Barbara A. Jantausch

Relationship among vesicoureteral reflux, P-fimbriated Escherichia coli, and acute pyelonephritis in children with febrile urinary tract infection

Ninety-four children with febrile urinary tract infection were studied prospectively to determine the relationship between vesicoureteral reflux, P-fimbriated Escherichia coli, and acute pyelonephritis, and to evaluate the diagnostic reliability of commonly used clinical and laboratory observations. By using renal scan with dimercaptosuccinic acid labeled with technetium 99m as the standard of reference, we documented acute pyelonephritis in 62 (66%) of 94 patients. Vesicoureteral reflux was demonstrated in 29 (31%) of the total group and in only 23 (37%) of 62 patients with pyelonephritis. Of the 70 E. coli urinary isolates, 48 (69%) were P-fimbriated, including 30 (64%) of 47 isolates from patients with pyelonephritis and 18 (78%) of 23 isolates from patients with normal renal scans. The prevalence of P-fimbriated E. coli in patients with pyelonephritis and vesicoureteral reflux was 46%, compared with 71% in those with pyelonephritis who had no concurrent vesicoureteral reflux (p = 0.222). Multiple clinical and laboratory variables commonly used in the diagnosis of acute pyelonephritis did not adequately predict the presence or absence of parenchymal involvement. These data show the following: (1) Acute pyelonephritis in the absence of demonstrable vesicoureteral reflux is common. (2) Febrile urinary tract infections in children are commonly associated with P-fimbriated E. coli, both in the presence and absence of vesicoureteral reflux. (3) The presence of P fimbriae alone does not fully explain the pathophysiology of renal parenchymal invasion by bacteria in the absence of vesicoureteral reflux. (4) The diagnosis of acute pyelonephritis in children with febrile urinary tract infections on the basis of clinical and laboratory observations is unreliable.

Linezolid versus vancomycin in the treatment of known or suspected resistant gram-positive infections in neonates.

Background. Gram-positive infections caused by susceptible and resistant strains of Staphylococcus aureus, coagulase-negative staphylococci and enterococci are increasing problems in neonates. Linezolid, a new oxazolidinone, is active against these pathogens and has recently been approved by the Food and Drug Administration for treating Gram-positive infections in pediatric patients. Objective. To compare the clinical efficacy and safety of intravenous and oral linezolid with vancomycin (10 to 15 mg/kg every 6 to 24 h) in neonates (age 0 to 90 days). Methods. Hospitalized infants with known or suspected hospital-acquired pneumonia, complicated skin or skin structure infections, bacteremia or other infections (e.g. pyelonephritis, abdominal abscess) were eligible. Test-of-cure clinical response was evaluated at follow-up. Results. Sixty-three neonates, randomized 2:1 to linezolid (n = 43) or vancomycin (n = 20) were included in the intent-to-treat group. Clinical cure rates at follow-up in the intent-to-treat group were higher, but not significantly different, for linezolid vs. vancomycin (78%vs. 61%; P = 0.196). Corresponding cure rates in clinically evaluable patients were 84%vs. 77% (P = 0.553) for linezolid and vancomycin, respectively. Pathogen eradication rates were as follows in the linezolid and vancomycin groups, respectively:S. aureus (67% vs. 60%; P = 0.850); coagulase-negative staphylococci (88%vs. 100%; P = 0.379); and enterococci (71%vs. 0%; P = 0.168). Results for hematology and chemistry assays were similar between treatment groups. Fewer linezolid-treated neonates had drug-related adverse events than vancomycin-treated neonates (12%vs. 32%; P = 0.058). Conclusions. Linezolid is well-tolerated and as effective as vancomycin in the treatment of resistant Gram-positive infections in neonates.

Urinary interleukin-6 and interleukin-8 in children with urinary tract infection

Abstract Urinary interleukin-6 (UIL-6) and urinary interleukin-8 (UIL-8) concentrations were measured by immunoassay in 39 and 34 patients respectively, hospitalized with febrile urinary tract infection (UTI), and in 37 and 32 age-, race- and sex-matched febrile control children respectively, with negative urine cultures. UIL-6 and UIL-8 concentrations, measured in picograms per milliliter and corrected for creatinine, were compared with clinical and laboratory indicators of inflammation and bacterial virulence factors of Escherichia coli. Median UIL-6 concentrations at the time of admission were 397 pg/ml (range 0–65,789 pg/ml) in the 37 patients compared to 0 pg/ml (range 0–473.8 pg/ml) in the 37 controls (P<0.0001). Median UIL-8 concentrations at the time of admission were 5809 pg/ml (range 0–347,368 pg/ml) in the 32 patients compared to 0 pg/ml (range 0–2231 pg/ml) in the 32 controls (P<0.0001). UIL-6 and UIL-8 concentrations were lower (P<0.0001 for UIL-6 and P=0.0005 for UIL-8) in follow-up urine samples from UTI patients, obtained 48 h after the initiation of antibiotic therapy. UIL-6 and UIL-8 concentrations were statistically significantly correlated with urine white blood cells (WBC). UIL-8 concentrations were elevated in patients with E. coli organisms producing hemolysin. UIL-6 and UIL-8 are elevated in children with febrile UTI and decrease in response to antibiotic therapy. Magnitude of UIL-8 response is associated with hemolysin production, a bacterial virulence factor of E. coli. UIL-6 and UIL-8 concentrations are statistically correlated with urine WBC. UIL-6 and UIL-8 may be mediators of inflammation in children with febrile UTI.

Eradication of disseminated adenovirus infection in a pediatric hematopoietic stem cell transplantation recipient using the novel antiviral agent CMX001.

Adenovirus infection is a serious and often fatal complication in hematopoietic stem cell transplant patients. There are currently no FDA-approved therapies for adenovirus infection, with only anecdotal, off-label uses described for a variety of anti-viral agents or immune therapies. We report the first case of successful eradication of disseminated adenovirus infection by the novel antiviral agent CMX001 in a severely immunocompromised pediatric stem cell transplant recipient following failure to respond to intravenous cidofovir. Complete clinical and virologic response was documented; virologic and pharmacokinetic data are reported. CMX001 is a promising new oral antiviral agent under development for the prophylaxis and treatment of severe infections caused by double-stranded DNA viruses including adenovirus in immunocompromised patients.

Human parechovirus-3 infection: emerging pathogen in neonatal sepsis.

Human parechovirus-3 (HPeV-3) is an emerging pathogen that has been described as a cause of neonatal sepsis. Human parechoviruses are a family of viruses closely related to enteroviruses; however, enteroviral PCR will not detect HPeVs. We present clinical details of neonatal meningoencephalitis and hepatitis-coagulopathy syndrome caused by HPeV-3 infection.

Surveillance of Clinical Isolates of Respiratory Syncytial Virus for Palivizumab (Synagis)–Resistant Mutants

Premature infants and those with chronic lung disease or congenital heart disease are at high risk of severe respiratory syncytial virus (RSV) disease. Palivizumab (Synagis), a humanized anti-RSV monoclonal antibody, has been used extensively since 1998 to prevent severe RSV disease in high-risk infants. To monitor for possible palivizumab-resistant mutants, an immunofluorescence binding assay that predicts palivizumab neutralization of RSV was developed. RSV isolates were collected at 8 US sites from 458 infants hospitalized for RSV disease (1998-2002). Palivizumab bound to all 371 RSV isolates able to be evaluated, including 25 from active-palivizumab recipients. The palivizumab epitope appears to be highly conserved, even in infants receiving prophylaxis with palivizumab.

Association of Lewis blood group phenotypes with urinary tract infection in children.

Many blood group antigens, genetically controlled carbohydrate molecules, are found on the surface of uroepithelial cells and may affect bacterial adherence and increase the frequency of urinary tract infection (UTI) in adults. Sixty-two children aged 2 weeks to 17 years (mean, 2.3 years) who were hospitalized with fever in association with UTIs caused by Escherichia coli had complete (n = 50) or partial (n = 12) erythrocyte antigen typing to determine the role of erythrocyte antigens and phenotypes in UTI in children; 62 healthy children undergoing nonurologic elective surgery, matched 1 to 1 for age, sex, and race to the patient group, formed the control group. In univariate tests, patients and control subjects did not differ in ABO, Rh, P, Kell, Duffy, MNSs, and Kidd systems by the McNemar test of symmetry (p > 0.05). The frequency of the Lewis (Le) (a-b-) phenotype was higher (16/50 vs 5/50; p = 0.0076) and the frequency of the Le(a + b +) phenotype was lower (8/50 vs 16/50; p = 0.0455) in the patient population than in the control subjects. A stepwise logistic regression model to predict UTI with the explanatory variables A, B, O, M, N, S, s, Pl, Lea, and Leb showed that only the Lea and Leb antigens entered the model with p < 0.1. The Le(a-b-) phenotype was associated with UTI in this pediatric population. The relative risk of UTI in children with the Le(a-b-) phenotype was 3.2 (95% confidence interval, 1.3 to 7.9). Specific blood group phenotypes in pediatric populations may provide a means to identify children at risk of having UTI.

Linezolid for the treatment of children with bacteremia or nosocomial pneumonia caused by resistant gram-positive bacterial pathogens.

Background. Nosocomial infections, particularly hospital-acquired pneumonia (HAP) and bacteremia, are an increasing concern in pediatric hospitals and pediatric intensive care units. Gram-positive pathogens are a leading cause of these infections in children. Linezolid is well-tolerated and as effective as vancomycin in the treatment of these infections in adults. Objective. To evaluate the clinical effectiveness and safety of iv/oral linezolid and iv vancomycin in children with resistant Gram-positive HAP or bacteremia. Methods. Hospitalized children <12 years of age were randomized 2:1 to linezolid or vancomycin. Patients received linezolid 10 mg/kg iv every 8 h with the option to change treatment to oral linezolid suspension 10 mg/kg every 8 h or iv vancomycin 10 to 15 mg/kg every 6 to 24 h. Clinical response was evaluated at follow-up. Results from an analysis of patients with HAP or bacteremia are presented. Results. Thirty-nine patients (linezolid, 23; vancomycin, 16) with HAP and 113 patients with bacteremia (linezolid, 81; vancomycin, 32) were included in the intent-to-treat group. Clinical cure rates for clinically evaluable patients with HAP did not differ between treatment groups (linezolid, 90.0% and vancomycin, 100%; P = 0.305). No significant difference was seen in clinical cure rates in the clinically evaluable population between the linezolid and vancomycin groups for patients with catheter-related bacteremia (84.8 and 80.0%, respectively; P = 0.716) or patients with bacteremia of unknown source (79.2 and 69.2%, respectively; P = 0.501). In this subset fewer linezolid-treated patients had drug-related adverse events than did vancomycin-treated patients (19.4%vs. 28.3%; P = 0.230). Similar percentages of patients with laboratory abnormalities, including selected hematologic parameters, were seen in both treatment groups. Conclusions. Intravenous/oral linezolid was well-tolerated and as effective as vancomycin in treating children with resistant Gram-positive HAP or bacteremia.

Late-onset Central Nervous System Shunt Infections with Propionibacterium acnes: Diagnosis and Management

Patient 1 A12-year-old female presented to Children’s National Medical Center for evaluation of a 4-day history of anorexia, worsening headaches, nausea, emesis, and a 4-week history of intermittent left upper quadrant abdominal pain. Her past medical history included subtotal resection and chemotherapy for an astrocytoma diagnosed at 6 years of age. The postoperative sequelae included ventriculoperitoneal (VP) shunt placement with the most recent revision occurring 9 months before the present admission. Physical examination revealed an alert, conversant child in no apparent distress. Vital signs included a temperature of 34.9°C orally, pulse rate of 52 beats/ minute, respiratory rate of 20 breaths per minute, and blood pressure of 98/47 mmHg. Head and neck examination disclosed a right frontal shunt without palpable tenderness over the shunt. Chest examination identified a PortacathTM in place. No tenderness or masses were found on abdominal examination. Neurologic examination found equally reactive pupils with strength intact. Findings from respiratory tract and cardiac examinations were normal. The initial leukocyte count was 6,300/mm3 with 63% segmented neutrophils, 9% band forms, 6% monocytes, 17% lymphocytes, and 5% promyelocytes and metamyelocytes. The hemoglobin level was 10.5 g/dL. Examination of cerebrospinal fluid (CSF) demonstrated a pleocytosis of 52 white blood cells/mm3 with 42% segmented neutrophils, 33% monocytes, and 25% lymphocytes. No erythrocytes were noted. The CSF Gram stain exhibited no organisms or cells. The CSF glucose was 55 mg/dL and the total protein was 28 mg/dL. Blood, urine, and CSF were obtained for culture. A shunt radiographic series and computerized tomography (CT) abdominal scan showed no abnormalities. A head CT scan showed interval enlargement of the ventricular system and a calcified hypothalamic mass that was unchanged from prior studies. The ventricular catheter was in the right frontal horn of the brain. A diagnosis of shunt obstruction was made based on the initial history, CSF finding, and CT scan results; a shunt revision was performed. Treatment with intravenous oxacillin was instituted. On hospital day 3, the patient developed seizures because of hyponatremia. On hospital day 4, the Infectious Diseases Service was consulted after a Gramstained smear of the CSF-en-

Escherichia coli virulence factors and 99mTc-dimercaptosuccinic acid renal scan in children with febrile urinary tract infection

Correlation of virulence factors of Escherichia coli with renal inflammation documented by 99mTe-dimercaptosuccinic acid renal scan was undertaken in 59 children with febrile urinary tract infections to identify more accurately the role of bacterial virulence factors in the development of pyelonephritis. P fimbriae were present in 63% of isolates from the positive scan group and 83% of those from the negative scan group (P = 0.126). Multivariate regression analysis showed no significant role for established E. coli virulence factors in the development of pyelonephritis. The pap genome was independently associated with negative scan (P < 0.007) and with the absence of reflux (P = 0.031). E. coli pyelonephritogenic clone O16:K1:H6 was isolated from negative scan patients and did not produce hemolysin. We conclude that P fimbriae are important in the development of febrile urinary tract infection regardless of the level of infection. Virulent E. coli clones described in prior Scandinavian urinary tract infection studies were not common causes of pyelonephritis in our patient population.