Optimization of Artificial Siderophores as 68Ga-Complexed PET Tracers for In Vivo Imaging of Bacterial Infections.

The diagnosis of bacterial infections at deep body sites benefits from noninvasive imaging of molecular probes that can be traced by positron emission tomography (PET). We specifically labeled bacteria by targeting their iron transport system with artificial siderophores. The cyclen-based probes contain different binding sites for iron and the PET nuclide gallium-68. A panel of 11 siderophores with different iron coordination numbers and geometries was synthesized in up to 8 steps, and candidates with the best siderophore potential were selected by a growth recovery assay. The probes [68Ga]7 and [68Ga]15 were found to be suitable for PET imaging based on their radiochemical yield, radiochemical purity, and complex stability in vitro and in vivo. Both showed significant uptake in mice infected with Escherichia coli and were able to discern infection from lipopolysaccharide-triggered, sterile inflammation. The study qualifies cyclen-based artificial siderophores as readily accessible scaffolds for the in vivo imaging of bacteria.

In vitro evaluation of 99m Tc-sultamicillin for infection imaging.

Early detection of the site of infection non-invasively with radiolabeled molecules is important for the success of treatment. Technetium-99m labeled antibiotics have the potential to discriminate between bacterial infection and sterile inflammation. Sultamicillin is the tosylate salt of the double ester of sulbactam plus ampicillin. In this study, sultamicillin was labeled with 99m Tc according to the stannous chloride method. Quality control studies of radiolabeled sultamicillin were performed by radiochromatographic methods. In vitro binding assays were performed in live and heat-killed gram-positive Staphylococcus aureus and gram-negative Escherichia coli strains. The radiolabeling yield of 99m Tc-sultamicillin was determined as 97.8% ± 3.1% (n = 5). The maximum bacterial uptake of 99m Tc-sultamicillin was 80.7% ± 11.00% at 4 h for living S. aureus and 93.2% ± 4.40% at 2 h for E. coli. Bacterial uptake study results show that sultamicillin has the potential to be a nuclear imaging agent, especially in infections caused by gram-negative E. coli and gram-positive S. aureus.

A Neonatal Imaging Model of Gram-Negative Bacterial Sepsis.

Neonates are at an increased risk of bacterial sepsis due to the unique immune profile they display in the first months of life. We have established a protocol for studying the pathogenesis of E. coli O1:K1:H7, a serotype responsible for high mortality rates in neonates. Our method utilizes intravital imaging of neonatal pups at different time points during the progression of infection. This imaging, paralleled by measurement of bacteria in the blood, inflammatory profiling, and tissue histopathology, signifies a rigorous approach to understanding infection dynamics during sepsis. In the current report, we model two infectious inoculums for comparison of bacterial burdens and severity of disease. We find that subscapular infection leads to disseminated infection by 10 h post-infection. By 24 h, infection of luminescent E. coli was abundant in the blood, lungs, and other peripheral tissues. Expression of inflammatory cytokines in the lungs is significant at 24 h, and this is followed by cellular infiltration and evidence of tissue damage that increases with infectious dose. Intravital imaging does have some limitations. This includes a luminescent signal threshold and some complications that can arise with neonates during anesthesia. Despite some limitations, we find that our infection model offers an insight for understanding longitudinal infection dynamics during neonatal murine sepsis, that has not been thoroughly examined to date. We expect this model can also be adapted to study other critical bacterial infections during early life.

Differentiation of Myositis-Induced Models of Bacterial Infection and Inflammation with T2-Weighted, CEST, and DCE-MRI.

We used T2 relaxation, chemical exchange saturation transfer (CEST), and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) to assess whether bacterial infection can be differentiated from inflammation in a myositis-induced mouse model. We measured the T2 relaxation time constants, %CEST at 5 saturation frequencies, and area under the curve (AUC) from DCE-MRI after maltose injection from infected, inflamed, and normal muscle tissue models. We applied principal component analysis (PCA) to reduce dimensionality of entire CEST spectra and DCE signal evolutions, which were analyzed using standard classification methods. We extracted features from dimensional reduction as predictors for machine learning classifier algorithms. Normal, inflamed, and infected tissues were evaluated with H&E and gram-staining histological studies, and bacterial-burden studies. The T2 relaxation time constants and AUC of DCE-MRI after injection of maltose differentiated infected, inflamed, and normal tissues. %CEST amplitudes at -1.6 and -3.5 ppm differentiated infected tissues from other tissues, but these did not differentiate inflamed tissue from normal tissue. %CEST amplitudes at 3.5, 3.0, and 2.5 ppm, AUC of DCE-MRI for shorter time periods, and relative Ktrans and kep values from DCE-MRI could not differentiate tissues. PCA and machine learning of CEST-MRI and DCE-MRI did not improve tissue classifications relative to traditional analysis methods. Similarly, PCA and machine learning did not further improve tissue classifications relative to T2 MRI. Therefore, future MRI studies of infection models should focus on T2-weighted MRI and analysis of T2 relaxation times.

Construction of biocompatible bovine serum albumin nanoparticles composed of nano graphene oxide and AIEgen for dual-mode phototherapy bacteriostatic and bacterial tracking.

BACKGROUND: Efficient and highly controllable antibacterial effect, as well as good biocompatibility are required for antibacterial materials to overcome multi-drug resistance in bacteria. Herein, nano graphene oxide (NGO)-based near-infrared (NIR) photothermal antibacterial materials was schemed to complex with biocompatible bovine serum albumin (BSA) and aggregation-induced emission fluorogen (AIEgen) with daylight-stimulated ROS-producing property for dual-mode phototherapy in the treatment of antibiotic resistance bacteria. RESULTS: Upon co-irradiation of daylight and NIR laser, NGO-BSA-AIE nanoparticles (NPs) showed superiorly antibacterial effect (more than 99%) both against amoxicillin (AMO)-resistant Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) by comparison with sing-model phototherapy. Meanwhile, the NGO-BSA-AIE NPs displayed prominent stability and excellently controllable biocompatibility. More importantly, under daylight irradiation, the AIEgen not only produced plentiful ROS for killing bacteria, but also presented fluorescence image for tracking bacteria. CONCLUSIONS: Hence, the designed system provided tempting strategy of employing light as impetus for tracking bacterial distribution and photothermal/photodynamic synergistic treatment of antibiotic resistance antibacterial.

Infected Abdominal Aortic Aneurysm After Transrectal Ultrasound-Guided Biopsy of the Prostate: A Report of Two Cases.

Primary infected abdominal aortic aneurysm (AAA) is an uncommon presentation which can be associated with significant morbidity and mortality. In this report, we present 2 cases of infected AAAs less than 10 days after a transrectal ultrasound-guided (TRUS) prostate biopsy. A 63-year-old male presenting with sepsis and back pain 9 days after TRUS biopsy was found to have a 27-mm ectatic abdominal aorta which expanded to 59 mm in the course of a week, despite antibiotic therapy. He underwent successful surgical excision of the infected aortic aneurysm and reconstruction using a vein. A 55-year-old male presented similarly, 7 days after prostate biopsy with a 60-mm aortic aneurysm. His aneurysm ruptured 2 days before planned intervention-he did not survive an emergency repair. In both cases, aortic tissue biopsies confirmed growth of Escherichia coli. Preexistence of an aortic aneurysm was not known in either case as neither patient had imaging of the abdominal aorta. We postulate the pathophysiology was due to hematogenous spread.

Comparison of CSF and MRI Findings among Neonates and Infants with E coli or Group B Streptococcal Meningitis.

BACKGROUND AND PURPOSE: Group B Streptococcus and Escherichia coli (E coli) are the 2 most common causes of bacterial meningitis in neonates. The purpose of this study was to determine whether CSF and/or MR imaging findings differ between infants with group B streptococcal or E coli meningitis. MATERIALS AND METHODS: A retrospective review was performed among neonates (younger than 28 days) and infants (younger than 120 days) with proved group B streptococcal (n = 57) or E coli meningitis (n = 50). A CSF or blood culture positive for Streptococcus or E coli and an elevated CSF white blood cell count were used as the criterion standard. Independent, blinded review of brain MRIs obtained within 21 days of presentation were performed by 2 board-certified neuroradiologists. CSF laboratory values and MR imaging findings were compared between the groups. RESULTS: There was no statistically significant difference between the mean age at presentation for patients with group B streptococcal (40 days; range, 2-111 days) versus patients with E coli meningitis (31 days; range, 12-115 days) (P = .18). There was no statistically significant difference in the CSF white blood cell count, glucose, or protein. There was a significant difference between group B streptococcal and E coli meningitis in the frequency of hydrocephalus (0% versus 22%, P = .001) and infarct (40% versus 14%; P = .038), respectively. There was no statistically significant difference in leptomeningeal enhancement, cerebritis, ventriculitis, abscess/granuloma, subdural effusion, extra-axial purulent material, intraventricular purulent material, hemorrhage, and sinus thrombosis. CONCLUSIONS: Although neonates and infants with group B streptococcal or E coli meningitis had similar age and CSF laboratory values, patients with group B streptococcal meningitis more frequently demonstrated infarcts, while those with E coli meningitis more frequently had early onset of hydrocephalus.

Raman microspectroscopy differentiates perinatal pathogens on ex vivo infected human fetal membrane tissues.

Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is a major cause of chorioamnionitis and neonatal sepsis. This study evaluates Raman spectroscopy (RS) to identify spectral characteristics of infection and differentiate GBS from Escherichia coli and Staphylococcus aureus during ex vivo infection of human fetal membrane tissues. Unique spectral features were identified from colonies grown on agar and infected fetal membrane tissues. Multinomial logistic regression analysis accurately identified GBS infected tissues with 100.0% sensitivity and 88.9% specificity. Together, these findings support further investigation into the use of RS as an emerging microbiologic diagnostic tool and intrapartum screening test for GBS carriage.

Characteristics and Findings of Childhood Urinary Tract Infection in the Last Decade.

BACKGROUND: The strong association between kidney and urinary tract anomalies and childhood urinary tract infection (UTI) often leads to imaging tests being performed. -Objective: To describe the epidemiology, characteristics, and imaging findings in Thai children with UTI and compare results between boys and girls. METHODS: We retrospectively reviewed the medical records of children with UTI aged < 15 years. Demographic characteristics and findings of investigations are presented. RESULTS: One hundred seventy-eight boys and 170 girls with 432 UTI episodes were identified. The median (interquartile range) age at presentation was 1.4 (0.6-3.4) years, 1.0 for boys and 2.1 for girls (p < 0.001). Renal ultrasound, voiding cystourethrogram and 99mTc dimercaptosuccinic acid (DMSA) renal scans were performed in 273, 223 and 113 children, respectively. Overall, 283 children (81.3%) had at least one imaging study done and anomalies of the kidney and urinary tract were detected in 158 (45.4%). Primary vesicoureteral reflux was detected in 73 (32.7%) children. The remaining abnormalities were hydronephrosis (n = 54). DMSA scans detected 54 children with dysplastic or scarred kidneys. CONCLUSIONS: First UTI in a group of Thai children occurred in approximately equal proportion in boys and girls but boys were younger at diagnosis. Kidney and urinary tract anomalies were detected in half of the children.

An unexpected case of iatrogenic Escherichia coli endogenous pan-endopthalmitis after ERCP-associated biliary sepsis: A case report.

INTRODUCTION: Endogenous endopthalmitis is a diagnostically challenging ophthalmic and medical emergency. It has the ability to manifest at any age and is associated with a number of predisposing factors. The rapid progression of disease poses catastrophic risk for adverse outcomes both localised and systemic. To our knowledge, we describe the first reported iatrogenic case of endogenous Escherichia coli-induced endopthalmitis progressing to pan-endopthalmitis as a consequence of endoscopic retrograde cholangiopancreatography. DIAGNOSIS, INTERVENTIONS AND OUTCOMES: The patient presented with reduced visual acuity and painless red eye; however, apart from biochemistry results suggesting biliary sepsis, no other clinical features of acute disease were noted. Despite rigorous systemic and intravitreal treatment, the rapid progression of disease led to irreversible damage to the eye. CONCLUSION: Clinicians must maintain a very high index of suspicion when encountering patients after interventional procedures, as misdiagnosis by trained ophthalmologists for endogenous endopthalmitis remains a common occurrence. Prompt identification and diagnosis ensured our patient avoided evisceration and early ophthalmic biopsies guaranteed the correct systemic intervention was started to address the severe subsequent septicaemia.

Magnetic resonance imaging appearance of the brain and cervical spinal cord in an edema disease affected pig.

A 7-week-old male pig was presented with signs of a central nervous system disorder. An MRI of the head and cervical spine was performed immediately after euthanasia. The MRI revealed multifocal bilaterally symmetric T2-weighted hyperintense lesions in the brain and spinal cord, likely due to a toxic metabolic process. Histopathological examination supported the MRI findings and confirmed the diagnosis of edema disease due to Shiga-like toxin produced by Escherichia coli. This is the first case published of the MRI findings in an edema disease affected pig.

Susceptibility of 99mTc-Ciprofloxacin for Common Infection Causing Bacterial Strains Isolated from Clinical Samples: an In Vitro and In Vivo Study.

99mTc-ciprofloxacin scintigraphy is useful in the detection of gram-positive and gram-negative bacterial infections and also for differentiating the infection from aseptic inflammation. However, due to growing bacterial resistance to antibiotics, the 99mTc-ciprofloxacin no longer can be effective in broad-spectrum infection imaging as it is gradually losing specificity. In this study, we are presenting our findings regarding the in vitro and in vivo susceptibility of 99mTc-ciprofloxacin for multi-drug-resistant Staphylococcus aurous, Escherichia coli, and Pseudomonas aeruginosa bacterial strains which were isolated from clinical samples. The results of radiosynthesis of 99mTc-ciprofloxacin showed more the 95% radiochemical purity and less than 5% radioactive impurities. In vitro 99mTc-ciprofloxacin susceptibility test showed that E. coli offered more resistant to 99mTc-ciprofloxacin as compared to S. aurous and P. aeruginosa. In vivo study using bacterial infection induced rabbit model also revealed lowest uptake by E. coli lesion. The T/NT values were obtained 1.96 ± 0.15 in the case of E. coli; 2.81 ± 0.51 in the case of S. aurous; and 2.32 ± 0.66 in the case of P. aeruginosa at 4 h post-injection. The SPECT infection imaging of S. aurous, E. coli, and P. aeruginosa bacterial infection induced rabbit models also indicated the clear accumulation in S. aurous and P. aeruginosa lesions while negligible uptake by E. coli lesion further verify the in vitro and in vivo susceptibility profile. On the bases of the results obtained, the 99mTc-ciprofloxacin showed selective and poor broad spectrum SPECT infection imaging.

Imaging Inflammation and Infection in the Gastrointestinal Tract.

A variety of seemingly non-specific symptoms manifest within the gastrointestinal (GI) tract, particularly in the colon, in response to inflammation, infection, or a combination thereof. Differentiation between symptom sources can often be achieved using various radiologic studies. Although it is not possible to provide a comprehensive survey of imaging gastrointestinal GI tract infections in a single article, the purpose of this review is to survey several topics on imaging of GI tract inflammation and infections. The review discusses such modalities as computed tomography, positron emission tomography, ultrasound, endoscopy, and magnetic resonance imaging while looking at up-an-coming technologies that could improve diagnoses and patient comfort. The discussion is accomplished through examining a combination of organ-based and organism-based approaches, with accompanying selected case examples. Specific focus is placed on the bacterial infections caused by Shigella spp., Escherichia coli, Clostridium difficile, Salmonella, and inflammatory conditions of diverticulitis and irritable bowel disease. These infectious and inflammatory diseases and their detection via molecular imaging will be compared including the appropriate differential diagnostic considerations.

Infected cyst in patients with autosomal dominant polycystic kidney disease: Analysis of computed tomographic and ultrasonographic imaging features.

PURPOSE: To investigate the imaging features of cyst infection in autosomal dominant polycystic kidney disease (ADPKD) patients using computed tomography (CT) and ultrasonography (US). MATERIALS & METHODS: The institutional review board approved this retrospective study. Fifty-one episodes with proven cyst infection in forty-three ADPKD patients were included. Two experienced abdominal radiologists reviewed CT and US images and evaluated the following imaging features in consensus: cyst size, location, cyst shape, intracystic attenuation, intracystic echogenicity, intracystic heterogeneity, wall thickness, the presence of fluid-fluid level, septation, intracystic gas, pericystic fat infiltration, and pericystic hyperemia. Intracystic attenuation was measured for all infected cysts and two presumed normal cysts and compared using the Wilcoxon rank-sum test. RESULTS: On CT scans, the median size of infected cysts was 5.5 cm (range: 2.3-18.8 cm) and 46 of 51 (90.2%) infected cysts were located in the subcapsular region. Most (48 of 51, 94.1%) infected cysts showed lobulated, focal bulging or irregular shape. Discernible wall thickening (84.1%) was the most frequently found imaging feature of infected cysts followed by relatively higher intracystic attenuation compared to normal cysts (79.1%) and pericystic fat infiltration (52.9%). Fluid/fluid level was found in 3 of 51 (5.9%) infected cysts and intracystic gas was found in 3 of 51 (5.9%) infected cysts, respectively. For hepatic cysts, 11 of 14 (78.6%) infected cysts showed pericystic hyperemia. Intracystic attenuation was significantly higher in infected cysts (median; 19.0 HU) than in presumed normal cysts (median; 8.5 HU) (P<0.001), and exceeded 25 HU in 18 (35.3%) of 51 infected cysts. Among the 41 infected cysts for which US images were available, 35 (85.1%) showed heterogeneous echogenicity. CONCLUSION: Minute imaging features such as minimal wall thickening or relatively high attenuation compared to normal cysts would be helpful to detect infected cysts in ADPKD patients.

Synthesis and evaluation of a [18F]formyl-Met-Leu-Phe derivative: A positron emission tomography imaging probe for bacterial infections.

The tripeptide formyl-Met-Leu-Phe (fMLF) is a prototype of N-formylated chemotactic peptides for neutrophils owing to its ability to bind and activate the G protein-coupled formyl peptide receptor (FPR). Here, we developed an 18F-labeled fMLF derivative targeting FPR as a positron emission tomography (PET) imaging probe for bacterial infections. The study demonstrates that the fMLF derivative fMLFXYk(FB)k (X = Nle) has a high affinity for FPR (Ki = 0.62 ±â€¯0.13 nM). The radiochemical yield and purity of [18F]fMLFXYk(FB)k were 16% and >96%, respectively. The in vivo biodistribution study showed that [18F]fMLFXYk(FB)k uptake was higher in the bacterial infected region than in the non-infected region. We observed considerably higher infection-to-muscle ratio of 4.6 at 60 min after [18F]fMLFXYk(FB)k injection. Furthermore, small-animal PET imaging studies suggested that [18F]fMLFXYk(FB)k uptake in the bacterial infected region was clearly visualized 60 min after injection.