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