Sweatman - Bacterial Infections Flashcards
What is the most important factor in successful pneumonia treatment?
- 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
What are the 4 pneumonia classifications? List some subclassifications (table).
What are the most common causes of pneumonia by age group?
How do alcohol consumption and diabetes affect pulmonary function?
- 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
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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
What is Legionnaires disease? How is it treated?
- Atypical causative agent for pneumonia
- Risk factors: men >50 y/o, smokers, chronic lung disease, and immuno-compromised pts (drug- or disease-induced)
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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)
What is the general approach for treating CAP?
- 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
Describe the decision tree for treating CAP.
- 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
What are the MOA’s of the 7 classes of anti-CAP drugs?
What are the common drug resistances to 6 of the classes of anti-CAP drugs (excl. Carbopenem)?
What drugs are most commonly used in the treatment of nosocomial pneumonia?
- 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
Briefly characterize nosocomial pneumonia.
- 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
What is aspiration pneumonia? How do you treat it?
- Gastric acid or foreign body
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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
What are the MOA’s and resistance to Clindamycin and Vanc?
When might you use oral dosing? Parenteral?
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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)
What 3 parameters are important in defining drug activity? How do these determine the PK (pharmacokinetic)/PD (pharmacodynamic) profile of a drug?
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
What are the predictive PD parameters for the different drug classes (table)? What do these mean for a practicing physician?
- Drugs not always dosed in close accordance w/serum drug half-lives
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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
Which drugs need to be adjusted for renal impairment? Which do not?
- YES: Amoxicillin, Ampicillin, Cefazolin, Cefepime, Ceftazidime, Gentamicin, Imipenem, Levofloxacin, Meropenem, Piperacillin, Vanc
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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
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
What are the pregnancy recommendations for the antimicrobials (table)?
