Download MBBS General Medicine PPT 2 Gp Infections Part II Lecture Notes

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)



Approach to Infectious Diseases and their prevention


Antibiotic stewardship practices


Community-Acquired Infections


Health Care?Associated Infections


Gram-Positive Bacteria (part-1)


Gram-Positive Bacteria (part-2)


Gram-Negative Bacteria (part-1)


Gram-Negative Bacteria (part-2)


Spirochetal Diseases


Diseases Caused by Atypical/Miscellaneous Bacterial Infections


Revision-cum-exam on bacteria (Must to know type)


Infections Due to DNA Viruses



Infections Due to RNA Viruses (part 1)


Infections Due to RNA Viruses (part 2)


HIV/AIDS ? part 1


HIV/AIDS ? part 2


Fungal Infections


Parasitic Infections (part 1)


Parasitic Infections (part 2)


Revision-cum-exam on Virus, Fungal, and Parasite (Must to know type)



Clostridial Infections

Gas gangrene

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


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



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

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


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


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


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;
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)

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


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


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 overlap greatly with those of other infections
It presents with several clinical syndromes (meningitis and septicemia are most


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


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)

"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

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

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


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


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

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


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

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


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
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


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

Meticulous intensive care and immediate administration of botulinum

antitoxin (Botulism Antitoxin Heptavalent OR Botulism Immune Globulin


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

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


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


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%

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


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


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