Term
|
Definition
Beta-‐Lactams
• Polymixins
• Vancomycin |
|
|
Term
| Protein Synthesis 30S Ribosomal Inhibitors |
|
Definition
• Tetracyclines
• Streptomycin |
|
|
Term
| Protein Synthesis 50S Ribosomal Inhibitors |
|
Definition
• Macrolides
(erythromycin,
azithromycin)
• Chloramphenicol
• Oxazolidinones |
|
|
Term
|
Definition
|
|
Term
|
Definition
Inhibition of cell wall synthesis
2. Disruption of cell membrane structure or function
3. Inhibition of protein synthesis
4. Inhibition of nucleic acid synthesis, structure or function
5. Block metabolic reactions |
|
|
Term
|
Definition
Kill bacterial directly
Chloramphenicol
Erythromycin
Clindamycin
Sulfonamides
Trimethoprim
Tetracyclines |
|
|
Term
|
Definition
Prevent bacterial from growing
Aminoglycosides
Beta-lactams
Vancomycin
Quinolones
Rifampin
Metronidazole |
|
|
Term
| T/F: Antibiotics that inhibit bacterial protein synthesis target the 80S ribosomes and therefore do not affect eukaryotes which have 70S ribosomes. |
|
Definition
|
|
Term
|
Definition
• Bind to 30S subunit and interferes with the attachment of the tRNA
carrying amino acids to the ribosome
• The term "tetracycline" is also used to denote the four-ring system of this
compound;
Block attachment of tRNA
(Tetracycline, Doxycycline, Minocycline)
• Broad spectrum and low cost
• Bacteriostatic |
|
|
Term
|
Definition
Inhibitors of 30S ribosome subunit
Bind to bacterial ribosome on 30S subunit; and blocks formation of
initiation complex. Both actions lead to mis-incorporation of amino acids
– Causes Misreading of mRNA
(Streptomycin, neomycin, gentamycin) |
|
|
Term
Which of the following statements about aminoglycosides is TRUE?
A) include streptomycin
B) bind to the 30S ribosomal subunit of the bacterial ribosome
C) cause misreading of the mRNA code
D) A and B
E) A, B and C |
|
Definition
|
|
Term
Which of the following mechanisms can make a bacterium resistant to tetracycline?
A) chemical modification of the drug
B) pumping the drug out of the cell
C) enhancing the binding of the drug to the ribosome
D) A and B
E) A, B and C |
|
Definition
|
|
Term
|
Definition
• Source: Isolated from Streptomyces venezuelae; longer derived from
natural source.
• well absorbed after oral administration
• Very broad spectrum (almost all bacteria except Pseudomonas
aeruginosa)
• Very toxic, restricted uses, can cause irreversible damage to bone marrow |
|
|
Term
|
Definition
The macrolides inhibit translocation by binding to 50S ribosomal subunit
the presence of a macrolide ring, a large macrocyclic lactone ring
Eg. (Erythromycin,Clarithromycin (Biaxin),Azithromycin (Zithromax; Zitromax),Roxithromycin (Rulid),Dirithromycin (Dynabac))
• made by Streptomyces
• Narrow spectrum (Gram +, Mycoplasma, T.
palidum)
• Bacteriostatic
• It may be given orally or parenterally
• Macrolides are widely distributed in thebody
• Generally safe drugs |
|
|
Term
|
Definition
• Also inhibits protein synthesis (attaches to bacterial ribosomes)
• Erythromycin has a narrow Gram (+) spectrum
• (side effects: fairly low toxicity!)
– Given to children
• Taken orally for Mycoplasma pneumonia, legionellosis, Chlamydia, pertussis,
diptheria
• and as a prophylactic prior to intestinal surgery
• Newer semi-synthetic macrolides – clarithomycin, azithromycin |
|
|
Term
Erythromycin binds to the ______ subunit of bacterial ribosomes thereby inhibiting
peptide chain _______.
A) 50S; initiation
B) 50S; elongation
C) 30S; initiation
D) 30S; elongation
E) 30S; termination |
|
Definition
|
|
Term
|
Definition
Oxazolidinones inhibits protein synthesis by preventing formation of the ribosome complex that initiated protein synthesis
Linezolid
• Narrow-spectrum (Gram-positives)
• Totally synthetic, hard to have resistant bacterial
• It is used for the treatment of serious infections caused by
Gram-positive bacteria that are resistant to several other
antibiotics
• Discovered in the 1990s and first approved for use in 2000
• Linezolid is very expensive, costing approximately US$100
per pill in the United States |
|
|
Term
|
Definition
(Zyvox)
• When used for short periods, linezolid is a relatively safe
drug.
• Bone marrow suppression, may occur during linezolid long-term treatment;
• when given by mouth: the entire dose reaches the bloodstream, as if it had been given intravenously. |
|
|
Term
| Biosynthesis of Penicillins (AA's) |
|
Definition
|
|
Term
|
Definition
First Generation Cephalosporins
• More active than penicillin G against some Gram (‐) bacteria
• Less likely to cause allergic reactions than penicillins
• Useful against ‐lactamase producing strains of S. aureus
• Not active against Pseudonomas aeruginosa
• Poorly absorbed from the GIT
• Administered by injection
• Metabolised to afford a free 3‐hydroxymethyl group (deacetylation)
• Metabolite is less active |
|
|
Term
|
Definition
First Generation Cephalosporins
• The pyridine ring is stable to metabolic degradation
• The pyridine ring is a good leaving group
• Exists as a zwitterion ‐ soluble in water
• Poorly absorbed through the GIT
• Administered by injection |
|
|
Term
|
Definition
First Generation Cephalosporins
• The 3‐methyl group is a poor leaving group
• Methyl group is bad for activity but helps oral absorption
• Can be administered orally
• The hydrophilic amino group at the ‐carbon of the side chain helps to
compensate for the loss of activity due to the 3‐methyl substituent |
|
|
Term
|
Definition
2nd Generation Cephalosporins
• Isolated from a culture of Streptomyces clavuligerus
• First ‐lactam to be isolated from a bacterial source
• Modifications carried out on the 7‐acylamino side chain
• Resistant to esterases due to the urethane substituent |
|
|
Term
|
Definition
2nd Generation Cephalosporins
• Broader spectrum of activity than most first generation cephalosporins
• Greater resistance to ‐lactamase enzymes
• The 7‐methoxy group may act as a steric blocker
• The urethane group is stable to metabolism |
|
|
Term
|
Definition
2nd Generation Cephalosporins
Oximinocephalosporins:
• Much greater stability against some ‐lactamases
• Resistant to esterases due to the urethane group
• Wide spectrum of activity
• Useful against organisms that have gained resistance to penicillin
• Not active against P. aeruginosa
• Used clinically against respiratory infections |
|
|
Term
|
Definition
3rd Generation Cephalosporins
Oximinocephalosporins:
• Injectable cephalosporin
• Excellent activity vs. P. aeruginosa and other Gram (‐) bacteria
• Can cross the blood brain barrier
• Used to treat meningitis |
|
|
Term
|
Definition
5th Generation Cephalosporins
(Telfaro)
• Approved by the FDA in 2010
• Active against (MRSA)
• Active against Gram (+) bacteria
• Under investigation for community‐acquired pneumonia and complicated skin
infections |
|
|
Term
|
Definition
• Isolated from Streptomyces cattleya
• Potent and wide range of activity vs Gram (+) and Gram (-) bacteria
• Active against Pseudomonas aeruginosa
• Low toxicity
• High resistance to -lactamases
• Poor stability in solution (ten times less stable than Pen G) |
|
|
Term
|
Definition
Carbapenem
• Approved by the FDA in 2007
• An ultra‐broad spectrum injectable antibiotic effective against
gram (+) and gram (‐) bacteria
• Particularly active against Pseudomonas aeruginosa
• Not active against MRSA |
|
|
Term
|
Definition
• Monocyclic ‐lactam ring
• Moderately active in vitro against narrow group of Gram (‐) bacteria
• Activevs. Pseusomonas aeruginosa
• Inactive vs. Gram (+) bacteria
• Different spectrum of activity from penicillins
• Thought to operate by a different mechanism from penicillins
• Lowtoxicity |
|
|
Term
|
Definition
Mono‐bactam
• Administered i.v.
• Can be used for patients with allergies to penicillins and
cephalosporins
• No activity vs. Gram (+) or anaerobic bacteria
• Active vs. Gram (‐) aerobic bacteria |
|
|
Term
|
Definition
Clavulanic acid
• Isolated from Streptomyces clavuligerus
• Weak, unimportant antibacterial activity
• Powerful irreversible inhibitor of b‐lactamases ‐ suicide substrate
• Used as a sentry drug for ampicillin
• Augmentin = ampicillin + clavulanic acid
• Allows less ampicillin per dose and an increased activity spectrum
• Timentin = ticarcillin + clavulanic acid |
|
|
Term
|
Definition
• Suicide substrates for b‐lactamase enzymes
• Sulbactam has a broader spectrum of activity against b‐lactamases
than clavulanic acid, but is less potent
• Unasyn = ampicillin + sulbactam |
|
|
Term
|
Definition
• Suicide substrates for b‐lactamase enzymes
• Tazobactam has a broader spectrum of activity against b‐lactamases
than clavulanic acid, and has similar potency
• Tazocin or Zosyn = piperacillin + tazobactam |
|
|
Term
|
Definition
Cyclic Lipopeptides
• New class of antibiotic isolated from Streptomyces roseosporus
• Disrupts multiple aspects of bacterial cell membrane function
• Inserts into the cell membrane and aggregation of daptomycin alters the
curvature of the membrane, which creates holes that leak ions.
• Often effective against resistant gram (+) infections |
|
|
Term
|
Definition
Staphylococci
Streptococci
Enterococci
Mircococci
Bacillus cereus
Bacillus anthracis
Corynebacterium diptheriae
Listeria monocytogenes
Lactobacillus acidophilus
Gardnerella vaginalis
Nocardia asteroides |
|
|
Term
| Gram-positive (anaerobic) |
|
Definition
Streptococci Peptostreptococcus sp.
Streptococci Peptococcus sp.
Clostridium difficile
Clostridium perfringens
Clostridium tetani
Clostridium botulinum
Propionibacterium acnesis |
|
|
Term
| Gram-negaitve (anaerobic) |
|
Definition
Bacteroides fragilis
Prevotella sp.
Fusobacterium |
|
|
Term
| 3rd Gen Cephalosporins: Adverse effects |
|
Definition
Few and Low
Hypersensitivity
Superinfection risk
Nearly no nephro tox |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
best anti-pseudomonal
3rd gen |
|
|
Term
|
Definition
70% eliminated via bile
3rd gen |
|
|
Term
| Spectum of activity and clinical use of Cephalosporins |
|
Definition
All active against most G+ cocci (including penicillinase-producing)
many stains of G- bacilli
Relatively ineffective against enterococci |
|
|
Term
|
Definition
[Cephalothin, cefazolin, cephalexin)
Strongest action on G+, weakest on G-
Certain nephro tox to a certain degree
Not effective against pseudomonas
Camparitivly stable against B-lactamase
Cheifly used in treating penicillinase-productive aurococcus (S. aureus) and surgical prophylaxis
No CNF penetration |
|
|
Term
|
Definition
(cefamandole, cefoxitin, cefaclor, cefonicid, cefuroxime, cefotetan, cefprozil)
Similar or less G+ activity than 1st gen
G- activity increased
Some effective against anaerobes (B.fragilis)
Ineffective against p.aeruginosa
Stable to B-lactimases
Less nephrotoxicity
Cefuroxime only 2nd gen to cross BBB for use in meningitis (H.influenza/sepsis) |
|
|
Term
|
Definition
(cefotaxime, ceftizoxime, ceftriaxone, cefoperazone, ceftazidime, cefixime, cefpodoxime)
Broadest spectrum
Highest G- activity
Lowest G+ activity
Highest resistance to B-lactimase
Best CSF penetration
No nephrotoxicity
Ceftizoxime: good activity B.fragilis
Some effective agains P.aeruginosa and enteric bacilli |
|
|
Term
|
Definition
IV
— Once daily dosing (95% protein bound long half-‐life)
— Spectrum: Strep. pneumoniae, most Enterbacteriaceae,
— Excretion: 50% urine, 50% Mbile no need to adjust for renal insufficiency
— CSF penetration: 5-‐15% in meningitis, 1.5% with out inflammation
— DoC: bacterial meningitis, CAP, Strep. viridans endocarditis (+gent)
— ADRs
— Cholestasis
— Elevated bilirubin (displacement)
— Diarrhea |
|
|
Term
|
Definition
IV
. Spectrum: Strep pneumo, Neisseria spp., most Gram (--‐) enterics, M. catarrhalis and H. flu (including β--‐ Lactamase +)
. DoC: bacterial meningitis (esp. in peds + amp if < 4 weeks), CAP, complicated UTI/pyelonephritis, Bacterial Peritonitis |
|
|
Term
|
Definition
IV
. Spectrum: Enteric GNR (including Pseudomonas; some Acinetobacter)
. No anaerobic activity (same for cefotaxime and ceftriaxone)
DoC: Pseudomonas infections (UTIs, pneumonia, meningitis, abdominal). |
|
|
Term
|
Definition
(Maxipime)
. Broad spectrum including Pseudomonas
. More resistant to beta--‐lactamase Than 3rd generation
. Enhanced activity against certain Gram negative bacilli, including Enterobacter, Citrobacter and Serratia.
. Uses. Severe Community Acquired Pneumonia requiring Intensive Care.
. Not effective v ESBL producing organisms.
IV
. NON--‐Spectrum MRSA, C. diff, Burkholderia, Stenotrophomonas, gram--‐negative anaerobes
. Stable vs. de--‐repressed chromosomal β--‐lactamases, but not ESBL
. Less β--‐lactamase induction than 3rd Cephs
. DoC: HAP, febrile neutropenia
4th gen Cephalosporins |
|
|
Term
| Therapeutic uses of Cephalosporins |
|
Definition
1. Alternatives to penicillin in allergic pts
2. Upper respitory tract infections and otitis media (cefaclor, cefixime, cefuroxime axetil, cefprozil)
3. Septicaemia caused by G- bacteria (P.aeruginosae) A penicillin (eg. piperacillin/ticarcillin) + aminoglycoside OR a cephalosporin (eg. ceftazidime) + AG
4. UTI (cefuroxime, cefixime)
5. Prophlaxis in surgery Appendectomy ( bowel anaerobes ) eg. Cefoxitin Obstetrical &gynecological, urological, orthopedic procedures, Etc ( S. aureus
& S. epidermidis ) eg. Cefazoline
6. Meningitis--‐ N. Meningitidis Ceftriaxone Cefotaxime( pref. in neonate)
7. Gonococcal infections Ceftriaxone |
|
|
Term
|
Definition
Monobactam
1. Highly resistant to B-lactamases
2. Highly active vs. aerobic G- (P.aeruginosa & penicillinase H.influenzae and gonococci) but poorly active vs. G+ cocci and anaerobs
3. Spectrum similar to aminoglycosides |
|
|
Term
|
Definition
Carbapenems
Hydrolyzed by dehydropeptidase so formulation contains cilastatin (inhibitor)
2.Spectrum is broadest of b-lactams
3. G+ and G- (not methicillin-resistant staph), enterobacteriaceae, P.aeruginosa, anaerobs, B.fragilis
4. Gonococci and H.influenzae risistant tonatral penicillin and ampicillin are susceptible to imipenem
5. Mainly used in UTI, respiratory, skin,soft tissue
6. Also staphylococcal endocarditis, (NOT CNS infections) |
|
|
Term
|
Definition
Topical Application
§Against G+ |
|
|
Term
|
Definition
Clycopeptide
Important “last line” against antibiotic Resistant S. Aureus |
|
|
Term
|
Definition
MOA: Binds to precursor units of bacterial cell walls, inhibiting cell wall synthesis, also inhibits RNA synthesis
Bactericidal antibiotic for G+ in conc of 0.5-10 ug/mL
Pharm effect
1. Very effective against staph including B-lactamaces and G+ cocci like streptococcus viridans, enterococci, and pneumococcus
2. Also clostridium, corynebacterium diphtheria, and bacillus anthracis
Clinical Use
Orrally for antibiotic associated Pseudomembranous colitis by C.difficile
IV for serious G+ coccal infections like enteroclitis, septicemia (especially for those caused by penicillin resistant pneumococcus and staphylococci
AE
1. Phlebitis at injection site
2. Nephro and oto tox (rare with monotherapy[risk factors: renal impairment, prolonged therapy, high doses, high serum conc, other meds])
3. Red-man/red-neck syndrome |
|
|
Term
|
Definition
| Member of th Lipopeptide class of antibiotics, similar to daptomycin |
|
|
Term
|
Definition
• Friulimicin B is A naturally Occurring cyclic lipopeptide, produced by the Actinomycete Actinoplanes Friuliensis •
It consists Of a macrocyclic Decapeptide core and a lipid tail, nterlinked by an exocyclic amino acid •
Excellent activity against gram--‐positive pathogens, including multidrug--‐resistant strains. •
Friulimicin is water and amphiphilic, with an overall negative charge. Amphiphilicity is enhance in presence of Ca2+, which is also indispensable for antimicrobial activity. |
|
|
Term
|
Definition
Daptomycin- do not use in PNA
Vancomycin
Telavancin- Not FDA approved for PNA
Ceftaroline-5th generation cephalosporin. FDA approval for CAP
Quinupristin-dalfopristin
Linezolid
Tigecycline
clindamycin |
|
|
Term
|
Definition
Cefepime
Ceftazidime
Imipenem
Meropenem
Doripenem
Piperacillin-tazobactam
Ticarcillin-Clavulanate
Gentamicin
Tobramycin
Amikacin
Aztreonam |
|
|
Term
|
Definition
Serratia
Pseudomonus
Acineterbactor
Citerobacter
Enterobacter
G- bacilli that predict major problems |
|
|
Term
| CAP: Empiric treatment of non-hospitalized patients; In a previously healthy patients and no abx therpy in past 3 months |
|
Definition
Macrolide: Clarithromycin or if H. influenzae is suspected Azithromycin
Alternative doxycycline |
|
|
Term
| CAP: Empiric treatment of non-hospitalized patients;Comorbidities or high risk of Strep Pneumo resistance to macrolides (COPD, Diabetes, chronic renal or liver failure, CHF, malignancy, asplenia, or immunosuppression), or recent antibiotic therapy in past 3 months |
|
Definition
Respiratory fluoroquinolone (moxifloxacin, gemifloxacin or levofloxacin) [cover pneumo better)
Macrolide (or doxy) + high dose amoxicillin (1g TID) or augmentin (2g BID)
Macrolide (or doxy) + cephalosporin (ceftriaxone, cefuroxime, or cefpodoxime) |
|
|
Term
| Empiric CAP Tx for Hospitalized Patients |
|
Definition
Respiratory Quinolone (moxi, gemi or levofloxacin)
Macrolide (or doxycycline)Plus B-lactam: cefotaxime, ceftriaxone, ampicillin, ertapenem |
|
|
Term
| Empiric CAP Tx for ICU-Hospitalized Patients |
|
Definition
Respiratory Quinolone (moxi, gemi or levofloxacin) Plus B-lactam: cefotaxime, ceftriaxone, ampicillin-sulbactam
Azithromycin Plus B-lactam: cefotaxime, ceftriaxone, ampicillin-sulbactam |
|
|
Term
| Duration of Treatment (CAP) |
|
Definition
ISDA guidelines
Minimum of 5 days (LOE I)
Therapy should not be stopped until the patient is afebrile for 48-72 hours
Longer duration if complicated by extrapulmonary infection
Generally 7-10 days |
|
|
Term
| Therapy Selection of HAP, VAP and HCAP |
|
Definition
Risk factors for MDR pathogens
Resident flora in hospital
Presence of underlying diseases
Available culture data |
|
|
Term
| HCAP, HAP and VAP early onset |
|
Definition
Less than 5 days
No risk factors for MDR organisms: S. pneumoniae, Haemophilus influenzae, methicillin-sensitive S aureus (MSSA), Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., and Proteus spp.)
Therapy: ONE of the following
Third generation cephalosporin
Cefotaxime
Ceftriaxone
Fluoroquinolone
Levofloxacin, moxifloxacin, ciprofloxacin
Ampicillin/sulbactam
Ertapenem |
|
|
Term
| HCAP, HAP, and VAP late onset or risk for MDR organisms |
|
Definition
Ceftazidime or cefepime + aminoglycoside or fluroquinolone
Imipenem, meropenem or doripenem + aminoglycoside or fluroquinolone
Piperacillin/tazobactam + aminoglycoside or fluroquinolone
+ Vancomycin or Linezolid if MRSA risk factors |
|
|
Term
| Duration of treatment (HCAP, HAP, and VAP) |
|
Definition
7 to 8 days good clinical response
14 days if pneumonia due to Pseudomonas aeruginosa
21 days if MRSA |
|
|
Term
|
Definition
Gram Positive
Cocci
Staphylococcus spp.(CONS)
Streptococcusspp.
Rods
Corynebacterium spp.
Proprionibacterium spp
Gram Negative
Cocci
N/A
Rods
Acinetobacter spp.
Other
N/a |
|
|
Term
|
Definition
Gram Positive
Cocci
Streptococcus spp.
Micrococcus spp.
Peptococcus spp.
Peptostreptococcus spp.
Rods
Actinomyces spp.
Corynebacterium spp.
Gram Negative
Cocci
Neisseria spp.
Rods
Haemophilus spp.
Other
N/A |
|
|
Term
|
Definition
Gram Positive
Cocci
Staphylococcus spp.
Streptococcus spp.
Rods
N/A
Gram Negative
Cocci
Neisseria spp.
Rods
Haemophilus spp.
Bacteroides spp.
Other
Candida spp. |
|
|
Term
|
Definition
Gram Positive
Cocci
Enterococcus spp.
Peptostreptococcus spp.
Rods
Clostridium spp.
Lactobacillus spp.
Gram Negative
Cocci
Rods
Enterobacteriaceae (E.coli,Klebsiella spp.)
Fusobacterium spp.
Bacteroides spp.
Other
Candida spp. |
|
|
Term
|
Definition
Gram Positive
Cocci
Staphylococcus spp.
Streptococcus spp.
Rods
Corynebacterium spp.
Lactobacillus spp.
Gram Negative
Cocci
N/A
Rods
Enterobacteriaceae
Prevotella spp.
Other
Mycoplasma spp. |
|
|
Term
| Resistance Streptococcus pneumoniae |
|
Definition
Mechanism of Resistance
Penicillin binding protein 3 (PBP3) mutation
Treatment
Low level resistance - Increase dose
High level resistance - Avoid agent |
|
|
Term
| Resistance Haemophilus influenzae |
|
Definition
Mechanism of Resistance
β-lactamase
Treatment
Add β-lactamase inhibitor |
|
|
Term
| Resistance Moraxella catarrhalis |
|
Definition
Mechanism of Resistance
β-lactamase
Treatment
Add β-lactamase inhibitor |
|
|
Term
| The addition of the β-lactamase inhibitor clavulanic acid to amoxicillin found in Augmentin® provides an increased spectrum of action and restored efficacy against PNS(penicillin non-susceptible) S. pneumoniae. |
|
Definition
|
|
Term
| Indications for HD amoxicillin-clavulaunate (Augmentin®) |
|
Definition
Failed first-line antimicrobial regimen
Geographic regions with high endemic rates (≥10%) of invasive PNS S.
pneumoniae
Severe infection (evidence of systemic toxicity with fever ≥102°F and threat of
suppurative complications – orbital cellulitis, intracranial infection)
Attendance at daycare
Age <2 or >65 years of age
Recent hospitalization
Antibiotic use within the past month
Immunocompromised patients |
|
|
Term
| Respiratory fluoroquinolones |
|
Definition
Highly active against all common respiratory pathogens
• PNS S. pneumoniae
• β-lactamase-producing H. influenzae
• M. catarrhalis
• Ciprofloxacin lacks adequate S. pneumoniae coverage to
be considered a respiratory fluoroquinolone
Eight randomized-controlled trials (meta-analysis)
confirmed no benefit of newer respiratory
fluoroquinolones to β-lactams in clinical outcomes in
treating bacterial sinusitis |
|
|
Term
| Adverse events of fluoroquinolones |
|
Definition
CNS events (Seizures, headaches, dizziness, sleep disorders)
Peripheral neuropathy
Photosensitivity with skin rash
Disorders of glucose homeostasis (Hypoglycemia, hyperglycemia)
QT prolongation
Hepatic dysfunction
Skeleto-muscular complaints (Achilles tendon rupture: 15-20 per
100,000 in adults; Achilles tendon rupture rare in children) |
|
|
Term
| Respiratory fluoroquinolones |
|
Definition
Failed 1st-line agents
▫ History of allergic type-1 hypersensitivity to penicillin
▫ 2nd line therapy for patients at risk for PNS S. pneumoniae |
|
|
Term
|
Definition
Highly active against all recent respiratory pathogens
Favorable PK/PD properties (similar to fluoroquinolones)
• High-level cross resistance in one Swedish study:
– Resistance was 24% among PNS S. pneumoniae vs 2% in
penicillin-susceptible isolates
• SE: Gastrointestinal, photosensitivity
• Avoid in children ≤8 years old
▫ Accumulates in calcium-rich tissue
during dental development |
|
|
Term
|
Definition
• High likelihood for macrolide resistance in
▫ Prior antibiotic use (macrolides, β-lactams, TMP/SMX)
• Excellent PK/PD properties
• No longer recommended for empiric antimicrobial therapy of
S. pneumoniae infections |
|
|
Term
| Trimethoprim-sulfamethoxazole(TMP/SMX) |
|
Definition
2005-2007 data reveal high rates of resistance among both S. pneumoniae and H. influenzae
High likelihood for TMP/SMX resistance in
▫ Prior antibiotic use (TMP/SMX, macrolides, penicillin)
▫ Macrolide- or penicillin-resistant S. pneumoniae
– >80% higher resistance
• No longer recommended for empiric antimicrobial
treatment of acute bacterial rhinosinusitis |
|
|
Term
| Outpatient treatment (adults)1st-line empiric coverage |
|
Definition
Amoxicillin-clavulanate (Augmentin®) 500mg/125mg PO tid or
875mg/125mg PO bid |
|
|
Term
| Outpatient treatment(adults) β-lactam allergy |
|
Definition
Doxycycline (Vibramycin®) 100 mg PO bid or 200 mg PO daily
(can also be used 2nd-line empiric therapy)
▫ Levofloxacin (Levaquin®) 500 mg PO daily
▫ Moxifloxacin (Avelox®) 400 mg PO daily |
|
|
Term
| Outpatient treatment(adults) Risk for antibiotic resistance or failed initial therapy |
|
Definition
Amoxicillin-clavulanate (Augmentin®) 2000mg/125 mg PO bid
▫ Levofloxacin (Levaquin®) 500 mg PO daily
▫ Moxifloxacin (Avelox®) 400 mg PO daily |
|
|
Term
|
Definition
Adults:
▫ Uncomplicated bacterial rhinosinusitis:
– 5-7 days
Children:
▫ 10-14 days |
|
|
Term
|
Definition
• Intranasal saline irrigation
▫ Provides symptom relief in kids and adults
▫ Can cause nasal burning, irritation, nausea with irrigation
▫ Less tolerated in babies and young children
• Intranasal corticosteroids (INCS)
adjunctively with antibiotics
▫ Reduces mucosal swelling and promotes drainage
▫ Especially useful if history of allergic rhinitis
▫ Minimal short-term adverse events
• Focus on hydration, analgesics,
antipyretics, saline irrigation, INCS
• Topical/oral decongestants,
antihistamines, or mucolytics are not
recommended (IDSA 2012; AAP 2013)
▫ May provide symptomatic relief in acute viral
rhinosinusitis
– Subjective improvements in nasal airway patency
▫ Topical decongestants may itself induce
inflammation in the nasal cavity
▫ Antihistamines dry secretions and impair sinus
drainage (may be useful in those with allergic
rhinosinusitis) |
|
|
Term
|
Definition
Protein-polysaccharide conjugate
Target = infant immunogenicity
Stimulate T
T-cell response
immunity response in infants via
Memory
cytotoxic T cells
Memory helper T cells
Post vaccine exposure = booster effect
Either via revaccination or natural exposure |
|
|
Term
Vaccines
- Polysaccharides |
|
Definition
Plain polysaccharide component
2 saccharides and 1 phosphate molecules
Stimulate T-cell-independent immune response
B-cell proliferation and antibody response
Concerns
Lack of response in age < 2 years
immune response post repeat dosing
Minimal impact on nasal carriage of bacteria |
|
|
Term
|
Definition
Inactivated bacterial
Diphtheria/Tetanus/Pertussis |
|
|
Term
|
Definition
Inactivated bacterial
Diphtheria/Tetanus/Pertussis |
|
|
Term
|
Definition
Inactivated bacterial toxoids
Diphtheria/Tetanus/Pertussis |
|
|
Term
|
Definition
Inactivated bacterial toxoids
Diphtheria/Tetanus/Pertussis |
|
|
Term
| Diphtheria/Tetanus/Pertussis Target |
|
Definition
Diphtheria
Corynebacterium diptheriae
Tetanus
Clostridium tetani
Pertussis
Bordetella pertussis |
|
|
Term
|
Definition
Toxin mediated illness
Myocarditis, neuritis, thrombocytopenia,
respiratory failure, and death |
|
|
Term
|
Definition
Transmission via environment
Interrupts neurotransmitters
Muscle spasms, lockjaw, CNS complications |
|
|
Term
|
Definition
Variable severity and prognosis
Cyclic pattern
- epidemic nature
Disease progression
Catarrhal phase
Paroxysmal phase
aroxysmal Convalescent phase
Progressive flu like s/sx leading to classic
whooping cough |
|
|
Term
| Current vaccines - Diphtheria |
|
Definition
DTaP
– 5 dose series in infant early childhood
10 year immunity
Tdap
Minimum age 10 years for Boostrix
®
Minimum age 11 years for Adacel
®
DT
– pediatric strength booster
Td
– adult strength booster - every 10 years
Unimmunized adult
- 3 dose series |
|
|
Term
| Current vaccines - Tetanus |
|
Definition
Tdap
Tetanus & diphtheria toxoids & pertussis
vaccine
Minimum age = 10 years
Td
Tetanus/diphtheria
toxoid
Adult formulation
TT
Tetanus
toxoid
May be used for adults or children |
|
|
Term
| Current vaccines - Pertussis |
|
Definition
Single dose booster (post DTaP series)
2008 recommendations:
ALL age 11
11-12 years
Catch
Catch-up dose for ages 13 13-18 years
For all ages > 18 years previously vaccinated with
Td
With a suggested 5
5-year gap between the
Tdap and Td |
|
|
Term
| Haemophilus influenzae type b (Hib) |
|
Definition
Vaccine Type
Inactivated bacterial, conjugate
Target
Haemophilus influenzae (type b b)
Disease clinical manifestations
Pneumonia, meningitis, sepsis, etc
High infant/pediatric mortality
Post vaccination era, 99%
in disease |
|
|
Term
| Haemophilus influenzae type b (Hib) Current vaccines |
|
Definition
Conjugate vaccine introduced in 1995
Primarily for children under age of 5 years
Natural immunity if > 5 years
3-dose childhood primary vaccination series
Single dose for high risk groups
with partial
or unvaccinated status
Leukemia or malignant neoplasms
Anatomic or functional asplenia
Immunocompromised conditions |
|
|
Term
|
Definition
Vaccine Type
Inactivated viral
Target
Hepatitis A virus (HAV)
Disease clinical manifestations
Most common hepatitis prior to 2004
Fatigue, loss of appetite, N/V, abdominal pain
Dark urine, clay
clay-colored BM
Joint pain, jaundice |
|
|
Term
| Hepatitis A Current vaccines |
|
Definition
2013 Recommendation:
2 dose vaccination series
Dose # 1 at 1 yr (dose = 0.5 mL)
Dose # 2
six months after first dose (dose = 1 mL)
Certain high
high-risk adolescents |
|
|
Term
|
Definition
Vaccine Type
Inactivated viral (recombinant)
Target
Hepatitis B virus (HBV)
epatitis
Disease clinical manifestations
Flu-like s/sx
Dark urine, jaundice
Hepatomegaly, liver failure
Hepatocellular carcinoma and death |
|
|
Term
| Hepatitis B Current vaccines |
|
Definition
2 main vaccine manufacturers
3 vaccine formulations
Pediatric formulations
Adults formulations
Dialysis formulations
Dose volumes defer
Formulations sometimes NOT interchangeable |
|
|
Term
| Human Papilloma Virus (HPV) |
|
Definition
Vaccine Type
Inactivated viral
Target
Coverage = 4 types of HPV
2 types that cause 70% of cervical cancers
2 types that cause 90% of genital warts
Disease clinical manifestations
Most common sexually transmitted
infection
in the US
> 6 million NEW infections/year |
|
|
Term
| Human Papilloma Virus (HPV) Current vaccines |
|
Definition
Current vaccines
Gardasil
Quadrivalent (types 6, 11, 16, 18)
Licensed for
males and females 9 through 26
years.
Cervarix
– Bivalent
Bivalent (types 16, 18)
Licensed for females 10 through 26 years
Added as a recommendation in 2007
3 dose schedule (at 0, 1 to 2, 6 months)
Recent concerns/controversies
Safety of the vaccines
Long
Long-term effects
Moral objectives and perceived
risk of
promiscuity in adolescents
Need for long
long-term boosters
Cost (3
3-dose series ~ $360)
Especially for males |
|
|
Term
|
Definition
Vaccine Type
Inactivated
influenza vaccine (IIV IIV)
Live -attenuated influenza vaccine (LAIV)
Target
Vaccine based off projected
“problematic problematic”
serotypes for 2013 2013-14 season
2013
2013-14 influenza vaccine antigens:
A/California/7/2009 (H1N1)-like
A/Victoria/361/2011 (H3N2) – like
B/Massachusetts/2/2012–like (new)
B/Brisbane/60/2008-like
Disease clinical manifestations
Common
“flu flu” like s/sx
Fever/chills/cough/sore throat/HA
Runny or stuffy nose
Muscle/body aches or fatigue
Vomiting and diarrhea
Severe illness
Pneumonia
Life
Life-threatening complications
Death |
|
|
Term
| Influenza Current vaccines |
|
Definition
ACIP recommendations
Inactivated Influenza Vaccine
(IIV IIV) *
Trivalent = preferred
Injection(3 types) -match age with vaccine product
Live
Live-attenuated influenza vaccine (LAIV)
Intranasal
Quadrivalent
For age ≥ 2 to 49 years
Do NOT use in high risk group
General vaccine criteria
ALL children ≥ 6 months of age
Postpartum and breastfeeding moms
ALL household and caregivers
ALL healthcare personnel
MUST immunize HIGH risk pts
asthma/chronic lung/cardiac conditions
SCD, DM and immunosuppression
neurologic conditions (new)
Age-based dosing
Age 5 months and less
Do NOT administer vaccine
Age 6 months to 8 years
See dosing algorithm (next slide)
Dose for age 6-35 months = 0.25 mL
Dose for age ≥ 36 months dose = 0.5 mL
Age 9 years and greater
0.5 mL |
|
|
Term
|
Definition
Vaccine Type
Live attenuated viral
Target
Measles rubeola
Disease clinical manifestations
Rash all over the body
Red eyes, rhinorhea, fever, cough
Severe forms = pneumonia, encephalitis |
|
|
Term
|
Definition
Vaccine Type
Live attenuated viral
Target
Mumps virus
Disease clinical manifestations
Reactive inflammatory processes
Lymphadenopathy and jaw swelling
Testicles (occasional sterility)
CNS
Deafness and brain damage |
|
|
Term
|
Definition
Vaccine Type
Live attenuated viral
Target
Rubella virus
Disease clinical manifestations
Rash (German measles)
F, malaise, lymphadenopathy, and URI s/sx
Joint pain |
|
|
Term
|
Definition
M-M-R II (MMR)
ProQuad (MMRV) – includes Varicella
Minimum age = 1 year
Exception = outbreak containment
2 vaccine series4 to 6 years
1st dose at 12 to 15 months
2nd dose at 4 to 6 years |
|
|
Term
|
Definition
Vaccine Type
Inactivated bacterial
Target
Neisseria meningitidis
Disease clinical manifestations
Meningitis and sepsis
Highest risk
= infants & teenagers
Commonly result in localized
“out breaks breaks”
College freshmen dormitories
Crowded living spaces |
|
|
Term
| Meningococcal Vaccine Current vaccines |
|
Definition
Menectra
®
Meningococcal
conjugate vaccine (MCV4)
Route = IM
1° target vaccination group
Age 11 to 18 years routine vaccination
Other target vaccination groups
Age Range 9 to 23
months
Complement component deficiency
Age 2 to 10
years AND age 19 to 55 years
Complement component deficiency
Functional or anatomic asplenia
Menveo®
Meningococcal
conjugate vaccine (MCV4)
Route = IM
1° target vaccination group
Age 11 to 18 years routine vaccination
Other target vaccination groups
Age 2 to 10
years AND age 19 to 55 years
Complement component deficiency
Functional or anatomic asplenia
Menomune
®
Meningococcal
polysaccharide vaccine (MPSV4)
Route = SC
Target vaccination groups
Age 56 years and older
If given in error to age 2 to 55 years, then follow
follow-
up with conjugate booster |
|
|
Term
|
Definition
Vaccine Type
Inactivated bacterial
Target
Streptococcus pneunomiae
Disease clinical manifestations
Highest risk = < 2 years and > 65 years
URI, sinusitis, AOM, pharyngitis, pneumonia
Bacteremia, meningitis, and sepsis |
|
|
Term
| Pneumococcal Vaccine Current vaccines |
|
Definition
2 types of vaccines
Pneumococcal Conjugate Vaccine (PCV13)
Prevnar
®
Pneumococcal Polysaccharide Vaccine (PPSV23)
Pneumovax
®
Caution: NOT interchangeable |
|
|
Term
| Pneumococcal Conjugate Vaccine (PCV) |
|
Definition
Current PCV covers 13 serotypes
Significant invasive pneumococcal dz
1° target vaccination group
Age 23 months and less
Routine childhood vaccination series
4 dose series
Other target vaccination groups
Age 24 to 59 months
SCD, splenic dysfunction, HIV, chronic illnesses
and immunocompromised |
|
|
Term
| Pneumococcal Polysaccharide Vaccine (PPSV23) |
|
Definition
Current PPSV covers 23 serotypes
1° target vaccination groups
Age
≥ 65 years (ever
Age 2 to 64 years
CHF, cardiomyopathy, DM, liver dz
Functional or anatomic asplenia
Asthma, CLD, smokers
Cochlear implants
HIV, leukemia, lymphoma
CRF or nephrotic syndrome |
|
|
Term
|
Definition
Vaccine Type
Live viral
Target
Rotavirus
Disease clinical manifestations
Leading cause of gastroenteritis in infants
Dehydration
Hospitalizations
Death
Rotashield – With drawn from the market in 1999 (intussusceptions)
RotaTeq: pentavalent, oral vaccine
3 doses at 2, 4 and 6 months of age
Rotarix: monovalent, oral vaccine
2 dose vaccination series (6 months apart)
Dose #1 at 6 to 14 weeks
Dose #2 at 14 to 24 weeks |
|
|
Term
|
Definition
Vaccine Type
Live viral
Target
Varicella
Varicella-zoster virus
Disease clinical manifestations
Chicken pox and cellulites
Sever dehydration
Pneumonia and encephalitis |
|
|
Term
| Varicella A Current vaccines |
|
Definition
Series changed to include total of 2 doses
Dose #1 at age 12-18 months
Dose #2 at 4-6 yrs
2008 recommendations are:
2 doses for unvaccinated child < 13 years (with a 3 month interval)
2nd dose for previously vaccinated child with 1 dose (with a 3 month interval) |
|
|
Term
|
Definition
Should NOT receive LIVE vaccines
May receive:
Inactivated vaccines
Immunoglobulins
Household contact:
MMR, influenza, varicella, and rotavirus
vaccines are recommended
Should
NOT receive oral polio vaccine |
|
|
Term
|
Definition
Inactivated vaccines or Toxoids = Yes
Immunoglobulins = Yes (when necessary)
Live Vaccines = NO
OK to give MMR to close contacts
OK to give live vaccines to leukemia patients
3 months post last chemotherapy cycle
Zoster vaccines at least 2 weeks prior
Influenza vaccine 2 weeks prior or in
between cycles |
|
|
Term
|
Definition
Inactivated vaccines = Yes
Immunoglobulins = Yes (when necessary)
Live Vaccines
MMR, Varicella, and Zoster
should be considered for
asymptomatic or
mildly symptomatic pts
ONLY if CD4 counts are > 200/mm
mm3
NO to LAIV |
|
|
Term
| Solid Organ Transplant Population |
|
Definition
Best to immunize prior to transplantation
Post transplant
NO live vaccines
Life long immunosuppressive regimens
response to hepatitis B vaccine
Unpredictable response to most vaccines |
|
|
Term
| Stem Cell Transplant Population |
|
Definition
Re-immunize post transplantation
Influenza vaccines
– 6 months post
Inactivated vaccines
– 12 months post
PPSV23
Hib
Some live vaccines
– 24 months post
MMR |
|
|
Term
| Live Vaccines & Corticosteroids |
|
Definition
Administer if:
Topical corticosteroids
Physiologic maintenance doses
Low to moderate doses
Less than 2 mg/kg/day
or 20 mg/day
With high dose steroids:
Course < 14 days = after end of course
Course
≥ 14 days = wait 1 month |
|
|
Term
|
Definition
Most vaccines = pregnancy category C
AVOID live vaccines
Defer to postpartum
Use immunoglobulins (when necessary)
Influenza = Must-have
Postpartum must-have = TdaP
Passive protection to infant against pertussis |
|
|
