Fusobacterium/Peptostreptococcus - A Case Report of Community- Acquired Empyema Resulting in Surgical Decortication with Prolonged Antibiotic Therapy: A Case Series and Review of the Literature.

Background: Infections caused by anaerobic bacteria occur frequently and can be serious and life-threatening. Anaerobes are a rare cause of community-acquired pneumonia with Streptococcus pneumonia and respiratory viruses being the most frequently detected pathogens. We, herein, report a case of Fusobacterium/Peptostreptococcus parapneumonic effusion with empyema in a patient without risk factors for aspiration pneumonia. This case presents an opportunity to discuss an unusual case of community-acquired empyema secondary to anaerobic infection in a patient without the common risk factors for aspiration.

Case Presentation: A 59-year-old male patient without significant past medical history apart from a twenty-five-year history of smoking presented due to left flank pain and shortness of breath. Findings of a complicated parapneumonic effusion were found on imaging, resulting in surgical decortication and prolonged antibiotic therapy.

Discussion: Parapneumonic effusions and empyema are relatively common complications of pneumonia. It is important to note that the incidence of anaerobic empyema has been on the rise due to more modern culturing techniques.

Conclusion: This case highlights an unusual presentation of community-acquired empyema secondary to anaerobes without any risk factors for aspiration pneumonia. Therefore, clinicians should consider the possibility of anaerobic coverage in the treatment of community-acquired empyema in the appropriate setting.

Peptostreptococcus anaerobius is a potential diagnostic biomarker of colorectal cancer.

Accumulating evidences have shown that Peptostreptococcus anaerobius (P.a) is abundantly enriched in the fetus of colorectal cancer (CRC) patients. P.a is reported able to invade colorectal tissues. This study intends to uncover the clinical significance of P.a in CRC. Mucosal tissues collected from CRC cases (n=109) and precancerous healthy ones (n=65) were subjected to the determination of the absolute copy number of P.a by droplet digital PCR. The positive rate of P.a in mucosal tissues of CRC and healthy ones was 79.8% (87/109), and 55.4% (36/65), respectively. The average absolute copy number of P.a in them was 2.3 copy/ng DNA, and 0.32 copy/ng DNA, respectively. The abundance of P.a in mucosal tissues of CRC, and age and TNM staging of CRC cases were correlated to its survival. The abundance of P.a in CRC cases was remarkably correlated to the relative level of SQLE. The abundance of P.a can be monitored to predict the prognosis of CRC.

Actividad antimicrobiana in vitro del extracto de hojas de Bixa orellana L. contra bacterias anaerobias asociadas a la vaginosis bacteriana y Lactobacillus spp / In vitro antimicrobial activity of Bixa orellana L. leaves extract against anaerobic bacteria associated to bacterial vaginosis and Lactobacillus spp.

Objetivos . Describir la actividad antimicrobiana in vitro del extracto metanólico de las hojas de Bixa orellana L. contra las bacterias anaerobias asociadas a la vaginosis bacteriana y Lactobacillus spp. Materiales y métodos . Se incluyeron en el estudio ocho cepas de referencia ATCC; Gardnerella vaginalis, Prevotella bivia, Peptococcus niger, Peptostreptococcus anaerobius, Mobiluncus curtisii, Atopobium vaginae, Veillonella parvula y Lactobacillus crispatus, y 22 aislamientos clínicos; once aislados de Gardnerella vaginalis y once aislados de Lactobacillus. La susceptibilidad antimicrobiana se determinó mediante el método de difusión en agar. La concentración mínima inhibitoria (CMI) y la concentración bactericida mínima (CBM) fueron determinadas utilizando el método de dilución en agar y un método de dilución modificado, respectivamente. Resultados . Todas las cepas de referencia ATCC tuvieron un alto nivel de susceptibilidad al extracto, con excepción de P. vibia, V. parvula y L. crispatus. Interesantemente, los aislamientos clínicos de G. vaginalis y la cepa ATCC de G. vaginalis fueron los más susceptibles al extracto dados los bajos valores de CMI (1,0 - 2,0 mg/mL) y CBM (1,0 - 4,0 mg/mL), mientras que, los aislamientos clínicos de Lactobacillus spp. y la cepa ATCC de L. crispatus fueron los menos susceptibles debido a los altos valores de CMI (32,0 mg/mL) y CBM (≥ 32,0 mg/mL). Conclusiones . Los experimentos in vitro sugieren que el extracto posee propiedades antibacterianas selectivas dada su alta actividad contra bacterias anaerobias asociadas a vaginosis bacteriana y baja actividad contra especies de Lactobacillus.

Objective. To describe the in vitro antimicrobial activity of the methanolic extract of Bixa orellana L. leaves against anaerobic bacteria associated to bacterial vaginosis and Lactobacillus spp. Materials and methods. Eight ATCC reference strains; Gardnerella vaginalis, Prevotella bivia, Peptococcus niger, Peptostreptococcus anaerobius, Mobiluncus curtisii, Atopobium vaginae, Veillonella parvula, and Lactobacillus crispatus, and twenty-two clinical isolates; eleven Gardnerella vaginalis and eleven Lactobacillus strains, were included in the study. The antimicrobial susceptibility was determined by the agar diffusion method. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined by using agar dilution and a modified dilution plating method, respectively. Results. All ATCC reference strains showed high levels of susceptibility to the extract, except P. vibia, V. parvula and L. crispatus. Interestingly, all G. vaginalis clinical isolates and the G. vaginalis ATTC strain were the most susceptible to the extract, given their low MIC (1.0 - 2.0 mg/mL) and MBC (1.0 - 4.0 mg/mL) values, whereas, the Lactobacillus spp. clinical isolates and the L. crispatus ATCC strain were the least susceptible bacteria given their high MIC (32.0 mg/mL) and MBC (≥ 32.0 mg/mL) values. Conclusions. In vitro experiments suggest that the extract possesses selective antimicrobial properties given its high activity against bacterial vaginosis-associated anaerobic bacteria and low activity against Lactobacillus species.

Vaginal Microbial Environment Skews Macrophage Polarization and Contributes to Cervical Cancer Development.

As a common female reproductive system malignancy, cervical cancer (CC) disturbs numerous women's health. This study demonstrates the role of the vaginal microbial environment (Peptostreptococcus anaerobius) in cervical cancer. Functional assays, including cell proliferation assay, tube formation assay, and immunofluorescence staining, revealed the effect of Peptostreptococcus anaerobius-treated macrophages on cell proliferation and the angiogenesis process. The tube formation assay disclosed the function of Peptostreptococcus anaerobius-treated macrophages on angiogenesis. In vivo assays were also established to explore the impact of Peptostreptococcus anaerobius-treated macrophages on tumor migration. The results revealed that Peptostreptococcus anaerobius-induced macrophages boosted cervical cancer migration and angiogenesis both in vitro and in vivo. Then, this study unveiled that Peptostreptococcus anaerobius-induced macrophage secreted VEGF to stimulate the angiogenesis in cervical cancer. As a whole, Peptostreptococcus anaerobius-induced macrophage facilitates cervical cancer development through modulation of VEGF expression.

Brain abscesses caused by anaerobic bacteria.

OBJECTIVES: The objective of this study was to review the characteristics, causative bacteria, treatment and outcomes of brain abscesses due to anaerobes in our health setting. METHODS: A retrospective analysis of all brain abscesses caused by anaerobic bacteria over the period 2005-2021 was performed. RESULTS: Out of 300 brain abscesses identified during the study period, 31 were produced by anaerobic pathogens, either alone (monomicrobial infection) or together with aerobic and/or anaerobic bacteria (polymicrobial infection). The mean age of the 31 patients was 53 years, and 61.2% were male; 51.6% of infections were polymicrobial, with only four (12.9%) caused by anaerobic bacteria alone. Forty-three anaerobic bacteria were isolated: Cutibacterium acnes in thirteen (41.9%), Parvimonas micra in eight (25.8%), and Prevotella spp. in seven (22.5%). The most frequent etiologies were local neurosurgery (13/41.9%) and contiguous otogenic, oral, or sinus foci of infection (8/28.8%). Cancer was present in eight patients (28.8%), headaches in seventeen (54.8%), and fever in nine (28.8%). All patients received both surgery and antimicrobial therapy. The abscess was in the frontal region in 12 patients (38.7%) and in the parietal region in 11 (35.4%). A good outcome was obtained in all patients. CONCLUSIONS: Anaerobes were isolated in 10.3% of patients with brain abscesses in our health setting, similar to other reports. C. acnes was the most frequently detected anaerobe, especially in neurosurgical patients.

Super-taxon in human microbiome are identified to be associated with colorectal cancer.

BACKGROUND: Microbial communities in the human body, also known as human microbiota, impact human health, such as colorectal cancer (CRC). However, the different roles that microbial communities play in healthy and disease hosts remain largely unknown. The microbial communities are typically recorded through the taxa counts of operational taxonomic units (OTUs). The sparsity and high correlations among OTUs pose major challenges for understanding the microbiota-disease relation. Furthermore, the taxa data are structured in the sense that OTUs are related evolutionarily by a hierarchical structure. RESULTS: In this study, we borrow the idea of super-variant from statistical genetics, and propose a new concept called super-taxon to exploit hierarchical structure of taxa for microbiome studies, which is essentially a combination of taxonomic units. Specifically, we model a genus which consists of a set of OTUs at low hierarchy and is designed to reflect both marginal and joint effects of OTUs associated with the risk of CRC to address these issues. We first demonstrate the power of super-taxon in detecting highly correlated OTUs. Then, we identify CRC-associated OTUs in two publicly available datasets via a discovery-validation procedure. Specifically, four species of two genera are found to be associated with CRC: Parvimonas micra, Parvimonas sp., Peptostreptococcus stomatis, and Peptostreptococcus anaerobius. More importantly, for the first time, we report the joint effect of Parvimonas micra and Parvimonas sp. (p = 0.0084) as well as that of Peptostrepto-coccus stomatis and Peptostreptococcus anaerobius (p = 8.21e-06) on CRC. The proposed approach provides a novel and useful tool for identifying disease-related microbes by taking the hierarchical structure of taxa into account and further sheds new lights on their potential joint effects as a community in disease development. CONCLUSIONS: Our work shows that proposed approaches are effective to study the microbiota-disease relation taking into account for the sparsity, hierarchical and correlated structure among microbes.

Biomaterial-mediated modulation of oral microbiota synergizes with PD-1 blockade in mice with oral squamous cell carcinoma.

Because a host's immune system is affected by host-microbiota interactions, means of modulating the microbiota could be leveraged to augment the effectiveness of cancer therapies. Here we report that patients with oral squamous cell carcinoma (OSCC) whose tumours contained higher levels of bacteria of the genus Peptostreptococcus had higher probability of long-term survival. We then show that in mice with murine OSCC tumours injected with oral microbiota from patients with OSCCs, antitumour responses were enhanced by the subcutaneous delivery of an adhesive hydrogel incorporating silver nanoparticles (which inhibited the growth of bacteria competing with Peptostreptococcus) alongside the intratumoural delivery of the bacterium P. anaerobius (which upregulated the levels of Peptostreptococcus). We also show that in mice with subcutaneous or orthotopic murine OSCC tumours, combination therapy with the two components (nanoparticle-incorporating hydrogel and exogenous P. anaerobius) synergized with checkpoint inhibition with programmed death-1. Our findings suggest that biomaterials can be designed to modulate human microbiota to augment antitumour immune responses.

Impact of Fusobacterium nucleatum in the gastrointestinal tract on natural killer cells.

BACKGROUND: Gut microbial dysbiosis contributes to the development and progression of colorectal cancer (CRC). Natural killer (NK) cells are involved in early defense mechanisms to kill infective pathogens and tumor cells by releasing chemokines and cytokines. To better understand the relationship between the gut microbiome and CRC, it was hypothesized here that a high abundance of Fusobacterium nucleatum (F. nucleatum) in the gastrointestinal tract could cause reduced NK cell activity. AIM: To identify associations between gastrointestinal tract F. nucleatum levels and NK cell activity. METHODS: In vitro experiments were performed on NK cells treated with F. nucleatum, Peptostreptococcus anaerobius, and Parvimonas micra to identify the effects of gut microbiome species on NK cells. Following 24 and 48 h of treatment, NK cell counts were measured. In parallel studies, C57BL/6 mice were given broad-spectrum antibiotics in their drinking water to reduce resident gut flora. After 3 wk, the mice received the various bacterial species or phosphate-buffered saline (PBS) via oral gavage every 2 d for 6 wk. At the study end, blood samples were acquired to perform NK cell activity assessment and cytokine analysis. Intestinal tissues were collected and analyzed via immunohistochemistry (IHC). RESULTS: The data show that after 3 wk of broad-spectrum antibiotic treatment, levels of total bacteria and F. nucleatum were markedly decreased in mice. Gavage of F. nucleatum significantly decreased NK cell activity relative to the activities of cells from mice treated with antibiotics only and PBS. The administration of F. nucleatum decreased the proportion of NK46+ cells based on IHC staining and increased the production of interleukin-1ß and tumor necrosis factor-α. CONCLUSION: High levels of F. nucleatum in the gastrointestinal tract reduced NK cell activity in mice, and the decrease in NK cell activity might be affected by increased pro-inflammatory cytokines after F. nucleatum treatment.

A Retrospective Chart Review of Inflamed Epidermal Inclusion Cysts.

BACKGROUND: Epidermal inclusion cysts (EIC) are one of the most common forms of cysts found on and/or underneath the skin. Inflamed EICs typically show signs and symptoms such as pain and erythema, mimicking cutaneous abscess. However, prior studies have demonstrated at least 20% of lesions are culture negative. OBJECTIVE: To determine the rate of culture positivity in mild inflamed epidermal inclusion cysts, in particular to identify whether empiric antibiotics are warranted. METHODS: In a retrospective chart review 76 cases of inflamed EIC that were mild (lacking systemic symptoms) were analyzed who presented to the department of dermatology at Mount Sinai between 2016–2019. RESULTS: Of cultures taken from inflamed cysts, 47% resulted in no bacterial growth or growth of normal flora, 38.4% resulted in growth of aerobic bacteria with methicillin-resistant Staphylococcus aureus (8%), Staphylococcus lugdunensis (5%), and methicillin-sensitive Staphylococcus aureus (13%) predominating, and 9.3% resulting in growth of anaerobic bacteria with Finegoldia magna, Peptostreptococcus, and Cutibacterium acnes presenting. Review of prescribed treatment regimens often involved antibiotic medication, despite a high prevalence of negative culture. CONCLUSIONS: Almost half of cases of mild inflamed EIC (lacking systemic symptoms) cultured will not grow pathogenic bacteria, therefore incision and drainage with culture and appropriate therapy is a viable therapeutic option in uncomplicated inflamed EIC lesions. In this way, over prescription of antibiotics can be minimized. J Drugs Dermatol. 2021;20(2):199-202. doi:10.36849/JDD.5014.

Parvimonas micra, Peptostreptococcus stomatis, Fusobacterium nucleatum and Akkermansia muciniphila as a four-bacteria biomarker panel of colorectal cancer.

Dysbiosis of the gut microbiome has been associated with the pathogenesis of colorectal cancer (CRC). We profiled the microbiome of gut mucosal tissues from 18 CRC patients and 18 non-CRC controls of the UKM Medical Centre (UKMMC), Kuala Lumpur, Malaysia. The results were then validated using a species-specific quantitative PCR in 40 CRC and 20 non-CRC tissues samples from the UMBI-UKMMC Biobank. Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were found to be over-represented in our CRC patients compared to non-CRC controls. These four bacteria markers distinguished CRC from controls (AUROC = 0.925) in our validation cohort. We identified bacteria species significantly associated (cut-off value of > 5 fold abundance) with various CRC demographics such as ethnicity, gender and CRC staging; however, due to small sample size of the discovery cohort, these results could not be further verified in our validation cohort. In summary, Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were enriched in our local CRC patients. Nevertheless, the roles of these bacteria in CRC initiation and progression remains to be investigated.

Network Analysis of Gut Microbiome and Metabolome to Discover Microbiota-Linked Biomarkers in Patients Affected by Non-Small Cell Lung Cancer.

Several studies in recent times have linked gut microbiome (GM) diversity to the pathogenesis of cancer and its role in disease progression through immune response, inflammation and metabolism modulation. This study focused on the use of network analysis and weighted gene co-expression network analysis (WGCNA) to identify the biological interaction between the gut ecosystem and its metabolites that could impact the immunotherapy response in non-small cell lung cancer (NSCLC) patients undergoing second-line treatment with anti-PD1. Metabolomic data were merged with operational taxonomic units (OTUs) from 16S RNA-targeted metagenomics and classified by chemometric models. The traits considered for the analyses were: (i) condition: disease or control (CTRLs), and (ii) treatment: responder (R) or non-responder (NR). Network analysis indicated that indole and its derivatives, aldehydes and alcohols could play a signaling role in GM functionality. WGCNA generated, instead, strong correlations between short-chain fatty acids (SCFAs) and a healthy GM. Furthermore, commensal bacteria such as Akkermansia muciniphila, Rikenellaceae, Bacteroides, Peptostreptococcaceae, Mogibacteriaceae and Clostridiaceae were found to be more abundant in CTRLs than in NSCLC patients. Our preliminary study demonstrates that the discovery of microbiota-linked biomarkers could provide an indication on the road towards personalized management of NSCLC patients.

Choosing the Right Essential Oil for a Mouthwash: Chemical, Antimicrobial and Cytotoxic Studies.

Thirteen commercial essential oils were assessed for their possible inclusion in a mouthwash formulation based on their inhibitory effect against potentially pathogenic anaerobic oral bacterial isolates from subgingival plaque, and their cytotoxicity towards gingival cells. The essential oils, originating from species belonging to seven major aromatic plant families, were chosen to provide the necessary diversity in chemical composition that was analyzed in detail by GC and GC/MS. Multivariate statistical analysis, performed using the in vitro microbiological/toxicological assays and compositional data, revealed that the major components of the essential oils were probably not the main carriers of the activities observed. A formulation of 'designer' mouthwashes is proposed based on the selective action of certain essential oils towards specific bacterial isolates (e. g., Citrus bergamia vs. Parvimonas micra), and non-toxicity to gingival cells at antimicrobially active concentrations.

Enterobacter cloacae Periprosthetic Joint Infection After Bariatric Surgical Anastomotic Leak.

Four weeks after a bilateral total knee arthroplasty (TKA), an immunocompetent, 61-year-old, Caucasian man presented with a periprosthetic joint infection (PJI) of the left knee by Enterobacter cloacae (an enteric bacteria). The most likely source of his infection was due to an anastomotic leak after a bariatric surgery done 6 months before TKA. There is a growing focus on stratifying the risk of PJI after TKA. Hematogenous seeding of enteric bacteria leading to PJI is an unexplored risk that will become more prevalent as bariatric procedures before TKA continue to increase in frequency. We present a patient who demonstrates this PJI risk with a rare microbe (E cloacae).

Essential Oil from Psidium cattleianum Sabine (Myrtaceae) Fresh Leaves: Chemical Characterization and in vitro Antibacterial Activity Against Endodontic Pathogens

Abstract Endodontic infections result from oral pathogenic bacteria which reach and infect dental pulp, as well as surrounding tissues, through cracks, unrepaired caries and failed caries restorations. This study aims to determine the chemical composition of essential oil from Psidium cattleianum leaves (PC-EO) and to assess its antibacterial activity against endodontic bacteria. Antibacterial activity of PC-EO was evaluated in terms of its minimum inhibitory concentration (MIC) values by the broth microdilution method on 96-well microplates. Bacteria Porphyromonas gingivalis (MIC = 20 µg/mL), Prevotella nigrescens (MIC = 62.5 µg/mL), Fusobacterium nucleatum (MIC = 12.5 µg/mL), Actinomyces naeslundii (MIC = 50 µg/mL), Bacteroides fragilis (MIC = 12.5 µg/mL), Aggregatibacter actinomycetemcomitans (MIC = 6.25 µg/mL) and Peptostreptococcus anaerobius (MIC = 62.5 µg/mL) were evaluated and compared to chlorhexidine dihydrochloride (CDH), the positive control. PC-EO was obtained by hydrodistillation with the use of a Clevenger-type apparatus whereas its chemical composition was analyzed by gas chromatography-flame ionization detection (GC-FID) and gas chromatography-mass spectrometry (GC-MS). Viridiflorol (17.9%), β-caryophyllene (11.8%), 1,8-cineole (10.8%) and β-selinene (8.6%) were the major constituents found in PC-EO, which exhibited high antibacterial activity against all endodontic pathogens under investigation. Therefore, PC-EO, a promising source of bioactive compounds, may provide therapeutic solutions for the field of endodontics.

Peptostreptococcus anaerobius promotes colorectal carcinogenesis and modulates tumour immunity.

Emerging evidence implicates a role of the gut microbiota in colorectal cancer (CRC). Peptostreptococcus anaerobius (P. anaerobius) is an anaerobic bacterium selectively enriched in the faecal and mucosal microbiota from patients with CRC, but its causative role and molecular mechanism in promoting tumorigenesis remain unestablished. We demonstrate that P. anaerobius adheres to the CRC mucosa and accelerates CRC development in ApcMin/+ mice. In vitro assays and transmission electron microscopy revealed that P. anaerobius selectively adheres to CRC cell lines (HT-29 and Caco-2) compared to normal colonic epithelial cells (NCM460). We identified a P. anaerobius surface protein, putative cell wall binding repeat 2 (PCWBR2), which directly interacts with colonic cell lines via α2/ß1 integrin, a receptor frequently overexpressed in human CRC tumours and cell lines. Interaction between PCWBR2 and integrin α2/ß1 induces the activation of the PI3K-Akt pathway in CRC cells via phospho-focal adhesion kinase, leading to increased cell proliferation and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation. NF-κB in turn triggers a pro-inflammatory response as indicated by increased levels of cytokines, such as interleukin-10 and interferon-γ in the tumours of P. anaerobius-treated ApcMin/+ mice. Analyses of tumour-infiltrating immune cell populations in P. anaerobius-treated ApcMin/+ mice revealed significant expansion of myeloid-derived suppressor cells, tumour-associated macrophages and granulocytic tumour-associated neutrophils, which are associated with chronic inflammation and tumour progression. Blockade of integrin α2/ß1 by RGDS peptide, small interfering RNA or antibodies all impair P. anaerobius attachment and abolish P. anaerobius-mediated oncogenic response in vitro and in vivo. Collectively, we show that P. anaerobius drives CRC via a PCWBR2-integrin α2/ß1-PI3K-Akt-NF-κB signalling axis and identify the PCWBR2-integrin α2/ß1 axis as a potential therapeutic target for CRC.

The Oral Microbiota May Have Influence on Oral Cancer.

The oral microbiota plays an important role in the human microbiome and human health, and imbalances between microbes and their hosts can lead to oral and systemic diseases and chronic inflammation, which is usually caused by bacteria and contributes to cancer. There may be a relationship between oral bacteria and oral squamous cell carcinoma (OSCC); however, this relationship has not been thoroughly characterized. Therefore, in this study, we compared the microbiota compositions between tumor sites and opposite normal tissues in buccal mucosal of 50 patients with OSCC using the 16S rDNA sequencing. Richness and diversity of bacteria were significantly higher in tumor sites than in the control tissues. Cancer tissues were enriched in six families (Prevotellaceae, Fusobacteriaceae, Flavobacteriaceae, Lachnospiraceae, Peptostreptococcaceae, and Campylobacteraceae) and 13 genera, including Fusobacterium, Alloprevotella and Porphyromonas. At the species level, the abundances of Fusobacterium nucleatum, Prevotella intermedia, Aggregatibacter segnis, Capnocytophaga leadbetteri, Peptostreptococcus stomatis, and another five species were significantly increased, suggesting a potential association between these bacteria and OSCC. Furthermore, the functional prediction revealed that genes involved in bacterial chemotaxis, flagellar assembly and lipopolysaccharide (LPS) biosynthesis which are associated with various pathological processes, were significantly increased in the OSCC group. Overall, oral bacterial profiles showed significant difference between cancer sites and normal tissue of OSCC patients, which might be onsidered diagnostic markers and treatment targets. Our study has been registered in the Chinese clinical trial registry (ChiCTR1900025253, http://www.chictr.org.cn/index.aspx).

Pharmacological inhibition of bacterial ß-glucuronidase prevents irinotecan-induced diarrhea without impairing its antitumor efficacy in vivo.

Irinotecan (CPT-11), a first-line chemotherapy for advanced colorectal cancer, causes serious diarrhea in patients receiving treatment. The underlying mechanism has been shown that the active metabolite of CPT-11, SN-38, is metabolized to the inactive metabolite SN-38 glucuronide (SN-38 G) during hepatic glucuronidation, and subsequently is exported into the intestine, where SN-38 G is hydrolyzed by bacterial ß-glucuronidase (ßG) to be SN-38, thus leading to intestinal toxicity. Thus, inhibition of the intestinal bacterial ßG activity is expected to prevent CPT-11-induced diarrhea. However, the effects of such inhibition on serum pharmacokinetics of SN-38, the key determinant of CPT-11 treatment, are uncertain. Here, we determined the effects of a potent E. coli ßG (eßG)-specific inhibitor pyrazolo[4,3-c]quinoline derivative (TCH-3562) for the potential use in preventing CPT-11-induced diarrhea. TCH-3562 exhibited efficacious inhibitory potency of endogenous ßG activity in two anaerobes, Eubacteriumsp. and Peptostreptococcus anaerobius. Oral administration of TCH-3562 also effectively reduced the bacterial ßG activity in mice intestine. Moreover, pharmacokinetic analysis of TCH-3562 revealed a relatively low amount of TCH-3562 was detected in the plasma whereas the majority of TCH-3562 was found in the feces. Importantly, co-treatment of CPT-11 and TCH-3562 did not decrease active SN-38 level in mice plasma. Finally, we established that TCH-3562 as an adjuvant treatment showed protective effects on CPT-11-induced diarrhea and had no negative effects on the therapeutic efficacy of CPT-11 in tumor-bearing mice. Therefore, inhibition of the intestinal bacterial ßG activity by the specific inhibitor, TCH-3562, is promising to prevent CPT-11-induced diarrhea while maintaining its anti-tumor efficacy that may have clinical potentials for the treatment with CPT-11.

Septic arthritis of knee joint due to Parvimonas micra.

Parvimonas species are anaerobic, Gram-positive cocci that are a constituent of normal oral and gastrointestinal flora. We present a case of right knee joint septic arthritis due to Parvimonas micra in an immunocompromised patient. A 61-year-old male renal and pancreatic transplant recipient on immunosuppressive therapy was admitted to our hospital due to intense pain, joint swelling and inability to move his right knee over the past 9 months. After synovial fluid was drawn, cultures were positive for P. micra, an anaerobic pathogen that is part of the flora of the oral cavity. We report a rare causative pathogen for septic arthritis in an immunocompromised patient.

Spondylodiscitis due to Parvimonas micra diagnosed by the melting temperature mapping method: a case report.

BACKGROUND: It has been suggested that more than 100 bacterial species can be identified using only seven universal bacterial primer sets in the melting temperature (Tm) mapping method and that these findings can be obtained within 3 h of sterile site collection. CASE PRESENTATION: A 67-year-old Japanese man with type 2 diabetes visited our hospital complaining of progressive lower back pain for 2 months. The patient was suspected to have spondylodiscitis on magnetic resonance imaging of the spine. Blood culture and transcutaneous vertebral biopsy were subsequently performed. Using the Tm mapping method, Parvimonas micra was detected from a transcutaneous vertebral biopsy specimen in 3 h. Gram-positive cocci were also detected by Gram staining and P. micra was identified directly from the anaerobic blood culture by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Four days after admission, the biopsy specimen culture isolate was identified as P. micra. CONCLUSIONS: The Tm mapping method may be useful for the diagnosis of bacterial infections where diagnosis is challenging because of the difficulty of culturing.

Osteomyelitis of the jaw (with pathological fracture) following extraction of an impacted wisdom tooth. A case report.

Osteomyelitis is an infection and inflammation associated with the bone structures: bone marrow, cortical bone, periosteum, blood vessels and nerves. Although it does not have a frequent presentation, it can sometimes lead to complications such as pathological fractures or even septicemia. We present a clinical case study, to assess the relationship between osteomyelitis of the jaw and pathological fractures, after the extraction of an impacted wisdom tooth. This case highlights a rare complication following the surgical removal of mandibular third molar; a slow evolution of the pathology following an extraction should lead to close monitoring of the patient both clinically and radiographically, albeit osteomyelitis is a rare complication, it should be included as one of the differential diagnosis of persistent post-extraction pain.