Dr. James Cutrell gives part 2 of his Intro to Antibiotics during the Back to Basics lecture series

1. INTRO TO ANTIBIOTICS:
PART II – CLINICAL PEARLS
July 28, 2015
Dr. James Cutrell
Infectious Diseases

2. Outline
• Empiric Rx for Clinical Syndromes
• Pathogen-Directed Rx
• Pharmacologic Strategies
Thanks for all the great questions
submitted!
Prize Winner: R3 Julie Lin

3. Questions to Ask When Starting an Abx
• Is an antibiotic indicated based on clinical findings?
• Have appropriate cultures been sent before starting
antibiotics?
• What is appropriate empiric Rx based on the most likely
pathogens?
• Are there important host factors to consider?
• What is the best drug dose and route of administration?
• What is the anticipated duration of therapy?
Reese RE et al. Principles of Antibiotic Use. In: A Practical Approach to Infectious Diseases 5th ed. 2003

4. Empiric Rx for Clinical Syndromes
• Community Acquired Pneumonia
• Nosocomial Pneumonia (HCAP/HAP/VAP)
• Bacterial meningitis
• Diabetic foot infection and osteomyelitis
• Neutropenic fever
• Severe sepsis / septic shock
• CAUTI / Asymptomatic Bacteriuria

5. Question #1
• A 35 yo male with no significant PMHx is admitted with 2 days of
acute onset SOB, cough, fevers, and rigors. Admission WBC is 22k
and CXR confirms a RLL lobar consolidation. Arrival BP is 85/55 and
remains low despite initial aggressive fluid resuscitation in ED.
Sputum gram stain is negative; sputum and blood Cx are pending.
• What are guideline-recommended empiric abx Rx?
1) Levofloxacin
2) Ceftriaxone + Vancomycin
3) Ceftriaxone + Azithromycin
4) Vancomycin + Piperacillin-tazobactam

6. CAP: Empiric Rx
• What are the most common pathogens in CAP?
- Strep pneumoniae - Mycoplasma
- H. influenzae - Chlamydophila
- Respiratory viruses - Legionella (severe)
“Atypicals”
Setting Empiric Rx*
Outpt, healthy w/o recent abx Macrolide or doxycycline
Outpt, comorbid disease Respiratory FQ OR
PO Beta-lactam + macrolide
Inpt, non-ICU IV Beta-lactam + macrolide OR Resp FQ
Inpt, ICU IV Beta-lactam + macrolide OR
IV Beta-lactam + Resp FQ
Without specific risk factors, MRSA or resistant GNR are rare in CAP pts
* Oral BL= amox or amox/cl; IV BL= CTX, cefotaxime, amp/sulb, ertapenem
IDSA CAP Guidelines. Clinical Infectious Diseases 2007; 44:S27–72.

7. CAP: When to consider other bugs?
• When to consider PseA or other resistant GNRs?
• Bronchiectasis or COPD + frequent steroids/antibiotics
• Chronic alcoholism
• Recent hospitalization in last 90 days (see HCAP)
• When to consider community acquired MRSA?
• Risk factors: ESRD, IVDA, recent FQ, recent or concurrent flu
• Presentation: Cavitary/necrotizing PNA or rapid pleural effusion;
Skin lesions; Gross hemoptysis; Severe, multilobar PNA in young
• CA-MRSA PNA is dramatic, not subtle, presentation
• MRSA and above GNR easily seen on adequate
sputum Gram stain and Cx
IDSA CAP Guidelines. Clinical Infectious Diseases 2007; 44:S27–72.

8. Nosocomial Pneumonia
• General term which includes:
• Hospital-acquired PNA (HAP)
• PNA beginning 48 hours after admission
• Ventilator-associated PNA (VAP)
• PNA beginning 48-72 hours after intubation
• Healthcare-associated PNA (HCAP)
• PNA in non-hospitalized patient with extensive HC contact and
perceived risk for MDR bacteria based on specific criteria
ATS/IDSA Guidelines for Management of HAP, VAP, HCAP. AJRCCM 2005.

9. Nosocomial PNA Empiric Rx Algorithm
• MDR Risk Factors:
• Hospitalization ≥ 5 days
• Abx in prior 90 days
• Immunosuppressive
disease or therapy
• High frequency of
community or hospital
abx resistance
• Presence of HCAP risk
factors
ATS/IDSA Guidelines for Management of HAP, VAP, HCAP. AJRCCM 2005.

10. Defining Risk Factors for MDR Pathogens
Original HCAP Criteria Proposed PNA-specific criteria*
•Hospitalization for ≥ 2 days in last 90 d
•Residence in NH or LTAC
•Home infusion or IV Abx
•Hemodialysis
•Home wound care
•Family with MDR pathogen
•Immunosuppressive disease or Rx
•Hospitalization for ≥ 2 days in last 90 d
•Abx use in last 90 days
•Non-ambulatory status
•Tube feedings
•Immunocompromised status
•Use of gastric acid suppresants
Adapted from Wunderink RG, Waterer GW. N Engl J Med 2014;370:543-551.
* Risk for MDR pathogens increases with ≥ 2 risk factors and
risk factors for MRSA likely unique

11. Empiric Abx Rx for Early-onset HAP/VAP
without MDR Risk Factors
Potential Pathogens Recommended Abx
Streptococcus pneumoniae
Haemophilus influenzae
MSSA
Abx-sensitive enteric GNR
Escherichia coli
Klebsiella pneumoniae
Enterobacter spp.
Proteus spp.
Serratia marcescens
Ceftriaxone 2 gm IV q day
OR
Levofloxacin 750 mg IV q day or
Moxifloxacin 400 mg IV q day
OR
Ampicillin/sulbactam 3 gm IV q 6h
OR
Ertapenem 1gm IV q day
ATS/IDSA Guidelines for Management of HAP, VAP, HCAP. AJRCCM 2005.
Same abx recommended regardless of disease
severity

12. Empiric Abx Rx for Late-onset HAP/VAP
or with MDR Risk Factors
Potential Pathogens
Early-onset pathogens +
Pseudomonas aeruginosa
ESBL Klebsiella pneumoniae
MRSA
Acinetobacter spp.
Stenotrophomonas maltophila
Legionella pneumophila
ATS/IDSA Guidelines for Management of HAP, VAP, HCAP. AJRCCM 2005.
Same abx
recommended
regardless of disease
severity
Combination Abx Therapy

13. Bacterial Meningitis
• Empiric Rx determined by age and other host risk factors
Pt Factors Suspected
Organisms
Empiric Abx
Age 2-50 yo Strep pneumo
N. Meningitidis
Ceftriaxone 2 q12h +
Vancomycin (high dose)
Age > 50 or risk factors
(Immunosuppressed,
alcoholism, steroids)
Strep pneumo
N. Meningitidis
Listeria
Aerobic GNR
Ceftriaxone 2g q12h +
Vancomycin (high dose) +
Ampicillin 2g q4h
Nosocomial (Post-NSG,
CSF shunt)
Staph aureus
CONS
GNR (incl. PseA)
Vancomycin (high dose) +
Cefepime 2g q8h or
Meropenem 2 g q8h
Remember piperacillin-tazobactam does not achieve good penetration
into the CSF
# High dose vancomycin = Loading dose followed by 30-45 mg/kg divided in 2-3 doses
IDSA Bacterial Meningitis Guidelines. Clinical Infectious Diseases 2004; 39:1267–84.

14. Diabetic Foot Infections
Severity Empiric Rx (Representative agents) Duration #
Mild Clinda, Cephalexin, Amox-Clav, Doxy,
TMP-SMX
1-2 wks, po
Moderate* Amp-sulbactam, ertapenem, ceftriaxone,
FQ + clinda
2-3 wks, +/-
IV at start
Severe MRSA coverage (vanc, linezolid, dapto) +
GNR/anaerobic (pip-tazo or carbapenem
or cefepime/flagyl)
2-3 wks, + IV
at start
* Assess for risk factors for MRSA or PseA which may alter empiric Rx
# Presence of diabetic foot osteomyelitis will require longer duration
IDSA Diabetic Foot Infection Guidelines: CID 2012; 54(12)132-73.
If patient does not have signs of sepsis, hold abx and get deep
tissue or bone biopsy for Cx!

15. Neutropenic Fever
• Low-risk, outpatients: Cipro + Amox/Clav
• Inpatients: Anti-PseA beta-lactam monotherapy
• Cefepime 2 g IV q8h
• Pip-Tazo 4.5 g q6h or 3.375 g q8h Extended infusion
• Meropenem 2 g q8h or Imipenem 1 g q6h
• Do not routinely add MRSA or double PseA coverage
unless PNA or shock!
• When to add Vancomycin: PNA, suspected skin or catheter
infxn, shock; De-escalate Vanc if Cx negative at 2-3 d
• Consider addition of antifungals if persistent fever > 4 d
IDSA Neutropenic Fever Guidelines. Clinical Infectious Diseases 2011;52(4):e56–e93.

16. Severe Sepsis/Septic Shock: Principles
• Goal is “ the administration of effective IV abx within 1st hour of
recognition of septic shock (grade 1B) or severe sepsis (grade 1C).”
• Initial empiric Rx should include “one or more drugs active against all
likely pathogens with adequate penetration into tissues presumed to
be source of sepsis (grade 1B).”
• Abx should be “reassessed daily for potential de-escalation (grade 1B).”
• “Combination therapy, when used empirically for severe sepsis,
should not be continued more than 3-5 days” but de-escalate to
single-agent therapy as soon as susceptibilities are known (grade 2B).
• Source control undertaken in first 12 hours if feasible (grade 1C).
Surviving Sepsis Campaign International Guidelines: 2012 Crit Care Med Feb 2013; 41(2): 580-637.

17. Severe Sepsis/Septic Shock: Empiric Rx
• Empiric Rx depends on host factors, recent abx exposure, allergies, clinical
syndrome and likely site of infection, local antibiogram and pt’s prior
infections or colonization
• Combination therapy recommended in neutropenics with severe sepsis, those
with prior MDR pathogens, and respiratory failure or septic shock patients
(grade 2B)
• Practically, this usually means vancomycin + anti-Pseudomonal beta-lactam +
either aminoglycoside or anti-Pseudomonal FQ
Surviving Sepsis Campaign International Guidelines: 2012 Crit Care Med Feb 2013; 41(2): 580-637.
Clinical Scenario Suggested Potential Regimen
GI source Vanc + Pip/Tazo + AG or FQ
GU/Pulmonary source Vanc + Pip/Tazo or Cefepime + AG or FQ
CNS source Vanc + Cefepime or Carbapenem +/- FQ
Prior or high-risk for ESBL Vanc + Carbapenem + Aminoglycoside

18. Question #2
• 72 yo diabetic male with PMHx of BPH presents for
routine clinic visit. He notes that his urine has been
darker than usual but denies dysuria, frequency, or pain
with urination. No fevers and PE is normal. UA shows
15-20 WBC, + LE and Urine Cx shows ≥ 105 cfu/mL ESBL
E. coli in the urine.
• What is the recommended Rx?
1) Meropenem
2) Ertapenem
3) Fosfomycin
4) Bactrim
5) No treatment indicated

19. CAUTI and Asymptomatic Bacteriuria
• CAUTI
• Signs or symptoms of UTI + ≥ 103 cfu/mL of ≥ 1urinary pathogen
• CA-ASB: asymptomatic + ≥ 105 cfu/mL of ≥ 1urinary pathogen
• Presence or absence of pyuria or cloudy, malodorous urine does
NOT distinguish CA-ASB from CAUTI
• Should NOT screen for or treat CA-ASB except in select situations
(see below)
• Asymptomatic Bacteriuria (ASB)
• Screening and treatment only in pregnancy or prior to urologic
procedure (TURP or bleeding anticipated)
• Pyuria or certain colony threshold (≥ 105 cfu/mL) are NOT an
indication for treatment

20. Pathogen-Directed Rx
• MRSA
• VRE
• ESBL
• Mycobacteria

21. MRSA
• PO options acceptable for SSTI or
completion of osteo Rx; IV
preferred for invasive disease
• Vanc empiric drug of choice in most
serious infections
• If vanc intolerance or failure:
• PNA Linezolid, Ceftaroline
• Bacteremia/Endocarditis
Daptomycin, Ceftaroline (?)
• CNS  Linezolid
• Osteo  Dapto, Ceftaroline
MRSA
Oral TMP-SMX
Clindamycin
Doxycycline, Minocycline
Rifampin (only in combination)
Quinolones (variable susc.)
Linezolid,Tedizolid
IV Vancomycin
Linezolid (PO/IV)
Daptomycin
Ceftaroline
Tigecycline
Quinupristin-Dalfopristin
Dalbavancin
Oritavancin
Tedizolid (PO/IV)
Vanc MIC ≥ 2 associated with
higher rates of Rx failure so
consider alternative agents
IDSA MRSA Guidelines. Clinical Infectious Diseases 2011;1–38.

22. MRSA Bacteremia: Basics
• Uncomplicated bacteremia
• Must meet all of following: No IE (by TEE); No prostheses; Negative f/u
blood cultures at 2-4 days; Defervescence within 72 h of effective
therapy; No metastatic infection
• Vancomycin or Daptomycin for minimum 2 weeks
• Complicated bacteremia or endocarditis
• 4-6 weeks at minimum
• No benefit to adding gentamicin or rifampin for native valve IE
• Treatment failure
• Generally defined as persistent bacteremia around day 7 of therapy
(median time to clearance of MRSA bacteremia is 7-9 days)
• May also define failure as patient getting worse on current tx
• Remember SOURCE CONTROL!!!
IDSA MRSA Guidelines. Clinical Infectious Diseases 2011;1–38.

23. VRE
• Vancomycin-resistant Enterococcus (VRE)
• GI or GU infections in patients with prior abx
• Bacteremia, endocarditis in those with extensive HC exposure
• E. faecalis: Often remains sensitive to ampicillin, beta-lactams
• E. faecium: Often multi-drug resistant
• Cystitis Rx
• Consider Nitrofurantoin or Fosfomycin
• Invasive infections Rx
• Amp-sens VRE faecalis: Amp, Amp/Sulb, Pip/Tazo, Imi/Meropenem active
• Linezolid, High dose Daptomycin (8-12 mg/kg daily), Tigecycline 
Consult ID for assistance

24. Question #3:
• 73 yo male presents with fever and flank pain consistent
with pyelonephritis. UCx is shown to right.
• Which agent(s) would not be a reliably effective Rx?
1) Amikacin
2) Ertapenem
3) Piperacillin-
tazobactam
4) Meropenem
5) Fosfomycin

25. ESBL
• Extended spectrum beta-lactamases (ESBL)
• Family of heterogeneous enzymes, 100s of different types
• Mostly seen in E. coli, Klebsiella spp. but other GNR may produce
• Causes resistance to PCN, cephalosporins and aztreonam
• Do not inactivate carbapenems
• Do not affect non-beta lactams abx, but co-resistance common
• Rx options:
• Cystitis: Fosfomycin, Nitrofurantoin, Bactrim, FQ if sensitive
• Serious infections: Carbapenems preferred
• Rx failures seen with Cefepime (? inoculum effect) but may be able to
overcome with higher doses and continuous infusion based on MIC
Lee N-Y, et al. Clinical Infectious Diseases 2013;56(4):488–95.

26. Mycobacteria: TB and non-TB
• Require multi-drug therapy for prolonged duration
• Suspected M. tuberculosis is only situation where empiric
mycobacterial Rx is routinely initiated
• ID and abx susceptibilities critical to guide NTM Rx and
should only be done with ID or pulmonary consultation
• Diagnosis and Rx of NTM disease (esp. pulm) requires:
• Clinical Symptoms +
• Compatible Radiographic Findings +
• Microbiologic culture (2 positive sputum or 1 BAL/Bx specimen)
ATS/IDSA NTM Guidelines. Am J Respir Crit Care Med Vol 175. pp 367–416, 2007.

27. Pharmacologic Strategies and Tips
• Therapeutic Drug Monitoring
• Combination Therapy
• Fluoroquinolones
• Antifungals
• “The Art of De-escalation”

28. Therapeutic Drug Monitoring (TDM)
• Why do we do “drug levels” for certain drugs?
• Variable, unpredictable pharmacokinetics
• Correlation between drug concentration and efficacy or toxicity
• Vancomycin
• Check trough before 4th or 5th dose on steady dose
• Goal troughs: > 10 mcg/mL; 15-20 mcg/mL for serious infections (bacteremia,
endocarditis, PNA, meningitis, osteo)
• Aminoglycosides
• Once-daily dosing for GNR: Random level 8-12 hrs after dose to adjust with
nomogram, Trough < 1 mcg/mL (only for renal failure)
• Synergy for GPC endocarditis: Peak 2-4 mcg/mL, Trough <1 mcg/mL
• Azoles (treatment of invasive fungal infections)
• Voriconazole: goal troughs 1.0 - 5.5 mcg/mL
• Itraconazole: goal troughs > 1.0 mcg/mL (itra + hydroxy-itra by HPLC)
• Posaconazole: goal troughs > 0.7 mcg/mL

29. Combination Therapy
• Standard of care for certain infections (e.g. TB, HIV)
• Recommended for prosthetic device infections
• Vancomycin/Gent/Rifampin for MRSA prosthetic valve IE
• Addition of rifampin for Staph PJI and hardware infections
• Recommended for necrotizing or severe SSTI
• Addition of clindamycin or linezolid to beta-lactam in order to inhibit
toxin production, esp. Group A Strep TSS or necrotizing fasciitis
• Recent prospective, population-based surveillance from Australia
showed substantial reduced mortality (OR 0.28 [95% CI, 0.1-0.8])
with addition of clindamycin in invasive GAS infections
Carapetis J, et al. Clin Infect Dis. (2014) 59 (3): 358-365.

30. Combination Therapy: What about PseA?
• Empiric combo Rx: Yes, increases chances of at least 1
active drug if serious infection (neutropenic bacteremia,
severe sepsis/shock) or high MDR risk
• Definitive Rx: No convincing data of mortality benefit
Vardakas VZ, et al. International Journal of Antimicrobial Agents 41 (2013): 301-310.

31. Combination GNR Rx: Don’t forgetAminoglycosides!
• Empiric AG likely superior to FQ as 2nd agent due to 1)
trend toward better outcomes in critically ill and 2) higher
likelihood to add additional GNR coverage
Beardsley, et al. Chest 2006; Nair G, et al. Crit Care Clin, 2013
PseA E. coli K. pneumo
If resistant to Pip/Tazo: N=44 N=52
Levofloxacin
Gentamicin
Tobramycin
25%
34%
61%
33%
83%
75%
If resistant to Cefepime: N=62 N=144 N=32
Levofloxacin
Gentamicin
Tobramycin
24%
19%
40%
17%
54%
40%
47%
38%
25%
If resistant to Meropenem: N=46
Levofloxacin
Gentamicin
Tobramycin
17%
28%
50%
Data courtesy of Dr.
Francesca Lee, UHSP
% Susceptibility to 2nd Gram Negative Agent, UHSP Data

32. Fluoroquinolones: Comparisons
Ciprofloxacin Levofloxacin Moxifloxacin
Dose 400 mg IV BID-TID
500-750 mg PO BID
750 mg qd PO
or IV
400 mg qd PO
or IV
Elimination Renal Renal Mixed
Urinary
penetration
Good Good Poor
Staph spp. +/- +/- +/-
Strep spp. No Yes Yes
Pseudomonas Yes-high dose Yes-high dose No
Anaerobes No No Yes
QTc effect +/- + ++
• Ciprofloxacin has best Gram negative activity
• Moxifloxacin has best Gram positive and anaerobe activity
• Levo and moxi = “respiratory FQ” due to S. pneumoniae activity

33. Question #4:
• 52 yo male with ESLD presents with 4 days of fevers,
increasing ascites, SOB and AMS with headache. Started
on broad-spectrum abx without much improvement and
now obtunded, and on day #3 admission blood Cx
growing yeast.
• What is the most appropriate empiric anti-fungal Rx?
1) Fluconazole
2) Ambisome
3) Micafungin
4) Voriconazole
Or call the
Micro lab to ask
what the yeast
looks like

34. Anti-Fungals: Spectrum of Activity
• Azoles (fluc-, itra-, vori-, posaconazole)
• Echinocandins (caspo-, anidula-, micafungin)
• Polyenes (amphotericin B, liposomal AmB)
Mayo Clin Proc. Aug 2011;86(8):805-817

35. Anti-Fungals: Empiric Rx
• Rx depends on host factors and most likely pathogens
Clinical Scenario Likely Fungal
Pathogens
Appropriate Empiric
Antifungal
Sepsis in ICU pt (TPN,
CVC, abd surgery,
long-term abx)
Candida (incl azole-
resistant spp.)
Micafungin
Neutropenic fever* Candida (incl resistant
spp.), Molds
(Aspergillus, Mucor)
Ambisome
Micafungin
Voriconazole
Sepsis in IC host
(AIDS, cirrhosis, TNF-
inhibitors, SOT/BMT)
Endemic fungi (Histo,
Crypto, Cocci);
Candida; Molds
(Aspergillus, Mucor)
Ambisome
Yeast in UA from Foley
or ET aspirate
Candida spp. (likely
colonization)
None; Only azoles
reliably penetrate urine
* Consider site of infection and prior fungal prophylaxis

36. “The Art of De-escalation”: Example of PNA
ATS/IDSA Guidelines for Management of HAP, VAP, HCAP. AJRCCM 2005.
Must consider
patient’s clinical
status AND
culture results

37. Tools for Abx De-escalation
• Critical to de-escalation is obtaining lower respiratory tract
cultures prior to starting or changing abx within last 72
hours
• Tools for Abx De-escalation
• Gram stain and Culture
• Physiologic parameters (e.g., CPIS score)
• Biomarkers
• No single marker or tool is sufficiently accurate by itself
but must be interpreted in context of overall pt. status
ATS/IDSA Guidelines for Management of HAP, VAP, HCAP. AJRCCM 2005.

38. Nosocomial PNA: Microbiologic Cultures
• Gram stain and Culture
• Negative tracheal aspirate (no WBCs or bacteria) has very high NPV
(94%) for VAP
• Quantitative cut-offs for infection vs. colonization:
• ET aspirate: >106 cfu/mL
• Bronchoscopic BAL: > 104-105 cfu/mL
• PSB: > 103 cfu/mL
• MRSA and MDR gram-negatives readily cultured so their absence
in high quality LRT specimen reliable
Translation: If MRSA does not grow, it probably isn’t there and
Vancomycin can be stopped!
ATS/IDSA Guidelines for Management of HAP, VAP, HCAP. AJRCCM 2005.

39. Biomarkers
• Various biomarkers have been studied (procalcitonin [PCT], CRP, etc.)
but have failed to reliably aid initial VAP diagnosis
• However, RCT and meta-analysis suggest serial PCT measurements
can be used to safely de-escalate abx/reduce Rx duration (average
decrease of 3-4 abx days compared to control)
• Key Points for Procalcitonin Use in ICU:
• Need in-house testing to be clinically useful
• Should NOT use to withhold or delay initial empiric abx in suspected
severe infections or high-risk ICU patients
• Can be useful to de-escalate or shorten duration of abx Rx
• PCT should be used for validated indications (sepsis and respiratory
infections) with the guide of an interpretive algorithm or its real-world utility
is diminished (Unpublished VANTHCS data to be presented ICAAC 2014)
Bouadma L, et al. Lancet, 2010; Tang H, et al. Infection, 2009; Schuetz P, et al. Cochrane Database Syst
Rev, 2012; Schuetz P, et al. Arch Intern Med. 2011;171(15):1322-1331

40. Proposed PCTAlgorithm for High-Acuity
Infections in ICU Setting
Schuetz P, et al. Arch Intern Med. 2011;171(15):1322-1331.

41. De-escalation: What can you do?
De-escalate/stop antibiotics or shorten
duration of therapy when appropriate
• Importance of “antibiotic timeout” to reassess clinical status
and culture results at 48-72 hours
• Multiple RCT and meta-analyses demonstrate non-inferior
outcomes with shorter Rx courses
• VAP (Non-PseA)= 8 days
• Cellulitis = 5 days ≈ 10 days
• UTI or pyelonephritis = 7 days
• CAP = 5 days (with high dose FQ)
Bartlett J, et al. Clin Infect Dis. 2013; 56(10):1445-50.

42. New FDA-Approved Antibiotics (2014-15)
Drug Name Indication Spectrum of
Activity
Comments
Tedizolid
(Sivextro)
Acute bacterial skin
and skin structure
infection (ABSSSI)
Gm + including MRSA
and VRE
Similar to linezolid,
except qday dosing
Dalbavancin
(Dalvance)
ABSSSI Gm+ including MRSA Prolonged ½ life
Oritavancin
(Orbactiv)
ABSSSI Gm + including MRSA Prolonged ½ life
Ceftolozane-
tazobactam
(Zerbaxa)
Treatment of cIAI and
cUTI
MDR-GNRs including
MDR-PseA
Inadequate anaerobic
coverage alone
Ceftazidime-
avibactam
(Avycaz)
Treatment of cIAI and
cUTI
MDR-GNRs including
PseA, ESBL and some
CRE
Inadequate anaerobic
coverage alone
Isavuconazonium
(Cresemba)
Invasive aspergillosis
and mucormycosis
Mold infections
including aspergillus,
Mucor
Non-inferior to vori for
aspergillus; limited
data in single arm trial
for Mucor

43. Conclusions
• Consider the most likely pathogens and utilize guidelines
to help determine empiric abx Rx
• In critically ill patients, early broad spectrum abx are
appropriate, but don’t forget to get cultures and reassess
clinical status and chance to de-escalate Rx
• Respect MRSA bacteremia and ensure all criteria met for
uncomplicated before giving short course Rx
• Use the minimum necessary duration of abx based on
type of infection and clinical response

44. Questions?