Infants under two months of age with urinary tract infections are showing increasing resistance to empirical and oral antibiotics.

AIM: Data on antimicrobial resistance in uropathogens in infants up to the age of three months are limited. This study characterised resistance patterns in Gram-negative uropathogens in infants up to the age of two months. METHODS: Previously healthy young infants with urinary tract infections (UTIs) were studied retrospectively. Antimicrobial susceptibility was evaluated. Multidrug resistance (MDR) was defined as resistance to at least three antibiotic classes. Clinical, laboratory and outcome data were compared between infants with UTIs caused by bacteria sensitive and resistant to empirical and to oral therapy. RESULTS: We evaluated 306 UTI episodes with 314 pathogens. The following resistance rates were observed: ampicillin 73.7%, cefazoline 22.1%, ampicillin/clavulanate 21.8%, cefuroxime 7.8%, gentamicin 7%; MDR 11.8%; resistant to empirical treatment 7.3% and resistant to available oral antibiotics 8.6%. Our study showed that pathogens resistant to empirical and oral therapy were more frequently isolated in non-Jewish (Arab) infants and in those of ≥30 days of age. Resistance to empirical treatment and oral antibiotics also resulted in longer mean hospital stays. CONCLUSION: Resistance to antibiotics challenges empirical therapy and compromises oral treatment options in young infants with UTIs. Antimicrobial resistance patterns should be monitored in infants to determine appropriate empirical antibiotic therapy protocols.

Antenatal Bartter syndrome presenting as hyperparathyroidism with hypercalcemia and hypercalciuria: a case report and review.

Antenatal type I Bartter syndrome (ABS) is usually identified by the presence of polyhydramnios, premature delivery, hypokalemia, metabolic alkalosis, hypercalciuria, and nephrocalcinosis caused by mutations in the Na-K-2Cl cotransporter (NKCC2)-encoding SLC12A1 gene. In this report, we describe a novel presentation of this syndrome with hypercalcemic hypercalciuric hyperparathyroidism, and review the literature of the variable atypical presentations of ABS.

Factors associated with bacteremia in young infants with urinary tract infection.

BACKGROUND: Urinary tract infection (UTI) is the most frequent severe bacterial infection in infants. Up to 31% of infants with UTI have bacteremia. METHODS: We retrospectively identified all infants aged 0-2 months who were managed in our hospital with UTI during a 1-year period. Those with bacteremia were compared with those without bacteremia, according to the following variables: ethnicity, age, gender, white blood cell and polymorphonuclear counts, C-reactive protein, urinalysis and blood creatinine values as related to age-appropriate norms, imaging and outcome. RESULTS: We identified 81 infants with 82 episodes of UTI. Most occurred in males (72.8%) and 35 (42.7%) were in infants of non-Jewish origin. In 14/81 (17.3%) of episodes, Escherichia coli was cultured from blood. In multivariate analysis, increased blood creatinine levels (P = 0.004) and non-Jewish origin (P = 0.006) were associated with bacteremia. Time to defervescence was significantly longer in bacteremic versus nonbacteremic children (P = 0.018). Duration of hospitalization was longer in bacteremic infants-10 (7-17) days in bacteremic versus 7 (1-14) days in nonbacteremic children (P < 0.001). CONCLUSIONS: In infants aged 0-2 months with UTI, increased blood creatinine value at admission was associated with bacteremia. This value provides an additional clue on admission, independent of personal judgment, to help identify infants at higher risk for bacteremia, prolonged hospitalization and possible complications.

Female polysomy-X and systemic lupus erythematosus.

OBJECTIVES: Systemic lupus erythematosus (SLE) occurs more commonly in females than in males. Recent evidence suggests that genetic factors transmitted by the X-chromosome may confer increased risk for autoimmune disease in general, and for SLE in particular. It is therefore possible that X-chromosome polysomy might confer further increased risk for lupus. In addition to describing the clinical and immunologic features of a young woman with polysomy-X and SLE, we sought to review all other published cases associating female or male polysomy-X with SLE or other forms of autoimmunity. METHODS: We report a case of a prepubertal girl with polysomy-X and SLE. We performed a systemic literature review for cases of polysomy-X and SLE and summarize previously published cases. In addition, we reviewed reports concerning the possible association between SLE and other connective tissue diseases and male polysomy-X. RESULTS: An 11-year-old girl with tetrasomy-X (48 XXXX karyotype) presented with prolonged fever. Workup led to the diagnosis of SLE, and subsequent renal biopsy revealed mild diffuse mesangial proliferative glomerulonephritis. Two additional cases of SLE in women with 47 XXX and one of 48 XXXX karyotype were found in a literature review and compared to the present case. We identified studies that found X-chromosome polysomy to be over-represented in male patients with SLE and case descriptions of connective tissue diseases occurring in patients with polysomy-X. CONCLUSION: No consistent pattern of disease was observed in female polysomy patients with SLE. Taken together with the data concerning the frequency of polysomy-X among males with SLE, our findings provide additional support for the hypothesis that X-chromosome polysomy may confer increased susceptibility to SLE. Molecular mechanisms that might account for this phenomenon are discussed.

Dent Disease with mutations in OCRL1.

Dent disease is an X-linked renal proximal tubulopathy associated with mutations in the chloride channel gene CLCN5. Lowe syndrome, a multisystem disease characterized by renal tubulopathy, congenital cataracts, and mental retardation, is associated with mutations in the gene OCRL1, which encodes a phosphatidylinositol 4,5-bisphosphate (PIP(2)) 5-phosphatase. Genetic heterogeneity has been suspected in Dent disease, but no other gene for Dent disease has been reported. We studied male probands in 13 families, all of whom met strict criteria for Dent disease but lacked mutations in CLCN5. Linkage analysis in the one large family localized the gene to a candidate region at Xq25-Xq27.1. Sequencing of candidate genes revealed a mutation in the OCRL1 gene. Of the 13 families studied, OCRL1 mutations were found in 5. PIP(2) 5-phosphatase activity was markedly reduced in skin fibroblasts cultured from the probands of these five families, and protein expression, measured by western blotting, was reduced or absent. Slit-lamp examinations performed in childhood or adulthood for all five probands showed normal results. Unlike patients with typical Lowe syndrome, none of these patients had metabolic acidosis. Three of the five probands had mild mental retardation, whereas two had no developmental delay or behavioral disturbance. These findings demonstrate that mutations in OCRL1 can occur with the isolated renal phenotype of Dent disease in patients lacking the cataracts, renal tubular acidosis, and neurological abnormalities that are characteristic of Lowe syndrome. This observation confirms genetic heterogeneity in Dent disease and demonstrates more-extensive phenotypic heterogeneity in Lowe syndrome than was previously appreciated. It establishes that the diagnostic criteria for disorders resulting from mutations in the Lowe syndrome gene OCRL1 need to be revised.

Structural and functional characterization of factor H mutations associated with atypical hemolytic uremic syndrome.

Genetic studies have demonstrated the involvement of the complement regulator factor H in nondiarrheal, nonverocytotoxin (i.e., atypical) cases of hemolytic uremic syndrome. Different factor H mutations have been identified in 10%-30% of patients with atypical hemolytic uremic syndrome (aHUS), and most of these mutations alter single amino acids in the C-terminal region of factor H. Although these mutations are considered to be responsible for the disease, the precise role that factor H plays in the pathogenesis of aHUS is unknown. We report here the structural and functional characterization of three different factor H proteins purified from the plasma of patients with aHUS who carry the factor H mutations W1183L, V1197A, or R1210C. Structural anomalies in factor H were found only in R1210C carriers; these individuals show, in their plasma, a characteristic high-molecular-weight factor H protein that results from the covalent interaction between factor H and human serum albumin. Most important, all three aHUS-associated factor H proteins have a normal cofactor activity in the proteolysis of fluid-phase C3b by factor I but show very low binding to surface-bound C3b. This functional impairment was also demonstrated in recombinant mutant factor H proteins expressed in COS7 cells. These data support the hypothesis that patients with aHUS carry a specific dysfunction in the protection of cellular surfaces from complement activation, offering new possibilities to improve diagnosis and develop appropriate therapies.

Ambulatory blood pressure monitoring in children and adolescents.

With recent technological advances, 24-hour ambulatory blood pressure (BP) monitoring (ABPM) has become a useful tool for the evaluation, diagnosis, and management of hypertensive children. It provides a more accurate representation of an individual's BP rather than intermittent casual or office BP measurements. Hence, ABPM is being used more often to assess the BP of children. In this comprehensive review, we provide the reader with the available literature on ABPM, discuss the advantages and limitations of ABPM, and the interpretation of ABPM data. The role of ABPM in various clinical conditions and hypertension research in children is presented.

Childhood hyperuricemia and acute renal failure resulting from a missense mutation in the HPRT gene.

A 6-year-old boy was determined to have partial hypoxanthine phosphoribosyl transferase (HPRT) enzyme deficiency without the phenotypic features of Lesch-Nyhan syndrome. He presented with recurrent acute renal failure (ARF) from hyperuricemia. Treatment with allopurinol prevented further attacks of renal failure. T lymphocyte cultures were used to sequence the HPRT cDNA and a novel single nucleotide substitution at codon 65 in exon 3 was found (193C>T, 65leu>phe). This mutation was confirmed by genomic DNA sequencing and was also detected in his heterozygous, asymptomatic mother and sister. Unlike the cells from patients with classic Lesch-Nyhan syndrome, the in vitro cultures of our patient's T-lymphocytes did not proliferate in the presence of purine analogue 6-thioguanine (TG). This report highlights the unusual occurrence of recurrent ARF in a child with partial HPRT enzyme deficiency. The absence of TG resistance in vitro with this mutation shows that even small alterations in enzyme activity in vivo can result in disease symptoms, in this instance, hyperuricemia sufficient to cause ARF. Atypical HPRT mutations should also be considered in cases of unusual renal failure, because correct diagnosis can allow appropriate treatment, as well as informed genetic counseling.