What are the most effective antibiotics for treating C. difficile infection. How do different antibiotics impact gut microbiota during C. diff treatment. Which antibiotic treatments show the best outcomes for preventing C. diff recurrence. What are the latest research findings on antibiotic therapies for C. difficile.

Understanding C. Difficile Infection and Its Treatment Challenges

Clostridium difficile (C. diff) infection is a serious and potentially life-threatening condition that affects the gastrointestinal tract. It often occurs as a result of antibiotic use, which disrupts the normal balance of gut bacteria. Ironically, while antibiotics can trigger C. diff infection, they are also the primary treatment for this condition. However, choosing the right antibiotic is crucial for effective treatment and preventing recurrence.

Why is treating C. diff infection challenging? The main difficulty lies in the fact that C. diff is a spore-forming bacterium, which means it can persist in the environment and resist many standard antibiotics. Additionally, the use of broad-spectrum antibiotics can further disrupt the gut microbiome, potentially exacerbating the condition or increasing the risk of recurrence.

First-Line Antibiotic Treatments for C. Difficile Infection

When it comes to treating C. difficile infection, several antibiotics have proven effective. The choice of antibiotic often depends on the severity of the infection and whether it’s a first occurrence or a recurrence.

Vancomycin: A Powerful Weapon Against C. Diff

Vancomycin is widely considered one of the most effective antibiotics for treating C. difficile infection. How does vancomycin work against C. diff? It targets the cell wall of the bacteria, preventing them from reproducing and ultimately killing them. Vancomycin is particularly effective because it’s poorly absorbed in the gut, allowing it to concentrate where it’s needed most.

Metronidazole: An Alternative for Mild Cases

For mild to moderate cases of C. diff infection, metronidazole has been a long-standing treatment option. It works by disrupting the DNA of the bacteria. However, recent studies have shown that vancomycin may be more effective than metronidazole, even in milder cases.

Fidaxomicin: A Newer, Targeted Approach

Fidaxomicin is a newer antibiotic that has shown promising results in treating C. difficile infection. What makes fidaxomicin unique? It has a narrow spectrum of activity, primarily targeting C. diff while preserving much of the normal gut flora. This targeted approach may help reduce the risk of recurrence.

Comparative Effectiveness of Antibiotic Treatments

Understanding the relative effectiveness of different antibiotics is crucial for optimal treatment of C. difficile infection. Several studies have compared the outcomes of various antibiotic regimens.

• A study by Stevens et al. (2017) compared the effectiveness of vancomycin and metronidazole in preventing recurrence and death in patients with C. diff infection. The results showed that vancomycin was associated with a lower risk of recurrence compared to metronidazole.
• Cornely et al. (2012) conducted a double-blind, randomized controlled trial comparing fidaxomicin to vancomycin. They found that fidaxomicin was non-inferior to vancomycin in terms of clinical cure rates and was associated with a lower rate of recurrence.
• Mullane et al. (2011) investigated the efficacy of fidaxomicin versus vancomycin in patients taking concomitant antibiotics for other infections. Their findings suggested that fidaxomicin might be more effective in this scenario, possibly due to its narrower spectrum of activity.

Impact of Antibiotics on Gut Microbiota During C. Diff Treatment

The use of antibiotics to treat C. difficile infection inevitably impacts the gut microbiota. Understanding these effects is crucial for developing more effective treatment strategies and reducing the risk of recurrence.

How do different antibiotics affect the gut microbiome? A study by Theriot et al. (2014) found that antibiotic-induced shifts in the mouse gut microbiome and metabolome increased susceptibility to C. difficile infection. This highlights the delicate balance that must be maintained when treating C. diff.

Antharam et al. (2013) observed intestinal dysbiosis and depletion of butyrogenic bacteria in C. difficile infection. These findings suggest that preserving or restoring beneficial gut bacteria could be an important aspect of effective C. diff treatment.

The Role of Secondary Bile Acids

Interestingly, research by Thanissery et al. (2017) revealed that secondary bile acids produced by gut microbiota can inhibit C. diff spore germination, growth, and toxin activity. This underscores the importance of maintaining a healthy gut microbiome during and after antibiotic treatment for C. diff.

Strategies to Prevent C. Difficile Recurrence

Preventing recurrence is a major challenge in C. difficile treatment. Several strategies have been explored to reduce the risk of recurrence after initial antibiotic therapy.

Antibiotic Tapering and Pulsing

One approach to prevent C. diff recurrence is the use of antibiotic tapering and pulsing. This involves gradually reducing the dose of the antibiotic over time, followed by intermittent dosing. How does this strategy work? It aims to suppress C. diff while allowing the normal gut flora to recover.

Probiotics and Fecal Microbiota Transplantation

Probiotics and fecal microbiota transplantation (FMT) have gained attention as potential adjuncts to antibiotic therapy. These approaches aim to restore a healthy gut microbiome, which can help prevent C. diff recurrence. While more research is needed, initial results have been promising, particularly for FMT in cases of recurrent C. diff infection.

Emerging Antibiotic Therapies for C. Difficile

Research into new antibiotic treatments for C. difficile infection is ongoing. Several promising candidates are in various stages of development and clinical trials.

Ridinilazole: A Potential Game-Changer

Ridinilazole is a novel antibiotic specifically designed to target C. difficile while minimizing disruption to the gut microbiome. Early clinical trials have shown promising results, with potentially higher cure rates and lower recurrence rates compared to existing treatments.

Cadazolid: A Dual-Action Approach

Cadazolid is another antibiotic in development that combines the mechanisms of action of oxazolidinones and quinolones. This dual approach could potentially provide more effective treatment for C. diff infection, especially in cases resistant to current therapies.

The Role of Non-Antibiotic Approaches in C. Difficile Management

While antibiotics remain the primary treatment for C. difficile infection, non-antibiotic approaches are increasingly being explored as complementary or alternative strategies.

Immunotherapies and Vaccines

Research is underway to develop immunotherapies and vaccines against C. difficile. These approaches aim to boost the body’s natural defenses against the infection, potentially reducing the need for antibiotics or enhancing their effectiveness.

Bacteriophage Therapy

Bacteriophages, viruses that specifically target bacteria, are being investigated as a potential treatment for C. diff infection. This approach could offer a highly targeted method of eliminating C. diff while sparing beneficial gut bacteria.

Optimizing Antibiotic Use for C. Difficile Treatment

Effective treatment of C. difficile infection requires not just choosing the right antibiotic, but also optimizing its use. This involves considering factors such as dosage, duration of treatment, and potential combination therapies.

Tailoring Treatment to Patient Characteristics

Individualizing antibiotic treatment based on patient characteristics can improve outcomes. Factors to consider include the severity of infection, previous antibiotic exposure, and the patient’s overall health status. For instance, fidaxomicin might be particularly beneficial for patients at high risk of recurrence or those taking concomitant antibiotics for other infections.

Combination Therapies

In severe cases of C. difficile infection, combination antibiotic therapy may be considered. Bass et al. (2013) compared treatment outcomes with vancomycin alone versus combination therapy in severe C. difficile infection. While more research is needed, combination approaches may offer benefits in certain clinical scenarios.

As our understanding of C. difficile infection and its treatment continues to evolve, it’s clear that a multifaceted approach is necessary. This includes not only selecting the most appropriate antibiotic but also considering the impact on the gut microbiome, implementing strategies to prevent recurrence, and exploring novel therapies. By integrating these various aspects, we can hope to improve outcomes for patients with this challenging infection.

Antibiotic Treatments for Clostridium difficile Infection Are Associated with Distinct Bacterial and Fungal Community Structures

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What you need to know about Clostridium difficile

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According to the Centers for Disease Control and Prevention (CDC), Each year, more than 2 million people in the United States get infections from germs that are resistant to antibiotics– and at least 23,000 people die as a result. C. difficile infections—which can occur after using antibiotics—kill at least another 15,000 Americans a year.

What is Clostridium difficile (or C. diff) infection?

Your body has a lot of “good” and necessary bacteria. It also has some “bad” or dangerous bacteria. Clostridium difficile (C. diff) is part of the normal bacteria found in some people’s intestines or colons. Fortunately, when you are healthy and are not taking antibiotics, the millions of good bacteria in your system keep the C. diff under control and in smaller numbers. However, when you take an antibiotic, the levels of good bacteria are reduced down to a smaller number. This makes it possible for the C. diff to overpopulate your intestine or colon. When this happens, you may get the illness called Clostridium difficile colitis.

C. diff produces spores when attacked by antibiotics. The spores can live in the open air or in dirt for up to two years. Normal disinfectants are not effective against the spores. This means that even if you kill the C. diff bacteria, spores can still be present. This is why you can get rid of the C. diff symptoms when being treated with medicine, but it can come back later.

What are the symptoms of C. diff infection?

When you have an imbalance of bacteria and C. diff takes over, it creates two main types of toxins that affect your body and give you the symptoms of the actual disease. The toxins attack your intestinal wall and, when left untreated, may cause an ulcer or sore. The symptoms are similar to severe food poisoning. At first, your symptoms may include diarrhea and cramping. The later stages are flu-like symptoms, including weakness, dehydration, fever, nausea, vomiting, and—in advanced stages—blood in your stool/feces. If a patient is left untreated, he/she can die from it. C. diff is linked to 14,000 deaths in America each year.  

How is C. diff diagnosed?

First, you must have some symptoms listed above. You must see your doctor to be diagnosed and treated. A special test is needed to officially determine whether or not you have C. diff; this requires the lab to test a sample of your stool. If a diagnosis of C. diff is made, a gastroenterologist, a doctor who is trained to deal with illnesses of the gastrointestinal tract (stomach and intestines), will most likely help treat your C. diff.  The gastroenterologist may perform a colonoscopy to assess the damage to your intestines and the presence of the C. diff and polyps (a fleshy growth on the inside of the colon).

Some regular physicians can treat and cure you. If you have a stubborn case of C. diff, you may ask your physician to refer you to a specialist. There have been cases where non-specialist physicians did not know enough about C. diff and actually aggravated the condition by misdiagnosing or prescribing another antibiotic or medicine that encouraged C. diff overpopulation.

Who is at risk for C. diff infections?

Although people, including children, with no known risk factors have acquired C. diff infection, the following groups of people are at greatest risk:

1. Those who are now taking or have recently taken antibiotics. The risk goes up if you take broad-spectrum drugs that target a wide range of bacteria, use multiple antibiotics, or take antibiotics for a long period of time.
2. Adults who are 65 years of age or older. The risk of becoming infected with C. diff is 10 times greater for people age 65 and older than it is with younger people.
3. Those who are now or have recently been hospitalized, especially for an extended period.
4. Those who live in a nursing home or long-term care facility.
5. Those who have a serious underlying illness or a weakened immune system as a result of a medical condition or treatment (such as chemotherapy).
6. Those who have had abdominal surgery or a gastrointestinal procedure.
7. Those who have a colon disease such as inflammatory bowel disease or colorectal cancer.
8. Those who have had a previous C. diff infection.

How is C. diff treated?

Antibiotics are usually the cause of recurrent cases of C. diff.  Ironically, two very powerful antibiotics are used to treat the disease! The most common and least expensive drug used is Flagyl (metronidazole). If Flagyl is ineffective, then Vancocin (vancomycin) is prescribed.

In rare cases, C. diff may not respond well to antibiotics, with infections persisting for months and even years. New studies have shed light on a treatment that was once considered  a last resort by many doctors. The treatment is called fecal bacteriotherapy; this means that someone else’s “healthy” stool is transplanted inside of the C. diff patient. The new study shows that donor stool transplantation effectively cured 90 percent of patients’ recurrent C. diff infections. Transplanting donor stool is effective because it replaces the good bowel flora that was killed off by the use of antibiotics and naturally combats the invasive bacterium.

How can C. diff be prevented?

Hospitals and other healthcare facilities follow strict infection-control guidelines to prevent C. diff. If you have a friend or family member in a hospital or nursing home, don’t be afraid to remind caregivers to follow the recommended precautions.

1. Hand washing. Healthcare providers should practice good hand hygiene with soap and warm water or alcohol-based hand rubs before and after treating each person in their care. Visitors also should be diligent about hand hygiene before and after leaving the room or using the bathroom and should not use the patient’s sink or bathroom. Patients need to practice good hand hygiene as well.
2. Contact precautions. People who are hospitalized with C. diff have a private room or share a room with someone who has the same illness. Hospital staff and visitors should wear disposable gloves and gowns while in the room.
3. Careful cleaning. In any setting, all surfaces should be carefully disinfected with a product that contains chlorine bleach. C. diff spores cannot survive routine cleaning products that contain bleach.
4. Appropriate use of antibiotics. Antibiotics are sometimes prescribed when they are not needed. Antibiotics will not cure viral illnesses, such as the common cold. Take a “wait-and-see” attitude with simple ailments. Remember: “Snort. Sniffle. Sneeze. No antibiotics, please!” If you do need an antibiotic, ask your doctor to prescribe one that has a narrow range and that you take for the shortest time possible.

Additional resources
APIC—The ABC’s of Antibiotics
The Centers for Disease Control and Prevention—Clostridium difficile infection
The Centers for Disease Control and Prevention—Get Smart: Know when antibiotics work
The Centers for Disease Control and Prevention—Vital Signs: Stopping Clostridium difficile infections
MedLine Plus—Clostridium difficile Infections

causes, symptoms, diagnosis and treatment

Meningomyelitis

Meningitis

Tabes dorsalis

Paralysis

Photophobia

Confusion

Convulsions

Vomiting

Urinary disorders

10235

07 October

Neurosyphilis: causes, symptoms, diagnosis and treatment.

Definition

Neurosyphilis is an infectious lesion of the nervous system caused by the invasion of a fetus (congenital syphilis) or an adult (acquired syphilis) by Treponema pallidum.
Currently, damage to the nervous system in patients with syphilis is detected in 15-20% of cases. Neurosyphilis accounts for 7-9% of all organic diseases of the nervous system.

Many authors call the increased frequency of damage to the nervous system one of the main signs of the modern course of syphilis.

Causes of neurosyphilis

All forms of neurosyphilis develop as a result of penetration into the vessels, membranes and substance of the nervous tissue (through the blood and lymph) of the syphilis pathogen Traeponema pallidum.

In the initial stages of the disease, spread through the blood predominates: the pathogen enters the bloodstream a few hours after infection and is fixed in the blood vessels, and from there it enters the lymphatic capillaries of the nerve sheaths and other structures of the nervous system. Lymphogenous (through the lymph) penetration is the main one, but occurs later and more slowly.

Along with the sheaths of the nerves, the infection affects the vessels of the nervous system and the entire apparatus of the nervous system. Over time, local immunity is developed, and the connective tissue loses the ability to delay pale treponemas, neutralizing them. Then the latter penetrate the central nervous system, causing irreversible changes.

Syphilis is divided into the following stages: primary syphilis, secondary syphilis, latent and late forms. Syphilitic meningitis can develop in the primary (rarely) and secondary periods. Characteristic neurological symptoms, united by the term “neurosyphilis”, develop with tertiary syphilis.

Classification of the disease

Classification of syphilis of the nervous system according to ICD-10:

Late congenital neurosyphilis (juvenile neurosyphilis).

Neurosyphilis with symptoms.

Asymptomatic neurosyphilis.

Neurosyphilis, unspecified.

Classification of neurosyphilis by stages:

• Latent neurosyphilis – in this form there are no clinical manifestations, but pathological changes are detected when examining the patient’s cerebrospinal fluid.
• Early neurosyphilis develops against the background of primary or secondary syphilis, mainly in the first 2 years of the disease. But it can occur within 5 years from the moment of infection. It proceeds with damage mainly to the vessels and membranes of the brain.

  Early manifestations of neurosyphilis include acute syphilitic meningitis, meningovascular neurosyphilis, and syphilitic meningomyelitis.

• Late neurosyphilis occurs no earlier than 7-8 years from the moment of infection and corresponds to the period of tertiary syphilis. It is characterized by inflammatory-dystrophic damage to the brain. Late forms of neurosyphilis include dorsal tabes, progressive paralysis and syphilitic gumma of the brain.

Symptoms of neurosyphilis

Acute syphilitic meningitis which is characterized by symptoms of acute meningitis (inflammation of the meninges): severe headaches stiff neck or neck pain, photophobia, confusion, drowsiness, convulsions, joint pain, cold limbs , vomit.

Syphilitic meningitis often manifests after 1-2 years of illness. A predisposing factor is too early termination of the course of treatment or inadequate therapy.

Syphilitic meningomyelitis is one of the most common forms of spinal cord syphilis. Meningomyelitis can be acute, but more often subacute and chronic. The symptoms of the membranes are accompanied by damage to the spinal cord itself with the development of paraparesis – a decrease in muscle strength in the arms or legs. The lumbar part of the spinal cord is not so often affected, with characteristic flaccid paralysis of the lower extremities, urinary incontinence and the appearance of pressure sores. With localization in the cervical part of the spinal cord – tetraparesis – a simultaneous decrease in muscle strength in both arms and legs.

Meningovascular neurosyphilis – this form of the disease occurs when the inner lining of the brain vessels is damaged. Clinical manifestations depend on the predominant lesion of small or large vessels, as well as on the location, size and number of focal disorders caused by the vascular process (strokes, hemiparesis, paralysis, speech disorder, epileptic seizures).

It can manifest itself as an acute cerebrovascular accident similar to a stroke, a few weeks before which the patient begins to experience headaches, sleep disturbances, and dizziness.

Tabes dorsalis : syphilitic myelopathy develops 8-12 years after infection. About 30% of patients with neurosyphilis are patients with dorsal tabes, men suffer 4-7 times more often than women. In the clinical picture, the first symptoms are sensory disturbances: vibration sensitivity decreases (sensitivity to mechanical vibrations acting on the skin) and joint-muscular feeling, due to which the position of the body in space is felt and movements are coordinated.

Sensitivity to pain decreases, sensory ataxia is manifested – a specific violation of gait and coordination of movements: the patient puts his legs disproportionately wide, excessively bends and over-extends them at the knees and hip joints, hits the floor with his heel with force.

One of the first signs of the disease is a violation of urination, while the bladder becomes atonic. In 90% of patients suffering from spinal dryness, pupillary disorders develop: narrow, irregularly shaped pupils completely or partially lose their reaction to light, and 20% of patients develop the classic Argyle Robertson syndrome (irregularly shaped constricted pupils that do not respond to light.), in 25% cases of optic nerve atrophy.

Progressive paralysis may occur in patients 10-20 years old. This type of disease is associated with the penetration of treponema into brain cells and their subsequent destruction. Mental disorders are often more pronounced than neurological. A typical manifestation of progressive paralysis is progressive dementia, loss of criticism of one’s condition, aggression, and speech disorders. Often there are mental deviations such as depressive or manic states, hallucinatory syndrome, delusional ideas.

Neurosyphilis in the form of progressive paralysis can be accompanied by impaired pelvic functions in the form of urinary and fecal incontinence, impaired fine motor skills of the limbs in the form of trembling when performing purposeful movements, and a decrease in muscle strength and tone.

Syphilitic gum is extremely rare. Gumma is most often localized at the base of the brain, less often in the medulla. Compression of the cranial nerves by gumma leads to damage to the oculomotor nerves and disruption of the movements of the eyeballs. The growth of gumma causes an increase in intracranial pressure and an increase in signs of compression of the brain substance: impaired consciousness, headaches, vomiting, psychomotor agitation, unilateral pupil dilation, etc. are possible.

Congenital neurosyphilis is rarely diagnosed because all pregnant women are tested for syphilitic infection several times during pregnancy. If intrauterine infection could not be avoided, the clinical picture of neurosyphilis will be the same as in an adult (except for the dorsal tabes).

Diagnosis of neurosyphilis

Laboratory tests for syphilis:

Non-specific antiphospholipid (reagin) test – a modern analogue of the Wasserman reaction.

RPR test (Rapid Plasma Reagin Test)

Synonyms: Blood test for syphilis; Nonspecific antiphospholipid (reagin) test, a modern analogue of the Wasserman reaction (RW). nontreponemal test; Rapid plasma reagin test; Syphilis screen…

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Specific diagnostic treponemal test used for screening and complex diagnosis of syphilis (total antibodies to the causative agent of syphilis IgG/IgM).

Determination of Treponema pallidum (Treponema pallidum) DNA in blood serum by polymerase chain reaction (PCR) with real-time detection.

Treponema pallidum, determination of DNA (Treponema pallidum, DNA) in blood serum

Determination of Treponema pallidum DNA (Treponema pallidum) in blood serum by polymerase chain reaction (PCR) with real-time detection.

Ill…

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Determination of Treponema pallidum (Treponema pallidum) DNA in scrapings of epithelial skin cells by polymerase chain reaction (PCR) with real-time detection.

Treponema pallidum, DNA detection (Treponema pallidum, DNA) in skin epithelial cell scraping

Determination of Treponema pallidum (Treponema pallidum) DNA in scrapings of epithelial skin cells by polymerase chain reaction (PCR) with real-time detection. ..

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The study of IgG antibodies to the antigens of the causative agent of syphilis Treponema pallidum by immunoblot is used as an additional specific treponemal test.

Syphilis immunoblot IgG (anti-Treponema pallidum IgG immunoblot)

The study of IgG antibodies to the antigens of the causative agent of syphilis Treponema pallidum by immunoblot is used as an additional specific treponemal test …

Up to 6 business days

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2 040 RUB

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Determination of Treponema pallidum (Treponema pallidum) DNA in cerebrospinal fluid by polymerase chain reaction (PCR) with real-time detection.

Treponema pallidum, detection of DNA (Treponema pallidum, DNA) in cerebrospinal fluid

Determination of Treponema pallidum (Treponema pallidum) DNA in cerebrospinal fluid by polymerase chain reaction (PCR) with real-time detection….

Up to 1 business day

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475 RUB

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Instrumental examinations:

MRI of the brain.

MRI of the brain

Safe and informative scanning of brain structures for the diagnosis of its pathologies.

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CT scan of the brain and skull

Scanning of the brain, skull and surrounding tissues, which allows diagnosing various pathologies.

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Differential diagnosis of neurosyphilis is carried out with meningitis of another genesis, vasculitis, brucellosis, sarcoidosis, borreliosis, tumors of the brain and spinal cord, etc.

Which doctors to contact

dermatovenereologist jointly with
neurologist.

Treatment of neurosyphilis

Treatment of neurosyphilis is carried out in a hospital setting.

Patients with visual and auditory involvement are treated with intravenous antibiotics immediately after diagnosis.

Penicillin preparations are used in high doses for 2 weeks. In patients allergic to the penicillin series, antibiotics of the cephalosporin group are used.

On the first day of treatment for neurosyphilis, a temporary worsening of neurological symptoms may occur, accompanied by an increase in body temperature, intense headache, tachycardia, lowering blood pressure, joint pain. In such cases, treatment is supplemented with the appointment of anti-inflammatory and corticosteroid drugs.

The effectiveness of therapy is assessed by improvement in cerebrospinal fluid and clinical data.

Complications

After meningovascular syphilis, dysfunction of the pelvic organs, paresis, speech disorder and other residual effects that lead to disability may persist.

Late forms of syphilitic infection are more difficult to treat. Typically, neurological manifestations remain with the patient for life.

Damage to the spinal nerves (taxus) is practically not cured and neurological symptoms do not have a reverse development.

Congenital neurosyphilis always leads to neurological abnormalities that prevent the normal development of the child’s body.

Prevention of neurosyphilis

Primary prevention does not exist.

Public health education and screening of risk groups recommended.