Therapeutic effect of antibiotics in the compromised host : an experimental study

The present study was performed in a model of Klebsiella pneumoniae pneumonia and septicemia in rats. This experimental model was used because in leukopenic patients septicemia is a real threat, and K.pneumoniae is one of the pathogens that may be recovered [68, 74, 99, 116, 122, 124]. The experimental design including the infectious disease model is described in chapter 2. The role of the antibiotic dosage schedule as a determinant of therapeutic activity was investigated in relation to various factors such as the severity of infection (chapter 3) , the presence of host defense factors (chapter 4), and the kinetics of antibacterial activity in vitro and in vivo for different classes of antibiotics (chapter 5) . From the three classes of antibiotics, the 8-lactams, the aminoglycosides and the quinolones, ceftazidime, gentamicin and ciprofloxacin were selected as investigational drug, respectively, because of their antibacterial activity against clinically important pathogens and their broad antibacterial spectrum. In addition, the in vitro susceptibility in terms of MBC values of the K.pneumoniae strain used was similar for the three drugs tested, which facilitated a good evaluation of their therapeutic efficacy. The therapeutic effect of ceftazidime, gentamicin and ciprofloxacin in relation to the duration of infection and the bacterial growth rate is described in chapter 6. Finally in chapter 7 the experimental results obtained are discussed with reference to the observations of other investigators. The chapters 3 through 6 represent the appendix papers

Helicobacter species are not detectable by 16S rDNA PCR in bile from Dutch patients with common bile duct stones.

BACKGROUND: Some Helicobacter species colonize the intestinal tract. To explore the possible relation between Helicobacter spp. and gallbladder disorders, we have investigated their presence in bile of patients with biliary obstruction and dilatation of the bile ducts. METHODS: Bile was sampled from 31 Dutch patients with biliary obstruction identified by jaundice and dilatation of the bile ducts on ultrasound. Samples (n = 31) were obtained immediately following cannulation of the common bile duct (CBD) by endoscopic retrograde cholangiopancreatography (ERCP) (n = 29) or by peri-operative puncture of the gallbladder (n = 2). DNA was isolated from bile by binding to diatoms. Helicobacter spp. were detected by a sensitive (detection limit 1 CFU per reaction tube) 16S rDNA PCR with genus-specific primers. Duplicate samples were spiked with Helicobacter pylori DNA and subjected to PCR in order to check for inhibition. RESULTS: 28 patients had CBD stones (bile collected by ERCP (n = 26) or operatively (n = 2)), 2 had a pancreatic head tumor, and in 1 no abnormalities were found. In 1 of 21 amplifiable bile samples (10/31 inhibited) from Dutch patients with CBD stones, H. pylori 16S rDNA was found. CONCLUSION: Our data indicate that CBD stones in Dutch patients are not associated with the presence of Helicobacter spp. in bil

Preventing Surgical-Site Infections in Nasal Carriers of Staphylococcus aureus

BACKGROUND Nasal carriers of Staphylococcus aureus are at increased risk for health care-associated infections with this organism. Decolonization of nasal and extranasal sites on hospital admission may reduce this risk. METHODS In a randomized, double-blind, placebo-controlled, multicenter trial, we assessed whether rapid identification of S. aureus nasal carriers by means of a real-time polymerase-chain-reaction (PCR) assay, followed by treatment with mupirocin nasal ointment and chlorhexidine soap, reduces the risk of hospital-associated S. aureus infection. RESULTS From October 2005 through June 2007, a total of 6771 patients were screened on admission. A total of 1270 nasal swabs from 1251 patients were positive for S. aureus. We enrolled 917 of these patients in the intention-to-treat analysis, of whom 808 (88.1%) underwent a surgical procedure. All the S. aureus strains identified on PCR assay were susceptible to methicillin and mupirocin. The rate of S. aureus infection was 3.4% (17 of 504 patients) in the mupirocin-chlorhexidine group, as compared with 7.7% (32 of 413 patients) in the placebo group (relative risk of infection, 0.42; 95% confidence interval [CI], 0.23 to 0.75). The effect of mupirocin-chlorhexidine treatment was most pronounced for deep surgical-site infections (relative risk, 0.21; 95% CI, 0.07 to 0.62). There was no significant difference in all-cause in-hospital mortality between the two groups. The time to the onset of nosocomial infection was shorter in the placebo group than in the mupirocin-chlorhexidine group (P = 0.005). CONCLUSIONS The number of surgical-site S. aureus infections acquired in the hospital can be reduced by rapid screening and decolonizing of nasal carriers of S. aureus on admission. (Current Controlled Trials number, ISRCTN56186788.

Type of intracranial hemorrhage after endovascular stroke treatment: association with functional outcome

Background: Intracranial hemorrhage (ICH) is a frequent complication after endovascular stroke treatment. Objective: To assess the association of the occurrence and type of ICH after endovascular treatment (EVT) with functional outcome. Methods: We analyzed data from the MR CLEAN-NO IV and MR CLEAN-MED trials. Both trials included adult patients with ischemic stroke with a large vessel occlusion in the anterior circulation, who were eligible for EVT. ICH was classified (1) as asymptomatic or symptomatic (concomitant neurological deterioration of ≥4 points on the NIHSS, or ≥2 points on 1 NIHSS item), and (2) according to the Heidelberg Bleeding Classification. We used multivariable ordinal logistic regression analyses to assess the association of the occurrence and type of ICH with the modified Rankin Scale score at 90 days. Results: Of 1017 included patients, 331 (33%) had an asymptomatic ICH, and 90 (9%) had a symptomatic ICH. Compared with no ICH, both asymptomatic (adjusted common OR (acOR)=0.76; 95% CI 0.58 to 0.98) and symptomatic (acOR=0.07; 95% CI 0.04 to 0.14) ICH were associated with worse functional outcome. In particular, isolated parenchymal hematoma type 2 (acOR=0.37; 95% CI 0.14 to 0.95), combined parenchymal hematoma with hemorrhage outside infarcted brain tissue (acOR=0.17; 95% CI 0.10 to 0.30), and combined hemorrhages outside infarcted brain tissue (acOR=0.14; 95% CI 0.03 to 0.74) were associated with worse functional outcome than no ICH. Strength of the association of ICH with functional outcome depends on the type of ICH. Although the association is stronger for symptomatic ICH, asymptomatic ICH after EVT is also associated with worse functional outcome

Clinical consequence of vessel perforations during endovascular treatment of acute ischemic stroke

Purpose: Endovascular treatment (EVT) of acute ischemic stroke can be complicated by vessel perforation. We studied the incidence and determinants of vessel perforations. In addition, we studied the association of vessel perforations with functional outcome, and the association between location of perforation on digital subtraction angiography (DSA) and functional outcome, using a large EVT registry. Methods: We included all patients in the MR CLEAN Registry who underwent EVT. We used DSA to determine whether EVT was complicated by a vessel perforation. We analyzed the association with baseline clinical and interventional parameters using logistic regression models. Functional outcome was measured using the modified Rankin Scale at 90 days. The association between vessel perforation and angiographic imaging features and functional outcome was studied using ordinal logistic regression models adjusted for prognostic parameters. These associations were expressed as adjusted common odds ratios (acOR). Results: Vessel perforation occurred in 74 (2.6%) of 2794 patients who underwent EVT. Female sex (aOR 2.0 (95% CI 1.2–3.2)) and distal occlusion locations (aOR 2.2 (95% CI 1.3–3.5)) were associated with increased risk of vessel perforation. Functional outcome was worse in patients with vessel perforation (acOR 0.38 (95% CI 0.23–0.63)) compared to patients without a vessel perforation. No significant association was found between location of perforation and functional outcome. Conclusion: The incidence of vessel perforation during EVT in this cohort was low, but has severe clinical consequences. Female patients and patients treated at distal occlusion locations are at higher risk.</p

Clinical consequence of vessel perforations during endovascular treatment of acute ischemic stroke

Purpose: Endovascular treatment (EVT) of acute ischemic stroke can be complicated by vessel perforation. We studied the incidence and determinants of vessel perforations. In addition, we studied the association of vessel perforations with functional outcome, and the association between location of perforation on digital subtraction angiography (DSA) and functional outcome, using a large EVT registry. Methods: We included all patients in the MR CLEAN Registry who underwent EVT. We used DSA to determine whether EVT was complicated by a vessel perforation. We analyzed the association with baseline clinical and interventional parameters using logistic regression models. Functional outcome was measured using the modified Rankin Scale at 90 days. The association between vessel perforation and angiographic imaging features and functional outcome was studied using ordinal logistic regression models adjusted for prognostic parameters. These associations were expressed as adjusted common odds ratios (acOR). Results: Vessel perforation occurred in 74 (2.6%) of 2794 patients who underwent EVT. Female sex (aOR 2.0 (95% CI 1.2–3.2)) and distal occlusion locations (aOR 2.2 (95% CI 1.3–3.5)) were associated with increased risk of vessel perforation. Functional outcome was worse in patients with vessel perforation (acOR 0.38 (95% CI 0.23–0.63)) compared to patients without a vessel perforation. No significant association was found between location of perforation and functional outcome. Conclusion: The incidence of vessel perforation during EVT in this cohort was low, but has severe clinical consequences. Female patients and patients treated at distal occlusion locations are at higher risk.</p

Prioritizing a research agenda on built environments and physical activity: a twin panel Delphi consensus process with researchers and knowledge users

BACKGROUND: The growth of urban dwelling populations globally has led to rapid increases of research and policy initiatives addressing associations between the built environment and physical activity (PA). Given this rapid proliferation, it is important to identify priority areas and research questions for moving the field forward. The objective of this study was to identify and compare research priorities on the built environment and PA among researchers and knowledge users (e.g., policy makers, practitioners).METHODS: Between September 2022 and April 2023, a three-round, modified Delphi survey was conducted among two independent panels of international researchers (n = 38) and knowledge users (n = 23) to identify similarities and differences in perceived research priorities on the built environment and PA and generate twin 'top 10' lists of the most important research needs.RESULTS: From a broad range of self-identified issues, both panels ranked in common the most pressing research priorities including stronger study designs such as natural experiments, research that examines inequalities and inequities, establishing the cost effectiveness of interventions, safety and injuries related to engagement in active transportation (AT), and considerations for climate change and climate adaptation. Additional priorities identified by researchers included: implementation science, research that incorporates Indigenous perspectives, land-use policies, built environments that support active aging, and participatory research. Additional priorities identified by knowledge users included: built environments and PA among people living with disabilities and a need for national data on trip chaining, multi-modal travel, and non-work or school-related AT.CONCLUSIONS: Five common research priorities between the two groups emerged, including (1) to better understand causality, (2) interactions with the natural environment, (3) economic evaluations, (4) social disparities, and (5) preventable AT-related injuries. The findings may help set directions for future research, interdisciplinary and intersectoral collaborations, and funding opportunities.</p