GRAM POSITIVE BACTERIAL INFECTIONS

Dr. Pauline Solis | May 13, 2021

Trans by: Aragon, Banatao

OUTLINE  Chemotaxis defects - Job syndrome, Chediak-Higashi

I. Gram Positive Bacteria ii. S. pyogenes syndrome, Wiskott-Aldrich syndrome
A. Staphylococci iii. S. agalactiae  Phagocytosis and killing defects - neutropenia, chronic
i. S. aureus C. Non-group A or B granulomatous disease
B. Streptococcus Streptococci  Humoral immunity in infants thru transplacental transfer of
i. S. pneumonia D. Enterococcus antibodies
I. GRAM POSITIVE BACTERIA  Older children- antibody development thru colonization or
minor infections.
A. STAPHYLOCOCCI
 Aerobic, gram-positive, grow in pairs and clusters Clinical Manifestations
 Part of normal flora of humans; found on fomites, dust
 Catalase-positive
 Coagulase-positive: S. aureus - more virulent
 Coagulase-negative: S. epidermidis, S. saprophyticus, S.
haemolyticus
 Associated with infections of indwelling catheters
STAPHYLOCOCCUS AUREUS
 Virulence factors
 Teichoic acid - mediates adhesion to mucosal cells
 Slime layer - polysaccharide capsule prevents
opsonophagocytosis
 Coagulase and/or clumping factor - cause large clumps
of organisms preventing effective phagocytosis; important
in abscess formation
 Protein A - absorb serum immunoglobulins, prevents
antibacterial antibodies from acting as opsonins thus [ppt of Dr.Solis]
Figure 1. Pathogenesis of S. aureus
inhibiting phagocytosis
 Catalase - inactivates hydrogen peroxide, promoting
intracellular survival  Pyogenic infections of the skin and soft tissue
 Penicillinase or β-lactamase - inactivates penicillin and  Impetigo, furuncles, cellulitis, abscess, lymphadenitis,
lipase paronychia, omphalitis, wound infection
 Panton-Valentine leukocidin (PVL) – associated with  Toxin-mediated diseases
invasive skin disease by combining with the phospholipid
 food poisoning, staphylococcal scarlet fever, scalded skin
of the phagocytic cell membrane, producing increased
permeability, leakage of protein, and eventual death of the syndrome, toxic shock syndrome (TSS)
cell
 Exfoliatins A and B - split the desmosome and alter the
intracellular matrix in the stratum granulosum Pneumonia Primary (1°) /hematogenous - septic emboli
 produce localized (bullous impetigo) or generalized from right - sided endocarditis or septic
(SSSS, staphylococcal scarlet fever) skin thrombophlebitis ± intravascular devices
complications Secondary (2°) - after a viral infection
Necrotizing pneumonia - associated with
 Enterotoxins (types A, B, C1, C2, D, E) - preformed
empyema, pneumatoceles, pyopneumothorax,
toxins associated with food poisoning
bronchopleural fistulas
 Toxic shock syndrome toxin-1 (TSST-1)
Bacteremia and Primary or associated with any localized
 Superantigen that induces production of IL-1 and
sepsis infection, single deep seated focus (heart
TNF resulting in hypotension, fever, and multisystem valves, lungs, joints, bones, abscesses
involvement Osteomyelitis, S. aureus as most common cause
suppurative
Epidemiology arthritis in
 Colonizers – nose, skin, umbilicus, vagina, perianal area children
 Transmission: auto-inoculation or direct contact Endocarditis S. aureus – common cause of acute native-
 Handwashing is essential valve endocarditis
 Invasive disease may follow colonization Renal and
perinephric
 Factors that increase the likelihood of infection
abscess
 Wounds, skin disease, VPS, catheterization,
Food poisoning 2-7 hr after preformed enterotoxins ingestion
corticosteroid, malnutrition, and azotemia
from contaminated food → sudden severe
 Influenza - predispose to secondary bacterial infection
vomiting, watery diarrhea
with staphylococci. rarely persist longer than 12-24 hrs

Pathogenesis Staphylococcal Scalded Skin Syndrome (SSSS)

 Barriers to infection – intact skin and mucous membranes  Production of staphyloccal exfoliatin A that causes
 Trauma, surgery, foreign bodies, burns intraepidermal of cells within the epidermal granular cells

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 Spectrum: bullous impetigo to generalized involvement
 Faint, red eruption in face, neck, axilla and groin
 Skin is tender with crusting around eyes, mouth and neck
 Rubbing of skin causes epidermal separation leaving a
shiny, moist, red surface underneath (Nikolsky sign)
 Management
 proper hydration, electrolyte correction
 antibiotics – oxacillin (MSSA); clindamycin, vancomycin
(MRSA)
Figure 2. Scalded Skin Syndrome [ppt of Dr.Solis]
Toxic Shock Syndrome
 Acute multisystem disease - fever, hypotension,
erythematous rash with desquamation of hands and feet;
vomiting, diarrhea, myalgias, nonfocal neurologic problems,
conjunctival hyperemia, strawberry tongue
 Caused by TSST-1–producing and some enterotoxin-
producing strains of S. aureus, which colonize the vagina or
cause focal sites of staphylococcal infection
 Mostly in menstruating women who use tampons or other
vaginal devices (diaphragm, contraceptive sponge)
 Also in children, nonmenstruating women, and men with an
identifiable focus of S. aureus infection
 Clinical diagnosis (3 major + ≥3 minor criteria)
 Recovery in 7-10 days
 Antibiotics, removal of vaginal devices, fluid management
Treatment
 Abscesses – incision and drainage
 Foreign bodies – removal of infected devices
 Antibiotics – choice must be based on local susceptibility
patterns
 Parenteral therapy for serious infections
 Dose, route, and duration of treatment depend on the site
of infection,
 patient response, susceptibility of organism recovered
from blood or
 from site of infection
 Oxacillin, 1st gen cephalosporin (cefazolin), 2nd gen
(cephalexin) – MSSA
 Clindamycin – bacteriostatic → not given for
endocarditis, brain abscess, meningitis
 For treatment of TSS to inhibit toxin production
 Vancomycin, Linezolid, Trimethoprim-sulfamethoxazole
 Ceftaroline – 4th gen ceph approved for adult use (MRSA
SSTI)
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Prognosis
 High fatality rate for untreated bacteremia
 S. aureus pneumonia can be fatal at any age
 High morbidity and mortality in young infants and in those
with delayed treatment
 Prognosis – influenced by nutrition al status, immunologic
competence, and the presence or absence of other debilitating
diseases
Prevention
 Proper handwashing techniques - most effective
 Isolation precaution hospitalized patients
 Hypochlorite and chlorhexidine wash
 Nasal mupirocin t to prevent recurrences
 Food poisoning - exclude individuals with S. aureus infections
of the skin from food preparation and handling
 Prepared foods should be eaten immediately or refrigerated
appropriately
B. STREPTOCOCCI
STREPTOCOCCUS PNEUMONIAE
 Pneumococcus
 Gram-(+), lancet-shaped, polysaccharide encapsulated
diplococcus, singly or in chains
 >90 serotypes identified
 encapsulated strains cause most serious disease in
humans → impede phagocytosis
 Major cause of life-threatening diseases (IPD) – pneumonia,
meningitis, sepsis
 Important cause of secondary bacterial pneumonia in
patients with influenza
Epidemiology
 Most healthy individuals carry various S. pneumonia serotypes
in their upper respiratory tract
 >90% of children 6 months to 5 years old, harbor S.
pneumoniae in nasopharynx at some time
 Carriage does not consistently induce local or systemic
immunity sufficient to prevent later reacquisition of the
same serotype
 Carriage rate peaks on the 1st and 2nd yr of life →
gradually decline
 Increased susceptibility to pneumococcal infection
 High prevalence of colonization
 Decreased ability produce antibody against the T-cell
independent polysaccharide antigens in <2yrs old
 Transmission via respiratory droplet
 Increased frequency and severity of pneumococcal disease in:
 Sickle cell disease
 Asplenia - deficient opsonization and absence of
clearance by the spleen of circulating bacteria
 Deficiencies in humoral (B cell) and complement-
mediated immunity
 HIV infection
 Malignancies - leukemia, lymphoma
 Chronic heart, lung, or renal disease (nephrotic
syndrome)
 CSF leak
 Cochlear implants
Clinical Manifestations
 Signs and symptoms are related to the anatomic site of disease
 Invasive Pneumococcal Disease (IPD) – pneumonia, sepsis,
meningitis
 Otitis media, sinusitis, osteomyelitis, arthritis, endocarditis
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Diagnosis
 Recovery of S. pneumoniae from the site of infection or from
blood
 Blood cultures should be obtained in children with pneumonia,
meningitis, arthritis, osteomyelitis, peritonitis, pericarditis, or
gangrenous skin lesions
 Pronounced leukocytosis, WBC >15,000/mm3
 Severe cases →WBC count may be low
Treatment
 Empiric therapy depends on local susceptibility patterns
 High-level β-lactam resistance and MDR strains
 Penicillins – for susceptible strains
 Lincosamide (clindamycin) or macrolides (erythromycin,
clarithromycin, azithromycin – for penicillin allergic patients
 Cephalosporins
 Cefuroxime
 Ceftriaxone/Cefotaxime
 High dose amoxicillin (80-100mkday) for otitis media
 Others –Vancomycin
Prognosis
 Depends on
 Integrity of host defenses
 Virulence and numbers of infecting organism
 Age of host
 Site and extent of the infection
 Adequacy of treatment
 Pneumococcal meningitis - sensorineural hearing loss in 20
- 30%
 Other serious neurologic sequelae - paralysis, epilepsy,
blindness, intellectual deficits
Prevention
 Pneumococcal polysaccharide vaccines
 PPSV23
 Unpredictable immunologic responsiveness and efficacy
following administration in children <2 yr of age.
 Contains purified polysaccharide of 23 pneumococcal
serotypes responsible for >95% of cases of invasive
disease
 Pneumococcal conjugate vaccines (PCV)
 Provoke protective antibody responses in 90% of infants
given these vaccines at 2, 4, and 6 mo of age
 Enhanced responses (e.g., immunologic memory) are
apparent after booster doses given at 12-15 mo of age
 Reduce nasopharyngeal carriage of vaccine serotypes by
up to 60-70%
 13-valent vaccine (latest)
C. STREPTOCOCCUS PYOGENES
 Group A streptococci (GAS)
 Gram (+) coccoid-shaped, grow in chains
 Broadly classified as β- or α-hemolytic, γ- nonhemolytic
 Most common and only clinically significant GAS that infects
children and adolescents
 Pharynx – most common site of infection followed by skin
(pyoderma, impetigo)
 Non-suppurative complications
 Acute rheumatic fever – sequela of pharyngitis NOT skin
infection
 Acute glomerulonephritis – sequela of pharyngitis or
skin infection
 Serotyping based on M protein antigen
 M types commonly associated with pharyngitis rarely
cause skin infections and vice versa
 Pharyngeal strains (M type 12) - associated with
glomerulonephritis
 Skin strains (M types 49, 55, 57, and 60) – nephritogenic
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 A few of the pharyngeal serotypes, but none of the skin
strains, have been associated with acute rheumatic fever
 Rheumatogenic potential is not solely dependent on the
serotype but is a characteristic of specific strains within
several serotypes skin infection
 Humans - natural reservoir
 Highly communicable
 Can cause disease in normal individuals of all ages who do not
have type-specific immunity against the particular serotype
involved
 Rate of pharyngeal infections highest in 5-15 y/o
 Children with untreated acute pharyngitis spread GAS via
salivary droplets and nasal discharge
 Incubation period for pharyngitis - 2-5 days
Pathogenesis
 Virulence of GAS depends primarily on the M protein rich
 Strains rich n M protein resist phagocytosis
 M protein antigen stimulates the production of type-
specific protective antibodies.
 Streptococcal pyrogenic exotoxins A,B, and C
 Rash of scarlet fever
 Elaborated by streptocci that are infected with a particular
bacteriophage
 Appear to be involved in the pathogenesis of invasive GAS
disease including streptococcal toxic shock syndrome
 Non-bullous and bullous impetigo
Erysipelas
 Acute GAS infection involving deeper layers of the skin and
connective tissue
 Swollen, red, and very tender skin with sharply defined, slightly
elevated border with associated systemic symptoms
Perianal Streptococcal Disease
 Well-demarcated, perianal erythema with anal, pruritus, painful
defecation, blood-streaked stools
 Flat, pink to beefy perianal erythema with sharp margins
extending as far as a 2cm from the anus w/o systemic SSx
Invasive GAS infection
 Isolation of GAS from a normally sterile body site
 Toxic shock syndrome - shock + multiorgan system
failure early in the course
 Necrotizing fasciitis - extensive local necrosis of
subcutaneous soft tissues and skin
 Systemic infection not TSS or necrotizing fasciitis
 Bacteremia with no identified focus
 Meningitis, pneumonia, peritonitis, puerperal sepsis,
osteomyelitis, suppurative arthritis, myositis, surgical
wound infection.
 Exact pathogenesis unknown but pyrogenic
exotoxins are implicated
 superantigens
Scarlet Fever
 URTI associated with a characteristic rash
 Caused by pyrogenic exotoxin (erythrogenic toxin)-
producing GAS in individuals who do not have antitoxin
antibodies
 Rash appear within 24-48 hours after onset of symptoms to the
neck with facial sparing, trunk and extremities
 Characteristics:
 Diffuse,finely popular, erythematous, blanching
 Often more intense along the creases of the elbows,
axillae, and groin
 Fades with desquamation after 3 days
 PE of pharynx : same findings as GAS pharyngitis
 Tongue with swollen prominent papillae: strawberry
appearance
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  Acute post-streptococcal glomerulonephritis
 Syndrome characterized by the onset of acute arthritis
following an episode of GAS pharyngitis in a patient whose
illness does not otherwise fulfill the Jones criteria for the
diagnosis of acute rheumatic fever
 Pediatric Autoimmune Neuropsychiatric Disorders
Associated with Streptococcus pyogenes (PANDAS)
 A group of neuropsychiatric disorders
(particularly obsessive-compulsive disorders, tic
disorders, and Tourette syndrome) for which a
possible relationship with GAS infections has
been suggested

Prognosis
 Excellent with complete recovery if properly treated
 ARF is prevented if treatment is given within 9 days of onset
 No evidence that acute PSGN can be prevented once
pharyngitis or pyoderma with a nephritogenic strain of GAS has
occurred.

Prevention
 The only specific indication for long-term use of antibiotics to
prevent GAS infections is for patients with a history of acute
rheumatic fever or rheumatic heart disease
 No vaccine available yet

Rheumatic fever
 Substantial evidence to support the link between GAS upper
pharyngitis tract infections and acute RF and RHD.
 2/3 patients with an acute RF have a history of an URTI
several weeks before
Figure 3. Scarlet Fever [ppt of Dr.Solis]  Peak age and seasonal incidence of acute RF closely
parallel GAS infection
Diagnosis  Patients with acute RF almost always have serologic
 Culture of a throat swab - remains the standard for the evidence of a recent GAS infection, with antibody titers
documentation of GAS in URT and for confirmation of the higher than those seen in patiets with GAS infections
clinical diagnosis of acute GAS pharyngitis. without acute RF.
 Rapid antigen detection tests  Outbreaks of GAS pharyngitis in closed communities, may
 Elevation or increasing streptococcal antibody titer- be followed by outbreaks of acute rheumatic fever
retrospective  Antimicrobial therapy that eliminates GAS from the
 Anti-streptolysin O assay (ASO) pharynx also prevents initial episodes of acute rheumatic
 Not specific to GAS fever, and long term continuous prophylaxis that prevents
GAS pharyngitis, also prevents recurrences of acute
Treatment rheumatic fever.
 Rheumatogenicity
 Antibiotics for GAS pharyngitis
 Not all of the serotypes of GAS can cause rheumatic fever
 Prevent acute rheumatic fever, shorten clinical course,
 Serotypes of GAS (M types 1,3,5,6,18,24) are more
reduce transmission, prevent suppurative complications
frequently isolated from patients with acute rheumatic
 Penicillin-drug of choice
fever
 Pen V, Pen G
 Pathogenicity
 Amoxicillin, 2nd gen cephalosporins
 No animal model
 Alternatives for Penicillin-allergic patients
 Cytotoxicity theory
 Macrolides-erythromycin, clarithromycin
 Immune-mediated pathogenesis
 Azalides- erythromycin, clarithromycin
 No clinical or Laboratory finding is pathognomonic for acute
 Clndamycin rheumatic fever, diagnosis using Jones Criteria
 Treatment course-10days
 To achieve maximal pharyngeal eradication rates of GAS
and prevention of RF
 Topical antibiotics for isolated superficial lesions without
systemic symptoms
 Mupirocin
 Necrotizing fasciitis
 Immediate surgical exploration or biopsy is required
 Debridement
 Streptococcal TSS
 Require rapid and aggressive fluid replacement
 Management of respiratory or cardiac failure
 Anticipatory management of multiorgan system failure

Complications
 Acute rheumatic fever
Trans # 24 Bacterial Infections – Gram Positive Bacteria 4 of 6
 3 circumstances in which the diagnosis of acute rheumatic Carditis  Subclinical carditis - without a
fever can be made without strict adherence to the Jones murmur of valvulitis but with
criteria echocardiographic evidence of
 Chorea- may occur as the only manifestation of ARF valvulitis
 Indolent carditis- may be the only manifestation in  Clinical carditis (with a valvulitis
patients who first come to medical attention months after murmur) as fulfilling the major
the onset of ARF criterion of carditis in all
 Recurrence of acute RF particularly in high risk populations
population  Endocarditis (valvulitis) is a
universal finding rheumatic
carditis – mitral and aortic valves
 Tachycardia, heart murmur
 Occur in ~50-60%
 Recurrent attacks of acute RF in
patients who had carditis with
their initial attack are associated
with high rates of carditis with
increasing severity of cardiac
disease
Sydenham chorea  Isolated, frequently subtle,
movement disorder
 Emotional lability, incoordination,
poor school performance,
uncontrollable movements, and
facial grimacing are
characteristic
 ~10-15% of patients
 Onset is insidious, may occur
months after GAS infection
 Demonstration of :
(1) milkmaid’s grip (irregular
contractions and relaxations of
the muscles of the fingers while
squeezing the examiner's
fingers),
(2) spooning and pronation of
the hands when the patient's
arms are extended, (3) wormian
darting movements of the
tongue on protrusion, and
(4) examination of handwriting
to evaluate fine motor
movements
 Rarely leads to a permanent
neurologic sequelae
Erythema Marginatum  rare (~ 1% ) but characteristic
rash of acute RF
 non-pruritic, erythematous,
serpiginous, macular lesions with
pale centers occurring on the
trunk/extremities with facial
sparing
5 Major Criteria Description
Subcutaneous  consist of firm nodules
Migratory  Occurs in ~75% of patients with nodules approximately 0.5-1 cm in
polyarthritis ARF; larger joints of knees, diameter along the extensor
ankles, wrists, and elbows surfaces of tendons near bony
 classically hot, red, swollen, prominences
exquisitely tender joints  <1%; correlated with significant
 Migratory - severely inflamed heart disease
joint can become normal within 1-
3 days without treatment, even as TREATMENT
1 or more other large joints
become involved  Antibiotics for 10 days for initial attacks
 Dramatic response even with  Anti-inflammatory therapy-aspirin, steroids
low-dose salicylates  Sedatives/anticonvulsants for sydenham chorea
 Almost never deforming  Long term antibiotics prophylaxis to prevent recurrences,
infective endocarditis

STREPTOCOCCUS AGALACTIAE
 Group B streptococci (GBS)
 Major cause of neonatal bacterial sepsis in the USA

Trans # 24 Bacterial Infections – Gram Positive Bacteria 5 of 6

 Facultative anaerobic gram-positive cocci, in chains or
diplococci
 Capsular polysaccharide as a major virulence factor
 Maternal vaginal or rectal colonization by GBS as a major risk
for early neonatal infection
Clinical Manifestations
 Early onset neonatal GBS disease
 Within the 1st g days of life
 Associated with chorioamnionitis, prolonged rupture of
membranes, and premature labor
 Infants are ill at the time of delivery or within the 1 st
24hours of birth
 Manifestations are sepsis (50%), pneumonia (30%),
meningitis (15%)
 Late-onset neonatal GBS disease
 Occurs on or after 7 days of life
 Bacteremia (45-60%), meningitis (25-35%), focal
infections (20%)-bone and joints, skin and soft tissue,
urinary tract, or lungs.
Diagnosis
 Diagnosis is thru isolation and identification of the organism
from a normally sterile site like blood, urine, CSF.
 Isolation of GBS from gastric or tracheal aspirates, skin or
mucous membranes indicates colonization and is NOT
diagnostic invasive disease
 Antigen detection methods using group B polysaccharide-
specific antiserum-latex particle agglutination
 Urine, blood, CSF samples
 Nonspecific CBC and CXR findings
 Cause disease only in children with damaged mucosal
surfaces or impaired immune response
 Emergence as a cause of nosocomial infection is
predominantly due to their resistance to antibiotics
commonly used in the hospital setting
 Neonatal septicemia, meningitis, endocarditis
 Nosocomial UTI
 Catheter-related infections
Treatment
 Highly resistant to Cephalosporins and semisynthetic
Penicillins (oxacillin)
 Moderately resistant to extended-spectrum penicillins such as
Tiicarcillin and Carbenicillin
 Ampicillin, Imipenem, and Penicillin are the most active B-
lactams against enterococci
 Some strains of E.faecalis and E. faecium demonstrate
resistance due to mutations in penicillin binding protein 5
or production of plasmid encoded B-lactamase
(E.faecalis)-completely resistant to penicillins
 Use of combination of penicillin plus a B-lactamase
inhibitor, imipenem or vancomycin
 Vancomycin resistant enterococci
 Use Linezolid, daptomycin, Tigecycline
V. REFERENCES
PowerPoint presentation & Lecture of Dr. Solis

Treatment
 Penicillin G- antibiotic of choice for confirmed GBS infection
 Initial empirical therapy of neonatal sepsis- ampicillin +
aminoglycosides or Cefotaxime
 For broad coverage pending organism identification and
synergistic bactericidal activity
 Prognosis
 Favorable outcome for focal infections
 Neurodevelopmental delay due to meningitis
E. NON-GROUP A or B STREPTOCOCCI
 B-hemolytic streptococci of Lancefield groups C to H and
K to V
 Group C and G - most common cause of human disease
 Normal flora of pharynx, skin, GI and GU tracts
 Wound infections, puerperal sepsis, cellulitis, sinusitis,
endocarditis, brain abscess, sepsis, nosocomial infections
 A-hemolytic streptococci that cannot be classified within a
Lancefield group- the viridans streptococci (S.bovis, S. mitis, S.
mutans, S. sanguinis, etc.)
 Normal flora of pharynx, nose, skin, GU tract
 Endocarditis, human bite infections
 Penicillin as antibiotics of choice
F. ENTEROCOCCUS
 Gram (+), catalase-negative facultative anaerobes
 Normal inhabitants of GI tract of humans and animals
 Found in oral secretions, dental plaque, URT, skin vagina
 E.faecalis- 80% of enterococcal infections
 E-faecium-20%
 Indigenous flora- presumed source of enterococcal infection
 Notorious for their frequent resistance to antibiotics
 Direct spread from person to person or from contaminated
medical devices-nursery, ICU

Clinical Manifestations
 Not aggressively invasive

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