Yong-Kwei Tsau

Antibiotic Resistance Patterns of Community-Acquired Urinary Tract Infections in Children With Vesicoureteral Reflux Receiving Prophylactic Antibiotic Therapy

OBJECTIVE. The goal was to examine bacterial antimicrobial resistance of recurrent urinary tract infections in children receiving antibiotic prophylaxis because of primary vesicoureteral reflux. METHODS. We reviewed data retrospectively for children with documented vesicoureteral reflux in 2 hospitals during a 5-year follow-up period. The patients were receiving co-trimoxazole, cephalexin, or cefaclor prophylaxis or prophylaxis with a sequence of different antibiotics (alternative monotherapy). Demographic data, degree of vesicoureteral reflux, prophylactic antibiotics prescribed, and antibiotic sensitivity results of first urinary tract infections and breakthrough urinary tract infections were recorded. RESULTS. Three hundred twenty-four patients underwent antibiotic prophylaxis (109 with co-trimoxazole, 100 with cephalexin, 44 with cefaclor, and 71 with alternative monotherapy) in one hospital and 96 children underwent co-trimoxazole prophylaxis in the other hospital. Breakthrough urinary tract infections occurred in patients from both hospitals (20.4% and 25%, respectively). Escherichia coli infection was significantly less common in children receiving antibiotic prophylaxis, compared with their initial episodes of urinary tract infection, at both hospitals. Children receiving cephalosporin prophylaxis were more likely to have an extended-spectrum β-lactamase-producing organism for breakthrough urinary tract infections, compared with children with co-trimoxazole prophylaxis. Antimicrobial susceptibilities to almost all antibiotics decreased with cephalosporin prophylaxis when recurrent urinary tract infections developed. The extent of decreased susceptibilities was also severe for prophylaxis with a sequence of different antibiotics. However, antimicrobial susceptibilities decreased minimally in co-trimoxazole prophylaxis groups. CONCLUSIONS. Children receiving cephalosporin prophylaxis are more likely to have extended-spectrum β-lactamase-producing bacteria or multidrug-resistant uropathogens other than E coli for breakthrough urinary tract infections; therefore, these antibiotics are not appropriate for prophylactic use in patients with vesicoureteral reflux. Co-trimoxazole remains the preferred prophylactic agent for vesicoureteral reflux.

Effective Duration of Antimicrobial Therapy for the Treatment of Acute Lobar Nephronia

OBJECTIVE. Effective treatment of acute lobar nephronia (ALN) can prevent its progression to renal abscess. The goal of this prospective study was to compare the treatment efficacy for pediatric patients who had ALN with a 3- vs 2-week intravenous plus oral antimicrobial-therapy regimen. METHODS. Patients who were suspected of having an upper urinary tract infection underwent a systematic scheme of ultrasonographic and computed tomographic (CT) evaluation for ALN diagnosis. Patients with positive CT findings were enrolled and randomly allocated with serial entry for either a total 2-week or a 3-week antibiotic treatment regimen. Antibiotics were changed from an intravenous form to an oral form 2 to 3 days after defervescence of fever. Follow-up clinical evaluations and urine-culture analyses were performed 3 to 7 days after cessation of antibiotic treatment. Patients with persistent infection or relapse were considered as treatment failures. RESULTs. A total of 80 patients with ALN were enrolled. Forty-one patients were treated with a 2-week antimicrobial protocol, and the other 39 patients were treated with a 3-week course. Seven treatment failures, 1 persistent infection, and 6 infection relapses were identified, all of which were in the 2-week treatment group. Prolonged fever before admission and positive Escherichia coli growth (>105 colony-forming units per mL) in urine culture were noted as risk factors for treatment failure. All treatment failures were managed successfully with an additional 10-day antibiotic course. CONCLUSION. A total of 3 weeks of intravenous and oral antibiotic therapy tailored to the pathogen noted in cultures should be the treatment of choice for pediatric patients with ALN.

Effective ultrasonographic predictor for the diagnosis of acute lobar nephronia

Background. Correct identification of acute lobar nephronia (ALN) is necessary to prevent progression to renal abscess. The goal of this retrospective study was to determine whether the sonographic finding of severe nephromegaly (i.e. renal length greater than mean + 3 sd) is a preselection criterion for computed tomographic (CT) scanning in diagnosing pediatric ALN among children with an acute upper urinary tract infection. Design/methods. We evaluated a new imaging work-up scheme to detect pediatric ALN. All patients with urinary tract infection were evaluated with ultrasonography. If a markedly enlarged kidney or focal mass was present sonographically, CT scanning was done immediately. CT scanning was also performed when the patient had borderline nephromegaly and remained febrile for 72 h after start of antibiotic treatment. ALN diagnosis was made on the basis of positive CT findings. Results. Thirty patients with ALN (13 left, 7 right, 10 bilateral) and one with acute pyelonephritis were identified. ALN in all patients resolved after 3 weeks of antibiotic treatment. Thirty-nine of the 62 kidneys evaluated showed severe nephromegaly, and 10 had focal renal masses. With CT diagnosis of ALN as the reference standard, the sensitivity of severe nephromegaly was 90.0% and the specificity was 86.4%. When the focal renal mass was added as a combining predictor, the sensitivity further increased to 95%. Conclusions. Pediatric ALN was effectively predicted using sonographic findings of severe nephromegaly and/or focal mass before CT scanning.

Renal abscess in children: a 10-year clinical and radiologic experience in a tertiary medical center.

Renal abscess is a rare disease in childhood and early diagnosis is essential to minimize the renal damages. Experiences gained from this 10-year study on patients with CT-proved diagnosis include the varied clinical presentations and use of sonographic-marked nephromegaly and focal mass as indications for further CT diagnosis.

Renal Ultrasonography Should Be Done Routinely in Children with First Urinary Tract Infections

OBJECTIVES To assess the consequences of renal ultrasonography (RUS) in the treatment of children younger than 5 years of age with a first febrile urinary tract infection. METHODS We retrospectively reviewed the results of imaging studies, including RUS, computed tomography, and voiding cystourethrography in children with a first febrile urinary tract infection during a 2-year period. Children with known urologic anomalies, other underlying diseases, or simultaneous combined illnesses were excluded. Children with nephromegaly were diagnosed with acute lobar nephronia by computed tomography. RESULTS A total of 390 children were included in this study. Of the 390 children, 112 (28.7%) had abnormal RUS findings. The children with abnormal RUS findings of nephromegaly, small kidney, intermittent hydronephrosis, or a double collecting system had a significantly greater incidence of vesicoureteral reflux than children with normal RUS findings. Additionally, the occurrence of high-grade vesicoureteral reflux in children with abnormal RUS findings was more frequent than in children with normal RUS findings. CONCLUSIONS The results of our study indicate that it is worth performing RUS in children with a first febrile urinary tract infection because abnormal kidney size or other specific structural ultrasound findings should be investigated, in addition to isolated hydronephrosis.

High-Volume Continuous Venovenous Hemofiltration as an Effective Therapy for Acute Management of Inborn Errors of Metabolism in Young Children

Background/Aim: Renal replacement therapies (RRTs) have been used for the acute management of inborn errors of metabolism. Hemodialysis is the most effective modality. The aim of this article is to demonstrate that high-volume hemofiltration can offer an alternative way to effectively remove small molecules. Methods: Eight patients presented with acute neurological deterioration due to ammonia or organic acid accumulation. Different RRTs were applied, including continuous venovenous hemofiltration (CVVH, n = 7), continuous arteriovenous hemofiltration (CAVH, n = 2), continuous venovenous hemodialysis (CVVHD, n = 1), intermittent hemodialysis (HD, n = 1), and peritoneal dialysis (PD, n = 2). Results: Ammonia 50% reduction time in HD was 1.7 h while in CVVH it was 2–14.5 h. The greater the ultrafiltration flow was, the sooner patients regained consciousness. CAVH, CVVHD or PD was not sufficient enough.Conclusion:CVVH also has a good clearance for organic acid and ammonia if applying high-volume hemofiltration (>35 ml/kg/h). It can be therefore be considered as an alternative therapy if infant HD is not available.

Universal Hepatitis B Vaccination Reduces Childhood Hepatitis B Virus–Associated Membranous Nephropathy

OBJECTIVE: To compare the incidence of hepatitis B virus (HBV)-associated membranous nephropathy (HBVMN) before and after universal HBV vaccination and to identify factors underlying the change. METHODS: This study included 471 hospitalized children with nephrotic syndrome (NS) and 488 long-term follow-up hepatitis B surface antigen (HBsAg)-carrier children. Horizontal transmission (negative maternal HBsAg status) of HBVMN and HBV was assessed, and the incidence of HBVMN was compared before and after initiation of the universal HBV vaccination program started in 1984. RESULTS: The frequency of HBVMN in children with NS was 11.6% between 1974 and 1984, 4.5% between 1984 and 1994, 2.1% between 1994 and 2004, and 0% between 2004 and 2009. Similarly, the number of HBsAg-seropositive children with NS (mainly via horizontal infection) decreased after universal vaccination. The prevaccination frequency of HBV horizontal transmission in chronic HBsAg carriers from the general population was 36.5% compared with 5% in the postvaccination period. The incidence of HBVMN in these carriers revealed a parallel decline. CONCLUSIONS: Our results revealed a significant decrease in the frequency of HBVMN in children with NS and in long-term follow-up HBsAg carriers. Children with HBVMN are primarily infected with HBV via horizontal transmission; thus, the significant reduction in horizontal transmission in HBsAg-carrier children in the general population after universal HBV vaccination may explain the reduction of HBVMN in the vaccinated population. These findings confirm the effectiveness of HBV vaccination on reducing the incidence of HBVMN, possibly through a significant decline in horizontal HBV infection.

Clinical courses of children with acute lobar nephronia correlated with computed tomographic patterns

Background: Acute lobar nephronia (ALN) is a complicated acute renal infection that is part of the progression of the inflammatory process of acute pyelonephritis that can progress to renal abscess if left untreated. We examined the place of ALN in the spectrum of upper urinary tract infections. Methods: The medical records of all patients diagnosed with ALN by computed tomography (CT) were reviewed retrospectively in terms of their demographic characteristics, clinical presentations, and laboratory findings. The patterns of the ALN lesions were checked on all contrast-enhanced CT films and the volume of the CT lesions (the extent of renal involvement) was estimated in every patient. Then, the correlation between the clinical presentation and CT lesions was examined. Results: Two distinct CT patterns of ALN lesions were observed in 127 patients: 94 simple ALN and 33 complicated ALN. Simple ALN appeared as striated or wedge-shaped, poorly defined regions of homogeneously decreased nephrographic density, whereas the lesions of complicated ALN showed heterogeneously decreased nephrographic density after contrast enhancement. The volume fraction of the CT lesions correlated well with the duration of fever before (P = 0.006) and after (P < 0.001) treatment in patients with simple ALN, while only the correlation between the fever duration after treatment and the volume fraction of the CT lesions (P < 0.001) was significant in patients with complicated ALN. Patients with complicated ALN were generally older (P = 0.004) and febrile longer after starting antibiotic treatment (P < 0.001). All treatment failures were in the complicated ALN group. Conclusions: Children with ALN comprise 2 groups with different clinical presentations and treatment responses: simple ALN and complicated ALN. We suggest that simple ALN be regarded as a continuation of acute pyelonephritis and require 2 weeks of antibiotic treatment, while complicated ALN is a distinct more severe form requiring a 3-week or longer therapy regimen as the treatment of choice.

Drug susceptibility and treatment response of common urinary tract infection pathogens in children

BACKGROUND/PURPOSE To document the trends of sensitivity and to find whether it is necessary to change antibiotics in selected patients according to the sensitivity test results in our clinical practice. METHODS We collected urine culture results from 0-18-year-old patients in the National Taiwan University Hospital from January 1, 2003 to October 31, 2012. Their medical chart was reviewed to identify true pathogens responsible for their urinary tract infection (UTI). We checked the percentage of susceptibility of these pathogens to ampicillin, amoxicillin-clavulanate (AMC), cefazolin, cefmetazole, ceftriaxone, gentamicin, and trimethoprim-sulfamethoxazole (TMP-SMX) according to the Clinical and Laboratory Standards Institute (CLSI) guideline. The extended-spectrum-beta-lactamases (ESBLs) rate was also checked. In addition, we reviewed the treatment response of different antibiotics. Defervescence within 48 hours after initial antibiotics use was considered responsive. RESULTS A total of 7758 urine cultures positive for Escherichia coli infection were collected during the 10-year period. The E. coli cefazolin susceptibility rate was 62-73% during 2003-2010, but it dropped to 23% in 2011 and 28% in 2012 after the new CLSI guideline (M100-S21) was released. However, other antibiotics did not show a significant difference. In UTI caused by E. coli, on average, the sensitivity rates for various antibiotics were as follows: cefmetazole, 90%; ceftriaxone, 85%; gentamicin, 77%; AMC, 61%; TMP-SMX, 47%; and ampicillin, 20%. The ESBL rate was also found to increase (2-11%; p < 0.01). The overall response rate of UTI caused by E. coli to first-line antibiotics such as first-generation cephalosporin and/or gentamicin was 78%. CONCLUSION The susceptibility of common urinary tract pathogens to cefazolin has decreased dramatically since 2010. This trend may be due to the change in the CLSI guideline. Although the susceptibility rate to first-line empirical antibiotics shows a decreasing trend, we found that the clinical response was acceptable for our first-line empirical antibiotics.

Genetic polymorphisms and susceptibility to parenchymal renal infection among pediatric patients.

Background: Patient susceptibility to bacterial urinary tract infections, which is determined by complex pathogen-host interactions, varies between individuals due to genetic variation. The neutrophil-dependent innate immune system is an important part of keeping the urinary tract sterile. This study was performed to explore single nucleotide polymorphisms (SNPs) in genes associated with neutrophil-dependent immunity in pediatric patients with severe parenchymal infections. Methods: The subjects included patients who fulfilled the diagnostic criteria of acute pyelonephritis (APN) and acute lobar nephronia (ALN) without underlying disease or structural anomalies (excluding vesicoureteral reflux). Genotyping of the genes encoding toll-like receptor 4 (TLR-4), interleukin-8 (IL-8), and IL-8 receptors CXCR1 and CXCR2 was performed by matrix-assisted laser desorption/ionization time-of-flight-based mini-sequencing analysis. Results: A total of 17 SNPs, including missense SNPs and those located in promoter regions, were initially selected for genotyping. Only 4 SNPs with a heterozygosity rate >0.01 were evaluated further. The observed genotype frequencies satisfied Hardy-Weinberg equilibrium. Statistical analysis revealed that only IL-8 (rs4073, −251A>T) showed significant differences in genotype and allele frequency between the control and APN or ALN cases. Following the elimination of vesicoureteral reflux, which is a significant risk factor for severe parenchymal infection, a single SNP in IL-8 (rs4073) was found to be associated with clinically severe ALN. Conclusions: The AA genotype and A allele of the IL-8 SNP is related to patient susceptibility to parenchymal infection and is correlated with the severity of infection in pediatric APN and ALN patients, probably due to the upregulation of IL-8 expression.