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MI Immuno/Heme > Micro & ABx > Flashcards

Micro & ABx Flashcards

1
Q

Virulence Facotr

A

Any pathogen component that aids in establishment of an infection (colonization, immune evasion, entry or exit from a host)

May not be essential for viability but is important in pathogenesis

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2
Q

What genera of bacteria does not contain peptidoglycan?

A

Mycoplasma

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3
Q

Gram +

A

Cyctoplasmic membrane surrounded by many layers of peptidoglycan

Distributed through these layers are teichoic and lipotechoic acids (only found in Gram + bacteria - promote birulence by aiding attachement to host structures and increasing viability)

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4
Q

Endotoxin

A

Lipopolysaccharide (LPS) exhibited on the outer leaflet of Gram negative bacteria

Stimulates the innate immune response

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5
Q

Gram-negative

A
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6
Q

Glycocalyx

A

“slime layer”

Loose layer of polysaccharides the surround bacteria - helps bacteria attach/adhere to surfaces and aids in biofilm formation

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7
Q

K antigen

A

Capsular polysaccharide
Capsule - outside of cell wall

Anti-phagocytic

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8
Q

Pili/fimbrae

A

Filamentous appendages that help bacteria sense and attach to their environment (including host cells)

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9
Q

H antigen

A

Flagella

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10
Q

What propels bacteria during chemotaxis?

A

Rotation of their flagella

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11
Q

Plasmids

A

Small, circular, extrachromosomal DNA - often contain virulence genes

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12
Q

Bacterial ribosomes

Sed rate

A

70s

(50s+30s)

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13
Q

Spores

A

Found in Gram-positive rods (clostridium and bacillus)

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14
Q

Facultative vs. obligate intracellular bacteria

A

Facultative - can grow extracellularly in the environment or lab and also grow inside of a host cell in the body

Obligate - cannot be grown on artificial culture medium - require host (in lab and in the body)

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15
Q

Most bacterial pathogens are?

In response to environmental oxygen

A

Facultative anaerobes

Have enzymes that protect from oxygen free radicals (superoxide dismutase, catalase, etc.)

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16
Q
A
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17
Q

Bacterial environmental sensing

A

Two-component signal transduction systems:

Sense the environment (histidine kinase)

Relay signals inwards (response regulator)

Influcne movement, gene regulation, and virulence factor expression

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18
Q

What are the function of siderophores

A

Acquisition of iron from host complexes via secreted bacterial molecules possessing a high affinity for iron ions

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19
Q

Fastidious bacteria

A

Can not grow without specific nutrient supplementation on aritificial media

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20
Q

Describe the Gram-negative cell envelope starting with the layer closest to the cytoplasm and moving to the external environment

A

Inner Membrane -> Periplasm -> Peptidoglycan -> Outer Membrane

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21
Q

Primary secretion system used by Gram-positive bacteria

A

The general secretory pathway

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22
Q

Primary secretory system for Gram-negative bacteria

A

Type III secretion system (T3SS)

Major virulence factor for Gram-negative pathogens

Referred to as a needle-like apparatus

T3SS effector molecules - numerous functions - bacterial attachemnt, immune system evasion, promotes interaction w/ host cell cytoskeleton, and cytotoxicity.

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23
Q

O-antigen

A

Lipopolysaccharide (LPS)

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24
Q

What is the only bacteria that utilizes sterols?

A

Mycoplasma

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25
Q

Bacterial chromosome

A

1-5 million bp (small)

Single, circular, haploid chromosome that lacks introns

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26
Q

Lipid A

A

Lipid component of endotoxin responsible for the toxicity of gram-negative bacteria

Most interior portion of LPS

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27
Q

Regulons

A

Functional groups consisting of several operons - the promoters driving these different operon are coordinately regulated (turned on and off at the same time)

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28
Q

Reverse mutations

A

Change the phenotype of a mutant back to that of the wild-type

True reversions - return genotype back to wild-type

Supressor mutations - return phenotype, not genotype to wild-type

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29
Q

Prototrophic bacteria

A

Baceria that can synthesize all essential nutrients

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30
Q

Conditional mutations

A

Mutations that produce proteins that are functional only under specific environmental conditions

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31
Q

Auxotrophs

A

Mutant bacteria that have lost the ability to synthesize all essential nutrients - must obtain nutrients or precursors from their environment

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32
Q

Bacterial single strand repair

A

Excision repair

Photoactivation

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33
Q

Bacterial double strand repair

A

Mismatch repair (recombinatorial repair)

Error-prone repair - emergency system that only bacteria use (damaged DNA is replaced with random sequences)

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34
Q

Bacterial recombination

A
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35
Q

Positive regulation of operon

A

System that directly increases RNA polymerase affinity for a particular promoter

Activator proteins turn this system on

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36
Q

Negative regulation of operon

A

System that directly decreases RNA polymerase affinity for a particular promoter

Repressor proteins turn this system off

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37
Q

Cis- acting elements

A

DNA sequence elements that must be present on the same piece of DNA w/ the gene of interest to function on that gene

Promoters
Operators
Enhancers
Terminators

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38
Q

During which phase of growth are bacteria most likely to begin forming spores

A

The stationary phase (nutrients/resources are becoming scare, there is also accumulation metabolic by-products/waste)

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39
Q

Trans-acting factors

A

Encode gene products that can act from a distance and upon genes located on different pieces of DNA (most are proteins)

Repressors
Activators
Co-repressors
Inducers

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40
Q

What cis-acting element is composed of RNA sequences

A

Terminators are RNA sequences (encoded in the DNA) that tell the RNA polymerase to stop at the end of a gene or operon

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41
Q

Activator vs. inducer

A

Both trans-acting factors

Activator - proteins that bind to the enhancer, promoter, and/or operator sites in a gene and increases the affinity in which RNA polyerase binds to promoter sequences

Inducer - factors (often metabolites) that either bind to activator proteins and activate them or bind to repressors and inactivate them

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42
Q

In bacteria, what factors recognize cis-DNA at the Pribnow box?

A

Sigma (σ) factors recognize cis-DNA sequences in the promoter (-10 and -35 regions-referred
to as the Pribnow box).

Once the σ-factor is bound to
DNA, RNA polymerase (RNAP) is recruited to that site and transcription can begin. Sigma-factor/DNA interaction puts the RNA polymerase in the correct
position and is required for transcriptional initiation.

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43
Q

What determines bacterial transcription frequency?

A

Ultimately determine by how tightly RNA polymerase is bound (holoenzyme binds to the promoter DNA)

RNAP/DNA affinity:

Increase - activator binding
Decreased - repressor binding

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44
Q

lac repressor

A

Negative regulation

If there is not lactose present, the lac repressor binds to the operator site and reduces RNAP binding

When lactose (inducer) binds the repressor, its affinity for the operator site is reduced - falls off - allows RNAP to bind the lac promoter

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45
Q

Catabolite activator protein (CAP)

A

Postive regulation of lac operon

When CAP is bound to cAMP, it binds to the lac promoter and increases RNAP activity

When glucose is present, the amount of cAMP in the cell is low, reducing CAP-mediated activation of lac gene transcription

The level of cAMP is inversely regulated by glucose.

High glucose = low cAMP
Low glucose = high cAMP

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46
Q

Attenuation

Operan gene regulation

A

Requires simultaneous transcription and translation of the mRNA - used to tightly regulate several bacterial AA biosynthetic operons (i.e. Trp and His operons)

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47
Q

Trp operon

A

Increased [Trp]intracell - Trp binds Trp repressor (TrpR) protein which suppresses transcription initiation (negative regulation)

Decreased [Trp]intracell - ribosome stalls at the Trp codons b/c it can’t find a charged trp-tRNA but the polymerase continues transcription

Leader region 2 base-pairs to region 3 which blocks formation of the terminator structure - transcript is elongated to the end of the operon and Trp biosynthetic enzymes are translated from the full-length mRNA

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48
Q

What part of the Trp operon contains an attenuator site?

A

The Trp RNA leader sequence contains an attenuator site which contains two adjacent Trp codons (in region 1)

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49
Q

Horizontal gene transfer

A

Moving genetic information between bacteria (transformation, conjugation, and transduction)

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50
Q

Bacillus antracis

Capsule

A

poly D-glutamic acid capsule instead of polysaccharide capsule

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51
Q

Temperate phage

A

A phage that can undergo both lysogenic and lytic replication

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52
Q

A mutation occurs in the TrpR gene preventing it from binding tryptophan. What would be the consequence of the mutation on regulation of the trp operon in a cell with plenty of tryptophan present?

A

TrpR would not bind to the trp operator and attenuation would prevent expression of the trp operon.

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53
Q

Amino acid based vs glycolytic based operons

A

AA - +/- regulation and attenuation

Glycolytic - only +/- regulation

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54
Q

Virulent phage

A

Only undergoes lytic replication cycle

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55
Q

Helper phage

A

Phage that provides an essential function for the lytic replication of a defective phage

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56
Q

Specialized transduction

A

occurs when the genome of a temperate phage is incorrectly excised from the host genome prior to initiation of the lytic cycle. In this case a small piece of host DNA adjacent to the phage genome integration site is excised along with the phage genome. The incorrectly-excised phage genome (with a bit of
host DNA attached to one end) is packaged into a phage capsid and transferred into any new host cell that the transducting phage infects

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57
Q

Why does heat shocking a bacterial colony indicate whether a lytic phage is present?

A

Becuase heat shocking the bacteria also heat shocks the phage, causing it to enter the lytic cycle of viral - causes the infected bacterial cells to lyse (evident upon viewing growth plate)

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58
Q

Most common disease presentation of Staphylococcus aureus

A

Skin/soft tissue

Gram (+) cocci in clusters

Facultative anaerobe

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59
Q

Most common disease presentation of Streptococcus pyogenes

A

Respiratory

Catalase (-)

aka Strep A

Gram (+) cocci in chains

Does not have catalase (differentiates from S. aureus)

Sensitive to Bacitracin disk

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60
Q

Most common disease presentation of Neisseria meningitidis

A

CNS

Gram (-) cocci

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61
Q

Most common disease presentation of Legionella pneumonphilia

A

Respiratory

Gram (-) Bacilli

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62
Q

Most common disease presentation of Streptococcus pneumonia

A

Respiratory

Gram (+) diplococci

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63
Q

Most common disease presentation of Streptococcus agalactiae

A

CNS

aka Strep B

Most commonly infantile meningitis - agalactia = without milk (infant does not feed)

Gram (+) cocci chains

Does not have catalase
Resistant to bacitracin
Hippurate (+)
cAMP test (+)

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64
Q

Most common disease presentation of Clostridium perfringen

A

GI and soft-tissue

Gram (+) Bacilli

Spore-forming (but rarely observed)

Non-motile

Encapsulated

Anaerobic

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65
Q

Most common disease presentation of Haemophilus influenzae

A

Respiratory

Gram (-) coccobacillus

Also CNS

Both catalase and oxidase (+)

Hib is most common and feared

Can colonize - if found in throat/nasopharynx

Disease state - found in CSF/blood/synovial joint

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66
Q

Most common disease presentation of Clostridium difficile

A

GI

Gram (+) Bacilli (pleomorphic)

Spore-forming (sub-terminal)
Obligate anaerobe
Motile
Ubiquitous in nature

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67
Q

Most common disease presentation of Campylobacter jejuni

A

GI

Gram (-) Bacilli - seagull ribbone shaped

Also CNS and skeletal/joint
Micro-auerophilic
Thermophilic
Oxidase and catalase (+)

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68
Q

Most common disease presentation of E. coli

A

GI and GU/Renal

Gram (-) Bacilli

Also Respiratory

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69
Q

Most common disease presentation of Salmonella enterica

A

GI

Gram (-) Bacilli

Also Skeletal/Joint

Transmission: improperly cooked food and animal contact

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70
Q

Most common disease presentation of Shigella spp.

A

GI

Gram (-) Bacilli

Also Skeletal/Joint

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71
Q

Most common disease presentation of Pseudomonas aeruginosa

A

Respiratory/GU/Renal/CV and skin/soft tissue

Gram (-) Bacilli

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72
Q

Most common disease presentation of Bacteroides fragilis

A

Skin/soft tissue

Gram (-) Bacilli

Associated with 80% of intra-abdominal infections

Polysaccharide capsule

Resistance to penicillin

Susceptible to metronidazole, carbapenems, piperacillin-tazobactam

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73
Q

Most common disease presentation of Fusobacterium spp.

A

Skin/soft tissue

Oppurtunistic - normal flora of oropharynx, GI, and female GU

Gram (-) rod

Clindamycin sensitive
Make significant amounts of butyric acid (differentiates it from other anaerobes)

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74
Q

What Gram (+) cocci can commonly become systemic?

A

S. aureus and Streptococcus pyogenes

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75
Q

What Gram (-) Cocci can become systemic?

A

Neisseria meningitidis

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76
Q

Mycobacterium tuberculosis

A

Acid fast (+) - does not Gram stain

Aerobic bacilli - thin branching filaments

First-line Tx: Isoniazid, rifampin, ehtambutol, and pyrazinamide

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77
Q

Mycoplasma pneumoniae

A

Atypical pneumonia - walking pneumonia

Community-acquired respiratory distress syndrome toxin (CARDS toxin) - ADP-ribosylating and vacuolating cytotoxin - swelling of airway and nuclear fragmentation of airway epithelia (contributes to ciliostasis)

Does not have peptidoglycan
Only bacteria thats lipid bilayer contains sterols

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78
Q

PPG backbone

A

Alternating units of N-acetrylglucosamine (NAG) and N-acetylemuramic acid (NAM)

Cross-linking between tetrapeptide side-chains form meshwork of PPG chains

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79
Q

What PPG monosaccharide is specific to bacteria?

A

N-acetylmuramic acid

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80
Q

PPG tetrapeptide side-chains

A

D-AA’s and diaminopimelic acid (m-DAP)

m-DAP is found only in Gram (-) bacteria

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81
Q

PPG Biosynthesis

A
  1. Glucoasamine is converted to MurNAc (NAM)
  2. A pentapeptide side-chains is added to NAM
  3. NAM-pentapeptide is attached to a bactoprenol carrier in the cytoplasmic membrane
  4. NAG is attached to NAM-pentapeptide forming subunit
  5. Some bacteria add additional AA’s to the side-chain at the 3rd position of the peptide to lengthen the cross-link
  6. The bactoprenol carrier translocates the PPG subunit outside of the cell. It is attached to the existing PPG backbone
  7. Side-chains are crosslinked by carboxypeptidase and transpeptidase
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82
Q

Enzymes that crosslink PPG

aka penicillin binding proteins (PBP)

A

Carboxypeptidase - breaks bond b/w fourth and fifth AA’s (D-ala/D-ala)

Transpeptidase - forms bond between the D-ala (fourth) and L-lys (Gram-positives) or m-DAP (Gram-negatives) in the third position of the AA side-chain

When PBPs are bound to beta-lactam abxs - no longer cross-link PPG - results in bacterial lysis due to osmotic pressures

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83
Q

Autolysins

Bacterial PPG

A

Degrade PPG - even if synthesis stops

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84
Q

PPG as a bacterial PAMP

A

Stimulates immune response through TLR-2 and nucleotide oligomerization domain-like receptors (NODs) leading to macrophage stimulation, cytokine production, and complement activation

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85
Q

LPS domains

A
  1. Lipid A domain - stimulates TLR-4
  2. Core region - maintains permeability of outer membrane
  3. O-antigen - shields bacterial surface proteins and prevents immune recognition

O-antigen can be used in serotyping

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86
Q

Maximal TLR-4 stimulationg by LPS

A

Requires:

  1. Disaccharide (GlcN-GlcN)
  2. Two phosphates
  3. Six fatty acyl chains (12-14 carbon lengths)
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87
Q

ABx resistance

A

Intrinsic resistance (lack ABx target or targest is inaccessible)

ABx target mutations

Horizontal gene transfer

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88
Q

Macrolide resistance

A

Methylation of 23S rRNA prevent ABx binding but does not interfere with ribosome function

Also confers resistance to other 50S subunit inhibitors

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89
Q

Beta-lactamases

A

Enzymes that hydrolyze the beta-lactam ring - prevents interaction with PBPs

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90
Q

Bacterial tetracycline resistance

A

Mg-chelated tetracyclines are exported via the tetA efflux pump

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91
Q

Kirby-Bauer Disk Diffusion Test

A
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92
Q

Epsilometer test (E-test)

A
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93
Q

D test

A

Inducible clindamycin resistance

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94
Q
A
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95
Q

A 67-year-old male was brought to the emergency department with severe dehydration from vomiting and watery diarrhea. Two days ago, he had eaten at a local restaurant and had a traditional Thanksgiving meal that included turkey, stuffing, potatoes, and green beans. A bacterium was identified as the causative agent, which was a Gram (-) bacillus. Which of the following bacteria is MOST LIKELY responsible for this infection?

A

Campylobacter jejuni

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96
Q

A patient has a pus-filled boil on his back that has been drained. A sample was taken for laboratory culture and a Gram (+) coccus was identified as the causative agent. This bacterium was found to be resistant to penicillin. Which of the follow bacteria is MOST LIKELY responsible for this infection?

A

Staphylococcus aureus

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97
Q

An 18-year-old male presents to the emergency department with a severe headache, light sensitivity, and a stiff neck. The physician in charge obtains spinal fluid and a Gram stain is performed. The results suggest the etiologic agent is Neisseria meningitidis. Which of the following Gram stain and cellular morphologies would the physician most likely have seen in the CSF?

A

Gram (-) cocci

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98
Q

A 24-year-old female presents with her third urinary tract infection of the year. Which of the following bacteria is MOST LIKELY causing her infections?

A

Escherichia coli

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99
Q

A 10-year-old boy is taken to his pediatrician for a sore throat, headache, and icky feeling. Several of his classmates have the same symptoms. His immunizations are up-to-date. A throat culture is performed and the next day, Gram (+) cocci are identified from bacterial colonies that are beta hemolytic. Which of the following bacteria fit this profile?

A

Streptococcus pyogenes

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100
Q

While traveling to Central America, a 43-year-old male began having gastrointestinal illness, which he describes as painful, bloody, but small volume in size and somewhat greenish in color. He frequented many outdoor markets to purchase fruits and vegetables for consumption. A bacterium was grown on specialized medium that was characterized by the laboratory as a being Gram (-) bacillus. Which of the following bacteria is MOST LIKELY the causative agent?

A

Shigella flexneri

101
Q

An 84-year-old female presents to the emergency department with shortness of breath. An x-ray of her chest showed patchy infiltrates and right lower lobe consolidation. A Gram stain of a sputum sample showed Gram (+) diplococci. Growth on blood agar plates showed alpha-hemolytic colonies that are sensitive to optochin. Which is the following is most likely the etiologic agent?

A

Streptococcus pneumoniae

102
Q

bullous impetigo

A

S. aureus

Mediated by exfoliative toxins A and B (ETA and ETB) - desmosome degradation leads to bullous appearance

103
Q

Anaerobic Gram (-) rods

A

Bacertoides and Fuscobacteria

Bacertoides - stimulated by bile salt

Fuscobacteria - makes a significant amount of butyric acid

104
Q

Why rapidly Tx Strep throat with Abx

A

B/c Strep. pyogenes can manifest as rheumatic fever and glomerulonephritis

Antibodies can react to cardiac tissue due to mimicry of S. pyogenes surface proteins

105
Q

Viridans group of Streptococci

A

Found commonly in the mouth as normal flora

Following dental procedure or trauma - bacteria can become systemic in blood stream and cause endocarditis

106
Q

Streptococcus pyogenes (GAS)

Suppurative vs. Non-suppurative

A

Suppurative:

Pharyngitis
Scarlet fever
Pyroderma
Erisepelas
Cellulitis
Necrotizing fasciitis
Toxic shock syndrome

Non-suppurative:

Rheumatic fever
Glomerulonephritis

107
Q

Legionella disease

A

Legionnaires’ disease (5-30% mortality)

Pontiac fever (Not fatal - cannot isolate organism)

108
Q

Exotoxin vs. enterotoxin

A

Enterotoxin - affects just the GI tract

Exotoxin - can exert its effects anywhere

109
Q

What are the only type of bacteria that produce spores?

A

Gram (+) bacilli

110
Q

Gram (+) bacillus that can be transmitted from mother to developing fetus

A

Listeria monocytogenes

Does not produce spores
Associated with deli meats (also raw produce and dairy) but can also reside in water suppplies

111
Q

Normal flora in poultry GI tract that becomes pathogenic upon transmission

A

Campylobacter jejuni

Transmission most likely from improperly cooked poultry
Can also reside in water sources

112
Q

What Gram (-) baccilus can cause reactive arthritis?

A

“Can’t see, can’t pee, can’t climb a tree”

Campylobacter jejuni

“Can’t see, can’t pee, can’t climb a tree” - usually by the time reactive arthritis sxs are manifested, bacteria is not present (reactive process)

113
Q

What bacteria and serotype is associated with Guillain-Barre syndrome?

A

Campylobacter jejuni O:19

Antigenic cross-reactivity between oligosaccharides in the bacterial capsule and glycosphingolipids on the surfaces of neural tissue: molecular mimicry

Targets Schwann cells

114
Q

Most common cause of UTI

A

E. coli

115
Q

Most common cause of bacteremia

A

E. coli

116
Q

Traveler’s diarrhea pathogen

A

ETEC - enterotoxigenic E. coli

117
Q

What is enteroinvasive E. coli?

A

EIEC causes dystentery

118
Q

What bacteria is associated with significant amounts of bright-red blood in stool?

A

Enterohemorrhagic E. coli - EHEC

Can also cause nephritis

Shigella also cauases dysentery

119
Q

Kdo sugars

A

Have only ever been ID’d in Gram (-) bacteria

Part of the core region of LPS

120
Q

Common pathgenic E. coli

Serotype

A

O157:H7

121
Q

What is the most exterior domain of LPS?

A

The O-antigen domain

O-antigen shields some of the bacterial surface proteins that can be recognized by the innate immune response (complement proteins)

122
Q

What is the innermost domain of LPS?

A

The lipid A domain

Lipid A is the portion of LPS that is responsible for activating the PRR, Toll-like receptor 4.

123
Q

Beta-Lactam target

A

The D-ala-D-ala bond

124
Q

LPS (lipid A) signaling through TLR-4

A
125
Q

Defensins

A

Cationic antimicrobial proteins (disrupt the membrane)

126
Q

Macrolide resistance

A

Methylation of 23S rRNA prevents ABx binding to 50S ribosomal subunit

Plasmid-encoded methylase

127
Q
A
128
Q

Quinolone Resistance

A

Mutations in structural genes for DNA gyrase and topoisomerase IV

Mutation in gyrA gene in DNA polymerase

129
Q

Mutation in rpoB gene in RNA polymerase

A

Rifampin ABx resistance

130
Q

Common multi-drug resistance origin

A

Bacterial efflux pumps - transcription can be activated by presence of ABx

131
Q

Cell wall synthesis inhibitors

A

Penicillins/cephalosporins/carbapenems (beta-lactams)

Vancomycin

Others: Dalbavancin/telavancin/teicoplanin/bacitracin/fosfomycin

132
Q

Penicillins

A

Penicillin G/Oxacillin/Ampicillin/Amoxicilllin/Piperacillin

Beta-lactams

133
Q

Cephalosporins

A

Cephalexin

Cefuroxime

Ceftriaxone

Cefepime

Ceftaroline

Beta-lactams

134
Q
A
135
Q

Carbapenems

A

Imipenem+cilastatin
Meropenem

Monobactams

Aztrenam

Beta-lactams

136
Q

Aminoglycosides

A

Protein synthesis inhibitors

i.e. Gentamicin

137
Q

Macrolides

A

Protein synthesis inhibitors

i.e. azithromycin, clarithromycin, and erythromycin

138
Q

Streptogramins

A

Protein synthesis inhibitors

i.e. quinupristin/dalfopristin

139
Q

Tetracyclines

A

Protein synthesis inhibitors

Doxycycline/Tigecycline/minocycline

Is a bacteriostatic - antagonizes beta-lactams efficacy

140
Q

Lincosamides

A

Protein synthesis inhibitors

i.e. clindamycin

141
Q

Fluoroquinolones

A

Inhibitors of nucleic acid synthesis

i.e. ciprofloxacin

142
Q

RNA polymerase inhibitors

A

Rifampin/fidaxomicin

143
Q

Metronidazole

A

Inhibitor of nucleic acid synthesis

144
Q

Folate synthesis inhibitors

A

Treimethoprim-sulfamethoxazole

145
Q

Beta-lactamase production in Gram (+) vs. Gram (-) bacteria

A

Gram (+) bacteria typically produce large amounts of beta-lactamase

Gram (-) bacteria produce smaller amounts - but enzyme is concentrated in space between the outer and inner membranes (periplasmic space)

146
Q

Extended spectrum penicillin

A

Pipercillin+tazobactam - Tx’s Gram +/-

IV only

Spectrum include Baceteroides fragilis and Gram (-) Pseudomonas

147
Q

Penicillin G

A

Administered only via parenteral routs (low pH hydrolyzes)

Long acting IM depot forms (pen benzathine or pen procaine) to treat syphillis (T. pallidum)

148
Q

Pen V

A

Drug of choice for strep throat

149
Q

Amino penicillins

A

Have a broader spectrum compared to natural pen (some Gram (-) - community acquired infection such as H. influenzae, M cattahalis, Shigella, Proteus mirabilis)

Amoxicillin/Ampicillin

150
Q

Drug of choice for Listeria monocytogenes

A

Ampicillin

IV formulation w or w/o sulbactam

151
Q

Distribution and elimination of penicillins

A

Dist - does ot penetrate CNS well

Elimination - most are eliminated by kidneys

Penicillins are actively transported into urine by kidneys (Probenecid competes with transporters and prolongs penicillin excretion)

152
Q

What bacteria expresses ABx resistance through expression of the mecA gene?

A

MRSA

Altered PBPs

Pneumococcus also develops ABx resistance through altered PBPs

153
Q

Penicillin resistance expressed by Gram (-) bacteria

A

Increased expression of beta-lactamases

Active efflux pumps

Altered porins/decreased permeability of membrane - i.e. Pseudomonas aeruginosa

154
Q

Cephalexin

A

PO route

Often used to Tx infection of skin/soft-tissue (not MRSA)

1st gen cephalosporin

Tx’s Gram (+) cocci and some Gram (-)’s like E. coli, K. pneumoniae, and P. mirabilis

155
Q

What first generation cephalosporin is commonly used for surgical prophylaxis?

A

Cefazolin

156
Q

Second gen cephalosporins

A

Have more activity against Gram (-) baccilli - including H. influenzae and M. catarrhalis (common URI microbes)

Cefcalor - PO

Cefoxitin - parenteral - covers anaerobes (including Bacteroides fragilis)

157
Q

Ceftriaxone

A

3rd gen cephalosporin

Administered parenterally

Can cross BBB to Tx bacterial meningitis

Also has some activity against Borrelia burgdorferi (Lyme disease)

Good coverage form many Gram (-) bacilli (some +/- cocci too)

Ceftriaxone is primarily eliminated via biliary route

158
Q

Cefdinir

A

3rd gen cephalosporin

Administered PO

Sometimes used for URIs

Good coverage form many Gram (-) bacilli (some +/- cocci too)

159
Q

What 3rd gen cephalosporins can cross the BBB?

A

Ceftriaxone and cefotaxime

Cefepime and ceftazidime are also capable of crossing BBB and used to Tx meningitis

160
Q

Fourth gen cephalosporin with broad ABx activity - including against P. aeruginosa

A

Cefepime (parenteral)

Used for bacteria that are resistant to 3rd gen cephalosporins

161
Q

Fifth gen cephalosporin used to Tx MRSA skin infections

A

Ceftaroline (parenteral)

Also used to Tx intraabdominal infections (combined with metronidazole); complicated UTIs, hospital and ventilator acquired pneumonia

162
Q

Cephalosporins with low risk of cross-reactivity with pen allergies

A

Cefdinir (third gen)

Cefpodoxime (third gen)

Cefuroxime (second gen)

163
Q

Cross reactivity between pen allergy and cephalosporins

A

~1% of Pts allergic to penicillins may also be allergic to cephalosporins

If Pt has had a mild reaction to pen (i.e. only rash) - go for it

If Pt has had anaphylaxis w/ pens - avoid cephalosporins

164
Q

What cephalosporins are used to Tx Enterococci?

A

No cephalosporins are active against Enterococci

165
Q

First line Tx for gonorrhea

A

IM ceftriaxone

166
Q

Bactericidal classes of ABx

A

Penicillins
Cephalosporins
Carbapenems
Mono-bactams
Vancomycin
Aminoglycosides

167
Q

Carbapenem

A

Gram +’s: Staph and Strep (not MRSA)

Gram -: Pseudomonas and Enterobacter

Anaerobes: B. fragilis

168
Q

Mono-bactam

A

Narrow spectrum ABx class - Used to Tx against Gram (-) bacilli infections (including Pseudomonas)

i.e. Aztreonam

Used for Pt’s allergic to other beta-lactams

Resistant to many beta-lactamases

Administered parenterally and via inhalation for Pts w/ CF

169
Q

Vancomycin

MOA

A

Inhibits cell wall synthesis by binding to the D-ala D-ala of PPG and blocking cross-linking of the cell wall (bactericidal)

Usually administered via paerenteral route, but used PO to Tx Pts w/ C. diff.

Narrow spectrum - only Gram (+) bacteria - MRSA/C. diff.

Resistance is increasing among Enterococci (VRE) and S. aureus

170
Q

Adverse effects of Tx w/ vancomycin

A

Nephrotoxicity
Ototoxicity
Red man syndrome - rx’n that occurs due to histamine release when drug is administered too quickly - flushed, tachycardic, and hypotensive

171
Q

Polymyxin B

A

Cationic detergent that targets Gram (-) bacteria by poking holes in cell walls (used topically - skin and eye - due to risk of nephrotoxicity)

172
Q

Bacitracin

A

Inhibits cell wall synthesis by preventing transfer of mucopeptides to the growing cell wall - targets Gram (+) bacteria

Ingredient in triple antibiotic oinment

173
Q

Mupirocin

A

Inhibits isoleucyl-tRNA synthetase - prevents addition of isoleucine to growing peptides

Only Tx Staph and Strep infection (including MRSA and impetigo)

No cross-resistance w/ other ABx’s

174
Q

Aminoglycosides

MOA

A

Diffuse through bacterial porins of the outer bacterial membrane and are transported through the inner membrane by an O2-dependent active transporter. Entering the cytosol, aminoglycosides bind irreversibly to the 30S subunit:

  1. misreading of mRNA
  2. Production of aberrant proteins
  3. Blockade of protein synthesis

Bactericidal

175
Q

What blocks the transport of aminoglycosides?

A

Anaerobic conditions
Divalent cations
Acidic pH

Therefore - ineffective against anaerobes or bacteria in anaerobic conditions

176
Q

Spectrum of aminoglycosides

A

Treat serious Gram (-) infections - Pseudomonas and Enterobacteria

Often combine w/ beta-lactams to Tx sepsis, endocarditis, or ventilator-assisted pneumonia

177
Q

Adverse effect of aminoglycosides

A

Coclear toxicity
Vestibular toxicity
Nephrotoxicity

Neuromuscular blockade - inhibits release of ACh and can reduce sensitivity to the neurotransmitter (exacerbates myasthenia gravis)

178
Q

Tetracycline MOA

A

Bind to 30S subunit and block incoming aminoacyl-tRNA from entering the ribosomal A site

Bacteriostatic (unlike aminoglycosides which are bacteriocidal)

179
Q

Spectrum of tetracycline therapy

A

Broad spectrum ABx against Gram (+)/(-) bacterial and some atypical organisms and anaerobes:

Rickettsia (Typhus and Rocky Mountain Spotted fever), Mcyoplasma, Chlamydia, spirochetes (Borrelia burgdoferi, and Treponema pallidum), Erlichia, Vibrio cholerae, Brucell, Malaria, H. pylori

Doxycycline is also used to Tx community acquired MRSA

180
Q

What interferes w/ tetracycline absorption

A

Di- and trivalent cations - form insoluble chelates

181
Q

Chloramphenicol

A

Binds bacterial 50S ribosomal subunits and inhibits peptidyl transferase

Best known for causing gray baby syndrome - children < 12 mo. lack sufficient levels of glucuronyl transferase to effectively glucoronidate and metabolize the drug

Also risk of aplastic anemia

182
Q

Macrolides

MOA

A

Bind to the 50S subunit and block protein synthesis by preventing the translocation of tRNA from the A site to the P site

These drugs are usually bacteriostatic

183
Q

Erythromycin

A

Spectrum similar to Pen G (Gram (+) cocci)

Poor access to CNS

Eliminated in the bile and causes GI upset - sometimes used to promote GI motility due to its action at the motilin receptor

Not widely used

184
Q

Azithromycin

A

Wider spectrum compared to erythromycin - covering some Gram (-)’s - H. influenzae and Mycobacterium avium

Clarithromycin has similar coverage

185
Q

Fidaxomicin

A

Not absorbed and remains in GI tract - possible Tx for C. diff

Bactericidal macrolide (newest one)

186
Q

Macrolide ABx resistance

A
  1. 50S binding site is altered (methylation of the ribosome)
  2. Mutations at the 50S ribosome - affects Gram (+) cocci
  3. Actively effluxed (group A Strep or Strep pnuemoniae)
  4. Hydrolyzed (i.e. esterase produced by Enterobacter)
187
Q

Adverse effects of Tx w/ macrolides

A

Prolongation of QT interval - can lead to death due to ventricular arrhythmias

Eryhtromycin and clarithromycin inhibit CYP450 3A4 enzymes (azithromycin does not)

GI upset and cholestatic hepatitis (primarily erythromycin)

188
Q

Clindamycin

MOA

A

Lincosamide - similar MOA to macrolides

Binds 50S subunit and inhibits protein synthesis by interfering w/ bacterial protein synthesis by blocking translocation reactions

Bacteriostatic or bactericidal depending upon concentration, infection site, and organism

189
Q

Spectrum and use of clindamycin

A

Includes Gram (+) organisms - including community acquired MRSA and anaerobes (especially Bacteroides fragilis)

Adverse effects: C. diff and pseudomembranous colitis

190
Q

Linezolid

MOA and bioavailability

A

Inhibits the formation of 70S initation complex by binding to the 23S RNA of the 50S ribosomal subunit - no cross-resistance with other ABxs

100% PO bioavailability

Bacteriostatic

191
Q
A
192
Q
A
193
Q
A
194
Q

Lindezolid

Spectrum

A

Reserved to Tx infections caused by multi-drug resistant VRE, MRSA, and resistant pneumococci (Gram (+) bacteria)

195
Q

Lindezolid

Adverse effects

A

Myelosuppresion - have to monitor weekly for thrombocytopenia

If used for >2 wks - inhibits monamine oxidase - used w/ other drugs that impact monamine/serotonin transmission can cause hypertensive crisis and/or serotonin syndrome

Optic neuritis and peripheral neuropathy after prolonged usage (<28 days) due to mitochondrial dysfunction

196
Q

Lefamulin

MOA

A

Inhibits protein synthesis by binding to the 50S risbosomes in multiple locations

Only used to Tx community acquired pneumonia caused by S pneoniae, MSSA, H. influenzae, Lgionell, Mycoplasma pneumoniae, or C. pneumoniae

Bactericidal

197
Q

Adverse effects of lefamulin

A

Prolongs QT interval

May cause fetal harm

198
Q

Sulfamethoxazole

MOA

A

Inhibits bacterial folate synthesis by competing with para-aminobenzoic acid (PABA) and blocking the actions of dihydropteroate synthase - prevents conversion of dihydropteridine to dihydropteroid acid (critical first step in folate production)

Used alone - bacteriostatic

199
Q

Contraindications of Tx w/ sulfonamides

A

Warfarin (any highly protein-bound drug therapy)

Newborns or breastfeeding mothers - due to risk of bilirubin displacement, leading to hyperbilirubinemia and kernicterus

Pt’s w/ G6PD deficiency - can lead to hemolytic anemia

Acidic urine or dehydration - excreted through kidneys - may precipitate sulfa drugs and cause obstruction

200
Q

Bacterial resistance to sulfonamides

A

They develop resistance by overproducing PABA or via plasmid-encoded dihydropterate synthetase enzyme that has reduced affinity for sulfonamides

201
Q

Sulfonamide used to Tx inflammatory bowel disease

A

Sulfasalazine - broken down by gut flor into sulfapyridine and mesalamine - have anti-inflammatory properties

202
Q

Sulfonamide used to Tx burn Pts and prevent pseudomonal infections

A

Silver sulfadiazine

203
Q

Trimethoprim

MOA

A

Inhibits dihydrofolate reductase (final step in bacterial folate synthesis)

Used alone - bacteriostatic

Sulfamethoxazole-Trimethprim combo - bactericidal

204
Q

Flouroquinolone uses

A

Gram (-): E. coli, Salmonella, Shigella, Klebsiella, Moreaxella, Pseudomonas aeruginoas, Neisseria, Campylobacter, Haemophilus, Enterobacter

Gram (+): Staphylococcus, Streptococcus pnumoniae (pen-resistant strains)

Atypicals: Chlamydia, Mycoplasma, Legionella (causes of pneumonia)

Others: Brucella, Bacillus antracis, Mycobacterium (TB)

205
Q

Adverse effects of fluoroquinolones

A

QT interval prolongation

CNS effects: hallucinations, delirium, confusion, and seizures (especially among older adults) - fluoroquinolones interfere with GABA binding

Peripheral neuropathy

Muscle/tendon problems

Photosensitivity/rashes

Aortic aneurysm/rupture

206
Q

Ciprofloxacin

A

Fluoroquinolone used for UTIs and infections caused by Gram (-) bacteria

207
Q

Levofloxacin and moxifloxacin

A

Referred to as “respiratory fluoroquinolones” - effectve against pen-resistant Streptococcus pnumoniae

208
Q

Delafloxacin

A

Newer fluoroquinolone used for serious skin infections: broad-spectrum activity (including MRSA)

209
Q

Metronidazole

MOA

A

Disrupts bacterial and protozoal DNA synthesis by forming free radicals - causing DNA breaks

in anaerobic organisms - pyruvate-ferredoxin oxidoreductase generate ATP via oxidative decarboxylation of pyruvate. In this process, ferredoxin is reduced. Reduced ferredoxin gives an electron to metronidazole and transforms the drug into a free radical

Effective against anaerobic bacteria and certain parasites:

C. diff, H. pylori, Bacteroides fragilis, P. acnes, amebiasis, Gardnerella vaginalis, Giardia, and Trimononas vaginalis

210
Q

Metronidazole

Adverse effects

A

Metallic taste
Peripheral neuropathy
Seizures (rare)

Avoid alcohol - potential for disulfiram-like reaction

Not reccommended during pregnancy

Pancreatitis

Hemolysis - esp. in Pt’s w/ G6PD deficiency

Leukopenia

211
Q

First-line Tx against TB

A
212
Q

Second-line Tx against TB

A
213
Q

Rifampin

MOA

A

Inhibits DNA-dependent RNA polymerase (in TB - encoded for in the rpoB gene) - prevents RNA synthesis and leads to bacterial death - supresses initiation of RNA chain formation

Inhibits growth of most Gram (+) and Gram (-) bacteria

Able to cross into the CNS and inside macrophages

Metabolized in liver and is a potent CYP450 inducer

214
Q

Rifampin vs. Rifaximin

A

Rifampin is absorbed in GI tract

Rifaximin is not - used to Tx GI infection (i.e. E. coli) and small bowel bacterial overgrowth

Both inhibit DNA-dependent RNA polyermase

215
Q

Which of the following is only useful for treating gram positive organisms and anaerobes?

A. Cephalexin
B. Ceftazidime
C. Clindamycin
D. Clarithromycin

A

C. Clindamycin

Clindamycin - lincosamide - binds to the 23S rRNA of the 50S subunit

216
Q

Which drug that is used to treat MRSA, is 100% bioavailable in both tablet and intravenous formulations, but is limited by myelosuppression if taken for more than 2 weeks?

A. Clindamycin
B. Linezolid
C. Vancomycin
D. Doxycycline

A

B. Linezolid

Member of the oxazolidinone - binds to the 23S rRNA of the 50S subunit

217
Q

Which of the following is usually bacteriostatic?

A. Azithromycin
B. Amoxicillin
C. Ampicillin
D. Aztreonam

A

A. Azithromycin

218
Q

Which of the following binds to 30S ribosomal subunits and causes misreading of the genetic code, premature STOP codons, and disruption of polysomes – resulting in aberrant proteins being synthesized?

A. Tetracycline
B. Azithromycin
C. Gentamicin
D. Mupriocin

A

C. Gentamicin

Describes MOA for aminoglycosides

219
Q

Which of the following generations of cephalosporins is the MOST effective at treating gram positive cocci skin infections and is used for surgical prophylaxis?

A

First generation cephaloporins

220
Q

Nafcillin

A

Beta-lactamase resistant beta-lactam

221
Q

Aztreonam

Spectrum

A

Only Tx Gram (-) bacteria - similar spectrum to aminoglycosides but w/o the renal and ototoxicity

Mono-bactam that is resistant to beta-lactamases produced by Gram (-) bacteria

222
Q

Protein synthesis inhibitor ABx’s

A

Mupirocin
Aminoglycosides
Tetracyclines
Chloramphenicol
Macrolides
Clindamycin
Linezolid

223
Q

Tetracycline used to Tx community-acquired MRSA

A

Doxycycline

224
Q

ABx that has the highest incidence of causing a C. difficile infection

A

Clindamycin (up to 20%)

225
Q

Trimethorpim

MOA

A

Inhibits dihydrofolate reductase - not sulfa ABx but an anti-metabolite

Bacteristatic when used alon

226
Q

List common fluoroquinolones

A

Ciprofloxacin
Levofloxacin
Moxifloxacin

227
Q

Ciprofloxacin

A

Commonly used to Tx UTIs and infections caused by Gram (-) bacteria

Targets bacterial DNA gyrase

228
Q

Most fluoroquinolones are excreted by the kidneys, which is metabolized primarily by the liver?

A

Moxifloxacin

229
Q

Newish FQ that has broad-spectrum activity and used often used in serious skin/soft-tissue infections

A

Delafloxacin

230
Q

Metronidazole spectrum of activity

A

Effective against anaerobic bacteria and certain parasites

C. diif., H. pylori, Bacteroides fragilis, P. acnes, amebiasis, Garnerella vaginalis, Giardia, and Trichomonas vaginalis

231
Q

Isoniazid

MOA

A

INH is a prodrug activated by bacterial enzymes - inhibits the production of mycolic acid (essential part of the mycobacterial cell wall)

Converted by katG (a catalase-peroxidase)

INH interacts w/ mycobacterial NAD and NADP to produce adducts - one adduct iinhibits activities of enoyl acyl carrier protein reductase (InhA) and ketoacyl acyl carrier protein (KasA)

Inhibition of these enzymes** blocks synthesis of mycolic acid**

Another adduct inhibits mycobacterial dihydrofolate reductase

Overdose: INH overdose can lead to severe seizures and metabolic acidosis, often requiring aggressive treatment.

232
Q

Daptomycin

MOA

A

Cyclic lipopeptide that works by disrupting bacterial cell membranes

Effective against Gram (+) bacteria - including MRSA and Enterococcus

To Fx, daptomycin binds to Ca ions, then attaches to the bacterial membrane, causing depolarization

Only given IV

Rhadomyolysis - important side-effect

233
Q

Colistin

A

Powerful but toxic ABx given parenterally to Tx serious Gram (-) infections (i.e. E. coli, Klebsiella, Pseudomonas that have been resistant to other Tx)

Cationic detergent that pokes holes in bacterial membranes

234
Q

Nitrofurantoin

A

Protein and DNA synthesis inhibitors

Cleared by the kidneys

Impact w/ Pts with G6PD deficiency

235
Q

Standard Tx and duration of treatment for active TB infection:

A
236
Q

Streptomycin

A

Inhibits protein synthesis by targeting the 30S ribosomal subunit

237
Q

What is the reason that sulfonamides are not administered to newborns?

A

Kernicterus

238
Q

Which of the following inhibits DNA gyrase?

A. Rifampin
B. Ciprofloxacin
C. Metronidazole
D. Isoniazid

A

B. Ciproloxacin

239
Q

Which of the following drugs is transformed into a free radical that damages DNA and can be used to treat both bacterial and parasitic infections?

A. Nitrofurantoin
B. Metronidazole
C. Rifampin
D. Ethambutol

A

B. Metronidazole

240
Q

What medication is a prodrug that must be first converted into a free radical to become effeective?

A

Isoniazid

First-line Tx for TB

241
Q

What vitamin is given to prevent peripheral neuropathy in Pts taking isoniazid?

A

B6

242
Q

Which of the following inhibits bacterial dihydrofolate reductase?

A. Nitrofurantoin
B. Vancomycin
C. Ciprofloxacin
D. Trimethoprim

A

D. Trimethoprim

243
Q

Which of the following can cause vision problems where visual acuity can be lost and/or it becomes impossible to distinguish between red & green colors?

A. Rifampin
B. Isoniazid
C. Pyrazinamide
D. Ethambutol

A

Ethambutol

244
Q

What bacterial metabolic component does sulfamethoxazole competitively compete with?

A

Para-aminobenzoic acid (PABA)

245
Q

Rifampin effect on CYP450

A

Rifampin is a potent CYP450 inducer

246
Q
A
247
Q

Vancomycin resistance

A

Plasmid mediated and resistance transfers when bacteria also co-express conjugation genes

Vancomycin should be reserved for MRSA, enterococcal endocarditis

248
Q

Oxazolidinones

A

Protein synthesis inhibitors

i.e. linezolid

MI Immuno/Heme (24 decks)

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