Chapter 22: Infectious Disease I Background Flashcards
The Presence of an Infection is Determined by:
-signs and symptoms: fever, elevated WBC count, and site specific symptoms (dysuria wiht UTIs)
-Diagnostic findings such as culture results, xrays, and markers of inflammation (eg. procalcitonin)
Antibiotic selection is based on: (5 key components)
1.) Infection site and likely organisms at that site
2.) Infection severity and risk of multidrug resistant (MDR) pathogens (eg. CAP vs HAP)… infection that are hospital acquired often involve MDR organisms
3.) ABX characteristics (eg. spectrum of activity and ability to penetrate the site of infection)
4.) Patient characteristics including age, body weight, allergies, renal/ hepatic impairment, comorbidity, recent ABX use, colonization with resistant bacteria, immune function, pregnancy, etc.
5.) Treatment guidelines (IDSA, CDC)
Common Bacterial Pathogens for Selected Sites of Infection
CNS/ Meningitis
- Streptococcus pneumoniae
- Neisseria Meningitidis
- Haemophilus influenzae
- Group B Streptococcus/ EColi (young)
- Listeria (young/old)
Common Bacterial Pathogens for Selected Sites of Infection
Mouth
- Mouth flora (Peptostreptococcus)
- Anaerobic GNR (Prevotella)
- Viridan group streptococci
Common Bacterial Pathogens for Selected Sites of Infection
Upper Respiratory (sinus and throat)
- Streptococcus pyogenes
- Streptococcus pneumoniae
- Haemophilus influenzae
- Moraxella catarrhalis
Common Bacterial Pathogens for Selected Sites of Infection
Lower Respiratory (Community Acquired)
- Streptococcus pneumoniae
- Haemophilus influenzae
- Atypicals: Legionella, Mycoplasma, Chlamydophila
- Enteric gram neg rods (EColi, Klebsiella, Proteus) in alcohol use disorder
Common Bacterial Pathogens for Selected Sites of Infection
Lower Respiratory (Hospital Acquired)
- Staphylococcus aueus (MRSA)
- Pseudomonas aeruginosa
- Acinetobacter baumannii
- Enteric gram neg rods (including ESBL+, MDR)
- Streptococcus pneumoniae
Common Bacterial Pathogens for Selected Sites of Infection
Urinary Tract
- E. coli, Proteus, Klebsiella
- Staphylococcus saprophyticus
- Enterococci
Common Bacterial Pathogens for Selected Sites of Infection
Bone/ Joint
- Staphylococcus aureus
- Staphylococcus epidermidis
- Streptococci
- Neisseria gonorrhoeae
- GNR (only in specific situations)
Common Bacterial Pathogens for Selected Sites of Infection
Skin/ Soft Tissue
- Staphylococcus aureus
- Staphylococcus epidermidis
- Streptococcus pyogenes
- Pasteurella multocida
- +/- aerobic/anaerobic gram neg rods (in diabetics)
Common Bacterial Pathogens for Selected Sites of Infection
Heart/ Endocarditis
- Staphylococcus aureus, including MRSA
- Staphylococcus epidermidis
- Streptococci
- Enterococci
Common Bacterial Pathogens for Selected Sites of Infection
Intra-Abdominal
- Enteric GNR,
- Enterococci
- Streptococci
- Baeteroides species
Define Empiric Treatment and the use of Antibiogram
Empiric treatment - often started when microbiology results are pending. This empiric treatment is usually a broad spectrum abx (covers several types of different organisms) and can be guided by antibiogram.
An antibiogram combines culture data from patients at a single institution into one chart, such that all gram positive or gram neg organisms cultured at a hospital pver a specific time period (usually 1 year). It shows susceptibility patterns and can be used to monitor resistance trends over time. Antibiogram is also used to select empiric treatment.
Gram staining uses and limitations?
Cultures are taken from the infection site (e.g., lung
secretions, urine, blood, tissue from a wound or fluid from an abscess) and sent to the microbiology lab. The Gram stain categorizes the organism by shape (or morphology). The Gram stain provides quick, preliminary results (e.g.,Gram-negative rods), but does not identify the exact organism (e.g., Klebsiella pneumoniae). The Gram stain results provide a
clue about what organism may be causing the infection and an opportunity to adjust the empiric antibiotic regimen
Gram Staining
Gram positive vs gram negative vs atypical: how do they show up on gram staining?
- Gram-positive organisms: have a thick cell wall and stain dark purple or bluish from the crystal violet stain.
- Gram-negative organisms: have a thin cell wall and take up the safranin counterstain, resulting in a pink or reddish color
- Atypical organisms: do not have a cell wall and do not stain well
Gram-Positive
(appear dark purple): List morphology and name of the organisms
Gram-Negative
(appear pink): List morphology and name of the organisms
Atyplcals
(do not Gram stain well): List examples of Atypicals
Describe the process of identifying organisms and what is done to determine which ABX are useful as treatment (MICs)
The microbiology lab uses various methods to determine which organism is present in the sample; for example, some Gram-negative bacteria (e.g., E. coli) break down lactose (a sugar) in a unique way and some do not (e.g., Pseudomonas).
Staphylococci (gram positive occuring in clusters) can be differentiated with a coagulase (enzyme) test. Staphylococcus aureus s colagulase-positive; other staphylococcus species (eg epidermidis) are sometimes referred to as coagulase-negative staphylococci (CoNS).
Once organism is identified, susceptibility testing is performed to determine which ABX are useful for treatment. The bacteria is grown on agar and exposed to varying concentration of select ABX.
The lab identifies the minimum concentration
of each antibiotic that inhibits bacterial growth, which is called the minimum inhibitory concentration (MIC). MICs. The lab compares the MIC to the susceptibility breakpoint, which is the usual drug concentration that inhibits bacterial growth [and is determined by the Clinical & Laboratory Standards Institute (CLSI). An interpretation is made as to which drugs inhibit
growth (and at what concentration) and which drugs do not.
What is a culture and susceptibility report?
The culture and susceptibility ( C & S) report is usually available within 24- 72 hours. The C & S report identifies the organism and the results of the susceptibility testing. The empiric antibiotics can be streamlined to narrower spectrum treatment based on the C & S report. MICs are specific to each ABX and organism and should be compared amoung different ABX.
Look over: culture and susceptibility report. What does S - susceptible, I - intermediate, and R - resistant means?
- Susceptible (S): drug are effective and should be selected
- Intermediate (I): may be effective under specific circumstances (eg. high dose, extended infusion), but usually would not be selected over a drug that is reported as susceptible.
- Resistant (R): drug is resistant to organism and should not be selected!
The general steps on starting ABX and what to consider
- Empiric treatment: select empiric treatment based on the likely organisms at the at the infection site… also, is the patietn at risk for MRSA? MDR? provide coverage for that too. Use antibiogram and gram stain if avalible to guide tx choice.
- Streamline: When the C and S results are avalible, streamline to a more narrow spectrum antibiotics as soon as possible; if more than 1 organisms are presented… try to find abx that covers both! Consider IV:PO conversion if patient is clinically stable, eating, and if there is an appropriate PO option.
- Assess the patient : monitor for improvement of signs and symptoms. a lack of response can be multifactorial (ie. inadequate dose, nonadherance, uncontrolled sources, resistance, DDI). Determine the duration of treatment.. do not let abx continue unnecessarily.
Antibiotic resistance: what is it? and what are the 4 most common mechanism of resistance?
Abx resistance is the ability of an organism to multiply in the presence of a drug that normally limits its growth or kills it.
1. Intrinsic resistance
2. Selection pressure
3. Acquired resistance
4. Enzyme inactivation
Common mechanism of resistance?
Intrinsic Resistance
The resistance us NATURAL to the organism . For example, E.Coli is resistant to vancomycin b/c this antibiotic is too large to penetrate the bacterial cell wall of E.Coli!
Common mechanism of resistance?
Selection Pressure
Resistance occurs when abx kills off susceptible bacteria, leaving behind more resistant strains to multiply. For example, normal GI flora includes enterococcus. When abx (eg vancomycin) eliminates susceptible enterococci, vanco resistant enterococcus (VRE) can become predominant.
Common mechanism of resistance?
Acquired Resistance
Bacterial DNA containing resistant genes can be transferred between different species and/or picked up from dead bacterial fragments in the enviroment.
Common mechanism of resistance?
Enzyme Inactivation
Enzymes produced by bacteria breaks down the antibiotic rendering it useless!
- bacteria that produces beta lactamases break down beta lactams (eg penicillins) before they can bind to their site of activity. Beta Lactamase inhibitors (eg. Clavulanate, sulbactam, tazobactam, avibactam) are combined with some beta lactams to preserve or increase their spectrum of activities
- Extended spectrum beta-lactamases (ESBLs) are beta lactamases that can break down ALL penicillins and most cephalosporins. Organisms that produce ESBLs can be difficult to kill and serious infections involving these organisms are treated with carbapenems or newer cephalosporins/ beta lactamase inhibitors (ie. ceftazidime-avibactam IV; and ceftolozane-tazobactam PO)
- **Carbapenem-resistant enterobacterales **(CRE) are MDR gram negative organisms (eg. Klebsiella, Ecoli) that produce enzymes (eg. carbapenemase) capable of breakng down penicillins, most cephalosporins and carbapenems. CRE infections typically tx with combination of abx that include drugs such as polymyxins.. these drugs have high risk of toxicity.
List of Common Resistant Pathogens
- Klebsiella pneumoniae (ESBL, CRE)
- Escherichia coli (ESBL, CRE)
- Acinetobacter baumannii
- Enterococcus faecalis, Enterococcus faecium (VRE)
- Staphylococcus aeruginosa
C diff infection and how it occurs after the use of abx? Symptoms of C. diff?
When abx kills normal, healthy GI flora along with the targeted pathogens, it can result in an overgrowth of Clostridioides difficile, which can produce toxins that inflame the GI mucosa leading to C Diff infection!
Symptoms: mild (loose stools/ abdominal cramp) to severe (pseudomembranous colitis that requires colectomy). All abx have warning for risk of Cdiff but the highest risk is broad spec penicillins and cephalosporins, quinolones, carbapenems, and clindamycin!
Antibiotic MOAs: know the general MOA of each antibiotic/ where they work on the bacteria
1.) beta lactams: inhibit bacterial cell wall synthesis by binding to penicillin binding proteins. Thus preventing the final step of peptidoglycan synthesis in bacterial cell walls.
Hydrophilic agents/ ABX: examples and properties
Examples: beta lactam, aminoglycosides, vancomycin, daptomycin, polymyxins
Properties:
- small volume of distribution = less tissue penetration
- Mostly renally eliminated = drug accumulation and side effects (nephrotox, sz) can occur if dose is not renally adjusted
- low intracellular concentration = not active against atypical (intracellular) pathogens
- poor-mod bioavalability = IV:PO ration is NOT 1:1!
Lipophilic Agents agents/ ABX: examples and properties
Example: Quinlones, Macrolides, Rifampin, Linezolid, Tetracyclines
Properties:
- Large volume of distribution = better tissue penetration
- Mostly hepatically metabolized = potential for hepatox and DDI
- Achieve intracellular concentration = active against atypical pathogens
- Excellent bioavalibility = IV:PO ratio is often 1:1
Dose Optimization
Cmax:MIC; concentration -dependent killing: what does that mean/ abx examples
Drugs with concentration -dependent killing
(such as aminoglycosides, daptomycin, quinolones) can be dosed less frequently and in higher doses to maximize the concentration above the MIC.
- Goal: high peak (increase killing), low trough (decrease toxicity)
- Dosing strategies: larger dose, long interval
Time>MIC; time -dependent killing: what does this mean/ abx examples
Drugs with time -dependent killing (such as beta -lactams = penicillins, cephalosporins, carbapenems) can be dosed more frequently or administered for a longer duration to maximize the time above the MIC. Examples include extending the infusion time of beta -lactam antibiotics (e.g. from 30 minutes to 4 hours) or administering the drug as a continuous infusion.
- Goal: maintain drug level> MIc
- Dosing strategies: shorter dosing interval, extended or continous infusion
AUC:MIC; Exposure-Dependent: what does that mean/ abx example
Example: vancomycin, macrolides, tetracyclines, polymyxins
Goal: exposure over time
Dosing strategies: varies
PENICILLIN
Natural Penicillins: Penicillin V Potassium - brand name, dosage form, dose, consideration
- Brand: PenVK+
- Dosage forms: tablet, suspension
- Dose: PO 125-500mg Q 6-12hrs on empty stomach
- Consideration: A first-line treatment for strep throat and mild nonpurulent skin infections (no abscess)
PENICILLIN
Natural Penicillins: **Penicillin G Aqueous ** brand name, dosage form, dose
- Brand: Pizerpen-G
- Dosage form: IV injection
- Dose: 2-4 million units Q4-6H
PENICILLIN
Natural Penicillins: Penldllln G Benzathine: brand name, dosage form, dose, consideration/ BBW
- Brand: Bicillin L-A
- Dosage form: IM
- Dose: 1.2-2.4 million units x 1 (varies)
- BBW: Penicillin G benzathine: not for IV use; can cause cardio-respiratory arrest and death!
- Consideration: Drug of choice for syphilis (2.4 million units IM x 1)
PENICILLIN
Aminopenicillins: Amoxicillin - brand, dosage form, dose, consideration
- Brand: Moxatag
- Dosage form: tab, cap, chewable, suspension
- Dose: PO: dosing varies with formulation; 24-hr
ER tablet is taken once daily - Consideration: 1st line tx for acute otitis media (80-90 mg/kg/day). Drug of choice for infective endocarditis prophylaxis before ental procedures (2 grams PO x 1, 30-60 minutes before procedure). Used in H Pylori Treatment
PENICILLIN
Aminopenicillins: Amoxlclllln/Clavulanate - brand, dosage form, dose, consideration
- Brand: Augmentin
- Dosage form: tab, chewable, suspension
- Dose: PO: dosing varies with formulation; XR
tablet is taken Q12H with food - Consideration: CI - history of cholestatic jaundice or
Injection hepatic dysfunction associated with previous use…Severe renal impairment (CrCI < 30 ml/min): DO NOT USE ER Amox of amox/clav or 875 mg strength of
amoxicillin/clavulanate… Amoxicillin/clavulanate: use a 14:1 ratio to decrease, diarrhea caused by the clavulanate component!!!.. First-line treatment for acute otitis media (90 mg/kg/day) and for sinus infections (if an antibiotic is indicated)
PENICILLIN
Aminopenicillins: Ampicillin - brand, dosage form, dose, consideration
- Brand: N/A
- Dosage form: Injection, cap, suspension
- Dose: PO: 250-500 mg Q6H on an empty
stomach 1 hr before or 2 hrs after meals
IV/IM: 1-2 grams Q4-6H - Consideration: Ampicillin PO is rarely used due to poor bioavailability; amoxicillin is preferred if switching from IV ampicillin
PENICILLIN
Aminopenicillins: Ampicillln/Sulbactam - brand, dosage form, dose, consideration
- Brand: Unasyn
- Dosage form: Injection
- Dose: IV: 1.5-3 grams Q6H
- Consideration: Diluted in NS only!
**PENICILLIN **
Extended-Spectrum Penicillins: Piperaclllln/Tazobactam - brand, dosage form, dose, consideration
- Brand: Zosyn
- Dosage form: Injection
- Dose: IV: 3.375 grams Q6H or 4.5 grams Q6-8H
Prolonged or extended infusions: 3.375-4.5 grams IV Q8h(infused over 4 hours)
PENICILLIN
Antistaphylococcal Penicillins: list the 3 abx, dose, and consideration
Penicillin Drug Class General Side Effects and Monitoring
- SIDE EFFECTS
Seizures (with accumulation when not dose adjusted corrected in renal dysfunction), GI upset, diarrhea, rash (including SJS/TEN)/allergic reactions/anaphylaxis,
hemolytic anemia, renal failure, myelosuppression with prolonged use, increases LFTs - MONITORING
Renal function, symptoms of anaphylaxis with 1st dose, CBC and LFTs with prolonged courses
Penicillin Drug Interaction
■ Probenecid can INCREASE the levels of beta-lactams by interfering with renal excretion. This combination is sometimes used intentionally in severe infections to INCREASE antibiotic levels.
■ Beta-lactams (except nafcillin and dicloxacillin) can
enhance the anticoagulant effect of warfarin by inhibiting the production of vitamin K-dependent clotting factors. Nafcillin and dicloxacillin (CYP inducer) can inhibit the anticoag effects of warfarin.
■ Penicillins can INCREASE the serum concentration of methotrexate
**CEPHALOSPORINS **
Cefazolin: gen? dosage form? dose?
- 1st Gen
- IV/IM
- 1-2 grams Q8h
**CEPHALOSPORINS **
Cephalexin: brand? gen? dosage form? dose?
- Keflex
- 1st gen
- oral
- 250-500mg Q6-Q12h
**CEPHALOSPORINS **
Cefuroxime: gen? dosage form? dose?
- 2nd gen
- PO,IV,IM
- 250-1500mg Q8-12h
**CEPHALOSPORINS **
Cefotetan: brand, gen, dosage form, dose, warnings
- Cefotan (brand d/c but name still use in practice)
- 2nd gen
- IV/IM
- 1-2 grams Q12h
- warning: contains a side chain (N-methylthiotetrazole) whihc can increase bleeding and cause disulfiram like rxn with alcohol ingestion
**CEPHALOSPORINS **
Cefoxitin: gen, dosage form, dose
- 2nd gen
- IM/IV
- 1-2 grams Q 6-8h
**CEPHALOSPORINS **
Cefdinir: gen, dosage form, dose
- 3rd gen
- Oral
- 300 mg Q12hr or 600mg QD
**CEPHALOSPORINS **
Ceftriaxone: gen, dosage form, dose, CI, notes
- 3rd gen
- IV/IM
- 1-2 grams Q12-24hrs
- contraindications: hyperbilirubinemic neonates (causes biliary sludging kernicterus), concurrent use of calcium containing IV products in neonates less than 28 days … insoluble precipitates may form! so concurent admin should be avoided in all patients - but in adults it can be admin in same line but line needs to be flushed and admin at different tiem of day. HOWEVER. it’s CI in neonates!
- notes: no renal adjustments!, CNS penetration at high doses when meninges inflammed
**CEPHALOSPORINS **
**Cefotaxime: **gen, dosage form, dose
- 3rd gen
- IV/IM
- 1-2 grams Q4-12hrs
**CEPHALOSPORINS **
Ceftazidime: brand, gen, dosage form, dose
- Fortaz (d/c), Tazicef
- 3rd gen group 2
- IV/IM
- 1-2 grams Q8-12hrs
**CEPHALOSPORINS **
Cefepime: gen, dosage form, dose
- 4th gen
- IV/IM
- 1-2 grams Q8-12h
**CEPHALOSPORINS **
Ceftaroline fosamil: brand, gen, dosage form, dose
- Teflaro
- 5th gen
- IV
- 600mg Q 12h
**CEPHALOSPORINS **
list the 2 cephalosporins combination meds, brands, dosage forms, and dose
1.) ceftazidime/ avibactam (Avycaz), IV: 2.5 grams Q 8hrs (active againt CRE!)
2.) Ceftolozane/tazobactam (Zerbaxa). IV: 1.5-3 grams Q8h
**CEPHALOSPORINS **
Cephalosporins: general warnings and side effects
Warnings:
- cross reactivity with PCN allergy (<10%, higher risk with 1st gen cephalosporins) DO NOT use in patients with a type 1 hypersensitivity to PCN (swelling, angioedema, anaphylaxis)
Side Effects:
- SZ (with accumulation when not correctly dose/ renal adjusted), GI upset, diarrhea, rash/allergic rnx, anaphalaxis, hemolytic anemia (identify with positive coombs test), myelosupp. with long term use, increased LFTs, fever, serious skin rnx (SJS/TEN) - PRETTY MUCH SIMILAR TO PNC
Key feat of cephalosporins
Outpatient (oral) options.. what are each of these commonly use to treat in an outpt setting?
1. 1st gen: cephalexin
2. 2nd gen: Cefuroxime
3. 3rd gen: Cefdinir
- 1st gen: cephalexin - skin infection (MSSA), strep throat
- 2nd gen: Cefuroxime - acute otitis media, CAP
- 3rd gen: Cefdinir - acute otitis media
Key feat of cephalosporins
Inpatient (parenteral) options .. what are each of these commonly use to treat in an in patient setting? PART 1
1.) 1st gen: Cefazolin
2.) 2nd gen: Cefotetan and Cefoxitin
3.) 3rd gen: Ceftriaxone and Cefotaxime
1.) 1st gen: Cefazolin - surgical prophylaxis
2.) 2nd gen: Cefotetan and Cefoxitin - anaerobic coverage (B. fragilis), surgical prophylaxis
3.) 3rd gen: Ceftriaxone and Cefotaxime - CAP, meningitis, spontaneous bacterial peritonitis, pyelonephritis…note: ceftriaxone - no renal adj amd DO NOT use in neonates (0-28 days).
Key feat of cephalosporins
Inpatient (parenteral) options .. what are each of these commonly use to treat in an in patient setting? PART 2
1.) 3rd gen: Ceftazidime
2.) 4th gen: Cefepime
3.) Combination products: Avycar and Zerbaxa
4.) 5th gen: Ceftaroline
1.) 3rd gen: Ceftazidime - active against pseudomonas
2.) 4th gen: Cefepime - active against pseudeomonas
3.) Combination products: Avycar and Zerbaxa - used for MDR gram neg bugs (including pseudomonas)
4.) 5th gen: Ceftaroline - only beta lactam active agaisnt MRSA! commonly use: CAP, skin/soft tissue infections
**Carbapenem **
Doripenem: dosage form, dose, notes
Injection: IV: 500mg Q8hrs
NOTE: DO NOT use for tx for penumonia! (CAP or HAP)
Carbapenem
Imipenem/Cilastain and Imipenem/Cilastatin/Relebactam: brand name, dosage form, dose…why is imipenem a combination product?
1.) Imipenem/Cilastain (Primaxin IV) - IV: 250-1000mg Q6-8h
2.) Imipenem/Cilastatin/Relebactam (Recarbrio) - 1.25 grams Q6h
….NOTE: lmipenem is combined with cilastatin to prevent drug degradation by renal tubular
dehydropeptidase
Carbapenem
Meropenem and Meropenem/Vaborbactam: dosage form, dose
1.) Meropenem - IV: 500-1000mg Q8hr
2.) Meropenem/Vaborbactam (Vabomere) - IV: 4 grams Q8h (each dose infused over 3 hrs)
Carbapenem
Ertapenem: brand, dosage form, dose, note
- Brand: Invanz
- stable for normal saline NS only!
- IV/IM: 1 gram QD
- DOES NOT cover: PEA (pseudomonas, enterococcus, Acinetobacter)… commonly used for diabetes foot infection
Carbapenem
Carbapenem: Contraindication, warnings, side effects, monitoring, notes
- CI: anaphalaxis to beta lactam abx
- Warning: DO NOT use in patients with PNC allergy, CNS AEs (including sz, confusion)…risk increase with higher doses, renal impaired, or imipenem/cilastatin
- Side Effects: Diarrhea, rash/severe skin reaction (DRESS), bone marrow suppression with prolong use, increased LFTs
- Monitoring: Renal function, symptoms of anaphylaxis with 1st dose, CBC, LFTs
- NOTES: Carbapenems can decrease serum concentrations of valproic acid, leading to a loss of seizure control. Use with caution in patients at risk for seizures, or in combination with other drugs known to lower the seizure threshold (ie. clozapine, quinolones, bupropion, tramadol)
Carbapenem
Carbapenem: class effects, what do they NOT cover?, common uses?
- Class effect: all active against ESBL-producing bugs and (except Ertapenem) pseudomonas, do not use with PCN allergy, SZ risk
- What is NOT covered?: atypicals, VRE, MRSA, CDiff, Stentrophomonas. And Ertapenem does not cover PEA
- Common uses: polymicrobial infection (ie. Diabetes foot infection), empiric coverage when resistent is suspected, ESBL+ bugs