Download Auto-antibody formation against the Angiotensin Type 1 Receptor

Case Presentation – January 28th, 2015
Brian Skinner, PharmD
PGY-1 Pharmacy Resident
St. Vincent Indianapolis Hospital
Patient Case

JD is a 62yoM presenting to St. Vincent
Hospital with altered mental status, lethargy,
and fever

PMH: Meningioma s/p resection 10/2015.
 Patient developed a CSF leak and had a VP shunt
placed
 Developed shunt infection in October due to infection
with Enterobacter cloacae
 Treated with cefepime IV 1g q 8 hours
Patient Case

Home Medications











Acetaminophen 650mg po q 6 hour PRN
Aspirin 81mg po daily
Calcium 600+D po daily
Dexamethasone 2mg po daily
Divalproex sodium ER 1000mg po daily
Famotidine 20mg po BID
Glipizide ER 5mg po daily
Hydrocodone/APAP 5/325 po q 4 hours PRN pain
Milk of Magnesia 30mL po daily PRN
Ondansetron 4mg po q 8 hour PRN nausea
Simvastatin 20mg po daily
Patient Case
140
99
15
4.3
29
0.71
145
10.1
12.4
38.4
CSF Fluid Analysis
Color
Colorless
Appearance
Clear
RBC
WBC
Glucose
T. Protein
11
67
49
59
273
Clinical Course
Empiric Therapy
Cefepime 2g IV q 8 +
Vancomycin 1g IV q 12
Meningiomas
Largest subgroup of
all intracranial tumors
 Usually benign, slow
growing neoplasms
 Surgical resection is
common therapy
 Radiation can be
used if incomplete
resection

Forum (Genova). 2003;13(1):76-89.
VP Shunts

Derived from the Middle
English word shun

Diverts CSF fluid from
ventricles to peritoneum

Various shunts are
available
 Nomenclature is based
on where it drains
Ventricular Shunting Procedures. In: Youmans Neurological Surgery. 6th ed. 2011.
VP Shunts – Complications

Intraventricular hemorrhage

Obstruction

Over drainage of CSF

Infection
AACN Adv Crit Care. 2013;24(1)6-12.
CSF Shunt & Drain Infections. In: Principles & Practice of Infectious Disease. 8th ed. 2015.
Etiology of Infection
Most Common
Coagulase negative
Staphylococci spp.
Staphylococcus aureus
Other Etiologies
Candida albicans
Corynebacterium jeikeium
Streptococcus spp.
Mycobacterium spp.
Pseudomonas aeruginosa Stenotrophomonus spp.
Clin Infect Dis. 2004;39:1267-84.
AACN Adv Crit Care. 2013;24(1)6-12.
CSF Shunt & Drain Infections. In: Principles & Practice of Infectious Disease. 8th ed. 2015.
Empiric Treatment Options
Microorganism
Coag-negative Staph.
spp. & MRSA
Antibiotic
Vancomycin
Dosing
15mg/kg every 812 hours
Gram-negative Bacilli
(including
Pseudomonas spp.)
Ceftazidine
2g every 8 hours
Cefepime
2g every 8 hours
Meropenem
2g every 8 hours
N Engl J Med. 2010;362:146-54.
Clin Infect Dis. 2004;39:1267-84.
AACN Adv Crit Care. 2013;24(1)6-12.
Susceptibility Data
β -Lactamase Production
First “penicillinase” discovered in 1940 in
E. coli
 AmpC β-lactamase has been found in a
variety of organisms

 Chromosomal AmpC
 Plasmid AmpC
Clin Microbio Rev. 2009;22(1):161-182.
Verigene®
Antimicrob Agents Chemother. 2010;54(3):969-976.
AmpC β-lactamase Induction
B-Lactam Antibiotic
Penicillin, aminopenicillins, cefazolin
Inducer?
Strong
Substrate?
Good
Cefotaxime, ceftriaxone, ceftazidime,
cefepime
Cefoxitin, Imipenem
Weak
Poor
Strong
Poor
Induction involves a complex chemical
pathway that results in hyperproduction of
AmpC β-lactamase
 Binding of β-lactam antibiotic prevents
synthesis of intracellular compounds that
“turn off” AmpC β-lactamase production

Clin Microbio Rev. 2009;22(1):161-182.
Inducibility
Most cases reported
in the context of
Enterobacter spp.
 Informally labeled
“ESCPM” group

 Enterobacter spp.
 Serratia spp.
 Citrobacter spp.
 Providencia spp.
 Morganella spp.
Clin Microbio Rev. 2009;22(1):161-182.
Eur J Clin Microbiol. 1987;6(4)439-445.
Stable Derepression of AmpC Production
Permanent hyperproduction of AmpC βlactamase
 Antibiotic use selectively allows depressed
mutants to proliferate

Clin Microbio Rev. 2009;22(1):161-182
Stable Derepression of AmpC Production
Ann Intern Med. 1991;115(8): 585-590.
Cefepime and AmpC

Cefepime is structurally similar to
ceftazidime, but has decreased
susceptibility to AmpC β-lactamases

In vitro activity of 995 isolates in Australia
showed comparable susceptibilities to
carbapenems against AmpC-producing
species
Int J Antimicrob Agents. 2013;41:236-49.
Int J Antimicrob Agents. 2012;40:297-305.
Cefepime and AmpC
Antibiotic
Ceftriaxone
Cefepime
Pip/Tazo
Meropenem
Ciprofloxacin
Total
Responders
4 (47.1%)
16 (88.9%)
5 (71.4%)
11 (100%)
6 (100%)
43 (84.3%)
Non-responders
3 (42.9%)
2 (11.1%)
2 (28.6%)
0 (0%)
0 (0%)
8 (15.7%)
“…the clinical data proved that cefepime is a
reasonable alternative to carbapenems” for blood
stream infections caused by Enterobacter cloacae
Int J Antimicrob Agents. 2013;41:236-49.
Cefepime and AmpC

Inoculum effect
 Significant MIC increase when microbial
population size is increased

Case reports of treatment failure have
been seen in patient’s with a high inoculum
infection
J Antimicrob Chemother. 2004;54:1130-33
Carbapenems and Valproate

Significant interaction exists between
valproic acid and carbapenem antibiotics

Administration of carbapenems remarkably
decreases serum concentrations of
valproate

Mechanism of interaction is not well
defined

Interaction can not be overcome by
additional valproate administration
Ther Drug Monit. 2012;34:599-603
Carbapenems and Valproate
Design
• Retrospective study of patients receiving
carbapenem antibiotics and VPA from
2008-2010
Inclusion
Criteria
• Received VPA to control or prevent
seizures
• Had VPA concentrations checked regularly
• Received a carbapenem antibiotic
Exclusion
Criteria
• Stopped VPA before receiving carbapenem
antibiotics
• Use of drugs known to interact with VPA
Ther Drug Monit. 2012;34:599-603
Results
Ther Drug Monit. 2012;34:599-603
Patient Case





Shunt was externalized and changed to VP
drain
Divalproex was changed to levetiracetam
500mg po BID
4 days after starting meropenem, CSF
cultures were negative
VP shunt was replaced 8 days after
negative culture
Patient was discharged 3 days after shunt
replacement and will continue meropenem
for an additional 6 days as at an acute
rehab facility
Clinical Course
Empiric Therapy
Cefepime 2g IV q 8 +
Vancomycin 1g IV q 12
Day 3: E. cloacae
positive culture
Ceftriaxone 1g IV q 12
Day 4
Cefepime 2g IV q 8
Day 17: E. cloacae
positive culture
Meropenem 2g IV q 8
Case Presentation – January 28th, 2015
Brian Skinner, PharmD
PGY-1 Pharmacy Resident
St. Vincent Indianapolis Hospital