Update on Treatment of Surgical Infections

Michael A. West, MD, PhDDepartment of Surgery

University California San FranciscoSan Francisco, CA, USA

Balance of Factors Normally Prevents Infection

BacterialFactors

EnvironmentalFactors

Host Defenses

= Abscess

Virulence Factors: Polysaccharide Capsule of B. fragilis

Encapsulated Unencapsulated

Microbial Synergy

1 + 1 = 3

Microbial Synergy in“Mixed Infections”

0

20

40

60

80

100

1 2 3 4 5 6 7

Days

Mo

rtal

ity

(%)

E. coli 2 x 108

E. coli 2 x108 plusB. fragilis 2 x109

Oxidative Killing Mechanisms for Destruction of Microbes

Note: System REQUIRESmolecular Oxygen

O2 H2O

+ Cl-H2O2 H2O

Fe2+ Fe3+O2

SOD

O2·-

H+e-

HOCl 1O2

H2O2 ·OHO2·-

H2O

MP

O

hydrogenperoxide

hydroxylradical

singletoxygen

superoxideanion

hypochlorus acid

Diagnosis of Sepsis / Infection

Antibiotic TherapyIntravenous ABX should be started within 1 hr of

recognition of severe sepsis, after cultures obtained.

Initial empiric ABX should include > 1 drug with activity against likely pathogens.

GRADE 1B/C

GRADE 1B

Dellinger RP, et al., Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008 36: 296-327.

Antibiotic TherapyReassess anti-microbial regimen daily to optimize

efficacy

Duration of Rx should typically be limited to 7-10 days

GRADE 1C

GRADE 1D

Dellinger RP, et al., Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008 36: 296-327.

Glue Grant SOP for Antibiotic Administration in Critically Ill Patients with Severe Injury*

Yes

Clinical DxRequiring Treat withAntibiotics1

Site Infection

Identified?1

Empiric Broad Spectrum Rx 2: Coverage for Gm+ and Gm- aerobes and anaerobes.

Consider origin of infection (community vs. hospital), site,suspected pathogens, and local sensitivity

Empiric Rx: pip/tazo + vanco, imipenem + vanco, cefipime + flagyl + vanco

CatheterInfection?

(CVCI)

Yes

Cover Gm+ aerobes: MSSA, MRSA,

Staph epi, Empiric Rx: vanco,

linezolid

No

No

Skin/ Skin StructureInfection?

(SSSI)

Yes

No

Yes

Cover Gm+ & Gm+ aerobes, & anaerobes. Strep, Staph sp.

Empiric Rx: PCN, vanco, pip/tazo, (Note: clinda may inhibit toxin

production.]

Pneumonia?(+Quant Bact.)

VAP, HAP, HCAP

No

Yes

No

Yes

Cover Gm- and Gm+ aerobes. (MRSA, VRE), Pseudomonas, and

AcinetobacterEmpiric Rx: vanco or linezolid

plus pip/tazo, carbepenam aminoglycoside,or cefepime

IntraabdominalSource?

(IAI)No

Yes

> 4 dayadmit?

resist org? No

Yes

Cover Gm- aerobes & anaerobes.

Empiric Rx: pip/tazo, carbepenam, or tigecycline.

? ± anti-fungal)

Cover Gm- aerobe & anaerobes. Empiric Rx:: unasyn, ertapenem, moxifloxacin, or cipro/levaquin +

metronidazole

> 4 dayadmit?

resist org?

Nec. Fasc.?Severe SSSI?

Cover Gm- aerobe & anaerobes Empiric Rx: unasyn, cefoxitin, ertapenem, moxifloxacin, or

fluroquinolone + metronidazole

Cover Gm+ (& Gm-) aerobesEmpiric Rx: cefazolin, ertapenem,

moxifloxacin

Cont.

* West MA, et al., Patient-Oriented Research Core-Standard Operating Procedures for Clinical Care VII: Guidelines for antibiotic use in the trauma patient. J Trauma. 2008; 65:1511–1519.

Source ControlPts with sepsis should be evaluated for focus

amenable to source control (e.g., drain abscess, debride necrotic tissue, etc.) as rapidly as possible GRADE 1C

Source ControlPts with sepsis should be evaluated for focus

amenable to source control (e.g., drain abscess, debride necrotic tissue, etc.) as rapidly as possible (within 6 hours)

Once a focus is identified (e.g., abscess, GI perforation, cholangitis, etc.) source controls measures should be instituted ASAP afterresuscitation with least insulting intervention

GRADE 1C

GRADE 1D

Dellinger RP, et al., Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008 36: 296-327.

Intra-abdominal Surgical Infections

Classification of Peritonitis

Primary Secondary “Tertiary”

Types of Patients

Source of Bacteria

“Surgery” Required

# Bacterial Species

Immuno-compromised

Pts with CirrhosisChildren

Relatively“Normal”Patients

CompromisedICU Patients

MODS / MSOF

Exogenous Endogenous Endogenous

Single Multiple Multiple

Seldom Usually Varies

Defect in GI Tract

Serosa

Muscularis

Mucosa

Serosa

Muscularis

Mucosa

Serosa

Muscularis

Mucosa

Role of Aerobes and Anaerobes in a Rat Model of Intra-abdominal Sepsis

% ofsubjects

% Abscess

% Mortality

E. coli B. fragilis E. coli+ B. fragilis

0

20

40

60

80

100

Inoculum into Peritoneal Cavity

Pathogens in Intra-abdominal Infections

*E. coli and Bacteroides are the most commonly isolated microorganisms in intra-abdominal infections (Condon et al 1998, p. 657) Adapted from Condon RE et al. Intra-abdominal infections. In: Gorbach LG, Bartlett JG, Blacklow

NR, ets. Philadelphia, Pa: W.B. Saunders, Co; 1998.

2Veillonella4Staphylococcus aureus

3Propionibacteria5Pseudomonas aeruginosa

5Peptococci5Enterobacter spp.

5Fusobacteria6Other aerobes

8Peptostreptococci9Other Streptococci

14Other anaerobes10Klebsiella spp.

15Clostridia11Proteus spp.

24Other Bacteroides spp.*12Streptococcus faecalis

24Bacteroides fragilis*38Escherichia coli*

%Anaerobes%Aerobes

Surgical Infection Society (SIS) 2002 Guidelines:Antimicrobial Therapy for Intra-Abdominal

Infections1

1Mazuski JE, Sawyer RG, Nathens AB, et al. for the Therapeutic Agents Committee of the Surgical Infection Society. The Surgical Infection Society guidelines on antimicrobial therapy in intra-abdominal infections: an executive summary. Surg Infect. 2002;3:161-173 excerpted from page 165,

Table 4.

Single AgentsAM / SBT

CTTCEXERT

IMI / CILMER

PIP / TAZTIC / AMC

Combination regimensAMGs (AKN, GENT, NET, TOB) + an antianaerobe

AZT + CLINCXM + MTDCFL + MTD

Third/ fourth-generation CEPHs (CPM, CFX, CEF, CTZ, CXO) + an antianaerobe

Source Control in the Proximal GI Tract: Influence of Anatomic Location

III

III

IV

Intra-abdominal Sepsis: Treatment

Correct the primary pathology!!!? exploratory surgery

resect, patch, repair, debride, or drain underlying cause

Aggressive resuscitation and monitoringenormous "third space" fluid losses

Important role for appropriate antibiotics

knowledge of pathogens based on origin of bacterial inoculation

“Damage Control” Laparotomy

Focus treatment on immediately life-threatening injuries.

Non-life-threatening injuries can be treated at planned reoperation.

Avoids hypothermia.

Examples:- Pack liver injuries.- Delay bowel anastamoses, stoma- Delay vascular reconstruction IF feasible.

Patients Who May Benefit from Damage Control Approach

Kourkalis G, Surg Today (2002) 32:195–202

Hemodynamically unstable

Coagulopathy

Hypothermia (< 35°C)

Complex and major visceral injuries

Inability to control bleeding

Severe acidosis (<7.30)

Operative time > 90 minutes

Transfusion ≥ 10 U PRBC

Temporary Abdominal Closure

Temporary Abdominal Closure(plastic drape, JP drains, sponge)

Bogota Bag(sterile plastic sheet sewn to skin)

Topical Negative Pressure Therapy (VAC)

Admission Intra-abdominal Pressure in ICU Patients

Malbrain ML. Incidence and prognosis of intraabdominal hypertension in a mixed population of critically ill patients: A multiple-center epidemiological study. Crit Care Med 2004, 33: 315-322.

Predisposing Factors for IAH after Damage Control Surgery

Kourkalis G, Surg Today (2002) 32:195–202

Severe abdominal injuries

Spillage of intestinal contents (massive contamination)

Intra-abdominal packing for coagulation

Massive transfusions with bowel edema and/or congestion

Failure to control bleeding with resultant worsening acidosis and coagulopathy

Percutaneous Drainage for Abdominal Compartment Syndrome

Reckard JM, Management of intraabdominal hypertension by percutaneous catheter drainage.J Vasc Interv Radiol. 2005, 16:1019-21.

ACS TreatmentInitial Treatment

Treatment of underlying cause

Supportive care with monitoring

Optimized fluid resuscitation

Evacuation of intraluminal contents

- mechanical or pharmacologic

Mechanical ventilation

+/- Vasopressors

If no response to initial treatment

Surgical abdominal decompressionNeuromuscular blockade + mechanical ventilation

Dialysis

An G, Crit Care Med. 2008, 36(4):1304-10

WSACS Algorithm

www.wsacs.org/algorithms.php

Decompressive Laparotomy

Operating Room Bedside in ICU

The “downside” of late STSG closure of open abdomen

Courtesy of CC Cothren, MD, Denver Health Medical Center

Complicated (Severe) Skin and Soft Tissue Infections

Classification of SSTIs

• Superficial infections

– Cellulitis

– Impetiginous lesions

– Furuncles

– Simple abscesses

• Can be treated by surgical incision and drainage alone

• Deep soft tissue infections

• May require surgical intervention

– Infected ulcers

– Infected burns

– Major abscesses

• Significant underlying disease state, which complicates response to treatment

FDA. Available at: http://www.fda.gov/cder/guidance/2566dft.pdf. Accessed June 14, 2005.

Uncomplicated Complicated

Severe* Soft Tissue Infections(* severe = requires “surgical intervention” to treat)

• Extensive tissue destruction• High mortality rate• Mixed aerobic and anaerobic

– gram-negative and gram-positive bacteria• Recognize early and treat promptly

– Surgical Rx: debride all necrotic tissue– May require amputation– Worry about reconstruction later

Soft Tissue Gas on Radiographs: “Fournier” Gangrene

External Appearances Can Be Deceiving!

Aggressive (appropriate) Debridement is Cornerstone of Soft Tissue Surgical Treatment

Necrotizing Infection of Extremity

Completed Debridement

- often large open wounds

Vacuum-Assisted Wound Closure (VAWC)

Suliburk JW. Vacuum-Assisted Wound Closure Achieves Early Fascial Closure of Open Abdomens after Severe Trauma. J Trauma 2003, 55: 1155-1160.

Microbiology of Necrotizing Soft Tissue Infections

Monomicrobial

– Streptococcus pyogenes

– Streptococcus viridans

– Clostridium sp.

Rare monomicrobial– Aspergillus– Vibrio vulnificans

Polymicrobial most common

– Staphylococus aureus

– Anaerobic streptococci

– Aerobic gram-negative bacilli

– Bacteroides fragilis--unusual

Summary: Management of Surgical Infection

• Surgical infection/ sepsis recognition.

• Initiate antibiotics, resuscitation, and source control early!

• Surgical infections usually polymicrobial.

• Debridement, repair, resection are most important principles of surgical intervention.

• Damage control is not just for trauma.• High index of suspicion for IAH / ACS.• Broad applications for negative pressure therapy.

Thank You

THE END