Bacteria Flashcards
(131 cards)
1
Q
Draining sinus with “sulfur” granules?
A
Actinomyces or mycetoma
Not actually sulfur but hard grains of tangled bacteria…need several sections to see them sometimes
2
Q
What is a mycetoma?
A
Inoculation infection of subcutaneous tissue leading to draining sinuses with granules due to higher bacteria, fungi, or nocardia
3
Q
Actinobacillus - aggregatibacter actinomycetomcomitans
A
Gram negative cocco bacillus that often occurs in actino lesions, cause of HACEK
4
Q
Rhodococcus equi (Salmon colored horse)
A
Gram + cocco bacillus, very weakly acid fast
Salmon pink colonies on cx in 4-7 days
Causes subacute pna –> cavities –> bacteremia –> brain/skin abscess
- exposure to manure or horses
Usually causes infxn in IC pts - AIDS pts (don’t always need to have horse exposure)
Tx: vanco + mero/imipenem + FQ/rifampin x 2-3 weeks, then po FQ and azithro/rifampin
5
Q
Eikenella corrodens (Ike was a heart breaker, likes to bite...)
A
Anaerobe , small gram negative bacillus
in lung abscess or human bites
Spontaneous bacterial endocarditis (HACEK)
Tx: augmentin or clindamycin + bactrim or FQ + clindamycin
Tends to be resistant to flagyl
6
Q
Nocardiosis
Purple, beaded, branching
A
Gram + rods, weakly acid fast, aerobic,
Filamentous branching, beaded
lives in soil
Resp spread but can spread to Brain for brain abscess (usually IC host)
Sx: “CAP” failing standard abx, cavitary or non cavitary lung masses with hematogenous spread to brain and soft tissue
Check head CT and check for CGD
Tx: bactrim, carbapenems, minocycline, linezolid, augmentin, amikacin,
Nocardia farcinica - resistant to all abx
Nocardia asteroides - 80-90% US
Nocardia brasiliensis - cutaneous dz
7
Q
Actinomyces meyeri
A
Branching gram + rod, anaerobic
NOT acid fast
Causes infxn in mouth (lumpy jaw) lungs, appendix, uterus with IUD (can form molar tooth colonies)…contiguous spread as it can dissect through tissue planes
Can look like lung ca, often related to a breach in GI mucosa (like EGD)
If present on pap - just monitor (don’t remove IUD)
Dx: sulfur granule with gram + bacilli or Positive cx (not from oral flora)
Tx: penicillin
Or if pcn all: doxycycline
8
Q
Meliodosis - burkholderia pseudomallei
A
Gram negative rod, oxidase +
Occurs in soil and water in SE Asia, N. Austrailia, China, India,
* incr cases after tsunami or rain storm
Sx: acute, subacute, chronic pna or hematogenous abscesses in skin, bone, brain, and spleen
Tx: bactrim + ceftazidime OR carbapenem x 2 wks then bactrim +- doxycycline x 3 mos
9
Q
Glanders
Burkholderia mallei
A
- Aerobic small slender gram-negative rod causes disease known as glanders in animals (esp. horses) and rarely humans.
- Hard to see on Gram-stain. Grows slowly, best with glycerol. If suspected, warn lab since it can pose a lab hazard.
- May be erroneously identified as Pseudomonas sp.
Acq from nasal d/c or draining lymph nodes from horses, cats, in SE Asia, Africa or S. America; see in lab workers or terrorists or “government lab”
*characteristic musty odor when grown in the lab**
Sx: skin inoculation with fever, painful nodules, draining nodes, can be inhaled to cause acute ulcerative tracheobronchitis and pna
Tx: BACTRIM or ceftazidime or gent or imipenem or doxy or cipro
10
Q
Prevotella melaninogenica
A
Gram negative bacillus found in mouth
Usually black pigment on cx
Causes infxn in sinus, mastoid, lung, brain, mouth
11
Q
Bacteria in animal bites
A
Pasteurella, streptococcus, staph, fusobacterium, propionibacterium, moraxella, corynebacterium, bacteroides, prevotella, porphyromonas
12
Q
Post animal bite care?
A
- ) wound care - irrigate, debride
- ) ? Image to look for fx, osteo, foreign body
- ) no wound closure
- ) abx
- ) vaccines - tetanus, rabies
13
Q
Cat bite?
A
W/o tx, 70-100% get infected Pasteurella multocida (in saliva of >90% of cats) - small aerobic,gram negative bacillus
- also fusobacterium, bartonella henselae, rabies, staph aureus, streptococcal species
Tx: augmentin
If pcn all: doxy + flagyl or FQ +/- flagyl
14
Q
Dog bite?
A
Capnocytophaga canimorsus - pleomorphic, long thin fusiform gram negative bacillus, tapered at both ends
- causes severe infxn ( sepsis, DIC, peripheral symmetric gangrene of fingers/toes) in alcoholics, splenectomized pts
Tx: augmentin
Also consider pasteurella canis, only 2-10% of bites will get infected
15
Q
Which animal bites require Post Exp rabies prophylaxis?
A
Coyotes
Skunks
Raccoons
Feral cats
16
Q
Rat bite fever
A
USA: streptococcus moniliformis
Asia: spirillium minus (gram negative branching rod)
- consider in homeless pt with fever and severe Polymyalgia, mac pap rash, sepsis; blood cx with pleomorphic gram negative bacilli
Tx: penicillin or doxycycline
17
Q
Cellulitis empiric tx?
A
Tx for BOTH ca-MRSA and strep
Bactrim and amox/keflex
Bactrim - treats ca-MRSA but poor strep coverage
Doxy: treats ca-MRSA +/- strep pyogenes , bacteriostatic
Clindamycin: treats 80% of MRSA but 50% develop inducible clindamycin resistance
18
Q
Leech bite
A
Aeromonas hydrophilia
Gram negative bacillus
Can cause severe dz in IC - can present with sepsis and necrotizing fascitis
Tx: levofloxacin/cefepime/doxy + cipro
19
Q
Folliculitis
A
Purulence where hair follicles exit skin Staph aureus Pseudomonas (hot tub) Candida albicans Myassezia furfur ( tinea versicolor) P. Acnes Tx: topical antibacterial, warm compress,
20
Q
Impetigo
A
Infxn of superficial outer layers of epidermis with honey crust scales
More common in warm, humid env, after minor skin abrasions or insect bites
Due to streptococci
Tx: clindamycin/ doxy/keflex x7d
Or topical mupirocin or retapamulin
21
Q
Non bullous impetigo
A
Strep
Compl: post strep GN secondary to nephritogenic strains
22
Q
Erysipelas
A
Acute onset of painful, well demarcated rash
Rapid progression with or w/o lymphangitis
More common in pts with lymphatic destruction, venous stasis
Often confused with venous stasis
- secondary to strep groups A, B, C, G (not strep anginosus)
Tx: elevation, topical antifungals, pcn, clindamycin, cephalosporins
Avoid bactrim or macrolides
23
Q
Recurrent cellulitis
A
Treat predisposing conditions
If > 3-4 episodes/yr can consider po pcn, erythromycin, bid for 4-52 weeks or IM pcn q 2-4 weeks
24
Q
TSS from staph aureus
A
Staph aureus:
Produces TSST and exfoliative toxin, crosses mucous membranes
Secondary to tampons, surgery (bread taught, rhinoplasty)
Sx: n/v/d, renal failure, DIC, desquamating rash, erythroderma (Dev bullous lesions when touched),
- less likely to present with multi organ failure, mortality
25
TSS from strep
Produces TSST and pyrogenic exotoxin
Often from an infected cut or burns or infected varicella lesions (minor trauma)
Ovoid, catalase negative, produces pyrogenic exotoxins (A>>B&C) which lead to fever, pharyngitis (treat with PCN VK within 8-10 days to prevent rheumatic fever, no effect on GN), rash (scarlet fever), TSS
ASO Ab only present if pt with pharyngitis
Bacteremia, Painful, tissue necrosis with inflammation, hypotension, ARDS, incr LFTs, renal failure, DIC (multi organ failure)
30-70% mortality
Tx: clindamycin + pcn G +/- ivig
26
Check anti - DNAase B?
If patient has pharyngitis or pyoderma
27
Necrotizing fasciitis
Erysipelas progressing to loss of pain, decr skin sensation, hemorrhagic bullae, rapid progression of advancing border, DISPROPORTIONATE PAIN
Ddx: strep, staph, clostridial infxn (c. Perfringens - crepitus) (C. Septicum - sepsis in colon ca, mass hemolysis - pcn + clindamycin); synergy btw aerobes ( staph, e.coli) and anaerobes (bacteroides) can lead to melenys (btw staph and strep in LE or perineum) or fourniers gangrene - tx: vanco + zosyn
Dx: MRI
Tx: surgical exploration, pcn and clindamycin, +/- IVIG
28
Vibrio vulnificus
```
#1 cause of shellfish assoc death in US
ESP in liver pts, hemochromatosis, exposure to estuaries
```
Infected wounds look like bullae, can also have bacteremia
Tx: doxycycline + ceftriaxone or ceftazidime
29
Excess iron stimulates growth of?
```
Aeromonas hydrophilia
E.coli
Listeria monocytogenes
Rhizopus
Vibrio vulnificus
Yersinia enterocolitica
```
30
Erysipelothrix
Gram + rod
Meat handling cellulitis, poultry, hides, fish
Sx: subacute erysipelas/erysipeloid
Infects cut or abrasion on finger after exposure to swine or fish
Severe throbbing pain
Dx: aspirate/bx of deep dermis
Tx: pcn, cephalosporin, clindamycin, FQ
Tends to be vanco resistant
31
Seal bites?
Mycoplasma pneumoniae
32
Tinea pedis?
Strep erysipelas
33
Painless ulcerated Papule on wool sorters hands?
Cutaneous anthrax
34
Nail salon or whirlpool or tatoo parlor?
Infxn with mycoplasma fortuitum or mycoplasma chelonae
35
Pyomyositis
Bacterial infxn of muscle which can lead to abscess
1.) image - MRI/u/s or CT
2.) cx of blood or abscess
3.) empiric vanco + GN coverage in IC
4.) if MSSA - cefazolin/nafcillin
5,) drainage
6.) po abx for 2-3 weeks
36
Skin manifestations of neisseria?
Meningococcemia - purpura fulminans
| Gonococcemia - arthritis - dermatitis syndrome
37
Skin manifestations of pseudomonas?
Ecthyma gangrenosum - sharp delineated border, central necrosis, pale outer border
Gram negative rod, oxidase +, not glucose fermenter
Dx: punch bx - organisms within vessel walls
38
Erythrasma
Looks like tinea, often in obese
Coral red fluorescence on woods lamp
Secondary to corynebacterium minutissimum
Fails to respond to antimicrobials
Resolves with elevation, chronic, dependent edema
Tx: topical clindamycin/erythromycin or po erythromycin
39
Intertrigo
Assoc with obesity and DM
Macerated plaques within skin folds, secondary to friction and moisture
Incr pH promotes infxn
Tx: low potency steroids and silvadene, antifungals, or tacrolimus bid
40
Staph aureus
Gpc in clusters, catalase +, coagulase +
MSSA-pan sensitive, tx: pcn
MSSA-resistant to pcn , tx: nafcillin, oxacillin, cefazolin
41
Staph bacteremia
```
Get repeat blood 2-4 d after initial + cx
Get echo (TTE vs TEE)
```
If uncomplicated: pt defervesces in 72 hrs, nl echo, no prosthesis, no mets, follow up blood cx are negative
Tx: 14 d IV vancomycin or daptomycin
If complicated: 28 days of therapy
42
Staph lugdunensis
Type of CoNS
• S. lugdunensis infections more similar in type to S. aureus than other coagulase-negative staphylococci. After S. epidermidis, second leading cause of CNS endocarditis. May be cause of aggressive infection with high mortality
Organism often susceptible to methicillin, only ~25% of strains produce beta-lactamase.
Tx: vanco +/- rifampin
Add gent for PVE
Dirty feet smell in lab,
43
Complications of staph bacteremia
- Septic arthritis (6%) pain in joint (often knee), rare: SI joint, SC joint, symphysis pubis - tap jt, gram stain + only 50%
- vertebral osteo (3.3%) presents with back pain, dx with ct or MRI
- epidural abscess (2.5%) late Neuro sx: LE weakness, incontinence) dx: MRI
- deep tissue abscess in brain (seizure or fever), psoas, renal abscess (pyuria, pain)
- embolic events: lung -> hemoptysis, spleen -> LUQ pain, kidney -> pyuria or hematuria, Mesenteric A -> acute abd pain or GIB with incr lactate, stroke or MI
44
Cardiac device infxn?
Tx: complete device removal
45
MRSA meningitis?
IV vancomycin x 14d +/- rifampin
46
Staph suppurative thrombophlebitis , tx?
4 wks abx +/- anti coagulation
47
Pt in detroit with leg ulcer, cx with staph aureus, vanco mic>256...
Staph obtained a VAN A from a VRE
48
Pt with persistent MRSA bacteremia? Next step in mgmt?
Consider endo vascular source
Vancomycin/daptomycin + nafcillin or ceftaroline
49
MRSA
86% health care associated
14% community acquired
Now human and animal transmission to each other
Has mecA gene which encodes PB2a (altered penicillin binding protein)
Normal cell wall
Colonizes: nares, groin (perineum, rectum), umbilicus
Decolonize with mupirocin and chlorhexidine; bleach baths 1 cup per tub for 15 min twice a week for 3 months
50
MRSA - vancomycin
If sensitive to vanco, mic is = 2 and AUC/MIC > 400
- get E test to check for vanco sensitivity (e test looks for excess d-ala binding to vanco (ie thick cell wall)
Try not to use vanco if MIC > 2
Dose at 15-20 mg/kg, trough prior to 4th or 5th dose, goal: 15-20
Moa: inhibits cell wall synthesis of gram + by preventing NAM and NAG subunits
S/e: red man syndrome (histamine release with rapid infusion)
True allergy with skin rash, IgA dermatitis (bullous lesions), ITP (decr WBC and platelets), ototoxicity
Nephrotoxic at high doses
51
VISA
MIC 4-8
| Thickened cell wall
52
VRSA
MIC >/= 16
Remodeled cell wall (D-ala D-ala to D-ala D-lactate)
VAN-A is a plasmid from enterococcus faecalis with high vanco resistance
53
Empyema necessitatis
Infxn extending from lung across pleura and eventually leading to a draining skin lesion
Actinomyces (not ill)
TB (chronically ill)
Staph aureus (subacutely very ill)
53
VRE
E. Faecium >>> E. Faecalis
Resistance to vanco secondary to VAN A or VAN B plasmid
Causes cross resistance to teicoplanin
55
Daptomycin
Moa: binds to bacteria cell membrane and depolarizes it leading to potassium release and death of bacteria
Use: Ssti with MRSA, MSSA, e. Faecalis, right sided endocarditis
Pros: once daily dosing, BACTERICIDAL,
Cons: poor CNS penetration, emerging resistance on prolongued courses, dose reduce in renal failure
S/e: incr CK, eosinophilic pna (stop daptomycin, tx: steroids)
56
Linezolid
Moa: inhibits protein synthesis, bacteriostatic
Pros: good oral bioavailability, good for MRSA pna or infxn with visa, vrsa, cons, VRE
Cons: myelosuppression if use > 2 wks, serotonin syn with ssris and maoi, optic neuritis, lactic acidosis, neuropathy on long term use
Resistance mediated by horizontal transmission of cfr gene with mobile genetic elements or can emerge on therapy
57
MRSA prosthetic joint infxn tx?
Vanco, daptomycin or linezolid initially
Suppression with TMP/SMX, fluoroquinolone, tetracycline, doxycycline, or clindamycin + rifampin x 3-6 months.
58
Quinupristin-dalfopristin
| Synercid
Moa: streptogramin inhibits protein synthesis
Good for MRSA with decr susc to vanco or daptomycin or to treat vanco Resistant E. Faecium
Cons: no effect on E. Faecalis, expensive, incr bili, arthralgias, need central line, CYP p450 inhibition
59
Televancin
Lipoglycopeptide derivative of vancomycin
Moa: membrane depolarization and PG synthesis inhibition
Once daily glycopeptide for tx of MRSA, visa, vrsa Ssti and HAP
S/e: nephrotoxicity, taste disturbances
60
Ceftaroline
Anti-MRSA cephalosporin
Good for tx of MRSA, visa, strep pyogenes, gram negatives, MRSA pna, gram + anaerobes
Cons: no activity against pseudomonas, ESBL, acinetobacter
61
Mupirocin resistance?
In staph aureus via ILES-2 gene
62
CA-MRSA
RF: MSM, prison inmates, athletes, IVDU, inter familial
Distinct genotypes:
- Penton-valentine leukocidin (PVL) - causes extensive tissue necrosis and severe skin infxn
- USA 300 and 400
- SCC Mec IV or V
- ACME
63
HA-MRSA
More common
- SCC Mec type I, II, and III
- USA 100 and 200
64
Bactrim
Bacteriostatic
| Can see RTA, can inhibit proximal tubule secretion and blockade of collecting tubule sodium channel (incr K and incr Cr)
65
Ampicillin resistant E. Faecium mech of resistance?
Expresses PBP 5 on it's cell wall
66
Major resistance mechanisms of staph aureus?
Pcn - beta-lactamase
Nafcillin - PBP2a
Clindamycin - MLS B
67
Acute rheumatic fever
Autoimmune state induced by pharyngeal strep infxn
Dx: 2 major
1 major + 2 minor if supported by + throat cx
Major: carditis, polyarthritis, chorea, erythema marginatum, subQ nodules
Minor criteria: Arthralgia, fever, Incr WBC, incr ESR, incr CRP, prolongued PR interval
Acute GN from ag-ab complex deposition
68
Clindamycin and staph tx
Need to check MRSA for inducible resistance
| Good for S. Pyogenes, incr risk for c.dificile
69
Septic arthritis
Usually hematogenously acquired
- More common in rheumatoid arthritis
Can be staph, strep, pseuds, listeria, gram negatives depending on host and RF
70
21 yo F, IVDU, with fever and chest pain, new murmur, right SCJ pain...joint is aspirated with purulence, TEE with tricuspid veg...what empiric abx?
Vanco and cefepime given hx of IVDU
71
22 yo F with new sex partner and acute septic arthritis and skin pustules on leg...abx?
Ceftriaxone to cover gonorrhea and vanco to cover MRSA
72
45 yo M vacationing in Spain, develops fever, malaise and back pain, 3 weeks earlier he drank unpasteurized milk at a farm. He has fever to 101 and L sacroiliac pain...causative organism?
Brucella melitensis
- ingestion of unpasteurized milk
- predilection for SI joint
73
Ingestion of goat cheese or unpasteurized milk...
Brucella
74
Living or travel to SE Asia
Burkholderia pseudomallei
| Streptococcus suis
75
Fever in Postpartum F
Mycoplasma hominis
- mycoplasmas are the smallest free-living organisms known. They have no cell wall and therefore do not Gram stain.
- associated with pelvic inflammatory disease, and bacterial vaginosis
- Growth of "fried egg" colonies on glucose agar medium within 24–48 hours is characteristic
76
Joint infxn post arthroscopy?
Staph aureus,
Cons
Clostridium
Gram negative bacilli
77
Infxn post reconstructive surgery with tissue allograft?
Clostridium species
78
Non Gonococcal arthritis
80-90% monarticular (50% knee)
Sx: fever, pain, warmth, jt tenderness, effusion,
Anthrocentesis with purulent fluid (>50,000 WBC, >90% PMNs),
Gram stain + only 50%
Get synovial fluid cx and blood cx
Tx: based on gram stain
If gram stain negative: vanco + ctx/ceftazidime
79
Dissem Gonococcal infxn
More often in adol/ young adults
80
Joint infxn
Repeated needle inspiration, first 5-7d, until purulence is minimal
Arthroscopy-irrigation, lysis of adhesions, removal of purulent material in shoulders, knees and ankles
Open surgical drainage for hips, jt with poor response to tx, or if arthroscopy /aspiration is impractical
81
Septic arthritis tx?
IV tx x 2-4 weeks
4 wks for staph aureus/MRSA/GNR
**if gram negative is sensitive to fluoroquinolones, can switch to po for last half of tx
82
Viral arthritis
Syn fluid :
83
Reactive arthritis
Inflammatory arthritis after infxn elsewhere in the body
- enthesitus (Achilles' tendon/plantar fascitis)
- assymetric oligoarticular arthritis
Tx : NSAIDs
Causes: ssyc, chlamydia
Extraarticular manifestations: urethritis, conjunctivitis, uveitis, keratoderma blennorrhagicim (lesions on soles of feet), circinate balanitis, oral ulcers
84
TB or fungal arthritis?
Lower WBCs, decr PMNs
85
Prosthetic joint infxn
Suspect in pts with a sinus tract, persistent wound drainage, acute or chronic pain
Etiology: cons, staph aureus, mixed flora, GNR
- Early: 12 mos, staph aureus, cons, anaerobes, viridans strep, yeast
Dx:
1.) ESR, crp
2.) imaging: plain films to check for bony shift, abnl bone lucency, prosthesis shift, periosteal rxn
3.) ** aspiration and cx of joint fluid, prefer 2 cx if possible,
If going to OR, stop abx 2 weeks prior to incr yield of bx,get 5-7 specimens for cx
86
Prosthetic joint infxn - mgmt?
2-step:
1. ) removal of prosthesis and cement
2. ) Use spacer impregnated with abx for 2wks to few months
3. ) IV abx for 4-6 wks
* 8 wks if MRSA, VRE, enterococcus, fungi,
* p acnes : 4-6 wks pcn g, ctx, clindamycin, or vanco
Surgery 2 wks after completing abx to check cx at time of reimplantation
Success 90-96% in hip, 97% in knee
```
Debridement with retention:
If early (
```
87
Osteomyelitis
Contiguous osteo:
- foreign body: cons, staph aureus
- puncture injury to foot: pseudomonas
- malignant ext otitis: pseudomonas
- periodontal infxn: oral flora, Actinomyces
- soil contamination: staph aureus, clostridium, enterobacteriacea, bacillus, nocardia, atypical mycobacteria
Hematogenous osteo:
- scd: salmonella, staph, strep pneumo
- IC: aspergillus, candida, atypical mycobacteria, bartonella
88
Chronic osteo
Not a medical emergency, no need for urgent abx
Dx: MRI or CT if MRI is contraindicated( pacemaker or metal hardware) - (not plain films)
Get deep bone cx for ID
Tx: surg debridement, ID organism, 8 wks of abx
89
65 yo M with hematuria, cystoscopy with bladder CA, tx with intravesicular BCG, 2 mos later with fever and back pain...
Mycobacterium bovis
90
Vertebral osteo
Usually hematogenous spread
Sx: local pain and fever
Dx: MRI, blood cx
CT guided bx and aspiration off abx
Repeat with open bx if inconclusive
Tx: stabilize spine, 6-8 wks abx,
If hardware in late infxn, remove hardware, antimicrobial tx, f/u ESR/crp
Osteo after trauma/surgery: if hardware in place, suppress infxn with IV abx, po abx until union achieved, then remove hardware and tx remaining infxn
91
Penicillin
Moa: binds to DD transpeptidase (inhibits cell wall formation)
S/e: seizures, serum sickness, interstitial nephritis, decr WBC, decr ply, GI upset
Resistance: penicillinase
92
If pcn allergy...which abx are you also allergic to?
Allergic to all beta lactams: cephalosporins, carbapenems,
Can use aztreonam - no cross reactivity - has potential to cause seizures
93
Penicillin allergy
A - type 1; anaphylaxis, angioedema, IgE mediated
C - type 2: cy2toxic: Ab vs tissue Ag ( goodpastures, interstitial nephritis)
I - type 3: immune complex (ab +ag) sle, serum sickness
D - type 4: delayed hypersensitivity; macpap exanthems, ppd, transplant rejection, T lymphocytes, TB test, touching - contact dermatitis
94
Types of PCN
Pcn G - IV only
Benzathine PCN - IM, stable for prolongued low level concentration
PCN VK - oral
95
MSSA tx
- Nafcillin - activity depends on time above MIC (like all beta lactams)
Toxicity: neutropenia, fluid overload, AIN, decr WBC, diarrhea
- Oxacillin
Toxicity: hepatitis
96
What causes the pro inflammatory state of sepsis?
LPS binding to CD14 and activation of TLR. This activation promotes apoptosis of epithelial cells and lymphoid cells contributing to more bacterial translocation from the gut and to decreased immunocompetence, which in turn exacerbates the septic response
97
Bactrim
| Trimethoprim/sulfamethoxazole
MOA: TMP act synergistically with SMX by interfering with folic acid production. TMP binds to dihydrofolate reductase inhibiting the reduction of dihydrofolic acid to tetrahydrofolic acid (folinic acid). Sulfonamides are structural analog of p-aminobenzoic acid (PABA), it competitively inhibits dihydrofolic acid synthesis which is necessary for the conversion of PABA to folic acid.
Bacteriostatic
S/e; methemoglobinia in pts with G6PD def, rash, Stevens Johnson's, photosensitivity, pancytopenia, elev Cr, interstitial nephritis, aseptic meningitis, induce blockade of collecting tubules, thereby increasing potassium and creatinine
98
Clindamycin
Moa: protein synth inhibitor
Most CA MRSA are susceptible
Drug of choice for anaerobic lung abscess, inhibition of staph aureus, bacteriostatic
Increased c dificile risk
Resistance: MLSb (ribosomal target modification by Erm)
99
Tetracycline
Moa: inhibit protein synthesis by mainly binding to 30S ribosomal subunit and blocking binding of aminoacyl transfer-RNA.
Resistance: efflux pumps
S/e: photosensitivity, teeth discoloration, vertigo (Esp minocycline)
100
Vancomycin
Moa: Inhibits bacterial cell wall biosynthesis by binding to D-alanyl-D-alanine precursor thereby blocking peptidoglycan polymerization.
S/e: red mans syndrome, IgA bullous dermatitis, thrombocytopenia, can amplify aminoglycoside nephrotoxicity
101
Telavancin
Moa: semisynthetic, lipoglycopeptide antibiotic. Similar to vancomycin, telavancin inhibits bacterial cell wall synthesis by interfering cross-linking and polymerization of peptidoglycan. In addition, telavancin depolarizes the bacterial membrane and disrupts barrier function.
Approved for Ssti, HAP, and CAP
102
Linezolid
Moa: Linezolid inhibits the first step of protein synthesis by binding to f-met-t-RNA-mRNA-30s ribosome subunit.
Resistance:
Effective against MRSA/visa/vrsa, pcn resistant strep pneumo, VRE, m. Fortuitum, nocardia, better for MRSA pna
S/e: lactic acidosis, BM suppression, serotonin syndrome, peripheral neuropathy (hands >feet), optic neuropathy (d/c drug), decr platelets
103
Daptomycin
Moa: Daptomycin binds to bacterial membranes and causes rapid depolarization of membrane potential, which results in inhibition of protein, DNA and RNA synthesis. This leads to rapid cell death.
Use: MRSA, VRE, approved for complicated bacteremia (like vanco)
S/e: rhabdomyolisis, eosinophilic pna
If MRSA resistant to vanco and daptomycin, try daptomycin + oxacillin
104
Rifampin
Moa: Inhibits initiation of chain formation for RNA synthesis by inhibiting DNA-dependent RNA polymerase.
Resistance: mutation of the target polymerase
Penetrates biofilm and BBB
S/e: hepatitis, orange urine, flu like syn with interrupted tx, up regulates cyp p450
105
Macrolides
| Erythromycin, azithromycin, Clarithromycin
Moa: Macrolides inhibit protein synthesis by binding to 50S ribosomal subunits, inhibiting translocation of peptidase chain and polypeptide synthesis. The addition of nitrogen at position 9a of the lactone ring, gives azithromycin improved resistance to acid degradation, improved tissue penetration and activity against gram-negative organisms and a longer elimination half life
Resistance: via target site alteration, export of drug by macrolide efflux pump encoded by MEFA (like in strep throat)
S/e: nausea, vomiting, prolongued QTc, tinnitus, fatal interaction with colchicine
106
Metronidazole
Moa; unknown
Gold standard in treating bacteroides and most anaerobes
Resistance: mutation in ferredoxin gene, target change in nitroreductase activity
S/e: n/v, flushing, tachycardia, aseptic meningitis
107
Nitrofurantoin
S/e; GI intolerance,
• Hypersensitivity reactions with acute pulmonary symptoms: fever, cough, dyspnea w/ infiltrate and eosinophilia. Occurs within hrs-wks of dose.
• Lupus-like reaction
• Rash
```
RARE
• Methemoglobinemia and hemolytic anemia (with G6PD deficiency)
• Hepatitis +/- cholestatic jaundice
• Peripheral neuropathy
• Pancreatitis
• Pulmonary fibrosis with long-term use
• Lactic acidosis
```
108
Fosfomycin
One dose of powder in water,
• Treatment of uncomplicated urinary tract infections due to E. coli and E.faecalis.
Active against ESBL and most KPCs,
S/e: diarrhea,
109
Beta lactamase combinations
Bind to bacterial beta-lactamase
Amoxicillin-clavulanic acid: good for mild diverticulitis, E.coli, B. Fragilis,
MSSA,
S/e: diarrhea, hepatocellular or cholestatic liver toxicity,
Piperacillin-tazobactam - tx of aerobic/anaerobic GNR below and above the diaphragm,
S/e: interstitial nephritis, plt dysfunction, galactomannan contaminates zosyn and augmentin
110
What is the major determinant of efficacy of beta-lactam abx?
Time the level is above MIC
111
Aztreonam (monobactam)
Moa: inhibits mucopeptide synthesis (by preferentially binding to penicillin-binding protein 3 of susceptible gram-negative bacteria) in the bacterial cell wall, this results in the formation of defective cell walls and osmotically unstable organisms susceptible to cell lysis.
Purely gram negative coverage
Better for use in pts with pcn allergy
112
Cephalosporins
Moa: Cephalosporins are bactericidal and have the same mode of action as other β-lactam antibiotics (such as penicillins), but are less susceptible to β-lactamases. Cephalosporins disrupt the synthesis of the peptidoglycan layer forming the bacterial cell wall. The final transpeptidation step in the synthesis of the peptidoglycan is facilitated by transpeptidases[disambiguation needed] known as penicillin-binding proteins (PBPs). PBPs bind to the D-Ala-D-Ala at the end of muropeptides (peptidoglycan precursors) to crosslink the peptidoglycan. Beta-lactam antibiotics mimic the D-Ala-D-Ala site, thereby irreversibly inhibiting PBP crosslinking of peptidoglycan.
S/e: incr risk of c.dificile, ctx can cause pseudocholelithiasis secondary to crystal deposition in biliary tree (biliary sludge)
113
1st gen cephalosporins
```
cefadroxil
cefazolin
cephalexin
Duricef
Keflex
Ultracef
```
Narrow spectrum:
Spectrum of activity:
Good gram-positive cocci coverage: Streptococci, Staphylococci, Enterococci.
NOT effective against methicillin-resistant Staph. aureus, penicillin-resistant Strep. pneumoniae.
Modest gram-negative bacteria coverage: Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae, though susceptibilities may vary. Poor activity against Moraxella catarrhalis and Hemophilus influenzae.
Active against most penicillin-susceptible anaerobes found in the oral cavity, except Bacteroides fragilis group.
114
2nd gen cephalosporins
```
cefaclor (Ceclor, Raniclor)
cefamandole (Mandol)
cefprozil (Cefzil)
cefuroxime (Ceftin, Zinacef)
loracarbef (Lorabid), is a carbacephem, but it is sometimes grouped with the second-generation cephalosporins
Cephamycins:
```
cefmetazole (Zefazone)
cefotetan (Cefotan)
cefoxitin (Mefoxin)
Spectrum:
Spectrum of activity:
Gram-positive cocci: "True" 2nd generation cephalosporins are almost comparable to 1st generation agents against Streptococci. Slight loss of activity against Staphylococci (NOT active against methicillin-resistant strains). Cephamycins are less active against gram-positive cocci than 1st generation agents.
Gram-negative aerobes: Hemophilus influenzae, Moraxella catarrhalis, Proteus mirabilis, E. Coli, Klebsiella, Neisseria gonorrheae.
Anaerobes: Unlike 2nd generation cephalosporins, cephamycins (cefotetan, cefoxitin, and cefmetazole) have activity against anaerobic Bacteroides.
No efficacy against Pseudomonas, enterococci.
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3rd gen cephalosporins
```
cefcapene (Flomox)
cefdinir (Omnicef)
cefditoren (Spectracef)
cefetamet (Altamet)
cefixime (Suprax)
cefmenoxime (Bestcall, Bestron)
cefoperazone (Cefobid)
cefotaxime (Claforan)
cefpiramide
cefpodoxime (Vantin)
cefsulodin (Takesulin)
ceftibuten (Cedax)
ceftizoxime (Cefizox)
ceftriaxone (Rocephin)
latamoxef (or moxalactam) (Shiomarin), is an oxacephem
```
Ceftazidime (Fortaz, Tazicef, Tazidime) and Cefoperazone (Cefobid) are the two third generation cephalosporins with antipseudomonal activity.
Spectrum:
Spectrum of activity:
Gram-positive cocci: Limited activity against gram-positive cocci (particularly agents available in an oral formulation).
Cefotaxime, Ceftriaxone, and Ceftizoxime have the best gram-positive coverage of the third-generation agents: methicillin-susceptible Staphylococcus aureus (though less than 1st and some 2nd generation agents), very active against Groups A and B streptococci, and viridans streptococci. Cefotaxime and ceftriaxone are more active than ceftizoxime against Streptococcus pneumoniae.
Cefixime and Ceftibuten lack Staphylococcus activity.
NONE are active against methicillin-resistant Staphylococci, Enterococci, and Listeria.
Gram-negative bacteria: Very active against Hemophilus influenzae, Moraxella catarrhalis, Neisseria meningitidis, Enterobacteriaceae (Escherichia coli, Klebsiella species, Proteus (including strains resistant to aminoglycosides)), Providencia, Citrobacter, Serratia.
Anaerobes: Cefotaxime, ceftriaxone, and ceftizoxime have adequate activity against oral anaerobes.
Moxalactam has good activity against Bacteroides fragilis
116
4th gen cephalosporins
```
cefepime (Maxipime)
cefluprenam
cefozopran (Firstein)
cefpirome (Cefrom, Keiten, Broact, Cefir)
cefquinome
```
Fourth generation cephalosporins have the broadest spectrum of activity, with similar activity against gram-positive organisms as first generation cephalosporins. They also have a greater resistance to beta-lactamases than the third generation cephalosporins.
Cefepime and cefpirome are highly active against many resistant organisms that traditionally have been difficult to treat.
Spectrum of activity:
Gram-positive cocci: Streptococcus pneumoniae, Groups A and B streptococci, methicillin-susceptible Staphylococcus aureus (less potent than the 1st and 2nd generation agents).
Spectrum: Gram-negative bacteria: Increased activity compared to 3rd generation. Excellent activity against Enterobacteriaceae and Pseudomonas aeruginosa.
Minimal anaerobic coverage.
117
5th generation cephalosporins
ceftaroline fosamil (Teflaro)
Ceftaroline is unique in its activity against multidrug-resistant Staphylococcus aureus, including MRSA6, VRSA, and VISA. Ceftaroline is the ONLY beta-lactam with MRSA activity. it is also active against Enterococcus.
* active against daptomycin resistant MRSA, ok for MRSA pna
118
Abx with risk of c. Dificile
» High: clindamycin, 3rd generation cephalosporins (e.g., ceftriaxone, cefotaxime), fluoroquinolones (e.g., ciprofloxacin, levofloxacin, moxifloxacin)
» Medium: amoxicillin/clavulanate, other ß-lactams or ß-lactam/ß-lactamase inhibitor combinations, carbapenems (e.g., imipenem)
» Low or minimal risk: metronidazole, vancomycin (IV), aminoglycosides, nitrifurantoin, methenamine, fosfomycin, sulfonamides, tetracyclines.
119
ESBL
• Produced by e.coli, klebsiella, and proteus; plasmid mediated
Risk factors for ESBL- and KPC-associated infections include recent hospitalization, mechanical ventilation, residence in long-term care facility, recent abx use, immunocompromised host, and invasive devices. Also, imported cases from endemic areas.
Tx: carbapenem, tigecycline, colistan
** modified hodge test to detect resistance in a carbapenem
120
KPCs
CRE, which stands for carbapenem-resistant Enterobacteriaceae - high levels of resistance to antibiotics. Klebsiella species and Escherichia coli (E. coli) are examples of Enterobacteriaceae, a normal part of the human gut bacteria, that can become carbapenem-resistant. Types of CRE are sometimes known as KPC (Klebsiella pneumoniae carbapenemase) and NDM (New Delhi Metallo-beta-lactamase). KPC and NDM are enzymes that break down carbapenems and make them ineffective. Both of these enzymes, as well as the enzyme VIM (Verona Integron-Mediated Metallo-β-lactamase) have also been reported in Pseudomonas.
Tx: carbapenem, tigecycline, colistan
121
AmpC, beta lactamase resistance
Produced by acinetobacter, citron after, providencia, enterobacteriacea, serratia, and proteus
- resistance to penicillin and cephalosporins , it is inducible,
Tx: meropenem/imipenem
122
Carbapenems
Moa: A carbapenem antibiotic that inhibits mucopeptide synthesis in the bacterial cell wall, this results in the formation of defective cell walls and osmotically unstable organism which leads to cell lysis.
Resistance: metallo beta lactamases - spread via conjugate plasmids, in klebsiella, E. coli, pseudomonas, citrobacter, salmonella
KPCs, NDM - potent carbapenemase activities
Imipenem/cilastin - blocks dihydropeptide enzyme (beta lactamase) in kidney -> decreases nephrotoxicity
S/e: seizures
Tx: colistan, tigecycline
123
Aminoglycosides
Moa: Aminoglycosides inhibit protein synthesis by irreversibly binding to 30S ribosomal subunit. - BACTERICIDAL
Resistance mech: enzymatic alteration or methylation of ribosomal target or efflux pumps or change in cell wall permeability
Good for most gram negative and some mycobacteria but not for anaerobes or strep pneumo
Requires oxygen to work so not great for abscesses or decr PH
Safety: check peak levels to ensure efficacy and trough levels to minimize toxicity
Prognosis for recovery from ATN is excellent
Irreversible Cochlear or vestibular injury occurs in up to 15%
Ask about FHx of hearing issues on AG before giving
124
Fluoroquinolones
MOA: inhibit DNA topoisomerases (DNA gyrase and topoisomerase 4) by binding to DNA-enzyme complexes, thereby interfering with bacterial DNA replication and some aspects of transcription, repair, recombination, and transposition.
Resistance due to target change in topoisomerase and enzyme modification
Cipro- Good for enteric GN, incl proteus
Levo- treats staph, strep, and atypicals/CAP and GN incl proteus
Moxi - better for mycobacteria, same as levo spectrum but no pseudomonal coverage
Some chelation interactions in GI tract can decrease absorption
S/e: tendonopathy (esp biceps) (more common in older men, copd, and chronic prednisone use) prolongued QTc, risk of c.dificile, retinal detachment, and false positive urine for opiates
125
Abx with concentration dependent killing and long post abx effect (peak concentration/MIC ratio)
Fluoroquinolones
Aminoglycosides
Daptomycin
126
Abx with killing dependent on time above MIC (no persistent effect)?
All beta-lactams
127
Abx with killing dependent on time above MIC and persistent effect?
```
Macrolides
Vancomycin
Tetracycline
Linezolid
Clindamycin
```
128
Tigecycline
MOA: bacteriostatic, protein synthesis inhibitor by binding to the 30S, thereby blocking entry of Aminoacyl-tRNA into the A site of the ribosome during prokaryotic translation.
Deriv of minocycline
Active against MRSA, VSE/VRE, enterobacteriacea, acinetobacter, bacteroides, e.coli
NOT active against pseudomonas nor proteus
Don't use as monotherapy
Good for intraabdominal infxns
129
Colistan
Colistin is polycationic and has both hydrophilic and lipophilic moieties which interact with the bacterial LPS by displacing bacterial counter ions just like a detergent, solubilizing the membrane in an aqueous environment. This effect is bactericidal even in an isosmolaric environment.
Resistance via change in LPS binding sites
PEACHES: pseudomonas, enterobacter/klebsiella, acinetobacter, citrobacter, e.coli, salmonella, shigella
No activity against proteus, burkholderia, serratia,
S/e: can be nephrotoxic and neurotoxic
Broncho spasm when inhaled
130
Drug distribution
Volume of distribution is used in calculating loading dose (better than waiting 3-5 half lives for serious infxns)
Loading dose = volume of distribution x desired peak plasma concentration
131
Botryomycosis
usually described in immunocompromised pts: diabetes mellitus, MDS, cystic fibrosis or HIV
Skin lesions can be ulcerating
Bx: neutrophilic infiltrate with eosinophilic granules
Caused by staph aureus or pseudomonas
Mimics Actinomyces
