Man with headache and altered mental status.

PresentationAn 83-year-old man presented for headache and altered mental status. Four days prior, he underwent endoscopic sinus surgery for nasal polyps. Over the two previous days, he gradually developed a headache and was brought to the emergency department when his wife noted mild confusion and generalised weakness. His examination was notable for a heart rate of 101 beats per minute, clear nasal discharge, meningismus and confusion to the date with generalised weakness. A lumbar puncture revealed cloudy cerebrospinal fluid (CSF) with a white blood cell count of 3519x10ˆ9/L (95% neutrophils). A CT scan of the head was obtained (figure 1).emermed;38/7/519/F1F1F1Figure 1Non-contrast CT scan of the head in axial plane. QUESTION: What is the appropriate next step in management?Obtain MRI of the brain to localise ischaemic damage.Administer broad-spectrum antibiotics, including pseudomonal coverage.Consult otolaryngology to arrange functional endoscopic sinus surgery for CSF leak closure.Consult neurosurgery for surgical decompression of mass lesion(s).

Pseudomonal Meningoencephalitis With Ventriculitis Secondary to Bacteremia in a Burn Patient: A Novel Case.

Burn patients with large burn surface area involvement are at increased risk of infection due to the presence of large wounds, multiple surgeries, prolonged intensive care unit admission, and immunosuppression. Pseudomonas aeruginosa is the most commonly isolated organism in this population. Even with frequent infections in the burn population, meningitis and encephalitis are rare, and ventriculitis is exceptional. We report the case of a 66-year-old woman who developed P. aeruginosa bacteremia during her hospital course, causing secondary meningoencephalitis with ventriculitis. She was admitted for partial- and full-thickness burns affecting the neck, chest, abdomen, upper medial arms, and bilateral anteromedial thighs for an estimated 20% total body surface area burn. She met sepsis criteria and broad-spectrum antimicrobial coverage was initiated. Magnetic resonance imaging of the brain, performed for altered mental status, revealed meningitis and ventriculitis. Cerebrospinal fluid analysis demonstrated findings consistent with bacterial meningitis, with cultures positive for P. aeruginosa. Serial neuroimaging with computerized tomography revealed new areas of ischemia concerning for septic emboli. In the presence of altered mental status and fever of unknown origin, workup should remain broad. Even in the presence of another source, it is important to keep an open mind for the rarer intracerebral infection as it requires different management, including urgent evaluation of antibiotic selection and dosing to ensure central nervous system penetration, and neurosurgical evaluation.

Aortoduodenal Fistula After Endovascular Aortic Repair for an Inflammatory Abdominal Aortic Aneurysm: A Case Report.

Aortoenteric fistula after endovascular aortic repair for an abdominal aortic aneurysm is a rare but severe complication. Particularly, a case of inflammatory abdominal aortic aneurysm is extremely rare and there are only 3 reported cases. A 70-year-old man underwent endovascular aortic repair for impending rupture of an inflammatory abdominal aortic aneurysm and was medicated steroids for approximately 2 years. Four years after endovascular aortic repair, he developed endograft infection with an aortoduodenal fistula and a left psoas abscess. He underwent total endograft excision, debridement, in situ reconstruction of the aorta using prosthetic grafts with omental coverage, and digestive tract reconstruction to prevent leakage. Pseudomonas aeruginosa was detected in the infected aortic sac. The patient has not experienced recurrence of infection in the 35 months since his operation.

Post-acute COVID-19 associated with evidence of bystander T-cell activation and a recurring antibiotic-resistant bacterial pneumonia.

Here, we describe the case of a COVID-19 patient who developed recurring ventilator-associated pneumonia caused by Pseudomonas aeruginosa that acquired increasing levels of antimicrobial resistance (AMR) in response to treatment. Metagenomic analysis revealed the AMR genotype, while immunological analysis revealed massive and escalating levels of T-cell activation. These were both SARS-CoV-2 and P. aeruginosa specific, and bystander activated, which may have contributed to this patient's persistent symptoms and radiological changes.

Lateral position during severe mono-lateral pneumonia: an experimental study.

Patients with mono-lateral pneumonia and severe respiratory failure can be positioned in lateral decubitus, with the healthy lung dependent, to improve ventilation-perfusion coupling. Oxygenation response to this manoeuvre is heterogeneous and derecruitment of dependent lung has not been elucidated. Nine pigs (32.2 ± 1.2 kg) were sedated and mechanically ventilated. Mono-lateral right-sided pneumonia was induced with intrabronchial challenge of Pseudomonas aeruginosa. After 24 h, lungs were recruited and the animals were randomly positioned on right or left side. After 3 h of lateral positioning, the animals were placed supine; another recruitment manoeuvre was performed, and the effects of contralateral decubitus were assessed. Primary outcome was lung ultrasound score (LUS) of the dependent lung after 3-h lateral positioning. LUS of the left non-infected lung worsened while positioned in left-lateral position (from 1.33 ± 1.73 at baseline to 6.78 ± 4.49; p = 0.005). LUS of the right-infected lung improved when placed upward (9.22 ± 2.73 to 6.67 ± 3.24; p = 0.09), but worsened in right-lateral position (7.78 ± 2.86 to 13.33 ± 3.08; p < 0.001). PaO2/FiO2 improved in the left-lateral position (p = 0.005). In an animal model of right-lung pneumonia, left-lateral decubitus improved oxygenation, but collapsed the healthy lung. Right-lateral orientation further collapsed the diseased lung. Our data raise potential clinical concerns for the use of lateral position in mono-lateral pneumonia.

Radiologic Characteristics of Non-tuberculous Mycobacteria Infection in Patients with Bronchiectasis.

INTRODUCTION: Non-tuberculous mycobacteria pulmonary disease (NTM-pd) commonly complicates bronchiectasis. However, clinical and radiological features of NTM-pd and bronchiectasis are very similar. We aimed to develop a radiologic prediction tool for bronchiectasis to identify NTM-pd. METHODS: We reviewed clinical, laboratory and radiological data in patients with bronchiectasis. Radiologic features on CT scans and the individual components of the Bhalla scoring system were compared between people with and without NTM-pd. Logistic regression and receiver-operating curve (ROC) analysis were performed to predict NTM-pd. RESULTS: People with NTM-pd had more pulmonary segments with bronchiectasis (13 ± 5 vs. 11 ± 5, p = 0.03), presence of mucus plugging (47% vs. 19%, p < 0.0001) and tree in bud infiltrates (53% vs. 28%, p = 0.004). The total modified- Bhalla score was worse among people with NTM-pd (median [IQR] 11[9,13] vs. 9[8,12], p = 0.03). Logistic regression identified the number of pulmonary segments involved, presence of bullae, consolidations, and a total score of 10 or more to be independently associated with presence of NTM-pd. ROC analysis with radiographic variables only identified an AUC of 0.706 (95% CI 0.644-0.762). When people with chronic Pseudomonas infection were excluded from the ROC analysis, prediction for NTM was improved: AUC = 0.87 (95% CI 0.796-0.945). DISCUSSION AND CONCLUSIONS: Radiological features together with advanced age and female gender may predict NTM-pd among people with bronchiectasis. Infection with Pseudomonas aeruginosa may resemble NTM radiographically, and this prediction rule may better differentiate people with and without NTM-pd when Pseudomonas infection is not present.

Changes in mucociliary clearance over time in children with cystic fibrosis.

OBJECTIVES: (a) To quantify changes in mucociliary clearance (MCC) over time in children with cystic fibrosis (CF) and the relationship between MCC and rate of infection with Pseudomonas aeruginosa (PA); (b) to determine the impact of MCC on the evolution of CF lung disease; and (c) to explore the role of mucus composition as a determinant of MCC. METHODS: Children with CF, who had previously undergone an MCC measurement (visit 1), underwent the following tests 3 to 10 years later: (a) second MCC measurement (visit 2); (b) multiple breath washout to assess ventilation inhomogeneity, expressed as lung clearance index (LCI); (c) high resolution computed tomography lung scan (HRCT); and (d) induced sputum test. Number of PA + cultures/year between visits was documented and mucus dry weight was quantified in the children and adult controls. RESULTS: Nineteen children completed both visits. Median time between visits was 4.6 years. Clearance declined 30% between visits. Lower MCC on visit 2 was associated with more PA+ cultures/year between visits. Lower MCC values on visit 1 were associated with higher LCI values and higher HRCT scores on visit 2. Mucus dry weight was significantly higher in children with CF compared with controls. Higher dry weights were associated with lower MCC. CONCLUSIONS: Mucociliary clearance declines significantly over time in children with CF. The decline is associated with PA infection rate and is affected by mucus composition. Children with early slowing of MCC appear to be at risk for developing ventilation inhomogeneity and parenchymal lung damage when they are older.

Development of a Staphylococcus aureus reporter strain with click beetle red luciferase for enhanced in vivo imaging of experimental bacteremia and mixed infections.

In vivo bioluminescence imaging has been used to monitor Staphylococcus aureus infections in preclinical models by employing bacterial reporter strains possessing a modified lux operon from Photorhabdus luminescens. However, the relatively short emission wavelength of lux (peak 490 nm) has limited tissue penetration. To overcome this limitation, the gene for the click beetle (Pyrophorus plagiophtalamus) red luciferase (luc) (with a longer >600 emission wavelength), was introduced singly and in combination with the lux operon into a methicillin-resistant S. aureus strain. After administration of the substrate D-luciferin, the luc bioluminescent signal was substantially greater than the lux signal in vitro. The luc signal had enhanced tissue penetration and improved anatomical co-registration with infected internal organs compared with the lux signal in a mouse model of S. aureus bacteremia with a sensitivity of approximately 3 × 104 CFU from the kidneys. Finally, in an in vivo mixed bacterial wound infection mouse model, S. aureus luc signals could be spectrally unmixed from Pseudomonas aeruginosa lux signals to noninvasively monitor the bacterial burden of both strains. Therefore, the S. aureus luc reporter may provide a technological advance for monitoring invasive organ dissemination during S. aureus bacteremia and for studying bacterial dynamics during mixed infections.

Mucoid Pseudomonas aeruginosa infection in a cat with severe chronic rhinosinusitis.

A 6-year-old male neutered Bengal cat was presented to the University of Wisconsin Veterinary Care Hospital with a history of severe chronic rhinitis that was unresolved from kittenhood. In weeks prior to presentation, the cat's upper respiratory signs had significantly worsened and a left-sided facial swelling overlying the left frontal sinus was noted. Skull computed tomography, rhinoscopy, bilateral nasal biopsies, bacterial and fungal cultures of fluid from the left frontal sinus, and cryptococcal fungal antigen testing were performed. The cat was diagnosed with severe chronic rhinosinusitis and determined to have an infection with a mucoid variant of Pseudomonas aeruginosa (P aeruginosa). This case highlights an atypical cytomorphologic appearance of the well-known bacterial pathogen, P aeruginosa, an appearance that could be confused cytologically with other microorganisms, such as septate fungi. Mucoid variants of P aeruginosa are often associated with progressive lung or airway disease in people with cystic fibrosis and have not been previously documented in feline respiratory tract disease. This report also presents a brief review of chronic rhinosinusitis (CRS) in cats and describes a novel interventional treatment approach to feline CRS via sinusotomy and sinus flushing for severely affected cats.

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 of Pseudomonas aeruginosa infection with Ga-68 labelled pyoverdine for positron emission tomography.

Pseudomonas aeruginosa is an increasingly prevalent opportunistic pathogen that causes a variety of life-threatening nosocomial infections. Novel strategies for the development of new antibacterial treatments as well as diagnostic tools are needed. One of the novel diagnostic strategies for the detection of infection could be the utilization of siderophores. Siderophores are low-molecular-weight chelators produced by microbes to scavenge essential iron. Replacing iron in siderophores by suitable radiometals, such as Ga-68 for positron emission tomography (PET) imaging, opens approaches for targeted imaging of infection. Here we report on pyoverdine PAO1 (PVD-PAO1), a siderophore produced by P. aeruginosa, labelled with Ga-68 for specific imaging of Pseudomonas infections. PVD-PAO1 was labelled with Ga-68 with high radiochemical purity. The resulting complex showed hydrophilic properties, low protein binding and high stability in human serum. In vitro uptake of 68Ga-PVD-PAO1 was highly dependent on the type of microbial culture. In normal mice 68Ga-PVD-PAO1 showed rapid pharmacokinetics with urinary excretion. PET imaging in infected animals displayed specific accumulation of 68Ga-PVD-PAO1 in infected tissues and better distribution than clinically used 18F-fluorodeoxyglucose (18F-FDG) and 68Ga-citrate. Ga-68 labelled pyoverdine PAO1 seems to be a promising agent for imaging of P. aeruginosa infections by means of PET.

The burden of sinus disease in cystic fibrosis lung transplant recipients.

INTRODUCTION: Sinus disease (SD) in cystic fibrosis (CF) is a known risk factor for disease progression, the upper airways (UAW) being a site of primary colonization with Pseudomonas aeruginosa. UAW may function as reservoir for graft colonization after lung transplantation (LuTx), increasing risk of rejection. Aims of this study were to assess the burden of sinus disease in CF LuTx recipients, considering patient-reported symptoms, endoscopically documented signs and microbiological isolates, comparing colonization between upper and lower airways. METHODS: A prospective, observational study was performed on consecutive CF LuTx recipients, recording history, symptoms, and management of SD. Nasal lavage (NL) was evaluated for UAW colonization, with nasal inspection during bronchoscopy and bronchoalveolar lavage (BAL) used to assess lower airways if clinically indicated. RESULTS: Hundred and fifty-four patients were included. Symptoms of SD were reported in 96 (62%) individuals; 87 (56%) had prior sinus surgery. Only 8 (13%) of 60 individuals undergoing bronchoscopy presented completely normal findings of the nasal cavity. Thirty-six (60%) patients presented the same isolates on both NL and BAL. Polyps and mucosal alterations were significantly less frequently seen endoscopically in patients with normal flora in NL microbiology (respectively, 26% vs 70%, P = .003, and 35% vs 68%, P = .013). CONCLUSIONS: Symptoms of SD affected more than 60% of CF LuTx recipients. Nasal endoscopic inspection identified alterations in 55%. The majority of patients presented the same isolates both on NL and BAL performed on the same visit. These results strongly support a role of paranasal sinuses as "reservoir" for descending re-colonization of the lung graft.

A novel approach based on low-field NMR for the detection of the pathological components of sputum in cystic fibrosis patients.

PURPOSE: Development of a reliable, simple method to monitor lung condition in cystic fibrosis (CF) patients. Lung functionality assessment in CF patients is relevant, as most of them still die of respiratory failure. In lung mucus (sputum) of CF patients, components such as proteins, biopolymers, DNA, bacteria, and mucin are pathologically increased. As lung functionality is related to the amount of the pathological components in the sputum, their determination can help clinicians in monitoring lung condition and planning therapy. METHODS: Low-field NMR was used to evaluate the variation of the relaxation time (T2m ) of the water hydrogens present in CF sputum in relation to the amounts of the pathological components. Low-field NMR was tested in artificial samples (mucin or alginates), then in conditional sputum (saliva from healthy volunteers, added by different amounts of the pathological components), and finally in 12 patients' sputums, in which T2m was correlated to a commonly used lung monitoring test (i.e., forced expiratory volume in the first second). RESULTS: T2m significantly (P < 0.05) differed between samples with and without pathological components and between healthy and CF patients (P < 0.05), in which T2m correlated (r = 0.87) with FEV1 . CONCLUSIONS: The presented method can potentially become a valuable lung-monitoring tool in CF patients. Magn Reson Med 79:2323-2331, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Malignant external otitis: The shifting treatment paradigm.

IMPORTANCE: Malignant external otitis (MEO) is an aggressive infection occurring in immunocompromised hosts. Increasing antimicrobial resistance is making the disease more difficult to treat. OBJECTIVE: Determine if there has been a shift in the microbiology and outcomes of MEO. DESIGN: A retrospective case series at a tertiary care institution. SETTING: Inpatient and outpatient tertiary care hospital. PARTICIPANTS: 12 cases of recent MEO were reviewed. MAIN OUTCOMES AND MEASURES: The primary outcome was progression of disease. Secondary outcomes were drug resistance and complications of MEO. RESULTS: Only 4 patients were cured of MEO. Four patients expired during the study period and at least one of these deaths was a direct result of the MEO. 7 patients developed Cranial nerve palsies, and 3 patients developed abscesses. CONCLUSIONS: Select cases of MEO now require multi-drug and long-term parenteral antibiotic therapy with extended hospital stays.

Severely infected pneumoceles of the frontal sinus in patients with mental retardation and brain atrophy treated by endoscopic sinus surgery.

We herein present three cases of abnormally expanded frontal sinuses (pneumoceles) with severe infection in patients with mental retardation and brain atrophy. Two patients previously underwent laryngotracheal separation surgery, and bacteriological examinations of purulent nasal discharge revealed infections caused by drug-resistant bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii. As conservative medical treatments were ineffective, all three patients were treated by computed tomography-guided endoscopic sinus surgery. This navigation system is useful for safer surgery in the area of anatomic deformity. The clinical findings, possible etiologies and surgical treatment of these cases are discussed.