Changes in Penile Microbiome Following Pediatric Circumcision

 Mishra and colleges from several medical centers in the USA, Italy and India studied the characterization of Changes in Penile Microbiome Following Pediatric Circumcision. While microbiome and host regulation contribute independently to many disease states, it is unclear how circumcision in pediatric population influences subsequent changes in penile microbiome.

They analyzed 11 paired samples, periurethral collection, before and after circumcision, to generate microbiome and mycobiome profiling. Sample preparation of 16S ribosomal RNA and internal transcribed spacer sequencing was adapted from the methods developed by the National Institutes of Health Human Microbiome Project.

Several notable microbiome and mycobiome compositional differences were observed between pre- and postcircumcision patients. Pairwise comparisons across taxa revealed a significant decrease (p < 0.05, false discovery rate corrected) of microbiome organisms (Clostridiales, Bacteroidales, and Campylobacterales) and mycobiome (Saccharomycetales and Pleosporales) following circumcision. A total of 14 pathways were found to differ in abundance between the pre- and postcircumcision groups (p < 0.005, false discovery rate <0.1 and linear discriminant analysis score >3; five enriched and nine depleted). The pathways reduced after circumcision were mostly involved with amino acid and glucose metabolism, while pathways prior to circumcision were enriched in genetic information processing and transcription processes. 

The study found that bacteria and fungi involved in chronic inflammation appear to be more prevalent in uncircumcised boys. The investigators concluded that circumcision may reduce the risk of chronic inflammation of the penis later in life.

The study was published in European Urology Focus on December  2022. https://pubmed.ncbi.nlm.nih.gov/36566099/

 

Anti-anaerobic antibacterials may increase risk of adverse clinical outcomes in critically ill patients

 

Critically ill patients routinely receive antibiotics with activity against anaerobic gut bacteria. Yet in other disease states and animal models, gut anaerobes are protective against pneumonia, organ failure, and mortality.

Rishi Chanderraj et al. from the University of Michigan Medical School, Ann Arbor, MI; designed a translational series of analyses and experiments to determine the effects of anti-anaerobic antibiotics on the risk of adverse clinical outcomes among critically ill patients. Their finding were published in the Eur Respir J in October 2022. 

The authors conducted a retrospective single-center cohort study of 3032 critically ill patients, comparing patients who did and did not receive early anti-anaerobic antibiotics. The investigators retrospectively compared ICU outcomes (ventilator-associated pneumonia-free survival, infection-free survival, overall survival) in all patients, and changes in gut microbiota in a 116-patient subcohort. They also studied in murine models, the effects of anaerobe depletion in infectious (K. pneumoniae and S. aureus pneumonia) and noninfectious (hyperoxia) injury models.

The investigators found that early administration of anti-anaerobic antibiotics was associated with decreased VAP-free survival, infection-free survival, and overall survival. Patients who received anti-anaerobic antibiotics had decreased initial gut bacterial density (p=0.00038), increased microbiome expansion during hospitalization (p=0.011), and domination by Enterobacteriaceae spp. (p=0.045). Enterobacteriaceae were also enriched among respiratory pathogens in anti-anaerobic treated patients. In murine models, treatment with anti-anaerobic antibiotics increased susceptibility to Enterobacteriaceae pneumonia (p<0.05) and increased the lethality of hyperoxia (p=0.0002).

The investigators concluded that in critically ill patients, early treatment with anti-anaerobic antibiotics is associated with increased mortality. Mechanisms may include enrichment of the gut with respiratory pathogens, but increased mortality is incompletely explained by infections alone. Given consistent clinical and experimental evidence of harm, the widespread use of anti-anaerobic antibiotics should be reconsidered. Since the current study was retrospective, prospective studies are warranted to further evaluate this issue.

Oral Microbiome and SARS-CoV-2: Beware of Lung Co-infection

 

Bao et al. Sichuan University, Chengdu, China; presented a  review on the role of the oral microbiome in the current global pandemic.

The new coronavirus SARS-CoV-2, the cause of COVID-19, has become a public health emergency of global concern. Like the SARS and influenza pandemics, there have been a large number of cases coinfected with other viruses, fungi, and bacteria, some of which originate from the oral cavity. Capnocytophaga, Veillonella, and other oral opportunistic pathogens were found in the BALF of the COVID-19 patients by mNGS. Risk factors such as poor oral hygiene, cough, increased inhalation under normal or abnormal conditions, and mechanical ventilation provide a pathway for oral microorganisms to enter the lower respiratory tract and thus cause respiratory disease. Lung hypoxia, typical symptoms of COVID-19, would favor the growth of anaerobes and facultative anaerobes originating from the oral microbiota. SARS-CoV-2 may aggravate lung disease by interacting with the lung or oral microbiota via mechanisms involving changes in cytokines, T cell responses, and the effects of host conditions such as aging and the oral microbiome changes due to systemic diseases. Because the oral microbiome is closely associated with SARS-CoV-2 co-infections in the lungs, effective oral health care measures are necessary to reduce these infections, especially in severe COVID-19 patients. 

Porphyromonas pasteri and Prevotella nanceiensis in the sputum are associated with increased decline in lung function in individuals with cystic fibrosis

 

The role of anaerobic bacteria  in disease progression in cystic fibrosis (CF) was studied by Webb et al. from UnitedKingdom.  The authors hypothesized that the presence and relative abundance of the most prevalent, live, anaerobic bacteria in sputum of adults with CF were associated with adverse clinical outcomes.

The investigators performed 16S rRNA analysis using a viability quantitative PCR technique on sputum samples obtained from a prospective cohort of 70 adults with CF and collected clinical data over an 8 year follow-up period. They examined the associations of the ten most abundant obligate anaerobic bacteria present in the sputum with annual rate of FEV1 change. The presence of Porphyromonas pasteri and Prevotella nanceiensis were associated with a greater annual rate of FEV1 change. Similarly, the relative abundance of these live organisms were associated with a greater annual rate of FEV1 decline of -3.7 ml yr-1 and -5.3 ml yr-1  for each log 2 increment of abundance, respectively.

The authors concluded that the presence and relative abundance of certain anaerobes in the sputum of adults with CF are associated with a greater rate of long-term lung function decline.

Diagnosis of orthopaedic-implant-associated infections caused by slow-growing Gram-positive anaerobed

 Slow-growing Gram-positive anaerobic bacteria (SGAB) such as Cutibacterium acnes are increasingly recognized as causative agents of implant-associated infections (IAIs) in orthopaedic surgeries. SGAB IAIs are difficult to diagnose because of their non-specific clinical and laboratory findings as well as the fastidious growth conditions required by these bacteria. A high degree of clinical suspicion and awareness of the various available diagnostic methods is therefore important. A review by Ponraj et al.  overviews the current knowledge regarding SGAB IAI, providing details about clinical features and available diagnostic methodologies. In recent years, new methods for the diagnosis of IAI were developed, but there is limited knowledge about their usefulness in SGAB IAI. The authors conclude that further studies are required to determine the ideal diagnostic methodology to identify these infections so that they are not overlooked and mistakenly classified as aseptic failure.

                                                   Cutibacterium acnes gram stain

Complications of Otitis Media and Sinusitis Caused by Streptococcus anginosus Group Organisms in Children.

McNeil et al. from Texas Children'sHospital studied 95 children seen between 2011 to 2018 with complications of otitis media and sinusitis caused by Streptococcus anginosus Group (SAG) organisms.  SAG are nonmotile facultative anaerobes that are part of the normal oral cavity, throat, stool, and vagina flora. Cases included were those with Pott's puffy tumor, orbital abscesses, mastoiditis, epidural abscesses, subdural empyema, brain parenchymal abscesses or dural enhancement by imaging.

Streptococcus intermedius was most commonly isolated (80%) followed by Streptococcus constellatus (12.6%) and Streptococcus anginosus (7.4%); 50.5% of cases were polymicrobial. Among polymicrobial cases, Staphylococcus aureus was most frequently isolated. All patients underwent surgical intervention and 8.4% had persistent neurologic deficits. Complications of otitis media and sinusitis caused by SAG are associated with substantial morbidity.

The researchers concluded that intraorbital and intracranial infections in general and SAG in particular are becoming increasingly common at their medical center.

Streptococcus anginosus (Gram stain)

Increased Antimicrobial Resistance against metronidazole and carbapenem in clinical anaerobic isolates from Pakistan.

Increased Antimicrobial Resistance against metronidazole and carbapenem in clinical anaerobic isolates from Pakistan was recently reported by reported by Shafquat and colleagues  from , Aga Khan University Hospital,in Karachi, Pakistan.

 Of the 223 clinically significant isolates collected between 2014 and 2017, 39 (17.5%) were metronidazole resistant. Imipenem resistance was determined in 29 metronidazole resistant isolates and of these 7 (24.1%) were found to be resistant. Proportion of metronidazole resistant strains was highest amongst Bacteroides species. A significant increase in metronidazole resistance from 12.3% in 2010-2011 to 17.5% in the current study was found. Carbapenem resistance also emerged in the period 2014-2017.

Isolates from malignancy and transplant patients showed lower odds of developing metronidazole resistance. Prolonged hospital stay was not associated with metronidazole resistance.

The worldwide rising trend of metronidazole resistance and emergence of carbapenem resistance in anaerobic bacteria is alarming. Continued surveillance with strengthening of laboratory capacity regarding anaerobic susceptibility testing is urgently needed.

Establishing the bacterial etiology of necrotizing soft tissue infections using 16S sequencing detection

Necrotizing soft tissue infections (NSTIs) are the most severe and rapidly progressing class of skin and soft tissue infections (SSTIs). They are a surgical emergency and are associated with high mortality and morbidity. While NSTIs remain relatively rare, their incidence is steadily rising.

Earlier diagnosis and more focused antibiotic treatments can potentially improve patient outcome, but both of these solutions require a more accurate understanding of the microbial component of these infections.

Streptococcus and Staphylococcus species, especially S. aureus, are most commonly aerobic isolates and Clostridium spp. (C.perfringens and C. septicum) and Bacteroides fragilis group are the commonest anaerobes detected. Clostridium spp. are often found in monomicrobial infections and are associated with mortality rates greater than 50%. Certain gram negative rods, including Escherichia coli and Pseudomonas species, are also found,

While molecular detection methods, namely 16S sequencing, have not been traditionally used to identify the causative microorganisms in NSTIs, they are becoming more commonplace as a diagnostic tool for other types of SSTIs, especially for chronic wound infections. In chronic wound infections, 16S sequencing has revealed a higher than previously detected prevalence of obligate anaerobes. The use of 16S sequencing may lead to the detection of a higher than expected proportion of obligate anaerobes in NSTIs and consequently improve the care of patients with NSTIs.

Necrotizing fasciitis 

Impact of Inappropriate Therapy on Mortality associated with Anaerobic Bacteremia.

Kim et al. analyzed the incidence and risk factors related to mortality and assess clinical outcomes of anaerobic bacteremia during 2012 in Yonsei University Hospital, Seoul, Korea.

A total of 70 anaerobic bacteria were isolated from blood of 70 bacteremia patients. The history of cardiovascular disease as host's risk factor was statistically significant. The incidence of anaerobic bacteremia in was 2.3% per 100 positive blood culture patients, and the mortality rate in patients with clinically significant anaerobic bacteremia was 21.4%. anaerobic bacteremia was frequently noted in patients with malignancy.

The survival rate of bacteremia was significantly worse in patients who had inappropriate therapy compared with those underwent appropriate therapy. The most frequently isolated organism was Bacteroides fragilis (32 isolates, 46%), Bacteroides thetaiotaomicron (10, 14%), and non-perfringens Clostridium (7, 10%).

Non-surgical circumcisions with low risk of infection approved by WHO used to reduces HIV in Africa

The World Health Organization (WHO) approved expanded use of an Israeli developed device that allows medical workers to perform “painless circumcisions.” The PrePex device, created by Israel-based Circ MedTech, will be granted WHO prequalification on May 31 for use with males age 13 and above in 14 African countries.

Circumcision is one of the most effective ways to prevent the spread of AIDS – which affects nearly 30 million in Africa. Research and experience shows that male circumcision, when safely provided by well-trained health professionals, reduces the risk of heterosexually acquired HIV infection in men by approximately 60%. Circumcision can therefore play an important role in preventing the spread of HIV. Persuading adult to undergo circumcision is difficult mostly because it is painful. Furthermore surgical circumcision is done in a hospital or specialized clinic which are not available in the countryside.

PrePex which is produced by Circ Medtech is the first and so far only nonsurgical male circumcision device. Using the device does not require injected anesthesia, surgery, sutures, or sterile settings. The device, consisting of plastic and rubber rings that are placed on the penis and uses pressure to separate the foreskin from the head of the penis. The elastic pressure ring is applied to the foreskin, cutting off distal blood flow. The placement of PrePex band completely separate the foreskin from the glands penis. It causes death of all human cells within the foreskin preventing the spread of bacterial toxin or bacterial infection from the necrotic foreskin. After a week, the foreskin falls off, and the wound is treated with a salve.

PrePex Non Surgical Male Circumcision Procedure video

PrePex was found in studies conducted in association with the WHO to be safe and effective when performed by physicians and nurses, offering a virtually bloodless procedure that requires no injection of anesthesia, no knives, no sutures, and can be performed in a non-sterile environment. To date, more than 125,000 PrePex procedures have been conducted in 12 countries: Botswana, Kenya, Lesotho, Malawi, Rwanda, South Africa, Swaziland, Tanzania, Uganda, Zambia, Zimbabwe and Indonesia. More than 11 national Training Centers are located across Africa, training local healthcare professionals.

         PrePex Non Surgical Male Circumcision

Treating appendicitis with antibiotics

Surgical removal of the inflamed appendix has been the standard of care for over a 120 years.  More than 300,000 appendectomies are performed annually in the United States.  Even though appendectomy is generally well tolerated, it is a major surgical procedure and can be associated with postoperative morbidity.

A recent study by Salminen et al.  from Turku University Hospital in Finland found that three of four patients with appendicitis treated with antibiotics did not need to have their appendix surgically removed. Those who eventually needed the surgery were not harmed by postponing the procedure as there were no intra-abdominal abscesses or other major complications associated with delayed appendectomy.

The study illustrated that emergency appendectomy is only indicated in those with CT-proven complicated appendicitis that can cause the appendix to rupture, which make only about one in five of patients. In contrast, those with CT- proven uncomplicated appendicitis can be treated with antibiotics.

The investigator randomly assigned 273 patients with acute appendicitis to appendectomy and 256 to a 10-day course of antibiotics. Appendectomies were successful in all but one of 273 (0.4%) patients. Among 256 patients treated with antibiotics and followed for a year, 186 (73%) did not require surgery. However, 70 (27%) percent of the patients treated with antibiotics had to have their appendix removed within a year after treatment. No patient in the antibiotic group developed a serious infection resulting from delayed appendectomy, suggesting that the decision to delay appendectomy for uncomplicated acute appendicitis can be made with low likelihood of major complications resulting from delayed surgery.

These findings suggest that for CT-diagnosed uncomplicated appendicitis, an initial trial of antibiotics is reasonable followed by elective appendectomy for patients who do not improve with antibiotics or present with recurrent appendicitis. Because patients with complicated appendicitis, with appendicoliths, children, and pregnant women were excluded from this study, the results do not apply to these groups.

Future studies are warranted that should focus both on early identification of complicated acute appendicitis patients needing surgery and to prospectively evaluate the optimal use of antibiotic treatment in patients with uncomplicated acute appendicitis.

The pitfalls of antibiotic treatment should also be addressed in future studies. Broad spectrum antibiotics can promote the emergence resistant organisms as well as Clostridium difficile infections. These potential adverse effects may tilt the balance towards performing appendectomy.

Furthermore, inclusion of greater number of patients is required in future studies to evaluate the ability of antibiotics to prevent pelvic abscesses as effectively as surgery.

These study has highlighted the need consider discarding routine appendectomy for patients with uncomplicated appendicitis. Because of the availability of precise diagnostic capabilities like CT and effective broad-spectrum antibiotics, appendectomy may be unnecessary for uncomplicated appendicitis.

                                             

 

Alzheimer's disease and periodontists. Is there a connection?

Alzheimer's disease (AD) is a neurodegenerative disease which increases with age and is characterized by the salient inflammatory features, microglial activation, and increased levels of pro nflammatory cytokines which contribute to the inflammatory status of the central nervous system (CNS).Elevated blood inflammatory markers predict risk for dementia and incidence of cognitive impairment. Periodontitis is also considered to be one of the probable risk factors for AD.

Twomechanisms have been postulated to explain the association of periodontitis and AD. The first mechanism is due to the generation of a state of systemic/peripheral inflammation due to an increase in the levels of pro inflammatory cytokines, periodontopathic microorganisms and the host response cause. These pro inflammatory molecules are capable of compromising the blood brain barrier and enter the cerebral regions. This leads to priming/activation of microglial cells and the adverse repercussions leading to neuronal damage.

The second mechanism is thought to be due to direct invasion of brain by microorganisms present in the dental plaque biofilm. The brain is accessed either through the blood stream or via peripheral nerves. These microorganisms and their products elicit an inflammatory mechanism within the CNS resulting in cognitive impairment, such as that seen in AD. This inflammatory impairment is attributed to cytokine arbitrated interactions between neurons and glial cells.

The role of anti-inflammatory agents has been studied in the AD  Anti-inflammatory Prevention Trial  and hypothesized that the beneficial effect of anti-inflammatory drugs is evident only in the early, asymptomatic, phases of the disease.

Since periodontitis has a tendency to infiltrate the systemic circulation with inflammatory mediators and result in systemic disease outcome; thus, it would always be advisable and better option to prevent periodontal disease progression to prevent further systemic outcomes.

Inflammation could serve as a connecting link between periodontitis and AD. Further research including animal studies are warranted to explore the relationship between AD and periodontitis.

Gut bacteria effect on brain function: Can probiotics help depression and anxiety?

Emerging studies have suggested that pathogenic and non-pathogenic gut bacteria might influence mood-related symptoms and even behavior in animals and humans. Recent studies illustrated  that gastrointestinal pathogens can communicate with the central nervous system and influence behavior associated with emotion, anxiety in particular, even at extremely low levels and in the absence of an immune response. Investigators have also shown that the administration of certain probiotic bacteria may support resilience and positively alter stress-related emotional behavior in animals under experimental stress. These probiotics organisms have the potential to influence mood-regulating systemic inflammatory cytokines, decrease oxidative stress and improve nutritional status when orally consumed

Patients with chronic fatigue syndrome (CFS) and other functional somatic disorders have alterations in the intestinal microbial flora. A recent study evaluated the effect of probiotic on the emotional symptoms of 39 patients with CFS. The patients were randomized to receive either 24 billion colony forming units of Lactobacillus casei strain Shirota (LcS) or a placebo daily for two months.  A significant rise in both Lactobacillus and Bifidobacteria in those taking the LcS, and there was also a significant decrease in anxiety symptoms among those taking the probiotic vs controls (p = 0.01). These results provide support to the presence of a gut-brain interface that may be mediated by microbes that reside or pass through the intestinal tract.

This preliminary research suggest the possibility that probiotics might influence anxiety and depression. The results of the present study should be a stimulus for further research about the utility of probiotics and their effects on anxiety and depression.

Autism and gastrointestinal bacteria connection

Autism spectrum disorders (ASD) are neurodevelopmental disorders,  characterized by difficulties in social interactions, verbal and non-verbal communication, and stereotypic or repetitive behaviors.  Gastrointestinal (GI) distress is common in children with ASD and include,  abdominal pain, bloating, diarrhea and constipation. The high frequencies of these GI symptoms could be due to abnormal GI bacterial flora in individuals with ASD. The GI bacterial flora  are important for nutrition and metabolic processes and growing evidence suggest that they play a role in brain development, behavior, and gene expression via neural, endocrine, and immune pathways. Emerging research on the gut-microbiome-brain connection in both mice and humans has shed new light on the pathogenesis of various neurological diseases including ASD.

A total of 15 cross-sectional studies, with a combined sample of 562 individuals reported significant differences in the prevalence of GI bacteria between ASD children and controls, in some bacteria in the Firmicutes  (including Clostridium spp. ), Bacteroidetes  and Proteobacteria phyla. The level of the probiotic Bifidobacterium  spp. was lower in children with ASD than in controls. Some studies found an association between the severity of GI symptoms and the severity of autism.

Future research should explore whether administration of probiotic bacteria, and or antimicrobials could restore normal gut microbiota, reduce inflammation, restore epithelial barrier function, and potentially ameliorate behavioral symptoms associated with some children with ASD.

Is Fusobacterium associated with colon cancer?

Numerous cancers have been linked to microorganisms. Warren et al. from British Columbia Cancer Agency, Vancouver, Canada; investigated the relationship between gut mucosal microbiome and colorectal cancer using genetic methods. The investigation revealed an association between Fusobacterium species and colorectal carcinoma in eleven patients. These investigators have extended their studies with deeper sequencing of a much larger number (n = 130) of colorectal carcinoma and matched normal control tissues.

The new report has revealed differently abundant microbial genome sequence signatures of significance in tumor samples, including those belonging to the Fusobacterium, Campylobacter and Leptotrichia genera. These Gram-negative anaerobes are typically considered to be oral bacteria. However, tumor isolates for Fusobacterium and Campylobacter were genetically diverged from their oral counterparts and carry potential virulence genes. They also observed that sequence signatures from Fusobacterium co-occur with those from Leptotrichia and Campylobacter and that Fusobacterium and Campylobacter strains isolated from tumor tissue co-adhere in culture. A non-invasive assay to detect this polymicrobial signature of colorectal carcinoma may have utility in screening and risk assessment.

It remains unknown whether there is any etiological link between microorganisms and colorectal carcinoma. Any such link could provide a potential mode of intervention in the prevention of colonic cancer.

Fusobacterium necrophorum Gram stain

Propionibacterium acnes, an emerging pathogen: From acne to implant-infections

Propionibacterium acnes is a colonizer of the lipid-rich sebaceous glands of the skin. The pathogenicity of P. acnes has long been restricted to skin conditions. Its isolation from other anatomical sites or deep microbiological samples has often been considered as contamination. It is involved in the inflammation process of acne is well known, but until recently, it was neglected in other clinical presentations. P. acnes  has been considered to be of low virulence, but the new genomic, transcriptomic, and phylogenetic studies have allowed better understanding of this potential pathogen's importance in causing many chronic and recurrent infections, including orthopedic ( osteo-articular and spine )  and cardiac prosthetic, and breast or eye implant-infections, and neurosurgical infections of external ventricular shunts.

Hip Joint implant

These infections, are facilitated by the ability of P. acnes to produce a biofilm, requiring using anti-biofilm active antibiotics such as rifampicin. However, in the last 10 years, the rate of antibiotic-resistant bacteria has increased, especially for macrolides and tetracyclines. The antimicrobial susceptibility of P. acnes is not routinely performed in microbiology laboratories because of its susceptibility to a wide range of antibiotics.

Some antibiotics should be tested to adapt treatment because of the prevalence of antibiotic resistance in P. acnes: tetracycline, erythromycin, clindamycin, and cotrimoxazole. Furthermore, other antibiotics should be tested for severe infections, to optimize treatment and obtain a synergistic effect against P. acnes: penicillin, cephalosporins, vancomycin, quinolones, rifampicin, and the “new” antibiotics such as linezolid, daptomycin, and tigecycline, to which P. acnes is usually susceptible. Aminoglycosides and metronidazole are not active against P. acnes.

The treatment of severe infections caused by P. acnes includes a combination of antibiotics, administrated intravenously initially, and usually associated with optimal surgery (e.g., removal of the device and/or debridement of the surgical site). Penicillin G and ceftriaxone are still considered as first-line antibiotics for severe infections. Clindamycin, tetracycline, and levofloxacin are alternatives in those allergic to beta-lactams. Rifampicin and daptomycin are also active antimicrobial agents, effective also against P. acnes biofilm. Removal of the device associated with the infection is usually sufficient to reduce the inoculum causing chronic infection.

Gram stain of Propionibacterium acnes

Periodontal pathogens ( Porphyromonas gingivalis and Fusobacterium nucleatum) may promoting oral cancer ( Kaposi's sarcoma)

Kaposi's sarcoma  (KS) is a tumor caused by human herpesvirus 8 (HHV8, also known as Kaposi's sarcoma-associated herpesvirus, KSHV).  About 20% of HIV patients develop Kaposi's sarcoma (KS) lesions in the oral cavity while other patients never develop oral KS. It is not known if the oral micro environment plays a role in oral KS tumor development.

Xiaolan and colleagues from Case Western Reserve University, Cleveland, Ohio demonstrated that a group of metabolic by-products (short chain fatty acids), from bacteria that cause periodontal disease (Porphyromonas gingivalis and Fusobacterium nucleatum) promote lytic replication of KSHV. These new findings provide mechanistic support that periodontal pathogens create a unique micro environment in the oral cavity that contributes to KSHV replication and development of oral KS. However, more research is needed to find out if patients with KS suffer more often from periodontal disease and exhibit higher levels short chain fatty acids produced by the periodontal pathogens.

oral cavity Kaposi's sarcoma

Fecal transplants for the treatment of recurrent Clostridium difficile infection

Recurrent Clostridium difficile infection is difficult to treat, and failure rates for antibiotic therapy are high. Fecal microbiota transplantation has been shown to be a superior therapeutic modality for the treatment of recurrent C. difficile infection (RCDI) and disease is fecal transplantation. A recent review of 317 patients from 27 case-report series concluded that fecal transplantation was highly effective and resulted in disease resolution in 92% of patients involved in the study.

Van Nood and colleagues provided the first controlled study of treating RCDI with fecal transplantation. In an open-label, non-blinded manner, 43 adult patients were randomly assigned to oral vancomycin, oral vancomycin plus bowel lavage or vancomycin plus bowel lavage followed by fecal transplantation by nasoduodenal tube. Of the patients in the randomized group to receive fecal transplantation from a donor, clinical disease resolved in 81% (13/16) after the first infusion. An additional infusion from a different donor resulted in resolution in two additional patients. Of the control groups, clinical resolution occurred in 31% (4/13) of patients who received vancomycin alone, and in 23% (3/13) of those who received vancomycin plus bowel lavage.

Fecal transplantation appears to be a promising therapy for RCDI, but important unkowns exist. These include the most effective dose, method of preparation, route of administration, and the safety of using donor samples. With the publication of one controlled trial, more data are needed to address these concerns. 

Multidrug-Resistant Bacteroides fragilis isolated in the US

B. fragilis strains, especially in the US, are virtually always susceptible to metronidazole, carbapenems, and beta-lactam antibiotics. Although isolated cases of resistance to single agents have been reported, multidrug-resistant (MDR) B. fragilis strains are exceptionally rare. In May 2013, an MDR B. fragilis strain was isolated from the bloodstream and intra-abdominal abscesses of a patient who had recently received health care in India. The organism was resistant to metronidazole, imipenem, piperacillin/tazobactam, clindamycin, tcefotetan, ampicillin/sulbactam, and moxifloxacin. It was susceptible to minocycline, linezolid, and tigecycline. He was successfully treated with linezolid and ertapenem. This is only the second published case of MDR B. fragilis in the US.

Although B. fragilis has long been considered reliably susceptible to a number of broad-spectrum anti-anaerobic drugs, this case and others like it suggest clinicians should no longer rely on cumulative susceptibility data from surveys alone to direct treatment and should consider requesting susceptibility testing when treating serious infections caused by B. fraglis. They also underscore the need for improved antibiotic stewardship. 

American Surgical Society and American Society of Infectious Diseases guidelines for the treatment of abdominal infection.

In 2010 the American Surgical Society and American Society of Infectious Diseases have updated their guidelines for the treatment of abdominal infection.

The recommendations suggest the following:

For mild-to-moderate community-acquired infections in adults, the agents recommended for empiric regimens are: ticarcillin- clavulanate, cefoxitin, ertapenem, moxifloxacin, or tigecycline as single-agent therapy or combinations of metronidazole with cefazolin, cefuroxime, ceftriaxone, cefotaxime, levofloxacin, or ciprofloxacin. Agents no longer recommended are: cefotetan and clindamycin ( Bacteroides fragilis group resistance) and ampicillin-sulbactam (E. coli resistance) and aminoglycosides (toxicity).

 For high risk community-acquired infections in adults, the agents recommended for empiric regimens are: meropenem, imipenem-cilastatin, doripenem, piperacillin-tazobactam, ciprofloxacin or levofloxacin in combination with metronidazole, or ceftazidime or cefepime in combination with metronidazole. Quinolones should not be used unless hospital surveys indicate >90% susceptibility of E. coli to quinolones.

Aztreonam plus metronidazole is an alternative, but addition of an agent effective against gram-positive cocci is recommended. The routine use of an aminoglycoside or another second agent effective against gram-negative facultative and aerobic bacilli is not recommended in the absence of evidence that the infection is caused by resistant organisms that require such therapy.

Empiric use of agents effective against enterococci is recommended and agents effective against methicillin-resistant S. aureus (MRSA) or yeast is not recommended in the absence of evidence of infection due to such organisms.

Empiric antibiotic therapy for health care-associated intra-abdominal infection should be driven by local microbiologic results. Empiric coverage of likely pathogens may require multidrug regimens that include agents with expanded spectra of activity against gram-negative aerobic and facultative bacilli. These include meropenem, imipenem-cilastatin, doripenem, piperacillin-tazobactam, or ceftazidime or cefepime in combination with metronidazole. Aminoglycosides or colistin may be required.

Antimicrobial regimens for children include an aminoglycoside-based regimen, a carbapenem (imipenem, meropenem, or ertapenem), a beta-lactam/beta-lactamase-inhibitor combination (piperacillin-tazobactam or ticarcillin-clavulanate), or an advanced-generation cephalosporin (cefotaxime, ceftriaxone, ceftazidime, or cefepime) with metronidazole.

Infectious Diseases Society of America guideline for the diagnosis and treatment of diabetic foot infections.

Foot infections are a frequent and serious problem in individuals with diabetes. The Infectious Diseases Society of America recently published clinical practice guideline for the diagnosis and treatment of diabetic foot infections.  Diabetic foot infections (DFIs) usually starts as a wound, most often a neuropathic ulceration. While all wounds are colonized with microorganisms, the presence of infection is defined by ≥2 classic findings of inflammation or purulence.
Infections are then classified into:

·       Mild (superficial and limited in size and depth).

·       Moderate (deeper or more extensive).

·       Severe (accompanied by systemic signs or metabolic perturbations).

This classification system, along with a vascular assessment, helps determine which patients should be hospitalized, which may require special imaging procedures or surgical interventions, and which will require amputation.
Most DFIs are polymicrobial infections caused by aerobic gram-positive cocci (GPC), and especially staphylococci, the most common causative organisms. Aerobic gram-negative bacilli are frequently copathogens in infections that are chronic or follow antibiotic treatment, and obligate anaerobes may be copathogens in ischemic or necrotic wounds.
The Guidelines stat that wounds without evidence of soft tissue or bone infection do not require antibiotic therapy. For infected wounds, they suggest obtaining a post-debridement specimen (preferably of tissue) for aerobic and anaerobic culture. Empiric antibiotic therapy can be narrowly targeted at GPC in many acutely infected patients, but those at risk for infection with antibiotic-resistant organisms or with chronic, previously treated, or severe infections usually require broader spectrum regimens.
According to the Guidelines imaging is helpful in most DFIs; plain radiographs may be sufficient, but magnetic resonance imaging is far more sensitive and specific. Osteomyelitis occurs in many diabetic patients with a foot wound and can be difficult to diagnose (optimally defined by bone culture and histology) and treat (often requiring surgical debridement or resection, and/or prolonged antibiotic therapy).
It is recommended that in most DFIs some surgical intervention, ranging from minor (debridement) to major (resection, amputation) is performed. Wounds must also be properly dressed and off-loaded of pressure, and patients need regular follow-up. An ischemic foot may require revascularization, and some nonresponding patients may benefit from selected adjunctive measures. Employing multidisciplinary foot teams improves outcomes. The guidelines encouraged clinicians and healthcare organizations to monitor, and thereby improve, the outcomes and processes in caring for DFIs.

Diabetic foot ulcer

Clostridial Spores for Cancer Therapy

Solid tumor accounts for 90% of all cancers. The current treatment approach for most solid tumors is surgery; however it is limited to early stage tumors. Other treatment options such as chemotherapy and radiotherapy are non-selective, thus causing damage to both healthy and cancerous tissue.

Recent research has shifted towards understanding the tumor microenvironment and it's differences from that of healthy cells/tissues in the body and then to exploit these differences for treatment of the tumor. One such approach is utilizing anaerobic bacteria. Several strains of bacteria have been shown to selectively colonize in solid tumors, making them valuable tools for selective tumor targeting and destruction.

Clostridium-based cancer therapy is a promising approach for the treatment of solid tumours. Bacterial-based cancer therapy using Clostridium spp. offers a selective advantage in overcoming the obstacles of hypoxia and necrosis. Clostridium spp., being strictly anaerobic will only colonize in areas devoid of oxygen, and when systematically injected, spores germinate and multiply in the hypoxic/necrotic areas of solid tumors. Clostridium, although anaerobic, possesses the ability to sporulate, allowing them to remain dormant in environments where oxygen is present. However, when growth conditions are suitable (i.e., in the hypoxic/necrotic milieu of solid tumors), the Clostridium spores germinate and begin to colonize these areas. This aspect of Clostridium growth is being exploited for use in a number of various novel cancer treatment strategies currently being developed which utilize Clostridium as a vector to deliver therapeutics directly to the solid tumor site. Clostridial vectors can be safely administered as spores, and their efficacy in delivering and secreting therapeutic proteins has been demonstrated in a number of preclinical trials.

Clostridium spp. with spore formation.