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Metallo-β-lactamase-producing Enterobacteriaceae are emerging in the U.S. and are becoming a significant threat. Unfortunately, there is little recognition of the increasing reports of these organisms in U.S. children, a vulnerable population that may suffer severe long-term consequences., Metallo-β-lactamases (MBLs) are emerging as the most notable resistance determinants in Enterobacteriaceae. In many cases, the genes encoding MBLs are part of complex, mobile genetic elements that carry other resistance determinants. In the United States, there are increasing reports of MBL-producing Enterobacteriaceae, with New Delhi MBLs (NDMs) accounting for the majority of transmissible MBL infections. Many infections caused by NDM-producing bacteria are associated with international travel and medical tourism. However, little recognition of the introduction of MBL-producing Enterobacteriaceae into the pediatric community has followed. Reports suggest that this occurred as early as 2002. Here, we reflect on the unwelcome emergence of MBL-producing Enterobacteriaceae in US children and the available clinical and molecular data associated with spread. Since 2002, there have been disturbing reports that include the most readily transmissible MBLs, blaIMP, blaVIM, and blaNDM types. In the majority of children with available data, a history of foreign travel is absent.

OBJECTIVETo determine the prevalence and acquisition of extended-spectrum β-lactamases (ESBLs), plasmid-mediated AmpCs (pAmpCs), and carbapenemases (“MDR Enterobacteriaceae”) colonizing children admitted to a pediatric intensive care unit (PICU).DESIGNProspective study.SETTING40-bed PICU.METHODSAdmission and weekly thereafter rectal surveillance swabs were collected on all pediatric patients during a 6-month study period. Routine phenotypic identification and antibiotic susceptibility testing were performed. Enterobacteriaceae displaying characteristic resistance profiles underwent further molecular characterization to identify genetic determinants of resistance likely to be transmitted on mobile genetic elements and to evaluate relatedness of strains including DNA microarray, multilocus sequence typing, repetitive sequence-based PCR, and hsp60 sequencing typing.RESULTSEvaluating 854 swabs from unique children, the overall prevalence of colonization with an MDR Enterobacteriaceae upon admission to the PICU based on β-lactamase gene identification was 4.3% (n=37), including 2.8% ESBLs (n=24), 1.3% pAmpCs (n=11), and 0.2% carbapenemases (n=2). Among 157 pediatric patients contributing 603 subsequent weekly swabs, 6 children (3.8%) acquired an incident MDR Enterobacteriaceae during their PICU stay. One child acquired a pAmpC (E. coli containing blaDHA) related to an isolate from another patient.CONCLUSIONSApproximately 4% of children admitted to a PICU were colonized with MDR Enterobacteriaceae (based on β-lactamase gene identification) and an additional 4% of children who remained in the PICU for at least 1 week acquired 1 of these organisms during their PICU stay. The acquired MDR Enterobacteriaceae were relatively heterogeneous, suggesting that a single source was not responsible for the introduction of these resistance mechanisms into the PICU setting.Infect Control Hosp Epidemiol 2016;37:535–543

International audience; Coxiella burnetii endocarditis is a rare diagnosis in children. We present a case of Q fever endocarditis due to a new genotype, MST 54, and review recent literature on Q fever infections in children. Practitioners should consider Q fever in culture-negative endocarditis, particularly in children with congenital heart disease and history of travel or residence in endemic regions.

We report the first case of a child in the United States infected with an organism producing a Verona Integron-Encoded Metallo-β-Lactamase. This child succumbed to a ventilator-associated pneumonia caused by a Klebsiella pneumoniae producing this resistance mechanism.

Antibiotic resistance among gram-negative bacteria has reached critical levels. The rise of carbapenem resistance in Enterobacteriaceae carrying additional resistance genes to multiple antibiotic classes has created a generation of organisms nearly resistant to all available therapy. Carbapenem-resistant Enterobacteriaceae (CRE) infections are known to be associated with significant morbidity and mortality, and these pathogens have now made their way to the most vulnerable populations, including children. This review provides a brief overview of CRE, with a focus on CRE infections in children, and highlights available data on the epidemiology, clinical characteristics, carbapenemase types, risk factors, treatment, and outcomes of these multi-drug resistant infections in the pediatric population.

Macrolide resistance (MR) in group A Streptococcus (GAS) has been well documented in several countries and has become clinically significant since the large increases in macrolide usage during the 1970s. Macrolides are recommended as an alternative therapy for GAS pharyngitis, the most common cause of bacterial pharyngitis. Macrolide resistance has been associated with certain emm types, a sequence-based typing system of the hypervariable region of the GAS M-protein gene. Clinical failure of macrolide treatment of GAS infections can be associated with complications including acute rheumatic fever and rheumatic heart disease, the leading cause of acquired heart disease in children worldwide. Here we report 2 pediatric cases of MR and/or treatment failure in the treatment of GAS pharyngitis with the subsequent development of acute rheumatic fever. We also review the literature on worldwide MR rates, molecular classifications, and emm types, primarily associated with GAS pharyngeal isolates between the years of 2000 and 2010. The use of macrolides in the management of GAS pharyngitis should be limited to patients with significant penicillin allergy.

To identify a pediatric ventilator-associated condition definition for use in neonates and children by exploring whether potential ventilator-associated condition definitions identify patients with worse outcomes.Retrospective cohort study and a matched cohort analysis.Pediatric, cardiac, and neonatal ICUs in five U.S. hospitals.Children 18 years old or younger ventilated for at least 1 day.None.We evaluated the evidence of worsening oxygenation via a range of thresholds for increases in daily minimum fraction of inspired oxygen (by 0.20, 0.25, and 0.30) and daily minimum mean airway pressure (by 4, 5, 6, and 7 cm H2O). We required worsening oxygenation be sustained for at least 2 days after at least 2 days of stability. We matched patients with a ventilator-associated condition to those without and used Cox proportional hazard models with frailties to examine associations with hospital mortality, hospital and ICU length of stay, and duration of ventilation. The cohort included 8,862 children with 10,209 hospitalizations and 77,751 ventilator days. For the fraction of inspired oxygen 0.25/mean airway pressure 4 definition (i.e., increase in minimum daily fraction of inspired oxygen by 0.25 or mean airway pressure by 4), rates ranged from 2.9 to 3.2 per 1,000 ventilator days depending on ICU type; the fraction of inspired oxygen 0.30/mean airway pressure 7 definition yielded ventilator-associated condition rates of 1.1-1.3 per 1,000 ventilator days. All definitions were significantly associated with greater risk of hospital death, with hazard ratios ranging from 1.6 (95% CI, 0.7-3.4) to 6.8 (2.9-16.0), depending on thresholds and ICU type. Each definition was associated with prolonged hospitalization, time in ICU, and duration of ventilation, among survivors. The advisory board of the study proposed using the fraction of inspired oxygen 0.25/mean airway pressure 4 thresholds to identify pediatric ventilator-associated conditions in ICUs.Pediatric patients with ventilator-associated conditions are at substantially higher risk for mortality and morbidity across ICUs, regardless of thresholds used. Next steps include identification of risk factors, etiologies, and preventative measures for pediatric ventilator-associated conditions.

Background KPC-CRE are multidrug-resistant organisms (MDRO) associated with morbidity and mortality worldwide. KPC-CRE infection prevalence is increasing in the pediatric population; however, multi-centered pediatric data are lacking. We sought to identify factors for KPC-CRE infections in children and to classify genotypes of infecting strains. Methods We conducted a case–case–control study of patients (0–22 years) at 3 tertiary care medical centers in Chicago, 2008–2015. Case group 1 were children identified with KPC-CRE infections; case group 2 possessed carbapenem-susceptible Enterobacteriaceae (CSE) infections; controls (ctrls) were patients with completely negative cultures. Cases were matched to ctrls 1:1:3 by age, infection site, and hospital. Bivariate and stratified statistical analyses were performed. Molecular analysis was conducted on available isolates. Results We identified 18 KPC-CRE infections. Of 4 KPC-CRE available for molecular analysis, 3 were non-ST258 strains harboring blaKPC-2; no strains were related. Median age of KPC-CRE patients 16 (1–22) years. Differences in race, gender, LOS, and mortality were not significant. KPC-CRE and CSE infected patients were more likely to have prior MDRO (KPC-CRE 95%, CSE 11%, Ctrl 0%), long-term care facility admission (KPC-CRE 21%, CSE 17%, Ctrl 0%), and LOS >7 days before culture. Both KPC-CRE and CSE more likely had gastrointestinal (GI) comorbidities (OR: 21.9, KPC-CRE; 6.9, CSE) and >3 comorbidities (OR: 12.0, KPC-CRE; 3.5, CSE) compared with ctrls; however only KPC-CRE patients had more pulmonary and neurologic comorbidities (ORs 5.4 and 4.6), or GI and pulmonary devices (ORs 9.3 and 5.3). Compared with ctrls, CSE patients more often had prior fluoroquinolone use (OR 7.4), while KPC-CRE patients were more likely exposed to carbapenems or aminoglycosides (ORs 9.1 and 7.1). Conclusion In these children, factors associated with KPC-CRE infection reveal a high burden of disease and included pulmonary and neurologic comorbidities, GI and pulmonary devices, or exposure to carbapenems and aminoglycosides. Non-ST258 KPC-CRE strains were more common, and LOS and mortality rates were similar in all groups, which differs from adult reports. Control of CRE in children should focus on validating and mitigating these risk factors. Disclosures A. H. Bartlett, CVS Caremark: Consultant, Consulting fee; R. A. Bonomo, Merck: Grant Investigator, Research support; Allergan: Investigator, Research support; Wokhardt: Investigator, Research support; Glaxo Smith Kline: Investigator, Research support; Astra Zeneca: Investigator, Research support; Actavis: Speaker’s Bureau, Speaker honorarium

Background In theory, active surveillance of methicillin-resistant Staphylococcus aureus (MRSA) reduces MRSA spread by identifying all MRSA-colonized patients and placing them under contact precautions. In October 2007, Illinois mandated active MRSA surveillance in all intensive care units, including neonatal intensive care units (NICUs) and pediatric intensive care units (PICUs). We evaluated MRSA trends in a large metropolitan region in the wake of this law. Methods Chicago hospitals with a NICU or PICU were recruited for 8 single-day point prevalence surveys that occurred twice-yearly between June 2008 and July 2011 and then yearly in 2012 to 2013. Samples from all patients were cultured for MRSA (nose and umbilicus for neonates, nose and groin for pediatric patients). Hospital-reported admission MRSA-screening results also were obtained. Point prevalence cultures were screened for MRSA by using broth enrichment, chromogenic agar, and standard confirmatory methods. Results All eligible hospitals (N = 10) participated (10 NICUs, 6 PICUs). Hospital-reported adherence to state-mandated MRSA screening at admission was high (95% for NICUs, 94% for PICUs). From serial point prevalence surveys, overall MRSA prevalences in the NICUs and PICUs were 4.2% (89 of 2101) and 5.7% (36 of 632), respectively. MRSA colonization prevalences were unchanged in the NICUs (year-over-year risk ratio [RR], 0.93 [95% confidence interval (CI), 0.78-1.12]; P = .45) and trended toward an increase in the PICUs (RR, 1.25 [95% CI, 0.72-2.12]; P = .053). We estimated that 81% and 40% of MRSA-positive patients in the NICUs and PICUs, respectively, had newly acquired MRSA. Conclusions In a region with mandated active MRSA surveillance, we found ongoing unchanged rates of MRSA colonization and acquisition among NICU and PICU patients.

A 4-month-old boy with past medical history of eczema presented with fever and cough; a chest radiograph showed lung consolidation, and he was initially treated with amoxicillin for presumed community-acquired pneumonia. After several days, his fever persisted. He was also profoundly anemic. Antibiotic coverage was broadened because of the concern for resistant organisms; he began to improve and was discharged from the hospital. However, at 5 months of age, his fever returned, and he continued to demonstrate lung consolidation on chest radiograph. Additionally, he had lost weight and continued to be anemic. Splenic cysts were noted on abdominal ultrasound. He was diagnosed with an unusual etiology for his pneumonia and improved with the appropriate therapy. An underlying immunodeficiency was suspected, but initial testing was nondiagnostic. At 12 months of age, he presented with another infection, and the final diagnosis was made.

Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae present an ever-growing burden in the hospital and community settings, across all ages and demographics. Infections due to ESBL-containing pathogens continue to be associated with significant morbidity and mortality worldwide. With widespread empiric broad-spectrum β-lactam use creating selective pressure, and the resultant emergence of stable, rapidly proliferating ESBL-producing clones with continued horizontal gene transfer across genera, addressing this issue remains imperative. Although well characterized in adults, the epidemiology, risk factors, outcomes, therapies, and control measures for ESBL-producing bacteria are less appreciated in children. This analysis provides a brief summary of ESBL-producing Enterobacteriaceae in children, with a focus on recent clinical and molecular data regarding colonization and infection in nonoutbreak settings.

Background ESBL Ent infections are increasingly prevalent in the pediatric population; however, most ESBL Ent studies have focused on adults and/or CTX-M-type strains. We sought to characterize the molecular epidemiology of ESBL Ent strains and to identify factors associated with TEM- and SHV-type ESBL Ent (TEMSHV Ent) infections in children. Methods A case–control study of children (0–18 years) cared for by 3 Chicago hospitals during 2011–2016 was performed. Cases were 38 children with infections due to Ent harboring a lone TEM- or SHV-type ESBL as detected by DNA microarray (Check-Points®). PCR, DNA sequencing, Rep-PCR, plasmid typing, and phylogenetic grouping were also performed. Controls (ctrls) were 137 children with third-generation cephalosporin susceptible Ent infections matched by age and hospital. Demographics; patient residence; comorbidities; device, antibiotic, and healthcare exposures were evaluated. Bivariate and multivariable logistic regression analyses explored associations between predictors and TEMSHV Ent infection. Results Of 38 TEMSHV Ent infections, 74% were SHV-type and 26% TEM-type. The median age of TEMSHV Ent patients was 4.3 (0–17.9) years. Predominant organisms were Klebsiella spp. (34.2%) and E. coli (31.6%); 67% of E. coli were phylogroup B2. Most strains were unrelated; 47% were MDRO. On bivariate analysis, TEMSHV Ent patients were more likely to be male (53% vs. 34%, P = 0.04), have longer LOS after infection (35d vs. 14d, P < 0.001) but no difference in mortality, and have less UTIs (53% vs. 75%, P = 0.01) than ctrls. On multivariable analysis, children with TEMSHV Ent infections more often had recent inpatient care (OR 8.2), yet were diagnosed more frequently as outpatients (OR 25.6) and less often in NICUs (OR 0.036) than ctrls. TEMSHV Ent patients had more gastrointestinal (GI) (OR 23.7) and renal comorbidities (OR 4.2) vs. ctrls. Differences in race, gender, residential neighborhood, antibiotic exposure, and foreign bodies were not significant after controlling for other factors. Conclusion In children, factors associated with TEMSHV Ent infections include recent inpatient care and GI and renal comorbidities. Infections are associated with longer LOS but not greater mortality. Control of TEMSHV Ent infections in children should focus on validating and responding to these risk factors. Disclosures M. K. Hayden, Sage, Inc: Sage is contributing product to healthcare facilities participating in a regional collaborative on which I am a co-investigator. Neither I nor my hospital receive product., Sage is contributing product to healthcare facilities participating in a regional collaborative on which I am a co-investigator. Neither I nor my hospital receive product.; Clorox, Inc.: I have received funding from Clorox for an investigator-initiated clinical trial., Research support; CDC: Grant Investigator, Research grant; OpGen: receipt of in kind laboratory services, Research support; R. A. Bonomo, Merck: Grant Investigator and Investigator, Consulting fee and Research support; Allergan: Grant Investigator, Research support; Wockhardt: Grant Investigator, Research support; Glaxo Smith Kline: Grant Investigator, Research support; Astra Zeneca: Grant Investigator, Research support; Actavis: Speaker’s Bureau, Speaker honorarium

Pseudomonas aeruginosa is a Gram-negative pathogen commonly associated with nosocomial infections such as hospital-acquired pneumonia. It uses a type III secretion system to deliver effector proteins directly into the cytosol of host cells. Type III secretion in P. aeruginosa has been linked to severe disease and worse clinical outcomes in animal and human studies. The majority of P. aeruginosa strains secrete ExoS, a bifunctional toxin with GTPase-activating protein and ADP-ribosyltransferase activities. Numerous in vitro studies have investigated the targets and cellular effects of ExoS, linking both its enzymatic activities with inhibition of bacterial internalization. However, little is known about how this toxin facilitates the progression of infection in vivo. In this study, we used a mouse model to investigate the role of ExoS in inhibiting phagocytosis during pneumonia. We first confirmed previous findings that the ADP-ribosyltransferase activity of ExoS, but not the GTPase-activating protein activity, was responsible for bacterial persistence and decreased host survival in this model. We then used two distinct assays to demonstrate that ExoS inhibited phagocytosis during pneumonia. In contrast to the findings of several in vitro studies, this in vivo inhibition was also dependent on the ADP-ribosyltransferase activity, but not the GTPase-activating protein activity, of ExoS. These results demonstrate for the first time the antiphagocytic function of ExoS in the context of an actual infection and indicate that blocking the ADP-ribosyltransferase activity of ExoS may have potential therapeutic benefit., IMPORTANCE Pseudomonas aeruginosa is a major cause of hospital-acquired infections. To cause severe disease, this bacterium uses a type III secretion system that delivers four effector proteins, ExoS, ExoT, ExoU, and ExoY, into host cells. The majority of P. aeruginosa strains secrete ExoS, a bifunctional toxin with GTPase-activating protein and ADP-ribosyltransferase activities. In cell culture models, both enzymatic activities have been associated with decreased bacterial internalization. However, our study is the first to examine a role for ExoS in blocking phagocytosis in an animal model. We report that ExoS does inhibit phagocytosis during pneumonia. The ADP-ribosyltransferase activity, but not the GTPase-activating protein activity, of ExoS is necessary for this effect. Our findings highlight the ability of P. aeruginosa to manipulate the inflammatory response during pneumonia to facilitate bacterial survival.

Background. Extended-spectrum β-lactamase (ESBL)–producing Enterobacteriaceae infections are an emerging problem in children. We sought to identify risk factors and describe outcomes associated with pediatric ESBL-producing bacterial infections at 2 hospitals in Chicago, IL from 2008 to 2011. Methods. A case–case–control study of children aged 0–17 years was conducted. Cases of Escherichia coli, Klebsiella, and Proteus spp. ESBL-producing bacterial infections (n = 30) were compared to uninfected controls and in parallel, cases of non-ESBL–producing bacterial infections (n = 30) were compared to uninfected controls (n = 60). We then qualitatively compared these results. Results. Median age of cases was 1.06 years; 62% of isolates were from urine, and 60% were E. coli .B y multivariable analysis, ESBL cases were 5.7 and 3.3 times more likely to have gastrointestinal (P = .001; 95% confidence interval [CI] 1.9–17.0) and neurologic (P = .001; 95% CI 1.1–3.7) comorbidities, respectively, than controls; non-ESBL cases were also more likely to have gastrointestinal comorbidities than controls (P= .014; odds ratio 3.6; 95% CI 1.2–10.1). Study period prevalence remained stable (1.7%). Most (60%) infections occurred in the intensive care unit; however, 30% of children presented in the outpatient setting. Seventy-seven percent of isolates were multidrug resistant (ie, resistant to 3 antibiotic classes). Recurrence of infection occurred in 17% of ESBL cases. Crude mortality rates (7%) did not differ between cases and controls. Conclusions. The incidence of pediatric infection due to ESBL-positive Enterobacteriaceae was stable at 2 large tertiary-care medical centers over a 4-year period. Multidrug resistance in pediatric ESBL isolates is common. Risk factors for infection due to ESBL-producing bacteria include neurologic medical conditions.

We describe the first pediatric case of Gemella bergeriae endocarditis in a 15-year-old boy with tetralogy of Fallot and pulmonary atresia who presented with weight loss, chills, and cold intolerance. Blood cultures revealed Gram-positive cocci that failed to type with Lancefield group antiserum. The identification of the organism was confirmed by 16S rRNA gene sequencing.

Enterobacteriaceae infections resistant to extended-spectrum β-lactams are an emerging problem in children. We used a large database of clinical isolates to describe the national epidemiology of extended-spectrum β-lactamase (ESBL)-producing and third-generation cephalosporin-resistant (G3CR) Enterobacteriaceae.Antimicrobial susceptibilities of Klebsiella pneumoniae, Escherichia coli, and Proteus mirabilis reported to ∼300 laboratories participating in The Surveillance Network (TSN) between January 1999 and December 2011 were used to phenotypically identify G3CR and ESBL isolates cultured from patients18 years. Bi-annual trends in the prevalence of each phenotype were stratified by species, patient location, culture site, age, and region. Children of age 0-1 years were excluded from analysis as data were only available from 2010 onwards.Out of 368,398 pediatric isolates, 1.97% (7255) were identified as G3CR, and 0.47% (1734) as ESBL producers. The prevalence of both phenotypes increased, respectively, from 1.39% and 0.28% in 1999-2001 to 3% and 0.92% in 2010-2011. Trends were significant across all demographic and age groups, including outpatients, with the highest proportion of isolates in the 1-5-year-old age group. The majority of G3CR and ESBL isolates were E. coli (67.8% and 65.2%, respectively). Among ESBLs, resistance to ≥3 antibiotic classes was 74%. The lower regional prevalence of ESBL-producing bacteria in the upper Midwest relative to the rest of the country is consistent with recent local data.Rates of G3CR and ESBL infections in children are increasing in both inpatient and ambulatory settings nationally. The identification of host factors and exposures leading to infection in children is essential.

The Pseudomonas aeruginosa type III secretion system has been associated with poor outcomes in both animal models and human patients. Despite a large number of studies exploring the regulation of type III secretion in vitro, little is known about the timing of secretion during mammalian infection. Here we demonstrate that the exoU gene, which encodes the highly cytotoxic type III effector ExoU, is induced early during acute P. aeruginosa pneumonia. Immunofluorescence microscopy indicated that the amount of ExoU protein in the lung also increased over time. The importance of early expression was examined using a strain of P. aeruginosa with inducible production of ExoU. Delays in expression as short as 3 h led to reduced bacterial burdens in the lungs of mice and improved survival. Our results demonstrate that early expression of exoU is critical to bacterial survival during pneumonia and suggest that therapeutic interventions that delay ExoU secretion for even short periods of time may be efficacious., IMPORTANCE Pseudomonas aeruginosa is a major contributor to the large numbers of health care-associated infections occurring annually, particularly for immunocompromised patients. Although this organism possesses many virulence factors, the type III secretion system plays an especially important role in both animal models and humans. This system forms a needle-like apparatus that injects toxins directly into eukaryotic cells. The most toxic protein secreted by this molecular machine is ExoU, which causes rapid cell death. In this study, we demonstrated that exoU was expressed and ExoU was produced early during acute pneumonia in a mouse model. Delaying expression of exoU by as little as 3 h enhanced clearance of bacteria and survival of infected mice. Our findings highlight the importance of understanding the regulation of virulence factor expression during infection when designing therapeutic strategies to inhibit the toxic effects of these proteins.

Enterovirus is a known cause of central nervous system infection in the neonatal population and typically has a benign course; however, neurologic complications have been reported. We describe what we believe to be the first documented case of enteroviral meningoencephalitis complicated by central diabetes insipidus in a neonate.

Herpes simplex virus (HSV) of the newborn affects 1 in 3200 [1] live births in the United States, and can be acquired by the intrauterine or intrapartum route, or postnatally. Intrauterine or congenital infection represents the rarest form (5% of cases) [2] and frequently has devastating consequences such as congenital brain malformation and severe neurocognitive impairment leading to fetal or neonatal death [3]. Here we present two cases of fatal intrauterine HSV infection in monochorionic twin infants. CASE A 21-year-old secundigravida mother with twin gestation of 26-4/7 weeks presented with spontaneous rupture of membranes of clear amniotic fluid 11 hours prior to delivery. She had negative prenatal laboratory studies for hepatitis B, syphilis, human immunodeficiency virus (HIV), and an unknown group B streptococcus status. Her sexually transmitted infection history included chlamydia trachomatis infection treated during early pregnancy and no history of HSV in herself or her sexual partner. A structural survey 1 week prior to delivery revealed severe hydrops and hydranencephaly in the first twin, and moderate hydrocephalus in the second twin. The mother was afebrile, well-appearing, and reported no history of recent illness or genital lesions before or during either of her pregnancies. Both mother and father refused HSV serologic testing. The first twin boy was delivered via cesarean section with Apgar scores of 1, 2, and 3, at 1, 5, and 10 minutes, respectively. The infant was apneic, unresponsive to resuscitation efforts, and died shortly after birth. On autopsy, gestation was shown to be monochorionic–monoamniotic, and the placenta had evidence of acute chorioamnionitis; however, it was not tested for the presence of HSV. The intracranial cavity was composed of hemorrhagic fluid and fragments of parenchymal tissue with extensive necrosis and chronic inflammation, consistent with meningoencephalitis, and the liver was calcified and necrotic. Viral immunostaining revealed the presence of HSV in the adrenal gland and brain parenchyma, and no virus was detected in the liver. No viral cultures were performed on autopsy tissue due to formalin fixation, and surface cultures for HSV were not performed. The second twin boy had Apgar scores of 5, 7, and 8 at 1, 5, and 10 minutes, respectively. He was immediately intubated for respiratory distress, received inotropes and intravenous fluids for hypotension, and was given ampicillin and gentamicin for presumed sepsis. At 5 hours of life, vesicular skin lesions on the neck were noted on physical examination (PE). PE was otherwise unremarkable. HSV studies were sent from the skin lesion (neck), mucosal surfaces (eyes, mouth, rectum), and cerebrospinal fluid (CSF), and empiric acyclovir 20 mg/kg every 8 hours was started. Initial white blood cell (WBC) count, platelet count, liver function, and serum electrolytes were normal. The CSF revealed 111 WBC/mm 3 with a lymphocytic predominance, 7600 red blood cells/mm 3 , protein 1245 mg/dL, and glucose 21 mg/dL. Blood and CSF bacterial cultures were sterile. Toxoplasma immunoglobulin M antibody, cytomegalovirus (CMV), and parvovirus B-19 polymerase chain reaction (PCR) yielded negative results. PCR was positive for HSV type 2 (HSV-2) and negative for HSV type l from all five tested sites.

Acute necrotising ulcerative gingivitis is an acute onset disease characterised by ulceration, necrosis, pain and bleeding in gingival surfaces. It is predominantly seen in severely malnourished children and young adults with advanced HIV infection. We present a unique presentation in a young adult with high-grade osteogenic sarcoma.

Summary Objectives To determine risk factors in children for the acquisition of Brucella, clinical presentation, treatment, and disease outcomes. Methods A retrospective multicenter chart review was undertaken of children identified with brucellosis from 1986 to 2008 at three tertiary care centers in Chicago, Illinois, USA. The charts were reviewed for data regarding risk factors for acquisition, clinical presentation, and outcomes. Results Twenty-one charts were available for review. The median age was 6.5 years (range 2–14 years); 62% were female. Ethnic background was 67% Hispanic and 24% Arabic. Risk factors included travel to an endemic area (86%), particularly Mexico, and consumption of unpasteurized milk products (76%). Common findings included fever (95%), bacteremia (86%), elevated liver transaminases (80%), constitutional symptoms (76%), splenomegaly (60%), and hepatomegaly (55%). Relapse occurred in three of six subjects started on single drug treatment, but in only one of 15 subjects who started on two or more drugs ( p =0.053). No relapses occurred in children whose initial therapy included rifampin or those administered three-drug regimens. Conclusions Brucella is an infrequent pathogen but should be considered in children with compatible epidemiologic and clinical characteristics. Blood cultures should be obtained, and initial therapy with two or more drugs may decrease the risk of relapse.