Chapter 22 - Infectious Disease I - Background & Antibiotics by drug class Flashcards
(118 cards)
1
Q
Should you treat a bacterial urine infection if the patient is asymptomatic?
On what should you reply on in order to diagnose?
A
The presence of an infection is determined by signs and symptoms. For example, the presence of bacteria in a urine culture does not mean there is an infection.
The diagnosis is based on symptoms (e.g., dysuria, urgency, leukocytosis, fever) plus a positive urine culture.
2
Q
Antibiotic characteristics:
The spectrum of activity & the Ability to penetrate the site of infection depends on what?
A
Antibiotic characteristics include:
- The spectrum of activity
- Ability to penetrate the site of infection
– Lipophilic antimicrobials have better tissue penetration.
– Antibiotics that are not cleared renally may not achieve adequate drug concentrations in the urine.
3
Q
What are the patient characteristics that impact treatment choices?
A
- Age
- Body weight
- Renal and hepatic function
- Allergies
- Recent antibiotic use
- Colonization with resistant bacteria
- Recent environmental exposure
- Vaccination status
- Pregnancy status
- Immune function
- Comorbid conditions
4
Q
What is an Empiric Treatment and how do you choose it?
A
- Antibiotics are often started before the pathogen is identified.
- Broad- spectrum and is based on a best guess of the likely organisms causing the infection.
- Local resistance patterns (antibiogram) and antibiotic use guidelines should be considered when selecting empiric treatment.
5
Q
Common Bacterial Pathogens for Select Sites of Infection:
CNS/ Meningitis
A
1) Streptococcus pneumoniae
2) Neisseria meningitidis
3) Haemophilus influenzae
4) Group B Streptococcus/ E.coli (young)
5) Listeria (young/ old)
6
Q
Common Bacterial Pathogens for Select Sites of Infection:
Upper Respiratory
A
1) Streptococcus pyogenes
2) Streptococcus pneumoniae
3) Haemophilus influenzae
4) Moraxella catarrhalis
7
Q
Common Bacterial Pathogens for Select Sites of Infection: Mouth
A
1) Mouth flora (Peptostreptococcus)
2) Anaerobic GNR (Prevotella,others)
3) Viridans group Streptococci
8
Q
Common Bacterial Pathogens for Select Sites of Infection: Lower Respiratory (Community)
A
1) Streptococcus pneumoniae
2) Haemophilus influenzae
3) Atypicals: Legionella, Mycoplasma, Chlamydophilia
4) Enteric GNR (alcoholics)
9
Q
Common Bacterial Pathogens for Select Sites of Infection: Lower Respiratory (Hospital)
A
1) Staphylococcus aureus, including MRSA
2) Pseudomonas aeruginosa
3) Acinetobacter baumannii
4) Enteric GNR (including ESBL, MDR)
5) Streptococcus pneumoniae
10
Q
Common Bacterial Pathogens for Select Sites of Infection: Heart/Endocarditis
A
1) Staphylococcus aureus, including MRSA
2) Staphylococcus epidermidis
3) Streptococci
4) Enterococci
11
Q
Common Bacterial Pathogens for Select Sites of Infection: Intra-abdominal
A
1) Enteric GNR
2) Enterococci
3) Streptococci
4) Bacteroids sp
12
Q
Common Bacterial Pathogens for Select Sites of Infection: Skin/Soft Tissue
A
1) Staphylococcus aureus
2) Streptococcus pyogenes
3) Staphylococcus epidermidis
4) Pasteurella multocida = aerobic/anaerobic GNR (in diabetes)
13
Q
Common Bacterial Pathogens for Select Sites of Infection: Bone/Joint
A
1) Staphylococcus aureus
2) Staphylococcus epidermidis
3) Streptococci
4) Neisseria gonorrhoeae
5) GNR (only in specific situations)
14
Q
Common Bacterial Pathogens for Select Sites of Infection: Urinary Tract
A
1) E. coli
2) Proteus
3) Klebsiella
4) Staphylococcus saprophyticus
5) Enterococci
15
Q
Gram stain
A
Gram +: blue/ purple
Gram -: Pink
Atypical: do not stain
16
Q
Gram-Positive Shapes + organisms
A
Cocci:
1) Staph coccus sp: MRSA, MSSA
2) Pairs & chains:
- Strep. pneumoniae (diplococci)
- Streptococcus spp. (Strep. pyogenes)
- Enterococcus spp. (including VRE)
Rods:
- Listeria
- Monocytogenes
- Corynebactenum spp.
Anaerobes:
- Peptostreptococcus
- Propionibacterium acnes
- Clostridioides spp.
17
Q
Gram -ve Shapes & organisms
A
Cocci:
- Nisseria
Cocco bacilli
- Acinetobacter baumannii
- Bordetella pertussis
- Moraxella catarrhalis
Rods
1) Colonize gut “Enteric”
- Proteus mirabilis
- Escherichia coli
- Klebsiella spp.
- Serratia spp.
- Enterobacter cloacae
- Citrobacter spp
2) Do not colonize gut
- Pseudomonas aeruginosa
- Haemophilus influenzae
-Providencia spp.
3) Curved or spiral shaped Gram-negative rods
- H. pylori
- Campylobacter spp.
- Treponema spp.
- Borrelia spp.
- Leptospira spp.
Anaerobes
- Bacteroids fragilis
- Prevotella spp.
18
Q
Atypicals (do not Gram stain well)
A
- Chlamydia spp.
- Legionella spp.
- Mycoplasma pneumoniae
- Mycobacterium tuberculosis
19
Q
Whats the function of lactose?
A
- Gram-negative bacteria (E. coli) break down lactose (a sugar) in a unique way and some do not (Pseudomonas).
- Lactose can be used to help determine the types of bacteria that may be present.
20
Q
Give an example of synergy.
A
- Aminoglycosides and beta-lactams can be used together synergistically to treat certain invasive Gram-positive infections (Infective endocarditis);
- The beta-lactam allows the aminoglycoside to reach its intracellular target (the ribosome), where it causes lethal damage to the bacteria.
Both are hydrophilic
- Beta lactam: inhib cell wall
- Aminoglycoside: inhib protein synthesis (Ribosome)
21
Q
Antibiotics treatment thought process
A
1) Empiric Treatment:
- Likely organisms at the infection site (Lower respiratory tract, CNS, skin/soft tissue)
- Is the patient at risk for MRSA? MDR bacteria? (cover if yes)
- Use the antibiogram and Gram stain (if available) to guide the treatment selection.
2) Streamline
- C & S results are available –> narrow-spectrum antibiotics; if > 1 organism is present, try to find one antibiotic that will treat both.
- Consider IV:PO conversion if the patient is eating normally and there is an appropriate oral drug (that can penetrate the infection site).
3) Assess the Patient
- Throughout treatment, monitor for improvement
- The patient’s condition can override the culture information (If no improvement, perhaps an unidentified organism is the cause of the illness).
- With all antibiotics, set the duration of treatment; do not let antibiotics continue if not necessary.
22
Q
ASSESSMENT OF TREATMENT: MONITORING TREATMENT RESPONSE
A
- Clinical status of the patient:
1. Fever trend and other vital signs depending on the infection (O2 saturation in pneumonia)
2. WBC trend
3. Reduction in Sx of infection (Improved mentation in meningitis, dec pain/inflammation in cellulitus) - Radiographic findings (chest X-ray results)
- Repeat cultures negative (particularly blood and CNS cultures; sputum and urine cultures do not need to be repeated)
- Decreased markers of inflammation:
– Procalcitonin levels (more specific to bacterial infections)
– C-reactive protein (CRP)
– Erythrocyte sedimentation rate (ESR)
23
Q
REASONS FOR LACK OF RESPONSE:
A
1) Antibiotic factors
- Inadequate spectrum and/or dose
- Poor tissue penetration
- Drug-drug interactions
- Non-adherence
- Inadequate duration of treatment
- Inability to tolerate/ toxicity
2) Microbiologic factors
- Resistance
- Superinfection (C diff)
- Alternative etiology (viral, fungal, noninfectious cause (CHF exacerbation vs. pneumonia)]
3) Host factors
- Uncontrolled source of infection (Abscessor fluid collection, implanted devices with biofilm)
- Immunocompromised
24
Q
Intrinsic resistance:
A
The resistance is natural to the organism.
For example, E. coli is resistant to vancomycin because this antibiotic is too large to penetrate the bacterial cell wall of E. coli.
25
Selection pressure:
Resistance occurs when antibiotics kill off susceptible bacteria, leaving behind more resistant strains to multiply.
Ex: normal GI flora includes Enterococcus.
When antibiotics (Vancomycin) eliminate susceptible Enterococci, vancomycin-resistant enterococcus (VRE) can become predominant.
26
Acquired resistance:
- Bacterial DNA containing resistant genes can be transferred between different species and/or picked up from dead bacterial fragments in the environment.
27
Enzyme inactivation:
Enzymes produced by bacteria break down the antibiotic.
1) Beta-lactamases break down beta-lactams (penicillins only)
- Beta-lactamase inhibitors (clavulanate, sulbactam, tazobactam, avibactam)
2) Extended-spectrum beta-lactamases (ESBLs) are beta-lactamases that can break down all penicillins and most cephalosporins.
- Treated with carbapenems or newer cephalosporin/ beta-lactamase inhibitors.
3) Carbapenem-resistant Enterobacteriaceae (CRE) are MDR Gram-negative organisms (Klebsiella spp., E. coli) that produce enzymes (carbapenemase) capable of breaking down penicillins, most cephalosporins and carbapenems.
- CRE infections typically require treatment with a combination of antibiotics that include drugs such as the polymyxins, which have a high risk for toxicity.
- Newer, costly drugs, such as ceftazidime/ avibactam (Avycaz) are also used.
28
COMMON RESISTANT PATHOGENS
1) Klebsiella pneumoniae (ESBL,CRE)
2) Escherichiacoli (ESBL,CRE)
3) Acinetobacter baumannii
4) Enterococcus faecalis, Enterococcusfaecium (VRE)
5) Staphylococcus aureus (MRSA)
6) Pseudomonas aeruginosa
Remember: Kill Each And Every Strong Pathogen
- ESBL= extended-spectrum beta-lactamase
- CRE= carbapenem-resistan Etnterobacteriaceae
- VRE= vancomycin-resistant Enterococcus
29
CLOSTRIDIOIDES DIFFICILE INFECTION
- abx kill nl flora --> overgrowth in drug resistant organisms + superinfection (C diff)
- Inactive C. difficile spores are present in normal GIflora. When an antibiotic kills off the normal flora, C. difficile spores can become activated, producing toxins that inflame the GI mucosa.
- Sx: mild to severe
- All antibiotics have a warning for the risk of CDI, but the risk is highest with broad-spectrum penicillins and cephalosporins, quinolones, carbapenems, and clindamycin.
30
Antimicrobial stewardship program
1) pharmacokinetic monitoring of aminoglycosides and vancomycin,
2) Use of clinical decision support software to rapidly identify pathogens and shorten the time to starting effective treatment,
3) preauthorization of select antimicrobials,
4) prospective audit and feedback to prescribers of selected antibiotics and
5) timely transitions from IV to PO antibiotics.
31
Abx MOA
1) Bactericidal (kill bacteria)
- Cell wall and cell membrane inhibitors
- DNA/RNA inhibitors
- Aminoglycosides
2) Bacteriostatic (inhibit bacterial growth)
Most protein and folic acid synthesis inhibitors
32
Cell wall inhibitor drugs:
- Beta-lactams (penicillins, cephalosporins, carbapenems)
- Monobactams (aztreonam)
- Vancomycin, dalbavancin, telavancin, oritavancin
33
Cell membrane inhibitor drugs
- Polymyxin
- Daptomycin
- Telavancin
- Oritavancin
34
DNA/ RNA Inhibitor drugs
- Quinolones (DNA gyrase, topoisomerase IV)
- Metronidazole, tinidazole
- Rifampin
(Do not disturb cz the queen aam tekul rifa3i bl metro)
35
Folic acid synthesis inhibitor drugs
- Sulfonamides
- Trimethoprim* (Often combined with sulfamethoxazole to overcome resistance)
- Dapsone
36
Protein synthesis inhibitor drugs
- Aminoglycoside
- Macrolide
- Tetracycline
- Clindamycin
- Linezolid, Tedizolid
- Quinupristin/Dalfopristin
37
HYDROPHILIC AGENTS
Drugs:
1) Beta-lactams
2) Aminoglycasides
3) Glycopeptides
4) Daptomycin
5) Polymyxins
Characteristics:
1) Small volume of distribution - Poor tissue penetration
2) Renal elimination - Drug accumulation and side effects (nephrotoxicity, seizures) can occur if not dose adjusted
3) Low intracellular concentrations - Not active against atypical (intracellular) pathogens
4) Increased clearance and/or distribution in sepsis - Consider loading doses and aggressive dosing in sepsis
5) Poor/ moderate bioavailablity. Not used PO or IV:PO ratio is not 1:1
38
LIPOPHILIC AGENTS
Drugs:
1) Quinolones
2) Macrolides
3) Rifampin
4) Linezolid
5) Tetracyclines
Characteristics:
1) Large volume of distribution - Excellent tissue penetration including bone, lung, brain tissue.
2) Hepatic metabolism - Potential for hepatotoxicity & DDIs
3) Achieve intracellular concentration: Active against atypical intracellular pathogens
4) Clearance/distibution is changed minimally in sepsis. Dose adjustment is generally not needed in sepsis
5) Excellent bioavailablity. IV:PO ratio is often 1:1
39
DOSE OPTIMIZATION
Concentration VS Time dependent killing
1) Concentration-dependent killing (aminoglycosides):
- Dosed less frequently &
- Higher doses
- Maximize the concentration above the MIC
2) Time-dependent killing (Beta-lactams)
- Dosed more frequently or
- Administered for a longer duration
- Maximize the time above the MIC
-- Extending the infusion time of beta-lactam antibiotics (from 30 minutes to 4 hours) or administering the drug as a continuous infusion.
-- Studies have documented that extended/continuous infusions of beta-lactams reduce hospital length of stay, mortality and costs, particularly when treating pneumonia caused by MDR Gram-negative pathogens like Pseudomonas.
40
Cmax:MIC (concentration-dependent)
- Drugs
- Goal
- Aminoglycosides
- Quinolones
- Daptomycin
Goal:
-- High peak (inc killing)
-- Low trough (dec toxicity)
Dosing strategies: large dose, long interval
41
AUC:MIC (exposure-dependent)
- Vancomycin (cell wall inh)
- Macrolides (protein synth inh)
- Tetracyclines (//)
- Polymyxins (Cell membrane inh)
Goal: exposure over time
Dosing strategies: variable
42
Time> MIC (time-dependent}
Beta-lactams (penicillins, cephalosporins, carbapenems)
Goal: maintain drug level> MIC for most of the dosing interval
Dosing strategies: shorter dosing interval, extended or continuous infusions
43
BETA-LACTAM ANTIBIOTICS MOA
- Beta-lactam antibiotics have a chemical structure that is characterized by a beta-lactam ring.
- They inhibit bacterial cell wall synthesis by binding to penicillin- binding proteins (PBPs).
- This prevents the final step of peptidoglycan synthesis in bacterial cell walls.
1) Penicillins
2) Cephalosporins
3) Carbapenems
44
Penicillin Coverage
1) Natural penicillins:
- Gram-positive cocci: Streptococci
- Gram-positive cocci: Enterococci
- Gram-positive anaerobes (mouth flora)
-- No Gram-negative
-- No Gram-positive cocci: Staphylococci
-- No MRSA (Methicillin Resistant Staphylococcus aureus)
-- No atypical organisms
2) Antistaphylococcal penicillins
- Gram-positive cocci: Streptococci
- Gram-positive cocci: Methicillin-susceptible Staphylococcus aureus (MSSA)
-- No Enterococcus
-- No Gram-negative
-- No anaerobes
3) Aminopenicillins
- Streptococci
- Enterococci
- Gram-positive anaerobes (mouth flora)
+
- Gram-negative bacteria (Haemophilus, Neisseria, Proteus and E, coli) (HNPE)
4) Aminopenicillins + beta-lactamase inhibitors (clavulanate, sulbactam and tazobactam)
- Streptococci
- Enterococci
- Gram-positive anaerobes (mouth flora)
- Gram-negative bacteria (Haemophilus, Neisseria, Proteus and E, coli)
+
- MSSA
- More resistant strains of Gram-negative bacteria [Haemophilus, Neisseria, Proteus, E. coli and Klebsiella (HNPEK)
- Gram-negative anaerobes (B. fragilis)
5) Extended-spectrum penicillins + beta-lactamase inhibitor (piperacillin/tazobactam):
- Streptococci
- Enterococci
- Gram-positive anaerobes (mouth flora)
- MSSA
- More resistant strains of Gram-negative bacteria [Haemophilus, Neisseria, Proteus, E. coli and K!ebsiella (HNPEK)
- Gram-negative anaerobes (Bacteroides fragilis)
+
- Gram-negative (Expanded coverage) (Citrobacter, Acinetobacter, Providencia, Enterobacter, Serratia (CAPES)
- & Pseudomonas aeruginosa.
-- Penicillins do not cover MRSA
45
Natural Penicillins
- Penicillin V Potassium (Pen VK) PO (Empty stomach)
- Penicillin G Aqueous (Pfizerpen) IV
- Penicillin G Benzathine (Bicillin L-A) IM
- Penicillin G Benzathine & Penicillin G Procaine (Bicillin C-R) IM
-- not IV; can cause cardiorespiratory arrest/ death
Coverage:
- Gram-positive cocci: Streptococci
- Gram-positive cocci: Enterococci
- Gram-positive anaerobes (mouth flora)
46
Anti staphylococcal Penicillins
- Dicloxacillin PO
- Nafcillin IV/ IM
- Oxacillin: IV
Coverage:
- Gram-positive cocci: Streptococci
- Gram-positive cocci: Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred for MSSA soft tissue, bone and joint, endocarditis and bloodstream infections
- No renal dose adjustments
- Nafcillin is a vesicant - administration through a central
line is preferred; if extravasation occurs, use cold packs and hyaluronidase injections
47
Aminopenicillins
- Amoxicillin (Moxatag) PO, chewable
- Amoxicillin/Clavulanate (Augmentin, Augmentin ES-600) PO, Chewable
- Ampicillin: PO/ IV/ IM
- Ampicillin/Sulbactam (Unasyn): IV
Coverage:
- Streptococci
- Enterococci
- Gram-positive anaerobes (mouth flora)
+
- Gram-negative bacteria (Haemophilus, Neisseria, Proteus and E, coli) (HNPE)
(+ B lactamase inhibitor)
+
- MSSA
- More resistant strains of Gram-negative bacteria [Haemophilus, Neisseria, Proteus, E. coli and Klebsiella (HNPEK)
- Gram-negative anaerobes (B. fragilis)
Notes:
- Ampicillin PO is rarely used due to poor bioavailability; amoxicillin is preferred if switching from IV ampicillin
- Amoxicillin/clavulanate: use a 14:1 ratio to dec diarrhea caused by the clavulanate component
- IV ampicillin and ampicillin/sulbactam must be diluted in NS only
48
Extended-Spectrum Penicillins
- Piperacillin/Tazobactam (Zosyn)
Prolonged or extended IV infusions
- Piperacillin/tazobactam contains 65 mg Na per 1 gram of piperacillin
- each dose infused over 4 hours
Coverage:
- Streptococci
- Enterococci
- Gram-positive anaerobes (mouth flora)
- MSSA
- More resistant strains of Gram-negative bacteria [Haemophilus, Neisseria, Proteus, E. coli and K!ebsiella (HNPEK)
- Gram-negative anaerobes (Bacteroides fragilis)
+
- Gram-negative (Expanded coverage) (Citrobacter, Acinetobacter, Providencia, Enterobacter, Serratia (CAPES)
- Pseudomonas aeruginosa.
49
CONTRAINDICATIONS with aminopenicillins
Augmentin and Unasyn:
History of cholestatic jaundice or hepatic dysfunction associated with previous use
Severe renal impairment (CrCI < 30ml/min):
- Do not use ER PO amoxicillin and amoxicillin/ clavulanate (Augmentin XR)
- Or the 875 mg strength of amoxicillin/clavulanate
50
SIDE EFFECTS with penicillins
- Seizures (with accumulation when not correctly dose adjusted in renal dysfunction)
- GI upset
- Diarrhea
- Rash (including SJS/TEN)/ allergies/ anaphylaxis
- Hemolytic anemia (identified with a positive Coombs test)
- Renal failure
- Myelosuppression with prolonged use
- Inc LFT
51
Monitoring with Penicillin
- Renal function
- Symptoms of anaphylaxis with 1st dose
- CBC and LFTs with prolonged courses
52
Penicillin Drug Interactions
■ Probenecid can inc the levels of beta-lactams by interfering with renal excretion.
- This combination is sometimes used intentionally in severe infections to inc 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 can inhibit the anticoagulant effect of warfarin.
■ Penicillins can inc the serum concentration of methotrexate;
- They can dec the serum concentration of mycophenolate active metabolites due to impaired enterohepatic recirculation.
53
CLASS EFFECT
All penicillins should be avoided in patients with a beta-lactam allergy
Exceptions:
- Treatment of syphilis during pregnancy (all patients) and
- In HIV patients with poor compliance/follow-up
--> desensitize and treat with penicillin G benzathine
- All penicillins increase the risk of seizures if accumulation occurs (failure to dose adjust in renal dysfunction)
54
OUTPATIENT (ORAL) Penicillin Drugs
Penicillin VK
■ A first-line treatment for strep throat and mild nonpurulent skin infections (no abscess)
Amoxicillin
- First-line treatment for acute otitis media (pediatric dose: 80-90 mg/kg/day)
- Drug of choice for infective endocarditis prophylaxis before dental procedures (2 grams PO x 1, 30-60 minutes before procedure)
- Used in H. pylori treatment*
Amoxicillin/Claulanate (Augmentin)
■ First-line treatment for acute otitis media (pediatric dose: 90 mg/kg/day) and for sinus infections (if antibiotics indicated)
■ Use the lowest dose of clavulanate to dec diarrhea
Dicloxacillin
■ Covers MSSA only (no MRSA)
■ No renal dose adjustment needed
55
INPATIENT (PARENTERAL) Penicillin drugs
Penicillin G Benzathine (Bicillin L·A)
■ Drug of choice for syphilis (2.4 million units IM x 1)
■ Not for IV use; can cause death
Nafcillin and Oxacillin
■ Covers MSSA only (no MRSA)
■ No renal dose adjustment needed
Piperacillin/ Tazobactam (Zosyn)
- Only penicillin active against pseudomonas
- Extended infusion over 4 hrs can be used to maximize T > MIC
56
CEPHALOSPORINS as a class, they do not cover:
- Enterococcus
- Atypicals
57
1st G Ceph:
Drugs:
- Cefazolin
- Cefalexin (Keflex): PO 250 - 500 mg q 6 - 12h
- Cefadroxil
Coverage:
- Excellent activity against: (DOC btwn ceph)
-- MSSA (Staph)
-- Streptocossus
- Some activity (not good):
-- Gram Negative: Proteus, E. coli, Klebsiella (PEK)
58
2nd G Ceph:
Drugs:
- Cefuroxime (fur kello shaaer
- Cefotetan (Cefotan) (fet hitan)
- Cefaclor (fac)
- Cefoxitin (fok)
- Cefprozil (pro)
Coverage:
1) Cefuroxime:
- Staphylococci
- More resistant strains of S. pneumoniae
- Gram -ve: Haemophilus, Neisseria, Proteus, E.coli and Klebsiella (HNPEK).
2) Cefotetan and cefoxitin:
- Have added coverage of G-ve anaerobes (B. fragilis)
59
3rd G Ceph:
Group 1:
- Cefdinir PO
- Ceftriaxone (Rocefine) IV/IM
- Cefotaxime IV/IM
- Cefditoren PO
- Cefixime PO
- Cefopodoxime PO
- Ceftibuten PO
Coverage:
Ceftriaxone, cefotaxime and oral drugs:
- Resistant Streptococci (S. pneumoniae and viridans)
- Staphylococci (MSSA)
- G +ve anaerobes (mouth flora)
- Resistant strains of HNPEK
Group 2:
- Ceftazidime (Fortaz)
Coverage:
- No G +ve activity
- Covers Pseudomonas
60
4th G Ceph
Cefepime
- Broad G -ve activity:
-- HNPEK
-- CAPES
-- Pseudomonas
- G +ve activity similar to ceftriaxone:
-- Resistant Streptococci (S. pneumoniae and viridans)
-- Staphylococci (MSSA)
-- G +ve anaerobes (mouth flora)
61
5th G
Ceftaroline Fosamil (Teflaro)
- G -ve activity similar to ceftriaxone
--- Resistant strains of HNPEK
- Broad G +ve
- Only beta-lactam that covers MRSA
62
Ceph & Beta-lactamase inhibitor combinations:
- Ceftazidime/avibactam
- Ceftolozane/ tazobactam
Have a similar spectrum as ceftazidime but with added activity against MDR Pseudomonas and other MDR Gram-negative rods.
Coverage:
- No G+ve
- Pseudomonas
- MDR Pseudomonas
- MDR G -ve rods
63
Siderophore cephalosporin:
- Cefiderocol (Fetroja)
- Uses the iron transport system to enter the G -ve cell wall.
- It is approved for complicated UTI/ pyelonephritis
- Coverage:
-- E.coli
-- Enterobacter
-- Klebsiella
-- Proteus
-- Pseudomonas
64
Cephalexin
- Brand
- Dose
- Keflex
- PO: 250 - 500 mg q 6 - 12 hrs
65
CONTRAINDICATIONS (CEFTRIAXONE)
- Hyperbilirubinemic neonates (causes biliary sludging, kernicterus (Bilirubin induced brain dysfunction))
- Concurrent use with calcium-containing IV products in neonates <= 28 days old
66
Warnings with cephalosporin
- Cross-sensitivity with PCN allergy (< 10 % higher risk with 1st G ceph):
Do not use in pts with type 1 hypersensitivity to PCN (swelling, angioedema, anaphylaxis)
- Cefotetan contains a side chain [N-methylthiotetrazole (NMTT or 1-MTT)] which can inc the risk of bleeding & cause a disulfiram-like reaction with alcohol ingestion
- Anaphylaxis/ hypersensitivity reactions
- Some drugs can inc INR in patients taking warfarin
67
SE of Ceph
- Seizures (with accumulation when not correctly dose
adjusted in renal dysfunction)
- GI upset, diarrhea
- Rash/allergic reactions/anaphylaxis
- Acute interstitial nephritis
- Hemolytic anemia (identified with a positive Coombs test)
- Myelosuppression with prolonged use, inc LFTs, drug fever, serious skin reactions (SJS/TEN)
68
Monitoring of Ceph
- Renal function
- Signs of anaphylaxis with 1" dose
- CBC
- LFTs
69
Notes with Ceph
- All cephs require renal adjustment except:
- Ceftazidime/ Avibactam has activity against:
- How should you adjust Cefiderocol with renal function?
- Ceftriaxone:
-- No renal adjustment
-- CNS penetration at high doses (2 grams Q12H) when meninges inflamed
- Cefixime available in a chewable tablet
- Ceftazidime/avibactam:
Activity against some carbapenem-resistant Enterobacteriaceae (CRE)
- Cefiderocol (Fetroja):
Increase to 2 grams Q6H if CrCI >= 120 ml/min
70
Ceph combination
Ceftazidime/ Avibactam
Ceftolozane/ Tazobactam
71
Cephalosporin Drug Interactions
- Drugs that dec stomach acid can dec the bioav of some oral ceph.
- Cefuroxime, cefpodoxime, cefdinir and cefditoren should be separated by two hours from short-acting antacids.
H2RAs and PPis should be avoided.
- Insoluble precipitates may form when ceftriaxone is administered with calcium-containing IV fluids (do not use together in neonates).
- In adults, the IV line should be flushed with a compatible fluid between administration of each product.
72
Class effect Ceph
■ Due to a small risk of cross-reactivity, do not choose a ceph on the exam if the patient has a penicillin allergy
-- exception: pediatric patients with acute otitis media
■ Risk of seizures if accumulation occurs (failure to dose adjust in renal dysfunction)
73
OUTPATIENT (ORAL) common uses
1) Cefalexin (Keflex)
2) Cefuroxime
3) Cefdinir
1st Generation: Cephalexin (Keflex)
■ Common uses: skin infections (MSSA), strep throat
2nd Generation: Cefuroxime
■ Common uses: acute otitis media, community acquired pneumonia (CAP), sinus infection (if antibiotics indicated)
3rd Generation: Cefdinir
■ Common uses: CAP, sinus infection (if antibiotics indicated)
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INPATIENT (PARENTERAL) Ceph common uses
1) Cefazolin
2) Cefotetan, Cefoxitin
3) Ceftriaxone, Cefotaxime
1st Generation: Cefazolin
■ Common use: surgical prophylaxis
2nd Generation: Cefotetan and Cefoxitin
■ Anaerobic coverage (B.fragilis)
■ Common use: surgical prophylaxis (colorectal procedures)
■ Cefotetan can cause a disulfiram-like reaction with alcohol ingestion
3rd Generation: Ceftriaxone and Cefotaxime
■ Common uses: CAP, meningitis, spontaneous bacterial peritonitis, pyelonephritis
■ Ceftriaxone
- No renal dose adjustment
- Do not use ceftriaxone in neonates (age 0-28 days)
Ceftazidime (3rd Generation) and Cefepime (4th Generation)
■ Active against Pseudomonas
Ceftolozane/ Tazobactam and Ceftazidime/ Avibactam
■ Used for MDR G -ve organisms (including Pseudo)
Ceftaroline
■ Only beta-lactam active against MRSA
■ Common uses: CAP, skin and soft tissue infections
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When studying the carbapenems (on the next page), think of how you would approach a case on the exam in which one of the answer choices is Invanz 1 gram IV Q24H.
How can you decide if this is the best answer choice?
Assess the following, using the underlined information in the carbapenem drug table:
- Allergies:
if the patient has a penicillin allergy, there is likely a better answer choice because of the possibility of cross-reactivity.
- Culture and susceptibility:
if the culture is growing ESBL-positive £. coli, ertapenem may be a good choice.
If Pseudomonasis growing, ertapenem can be immediately ruled out based on a lack of activity against this pathogen.
- Past medical history and medication profile:
if the patient has a history of seizures or takes a seizure drug, such as phenytoin, there is likely a better choice than a carbapenem, which can increase the risk for seizures.
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CARBAPENEMS coverage
- Very broad spectrum
- Reserved for MDR Gram-negative infections
- Active against most Gram-positive, Gram-negative (including ESBL-producing bacteria) and anaerobic pathogens
- They provide no coverage of atypical pathogens, MRSA, VRE ,C.difficile or Stenotrophomonas
Ertapenem is different:
- Has no activity against Pseudomonas, Acinetobacter or Enterococcus
Carbapenem/beta-lactamase inhibitor combinations are typically reserved for highly resistant infections (e.g., CRE) that are not able to be treated with a single entity carbapenem.
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List the carbapenem drugs
- Doripenem
- lmipenem/Cilastatin
- Meropenem (Merrem)
- Ertapenem (lnvanz)
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CI to carbapenem
Anaphylactic reactions to beta-lactam antibiotics
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Warning in carbapenem
- Do not use in patients with PCN allergy (small risk of cross-reactivity)
- CNS adverse effects, including states of confusion and seizures
- Doripenem: do not use for the treatment of pneumonia, including healthcare- associated pneumonia (HAP) and ventilator-associated pneumonia (VAP)
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SE with Carbapenem
- Diarrhea, rash/severe skin reaction (DRESS)
- Seizures with higher doses and in patients with impaired renal function (mainly imipenem)
- Bone marrow suppression with prolonged use
- Inc LFTs
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Monitoring with carbapenem
- Renal function
- Symptoms of anaphylaxis with 1st dose
- CBC
- LFTs
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Why is imipenem combined with cilastatin?
Imipenem is combined with cilastatin to prevent drug degradation by renal tubular dehydropeptidase
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Ertapenem
- Brand
- For what is it commonly used?
- lnvanz
- Stable in NS only
- No coverage of Pseudomonas, Acinetobacter or Enterococcus
- Commonly used for diabetic foot infections
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Carbapenem Drug Interactions
■ Carbapenems can dec serum concentrations of valproic acid, leading to a loss of seizure control.
■ Use with caution in patients with a history of seizure disorder, or in combination with other drugs known to lower the seizure threshold (ganciclovir, quinolones, bupropion, tramadol).
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Class effects of carbapenem
■ All active against ESBL-producing organisms and (except ertapenem) Pseudomonas
■ Do not use with penicillin allergy
■ Seizure risk (with higher doses, failure to dose
adjust in renal dysfunction, or use of imipenem/cilastatin)
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Remember what Carbapenems do not cover:
■ Atypicals, VRE, MRSA, C. difficile, Stenotrophomonas
■ ErtAPenem does not cover PEA:
- Pseudomonas
- Enterococcus
- Acinetobacter
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Common uses of carbapenems
■ Polymicrobial infections (severe diabetic foot infection)
■ Empiric therapy when resistant organisms suspected
■ ESBL-positive infections
■ Resistant Pseudomonas or Acinetobacter infx (except ertapenem)
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How are carbapenems administered?
- All are IV only.
- Ertapenem must be diluted in normal saline.
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Monobactams drugs
Aztreonam
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Monobactam
- MOA
- Does it cross react with beta lactams?
- Coverage?
- Similar to beta-lactams
- Inhibits bacterial cell wall synthesis by binding to penicillin- binding proteins (PBPs), which prevents the final step of peptidoglycan synthesis in bacterial cell walls.
- The monobactam structure makes cross-reactivity with a beta-lactam unlikely.
- Aztreonam is primarily used when a beta-lactam allergy is present.
- Aztreonam coverage:
-- Covers many Gram-negative organisms, including Pseudomonas
-- No Gram-positive or anaerobic activity
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Aztreonam brand
Azactam
- Injection
- Can be used with a penicillin allergy
- CrCI < 30 ml/min: dose adjustment required
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MRSA coverage
Ceftaroline
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MSSA S aureus
- Oxacillin
- Nafcillin
- Amox/ Clav
- Amp/ Sulbactam
- Pip/tazo
- Cefazolin
- Cefalexin
- Cefuroxime
- Cefotetan
- Cefoxitine
- Cefotaxime
- Ceftriaxone
- Cefepime
- Ceftaroline
- Ceftazidime/ Avibactam
- Ceftolozane/Tazobactam
- Imipenem/Cilastatin
- Meropenem
- Doripenem
- Ertapenem
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S. Pneumonia, Viridans group Streptococcus
- Penicillin
- Amoxicillin
- Oxacillin
- Nafcillin
- Amox/ Clav
- Amp/ Sulbactam
- Pip/tazo
- Cefazolin
- Cefalexin
- Cefuroxime
- Cefotetan
- Cefoxitine
- Cefotaxime
- Ceftriaxone
- Cefepime
- Ceftaroline
- Ceftazidime/ Avibactam
- Ceftolozane/Tazobactam
- Imipenem/Cilastatin
- Meropenem
- Doripenem
- Ertapenem
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Enterococcus (Not VRE)
- Amoxicillin
- Amoxicillin/Clavulanate
- Ampicillin/Sulbactam
- lmipenem/Cilastatin
- Meropenem
- Doripenem
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PEK (Proteus, E. coli, Klebsiella) (Gram -ve)
- Amoxicillin (No klebsiella coverage)
- Amoxicillin/Clavulanate
- Ampicillin/Sulbactam
- Piperacillin/Tazobactam
- Cefazolin
- Cephalexin
- Cefuroxime
- Cefotetan
- Cefoxitin
- Cefotaxime
- Ceftriaxone
- Ceftazidime
- Aztreonam
- Cefepime
- Ceftaroline
- Ceftazidime/ Avibactam
- Ceftolozane/Tazobactam
- lmipenem/Cilastatin
- Meropenem
- Doripenem
- Ertapenem
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HNPEK
Like PEK
But without cefazolin and cefalexin
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CAPES
- Piperacillin/Tazobactam
- Cefotaxime
- Ceftriaxone
- Ceftazidime
- Aztreonam
- Cefepime
- Ceftaroline
- Ceftazidime/ Avibactam
- Ceftolozane/Tazobactam
- lmipenem/Cilastatin
- Meropenem
- Doripenem
- Ertapenem
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Pseudomonas
- Piperacillin/Tazobactam
- Ceftazidime
- Aztreonam
- Cefepime
- Ceftazidime/ Avibactam
- Ceftolozane/Tazobactam
- lmipenem/Cilastatin
- Meropenem
- Doripenem
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G +ve anaerobes (Mouth flora)
- Penicillin
- Amoxicillin
- Amox/ Clav
- Amp/ Sulbactam
- Pip/tazo
- Cefazolin
- Cefalexin
- Cefotetan
- Cefoxitine
- Cefotaxime
- Ceftriaxone
- Cefepime
- Ceftaroline
- Ceftazidime/ Avibactam
- Ceftolozane/Tazobactam
- Imipenem/Cilastatin
- Meropenem
- Doripenem
- Ertapenem
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B. Fragilis
- Amoxicillin/Clavulanate
- Ampicillin/Sulbactam
- Cefotetan
- Cefoxitin
- Ceftazidime/ Avibactam
- Ceftolozane/Tazobactam
- Imipenem/Cilastatin
- Meropenem
- Doripenem
- Ertapenem
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Atypical Organisms
No coverage in beta lactams
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AMINOGLYCOSIDES MOA
- Bind to ribosome
- Interferes with bacterial protein synthesis
- Defective bacterial cell membrane
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AMINOGLYCOSIDES coverage
- Gram -ve
- Pseudomonas
- Usually not given empirically as monotherapy
- Gentamicin and streptomycin: used empirically with Beta lactams or Vanco for synergy
-- when treating Gram-positive infections (enterococcal endocarditis)
- Streptomycin and amikacin are used as second-line treatments for Mycobacterial infections.
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What are the two dosing strategies for aminoglycosides?
1) Traditional dosing:
- Lower doses
- More frequently
2) Extended interval dosing:
- Higher doses (to attain higher peaks)
- Less frequently
-- Less accumulation of drug
-- Lower risk of nephrotoxicity
-- Decreased cost.
---> While there is a better chance of achieving the target Cmax:MIC, this dosing strategy has not been shown to be clinically superior to traditional dosing.
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GOOD NEWS with aminoglycosides
- Kill Gram-negative pathogens fast
- Are synergistic with beta-lactams for some Gram-positive organisms
- Low resistance
- Low drug cost
--Concentration-dependent activity
--Have a post-antibiotic effect (the bacterial killing continues after the serum level drops below the MIC)
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BAD NEWS with aminoglycosides
They have notable toxicities that require monitoring:
- Renal damage
- Ototoxicity, which may be irreversible (hearing loss/tinnitus/ balance problems)
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How can you use aminoglycosides in a smart way?
Take advantage of the concentration-dependent kinetics ➔ give larger doses less frequently
➔ this gives the kidneys time to recover between doses
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List aminoglycoside drugs
- Gentamicin
- Tobramycin (inhalation for CF)
- Amikacin
- Streptomycin
- Plazomicin: For complicated UTI only
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Which weight should you use for dosing of aminoglycosides
- If underweight (< ideal body weight) use total body for dosing
- If normal weight (not obese or underweight): ideal body weight or total body weight can be used for dosing (follow the hospital protocol)
- If obese, use adjusted body weight for dosing
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Traditional IV Dosing of Gentamicin and tobramycin
1-2.5 mg/kg/dose;
- Lower doses are used for Gram-positive infections;
- Higher doses are used for Gram-negative infections
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Renal Dose Adjustments (Traditional Dosing) of aminoglycosides
CrCI > 60 ml/min: Q8H (To know)
CrCI 40-60 ml/min: Q12H
CrCI 20-40 ml/min: Q24H
CrCI < 20 ml/min: 1x dose, then dose per levels
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Extended Interval IV Dosing (Gentamicin/Tobramycin)
- 4-7 mg/kg/dose (commonly 7 mg/kg)
- Frequency (dosing interval) is determined by a nomogram but starts at Q24H if renal function is normal
- Avoid when clearance and/or volume of distribution are altered [pregnancy, ascites, burns, cystic
fibrosis, CrCI < 30 ml/min (including end-stage renal disease on dialysis)]
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BBW with aminoglycosides
- Nephrotoxicity
- Ototoxicity (hearing loss, vertigo, ataxia)
- Neuromuscular blockade
- Respiratory paralysis
- Avoid with other neurotoxic/nephrotoxic drugs,
- Fetal harm if given in pregnancy
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Warnings with aminog
Use caution in patients with impaired renal function, in the elderly, and those taking other nephrotoxic drugs (amphotericin B, cisplatin, polymyxins, cyclosporine, loop diuretics, NSAIDs, radiocontrast dye, tacrolimus and vancomycin)
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SE with aminogly
Nephrotoxicity (acute tubular necrosis), hearing loss (early toxicity associated with high-pitched sounds), vestibular toxicity (resulting in balance deficits)
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Monitoring with aminogly
Drug levels, renal function, urine output, hearing tests
- Traditional dosing: draw a trough level right before (or 30 minutes before) the 4th dose; draw a peak level 30 min after the end of the 30-minute infusion for the 4th dose
- Extended interval dosing: draw a random level per the timing on the nomogram
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Notes with aminog
- Amikacin is the most active against Pseudomonas
- The clinical definition of obesity varies (but TBW > 120% IBW is commonly used for drug dosing); on the exam, obesity will be obvious, and may be stated in the question, indicating that adjusted body weight should be used for weight-based dosing
- Plazomicin is reserved for MDR Gram-negative UTls and should only be used when there are no alternative treatment options
