Patient Case Presentation During Internal Medicine Rotation

1. Can We Spare ‘Em?
Exploring a Carbapenem-Sparing
Strategy in ESBL Bacteremia
Anna Sandler, PharmD Candidate, 2023
1

2. Learning Objectives
 Review the mechanism of beta lactamases and
common organisms that may harbor them.
 Describe the current treatment of extended-
spectrum beta-lactamase (ESBL) bacteremia
infections.
 Evaluate literature and apply findings to a patient
case.
2

3. Patient case: OK is not Okay
OK is an 88-year old female presenting from a nursing home with a
chief complaint of abdominal pain and altered mental status that
were first noticed a few days ago. In the emergency department (ED)
the patient is disoriented and tachycardic.
What are some things you
would like to know?
What labs do you want to
run?
08.30.2022 08.31.2022 Future?

4. Patient case: OK is not Okay
• GERD
PTA VS
PMH Labs
4
• HTN
• HLD
• Dementia
• Hypothyroidism
• Levothyroxine 88
mcg PO daily
• Donepezil 10 mg
PO QHS
• Lisinopril 20 mg
PO daily
• Metoprolol tartrate
12.5 mg PO BID
• Temp: 100.9°F
• HR: 127
• RR: 22
• BP: 93/62
• SpO₂ 98%
• Na: 136
• K: 3.9
• Glucose: 470
• SCr: 0.68
• CrCl= 45
• AST: 33
• ALT: 24
• WBC: 22.3
OK is an 88-year old female presenting from a nursing home with a
chief complaint of abdominal pain and altered mental status that
were first noticed a few days ago. In the emergency department the
patient is disoriented and tachycardic.
What is your
differential at
this point?
08.30.2022 09.02.2022 Future?

5. Patient case: OK is not Okay
• GERD
ID history CTA
UA CXR
5
The ED physician orders urine and blood cultures. The patient
presents similarly to her previous bacteremia infection, so empiric
coverage with meropenem is started and ID is consulted.
What would you
like to know before
we start empiric
antibiotics?
08.30.2022 09.02.2022 Future?
• Leukocytes (+)
• Leukocyte
esterase (trace)
• Nitrite (-)
• Bacteria (few)
• ESBL bacteremia
secondary to
pyelonephritis
(1/2022)
• Negative • Negative

6. Patient case: OK is not Okay
• GERD
ID hx 1/2022 course
UA 8/30/2022 cxs
6
The ID physician is working really hard to be a good steward and
reduce development of resistance to carbapenems. He is considering
switching the patient to piperacillin/tazobactam since it is active
against ESBLs, but consults you as the pharmacist just in case.
08.30.2022 09.02.2022 Future?
• Leukocytes (+)
• Leukocyte
esterase (trace)
• Nitrite (-)
• Bacteria (few)
• ESBL
bacteremia
secondary to
pyelonephritis
(2/2021)
• Treated with
meropenem 500
mg Q8H X 10
days
• Blood: E. coli
• Urine: E. coli
• (+) ST131 and
CTX-M
Centers for Disease Control and Prevention, https://www.cdc.gov/hai/organisms/ESBL.html,
accessed September 13, 2022

7. Clinical Question
7
Is piperacillin/tazobactam an
appropriate agent for OK?
08.30.2022 09.02.2022 Future?

8. Background Previous trials MERINO Conclusions
8
ESBL-producing organisms: a global
health concern
• Commonly produced by gram negative
rod bacteria: Enterobacterales family
(ESBL GNRs)
• ESBL GNRs spread rapidly, may
complicate infections, and even pass on
resistance
• 2017: > 197,000 hospitalized patients;
>9,000 deaths
Centers for Disease Control and Prevention, https://www.cdc.gov/hai/organisms/ESBL.html,
accessed September 13, 2022
Yearly
total cases
Year

9. 9
A Review of Beta Lactam Pharmacology
Tmedweb. https://tmedweb.tulane.edu/pharmwiki/doku.php/betalactam_pharm. Accessed September 13, 2022
Bind penicillin
binding proteins
(PBP)
Inactivate
transpeptidase
Inhibition of
cross-linking
Interruption of
cell wall
synthesis
Background Previous trials MERINO Conclusions

10. 10
Beta lactam resistance: Beta Lactamases
Bioscience Notes. https://www.biosciencenotes.com/extended-spectrum-beta-lactamases-esbls/.
Accessed September 13, 2022
Pngitem. https://www.pngitem.com/middle/immJhbR_two-teams-tug-of-war-hd-png-download/
Accessed September 13, 2022
• Beta lactamases hydrolyze the
beta lactam ring, a core
structural feature needed to bind
to PBPs
• Common enzyme: CTX-M-15
• Risk factors:
• Receipt of antibiotics within last 30-
days
• Residence in a nursing home
• Chronic renal failure
Background Previous trials MERINO Conclusions

11. 11
Mechanisms of Resistance
Penicillins BLBLIs Cephalosporins Carbapenems
Penicillinases and
beta lactamases
X
ESBLs X * X
Carbapenemase X * X X
Organism
ESBLs • Eschiera Coli
• Klebsiella spp.
• Serratia
• Proteus
• Citrobacter
Extended-spectrum beta-lactamases. UpToDate. Accessed
September 13, 2022
Tamma and Rodriguez-Bano (2017), Clin Infect Disease. 2017
Apr 1; 64 (7): 972-980. Accessed September 13, 2022
Background Previous trials MERINO Conclusions
* Beta lactam/beta
lactamase inhibitors
(BLBLIs):
• Piperacillin/tazobactam
• Amoxicillin/clavulanate
• Ceftazidime/avibactam
Used in serine carbapenemase-
resistant organisms (CREs)

12. 12
Pathogenesis of ESBL blood stream
infections
Entry
Failure of host
immune
response
Colonization,
Replication,
Spread
• Evasion
• Compromised
immune system
• Hospitals
• Catheters
• Post-op
• If not cleared
spontaneously from
the bloodstream
Smith DA and Nehring SM. StatPearls. StatPearls Publishing; 2022. Accessed September 19, 2022.
Background Previous trials MERINO Conclusions

13. Clinical Presentation and Diagnosis
•Respiratory
•Hepatic
•Cardiovascular
•CNS
•Renal
Sepsis and Organ dysfunction
•Hypotension and fever
Vitals
•Disorientation
•Signs and symptoms associated with underlying source
(e.g., flank pain in a UTI)
Other
13
UpToDate. https://www.uptodate.com/contents/gram-negative-bacillary-bacteremia-in adults
Accessed September 13, 2022
Diagnosis:
• Non-susceptibility to
ceftriaxone (MIC ≥2
mcg/mL) as a proxy
• Detection of genes
Background Previous trials MERINO Conclusions

14. 14
Initiate prompt
empiric antibiotics
Tailor definitive
therapy and de-
escalate when
appropriate
Treatment
Goals
Background Previous trials MERINO Conclusions

15. 15
Current Treatment of ESBL infections
ESBL infections
Cystitis
Complicated
Carbapenem
Fluoroquinolone
TMP/SMX
Uncomplicated
TMP/SMX
Nitrofurantoin
Amoxicillin/clavulanate
Other Carbapenem Oral step down therapy*
* Oral step down therapy with fluoroquinolones and TMP/SMX may be reasonable if susceptibility is demonstrated, patient is
hemodynamically stable, and source control measures have occurred
Tamma PD et al. 2021. Clin Infect Dis. 2021;72(7):e169-e183. Accessed Sep 19, 2022.
Background Previous trials MERINO Conclusions

16. 16
Current Treatment of ESBL infections
ESBL infections
Cystitis
Complicated
Carbapenem
Fluoroquinolone
TMP/SMX
Uncomplicated
TMP/SMX
Nitrofurantoin
Amoxicillin/clavulanate
Other Carbapenem Oral step down therapy*
• Oral step down therapy with fluoroquinolones and TMP/SMX may be reasonable if susceptibility is demonstrated, patient is
hemodynamically stable, and source control measures have occurred
Tamma PD et al. 2021. Clin Infect Dis. 2021;72(7):e169-e183. Accessed Sep 19, 2022.
Background Previous trials MERINO Conclusions

17. Class/MOA Infections
17
Piperacillin and tazobactam (Zosyn (®)
• Beta
lactam/Beta
lactamase
inhibitor
• Intra-abdominal
• Pneumonia
• Skin and soft
tissue
• Cystic fibrosis
• Sepsis
• Complicated UTIs
Spectrum of
Activity
• Gram positive
• Strep spp.
• MSSA
• Enterococci
• Gram negative
• GNRs
• ?ESBLs
• Anaerobes
Piperacillin and tazobactam: Drug Information. UpToDate. Accessed Sep 19, 2022
Background Previous trials MERINO Conclusions

18. PK AEs, Monitoring
Dosing,
Administration
18
• Adult Vd: 0.243 L/kg
• Both components ~ one
third protein bound
• Adult t1/2
• Piperacillin: 0.7-1.2
hours
• Tazobactam: 0.7-0.9
hours
• Renally excreted
• C. diff. infection
• Nephrotoxicity
• Seizures
• Myelosuppression
• Leukopenia
• Thrombocytopenia
• 3.375 g or 4.5 g
Q8H administered
over 4 hours or…
• 3.375 g or 4.5 g
Q6H over 30 min
Piperacillin and tazobactam (Zosyn (®)
Piperacillin and tazobactam: Drug Information. UpToDate. Accessed Sep 19, 2022
Background Previous trials MERINO Conclusions

19. • Carbapenem
• Binds PBPs to
inhibit cell wall
synthesis
Class/MOA Indications
• Intrabdominal
• Meningitis
• Skin
• Gram-negative
bacteremia
• Cystic fibrosis
• Diabetic foot
infection
19
Meropenem (Merrem (®)
Spectrum of
Activity
• Gram positive
• Strep spp.
• MSSA
• Enterococci
• Gram negative
• GNRs
• ESBLs
• Anaerobes
Meropenem: Drug information. UpToDate. Accessed Sep 19, 2022
Background Previous trials MERINO Conclusions

20. PK ADRs
• Administered as an
IV infusion
• Most cases: 500 mg
Q6H over 30 min
• Critically ill: 1 gm
Q8H over 3 hours
• CNS or MIC > 2: 2
gm Q8H over 3
hours
Dosing, Administration
20
• Time to peak: ~1
hour (tissues); CSF:
2-3 hours
• Adult Vd: 15-20 L
• Protein binding:
~2%
• Adult t1/2: 1 hour
• Renally excreted
(70%)
• CNS toxicity:
seizures, delirium
• C. diff
• Hypersensitivity
reactions
Meropenem (Merrem (®)
Fehrenbacher L, VLRavenna. AAH Adult Meropenem Dosing
Strategy. AAH antimicrobial Stewardship Programs 2019.
Accessed Sep 19, 2022.
Background Previous trials MERINO Conclusions

21. 21
Antibiotic Therapy for Klebsiella pneumoniae
Bacteremia: Implications of Production
of Extended-Spectrum b-Lactamases
David L. Paterson, Wen-Chien Ko, Anne Von Gottberg et al. 2004
Paterson DL, Ko WC, Von Gottberg A, et al. Clin Infect Dis. 2004;39(1):31-37. Accessed Sep 19, 2022.
Background Previous trials MERINO Conclusions

22. 22
Paterson DL, Ko WC, Von Gottberg A, et al. Clin Infect Dis. 2004;39(1):31-37. Accessed Sep 19, 2022.
Background Previous trials MERINO Conclusions
•> 6 years old
•Positive blood cultures for K. pneumonia
Inclusion Criteria
•Prospective, observational study performed in 12 hospitals
•South Africa, Taiwan, Australia, Argentina, USA,
Belgium, Turkey
•Univariate and Multivariate analyses
Design
• Carbapenem therapy versus other antibiotics and 14-day
mortality
Interventions and Outcome

23. Results-Baseline Characteristics
Characteristic
Carbapenem
(n=42)
Non-carbapenem (n=29) P
Male no. (%) 28 (66.7) 14 (48.3) 0.15
Pneumonia no. (%) 9 (21.4) 7 (24.1) 0.79
Intra-abdominal no. (%) 6 (14.3) 10 (34.5) 0.08
UTI no. (%) 8 (19.0) 2 (6.9) 0.18
ICU admission no. (%) 15 (35.7) 13 (44.8) 0.47
Any immunocompromise
no. (%)
24 (57.1) 7 (24.1) 0.006
Previous LOS (median
days)
11.5 15.0 0.16
25
• Total of 455 episodes of K. pneumonia bacteremia
• ESBL-bacteremia: 85 (18.7%)
Paterson DL, Ko WC, Von Gottberg A, et al. Clin Infect Dis. 2004;39(1):31-37. Accessed Sep 19, 2022.
Background Previous trials MERINO Conclusions

24. Results-Antibiotic use and Outcomes
26
• A total of 20 out of the 85 ESBL cases died within 14 days
• Use of carbapenem therapy* (mainly imipenem) associated
with significantly lower 14 day mortality due to ESBL-
producing K. pneumoniae
Primary
outcome
Carbapenem
therapy
Non-Carbapenem
therapy
OR (95% CI)
14-day
mortality
2 (4.8%) 8 (27.6) 0.173 (0.039-
0.755); P= 0.012)
Paterson DL, Ko WC, Von Gottberg A, et al. Clin Infect Dis. 2004;39(1):31-37. Accessed Sep 19, 2022.
Background Previous trials MERINO Conclusions
* Either monotherapy or
combination therapy in 5-day
period after first blood xz

25. Strengths and Weaknesses
28
• Observational trial
• Confounding variables
• Only evaluated K.
pneumoniae bacteremia
• Combination and
sequential carbapenem
therapies
• Multicenter and
international
Paterson DL, Ko WC, Von Gottberg A, et al. Clin Infect Dis. 2004;39(1):31-37. Accessed Sep 19, 2022.
Background Previous trials MERINO Conclusions

26. Conclusions
29
Outcomes
Prospective
Prior
case
reports
Carbapenems recommended
Paterson DL, Ko WC, Von Gottberg A, et al. Clin Infect Dis. 2004;39(1):31-37. Accessed Sep 19, 2022.
Background Previous trials MERINO Conclusions

27. 30
Tamma PD, et al. Clinical Infectious Diseases. Published online January 13, 2015. Accessed Sep 19, 2022.
Carbapenem Therapy Is Associated With Improved
Survival Compared With Piperacillin-Tazobactam for
Patients With Extended-Spectrum β-Lactamase
Bacteremia
Pranita D. Tamma, Jennifer H. Han, Clare Rock et al. 2015
Background Previous trials MERINO Conclusions

28. 31
•Determine impact of empiric piperacillin/tazobactam (PTZ)
treatment compared with empiric carbapenem treatment
before carbapenem definitive treatment on 14-day
mortality in patients with an ESBL bacteremia
Objective
•Single-center, retrospective trial
•John Hopkin’s Hospital 2007-2014
•Cox-Proportional Hazards Model
Design
• Empiric PTZ versus carbapenem prior to definitive
carbapenem
Intervention
Tamma PD, et al. Clinical Infectious Diseases. Published online January 13, 2015. Accessed Sep 19, 2022.
Background Previous trials MERINO Conclusions

29. Results-Baseline Characteristics
Characteristic
PTZ/Carbapenem (n=
103)
Carbapenem (n=
110)
P
Age, mean 48.2 48.0 0.89
UTI (%) 19.3 18.4 0.87
Intra-abdominal (%) 16.3 15.1 0.82
Pneumonia (%) 9.8 11.3 0.77
Catheter-related 46.3 44.1 0.77
Structural lung disease 7.7 7.0 0.86
Immunocompromised 54.6 57.9 0.92
33
• Adjusted Cohort of ESBL-bacteremia: N= 213
0.
Tamma PD, et al. Clinical Infectious Diseases. Published online January 13, 2015. Accessed Sep 19, 2022.
Background Previous trials MERINO Conclusions

30. Results
34
Characteristic Multivariable analysis
Adjusted HR 95% CI, P value
PTZ 1.92 1.07-3.45; P=
0.03
14-day mortality
Tamma PD, et al. Clinical Infectious Diseases. Published online January 13, 2015. Accessed Sep 19, 2022.
• 17 deaths (17%) in PTZ group, 9
(8%) in the carbapenem group
PTZ
Carbapenem
Background Previous trials MERINO Conclusions

31. Strengths and Weaknesses
35
• Retrospective study
• Only looked at empiric
therapy
• Single-center
• Data from > 7 years
• Data from > 7 years
Tamma PD, et al. Clinical Infectious Diseases. Published online January 13, 2015. Accessed Sep 19, 2022.
Background Previous trials MERINO Conclusions

32. Conclusions
36
PTZ inferior to
carbapenems
Outcomes
Prior
case
reports
Researchers
• Consider early carbapenem
therapy in patients at high
risk of invasive ESBL
infections
Tamma PD, et al. Clinical Infectious Diseases. Published online January 13, 2015. Accessed Sep 19, 2022.
Background Previous trials MERINO Conclusions

33. Effect of Piperacillin-Tazobactam vs.
Meropenem on 30-day Mortality for
Patients with E. Coli or Klebsiella
pneumoniae Bloodstream Infection and
Ceftriaxone Resistance
Patrick N.A. Harris; Paul A. Tambyah; David C. Lye et al.
2018
37
Harris et al. 2018. JAMA. 2018 Sep;320(10):984-994. Accessed September 10, 2022
Background Previous trials MERINO Conclusions

34. 38
•Evaluate the effect of a carbapenem-sparing regimen for
bloodstream infections caused by ceftriaxone or cefotaxime-
non-susceptible E. coli or Klebsiella spp.
Objective
•International, multicenter, open-label, non-inferiority
randomized controlled trial
Design
• Piperacillin/tazobactam versus meropenem
Intervention
Harris et al. 2018. JAMA. 2018 Sep;320(10):984-994. Accessed September 10, 2022
Background Previous trials MERINO Conclusions

35. •≥ 18 years old
•≥ One positive blood culture not susceptible to ceftriaxone
or cefotaxime but susceptible to piperacillin/tazobactam
Inclusion Criteria
•Allergy to either antibiotic
•Expected survival ≤ 96 hours
Exclusion Criteria
39
Harris et al. 2018. JAMA. 2018 Sep;320(10):984-994. Accessed September 10, 2022
Background Previous trials MERINO Conclusions

36. Randomization with stratification
40
Harris et al. 2018. JAMA. 2018 Sep;320(10):984-994. Accessed September 10, 2022
Randomization
E. coli
Pip/tazo
meropenem
Klebsiella spp.
Pip/tazo
meropenem
Strata:
• Infecting organism
• Source of infection (urine or other)
• Severity of disease
1:1
1:1
Background Previous trials MERINO Conclusions

37. 41
Harris et al. 2018. JAMA. 2018 Sep;320(10):984-994. Accessed September 10, 2022
Timeline
Follow 30 days after randomization
Treatment X 4-14 days, daily clinical monitoring
Piperacillin/tazobactam 4.5 g IV
Q6H
Meropenem 1 g IV Q8H
Randomization
Everyone
Blood cxs: day 3 or if
febrile  day 5
Background Previous trials MERINO Conclusions

38. Outcome Description Statistical Test
Primary • All cause mortality at 30 days post
randomization
Secondary • Time to clinical and microbiologic
resolution
• Clinical and microbiologic success at
day 4
• Relapsed bloodstream infection
Outcomes-Efficacy
14%/10%
mortality in
control/study
Noninferiority
margin: 5%
454
patients 80% power
43
Harris et al.2018. JAMA. 2018 Sep;320(10):984-994. Accessed September 10, 2022
• Population= per
protocol (≥ 1 dose)
• Tests: Proportion
analyses risk
difference + 1-sided
97.5% CI
Non-inferiority=
Upper bounds of
97.5% CI < 5%
Background Previous trials MERINO Conclusions

39. 44
Data and Safety Monitoring Board (DSMB)
Enrollment
start
Interim
Analysis #1
Interim
Analysis #2
Interim
Analysis #3
Enrollment
start
Interim
Analysis #1
Interim
Analysis #2
Interim
Analysis #3
Planned
Reality
Harris et al. 2018. JAMA. 2018 Sep;320(10):984-994. Accessed September 10, 2022
50 patients 150 patients 340 patients
STOP
Background Previous trials MERINO Conclusions

40. Results-Baseline Characteristics
Characteristic Pip/tazo (n=188) Meropenem (n=191)
Median age (IQR) 70 (55-78) 69 (59-78)
E. Coli no. (%) 162 (86.2) 166 (86.9)
E. Coli –less severe no. (%) 159 (84.6) 162 (84.8)
K. pneumoniae no. (%) 26 (13.8) 25 (13.1)
K. pneumoniae-less severe no. (%) 23 (12.2) 25 (13.1)
Urinary source no. (%) 103 (54.8) 128 (67.0)
Intrabdominal source no. (%) 34 (18.1) 28 (14.7)
Mod-severe renal dysfunction no. 31 (16.5) 30 (15.7)
ICU admission no. (%) 13 (7.0) 14 (7.5)
Empiric BL/BLI no. (%) 38 (20.2) 49 (25.7)
Empiric Carbapenem no. (%) 26 (13.8) 28 (14.7)
Other empiric therapy no. (%) 124 (66.0) 114 (59.7) 45
Harris et al. 2018. JAMA. 2018 Sep;320(10):984-994. Accessed September 10, 2022
Background Previous trials MERINO Conclusions

41. Results-Primary Outcome
Endpoint Pip/tazo (n=187) Meropenem
(n=191)
Risk Difference
(97.5% CI)
30-day all-cause
mortality no. (%)
23 (12.3) 7 (3.7) 8.6% (-∞ to 14.5%)
P = 0.90
46
Primary analysis
Harris et al. 2018. JAMA. 2018 Sep;320(10):984-994. Accessed September 10, 2022
Background Previous trials MERINO Conclusions

42. Results-Secondary Outcomes
47
Harris et al. 2018. JAMA. 2018 Sep;320(10):984-994. Accessed September 10, 2022
Endpoint Pip/Tazo (177) Meropenem (185)
Clinical +
microbiologic
success
121 (68.4) 138 (74.6)
Clinical+ Microbiologic success
• Not statistically significant
• Between-group difference:
-6.2 ; 95% CI (-15.5% to 3.1%)
Background Previous trials MERINO Conclusions

43. Results-Secondary Outcomes
48
Harris et al. 2018. JAMA. 2018 Sep;320(10):984-994. Accessed September 10, 2022
Endpoint Pip/Tazo (187) Meropenem (191)
Microbiologic
relapse
9 (4.8) 4 (2.1)
Relapse
• Not statistically significant
• Between-group difference:
2.7 (-1.1 to 7.1)
Background Previous trials MERINO Conclusions

44. Results-Safety
49
Harris et al. 2018. JAMA. 2018 Sep;320(10):984-994. Accessed September 10, 2022
• Meropenem: 3/191 (1.6%)
Serious Adverse Event Association to study drug? Treatment group
Rash requiring cessation of drug Yes Pip/tazo
Renal dysfunction requiring
cessation of drug
Yes Pip/tazo
Dyspnea, fever/chills/ malaise,
neg. cx
Possibly Pip/tazo
Upper limb venous thrombosis No Pip/tazo
Readmission with colitis Possibly Pip/tazo
Serious AEs
• Piperacillin/tazobactam: 5/188 (2.7%)
No fatal AEs
linked to either
study drug
Background Previous trials MERINO Conclusions

45. Strengths and Weaknesses
50
• Multicenter
• Randomization with
stratification
• Similar infectious
source and organism
to patient OK
Harris et al. 2018. JAMA. 2018 Sep;320(10):984-994. Accessed September 10, 2022
• Prior empiric treatment with
meropenem or pip/tazo
• Lower representation of older
individuals
• Few comorbidities represented
• Low high-risk disease
representation
• Unblinded
Background Previous trials MERINO Conclusions

46. Conclusions
51
Pip/tazo not recommended
DSMB
Primary
+ per
protocol
X non-
inferior.
Researchers
• Definitive treatment with
piperacillin/tazobactam did not
result in noninferior 30-day
mortality
• Findings do not support use of
pip/tazo in ESBL bacteremia
Presenter
• Results of this trial are consistent
with prior observations and confirm
that carbapenems should currently
be the mainstay of gram-negative,
ESBL bacteremia infections.
Harris et al. 2018. JAMA. 2018 Sep;320(10):984-994. Accessed September 10, 2022
Background Previous trials MERINO Conclusions

47. Here we go again: OK is not Okay
• GERD
ID hx 1/2022 course
UA 8/30/2022 cxs
52
The ID physician is working really hard to be a good steward and
reduce development of resistance to carbapenems. He is considering
switching the patient to piperacillin/tazobactam since it is active
against ESBLs, but consults you as the pharmacist just in case.
• Leukocytes (+)
• Leukocyte
esterase (trace)
• Nitrite (-)
• Bacteria (few)
• ESBL
bacteremia
secondary to
pyelonephritis
(2/2021)
• Treated with
meropenem 500
mg Q8H X 10
days
• Blood: E. coli
• Urine: E. coli
• (+) ST131 and
CTX-M
• MIC meropenem
< 2 mcg/mL
Centers for Disease Control and Prevention, https://www.cdc.gov/hai/organisms/ESBL.html,
accessed September 13, 2022
Background Previous trials MERINO Conclusions

48. ESBL
bacteremia
CrCl = 45
Not critically ill
MIC < 2
Recommend
Meropenem
53
Fehrenbacher L, VLRavenna. AAH Adult Meropenem Dosing Strategy. AAH antimicrobial Stewardship Programs 2019.
Accessed Sep 19, 2022.
Background Previous trials MERINO Conclusions
Approach to
treatment

49. 54
Fehrenbacher L, VLRavenna. AAH Adult Meropenem Dosing Strategy. AAH antimicrobial Stewardship Programs 2019.
Accessed Sep 19, 2022.
Yahav D et al. Clinical Infectious Diseases. 2019;69(7). Accessed Sep 19, 2022.
Meropenem 500 mg IV
Q8H infused over 30 min X
7-14 days
MIC < 2,
CrCl 45
Uncomplicated
Not
critically
ill
What will help us guide
duration?
When do we consider
increased dosing/extended
infusion?
What do we need to monitor
?
Background Previous trials MERINO Conclusions

50. Background Previous trials MERINO Conclusions
Predicting the Future
Antibiotic(s) Trial Info
• Piperacillin/tazobactam
• Meropenem
PETERPEN trial: PipEracillin
Tazobactam Versus
mERoPENem for Treatment of
Bloodstream Infections Caused
by Cephalosporin-resistant
Enterobacteriaceae
• Recruiting, estimated
completion date: April 2024
• Randomized, controlled open-
label trial
• Non-inferiority study
Promising in-vitro /post-hoc
studies: Ceftazidime-avibactam
Ceftolozane-tazobactam
Eravacycline
Farrell DJ, et al. Antimicrob Agents Chemother. 2013
Dec;57(12):6305-10.
Levasseur P, et al. Antimicrob Agents Chemother. 2015
Apr;59(4):1931-4.

51. Background Previous trials MERINO Conclusions
Thank you for your
time!
56

52. 57
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Appendix
Paterson DL, Ko WC, Von Gottberg A, et al. Clin Infect Dis. 2004;39(1):31-37. Accessed Sep 19, 2022.
Univariate analysis in
Paterson et al. 2004

55. 60
Appendix
Harris et al.2018. JAMA. 2018 Sep;320(10):984-994. Accessed September 10, 2022
Stratification in
MERINO trial

56. Can We Spare ‘Em?
Exploring a Carbapenem-Sparing
Strategy in ESBL Bacteremia
Anna Sandler, PharmD Candidate, 2023
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