backed into a bacteremia corner 093021

10/8/21

1

2021 Annual Meeting & ExhibitionNovember 4-7, 2021 | San Diego, California

Backed into a Bacteremia Corner

Crystal K. Howell, PharmD, BCIDP, BCPSJohn W. Millard, PharmD, BCGP, BCIDP, BCPS

1


Meet the SpeakersCrystal K. Howell, PharmD, BCIDP, BCPS• Current Role: Assistant Professor at the University of North Texas

Health Science Center College of Pharmacy• PGY2 in Infectious Diseases: Emory University Hospital Midtown and

Emory University Hospital

• PGY1: Emory University Hospital

John W. Millard PharmD, BCGP, BCIDP, BCPS• Current Role: Clinical Pharmacist Practitioner at the Robert J. Dole VA

Medical Center • VISN-15 Antimicrobial Stewardship Commission Co-Chairman

• Adjunct clinical assistant professor at the Kansas University School of Pharmacy

2

10/8/21

2


Disclosure

• Disclosures:• Dr. Howell does not have any conflicts of interest in relation to this activity• Potential conflicts of interest for Dr. Millard:

• Invested into the TSP funds with no control over individual assets allocation and as a result may directly own portions of the companies which products are herewith in discussed

• Presenter holds medical device and utility patents in diagnostic modalities regarding neurological and meningeal infectious etiology and are outside the scope of this presentation

• Disclaimers:• The views expressed in this presentation reflect those of the presenter, and

not those of the Department of Veteran Affairs.

3


Learning Objectives

1. Interpret criteria for appropriate oral treatment of bacteremia.2. Utilize alternative pharmacokinetic administrations of

antimicrobials for bacteremia to optimize antimicrobial activity.3. Integrate new data for long-acting glycopeptides and bacteremia

into practice.4. Apply site and microbiology specific concepts to patient cases.

4

10/8/21

3


When Can PO Therapy Be Used for Bacteremia?

5


Recent Literature That Indicates PO Might Be Okay

Iversen, et al. N Engl J Med 2019;380:415-24. Li, et al. N Engl J Med 2019;380:425-36.

6

10/8/21

4


What is Uncomplicated Bacteremia?MRSA Guideline Criteria for Uncomplicated Bacteremia:

• No endocarditis (IE)• No prostheses• Blood cultures clear within 2 - 4

days • Defervescence within 72hrs of

therapy• No evidence of metastases

Newer Data on Risk Factors for Prolonged / Recurrent Bacteremia:• MRSA > MSSA• IE or other endovascular cause• Lack of or delayed ID consult• ICU admission• Lack of source control• > 3 days of bacteremia• Pitt bacteremia score/ APACHE II score• Black race• Hemodialysis

Liu et al. Clin Infect Dis 2011;1-38Minejima et al. Clin Infect Dis 2020;3;70(4):566-573Choi et al. Clin Infect Dis 2021;1;71(11):1891-1899

MRSA = Methicillin-resistant Staphylococcus aureus, MSSA = Methicillin-susceptible Staphylococcus aureus, ID = infectious diseases, IE = infective endocarditis, ICU = intensive care unit

7


Oral Step Down Therapy Can Improve Transitions of Care Without Increasing Risk of Harm

Citation Bacteria Intervention Efficacy Outcomes Other

Tamma JAMA Internal Med 2019

Enterobacteriaceae bacteremia with source control

Empiric IV then either IV or (PO FQ or SMX/TMP) or PO beta-lactam

• No difference in mortality between PO and IV (13.1% vs 13.4%, NS)

• No difference in mortality between PO groups (11% vs 12.3%, NS)

• ↓ LOS (5d PO vs 7d IV)• ↓ 30d recurrence in beta-lactam vs

FQ or SMX/TMP (0% vs 0.6%)

• ~3 vs 14d of IV • ~14 DOT• ~ 40% of source

were urinary tract

Willekens CID 2018

Staphylococcus aureus low-riskbacteremia

Standard IV therapy then changed to PO linezolid or kept on IV

PO Linezolid had: • ↓ 90d relapses (2.2% vs 4.4%)• Protective in risk factor analysis of

30d mortality• ↓ LOS (8 vs 19d)

• ~ 7 d of IV• ~ 15 DOT

Tamma et al. JAMA Intern Med 2019;179(3):316-323Willekens et al. Clin Infect Dis 2019;69(3):381-387

IV = intravenous, PO = oral, FQ = fluoroquinolone, SMX/TMP = sulfamethoxazole/trimethoprim, LOS = length of stay, DOT = duration of therapy

8

10/8/21

5


Not All Beta-lactams Have Low BioavailabilitySelect Drugs Oral Absorption

Cefaclor 93%

Cefadroxil “well-absorbed”, 90%

Cefprozil 95%

Cephalexin* 90%

• Modifications to R1 of the cephalosporin nucleus increases oral absorption

• Some ester prodrugs can also enhance bioavailability

Select Drugs Oral Absorption

Amoxicillin 75%

Amoxicillin/clavulanate “well-absorbed”, 75%

Lexicomp Online, Lexi-Drugs; Micromedex® (electronic version); Johns Hopkins ABX Guide.;Doi Y. Chapter 20 Penicillins and B-Lactamase Inhibitors. In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. Ninth Edition;Lepak AJ et al. Chapter 21 Cephalosporins. In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. Ninth Edition.

Image created with the support of: https://chem-space.com/search

*Cephalexin susceptibility not routinely done, infer susceptibility from cefazolin

9


Oral Beta Lactams Have Some Retrospective Data For Treatment of Bacteremia

Citation Bacteria Intervention Efficacy Outcomes Other Info

Saad BMC ID 2020 E. coli bacteremia from a urine source

Empiric IV beta-lactam then step - down to PO FQ or PO beta-lactam

• ↓Clinical cure: 98% FQ vs 94% in beta-lactam (p = 0.13)

• No difference in 30d mortality, CDI, or LOS (~6 d)

• ~ 5 d of IV• ~ 14 DOT

Sutton JAMA Network Open 2020

Enterobacteralesbacteremia from a urine source

Empiric IV then step -down to PO either (SMX/TMP or FQ) or beta-lactam

• No difference in composite 30d mortality or recurrent bacteremia

• ~ 5 d of IV

Arensman AAC 2020

Uncomplicated Streptococcalbacteremia

Empiric IV then step -down to PO FQ or beta-lactam

• No difference in clinical success (~92%)

• No difference in reason for clinical failures

• No difference in adverse events including CDI

• ~5 d of IV• ~14 DOT

Saad S et al. BMC Infectious Diseases 2020;20:785; Sutton et al. JAMA Network Open. 2020;3(10):e2020166; Arensman et al. Antimicrob Agents Chemother 64:e01515-20

IV = intravenous, PO = oral, FQ = fluoroquinolone (not moxifloxacin for urine sources), SMX/TMP = sulfamethoxazole/trimethoprim, CDI = Clostridioides difficile infection, LOS = length of stay, DOT = duration of therapy

10

https://chem-space.com/search

10/8/21

6


Bacteriostatic Drugs Require Higher Concentrations to Kill As Quickly But Still Kill

Bacteriostatic: 103 decrease in bacterial density after 24 hours at concentrations > 8 fold above the MIC

Bactericidal:103 decrease in bacterial density after 24 hours at concentrations ≤ 4 fold above the MIC

Time (hours)

0 2 4 6 8

1010

108

106

104

102

1

Viab

le ce

ll de

nsity

(CFU

s)

Viab

le ce

ll de

nsity

(CFU

s)

0 2 4 6 8

1010

108

106

104

102

1

Time (hours)

Legend:Unexposed organism

Antibiotic exposed organism

Spellburg B. Chapter 17 Principles of Antiinfective Therapy. In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. Ninth Edition;Pai MP et al. Chapter 19 Pharmacokinetics and Pharmacodynamics of Antiinfectives Agents. In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. Ninth Edition.

11


Systematic Review of 56 Randomized Controlled Trials- 49 (81%) of articles found no difference between bacteriostatic and

bactericidal agents- Six trials demonstrated bacteriostatic superiority over bactericidal agents- One trial had a bactericidal agent that was more effective than the

bacteriostatic agent

Wald-Dickler et al. Clin Infect Dis 2018;66(9):1470–4

12

10/8/21

7


When to Consider Oral Therapy for Bacteremia

Consider PO• Uncomplicated with source

control• Organism susceptibility• Organism without much

virulence?• Initial IV therapy completed• Anticipated duration 14 days• Patient can tolerate PO• High bioavailability PO agent

Stick with IV• Endovascular source or

complicated bacteremia• Unable to tolerate PO• Low bioavailability• Multidrug resistant organism

(MDRO)

13


Self Assessment Case 1.

75 yo F admitted from an assisted living facility (ALF) with pan-S Enterococcus faecalis bacteremia secondary to gut translocation from severe constipation associated with narcotics PMH: COPD, OA, HTN; Ht 5’3’’, Wt 55kgInsurance: Medicare, per social work in the donut holeHospital Course: Rapid defervescence after empiric therapy

- Empiric therapy: vancomycin and piperacillin/tazobactam- Micro:

Enterococcus faecalis is ampicillin susceptibleCleared blood cultures within 48 hours

- ID consult De-escalated to ampicillin continuous infusionAnticipated duration: 14 days from 1st negative blood culture

14

10/8/21

8


Self Assessment Question 1.

She is now on D12 of therapy after the first negative blood culture with a negative transesophageal echocardiogram (TEE) and ID is trying to help with outpatient IV therapy. Her ALF will not approve ampicillin or ampicillin/sulbactam for stability/nursing reasons. ID consults pharmacy for PO options. Which of the following options would be BEST for this 75 yo patient in the Medicare donut hole?

• Ampicillin 500mg PO q 6 h x 14 days• Amoxicillin/ clavulanate 875/125 mg PO bid x 12 days• Cephalexin 500mg PO q 6 h x 12 days• Daptomycin 10mg/kg IV q24h

15


Optimizing Pharmacokinetics (PK) and Pharmacodynamics (PD) in

Complicated Bacteremia

16

10/8/21

9


When Patients Don’t Read the Textbook…. Examples of When Source Control Isn’t An Option

Patient

• Not a surgical or transplant candidate• Surgical complications already

exist• Foreign device dependent

• Ex: can’t do a line holiday, ICD dependent, etc.

• Challenging social situations

Bug/ Disease

• Hardware +/- biofilm• Not big enough of a fluid

collection to drain• Comorbidities +/- drugs that

impair immune function

17


In-Vitro See-Saw Benefit of Combination Therapy with Daptomycin and Beta-lactams

Daptomycin uses calcium to become positively charged then binds to negative

phospholipids in the cell membrane

Monotherapy Mechanism of Action

Combination Therapy Mechanism of Action

Beta-lactams decrease cell positivity allowing a stronger attraction between

daptomycin and the negative phospholipidsMunita et al. Chapter 31 Daptomycin and Quinupristin-Dalfopristin.. In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. Ninth Edition.; Jenson et al. Antimicrob Agents Chemother 2020;64(9):e00890-20; Mehta et al. Antimicrob Agents Chemother 2012;56(12):6192-200

18

10/8/21

10


In-Vivo Controversial Combinations for Clearing Bacteremia with Staphylococcus aureus

Blood Culture Clearance

Daptomycin+ ???

MSSA

MRSAMethicillin Susceptible

Staphylococcus aureus (MSSA) Bacteremia:

Rifampin + gentamicin + nafcillinfor endocarditis

X Beta-lactam + daptomycinX DASH trial: daptomycin + anti-

staphylococcal beta-lactam CAMERA-2: flucloxacillin + vancomycin or daptomycin

Methicillin Resistant Staphylococcus aureus (MRSA)

Bacteremia:

Rifampin + gentamicin + vancomycin for endocarditis

X Beta-lactam + daptomycinDaptomycin + ceftarolineDaptomycin + fosfomycin (IV)

Grillo, et al. Clin Infect Dis 2019;69(9):1480–8; Jorgensen, et al. Clin Infect Dis 2020;71(1):1–10; Cheng, et al. Clin Infect Dis. 2021;72(9):e196-e203; Tong, et al. JAMA. 2020;323(6):527-537. Baddour, et al. Circulation. 2015 Oct 13;132(15):1435-86; Geriak, et al. Antimicrob Agents Chemother. 2019;63(5):e02483-18. Pujol, et al. Clin Infect Dis. 2021;72(9):1517-1525

19


Combination vs Monotherapy for Gram Negative Resistant Organisms• Empiric therapy -> Antibiogram!• Combination vs monotherapy anti-Pseudomonal agents

• Balance of efficacy and safety• Determined by local resistance rates• Optimize PK/PD where possible

• Ex: extended interval dosing for concentration-dependent aminoglycosides, extended intervals for time-dependent beta-lactams to overcome intermediate resistance

• Organisms that typically require combination therapy• Acinetobacter baumanii• +/- carbapenem producing Enterobacterales

Tamma et al. Clin Infect Dis. 2021;72(7):e169-e183

20

10/8/21

11


Indulge With Extended and Continuous Infusions

Plasma Concentration

Time

Minimum Inhibitory Concentration (MIC)

Time > MIC

Cp

AUC / MIC

Cp / MIC

Spellburg B. Chapter 17 Principles of Antiinfective Therapy. In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. Ninth Edition. Pai MP, et al. Chapter 19 Pharmacokinetics and Pharmacodynamics of Antiinfectives Agents. In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. Ninth Edition.

21


The Goal for Beta-lactams is to Have the Drug Concentration Above the MIC Around Half of the Dosing Interval

Plasma Concentration

Time

MIC

Beta-lactam Goal % of Time > MIC = ~ 50%

Lepak AJ, et al. Chapter 21 Cephalosporins. In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. Ninth Edition.

22

10/8/21

12


Biofilm Bonanza

Biofilm Penetration

• Rifampin• Combination

therapy

Lock Therapy

• Ethanol locks• Antibiotic locks

Novel Agents

• Bacteriophage therapy

• Photodynamic therapy

• Nanoparticles• Anti-platelet drugs

Sticky Bug Conglomeration Slimy Biofilm

Lancellotti P et al. JAMA Cardiol. 2019;4(6):596-599; Hoiby N et al. Clin Microbiol Infect. 2015;21 Suppl 1:S1-25; Suresh MK, et al. Int J Med Microbiol. 2019;309(1):1-12; Hu X et al. Front Microbiol. 2018;9:1299; Haddad LE, et al. Clin Infect Dis. 2019;69(1):167-178; Fabijan AP, et al. Nat Microbiol. 2020;5(3):465-472; Chegini Z, et al. Ann Clin Microbiol Antimicrob. 2020;19(1):45.; Aslam Curr Opin Infect Dis. 2020;33(4):298-303. Gordilloa Altamirano FL et al. Clin Microbiol Rev. 2019;32(2):e00066-18; Caflisch KM, et al. Expert Rev Anti Infect Ther. 2019;17(12):1011-1041

23


Self Assessment Case 2.67 yo M is being transferred from an acute care hospital to your skilled nursing facility on treatment for ventilator associated pneumonia secondary to Pseudomonas aeruginosa.

Drug MIC Interpretation

Ceftazidime ≥ 32 R

Cefepime ≥ 32 R

Ciprofloxacin ≥ 2 R

Gentamicin ≥ 16 R

Meropenem 4 I

Piperacillin/ tazobactam

> 64/4 R

Tobramycin ≥ 16 R

PMH: DM, COVID 8 mo ago with significant residual lung disease, HFpEF, LVAD, not a transplant candidate

Ht 6’7’’, Wt 120kg (dry), other labs WNL for chronic disease states

Hospital Course: - Empiric therapy: vancomycin +

piperacillin/tazobactam + tobramycin- ID prescribed meropenem 2g IV q8h as an

extended infusion over 4 hrs

BAL Culture: Pseudomonas aeruginosa

24

10/8/21

13


Self Assessment Question 2. Your facility has a policy against q8h medications because of the nursing requirements and asks you if it’s really needed for this patient. Which of the following is the BEST rationale for why this patient requires 2g as an extended infusion q8h.

A. Meropenem has a post antibiotic effect time that allows it to be dosed q12h so this patient should be changed to 2g IV q12h

B. Carbapenems are AUC > MIC dependent and must be dosed this way with therapeutic drug monitoring

C. The patient should be transferred back to the hospital to complete treatment with meropenem or be switched to extended interval aminoglycoside like tobramycin

D. 2g of meropenem is needed to overcome the intermediate MIC; extended infusions are needed to reach the target time > MIC of ~ 50%

25


Glycopeptides and Lipoglycopeptides and

Bacteremia

26

10/8/21

14


Full Circle• Drug of choice for MRSA infections = vancomycin

• 2009 guideline recommendation(s)• No more vancomycin peak levels • Targeting AUC/MIC of 400 or greater• Trough concentration of 15 – 20 mcg/mL acts as surrogate marker

• 2020 guideline recommendation(s)• Trough-only monitoring targeting 15 – 20 mcg/mL is no longer

recommended

Rybak et al. Clin. Infect. Dis. 2020;71(6):1361-1364

27


Preferred Dosing Methodology???• Bayesian statistics• Draw peak at least 1 hour after the end of infusion• Draw trough level at end of the dosing interval

• With a large sample of vancomycin data loaded into the Bayesian prior, it may be sufficient for a lone vancomycin trough level to estimate AUC

• PK equations drawing levels at steady state• Draw peak level at least 1 hour after the end of infusion• Draw trough level at end of the dosing interval

Rybak et al. Clin. Infect. Dis. 2020;71(6):1361-1364Broeker et al. Clin Microbiol Infect. 2019 Oct;25(10):1286.e1-1286.e7

28

10/8/21

15


Standard of practice – Staphylococcus aureus bacteremia

• 1st line• Parenteral antibiotics for 2 – 6 weeks• Peripherally inserted central catheter (PICC)• Outpatient parenteral antibiotic therapy program (OPAT)• Skilled nursing facility

• Exclusions from 1st line options• People who inject drugs (PWID)• Repeated discharges against medical advice (AMA)• Social, behavioral, or health system barriers

Liu C. et al. Clin. Infect. Dis. 2021;52(3):e18-e55Bork et al. Infect Dis Ther. 2019;8(2):171-184.

29


Lipoglycopeptides

• Dalbavancin and Oritavancin have extremely long half-life’s• Found to be non-inferior to vancomycin• FDA approved for acute bacterial skin and skin structure infections (ABSSSI)

• Spectrum of activity?• Yes: MRSA, MSSA, Streptococcus, Enterococcus faecalis• Unclear: Vancomycin resistant Enterococcus, Enterococcus faecium

Medication Dose Duration & Administration Half-life

Dalbavancin 1500 mg 1 dose over 30 minutes 204 hours vs 345 hours

Dalbavancin 1000 mg x 1 dose over 30 minutes then 7 days later another dose of 500 mg over 30 minutes

204 hours

Oritavancin 1200 mg 1 dose over 3 hours 245 hours

Dalvance™ (dalbavancin) [package insert]Orbactiv™ (oritavancin) [package insert]

30

10/8/21

16


What does the literature say…

Citation Study design Infection Population Outcome Microbiology/Other

Raad, 2005 RCT CRBSI 33(DAL)/34(VAN) Test of cure:DAL 87% CI [73.2 – 100%]VAN 50% CI [31.5 – 68.5%]

MSSA, MRSA, CoNS, Enterococcus faecalis

Redell, 2019 Retrospective observation

SSTI/bacteremia N= 401/9 (ORI) Clinical success:89%/100%

Cohort n = 32 received multi-dose with clinical success 93.8%

RCT: randomized control trial, CRBSI: catheter related blood stream infection, DAL: dalbavancin, VAN: vancomycin, MSSA: methicillin-susceptible Staphylococcus aureusMRSA: methicillin-resistant Staphylococcus aureus, CoNS, coagulase-negative Staphylococci, ORI: oritavancin, SSTI: skin and soft tissue infection

Raad I. et al. Clin. Infect. Dis. 2005; 40:374-80Redell M. et al. Open Forum Infect Dis. 2019;6(11):ofz479

31


Lipoglycopeptides in practice

• Increasing amount of literature supporting use in additional infections• Osteomyelitis• Osteoarticular joint infections• Bacteremia• Infective Endocarditis

Medication Dose Duration Half-life

Dalbavancin 1500 mg 1 dose every 14 days 204 hours vs 345 hours

Oritavancin 1200 mg 1 dose every ~9 – 14 days

245 hours

Ajaka et al. Antibiotics. 2020 Oct 15;9(10):700.Redell et al. Open Forum Infect Dis. 2019;6(11):ofz479

32

10/8/21

17


Lipoglycopeptides clinical pearls

• Patient(s) selection• Gram positive infection• Social, behavioral, or health system barriers, frequent AMAs, or PWID• Documented negative blood cultures prior to therapy initiation

• Poor outcomes for PWID with IE

•What risks are there in treating these patients?

Ajaka et al. Antibiotics. 2020 Oct 15;9(10):700. Schranz Clin Infect Dis. 2020;71(3):572-573Bork et al. Infect Dis Ther. 2019;8(2):171-184 Redell et al. Open Forum Infect Dis. 2019;6(11):ofz479

33


Patient Case #3

• RW is a 62-year-old male who presented to the ED after experiencing 5 days of shortness of breath, chills, weakness, and decreased appetite. The ED provider noted suspected needle tracks on RLE with associated erythema. Patient admits to using IV meth and “missed his mark about 7 days ago”. • PMH: Polysubstance dependence, PWID, Hypertension, Diabetes

mellitus, Seizures, HFrEF, Hyperlipidemia, MDD, PTSD• Vitals: T 98.9⁰F; BP 148/53; HR 118; RR 29 • Labs: WBCs 24.7; bands 18%; SCr 0.66 mg/dL, Lactic acid 3.0• UA: WBCs 21-30, RBCs 3-5, LE large, nitrite negative

34

10/8/21

18


Patient case #3

• Urine and blood cultures identify the following bacterial isolate: MRSA

• Repeat blood cultures are 5 days negative today and RW is threatening to leave AMA

• Transition of care pharmacist reports that patient is only adherent with his prazosin, citalopram, and carvedilol medications

35


Self-Assessment Question 3

Identify the optimal antimicrobial agent for RW.

A. Vancomycin 750 mg IV every 12 hour for 9 daysB. Oritavancin 1200 mg IV nowC. Dalbavancin 500 mg IV now, and Dalbavancin 1000 mg IV on day 7D. Linezolid 600 mg PO every 12 hour for 9 days

36

10/8/21

19


Microbiological Nuance and Bacteremia

37


Culture of Culturing

• Pathogen or contaminant?

• Ideally draw blood cultures prior to antibiotic therapy

• Blood culture technique1. Disinfect skin for venipuncture2. Disinfect bottle top tubes3. Allow to dry4. 2 or 3 blood culture sets from separate venipuncture sites

approximately 15 minutes apart

Septimus Ed. https://www.cdc.gov/antibiotic-use/core-elements/collecting-cultures.html.

38

https://www.cdc.gov/antibiotic-use/core-elements/collecting-cultures.html

10/8/21

20


Blood culture – what now?

• Typically each set of blood cultures have two different tubes• Aerobic tube filled 1st with anaerobic tube filled 2nd

• Laboratory confirmed bloodstream infection1. One positive blood culture with recognized pathogen2. Skin flora present in two or more cultures drawn on separate occasions for

identical organism plus clinical symptoms• Skin flora examples: Staphylococcus epidermidis, Staphylococcus hominis,

Staphylococcus capitis, Micrococcus, Bacillus species…etc


39


Culture of Culturing – Catheter site

• Central vascular catheters (CVCs)

• Blood culture technique1. Disinfect skin for venipuncture2. Disinfect bottle top tubes3. Allow to dry4. 1 or 2 blood culture sets from separate venipuncture sites

approximately 15 minutes apart and an additional set of blood cultures through the catheter device or line


40



10/8/21

21


Catheter-related blood stream infection (CR-BSI)?

• Laboratory suspected CR-BSI• Both cultures from catheter and venipuncture must be positive for same

organism with clinical signs and symptoms and no other recognized source

• Laboratory suspected contaminant• Positive culture from the catheter with negative venipuncture culture• Positive cultures from the catheter for organism A and organism B from

venipuncture

• Catheter tip culture alone are not diagnostic for CR-BSI


41


CR-BSI Pathogenesis

• Recognized routes• Migration of skin organisms into the cutaneous catheter tract and

colonization of catheter tip• Direct organisms cross-contamination of catheter from non-sterile source• Hematogenous catheter seeding from alternative source• Contaminated fluid infusion e.g. non-sterile admixture or compounding

Grady et al. Clin. Infect. Dis. 2011;52(9):e162-93

42


10/8/21

22


Recognized blood stream pathogens

Gram Positive bacteria

• Staphylococcus aureus (20 – 25%)

• Enterococcus species (5 – 10%)

• Streptococcus pneumoniae (2 – 4%)

• Streptococcus agalactiae (2%)• Other Streptococcus species (~1%)

Gram Negative bacteria

• Escherichia coli (10 – 19%)

• Klebsiella species (6 – 8%)

• Pseudomonas (5%)

• Enterobacter (2 – 3%)

• Proteus mirabilis (~1%)

Grady et al. Clin. Infect. Dis. 2011;52(9):e162-93Diekemia et al. Antimicrob. Agents Chemother. 2019;63(7): e00355-19Lutwick L, et al. In: Memish ZA. Guide to Infection Control in the Healthcare Setting. Brooklyn, MA: International Society for Infectious Diseases

43


Recognized blood stream pathogen - Yeast

Grady et al. Clin. Infect. Dis. 2011;52(9):e162-93Lutwick L, et al. In: Memish ZA. Guide to Infection Control in the Healthcare Setting. Brooklyn, MA: International Society for Infectious Diseases

• Represents challenging cause of sepsis and septic shock

• High degree of morbidity and mortality

• Account for 10% of BSIs• Risk Factors: CVCs, abdominal

surgeries, abdominal perforations, broad spectrum antibiotics, neutropenic

Candida species

• Commonly isolated from urinary and pulmonary cultures and not typically considered pathogenic in these settings

Why so challenging???

44

10/8/21

23


Containment(s) or Pathogen?• Laboratory confirmed bloodstream infection

2. Skin flora present in two or more cultures drawn on separate occasions for identical organism plus clinical symptoms

Coagulase negative Staphylococcus

• Most isolated BSI organism(s)

• Represents challenging differential

• Skin flora

• Accounts for up to 31% of BSIs

Grady et al. Clin. Infect. Dis. 2011;52(9):e162-93Becker et al. Clin Microbiol Rev. 2014;27(4):870Wisplinghoff et al. Clin Infect Dis. 2004;39(3):309-317

Lutwick L, et al. In: Memish ZA. Guide to Infection Control in the Healthcare Setting. Brooklyn, MA: International Society for Infectious Diseases

45


Patient case #4

• Patient KS is a 56-year-old female who presented to the ED for worsening RLE erythema surrounding a diabetic foot ulcer. Blood cultures were drawn and an MRI was obtained that is negative for osteomyelitis – an ulcer is seen in the plantar soft tissues with surrounding soft tissue edema which may represent cellulitis. Patient declined admission and was discharged from the ED on amoxicillin/clavulanate and doxycycline.• All other laboratory data within normal limits• Blood culture 1 set of 2 sets are reported as positive

46

10/8/21

24


Self-Assessment Question 4

After contacting the lab it was reported that 1 blood culture tube in set 1 identified S. epidermidis. All other culture tubes are no growth final result. Identify the best answer below:

A. No treatment, skin flora identified in one blood culture set and represents a contaminant

B. No treatment, skin flora identified in two blood culture sets and represents a contaminant

C. Treatment recommended, pathogen identified in one blood culture set and represents an infection

D. Treatment recommended, pathogen identified in two blood culture sets and represents an infection

47


Coagulase negative Staphylococcus differential

• What if patient KS had both blood culture sets result positive for S. epidermidis?• Skin flora present in two or more cultures drawn on separate occasions

for identical organism plus clinical symptoms

Question Answer

Clinical symptoms present?

Skin flora present?

Skin flora present in 2 or more cultures?

Identical organism in 2 or more cultures?

48

10/8/21

25


Coagulase negative Staphylococcus differential

Blood Culture Set 1 Blood Culture Set 2

Camerer et al. J Clin Microbiol. 2011 Sep;49(9):3355-7Seybold et al. Infection. 2009 Jun;37(3):256-60Al Wohoush et al. Clin Microbiol Infect. 2011 Apr;17(4):569-71

49


BSI – Clinical Pearls• Staphylococcus aureus always considered pathogenic from any site

• If cultured from urinary source BSI should be ruled out

• Candida identified in blood culture is a pathogen• Certain skin floral considered S. aureus “like” in virulence and

propensity to cause infection: S. lugdunensis• Bacteria isolated in blood culture can help provider key in on source

• Intra-abdominal: Enterococcus, poly-microbial, Bacteroides• Urine: Enterobacterales• Pulmonary: S. pneumoniae, H. influenzae• Unknown source?

Becker et al. Clin Microbiol Rev. 2014;27(4):870Frank et al. Clin Microbiol Rev. 2008;21(1):111

50

Documents

backed into a bacteremia corner 093021