prof.dr.D.Hompes, Surgical Oncology
(Based on Schwartz’s Principles of Surgery, 10th edition)
Surgical Infections
“All creatures great and small”
Historical background (1)
Ignaz Semmelweis
• Vienna, 1861
• Puerperal (“childbed”) fever:
training ward 9.1%
Midwives 3.4%
Chlorine water 1.5%
Historical background (2)
Louis Pasteur
• Paris, 1860
• “germ theory”
contagious disease = caused by
specific ‘microbes’, foreign to the
infected organism
Sterilization
Staphylococcus, streptococcus
pneumoniae
Historical background (3)
Joseph Lister• Glasgow, 1859
• >50% mortality due to infection
after amputation
Carbolic acid (phenol)
N=12 patients
- 10 no amputation
- 1 amputation
- 1 non-wound related death
Historical background (4)
Robert Koch• Wollstein, 1878
• “Koch’s postulates”
• Culture bacillus anthracis
• Cholera
• TBC
Historical background (5)
Charles McBurney
•New York, 1889
•Appendectomy
= “source control”
Treves
1902
Historical background (6)
Alexander Fleming
• London, 1928
• Inhibition of growth of
staphylococcus around
a mold colony
(penicillum notatum)
Penicillin
Historical background (7)
• F.Meleney, W.Altemeier, … (surgeons!)
Aerobes & anaerobes can synergize to cause serious soft tissue and intra-
abdominal infections
Concepts:
- resident microbes = non-pathogenic until they enter a sterile body cavity
at surgery
- Most surgical infections = polymicrobial
• William Osler (USA, 1904)
“Except on a few occasions, the patient appears to die from the body’s
response to infection than from it…”
Cytokines host inflammatory response
Pathogenesis of infection
HOST DEFENSES
• Prevent invasion
• Limit proliferation
• Contain/eradicate invading microbes
Site-specific defenses
Freely circulating components
CAVE: perturbation of 1 or more components
(e.g. Immunosuppressants, burns, …)
Host defenses
SKIN- Epithelial surface
- Chemicals from sebaceous glands
- Shedding of epithelial cells
- Endogenous / resident flora:
Gram positive: staphylococcus / streptococcus
corynebacterium / propionibacterium
Infra-umbilical region:
+ enterococcus faecalis & faecium
E.Coli
other enterobacteriaceae
yeast (e.g. candida albicans)
CAVE: skin disease overgrowth barrier breaches
introduction
Host defenses
RESPIRATORY TRACT
Upper- respiratory mucus- ciliated cells- coughing
Lower- alveaolar macrophages:
phagocytosis
Host defensesUROGENITAL TRACT BILIARY T TRACT &
PANCREATIC DUCTAL TRACT
DISTAL RESPIRATORY TRACT
No commensals!CAVE:
- barriers affected by disease
(e.g. malignancy)
- External source (e.g. catheter)
Oropharynx vast number microbes
highly acidic, low motilitygastric mucosa: 102-103 CFU/ml
microbial proliferationterminal ileum: 105-108 CFU/ml
low oxygen, staticexponential growthdistal colorectum: 1011-1012 CFU/mlanaerobic > aerobic (100:1)
Host defenses
GASTRO-INTESTINAL TRACT
Host defensesDistal colorectum
most extensive host endogenous flora
ANAEROBIC AEROBIC
Bacteroides fragilis
Bacteroides distasonis
Bacteroides thetaiomicron
Bifidobacterium
Clostridium
Eubacterium
Fusobacterium
Lactobacillus
Peptostreptococcus
species
E.Coli
Other enterobacteriaceae
Enterococcus faecalis &
faecium
Candida albicans
Others Candida species
Effective prevention of invasione.g. Shigella, Vibrio, Salmonella
BUT: CAVE perforation!
Host defensesMicrobes enter sterile body cavity additional host defenses
1. Primitive, non-specific
- Physical barriers
- Proteins (lactoferrin, transferrin) sequester Fe
- Fibrinogen polymerizes to fibrin: trapping
- Diaphragm, omentum, intestinal ileus
2. Tissue defense mechanisms
- Resident macrophages: cytokine synthesis (TNFα, Il1β, Il6, Il8, INFγ)
- Low levels of complement proteins en Ig
counterregulation response binding proteins (TNF-BP)
cytokine receptor antagonists (Il1ra)
anti-inflammatory cytokines (Il4 & Il10)
Host defenses3. Interaction with microbes
• opsonization (C1q, C3bi, IgFc)
phagocytosis
microbial destruction extracellular (C5b6-9 membrane attack complex)
intracellular (phagocytic vacuoles)
• Complement pathways
direct contact with/via IgM > IgG binding to microbes
release complement protein fragments (C3a, C4a, C5a)
enhance vascular permeability
• Bacterial cell wall components & enzymes from leukocyte phagocytic vacuoles
• C5a, microbial wall peptides, macrophage cytokines (e.g.Il8)
influx inflammatory fluid & diapedesis of PMN
Definitions
Initial number of microbes
Rate of microbial proliferation
Virulence
Potency of host defenses
Eradication
Containment
Locoregional infection
Distant spread (metastasic abscess)
Systemic infection
(bacteremia/fungemia)
= failure of local host defenses
Magnitude
of response
Definitions
Identification microorganisms
Inflammatory response
- Rubor
- Calor
- Dolor
Systemic manifestations-Elevated T°-Elevated WBC-Tachycardia-Tachypnea
Infection SIRS
Sepsis
Severesepsis
Septicshock
Polytrauma
Aspiration
Pancreatitis
Burn
Malignancy
Transfusion reaction
DefinitionsCriteria / Indicators for SIRS
General variables
- Fever (core T°>38,3°C)- Hypothermia (core T°<36°C)- Heart rate >90bpm- Tachypnea- Altered mental status- Significant edema or positive fluid balance (>20ml/kg over 24h)- Hyperglycemia in the abscence of diabetes
Inflammatory variables
- Leukocytosis (WBC>12.000)- Leukopenia (WBC<4000)- Bandemia (>10% band forms)- Plasma C-reactive protein >2 s.d. above normal value- Plasma protocalcitonin > 2 s.d. above normal value
Hemodynamic variables
- Arterial hypotension (SBP <90mmHg, MAP <70, or decrease SBP >40mmHg)- SvO2 <70%- Cardiac index >3,5L/min/m2
Organ dysfunction variables
Arterial hypoxemiaAcute oliguriaCreatinine increaseCoagulation abnormalitiesIleusThrombocytopeniaHyperbilirubinemia
Tissue perfusion variables
HyperlactemiaDecreased capillary filling
Microbial products:
- endotoxins (G-)
- Peptidoglycans/teichoic acids (G+)
- Cell wall components
Pro-inflammatory mediators
SEPSIS
=
SIRS
+
local or systemic source of infection
Definitions
• SEVERE SEPSIS= sepsis with new onset organ failure
- need for ventilatory support
- oliguria unresponsive to aggressive fluid resuscitation
- hypotension requiring vasopressors
Mortality = 51/100.000/year
• SEPTIC SHOCKacute circulatory failure
arterial hypotension (SBP <90mmHg) despite adequate fluidresuscitation
= most severe manifestation of infection
Mortality = 45-60%
40%
Microbiology of infectious agentsCommon pathogens in surgical patients
Microbiology of infectious agents
• Bacteria- Majority of surgical infections
- Classification:
- Gram-staining
- Morphology: cocci or bacilli
- Division: single, pairs (diplococci),
clusters (staphylococci),
chains (streptococci)
- Presence & location of spores
- Anaerobic organisms:
e.g. Propionibacterium acnes
unable to grow / divide poorly in air
skin, oropharynx, colorectum
- Mycobacterium
(M.Tuberculosis / M.avium-intracellulare / M.Leprae) & Nocardia
acid-fast bacilli, slow growing (DNA-based analysis)
Gram-positive Gram-negative
Blue stain Red stain
Aerobic skin
commensals
- Staphylococcus
aureus & epidermidis
- Streptococcus
pyogenes
SSI
(alone or in conjunction
with other pathogens)
Most frequent:
Enterobacteriaceae
- E.Coli
- Klebsiella pneumonieae
- Serratia marcescens
- Enterobacter
- Citrobacter
- Acinetobacter
Pseudomonas
- Pseudomonas aeruginosa
- Pseudomonas fluorescens
- Pseudomonas xanthomonas
Enteric organisms
- Enterococcus faecalis
& faecium
Nosocomial infections
in
immunocompromised
or chronically ill
patients
(low virulence in healthy
individuals)
Microbiology of infectious agents
• Fungi
- Special stains (e.g. KOH, Giemsa, …)
- Observation form of branching and septation
- Growth characteristics in special media
- Growth at different temperature (25°C vs. 37°C)
1. Nosocomial infections as part of polymicrobial infections or fungemia
(e.g. C.Albicans)
1. Rare causes of aggressive soft tissue infections
(e.g. Mucor)
3. Opportunistic pathogens immunocompromised host
(e.g. Aspergillus, Cryptococcus)
Microbiology of infectious agents
• FungiANTIFUNGAL ADVANTAGES DISADVANTAGES
Amphotericin B Broad-spectrum, inexpensive Renal toxicity premeds, IV only
Liposomal Amphotericin B Broad-spectrum Extensive, IV only, renal toxicity
Azoles
Fluconazole IV and PO availibility Narrow-spectrum, drug interactions
Itraconazole IV and PO availibilty Narrow-spectrum, no CSF penetration
Drug interactions, decreased cardiac
contractility
Posaconazole Broad-spectrum, zygomycete activity PO only
Voriconazole IV and PO availibility, broad-spectrum IV diluent accumulates in renal failure (PO)
Visual disturbances
Echinocandins
Anidulafungin,
caspofungin, micafungin
Broad-spectrum IV only, poor CNS penetration
Microbiology of infectious agents
• Viruses
- Small size & necessity for growth within cells
difficult to culture: longer time than optimal
for clinical decision making
- Identification: host antibody response (indirect)
presence of viral DNA or RNA (e.g. PCR)
- Mostly in immunocompromised host (e.g. immunosuppressionafter Tx)
- adenoviruses, CMV, EBV, HSV, Varicella zoster virus
CAVE: HBV, HCV, HIV transmission to health care workers
Prevention and treatment
General principles
• “Prophylaxis”
= reduction of presence of endogenous & exogenous microbes
• Scrub OR personnel
• Desinfection operative site (+ hair removal)
• Intra-operative sterility
Reduction inoculum
• Antimicrobial agents?
- If ingress of high numbers of microbes (e.g. colonic resection)
- If infection would have high consequences (e.g. prosthetic graft)
Prevention and treatment
Source control !!!I. “Ubi pus, ibi evacua”
• Drainage purulent material
(e.g. abscess drainage)
• Débridement of all infected/devitalized tissue
(e.g. necrotizing soft tissue infection)
• Removal of foreign bodies at infection site
• Remediate underlying cause of infection
(e.g. bowel perforation)
II. Antimicrobial agents
• Secondary importance to effective surgery
CAVE: delay in operative intervention increased morbidity (& mortality)
Prevention and treatment
Appropriate use of antimicrobial agents
1. Prophylaxis
• = administration of antimicrobial agent(s) BEFORE surgery
number of microbes that enter soft tissue / body cavity
selection according to microbes likely to be present
• Limited to time before & during surgery
(≈ 1 dose, certain types of surgery)
• BUT: complex, prolonged procedures > serum t1/2!
(addtional dose)
• NB: Postoperative ???
Prevention and treatment
Prevention and treatment
2. Empiric therapy
• When high risk of surgical infection e.g. ruptured appendicitis
• When significant contamination e.g. colonic spillage
Intra-operative findings: increased risk of infection
Prophylaxis Empiric therapy
• Critically ill patients with potential site of infection + sepsis
• Short: 3-5 days (cultures! clinical evolution!)
• Empiric therapy therapy if established infection
Prevention and treatment3. Therapy for established infection
MONOMICROBIAL
• Frequently nosocomial in postoperative patients
(e.g. UTI, pneumonia, bacteremia)
• SIRS + evidence of local infection
initiate empiric therapy: at first broadspectrum, based on
- initial evidence (Gram staining)
- institutional & unit-specific drug
sensitvity patterns
de-escalation / therapy refinement
Patient response
Culture & sensitivity
results (48-72h)
Prevention and treatment3. Therapy for established infection
POLYMICROBIAL
• Source controle (!!!) + antimicrobial agents
• Cultures: lesser importance:
Only limited cadre of microbes predominate
(<< large number present at initial contamination)
modification AB regimen: based on cultures & clinical
course!!!
• e.g. perforated appendicitis, bowel perforation
R/ agents directed against aerobes & anaerobes
during ≥3-5 days
• Failure? mostly due to inadequate source control !!!
Prevention and treatment
4. Duration of therapy
• Decision at prescription
• Prophylaxis: single dose immediately prior to incision
• Empiric therapy: ≤ 3-5 days
curtail!
• CAVE: SIRS <50% of patients harbor infection
(Chest 1998)
Therapy duration
Monomicrobial
UTI
Pneumonia
Bacteremia
Osteomyelitis
Endocarditis
Prosthetic infection (when device removal = hazardous)
3-5 days
7-10 days
10-14 days
6-12 weeks
Serious / recrudescent infection
Multidrug-resistant pathogen
≥2 agents
1-2 weeks IV, then PO if:
- Clinical improvement
- High serum levels reached PO
Peritonitis
Penetrating GI trauma, no extensive contamination
Perforated / gangrenous appendicitis
Peritoneal soilage from perforated viscus
Moderate contamination
Extensive contamination
Immunosuppressed host
12-24 h
3-5 days
5-7 days
7-14 days
7-14 days
Prevention and treatment
Prevention and treatment
Later phases of postoperative AB treatment of serious intra-
abdominal infection:
• Lack of increased WBC Infection
• Lack of band forms of PMN on peripheral smear =
• Lack of fever [<38.6°C] eradicated
•Presence of indicators ≠ continuing / altering AB treatment
extra-abdominal infection?
residual / ongoing intra-abdominal infection? [source control !!!]
Prevention and treatment
Prevention and treatment
Prevention and treatment
Prevention and treatmentALLERGY
• check medical history BEFORE prescription!
• “True” allergic symptoms: e.g. urticaria, bronchospasm, anaphylaxis
≠ indigestion, nausea
• Penicillin allergy incidence 0,7-10%
avoid any beta-lactam drugs
incidence of cross-reactivity low:
carbapenems 1%
cephalosporins 5-7%
monobactams extremely small
• Severe allergic reaction to certain AB preclude use of any agent
in that class, unless “lifesaving”
• (intradermal testing)
• (Desensitization)
Prevention and treatment
MISUSE
• Increasing frequency
• Adverse events: toxicity, allergy
• Costs!
• °new infections e.g. Clostridium difficile colitis
• Multiagent drug resistance of nosocomial pathogens
“super bugs” !!!
Prevention and treatment
RULES TO BE OBEYED…
• Limit prophylaxis to period of operative procedure
• Do not convert prophylaxis into empiric therapy, unless well-
defined conditions
• Set duration of AB treatment from the outset
• Curtail AB administration, when no clinical or microbiological
evidence of infection
• Limit therapy to short course whenever possible
Infections of significance in surgical patients
Surgical site infections (SSI) (30 days postop.)
Incisional SSI
» Superficial (skin, subcutis)
» Deep
Organ / space SSI
Factors:
1. Degree of microbial contamination of the wound during surgery
2. Duration of the procedure
2. Host factors e.g. DM, obesity, malnutrition, immune suppression, …
Infections of significance in surgical patients
Risk Factors for SSI
Patient factors Older age
Immune suppression
Obesity
Diabetes mellitus
Chronic inflammatory process
Malnutrition
Smoking
Renal failure
Peripheral vascular disease
Anemia
Radiation
Chronic skin disease
Carrier state (e.g. chronic staphylococcus carriage)
Recent operation
Local factors Open compared to laparoscopic surgery
Poor skin preparation
Contamination of instruments
Inadequate antibiotic prophylaxis
Prolonged procedure
Local tissue necrosis
Blood transfusion
Hypoxia, hypothermia
Microbial factors Prolonged hospitalization (leading to nosocomial organisms)
Toxin secretion
Resistance to clearance (e.g. capsula formation)
Infections of significance in surgical patients
Wound class Definition Expected
infection rates
Clean Class I No infection, only skin microflora potentially
contaminate the wound, no hollow viscus that
containes microbes is entered
1.0-5.4%
Class ID Class I in which a prosthetic device (e.g. mesh or
valve) is inserted
Clean/contaminated Class II Hollow viscus with indigenous bacterial flora is
opened under controlled circumstances, without
spillage
2.1-9.5%
Elective colorectal surgery 9-25%
Contaminated Class III Open accidental wounds encountered early after
injury, extensive introduction in normally sterile area
(due to major breaks in sterile techniques, gross
spillage of viscus content, incision through inflamed
tissue)
3.4-13.2%
Dirty Class IV Traumatic wounds with significant delay in treatment
and in which necrotic tissue is present, wounds
created in presence of overt infection (purulent
material) or created to access a perforated viscus
accompanied by a high degree of contamination
3.1-12.8%
Prophylaxis
Infections of significance in surgical patients
• Surgical management
- Class I & II wounds: primary closure
- Class III & IV wounds: 25-50% SSI superficial part packed open
- heal by secondary intention
- delayed primary closure
BUT: Class III after appendectomy (gangrenous/perforated appendicitis):
primary closure if AB against aerobes & anaerobes 3-4% SSI
Infections of significance in surgical patients
• Hyperglycemia
• Adverse effect on WBC function
• Diabetic patients increased SSI rates
e.g. hyperglycemia in cardiac surgery patients (bypass)
• Appropriate blood sugar control !!!
• Effective therapy for incisional SSIs?
• Incision & drainage without AB heal by secondary intention or VAC
• AB? if cellulitis, concurrent SIRS
culture results rarely direct treatment
• Topical AB & antiseptics? unproven
Infections of significance in surgical patients
Intra-abdominal infections “PERITONITIS”
PRIMARY microbial peritonitis
• Cause > hematogenous dissemination from distant source or direct inoculation
• Patients Ascites +++ for medical reasons or peritoneal dialysis from renal failure
• S/ ascites, diffuse tenderness & guarding without localized findings,
no pneumoperitoneum, paracentesis: >100WBCs/ml,
microbes with single morphology on G stain (monomicrobial)
• Cultures dialysis patients: Gram-positive
others: E.Coli, K.Pneumoniae, pneumococci, others
• R/ AB (cultures!), 14-21 days,
removal of indwelling devices if necessary
Surgery = rarely required
Infections of significance in surgical patients
SECONDARY microbial peritonitis
• Cause perforation / severe inflammation & infection of an intra-abdominal organ
(e.g.colonic perforation = most morbid)
• R/ Source control + AB directed against aerobes & anaerobes
conversion IV PO when ileus resolves
low failure rates (response 70-90%), mortality 5-6%
failure: - abscess
- leakage GI anastomosis postop.peritonitis
- tertiary persistent peritonitis
CAVE: inability to controle infection source mortality >40%
Infections of significance in surgical patients
TERTIARY (persistent) peritonitis
• Poorly understood entity
1. More common in immunosuppressed patients
(i.e. inadequate host defenses*)
2. Microbes: E.faecalis & faecium, S.epidermidis, C.albicans, P.Aeruginosa, …
* Combination!
* Lack of responsiveness to initial AB? (resistance!)*
* Even with effective AB therapy: mortality >50% !!!
Infections of significance in surgical patients
INTRA-ABDOMINAL ABSCESS
• Mostly: CT-guided percutaneous drainage
• Surgery? - multiple abscesses
- proximity to vital structures (at risk at percutaneous drainage)
- ongoing source of contamination
• AB? Short course (3-7 days), directed against aerobic & anaerobic activity
• Drain removal? Cavity collapse
<10-20ml/d.
no evidence of ongoing infection source
improved clinical condition
Infections of significance in surgical patients
Organ-specific infectionsHepatic abscess• 15/100.000 admissions/year
• 80% pyogenic
20% parasitic and fungal– Manipulation biliary tract
– Pylephlebitis > neglegted appendicitis, diverticulitis
– <50% e causa ignota
• Aerobic: E.Coli, K.Pneumoniae, enteric bacilli, enterococci, Pseudomonas
Anaerobic: Bacteroides, anaerobic streptococci, Fusobacterium
• R/ small (<1cm), multiple: sampling, 4-6 weeks AB
larger: percutaneous drainage
Infections of significance in surgical patients
Splenic abscess
• Extremely rare
• R/ cfr. Hepatic abscess
Recurrent hepatic or splenic abscess
• Surgical unroofing & marsupialization
• splenectomy
Infections of significance in surgical patients
Secundary pancreatic infections• e.g. infected pancreatic necrosis, pancreatic abscess
• In 10-15% of patients with severe pancreatitis with necrosis
• ce CT at diagnosis (CT Severity Index (CTSI))
• > grade C Monitoring in ICU
(APACHE II / Ranson score)
• follow-up CTs
Infections of significance in surgical patientsSecundary pancreatic infections
• Prevention:
- Prophylactic AB???
- Enteral (+parenteral nutrition)
• Diagnosis of secondary infection:
- Persistent SIRS (fever, ↑WBC, organ dysfunction)
- Initial recuperation sepsis after 2-3 weeks
- CT-guided aspiration: Gram’s stain & cultures: positive
- Gas within pancreas on CT
• Surgery:
- Repeated débridement (median 4x) of infected pancreatic necrosis: timing: delay >2-4
weeks after onset ( maturation of fluid collection): transgastric vs retroperitoneal vs
endoscopic vs lumbar vs open approach (experience & multidisciplinarity!)
- + Jejunal feeding tube, gastrostomy, CCE (if indicated & condition permits)
Infections of significance in surgical patients
Infections of the skin and soft tissue• Classification: according to need for surgery
• Superficial: Cellulitis, Erysipelas, Lymfangitis
– only AB (active against Gram+ skin microflora)
– Local source of infection?
• Furuncles or boils
– Spontaneous drainage or surgical I & D
– AB?
If significant cellulitis of if no rapid resolution after I & D
CAVE: MRSA
(if persistence after I & D and adequate AB)
Infections of significance in surgical patients
Aggressive soft tissue infections• Rare
• Difficult diagnosis
failure 80-100% mortality
rapid recognition 16-25% mortality
• Delineation based on involved soft tissue layers & pathogens
• At risk: - elderly BUT
- immunosuppressed also healthy
- diabetic individuals !!!
- peripheral vascular disease (streptococci)
• Compromise of fascial blood supply to some degree
+ introduction exogenous microbes
Infections of significance in surgical patients
• Clinical findings
– Sepsis / septic shock eci
– “Dishwater pus” evecuation from entry site
(mostly extremities, perineum, torso)
– Skin changes (bronze hue, brawny induration), blebs, crepitus
– Pain at infection site, out of proportion to physical manifestations
IMMEDIATE SURGERY !!!
exposure / direct visualization potentially infected tissue (deep!)
+ radical resection infected areas (amputation, disfiguring surgery)
CAVE: incomplete higher rates of morbidity & mortality
• NO Imaging DELAY! confusing!
Infections of significance in surgical patients
• Gram’s stain (tissue fluid)
• AB directed against gram-positive & gram-negative aerobes and
anaerobes (e.g.Vanco+carbapenem) + high-dose aquaeous penicillin G
50% polymicrobial cfr.sec.peritonitis
(gram positive cocci more common)
50% monomicrobial S.Pyogenes, P.Aeruginosa,
C.Perfringens
• Repeat surgical exploration + additional resection
• Hyperbaric oxygen? Gas-forming organisms
Infections of significance in surgical patients
Postoperative nosocomial infections
1. UTI
• US WBCs, bacteria, leukocyt esterase +
• UC symptomatic: >104 CFU/ml
asymptomatic: >105 CFU/ml
• AB: single agent, 3-5days
• Remove urinary catheter ASAP
Infections of significance in surgical patients
2. Pneumonia• Pathogens common in nosocomial environment
• Prolonged mechanical ventilation
• Purulent sputum, ↑WBC, fever
• New chest X-ray abnormalities
• Sputum culture + Gram’s stain, (BAL)
• Weaning ASAP
• Postop. abdomino-thoracic surgery: respiratory physiotherapy !!!
• CAVE: aspiration pneumonia!!!
Infections of significance in surgical patients
3. Bacteremia• Indwelling vascular catheters !
e.g. physiologic monitoring vascular access
drug delivery hyperalimentation
• 25% colonized, 5% associated with bacteremia
• Risk of infection:
– Duration of catheterization
– Insertion / manipulation under emergency / non-sterile
conditions
– Multilumen catheters
NB: peripherally inserted CVC: similar risk
Infections of significance in surgical patients
• Diagnosis:
Often asymptomatic, only ↑ WBC
Blood cultures from peripheral site & through the catheter
• Catheter removal if:
– Obvious purulence at exit site of skin tunnel
– Severe sepsis without other obvious infection site
– Bacteremia Gram negative aerobes or fungi
• Low-virulence microbes (e.g.S.epidermidis):
• Can be treated in 50-60%
• 14-21 days of AB
• When no other vascular access site
Infections of significance in surgical patients
Sepsis
• Increasing incidence, but mortality rates dropping to 30%
TREATMENT
• RESUSCITATION FLUIDS
CVP 8-12mmHg, MAP ≥ 65 mmHg,
urinary output ≥ 0.5ml/kg/h
early placement CVC!
Delay until ICU > 3 hours = poor outcome !
Infections of significance in surgical patients
TREATMENT
• EARLY EMPIRIC AB
– ASAP broad-spectrum against most likely microbes
CAVE: delay = mortality !!!
– Cultures !
– Early identification & treatment of septic sources !
Infections of significance in surgical patients
TREATMENT
• VASOPRESSORS AND INOTROPES
– e.g. norepinephrine, dopamine, vasopressin
– Monitoring SvO2, plasma lactate levels, MAP
reduce risk of vasopressor-induced perfusion deficits
• Pulmonary artery catheterization?
no clear benefit use
Infections of significance in surgical patients
TREATMENT
• ADJUNCTIVE TREATMENTS
- Low-dose corticosteroids
if septic shock unresponsive to fluids & vasopressors
- Acute lung injury mechanical ventilation
TV 6-7 ml/kg
pulmonary airway plateau pressures ≤ 30cmH2O
- Red blood cell transfusion
if Hb < 7 mg/dl
sooner if severe CAD, ongoing blood loss, severe hypoxemia
Infections of significance in surgical patients
RESISTANT ORGANISMS
• Drivers: genetic (e.g. receptors) + AB selection!
• > worldwide use of AB in people, agriculture and animals
• In all classes of AB
• Resistance mechanisms
• Intrinsic (natural resistance)
• Mutational and mediated by changes in chromosomal make-up of the organism
• Extrachromosomal transfer of genetic material via transposons and plasmids
• Important examples:
• MRSA CAVE: chronically ill, SSI
• ESBL-producing enterobacteraceae (Klebsiella, E.Coli)
• VRE (E.Faecium)
CAVE: co-infection!
Infections of significance in surgical patients
Blood-borne pathogens
General precautions against patient-to-healthcare worker
transmission:
1. Routine use of barriers when anticipating contact with blood & body
fluids
2. Washing of hands / other skin surfaces immediately after contact
with blood or body fluids
3. Careful handling and disposal of sharp instruments during and after
use
Infections of significance in surgical patients
HIV• Risk of transmission patient-to-surgeon = low
• Risk of transmission after needlestick = 0,3%
• Postexposure prophylaxis ↓↓ risk of seroconversion after
occupational exposure to HIV
- within hours rather then days
- if significant exposure to HIV-positive patient, 2- or 3-drug regimen
- If patient’s HIV-status unknown, but high risk of HIV infection
• Risk = related to:
HIV prevalence in population being cared for
(number of) percutaneous lesions suffered during care
use of postoperative prophylaxis
NO: 1/200.000
YES: 1/10.000.000
Infections of significance in surgical patients
HBV
• DNA virus
• Affects only humans
• Primary infection = generally self-limiting
• Can cause fulminant hepatitis or progress to chronic carrier
state
30% death of chronic liver disease or HCC
• Surgeons & other healthcare workers = at high risk
HBV vaccine!!!
Infections of significance in surgical patients
HCV
• RNA flavivirus
• Confined to humans and chimpanzees
• 75-80% of infected patients chronic carrier state 75%
chronic liver disease
• Not transmitted efficiently through occupational exposures to
blood
seroconversion after accidental needlestick = 1.8%
• No vaccine available!
• No protective effect from HCV Ig
•R/ ribavirin en gamma-interferon
Biologic warfare agents
General remarks
• Definition:
Use of infectious organisms as potential biologic
weapons, as an alternative to nuclear weapons as
weapons of mass destruction
• Selection:
typical agent = selected for the ability to be spread via
inhalation route
(most efficient mode of mass exposure)
• US program involving biologic agents: halted in 1971, but...
Biologic warfare agentsBacillus anthracis (Anthrax)• Gram-positive rod
• Zoonotic disease, > domesticated & wild herbivores
• Inhalation anthrax: exposure history!, 1- to 6-day incubation period
malaise, myalgia, fever
after short period: worsening of S/
+ respiratory distress, chest pain, diaphoresis
chest X-ray: widened mediastinum + pleural effusions
• (rapid antigen tests under development)
• Postexposure prophylaxis: ciprofloxacin or doxocyclin (amoxicillin if
proven penicillin-sensitive)
• R/ ciprofloxacin + clindamycin (blocks toxin production) + rifampin
(penetrates CNS & intracellular locations)
exposure followed by symptoms
=high mortality
Biologic warfare agents
Yersinia pestis (Plague)• Gram-negative bacillus
• Naturally occuring: transmitted via flea bites from rodents
• Clinical manifestations:
* aerolized bacteria: epidemic pneumonia with blood-tinged sputum
* fleas as carriers: bubonic plague
Symptoms: painful lesions (bubo)
fever, severe malaise
exposure to fleas
• Diagnosis: aspirate of bubo + direct antibody stain
• Postexposure prophylaxis: doxocyclin
• R/ streptomycin, aminoglycosides, doxocyclin, ciprofloxacin, levofloxacin
or chloramphenicol
Biologic warfare agentsSmallpox• Variola virus
• Eradication in late 1970s
• CAVE: prolonged viability !
• Potential for reverse genetic engeneering (known sequence)
• US: vaccination program for key healthcare workers
• Highly infectious in aerolized form
• Clinical S/ incubation period 10-12 days
malaise, fever, vomiting, headache
centripetal rash (face extremities)
• Postexposure prophylaxis: smallpox vaccine, effective up to 4 days
postexposure
• R/ cidofovir (demonstrated activity in animal models)
Mortalityup to30%
Biologic warfare agents
Francisella tularensis (Tularemia)• Gram-negative aerobic
• Principal reservoir: tick
• Inoculation proliferates within macrophages
• Potential bioterrorist threat:
Very high infectivity after aerosolization
tularemia pneumonia: cough
pneumonia on chest X-ray
85%: enlarged lymph nodes
• Diagnosis: acute phase agglutination tests (cultures from tissue
samples = difficult)
• R/ aminoglycosides or second-line agents (e.g. doxocyclin &
ciprofloxacin)
Keypoints