Should the risk of Fusobacterium necrophorum pharyngotonsillitis influence prescribing empiric antibiotics for sore throats in adolescents and young adults?

Fusobacterium necrophorum, a gram-negative anaerobe, causes pharyngotonsillitis primarily in adolescents and young adults (approximately 15-30 years old). The same age group has the highest incidence of peritonsillar abscess and the Lemierre syndrome. The same organism, F. necrophorum, is the most common cause of peritonsillar abscess in this age group and causes at least 80% of Lemierre syndrome cases. We outline the case for empiric antibiotic treatment of some patient in this age group who have a significant probability that F. necrophorum is the cause of their pharyngotonsillitis.

Chemical composition and antibacterial activity of essential oils against pathogens often related to cattle endometritis.

INTRODUCTION: Endometritis is a condition marked by inflammation of the endometrium that affects dairy cows from 21 days after parturition, causing damage to herd fertility and economic losses on farms. The use of active compounds obtained from plant sources has gained importance as disease treatment agents in farm animals due to the high resistance rates currently observed against traditional antibiotics commonly used. The study was carried out to examine the chemical composition and to investigate the antibacterial activity of rosemary, cinnamon, cloves, eucalyptus, lemon, oregano and thyme essential oils against the reference strain of Escherichia coli (ATCC 25922), Fusobacterium necrophorum (ATCC 25286), Trueperella pyogenes (ATCC 19411) and Staphylococcus aureus (ATCC 29213), considered as typical bacteria causing endometritis. METHODOLOGY: The chemical composition of the seven essential oils were analyzed by GC-MS and their antibacterial activity was evaluated by the disc diffusion method. RESULTS: Thirty-six components were identified in total using GC-MS analyzes. The main compounds were cinnamaldehyde (86.5% for cinnamon essential oil), eugenol (85.7% for clove essential oil), 1,8-cineol (80% for eucalyptus and 47.8% rosemary essential oils), limonene (65.5% for lemon essential oil), carvacrol (72.1% for oregano essential oil) and thymol (48.8% for thyme essential oil). The disc diffusion assay revealed that cinnamon, clove, oregano, and thyme essential oils showed the best results compared to the other three essential oils, showing the largest zone of inhibition against all bacteria evaluated. CONCLUSIONS: These findings indicated that essential oils are a potential agent to be used as an alternative for bovine endometritis treatment.

Bactericidal activity of hexylresorcinol lozenges against oropharyngeal organisms associated with acute sore throat.

OBJECTIVE: For the majority of people with acute sore throat, over-the-counter treatments represent the primary option for symptomatic relief. This study evaluated the in vitro bactericidal activity of lozenges containing the antiseptic hexylresorcinol against five bacteria associated with acute sore throat: Staphylococcus aureus, Streptococcus pyogenes, Moraxella catarrhalis, Haemophilus influenzae and Fusobacterium necrophorum. RESULTS: Hexylresorcinol 2.4 mg lozenges were dissolved into 5 mL of artificial saliva medium. Inoculum cultures were prepared in triplicate for each test organism to give an approximate population of 108 colony-forming units (cfu)/mL. Bactericidal activity was measured by log reduction in cfu. Greater than 3log10 reductions in cfu were observed at 1 min after dissolved hexylresorcinol lozenges were added to S. aureus (log10 reduction cfu/mL ± standard deviation, 3.3 ± 0.2), M. catarrhalis (4.7 ± 0.4), H. influenzae (5.8 ± 0.4) and F. necrophorum (4.5 ± 0.2) and by 5 min for S. pyogenes (4.3 ± 0.4). Hexylresorcinol lozenges achieved a > 99.9% reduction in cfu against all tested organisms within 5 min, which is consistent with the duration for a lozenge to dissolve in the mouth. In conclusion, in vitro data indicate that hexylresorcinol lozenges offer rapid bactericidal activity against organisms implicated in acute sore throat.

Mixed species biofilms of Fusobacterium necrophorum and Porphyromonas levii impair the oxidative response of bovine neutrophils in vitro.

Biofilms composed of anaerobic bacteria can result in persistent infections and chronic inflammation. Host immune cells have difficulties clearing biofilm-related infections and this can result in tissue damage. Neutrophils are a vital component of the innate immune system and help clear biofilms. The comparative neutrophilic response to biofilms versus planktonic bacteria remains incompletely understood, particularly in the context of mixed infections. The objective of this study was to generate mixed species anaerobic bacterial biofilms composed of two opportunistic pathogens, Fusobacterium necrophorum and Porphyromonas levii, and evaluate neutrophil responses to extracellular fractions from both biofilms and planktonic cell co-cultures of the same bacteria. Purified bovine neutrophils exposed to culture supernatants from mixed species planktonic bacteria showed elevated oxidative activity compared to neutrophils exposed to biofilms composed of the same bacteria. Bacterial lipopolysaccharide plays a significant role in the stimulation of neutrophils; biofilms produced substantially more lipopolysaccharide than planktonic bacteria under these experimental conditions. Removal of lipopolysaccharide significantly reduced neutrophil oxidative response to culture supernatants of planktonic bacteria. Oxidative responses to LPS-removed biofilm supernatants and LPS-removed planktonic cell supernatants were similar. The limited neutrophil response to biofilm bacteria observed in this study supports the reduced ability of the innate immune system to eradicate biofilm-associated infections. Lipopolysaccharide is likely important in neutrophil response; however, the presence of other extracellular, immune modifying molecules in the bacterial media also appears to be important in altering neutrophil function.

In vivo antianaerobe activity of DS-8587, a new fluoroquinolone, against Fusobacterium necrophorum in a mouse model.

DS-8587 is a novel parenteral fluoroquinolone, which has an activity equivalent to sitafloxacin against various pathogens including anaerobes. We examined the in vivo anti-anaerobic activity of DS-8587, and compared it with that of levofloxacin (LVFX), using a murine model of Fusobacterium necrophorum-induced liver abscess developed via blood borne infection. Mice with liver abscess infection caused by F. necrophorum were treated with saline (control), DS-8587 (0.8, 4, and 20 mg/kg twice daily), or LVFX (20 and 100 mg/kg) for a day. After treatment, the number of viable bacteria in liver was analyzed. We also analyzed the pharmacokinetics of these agents in plasma and the liver after initial treatment. The MICs of DS-8587 and LVFX were 0.015 and 1 mg/mL, respectively. DS-8587 eradicated the viable bacteria in the liver even at doses as low as 4 mg/kg. In contrast, the liver bacteria were not eradicated in any of the LVFX-treated mice even at a dose of 100 mg/kg (P < 0.05 compared with DS-8587, 4 or 20 mg/kg). The pharmacokinetic parameter AUC/MIC ratios for DS-8587 (4 mg/kg) and LVFX (100 mg/kg) were 96.7 and 60.8 in plasma and 600 and 145.6 in the liver, respectively. The AUC/MIC ratio showed the best correlation with efficacy of DS-8587. DS-8587 significantly reduced the number of viable bacteria in a murine model of F. necrophorum-induced liver abscess compared to LVFX. Our study demonstrated that the anti-anaerobic activity of quinolones in vivo was different from the MICs in vitro.

Application of chitosan microparticles for treatment of metritis and in vivo evaluation of broad spectrum antimicrobial activity in cow uteri.

Uterine disease such as metritis is associated with multiple bacterial infections in the uteri after parturition. However, treatment of metritis is challenging due to considerably high antibiotic treatment failure rate with unknown reason. Recently, chitosan microparticles (CM) have been developed to exert broad spectrum antimicrobial activity against bacterial pathogens, including multi-drug resistant bacteria, without raising CM resistant mutants. In this study, we tested, using metagenomics analysis, if CM maintain strong antimicrobial activity against pathogenic bacteria such as Fusobacteriaceae and Bacteroidaceae in cow uteri and evaluated CM's potency as an alternative antimicrobial agent to cure metritis in cows. Here, we report that efficacy of CM treatment for metritis was comparable to the antibiotic ceftiofur, and CM greatly altered uterine microflora of sick animals to healthy uterine microflora. Among uterine bacteria, CM significantly decreased Fusobacterium necrophorum, which is known pathogenic bacteria within the uterus. Taken together, we observed the broad spectrum antimicrobial activity of CM in vivo with an animal model, and further evaluated treatment efficacy in cows with metritis, providing insights into promising use of CM as an alternative antimicrobial agent for controlling uterine disease.

Clival osteomyelitis and hypoglossal nerve palsy--rare complications of Lemierre's syndrome.

An increasingly reported entity, Lemierre's syndrome classically presents with a recent oropharyngeal infection, internal jugular vein thrombosis and the presence of anaerobic organisms such as Fusobacterium necrophorum. The authors report a normally fit and well 17-year-old boy who presented with severe sepsis following a 5-day history of a sore throat, myalgia and neck stiffness requiring intensive care admission. Blood cultures grew F. necrophorum and radiological investigations demonstrated left internal jugular vein, cavernous sinus and sigmoid sinus thrombus, left vertebral artery dissection and thrombus within the left internal carotid artery. Imaging also revealed two areas of acute ischaemia in the brain, consistent with septic emboli, skull base (clival) osteomyelitis and an extensive epidural abscess. The patient improved on meropenem and metronidazole and was warfarinised for his cavernous sinus thrombosis. He has an on-going left-sided hypoglossal (XIIth) nerve palsy.

Importance of blood cultures to aid the diagnosis of Lemierre's syndrome.

This is a case report of Lemierre's syndrome, a septic thrombophlebitis of the internal jugular vein (IJV) usually preceded by pharyngitis and bacteraemia with an anaerobic organism. Fusobacterium necrophorum is ananaerobic Gram-negative bacillus and is the most common organism reported to cause Lemierre's syndrome which usually occurs one to three weeks post pharyngitis or oropharyngeal surgery. A 21-year-old patient presented with signs of sepsis and a history of sore throat, fever, and tender cervical lymph nodes. Blood cultures grew F. necrophorum and Computed Tomography (CT) showed a filling defect in the left retromandibular vein and thrombosis in the left internal jugular vein (IJV) consistent with Lemierre's syndrome. This is an uncommon condition which normally occurs in young individuals and diagnosis is often delayed.

Cell Based Drug Delivery: Micrococcus luteus Loaded Neutrophils as Chlorhexidine Delivery Vehicles in a Mouse Model of Liver Abscesses in Cattle.

The recent WHO report on antibiotic resistances shows a dramatic increase of microbial resistance against antibiotics. With only a few new antibiotics in the pipeline, a different drug delivery approach is urgently needed. We have obtained evidence demonstrating the effectiveness of a cell based drug delivery system that utilizes the innate immune system as targeting carrier for antibacterial drugs. In this study we show the efficient loading of neutrophil granulocytes with chlorhexidine and the complete killing of E. coli as well as Fusobacterium necrophorum in in-vitro studies. Fusobacterium necrophorum causes hepatic abscesses in cattle fed high grain diets. We also show in a mouse model that this delivery system targets infections of F. necrophorum in the liver and reduces the bacterial burden by an order of magnitude from approximately 2•106 to 1•105.

Lemierre syndrome associated with 12th cranial nerve palsy--a case report and review.

Since the widespread availability and use of antibiotics the prevalence of Lemierre syndrome (L.S.) has decreased. It is a well-described entity, consisting of postanginal septicaemia with thrombophlebitis of the internal jugular vein with metastatic infection, most commonly in the lungs. The most common causative agent is a gram-negative, non-spore-forming obligate anaerobic bacterium, Fusobacterium necrophorum (F.n.). We describe the unusual clinical features of a 12-year-old boy with Lemierre syndrome with isolated hypoglossal nerve palsy - the latter symptom is an extremely rare manifestation of this disease.

Impact of systemic antimicrobials combined with anti-infective mechanical debridement on the microbiota of generalized aggressive periodontitis: a 6-month RCT.

AIM: To compare the effects of systemic amoxicillin (AMX) plus metronidazole (MET) or placebos combined with anti-infective mechanical debridement on the sub-gingival microbiota of generalized aggressive periodontitis (GAP). MATERIAL AND METHODS: The study was a 6-month randomized, double-blinded, placebo-controlled clinical trial. Thirty-one subjects received full-mouth ultrasonic debridement followed by scaling and root planing with chlorhexidine rinsing, brushing and irrigation. During mechanical therapy, subjects received systemic AMX (500mg)+MET (250mg) or placebo, t.i.d. for 10 days. Sub-gingival samples were obtained from each patient and analysed for their composition by checkerboard at baseline, 3 and 6 months post-therapy. Significant differences between groups over time were examined by General Linear Model of Repeated Measures. RESULTS: High levels of periodontal pathogens, as well as some "non-periodontal" species were observed. Most of the periodontal pathogens decreased significantly over time (p<0.05), whereas "non-periodontal" bacteria tended to increase in both groups. Sites that showed attachment loss and probing depth increase harboured higher levels of Dialister pneumosintes, Campylobacter rectus, Fusobacterium necrophorum, Prevotella tannerea and Peptostreptococcus anaerobius than sites that improved after both therapies (p<0.05). CONCLUSIONS: Systemic AMX+MET or placebos adjunctive to anti-infective mechanical debridement were comparable in lowering periodontal pathogens up to 6 months after treatment. Species not commonly associated with GAP were less affected by both therapies.