Anaerobes- gram positive

gram positive anaerobes

• clostridium spp.

• actinomyces

• peptostreptococcus

• cutibacterium

Clostridium Spp.

the genus clostridium includes more than 200 species, though only a few are clinically significant

Clostridium Spp. Morphology

• gram positive, rod shaped (bacilli) typically large in siz

• spore forming- produce oval or spherical endospores that enable survival under harsh environmental conditions

  • naturally resistant to antimicrobials

Clostridium Spp. Metabolism

• obligate anaerobe- oxygen is toxic to most species

• produce a variety of volatile fatty acids and gases (H₂, CO₂, NH₃ ), giving cultures a putrid odor

Clostridium Spp. Habitat

• widely distributed in soil, sediment, and decaying organic matter

• also part of the normal intestinal microbiota in humans and animals

• endospores persist in the environment for long periods, acting as infection reserves

Clostridium Spp. pathogenicity

• pathogenic species produce potent exotoxins, among the most powerful known to humans

• diseases often result from toxin-mediated mechanisms rather than direct bacterial invasion

• infections are typically endogenous (intestinal overgrowth) or exogenous (environmental contamination of wounds or food)

C. Diff infection epidemiology

• most common nosocomial infection

• 1-3% of healthy adults are colonized

  • 5-15% of patients w/o diarrhea exposed to antibiotics

  • higher rates of colonization in newborns/infants

• Immunoessence as people age- lose their ability to fight off C. diff

• C diff is an opportunistic bug

  • after taking antibiotics and all of the good bacteria is killed off, if a patient inhales a C. diff spore it is likely they will get an infection

Reasons for C. Diff increasing incidience

• overuse of antimicrobials in general and secondary to multi-drug resistant organisms

  • community and inpatient

• Emergence of more fit and capable strains

  • binary toxin

• Growing elderly population

• promotion of alcohol based, waterless hand sanitizers

• use of PCR technology

  • super sensitive to C. Diff

C. Diff virulence

• gram positive anaerobe, spore-forming

  • infection generally secondary to disrupted normal gut flora

• Toxin A (enterotoxin) and Toxin B (cytotoxin)

C. Diff- clinical presentation

• acute onset

• watery diarrhea (could be greater than 10 per day)

• leukocytosis (wbc increase)

  • may be acute and extreme (>30k possible)

• abdominal cramping

• complication/extensive disease

  • pseudomemranous colitis

    • white plaques on the colon

    • causes significant damage to endothelial lining of the colon

  • colonic damage

C. Diff- general risk factors

• antibiotic exposure

• PPI exposure

• infection control

• Patient specific factors

  • alterations in normal gut flora

    • PPIs make stomach less acidic which makes it easier for bacteria to survive in and get through

    • only relevant with long term use (3-4 weeks)

  • Age

  • immunosuppression- antitoxin AlgG levels

  • compromise of intestinal peristalsis = decrease elimination of organism and toxins

    • doesn’t increase risk of C. diff but makes it more likely to be severe

• PPIs and low risk antibiotics make a patient high risk

C. Diff High risk antibiotics

• clindamycin

• 2nd and 3rd generation cephalosporins

• fluoroquinolones

• carbapenems

• penicllins (+ BLI)

C. Diff low risk antibiotics

• tetracyclines

• vancomycin

• metronidazole

• linezolid

• nitrofurantioin

• SMX/TMP

C. Diff diagnositic tools: Glutamate Dehydrogenase

• common C. diff antigen

  • present in almost every strain of C. diff

  • present in toxin and nontoxin producing strands

• often used as adjust to detect toxin

• intial screening

• 85% sensitive

• 70-80 specific

C. Diff diagnositic tools: EIA (A or A/B)

• detects toxin A and B; rapid and inexpensive

• 2nd line test- after a positive GDH

• 75% sensitive

• 95-98% specific

C. Diff diagnositic tools: real time PCR for toxin B (NAAT)

• detects toxin in genes; results in hours

• 2nd line test

• >95% sensitive

• 80-100 specific

C. Diff diagnostic Guidance

• only submit stool specimens on patients with unexplained and new onset > 3 unformed stools in 24 hours

  • not to submit stool specimens from patients who received laxatives within 24-48 hrs

  • not to submit stool specimens from patients recently initiated on tube feeds or with recent rate changes

• only test unformed stools

• do not perform repeat testing (within 7 days) during the same episode of diarrhea

C. Diff- treatment overview

• infection control measures

• initiate antibiotics targeted at C. diff

  • PO vanc (IV wont make it into the colon)

  • Fidaxomicin

• Discontinuation of all unnecessary antimicrobial therapies or change to low risk

  • antibiotic stewardship

• Discontinue other contributing agents

• LIKE PPIs

C. diff infection control measures

• patient isolation in a single room

  • preferably with a bathroom

• strict contact precautions

• terminal room cleansing with 1:10 bleach

• avoidance of rectal thermometers

• soap and water (and scrubbing) for hand washing

• antibiotic stewardship and control

Clostridium Botulinum

• gram-positive

• spore-forming

• obligate anaerobic bacillus

• widely distributed in soil, dust, sediments and animal intestines

• produces the botulinum neurotoxin (BoNT)- one of the most potent toxins known

Clostridium Botulinum- exposure routes

• foodborne

  • from dented cans

• Wound

  • can get into open wounds

  • was common during wartime

• Infants

  • can’t have natural honey bc of the risk

  • their immune system is too weak to fight it off

• Adult infections

• Inadvertent

  • injections

  • almost unheard of bc botox is therapeutically altered

Clostridium Botulinum- botulism toxin

• A, B, E are clinically relevant in human infection

• A is used in Botox

Clostridium Botulinum- neurotoxin

• botulinum neurotoxin reaches nerve terminals at the neuromuscular junction

  • binds to the neuronal membrane, moves into the cytoplasm of the axon terminal, and acts to block excitatory synaptic transmission

  • four steps:

    • toxin binds to receptors on the neuron

    • internalization (endocytosis): toxin enters into the neuron

    • Cleaves SNARE proteins

    • Blocks acetylcholine release (excitatory) into the synaptic cleft, thus preventing firing of signal for muscle contraction

• Result = flaccid paralysis (typically descending )

Clostridium tetani

• gram positive

• spore forming

  • heat stable

• ubiquitous in environment

  • tetanus is EVERYWHERE

• racket shaped

4 types of tetanus

• generalized (80% of infection)

  • tetanospasmin = active toxin

  • locked jaw

• Localized

  • doesn’t affect the whole body

• Cephalic

• Neonatal

  • happens when there is a birth in a contaminated environment

  • typically with amish

generalized tetanus presentation

• incubation period can be 3-12 days long

  • average is 7 days

• enters peripheral nerves and travels to the spinal cord

• lock jaw is the first symptom- progresses to neck/back (reflex spasms)

• respiratory/cardiovascular system

  • typically the reason for death

  • 30% fatality rate

  • prevention is key

How is the tetanus neurotoxin different than the botulinum toxin

• only use motor neurons and target neurons in the CNS (why tetanus is typically in neck, jaw and back)

• typically uses axon transport as priamry moder

• not absorbed through the GI tract- direct inoculation of wounds

• result is spastic paralysis instead of flaccid paralysis

  • spastic because it inhibits GABA and other inhibitory neurotransmitters

tetanus prevention

• vaccination

  • part of the ACIP childhood series

  • refer to ACIP guidelines

• Booster- TDAP

  • every 10 years

  • or when you get a significant wound and then 5 years after than

Clostridium Perfringens

• major illnesses

  • food borne illness

    • beef, poultry, precooked foods that sit warm for a long time

    • survive best in 40-140 degrees f

    • gastroenteritis is usually self limiting

  • Gas gangrene

    • can happen when an open wound is exposed

    • like on a farm

• Severe tissue necrosis caused by toxin release

• signs

  • gas on imaging

  • purulence

  • fetid odor

  • significant necrosis

• Source: soil, environment, intestines of humans/animals

Actinomyces Spp.

• anaerobic, gram-positive bacilli

• typically thin, branching (filamentous) however, may be short and club shapped

• fastidious (only grow if certain nutrients are present)

• prolonged incubation may be necessary before lab confirmation-diagnosis often made by histopathology not by culture

• normal flora of mouth, gut, genital tract

• typically in mixed infections

Actinomyces Spp. presentation

• cervicofacial: presents as a swollen erythematosus process in the jaw area (lumpy jaw)

  • most common and classical presentation

• Thoracic: presents with mild fever, cough, and purulent sputum; lung tissue may be destroyed; sinus tracts may erupt through the chest wall and invade the ribs

Peptostreptococcus

• anaerobic, gram positive cocci

• small cocci, may be seen in short chains and pairs

• non-spore forming

• many species have been reassigned to new genera

• lives in the mouth

  • found in cavaties

  • not

Peptostreptococcus presentation

• part of normal microbiota of skin, oral cavity, upper respiratory tract, GI tract, and female GU tract

• most often in polymicrobial infections- associated with abcesses, can include oral cavities

  • less commony ABSSI, IAI, and infections of the female genital tract

Cutibacterium

• formerly known as propionibacterium

• anaerobic, gram positive bacilli

• metabolic products include propionic acid

• non-spore forming

• highly pleomorphic showing curved, clubbed, or pointed ends and occasionally cocoid or spherical forms

• slow growing often > 5-6 daays

• may take up to 14 days to recover clinically significant isolates

Cutibacterium cont.

• normal microbiome of skin, oral cavity, large intestine, conjunctiva, and external ear canal

• cutibacterium acnes: associated with acne

  • can also cause postsurgical wound infections, particularly from prosthetic devices

  • difficult to determine if true pathogen or contaminant

    • if in CSF or cultures from upper body surgery take it seriously

lactobacillus

• gram positive, non-spore forming, facultative anaerobic rod

• found naturally in the human microbiota, especially in oral cavity, gastrointestinal tract and vagina

• contribute to gut health by competing with pathogens and modulating the immune system

• used as probiotics in foods and supplements

• involved in fermentation of foods- yogurt, kefir, sauerkraut, pickles, sourdough,

• usually non-pathogenic and beneficial, but can cause opportunistic infections

  • bacteremia or endocarditis in immunocompromised or critically ill patients

  • rare