Id Week 2

Front 1

staphylococcus aureus: hemolytic? gram? definitive characteristics?

Back 1

yes hemolytic
gram +
golden
coagulase +
catalase +

Front 2

three categories of the major important staphylococci

Back 2

staphylococcus aureus
S. epidermidis
S. saprophyticus

Front 3

S. aureus
S. epidermidis
S. saprophyticus
which is coag +?

Back 3

S. aureus

Front 4

S. aureus
S. epidermidis
S. saprophyticus
which is susceptible to Novobiocin?

Back 4

S. aureus and S. epidermidis

Front 5

S. aureus
S. epidermidis
S. saprophyticus
which can grow without oxygen?

Back 5

S. aureus and S. epidermidis


NOT:
S. Saprophyticus

Front 6

Causes of UTI in women

Back 6

1) E. coli 90%
2) S. saprophyticus 5%
TX: antibiotics

Front 7

What are structural characteristics of the staphylococci?

Back 7

Protein A in the cell wall - for prevention of phagocytosis

Coagulase on the surface - also antigentic

Collagen/Elastin/Fibronectin binding proteins

Clumping factor anchored in the cell wall peptidoglycan

Front 8

What do staphylococci secrete in the stationary phase?
(3)

Back 8

Enterotoxin B, TSST-1, alpha-toxin

Front 9

peptidoglycan of the staphylococci

Back 9

stability
50% of the weight
carbohydrate strands crosslinked by oligopeptides
elicit TNF-production
PMN toxicity
Endotoxin-like activity
Complement activation
elicit opsonic antibody
40% teichoic acid -

Front 10

teichoic acid in the staphylococcus wall

Back 10

40%, ribitol techioic acids covalently bound to peptidoglycan, adherence ligands to mucosal receptor sites, when bounds they elicit specific antibody formation

Front 11

what about the staph capsule?

Back 11

so there is this exopolysaccharide that we call microcapsule not visible by LM & is just external to cell wall:
- basis for serotyping
->80% of disease caused by serotypes 5&8
-immunogenic
-Antibody facilitates opsonophagocytosis
-only a few strains have the capsule & it's not clinically important
-slime is loosely adherent & may be important in pathogenesis (especially for prosthetics)

Front 12

MSCRAMMS

Back 12

microbial surface components recognizing adhesive matrix molecules

many staphylos have proteins with structural similarity - secretory signal sequence or ligand binding domain at N terminus
- (+) charged AA extend into cytoplasm
-hydrophobic membrane-spanning domain
-C-terminus cell wall anchoring region

Front 13

protein A

Back 13

staphylococcus,
in cell wall
binds Fc region of all human IgG subclasses except IgG3
antiphagocytic

Front 14

staphylococcus enzymes

Back 14

catalase (H2O2 --> H2O + O2) hyaluronidase (hydrolyzes hyaluronic acid facilitating spread), coagulase (interacts with fibrinogen D causing clumping - used to distinguish S. aureus from coagulase negative Staph. )

Front 15

staphylococcus toxins

Back 15

alpha, beta, gamma, delta act on cell membranes to disrupt them

panton valentine leukocidin present in most community acquired MRSA

enterotoxins A B C D E cause food poisoning (peristalsis - also superantigens)

Toxic Shock Syndrome Toxin I (TSST-1) - cause clonal expansion of resting T-cells & results in massive cytokine release (Ab to TSST-1 is protective; however, 85% of individuals who experience disease subsequently fail to make Ab)

Front 16

exfoliatins

Back 16

responsible for the scalded skin syndrome;
act on cells at the lvl of stratum granulosum to produce rash blisters & exfoliation
-act as superantigens
-antibody is protective

Front 17

first step of the staphylococcus infection?

Back 17

adherence

Front 18

colonization of staphylococcus aureus?

Back 18

30-50% colonized in the nasopharynx or nose;
10-20% are persistently colonized by the same strain;

Front 19

who's more prone to staphylococcus aureus?

Back 19

Physicians & nurses, as well as persons who have breaks in the skin for any reason, are more likely to carry S. aureus:
Skin conditions like atopic dermatitis & eczema;

Individuals who use needles for any reason are more likely to be colonized by S. aureus.

Front 20

Phagocytosis by _______may allow for persistence of staphylococcus

Back 20

non-professional phagocytes(e.g., endothelial cells

Front 21

Stimulation of_________may allow for accumulation of organisms. (staphylococcus invasion after adherence)

Back 21

Stimulation of tissue factor production may allow for accumulation of organisms.

Front 22

how do the extracellular products of S.aureus affect PMNs?

Back 22

Extracellular products of S. aureus stimulate PMN chemotaxis into infected sites.

Opsonization of S. aureus:
Non-immune subjects require complement;
Ig to peptidoglycan, teichoic acids or microcapsule in immune subjects;
Protein A impairs phagocytosis;
Deficiencies of Ig or complement impairs opsonization.

Front 23

how many S. aureus are needed to infect my intact skin compared to one with a suture?

Back 23

>10,000,000 S. aureus are necessary to cause infection of intact skin;
In the presence of a suture, the number of S. aureus necessary to cause infection drops to 100 organisms;
Traumatized tissue, blood clots & inflammatory material also predispose to infection by acting as foci of decreased resistance.

Front 24

infections of the skin depending on how deep it is - what are they?

Back 24

Impetigo - just epidermis
Erysipelas - dermis
Cellulitis - dermis + subcutaneous fat
Necrotizing fasciitis - subcutaneous fat + fascia

folliculitis - along the hair follicle

Front 25

furuncle

Back 25

Deep-seated infections around hair follicles.
Recurrent furunculosis is seen in individuals who become colonized in nares, and other areas.
Treat with hot compresses, I & D as necessary and appropriate antibiotics.

Front 26

carbuncle

Back 26

= boils; Deep-seated infections around hair follicles that result from coalescence of furuncles.
Treat with hot compresses, I & D as necessary and appropriate antibiotics

Front 27

impetigo

Back 27

Superficial skin infection with papule-vesicle-pustule-crust stages;
Disease can be spread to other family members via fomites (e.g., hand towels);

Front 28

what skin infection is most likely due to S. aureus?

Back 28

Bullous impetigo is particularly characteristic of S. aureus.

Front 29

Hidradenitis Suppurativa

Back 29

Disfiguring infection affecting the apocrine sweat glands that involves the axilla, groin & perineum, most commonly in African-American people.
Therapy requires antistaphylococcal antibiotic &, frequently, surgical debridement.

Front 30

most complicated staphylococcal soft tissue infections are associated with ????

Back 30

with collections of pus that must be drained.

Compared to the dish water type pus with streptococcus – this here is much more and

Front 31

most common cause of pyomyositis

Back 31

S. aureus -- pus inside the muscle - must be drained

Front 32

bacteremia with S. aureus?

Back 32

common and occurs as a primary bacteremia (ex: endocarditis) or as a secondary to another site of infection (skin abcess, IV catheter, pneumonia)

Front 33

Clinical Clues That May Help Determine if a S. aureus Bacteremia is Due to a Complicated Infection and/or Endocarditis

Back 33

with any of these we must treat as if endocarditis:
1) younger pateint without underlying illness
2) community-acquired (illicit drugs)
3) no recognizable primary infections
4)skin evidence of systemic infections
5) + echocardiogram (TEE)
6) failure to defervesce by 72 hours on therapy
7) + blood culture at 48-96 h on therapy

Front 34

S. aureus treatment

Back 34

identify focus, drain
treat w/ vancomycin as if it were a strain resistant to methicillin
adjust therapy once results of susceptibility show a methicillin susceptible strain:
Vancomycin is an inferior agent if organism turns out to be methicillin susceptible

Repeat blood cultures at 48-96 hours to document clearing of bacteremia;
If there is evidence of complicated infection/endocarditis, duration of therapy should be at least 4 weeks; otherwise, 2 weeks is probably sufficient.

Front 35

most common cause of osteomyellitis?

Back 35

S. aureus

3 pathophysiologic processes result in osteomyelitis:
Bacteremic spread to long bones of children & vertebrae of adults;
Contiguous to another site of infection;
Vascular insufficiency.
Treat with surgical debridement & prolonged antibiotic therapy

Front 36

diseases from Staphylococcus aureus?
spread (not toxins)

Back 36

osteomyeltis, septic arthritis (bacteremic spread, trauma, infected prosthesis), bacteremia, folliculitis (foruncles and carbuncles), impetigo, erysipelas, cellulitis/abscess, pyomyositis, necortizing fasciitis, Hidradenitis Suppurativa (disfiguring, apocrine sweat glands, african american), pneumonia (
1) Aerogenous from aspiration of oral flora, occurring in mechanically ventilated or debilitated patients or following severe viral respiratory infections.

2) Hematogenous from another source:
Usually parenteral drug addicts who have endocarditis, or in patients with infected indwelling intravenous catheters.
)

Front 37

Staphylococcus infections caused by effects of toxins

Back 37

Staphylococcus scalded skin sydrome
(large bullae and + nokolsky sign; due to exfoliatin; < 5 years; associated with local S. aureus infection of nasopharynx, umbilicus or Urinary tract; RX: antibiotics active against S. aureus; supportive skin care; management of fluid & electrolyte losses.)

Front 38

CDC

Back 38

center of disease control

Front 39

Definition for The Staphylococcal Toxic Shock Syndrome

Back 39

Hypotension: Systolic BP under 90 mm Hg.
Fever: Temperature over 38.9oC
Rash: Diffuse macular erythroderma;
Desquamation 1-2 weeks after onset of illness, particularly of palms & soles;

Multisystem involvement: more than 3 of the following:
GI: vomiting or diarrhea;
Muscular: severe myalgia or up CPK;
Mucous membrane – vaginal, oropharyngeal or conjunctival hyperemia;
Renal: BUN &/or creatinine > 2X ULN;
Hepatic: Total bilirubin, AST or ALT > 2X ULN;
Hematologic: platelets under 100,000;
CNS: disorientation or alterations in consciousness.
Negative results for Rocky Mountain spotted fever, leptospirosis, or rubeola;
Negative blood, throat or CSF cultures (except for S. aureus).

Front 40

compare the mortality of the staphylococcus vs streptococcus shock syndrome

Back 40

streptococcus has much higher mortality (50%!)

Front 41

food poisoning

Back 41

enterotoxin from staphylococcus;

Explosive onset 2-6 hours after ingestion;
No fever;
Vomiting is prominent;
Usually resolves, with supportive care only, within 12-24 hours.

Front 42

where do we get coag - staphylococci from ?

Back 42

since they have low virulence, with the exception of some cases of native valve endocarditis, the majority of coagulase-negative staphylococcal infections are hospital-acquired and associated with altered immunity or breaks in the normal integrity of tissues.

Front 43

Pathogenesis of Infection Due to Coagulase (-) Staphylococci

Back 43

Exopolysaccharide (slime) is the factor that has received the majority of attention:
Important for initial adherence;
Important for resistance to phagocytosis by PMN;
Associated with multiple antibiotic resistances.

Front 44

Well-Documented Infections Caused by Coagulase Negative Staphylococci

Back 44

Urinary tract infections:
Hospital acquired – usually S. epidermidis in association with a urinary catheter;
Outpatient – S. saprophyticus is 2nd most common cause of UTI in young women.
Bacteremia in critically ill or immunosuppressed patients, related to vascular catheters.
Native valve endocarditis:
Unusual, & occurs in:
Patients with abnormal cardiac valves;
Parenteral drug addicts.

Front 45

Staphylococcus cohnii

Back 45

Staphylococcus cohnii is a rare opportunistic pathogen for humans causing urinary tract infections, wound infections, endocarditis, and septicemia.

Front 46

The great majority of infections with coagulase-negative staphylococci occur in association with ???

Back 46

indwelling foreign devices (prostheses):

Intravenous & intraarterial catheters;
Hemodialysis shunts & catheters;
Cerebrospinal fluid shunts;
Peritoneal dialysis catheters;
Pacemaker wires & electrodes;
Prosthetic orthopedic joints;
Vascular grafts;
Prosthetic cardiac valves.


Diagnosis of infections due to CNS can be problematic because of the difficulty differentiating true infection from contamination

One must pose the following questions in an attempt to assess the possibility of true infection:
1. Does the patient have a clinical scenario consistent with a coagulase-negative staphylococcal infection?
2. Are there other likely explanations for fever or is there an infection at another site?
3. Does the patient have >1 positive blood cultures?

Front 47

Staphylococcus aureus Antibiotic Susceptibility

Back 47

Penicillin was “discovered” in 1929 when Fleming made the observation that a contaminating colony of Penicillium mould inhibited the growth of S. aureus on a culture plate.

Front 48

penicillin resistance of the S. aureus due to ?

Back 48

-lactamase mediated penicillin resistance:
Prior to the early 1940s, virtually all S. aureus were susceptible to penicillin.
In 1944, Kirby described -lactamase production by S. aureus, although penicillin was not yet in clinical use.
From 1944 to 1947, after penicillin became readily available, S. aureus penicillin susceptibility dropped from 100% to <25%.

Extracellular enzyme that disrupts the -lactam ring of penicillins & results in penicillin resistance:
Inducible & coded on plasmids; 99.9% expression.
Order of susceptibility to -lactamase:
penicillin>>>>dicloxacillin>cloxacillin>oxacillin>nafcillin
Clinically significant; only 5% of S. aureus are now susceptible to penicillin.

Intrinsic resistance: MRSA:
Semisynthetic antistaphylococcal penicillins (methicillin, etc.) were introduced in 1960; however, even before widespread clinical use, resistance was described:
In the 1970s, strains resistant to methicillin & other antibiotics were reported from Australia, and eventually spread to the U.S.


Methacillin resistance on a chromosome (Inducible & carried on a chromosomal mecA gene (which is also carried on a mobile staphylococcal chromosomal cassette – SCCmec);, but the penicillin resistant is on a plasmid;

Front 49

risk factors for getting Health care associated MRSA?

Back 49

Risk factors associated with acquisition of HA-MRSA include:
Hemodialysis; CAPD; IV drug abuse; dermatitis; IDDM; burns; exposure to antibiotics (cephalosporins, quinolones, aminoglycosides); prolonged hospitalization; & greater severity of underlying illnesses.
Organisms tend to be resistant to multiple classes of antibiotics, not just beta-lactams.

Front 50

CA-MRSA?

Back 50

Genetically, CA-MRSA are different than HA-MRSA, and carry the small, unique SCCmec Type IV mobile genetic elements.
This suggests that these organisms did not originate from hospital strains that disseminated into the community.
The majority of infections are skin & soft tissue (frequently complicated), but patients have developed invasive pneumonias, bacteremias, endocarditis & osteomyelitis.
>60% of staphylococcal isolates from the community are CA-MRSA in many Houston hospitals (TCH, MEDVAMC, Ben Taub, etc.)
being erroneously attributed to brown recluse spider bites.

Front 51

Typical Antibiograms for Community- & Hospital-Associated MRSA

Back 51

Community Hospital
Oxacillin R R
Erythromycin S or R R
Clindamycin S* R
Gentamicin S R
TMP/SMX S S
Ciprofloxacin S R
Minocycline S S

Front 52

MRSA strains that demonstrate discordance between erythromycin susceptibility & clindamycin susceptibility (ClinS/EryR) may have 2 responsible mechanisms that have clinical significance:

Back 52

msrA  encodes an ATP-dependent efflux pump that confers resistance only to 14- & 15-membered ring macrolides & type B streptogramins, but not to lincosamides (e.g., clindamycin, which will be sensitive).


iMLS  inducible macrolide-lincosamide-streptogramin B resistance due to presence of erythromycin ribosomal methylase (erm) genes.
Clindamycin therapy induces resistance.
detect with double-disk diffusion assay (D test).

Front 53

Possible Therapies for Hospital Associated-MRSA Infections

Back 53

Parenteral therapies Dose
Vancomycin 1
Linezolid (Zyvox®)
Quinupristin/dalfopristin
(Synercid®)
Daptomycin (Cidecin®)

Oral therapies
Linezolid (Zyvox®)
Minocycline
TMP/SMX
Clindamycin* (must be erythromycin suscptible)
TMP/SMX
Minocycline
Ciprofloxacin
Linezolid

Front 54

VISA strains of MRSA

Back 54

Vancomycin intermediate strains of S. aureus

9 reported cases of VISA in Japan (5 patients) and USA (4 patients: MI, FL, NJ, TX);
Most patients had indwelling catheters (frequently, a dialysis catheter);
All patients had received prolonged vancomycin therapy, usually inappropriately;
MIC90 for vancomycin = 8 g/ml;
Mechanism of resistance not well delineated  thicker cell wall?
Remain susceptible to other antibiotics (TMP/SMX, minocycline, rifampin). Patients appear to respond to vancomycin + beta-lactamase combinations.

must use MUCH more

Front 55

how did this truly vancomycin-resistant S. aureus originate?

Back 55

It has recently been shown that S. aureus produces a sex pheromone that can stimulate an enterococcal vancomycin-resistant conjugative plasmid.
It is highly likely this occurred in patients’ wounds that were colonized with both VRE & MRSA.

Front 56

Corynebacterium diphtheria antidote

Back 56

anti-toxin developed in 1925 - started the Iditarod;
still in countries w/o active vaccine.

Front 57

corynebacterium diphteria morphology

Back 57

gram + rods
gravis / mitis / intermedius (different colony sizes)

Front 58

corynebacterium diphteria media

Back 58

tellurite - must inform lab
grows black colonies

Front 59

corynebacterium diphteria pathogenesis

Back 59

transmission is via droplets or direct contact; humans are only host; incubation 2-4days, carrier state is significant (only pathogen if it can make the toxin)

colonization: multiply on mucous membranes (no invasion)

virulence: potent protein exotoxin: Diphtheria toxin

Front 60

corynebacterium diphteria exotoxin

Back 60

encoded by beta-phage - the plasmid brings in the dtx gene.

Fe represses the transcription. that's how it knows it's inside the cell- here there is very little Fe and the repressor is lifted;

Front 61

corynebacterium diphteria hemolysis

Back 61

NONE

Front 62

corynebacterium diphteria is???__

Back 62

fastidious (requires nicotinic acid, pantothenic acid and other vitamis) - must alert the lab!

Front 63

corynebacterium diphteria A-B toxin?

Back 63

AB toxin is made - starts from a single polypaptide that get's processed;

free toxin (ABE units) binds and enters via RME (+clathrin); acidifcation --> insertion into membrane --> catalytic molecule enters cell and ribosylates the elongation factor 2 = death @ 40ng

Front 64

Elongation factor 2

Back 64

there is a funny amino acid on this protein - diphthemide -
the bacteria can ribosylate that

Front 65

corynebacterium diphteria types of disease

Back 65

Respiratory: droplets as transmission, sore throat, fever, enlarged lymph nodes and edema in neck, malaise; pseudomembrane of neutrophils+fibrin+epithelial cells covers throat; systemically: myocardial damage, arrhythmia, myocarditis, congestive heart failure, cranial + peripheral neuropathy and paralysis

Cutaneus: common in homeless + tropics; direct contact; impetigo-like lesions on arms or legs, localized ulcers, systemic effects are rare

Front 66

sore throat and swolen Bull-nack of the diphtheria vs mumps?

Back 66

mumps the child is still active, seems ok.
diphtheria child is down/in bed/low grade fever; 10-25% - cardiac arrest 2-3wks after onset!

Front 67

cutaneus corynebacterium diphteria is a _____ for the respiratory form.

Back 67

reservoir of spread;

Front 68

loeffler agar / telluria

Back 68

for corynebacterium diphteria

Front 69

determine if they have the toxin?

Back 69

PCR, Elek immunodiffusion; Schick test

Front 70

corynebacterium diphteria antitoxin

Back 70

DAT - antitoxoid horse serum;
Iditarod 1925 dog race to Nome to deliver the antitoxin;

also must give vaccination - bc the disease is not vaccinating;
no lifetime immunity;
circulating toxin must be eliminated;

Front 71

corynebacterium diphtheria vaccines

Back 71

2 mo DTaP
4 mo DTaP
6 mo DTap
15-18 mo DTap
4-6 years DTap

booster every 10 yrs: Tdap

Front 72

Listeria Monocytogenes where?

Back 72

dairy cattle, water, food, cabbage, Jalisco cheese, chicken,

Front 73

Listeria Monocytogenes morphology

Back 73

Gram +, motile, rod, grows on tellurite, grows at 4 degrees in the fridge, catalase +, weakly hemolytic (listerolysin), resistant to high salt + bile;

Front 74

Listeria Monocytogenes pathogenesis

Back 74

interacellular; actin tail spreads it to another cell;

Front 75

Listeria Monocytogenes virulenece

Back 75

listerolysin allows escape from phagosome, internalin - facilitastes the entry into the cell; ActA - assembles actin tail; phosopholipases - phagosome escape and cell to cell spread

Front 76

Listeria Monocytogenes syndromes

Back 76

febrile gastroenteritis
maternal listeriosis
sepsis
meningitis
focal infection

normally it will activate APC - TH1 - macrophage, but immuno-compromised people are at risk

Front 77

Listeria Monocytogenes TX

Back 77

antibiotics: use one that can penetrate host cells;
pasteurization + sterilization
avoid unpasteurized foods by pregnant women and the immunocompromised

Front 78

Listeria Monocytogenes motile?

Back 78

at 22 but not at 37 celcius

Front 79

Bacillus anthracis

Back 79

gram +
non-motile - box cars
spore forming

Front 80

Bacillus anthracis disease

Back 80

cutaneous: 95%, arms neck fase, small ppule then necrotic eschar surrounded by inflammation, swelling, painless lesion

Intestinal:
spore ingestion contaminated meat; nausea, vomiting and diarrhea result from GI invasion;

Pulmonary: woolsorters disease
aquired by inhalation of spores (hides or raw wool); initial influenza-like symptoms progress to severe respiratory distress ( not a true pneumonia)
usually fatal within 1-2 days of onset acute symptoms;

Front 81

Bacillus anthracis genes/plasmids

Back 81

require the protein capsule + the LF(lethal factor, MKKK), EF(edema factor) and PA(protective antigen) products;

tripartite toxin is 2 activity domains + 1 binding;

aerosols/skin contact

Front 82

Bacillus anthracis TX

Back 82

antibiotics: 6 wk ciprofloxacin / deoxycyline;

Front 83

Bacillus cererus

Back 83

fried rice;
gram + rod
motile
no capsule
makes spores
resistant to penicillin
secretes lecithinase- cleaves lipids--- ocular disease

Front 84

Bacillus cererus diseases

Back 84

food posioning
GI - delayed, diarrhea, different toxin

both are self-limiting

invasive: eye infection, cellulitis in immuno-compromised
pneumonia - rare
cutaneous infection - new

Front 85

Bacillus cererus enterotoxins

Back 85

lecithinase + hemolysin

Front 86

NFGNB (4)

Back 86

Pseudomonas aeruginosa
Stenotrophomonas maltophilus
Burkholderia cepacia complex
Acinetobacter species

Front 87

patient risk factors of NFGNB

Back 87

acquire resistance; use diverse carbon sources; ventilator; beds; susceptible patients, broad antibiotic amoxa-smash-em-all tx; loss of normal boundaries (catheter, surgery, neutropenia)


1) contact with health care system (espcially admission ICU)
2) reciept of broad-spectrum antibiotics
3) immunocompromised state
4) Bkdn of typical barriers (catheter, surgery, burns....)
5) Breakdown in infection control practices

Front 88

major kinds of infections caused by each of the NFGNB

Back 88

?

Front 89

discern importance of distinguishing NFGNB colonization from infection

Back 89

?

Front 90

Pseudomonas aeruginosa

Back 90

leading one, slime in the hot-tub, slime in ventillator water, they are considered less pathogenic, possibly less of an issue

catheter related bacteremia/UTI
ventilator related pneumonia
chronic lung infection in cystic fibrosis
bacteremia with neutropenic pt

causes: ecthyma gangrenosum in pt with PA bacteriemia

Science:
LPS protects from complement, leads to septic shock; SLIME production leads to BIOFILM formation - difficult to eradicate - must pull plastic out

Front 91

CF patients ID?

Back 91

Pseudomonas aeruginosa

major cause of respiratory failure
PA often acquired early in life, turn to slime producing variants
-genetic adaption to minimize host ability to identify them

Front 92

TX of PA

Back 92

NOT penicillin;
inherently resistant to most beta-lactams, macrolides, sulfas, tetracylines

susceptibility is highly varied - efflux pumps!
multi-drug resistance - efflux pump + polymyxin has become last resort (nephrotoxic)

need to give double-cover? 20% response with only one...
personal feeling: getting catheter out is more important than the second agent;

Front 93

Stenotrophomonas maltophila

Back 93

low virulence - more often colonizer

big for cancer patients
inherently resistant to carbapenem - increases the prevalence with increaseing carbapenem use;

hot spots: spain + latin america

Front 94

Major infections due to Stenotrophomonas m.

Back 94

more often colonizer
catheter-based bacteremia
ventilator assoc pneumonia
much rarer infections: (skin and soft tissue, nosocomial, caterther, UTI)

how sick u are is very important for the outcome -
(pt with broadspectrum AB especially carbapenems, maligancy, catherters..)

data bad; low # of true infected pt;
trimethoprim-suflamethoxazole has most experience (ticarcillin-clavulanate, quinolones,get the catheters out!)

Front 95

Actinetobacter

Back 95

Suck DNA out - rapidly adapting; Ben taub problem; soldier problem,
hard to identify
Acinetobacter baumanii
100% of soil samples,
colonizes 25% skin, contaminates blood cultures common, most common NFGNB carried on hands of health care personnel;
can persist for wks in linens

common AB infections:
-more often colinizes
ventilator related pneumonia
catheter assoc. bacteremia
-stomach open in Ben Taub- tertiary peritonitis

Front 96

AB TX

Back 96

prevention is better;
variable resistance
use ampicillin-sulbactam
sulbactam has intrinsic activity
polymyxin has also been used

Front 97

Burholdaria (3)

Back 97

pseudomallei (meliodosis) and mallei (glanders),
don't cause disease

BCC does cause disease mainly with pt of CF and chronic granulomatous disease (CGD)

nomenclature genomovar II and III stains predominate among CF

agro-industry loves this antibiotic

Front 98

BCC and CF

Back 98

isolated from 5% of CF

range of asymptomatic colonization to bacteremia and death;
can be transmitted patient-to-patient
carriers may have increased risk of post-transplant

Front 99

BCC and GCD

Back 99

major cause of pneumonia among CGD pt

may result in bacteremia and death; #2 cause of death in CGD after Aspergillus

BCC can cause syndromes similar to other NFGNB but at much lower rates

Front 100

BCC and Virulence

Back 100

multi-chromosomal, highly resistant kind of like pseudomonas

Front 101

NFGNB summary points

Back 101

environmental isolates that colonize and cause disease in distinct clinical circumstances

understand pt likely to have NFGNB infections important to establish effective therapy as early as possible

Do not attempt to sterilize pt with NFGNB

Front 102

Citrobacter species

Back 102

enterobacteriaceae

C. freundii
C. koseri
C. diversus

Front 103

Enterobacter species?

Back 103

enterobacteriaceae

E. cloacae
E. aerogenes

Front 104

Klebsiella species

Back 104

enterobacteriaceae

K. pneumoniae
K. oxytoca

non-motile
slime

Front 105

Morganella species

Back 105

enterobacteriaceae

M. morganii

Front 106

Proteus species

Back 106

enterobacteriaceae


P. mirabilis
P. vulgaris

swarms and smells

Front 107

Providencia species?

Back 107

enterobacteriaceae

P. stuartii
P. rettgeri

Front 108

Salmonella species?

Back 108

enterobacteriaceae

S. enterica
S. serovars typhi
S. enteritidis

lactose -

Front 109

Serratia species

Back 109

enterobacteriaceae

S. marcescens

RED

lactose -

Front 110

Shigella species

Back 110

enterobacteriaceae

S. dysenteriae
S. flexneri
S. boydii
S. sonnei

non motile

lactose -

Front 111

Yesinia species

Back 111

enterobacteriaceae

Y.enterocolitica
Y. pseudotuberculosis
Y. pestis

lactose -

Front 112

Tests to identify enterobacteriaceae

Back 112

oxidase +
can reduce nitrate to nitrite
grow them selectively and dfferentially
check lactose fermentation (MacConkey lactose agar) [klebsiella, e.coli, enterobacter are +]

Front 113

Peritrichous flagellae example

Back 113

E. coli
flagella all around

Front 114

capsule functions

Back 114

resistence to dessication,
to complement

biofilm formation
camouflage

Front 115

LPS

Back 115

O-polysaccharide - shields like a capsule
KDO-core carbohydrate; repells negative charges and allows Ca2+ to come in and destabilize the membrane so lysozyme can get in
Lipid A = endotoxin -

Lipid A and KDO are unique and conserved for gram negative

inner layer of outer membrane of gram - bacteria

Front 116

LOS

Back 116

Neisseria, Haemophilus
don't live in gut, not source of diarrhea
missing O antigen
sensitive to bile salt

Front 117

what are those membrane blebs on E. coli??

Back 117

endotoxin - cause sepsis

Endotoxin is embedded in the membrane, not secreted—but is shed in membrane blebs

Front 118

virulence factors of E. coli

Back 118

Adhesins
Toxins
Iron acquisition
Capsules
LPS
Plasmids

Front 119

Exo- and Endo- toxins

Back 119

Exotoxins
Secreted across membranes into environment
Gram pos and neg
Protein
Rarely pyrogenic


Endotoxins
Physically attached to outer membrane, structural component
Gram negative only
Lipopolysaccharide
Highly pyrogenic


pyrogen free = endotoxin free

Front 120

Siderophores

Back 120

small molecular weight, high-affinity iron-binding compounds that can scavenge the iron away from the high-affinity iron-binding proteins in the host to present it as a ferric-siderophore complex to the cognate outer membrane protein receptors and subsidiary iron transport proteins (Fig. 1).
Yesinia – more common in people with Fe overload


like a slimy hand out of the cell and back in with the iron

Front 121

febrile diarrhea vs. bacteremia after cardiac procedures and oncology patients after getting infusions

outbreaks

Back 121

febrile diarrhea: salmonella

red: serratia marcescens

Front 122

Identify Enterobactericeae

Back 122

oxidase +
reduce nitrate to nitrite (urine test)

Bacteria are easy to grow -
-selective (others die in those conditions)
-differential (colors)

Front 123

Lactose +

Back 123

Klebsiella, Enterobacter, E. coli (no S / P )

Front 124

fct of capsule

Back 124

shield, camouflage, resistance to drying, biofilm formation (anti antibiotics...)

Front 125

KDO?

Back 125

core part of the LPS (also OPS and Lipid A) = all together it's endotoxin

OPS - different types, antigenig, shild
KDO - conserved, neg charge

Front 126

LOS

Back 126

lipo-oligo saccharide

sensitive to bile salts

Neisseria
Haemophilus
can't cause diarrhea
missing the long O antigen

LPS needed so survive digestion

Front 127

Virulence factors of E. coli

Back 127

Adhesins, Toxins (hemolysin, Lipid A...), Iron Acquisition (siderophores), Capsules, LPS, Plasmids

always relationship between host, environment and organism.

Front 128

Endo vs. Exotoxins

Back 128

Exotoxin: secrete across membranes into environment, gram + and -, protein, rarely pyrogenic

Endotoxin:
physically attached, gram -
highly pyrogenic
lipopolysaccharide

"pyrogenic free" = "endotoxin - free"

Front 129

Who's more susceptible to Siderophore-lacking bacteria - such as Yersina?

Back 129

during times of Fe overload -
can make it in environment with lots of Fe -

dialysis anemic pt get Fe - more susceptible

Front 130

careful with TX when phages are involved

Back 130

Treating with antibiotics will make them sicker because the phages inside the bacteria will sense danged and will want to come out and replicate

Front 131

nosocomial epidemic
discovered at MD Anderson

Back 131

Serratia marcescens

TB doesnt grow on agar
candida albicans - white
pseudomonas albuginosa - green

IV Mg syringes
heparin pefilled syringes

Front 132

628 persons reported from 47 states
73% female
Diarrhea, abdominal cramps, fever, dysuria
20% hospitalized
Associated with consumption of peanut butter
Identified by PulseNet to be the same strain
Molecular subtyping network

Back 132

Salmonella

Front 133

pulse net?

Back 133

pulse gel electrophoresis - see if they're related strains

Front 134

Enterobactericeae nosocomial

Back 134

pt own flora, then they get breaks in the local immunity and get sick from it;

medical devices

hospital acquired organisms frequently MDR

The patient’s own flora usually the source
Exogenous sources can cause multi-patient outbreaks
Medical devices break normal host defenses and increase risk of infection
Hospital-acquired organisms frequently multi-drug resistant

Front 135

E. coli and Nosocomial UTI

Back 135

Community acquired UTI: 80% from E. coli
Nosocomial UTI: 40%
Usually catheter-related
Other sources of nosocomial UTI:
Gram negatives:
Klebsiella, Enterobacter, Serratia, Proteus, Providencia
Non-Enterobacteriaceae: Pseudomonas
Gram positive bacteria, Candida
Major source of gram-negative bacteremia

Front 136

who has a Resistant to ampicillin
Chromosomally-encoded β-lactamase

Back 136

Klebsiella - so add a β-lactamase inhibitor to increases the zones

Front 137

Proteus mirabilis

Back 137

Associated with long-term use of urinary catheters
Produces urease, which causes crystal formation
Highly motile
Proteus was the son of a sea god who could change his shape
Biofilm-forming organism


sea-god

bacteria don't jump! safe to sniff -

Front 138

Morganella
Providencia

Back 138

Essentially very close cousins of Proteus
Seen in individuals with long-term catheters
Nursing homes
Long-term care facilities
Spinal cord injury


cousin of proteus
swarms too

Front 139

Enterobacter

Back 139

Lactose fermenters, mucoid
Sources
Most common: endogenous intestinal flora
Patient-to-patient spread
Common source outbreaks
Opportunistic pathogen
Antimicrobial resistance is a treatment issue
Inducible, chromosomal β-lactamase
High baseline mutation rate
MDR and ESBL (extendend spectrum beta lactamase) plasmids
Resistance may emerge during treatment

Front 140

serratia naming

Back 140

has nothing to do with serratius - that was the steam boat inventor

holy communion turning red - "blood"

Front 141

citrobacter diversus

Back 141

brain abscesses in babies

Front 142

1 day history of fever and bloody sputum
T99, P150, BP 102/72, RR40, 02 88%
Diaphoretic male in respiratory distress
Rales over left lung field
Chest CT: mass in LUL with shift of mediastinum, smaller mass in RUL
Biospy taken

Back 142

Klebsiella pneumonia

Friedländer’s pneumonia and sepsis caused by Klebsiella pneumoniae
Fulminating lobar pneumonia
Frequently in alcoholics,
Predilection for upper lobes
Currant jelly sputum in 50%
Radiologic appearance: mass lesion with bulging fissure
Causes 1% of community-acquired pneumonia


But you will see this infection most likely in your career, particularly at VA or Ben Taub – the alcoholism promotes this – how?


empyema - nasty one

Front 143

63 yo wm with chronic OA (osteoarthritis), prior R knee repair
Underwent R knee total joint arthroplasty
3 weeks later with increased pain and swelling
4 weeks after TKA had fever and copious drainage from wound
Gross purulence seen during surgery

Back 143

crystal + bile film

P. mirabilis, like Klebsiella pneumoniae, can cause both uncomplicated and complicated pyelonephritis, whereas other Proteus species are more often associated with complicated pyelonephritis. A, On blood agar, Proteus produces swarming colonies, spreading a grayish-blue uniform film all over the media surface. This migration occurs in periodic cycles, producing concentric zones. B, On MacConkey agar, uncolored (nonlactose-fermenters) and swarming colonies can be observed.


Underwent polymer exchange
One stage procedure
Metal hardware left in place
Treated with ciprofloxacin
Wound dehiscence with foul drainage 10 days later
Plan for 2-stage exchange

Front 144

what saves lives?

Back 144

water

not antibiotics or vaccines

Front 145

Pathogenesis by ETEC strains

Back 145

Fimbriae adhere to intestinal mucosa
Elaborate one or both of two enterotoxins
Heat stable (ST) increases cGMP
Heat labile (LT) increases cAMP
Very similar to cholera toxin
AB toxin
Both act on the CFTR to cause secretion of chloride into the lumen
Enterotoxin = an exotoxin that acts upon GI epithelium to increase fluid secretion


Many different fimbriae, and they play a major role in pathogenesis.

Heat stable toxin: small, poorly immunogenic molecule that is similar to endogenous peptide hormones guanylin and uroguanylin

Heat labile: one A subunit and 5 B subunits, close homology with cholera toxin.

CFTR: cystic fibrosis transmembrane receptor—actively secretes chloride into the intestinal lumen. Sodium and water follow passively.

Front 146

Enterohemorrhagic E. coli (EHEC)

Back 146

part of the Shiga toxin producing e.coli


Cause of outbreaks of bloody diarrhea
Bagged spinach, Taco Bell, hamburger meat
Shiga toxin kills the host cell
Destroys ribosomal protein synthesis
Reservoir: GI tract of cattle and large herbivores
Organisms survive in the environment
Outbreak sources: ground beef, petting zoos, fresh produce

Front 147

O157:H7

Back 147

is the most important clone of EHEC

Produces shiga toxin
SLT-1 and SLT-2 (Stx1 and Stx2)
Encoded on bacteriophage
Has LEE pathogenicity island
Locus of enterocyte effacement
Attaching and effacing effect (can erode the intestinal villi)
Loss of microvilli
Also found in EPEC

Front 148

STEC: vs
EHEC

Back 148

STEC: shiga toxin-producing E. coli
EHEC are essentially STEC that also have the LEE pathogenicity island

Front 149

Clinical Presentation of EHEC

Back 149

Severe abdominal cramping followed by watery and bloody diarrhea
Fever frequently absent
Hemolytic uremic syndrome (HUS)
Occurs in 5-10% of individuals with EHEC
Microangiopathic hemolytic anemia
Organs become ischemic, esp. kidneys

Front 150

Management of EHEC

Back 150

Laboratory diagnosis
Streak sample on sorbitol-MacConkey agar
PCR for genes encoding shiga toxin
Enzyme immunoassays for shiga toxin in stool
Treatment: supportive
Antibiotics contraindicated

Prevention
Cook ground beef, wash hands

Front 151

Enteropathogenic E. coli (EPEC

Back 151

Leading cause of severe diarrhea in babies (<6 months) in developing countries
Pathogenesis: attaching and effacing effect on intestinal epithelial cells
Results in loss of microvilli
Causes watery diarrhea, can be severe
Also vomiting, low grade fever
Protracted disease causes malnutrition
Breastfeeding is highly protective
Inhibits adherence, contains protective antibodies against virulence factors


actin pedastool -

Front 152

Enteroaggregative E. coli (EAEC)

Back 152

Typical stacked brick adherence pattern
Second most common cause of travelers’ diarrhea

Front 153

case: Elective rotation in Guadalajara, Mexico
7 days after arrival develops watery diarrhea, nausea, abdominal cramps
No fever
No blood or mucus in the stool
Had eaten undercooked chicken 3 hours prior to onset
Stool without fecal leukocytes

Back 153

ETEC

not the chicken, that was too soon before

Front 154

candida is always?

Back 154

a fungus

Front 155

Shigella

Back 155

Causative agent of bacillary dysentery
“Dysentery” coined by Hippocrates
Frequent passage of stool containing blood and mucus
Straining and painful defecation
Bacillary dysentery has had a powerful influence on military campaigns
Long campaigns and sieges produce epidemics
Four species: S. sonnei, S. flexneri, S. dysenteriae, S. boydii

Front 156

During the Civil War, 20% of Confed soldiers and 10% of Union soldiers died of infections—

which ones?

Back 156

infections—shigellosis and measles led the list. A Confed soldier was 10X more likely to die of infection than in battle.
Heavier toll ascribed to bacillary dysentery than to war-related injuries

Front 157

Pathogenesis of Shigellosis

Back 157

One of the most communicable bacterial diarrheas
Shigella appear to survive the low gastric pH
Shigella (like EIEC) invade colonic epithelial cells
Superficial infection confined to mucosa
Invasion followed by intracellular multiplication, spread to adjacent cells, severe inflammation, and destruction of colonic mucosa
Microabscesses coalesce to large abscesses that slough
Inflammation and ulceration lead to abdominal pain and dysentery
Invasiveness appears to be more important than shiga toxin

Front 158

Clinical Presentation of Shigellosis

Back 158

History
Acute diarrhea with systemic symptoms
Lasts 48 hours
Intrafamiliar spread with 1-3 day interval
Organism initially multiplies in small bowel
Fever, abd cramps, voluminous watery stool
High numbers of organisms in stool
Organism then invades colonic mucosa
Increased # of stools with small volume
Blood or mucus in stools (dysentery)
Fecal urgency, tenesmus
Lower bacterial counts in stools

Front 159

Management of Shigellosis

Back 159

Diagnosis
Stool culture
Fecal leucocytosis
Stool assay for Shiga toxin
Treatment
Antibiotics shorten duration and decrease transmission
Replace fluid losses
Avoid antimotility agents
Prevention
Chlorinated water supply
Hand washing
Breast feeding

Antibiotic choice: fluoroquinolones, cephalosporins, azithromycin

Front 160

Enteric Infection:

Non-inflammatory

Inflammatory


Invasive

Back 160

Non-inflammatory includes ETEC, rotavirus, EPEC, EAEC, Bacillus cereusVibrio cholerae, C. perfringens, S. aureus, Giardia lamblia, Cryptosporidium parvum, and Norwalk-like viruses.

Inflammatory (yes Fecal WBC, dysentery but not fever) includes EHEC, Salmonella enteritidis, Shigella
Vibrio parahemolyticus, Clostridium difficile, Campylobacter jejuni


Invasive of the system: fever, yes fecal WBC Salmonella typhi, Yersinia

Front 161

Immunologic Complications of Enteric Infections

Back 161

Triggered by Shigella, Salmonella, Campylobacter, or Yersinia
Patients with HLA-B27 antigen at risk for post-infection reactive arthritis
Reiter’s syndrome (imflammation in the tendon inserion site : enthesopathy)
Arthritis, uveitis, balanitis (balanitis begins as a vesicle and evolves into a shallow, usually painless, ulcer or plaque. Superficial painless ulceration can also at times be observed on the tongue and palate.)
Erythema nodosum

Front 162

Salmonella

Back 162

Classification: 2 species, multiple subspecies and serotypes
Nomenclature: Genus plus serotype
2 types of infections
Gastroenteritis (nontyphoidal)
Typhoid or enteric fever (not typhus)
Estimated 1.4 million nontyphoidal Salmonella infections in US per year
Persons at highest risk: young, elderly, HIV

Front 163

Salmonella Diarrhea

Back 163

Salmonella Gastroenteritis: Sources

Food items
Raw poultry, eggs, dairy products, fresh produce
Most recently peanut butter
Eggs become contaminated transovarially
Pets
Turtles, lizards, amphibians


Self-limited acute illness
Incubation period 6 to 48 hours
Nausea, vomiting, diarrhea
Non-bloody stools
Fevers, cramps, chills, headache
Treatment
Antibiotics only to at-risk persons
May prolong duration of carriage

Mice, rats, and hamsters
Breastfeeding protective
Case-control study

Front 164

Salmonella Pathogenesis

Back 164

Salmonella ingested, pass to intestine
Several routes of intestinal invasion
Through microfold (M) cells
Bacterial mediated endocytosis
Membrane ruffles engulf bacteria in large vesicles
Disruption of tight junctions
Typhoid fever:
Bacteria pass through mucosa, enter Peyer’s patches
Bacteria invade macrophages and disseminate
Enterocolitis
Intestinal invasion and neutrophil recruitment trigger inflammation


Salmonella hijack the cell and cause it to take up the salmonella -
see the ruffles and rosettes taking up the salmonella? wow!

Front 165

Typhoid Fever: Salmonella Typhi and Salmonella Paratyphi

Back 165

Increasingly seen in travelers to Asia
Travelers to India who stay with friends and relatives
Humans and primates are the only reservoir
Bacteria disseminate to spleen, bone marrow, gall bladder

not diarrhea, but they have:
Enterocolitis with diarrhea not common
Usually resolves before onset of fever
Low grade fever becomes high grade by second week
Headache, malaise, chills, muscle pains
Complications
Neuropsychiatric (delirium, psychosis)
Intestinal perforation
Diagnosis: blood or bone marrow biopsy

Front 166

Antimicrobial therapy for typhoid fever

Back 166

Antimicrobials that target intracellular bacteria are used to treat disease
Quinolones, 3rd generation cephalosporins
Aminoglycocides are ineffective against intracellular bacteria
Antimicrobial resistance is high among isolates from developing could

Front 167

mycotic anuerism

Back 167

from salmonella

Front 168

Salmonella: Chronic Carriage

Back 168

Defined as persistence of the organism in the stool for > 1 year
Occurs in 0.2 to 0.6% of patients with nontyphoidal salmonellosis
Example: typhoid Mary
Risk factors: biliary abnormalities

Front 169

Yersinia

Back 169

Pathogens
Yersinia pestis
Yersinia enterocolitica
Yersinia pseudotuberculosis
Zoonotic infections
Humans are incidental hosts

Front 170

Yersinia enterocolitica

Back 170

Invasive intestinal pathogen
Many strains produce heat-stable toxin
Similar to ST of ETEC
Pathogenesis: ingestion followed by mucosal ulcerations in terminal ileum, necrosis of Peyer’s patches, enlargement of mesenteric nodes
Mimics appendicitis

Front 171

Epidemiology of Y. enterocolitica

Back 171

Relatively common cause of diarrhea in Northern Europe
Found in domestic animals, fresh water
Can grow at 4ºC
Refrigerated meats can be source of infection
Frequently isolated from pig GI tract
Winter peak in US children linked to chitterlings
Iron overload increases risk for infection
Yersinia enterocolitica does not make a siderophore

thalassemias, hemolytic anemias—people requiring recurrent transfusions. Also can multiply in banked blood. Yersinia enterocolitica does not make a siderophore but can use host-chelated iron or iron bound to exogenous chelating

Front 172

Yersinia pestis

Back 172

fleas - have the ideal body temperature
the coagulase is made - then the next bite - the blood is regurgitated into the person who got bitten;
bipolar staining

Transmitted by bite of infected flea
Bubonic and septicemic plague
In US carried by wild rodents and their fleas
Mainly in AZ, NM, CO
Hunters, veterinarians, campers, and owners of infected cats at risk
Rarely transmitted by inhalation

Front 173

Bubonic plague

Back 173

Infected flea bites a susceptible host
Bacteria proliferate in regional lymph nodes
Sudden onset of fever, chills, weakness, headache
Bubo appears: intensely painful, swollen node
Bacteremia follows
High density bacteremia
Leads to gram negative septic shock
Bleeding diathesis results in purpura
Blockage of vessels leads to necrosis of fingers, toes

Front 174

pneumonic plague

Back 174

In infected person, bacteria from the bloodstream invade the lung and cause pneumonia
Sputum itself contains large numbers of plague bacilli
Coughing creates aerosols which are inhaled by susceptible persons
Pneumonic plague spreads very rapidly and has higher mortality rate than bubonic plague

rapid, hemorrhagic pulmonary failure
50% mortality;

14% overall plague mortalilty

Front 175

Lettuce and spinach was the source of a recent outbreak of STEC. What is the most likely route of pathogenesis?
People sneezed on salad bars
Food workers did not wash hands
Contamination from raw chicken in grocery cart
Contaminated manure at the farm
Contaminated wash water during packaging
Bioterrorist plot

Back 175

Contaminated manure at the farm.
Pre-harvest crop contamination is likely because:
E. coli O157:H7 persists in the environment
Organisms pass from manure into the irrigation water
Viable STEC have been recovered from inner tissues of lettuce grown in contaminated manure

Front 176

55 yo healthy male with “golf-ball” sized lump in his right axilla
10 cm abscess found at I&D
Gram stain with many GNR
Required repeat I&D
Resolved on ciprofloxacin
Patient worked extensively with pork as a meat cutter

Salmonella typhimurium
Salmonella typhi
Listeria
Yersinia enterocolitica
shigella
?

Back 176

Yersinia enterocolitica

Front 177

Recognize major human infections caused by Legionella, Mycoplasma, and Chlamydia (LMC) species

Back 177

Legionella: Legionnaires disease (feel bad in general with pulmonic symptoms, clues that it's not just pneumococcus: low sodium! )


Mycoplasma:
causes upper respiratory infections
Bronchitis, tracheriits, pharyngitis,… mycoplasma pneumonia
Mucosa: genital and respiratory
extrapulmonary associated symptoms:
Causes pronounced lymphocyte stimulation
Cold agglutinin disease
Stevens-Johnson syndrome
Autoimmune encephalitis/meningitis
Cold agglutinins are IgM antibodies against red cell antigens
Cause clumping of RBCs at 4○

Chlamydia trachomatis:
Ocular trachoma is a leading cause of blindness world-wide
Starts with chronic follicular conjunctivitis that leads to long-term scarring and corneal opacities

Sexually Transmitted Diseases
Caused by C. trachomatis:
Women in US
Salpingitis, cervicitis infertility, ectopic pregnancy
Men in US
Urethritis, prostatitis, epididymitis
Can result in reactive arthritis (Reiter’s)
Infants in US (acquired from mom)
Conjunctivitis, pneumonia
Lymphogranuloma venereum in tropical countries

C. pneumoniae Infection:
Historically known as TWAR agent
Refers to laboratory designation
Accounts for ~15% of community-acquired pneumonia
Similar to M. pneumoniae also causes URI
By early adulthood ~50% of persons have been exposed
Usually causes “walking” pnuemonia but can be severe in elderly

C. psittaci Infection
Psittacosis is a multi-system zoonosis that frequently includes pneumonia
Non-specific illness that often includes fever, pharyngeal erythema, hepatitis
Wide range of illness that can involve any organ system
Usually acquired from sick birds
Common in poultry-farmers (especially turkeys), abattoir-wokers, and vets

Front 178

Identify patient risk factors for acquisition of LMC infections

Back 178

Legionella: warm water is optimal environment + amoeba; high # in man made aquatics - broccolli spray at grocery store - in water ! -- or water fountain at the reunion;
- it's a short lived outbreak

Legionnaires disease associated with travel and Patients with decreased cellular immunity at increased risk (Age, steroids, diabetes, ESRD, etc.)


Mycoplasma pneumonia:
Easily transmitted
Outbreaks in families and closed confines with 2-3 week incubation period
URI symptoms predominate
Minority progress to tracheobronchitis or walking (non-severe) pneumonia
Cough pronounced
Patchy or interstitial infiltrates on chest x-ray (worse than clinical disease)

Front 179

Know methods for diagnosing LMC infections

Back 179

Legionella:
Unusual cell wall means stains poorly on Gram-stain
Direct fluorescent antibody on sputum
Urinary antigen detects only L. pneumophila serotype 1
Serology rarely used except in epidemiologic investigations
Bronchoscopy is more effective

Mycoplasma: No cell-wall therefore not seen on Gram-strain
Difficult to culture
Serologic tests are mainstay of diagnoses but rarely used clinically
Acute and convalescent IgM and IgG
Cold agglutinin tests can be used
In light of low pathogenicity usually rely on no therapy or empiric therapy


Chlamydia Diagnosis
Only grows in cell-lines
Not seen on Gram-stain
Nucleic acid amplication techniques are mainstay of diagnosis for genital infection
More sensitive and specific vs. culture
Widely available in conjunction with Neisseria gonorrhea (DNA probes)
Serologic testing used for C. pneumoniae and C. psittaci but less than ideal

Front 180

Relate LMC physiology to drug susceptibility and treatment options

Back 180

not susceptible to the beta lactams if they don't have the cell wall;


Legionella:
Intracellular pathology means drugs must be able to get into cells
No randomized trials
Azithromycin (macrolide) or quinolones are 1st line agents
Most experience with macrolides
Best in vitro results with quinolones


Mycoplasma:
Cell-wall active agents don’t work
Penicillins, cephalosporins
Most experience is with macrolides
Forms basis of treatment recommendations for azithromycin and clarithromycin for community-acquired pneumonia
Quinolones and tetracyclines also active

Chlamydia:
Cell-wall active agents not useful
Must get intracellularly
Genital infections
High dose azithromycin, 7 days of doxycycline or quinolone
Pneumonia
5-10 day course of macrolides
Psittacosis
10-21 days of doxycycline

Front 181

atypical ?

Back 181

not the normal cell wall

Atypical pneumonia coined in 1940’s
Pneumonia that did not respond to penicillin
No agent found on Gram-stain or culture
Majority of atypical pneumonias are likely caused by M. pneumoniae
Can actually be cultured but has very long doubling time

walking pneumonia = atypical

Front 182

Legionella

Back 182

Wide variety of organisms found in a variety of water habitats
Fastidious extracellular growth
Considered an intracellular pathogen
L. pneumophilia causes majority of serious infections
Legionnaires’ disease
Severe multi-system infection including pneumonia
Pronounced extra-pulmonic symptoms
Low sodium, increased LFTs
Often associated with travel
Patients with decreased cellular immunity at increased risk
Age, steroids, diabetes, ESRD, etc.

Pontiac fever:
Self-limited febrile illness only diagnosed in an outbreak setting
Very high attack rates with 80-90% of those exposed becoming ill
Aerosolized water source
Fever, myalgia, headache predominate
Resolves in 3-5 days
(feels like the flu, but there might be an outbreak, but it's self -limiting; some ppl progress to the pneumonia others don't)

Pathogenesis:
Enter lungs via aerosol
Multiply in phagosomes!
Host cell ruptures
like a virus!! it's an intracellular organism;
Must give Tx that get into the cells – beta-lactams cannot get in – hallmark of the antibiotic
You’re not coughing it up that much- it’s intracellular – that’s why bronchoscopy is more helpful

Front 183

Mycoplasma Species

Back 183

Ubiquitous colonizers and pathogens of both plants and animals
Smallest free-living organisms!! very close to the virus - but able to live free;
Major infections include:
URI and atypical pneumonia (M. pneumoniae)
Gential disease (M. hominis, Ureaplasma urealyticum)

Front 184

M. pneumoniae

Back 184

Atypical pneumonia coined in 1940’s
Pneumonia that did not respond to penicillin
No agent found on Gram-stain or culture
Majority of atypical pneumonias are likely caused by M. pneumoniae
Can actually be cultured but has very long doubling time


Easily transmitted
Outbreaks in families and closed confines with 2-3 week incubation period
URI symptoms predominate
Minority progress to tracheobronchitis or walking (non-severe) pneumonia
Cough pronounced
Patchy or interstitial infiltrates on chest x-ray (worse than clinical disease)


Causes pronounced lymphocyte stimulation
Cold agglutinin disease
Stevens-Johnson syndrome
Autoimmune encephalitis/meningitis
Cold agglutinins are IgM antibodies against red cell antigens
Cause clumping of RBCs at 4○


M. pneumoniae spreads person-to-person with 2-3 week incubation period

Front 185

Genital Disease due to Mycoplasma Species

Back 185

M. hominis, M. genitalium, Ureaplasma urealyticum commonly colonize the GU tract
Cause ~20% of non-gonococcal urethritis in men
Contribute to cervicits and other forms of PID in women

Front 186

Chlamydophila Species

Back 186

Obligate intracellular bacteria with unique life-cycle
Small genome
Depend on host for nutrients
Cause broad array of diseases in humans
Atypical pneumonia (C. pneumoniae)
Genital and eye disease (C. trachomatis)
Systemic illness (C. psittaci)


C. trachomatis
Most prominent Chlamydia species world-wide
Different serotypes cause different infections although reasons are unclear
Ocular trachoma is a leading cause of blindness world-wide
Starts with chronic follicular conjunctivitis that leads to long-term scarring and corneal opacities