What is the cell wall of prokaryotes (like bacteria) made of?
proteins, lipids, peptidoglycans
What is the cell wall of eukaryotes (such as fungi) made of?
mannans, glucans (polysaccharides)
Which type of organisms have ergosterol, where is it, and what is its purpose?
in the cell membrane
it is a target or binding site for many antifungals
What is the difference between the cell walls of G(+) and G(-) bacteria?
G(+) have a thick layer of peptidoglycan with many cross links
G(-) have a thinner layer of peptidoglycan with fewer cross links
What is a gram stain used for?
to classify bacteria as (+) or (-) on the basis of stain retention of the cell's peptidoglycan layer
G(+) stain purple
G(-) stain red
Name the 2 different types of media used to identify or differentiate between bacteria ad some examples of each.
Differential - Identity of an organism - e.g. Macconkey inhibits growth of G(+) and supports G(-) growth, especially GIT orgs; CHROM differentiates betw Candida spp
Selective - select specific bacteria from mixed cultures - e.g. Thayer-Martin allows Neisseria to grow
Name the 2 types of biochemical tests and what the results tell us.
1. Coagulase - if (+) the org is S. aureus; if (-) the org is other Staph spp
2. Catalase - if (+) the org is staphylococci; if (-) the org is streptococci
What is the purpose of the Lancefield serogroup test?
To group Strep spp. It can tell us where the infx came from.
What do respiration/fermentation tests tell us?
if a bacteria has the ability to use lactose or glucose to produce acid or alcohol
e.g. of non-fermenters - Pseudomonas, Acinetobacter
What does a hemolysis test on blood agar tell us about a bacteria?
If alpha, they are partially hemolytic - a small zone is cleared. e.g. S. pneumoniae
If beta, they are completely hemolytic - a large zone is cleared. e.g. S.pyogenes
If gamma, they are not hemolytic.
What do serologic tests detect?
Nonspecific or specific antibodies
Presence and quantity can aid in identification of pathogen
If an unknown bacteria is a cluster of G+ cocci, what test might be used to determine the identity?
A coagulase test.
If (+) they'd probably be Staph aureus
If (-) they'd probably be Staph epidermidis
If an unknown G+ bacteria is cocci in pairs or chains, what is its likely identity?
Streptococci or Enterococcus
If they are Streptococci, they could be Alpha or Beta hemolytic.
If Alpha, likely identity is S. pneumoniae or Viridans group
If Beta, Group A may be S pyogenes, Group B may be S. agalactiae, Group D may be S. bovis, or others
Gram + bacilli are unusual, but what are some of the more likely of this type of bacteria we may encounter?
Gram negative bacilli are usually what type of bacteria?
Examples of coliform enterobacteriaceae
Examples of non-coliform enterobacteriaecae
Are enterobacteriaceae fermentors or non-fermentors?
Name some non-fermentors
Is Neisseria G(+) or (-)? Aerobic or anaerobic? Cocci or Bacilli?
Aerobic G(-) cocci
Name 3 G(+) anaerobes
Name one G(-) anaerobe and why it is a concern
Concerning because it is inherently resistant to Abx
Name 3 atypical bacteria and the reason they're considered atypical
Chlamydia spp - cell wall similar to G- but lack peptidoglycan
Mycoplasma spp - lack a cell wall
Legionella spp - G- but difficult to stain; difficult to grow on standard media; use serologic testing to identify
What is MIC? What is MBC?
Minimum Inhibitory Concentration - the lowest conc of an agt that inhibits the visible growth of an organism
Minimum Bactericidal Concentration - the lowest conc of an agt that results in a 99.9% reduction in colony forming units (kills the bacteria)
What does a bimodal susceptibility distribution indicate?
If the MBC is ______ times the MIC, the organism is tolerant
What are breakpoint values?
they help evaluate MIC results and guide clinical decisions
based on pkin and pdyn of drug, MIC distribution in the bacteria population, clinical efficacy
tell if bacteria is susceptible, intermediate, or resistant to particular drugs
What is an antibiogram?
a table telling the bug, drug, % susceptibility to various drugs
Is the true MIC ever determined?
Define virulence and virulence factors
Virulence is a quantitative measurement of pathogenicity - the likelihood a pathogen will cause a disease
Virulence factors are factors that allow a microbe to establish itself on or in a host and enhance its potential to cause disease
What are the 5 steps of pathogenesis?
1. Colonize the host
2. Gain access to the host
3. find a niche within the host
4. Evade host defenses
5. Multiply within the host
What are adhesions? Name 4.
Microbial structures that mediate adherence of binding of a microbe to the host. Susceptible hosts have receptors for the adhesions.
Why might microbes produce biofilms? What are 2 pathogens that commonly produce biofilms?
to facilitate binding to target cells
to elude host defenses and Abx
How does a microbe maintain viability once inside a host?
Must evade host defenses by:
Producing antiphagocytic capsule
Producing toxins or destructive enzymes
What are exotoxins? What are endotoxins?
Exotoxins - bacterial proteins that the bacterium releases during exponential growth that are toxic for target cells
Endotoxins - intracellular and cell-associated toxic components of G(-) microbes - lipopolysaccharides
List 3 factors that have contributed to the emergence of antimicrobial resistance
1. Inappropriate antibiotic use by clinicians
2. lack of pt education or ineffective education
3. widespread antimicrobial use in the food production industry
Difference between primary and secondary resistance
Primary is naturally occurring and no exposure to antimicrobials is required; secondary follows exposure to antimicrobials
Primary is predictable; secondary is not
Primary is also known as inherent, intrinsic, or native; secondary is also known as acquired
How does secondary resistance come about?
Selection of resistant subpopulations
Genetic alterations - spontaneous mutations or acquisition of new genetic material
List 3 common mechanisms of antimicrobial resistance
1. antibiotic inactivating enzymes
2. alteration of antimicrobial target or active site
3. alterations in bacterial cellular membranes
how do beta-lactamases work?
inactivate beta-lactam antibiotics by splitting the beta-lactam ring at the amide bond
What are ESBLs and what are they active against?
Active vs. all beta lactams except cephamycins, cefepime, carbapenems
Inhibited by beta-lactamase inhibitors such as sulbactam, clavulanate, and tazobactam
Are AmpC-type beta-lactamases inhibited by beta-lactamase inhibitors?
Examples of resistance by alteration of the antimicrobial target or active site
penicillin binding proteins (PBPs)
ribosomal binding sites
cell wall precursors
Examples of resistance by alterations in bacterial cellular membranes
porin channels (change in # or size)
What is MRSA's resistance secondary to? What is the treatment of choice?
vancomycin (linezolid and daptomycin may also be used)
What may be a good treatment option for VISA?
What therapy is necessary for a cidal effect in enterococcus? Name 3 treatment strategies.
combo therapy with an aminoglycoside (with penicillin or vanco - these are static alone)
1. vanco, linezolid, daptomycin, and streptogramins
2. intermittent vs. continuous infusions of beta-lactams and vanco
3. traditional vs once-daily dosing of AGs
List 6 strategies to prevent the spread of antibiotic resistance
1. patient education
2. knowledge of local susceptibility patterns
3. prescriber education
4. develop guidelines for appropriate antimicrobial usage
6. hand washing
Can penicillins still work in pen-resistant S. pneumoniae?
Do AGs exhibit time-dependent or concentration-dependent bactericidal activity?
What are the 2 major toxicities assoc with AGs? What factor is best correlated to toxicity?
ototoxicity & nephrotoxicity
prolonged course of AG tx
What are the main goals of high-dose, extended-interval (once daily) AG dosing? How is the dosing interval determined?
Optimize bactericidal activity
Dosing interval determined and evaluated using a nomogram
(basically a LD is given every time and the conc goes down to 0 in between doses each time)
How many half-lives does it take to reach steady state?
approx 5 (assuming renal fxn is stable)
How do we empirically dose vanco?
based on pt's weight (TBW) and CrCl
Does Vanco exhibit concentration-dependent or concentration-independent killing?
concentration-independent (time-dependent) - time above MIC
What are the usual vanco target drug concentrations?
Trough: 5-20 mg/ml
What is "red man syndrome"? How can it be prevented?
Hypotensive rxn assoc with rapid infusion of vancomycin. D/T a vanco-induced histamine release.
Prevent by slowing the infusion and/or premedicating with an antihistamine
A pt has a sinus infx susceptible to both amoxicillin and ampicillin. Which do you choose and why?
Amoxicillin because it has better bioavailability, you can give it with or without food, there is less frequent dosing than with ampicillin (bid or tid as opposed to qid)
An MD wants to prescribe Augmentin 500 mg TID for a pt with recurrent sinusitis. The pt can't swallow Augmentin 500 mg tabs. He writes for Augmentin 250 mg 2 tabs TID. Is this a good idea? Why?
No. Too much clavulanic acid - leads to diarrhea.
A pt has a severe pen allergy. Can the pt receive azetreonam? A carbapenem?
Which FQs inhibit DNA gyrase? Topoisomerase IV? What is the advantage of inhibiting Topo IV?
All FQs inhibit DNA gyrase
3rd and 4th Generation FQs inhibit Topo IV
Advantage - less resistance and enhanced G(+) activity
Why shouldn't pediatric pts generally receive FQs? Which pediatric pts sometimes receive FQs?
Because they can cause cartilage malformations
A pt develops a sternal wound infx following bypass surgery after an acute MI. He is placed on vanco. The pt is now complaining of severe itching on his face and neck. The nurse just hung the vanco bag on this pt about 10 minutes ago. He has been receiving vanco for about 7 days. What is the most plausible explanation for this event? How can you treat/prevent this rxn?
Red Man Syndrome
slow rate of infusion, give diphenhydramine, give fluids, dilute, change Abx
What is the difference in indications for vanco PO and IV?
PO is for C. diff
IV is for G(+) resistant infx like MRSA and MRSE
Describe the ototoxicity and nephrotoxicity that can occur with AGs
Ototoxicity - Cochlear and Vestibular - May or may not be reversible.
Nephrotoxicity - selectively toxic to proximal tubule - can cause acute tubular necrosis and glomerular nephrotoxicity
Related to prolonged duration of therapy or concurrent ototoxic or nephrotoxic drugs
Which macrolide would you not use for bacteremia because of its extensive tissue penetration?
Why should you drink a full glass of water with TCs and not take any doses at bedtime?
to prevent esophageal ulcerations
Which of the following Abx can be used to treat CAP in a pt on antiarrhythmics? moxifloxacin, azithromycin, doxycycline
no, no, yes
You have a pt on clindamycin who developed severe diarrhea and is C difficile (+) by toxin assay. How would you manage the diarrhea? List abx that can be used to treat AAD.
Stop the clindamycin
Give metronidazole 1st line PO x 10 days
Vanco is 2nd line x 10 days
List unique SEs of metronidazole. What drug intx would you caution a pt about?
According to PORT scores, which risk classes treat pts as inpatients, and which treat as outpatients?
Risk Class I, II: outpatient
Risk Class III: outpatient or brief inpatient
Risk Class IV, V: inpatient
Explain the CURB-65 Index and what it is used for
Used to determine need for hospitalization and need for ICU admission
Score based on how many of the following a patient has:
BUN > 20 mg/dL
Resp Rate >/= 30 breaths/min
Low BP (systolic < 90 or diastolic </= 60)
Age >/= 65 years
If the score is 0-1 treat as outpatient
If the score is 2 admit to ward
If the score is 3 or more admit to ICU
Risk factors for drug-resistant S.pneumoniae
extremes of age (< 5 or > 65)
antibiotic use within the past 3 months
exposure to a child in daycare
recurrent otitis media
multiple medical comorbidities
Outpatient treatment for pneumonia
If no recent Abx exposure, treat with macrolide (azithromycin or clarithromycin) or doxycycline
If pt has comorbidities or Abx exposure within last 3 months, treat with macrolide plus high-dose amoxicillin (or amox/clav) OR a FQ (levo, moxi, gemi)
Inpatient treatment of pneumonia in the medical ward
Same if pt has had recent abx exposure or not.
Macrolide plus beta-lactam OR FQ
Options for beta-lactams - cefotaxime, ceftriaxone, ampicillin/sulbactam, ertapenem
Inpatient treatment of pneumonia in the ICU
If Pseudomonas infx is not an issue, give a beta lactam + either a macrolide or a FQ
If Pseudomonas infx is an issue, give Anti-pseudomonal agt plus ciprofloxacin, OR an Antipseudomonal agt plus an AG + a FQ or macrolide Antipseudomonal agents are piperacillin/tazobactam, imipenem, meropenem, cefepime
Organisms likely to cause pneumonia
S. pneumoniae, M. pneumoniae, C. pneumoniae, H. influenzae
What is the minimum duration of therapy for pneumonia? How long should a pt be afebrile?
Min 5 days
afebrile for at least 48-72 hours
CAP assoc signs of clinical instability
temp > 37.8
pulse > 100 bpm
resp rate > 24 breaths/min
systolic bp < 90
O2 sat < 90%
inability to maintain oral intake
mental status changes
What is HAP
hospital acquired pneumonia - it occurs 48 h or more after admission and was not incubating at the time of admission
What is VAP?
ventilator-associated pneumonia - it arises more than 48-72 hours after endotracheal intubation
What is HCAP?
Healthcare associated pneumonia
Risk factors for HCAP
pt hospitalized in an acute care hospital for > 2 days within 90 days of infection
pt resided in a nursing home or LTC facility
Pt received recent IV Abx, chemotherapy, or wound care within the past 30 days
pt attended a hospital or hemodialysis clinic
Empiric antibiotic therapy for nosocomial pneumonia
if not late onset or no risk factors for MDR pathogens, treat with ceftriaxone, FQ, Amp/sulbactam, or ertapenem
if late onset (>/= 5 days) or risk factors for MDR pathogens, give an anti-psa ceph, or an anti-psa carbapenem, or pip/tazo PLUS an anti-psa FQ or an AG (also give vanco or linezolid if MRSA is suspected)
What should be ordered in all pts with suspected pneumonia?
a chest x-ray - helpful with diagnosis, assessing need for hospitalization, and possible etiology
note: a CXR is not very valuable for monitoring pt response to therapy b/c it lags behind the clinical picture by about 3 days
What are the major antigenic determinants of influenza A viruses?
hemagglutinin - mediates attachment and entry of virus into host cells
neuraminidase - facilitates the spread of virons
3 steps in the pathogenesis of influenza
1. virus enters human via inhalation of virus-containing respiratory secretions
2. Virus is internalized in resp tract epithelial cells
3. Replicates within cells and is then released throughout the body
Clinical course of influenza
1-4 days of incubation
abrupt onset of sx
fever, chills, headache, myalgia, persist for about 3 days
resp sx may persist 3-4 d after fever subsides
convalescence 1-2 weeks
What is the duration of infectivity for influenza?
5 days after illness onset for adults
Children shed virus for several days before onset to > 10 days after onset of sx
What is ILI?
characterized by a fever AND a cough AND/OR a sore throat in the absence of a known cause
What drugs are approved for treatment and prophylaxis of influenza?
Neuraminidase inhibitors (oseltamivir and zanamivir)
must be administered within 48 h of symptom onset
Which influenza medication is safe in pregnancy?
Which influenza med is CI'd in asthma pts?
who should receive the influenza vaccine?
anyone who wants to reduce the risk of getting influenza
kids 6 mo - 18 yr
those > 50 years old
those with chronic medical conditions
residents of LTC facilities
those with conditions that increase risk of aspiration
persons who live with or care for high-risk persons (health care workers, household contacts of those < 5 and > 50 years, esp those < 6 mo, or with other high risk conditions)
What are the different ways to classify intraabdominal infx?
1. by location - can be localized (e.g. abscess, abdominal penetration trauma wound) or generalized (e.g. peritonitis)
2. by complexity - can be uncomplicated (involving single site/organ, not into peritoneal cavity - e.g. appendicitis, cholecystitis) or complicated (involving several sites/organs in add'n to source of infx; infx extends into peritoneal cavity - e.g. peritonitis, intra-abdominal abscess)
3. by acquisition locale - can be community-acquired or health-care associated (nosocomial)
Which type of IAIs usually require both source control and antimicrobial therapy?
Community-onset health care-associated (IAI) infx include cases involving pts with at least one of the following health care risk factors. How is hospital-onset infx different?
1. presence of an invasive device at time of admission
2. hx of MRSA infx or colonization
3. hx of surgery, hospitalization, dialysis, or residence in a LTCF in the 12 mo preceding the culture date
Hospital-onset infx - pts have positive culture from a normally sterile site obtained more than 48 h after admission to hospital
Is appendicitis complicated or uncomplicated? How is it treated?
managed by surgical intervention
What is cholecystitis?
sudden inflammation of gallbladder (often not infectious)
When does IAI result from diverticulitis?
When a perforation occurs and colonic contents move into the peritoneal cavity
How is peritonitis classified?
Primary: aka SBP (spontaneous bacterial peritonitis) - no identified source - in adults with liver disease and/or ascites
Secondary: most common form - almost always community-acquired - may affect anyone
Tertiary: complication of improperly managed primary or secondary peritonitis or other abdominal medical procedures - healthcare facility-acquired - occurs in critically ill or immunocompromised pts
Peritoneal-dialysis associated: only in pts who receive peritoneal dialysis
Common causes of peritonitis and abscess
Which classes of peritonitis require urgent medical attention?
all of them require urgent medical attention
pts with secondary and tertiary are usually in acute distress and their conditions deteriorate rapidly
pts with primary or peritoneal dialysis-associated are not usually in acute distress
What is ileus?
the absence of peristalsis in the intestine
because primary peritonitis (SBP) has highly variable and non-specific presentation, how is it diagnosed? When do we initiate empiric antibiotic treatment?
Must use paracentesis with lab testing of the ascites to confirm diagnosis
PMN cell count of > 250/mm3 is diagnostic of SBP and warrants empiric antibiotic therapy
What can happen in severe cases of IAI?
if no intervention is performed, multi-organ failures, severe systemic inflammatory response (SIRS), death
What are the most common anaerobes involved in peritonitis?
Describe the microbiology of IAI
Primary (SBP): usually monomicrobial, common orgs are Streptococci spp, E. coli, and Klebsiella spp
Secondary: usually polymicrobial with a mix of aerobic and anaerobic bacteria
Tertiary: associated with nosocomial microbes such as MRSA, VRE, Pseudomonas, coagulase-negative staph, candida (fungi), and those assoc with secondary
Peritoneal dialysis-associated: often involves enteric organisms and those found on the skin such as staph
Abscess: anaerobes commonly
What is the typical treatment for uncomplicated IAIs?
surgical source control only
antimicrobials not required unless there is anticipated complication
For appendicitis only prophylactic and perioperative abx for the surgery are required - no full course of routine abx is necessary
For bowel injuries d/t penetrating or blunt trauma that are repaired within 12 hours and with no complications, antibiotics should be used for less than 24 hours post surgery (and prophylactic and perioperative abx)
Treatment for abscess
abx therapy is just an adjuvant
Treatment for secondary or tertiary peritonitis
Infx source control
Empiric IV abx ASAP
4-7 day course of abx therapy
Treatment for SBP
May need IV fluids and/or surgical source control
If fluid from ascites confirms diagnosis of SBP (PMN > 250) abx therapy is needed
DOC is IV cefotaxime
beta lactam/beta lactamase inhibitor combos and carbapenems would work but are too broad spectrum, so are inappropriate as empiric tx. Also avoid AGs.
Optimal duration of therapy is 5 days minimum
What is the treatment for peritoneal dialysis-assoc peritonitis?
may need IV fluids and surgical source control
culture the dialysate to id the orgs, then determine abx susceptibilities
empiric IV abx - followed by monotx with vanco, or a 1st gen ceph (e.g. cefazolin) given IP (would use vanco if pt is allergic to pens or if MRSA is suspected or confirmed)If more severe, can add AG given IP to the ceph
Can admin the abx QD (intermittent dosing), and the dwell time must exceed 6 hours each time
Duration of tx is usually 10-14 days
For IP abx therapy which abx are ok to mix in the same dialysis solution? Which should not and why?
vanco, AGs, cephs can all be mixed in same dialysis sol'n
AGs should not be mixed with pens because of chemical incompatibility (acid/base rxn)
What is the duration of therapy for community-acquired peritonitis?
What abx is the main component in combo therapy for community-acquired IAI? Which agents should not be used?
metronidazole is main component (mostly used with a ceph or levo)
Don't use amp/sulbactam d/t E.coli resistance, cefotetan and clindamycin d/t Bacteroides resistance, AGs b/c other agents are less toxic and equally or more effective
Empiric antifungal tx is not necessary
Don't use oral agents initially
Appropriate options for healthcare-acquired complicated IAI (tertiary peritonitis)