Chapter 22 - Infectious Disease I - Background & Antibiotics by drug class Flashcards
Should you treat a bacterial urine infection if the patient is asymptomatic?
On what should you reply on in order to diagnose?
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.
Antibiotic characteristics:
The spectrum of activity & the Ability to penetrate the site of infection depends on what?
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.
What are the patient characteristics that impact treatment choices?
- 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
What is an Empiric Treatment and how do you choose it?
- 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.
Common Bacterial Pathogens for Select Sites of Infection:
CNS/ Meningitis
1) Streptococcus pneumoniae
2) Neisseria meningitidis
3) Haemophilus influenzae
4) Group B Streptococcus/ E.coli (young)
5) Listeria (young/ old)
Common Bacterial Pathogens for Select Sites of Infection:
Upper Respiratory
1) Streptococcus pyogenes
2) Streptococcus pneumoniae
3) Haemophilus influenzae
4) Moraxella catarrhalis
Common Bacterial Pathogens for Select Sites of Infection: Mouth
1) Mouth flora (Peptostreptococcus)
2) Anaerobic GNR (Prevotella,others)
3) Viridans group Streptococci
Common Bacterial Pathogens for Select Sites of Infection: Lower Respiratory (Community)
1) Streptococcus pneumoniae
2) Haemophilus influenzae
3) Atypicals: Legionella, Mycoplasma, Chlamydophilia
4) Enteric GNR (alcoholics)
Common Bacterial Pathogens for Select Sites of Infection: Lower Respiratory (Hospital)
1) Staphylococcus aureus, including MRSA
2) Pseudomonas aeruginosa
3) Acinetobacter baumannii
4) Enteric GNR (including ESBL, MDR)
5) Streptococcus pneumoniae
Common Bacterial Pathogens for Select Sites of Infection: Heart/Endocarditis
1) Staphylococcus aureus, including MRSA
2) Staphylococcus epidermidis
3) Streptococci
4) Enterococci
Common Bacterial Pathogens for Select Sites of Infection: Intra-abdominal
1) Enteric GNR
2) Enterococci
3) Streptococci
4) Bacteroids sp
Common Bacterial Pathogens for Select Sites of Infection: Skin/Soft Tissue
1) Staphylococcus aureus
2) Streptococcus pyogenes
3) Staphylococcus epidermidis
4) Pasteurella multocida = aerobic/anaerobic GNR (in diabetes)
Common Bacterial Pathogens for Select Sites of Infection: Bone/Joint
1) Staphylococcus aureus
2) Staphylococcus epidermidis
3) Streptococci
4) Neisseria gonorrhoeae
5) GNR (only in specific situations)
Common Bacterial Pathogens for Select Sites of Infection: Urinary Tract
1) E. coli
2) Proteus
3) Klebsiella
4) Staphylococcus saprophyticus
5) Enterococci
Gram stain
Gram +: blue/ purple
Gram -: Pink
Atypical: do not stain
Gram-Positive Shapes + organisms
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.
Gram -ve Shapes & organisms
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.
Atypicals (do not Gram stain well)
- Chlamydia spp.
- Legionella spp.
- Mycoplasma pneumoniae
- Mycobacterium tuberculosis
Whats the function of lactose?
- 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.
Give an example of synergy.
- 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)
Antibiotics treatment thought process
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.
ASSESSMENT OF TREATMENT: MONITORING TREATMENT RESPONSE
- 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)
REASONS FOR LACK OF RESPONSE:
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
Intrinsic resistance:
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.
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.
Acquired resistance:
- Bacterial DNA containing resistant genes can be transferred between different species and/or picked up from dead bacterial fragments in the environment.
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.
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
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.
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.
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
Cell wall inhibitor drugs:
- Beta-lactams (penicillins, cephalosporins, carbapenems)
- Monobactams (aztreonam)
- Vancomycin, dalbavancin, telavancin, oritavancin
Cell membrane inhibitor drugs
- Polymyxin
- Daptomycin
- Telavancin
- Oritavancin
DNA/ RNA Inhibitor drugs
- Quinolones (DNA gyrase, topoisomerase IV)
- Metronidazole, tinidazole
- Rifampin
(Do not disturb cz the queen aam tekul rifa3i bl metro)
Folic acid synthesis inhibitor drugs
- Sulfonamides
- Trimethoprim* (Often combined with sulfamethoxazole to overcome resistance)
- Dapsone
Protein synthesis inhibitor drugs
- Aminoglycoside
- Macrolide
- Tetracycline
- Clindamycin
- Linezolid, Tedizolid
- Quinupristin/Dalfopristin
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
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
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.
Cmax:MIC (concentration-dependent)
- Drugs
- Goal
- Aminoglycosides
- Quinolones
- Daptomycin
Goal:
– High peak (inc killing)
– Low trough (dec toxicity)
Dosing strategies: large dose, long interval
AUC:MIC (exposure-dependent)
- Vancomycin (cell wall inh)
- Macrolides (protein synth inh)
- Tetracyclines (//)
- Polymyxins (Cell membrane inh)
Goal: exposure over time
Dosing strategies: variable
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
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
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
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)
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
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
