Antimicrobial prophylaxis ICU Brisbane Feb 2018 Shortened … · 1 ANTIMICROBIAL PROPHYLAXIS...

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ANTIMICROBIAL PROPHYLAXIS STRATEGIES IN ICU

Department of

Intensive Care MedicineRoyal Brisbane Hospital University of Queensland

Professor Jeffrey Lipman


Royal Brisbane and Women’s Hospital does not do solid organ transplantation, so this lecture will not cover antifungal prophylaxis where the latter may be important

DISCLAIMER 1


We use “standard protocols” for the “long term” prophylaxis of immune compromised host (eg haematology transplanted pts) and again I will not be talking about these protocols

DISCLAIMER 2

1. Prophylaxis = very short course – see later

2. Pre-emptive therapy – short course (maybe 5 days) for dirty wound etc

In Hong Kong the neurosurgeons gave/give ab’s for as long as drain in-situ – NOT PROPHYLAXIS…

STUPIDITY – NO EVIDENCE BASE


My definitions

EMINENCE BASE vs EVIDENCE BASE

Not too much evidence based literature


THE PROBLEM (definition)

Surgical site infections (SSIs) are infections of the incision or organ or space that occur after surgery.

It has been estimated that approximately half of SSIs are preventable by application of evidence‐based strategies

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Between 2006 and 2009, SSIs complicated approximately 1.9% of surgical procedures in the United States. However, the number of SSIs is likely to be underestimated given that +/‐ 50% of SSIs become evident after discharge.

Estimated mean attributable costs of SSIs range from $10 443‐$25 546 per infection, with MRO and prosthetic joint infections even more expensive

Lancet Infect Dis 2018;18:516-525 (May)

Limiting the eligible study cohort to patients undergoing clean–contaminated, contaminated, and dirty surgical procedures, the investigators report an overall 30-day SSI incidence of 12·3%, ranging from 9·4% in high-HDI countries to 23·2% in low-HDI countries.

Am J Infect Control 1999;27:97-132

f. Antimicrobial prophylaxisSurgical antimicrobial prophylaxis (AMP) refers to a very brief course of an antimicrobial agent initiated just before an operation begins. AMP is not an attempt to sterilize tissues, but a critically timed adjunct used to reduce the microbial burden of intraoperative contamination to a level that cannot overwhelm host defenses.


f. Antimicrobial prophylaxisSurgical antimicrobial prophylaxis (AMP) refers………..

Motherhood statements


Four principles must be followed to maximize the benefits of AMP:

Use an AMP agent for all operations or classes of operations in which its use has been shown to reduce SSI rates based on evidence from clinical trials or for those operations after which incisional or organ/space SSI would represent a catastrophe



Use an AMP agent that is safe, inexpensive, and bactericidal with an in vitro spectrum that covers the most probable intraoperative contaminants for the operation

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Time the infusion of the initial dose of antimicrobial agent so that a bactericidal concentration of the drug is established in serum and tissues by the time the skin is incised



Maintain therapeutic levels of the antimicrobial agent in both serum and tissues throughout the operation and until, at most, a few hours after the incision is closed in the operating room. Because clotted blood is present in all surgical wounds, therapeutic serum levels of AMP agents are logically important in addition to therapeutic tissue levels.



Maintain therapeutic levels of the antimicrobial agent in both serum and tissues throughout the operation……………..

ANOTHER MOTHERHOOD STATEMENT as no one had done tissue levels during surgery then!

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JAMA Surg. 2017;152(8):784-791.

JAMA Surg. 2017;152(8):784-791

EVIDENCE REVIEW A targeted systematic review of the literature….. from 1998 through 2014. A modified Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was used …….. 5759 titles and abstracts screened……… After exclusions, 170 studies were extracted into evidence tables, appraised, and synthesized.

EVIDENCE BASE vs EMINENCE BASE

Authors ultimately provide 42 statements, including 8 Category 1A, 4 Category 1B, 5 Category II, and 25 areas for which they made no recommendation or considered the area unresolved

JAMA Surg. 2017;152(8):784-791

Parenteral Antimicrobial Prophylaxis

1A.1. Administer preoperative antimicrobial agents only when indicated based on published clinical practice guidelines and timed such that a bactericidal concentration of the agents is established in the serum and tissues when the incision is made. (Category IB–strong recommendation; accepted practice.)

JAMA Surg. 2017;152(8):784-791


1A.2. No further refinement of timing can be made for preoperative antimicrobial agents based on clinical outcomes. (No recommendation/unresolved issue.)

•1B. Administer the appropriate parenteral prophylactic antimicrobial agents before skin incision in all cesarean section procedures. (Category IA–strong recommendation; high‐quality evidence.)

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JAMA Surg. 2017;152(8):784-791


1C. The literature search did not identify randomized controlled trials that evaluated the benefits and harms of weight‐adjusted parenteral antimicrobial prophylaxis dosing and its effect on the risk of SSI. (No recommendation/ unresolved issue.)

JAMA Surg. 2017;152(8):784-791


1D. The search did not identify sufficient randomized controlled trial evidence to evaluate the benefits and harms of intraoperative redosing of parenteral prophylactic antimicrobial agents for the prevention of SSI. (No recommendation/unresolved issue.)

JAMA Surg. 2017;152(8):784-791


1E. In clean and clean‐contaminated procedures, do not administer additional prophylactic antimicrobial agent doses after the surgical incision is closed in the operating room, even in the presence of a drain. (Category IA–strong recommendation; high‐quality evidence.)

BOWEL BACTERIAL LOAD

MORE BACTERIA IN/ON OUR BODY THAN CELLS

10 quadrillion cells 100 quadrillion bacterialcells

ANTIBIOTICS KILL BACTERIA, BUT NOT ALL

DARWINIAN PRINCIPLE

Survival of the fittestBacteria WILL BECOME RESISTANTAntibiotics kill bacteria……

(….but you can’t kill all)

The main risk factor for IR-GNB colonization was prior imipenem exposure. The odds ratio for colonization was already as high as 5.9 (95% confidence interval [95% CI], 1.5 to 25.7) after 1 to 3 days of exposure and increased to 7.8 (95% CI, 2.4 to 29.8). In conclusion, even brief exposure to imipenem is a major risk factor for IR-GNB carriage.

after 1 to 3 days of exposure

Antimicrob Agents Chemother 2013;57:1488-95

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Drugs Aging 2017;34:489-498

Narrative review. Uses >65 as “elderly”

“…Elderly patients with surgical site infection have a fivefold higher risk of dying compared with uninfected patients in the same age group…”

J Hosp Infect 2017;97:105-14

Perioperative prophylaxisSix trials evaluated perioperative prophylaxis. Another trial evaluated perioperative plus early post burn prophylaxis

J Hosp Infect 2017;97:105-14

Perioperative prophylaxisSix trials evaluated perioperative prophylaxis. Another trial evaluated perioperative plus early post burn prophylaxis

Based on the available evidence, the use ofprophylaxis is not recommended for most burn wound cleaning or debridement procedures. However, for severe burn patients undergoing aggressive procedures, antibiotic prophylaxis may be useful, although the strength of recommendation is weak.

Tissue pharmacodynamics during surgery using microdialysis

0

1

2

3

4

5

6

7

8

9

10

-1 0 1 2 3 4 5 6 7 8 9

Time (hours)

Ce

ph

alo

thin

(u

g/m

l)

5xMIC E.Coli

= 1g/ml

Time above 5x minimum inhibitory concentration

T>5xMIC E.coli(minutes) Surgery

Duration(minutes)

ID Burn TBSA

Non-Burn

Burn

3 35 % 175 140 135

4 48 % >120 140 270

5 45 % 205 150 520

7 28 % 100 95 330

8 45 % >70 100 370

9 54 % 120 145 445

11 40 % 310 130 480

42± 8%

182± 74

129± 20

364± 124

Mean ±SD

Surgery duration not exceeding T>5xMIC E.coli indicated as:

Surgery DurationPatient 11

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Prophylaxis beware PK and duration

Dalley et al J Antimicrob Chemother 2007:60:166-9

Antibiotic Usage In a 60% Burn Patient

DISCUSSION POINTS

• Timing

• Duration

• What to give

• Dosing

DISCUSSION POINTS

• Timing

• Duration

• What to give

• Dosing

Medicine (Baltimore) 2017 Jul;96(29):e6903AbstractThe aim of the study was to assess the effect of timing of preoperative surgical antibiotic prophylaxis (SAP) on surgical site infection(SSI) and compare the different timing intervals.

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Medicine (Baltimore) 2017 Jul;96(29):e6903

Major medical databases were searched from 1990 to 2016. The primary outcome was SSI after pre operative-SAP comparing different timing intervals.

Fourteen papers with 54,552 patients were included in this review.


There was no significant difference when SAP was administered 120–60 minutes prior to incision compared to administration 60–0 minutes prior to incision.


There was no significant difference when SAP was administered 120–60 minutes prior to incision compared to administration 60–0 minutes prior to incision. Studies investigating different timing intervals within the last 60 minutes time frame reported contradictive results.


The risk of SSI almost doubled when SAP was administered after first incision (OR:1.89; 95%CI:[1.05–3.40]) and was 5 times higher when administered more than 120 minutes prior to incision (OR5.26; 95%CI:[3.29–8.39])

Lancet Infect Dis 2017;17:605-14

1. Administration of surgical antimicrobial prophylaxis (SAP) for the prevention of surgical site infection (SSI) is recommended within 60 min before incision. This trial compared early versus late administration of SAP before surgery.

2. SAP early in the anaesthesia room or late in the operating room. SAP consisted of single-shot, IV of 1·5 g of cefuroxime combined with 500 mg metronidazole in colorectal surgery.

Lancet Infect Dis 2017;17:605-14

3. 5580 patients were randomised 4. Early administration of SAP did not significantly

reduce the risk of SSI compared with late administration (odds ratio 0·93, 95% CI 0·72–1·21, p=0·601)

5. Our findings do not support any narrowing of the 60-min

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DISCUSSION POINTS

• Timing

• Duration

• What to give

• Dosing

JAMA Surg. 2017;152(8):784-791


1E. In clean and clean‐contaminated procedures, do not administer additional prophylactic antimicrobial agent doses after the surgical incision is closed in the operating room, even in the presence of a drain. (Category IA–strong recommendation; high‐quality evidence.)

DISCUSSION POINTS

• Timing

• Duration

• What to give

• Dosing


We do surveillance cultures (skin, perineum, resp) on admission and twice a week.

Peri-operative antibiotics will include targeting these organisms.

DISCUSSION POINTS

• Timing

• Duration

• What to give

• Dosing

Tissue pharmacodynamics during surgery using microdialysis

0

1

2

3

4

5

6

7

8

9

10

-1 0 1 2 3 4 5 6 7 8 9

Time (hours)

Ce

ph

alo

thin

(u

g/m

l)

5xMIC E.Coli

= 1g/ml

Time above 5x minimum inhibitory concentration

T>5xMIC E.coli(minutes) Surgery

Duration(minutes)

ID Burn TBSA

Non-Burn

Burn

3 35 % 175 140 135

4 48 % >120 140 270

5 45 % 205 150 520

7 28 % 100 95 330

8 45 % >70 100 370

9 54 % 120 145 445

11 40 % 310 130 480

42± 8%

182± 74

129± 20

364± 124

Mean ±SD

Surgery duration not exceeding T>5xMIC E.coli indicated as:

Surgery DurationPatient 11

10

Prophylaxis beware PK and duration

Dalley et al J Antimicrob Chemother 2007:60:166-9

DISCUSSION POINTS

• Timing

• Duration

• What to give

• Dosing Repeat dosing after 3 or 4 hours, particularly burns

• Timing Data rich

• Duration Witchcraft

• What to give Eminence based

• Dosing Eminence based

Whom to give it to……(?)

CONCLUSIONS

“…influence of social factors in antimicrobial decision making. For example, the existence of guideline discordant prescribing “etiquette” has consistently been observed within hospitals and evidence is clear regarding the significant role of hierarchy (and consequent fear of disapproval)…”

J Hosp Infect 2018;99:124-126

J Hosp Infect 2018;99:124-126

“…It has been suggested that surgery as a specialty, particularly in the operating theatre environment, may adhere more strongly than other specialties to hierarchical structures….”

…These included clinicians wanting to act according to a sense of what is right” and consistent with the hospital’s “school of thought”……

J Hosp Infect 2018;99:124-126

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Physical presence in the operating theatre is perceived by surgeons to limit the antimicrobial stewardship (AMS) influence on SAP decision making.

J Hosp Infect 2018;99:124-126 1 Chlohexidine skin preparation with no IV antimicrobial prophylaxis for standard ICU procedures (Catheter insertions, IDCs, EVDs etc)

2 Chlohexidine baths

CHLORHEXIDINE in ICU

1 Chlohexidine skin preparation with no IV antimicrobial prophylaxis for standard ICU procedures (Catheter insertions, IDCs, EVDs etc)

2 Chlohexidine baths

CHLORHEXIDINE in ICUJAMA 2015;313:365-6

“..Widespread treatment of pts with antimicrobials has never been a good idea…..……the largest benefit appears to be in settings where the baseline prevalence of MDROs is high..”

Selective Decontamination of the Digestive Tract (SDD)

This cluster randomised (by ICU) trial may be coming to you soon

(cluster randomisation by ICU)

HAND HYGIENE

ONE OF MANY PRODUCTS

AT LEAST TWO AT EVERY BEDSIDE

BASIN AT EVERY BEDSIDE

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TerminalCleaning

CLEANING

SITE/LOCATION RESULT SITE/LOCATION RESULT

1 Large glass door slide handle O 1 Left bench top +

2 Beds controller + 2 Right bench top +

3 Phone handle - inside O 3 Back of chair rest +

4 Edge of keyboard rest O 4 Right pendulum touch screen - alarm button O

5 Top of touch screen monitore on pendant O 5 Right pendulum handle +

6 Bench top of left bench O 6 Light handle +

7 Soap dispenser O 7 Left bed rail +

8 Top of back of chair O 8 Left pendulum bench +

9 Top of right side bench + 9 Bottom right corner of mattress +

10 Inside of paper towel dispenser outside of entry door O 10 Hand Wash touch plate +

11 11 Hand towel dispenser +

12 12 Mouse - left touch button +

13 13 Computer keyboard - enter key O

CLEANING

Antimicrobial prophylaxis ICU Brisbane Feb 2018 Shortened … · 1 ANTIMICROBIAL PROPHYLAXIS...

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