ABX Problems and Pitfalls Flashcards
Is Penicilin G narrow spectrum or broad?
narrow
Is Pen G penicillinase susceptible?
Yes
What are some common bugs Pen G is used against?
common Strep, meningococcal, G+ rods, spirochetes
What is the drug of choice for syphilis?
Pen GProcain and benzithine are forms of Pen G administered IM (extended t1/2)
What is Pen V used for primarily?
oropharyngeal infections
Are Nafcillin and Oxacillin narrow spectrum or broad? Are they penicllinase susceptible?
Narrow; no
What are Nafcillin and Oxacillin commonly used for?
staphylococcal infections
Are Ampicillin and Amoxicillin narrow or broad spectrum? Penicillinase susceptible?
Broad; yes
What are some common bugs that Ampicillin and Amoxicillin are used for?
E. coli, Proteus mirabilis, H. influenzae, and Moraxella catarrhalis
T or F. The gastric acid environment of the stomach neutralizes penicillins
T, limiting their oral use
MOST penicillins are eliminated unchanged renally. Exceptions?
Nafcillin and ampicillin undergo hepatic elimination
Side effects of Penicillins?
All- allergic reactions Ampicillin and amoxicillin- rashAmpicillin, Amox, and Clav- diarrheaAll- hemolytic anemiaHigh dose piperacillin, ticaracillin or nafcillin- platelet dysfunction(disrupts calcium)Rare- Oxacillin, Ampicillin, Amoxcillin- hepatic damage, seizures and muscle irritability after high dose in renally impaired patients
Should Penicillins be taken with a full glass of water?
Yespenicillins don’t effect CYPs at all
Do Penicillins have an effect on OCs? If so, what is it? If not, why?
Yes, they decrease the effectiveness of oral contraceptives (mechanism is via enterohepatic circulation). Advise to take additional precautionary measures
What other antibiotic is a major inhibitor of OCs?
rifampin
What would Cefazolin (1st gen) be used to treat?
Staph, strep, E.coli, K. pneumoniae
Which 2nd generation cephalosporin is effective against H. influenzae?
Cefuroxime
Which 2nd generation cephalosporins are effective against Bacteriodes spp.?
Cefoxitin and cefotetan
Which bug are Cefotaxime, Ceftriaxone, and Ceftizoxime (3rd gen) particularly ineffective against?
Pseudomonas aeruginosa. Effective against other gram-
What are other cephalosporins that are more effective against Pseudomonas aeruginosa?
Ceftazidime (3rd gen) and Cefepime (4th gen)
How are most cephalosporins excreted?
renal. Thus, would need to alter dose if patient had kidney insufficiency
Which cephalosporin is not renally excreted?
Ceftriaxone- biliary excretion. Thus, no need to adjust dose for renal insufficiency
How are most cephalosporins given?
IV, some PO
Only a select few (4) reach CSF levels high enough to treat meningitis. Namely:
Ceftriaxone, Cefotaxime CeftazidimeCefepime
How should you advise a patient to take cephalosporins?
full treatment course should be taken. Take with food or milk to lessen GI distress
How should you advise patients taking cephalosporins regarding alcohol use?
Do not consume alcohol within 72 hr
Why shouldn’t a patient on cephalosporins drink alcohol?
they have been known to induce disulfram-like effect (especially with cefotetan)
What is a disulfram-like effect?
Acetaldehyde toxic effects are characterized by facial flushing, nausea, vomiting, tachycardia and hypotension, symptoms known as acetaldehyde syndrome, disulfiram-like reactions or antabuse effects.Antabuse is given to alcoholics to induce these symptoms to stop them from drinking
What are some adverse effects of cephalosporins that should be reported immediately?
severe diarrhea, vomiting, skin rash, mouth sores, mouth swelling, breathing issues
What are some very frequent adverse effects of ALL cephalosporins?
1) thrombophlebitis with IV administration 2) Serum-sickness like reaction with prolonged parenteral administration
What is a very frequent adverse effect that of cephalosporins that is especially true of ceftixime?
moderate-severe diarrhea
What are some occasional adverse effects of cephalosporins?
1) hypersensitivity reaction2) Pain at injection site
What are some occasional adverse effects of cefaclor (cephalosporins) in children?
rash and arthritis “serum sickness”
Other possible rare cephalosporin adverse effects?
hemolytic anemia, renal dysfunction, seizures, encephalopathy
What is a possible effect of long term cefazolin use?
bleeding dysfunction
Is Aztreonam beta-lactamase resistant?
Yes
What kinds of bugs is Aztreonam used for?
Klebsiella, pseudomonas, Serratia
What would Aztreonam never be used to treat?
gram positive bacteria or anaerobes- INEFFECTIVE
Are Carbapenems (Imipenem and Meropenem) susceptible to beta-lactamases?
low-susceptibility
What is Imipenem administered with?
Cilastin, a renal dehydropeptidase inhibitor
What are carbapenems commonly to treat?
gram +ve cocci, gram -ve rods and anaerobes
How Aztreonam administered?
IV/IM
How is Aztreonam excreted?
renal elimination with minor hepatic metabolic conversion
How are Carbapenems eliminated?
renal. Thus, dose adjustment for renal dysfunction necessary
How are Carbapenems administered?
IM/IV or IV (Meropenem)
What are some potential adverse effects of Aztreonam?
1) injection site reaction2) GI pain3) elevated ALT or AST4) Rare- thrombocytopenia
What are some potential adverse effects of Carbapenems?
1) Injection site pain2) fever3) urticaria, rash, or pruritis (meorpenem)4) GI disturbance5) Rare- seizures (Meropenem MUCH LESS LIKELY to cause seizures compared to Imipenem), CDAD (C. diff associated disease)
How is vancyomycin given usually?
parenteral- well-distributed in tissue
When would vanco be given orally?
for C. diff infection
How is vanco eliminated?
unchanged in urine- thus, dose adjustment in renal failure necessary
What are some frequent adverse effects of vanco?
thrombophlebitis, fever, and chills
What are some occasional adverse effects of vanco?
loss of hearing with large or prolonged dosing (more than 10 days)renal damageRed Man syndrome
What are some rare adverse effects of vanco?
peripheral neuropathy, hypotension, exfoliative dermatitis, thrombocytopenia
What is Fosfomycin used for? How does it work?
used primarily for uncomplicated UTI. It is given orally and eliminated via urine. In the urine it is effective enough to kill urinary pathogens (i.e. MIC is reached)
What are some possible adverse effects of fosfomycin?
diarrhea and vaginitis
What is daptomycin used to treat? How is it given?
gram+ infection (MRSA and vanco-resitant entercoccus faecalis/faecium); parenteral
How is dapto eliminated?
renal.
Side effects of dapto?
fever, headache, rash, injection site reactionRarely- elevated CPK and rhabdomyolysis, peripheral neuropathy, CDAD
Dapto use should be monitored closely. Especially if the patient is taking ______.
HMG-CoA reductase inhibitors
What are some common uses of tetracyclines?
chlamydiae, mycoplasma, rickettsiae spirochetes, H. pylori
How is Tetracycline given?
PO
How is Tigecycline given?
IV
How are tetracyclines eliminated?
renal and hepatic doxycycline- hepatic
Is tissue distribution of tetracyclines good? What about CSF?
good penetration of tissues including CSF
Side effects of tetracyclines?
1) GI distress (less for doxycycline)2) severe renal damage with IV3) tooth staining; photo-toxicity4) RARE-Hairy tongue- bacterial or yeast outgrowth (common in heavy tobacco users, oxidizing mouthwashes)
What side effect is especially common minocycline?
vomiting and vertigo (CNS effect)
What are macrolides and ketolides commonly used to treat?
commonuity acquired pneumonia, pertussis, cornyebacteria, chamydiarenal and hepatic elimination
What is clarithromycin inactive against?
gram- spp.
What would telithromycin be used for?
mild-moderate community-acquired pneumonia ONLY
How is clarithromycin given?
PO
How is telithromycin given?
PO
How are erythromycin and azithromycin given?
PO/IV
Where are macrolides and ketolides commonly distributed to?
wide tissue distribution with accumulation in macrophages, spleen, liver, kidneys, and particularly the lungs
Which macrolides/ketolides are CYP3A4 inhibitors?
erthyromycin and telithromycin,and clarithromycin to a lesser extent
How does azithromycin affect CYPs?
It does not
What are SOME drugs you would want to monitor closely/adjust dosing if given concurrently with macrolides?
1) Midazolam with E or C2) Clozapine 3) Theophylline4) Warfarin
Common adverse reactions to macrolides?
Reversible dose-related hearing loss, GI pain, increased hepatic enzymes, abnormal vision, injection site reactions
How can macrolides affect the heart?
QT prolongation, Torsades de pointes
Many experts advise against telithromycin use. Why?
can cause serious and fatal hepatotoxicity and cause serious visual disturbances
What disease can telithromycin greatly exacerbate?
Myasthenia gravis
How should tetracyclines be taken?
take full course, with full glass of water, no alcohol, avoid diary products (Milk)**avoid sun or tanning lamps
What would clindamycin be used for?
skin, soft tissue, and anaerobic infections outside CNS
How is clindamycin administered?
PO/IV- good distribution with both
How is clindamycin eliminated?
mostly hepatic with minimal renal excretion.
Would you need to adjust clindamycin dose for renal dysfunction? Hepatic dysfunction?
Hepatic ONLY
What are some possible side effects of clindamycin?
diarrhea, hypersensitivityoccasional CDADRarely blood dyscrasia, hepatotoxicity, polyarthritis
What is Chloramphenicol commonly used to treat?
H. influenza, Salmonella, CNS bacteriodes infections, vanco-resistant Enterococcusgood for pneumococcal or meningococcal meningitis
How is Chloramphenicol given?
IV
How is Chloramphenicol eliminated?
more than 90% are glucuronidated in the liver; and then fecal elimination
In what group is Chloramphenicol especially dangerous in? Why?
neonates have immature hepatic function leading to drug accumulation (Grey Baby Syndrome- cyanosis, hypotension, and often death)
How is Chloramphenicol distributed?
widely distributed; lowest levels in brain and CSF
Side effects of Chloramphenicol?
black box warning- serious and fatal blood dyscrasia; some reports of aplastic anemia ending in leukemia
What is Linezolid used to treat?
Enterococcus faecium and faecalis, including vanc. resistantMRSA, Staph. epi and penicillin resistant Strep pneumoniaegiven PO or IV
How is Linezolid distributed?
widespread with great CSF penetration and good brain penetration
Side effects of Linezolid?
reversible thrombocytopenia with prolonged administration, peripheral and optic (nerve) neuropathy (loss of vision), serotonin syndrome with pts taking SSRIs (selective serotonin re-uptake inhibitors)
How do aminoglycosides work?
block formation of translation initiation complex, causing mis-readingwork in an oxygen-dependent manner
Are aminoglycosides effective against gram positive bugs?
No, gram- only. Synergistic with beta-lactams
What is Amikacin (aminoglycoside)used for?
generally reserved for bacteria known or suspected of being resistant to the other aminoglycosides
What is Genatmicin (aminoglycoside) used for?
hospital-acquired infections; H. influenzae, M. catarrhalis, Shigella
What is Tobramycin used for?
similar to gentamicin;In vitro studies suggest higher activity vs. P. aeruginosa & lower activity vs. Serratia
How are amingoglycosides administered?
parenteral (neomycin cant because of toxicity)
How are aminoglycosides eliminated?
100%- renal function is critical here
Side effects of aminoglycosides?
BLACK BOX WARNING:*1) neuro and ototoxicity (ear)- avoid with concurrent neurotoxic agents 2) nephrotoxicity– avoid with concurrent nephrotoxic agents 3) Neuromuscular blockade- respiratory paralysis possibleagranulocytosis, anaphylactoid reactions, dermal reactions
What do you need to monitor when giving aminoglycosides?
BUN/Cr, serum drug levels, audiometry
What is clotrimoxazole given for?
urinary tract infections, shigellosis, otitis media, traveller’s diarrhea, bronchitis, Pneumocystis jiroveci pneumonia, Nocardia, MRSA infections
How is clotrimoxazole given?
PO, or IV for serious infection
How is clotrimoxazole eliminated?
equal hepatic and renal. Dose adjustment for both dysfunction
Side effects of clotrimoxazole?
Allergic reactions are common esp. with HIV Occasional: elevated SCr, hyperkalemia ; renal insufficiency
What are the fluoroquinolones?
ciprofloxacin, ofloxacin, levofloxacin, Gemifloxacin, Moxifloxacin
How is cipro eliminated?
hepatic and renal with significant CYP metabolism• Inhibit CYP1A2, 3A4
How is olfoxacin eliminated?
mostly renal and uncharged
How is levofloxacin eliminated?
mostly renal and uncharged
How is gemifloxacin eliminated?
eliminated largely unchanged; stool over urine
How is moxifloxaxin eliminated?
eliminated largely as parental conjugates in stool and urine
Which fluoroquinolones require dose adjustment in renal dysfunction?
All but moxifloxacin
Side effects of fluoroquinolones?
BLACK BOX* tendonitis and tendon rupture risk in all ages, especially in elderly, patients on corticosteroids and pts with heart/lung/kidney transplantmay exacerbate weakness in pts with myasthenia gravis
Rare side effects of fluoroquinolones?
cardiovascular toxicity, arrythmias, and QT prolongationacute renal failureDermatologic rashes, Stevens-Johnson syndrome and photosensitivity
What event can cause increased accessibility to the CSF via inhibited P-gp activity?
inflammation of meningesAlso there is less CSF production to block drug access and the inflammed meninges are leakier
Which antimicrobials should not be given during pregnancy?
clarithromycin, tetracyclines, and sulfonamides (Clotrimoxazole)
How are quinupristin-dalfopristin administered?
IV
How are quinupristin-dalfopristin eliminated?
mostly heptic with minimal renal
Is quinupristin-dalfopristin disrtibution good?
yes
Drug interactions with quinupristin-dalfopristin?
strong CYP3A4 inhibitor
Side effects of quinupristin-dalfopristin?
frequent thrombophlebitis, arthralgia, myalgianot common b/c of use of linezolid or dapto
The post-antibiotic effect states that continued inhibition of microbial expansion/activity after serum drug level falls. How?
1) slow recovery after reversible nonlethal damage to cell structures 2) persistence of the drug at a binding site or within the periplasmic space3) the need to synthesize new enzymes before growth can resume4) postantibiotic leukocyte enhancement (PALE)
