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OBJECTIVE: The identification of severe bacterial infection (SBI)in children with fever without source (FWS) remains a diagnostic problem. The authors previously developed in their Swiss population a risk index score, called the Lab-score, associating three independent predictors of SBI, namely C reactive protein (CRP), procalcitonin (PCT) and urinary dipstick. The objective of this study was to validate the Lab-score in a population of children with FWS different from the derivation model. METHODS: A prospective study, conducted in Padova, on 408 children aged 7 days to 36 months with FWS was recently published. PCT, CRP, white blood cell count (WBC) and urinary dipstick were determined in all children. The Lab-score was applied to this population and the diagnostic characteristics for the detection of SBI were calculated for the Lab-score and for any single variable used in the Italian study. RESULTS: For the identification of SBI, the sensitivity of a score >/=3 was 86% (95% CI 77% to 92%) and the specificity 83% (95% CI 79% to 87%). The area under the receiver operating characteristic curve for the Lab-score (0.91) was significantly superior to that of any single variable: 0.71 for WBC, 0.86 for CRP and 0.84 for PCT. The Lab-score performed better than other laboratory markers, even when applied to children of different age groups (12 months). The results obtained in this validation set population were comparable with those of the derivation set population. CONCLUSIONS: This study validated the Lab-score as a valuable tool to identify SBI in children with FWS.

Introduction: Fever is a common cause of paediatric admissions in emergency departments. An aetiological diagnosis is difficult to obtain in those less than 3 months of age, as they tend to have a higher rate of serious bacterial infection (SBI). The aim of this study is to find a predictor index of SBI in children under 3 months old with fever of unknown origin. Methods: A study was conducted on all children under 3 months of age with fever admitted to hospital, with additional tests being performed according to the clinical protocol. Rochester criteria for identifying febrile infants at low risk for SBI were also analysed.A predictive model for SBI and positive cultures was designed, including the following variables in the maximum model: C-reactive protein (CRP), procalcitonin (PCT), and meeting not less than four of the Rochester criteria. Results: A total of 702 subjects were included, of which 22.64% had an SBI and 20.65% had positive cultures. Children who had SBI and a positive culture showed higher values of white cells, total neutrophils, CRP and PCT. A statistical significance was observed with less than 4 Rochester criteria, CRP and PCT levels, an SBI (area under the curve [AUC] 0.877), or for positive cultures (AUC 0.888). Using regression analysis a predictive index was calculated for SBI or a positive culture, with a sensitivity of 87.7 and 91%, a specificity of 70.1 and 87.7%, an LR+ of 2.93 and 3.62, and a LR− of 0.17 and 0.10, respectively. Conclusions: The predictive models are valid and slightly improve the validity of the Rochester criteria for positive culture in children less than 3 months admitted with fever. Resumen: Introducción: La fiebre es motivo frecuente de consulta pediátrica y en menores de 3 meses su diagnóstico etiológico es difícil, siendo un grupo de pacientes con mayor tasa de infección bacteriana grave (IBG). Nuestro objetivo es encontrar un modelo predictivo de IBG en menores de 3 meses con fiebre sin foco. Métodos: Se estudió a los niños menores de 3 meses con fiebre sin foco ingresados, realizándose pruebas complementarias según protocolo clínico. Se analizaron además los criterios de Rochester de bajo grado de IBG. Se diseñó un modelo predictivo de IBG y cultivo positivo, incluyendo las siguientes variables en el modelo máximo: proteína C reactiva (PCR), procalcitonina (PCT) y cumplimiento o no de menos de 4 criterios de Rochester. Resultados: Se incluyó a 702 sujetos; el 22,64% presentaba IBG y el 20,65% cultivos positivos. Los que presentaban IBG y cultivo positivo presentaron más leucocitos, neutrófilos totales, PCR y PCT. Se obtuvieron significación estadística en puntuación de Rochester menor de 4 y valores de PCR y PCT para IBG (área bajo la curva [ABC] 0,877) y para cultivos positivos (ABC 0,888). Con la regresión se obtuvieron unas fórmulas de predicción de IBG y cultivo positivo con sensibilidad del 87,7 y el 91%, especificidad del 70,1 y el 87,7%, CPP de 2,93 y 3,62 y CPN de 0,17 y 0,10, respectivamente. Conclusiones: Los modelos predictivos son válidos y mejoran discretamente la validez de los criterios de Rochester para cultivo positivo en menores de 3 meses ingresados con fiebre.

The incidence and clinical spectrum of severe bacterial infection were studied in 89 patients with thalassemia major that was diagnosed between January 1971 and March 2002. There were 20 patients with 24 episodes of severe bacterial infection, resulting in an incidence of 1.6 infections per 100 patient-years. The clinical spectrum included liver abscess (6 cases), septicemia (6 cases), soft-tissue infection (2 cases), osteomyelitis (2 cases), corneal ulcer (1 case), enteritis (1 case), and abscesses of the lung, kidney, intra-abdominal region, retropharynx, gums, and buttocks (1 case each). The leading causal microorganisms were gram-negative bacilli, especially Klebsiella pneumoniae (10 of 20 isolates). Other responsible pathogens were Pseudomonas aeruginosa (2/20), Vibrio vulnificus (2/20), Acinetobacter baumanii (1/20), Streptococcus intermidius (1/20), Yersinia enterocolitica (1/20), Staphylococcus aureus (1/20), Escherichia coli (1/20), and Salmonella species (1/20). Splenectomy and delays in the start of iron-chelating therapy were 2 independent risk factors.

53 patients with planned antibiotic therapy for the treatment of acute exacerbation of chronic bronchitis as an example of a severe bacterial infection requiring antibiotics were included in a prospective, multicentre, double-blind, placebo-controlled study. The chronic bronchitis was staged by forced expiratory volume of the 1st second (FEV1) measured in the infection-free interval prior to the current episode and had to be between 35 and 75% for the predicted value. Patients were randomly assigned to receive newer macrolide antibiotics plus either Esberitox® N or placebo. Antibiotic therapy was administered according to generally accepted guidelines and Esberitox N or placebo was given for 28 days. The baseline-adjusted means for FEV1 (%) on day 10 were 68.7 points for the Esberitox N group and 59.2 points for the placebo group (p = 0.0303). For FEV1 the difference between the two treatment groups was 267 ml (p = 0.0499). The time to half maximal improvement was 5.7 days in the Esberitox N group compared to 12.8 days in the placebo group. The treatment was well tolerated; no serious adverse events were documented. In conclusion, comedication of antibiotics with Esberitox N in subjects with acute exacerbation of chronic bronchitis seems to be of benefit for the patient. Apparently, therapy with Esberitox N leads to a faster recovery from this severe bacterial infection, possibly via preventing an impairment of the host’s immune system which might otherwise occur as a consequence of aggressive antimicrobial therapeutics.

Objectives To assess the risk of gentamicin toxicity and potential number of neonates exposed annually to this risk, through treatment with WHO-recommended first-line antibiotics (gentamicin with penicillin) for the 6.9 million neonates with possible serious bacterial infection (PSBI). Methods Systematic literature review and assessment of the evidence using Cochrane and GRADE criteria. Meta-analysis was undertaken for pooled estimates where appropriate. Results Eleven studies (946 neonates) were included (nine randomised controlled trials and two prospective cohort studies). Six trials reported consistently measured ototoxicity outcomes in neonates treated with gentamicin, and the pooled estimate for hearing loss was 3% (95% CI 0–7%). Nephrotoxicity could not be assessed due to variation in case definitions used. Estimates of the number of neonates potentially affected by gentamicin toxicity were not undertaken due to insufficient data. Conclusion Given wider scale-up of outpatient-based and lower-level treatment of PSBI, improved data are essential to better assess the risks from neonatal gentamicin treatment without assessment of blood levels, to maximise benefit and reduce harm.

Background Febrile neutropenia (FN) remains a frequent complication in pediatric onco;logy, requiring emergency hospitalization and empirical broad spectrum antibiotics. The distinction of patients at high versus low risk for severe bacterial infection (SBI) is not fully established. The purpose of this study was to define a rule predicting the risk to develop SBI in children and adolescents with FN, based on information accessible at presentation. Procedure Information accessible within 2 hr from presentation was collected retrospectively on all pediatric cancer patients presenting with FN from 1993 to 2001 in a single institution. Patients with established SBI at presentation were excluded. After univariate analyses, two multivariate models predicting the risk of SBI were constructed and their performance evaluated using crossvalidation. Results An SBI developed in 106 (37%) of 285 episodes of 111 children. The logistic regression model outperformed the decision tree model in predicting SBI. It was based on seven variables: bone marrow involvement, no clinical signs of viral infection, high level of C-reactive protein, high hemoglobin, low leukocyte count, presence of central venous catheter, and diagnosis of pre-B-cell leukemia. At 96% sensitivity, the crossvalidated specificity was 26%, and the negative predictive value 91%. Conclusions Combining selected information accessible at presentation, SBI in FN can be predicted with clinically useful specificity maintaining very high sensitivity. Induction therapy and absence of clinical signs of viral infection were identified as new predictors of SBI. The results of this study need confirmation and refinement in prospective studies, aiming at more selective management of FN in pediatric oncology. Med Pediatr Oncol 2003;41:436–443. © 2003 Wiley-Liss, Inc.

Bacterial infections are a leading cause of the 2·9 million annual neonatal deaths. Treatment is usually based on clinical diagnosis of possible severe bacterial infection (pSBI). To guide programme planning, we have undertaken the first estimates of neonatal pSBI, by sex and by region, for sub-Saharan Africa, south Asia, and Latin America.We included data for pSBI incidence in neonates of 32 weeks' gestation or more (or birthweight ≥1500 g) with livebirth denominator data, undertaking a systematic review and forming an investigator group to obtain unpublished data. We calculated pooled risk estimates for neonatal pSBI and case fatality risk, by sex and by region. We then applied these risk estimates to estimates of livebirths in sub-Saharan Africa, south Asia, and Latin America to estimate cases and associated deaths in 2012.We included data from 22 studies, for 259 944 neonates and 20 196 pSBI cases, with most of the data (18 of the 22 studies) coming from the investigator group. The pooled estimate of pSBI incidence risk was 7·6% (95% CI 6·1-9·2%) and the case-fatality risk associated with pSBI was 9·8% (7·4-12·2). We estimated that in 2012 there were 6·9 million cases (uncertainty range 5·5 million-8·3 million) of pSBI in neonates needing treatment: 3·5 million (2·8 million-4·2 million) in south Asia, 2·6 million (2·1 million-3·1 million) in sub-Saharan Africa, and 0·8 million (0·7 million-1·0 million) in Latin America. The risk of pSBI was greater in boys (risk ratio 1·12, 95% CI 1·06-1·18) than girls. We estimated that there were 0·68 million (0·46 million-0·92 million) neonatal deaths associated with pSBI in 2012.The need-to-treat population for pSBI in these three regions is high, with ten cases of pSBI diagnosed for each associated neonatal death. Deaths and disability can be reduced through improved prevention, detection, and case management.The Wellcome Trust and the BillMelinda Gates Foundation through grants to Child Health Epidemiology Reference Group (CHERG) and Save the Children's Saving Newborn Lives programme.

Introduction Suboptimal care is frequent in the management of severe bacterial infection. We aimed to evaluate the consequences of suboptimal care in the early management of severe bacterial infection in children and study the determinants. Methods A previously reported population-based confidential enquiry included all children (3 months- 16 years) who died of severe bacterial infection in a French area during a 7-year period. Here, we compared the optimality of the management of these cases to that of pediatric patients who survived a severe bacterial infection during the same period for 6 types of care: seeking medical care by parents, evaluation of sepsis signs and detection of severe disease by a physician, timing and dosage of antibiotic therapy, and timing and dosage of saline bolus. Two independent experts blinded to outcome and final diagnosis evaluated the optimality of these care types. The effect of suboptimal care on survival was analyzed by a logistic regression adjusted on confounding factors identified by a causal diagram. Determinants of suboptimal care were analyzed by multivariate multilevel logistic regression. Results Suboptimal care was significantly more frequent during early management of the 21 children who died as compared with the 93 survivors: 24% vs 13% (p = 0.003). The most frequent suboptimal care types were delay to seek medical care (20%), under-evaluation of severity by the physician (20%) and delayed antibiotic therapy (24%). Young age (under 1 year) was independently associated with higher risk of suboptimal care, whereas being under the care of a paediatric emergency specialist or a mobile medical unit as compared with a general practitioner was associated with reduced risk. Conclusions Suboptimal care in the early management of severe bacterial infection had a global independent negative effect on survival. Suboptimal care may be avoided by better training of primary care physicians in the specifics of pediatric medicine.

Fever with no clear source of infection in children under 3 years old carries a small but important risk of sepsis and meningitis. This review describes the bacterial causes of such infection and the appropriate management in different age groups Fever in infants has been defined as a rectal temperature of 38°C (100.4°F) or higher. In older children, a rectal temperature of 38.4°C (101.1°F) or an oral temperature of 37.8°C (100°F) is generally considered abnormal.1 Most young children with fever and no focus of infection present with a self limiting viral illness that does not need any treatment and disappears without sequelae. Urinary tract infection is another important cause of fever in young children who are febrile with no focus of infection.2 However, a few children may eventually develop occult bacteraemia that may be associated with serious bacterial infection. Multiple studies have tried to identify children who seem well but have a serious infection and to evaluate the potential treatments. This review discusses the bacterial causes, essential diagnostic tests, clinical assessment, judicious use of antibiotics, and follow up in unexplained, difficult to diagnose bacterial infection causing fever in young children. I gathered information by searching Medline, using personal archives, and reading relevant literature. The review and recommendations are based on observational studies and systematic reviews. Many organisms can cause febrile occult infection in young children. Their distribution is seasonal and varies in different age groups. Substantial overlap exists, however (box 1). The main bacterial causes of infection in children aged under 1 month are listed in box 1. Viral agents (mostly Herpes simplex and enteroviruses) can also cause life threatening febrile infection in this age group.3 Most infections in children over 3 months are caused by Streptococcus pneumoniae (in non-immunised children), Neisseria meningitidis, or Salmonella spp. Staphylococcus …

BACKGROUND: Survivors of neonatal infections are at risk of neurodevelopmental impairment (NDI), a burden not previously systematically quantified and yet important for program priority setting. Systematic reviews and meta-analyses were undertaken and applied in a three-step compartmental model to estimate NDI cases after severe neonatal bacterial infection in South Asia, sub-Saharan Africa, and Latin America in neonates of >32 wk gestation (or >1,500 g). METHODS: We estimated cases of sepsis, meningitis, pneumonia, or no severe bacterial infection from among estimated cases of possible severe bacterial infection ((pSBI) step 1). We applied respective case fatality risks ((CFRs) step 2) and the NDI risk among survivors (step 3). For neonatal tetanus, incidence estimates were based on the estimated deaths, CFRs, and risk of subsequent NDI. RESULTS: For 2010, we estimated 1.7 million (uncertainty range: 1.1-2.4 million) cases of neonatal sepsis, 200,000 (21,000-350,000) cases of meningitis, 510,000 cases (150,000-930,000) of pneumonia, and 79,000 cases (70,000-930,000) of tetanus in neonates >32 wk gestation (or >1,500 g). Among the survivors, we estimated moderate to severe NDI after neonatal meningitis in 23% (95% confidence interval: 19-26%) of survivors, 18,000 (2,700-35,000) cases, and after neonatal tetanus in 16% (6-27%), 4,700 cases (1,700-8,900). CONCLUSION: Data are lacking for impairment after neonatal sepsis and pneumonia, especially among those of >32 wk gestation. Improved recognition and treatment of pSBI will reduce neonatal mortality. Lack of follow-up data for survivors of severe bacterial infections, particularly sepsis, was striking. Given the high incidence of sepsis, even minor NDI would be of major public health importance. Prevention of neonatal infection, improved case management, and support for children with NDI are all important strategies, currently receiving limited policy attention.

Serum lipopolysaccharide-binding protein is increased in a subset of non-infected ascitic cirrhotic patients, a finding previously related to bacterial passage from the gut to the circulation without overt infection. We prospectively analysed the risk factors associated with a first episode of severe bacterial infection in 84 ascitic cirrhotics, followed up for a median of 46 weeks. The cumulative probability of such infection in patients with raised and normal lipopolysaccharide-binding protein was 32.4% and 8.0% (p=0.004), respectively. Increased lipopolysaccharide-binding protein was the only factor independently associated with severe bacterial infection in a multivariate analysis (relative risk 4.49, 95% CI 1.42-14.1). Monitoring of serum lipopolysaccharide-binding protein could, therefore, help to target cirrhotic patients with ascites for antibiotic prophylaxis.

Serious bacterial infections in infants under 2-years-of-age with fever without a source remains, despite advances in vaccination, a matter of concern for both physicians and parents. Having cost-effectiveness information is relevant to guide decision making in clinical practice in this scenario. Objective: To determine the cost-effectiveness of four different strategies of screening in Argentina for serious bacterial infection in children presenting with fever without a source. Materials and methods: We designed a decision tree to model a hypothetical cohort of 10,000 children with fever without a source. We compared the incremental cost-effectiveness of four strategies to detect serious bacterial infection: Rochester criteria + C reactive protein test, Rochester criteria + procalcitonin test, Rochester criteria, and expectant observation. Results: Rochester criteria + C reactive protein test was the most cost-effective strategy with USD$ 784 for each correctly diagnosed case versus USD$ 839 of Rochester criteria + procalcitonin test, USD$ 1,116 of expectant observation or USD$ 1,193 of Rochester criteria. When the probability of serious bacterial infections was equal or less than 14%, the strategy of choice was expectant observation. Conclusions: The Rochester criteria + C reactive protein test was the most cost-effective strategy to detect serious bacterial infection in one to three months old children with fever without a source. However, in low risk settings for such infection, the strategy of choice is expectant observation.

BACKGROUND: Survivors of neonatal infections are at risk of neurodevelopmental impairment (NDI), a burden not previously systematically quantified and yet important for program priority setting. Systematic reviews and meta-analyses were undertaken and applied in a three-step compartmental model to estimate NDI cases after severe neonatal bacterial infection in South Asia, sub-Saharan Africa, and Latin America in neonates of >32 wk gestation (or >1,500 g). METHODS: We estimated cases of sepsis, meningitis, pneumonia, or no severe bacterial infection from among estimated cases of possible severe bacterial infection ((pSBI) step 1). We applied respective case fatality risks ((CFRs) step 2) and the NDI risk among survivors (step 3). For neonatal tetanus, incidence estimates were based on the estimated deaths, CFRs, and risk of subsequent NDI. RESULTS: For 2010, we estimated 1.7 million (uncertainty range: 1.1-2.4 million) cases of neonatal sepsis, 200,000 (21,000-350,000) cases of meningitis, 510,000 cases (150,000-930,000) of pneumonia, and 79,000 cases (70,000-930,000) of tetanus in neonates >32 wk gestation (or >1,500 g). Among the survivors, we estimated moderate to severe NDI after neonatal meningitis in 23% (95% confidence interval: 19-26%) of survivors, 18,000 (2,700-35,000) cases, and after neonatal tetanus in 16% (6-27%), 4,700 cases (1,700-8,900). CONCLUSION: Data are lacking for impairment after neonatal sepsis and pneumonia, especially among those of >32 wk gestation. Improved recognition and treatment of pSBI will reduce neonatal mortality. Lack of follow-up data for survivors of severe bacterial infections, particularly sepsis, was striking. Given the high incidence of sepsis, even minor NDI would be of major public health importance. Prevention of neonatal infection, improved case management, and support for children with NDI are all important strategies, currently receiving limited policy attention.

The objective of this study was to identify a short list of valid signs for the development of standard case management guidelines for severe bacterial infection (SBI) in newborn infants, an important cause of neonatal deaths in low-income countries. The reported and observed signs of 83 sick neonates admitted during 12 consecutive months were recorded. At discharge, 50 cases were classified, using predefined criteria, as SBI, mostly pneumonia, and 33 as other disease. The neonates with other diseases were significantly younger than those with SBI. None of the reported and observed signs, when used alone, had a high sensitivity, an important feature for a severe disease amenable to effective treatment. The best sensitivity (74 per cent) was obtained when a doctor observed severe chest indrawing or fast breathing or 'not looking well'; the specificity was 67 per cent and the positive predictive value 77 per cent. The sensitivity of reported difficult breathing and of observed severe chest indrawing, when measured only for the diagnosis of pneumonia, improved to 77 per cent, with a specificity of 84 per cent and 66 per cent, respectively. Reported fever and the observation that the neonate was 'not looking well' were the best independent predictors of SBI on logistic regression analysis. Simple standard case management (SCM) guidelines based only on reported and observed clinical signs would not identify the majority of neonates with SBI at primary health care level.

Background: Bacterial infections are a leading cause of the 2·9 million annual neonatal deaths. Treatment is usually based on clinical diagnosis of possible severe bacterial infection (pSBI). To guide programme planning, we have undertaken the first estimates of neonatal pSBI, by sex and by region, for sub-Saharan Africa, south Asia, and Latin America. Methods: We included data for pSBI incidence in neonates of 32 weeks' gestation or more (or birthweight ≥1500 g) with livebirth denominator data, undertaking a systematic review and forming an investigator group to obtain unpublished data. We calculated pooled risk estimates for neonatal pSBI and case fatality risk, by sex and by region. We then applied these risk estimates to estimates of livebirths in sub-Saharan Africa, south Asia, and Latin America to estimate cases and associated deaths in 2012. Findings: We included data from 22 studies, for 259 944 neonates and 20 196 pSBI cases, with most of the data (18 of the 22 studies) coming from the investigator group. The pooled estimate of pSBI incidence risk was 7·6% (95% CI 6·1-9·2%) and the case-fatality risk associated with pSBI was 9·8% (7·4-12·2). We estimated that in 2012 there were 6·9 million cases (uncertainty range 5·5 million-8·3 million) of pSBI in neonates needing treatment: 3·5 million (2·8 million-4·2 million) in south Asia, 2·6 million (2·1 million-3·1 million) in sub-Saharan Africa, and 0·8 million (0·7 million-1·0 million) in Latin America. The risk of pSBI was greater in boys (risk ratio 1·12, 95% CI 1·06-1·18) than girls. We estimated that there were 0·68 million (0·46 million-0·92 million) neonatal deaths associated with pSBI in 2012. Interpretation: The need-to-treat population for pSBI in these three regions is high, with ten cases of pSBI diagnosed for each associated neonatal death. Deaths and disability can be reduced through improved prevention, detection, and case management. Funding: The Wellcome Trust and the Bill and Melinda Gates Foundation through grants to Child Health Epidemiology Reference Group (CHERG) and Save the Children's Saving Newborn Lives programme. © 2014 Seale et al.

Introduction Severe sepsis is a disease of the microcirculation, with endothelial dysfunction playing a key role in its pathogenesis and subsequent associated mortality. Angiogenesis in damaged small vessels may ameliorate this dysfunction. The aim of the study was to determine whether the angiogenic factors (vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), and angiopoietin-1 (Ang-1) and -2 (Ang-2)) are mortality indicators in Malawian children with severe bacterial infection. Methods In 293 children with severe bacterial infection, plasma VEGF, PDGF, FGF, and Ang-1 and Ang-2 were measured on admission; in 50 of the children with meningitis, VEGF, PDGF, and FGF were also measured in the CSF. Healthy controls comprised children from some of the villages of the index cases. Univariable and multivariable logistic regression analyses were performed to develop a prognostic model. Results The median age was 2.4 years, and the IQR, 0.7 to 6.0 years. There were 211 children with bacterial meningitis (72%) and 82 (28%) with pneumonia, and 154 (53%) children were HIV infected. Mean VEGF, PDGF, and FGF concentrations were higher in survivors than in nonsurvivors, but only PDGF remained significantly increased in multivariate analysis (P = 0.007). Mean Ang-1 was significantly increased, and Ang-2 was significantly decreased in survivors compared with nonsurvivors (6,000 versus 3,900 pg/ml, P = 0.03; and 7,700 versus 11,900 pg/ml, P = 0.02, respectively). With a logistic regression model and controlling for confounding factors, only female sex (OR, 3.95; 95% CI, 1.33 to 11.76) and low Ang-1 (OR, 0.23; 95% CI, 0.08 to 0.69) were significantly associated with mortality. In children with bacterial meningitis, mean CSF VEGF, PDGF, and FGF concentrations were higher than paired plasma concentrations, and mean CSF, VEGF, and FGF concentrations were higher in nonsurvivors than in survivors (P = 0.02 and 0.001, respectively). Conclusions Lower plasma VEGF, PDGF, FGF, and Ang-1 concentrations and higher Ang-2 concentrations are associated with an unfavorable outcome in children with severe bacterial infection. These angiogenic factors may be important in the endothelial dysregulation seen in severe bacterial infection, and they could be used as biomarkers for the early identification of patients at risk of a poor outcome.

Background The term “cutaneous vasculitis” (CV) includes a wide and heterogeneous spectrum of syndromes with histopathological findings that have in common vascular inflammation and blood vessel damage. Sometimes, CV can be a clinical manifestation of a severe underlying infection and its clinical features may be indistinguishable of a non-infectious CV. However, the treatment is very different: antibiotics in the case of a CV in the setting of a severe bacterial infection and immunosuppressive agents in all other cases. Objectives Our objective was to compare the histopathological findings of skin biopsies from patients with CV associated with severe bacterial infection and those with non-infectious CV with more or less systemic involvement. Methods We selected 3 groups from a series of patients with CV: group a) CV associated with severe bacterial infection; group b) CV without severe bacterial infection but with systemic involvement, group c) CV without systemic involvement. Only cases with available skin biopsies in optimal conditions for analysis were included. We reviewed the samples by light microscopy using H&E and Schiff periodic acid stains. A comparative study between the group a) with the other two groups (b and c) was performed. Severe bacterial infection was considered when the patient required hospitalization and received antibiotics. Results Group a) was integrated by 12 patients (2 women/10 men; mean age; 56±15 years). The underlying severe bacterial infections were: pneumonia (n=5), meningitis (n=3), urinary tract infection (n=1), infectious arthritis of the knee (n=1), abdominal sepsis (n=1) and mediastinitis (n=1). In the group b) 21 patients were included (10 women/11 men; mean age, 52±18 years). The underlying conditions in this group were: Henoch-Schoenlein purpura (n=9), panarteritis nodosa (n=4), microscopic polyangiitis (n=2), cryoglobulinemia (n=2), neoplasia (n=2), systemic lupus erythematosus (n=1) and Sjogren syndrome (n=1). Finally, in group c) 19 patients were included (12 women/7 men; mean age: 59±24 years). The results of histopathological comparison of group a) with the groups b) and c) are shown in the table. Conclusions In this series we observed that patients with CV associated with severe bacterial infection have more tissue neutrophilia and tend to develop more pustular dermatosis. Rather, not lymphocytosis or tissue eosinophilia was observed. However, these results need to be tested in prospective studies with larger number of patients. Acknowledgements This study was supported by a grant from “Fondo de Investigaciones Sanitarias” PI12/00193 (Spain). This work was also partially supported by RETICS Programs, RD08/0075 (RIER) and RD12/0009/0013 from “Instituto de Salud Carlos III” (ISCIII) (Spain). Disclosure of Interest None declared

Background The prognosis of febrile neutropenia (FN) in childhood cancer has been considerably improved by the intensification of treatment, including systematic hospitalization and broad-spectrum antibiotics. As only few children present with a severe bacterial infection (SBI), clinical decision rules have been developed to distinguish those at risk for SBI. The aim of this study was to evaluate the reproducibility of six clinical decision rules proposed in the literature and to compare their performance. Methods This retrospective two-center cohort study included all episodes of chemotherapy-induced FN in children admitted between January 2005 and December 2006. Each rule was applied to our patients. Their sensitivity (Se) and specificity (Sp) were calculated and compared with the authors' results, to assess reproducibility. The most predictive rule was defined in advance as that yielding 100% Se, the highest Sp, and the greatest simplicity for bedside application. Results Three hundred seventy-seven episodes of FN in 167 patients were collected; 64 episodes were associated with SBI, including 36 with bacteremia. Four of the six rules were reproducible, but none were able to be validated. The most predictive rule for bacteremia had 96% Se (95% confidence interval (CI): 79–99%) and 25% Sp (95% CI: 19–33%), and the most predictive rule for SBI had 95% Se (95% CI: 87–98%), but no power of discrimination (Sp = 5%, 95% CI: 3–8%). Conclusion This study emphasizes the difficulty in identifying standardized decision rules in the management of a condition with numerous clinical variables like FN. Pediatr Blood Cancer. 2010;55:662–667. © 2010 Wiley-Liss, Inc.

Inhibitors of 3-hydroxy-methylglutaryl-coenzyme A (HMG-CoA) reductase have been used increasingly for the treatment of hypercholesteroaemia. Rare adverse effects of rhabdomyolysis, myopathy, cataracts, rashes, gastrointestinal symptoms, insomnia, hyperkalaemia and proteinuria have been reported. [1] In addition, a few cases of thrombocytopenia have been reported in postmarketing surveys and case reports. [2-4] In the case presented here, severe thrombocytopenia appeared to have been caused by simvastatin. The condition responded poorly to initial corticosteroid treatment, but thrombocyte recovery was initiated after severe bacterial infection. The initial thrombocyte recovery response may be via a cytokine with thrombopoietic activity such as interleukin (IL)-6, which has been shown to be released during the severe inflammatory process. [5-8]