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.

Inflammatory Myofibroblastic Tumor of the Lung: Two Progressing Pulmonary Nodules in a 25-Year-Old Adult With a Moraxella catharalis Infection.

Inflammatory myofibroblastic tumor of the lung is a rare pulmonary lesion of intermediate biologic potential. Approximately half of all inflammatory myofibroblastic tumors show a rearrangement of the anaplastic lymphoma kinase (ALK) gene locus with potentially aberrant kinase expression. We present a 25-year-old man with recurrent exertional hemoptysis and two progressing pulmonary nodules in the right lung shown by computed tomography. After an anterolateral thoracotomy, pathologic studies revealed an inflammatory myofibroblastic tumor with rearrangement in the ALK gene, although aberrant expression of the anaplastic lymphoma kinase was not detected. In preoperative bronchial washings Moraxella catharalis was found.

The role and regulation of Moraxella catarrhalis-induced human beta-defensin 3 expression in human pulmonary epithelial cells.

BACKGROUND: Bacterial colonisation with Moraxella catarrhalis may partly sustain chronic inflammation in the lower airways of patients with chronic obstructive pulmonary disease (COPD). In addition, this bacterium causes infectious exacerbations of COPD, which often necessitate treatment with antibiotics. Antimicrobial peptides are the body's own antibiotic substances with bactericidal and bacteriostatic, as well as immunomodulatory function. In particular, human beta-defensin 3 (hBD-3) exerts an antimicrobial effect against an extraordinarily broad spectrum of pathogens. We therefore investigated the role of hBD-3 in infections of pulmonary epithelial cells with M. catarrhalis. METHODS: The antimicrobial activity of hBD-3 vs. M. catarrhalis was evaluated in an antimicrobial susceptibility assay. We analyzed hBD-3 secretion of M. catarrhalis-infected pulmonary epithelial cells using ELISA. The role of M. catarrhalis-specific virulence factors, toll-like receptors (TLR) 2 and 4, MAPK pathways, and transcription factors AP-1 and NF-κB in the induction and regulation of hBD-3 expression were explored with specific inhibitors, small interference RNA, Western Blot, and chromatin immunoprecipitation (ChIP) assays. RESULTS: HBD-3 exhibited a strong bactericidal effect against M. catarrhalis. M. catarrhalis induced hBD-3 expression in pulmonary epithelial cells, which was dependent on M. catarrhalis membranous lipoolygosaccharide (LOS), while the surface proteins UspA1 and UspA2 were not involved. Gene silencing of TLR2, but not TLR4, led to a reduced hBD-3 secretion after stimulation with M. catarrhalis or M. catarrhalis LOS. Inhibition of MAPKs ERK1/2 and JNK, but not p38, reduced hBD-3 secretion. HBD-3 expression was mediated through the recruitment of AP-1 to the hBD-3 gene promoter and was independent of NF-κB. CONCLUSION: The immune response of pulmonary epithelial cells towards M. catarrhalis involves secretion of hBD-3, which has a bactericidal effect against this pathogen. Binding of M. catarrhalis virulence factor LOS to TLR2 causes an ERK1/2- and JNK-dependent induction of AP-1-related transcription of the hBD-3 gene, resulting in the production and secretion of hBD-3.

Reactivated Moraxella osteitis presenting as granulomatous disease.

Granulomatous infections are commonly associated with mycobacteria, brucellosis, actinomycosis, nocardiosis, spirochetes, and fungi. Rarely, granuloma formation is a host response to other bacterial infection. Osteomyelitis and osteitis that reactivate many years after the primary episode is a known phenomenon. A reactivation that presents as a granulomatous disease is rare. We present a case of reactivated osteitis due to Moraxella osloensis with consecutive granuloma formation.

In search of a candidate pathogen for giant cell arteritis: sequencing-based characterization of the giant cell arteritis microbiome.

OBJECTIVE: To characterize the microbiome of the temporal artery in patients with giant cell arteritis (GCA), and to apply an unbiased and comprehensive shotgun sequencing-based approach to determine whether there is an enrichment of candidate pathogens in the affected tissue. METHODS: Temporal artery biopsy specimens were collected from patients at a single institution over a period of 4 years, and unbiased DNA sequencing was performed on 17 formalin-fixed, paraffin-embedded specimens. Twelve of the 17 patients fulfilled the clinical and histopathologic criteria for GCA, and the other 5 patients served as controls. Using PathSeq software, human DNA sequences were computationally subtracted, and the remaining non-human DNA sequences were taxonomically classified using a comprehensive microbial sequence database. The relative abundance of microbes was inferred based on read counts assigned to each organism. Comparison of the microbial diversity between GCA cases and controls was carried out using hierarchical clustering and linear discriminant analysis of effect size. RESULTS: Propionibacterium acnes and Escherichia coli were the most abundant microorganisms in 16 of the 17 samples, and Moraxella catarrhalis was the most abundant organism in 1 control sample. Pathogens previously described to be correlated with GCA were not differentially abundant in cases compared to controls. There was not a significant burden of likely pathogenic viruses. CONCLUSION: DNA sequencing of temporal artery biopsy specimens from GCA cases, in comparison with non-GCA controls, showed no evidence of previously identified candidate GCA pathogens. A single pathogen was not clearly and consistently associated with GCA in this case series.

Psychrobacter immobilis septicemia in a boy with X-linked chronic granulomatous disease and fulminant hepatic failure.

A 16-year old boy with chronic granulomatous disease (CGD) developed Psychrobacter immobilis septicemia during a course of fulminant hepatic failure. The patient died despite aggressive management with antimicrobials and corticosteroids. While Psychrobacter immobilis rarely affects humans, it should be considered an organism that can cause sepsis in patients with CGD.

A rare case of recurrent frontal osteoma complicated by mucopyocele with an unusual organism, Moraxella catarrhalis.

OBJECTIVE: We report a rare case of recurrent frontal osteoma complicated by mucopyocele and intracranial abscess. Furthermore, we report an unusual organism, Moraxella catarrhalis, as the infectious agent. Finally, we demonstrate that endovascular embolization may be part of the treatment paradigm of frontal osteomas in selected cases. CASE DESCRIPTION: A 71-year-old man with a previous history of craniotomy presented to the emergency room with 24 hours of headache episodes, confusion, lethargy, and spells of low-grade fever. Imaging and angiography revealed a complex frontal lesion involving the frontoethmoidal sinuses that extended into the medial orbit and anterior skull base with multiple feeding vessels from the middle meningeal artery. The initial diagnosis of recurrent meningioma was made based on imaging data. The patient underwent partial angiographic embolization of the lesion followed by microneurosurgical complete resection. Pathology revealed a synchronous presentation of an osteoma and mucopyocele with intracranial abscess caused by M. catarrhalis. CONCLUSION: Synchronous presentation of a frontal osteoma with mucopyocele is a rare event. However, the case of a recurrent osteoma complicated by infection with M. catarrhalis has not been reported in the literature, nor a treatment paradigm that included preoperative partial endovascular embolization.

In young children, persistent wheezing is associated with bronchial bacterial infection: a retrospective analysis.

BACKGROUND: Young children with persistent wheezing pose a diagnostic and therapeutical challenge to the pediatrician.We aimed to evaluate bacterial bronchial infection as a possible reason for non response to conventional asthma therapy, and to identify and characterise the predominant pathogens involved. METHODS: We retrospectively analysed microbiological and cytological findings in a selected population of young wheezers with symptoms unresponsive to inhaled corticosteroid (ICS) therapy, who underwent flexible bronchoscopy with bronchoalveolar lavage (BAL). Procedural measures were taken to limit contamination risk and quantitative bacterial culture of BAL fluid (significance cut-off ≥ 104 colony-forming units/ml) was used. Modern microbiological methods were used for detection of a wide panel of pathogens and for characterisation of the bacterial isolates. RESULTS: 33 children aged between 4 and 38 months, without structural anomalies of the conductive airways were evaluated. Significant bacterial BAL cultures were found in 48,5 % of patients. Haemophilus influenzae was isolated in 30,3 %, Streptococcus pneumoniae in 12,1 % and Moraxella catarrhalis in 12,1 %. All H. influenzae isolates were non-encapsulated strains and definitely distinguished from non-haemolytic H. haemolyticus. Respiratory viruses were detected in 21,9 % of cases with mixed bacterial-viral infection in 12,1 %. Cytology revealed a marked neutrophilic inflammation. CONCLUSIONS: Bacterial infection of the bronchial tree is common in persistent preschool wheezers and provides a possible explanation for non response to ICS therapy. Non-typeable H. influenzae seems to be the predominant pathogen involved, followed by S. pneumoniae and M. catarrhalis.

Pulmonary thin-section CT findings in acute Moraxella catarrhalis pulmonary infection.

OBJECTIVE: Moraxella catarrhalis is an important pathogen in the exacerbation of chronic obstructive pulmonary disease. The aim of this study was to assess the clinical and pulmonary thin-section CT findings in patients with acute M. catarrhalis pulmonary infection. METHODS: Thin-section CT scans obtained between January 2004 and March 2009 from 292 patients with acute M. catarrhalis pulmonary infection were retrospectively evaluated. Clinical and pulmonary CT findings in the patients were assessed. Patients with concurrent infection including Streptococcus pneumoniae (n = 72), Haemophilus influenzae (n = 61) or multiple pathogens were excluded from this study. RESULTS: The study group comprised 109 patients (66 male, 43 female; age range 28-102 years; mean age 74.9 years). Among the 109 patients, 34 had community-acquired and 75 had nosocomial infections. Underlying diseases included pulmonary emphysema (n = 74), cardiovascular disease (n = 44) or malignant disease (n = 41). Abnormal findings were seen on CT scans in all patients and included ground-glass opacity (n = 99), bronchial wall thickening (n = 85) and centrilobular nodules (n = 79). These abnormalities were predominantly seen in the peripheral lung parenchyma (n = 99). Pleural effusion was found in eight patients. No patients had mediastinal and/or hilar lymph node enlargement. CONCLUSIONS: M. catarrhalis pulmonary infection was observed in elderly patients, often in combination with pulmonary emphysema. CT manifestations of infection were mainly ground-glass opacity, bronchial wall thickening and centilobular nodules.

Otitis media: viruses, bacteria, biofilms and vaccines.

Otitis media typically presents as either acute otitis media (AOM), with symptoms including fever, otalgia, otorrhoea or irritability and short duration; or as otitis media with effusion (OME), which is often asymptomatic and characterised by accumulation of fluid in the middle ear. Diagnostic certainty of otitis media is challenging, given the young age of patients and variability of symptoms. Otitis media predominantly occurs as coincident to viral upper respiratory tract infections and/or bacterial infections. Common viruses that cause upper respiratory tract infection are frequently associated with AOM and new-onset OME. These include respiratory syncytial virus, rhinovirus, adenovirus, parainfluenza and coronavirus. Predominant bacteria that cause otitis media are Streptococcus pneumoniae, Moraxella catarrhalis, and non-typeable Haemophilus influenzae. Antibiotic therapy does not significantly benefit most patients with AOM, but long-term prophylactic antibiotic therapy can reduce the risk of otitis media recurrence among children at high risk. In Australia, 84% of AOM is treated with antibiotic therapy, which contributes to development of antibiotic resistance. Vaccine development is a key future direction for reducing the world burden of otitis media, but requires polymicrobial formulation and ongoing monitoring and modification to ensure sustained reduction in disease burden.

Moraxella catarrhalis acquisition, airway inflammation and protease-antiprotease balance in chronic obstructive pulmonary disease.

BACKGROUND: Moraxella catarrhalis causes approximately 10% of exacerbations in chronic obstructive pulmonary disease (COPD) and also colonizes the lower airway in stable patients. Little is known about the effects of colonization by M. catarrhalis on airway inflammation and protease-antiprotease balance, and how these changes compare to those seen during exacerbations. Since COPD is a progressive inflammatory disease, elucidating the effects of bacterial colonization and exacerbation on airway inflammation is relevant to understanding disease progression in COPD. Our aims were (1) Analyze changes in airway inflammation in colonization and exacerbation of COPD due to M. catarrhalis; (2) Explore protease-antiprotease balance in colonization and exacerbation due to M. catarrhalis. Our hypothesis were (1) Acquisition of a new strain of M. catarrhalis in COPD increases airway inflammation from baseline and alters the protease-antiprotease balance towards a more proteolytic environment; (2) These changes are greater during exacerbations associated with M. catarrhalis as compared to colonization. METHODS: Thirty-nine consecutive COPD patients with 76 acquisitions of a new strain of M. catarrhalis over a 6-year period were identified in a prospective study. Seventy-six pre-acquisition sputum supernatant samples, obtained just before acquisition of M catarrhalis, and 76 acquisition samples (34 were associated with exacerbation, 42 with colonization) were analyzed for IL-8, TNF-alpha, Neutrophil Elastase (NE) and Secretory leukocyte protease inhibitor (SLPI). Changes were compared in paired samples from each patient. RESULTS: IL-8, TNF-alpha and NE were significantly elevated after acquisition of M. catarrhalis, compared to pre-acquisition samples (p =< 0.001 for all three). These changes were present in colonization (p = 0.015 for IL-8; p =< 0.001 for TNF-alpha and NE) as well as in exacerbation (p =< 0.001 for all three), compared to pre-acquisition levels. SLPI was significantly lower after acquisition (p =< 0.001), in colonization (p =< 0.001) as well as in exacerbation (p = 0.004), compared to pre-acquisition levels. SLPI levels correlated negatively with NE levels (R2 = 0.07; p = 0.001). CONCLUSION: Acquisition of M. catarrhalis in COPD causes increased airway inflammation and worsening protease-antiprotease imbalance during exacerbations and also in colonization, even in the absence of increased symptoms. These effects could contribute to progression of airway disease in COPD.

The respiratory pathogen moraxella catarrhalis binds to laminin via ubiquitous surface proteins A1 and A2.

Moraxella catarrhalis is one of the leading causes of exacerbations in chronic obstructive pulmonary disease (COPD). In the present article, we show that moraxella (n=15) binds to the major basement-membrane glycoprotein laminin, which is thickened in the airways of smokers. Using clinical strains of M. catarrhalis and their corresponding ubiquitous surface protein (Usp) A1/A2 mutants, we demonstrate that UspA1 and UspA2 are important for the laminin interaction. Binding assays with recombinant proteins demonstrated that the binding regions are localized within the N-terminal fragments, where both proteins form a globular head. Thus, UspA1/A2-dependent interactions with laminin might promote bacterial adhesion, particularly in smokers with COPD.

Invasive infection due to Moraxella lacunata, an unusual pathogen.

Moraxella lacunata, a commensal bacterium, is associated with serious invasive disease. We describe a patient with diabetic nephropathy who developed septicemia with metastatic abscesses in the liver and spleen due to Moraxella lacunata. The patient also had multiple ring enhancing lesions in both the cerebral hemispheres, possibly due to the same organism.

Alkanindiges hongkongensis sp. nov. A novel Alkanindiges species isolated from a patient with parotid abscess.

A bacterium was isolated from the abscess pus of a 72-year-old patient with Warthin's tumor and parotid abscess. The cells were aerobic, non-motile, Gram-negative but difficult to be destained, non-sporulating, coccobacillus. The bacterium grew poorly on sheep blood agar and MacConkey agar as non-hemolytic colonies of 0.5 mm in diameter after 24h of incubation at 37 degrees C in ambient air. Growth was enhanced by Tween 80. It produces catalase but not cytochrome oxidase. Sequencing of the cloned 16S rRNA PCR products of the bacterium revealed three different 16S rRNA gene sequences, with 12 - 31 bp differences among them. Phylogenetic analysis showed that the bacterium is closely related to Alkanindiges illinoisensis, with 5.0 - 5.9% differences between the 16S rRNA gene sequence of the bacterium and that of A. illinoisensis. Tryptophan auxotrophic strain of Acinetobacter trpE27 transformed with DNA extracted from the bacterium was unable to grow on tryptophan deficient medium, indicating that the bacterium was not a strain of Acinetobacter. The G+C content of the bacterium (mean +/-SD) was 46.9+4.3%. A new species, Alkanindiges hongkongensis sp. nov., is proposed, for which HKU9T is the type strain. Isolates with "small colonies" that are apparently Acinetobacter-like species should be carefully identified. Growth enhancement with aliphatic hydrocarbons should be looked for and 16S rRNA gene sequencing performed in order to find more potential cases of Alkanindiges infections, as well as to define the epidemiology, clinical spectrum, and outcome of infections associated with this genus.

Moraxella catarrhalis coaggregates with Streptococcus pyogenes and modulates interactions of S. pyogenes with human epithelial cells.

The pathogens Streptococcus pyogenes and Moraxella catarrhalis colonize overlapping regions of the human nasopharynx. We have found that M. catarrhalis can dramatically increase S. pyogenes adherence to human epithelial cells and that species-specific coaggregation of these bacteria correlates with this enhanced adherence.

Concomitant spine infection with mycobacterium tuberculosis and pyogenic bacteria: case report.

STUDY DESIGN: A case report of an extremely rare condition describing lumbar spine tuberculosis associated with concurrent pyogenic infection is presented. OBJECTIVE: To establish that isolation of pyogenic bacteria from an infected spine does not exclude the possibility of spine tuberculosis. SUMMARY OF BACKGROUND DATA: During a MEDLINE data search from January 1960 through October 2001, no cases of combined spine tuberculosis and pyogenic infection were found. METHODS: A 52-year-old man reported left-side gluteal swelling, backache, and fever of 20 days duration. A similar swelling in the same location had occurred 12 years previously, and an operation was performed at that time. Preoperative syringe-aspirated material from a gluteal abscess was sent for ordinary bacteriologic culture (for only aerobic pyogenic bacteria). During the operation, a needle-aspirated specimen of evacuated pus was subjected to direct microscopy and culture. Direct Gram stain for pyogenic bacteria and direct Ziehl-Neelsen stain for mycobacteria were performed. Cultures for aerobes, anaerobes, mycobacteria, and fungi were made. RESULTS: The preoperative specimen culture showed growth of Nocardia asteroids and Moraxella catarrhalis, whereas the operative specimen showed Gram-positive cocci and acid-fast bacilli on direct smears. The operative cultures yielded growth of Nocardia asteroids, Moraxella catarrhalis, and Mycobacterium tuberculosis. Plain lumbar spine radiograph showed psoas muscle calcification. CONCLUSIONS: It is concluded from this case that recovery of pyogenic bacteria from an infected spine does not exclude spine tuberculosis. It is recommended, therefore, that mycobacterial investigations be performed for cases that have evidence of tuberculosis, even when pyogenic microorganisms already have been isolated. The clues that raise suspicion of tuberculosis in patients with pyogenic spine infection include chronic infection that does not respond to ordinary antibiotics, isolated pyogenic bacteria of low virulence, psoas muscle calcification, and immunosuppression.