Infectious Disease Flashcards
1
Q
Minimum inhibitory concentration (MIC)
A
Lowest antimicrobial concentration that prevents visible growth of an organism after ~24 hours of incubation in a specified growth medium
2
Q
Minimum Bactericidal Concentration (MBC)
A
Lowest concentration of drug that kills 99.9% of the total initially viable cells or greater reduction in the starting inoculum)
3
Q
Post-antibiotic Effect (PAE)
A
- Persistent suppression of an organism’s growth after a brief exposure to an antibiotic
- Primary clinical application - allow for less frequent administration of antimicrobials while still maintaining adequate antibacterial activity (e.g., extended-interval aminoglycoside administration)
4
Q
Synergy
A
Using combination of antibiotics that result in activity that is greater than the activity of either agent alone
5
Q
Antibiogram
A
Local antimicrobial susceptibility data gathered from recent cultures obtained from patient at that institution
Culture Reports:
- S = “susceptible”
- I = “intermediate or indeterminate”
- R = “resistant”
6
Q
PROPHYLACTIC THERAPY
A
- Treating patients who are not yet infected or have not yet developed disease.
- Goal: prevent infection in some patients or to prevent development of a potentially dangerous disease in those who already have evidence of infection
7
Q
PRE-EMPTIVE THERAPY
A
- Early, targeted therapy in high-risk patients who already have a laboratory or other test indicating that an asymptomatic patient has become infected
- Goal: Delivery of therapy prior to development of symptoms
8
Q
EMPIRICAL THERAPY IN THE SYMPTOMATIC PATIENT
A
Before consideration is given in selecting an antimicrobial agent, is to determine if the drug is indicated
9
Q
DEFINITIVE THERAPY WITH KNOWN PATHOGEN
A
- Once a pathogen has been isolated and susceptibilities results are available, therapy should be streamlined to a narrow targeted antibiotic.
- Goal: Maximize efficacy and minimize toxicity
10
Q
POST-TREATMENT SUPPRESSIVE THERAPY
A
- In some patients, after the initial disease is controlled by the antimicrobial agent, therapy is continued at a lower dose if the infection is not completely eradicated and the immunological or anatomical defect that led to the original infection is still present.
- For example, in HIV and post-transplant patients as a secondary prophylaxis
11
Q
Mechanism of Resistance
A
Emergence of Resistance is associated with:
- Evolution
- Clinical/environmental practices
Resistance may develop because of:
- Reduced entry of antibiotic into pathogen
- Enhanced export of antibiotic by efflux pumps
- Release of microbial enzymes that destroy the antibiotic
- Alteration of microbial proteins that transform prodrugs to the effective moieties
- Alteration of target proteins
- Development of alternative pathways to those inhibited by the antibiotic
12
Q
Mechanism of Action:
Cell Wall Inhibitors
A
Cell Wall Inhibitors:
Beta-lactams
- Inhibits peptidoglycan synthesis; peptidoglycan is a component of the cell wall that provides rigid mechanical stability
Glycopeptides (Vancomycin)
- Inhibit cell wall synthesis by binding with high affinity to the D-alanyl-D-alanine terminus of cell wall precursor units
Lipopeptides (Daptomycin)
- Binds to bacterial membranes, resulting in depolarization, loss of membrane potential, and cell death
13
Q
MoA:
Protein Synthesis Inhibitors (50S)
A
Protein Synthesis Inhibitors
Lincosamides (Clindamycin)
- Inhibits protein synthesis by binding to 50S ribosomal subunit
Macrolides
- Inhibits protein synthesis by binding reversibly to 50S ribosomal subunits
Oxazolidinones (Linezolid)
- Inhibits protein synthesis by binding to the P site of 50S ribosomal subunit and preventing formation of the larger ribosomal-fMet-tRNA complex that initiates protein synthesis
Chloramphenicol
- Inhibits protein synthesis by binding reversibly to 50S ribosomal subunits and inhibits peptide bond formation
14
Q
MoA:
Protein Synthesis Inhibitors (30S)
A
Protein Synthesis Inhibitors
Tetracyclines
- Inhibits protein synthesis by reversibly binding to 30S ribosomal subunit and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Aminoglycosides
- Inhibits protein synthesis by irreversibly binding to 30S ribosomal subunit and leads to cell death; protein synthesis is inhibited by the following:
- Interference with protein synthesis initiation
- Causing misreading of the mRNA template and incorporation of incorrect amino acids into the growing polypeptide chains
- Breakup of polysomes into nonfunctional monosomes
15
Q
MoA:
Antifolate Antibiotics
A
Antifolate Antibiotics
Sulfonamides
- Competitive inhibitors of dihydropteroate synthase, the bacterial enzyme responsible for incorporation of PABA into dihydropteroic acid, the immediate precursor of folic acid
- Sensitive microorganisms are those that must synthesize their own folic acid otherwise it won’t work
Trimethoprim
- Inhibits bacterial dihydrofolate reductase, an enzyme downstream from the one that sulfonamides inhibit in the same biosynthetic sequence
16
Q
MoA:
DNA Gyrase Inhibitors
A
DNA Gyrase Inhibitors
Quinolones
- Block DNA synthesis by inhibiting Bacterial topoisomerase II (DNA gyrase) and topoisomerase IV preventing the relaxation of positively supercoiled DNA required for normal transcription and replication [broad spectrum, emerging resistance]
17
Q
Beta-Lactam Antibiotics
A
Penicillins
Penicillin
- Penicillin G / VK; Penicillin G Benzathine; Penicillin G Procaine
- Susceptible to hydrolysis by β-lactamases
Anti-staphylococcal penicillin
- Nafcillin; Oxacillin; Dicloxacillin
- Resistant to staphylococcal β-lactamases
Extended-spectrum penicillin
- Ampicillin; Amoxicillin (Amoxil); Piperacillin; Ticarcillin
- Improved activity against Gram-negative rods
- Relatively susceptible to hydrolysis by β-lactamases
- Combined with β-lactamase inhibitors (clavulanate, tazobactam) to prevent resistance
18
Q
Penicillins pharmacokinetics
A
Not well absorbed from the GI
- Except penicillin VK and amoxicillin – only oral
- Penicillin G is not acid stable, only parenteral (syphillis)
Primarily excreted in the urine in the unchanged form
Do not penetrate well into the cerebrospinal fluid (CSF) in the absence of meningeal inflammation
- Except Ampicillin – achieves therapeutic concentrations in most body fluids
Procaine or benzathine penicillin provide tissue depots (for IM)
- Procaine absorbed over several hours; benzathine over several days
19
Q
Penicillins side effects
A
- Allergic reactions ~0.01 to 5% – skin rashes ranging from maculopapular eruptions to exfoliative dermatitis, urticaria, and reactions resembling serum sickness (chills, fever, edema, arthralgia)
- Higher rate of maculopapular rash with ampicillin
- Rare: Hematologic toxicity (anemia, leukopenia, thrombocytopenia)
- Sodium overload from parenteral (caution with renal impairment)
20
Q
Anti-Staphylococcal Penicillin
A
- Oxacillin - May enhance anticoagulant effect of warfarin
- Nafcillin – Higher risk of drug interactions (nasty)
- Decrease opioid concentrations; may decrease anticoagulant effect of warfarin
- Predominantly excreted through biliary system - Caution with accumulation in jaundiced neonates
- Higher risk of extravasation
21
Q
β-Lactamase Inhibitors
A
• Sulbactam, clavulanic acid, tazobactam
- Only used in combination with a penicillin
- Dosing always based on penicillin component
- Combination extends spectrum of activity to include β-lactamase producing organisms
• Clavulanic Acid – higher diarrhea and GI effects when administered orally with amoxicillin (augmentin). Can be ameliorated with probiotic use.
22
Q
Cephalosporins
A
Beta-lactam Abx
Generations based on spectrum of activity
1st gen– higher gram+ coverage (skin flora, post-op)
2nd gen– some gram+ coverage, some gram-
3rd gen– coverage of gram+ varies, high gram- coverage
- drug of choice for Streptococcus pneumo;
- ceftaz – only 3rd gen with Pseudomonas coverage
4th gen– broad coverage including Pseudomonas
5th gen– unique cephalosporin with broad coverage
- including Enterococcus and MRSA (only cephalosporin with this coverage, but not first-line for MRSA)
23
Q
Cephalosporins pharmacokinetics, side-effects
A
PK:
- Primarily excreted via kidneys mainly by glomerular filtration
- Adjust doses in patients with renal insufficiency
- CTX has significant biliary excretion
- Avoid in the 1st month of life due to kernicterus risk
- Most have good penetration into tissues & fluid compartments
- Optimal for CSF: cefotaxime, CTX, cefepime
SE:
- Skin Rashes (1-3%); Anaphylactic (0.1%); thrombocytopenia
24
Q
Carbapenems (IV)
A
PK:
- Broad spectrum class of antibiotics (-penems)
- Widely distribute to different body tissues including CSF
- Renally excreted
- Adjust in renal impairment
- Imipenem always combined with cilastatin to reduce nephrotoxicity
SE:
- Commonly GI related
- Seizures higher with imipenem versus meropenem
- Increased liver enzymes, thrombocytopenia
25
Monobactams – Aztreonam (IV)
**PK:**
* Patients allergic to penicillin/cephalosporins do not react to aztreonam
* No significant antibacterial activity against gram+ organisms or anaerobes
* Renally eliminated
* Adjust in renal impairment
* Distributed widely into most body tissues and fluids included CSF
**SE**: rash, diarrhea, fever
26
Aminoglycosides (IV)
*Gentamicin, Tobramycin, Amikacin*
* Concentration-dependent bactericidal activity
* Higher [], better the kill
* Exert a post-antibiotic effect (PAE)
* Synergism with other antibiotics (cell-wall active)
**PK:**
* Distributed into extracellular water (consider age related changes of %water)
* Patients with CF – higher Vd and Cl, require higher doses
* Extensively renally cleared
* Preemies required longer intervals
* Does not penetrate into the CSF (only in neonates)
27
Aminoglycosides PK & SE
* **Efficacy**: Related to peak serum concentration to MIC ratio (desired ratios of 5-10)
* Measure Peak concentration levels
* Goals depend on indication, with lower goals for UTI
* Multiple Daily Dosing/Traditional Dosing:
* Gentamicin/Tobramycin – Peak Goal 4-12 mcg/mL; synergy 3-5 mcg/mL
* Amikacin – Peak Goal 15-40 mcg/mL
* Once-Daily Dosing (ODD) - Higher peak is expected
* **Toxicity**: Related to trough concentration
* **Nephrotoxicity**: proximal tubular injury leading to cell injury
* **Ototoxicity**: cochleo- & vestibulotoxic; accumulate in inner ear
* Hearing loss usually bilateral, symmetrical, and permanent, (possible delayed onset of months)
* **Myotoxicity**: prolonged muscle weakness when utilized in combination with a muscle relaxant (up to a week after d/c)
* Measure Trough Concentration levels
* Goals depend on infection severity and renal function
* Multiple Daily Dosing/Traditional Dosing:
* Gentamicin/Tobramycin – Trough \< 2 mcg/mL
* Amikacin – Trough \< 8 mcg/mL
* Once-Daily Dosing (ODD): trough is undetectable
28
Glycopeptides: Vancomycin (IV)
* Vancomycin*
* (Telavancin; Dalbavancin; Oritavancin -- not used often in pediatrics w/o ID referral)*
* Cornerstone treatment of **gram+** infections
* Time-dependent bactericidal activity (exception: bacteriostatic for *Enterococcus* spp.)
* Time maintained above the MIC achieves better kill
* Synergism with other antibiotics (aminoglycosides or rifampin)
**PK:**
* Pediatric Patients have higher Cl, require shorter intervals (q6-8 vs adult q12)
* Extensively renally cleared
* Preemies required longer intervals
29
Vancomycin efficacy/toxicity
**Efficacy:**
* Related to % of time concentration remains above MIC (T\>MIC)
* Area under concentration-time curve to MIC ratio (AUC:MIC)
* Maximum concentration to MIC ratio (Cmax:MIC)
Resistance depends on MIC breakpoints
* Better treatment success with MIC of \<= 0.5 mg/L
* 1-2 is not enough
Measure Trough concentration levels: Goal 10-20 mg/L
* Higher end of range for complicated infections to improve penetration : Goal 15-20 mg/L
* Bacteremia, endocarditis, osteomyelitis, meningitis, and hospital-acquired pneumonia caused by MRSA/MSSA -- the [] will be lower in these areas than in the blood/harder to penetrate, requires higher trough
**Toxicity:**
* Infusion related reaction (**Red-man’**s syndrome) – histamine mediated rash of face, neck, upper trunk
* Increase infusion time from 1 hour to 2 hours; pretreat with diphenhydramine
* **Hematologic**– neutropenia, thrombocytopenia, eosinophili
* **Nephrotoxicity**– observed with higher trough concentrations and polypharmacy with other nephrotoxic medications (tacro, etc.)
* **Rare** **Ototoxicity**– potentially vestibulo-/cochleotoxic; tinnitus precedes hearing loss (r/t high peak, more common when vanc was made with more additives)
30
Fluoroquinolones
* Ciprofloxacin– approved for complicated UTIs & pyelonephritis
* Ciprofloxacin/levofloxacin– approved for inhalation anthrax and plague
* Moxifloxacin – ltd data in pediatrics
* Limit use due to emergence of resistance
**PK:**
* Large Vd, low protein binding– extensive tissue and fluid distribution
* Renally cleared (some have hepatic metabolism)
* Higher renal elimination in children \<5 years
**SE/ARx:**
* Adverse reactions/frequency differ among agents due to differences in chemical structure & specific interactions with organ systems...
* Adverse Reactions
* * GI related including *C. diff* (common)
* Dizzy, headache
* QT prolongation, Torsades (Levo \> Cipro)
* Arthropathy 1.5-1.8%
* Tendinopathy and tendon rupture– higher risk in athletes
31
Macrolides – Azithromycin (IV, PO)
**PK:**
* Distributes to tonsils, adenoid tissues, middle ear fluid (think resp)
* Concentrations persist in tissues for additional 5 days after 5 day course
* Slow elimination; Q12; t1⁄2 = 32-64 hr
* Renally eliminated
* Increases rate of gastric emptying (GI SE, erythromycin used)
**SE:**
Adverse Effects are dose-related
* Common – GI related
* Transient increase hepatic enzymes
* Rash 1.5%
* Headache
Drug Interactions – reduced efficacy with food, antacids, H2Blockers reduce oral absorption by 50%
32
Macrolides – Clarithromycin (PO)
**PK:**
* Not affected by food like other macrolides
* Renally eliminated
**SE:**
* Adverse Effects are dose related
* Common – GI related; headache
* Metallic taste
* Drug Interactions
* Inhibition of CYP3A4
33
Tetracyclines
*Doxycycline (IV, PO)*
**PK:**
* Distributes widely into tissues and fluids
* Renally eliminated
**SE:**
* Drug Interactions
* **Chelates** with antacids, dairy products, calcium, iron, aluminum, magnesium, PPIs
* Adverse Reactions
* Hypersensitivity syndromes, photosensitivity
* AAP liberalized recs for use of DOXY in children; other tetracyclines still not recommended for \<8y
* Recent comparative date suggest doxy not likely to cause visible teeth staining/enamel hypoplasia in kids \<8y
* Can be administered for short durations (\<21d) w/o regard to patient's age
* Doxy less readily binds to Ca++ than other tetracyclines
* Still not first line
34
Clindamycin (IV, PO)
Lincosamide abx (50S, shut down protein synth)
**PK:**
* Penetrates well into most tissues incl. **abscesses**, except CSF
* Metabolized by liver, excreted in bile and urine
**SE:**
* Common – GI s/sx, rash
* Impaired liver function, neutropenia
35
Sulfonamides
_**TMP-SMX** (IV, PO)_
* Combination is synergistic and bactericidal
* Optimum ratio 1:5 TMP:SMX
* Dosing always based on TMP
* IV, PO (IV less commonly utilized)
**PK:**
* Widely distributed in body tissues, fluids including CSF, middle ear, aqueous humor, bile
* Primarily liver metabolized
* ~30% renally elim
**SE:**
Drug interactions common
* Warfarin, phenytoin, digoxin, etc.
* GI
* Rash -- maculopapular rash, itching, diffuse erythema, morbilliform rash, erythema multiforme, pupura, photosensitivity/sunburn
* Mild, dose-related, reversible
* **SJS, toxic epidermal necrolysis**
* Renal effects:
* Decreased Cr
* HyperK
* Heme: anemia, thrombocytopenia
36
Antibiotic-Induced Drug Reactions
***C. difficile***
* Common culprits: Fluoroquinolones, clindamycin, and cephalosporins (especially **2nd** and **3rd** gen)
**Serum Sickness–Like Disease (SSLD)**
* Cutaneous eruption (urticarial or maculopapular)
* Culprits: ciprofloxacin, tetracyclines, sulfonamides, penicillins, cephalosporins
**Drug Rash with Eosinophilia and Systemic Symptoms (DRESS)**
* Tetracyclines, sulfonamides
**Drug Fevers**
* β-lactams, tetracyclines, sulfonamides
37
URI
* Most Common Bacterial Pathogens
* *Streptococcus* spp.
* *Haemophilus influenzae*
* *Moraxella catarrhalis*
* Viruses are most common causes
* Immunizations and education are key for prevention
38
AOM
**Goals of Therapy**
* Pain management is important!
* Acetaminophen or ibuprofen
* Prudent antibiotic usage – *Identify need for antibiotics*
* Prevention with vaccinations!
* No benefit in using decongestions or antihistamines
* Topical agents (benzocaine) – only brief benefit in those \> 5 yrs.
**Antibiotic therapy:**
*\*Must evaluate antibiotic therapy after 48-72 hours\**
* Verify if symptoms are resolved
* Evaluate if complications develop
39
Amoxicillin
**Amoxicillin** drug of choice in most patients for AOM
*(High dose preferred: 80-90mg/kg/day BID)*
* Proven effectiveness
* High middle ear concentrations
* Excellent safety profile
* Relatively narrow spectrum of activity
* Low cost
* Good taste
**Amoxicillin** is drug of choice if...
* Has not received amoxicillin in past 30 days
* OR does not have concurrent purulent conjunctivitis
* OR not allergic to penicillin
**Amoxicillin/Clavulanate** (added β-lactamase coverage) is drug of choice if...
* Has received amoxicillin in past 30 days
* OR has concurrent purulent conjunctivitis
* OR has hx of recurrent AOM unresponsive to amoxicillin
* \*\*Anytime β-lactamase producing organism is suspected\*\*
* Give up taste for extended coverage
40
PCN Allergy in Children
* Recent data suggest cross-reactivity among penicillin & cephalosporin is lower than historically reported \< 10%
* Higher cross-reactivity between penicillin + 1st gen
* Negligible cross-reactivity with 2nd and 3rd
**AAP Recommendation:**
* Cephalosporin recommended in cases w/o severe and/or recent PCN allergy reaction hx when skin test is not available
* Preferably – **cefdinir, cefuroxime, cefpodoxime, ceftriaxone** to be used in cases of AOM with PCN allergy
41
First Line ABX for AOM
Clinda used in true PCN anaphylactic reactions
Amox --\> augmentin --\> other cephalosporin --\> IM CTX --\> Clinda --\> Clinda + 3rd gen cephalosporin (would require cx)
42
AOM Dosing, Duration
**Amox** -- 80-90mg/kg/day divided BID
**Augmentin** -- 90mg/kg/day amoxicillin + 6.4mg/kg/day clavulanate (14:1 ratio) divided BID
* *Must use the 600mg/5mL suspension - only one w/ 14:1 ratio*
* *Diarrhea*
**CTX** -- 50mg/kg IM for 1-3 days
--------------
_Duration_
Traditional recommendation: 10 days
* \<2y and severe symptoms
Short course: 7 days
* \>2y and mild-moderate symptoms
43
Other AOM Options (pros/cons)
Clindamycin–
* lacks efficacy vs. *H. influenzae*
* may be good for suspected PCN-resistant *S. pneumoniae* (but not for MDR serotypes)
* recommended for pts with anaphylactic PCN allergies
Azithromycin–
* lacks efficacy vs. *H. influenzae* and *S. pneumoniae*
* recommended for pts with anaphylactic PCN allergies
TMP-SMX
* increased resistance, not recommended
Levofloxacin
* cx first, may be indicated if other therapies fail
Linezolid
* cx first, G+ only
44
Pertussis abx prophylaxis & treatment
**Azithromycin**
* \<6mo; 10mg/kg/day for 5d
* \>6mo; 10mg/kg/day for 1d, then 5mg/kg/day for 4d
**Clarithromycin**
* BID for 7 days, not for \<6mo
**Macrolide allergy**
* Bactrim BID for 14d, not for \<2mo
45
Pertussis PEP
**Pertussis Post-exposure Antimicrobial Prophylaxis (PEP)**
* Administer abx to any of the following within 21 days of exposure:
* All household contacts of a pertussis case
* High risk people OR people in close contact with high risk people
* Infants \< 1 year of age
* Women in their third trimester of pregnancy
* People with pre-existing health conditions that may be exacerbated by pertussis infection (immunocompromised, moderate to severe asthma)
* People in high risk settings including neonatal intensive care units, childcare settings, and maternity wards
46
ACUTE BACTERIAL RHINOSINUSITIS (ABRS)
* Viral
* Bacterial
* Most Common:
* *S. pneumoniae*
* *H. influenza*
* Least Common
* *M. catarrhalis*
* *Strep pyogenes, Staph aureus*
* G- bacilli, anaerobes
Bacterial or Viral?
**3 presentations most consistent with bacterial ABRS:**
* Persistent s/sx lasting for ≥ 10 days without clinical improvement
* Severe s/sx of high fever (≥ 39°C [102.2°F]) and purulent nasal discharge or facial pain lasting for at least 3-4 consecutive days at the beginning of illness
* Worsening s/sx characterized by new-onset fever, HA, or increase in nasal discharge following a typical viral URI that lasted 5-6 days and were initially improving (“double sickening”)
**Therapy**
* Nonpharm: rest, fluids, humidification
* AAP does not recommend antihistamines/decongestants
47
Acute Bacterial Rhinosinusitis (ABRS): risk of ABX resistance
***\*\*Affects length of treatment and use of second-line over first-line.***
* Age \< 2, attends daycare
* Prior antibiotics within past month
* Prior hospitalization past 5 days
* Immunocompromised
* Also consider:
* Geographic regions with high endemic rates (\> 10%) of invasive PCN-resistant *S. pneumoniae*
48
ABRS ABX Therapy
**Augmentin**
SD: 45mg/kg/day BID
HD: 90mg/kg/day BID
**Beta-lactam allergy\*\***
Non-type I hypersensitivity
Type I hypersensitivity
49
ACUTE PHARYNGITIS: etiology
**_Etiology_**
**Viruses** – MOST COMMON CAUSE
* Rhinovirus, adenovirus, HSV, influenza, paraflu
* Epstein–Barr virus
**Bacteria**
* MOST COMMON: Group A β-hemolytic Streptococcus (GABHS) or (GAS) (aka S. pyogenes; “strep throat”)
* In children \< 3 years of age, GAS rarely the cause
* Most common 5-15y
* Less common: Groups C and G *Streptococcus, Corynebacterium diphtheriae, Neisseria gonorrhoeae, Mycoplasma pneumoniae, Chlamydia pneumoniae*
50
Acute Pharyngitis: who's at risk?
Highest Risk
* Children 5-15 yr
* Parents of school-age children
* Adults who work with children
* Spread occurs via direct contact with droplets of saliva or nasal secretions
* Incubation period: 2-5 days
* **Effective antibiotic therapy reduces the infectious period to about 24h**
**Streptococcal Pharyngitis Severe Complication**
* Rheumatic Fever - most severe
* Inflammatory disease of organs
* Occurs ~19 days after onset
**J\<3NES** Major Criteria
**J**oint involvement
* *\<3**myocarditis
* *N**odules, subcutaneous
**E**rythema marginatum
**S**ydenham chorea
51
Acute pharyngitis: therapy
* Prescribe antibiotics only for proven cases of GAS pharyngitis
52
CAP Etiology
* Bacteria
* *Strep pneumo* most common
* Infants 4-16 weeks, consider *chlamydia*
* 5y-teens, consider *mycoplasma*
* Viral pneumonia most common (80%) in first 2-3y
53
CAP Treatment
**Outpatient (10 days)**
* Presumed bacterial:
* HD Amox +/- macrolide
* Alt: Augmentin +/- macrolide
* Presumed atypical, add a macrolide:
* Azithromycin
* Alt: Clarithromycin
* Alt: Doxycylcine if \>7y
* Influenza:
* Influenza antiviral therapy
-------------------------
**Inpatient**:
* First-line for otherwise healthy patients:
* Ampicillin or Pen G for *Strep pneumo*
* Danger town
* **Empiric therapy with 3rd gen cephalosporin (CTX or cefotaxime)
* If not fully immunized or regions with invasive pneumococcal strains, high-level PCN resistance, or life-threatening infx
* If suspected **atypical, add a macrolide** (mycoplasma, chlamydia)
* *Staph aureus*?
* Vanc or clinda
54
BACTERIAL MENINGITIS
* \<1mo- pathogens from birth canal/mom
* *GBS, Listeria, E.coli, Kleb* spp.
* Trx: **Ampicillin+cefotaxime** or **Amp+aminoglycoside**
* 1mo-2y- community organisms
* *Strep pneumo, N. meningitidis, H. influenzae, GBS, E. coli*
* Trx: **Cefotaxime+vanc** or **CTX+vanc**
* 2-50y-
* *Strep pneumo, N. meningitidis*
* Trx: **Cefotaxime+vanc** or **CTX+vanc**
* Vanc is back-up, stripped back after speciation
* Invasive NSGY procedure/trauma-
* *Staph aureus/epidermidis, pseudomonas*
* Trx: **Cefepime+vanc** OR **Ceftaz+vanc** OR **Meropenem**
* Carbapenems\>, G-,pseudomonas,CSF, Ceftaz\>pseudomonas, vanc\>staph
55
Bacterial Meningitis adjunctive therapy
Dexamethasone
* Purpose: inhibit TNF and IL-1
* Decrease inflammation \> edema \> ICP
**Dosing**: Q6 IV for 2-4d
**Timing**: Must admin 10-20m before/simultaneously with ABX
**Controversy:**
Decreases inflammation (some drugs need inflammation to allow for crossing into CSF)
* Improve neurological/audiological complications in Hib meningitis*
* Improved morbidity/mortality in adult Strep pneumo*
56
CSF Penetration (therapeutic)
57
Acyclovir (Valacyclovir)
* **MoA**: Requires three phosphorylation steps for activation
* Converted first to monophosphate derivative by virus-specified thymidine kinase and then to the di- and triphosphate compounds by host cell enzymes
* Active metabolite accumulates only in infected cells
* Acyclovir triphosphate inhibits viral DNA synthesis by two mechanisms
* 1. Competition with deoxyGTP for the viral DNA polymerase, resulting in binding to the DNA template as an irreversible complex
* 2. Chain termination following incorporation into the viral DNA.
58
Acyclovir Indications, PK, SE
* Treatment of HSV and VZV
* HSV meningitis – Requires higher dosing 20mg/kg/dose Q8 hours
**PK:**
* High [] in the kidneys, lungs, liver, heart
* CSF concentrations ~50% of those in plasma
* Renally eliminated
* Poor oral bioavailability
* Valacyclovir – higher oral bioavailability
**SE:**
Adverse Reactions
* PO – GI upset, rash
* IV – phlebitis, inflammation
* **Nephrotoxicity** – higher risk with IV and poorly hydrated patients (reversible)
* Obstructive nephropathy caused by formation of acyclovir crystals precipitating in renal tubules
* Prophylaxis– pre-hydrate patients with fluid bolus before IV acyclovir dose
* **Neurotoxicity** – higher risk with renal impairment
* Confusion, seizures, hallucinations
