Rothia mucilaginosa bacteremia: A 10‐year experience of a pediatric tertiary care cancer center

Rothia mucilaginosa is part of the oral and upper respiratory tract flora. Usually, this gram‐positive coccus is not pathogenic; however, in the setting of immunosuppressed hosts, it can cause life‐threatening infections as an opportunistic pathogen. Among a cohort of 1511 hematologic‐oncologic patients at a pediatric tertiary care cancer center, we identified five cancer patients (0.35%) within a period of 10 years having a proven Rothia mucilaginosa bacteremia (1 culture positive: n = 3/5; > 1 culture positive: n = 2/5). With prompt and adequate antibiotic treatment, infection resolved rapidly before recovery of neutrophils and without any sequelae, suggesting that Rothia mucilaginosa bacteremia without organ involvement is not exceptionally problematic in pediatric cancer patients.     

Bacteremia in children at the University Hospital in Riyadh, Saudi Arabia

Background  Bacteremia is a major pediatric health care problem despite the availability of new modalities in the management of this disease. The aim of the present study was to determine the incidence and pattern of bacteremia in pediatric group at a tertiary hospital in Riyadh, Saudi Arabia. Methods  This retrospective study was conducted at the Department of Pediatrics, College of Medicine, King Khalid University Hospital, Riyadh in the period of January 2003 to January 2005. Positive culture was found in 259 patients aged below 15 years with a total of 8244 admissions in the period. Results  The highest incidence of bacteremia was found in patients aged less than 1 year (57.9%), and the majority of patients (30.5%) were infants aged less than 1 month. Staphylococcus aureus was the most common isolated pathogen (18.7%). Prematurity was associated with 13.2% of the cases, and respiratory tract infection (10.1%) and fever (76.1%) were chief complaints. Conclusions   Staphylococcus aureus is the most common isolated pathogen. The most common primary infections are respiratory tract infection and septic meningitis. Klebsiella pneumoniae and E. coli are the most common isolated Gram-negative organisms.     

Early administration of Bifidobacterium breve to preterm infants: randomised controlled trial

AIM—To investigate the colonisation with Bifidobacterium breve of the bowels of very low birthweight (VLBW) infants.METHODS—The adverse effects of B breve were examined in 66 VLBW infants (preliminary study). A prospective randomised clinical study of 91 VLBW infants was also completed and these infants were followed up for three years. Precise viable bacterial counts of serial stool specimens were examined for the first eight weeks after birth in 10 infants. The colonisation rates of administered bacteria were examined using immunohistochemical staining of stool specimens with a B breve specific monoclonal antibody.RESULTS—In the preliminary study there were no side effects attributable to the bacteria. Immunohistochemical staining of stool specimens showed that the colonisation rates of the administered bacteria were 73% at 2 weeks of age, but only 12% in the control group. Early administration of B breve significantly decreased aspirated air volume from the stomach and improved weight gain.CONCLUSIONS—B breve can colonise the immature bowel very effectively and is associated with fewer abnormal abdominal signs and better weight gain in VLBW infants, probably as a result of stabilisation of their intestinal flora and accelerated feeding schedules.     

Novel mutations in SH3TC2 in a young Japanese girl with Charcot‐Marie‐Tooth disease type 4C

Charcot‐Marie‐Tooth disease type 4C (CMT4C) is an autosomal recessive demyelinating form of CMT characterized clinically by early onset and severe spinal deformities, and is caused by mutations in SH3TC2. We describe the case of a 10‐year‐old Japanese girl diagnosed with CMT4C. The patient developed progressive foot deformities such as marked pes cavus and ankle contracture, with mild muscle weakness in both legs, and generalized areflexia. On electrophysiological studies, motor nerve conduction velocity ranged from 22.3 m/s in the tibial nerve to 48.2 m/s in the median nerve. Sensory nerve conduction velocity ranged from 30.3 m/s in the sural nerve to 52.8 m/s in the median nerve. Sequence analysis of candidate genes identified two novel heterozygous mutations, c.229C>T and c.2775G>A, in SH3TC2. The patient was diagnosed as having CMT4C with novel mutations, making this the first documented Japanese pediatric case.     

Donor‐derived strongyloidiasis in a Saudi pediatric kidney transplant recipient: A case report and mini‐review

S. stercoralis infection has been identified as a donor‐derived infection in cases of solid organ transplant among recipients with no prior risk factor for parasitic exposure. Worldwide and regional reports from the adult kidney transplant population highlight this indirect method of infection and caution about delayed diagnosis, severe complications, and death related to donor‐derived S. stercoralis infection. We report a deceased‐donor‐derived S. stercoralis infection in a 12‐year‐old Saudi girl who underwent kidney transplantation. This is the first pediatric case reported outside the United States of America. Although she presented with mild bouts of gastrointestinal symptoms, the need for additional immune suppression put her at risk of serious complications. A literature review highlights the importance of awareness about S. stercoralis infections and complications in kidney transplant recipients, pretransplant screening of donors based on risk assessment, and the challenges with treatment availability and duration in this vulnerable population.     

Persistent coagulase-negative staphylococci bacteremia in very-low-birth-weight infants

This study sought to expand current knowledge on the clinical and epidemiological characteristics of persistent coagulase-negative Staphylococcus (CoNS) bacteremia in very-low-birth-weight (VLBW) infants. Background and disease-related data were collected prospectively on 143 VLBW infants diagnosed with CoNS bacteremia at a pediatric tertiary medical center in 1995–2003. Findings were compared between those with persistent (positive blood cultures for >72 h under appropriate treatment ) and nonpersistent disease. Fifty-eight infants (40.6%) were found to have persistent bacteremia. There were no between-group differences in maternal characteristics, mode of delivery, newborn characteristics, dwell time of central venous and umbilical catheters, complications of prematurity, or mean hospital stay. The persistent bacteremia group had significantly higher rates of hypothermia at presentation (37.9% vs. 17.6%, p < 0.04), creatinine >1.2 mg% on treatment day 7 (13.7% vs. 2.4%, p < 0.02; transient phenomenon), and endocarditis (p < 0.03); one infant had an aortic thrombus. Predominantly breast-fed infants had a higher rate of negative cultures within 72 h of appropriate treatment than predominantly formula-fed infants (60% vs. 19%, p < 0.02). In conclusion, persistence of CoNS bacteremia is common in VLBW infants. Endocarditis should be excluded in all infants with persistent disease. Breast-feeding is associated with a shorter disease duration.     

Colistin administration to pediatric and neonatal patients

Emergence of multidrug-resistant Gram-negative nosocomial pathogens has led to resurgence of colistin use. Safety and efficacy data regarding colistin use in pediatric patients are sparse, while optimal dosage has not been defined. We present a case series of neonates and children without cystic fibrosis treated with various doses of colistin intravenously. The records of patients who received colistin in a tertiary-care hospital from January 2007 to March 2009 were reviewed. Thirteen patients (median age 5 years, range 22 days to 14 years) received 19 courses of colistin as treatment of pneumonia, central nervous system infection, bacteremia, or complicated soft tissue infection. The isolated pathogens were Acinetobacter baumannii, Enterobacter cloacae, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. Daily dose of colistin (colistimethate) ranged between 40,000 and 225,000 IU/kg. Duration of administration ranged from 1 to 133 days. Other antimicrobials were co-administered in 18/19 courses. Increase of serum creatinine in one patient was associated with co-administration of colistin and gentamicin. Sixteen of 19 courses had a favorable outcome, and only two of the three deaths were infection-related. Colistin intravenous administration appears well tolerated even at higher than previously recommended doses and of prolonged duration.     

Effects of the influenza vaccine on pediatric kidney transplant outcomes

The influenza vaccine is critical for preventing influenza‐related complications in transplant patients. Previous studies demonstrated de novo donor‐specific antibody formation and rejection following the influenza vaccination. This risk has not been adequately assessed in the pediatric population. We performed a single‐center retrospective analysis of 187 unique pediatric kidney transplant recipients, transplanted from January 1, 2006, to December 31, 2015, assessing for an association of the influenza vaccination with various transplant outcomes. The influenza vaccine was received by 125 of 187 patients within the first year post‐transplant. Using log‐rank tests and Kaplan‐Meier curves, vaccinated patients had a significantly lower risk of mortality (P = 0.048). There were no differences in death‐censored graft survival (P = 0.253), graft survival (P = 0.098), or rejection (P = 0.195) between vaccinated and unvaccinated groups. To address the problem of multiple exposures for a yearly vaccine, Cox proportional hazards regression was utilized with post‐transplant vaccination status considered as a time‐dependent covariate; analyses were performed using both a 360‐ and 180‐day vaccination period following any post‐transplant influenza vaccination. In this model, being vaccinated did not result in a significant difference in mortality (HR 0.90 [0.16, 5.15], P = 0.91), death‐censored graft survival (HR 0.70 [0.31, 1.58], P = 0.39), graft survival (HR 0.69 [0.32, 1.49], P = 0.34), or rejection (HR 0.67 [0.37, 1.19], P = 0.17). Eight patients developed de novo donor‐specific antibodies following the first post‐transplant influenza vaccination; three then developed biopsy‐proven rejection. These results suggest influenza vaccination is safe in pediatric kidney transplant recipients, and larger prospective studies are required to conclusively confirm our findings.     

Increased p53 protein expression as a potential predictor of early relapse after hematopoietic stem cell transplantation in children with acute myelogenous leukemia

Dysregulation of genes involved in the cell cycle such as TP53, P21, P16, and PTEN plays a key role in oncogenesis. We have earlier reported increased expression of the TP53 encoded protein p53, in bone marrow samples from pediatric patients with more aggressive, rare chronic myeloid malignancies. The aim of this study was to investigate protein expression of p53, p21, p16, and PTEN before and after HSCT in pediatric patients with AML and evaluate whether any potential alterations could predict relapse after HSCT. Paraffin‐embedded bone marrow samples from 34 pediatric patients with AML were collected retrospectively from time of diagnosis as well as pre‐ and post‐HSCT. IHC was performed on tissue microarrays with antibodies against p53, p21, p16, and PTEN. Study material was analyzed by independent t‐tests and nonlinear regression. t‐Tests showed a statistical significant difference in p53 (p = 0.010) with overexpression in the group of patients who relapsed compared to the relapse‐free patients at >3–6 months post‐HSCT. Analysis of p53 protein expression by IHC may be a potential predictor for relapse after HSCT in children with AML.     

Impact of center volume and the adoption of laparoscopic donor nephrectomy on outcomes in pediatric kidney transplantation

Reports for pediatric kidney transplant recipients suggested better outcomes for ODN compared to LDN. Contemporary outcomes stratified by donor type and center volume have not been evaluated in a national dataset. UNOS data (2000‐2014) were analyzed for pediatric living donor kidney transplant recipients. The primary outcome was GF; secondary outcomes were DGF, rejection, and patient survival. Live donor nephrectomies for pediatric recipients decreased 30% and transitioned from ODN to LDN. GF rates did not differ for ODN vs LDN (P = .24). GF was lowest at high volume centers (P < .01). Donor operative approach did not contribute to GF. LDN was associated with less rejection than ODN (OR 0.66, CI 0.5‐0.87, P < .01). Analysis of the 0‐ to 5‐yr recipient group showed no effect of ODN vs LDN on GF or rejection. For the contemporary era, there was no association between DGF and LDN in the 0‐ to 5‐yr group (OR 1.12, CI 0.67‐1.89, P = .67). Outcomes of kidney transplants in pediatric recipients following LDN have improved since its introduction and LDN should be the approach for live donor nephrectomy regardless of recipient age. The association between case volume and improved outcomes highlights future challenges in organ transplantation.     

The Effects of Bifidobacterium breve Administration on Campylobacter Enteritis

We studied the effects of Bifidobacterium breve on Campylobacter enteritis. Patients with Campylobacter enteritis were divided into three groups (I. Erythromycin recipients; II. B. breve recipients; III. control) and studied with regard to the duration of diarrhea and carriage of Campylobacter jejuni in the stools. Additional studies were performed to observe the effects of B. breve on fecal flora. The results showed that there were no significant differences in the duration of diarrhea among the three groups. Comparison of the duration of C. jejuni carriage in the stools was as follows: KIKIII (P<0.01). Microbiological study of fecal flora demonstrated that the number of bifidobacterium was decreased in Campylobacter enteritis compared to the control, and an increase in the number of bifidobacterium could be recognized after the administration of B. breve. B. breve was useful in eradicating C. jejuni from the stools and restoring the normal intestinal flora in Campylobacter enteritis, although if was not effective in shortening the duration of diarrhea.     

Eplet incompatibility in pediatric renal transplantation

Eplet incompatibility appears to be a better predictor of the de novo appearance of DSA post‐Tx than HLA antigen matching in adults. We evaluated the HLA Matchmaker® software (version 2.1) in our pediatric cohort to predict the appearance of DSA post‐Tx. We included 70 pediatric patients (26 girls, 10 living donors, mean age 11.2 ± 3.9 years) after a first R‐Tx (January 2010‐August 2016), without prior immunization, having complete HLA typing (A, B, C, DRB1 and DQB1) and DSA follow‐up for at least one year. The mean of HLA and eplet incompatibilities was 4.7 ± 1.3 and 15.5 ± 6.1, respectively, with a correlation coefficient r² between these two variables of 0.34 (P < .001). The eplet load was 12.8 ± 5.0 in living donors vs 15.9 ± 6.2 in deceased donors (P = NS), 12.6 ± 6.1 in preemptive R‐Tx (n = 14) vs 16.3 ± 5.9 for non‐preemptive R‐Tx (P = .04). Seven patients (10%) developed DSA during the 3.5 ± 1.2 years post‐Tx. The eplet load was 13.7 ± 5.5 for those who developed DSA vs 15.7 ± 6.1 for the others (P = NS). In our single‐center series of pediatric R‐Tx with good HLA matching and lower eplet load than previously published series, eplet incompatibilities do not predict the development of DSA. The question of the HLA matching requirement and the daily interest of the HLA Matchmaker® software to help select the grafts remain open.     

Clostridium difficile infection mimics intestinal acute cellular rejection in pediatric multivisceral transplant—A case series

Clostridium difficile infection (CDI) is the most common health care‐associated infection in the United States. Thirty‐nine percent of intestinal transplant recipients may develop CDI. Induction of rejection has been reported as a rare event. To our knowledge, this will be the second report of an association between CDI and rejection in the literature. We describe our experience with four pediatric MVT recipients, three of whom on treatment of their CDI alone had resolution of biopsy findings of intestinal ACR. Our patients were males aged 2‐5 years old who had their first CDI post‐MVT occurring from 2 months to 15 months post‐transplant. All first episodes of CDI were treated with a 10‐14 day course of metronidazole with one additionally receiving vancomycin. All four recipients had recurrent CDI, and two recipients had septic shock as a manifestation of their CDI. Three recipients had biopsies showing mild rejection during episodes of CDI, and treatment of the CDI resulted in resolution of biopsy findings of rejection. Our case series suggests CDI may mimic ACR on intestinal biopsy. Treatment of rejection during active CDI carries the risk of over‐suppression and worsening of CDI. Our experience has taught us that surveillance endoscopy for rejection may be deceiving during an active CDI, and if mild acute rejection is noted during active CDI, treatment of rejection can be safely delayed and potentially avoided.     

Effects of opaque,weighted bottles on maternal sensitivity and infant intake

Caregivers' abilities to assess how much is in the bottle may lead to encouragement of infant bottle emptying and overfeeding. The present study assessed whether use of opaque, weighted bottles (as compared with conventional, clear bottles) improves feeding outcomes. Mothers with infants <32 weeks of age (n = 76) were assessed on two separate days. Mothers fed their infants from an opaque, weighted bottle on 1 day and a clear bottle on the other; conditions were counterbalanced. Blinded raters certified in the Nursing Child Assessment Feeding Scale scored all videos to determine maternal sensitivity. Infant intake was assessed by weighing the bottle before and after each feeding, and feeding outcomes included infant intake (mL), intake per kilogram body weight (mL/kg), meal duration (min), and feed rate (mL/min). Mothers exhibited significantly greater sensitivity (p = 0.041), fed their infants fewer millilitres per kilogram body weight (p = 0.049), and fed their infants at a significantly slower rate (p = 0.009) when using opaque compared with clear bottles. Infant clarity of cues was a significant moderator of effects of bottle type on intake per kilogram body weight (p = 0.028): Infants who exhibited greater clarity of cues were fed less during the opaque versus clear conditions whereas infants who exhibited poorer clarity of cues were fed similar amounts during both conditions. Effects of bottle type were not moderated by bottle contents (expressed breast milk vs. formula). In sum, promotion of opaque, weighted bottles for infant feeding may be a pragmatic approach to improve the quality and outcome of bottle‐feeding interactions.     

Determination of risk factors affecting mortality in patients with gastrointestinal perforation after pediatric liver transplantation

Gastrointestinal perforation (GIP) is one of the most serious complications occurring after liver transplantation (LT), especially in pediatric patients. This study aimed to determine the risk factors affecting mortality in pediatric patients with GIP after LT. GIP developed in 37 (10%) of 370 pediatric patients who underwent LT at our institute. Patients were divided into two groups: alive (n = 22) or dead (n = 15), and both groups were compared in terms of demographic and clinical parameters using univariate analysis. There was no statistically significant difference between groups in either demographic or clinical parameters, except for perforation site (P = 0.001) and median follow‐up (P = 0.001). Stomas arose in 17 (45.9%) patients: 76% of patients with stomas and 45% of those without survived (P = 0.052). Kaplan‐Meier analysis indicated that patients with stomas had a significantly higher overall survival (P = 0.029) and that patients with duodenal and colonic perforation had a significantly lower overall survival. Multivariate analysis showed that re‐perforation was an independent risk factor for mortality (P = 0.035; OR: 17.674; 95% CI for OR: 1.233‐253.32). Although there are many options for management of GIP, including primary repair, resection plus anastomosis, and resection plus end or loop ostomy, gastrointestinal diversion is still the best option.     

Factors predicting occult bacteremia in young children

A febrile child without a definite localizing sign of infection may be in initial phase of bacteremia which unless treated would result in systemic complication. These instances are referred to as “Occult bacteremia”. The common pathogens isolated in these children areStreptococcus pneumoniae, Hemophilus influenzae andNeisseria meningitidis. A hundred consecutive children in the age group of 3–36 months attending pediatric outpatient department and casualty were clinically evaluated using AIOS (acute illness observation scale) score and were subjected to complete blood counts, smear for malarial parasites, ESR and blood culture. In the 19-month study period, 4 instances of occult bacteremia were identified.Streptococcus pneumoniae was cultured in 3 cases andH. influenzae in one. A febrile and toxic child in the age group of 3–36 months has a high risk of occult bacteremia. High fever of temperature ≥ 102°F, ESR ≥ 15 mm/hour, and total leukocyte count ≥ 15,000 / mm³, in a child with AIOS score of ≥ 10 may be considered for more detailed investigations and early intervention with antimicrobial therapy.     

Pediatric superior vena cava syndrome: An evidence‐based systematic review of the literature

Superior vena cava syndrome (SVCS) results in vascular, respiratory, and neurologic compromise. A systematic search was conducted to determine the prevalence of pediatric SVCS subtypes and identify clinical characteristics/treatment strategies that may influence overall outcomes. Data from 101 case reports/case series (142 patients) were analyzed. Morbidity (30%), mortality (18%), and acute complications (55%) were assessed as outcomes. Thrombosis was present in 36%, with multi‐modal anticoagulation showing improved outcome by >50% (P = 0.004). Infant age (P = 0.04), lack of collaterals (P = 0.007), acute complications (P = 0.005), and clinical presentation may have prognostic utility that could influence clinical decisions and surveillance practices in pediatric SVCS.     

Outcome of antibody‐mediated rejection compared to acute cellular rejection after pediatric heart transplantation

Outcomes of ACR after pediatric HTx have been well described, but less has been reported on outcomes of AMR. We compared the clinical characteristics and cardiovascular outcomes (composite end‐point of death, retransplantation, or allograft vasculopathy) of pediatric HTx recipients with AMR, ACR, and no rejection in a retrospective single‐center study of 104 recipients. Twenty were treated for AMR; 15 were treated for ACR. Recipients with AMR had an increased frequency of congenital heart disease (90% vs ACR 67% vs no rejection 59%, P = .03), homograft (68% vs 7% vs 18%, P < .001), HLA sensitization (45% vs 13% vs 13%, P = .008), and positive cross‐match (30% vs 7% vs 9%, P = .046). AMR caused hemodynamic compromise more often than ACR (39% vs 4%, P = .02). AMR recipients had worse cardiovascular outcome than recipients with ACR or no rejection (40% vs 20% vs 8.6%, P = .003). In bivariate Cox analysis, AMR (HR 4.1, CI 1.4‐12.0, P = .009) and ischemic time (HR 1.6, CI 1.1‐2.3, P = .02) were associated with worse cardiovascular outcome; ACR was not. In summary, pediatric HTx recipients who develop AMR have worse cardiovascular outcome than recipients who develop only ACR or experience no rejection at all.     

Successful lung donation at the age of 6 weeks: Challenges and lessons learned

A clinical case of successful procurement and transplantation of bilateral lungs from 6‐week‐old infant with sepsis secondary to bacterial meningitis is reported. Forty‐one‐day‐old male infant (height 60 cm, weight 4 kg) died of cerebral edema secondary to Escherichia coli meningitis and bacteremia. Preretrieval assessment included the following: arterial gases; pO₂ 50.4 kPa (378 mm Hg), pCO₂ 4.9 kPa (37 mm Hg), on FiO₂ 100%, PEEP 5 cm H₂O. Fiberoptic bronchoscopy showed no secretions nor mucosal inflammation; CXR revealed clear lung fields and pleural spaces. Inspection revealed dense adhesions in pericardial cavity and purulent left hemithorax effusion (urgent Gram‐stain came back as negative) but there was no consolidation in the lung. Good compliance of the lungs on inflation/deflation test was observed. The lungs were retrieved using the technique described. The recipient was a 4‐month‐old infant with alveolar capillary dysplasia and malaligned pulmonary veins. Implantation of the lungs was performed via bilateral thoracosternotomy on cardiopulmonary bypass, cooling to 30°C. Elective support with nitric oxide was used postoperatively. Two years after the transplantation, the recipient doing well with normal lung function. Lung procurement from a 6‐week donor with infectious complications and prolonged ventilation is a challenging undertaking but can be successful and should be attempted whenever possible given the paucity of organs available for pediatric recipients.     

BK virus nephropathy in a pediatric heart transplant recipient with post‐transplant lymphoproliferative disorder: A case report and review of literature

BKV is known to cause allograft failure in kidney transplant recipients. It has been recently recognized to cause native kidney nephropathy in non‐kidney transplant recipients. This is a case report BKVN in a 15‐yr‐old HTx recipient who had PTLD and a review of pediatric cases in the literature. The patient was diagnosed with BKVN +189 months after transplantation and died thirty days after diagnosis of BKVN. We identified five other cases of BKVN in pediatric non‐kidney solid organ transplantation, of which all were HTx recipients. Overall, outcome was poor and BKV clearance was not achieved with reduction of immunosuppression and with current therapies. We strongly recommend that pediatric HTx recipients be tested for BKV infection if there is evidence of kidney dysfunction. We also recommend that they have an annual screening for BKV viruria and viremia with the assessment of kidney function.