Cabs 2010 Bcm

Front 1

Infant mortality rate in US in blacks vs overall

Back 1

blacks: 13.4 / 1000 Live Births

overall: 6.78 / 1000 live births

disparity in IMR

Front 2

At what age is the highest risk for infant mortality - due to SIDS or due to other

Back 2

SIDS: highest at 1 month, then 2nd peak at 3 months

other: peak at 2 months

Front 3

top 9 causes of death <1 year olds

Back 3

Top 2 are much more common than rest
1) perinatal 36%
2) anomalies 26%
3) SIDS 6%
4) injury
5) infection
6) lung
7) CV
8) GI
9) other

Front 4

Top 10 causes of death in 0-17 yo

Back 4

1) Injury 25%
2) perinatal 22%
3) anomalies 18%
4) SIDS 6%
5) infection
6) lung
7) Neuro
8) CV
9) GI
9) other

Front 5

Definition - Sudden Infant Death Syndrome (SIDS)

Back 5

Sudden infant death syndrome (SIDS) is the sudden death of an infant under one year of age with onset of the fatal episode apparently occurring during sleep

that remains unexplained after the performance of a complete autopsy, examination of the death scene and review of the clinical history.

Front 6

incidence of SIDS

Back 6

incidence has been decreasing over past 20yrs from 2.3 / 1000 (1985) to 0.67 / 1000 (2005)

2,200 infant deaths in 2005

whites consistently higher than blacks

Front 7

classic characteristics of SIDS

Back 7

>1 month but < 6 months (peak 2-4 months)
Previously healthy, no family history
Mild upper respiratory tract infection (viral)
Death occurs during sleep (midnight - 6 am)
Male
White
Winter (same incidence every day of the week)

Front 8

Maternal Risk Factors Associated With SIDS

Back 8

-Young, unmarried, multiparity
-Lower socioeconomic group, poor, under educated
***Significant association between poverty and SIDS
-Poor prenatal care, poor weight gain, anemia
-Smoking or drug use during pregnancy
-Lack of breast feeding (recently determined to be less important)

Front 9

prenatal care: within the US where are the lowest rates

Back 9

<82% in southern states, Nevada, DC
>90% (best) in North Dakota and mid-eastern states

for blacks specifically: <67% in Nevada, New Mexico, Oklahoma, Arkansas, Minnesota, Wisconsin, Penn, West Virginia, DC
76-83% (best): pacific states, central and some north east states

Front 10

Perinatal Risk Factors Associated With SIDS

Back 10

Prematurity, low birth weight, multiples
Monozygous twins > dizygous twins
Male
African-American or Native American
Low Apgar scores, respiratory distress
Poor feeding, vomiting or diarrhea
Previous SIDS death in sibling

Front 11

Postnatal Risk Factors Associated With SIDS

Back 11

Prone sleeping position
***Especially during first episode of prone sleeping
Soft or excessive bedding
Hyperthermia or hypothermia
No or late immunizations
Co-sleeping (adult, larger sibling, multiple)
May represent accidental smothering
Environmental smoking

Front 12

what sleeping position is risky for SIDS

Back 12

• Prone sleeping — Sleeping on the stomach, which increases the risk of SIDS by as much as 12-fold. Parents are urged to have their babies sleep supine, or on their backs, until they're 1 year old.

Front 13

Pathogenesis of SIDS?

Back 13

Problems with respiratory control
**Chronic hypoxia/suffocation theory
***Pre and postnatal hypoxia, pulmonary hypoplasia, delayed brain stem development

Cardiovascular abnormalities
**Arrhythmogenic theory (long QT)

Visceral dyskinesis
**Spasm/reflux/dysphagia theory

Infection
**Precocious immune response in presence of hypoxia, abnormal cytokine production (complement and IL-10)

It is unlikely that a single etiology is responsible for SIDS.
Genetically predisposed infant – plus something else
End point – hypoxia, coma, death

Front 14

Theory of chronic hypoxia as cause of SIDS

Back 14

acute hypoxia at birth --> chronic hypoxia inducing physiology or environment --> blunted hypoxic ventilatory response -- transitory hypoxia -- delayed fetal resetting + delayed response to hypercarbia + reduced sensitivity to hypoxia ---> failed auto-resuscitation --> SIDS at 3months

Front 15

Brainstem hypothesis in SIDS

Back 15

1) genetic factors + environmental --> abnormal medulla (50% of SIDS) = vulnerable infant

2) this causes decreased CO2 sensitivity, arousal deficit, respiratory pattern abnormality, altered BP recovery, altered temperature control, altered airway reflexes ---> convergence of these faulty reflexes - often the critical period or with an exogenous stressor -->

SIDS

Front 16

How does the 5HT system in the Medulla work? What happens if there is less 5HT the medulla?

Back 16

1) The baroreceptor in the aortic arch send a signal to the Solitary nucleus in the medulla (via X)

1b) other inputs are from the heart/BP/temperature

2) this causes an efferent signal to diaphragm via Raphe nucleus (5HT)


In a case of SIDS:
A) Decreased serotonergic receptors:
Males have fewer 5-HT1A receptors than females
B) Increased serotonergic neurons -
make and release serotonin
C) Increased number of immature serotonergic neurons
D) Insufficient amounts of serotonin transporter protein

Front 17

what's different in HR and RR in SIDS? cry?

Back 17

higher HR ~ 150 (vs 130)

faster respiration with lower volume

Higher pitched cry, hyper adductory vocal folds

Front 18

Long-QT Syndrome

Back 18

LQTS affects 1/5,000
6 identified chromosomal loci and 5 cardiac ion channel genes

SCN5A accounts for 5-10% of cases
Sodium channel gene
Mutation found in 2% of SIDS patients
Associated with sleep

Front 19

SIDS Recurrence Risk

Back 19

SIDS recurs in only 1-2% of siblings

Twins are at increased risk and have been reported to have simultaneous or subsequent SIDS deaths

All familial cases should be thoroughly evaluated for specific etiologies other than SIDS, particularly homicide

Front 20

Autopsy Findings in SIDS

Back 20

No pathology that explains death
Internal exam
Petechiae on thymus, pericardium and lungs
prominent lymphoid tissue
lung congestion and edema
blood in heart is liquid
bladder is empty


No pathology that explains death

Microscopic examination:
-Retention of fetal fat around adrenal glands
--Recent studies have not confirmed increased Hgb F
-Increased hematopoiesis in liver
-Gliosis in respiratory centers of brain
-Thickened pulmonary arteries, edema, hemorrhage
-Mild bacterial or viral pneumonia, gastroenteritis


Increased neuropeptides produced by pulmonary neuroendocrine cells

Front 21

Apparent Life-Threatening Event (ALTE)

Back 21

ALTE is an episode that is frightening
to an observer and is characterized by some
combination of apnea, color change,
marked change in muscle tone, choking
or gagging.

In some instances the observer fears that the infant
has died or would have died if there had not been
intervention.

Front 22

Clinical - ALTE

Back 22

Incidence 0.5-3%
Rare survivors have neurologic injury
40% will have recurrent episodes
2% will subsequently die
Only 1% of SIDS deaths are preceded by an ALTE episode
Etiology will be identified in 50-90% of cases

Front 23

Etiology of ALTE

Back 23

Morphologic causes
CNS; malformations, encephalitis, meningitis, IVH
Respiratory; infection, aspiration pneumonia, airway obstruction
GI; enteritis, gastroesophageal reflux
Metabolic; hypoglycemia, hypocalcemia
Cardiovascular; malformations, cardiomyopathy

Functional causes (may not have pathology)
Apnea
Gastroesophageal reflux
Bradycardia, arrhythmia
Seizure disorders

Front 24

Sudden Unexpected Infant Death

Back 24

Refers to an otherwise healthy infant/child who dies of unknown causes and is not otherwise a SIDS case, usually older
Many will be explained by autopsy
Those remaining cases will be, cause of death undetermined (unclassified sudden infant death)
Manner of death
natural, unnatural (accident or homicide [5-10%])

Front 25

"Natural Causes" of Infant Death

Back 25

Pulmonary lesions (asthma..)
Cardiac problems (myocarditis..)
Undiagnosed metabolic abnormalities (CF, diabetes, MCAD deficiency)
Acute infections (Waterhouse-Friderichsen syndrome = hemorrhagic adrenalits)
Sickle cell crisis
Dehydration

Front 26

Fatty Acid Oxidation Abnormalities: which is most common in infants

Back 26

Medium chain acyl CoA dehydrogenase deficiency (MCAD), other forms less common

Normal at birth

Acute illness with decreased oral intake results in hypoketotic hypoglycemia, neutral lipid accumulates in liver, steatosis, hepatic encephalopathy and death

Autosomal recessive, F>M
May account for 4% of sudden unexpected deaths

Front 27

Accidental Infant Death vs Suffocation

Back 27

Accidental Infant Death:
Poisoning
Asphyxia
Drowning
MVA
Suicide

Suffocation:
Suffocation may be accidental or intentional.
Suffocation occurs in children less than 3 years of age, most are less than 12 months of age.
2-10% of deaths determined to be SIDS, may be due to suffocation.
The autopsy findings in suffocation and SIDS are nearly identical, making scene investigation very important.

Front 28

Neonaticide

Back 28

The risk of homicide on the first day of life is 10x greater than at any other time.
Unwanted or illegitimate birth, the obvious sexual activity, mental illness, difficult relationship with parents, immaturity and a culture that promotes self-destructive impulses
42 states have “safe haven” laws

Incidence, 0.002% of all live born
male > female
black > white

85% committed by the mother
50% single
35% had other children
mean age 19 years (14-35 years)
50% no prenatal care, 25% denied being pregnant

Asphyxiation/strangulation 41%, drowning 26%

Front 29

“Battered Child Syndrome”

Back 29

50% occur < 3 years, 25% < 1 year but more likely to be fatal
Head injury is leading cause of death, followed by abdominal trauma
Occurs during episodes of crying, toilet training, and resentment towards spouse or child

Front 30

“Shaken Baby Syndrome”

Back 30

Violent backward and forward movement of the unsupported head
“Shaken baby impact syndrome” may be even more dangerous as the head is rapidly stopped usually against a solid object--acceleration and deceleration injury


Pathology
Subdural/subarrachnoid hemorrhage
Retinal hemorrhage
Increased intraocular pressure transmitted from the intracranial cavity through the optic nerve sheath
Shearing injury to vessels
Subdural and retinal hemorrhages are much more common in abusive head trauma than in accidental trauma

Front 31

Munchausen’s Syndrome by Proxy

Back 31

Fabricated or induced illness with repeated presentations for medical attention
Child with history of apnea, cyanosis, or seizures
Ultimately the child may be severely damaged or may die
Premeditated, usually by the mother who often has a medical background
Video monitoring during hospitalization

Front 32

what is this syndrome?

Back 32

Waterhouse-Friderichsen syndrome (WFS) or hemorrhagic adrenalitis is a disease of the adrenal glands most commonly caused by the bacterium Neisseria meningitidis. The infection leads to massive hemorrhage into one or (usually) both adrenal glands.[1] It is characterized by overwhelming bacterial infection meningococcemia, low blood pressure and shock, disseminated intravascular coagulation (DIC) with widespread purpura, and rapidly developing adrenocortical insufficiency.

Front 33

Dx?

Back 33

Asthma - a cause of pulm path in infant death

Front 34

Dx?

Back 34

Myocarditis - a cause of infant death

In medicine (cardiology), myocarditis is inflammation of heart muscle (myocardium). It resembles a heart attack but coronary arteries are not blocked.

Myocarditis is most often due to infection by common viruses, such as parvovirus B19, less commonly non-viral pathogens such as Borrelia burgdorferi (Lyme disease) or Trypanosoma cruzi, or as a hypersensitivity response to drugs

Front 35

SIDS triad

Front 36

SIDS triad?

Front 37

Dx?

Back 37

In SIDS, Thymus can be nl or starry sky - here

Front 38

Dx?

Back 38

cause of infant death - a metabolic disorder - in this case: defects in the enzyme complex known as medium-chain acyl dehydrogenase (MCAD) and reduced activity of this complex. This complex oxidizes medium chain fatty acids (Fatty acids having 6-12 carbons) while reducing FAD+ to FADH2

It is recognized as one of the more rare causes of sudden infant death syndrome (SIDS), although it may be better described as a mimic, rather than a cause, of SIDS.

Front 39

MIC?

Back 39

Minimum inhibitory concentrations indicate the minimal concentration of antibiotic that will inhibit bacterial growth.


Minimum inhibitory concentrations for most antibiotics are commonly characterized as either MIC50 or MIC90. These values indicate the percentage of isolates of a particular bacterium that will be inhibited with different concen-trations of a drug.
The MIC50 value indicates the concentration of antibiotic that will inhibit the growth of 50% of isolates, whereas an MIC90 indicates the concentration of antibiotic needed to inhibit 90% of isolates.

Front 40

pharmacokinetics and dynamics of Abx?

Back 40

PK = effect in humans - consider serum concentration profile and penetration to site of infection

PD = effect in bacteria - consider potency (MIC) and mechanism of killing

Front 41

time- and concentration-dependent anti-biotics

Back 41

For drugs that are concentration dependent, Peak/MIC or AUC/MIC are pre-dictors of clinical and microbiologic outcome.

For agents that are time dependent, it is necessary to prolong the duration of exposure, so the absolute concentration is not important. What is important in these drugs is the duration of contact time—the time that the concentration remains above the MIC (time above the MIC).

Front 42

Time above MIC (or time-dependent activity) is the parameter that best defines the activity of which antibiotics?

Back 42

penicillins, cephalosporins, monobactams, carbapenems

Front 43

The area under the curve AUC>MIC or the Peak>MIC (or concentration-dependent) are the parameters that best reflect the activity of which antibiotics?

Back 43

aminoglycosides, fluoroquinolones, azalides, macrolides, clindamycin, oxazolidinones, and ketolides

Front 44

what are the organisms we treat with natural penicillins 1st line?

Back 44

Group A and B Streptococcus, susceptible S. pneumoniae, N. meningitidis, Actinomyces israelii and Treponema pallidum

Front 45

What Abx are resistant to S.aureus beta-lactamase?

Back 45

Nafcillin/oxacillin

Front 46

Does Nafcillin/oxacillin affect enterococci?

Back 46

NO

Enterococcus is not inhibited by nafcillin or other penicillinase- resistant penicillins

Front 47

ß-lactamase + H. influenzae

antibitiotic??

Back 47

ß-lactamase inhibitors bind irreversibly to some ß-lactamases. Amoxicillin-clavulanate has excellent activity for ß-lactamase + H. influenzae
Amoxicillin-clavulanate is the drug of choice for animal and human bites due to activity against
P. multocida, Eikenella sp. S. aureus and anaerobes

Front 48

drug of choice for animal and human bites due to activity against
P. multocida, Eikenella sp. S. aureus and anaerobes

Back 48

Amoxicillin-clavulanate

Front 49

Treatment of GAS Pharyngitis

Back 49

Group AStrep Pharyngitis:

Although penicillin V is the drug of choice for treatment of GAS pharyngitis, amoxicillin equally is effective. A clinical isolate of GAS resistant to penicillin never has been documented.
Orally administered amoxicillin given as a single daily dose (50 mg/kg, maximum 1000 mg) for 10 days is as effective as orally administered penicillin V or amoxicillin given multiple times per day for 10 days.
For some patients who are allergic to penicillin, a 10-day course of a narrow-spectrum (first-generation) oral cephalosporin is indicated. Patients with immediate or type I hypersensitivity to penicillin should not be treated with a cephalosporin.
Erythromycin, clarithromycin, or azithromycin is acceptable for patients allergic to penicillins.

Front 50

Etiology of Acute Otitis Media

Back 50

47% H. influenzae (40% with b-lactamase)
33% S. pneumo (47% penicillin resistant strains)
8% M. cat (100% with b-lactamase)
4% S. pyogenes
3% S. aureus

Front 51

Acute Otitis Media with Temperature >39°C and/or Severe Otalgia:

antibiotic?

Back 51

Amoxicillin-clavulanate, 90 mg/kg per day of amoxicillin, with 6.4 mg/kg per day of clavulanate

If penicillin allergy:
Ceftriaxone, 1 or 3 days

Front 52

Acute Otitis Media without Temperature >39°C and/or Severe Otalgia:

antibiotic?

Back 52

Amoxicillin
80–90 mg/kg per day

Penicillin allergy:
Non-type I: cefdinir, cefuroxime, cefpodoxime;
type I: azithromycin, clarithromycin

Front 53

Extended Spectrum Antipseudomonas

Back 53

In general piperacillin is more active than ticarcillin for Pseudomonas sp ( as well as Burkholderia cepacia)

Addition of beta-lactamase inhibitor (clavulanate or tazobactam) does not increase activity against Pseudomonas sp.

ßeta-lactamase inhibitors extend the activity of piperacillin and ticarcillin against most ß-lactamase producing E. coli, Klebsiella sp, methicillin-susceptible S. aureus and anaerobes

Front 54

Cephalosporins - Spectrum of Activity
Selected Features of 1st Generation

1) activity against MSSA and GAS
2) activity against Enterococcus
3) activity against Listeria
4) activity against MRSA
5) activity against bacterial meningitis
6) surgical prophylaxis??

Back 54

Activity primarily for methicillin-susceptible
S. aureus and Group A streptococcus

No cephalosporin is active against Enterococcus sp or Listeria moncytogenes

Not active against methicillin-resistant staphylococci

Do not penetrate into CSF adequately for routine treatment of bacterial meningitis

Cefazolin useful for surgical prophylaxis due to its activity against S. aureus and S. pyogenes

Front 55

Cephalosporins - Spectrum of Activity-Selected Features of 2nd Generation

1) activity against GN enterics / Gram positives in comparison to 1st generation
2) activity against H.influenza / Moraxella
3) activity against URI / LRI
4) activity against bacterial meningitis?

Back 55

More active than 1st generation agents against Gram-negative enterics but less active against Gram-positive organisms
Useful activity against H. influenzae and Moraxella catarrhalis (Cefuroxime)
Useful for treatment of upper and lower respiratory infections; IV and oral formulations
Do not penetrate into CSF adequately for routine treatment of bacterial meningitis

Front 56

Cephalosporins - Spectrum of Activity-Selected Features of 3rd and 4th Generations

1) activity against GN enterics / Gram positives in comparison to 1st/2nd generation
2) activity against bacterial meningitis?
3) activity against Shigella resistant to ampicillin or bactrim
4) activity against pseudomonas?

Back 56

Improved activity for gram-negative but less active against gram positive (except streptococci) than 1st or 2nd generation cephalosporins except for S. pneumoniae (cefotaxime or ceftriaxone)
Penetrate well into CSF and are first line agents for treatment of bacterial meningitis. (cefotaxime/ceftriaxone)
Cefixime, cefpodoxime and cefdinir remain active against Shigella spp resistant to ampicillin or TMP-SMX
Ceftazidime and cefepime have important activity against Pseudomonas spp