In vivo Labeling and Intravital Imaging of Bacterial Infection using a Near-infrared Fluorescent D-Amino Acid Probe.

Bacterial infections still pose a severe threat to public health, necessitating novel tools for real-time analysis of microbial behaviors in living organisms. While genetically engineered strains with fluorescent or luminescent reporters are commonly used in tracking bacteria, their in vivo uses are often limited. Here, we report a near-infrared fluorescent D-amino acid (FDAA) probe, Cy7ADA, for in situ labeling and intravital imaging of bacterial infections in mice. Cy7ADA probe effectively labels various bacteria in vitro and pathogenic Staphylococcus aureus in mice after intraperitoneal injection. Because of Cy7's high tissue penetration and the quick excretion of free probes via urine, real-time visualization of the pathogens in a liver abscess model via intravital confocal microscopy is achieved. The biodistributions, including their intracellular localization within Kupffer cells, are revealed. Monitoring bacterial responses to antibiotics also demonstrates Cy7ADA's capability to reflect the bacterial load dynamics within the host. Furthermore, Cy7ADA facilitates three-dimensional pathogen imaging in tissue-cleared liver samples, showcasing its potential for studying the biogeography of microbes in different organs. Integrating near-infrared FDAA probes with intravital microscopy holds promise for wide applications in studying bacterial infections in vivo.

Synthesis and preclinical evaluation of novel 18F-vancomycin-based tracers for the detection of bacterial infections using positron emission tomography.

INTRODUCTION: Bacterial infections are a major problem in medicine, and the rapid and accurate detection of such infections is essential for optimal patient outcome. Bacterial infections can be diagnosed by nuclear imaging, but most currently available modalities are unable to discriminate infection from sterile inflammation. Bacteria-targeted positron emission tomography (PET) tracers have the potential to overcome this hurdle. In the present study, we compared three 18F-labelled PET tracers based on the clinically applied antibiotic vancomycin for targeted imaging of Gram-positive bacteria. METHODS: [18F]FB-NHS and [18F]BODIPY-FL-NHS were conjugated to vancomycin. The resulting conjugates, together with our previously developed [18F]PQ-VE1-vancomycin, were tested for stability, lipophilicity, selective binding to Gram-positive bacteria, antimicrobial activity and biodistribution. For the first time, the pharmacokinetic properties of all three tracers were compared in healthy animals to identify potential binding sites. RESULTS: [18F]FB-vancomycin, [18F]BODIPY-FL-vancomycin, and [18F]PQ-VE1-vancomycin were successfully synthesized with radiochemical yields of 11.7%, 2.6%, and 0.8%, respectively. [18F]FB-vancomycin exhibited poor in vitro and in vivo stability and, accordingly, no bacterial binding. In contrast, [18F]BODIPY-FL-vancomycin and [18F]PQ-VE1-vancomycin showed strong and specific binding to Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), which was outcompeted by unlabeled vancomycin only at concentrations exceeding clinically relevant vancomycin blood levels. Biodistribution showed renal clearance of [18F]PQ-VE1-vancomycin and [18F]BODIPY-FL-vancomycin with low non-specific accumulation in muscles, fat and bones. CONCLUSION: Here we present the synthesis and first evaluation of the vancomycin-based PET tracers [18F]BODIPY-FL-vancomycin and [18F]PQ-VE1-vancomycin for image-guided detection of Gram-positive bacteria. Our study paves the way towards real-time bacteria-targeted diagnosis of soft tissue and implant-associated infections that are oftentimes caused by Gram-positive bacteria, even after prophylactic treatment with vancomycin.

Bacterial osteomyelitis in pediatric patients: a comprehensive review.

Bacterial osteomyelitis, an inflammatory response in the bone caused by microorganisms, typically affects the metaphysis in the skeletally immature. Bacterial osteomyelitis possesses a significant diagnostic challenge in pediatric patients due to its nonspecific clinical presentation. Because the metaphysis is the primary focus of infection in skeletally immature patients, understanding the normal physiologic, maturation process of bones throughout childhood allows to understand the pathophysiology of osteomyelitis. Timely and accurate diagnosis is crucial to initiate appropriate treatment, and prevent long-term sequelae and efforts must be made to isolate the causative organism. The potential causative organism changes according to the age of the patient and underlying medical conditions. Staphylococcus Aureus is the most common isolated bacteria in pediatric pyogenic osteomyelitis whereas Kingella Kingae is the most common causative agent in children aged 6 months to 4 years. Imaging plays a pivotal role in the diagnosis, characterization, evaluation of complications, and follow up of bacterial osteomyelitis. Imaging also plays a pivotal role in the evaluation of potential neoplastic and non-neoplastic mimickers of osteomyelitis. In children, MRI is currently the gold standard imaging modality when suspecting bacterial osteomyelitis, whereas surgical intervention may be required in order to isolate the microorganism, treat complications, and exclude mimickers.

Visualizing Bacterial Infections With Novel Targeted Molecular Imaging Approaches.

Although nearly a century has elapsed since the discovery of penicillin, bacterial infections remain a major global threat. Global antibiotic use resulted in an astounding 42 billion doses of antibiotics administered in 2015 with 128 billion annual doses expected by 2030. This overuse of antibiotics has led to the selection of multidrug-resistant "super-bugs," resulting in increasing numbers of patients being susceptible to life-threatening infections with few available therapeutic options. New clinical tools are therefore urgently needed to identify bacterial infections and monitor response to antibiotics, thereby limiting overuse of antibiotics and improving overall health. Next-generation molecular imaging affords unique opportunities to target and identify bacterial infections, enabling spatial characterization as well as noninvasive, temporal monitoring of the natural course of the disease and response to therapy. These emerging noninvasive imaging approaches could overcome several limitations of current tools in infectious disease, such as the need for biological samples for testing with their associated sampling bias. Imaging of living bacteria can also reveal basic biological insights about their behavior in vivo.

Persistent Luminescence-Based Theranostics for Real-Time Monitoring and Simultaneously Launching Photodynamic Therapy of Bacterial Infections.

External light irradiation is usually required in bacterial infection theranostics; however, it is always accompanied by limited light penetration, imaging interference, and incomplete bacterial destruction. Herein, a feasible "image-launching therapy" strategy is developed to integrate real-time optical imaging and simultaneous photodynamic therapy (PDT) of bacterial infections into persistent luminescence (PL) nanoparticles (NPs). Mesoporous silica NPs are used as a substrate for in situ deposition of PL nanodots of ZnGa2 O4 :Cr3+ to obtain mPL NPs, followed by surface grafting with silicon phthalocyanine (Si-Pc) and electrostatic assembly of cyanine 7 (Cy7) to fabricate mPL@Pc-Cy NPs. The PL emission of light-activated mPL@Pc-Cy NPs is quenched by Cy7 assembly at physiological conditions through the fluorescence resonance energy transfer effect, but is rapidly restored after disassembly of Cy7 in response to bacterial infections. The self-illuminating capabilities of NPs avoid tissue autofluorescence under external light irradiation and achieve real-time colorimetric imaging of bacterial infections. In addition, the afterglow of mPL NPs can persistently excite Si-Pc photosensitizers to promote PDT efficacy for bacterial elimination and accelerate wound full recovery with normal histologic features. Thus, this study expands the theranostic strategy for precise imaging and simultaneous non-antibiotic treatment of bacterial infections without causing side effects to normal tissues.

Multimodal Imaging and Phototherapy of Cancer and Bacterial Infection by Graphene and Related Nanocomposites.

The advancements in nanotechnology and nanomedicine are projected to solve many glitches in medicine, especially in the fields of cancer and infectious diseases, which are ranked in the top five most dangerous deadly diseases worldwide by the WHO. There is great concern to eradicate these problems with accurate diagnosis and therapies. Among many developed therapeutic models, near infra-red mediated phototherapy is a non-invasive technique used to invade many persistent tumors and bacterial infections with less inflammation compared with traditional therapeutic models such as radiation therapy, chemotherapy, and surgeries. Herein, we firstly summarize the up-to-date research on graphene phototheranostics for a better understanding of this field of research. We discuss the preparation and functionalization of graphene nanomaterials with various biocompatible components, such as metals, metal oxides, polymers, photosensitizers, and drugs, through covalent and noncovalent approaches. The multifunctional nanographene is used to diagnose the disease with confocal laser scanning microscopy, magnetic resonance imaging computed tomography, positron emission tomography, photoacoustic imaging, Raman, and ToF-SMIS to visualize inside the biological system for imaging-guided therapy are discussed. Further, treatment of disease by photothermal and photodynamic therapies against different cancers and bacterial infections are carefully conferred herein along with challenges and future perspectives.

Likelihood of Bacterial Infection in Patients Treated With Broad-Spectrum IV Antibiotics in the Emergency Department.

OBJECTIVES: Best practice guidelines and quality metrics recommend immediate antibiotic treatment for all patients with suspected sepsis. However, little is known about how many patients given IV antibiotics in the emergency department are ultimately confirmed to have bacterial infection. DESIGN, SETTING, AND PATIENTS: We performed a retrospective study of adult patients who presented to four Massachusetts emergency departments between June 2015 and June 2018 with suspected serious bacterial infection, defined as blood cultures drawn and broad-spectrum IV antibiotics administered. Structured medical record reviews were performed on a random sample of 300 cases to determine the post hoc likelihood of bacterial infection, categorized as definite, likely, unlikely, or definitely none. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 300 patients with suspected serious bacterial infections, mean age was 68 years (sd 18), median hospital length of stay was 5 days (interquartile range, 3-8 d), 45 (15%) were admitted directly to ICU, and 14 (5%) died in hospital. Overall, 196 (65%) had definite (n = 115; 38%) or likely (n = 81; 27%) bacterial infection, whereas 104 (35%) were unlikely (n = 55; 18%) or definitely not infected (n = 49; 16%). Antibiotic treatment durations differed by likelihood of infection (median 15 days for definite, 9 for likely, 7 for unlikely, and 3 for definitely not infected). The most frequent post hoc diagnoses in patients with unlikely or definitely no bacterial infection included viral infections (28%), volume overload or cardiac disease (9%), drug effects (9%), and hypovolemia (7%). The likelihoods of infection were similar in the subset of 96 cases in whom emergency department providers explicitly documented possible or suspected sepsis and in the 45 patients admitted from the emergency department to the ICU. CONCLUSIONS: One third of patients empirically treated with broad-spectrum antibiotics in the emergency department are ultimately diagnosed with noninfectious or viral conditions. These findings underscore the difficulty diagnosing serious infections in the emergency department and have important implications for guidelines and quality measures that compel immediate empiric antibiotics for all patients with possible sepsis.

Radiolabeling and evaluation of a novel [99mTcN]2+ complex with deferoxamine dithiocarbamate as a potential agent for bacterial infection imaging.

In order to find a 99mTc-labeled deferoxamine radiotracer for bacterial infection imaging, deferoxamine dithiocarbamate (DFODTC) was successfully synthesized and it was radiolabeled with [99mTcN]2+ core to prepare the 99mTcN(DFODTC)2 complex. 99mTcN(DFODTC)2 was obtained with high radiochemical purity without further purification. The complex was lipophilic and exhibited good in vitro stability. According to the result of bacterial binding study, the binding of 99mTcN(DFODTC)2 to bacteria was specific. Biodistribution in mice study indicated that 99mTcN(DFODTC)2 had a higher uptake in bacterial infection tissues than in turpentine-induced abscesses at 120 min after injection, which showed that the radiotracer could differentiate between bacterial infection and sterile inflammation. SPECT/CT images showed that there was a clear accumulation in infection sites, suggesting that 99mTcN(DFODTC)2 could be a potential bacterial infection imaging radiotracer.

Cumulative radiation dose incurred during the management of complex pleural space infection.

BACKGROUND: Complex pleural space infections are commonly managed with antibiotics, pleural drainage, intrapleural fibrinolytic therapy, and surgery. These strategies often utilize radiographic imaging during management, however little data is available on cumulative radiation exposure received during inpatient management. We aimed to identify the type and quantity of radiographic studies along with the resultant radiation exposure during the management of complex pleural space infections. METHODS: Retrospective review of community network healthcare system from January 2015 to July 2018. Patients were identified through billing databases as receiving intrapleural fibrinolytic therapy and/or surgical intervention. Patient demographics, clinical outcomes, and inpatient radiographic imaging was collected to calculate cumulative effective dose. RESULTS: A total of 566 patients were identified with 7275 total radiographic studies performed and a median cumulative effective dose of 16.9 (IQR 9.9-26.3) mSv. Multivariable linear regression analysis revealed computed tomography use was associated with increased cumulative dose, whereas increased age was associated with lower cumulative dose. Over 74% of patients received more than 10 mSv, with 7.4% receiving more than 40 mSv. CONCLUSIONS: The number of radiographic studies and overall cumulative effective dose in patients hospitalized for complex pleural space infection was high with the median cumulative effective dose > 5 times normal yearly exposure. Ionizing radiation and modern radiology techniques have revolutionized medical care, but are likely not without risk. Additional study is warranted to identify the frequency and imaging type needed during complex pleural space infection management, attempting to keep ionizing radiation exposure as low as reasonably possible.

Cyanine-Dyad Molecular Probe for the Simultaneous Profiling of the Evolution of Multiple Radical Species During Bacterial Infections.

Real-time monitoring of the evolution of bacterial infection-associated multiple radical species is critical to accurately profile the pathogenesis and host-defense mechanisms. Here, we present a unique dual wavelength near-infrared (NIR) cyanine-dyad molecular probe (HCy5-Cy7) for simultaneous monitoring of reactive oxygen and nitrogen species (RONS) variations both in vitro and in vivo. HCy5-Cy7 specifically turns on its fluorescence at 660 nm via superoxide or hydroxyl radical (O2.- , . OH)-mediated oxidation of reduced HCy5 moiety to Cy5, while peroxynitrite or hypochlorous species (ONOO- , ClO- )-induced Cy7 structural degradation causes the emission turn-off at 800 nm. Such multispectral but reverse signal responses allow multiplex manifestation of in situ oxidative and nitrosative stress events during the pathogenic and defensive processes in both bacteria-infected macrophage cells and living mice. Most importantly, this study may also provide new perspectives for understanding the bacterial pathogenesis and advancing the precision medicine against infectious diseases.

Evaluation of Musculoskeletal and Pulmonary Bacterial Infections With [124I]FIAU PET/CT.

PURPOSE: Imaging is limited in the evaluation of bacterial infection. Direct imaging of in situ bacteria holds promise for noninvasive diagnosis. We investigated the ability of a bacterial thymidine kinase inhibitor ([124I]FIAU) to image pulmonary and musculoskeletal infections. METHODS: Thirty-three patients were prospectively accrued: 16 with suspected musculoskeletal infection, 14 with suspected pulmonary infection, and 3 with known rheumatoid arthritis without infection. Thirty-one patients were imaged with [124I]FIAU PET/CT and 28 with [18F]FDG PET/CT. Patient histories were reviewed by an experienced clinician with subspecialty training in infectious diseases and were determined to be positive, equivocal, or negative for infection. RESULTS: Sensitivity, specificity, positive-predictive value, negative-predictive value, and accuracy of [124I]FIAU PET/CT for diagnosing infection were estimated as 7.7% to 25.0%, 0.0%, 50%, 0.0%, and 20.0% to 71.4% for musculoskeletal infections and incalculable-100.0%, 51.7% to 72.7%, 0.0% to 50.0%, 100.0%, and 57.1% to 78.6% for pulmonary infections, respectively. The parameters for [18F]FDG PET/CT were 75.0% to 92.3%, 0.0%, 23.1% to 92.3%, 0.0%, and 21.4% to 85.7%, respectively, for musculoskeletal infections and incalculable to 100.0%, 0.0%, 0.0% to 18.2%, incalculable, and 0.0% to 18.2% for pulmonary infections, respectively. CONCLUSIONS: The high number of patients with equivocal clinical findings prevented definitive conclusions from being made regarding the diagnostic efficacy of [124I]FIAU. Future studies using microbiology to rigorously define infection in patients and PET radiotracers optimized for image quality are needed.

In Vivo Dynamic Monitoring of Bacterial Infection by NIR-II Fluorescence Imaging.

Time window of antibiotic administration is a critical but long-neglected point in the treatment of bacterial infection, as unnecessary prolonged antibiotics are increasingly causing catastrophic drug-resistance. Here, a second near-infrared (NIR-II) fluorescence imaging strategy based on lead sulfide quantum dots (PbS QDs) is presented to dynamically monitor bacterial infection in vivo in a real-time manner. The prepared PbS QDs not only provide a low detection limit (104 CFU mL-1 ) of four typical bacteria strains in vitro but also show a particularly high labeling efficiency with Escherichia coli (E. coli). The NIR-II in vivo imaging results reveal that the number of invading bacteria first decreases after post-injection, then increases from 1 d to 1 week and drop again over time in infected mouse models. Meanwhile, there is a simultaneous variation of dendritic cells, neutrophils, macrophages, and CD8+ T lymphocytes against bacterial infection at the same time points. Notably, the infected mouse self-heals eventually without antibiotic treatment, as a robust immune system can successfully prevent further health deterioration. The NIR-II imaging approach enables real-time monitoring of bacterial infection in vivo, thus facilitating spatiotemporal deciphering of time window for antibiotic treatment.

Pulmonary acute graft-versus-host disease and infections after allogeneic hematopoietic stem cell transplantation in pediatric recipients: A comparative study on CT.

OBJECTIVE: To compare the chest CT patterns of acute graft-versus-host disease (aGVHD) and infections within 100 days after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in pediatric recipients to help hematologist make definitive diagnosis as early as possible. METHODS: A total of 143 pediatric recipients from January 2015 to June 2019 who were diagnosed pulmonary aGVHD or infections within 100 days after allo-HSCT were enrolled in this study. Two observers evaluated the extent and distribution (unilateral, bilateral) of the CT patterns. The patterns were then classified as ground-glass opacity (GGO) (localized, patchy, diffuse), consolidation (localized, patchy, diffuse), reticulation (localized, patchy, diffuse), nodules (localized, multiple), bronchiectasis, pleural effusion, air trapping, tree-in-bud sign, and pneumomediastinum. The onset time and radiological patterns of the two cohorts were statistically compared. RESULTS: The mean onset time of aGVHD (n = 85) and infections group (viral n = 29, bacterial n = 22, fungal n = 7, total n = 58) was 36.89 ± 24.34 (range, 10-99 days) and 23.48 ± 20.65 days (range, 4-94 days) with a significant difference (P = .001). The top three underlying diseases were acute lymphoblastic leukemia (ALL) (n = 49, 57.6%); acute myeloid leukemia (AML) (n = 24, 28.2%); and aplastic anemia (AA) (7.1%) in aGVHD group and hemophagocytic syndrome (HPS) (n = 33, 56.9%); AA (n = 9, 15.5%); and ALL (n = 6, 10.3) in infection group. GGO (41.2%) in aGVHD prevailed on CT, whereas GGO (53.4%) and consolidations (43.1%) were more prevalent in infections. The distribution of GGO showed more diffuse in aGVHD (P = .031) and symmetric while patchier GGO prefers infections (P < .001). No differences were found in the reticulation. Nodules were more common in infections (P = .004) while pleural effusion was more common in aGVHD group (P < .035). CONCLUSION: Imaging patterns of aGVHD on CT differ substantially from that of infections. Physicians and radiologists should be aware of such radiological differences in order to give accurate treatment. Notably, definite diagnosis should be made in combination with clinical manifestations, signs, and laboratory tests.

New synthesis of 6″-[18 F]fluoromaltotriose for positron emission tomography imaging of bacterial infection.

6″-[18 F]fluoromaltotriose is a positron emission tomography tracer that can differentiate between bacterial infection and inflammation in vivo. Bacteria-specific uptake of 6″-[18 F]fluoromaltotriose is attributed to the targeting of maltodextrin transporter in bacteria that is absent in mammalian cells. Herein, we report a new synthesis of 6″-[18 F]fluoromaltotriose as a key step for its clinical translation. In comparison with the previously reported synthesis, the new synthesis features unambiguous assignment of the fluorine-18 position on the maltotriose unit. The new method utilizes direct fluorination of 2″,3″,4″-tri-O-acetyl-6″-O-trifyl-α-D-glucopyranosyl-(1-4)-O-2',3',6'-tri-O-acetyl-α-D-glucopyranosyl-(1-4)-1,2,3,6-tetra-O-acetyl-D-glucopyranose followed by basic hydrolysis. Radiolabeling of the new maltotriose triflate precursor proceeds using a single HPLC purification step, which results in shorter reaction time in comparison with the previously reported synthesis. Successful synthesis of 6″-[18 F]fluoromaltotriose has been achieved in 3.5 ± 0.3% radiochemical yield (decay corrected, n = 7) and radiochemical purity above 95%. The efficient radiosynthesis of 6″-[18 F]fluoromaltotriose would be critical in advancing this positron emission tomography tracer into clinical trials for imaging bacterial infections.

Advances in Optical Detection of Human-Associated Pathogenic Bacteria.

Bacterial infection is a global burden that results in numerous hospital visits and deaths annually. The rise of multi-drug resistant bacteria has dramatically increased this burden. Therefore, there is a clinical need to detect and identify bacteria rapidly and accurately in their native state or a culture-free environment. Current diagnostic techniques lack speed and effectiveness in detecting bacteria that are culture-negative, as well as options for in vivo detection. The optical detection of bacteria offers the potential to overcome these obstacles by providing various platforms that can detect bacteria rapidly, with minimum sample preparation, and, in some cases, culture-free directly from patient fluids or even in vivo. These modalities include infrared, Raman, and fluorescence spectroscopy, along with optical coherence tomography, interference, polarization, and laser speckle. However, these techniques are not without their own set of limitations. This review summarizes the strengths and weaknesses of utilizing each of these optical tools for rapid bacteria detection and identification.

Design, Preparation, and Evaluation of a Novel 99mTcN Complex of Ciprofloxacin Xanthate as a Potential Bacterial Infection Imaging Agent.

In order to seek novel technetium-99m bacterial infection imaging agents, a ciprofloxacin xanthate (CPF2XT) was synthesized and radiolabeled with [99mTcN]2+ core to obtain the 99mTcN-CPF2XT complex, which exhibited high radiochemical purity, hydrophilicity, and good stability in vitro. The bacteria binding assay indicated that 99mTcN-CPF2XT had specificity to bacteria. A study of biodistribution in mice showed that 99mTcN-CPF2XT had a higher uptake in bacterial infection tissues than in turpentine-induced abscesses, indicating that it could distinguish bacterial infection from sterile inflammation. Compared to 99mTcN-CPFXDTC, the abscess/blood and abscess/muscle ratios of 99mTcN-CPF2XT were higher and the uptakes of 99mTcN-CPF2XT in the liver and lung were obviously decreased. The results suggested that 99mTcN-CPF2XT would be a potential bacterial infection imaging agent.

Optical Identification of Middle Ear Infection.

Ear infection is one of the most commonly occurring inflammation diseases in the world, especially for children. Almost every child encounters at least one episode of ear infection before he/she reaches the age of seven. The typical treatment currently followed by physicians is visual inspection and antibiotic prescription. In most cases, a lack of improper treatment results in severe bacterial infection. Therefore, it is necessary to design and explore advanced practices for effective diagnosis. In this review paper, we present the various types of ear infection and the related pathogens responsible for middle ear infection. We outline the conventional techniques along with clinical trials using those techniques to detect ear infections. Further, we highlight the need for emerging techniques to reduce ear infection complications. Finally, we emphasize the utility of Raman spectroscopy as a prospective non-invasive technique for the identification of middle ear infection.

Infectious causes and outcomes in patients presenting with cerebral spinal fluid pleocytosis.

To evaluate the infectious etiologies, clinical features, and outcomes of patients with CNS infections at a tertiary care center. Patients that present with a pleocytosis in the cerebral spinal fluid (CSF), defined as a CSF WBC count > 5 cells/mm3, from July 2015 to June 2016 at a tertiary care hospital were analyzed for this report. Data from patients with confirmed (n = 43) and presumed (n = 51) CNS infections were analyzed. CNS infection was the leading known cause of CSF pleocytosis (n = 43, 18% of all patients with a pleocytosis in the CSF), and HSV-2 was identified as the leading causative pathogen (n = 10) followed by varicella zoster virus (n = 5). Fifty-three percent of patients with a pleocytosis in the CSF did not receive a diagnosis. In the patients that did not receive a diagnosis, CNS infection was presumed to be the cause in 51 patients (21% of patients with CSF pleocytosis). The mean time to diagnosis for patients with confirmed CNS infection was 16 days, but time to diagnosis was highly variable depending on the causative pathogen. There was a significant overlap in CSF parameters and peripheral white blood cell counts in patients diagnosed with a viral, bacterial, or fungal infection. Neuroimaging changes were present in only 44% of CNS infections. The overall mortality was 7% for CNS infections, and 17% of patients with a CNS infection had a severe neurologic deficit at presentation while only 3% had a severe deficit at the last neurologic assessment. This study provides new insights into the infectious causes of disease in a cohort of patients with pleocytosis in the CSF. The study provides new insights into the time to diagnosis and outcomes in patients that present with pleocytosis in the CSF.

The routes of infection spread in central skull-base osteomyelitis and the diagnostic role of CT and MRI scans.

BACKGROUND: Central skull-base osteomyelitis (CSBO) represents a life-threatening complication of external ear canal infection. Computed tomography (CT) and magnetic resonance imaging (MRI) play key roles in assessment of CSBO progression. METHODS: Twelve patients with CSBO were included in a retrospective clinical study. In total, 62 scans (30 CTs and 32 MRIs) were performed to evaluate the extent of inflammatory changes. The scans were read independently by two radiologists specialised in imaging of the head and neck. The regions under the skull base were specified using the online Anatomy Atlas of the skull base. To clarify the timeline, the time period was divided into four parts, and inflammatory changes in the skull-base regions were tracked. Data were statistically analysed. RESULTS: In early stages of the disease, CT scan detects inflammatory changes closely related to the stylomastoid foramen and medially to the posterior belly of the digastric muscle, changes which have been proved to be crucial for the diagnosis of CSBO. Later the infection spreads to the contralateral side causing demineralisation of the bones. CONCLUSION: Imaging methods play a crucial role not only in establishing the diagnosis, but also in anticipating the direction of infection spread underneath the skull base.

Radiosynthesis and validation of [Carboxy-11 C]4-Aminobenzoic acid ([11 C]PABA), a PET radiotracer for imaging bacterial infections.

In this practitioner protocol, the radiochemical synthesis of [11 C] PABA is described in detail, and a quality control summary of three validation productions is presented. The results indicate that the radiotracer product can be produced in good radiochemical yield (14% at end-of-synthesis (EOS)) at high specific activity (molar activity 11 Ci/µmole EOS; 407 GBq/µmole) and high chemical and radiochemical purity as a sterile, pyrogen-free solution suitable for injection conforming to current Good Manufacturing Practice (cGMP) requirements.