Download MBBS (Bachelor of Medicine, Bachelor of Surgery) General Medicine 2022 PPT 2 Gp Infections Part II Lecture Notes
Infectious diseases
4/5th Semester Classes on Infectious Diseases, 8-9AM, Tuesdays (LT-1)
Topics
1
Approach to Infectious Diseases and their prevention
2
Antibiotic stewardship practices
3
Community-Acquired Infections
4
Health Care?Associated Infections
5
Gram-Positive Bacteria (part-1)
6
Gram-Positive Bacteria (part-2)
7
Gram-Negative Bacteria (part-1)
8
Gram-Negative Bacteria (part-2)
9
Spirochetal Diseases
10
Diseases Caused by Atypical/Miscellaneous Bacterial Infections
11
Revision-cum-exam on bacteria (Must to know type)
12
Infections Due to DNA Viruses
1
13
Infections Due to RNA Viruses (part 1)
14
Infections Due to RNA Viruses (part 2)
15
HIV/AIDS ? part 1
16
HIV/AIDS ? part 2
17
Fungal Infections
18
Parasitic Infections (part 1)
19
Parasitic Infections (part 2)
20
Revision-cum-exam on Virus, Fungal, and Parasite (Must to know type)
DIPHTHERIA
Listeria
Clostridial Infections
Tetanus
Botulism
Gas gangrene
DIPHTHERIA
Nasopharyngeal and skin infection caused by Corynebacterium diphtheriae
Toxigenic strains most frequently cause pharyngeal diphtheria, nontoxigenic
strains commonly cause cutaneous disease
Cutaneous diphtheria is usually a secondary infection after primary skin lesions
due to trauma, allergy, or autoimmunity
In tropical latitudes, cutaneous diphtheria is more common than respiratory
diphtheria
In temperate climate, Pharyngeal one is most common during winter months
Risk factors for diphtheria outbreaks include older age, lack of vaccination,
alcoholism, low socioeconomic status, crowded living conditions
Carriers are defined as individuals who have positive cultures for C.
diphtheriae and who either are asymptomatic or have symptoms but lack
pseudomembranes
ETIOPATHOGENESIS
Unencapsulated, nonmotile, and nonsporulating with club-shaped bacillary
appearance and typically form palisades, known as "Chinese characters"
The specific laboratory media using tellurite, colistin, or nalidixic acid
Phenotypes:- nontoxigenic (tox?) and toxigenic (tox+) using corynebacteriophages
Under iron-limiting conditions leads to the optimal expression
Transmitted via the aerosol route, with only human reservoirs, IP-2?5 days
Diphtheria toxin is the primary virulence factor and is taken up in the bloodstream,
from which it is distributed to all organ systems in the body
In vitro, the toxin may be separated into two chains by digestion with serine
proteases: the N-terminal A fragment and the C-terminal B fragment
Delivery of the A fragment into the eukaryotic cell cytosol results in irreversible
inhibition of protein synthesis by NAD+-dependent ADP-ribosylation of elongation
factor 2
Pathologic findings of diphtheria include mucosal ulcers with a pseudomembranous
coating composed of an inner band of fibrin and a luminal band of neutrophils
CLINICAL MANIFESTATIONS
Should be considered when a patient has severe pharyngitis, particularly when there
is difficulty swallowing, respiratory compromise, or signs of systemic disease (e.g.,
myocarditis or generalized weakness)
Clinical diagnosis of diphtheria is IF sore throat; pseudomembranous lesions; and low-
grade fever
Most commonly, the pseudomembranous lesion is located in the tonsillopharyngeal
region
It is gray or whitish, sharply demarcated, tightly adherent to the underlying tissues
(Unlike streptococcal pharyngitis)
Massive swelling of the tonsils and may present with "bul -neck" diphtheria
Polyneuropathy (3?5 weeks after) and myocarditis are late toxic manifestations
Cranial nerve dysfunction typically precedes other neuropathy and typically
reversible in patients who survive the acute phase
Other complications include pneumonia, renal failure, encephalitis, cerebral
infarction, pulmonary embolism, and serum sickness from antitoxin therapy
Cutaneous Diphtheria IS characterized by punchedout ulcerative lesions with
necrotic sloughing or pseudomembrane formation
Diagnosis
The diagnosis of diphtheria is based on clinical signs and symptoms plus
laboratory confirmation
Laboratory diagnosis of diphtheria is based either on cultivation or on the
demonstration of local lesions with characteristic histopathology
A diagnosis of cutaneous diphtheria requires laboratory confirmation since
the lesions are not characteristic and are indistinguishable from other
dermatoses
Treatment
Patients in whom diphtheria is suspected should be hospitalized in respiratory
isolation rooms, with close monitoring of cardiac and respiratory function
Once a clinical diagnosis of diphtheria is made, diphtheria antitoxin should be
administered as rapidly as possible after a test dose
Antibiotics are used in the management of diphtheria primarily to prevent
transmission to susceptible contacts
Procaine penicillin G, 600,000 U IM q12h until the patient can swallow
comfortably; then oral penicillin V, 125?250 mg qid to complete a 14-day
course (or Erythromycin, 500 mg IV q6h, rifampin and clindamycin)
For patients in whom the organism is not eradicated after a 14-day course of
erythromycin or penicillin, an additional 10-day course followed by repeat
culture is recommended
Patients who recover from diphtheria should receive the appropriate vaccine if
diphtheria antitoxin titer of <0.01 U/mL
Prognosis and prevention
Risk factors for death include
bullneck diphtheria;
myocarditis with ventricular tachycardia;
atrial fibrillation;
complete heart block;
an age of >60 years or <6 months;
alcoholism;
extensive pseudomembrane elongation;
laryngeal, tracheal, or bronchial involvement
Interval between the onset of local disease and the administration of antitoxin
DTaP is currently recommended for children up to the age of 7
It is recommended that all adults receive a single dose of Tdap if they have not received it previously,
regardless of the interval since the last dose of Td (tetanus and reduced-dose diphtheria toxoids,
adsorbed); after that decennial Td booster
Close contacts of diphtheria patients should undergo throat culture and After samples for throat
culture obtained, antimicrobial prophylaxis should be considered for all contacts (7?10 days of oral
erythromycin or one dose of IM benzathine penicil in G, 1.2 mil ion units for persons 6 years of age)
OTHER CORYNEBACTERIAL INFECTIONS
Nondiphtherial corynebacteria, referred to as diphtheroids or coryneforms,
are frequently considered colonizers or contaminants; however, they have
been associated with invasive disease, particularly in immunocompromised
patients
Humans are the natural reservoirs for several coryneforms, including C.
xerosis, C. pseudodiphtheriticum, C. striatum, C. minutissimum, C. jeikeium,
C. urealyticum, and Arcanobacterium haemolyticum
Animal reservoirs are responsible for carriage of Arcanobacterium
pyogenes, C. ulcerans, and C. pseudotuberculosis
Soil is the natural reservoir for Rhodococcus equi
Listeria monocytogenes Infections
L. monocytogenes is of interest not only to clinicians but also to basic scientists as
a model intracellular pathogen that is used to study
A food-borne pathogen that can cause serious infections, particularly in
pregnant women and immunocompromised individuals
Broad host range of reservoirs, facultatively anaerobic, nonsporulating, motile,
grows over a broad temperature range
Commonly found in processed and unprocessed foods of animal and plant
origin
Like other enteric pathogens, L. monocytogenes induces its own internalization
by cells that are not normal y phagocytic
Weakly -hemolytic (an essential determinant of its pathogenicity, listeriolysin O
Expresses a surface protein, ActA, an essential actin-based motility system (Other
pathogens like Shigella, Mycobacterium, Rickettsia, and Burkholderia species
use a related pathogenic strategy that allows cell-to-cell spread)
There is an inverse relationship between toxicity and virulence--i.e., the more
cytotoxic the strain, the less virulent it is in animals
Symptoms/diagnosis/treatment
Symptoms overlap greatly with those of other infections
It presents with several clinical syndromes (meningitis and septicemia are most
common)
Listerial gastroenteritis typically develops within 48 h of ingestion of a large
inoculum of bacteria
A nonspecific flulike il ness with fever is a common presentation in pregnant
women F/B myalgias, arthralgias, backache, and headache
Granulomatosis infantiseptica is an overwhelming fetal infection with miliary
microabscesses and granulomas
It should be considered in all older or chronically ill adults with "aseptic"
meningitis (frequently subacute)
The diagnosis is typically made by culture of blood, cerebrospinal fluid (CSF), or
amniotic fluid
Ampicil in is the drug of choice with/out Gentamycin
Clostridial Infections
They are pleomorphic, gram variable, mostly motile (except C. perfringens, C.
ramosum, and C. innocuum, with variable oxygen tolerance
Produce more protein toxins than any other bacterial genus, including
neurotoxins, enterotoxins, cytotoxins, collagenases, permeases, necrotizing
toxins, lipases, lecithinases, hemolysins, proteinases, hyaluronidases, DNases,
ADPribosyltransferases, and neuraminidases
C. tetani and C. botulinum, cause specific clinical disease by elaborating single
toxin while, C. perfringens and C. septicum cause aggressive necrotizing
infections due to multiple toxins
Botulinum and tetanus neurotoxins are the most potent (LD- 0.2?10 ng/kg)and
Epsilon toxin of C. perfringens is the most lethal one (used as agent of
bioterrorism)
Widespread in nature, forming endospores, Commensals in the intestinal tract of
humans and animals, in the female genital tract, and on the oral mucosa (not
al commensal clostridia are toxigenic)
Tetanus
"The acute onset of hypertonia or ... painful muscular contractions (usually of the
muscles of the jaw and neck) and generalized muscle spasms without other apparent
medical cause"... CDC
Maternal tetanus is defined by the WHO as tetanus occurring during pregnancy or
within 6 weeks after the conclusion of pregnancy (whether wit
The spores or bacteria enter the body through abrasions, wounds, or (in the case of
neonates) the umbilical stump.h birth, miscarriage, or abortion)
In 20?30% of cases of tetanus, no puncture entry wound is found
Higher risks in old age, Injection drug users, and incomplete vaccination
Only those bacteria producing tetanus toxin (tetanospasmin) can cause tetanus
Although closely related to the botulinum toxins in structure and mode of action,
tetanus toxin undergoes retrograde transport into the central nervous system and thus
produces different clinical effects
Unlike other components of the endosomal contents, which undergo acidification
following internalization, tetanus toxin is transported in a carefully regulated pH-
neutral environment that prevents an acid induced conformational change
Prevents transmitter release and effectively blocks inhibitory interneuron discharge
CLINICAL MANIFESTATIONS
Broadly divided into generalized (including neonatal) and local
Muscles of the face and jaw often are af ected first
The incubation period and the period of onset are of particular
significance; shorter times are associated with worse outcome
The commonest initial symptoms are trismus (lockjaw), muscle pain and
stiffness, back pain, and difficulty swallowing
Autonomic disturbance is maximal during the second week of severe
tetanus, and death occurs due to cardiovascular events
DIAGNOSIS
The diagnosis of tetanus is based on clinical findings
Culture of C. tetani from a wound provides supportive evidence
Serum anti-tetanus immunoglobulin G may also be measured in a sample
taken before the administration of antitoxin or immunoglobulin; levels >0.1
IU/mL are deemed protective and do not support the diagnosis of tetanus
D/D- strychnine poisoning and dystonic reactions to antidopaminergic
drugs ? Episodic nature
TREATMENT
Management strategies aim to neutralize remaining unbound toxin and support
vital functions until the effects of the toxin have worn off
Patients should be nursed in calm, quiet environments because light and noise
can trigger spasms
Entry wound should be identified, cleaned, and debrided of necrotic material
Metronidazole (400mg rectally or 500 mg IV every 6 h for 7 days) is the preferred
antibiotic; Or penicillin, although this may exacerbate spasms
TIG is the preparation of choice (less likely to be associated with anaphylactoid
reactions); 3000?5000 IU as a single IM dose, a portion should be injected
around the wound; nowadays 50?1500 IU administered intrathecal y also
Equine derived antitoxin (available widely), 10,000?20,000U, after testing for
hypersensitivity
Spasms are controlled by heavy sedation with benzodiazepines
Cardiovascular stability (dif icult to treat) is improved by increasing sedation with
IV magnesium sulfate, morphine, or other sedatives
Patients must be given a full primary course of immunization
Prevention
Good wound care and immunization
Individuals sustaining tetanus-prone wounds should be immunized if
their vaccination status is incomplete or unknown or
if their last booster was given >10 years earlier
Patients sustaining wounds not classified as clean or minor should also
undergo passive immunization with TIG
Botulism
Ingestion of botulinum toxin in contaminated food (food-borne botulism)
Wound botulism
Infant botulism
Adult intestinal colonization botulism
Botulism symptoms have been reported in patients receiving injections of
botulinum toxin for cosmetic or therapeutic purposes (iatrogenic botulism;
Moreover, botulism was reported after inhalation of botulinum toxin in a
laboratory setting
Intentional Botulism
Pathogenesis
Consumption of home-preserved fish or vegetable products main source
Seven serologically distinct confirmed serotypes of botulinum toxin (A
through G); Human cases associated with serotypes A, B, E, and F
Four recognized species of clostridia: Clostridium botulinum, Clostridium
argentinense, Clostridium baratii, and Clostridium butyricum
Neurotoxin enters the vascular system and is transported to peripheral
cholinergic nerve terminals, including neuromuscular junctions,
postganglionic parasympathetic nerve endings, and peripheral ganglia
with Inhibition of acetylcholine release
CLINICAL MANIFESTATIONS
All forms of botulism manifest as a relatively distinct clinical syndrome of
symmetric cranial-nerve palsies followed by descending bilateral flaccid
paralysis of voluntary muscles, which may progress to respiratory
compromise and death
Weakness descends, often rapidly, from the head to involve the neck, arms,
thorax, and legs; occasionally, weakness is asymmetric
In some instances, unfortunately, the severe ptosis, expressionless face, and
weak phonation of patients with botulism have been interpreted as signs of
mental status changes due to alcohol intoxication, drug overdose,
encephalitis, or meningitis--a conclusion that delays an accurate diagnosis
DIAGNOSIS
Diagnosed primarily on clinical grounds, with laboratory confirmation by specific tests that
identify botulinum toxin in clinical and food samples (mouse bioassay, BEST METHOD)
The temporal occurrence of two or more cases with symptoms compatible with botulism is
essentially pathognomonic because other illnesses that resemble botulism do not usually occur
in clusters
Food history and the names of contacts who may have shared foods should be obtained
before illness progresses
Ascertainment of the patient's behavioral history related to injection drug use is critical
A history of recent abdominal surgery or antibiotic use may be important in the diagnosis of
adult intestinal colonization botulism
D/D-
Guil ain-Barre syndrome (GBS),
myasthenia gravis,
stroke syndromes,
Eaton-Lambert syndrome,
tick paralysis
poisoning by tetrodotoxin, shel fish, or
a host of rarer agents and antimicrobial drug?associated paralysis
TREATMENT
Meticulous intensive care and immediate administration of botulinum
antitoxin (Botulism Antitoxin Heptavalent OR Botulism Immune Globulin
Intravenous)
Persons of all ages (including infants) in whom botulism is suspected should
be hospitalized immediately
Suspect wounds and abscesses should be cleaned, debrided, and drained
promptly. The role of penicillin and metronidazole in treatment and
decolonization is unclear
POLYMICROBIAL INFECTIONS INVOLVING
CLOSTRIDIA
In the absence of devitalized tissue, the presence of clostridia does not
necessarily lead to infection (CLOSTRIDIAL WOUND CONTAMINATION)
It may appear in association with non-spore-forming anaerobes and facultative
or aerobic organisms
Often associated with severe local inflammation but may lack the characteristic
systemic signs of toxicity and rapid progression seen in other clostridial infections
The treatment of mixed aerobic/anaerobic infection of the abdomen, perineum,
or gynecologic organs should be based on Gram's staining, culture, and
antibiotic sensitivity information
Ampicillin or ampicillin/sulbactam combined with either clindamycin or
metronidazole is DOC
ENTERIC CLOSTRIDIAL INFECTIONS
Illness results from the ingestion of food containing at least ~1 Billion viable vegetative
cells, which sporulate and produce enterotoxin
The diarrhea develops within 7?30 h of ingestion is generally mild and self-limiting;
however, in the very young, the elderly, and the immunocompromised, symptoms
are more severe and occasionally fatal
Enterotoxin-producing C. perfringens type A has been implicated and has been
considered to play a role in antibiotic-associated diarrhea without
pseudomembrane
Enteritis necroticans (gas gangrene of the bowel) is caused by toxin and toxin
(Pathogenic) producing strains of C. perfringens type C
Necrotizing enterocolitis, associated with C. perfringens type A, in previously healthy
adults AND low-birth-weight (premature) infants hospitalized in neonatal intensive
care units, af ects ileum in contrast to jejunum in enteritis necroticans
They should undergo nasogastric suction and receive IV fluids; Pyrantel is given by
mouth, and the bowel is rested by fasting; Benzylpenicillin (1 mU) IV every 4 h, and
the patient is observed for complications requiring surgery
Surgical indications; gas in the peritoneal cavity, absent bowel sounds, rebound
tenderness, abdominal rigidity; however, the mortality rate ranges from 35% to 100%
CLOSTRIDIAL BACTEREMIA
By C. perfringens and C. tertium mostly, rarely C. septicum
C. tertium can be found in patients with malignancy or acute pancreatitis,
with or without neutropenic enterocolitis; and is resistant to metronidazole,
clindamycin, and cephalosporins
Positive C. septicum patients have some association with gastrointestinal
anomaly or underlying malignancy and in addition, with neutropenia of any
origin--and, more specifically, with neutropenic enterocolitis
Anaerobic blood cultures and Gram's stain interpretation remain the best
diagnostic tests
CLOSTRIDIAL SKIN AND SOFT-TISSUE
INFECTIONS
Necrotizing clostridial soft-tissue infections; Severe pain, crepitus, brawny induration
with rapid progression to skin sloughing, violaceous bul ae, and marked tachycardia
are characteristics
Traumatic gas gangrene: conditions predisposing include crush-type injury,
laceration of large or medium-sized arteries, and open fractures of long bones that
are contaminated with soil or bits of clothing containing the bacterial spores with IP-
6 h <4 days
Diagnosis is not difficult because the infection always begins at the site of significant
trauma, is associated with gas in the tissue, and is rapidly progressive Non-
inflammatory nature
Spontaneous (nontraumatic) gas gangrene: occurs via hematogenous seeding of
normal muscle with histotoxic from a gastrointestinal tract portal of entry
The first symptom may be confusion followed by the abrupt onset of excruciating
pain in the absence of trauma, along with fever, should heighten suspicion
THEY should undergo aggressive diagnostic studies to rule out gastrointestinal
pathology
Surgical exploration, Gram's staining, blood culture, and histopathologic
examination are main stay of diagnosis and treatment
Thank you
This post was last modified on 05 April 2022