neuroblastomen en andere typische embryonale tumoren bij … · 2019. 3. 8. · •tbc. historical...

Surgical Infections

Interuniversitair Postgraduaat Opleiding HEELKUNDE

2017-2018

Prof.dr.D.Hompes

Surgical Oncology

UZ Leuven

“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%


Louis Pasteur

•Paris, 1860

•“germ theory”

contagious disease = caused by

specific ‘microbes’, foreign to the

infected organism

Sterilization

Staphylococcus, streptococcus,

pneumococcus


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


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


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-

abd. Infections

Concept:

- 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 of from it…”

Cytokines host inflammatory response

Pathogenesis of infectionHOST 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 defensesSKIN

- Epithelial surface- Chemicals from sebaceous glands- Shedding of epithelial cells- Endogenous / resident flora:

Gram positive: staphylococcus / streptococcuscorynebacterium / propionibacterium

Infra-umbilical region:+ enterococcus faecalis & faecium

E.Coliother enterobacteriaceaeyeast (e.g. candida albicans)

CAVE: skin disease overgrowth barrier breachesintroduction

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 TRACTNo commensals!

CAVE:- barriers affected by disease

(e.g. malignancy)- External source (e.g. catheter)

Host defensesGASTRO-INTESTINAL TRACT

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 defensesDistal colorectum

most extensive host endogenous flora

ANAEROBIC AEROBIC

Bacteroides fragilisBacteroides distasonisBacteroides thetaiomicronBifidobacteriumClostridiumEubacteriumFusobacteriumLactobacillusPeptostreptococcus species

E.ColiOther enterobacteriaceaeEnterococcus faecalis & faecium

Candida albicansOthers 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

DefinitionsInitial 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 microorganismsInflammatory 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 SHOCK

acute circulatory failure

arterial hypotension (SBP <90mmHg) despite adequate fluid resuscitation

= most severe manifesation of infection

Mortality = 45-60%

40%

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 / 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

pyogenesSSI

(alone or in conjunctionwith other pathogens)

Most frequent: Enterobacteriaceae- E.Coli- Klebsiella pneumonieae- Serratia marcescens- Enterobacter- Citrobacter- AcinetobacterPseudomonas- Pseudomonas aeruginosa- Pseudomonas fluorescens- Pseudomonas xanthomonas

Enteric organisms- Enterococcus faecalis &

faeciumNosocomial infections

in immunocompromisedor chronically illpatients

(low virulence in healthyindividuals)

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)

2. Rare causes of aggressive soft tissue infections

(e.g. Mucor)

3. Opportunisic pathogens immunocompromised host

(e.g. Aspergillus, Cryptococcus)

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. immunosuppression after Tx)

- adenoviruses, CMV, EBV, HSV, Varicella zoster virus

CAVE: HBV, HCV, HIV transmission to health care workers

Microbiology of infectious agentsCommon pathogens in surgical patients

Prevention and treatment of surgical infections

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)


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


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 ???


Site Antibiotic Alternative (e.g. penicillin

allergic)

Cardiovascular surgery cefazolin, cefuroxim vancomycin

Gastroduodenal area cefazolin, cefotetan, cefoxitin, ampicillin-sulbactam fluoroquinolone

Biliary tract with active infection (e.g. cholecytitis)

ampicillin-sulbactam, ticarcillin-clavulanate, piperacillin-tazobactam

fluoroquinoloneplus clindamycin or metronidazole

Colorectal surgery, obstructed small bowel

cefazolin plus metronidazole, ertapenem, ticarcillin-clavulanate, piperacillin-tazobactam

gentamycin or fluoroquinoloneplus clindamycin or metronidazole

Head and neck cefazolin aminoglyosideplus clindamycin

Neurosurgical procedures cefazolin vancomycin

Orthopedic surgery cefazolin, ceftriaxone vancomycin

Breast, Hernia cefazolin vancomycin


2. Empiric therapy ( prophylaxis)

• When high risk of surgical infection e.g. ruptured appendicitis

• When significant contamination e.g. colonic spillage

• Critically ill patients with potential site of infection + sepsis

• Short: 3-5 days (cultures! clinical evolution!)


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 !!!


4. Duration of therapy

• Decision at prescription

• Empiric therapy ≤ 3-5 days

•Curtail!

•CAVE: SIRS <50% of patients harbor infection

(Chest 1998)

Therapy duration

MonomicrobialUTI

PneumoniaBacteremia

3-5 days7-10 days

10-14 days

OsteomyelitisEndocarditis

Prostethic infection(when device removal = hazardous)

6-12 weeks

Serious / recrudescent infectionMultidrug-resistant pathogen

≥2 agents1-2 weeks IV, then PO if:

-Clinical improvement-High serum levels reached PO

Peritonitis

Penetrating GI trauma, no extensive contamination

12-24h

Perforated / gangrenous appendicitis 3-5 days

Peritoneal soilage from perforated viscus- moderate contamination

-Extensive contamination-Immunosuppressed host

5-7 days7-14 days7-14 days


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 !!!]


MISUSE

• Increasing frequency

•Adverse events: toxicity, allergy

•Costs!

• New infections e.g. Clostridium difficile colitis

• Multiagent drug resistance of nosocomial pathogens

“super bugs” !!!


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

3. Host factors e.g. DM, obesity, malnutrition, immune suppression, …


• Risk Factors for SSI

Patient factors Older ageImmune suppressionObesityDiabetes mellitusChronic inflammatory processMalnutritionPeripheral vascular diseaseAnemiaRadiationChronic skin diseaseCarrier state (e.g. chronic staphylococcus carriage)Recent operation

Local factors Poor skin preparationContamination of instrumentsInadequate antibiotic prophylaxisProlonged procedureLocal tissue necrosisHypoxia, hypothermia

Microbial factors

Prolonged hospitalization (leading to nosocomial organisms)Toxin secretionResistance to clearance (e.g. capsula formation)


Wound class Definition Expectedinfection

rates

Clean Class I No infection, only skin microflora potentiallycontaminate the wound, no hollow viscus thatcontaines microbes is entered

1,0-5,4%

Class ID Class I & Prosthetic device is entered

Clean/contaminated Class II Hollow viscus with indigenous bacterial flora is opened 2,1-9,5%

Elective colorectal surgery 9,4-25%

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


• 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


• 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


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


SECONDARY microbial peritonitis

• Cause perforation / severe inflammation & infection of an intra-

abdominal organ (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%


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% !!!


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


Organ-specific infections

Hepatic 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


Splenic abscess

• Extremely rare

• R/ cfr. Hepatic abscess

Recurrent hepatic or splenic abscess

• Surgical unroofing & marsupialization

• splenectomy


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


Secundary pancreatic infections

•Prevention:

- 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

- Gas within pancreas on CT

•Surgery:

- Repeated débridement of infected pancreatic necrosis: remove infected inflammatory focus, pack

pancreatic bed with gauzes, closure abdomen on mesh, ∆ approach

- + Jejunal feeding tube, gastrostomy, CCE at index operation (if indicated & condition permits)


Infections of the skin and soft tissue

• Classification: according to need for surgery

• Superficial: Cellulitis, erysipelas, lymfangitis

– only AB

– 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)

http://www.huidziekten.nl/afbeeldingen/lymphangitis2.jpg

http://www.huidziekten.nl/afbeeldingen/lymphangitis2.jpg


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


• 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 procedures)

CAVE: incomplete higher rates of morbidity & mortality

• NO Imaging DELAY! confusing!


• 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

• IV Ig? Group A streptococcal infection + TSS

High risk of death: elderly, hypotension, bacteremia


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


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: repiratory physiotherapy !!!

•CAVE: aspiration pneumonia!!!


3. Bacteremia

• Indwelling vascular catheters !

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


• Diagnosis:

Often asymptomatic

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 patientsSepsis

• 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 !

•Vasopressors & inotropes

– e.g. norepinephrine, dopamine, vasopressin

– Effect on splanchnic perfusion!

– Monitoring SvO2, plasma lactate levels, MAP reduce risk of vasopressor-induced

perfusion deficits

• Pulmonary artery catheterization? no clear benefit use


EARLY EMPIRIC AB

• ASAP broad-spectrum against most likely microbes

CAVE: delay =mortality !!!

• Cultures !

• Early identification & treatment of septic sources !


ADJUNCTIVE TREATMENTS

• Low-dose corticosteroids

if septic shock unresponsive to fluids & vasopressors

(relative adrenal insufficiency)

• Recombinant human activated protein C (Xigris®)

survival benefit

in surgical patients: if septic shock sepsis and ≥ 2 organ failures

•Acute lung injury mechanical ventilation

TV 6ml/kg & pulmonary airway plateau pressures ≤30cmH2O

• Red blood cell transfusion if Hb < 7 mg/dl

sooner if severe CAD, ongoing blood loss, severe hypoxemia


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 patientsHIV

• 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 is unknown but there’s 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


HBV

• DNA virus

• Affects only humans

• Primary infection = generally self-limited (6% of infected are > 5 years of age)

• Can progress to chronic carrier state

30% death of chronic liver disease or HCC

• Surgeons & other healthcare workers = at high risk HBV vaccine!!!

• Postexposure: Hepatitis B immune globulin

+/-75% protection from HBV infection


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 = 2%

CAVE: late conversion! (6 – 12m!!!)

CAVE: false positive testing (if + PCR testing!)

• No vaccine available!

• No protective effect from HCV Ig

• antiviral R/ directly acting agents (po), if fibroscan F2-F4

95% evolution to AS+, PCR-

Biologic warfare agentsGeneral 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: worse

+ respiratory distress, chest pain, diaphoresis

chest X-ray: widened mediastinum + pleural effusions

• (rapid antigen tests)

• Postexposure prophylaxis: ciprofloxacin or doxocyclin (amoxicillin if peni-sensitive)

• R/ ciprofloxacin + clindamycin (blocks toxin production) + rifampin (penetrates CNS & intracellular locations)

exposure followed by symptoms

=high mortality

Biologic warfare agentsYersinia 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/ aminoglycosides, doxocyclin, ciprofloxacin & 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: 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 agentsFrancisella 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: cultures from tissue samples (difficult), acute phase agglutination tests

• R/ aminoglycosides or second-line agents such as doxocyclin & ciprofloxacin

Key points

Thank you !

neuroblastomen en andere typische embryonale tumoren bij … · 2019. 3. 8. · •tbc. historical...

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