Multidrug-resistant organisms (MDROs), such as vancomycin-resistant enterococci (VRE), cause serious infections, especially among high-risk patients in NICUs. When VRE was introduced and transmitted in our NICU despite recommended infection control practices, we instituted active surveillance cultures to determine their efficacy in detecting and controlling spread of VRE among high-risk infants.Active surveillance cultures, other infection control measures, and a mandatory in-service education module on preventing MDRO transmission were implemented. Cultures were performed on NICU admission and then weekly during their stay. Molecular DNA fingerprinting of VRE isolates facilitated targeting efforts to eliminate clonal spread of VRE. Repetitive sequence PCR (rep-PCR)-based DNA fingerprinting was used to compare isolates recovered from patients with VRE infection or colonization. Environmental VRE cultures were performed around VRE-colonized or -infected patients. DNA fingerprints were prepared from the products of rep-PCR amplification and analyzed using software to determine strain genetic relatedness.Active surveillance cultures identified 65 patients with VRE colonization or infection among 1,820 admitted to the NICU. Rep-PCR performed on 60 VRE isolates identified 3 clusters. Cluster 1 included isolates from 21 patients and 4 isolates from the environment of the index patient. Clusters 2 and 3 included isolates from 23 and 3 patients, respectively. Similarity coefficients among the members of each cluster were 95% or greater.Control of transmission of multi-clonal VRE strains was achieved. Active surveillance cultures, together with implementation of other infection control measures, combined with rep-PCR DNA fingerprinting were instrumental in controlling VRE transmission in our NICU.
Objective. To investigate the epidemiology of multidrug-resistant Enterobacteriaceae (MDRE) in hospitalized infants. Methods. From 2000 through 2005, active surveillance cultures for MDRE were performed for patients admitted to a 40-bed neonatal intensive care unit (NICU) that provides care for critically ill infants 6 months of age or younger. MDRE epidemiology and the genetic relatedness of MDRE strains determined by repetitive-sequence polymerase chain reaction were analyzed. Results. Active surveillance cultures revealed that 759 (23%) of 3,370 NICU infants (or approximately 1 in 5) developed MDRE colonization or infection and that 613 (72%) of the 853 isolates with epidemiologic data available were healthcare acquired. MDRE colonization occurred more frequently (in 653 infants [86%]) than did MDRE infection (in 106 [14%]). Of the 653 infants with MDRE colonization, 119 (18%) eventually became infected, with 29 (4%) acquiring sterile site infections. The most commonly isolated organisms were the Enterobacter species, accounting for 612 (71%) of the 862 isolates. Molecular epidemiologic analysis revealed that genetic-relatedness clustering (related clusters defined as having a genetic similarity coefficient greater than 95%) varied depending on microbial species. Clustering was detected for 36 (78%) of the 46 Enterobacter aerogenes isolates, 22 (45%) of the 49 Enterobacter cloacae isolates, and 13 (59%) of the 22 Klebsiella pneumoniae isolates. Conclusion. Hospitalized infants are at significant risk of acquiring MDRE, specifically Enterobacter species, at the study institution. Active surveillance cultures identified colonized patients who likely contributed to the institutional reservoir of MDRE. Molecular epidemiologic studies suggest that both patient-to-patient transmission and de novo acquisition of resistance play a role in the acquisition of these organisms, and that the clinical significance of such acquisition varies by species. The high percentage of E. aerogenes isolates that demonstrated genetic clustering suggests that monitoring the prevalence of this organism could serve as a useful measure of compliance with infection control procedures.
Hypoxia/reoxygenation (H/R) in vitro induced cerebral endothelial dysfunction is mediated by superoxide production. However, the intracellular pathways involved remain unclear. The present study was designed to investigate the involvement of Rho-kinase and its interaction with nitric oxide (NO) in cerebral endothelial dysfunction after H/R. Arterial diameter and intraluminal pressure were simultaneously measured in vitro on rat posterior cerebral arteries. Vascular NO production was determined by measuring stable NO metabolites nitrate/nitrite. H/R selectively inhibited cerebral vasodilation to the endothelium-dependent agonist acetylcholine (ACh, 0.01 to 10 μmol/L) and caused NO deficiency. H/R-impaired vasodilation to ACh was reversed by Y27632 (1 μmol/L), a specific inhibitor of Rho-kinase, but not by chelerythrine (1 μmol/L), a selective inhibitor of protein kinase C. Y27632 had no protective effect in the presence of NG-nitro-L-arginine methyl ester (L-NAME; 100 μmol/L), a specific endothelial NO synthase inhibitor. L-NAME (100 μmol/L) alone failed to modulate H/R-impaired vasodilation, so did L-arginine (3 mmol/L), a substrate for NO synthase. However, a stable NO donor diethylenetetra amine-NONOate (5 μmol/L) normalized H/R-impaired dilation to ACh. In conclusion, H/R-induced endothelial dysfunction is associated with activation of Rho-kinase-dependent pathway and NO deficiency. Pretreatment with either Y27632 or the stable NO donor profoundly prevented H/R-mediated cerebral endothelial dysfunction.
Venovenous extracorporeal membrane oxygenation (VV ECMO) using double lumen catheters is an alternative to venoarterial (VA) ECMO and allows for total blood flow using the patient’s cardiac output in comparison to partial blood flow provided during VA ECMO. Objective: To compare the effects of VV versus VA ECMO on renal blood flow. Design: Prospective study. Setting: Research laboratory in a hospital. Subject: Newborn lambs 1-7 days of age (n=15). Interventions: In anesthetized, ventilated lambs, fe-moral artery and vein were cannulated for monitoring and renal venous blood sampling. An ultrasonic flow probe was placed on the left renal artery for continuous renal blood flow measurements. Animals were randomly assigned to control (non-ECMO), VV ECMO and VA ECMO groups. After systemic heparinization, the animals were cannulated and studied at bypass flows of 120 mL-kg/min (partial bypass) for two hours in both ECMO groups and 200 mL/kg/min (full bypass) for an additional 30 min in the VA group. Changes in blood pressure and renal flow on ECMO and during ECMO bridge unclamping were recorded continuously. Plasma renin activity (PRA) levels were sequentially sampled. Results: Systemic blood pressure was not different in VV or VA ECMO at partial bypass flow. However, systemic blood pressure increased significantly at maximal bypass flow in the VA ECMO group. There was no change in renal flow in either VV or VA ECMO groups. PRA levels did not correlate with bypass flow change. During unclamping of the ECMO bridge, blood pressure and renal flow drop significantly in the VA group, but not in the VV group. Conclusion: VV and VA ECMO at partial bypass flows had comparable effect on blood pressure, renal blood flow and PRA level in this short-term study. However, unclamping of the ECMO bridges did differentially affect blood pressure and renal blood flow between VV and VA groups. We speculate that this repeated acute change in long-run VA ECMO support may play a role in the persistent hypertension seen in some patients.
