. Following discontinuation of preventative measures, a potential increase of respective infections outside of their usual seasons was a matter of concern. Method We aimed to illustrate annual distribution of confirmed viral infections between 2017 and 2021 based on 32,506 clinical samples in a German pediatric tertiary care center and to explore the impact of the COVID-19 pandemic on the epidemiology of these infections in children. Results While a decrease in overall viral infections was observed during the first and second lockdown period, an extraordinary increase in the number of viral respiratory infections, predominantly caused by human Rhino-/Enterovirus and respiratory syncytial virus (RSV), was observed after relaxation of preventive measures. Notably, Rhino-/Enterovirus infections increased 4-fold (2020 vs. 2019) and 16-fold (2021 vs. 2019). The occurrence of RSV was observed beginning from June to August 2021 and reached an all-time record with a 25- to 50-fold increase in numbers in September and October 2021 in relation to previous pre-pandemic years (2017–2019). In contrast, for non-respiratory viruses (i.e. Rota-/Norovirus), the effect on respective seasonal patterns was only minimal compared to previous years. Conclusion The observed increase in respiratory infections in children is worrying and is already causing hospitals to become overburdened. Enhanced vigilance will be key to face clinical challenges due to these epidemiological changes in viral disease patterns in the months to come.

Antibiotic consumption (AC) is a key component of antimicrobial stewardship programs to recognize local patterns of antibiotic use. Our aim was to measure AC in neonatal units, including neonatal (NICU)/paediatric (PICU) intensive care units in different countries. We conducted a multicenter, retrospective, cohort study in three NICUs, one neonatal ward, and three PICUs with a total of 84 beds. Global and individual AC in days of therapy (DOT) and DOT per 1000 patient-days were assessed. During the study period, 2567 patients were admitted, corresponding to 4961 patient-days in neonatal units and 9243 patient-days in PICUs. Multidrug-resistant Gram-negative bacteria and methicillin-resistant Staphylococcus aureus were more frequent in Brazil than in Germany. Average AC was 386.5 and 1335.5 DOT/1000PD in German and Brazilian neonatal units, respectively. Aminopenicillins plus 3rd generation cephalosporins were the most commonly prescribed antibiotics in German neonatal units, while aminopenicillins plus aminoglycosides were the class most commonly used in Brazilian NICU. Average AC was 888.1 and 1440.7 DOT/1000PD in German and Brazilian PICUs, respectively. Antipseudomonal penicillins were most commonly used in the German PICU, and glycopeptides were the most frequently prescribed in Brazilian PICUs. Carbapenems represented 2.3-14% of total DOTs in German neonatal units and 4% in the Brazilian NICU and 13.0% in the German PICU and 6-12.2% in Brazilian PICUs. We concluded that different patterns of most commonly prescribed antibiotics were observed in neonatal units and PICUs in these two countries, probably related to different local patterns of antibiotic resistance, with a higher antibiotic consumption in Brazilian study units.

Between 2015 and 2017, an estimated 200,000 to 400,000 children were seeking asylum each year in EU/EEA countries. As access to high-quality health care is important, we collected and compared current recommendations across Europe for a consensus recommendation on medical care for migrant (asylum-seeking and refugee) children. Existing recommendations were collected from published literature and identified through national representatives from paediatric societies of 31 EU/EEA countries through the European Academy of Paediatrics (EAP). Recommendations were systematically extracted and collected in a database. Those mentioned in at least one recommendation were evaluated for inclusion, and evidence on recommendations was specifically identified in literature searches focused on recent evidence from Europe. For eight EU/EEA countries, a national recommendation was identified. Growth and development, vision and hearing impairment, skin and dental problems, immunisations, anaemia, micronutrient deficiency, helminths, hepatitis B and C, human immunodeficiency virus, malaria, schistosomiasis, syphilis, tuberculosis, mental health disorder and sexual health were most frequently mentioned and therefore selected for inclusion in the recommendation. Conclusion: The current document includes general recommendations on ethical standards, use of interpreters and specific recommendations for prevention or early detection of communicable and non-communicable diseases. It may serve as a tool to ensure the fundamental right that migrant children in Europe receive a comprehensive, patient-centred health care.

Das Update ist eine Zusammenfassung des im neuen Handbuch (7. Auflage) erscheinenden Kapitels uber Infektion mit Humanem Immundefizienz-Virus (HIV) der Deutschen Gesellschaft fur padiatrische Infektiologie sowie der derzeit in Uberarbeitung befindlichen Leitlinie HIV-Infektion der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AMWF) im Kindesalter. Es werden die neuesten Empfehlungen hinsichtlich Therapie der padiatrischen HIV-Infektion, supportiven Therapien und Pravention der vertikalen HIV-Transmission und Postexpositionsprophylaxe nach akzidenteller HIV-Exposition vorgestellt.

BACKGROUND Vancomycin has been a first-line treatment for Gram-positive infections for decades. However, strategies for therapeutic drug monitoring (TDM) and dose-optimization in pediatrics remain controversial. In this study, we analyzed the impact of specific antibiotic stewardship interventions on efficacy and safety of vancomycin therapy. METHODS From September 2014 to May 2017, we conducted a prospective study to compare a control and a TDM intervention group in our tertiary care center. As part of an antibiotic stewardship program, we implemented internal guidelines on correct vancomycin dosing, TDM timing, as well as targeted trough level range and installed a pharmacokinetic (PK) consultation service to adapt vancomycin dosing to individually calculated PK parameters. As primary clinical outcomes, the percentage of patients with sustained therapeutic vancomycin trough levels and treatment days with therapeutic vancomycin trough levels, that is, 10-15 mg/L were analyzed. Secondary outcomes included nephrotoxicity, readmission rate and mortality. Median daily dose required to achieve therapeutic trough levels was examined. RESULTS Clinical outcomes for 90 control patients were compared with outcomes for 19 patients guided by a PK consultation service. Percentage of patients with sustained therapeutic vancomycin trough levels increased from 17.8% to 94.7% (P < 0.001) and percentage of treatment days with therapeutic vancomycin trough levels increased from 18.4% (117/637) to 665% (155/233, P < 0.001). Readmission rate decreased from 24.4% to 5.3% (P = 0.07). No differences in nephrotoxicity or mortality rate were observed between groups. A median daily dose of 72 mg/kg/d was required to achieve therapeutic trough levels. CONCLUSIONS Our data demonstrate that implementation of internal guidelines and a PK consultation service was associated with a profound improvement of vancomycin therapy and, therefore, patient safety.

A 12-week sentinel programme monitored SARS-CoV-2 in primary schools, kindergartens and nurseries. Out of 3169 oropharyngeal swabs, only two tested positive on rRT-PCR while general incidence rates were surging. Thus, children attending respective institutions are not significantly contributing to the pandemic spread when appropriate infection control measures are in place.

Background: Investigating the role of children in the COVID-19 pandemic is pivotal to prevent the virus spreading. In most cases, children infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) develop non-specific symptoms or are asymptomatic. Therefore, the infection rate among this age group remains unclear. Seroprevalence studies, including clinical questionnaires, may contribute to our understanding of the time course and clinical manifestations of SARS-CoV-2 infections. Methods: SARS-CoV-2-KIDS is a longitudinal, hospital-based, multicentre study in Germany on the seroprevalence of anti-SARS-CoV-2 immunoglobulin G, as determined by an Enzyme-Linked Immunosorbent Assay in children (aged ≤17 years). A study-specific questionnaire provided additional information on clinical aspects. Findings: This analysis included 10,358 participants recruited from June 2020 to May 2021. The estimated anti-SARS-CoV-2 seroprevalence increased from 2·0% (95% confidence interval (95% CI) 1·6, 2·5) to 10·8% (95% CI 8·7, 12·9) in March 2021, without major change afterwards and was higher in children with migrant background (on average 6·6% vs. 2·8%). In the pandemic early stages, children under three years were 3·5 (95% CI 2·2, 5·6) times more likely to be seropositive than older children, with the levels equalising in later observations. History of self-reported respiratory tract infections or pneumonia was associated with seropositivity (OR 1·8 (95% CI 1·4, 2·3);2·7 (95% CI 1·7, 4·1)). Interpretation: The majority of children in Germany do not have detectable SARS-CoV-2 IgG. To some extent, this may reflect the effect of differing containment measures implemented in the federal states. Detection levels might have been greater in certain age groups or migrant background. Lifting containment measurements is likely to cause a general increase in respiratory tract infections, which already pose a challenge to paediatric medical care during regular winter seasons. This challenge might become critical with additional infections caused by SARS-CoV-2.

BackgroundProlonged Emergency Department (ED) stay causes crowding and negatively impacts quality of care. We developed and validated a prediction model for early identification of febrile children with a high risk of hospitalisation in order to improve ED flow.MethodsThe MOFICHE study prospectively collected data on febrile children (0-18 years) presenting to 12 European EDs. A prediction models was constructed using multivariable logistic regression and included patient characteristics available at triage. We determined the discriminative values of the model by calculating the area under the receiver operating curve (AUC).FindingsOf 38,424 paediatric encounters, 9,735 children were admitted to the ward and 157 to the PICU. The prediction model, combining patient characteristics and NICE alarming, yielded an AUC of 0.84 (95%CI 0.83-0.84).The model performed well for a rule-in threshold of 75% (specificity 99.0% (95%CI 98.9-99.1%, positive likelihood ratio 15.1 (95%CI 13.4-17.1), positive predictive value 0.84 (95%CI 0.82-0.86)) and a rule-out threshold of 7.5% (sensitivity 95.4% (95%CI 95.0-95.8), negative likelihood ratio 0.15 (95%CI 0.14-0.16), negative predictive value 0..95 (95%CI 0.95-9.96)). Validation in a separate dataset showed an excellent AUC of 0.91 (95%CI 0.90- 0.93). The model performed well for identifying children needing PICU admission (AUC 0.95, 95%CI 0.93-0.97). A digital calculator was developed to facilitate clinical use.InterpretationPatient characteristics and NICE alarming signs available at triage can be used to identify febrile children at high risk for hospitalisation and can be used to improve ED flow.FundingEuropean Union, NIHR, NHS.

Objectives Hospitalisation is frequently used as a marker of disease severity in observational Emergency Department (ED) studies. The comparison of ED admission rates is complex in potentially being influenced by the characteristics of the region, ED, physician and patient. We aimed to study variation in ED admission rates of febrile children, to assess whether variation could be explained by disease severity and to identify patient groups with large variation, in order to use this to reduce unnecessary health care utilization that is often due to practice variation. Design MOFICHE (Management and Outcome of Fever in children in Europe, part of the PERFORM study, www.perform2020.org), is a prospective cohort study using routinely collected data on febrile children regarding patient characteristics (age, referral, vital signs and clinical alarming signs), diagnostic tests, therapy, diagnosis and hospital admission. Setting and participants Data were collected on febrile children aged 0–18 years presenting to 12 European EDs (2017–2018). Main outcome measures We compared admission rates between EDs by using standardised admission rates after adjusting for patient characteristics and initiated tests at the ED, where standardised rates >1 demonstrate higher admission rates than expected and rates Results We included 38,120 children. Of those, 9.695 (25.4%) were admitted to a general ward (range EDs 5.1–54.5%). Adjusted standardised admission rates ranged between 0.6 and 1.5. The largest variation was seen in short admission rates (0.1–5.0), PICU admission rates (0.2–2.2), upper respiratory tract infections (0.4–1.7) and fever without focus (0.5–2.7). Variation was small in sepsis/meningitis (0.9–1.1). Conclusions Large variation exists in admission rates of febrile children evaluated at European EDs, however, this variation is largely reduced after correcting for patient characteristics and therefore overall admission rates seem to adequately reflect disease severity or a potential for a severe disease course. However, for certain patient groups variation remains high even after adjusting for patient characteristics.

AIMS OF THE STUDY Invasive streptococcal infections affect more than half a million patients worldwide every year and have a high lethality. Little is known about the epidemiology and microbiological characteristics of streptococcal infections in Switzerland. This case series study aims to describe the demographics, known risk factors for streptococcal skin and soft tissue infections, clinical presentations, treatment and outcomes of patients admitted to the University Hospital Zurich between 2000 and 2014 with invasive streptococcal infections caused by Streptococcus pyogenes (group A Streptococcus), Streptococcus dysgalactiae ssp. equisimilis or the Streptococcus anginosus group, as well as the microbiological characteristics of the clinical isolates. METHODS Data collected retrospectively from patients hospitalised between 2000 and 2014 with invasive streptococcal infections were analysed. M protein gene (emm) typing of the bacterial clinical isolates was carried out according to the Centers for Disease Control and Prevention guidelines. RESULTS A total of 86 patients with invasive beta-haemolytic streptococcal infections were included in this study, of which 49% presented with necrotising fasciitis. The median age was 44 years and half were female. The most common risk factor was acute skin lesions. C-reactive protein levels were significantly higher in patients with necrotising fasciitis, as were acute renal failure and distributive shock. Beta-lactam antibiotics were given to most patients, and intravenous immunoglobulins were given to 18% of patients within the first 24 hours. All patients suffering from necrotising fasciitis underwent surgery. The overall case fatality rate was 8.1% at 30 days post admission. All Group A Streptococcus strains were susceptible to penicillin and clindamycin, and we found resistance to tetracycline in 11.9% of strains. The most common emm-type isolated was emm1 (44.4%). CONCLUSIONS Invasive beta-haemolytic streptococcal infections, the most severe presentation of which is necrotising fasciitis, remain a serious clinical issue and require rapid diagnosis and treatment. This is the first representative analysis monitoring clinical and microbiological characteristics of patients with a severe invasive beta-haemolytic streptococcal infection and treated in Zurich, Switzerland. In addition to the detailed reporting of various clinical and microbiological characteristics, we show that C-reactive protein levels, acute renal failure and distributive shock were higher in the patients with necrotising fasciitis. We also found a low case fatality rate compared to other reports. The detailed clinical data and microbiological characteristics depicted in this study will lead to a better understanding of regional differences in severe invasive streptococcal infections.

Recommendations regarding the optimal number of blood cultures in children are not available. The aim of this article is to describe the correlation between blood culture (BC) rates and laboratory-confirmed bloodstream infection (LCBSI) rates, on different paediatric wards of a tertiary-care centre in Germany. We conducted a retrospective cohort study in a paediatric university hospital, from 1st January to 31st December 2018. All blood cultures collected from neonatal (NICU) and paediatric intensive-care units (PICU), haematology/oncology, and general paediatric wards were included. There were no exclusion criteria. BC taken/1000 patients-days (BC rates/BCR) and LCBSI/1000 patient-days at risk (LCBSI rates) were calculated for each unit. A total of 6040 patients were admitted to the hospital with 3114 of them into wards studied. Of the 3072 BCs collected, 200 (6.5%) were positive. Collection of BCs was performed in 51/77 (66.2%) of admitted patients on NICU, in 151/399 (37.8%) of PICU patients, in 163/755 (21.6%) of haematology/oncology patients, and in 281/1883 (14.9%) of children on general paediatric wards. Gram-positive bacteria were the most commonly detected organisms in blood cultures from all wards with exception of NICU. The BCR in NICU, PICU, haematology/oncology wards, and general wards were 61.6, 196.2, 358.4, and 52.3, respectively. Excluding commensal pathogens and possible contaminations, the LCBSI rates in the same units were 2.4, 5.6, 4.4, and 1.0, respectively. We found different BCR values according the ward studied, being higher in patients with high risk of bloodstream infection such as haematology/oncology patients.

Background The prescription rate of antibiotics is high for febrile children visiting the emergency department (ED), contributing to antimicrobial resistance. Large studies at European EDs covering diversity in antibiotic and broad-spectrum prescriptions in all febrile children are lacking. A better understanding of variability in antibiotic prescriptions in EDs and its relation with viral or bacterial disease is essential for the development and implementation of interventions to optimise antibiotic use. As part of the PERFORM (Personalised Risk assessment in Febrile illness to Optimise Real-life Management across the European Union) project, the MOFICHE (Management and Outcome of Fever in Children in Europe) study aims to investigate variation and appropriateness of antibiotic prescription in febrile children visiting EDs in Europe. Methods and findings Between January 2017 and April 2018, data were prospectively collected on febrile children aged 0–18 years presenting to 12 EDs in 8 European countries (Austria, Germany, Greece, Latvia, the Netherlands [n = 3], Spain, Slovenia, United Kingdom [n = 3]). These EDs were based in university hospitals (n = 9) or large teaching hospitals (n = 3). Main outcomes were (1) antibiotic prescription rate; (2) the proportion of antibiotics that were broad-spectrum antibiotics; (3) the proportion of antibiotics of appropriate indication (presumed bacterial), inappropriate indication (presumed viral), or inconclusive indication (unknown bacterial/viral or other); (4) the proportion of oral antibiotics of inappropriate duration; and (5) the proportion of antibiotics that were guideline-concordant in uncomplicated urinary and upper and lower respiratory tract infections (RTIs). We determined variation of antibiotic prescription and broad-spectrum prescription by calculating standardised prescription rates using multilevel logistic regression and adjusted for general characteristics (e.g., age, sex, comorbidity, referral), disease severity (e.g., triage level, fever duration, presence of alarming signs), use and result of diagnostics, and focus and cause of infection. In this analysis of 35,650 children (median age 2.8 years, 55% male), overall antibiotic prescription rate was 31.9% (range across EDs: 22.4%–41.6%), and among those prescriptions, the broad-spectrum antibiotic prescription rate was 52.1% (range across EDs: 33.0%–90.3%). After standardisation, differences in antibiotic prescriptions ranged from 0.8 to 1.4, and the ratio between broad-spectrum and narrow-spectrum prescriptions ranged from 0.7 to 1.8 across EDs. Standardised antibiotic prescription rates varied for presumed bacterial infections (0.9 to 1.1), presumed viral infections (0.1 to 3.3), and infections of unknown cause (0.1 to 1.8). In all febrile children, antibiotic prescriptions were appropriate in 65.0% of prescriptions, inappropriate in 12.5% (range across EDs: 0.6%–29.3%), and inconclusive in 22.5% (range across EDs: 0.4%–60.8%). Prescriptions were of inappropriate duration in 20% of oral prescriptions (range across EDs: 4.4%–59.0%). Oral prescriptions were not concordant with the local guideline in 22.3% (range across EDs: 11.8%–47.3%) of prescriptions in uncomplicated RTIs and in 45.1% (range across EDs: 11.1%–100%) of prescriptions in uncomplicated urinary tract infections. A limitation of our study is that the included EDs are not representative of all febrile children attending EDs in that country. Conclusions In this study, we observed wide variation between European EDs in prescriptions of antibiotics and broad-spectrum antibiotics in febrile children. Overall, one-third of prescriptions were inappropriate or inconclusive, with marked variation between EDs. Until better diagnostics are available to accurately differentiate between bacterial and viral aetiologies, implementation of antimicrobial stewardship guidelines across Europe is necessary to limit antimicrobial resistance., Henriette Moll and colleagues assess how antibiotic prescribing rates differ across twelve emergency departments in eight European countries., Author summary Why was this study done? Respiratory infections, which are mainly caused by viruses, account for the majority of antibiotic use in children. In children with respiratory infections, antibiotic prescription rates vary across emergency departments (EDs) in Europe. In order to optimise antibiotic prescriptions, it is important to better understand variability and appropriateness in antibiotic prescriptions. What did the researchers do and find? In this prospective observational study, we included routine information of 35,650 children (median age 2.8 years) with fever attending 12 different EDs in Europe and calculated the proportion of antibiotic prescriptions and broad-spectrum antibiotic prescriptions. We adjusted for differences in population including age, comorbidity, disease severity, and focus and cause of infection. Across EDs, antibiotic prescription rates ranged between 22.4% and 41.6%, and of these prescriptions, broad-spectrum antibiotic rates ranged between 33.0% and 90.3%. Standardised antibiotic prescription rates ranged between 0.77 and 1.35, and standardised rates of broad-spectrum antibiotics ranged between 0.65 and 1.75. Prescriptions that were inappropriately indicated ranged from 0.6% to 29.3%, and inconclusive prescriptions ranged from 0.5% to 61.7%. The proportion of oral prescriptions with inappropriate duration ranged from 4.4% to 59.0%. What do these findings mean? In this study we found variation of prescription of antibiotics and broad-spectrum antibiotics between EDs in children with fever, even when correcting for age, comorbidity, disease severity, diagnostics, and focus and cause of infection. Variation was especially large in prescriptions for viral infections and infections of unknown cause. In this cohort of febrile children, one-third of prescriptions were of inappropriate or inconclusive indication, with variation between EDs. In addition, guideline concordance for respiratory and urinary infections varied widely across EDs. Generalisation of these results to all EDs in Europe should be undertaken with caution. Implementation of guidelines is needed to improve appropriate prescription of antibiotics, whilst new biomarkers will further improve antibiotic prescription.

Due to early antenatal screening and treatment, HIV mother-to-child transmission (MTCT) rarely occurs in Germany. The study aimed to investigate the impact on prevalence of HIV infection in the antenatal population and the incidence of late-presenting HIV-infected mothers attributable to increased numbers of refugees. Retrospective analysis and comparison were performed for all deliveries in HIV-infected pregnant women presenting to medical care in Munich (southern Germany) and Hamburg (northern Germany) covering two time periods, A (2010–2012) and B (2013–2015). In Munich, deliveries in HIV-infected pregnant women increased 1.6-fold from period A (n = 50) to B (n = 79) with late-presenting cases rising significantly from 2% (1/50) in period A to 13% (10/79) in B. In contrast, late-presenting cases in Hamburg decreased from 14% (14/100) in period A to 7% (7/107) in B, while the total number of HIV-infected women giving birth remained stable. From 2010 to 2015, one late-presenting pregnant woman transmitted HIV in Munich by presumed in utero mode of infection (case reviewed here), while no MTCT occurred in Hamburg. HIV infections diagnosed late in pregnancy and leading to delayed ART initiation are rising in Munich compared to Hamburg. Antenatal care of HIV-infected pregnant women in Munich appears to have been more affected by the recent refugee influx than Hamburg. Our study highlights the importance of screening all pregnant women for HIV early in pregnancy and providing timely health care access for pregnant refugees and asylum seekers to effectively prevent MTCT in Germany.

Kleinkinder mit Fieber stellen manchmal eine differenzialdiagnostische Herausforderung dar. Handelt es sich um eine unkomplizierte Erkrankung oder ist eine rasche, erweiterte Diagnostik erforderlich? Damit Sie die richtige Entscheidung treffen, sollten Sie auch seltene Ursachen kennen und die Alarmzeichen, die zu sofortigem Handeln zwingen.

ObjectiveTo retrospectively identify CF patients with methicillin resistant Staphylococcus aureus (MRSA) and to assess the long-term success of an eradication scheme introduced in 2002 for all newly colonized patients. PatientsAll microbiological results from all 505 CF patients followed between 2002 and 2012 were analyzed focusing on the detection of MRSA. MethodsRetrospective patient record analysis of MRSA positive CF patients regarding eradication and clinical outcome. ResultsWe identified 57 patients with MRSA, mean age 15.3 years (range: 0.6-36.9, incidence 0.9%/year). Of these, nine patients were lost to follow-up;seven chronically colonized patients were excluded from the intervention. Eradication was suggested to all patients, 37/41 gave their consent to the following two-step approach: (i) dual iv antibiotic treatment over 3 weeks, accompanied by hygienic directives and topical therapy for 5 days followed by a 6-week period with dual oral antibiotic therapy and inhalation with vancomycin. (ii) Each new MRSA detection was treated with 6 weeks inhalation of vancomycin and topical therapy for 5 days. Long-term eradication was rated by the microbiological status in the third year after first detection. MRSA was eradicated in 31 of 37 patients (84%) whose clinical course was stable (mean FEV1 one year before MRSA 80.4%, 3 years after MRSA 81.0%). ConclusionsMRSA colonization mandates complex and expensive hygienic measures which are not well accepted by patients. Therefore, MRSA eradication is desirable. Intensive therapy regimens may be successful in patients with CF and might help to maintain a stable clinical course. Pediatr Pulmonol. 2016;51:1010-1019. (c) 2016 Wiley-Blackwell.

Impfen ist einer der Hauptpfeiler der praventiven Medizin. Deshalb sollten Sie das Thema immer im Blick behalten und in der Sprechstunde regelmasig ansprechen. Der Beitrag fasst die wichtigsten Neuerungen der letzten STIKO-Empfehlungen zusammen und beschreibt ein „Mindest-Impfangebot“ fur Asylsuchende.

Migranten sind in Bezug auf ubertragbare Erkrankungen eine besonders vulnerable Gruppe. Mit welchen Infektionskrankheiten mussen Sie bei Fluchtlingen und ihren Kindern rechnen? Wie kann die Ubertragung eingeschleppter Krankheiten auf andere Patienten und das medizinische Personal verhindert werden?

Mycobacterium tuberculosis (M. tuberculosis) survives and multiplies inside human macrophages by subversion of immune mechanisms. Although these immune evasion strategies are well characterised functionally, the underlying molecular mechanisms are poorly understood. Here we show that during infection of human whole blood with M. tuberculosis, host gene transcriptional suppression, rather than activation, is the predominant response. Spatial, temporal and functional characterisation of repressed genes revealed their involvement in pathogen sensing and phagocytosis, degradation within the phagolysosome and antigen processing and presentation. To identify mechanisms underlying suppression of multiple immune genes we undertook epigenetic analyses. We identified significantly differentially expressed microRNAs with known targets in suppressed genes. In addition, after searching regions upstream of the start of transcription of suppressed genes for common sequence motifs, we discovered novel enriched composite sequence patterns, which corresponded to Alu repeat elements, transposable elements known to have wide ranging influences on gene expression. Our findings suggest that to survive within infected cells, mycobacteria exploit a complex immune “molecular off switch” controlled by both microRNAs and Alu regulatory elements.

Antibiotic stewardship programs (ASP) optimize antibiotic usage and combat antibiotic resistance of bacteria. The objective of this study was to assess the impact of specific ASP interventions on antibiotic consumption in general pediatric wards. We conducted a prospective study to compare a pre-intervention (Sept.–Dec. 2014) and post-intervention (Sept.–Dec. 2015) period. An ASP bundle was established including (1) infectious diseases (ID) ward rounds (prospective-audit-with-feedback), (2) ID consultation service, (3) internal guidelines on empiric antibiotic therapy. Medical records on four general pediatric wards were reviewed daily to analyze: (1) antibiotic consumption, (2) antibiotic dosage ranges according to local guidelines, and (3) guideline adherence for community-acquired pneumonia (CAP). Antibiotic prescribing for 273 patients (pre-intervention) was compared to 263 patients (post-intervention). Antibiotic prescription rate did not change (30.6 vs. 30.5%). However, overall days-of-therapy and length-of-therapy decreased by 10.5 and 7.7%, respectively. Use of cephalosporins and fluoroquinolones decreased by 35.5 and 59.9%, whereas the use of penicillins increased by 15.0%. An increase in dosage accuracy was noted (78.8 vs. 97.6%) and guideline adherence for CAP improved from 39.5 to 93.5%. Between the two study periods, no adverse effects regarding length of hospital stay and in-hospital mortality were observed. Our data demonstrate that implementation of an ASP was associated with a profound improvement of rational antibiotic use and, therefore, patient safety. Considering the relatively short observation period, the long-term effects of our ASP bundle need to be further investigated.

To retrospectively identify CF patients with methicillin resistant Staphylococcus aureus (MRSA) and to assess the long-term success of an eradication scheme introduced in 2002 for all newly colonized patients.All microbiological results from all 505 CF patients followed between 2002 and 2012 were analyzed focusing on the detection of MRSA.Retrospective patient record analysis of MRSA positive CF patients regarding eradication and clinical outcome.We identified 57 patients with MRSA, mean age 15.3 years (range: 0.6-36.9, incidence 0.9%/year). Of these, nine patients were lost to follow-up; seven chronically colonized patients were excluded from the intervention. Eradication was suggested to all patients, 37/41 gave their consent to the following two-step approach: (i) dual iv antibiotic treatment over 3 weeks, accompanied by hygienic directives and topical therapy for 5 days followed by a 6-week period with dual oral antibiotic therapy and inhalation with vancomycin. (ii) Each new MRSA detection was treated with 6 weeks inhalation of vancomycin and topical therapy for 5 days. Long-term eradication was rated by the microbiological status in the third year after first detection. MRSA was eradicated in 31 of 37 patients (84%) whose clinical course was stable (mean FEV1 one year before MRSA 80.4%, 3 years after MRSA 81.0%).MRSA colonization mandates complex and expensive hygienic measures which are not well accepted by patients. Therefore, MRSA eradication is desirable. Intensive therapy regimens may be successful in patients with CF and might help to maintain a stable clinical course. Pediatr Pulmonol. 2016;51:1010-1019. © 2016 Wiley Periodicals, Inc.

Bacterial artificial chromosome (BAC) vectors are important tools for microbial genome research. We constructed a novel BAC vector, pUvBBAC, for replication in both gram-negative and gram-positive bacterial hosts. The pUvBBAC vector was used to generate a BAC library for the facultative intracellular pathogen Listeria monocytogenes EGD-e. The library had insert sizes ranging from 68 to 178 kb. We identified two recombinant BACs from the L. monocytogenes pUvBBAC library that each contained the entire virulence gene cluster (vgc) of L. monocytogenes and transferred them to a nonpathogenic Listeria innocua strain. Recombinant L. innocua strains harboring pUvBBAC+vgc1 and pUvBBAC+vgc2 produced the vgc-specific listeriolysin (LLO) and actin assembly protein ActA and represent the first reported cloning of the vgc locus in its entirety. The use of the novel broad-host-range BAC vector pUvBBAC extends the versatility of this technology and provides a powerful platform for detailed functional genomics of gram-positive bacteria as well as its use in explorative functional metagenomics.

We report 15 imported louse-borne relapsing fever (LBRF) cases in refugees in Bavaria, Germany. One patient died. Epidemiological findings confirmed that all were young males from the Horn of Africa (12 from Somalia), who had similar migration routes converging in Sudan continuing through Libya and Italy. The majority likely acquired their infection during migration. Healthcare workers should be aware of LBRF in refugees passing through north Africa to ensure correct treatment and preventive measures.

A major limitation in the development and testing of new tuberculosis (TB) vaccines is the current inadequate understanding of the nature of the immune response required for protection against either infection with Mycobacterium tuberculosis (MTB) or progression to disease. Genome wide RNA expression analysis has provided a new tool with which to study the inflammatory and immunological response to mycobacteria. To explore how currently available transcriptomic data might be used to understand the basis of protective immunity to MTB, we analysed and reviewed published RNA expression studies to (1) identify a “susceptible” immune response in patients with acquired defects in the interferon gamma pathway; (2) identify the “failing” transcriptomic response in patients with TB as compared with latent TB infection (LTBI); and (3) identify elements of the “protective” response in healthy latently infected and healthy uninfected individuals.