Neonatal kidney size and function in preterm infants: what is a true estimate of glomerular filtration rate?

OBJECTIVES: To distinguish between cystatin C (CysC) and creatinine (Cr) as markers of estimated glomerular filtration rate (eGFR) in preterm infants and to correlate eGFR with total kidney volume (TKV) as a surrogate of nephron mass. STUDY DESIGN: Sixty preterm (<37 weeks' gestational age [GA]) and 40 term infants were enrolled at birth. Serum Cr and CysC levels were assessed during the first week of life. Renal ultrasounds were performed to assess kidney dimensions with calculation of the TKV as a surrogate of nephron mass. Six equations derived from reference inulin, iohexol, and iothalamate clearance studies were used to calculate eGFR. Multiple regression analysis was applied to assess the relative impact of neonatal measures on eGFR, including TKV, GA, and mean arterial pressure (MAP). RESULTS: Renal lengths correlated with GA and were within the reference values for intrauterine measurements. Estimation equations for glomerular filtration rate (GFR) based on Cr, CysC, and combined CysC + Cr demonstrated that Cr-based equations consistently underestimated GFR, whereas CysC and combined equations were more consistent with referenced inulin clearance studies. Term infants demonstrated significantly better eGFR than preterm infants. TKV, GA, and MAP correlated positively with eGFR, although only MAP and GA remained significant when adjusted for other covariates. CONCLUSIONS: Primary determinants of eGFR in preterm infants are GA and MAP. The CysC level is a superior biomarker to serum Cr in the assessment of GFR in premature infants.

PREFABL: predictors of failure of antibiotic locks for the treatment of catheter-related bacteraemia.

BACKGROUND: Antibiotic lock (ABL) solutions can effectively treat catheter-related bacteraemia (CRB) without the need for catheter exchange. This approach does not increase secondary infectious complications. We evaluated the risk factors that contribute to failure when CRB is treated with ABLs and systemic antibiotics in paediatric haemodialysis patients. METHODS: A retrospective chart review of 72 children on haemodialysis between January 2004 and June 2006 was performed. We evaluated risk factors for ABL treatment using patients' characteristics, CRB/catheter characteristics and patients' biochemical profiles. The first CRB of each catheter was included in the statistical analysis. Our end points were outcome at 2 weeks of treatment and at 6 weeks following treatment. Compound symmetry covariance structure was employed for statistical analysis. RESULTS: We treated 149 CRB in 50 patients. The incidence was 3.4 CRB/1000 catheter days. Thirty CRB failed to be cleared with the use of ABL and systemic antibiotics at 2 weeks of treatment (30/149, 20 vs 80%, P < 0.001). Twenty-four of these catheters required exchange. Thirty-nine of the treated catheters got re-infected within the next 6 weeks (39/125, 31 vs 69%, P < 0.001). CRB aetiology was the only statistically significant independent variable for 2-week outcome (P = 0.033). Coagulase-negative Staphylococcus CRB had higher odds of being cleared at 2 weeks compared with other CRB aetiologies. For the 6-week outcome, the statistically significant independent variables in the final model included age (P = 0.048) and serum phosphorous level (P < 0.001). Younger age and higher serum phosphorous levels were independent risk factors for failure at 6 weeks with re-infection. Area under the receiver operating characteristic (ROC) curve for the model of the 2-week outcome was 0.736 with the percentage of correct predictions at 81.2%. Area under the ROC curve for the model of the 6-week outcome was 0.689 with the percentage of correct predictions at 75.5%. CONCLUSIONS: CRB can effectively be treated with ABLs and systemic antibiotics. CRB aetiology is the only independent variable of early treatment failure. Younger age and higher serum phosphorous levels are independent risk factors for re-infection at 6 weeks.

Chlorhexidine-based antiseptic solutions effectively reduce catheter-related bacteremia.

The aim of this retrospective study was to investigate if the application of chlorhexidine-based solutions (ChloraPrep) to the exit site and the hub of long-term hemodialysis catheters could prevent catheter-related bacteremia (CRB) and prolong catheter survival when compared with povidone-iodine solutions. There were 20,784 catheter days observed. Povidone-iodine solutions (Betadine) were used in the first half of the study and ChloraPrep was used in the second half for all the patients. Both groups received chlorhexidine-impregnated dressings at the exit sites. The use of ChloraPrep significantly decreased the incidence of CRB (1.0 vs 2.2/1,000 catheter days, respectively, P = 0.0415), and hospitalization due to CRB (1.8 days vs 4.1 days/1,000 catheter days, respectively, P = 0.0416). The incidence of exit site infection was similar for the two groups. Both the period of overall catheter survival (207.6 days vs 161.1 days, P = 0.0535) and that of infection-free catheter survival (122.0 days vs 106.9 days, P = 0.1100) tended to be longer for the catheters cleansed with ChloraPrep, with no statistical significance. In conclusion, chlorhexidine-based solutions are more effective for the prevention of CRB than povidone-iodine solutions. This positive impact cannot be explained by decreased number of exit site infections. This study supports the notion that the catheter hub is the entry site for CRB.

Prophylaxis of catheter-related bacteremia using tissue plasminogen activator-tobramycin locks.

This retrospective study was designed to investigate the effectiveness of tissue plasminogen activator-tobramycin antibiotic lock solutions (TPA/tobra ABLs) for prophylaxis of catheter-related bacteremia (CRB) in high-risk children on long-term hemodialysis. During the first 6 months (Era 1), the high-risk group was defined. These patients received TPA/tobra ABL prophylaxis after every hemodialysis treatment for the next 6 months (Era 2). The prophylaxis regimen was applied once a week for the third 6-months period (Era 3). Primary endpoints were CRB and infection-free catheter survival. There were 16,412 catheter days, and 95 cases of CRB in 43 children. The incidence of CRB was 5.8/1,000 catheter days. Significant decrease in the incidence of CRB was observed when prophylactic TPA/tobra ABL was used in the high-risk group (P = 0.0201). There was a tendency for less CRB when prophylactic ABL was applied after every hemodialysis session compared with once a week (P = 0.0947). The catheters in the high-risk group had shorter survival times than those in the average-risk group in Era 1 (P < 0.0001). However, both the overall and infection-free survival of the catheters in the high-risk group significantly improved while the patients were receiving TPA/tobra ABL prophylaxis, becoming similar to the outcomes of the catheters in the average-risk group and exhibiting statistically non-significant differences (P = 0.5571 and P = 0.9711, respectively). In conclusion, the TPA/tobra ABLs may effectively reduce the rate of CRB, and this may prolong both the overall and infection-free survival times of the catheters in the high-risk group.

Controlling exit site infections: does it decrease the incidence of catheter-related bacteremia in children on chronic hemodialysis?

The aim of this retrospective study was to investigate whether the application of a chlorhexidine-impregnated dressing (Biopatch) at the exit site of tunneled-cuffed hemodialysis catheters has any effect on the incidence and etiology of catheter-related bacteremia (CRB). This study was carried out over a 5-year period in a single center, where, in the first 2(1/2) years, the exit sites were cleansed with betadine at every hemodialysis session and then covered with a transparent dressing (pre-Biopatch Era). During the next 2(1/2) years, Biopatch was applied to the exit site once a week after cleansing with betadine, and then covered with a transparent dressing (Biopatch Era). The application of Biopatch significantly decreased the incidence of exit site infections (ESI) (P<0.05). However, there was no difference in the incidence of CRBs or their microbiological distribution. The improved ESI rate had no effect on the overall catheter survival time. The antimicrobial sensitivities of the Gram-positive microorganisms were statistically different for the 2 different types of infections (P<0.05). In conclusion, even though Biopatch is effective in decreasing the incidence of ESI, it has no effect on the incidence of CRB, the etiology of CRB, or the overall catheter survival time. The distinct difference between the antimicrobial sensitivities of the ESI and CRB suggests that they are not a spectrum of the same pathogenesis. These preliminary data support the intraluminal pathogenesis of CRB, rather than the exit site as a possible entry point for the extraluminal route.

Antibiotic lock solutions allow less systemic antibiotic exposure and less catheter malfunction without adversely affecting antimicrobial resistance patterns.

There are current concerns that antibiotic lock solutions (ABL) can induce antimicrobial resistance in long-term hemodialysis patients. Retrospective chart review of 157 children on hemodialysis between January 1997 and June 2006 was performed. In ERA I, only systemic antibiotics were used. In ERA II, ABL were added to systemic antibiotics when needed. In ERA III, ABL were used for treatment of all cases of catheter-related bacteremia (CRB) and for CRB prophylaxis in high-risk patients. The study includes 111,325 catheter days. The CRB incidence was 3.9 CRB/1000 catheter days. There was significant decrease for the total systemic antibiotic exposure (P = 0.0484) and the percentage of catheters lost to malfunction (P = 0.001) in ERA III. Protocol ABL exposure was associated with a trend to increased tobramycin-gentamicin resistance for gram-positive CRBs (P = 0.2586) but with improved tobramycin-gentamicin resistance for gram-negative (P = 0.0949) and polymicrobial CRBs (P = 0.1776) and improved vancomycin resistance for gram-positive CRBs (P = 0.0985). This retrospective analysis does not support the premise that ABL use will promote antimicrobial resistance in the hemodialysis population. The decreased exposure to systemic antibiotics by vigorous ABL use may even improve the antimicrobial resistance patterns in this population in the long term.

Comparison of early versus late use of antibiotic locks in the treatment of catheter-related bacteremia.

BACKGROUND AND OBJECTIVES: This retrospective study compared the effectiveness of the timing of the antibiotic locks to clear catheter-related bacteremia in children on chronic hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The early antibiotic lock group received antibiotic locks along with systemic antibiotics from the very beginning of catheter-related bacteremia. The late antibiotic lock group was given only systemic antibiotics initially, and antibiotic locks were used late in the infection if the catheter-related bacteremia could not be cleared after resolution of symptoms. RESULTS: There were 264 catheter-related bacteremias in 79 children during 6 yr of observation. Early antibiotic locks were able to clear catheter-related bacteremia and resolve the symptoms more effectively without the need for catheter exchange when compared with late antibiotic locks. A total of 84 catheter-related bacteremias required wire-guided exchange of the catheters. Late antibiotic locks required wire-guided catheter exchange more frequently than the early antibiotic locks. The post-catheter-related bacteremia infection-free survival of the catheters after wire-guided exchange were significantly longer than those of both antibiotic lock groups. Recurrence of catheter-related bacteremia within 45 d after wire-guided exchange occurred at similar rates compared with the antibiotic lock groups. CONCLUSION: Antibiotic locks are significantly more effective in clearing catheter-related bacteremia when used early in infection, diminishing the need for catheter exchange. Wire-guided exchange has a late-onset advantage for infection-free survival compared with catheter in situ treatment. The recurrence rates in the first 45 d after catheter-related bacteremia are similar regardless of the treatment strategy.

Treatment of catheter-related bacteremia with tissue plasminogen activator antibiotic locks.

This retrospective study was completed to investigate the effectiveness of tissue plasminogen activator (TPA) antibiotic locks (ABL) along with systemic antibiotics (AB) to clear catheter-related bacteremia (CRB) in children on chronic hemodialysis. There were 76 CRBs in 37 children. CRBs were successfully cleared with AB/ABL in 63/76 (83%) cases. Ten of 76 (13%) CRBs were symptomatic at 48 h of treatment. These were seven polymicrobial, two gram-negative, and one Candida CRB. 13/76 (17%) episodes required catheter exchange, and all were wire-guided exchanges. TPA-ABL/AB cleared gram-positive and gram-negative CRBs significantly better than polymicrobial CRBs (p < 0.01). The infection-free survival and the rate of recurrence at 45 days was not statistically different between the TPA-ABL/AB group and the catheter-exchange group. If CRB was symptomatic at 48 h of treatment, recurrence at 6 weeks was more frequent with persistent use of TPA-ABL/AB (p < 0.05). There were no episodes of metastatic infections, catheter malfunction from occlusion, or catheter breakdown during the course of TPA-ABL treatments. In conclusion, TPA-ABL can be safely and effectively used in the management of CRB, increasing the probability of catheter survival and preserving the vascular access site. With the exception of polymicrobial CRB, there is no disadvantage in using TPA-ABL/AB over catheter exchange, as the infection-free survival and the rate of recurrence are comparable.

Posterior reversible encephalopathy syndrome in the pediatric renal population.

Posterior reversible leukoencephalopathy syndrome (PRES) clinically presents with seizures, severe headaches, and mental and visual changes. Our goal was to describe the clinical features, triggering factors, neuro-imaging findings, and electroencephalogram (EEG) findings in a pediatric cohort with renal disease. We retrospectively analyzed the records of 18 children with the diagnosis of PRES between January 2001 and June 2006 at the University of Miami/Holtz Children's Hospital, USA. There were 22 PRES episodes. The most common clinical presentation was generalized tonic-clonic seizures in 59% (13/22). The most common identified trigger of PRES was hypertensive crisis in 59% (13/22). Almost half of the children had no evidence of on-going uncontrolled hypertension; 44% (8/18) had normal funduscopic examination findings, and 50% (9/18) had no or mild left ventricular hypertrophy. Two of the 18 patients had recurrent PRES episodes, three episodes each. Diffuse slowing was the most common finding on the EEGs. Atypical magnetic resonance imaging (MRI) findings were more prevalent in the imaged cases (62% vs 25%, P < 0.05). All the computerized tomography (CT) scans were normal, despite the positive MRI findings in four cases when both types of imaging was used. All the episodes had total clinical resolution. In conclusion, despite the diverse initial trigger, acute hypertension seems to be the common pathogenic pathway for pediatric PRES. MRI seems superior to CT, with better sensitivity due to its high resolution and diffusion-weighted imaging. The lesions do not necessarily have to be in the posterior white matter and may not be totally reversible.

Prevention of catheter-related bacteremia in pediatric intestinal transplantation/short gut syndrome children with long-term central venous catheters.

Catheter-related bacteremia (CRB), along with liver failure is the leading cause of mortality and morbidity in parenteral nutrition dependent children. Immunosuppressant therapy following transplantation increases the risk of CRB. Previous reports in pediatric cancer patients have described the use of antibiotic lock solutions (ABL) for prophylaxis of CRB. In our institution, we evaluated five children (ages between one and four yr old), three with intestinal transplantation and two with short gut syndrome, who were high risk for recurrent CRB defined by their incidence of bacteremias in the observation period (>2 CRB/six months or life-threatening CRB). These children received the prophylactic ABL protocol with tobramycin-tissue plasminogen activator, four h per day, on alternating ports for six to eight months. Each patient was his/her own historical control. We observed decreased incidence of CRB's (p < 0.05), days of hospitalization due to CRB's (p < 0.0001), the days of intensive care admissions due to CRB (p < 0.0001), as well as the total days of systemic antibiotic exposure (p < 0.001). Catheter survival during the ABL era was longer but not reaching statistical significance. There was no advantage in removing and later replacing the catheter to wire-guided exchange while on systemic antibiotics. One patient presented with break-through bacteremia, septic shock and died. None of the catheters were lost to occlusion/malfunction. ABL did not induce an increased resistance to tobramycin. These preliminary findings suggest that ABL can be used safely and effectively in parenteral nutrition dependent children with long-term central venous catheters.