Rybak Section Flashcards
Colonization
potentially pathogenic organism is present at the body site but is NOT invading host tissue or eliciting a host immune response
Infection
pathogenic organism is present at the body site and is damaging host tissue and eliciting host responses and symptoms consistent with infection
Normal WBC
4500 - 11,000 cells/mm3
Mature Neutrophils
most common WBC
fight infections
Immature Neutrophils (bands)
increased during infection –> left shift
Eosinophils
allergic reactions & immune response to parasites
Basophils
hypersensitivity reactions
Lymphocytes
humoral (B cells) & cell mediated (T cells) immunity
Monocytes
mature into macrophages that scavenge foreign invaders
4 Mechanisms of Antibiotic Resistance
Altered cell wall proteins/decreased porin production
Efflux Pumps
Drug-Inactivating Enzymes
Modified Drug Target
Decreased Porin Production
What? –> mutations lead to loss of specific porins
Bugs:
- Enterobacterales
- P. aeruginosa vs carbapenems
Efflux Pumps
What? –> overexpression can lead to resistance
Bugs:
- P. aeruginosa vs carbapenems
- S. pneumoniae vs macrolides
B-lactamase Resistance Mechanisms
Narrow Spectrum B-lactamase –> Class A
Extended Spectrum B-lactamase (ESBL) –> Class A
Serine Carbapenemases –> Class A
Metallo-B-lactamase –> Class B
Cephalosporinases –> Class C
OXA-Type –> Class D
Extended Spectrum B-lactamase (ESBL)
What? –> plasmid-mediated enzymes that hydrolyze most penicillin’s, cephalosporins, and monobactams
** cannot inactive non-B-lactam agents
** cause additional resistance genes
Enzyme: CTX-M-15
Bugs:
- E. coli
- Klebsiella
- Proteus mirabilis
Treatment: carbapenems
* Zosyn if ONLY urinary
Serine Carbapenamases
What? –> resistance to whole B-lactam class
Enzyme: KPC
Bugs:
- E. coli
- E. cloaecae
- E. aerogenes
- Klebsiella
- Proteus mirabilis
Treatment:
- Ceftazidime/avibactam
- Meropenem/vaborbactam
- Imipnem/Cilastatin/relebactam
Metallo-B-lactamase
What? –> resistance to all B-lactam class EXCEPT monobactams
** cause additional resistance genes
Enzyme: NDM
Bugs:
- P. aeruginosa
- Acinetobacter
- Enterobacterales
Treatment: Cefiderocol
Cephalosporinases
What? inducible via chromosomally encoded ampC gene
Bugs: HECK-YES MaaM
Treatment:
1. Cefepime
2. Carbapenems
OXA-Type
What? –> heterogenous group
Bugs:
- P. aeruginosa
- Acinetobacter
- Enterobacterales
Treatment: Cefiderocol
Aminoglycoside-Modifying Enzymes
3 Mechanisms:
- acetylation
- nucleotidylation
- phosphorylation
Effect: impairs cellular uptake or binding to ribosome
Modified Drug Target - Vancomycin Resistance
Normal: binds to D-ala-D-ala terminus of the peptidolgycan layer to inhibit cell wall synthesis
Resistance: alters D-ala-D-ala into either D-ala-D-lac or D-ala-D-ser
Enzyme: VanA or VanB
Treatment:
- daptomycin
- linezolid
Modified Drug Target - Methicillin Resistant Staphylococcus Aureus (MRSA)
What? –> decreased affinity for PBP of antibiotics or decrease production of PBP by bacteria
** B-lactamase are not effective
Enzyme: mecA (PBP2A)
Treatment:
- Ceftaroline or Ceftobiprole
- Vancomycin
- Daptomycin
- Linezolid
