Transcript No Slide Title

Adverse Reactions
and Toxicity of
Antibiotics
Cary Engleberg, M.D.
Division of Infectious Diseases,
University of Michigan Medical School
A patient with enterococcal sepsis will be treated with
gentamicin. Which of the following additional
medications will potentiate the risk of
nephrotoxicity?
(more than one answer may be correct)
• Ampicillin
• Vancomycin
• Linezolid
• Daptomycin
• Rifampin
A patient with enterococcal sepsis will be treated with
gentamicin. Which of the following additional
medications will potentiate the risk of
nephrotoxicity?
(more than one answer may be correct)
• Ampicillin
• Vancomycin
• Linezolid
• Daptomycin
• Rifampin
Other commonly-used medications
that potentiate aminoglycoside
nephrotoxicity include. . .
–Amphotericin B
–Cyclosporine
–NSAIDs
–Iodinated IV contrast
A 33 year old woman is hospitalized for fever and back pain
and is diagnosed with E. coli pyelonephritis. She is treated,
based on in vitro susceptibility testing, with oral Bactrim.
Repeat laboratory testing is performed during the first week
after discharge, and the patient’s creatinine is noted to have
risen from 0.9 to 1.4. The patient feels well and appears
normal. What should you do next?
• Stop Bactrim; start ciprofloxacin
• Add ciprofloxacin to Bactrim
• Check for a change in the BUN
• Perform a renal stone protocol CT
A 33 year old woman is hospitalized for fever and back pain
and is diagnosed with E. coli pyelonephritis. She is treated,
based on in vitro susceptibility testing, with oral Bactrim.
Repeat laboratory testing is performed during the first week
after discharge, and the patient’s creatinine is noted to have
risen from 0.9 to 1.4. The patient feels well and appears
normal. What should you do next?
• Stop Bactrim; start ciprofloxacin
• Add ciprofloxacin to Bactrim
• Check for a change in the BUN
• Perform a renal stone protocol CT
Bactrim may interfere
with the renal tubular
secretion of creatinine.
This may cause a rise
in serum creatinine
that is not associated
with a decline in GFR.
Therefore, the BUN will
not have risen with the
creatinine.
No action is required.
A 56 year old man is treated for severe communityacquired MRSA skin and soft tissue infection with
vancomycin 1 gm q12h. On the 3rd day of treatment, the
patient develops a pruritic, maculopapular rash on the
trunk and extremities. The rash persists and worsens with
subsequent infusions. What should you do?
• Stop vancomycin, start
•
•
•
linezolid
Slow the infusion of
vancomycin
Continue treatment,
premedicate with
Benadryl
Change the IV line
A 56 year old man is treated for severe communityacquired MRSA skin and soft tissue infection with
vancomycin 1 gm q12h. On the 3rd day of treatment, the
patient develops a pruritic, maculopapular rash on the
trunk and extremities. The rash persists and worsens with
subsequent infusions. What should you do?
• Stop vancomycin, start
•
•
•
linezolid
Slow the infusion of
vancomycin
Continue treatment,
premedicate with
Benadryl
Change the IV line
The character of this rash (maculopapular), its location on the trunk and
extremities, and the persistence
between doses suggests that this a true
allergy to vancomycin. The drug should
be stopped.
The histamine-related “red man”
syndrome usually produces a transient,
confluent erythema involving the upper
body associated with infusions. This is
not an allergy and can be managed by
slowing the infusion rate.
A 33 year old woman presents with fever and erythema
multiforme involving her face, torso, and extremities,
including the palms and soles. There is erythema of the
conjunctivae and the oral mucous membranes. The tongue
is raw and reddened. Three days ago, she was given an
antibiotic for a minor skin infection. Which was the most
likely antibiotics given?
• Levofloxacin
• Metronidazole
• Dicloxacillin
• Bactrim
• Doxycycline
A 33 year old woman presents with fever and erythema
multiforme involving her face, torso, and extremities,
including the palms and soles. There is erythema of the
conjunctivae and the oral mucous membranes. The tongue
is raw and reddened. Three days ago, she was given an
antibiotic for a minor skin infection. Which was the most
likely antibiotics given?
Sulfonamides are associated with the
Levofloxacin
rare case of Stevens-Johnson
syndrome. The other antibiotics
Metronidazole
mentioned are much less likely to
Dicloxacillin
cause this serious skin reaction. The
patient will eventually desquamate
Bactrim
and have to be treated like a burn
Doxycycline
patient. Needless to say, the
antibiotic must be stopped
immediately.
•
•
•
•
•
A 25 year old man is taking doxycycline for a chlamydia
infection. He takes one 100mg pill at lunchtime and one
immediately before retiring to bed. He now presents to an
urgent care with excrutiating substernal pain at 7:00am.
What is the most likely explanation?
• Chlamydia pericarditis
• Myocardial infarction
• Pill ulcer
• Candida esophagitis
• Hiatal hernia
A 25 year old man is taking doxycycline for a chlamydia
infection. He takes one 100mg pill at lunchtime and one
immediately before retiring to bed. He now presents to an
urgent care with excrutiating substernal pain at 7:00am.
What is the most likely explanation?
• Chlamydia pericarditis
• Myocardial infarction
• Pill ulcer
• Candida esophagitis
• Hiatal hernia
Doxycycline is quite irritating,
and if a pill gets caught in the
esophagus because it is taken
with insufficient water or if the
patient remains supine (as this
patient was in bed), it can
produce an erosive ulcer. Tell
patients to drink plenty of water
and remain upright for at least
1-2 minutes after taking doxy.
A 45 year old diabetic man is treated for pseudomonas
osteomyelitis of a metatarsal bone after a penetrating injury by
a rusty nail through the bottom of his tennis shoe. He is given
IV Zosyn and oral ciprofloxacin. Early in treatment, he
develops a MRSA catheter infection and an episode of C.
difficile colitis. Accordingly, he is also given vancomycin and
oral metronidazole. After 3 weeks of therapy, his ANC drops to
800. Which antibiotic is most likely to be the cause?
• Zosyn
• ciprofloxacin
• vancomycin
• metronidazole
A 45 year old diabetic man is treated for pseudomonas
osteomyelitis of a metatarsal bone after a penetrating injury by
a rusty nail through the bottom of his tennis shoe. He is given
IV Zosyn and oral ciprofloxacin. Early in treatment, he
develops a MRSA catheter infection and an episode of C.
difficile colitis. Accordingly, he is also given vancomycin and
oral metronidazole. After 3 weeks of therapy, his ANC drops to
800. Which antibiotic is most likely to be the cause?
• Zosyn
• ciprofloxacin
• vancomycin
• metronidazole
Prolonged treatment with beta-lactams,
particularly piperacillin, nafcillin, and
ceftriaxone can provoke neutropenia. The
problem will resolve promptly when the
drug is discontinued.
Vancomycin can also cause neutropenia,
but this effect is much less common with
vancomycin than with beta-lactams.
The patient was switched from Zosyn to ceftazidime and
his neutropenia resolved. A week later he had an episode
of nausea with intractable vomiting for 2 hours. The most
likely cause was which of the following?
• Insulin overdose
• Two martinis
• Pseudomonas sepsis
• C. difficile relapse
• Starting lisinopril
The patient was switched from Zosyn to ceftazidime and
his neutropenia resolved. A week later he had an episode
of nausea with intractable vomiting for 2 hours. The most
likely cause was which of the following?
• Insulin overdose
• Two martinis
• Pseudomonas sepsis
• C. difficile relapse
• Starting lisinopril
Metronidazole has a
disulfiram (Antabuse®)-like
effect. If a patient on the
drug ingests alcohol, it may
provoke violent vomiting.
By contrast, vomiting is not a
symptom of C. difficile,
sepsis, or a prominent
adverse effect of lisinopril
An 82 year old man underwent a CABG and developed a
post-op Acinetobacter UTI associated with his Foley
catheter. He received cefazolin for surgical prophylaxis,
cefepime and one dose of tobramycin for his UTI, and was
discharged on ciprofloxacin. At home, he feels dizzy and
restless and was unable to sleep the first night out of the
hospital. What is the likely cause of these new symptoms?
• cefazolin
• cefepime
• tobramycin
• ciprofloxacin
• residual propofol
An 82 year old man underwent a CABG and developed a
post-op Acinetobacter UTI associated with his Foley
catheter. He received cefazolin for surgical prophylaxis,
cefepime and one dose of tobramycin for his UTI, and was
discharged on ciprofloxacin. At home, he feels dizzy and
restless and was unable to sleep the first night out of the
hospital. What is the likely cause of these new symptoms?
• cefazolin
• cefepime
• tobramycin
• ciprofloxacin
• residual propofol
Fluoroquinolones can cause
CNS when they concentrate in
the CNS. They are more likely
to cross the blood-brain barrier
in the elderly, accounting for the
increased frequency of
symptoms in this group.
A 65 year old man is scheduled to receive a 6
weeks course of ampicillin and gentamicin for
enterococcal endocarditis. Which of the following
tests should be done in follow-up?
• weekly CBC & diff.
• weekly creatinine
• weekly gentamicin
•
•
troughs
periodic hearing tests
Weekly blood cultures
A 65 year old man is scheduled to receive a 6
weeks course of ampicillin and gentamicin for
enterococcal endocarditis. Which of the following
tests should be done in follow-up?
• weekly CBC & diff.
• weekly creatinine
• weekly gentamicin
•
•
troughs
periodic hearing tests
Weekly blood cultures
Ampicillin and other beta-lactams may
cause cytopenias or interstitial
nephritis. Gentamicin is notoriously
nephrotoxic, and toxicity can be
avoided by monitoring the creatinine.
Gentamicin also cause otoxicity, and
occasional screening for high
frequency loss will identify this
problem before the patient becomes
conscious of it.
Blood cultures need not be repeated
once they have turn negative, unless
the patient becomes symptomatic
again.
A 34 year old woman undergoes a cholescytectomy in spite
of prolonged therapy for Lyme disease. No stones are
seen at surgery, but her pain resolves. What is the cause
of her RUQ pain?
• biliary Lyme disease
• Lyme hepatitis
• doxycycline
• ampicillin
• ceftriaxone
• herpes zoster
A 34 year old woman undergoes a cholescytectomy in spite
of prolonged therapy for Lyme disease. No stones are
seen at surgery, but her pain resolves. What is the cause
of her RUQ pain?
• biliary Lyme disease
• Lyme hepatitis
• doxycycline
• ampicillin
• ceftriaxone
• herpes zoster
Ceftriaxone is excreted into
the biliary tract and in high
doses may form sludge in
the gallbladder. Sometimes
this produces symptoms
and the false impression of
cholecystitis.
Lyme disease rarely ever
affects the liver or biliary
tract.
A 10 year old boy was bitten on the hand by his neighbor’s
cat and has been placed on Augmentin. Four days into
therapy he develops watery diarrhea (x4 per day). There is
no abdominal pain or fever. What is the most appropriate
course of action?
•
•
•
•
Continue Augmentin; call
back if fever or signs of
inflammatory enteritis
develop.
Discontinue Augmentin;
begin metronidazole
Continue Augmentin; add
metronidazole
Discontinue Augmentin;
obtain stool for C. difficile
toxin
A 10 year old boy was bitten on the hand by his neighbor’s
cat and has been placed on Augmentin. Four days into
therapy he develops watery diarrhea (x4 per day). There is
no abdominal pain or fever. What is the most appropriate
course of action?
•
•
•
•
Continue Augmentin; call
back if fever or signs of
inflammatory enteritis
develop.
Discontinue Augmentin;
begin metronidazole
Continue Augmentin; add
metronidazole
Discontinue Augmentin;
obtain stool for C. difficile
toxin
Watery diarrhea is very
common with Augmentin, and
although it can be associated
with C. difficile, this patient
has no specific symptoms of
colitis at this point. Most of
the time, diarrhea associated
with Augmentin is not due to
C. difficile and will resolve
even if the patient continues
the medication.
An 18 year old man with Crohn’s disease undergoes partial
colectomy for obstruction. A fluid collection containing E.
coli and VRE is drained. Because of problems with IV
access, a decision is made to treat orally with linezolid,
metronidazole, and ciprofloxacin and to follow-up with
periodic CT scans of the abdomen. Over the next 4-6
weeks of treatment, you need to watch for which of the
following adverse reactions?
• Peripheral
•
•
•
•
neuropathy
Thrombocytopenia
Anemia
Optic neuropathy
Tendon pain
An 18 year old man with Crohn’s disease undergoes partial
colectomy for obstruction. A fluid collection containing E.
coli and VRE is drained. Because of problems with IV
access, a decision is made to treat orally with linezolid,
metronidazole, and ciprofloxacin and to follow-up with
periodic CT scans of the abdomen. Over the next 4-6
weeks of treatment, you need to watch for which of the
following adverse reactions?
• Peripheral
•
•
•
•
both linezolid (rare) and
neuropathy
metronidazole
Thrombocytopenia linezolid (common)
Anemia
linezolid (not common)
Optic neuropathy
linezolid (rare)
Tendon pain
Fluoroquinolones rarely
a/w tendon ruptures
End of Program