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
2
Q
What genera of bacteria does not contain peptidoglycan?
A
Mycoplasma
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)
4
Q
Endotoxin
A
Lipopolysaccharide (LPS) exhibited on the outer leaflet of Gram negative bacteria
Stimulates the innate immune response
5
Q
Gram-negative
A
6
Q
Glycocalyx
A
“slime layer”
Loose layer of polysaccharides the surround bacteria - helps bacteria attach/adhere to surfaces and aids in biofilm formation
7
Q
K antigen
A
Capsular polysaccharide
Capsule - outside of cell wall
Anti-phagocytic
8
Q
Pili/fimbrae
A
Filamentous appendages that help bacteria sense and attach to their environment (including host cells)
9
Q
H antigen
A
Flagella
10
Q
What propels bacteria during chemotaxis?
A
Rotation of their flagella
11
Q
Plasmids
A
Small, circular, extrachromosomal DNA - often contain virulence genes
12
Q
Bacterial ribosomes
Sed rate
A
70s
(50s+30s)
13
Q
Spores
A
Found in Gram-positive rods (clostridium and bacillus)
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)
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.)
16
Q
A
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
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
19
Q
Fastidious bacteria
A
Can not grow without specific nutrient supplementation on aritificial media
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
21
Q
Primary secretion system used by Gram-positive bacteria
A
The general secretory pathway
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.
23
Q
O-antigen
A
Lipopolysaccharide (LPS)
24
Q
What is the only bacteria that utilizes sterols?
A
Mycoplasma
25
Bacterial chromosome
1-5 million bp (small)
Single, circular, haploid chromosome that lacks introns
26
Lipid A
Lipid component of endotoxin responsible for the toxicity of gram-negative bacteria
Most interior portion of LPS
27
Regulons
Functional groups consisting of several operons - the promoters driving these different operon are coordinately regulated (turned on and off at the same time)
28
Reverse mutations
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
29
Prototrophic bacteria
Baceria that can synthesize all essential nutrients
30
Conditional mutations
Mutations that produce proteins that are functional only under specific environmental conditions
31
Auxotrophs
Mutant bacteria that have lost the ability to synthesize all essential nutrients - must obtain nutrients or precursors from their environment
32
Bacterial single strand repair
Excision repair
Photoactivation
33
Bacterial double strand repair
**Mismatch repair** (recombinatorial repair)
**Error-prone repair** - emergency system that only bacteria use (damaged DNA is replaced with random sequences)
34
Bacterial recombination
35
Positive regulation of operon
System that directly increases RNA polymerase affinity for a particular promoter
Activator proteins turn this system on
36
Negative regulation of operon
System that directly decreases RNA polymerase affinity for a particular promoter
Repressor proteins turn this system off
37
Cis- acting elements
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
38
During which phase of growth are bacteria most likely to begin forming spores
The stationary phase (nutrients/resources are becoming scare, there is also accumulation metabolic by-products/waste)
39
Trans-acting factors
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
40
What cis-acting element is composed of RNA sequences
Terminators are RNA sequences (encoded in the DNA) that tell the RNA polymerase to stop at the end of a gene or operon
41
Activator vs. inducer
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
42
In bacteria, what factors recognize cis-DNA at the Pribnow box?
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.
43
What determines bacterial transcription frequency?
Ultimately determine by how tightly RNA polymerase is bound (holoenzyme binds to the promoter DNA)
RNAP/DNA affinity:
Increase - activator binding
Decreased - repressor binding
44
lac repressor
**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
45
Catabolite activator protein (CAP)
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
## Footnote
The level of cAMP is inversely regulated by glucose.
High glucose = low cAMP
Low glucose = high cAMP
46
Attenuation
##Footnote
Operan gene regulation
Requires simultaneous transcription and translation of the mRNA - used to tightly regulate several bacterial AA biosynthetic operons (i.e. Trp and His operons)
47
Trp operon
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
48
What part of the Trp operon contains an attenuator site?
The **Trp RNA leader sequence** contains an attenuator site which contains two adjacent Trp codons (in region 1)
49
Horizontal gene transfer
Moving genetic information between bacteria (transformation, conjugation, and transduction)
50
Bacillus antracis
| Capsule
poly D-glutamic acid capsule instead of polysaccharide capsule
51
Temperate phage
A phage that can undergo both lysogenic and lytic replication
52
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?
TrpR would not bind to the trp operator and attenuation would prevent expression of the trp operon.
53
Amino acid based vs glycolytic based operons
AA - +/- regulation and attenuation
Glycolytic - only +/- regulation
54
Virulent phage
Only undergoes lytic replication cycle
55
Helper phage
Phage that provides an essential function for the lytic replication of a defective phage
56
Specialized transduction
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
57
Why does heat shocking a bacterial colony indicate whether a lytic phage is present?
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)
58
Most common disease presentation of *Staphylococcus aureus*
Skin/soft tissue
| Gram (+) cocci in clusters
## Footnote
Facultative anaerobe
59
Most common disease presentation of *Streptococcus pyogenes*
Respiratory
Catalase (-)
aka Strep A
| Gram (+) cocci in chains
## Footnote
Does not have catalase (differentiates from S. aureus)
Sensitive to Bacitracin disk
60
Most common disease presentation of *Neisseria meningitidis*
CNS
| Gram (-) cocci
61
Most common disease presentation of *Legionella pneumonphilia*
Respiratory
| Gram (-) Bacilli
62
Most common disease presentation of *Streptococcus pneumonia*
Respiratory
| Gram (+) diplococci
63
Most common disease presentation of *Streptococcus agalactiae*
CNS
aka Strep B
Most commonly infantile meningitis - agalactia = without milk (infant does not feed)
| Gram (+) cocci chains
## Footnote
Does not have catalase
Resistant to bacitracin
Hippurate (+)
cAMP test (+)
64
Most common disease presentation of *Clostridium perfringen*
GI and soft-tissue
| Gram (+) Bacilli
## Footnote
Spore-forming (but rarely observed)
Non-motile
Encapsulated
Anaerobic
65
Most common disease presentation of *Haemophilus influenzae*
Respiratory
| Gram (-) coccobacillus
## Footnote
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
66
Most common disease presentation of *Clostridium difficile*
GI
| Gram (+) Bacilli (pleomorphic)
## Footnote
Spore-forming (sub-terminal)
Obligate anaerobe
Motile
Ubiquitous in nature
67
Most common disease presentation of *Campylobacter jejuni*
GI
| Gram (-) Bacilli - seagull ribbone shaped
## Footnote
Also CNS and skeletal/joint
Micro-auerophilic
Thermophilic
Oxidase and catalase (+)
68
Most common disease presentation of *E. coli*
GI and GU/Renal
| Gram (-) Bacilli
## Footnote
Also Respiratory
69
Most common disease presentation of *Salmonella enterica*
GI
| Gram (-) Bacilli
## Footnote
Also Skeletal/Joint
Transmission: improperly cooked food and animal contact
70
Most common disease presentation of *Shigella spp.*
GI
| Gram (-) Bacilli
## Footnote
Also Skeletal/Joint
71
Most common disease presentation of *Pseudomonas aeruginosa*
Respiratory/GU/Renal/CV and skin/soft tissue
| Gram (-) Bacilli
72
Most common disease presentation of *Bacteroides fragilis*
Skin/soft tissue
| Gram (-) Bacilli
## Footnote
Associated with 80% of intra-abdominal infections
Polysaccharide capsule
Resistance to penicillin
Susceptible to metronidazole, carbapenems, piperacillin-tazobactam
73
Most common disease presentation of *Fusobacterium spp.*
Skin/soft tissue
Oppurtunistic - normal flora of oropharynx, GI, and female GU
| Gram (-) rod
## Footnote
Clindamycin sensitive
Make significant amounts of butyric acid (differentiates it from other anaerobes)
74
What Gram (+) cocci can commonly become systemic?
*S. aureus* and *Streptococcus pyogenes*
75
What Gram (-) Cocci can become systemic?
*Neisseria meningitidis*
76
*Mycobacterium tuberculosis*
Acid fast (+) - does not Gram stain
Aerobic bacilli - thin branching filaments
First-line Tx: Isoniazid, rifampin, ehtambutol, and pyrazinamide
77
*Mycoplasma pneumoniae*
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)
## Footnote
Does not have peptidoglycan
Only bacteria thats lipid bilayer contains sterols
78
PPG backbone
Alternating units of N-acetrylglucosamine (NAG) and N-acetylemuramic acid (NAM)
Cross-linking between tetrapeptide side-chains form meshwork of PPG chains
79
What PPG monosaccharide is specific to bacteria?
N-acetylmuramic acid
80
PPG tetrapeptide side-chains
D-AA's and diaminopimelic acid (m-DAP)
## Footnote
m-DAP is found only in Gram (-) bacteria
81
PPG Biosynthesis
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
82
Enzymes that crosslink PPG
| aka penicillin binding proteins (PBP)
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
## Footnote
When PBPs are bound to beta-lactam abxs - no longer cross-link PPG - results in bacterial lysis due to osmotic pressures
83
Autolysins
## Footnote
Bacterial PPG
Degrade PPG - even if synthesis stops
84
PPG as a bacterial PAMP
Stimulates immune response through **TLR-2** and **nucleotide oligomerization domain-like receptors (NODs)** leading to macrophage stimulation, cytokine production, and complement activation
85
LPS domains
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
## Footnote
O-antigen can be used in serotyping
86
Maximal TLR-4 stimulationg by LPS
Requires:
1. Disaccharide (GlcN-GlcN)
2. Two phosphates
3. Six fatty acyl chains (12-14 carbon lengths)
87
ABx resistance
Intrinsic resistance (lack ABx target or targest is inaccessible)
ABx target mutations
Horizontal gene transfer
88
Macrolide resistance
Methylation of 23S rRNA prevent ABx binding but does not interfere with ribosome function
Also confers resistance to other 50S subunit inhibitors
89
Beta-lactamases
Enzymes that hydrolyze the beta-lactam ring - prevents interaction with PBPs
90
Bacterial tetracycline resistance
Mg-chelated tetracyclines are exported via the tetA efflux pump
91
Kirby-Bauer Disk Diffusion Test
92
Epsilometer test (E-test)
93
D test
Inducible clindamycin resistance
94
95
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?
*Campylobacter jejuni*
96
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?
*Staphylococcus aureus*
97
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?
Gram (-) cocci
98
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?
*Escherichia coli*
99
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?
*Streptococcus pyogenes*
100
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?
*Shigella flexneri*
101
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?
*Streptococcus pneumoniae*
102
bullous impetigo
*S. aureus*
Mediated by exfoliative **toxins A** and **B** (ETA and ETB) - desmosome degradation leads to bullous appearance
103
Anaerobic Gram (-) rods
*Bacertoides* and *Fuscobacteria*
## Footnote
*Bacertoides* - stimulated by bile salt
*Fuscobacteria* - makes a significant amount of butyric acid
104
Why rapidly Tx Strep throat with Abx
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
Viridans group of *Streptococci*
Found commonly in the mouth as normal flora
Following dental procedure or trauma - bacteria can become systemic in blood stream and cause endocarditis
106
Streptococcus pyogenes (GAS)
| Suppurative vs. Non-suppurative
Suppurative:
Pharyngitis
Scarlet fever
Pyroderma
Erisepelas
Cellulitis
Necrotizing fasciitis
Toxic shock syndrome
Non-suppurative:
Rheumatic fever
Glomerulonephritis
107
Legionella disease
Legionnaires' disease (5-30% mortality)
Pontiac fever (Not fatal - cannot isolate organism)
108
Exotoxin vs. enterotoxin
Enterotoxin - affects just the GI tract
Exotoxin - can exert its effects anywhere
109
What are the only type of bacteria that produce spores?
Gram (+) bacilli
110
Gram (+) bacillus that can be transmitted from mother to developing fetus
*Listeria monocytogenes*
## Footnote
Does not produce spores
Associated with deli meats (also raw produce and dairy) but can also reside in water suppplies
111
Normal flora in poultry GI tract that becomes pathogenic upon transmission
*Campylobacter jejuni*
## Footnote
Transmission most likely from improperly cooked poultry
Can also reside in water sources
112
What Gram (-) baccilus can cause reactive arthritis?
"Can't see, can't pee, can't climb a tree"
*Campylobacter jejuni*
## Footnote
"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
What bacteria and serotype is associated with Guillain-Barre syndrome?
*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
Most common cause of UTI
*E. coli*
115
Most common cause of bacteremia
*E. coli*
116
Traveler's diarrhea pathogen
ETEC - enterotoxigenic *E. coli*
117
What is enteroinvasive E. coli?
EIEC causes dystentery
118
What bacteria is associated with significant amounts of bright-red blood in stool?
Enterohemorrhagic E. coli - EHEC
Can also cause nephritis
## Footnote
Shigella also cauases dysentery
119
Kdo sugars
Have only ever been ID'd in Gram (-) bacteria
Part of the core region of LPS
120
Common pathgenic *E. coli*
| Serotype
O157:H7
121
What is the most exterior domain of LPS?
The O-antigen domain
## Footnote
O-antigen shields some of the bacterial surface proteins that can be recognized by the innate immune response (complement proteins)
122
What is the innermost domain of LPS?
The lipid A domain
## Footnote
Lipid A is the portion of LPS that is responsible for activating the PRR, Toll-like receptor 4.
123
Beta-Lactam target
The D-ala-D-ala bond
124
LPS (lipid A) signaling through TLR-4
125
Defensins
Cationic antimicrobial proteins (disrupt the membrane)
126
Macrolide resistance
Methylation of 23S rRNA prevents ABx binding to 50S ribosomal subunit
## Footnote
Plasmid-encoded methylase
127
128
Quinolone Resistance
Mutations in structural genes for DNA gyrase and topoisomerase IV
## Footnote
Mutation in gyrA gene in DNA polymerase
129
Mutation in rpoB gene in RNA polymerase
Rifampin ABx resistance
130
Common multi-drug resistance origin
Bacterial efflux pumps - transcription can be activated by presence of ABx
131
Cell wall synthesis inhibitors
Penicillins/cephalosporins/carbapenems (beta-lactams)
Vancomycin
## Footnote
Others: Dalbavancin/telavancin/teicoplanin/bacitracin/fosfomycin
132
Penicillins
Penicillin G/Oxacillin/Ampicillin/Amoxicilllin/Piperacillin
## Footnote
Beta-lactams
133
Cephalosporins
Cephalexin
Cefuroxime
Ceftriaxone
Cefepime
Ceftaroline
## Footnote
Beta-lactams
134
135
Carbapenems
Imipenem+cilastatin
Meropenem
Monobactams
Aztrenam
## Footnote
Beta-lactams
136
Aminoglycosides
Protein synthesis inhibitors
i.e. **Gentamicin**
137
Macrolides
Protein synthesis inhibitors
i.e. azithromycin, clarithromycin, and erythromycin
138
Streptogramins
Protein synthesis inhibitors
i.e. quinupristin/dalfopristin
139
Tetracyclines
Protein synthesis inhibitors
Doxycycline/Tigecycline/minocycline
## Footnote
Is a bacteriostatic - antagonizes beta-lactams efficacy
140
Lincosamides
Protein synthesis inhibitors
i.e. clindamycin
141
Fluoroquinolones
Inhibitors of nucleic acid synthesis
i.e. ciprofloxacin
142
RNA polymerase inhibitors
Rifampin/fidaxomicin
143
Metronidazole
Inhibitor of nucleic acid synthesis
144
Folate synthesis inhibitors
Treimethoprim-sulfamethoxazole
145
Beta-lactamase production in Gram (+) vs. Gram (-) bacteria
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
Extended spectrum penicillin
Pipercillin+tazobactam - **Tx's Gram +/-**
IV only
## Footnote
Spectrum include *Baceteroides fragilis* and Gram (-) *Pseudomonas*
147
Penicillin G
Administered only via parenteral routs (low pH hydrolyzes)
Long acting IM depot forms (pen benzathine or pen procaine) to treat syphillis (*T. pallidum*)
148
Pen V
Drug of choice for strep throat
149
Amino penicillins
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
Drug of choice for *Listeria monocytogenes*
Ampicillin
## Footnote
IV formulation w or w/o sulbactam
151
Distribution and elimination of penicillins
Dist - does ot penetrate CNS well
Elimination - most are eliminated by kidneys
## Footnote
Penicillins are actively transported into urine by kidneys (**Probenecid** competes with transporters and prolongs penicillin excretion)
152
What bacteria expresses ABx resistance through expression of the mecA gene?
MRSA
## Footnote
Altered PBPs
Pneumococcus also develops ABx resistance through altered PBPs
153
Penicillin resistance expressed by Gram (-) bacteria
**Increased expression of beta-lactamases**
Active efflux pumps
Altered porins/decreased permeability of membrane - i.e. ***Pseudomonas aeruginosa***
154
Cephalexin
PO route
Often used to Tx infection of skin/soft-tissue (not MRSA)
| 1st gen cephalosporin
## Footnote
Tx's Gram (+) cocci and some Gram (-)'s like *E. coli, K. pneumoniae, and P. mirabilis*
155
What first generation cephalosporin is commonly used for surgical prophylaxis?
Cefazolin
156
Second gen cephalosporins
Have more activity against Gram (-) baccilli - including ***H. influenzae*** and ***M. catarrhalis*** (common URI microbes)
## Footnote
Cefcalor - PO
Cefoxitin - parenteral - covers anaerobes (including ***Bacteroides fragilis***)
157
Ceftriaxone
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)
## Footnote
**Ceftriaxone is primarily eliminated via biliary route**
158
Cefdinir
3rd gen cephalosporin
Administered PO
Sometimes used for URIs
## Footnote
Good coverage form many Gram (-) bacilli (some +/- cocci too)
159
What 3rd gen cephalosporins can cross the BBB?
Ceftriaxone and cefotaxime
## Footnote
Cefepime and ceftazidime are also capable of crossing BBB and used to Tx meningitis
160
Fourth gen cephalosporin with broad ABx activity - including against *P. aeruginosa*
Cefepime (parenteral)
Used for bacteria that are resistant to 3rd gen cephalosporins
161
Fifth gen cephalosporin used to Tx MRSA skin infections
Ceftaroline (parenteral)
## Footnote
Also used to Tx intraabdominal infections (combined with metronidazole); complicated UTIs, hospital and ventilator acquired pneumonia
162
Cephalosporins with low risk of cross-reactivity with pen allergies
Cefdinir (third gen)
Cefpodoxime (third gen)
Cefuroxime (second gen)
163
Cross reactivity between pen allergy and cephalosporins
~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
What cephalosporins are used to Tx *Enterococci*?
No cephalosporins are active against *Enterococci*
165
First line Tx for gonorrhea
IM ceftriaxone
166
Bactericidal classes of ABx
Penicillins
Cephalosporins
Carbapenems
Mono-bactams
Vancomycin
Aminoglycosides
167
Carbapenem
Gram +’s: Staph and Strep (not MRSA)
Gram -: *Pseudomonas* and *Enterobacter*
Anaerobes: *B. fragilis*
168
Mono-bactam
Narrow spectrum ABx class - Used to Tx against Gram (-) bacilli infections (including Pseudomonas)
i.e. **Aztreonam**
## Footnote
Used for Pt's allergic to other beta-lactams
Resistant to many beta-lactamases
Administered parenterally and via inhalation for Pts w/ CF
169
Vancomycin
##Footnote
MOA
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.*
## Footnote
Narrow spectrum - only Gram (+) bacteria - MRSA/*C. diff.*
Resistance is increasing among *Enterococci* (VRE) and *S. aureus*
170
Adverse effects of Tx w/ vancomycin
Nephrotoxicity
Ototoxicity
**Red man syndrome** - rx'n that occurs due to histamine release when drug is administered too quickly - flushed, tachycardic, and hypotensive
171
Polymyxin B
Cationic detergent that targets Gram (-) bacteria by poking holes in cell walls (used topically - skin and eye - due to risk of nephrotoxicity)
172
Bacitracin
Inhibits cell wall synthesis by preventing transfer of mucopeptides to the growing cell wall - targets Gram (+) bacteria
| Ingredient in triple antibiotic oinment
173
Mupirocin
**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
Aminoglycosides
| MOA
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
## Footnote
Bactericidal
175
What blocks the transport of aminoglycosides?
Anaerobic conditions
Divalent cations
Acidic pH
## Footnote
Therefore - ineffective against anaerobes or bacteria in anaerobic conditions
176
Spectrum of aminoglycosides
Treat serious Gram (-) infections - Pseudomonas and Enterobacteria
Often combine w/ beta-lactams to Tx sepsis, endocarditis, or ventilator-assisted pneumonia
177
Adverse effect of aminoglycosides
Coclear toxicity
Vestibular toxicity
Nephrotoxicity
Neuromuscular blockade - inhibits release of ACh and can reduce sensitivity to the neurotransmitter (exacerbates myasthenia gravis)
178
Tetracycline MOA
Bind to 30S subunit and block incoming aminoacyl-tRNA from entering the ribosomal A site
## Footnote
**Bacteriostatic** (unlike aminoglycosides which are bacteriocidal)
179
Spectrum of tetracycline therapy
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
What interferes w/ tetracycline absorption
Di- and trivalent cations - form insoluble chelates
181
Chloramphenicol
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
Macrolides
| MOA
Bind to the 50S subunit and block protein synthesis by preventing the translocation of tRNA from the A site to the P site
## Footnote
These drugs are usually bacteriostatic
183
Erythromycin
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
## Footnote
Not widely used
184
Azithromycin
Wider spectrum compared to erythromycin - covering some Gram (-)'s - *H. influenzae* and *Mycobacterium avium*
| Clarithromycin has similar coverage
185
Fidaxomicin
Not absorbed and remains in GI tract - possible Tx for ***C. diff***
## Footnote
**Bactericidal** macrolide (newest one)
186
Macrolide ABx resistance
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
Adverse effects of Tx w/ macrolides
**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
Clindamycin
| MOA
Lincosamide - similar MOA to macrolides
Binds 50S subunit and inhibits protein synthesis by interfering w/ bacterial protein synthesis by blocking translocation reactions
## Footnote
Bacteriostatic or bactericidal depending upon concentration, infection site, and organism
189
Spectrum and use of clindamycin
Includes Gram (+) organisms - including community acquired MRSA and **anaerobes** (especially *Bacteroides fragilis*)
## Footnote
Adverse effects: *C. diff* and pseudomembranous colitis
190
Linezolid
| MOA and bioavailability
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
## Footnote
**Bacteriostatic**
191
192
193
194
Lindezolid
| Spectrum
Reserved to Tx infections caused by multi-drug resistant VRE, MRSA, and resistant pneumococci (Gram (+) bacteria)
195
Lindezolid
| Adverse effects
**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
Lefamulin
| MOA
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
## Footnote
**Bactericidal**
197
Adverse effects of lefamulin
Prolongs QT interval
May cause fetal harm
198
Sulfamethoxazole
| MOA
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)
## Footnote
Used alone - bacteriostatic
199
Contraindications of Tx w/ sulfonamides
**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
Bacterial resistance to sulfonamides
They develop resistance by overproducing PABA or via plasmid-encoded dihydropterate synthetase enzyme that has reduced affinity for sulfonamides
201
Sulfonamide used to Tx inflammatory bowel disease
Sulfasalazine - broken down by gut flor into sulfapyridine and mesalamine - have anti-inflammatory properties
202
Sulfonamide used to Tx burn Pts and prevent pseudomonal infections
Silver sulfadiazine
203
Trimethoprim
| MOA
Inhibits dihydrofolate reductase (final step in bacterial folate synthesis)
## Footnote
Used alone - bacteriostatic
**Sulfamethoxazole-Trimethprim combo - bactericidal**
204
Flouroquinolone uses
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
Adverse effects of fluoroquinolones
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
Ciprofloxacin
Fluoroquinolone used for UTIs and infections caused by Gram (-) bacteria
207
Levofloxacin and moxifloxacin
Referred to as "respiratory fluoroquinolones" - effectve against pen-resistant *Streptococcus pnumoniae*
208
Delafloxacin
Newer fluoroquinolone used for serious skin infections: broad-spectrum activity (including MRSA)
209
Metronidazole
| MOA
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
## Footnote
Effective against **anaerobic bacteria and certain parasites**:
C. diff, H. pylori, Bacteroides fragilis, P. acnes, amebiasis, Gardnerella vaginalis, Giardia, and Trimononas vaginalis
210
Metronidazole
| Adverse effects
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
First-line Tx against TB
212
Second-line Tx against TB
213
Rifampin
| MOA
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
Rifampin vs. Rifaximin
Rifampin is absorbed in GI tract
Rifaximin is not - used to Tx GI infection (i.e. E. coli) and small bowel bacterial overgrowth
## Footnote
Both inhibit DNA-dependent RNA polyermase
215
Which of the following is only useful for treating gram positive organisms and anaerobes?
A. Cephalexin
B. Ceftazidime
C. Clindamycin
D. Clarithromycin
C. Clindamycin
## Footnote
Clindamycin - lincosamide - binds to the 23S rRNA of the 50S subunit
216
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
B. Linezolid
## Footnote
Member of the oxazolidinone - binds to the 23S rRNA of the 50S subunit
217
Which of the following is usually bacteriostatic?
A. Azithromycin
B. Amoxicillin
C. Ampicillin
D. Aztreonam
A. Azithromycin
218
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
C. Gentamicin
| Describes MOA for aminoglycosides
219
Which of the following generations of cephalosporins is the MOST effective at treating gram positive cocci skin infections and is used for surgical prophylaxis?
First generation cephaloporins
220
Nafcillin
Beta-lactamase resistant beta-lactam
221
Aztreonam
| Spectrum
Only Tx Gram (-) bacteria - similar spectrum to aminoglycosides but w/o the renal and ototoxicity
## Footnote
Mono-bactam that is resistant to beta-lactamases produced by Gram (-) bacteria
222
Protein synthesis inhibitor ABx's
Mupirocin
Aminoglycosides
Tetracyclines
Chloramphenicol
Macrolides
Clindamycin
Linezolid
223
Tetracycline used to Tx community-acquired MRSA
Doxycycline
224
ABx that has the highest incidence of causing a *C. difficile* infection
Clindamycin (up to 20%)
225
Trimethorpim
| MOA
Inhibits dihydrofolate reductase - not sulfa ABx but an anti-metabolite
| Bacteristatic when used alon
226
List common fluoroquinolones
Ciprofloxacin
Levofloxacin
Moxifloxacin
227
Ciprofloxacin
Commonly used to Tx UTIs and infections caused by Gram (-) bacteria
| Targets bacterial DNA gyrase
228
Most fluoroquinolones are excreted by the kidneys, which is metabolized primarily by the liver?
Moxifloxacin
229
Newish FQ that has broad-spectrum activity and used often used in serious skin/soft-tissue infections
Delafloxacin
230
Metronidazole spectrum of activity
Effective against anaerobic bacteria and certain parasites
## Footnote
C. diif., H. pylori, Bacteroides fragilis, P. acnes, amebiasis, Garnerella vaginalis, Giardia, and Trichomonas vaginalis
231
Isoniazid
| MOA
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**
## Footnote
**Overdose**: INH overdose can lead to severe seizures and metabolic acidosis, often requiring aggressive treatment.
232
Daptomycin
| MOA
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
## Footnote
Only given IV
**Rhadomyolysis** - important side-effect
233
Colistin
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
Nitrofurantoin
Protein and DNA synthesis inhibitors
Cleared by the kidneys
Impact w/ Pts with G6PD deficiency
235
Standard Tx and duration of treatment for active TB infection:
236
Streptomycin
Inhibits protein synthesis by targeting the 30S ribosomal subunit
237
What is the reason that sulfonamides are not administered to newborns?
Kernicterus
238
Which of the following inhibits DNA gyrase?
A. Rifampin
B. Ciprofloxacin
C. Metronidazole
D. Isoniazid
B. Ciproloxacin
239
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
B. Metronidazole
240
What medication is a prodrug that must be first converted into a free radical to become effeective?
Isoniazid
| First-line Tx for TB
241
What vitamin is given to prevent peripheral neuropathy in Pts taking isoniazid?
B6
242
Which of the following inhibits bacterial dihydrofolate reductase?
A. Nitrofurantoin
B. Vancomycin
C. Ciprofloxacin
D. Trimethoprim
D. Trimethoprim
243
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
Ethambutol
244
What bacterial metabolic component does sulfamethoxazole competitively compete with?
Para-aminobenzoic acid (PABA)
245
Rifampin effect on CYP450
Rifampin is a potent CYP450 inducer
246
247
Vancomycin resistance
Plasmid mediated and resistance transfers when bacteria also co-express conjugation genes
## Footnote
Vancomycin should be reserved for MRSA, enterococcal endocarditis
248
Oxazolidinones
Protein synthesis inhibitors
i.e. linezolid
