Sweatman - Bacterial Infections Flashcards
(39 cards)
1
Q
What is the most important factor in successful pneumonia treatment?
A
- EARLY drug intervention
- Initial treatment broad and empiric, directed toward the most likely org -> narrowed once bug ID’d
- Sometimes no bug is identified, but pts can still be successfully managed
2
Q
What are the 4 pneumonia classifications? List some subclassifications (table).
A
3
Q
What are the most common causes of pneumonia by age group?
A
4
Q
How do alcohol consumption and diabetes affect pulmonary function?
A
- They can both NEGATIVELY impact pulmonary function
- Alcohol: current use is an independent risk factor for severe CAP; chronic drinkers have DEC saliva production, an important component of mucosal defense
-
Diabetes: higher risk for influenza and its complications, incl. pneumonia, possibly bc the disorder neutralizes the effects of protective proteins on the surface of the lungs
1. Everyone w/diabetes should have annual flu vax and a vax against pneumococcus
5
Q
What is Legionnaires disease? How is it treated?
A
- Atypical causative agent for pneumonia
- Risk factors: men >50 y/o, smokers, chronic lung disease, and immuno-compromised pts (drug- or disease-induced)
-
Tx: Azithromycin, Clarithromycin commonly used (Erythromycin is actually only drug labeled for this use)
1. Resp quinolones: Levofloxacin, Ciprofloxacin, or Moxifloxacin are good alternatives -> achieve good tissue levels in the lungs
2. Severely ill pts: combo of one of the above w/Rifampin (potential for drug-drug CYP interaxn of RIF and macrolides w/concurrent Rx a constant concern)
6
Q
What is the general approach for treating CAP?
A
- Categorize according to status (outpt, nursing home, hosp)
- Instigate broad spectrum coverage pending lab data
- There are NO hard and fast rules for drug choices -> must consider:
1. Individual pt factors
2. Local microbiological info, eg, resistance patterns
3. Response to initial therapy
7
Q
Describe the decision tree for treating CAP.
A
- 1st gen macrolide Erythromycin, 2nd gen Clarithromycin, and 3rd gen Azithromycin
- Aminoglycoside: think Gentamicin
- Recent pt tx w/corticosteroids or antimicrobial considered likely to have altered the balance of prevailing microflora, and drug treatment is adjusted accordingly
8
Q
What are the MOA’s of the 7 classes of anti-CAP drugs?
A
9
Q
What are the common drug resistances to 6 of the classes of anti-CAP drugs (excl. Carbopenem)?
A
10
Q
What drugs are most commonly used in the treatment of nosocomial pneumonia?
A
- Except for Vancomycin, all the other drugs have activity against gram (-) aerobes (i.e., H. influenzae & Pseudomonas)
1. Vanc reserved for tx of MRSA (IV only for systemic infection bc low bio-availability) - Some think Meropenem has fewer AE’s than Imipenem (IV beta-lactam), but spectrum of activity is comparable
- Cefepime 4th gen bc activity against some orgs that are resistant to Ceftazidime
11
Q
Briefly characterize nosocomial pneumonia.
A
- No etiologic agent identified in 50% of cases
- With loss of oropharyngeal fibronectin, there is a shift to gram (-) bacilli
1. Gram (+) more common in ICU and w/DM or head trauma - S. aureus now a prevalent pathogen -> incidence of MDR orgs is increasing
12
Q
What is aspiration pneumonia? How do you treat it?
A
- Gastric acid or foreign body
-
Oropharyngeal secretions: most commonly in reduced consciousness (or long-term intubation) -> loss of protective reflexes
1. Semi-recumbent positioning helps reduce incidence - 50% of isolates in hosp pts are for gram (-) enteric bacilli
1. 16% anaerobes (like H. influenzae), 12% S. aureus -
Treatment:
1. Indicated: Clindamycin
2. Alternative: Ampicillin/Sulbactam
13
Q
What are the MOA’s and resistance to Clindamycin and Vanc?
A
14
Q
When might you use oral dosing? Parenteral?
A
-
Oral drug delivery: costs less, has lower incidence of AE’s, and higher pt compliance
1. Generally reserved for mild infections in whom absorption not thought to be compromised
a. Food or other chelating drugs in GI tract
b. Hypotension; blood shunted away from GI tract
c. Lack of adherence - Route may switch from parenteral to oral in severely ill once infection controlled and oral dosing practical
1. May be possible sooner w/drug like Doxycycline and Fluoroquinolones (high oral bioavailability) and later if oral delivery can’t achieve comparable drug levels - Generally 3-6 days parenteral therapy will stabilize disease and reduce fever (benefit of parenteral admin is rapid attainment of required serum drug levels)
15
Q
What 3 parameters are important in defining drug activity? How do these determine the PK (pharmacokinetic)/PD (pharmacodynamic) profile of a drug?
A
A. AUC (area under the curve)/MIC (min inhibitory conc)
B. C(Max)/MIC
C. T>MIC
- Antimicrobial classes characterized as either:
1. Concentration dependent (A, B; fluoroquinolones, amino-glycosides): INC in AB conc = more rapid rate of bac death
2. Time dependent (C; beta-lactams): reduction in bac density proportional to time that conc exceeds MIC - Remember: serum drug conc does not always reflect local tissue drug levels
16
Q
What are the predictive PD parameters for the different drug classes (table)? What do these mean for a practicing physician?
A
- Drugs not always dosed in close accordance w/serum drug half-lives
-
Conc-dependent drugs: often given in lg doses (relative to the MIC) at long intervals relative to the serum half-life
1. Ex: once-daily dosing of aminoglycosides or 2g admin of Vanc in pts w/normal renal func -
Time-dependent drugs: usually dosed more freq, w/emphasis on need to maintain serum drug level above MIC for 30-50% of dose interval
1. Ex: some clinicians advocate prolonged or constant infusion of beta-lactams to ensure max T>MIC
17
Q
Which drugs need to be adjusted for renal impairment? Which do not?
A
- YES: Amoxicillin, Ampicillin, Cefazolin, Cefepime, Ceftazidime, Gentamicin, Imipenem, Levofloxacin, Meropenem, Piperacillin, Vanc
-
NO: Azythromycin (biliary), Ceftriaxone (renal/biliary), Clindamycin (renal/biliary), Doxycycline (biliary), Erythromycin (biliary), Linezolid (metabolism)
1. Basically, the macrolides, linezolid, and doxycycline are the only ones that do not need to be adjusted
18
Q
What are major toxicities for Amoxicillin and Ampicillin?
A
- Cross-reactivity with penicillin sensitivity
- GI distress
- Maculopapular rash
19
Q
What are the drug toxicities for Azithromycin?
A
- Cholestatic jaundice
- QT prolongation
20
Q
What are the major drug toxicities for the Cephalosporins (Cefazolin, Cefepime, Ceftazidime, Ceftriaxone)?
A
- Complete cross-reactivity with cephalosporins, partial cross-reactivity with penicillin hypersensitivity
- GI distress (disruption of the normal GI flora)
21
Q
What is the drug toxicity for Clyndamycin?
A
GI distress (disruption of the normal GI flora)
22
Q
What are the drug toxicities for Doxycycline?
A
- GI distress (disruption of the normal GI flora)
- Teeth discolored
- Photosensitivity
- DEC bone growth
- NOTE: bolded drugs are the ones Sweatman said to concentrate on when he was mentioning AE’s
23
Q
What are the drug toxicities for Erythromycin?
A
- CYP3A4/P-gp inhibitor
- Cholestatic jaundice
- QT prolongation
24
Q
What are the drug toxicities for Gentamicin?
A
- Nephro- and ototoxicity
- Nueromuscular paralysis
25
What are the drug toxicities for **Imipenem**?
- Partial cross-reactivity with pen/ceph hypersensitivity
- Seizures
26
What are the drug toxicities for **Levofloxacin**?
- Tendon rupture in adults
- Cartilage damage in young children
27
What are the drug toxicities for **Linezolid**?
- Bone marrow suppression
- Non-specific MAO inhibitor
28
What are the drug toxicities for **Meropenem**?
- Partial cross-reactivity with pen/ceph hypersensitivity
- Seizures
29
What are the drug toxicities for Piperacillin?
- Partial cross-reactivity with ceph hypersensitivity
- DEC coagulation
30
What are the drug toxicities for **Vanc**?
- Nephro- and ototoxicity
- _Red Man's syndrome_: pruritus, an erythematous rash on face, neck, and upper torso. Less frequently, hypotension and angioedema can occur. Patients commonly complain of diffuse burning and itching and of generalized discomfort. They can rapidly become dizzy and agitated, and can develop headache, chills, fever, and paresthesia around the mouth. In severe cases, patients complain of chest pain and dyspnea. In many patients, the syndrome is a mild, evanescent pruritus at the end of the infusion that goes unreported
31
Why is the presence of a beta-lactam ring important?
- _Prior allergic reaction to a penicillin will predispose a pt to a similar allergy w/a cephalosporin or carbapenem_ -\> doesn't guarantee that one will occur, but physicians need to be aware of prior allergy w/these related drug classes
- Not only in the penicillin family
32
What are the pregnancy recommendations for the antimicrobials (table)?
33
Which antimicrobials are generally safe for breastfeeding AND have NO teratogenic effects?
- Amoxicillin, Ampicillin
- Azithromycin
- Cefazolin, Cefepime, Ceftazidime, Ceftriaxone
- Ciprofloxacin
- Clindamycin
- Imipenem, Meropenem
- Vanc
34
Which drugs cannot be used during pregnancy? Of these, which are safe during breastfeeding, and which are not?
- _Generally safe for breastfeed_:
1. Erythromycin
2. Gentamicin
3. Levofloxacin
4. Trimethoprim
- _Caution w/breastfeeding_ (or avoid during breastfeeding):
1. Clarithromycin
2. Linezolid
3. Metronidazole
4. Piperacillin
- _Not safe with either_: Doxycycline
35
What are the combination drug products (4)?
- _Amoxicillin/Clavulanic acid_ (Augmentin)
- _Piperacillin/Tazobactam_ (Zosyn)
- _Ampicillin/Sulbactam_ (Unasyn)
1. These adjunctive agents are all irreversible inhibitors of bacterial beta-lactamases
- _Imipenem/Cilastin_ (Primaxin)
1. Cilastatin reversible, competitive inhibitor of renal dehydropeptidase-1 (DHP-1), enzyme that breaks down Imipenem to inactive BUT nephrotoxic metabolites
- **NOTE**: none of the additives possess any antimicrobial activity, but are metabolic inhibitors that preserve lifespan of the drug, and therefore its activity
36
What drug is inhibited by pulmonary surfactant? Why is this important?
- **Daptomycin**: NOT used for pulmonary infections
1. Although drug distributes into lung tissue, it is inhibited by surfactant
- Broad spectrum activity, incl. greater activity than Vanc against some gram (+) orgs -\> should _NOT BE USED TO TREAT PNEUMONIA_
37
What bugs cause bronchitis? What txs are indicated?
- Etiology varies by age, w/_bac primarily in older pts_
1. Mostly viral in younger pts
2. Older pts: M. pneumoniae, Strep pneumoniae, H. flu, Moraxella, and Bordatella pertussis
a. In _smokers, H. flu_ more common
- **Indicated**: Amoxicillin + Clavulanic acid, Azithromycin, Clarythromycin, Doxy
1. With resistance: Cipro
2. Oral drug tx more convenient, but both Doxy and Cipro may be used IV in more severe/urgent cases
38
What is the appropriate treatment for lung abscesses?
- Almost all _respond to medical mgmt w/in 2 wks_, resolving over 2-5 months
- _Anaerobes_: gram (+) cocci (community-acquired) or gram (-) bacilli (nosocomial)
- **Appropriate drugs**:
1. _Clindamycin_: superior to penicillin vs. bacteroides species
2. _Metronidazole + Ceftriaxone_ (3rd gen, IV): for nosocomial infections
a. Metronidazole is a pro-drug that interferes with nucleic acid synthesis (ONLY in anaerobes); can't use it alone due to incomplete coverage
- Tx initially involves IV drug therapy, w/transition to 2-mo oral regimen after a couple of weeks
39
Bacterial lung infection summary
- Do NOT delay drug therapy -\> early is best
- Initial therapy may involve IV admin with transition to oral tx once control is established
- For **CAP**, a macrolide (azithromycin) or respiratory quinolone (levofloxacine) is an appropriate 1st choice
1. Amoxicillin/Clavulanate is another option
- Broad spectrum drugs should be used initially for nosocomial infections -\> tailor once infective agent known
- Tx for abscess and aspiration pneumo should cover anaerobes
