Download SURGICAL INFECTIONS

Surgical Foundations: INFECTIONS Lecture # 1
Introduction and determinants of infection
January 14, 2014 - Dr. J M A Bohnen
Lectures 1-4 learning objectives: concepts, principles, exam prep on prevention and
management of important surgical infections
Lecture 1: Infection determinants: bacteria, local environment, host defenses, duration
Lecture 2: Anti-infective agents including prophylaxis
NB: Lects 2-4 topic order was changed on January 19, 2014,
AFTER Lect 1 given; topic order to the left of this box is revised
Lecture 3: Hospital acquired infections
Lecture 4: Abdominal and other serious surgical infections and correct
DETERMINANTS OF INFECTION
ORGANISMS
ENVIRONMENT
SYSTEMIC HOST DEFENCES
DURATION OF INFECTION
Will cover mainly BACTERIA + FUNGI; mention some VIRUSES AND PROTOZOA
BACTERIA
CLASSIFICATIONS OF BACTERIA
An organism’s first and last names are its genus (capital 1st letter) and species (all lower
case) respectively, italicized (or underlined) eg Bacteroides fragilis. After first writing the
full name, use only the genus capital letter, a period, then the species eg B. fragilis. Genus
and species names change because of advances in taxonomy, eg nucleotide sequencing.
2 key descriptors give clues to the source and therapy of infection:
1. Gram stain positive (blue) or negative (pink); rod (=bacillus) or coccus
2. O2 requirement (aerobe needs O2; facultative ok with or without O2; anaerobe: no O2
Gram stain: 1. Air dry slide 2. quick pass x2 thru flame 3. gentian violet 45 sec, gentle tap water rinse 4. Gram’s
iodine 45 sec, rinse 5. Etoh 3 sec, rinse 6. Etoh 6 sec, rinse, pour off water 7. Carbolfuchsin 45 sec 8. air dry
Exogenous infection: bacteria from OUTSIDE patient (e.g. surgeon’s hands);
Endogenous infection: from INSIDE (eg GI) or ON patient (skin)
Bold font and underlines in these notes are for emphasis, with no taxonomic significance
(underlines can be used like italics for microbe names - not done in these notes).
Some antibiotic abbreviations in these notes:
AG
= aminoglycoside
PRSP = penicillinase resistant synthetic penicillin (e.g. clox)
MRSA = methicillin resistant S. aureus; resists clox; Usually sens to vanco
Ceph = cephalosporin; ceph³ = 3rd gen ceph
VRE = vancomycin resistant enterococcus)
Doxy = doxycycline
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Examples of bacteria and some infections they cause:
Bacteria:
FACULTATIVE/AEROBES
Infection:
Some effective antibiotics:
GRAM + COCCI
Staphylococci:
S. aureus (coagulase pos)
wound, carbuncle
}
S. epidermidis (coag neg)
PRSP; ceph¹-2; Vanco
IVs, hip prostheses
PRSP-resistant staph resist cephs too: 90% of S. epi, 20% of S. aureus. S. epi is one of many
coag neg staphs, sometimes called “CNS”
Streptococci:
Group A (=S. pyogenes)
cellulitis
Pen
Group D stre[:
(S. bovis, S. equinus)
endocarditis
pen
Viridans strep
S. pneumoniae (="pneumococcus")
pneumonia
pen

Strep "group" is antigen serotype. "Hemolysis" is zone near colony on culture plate:
"alpha hemolysis" = "strep viridans" = small green zone, "beta hemolysis" = clear zone
Enterococci: previously Group D strep, in 1984 they became a genus, they are NOT STREP
E. faecalis, faecium, durans

abd infectin, UTI, bil
nosocomial
amp, AG, carbapenem
Unlike strep, enterococci generally insensitive to cephs, need a pen or amp plus AG;
vanco, imipenem are alternates; increasing amp + AG resist is serious, esp E. faecium
GRAM NEGATIVE COCCI
N. gonorrhoeae
PID
Ceftriaxone and
doxy
GRAM NEG RODS (= "enteric bacteria" + Pseudomonads)
LACTOSE FERMENTERS (LF)
E. coli, Klebsiella etc
Abd infection, UTI,
nosocomial
NON LACTOSE FERMENTERS (NLF)
Pseudomonas spp.
UTI, abd infection
Proteus (not mirabilis)
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ceph; AG ;
carbapenem ; quinol
AG;
ceph³;
carbapenem ; quinol
Nosocomial
Serratia
Enterobacter
NLFs generally more resistant (eg to cephs) than LFs. Other NLFs: Shigella, Salmonella,
Yersinia enterocolitica - a cause of mesenteric lymphadenitis.
ANAEROBES
GRAM POS COCCI
Peptostreptococcus
Peptococcus
Microaerophilic Strep
abd infection
brain abscess
synergistic gangrene (with Staph)
pen
pen
pen
gas gangrene
colitis
dental
pen
metro, vanco
pen
GRAM POS RODS
Clostridium spp
Clostridium difficile
Actinomyces
GRAM NEG RODS
Prevotella, Porphyromonas
(previously classed as
Bacteroides)
oral infections
Bacteroides spp
abd infection
Fusobacterium spp
brain abscess
pen, metro, clinda
cefoxitin, cefotetan,
imipenem,
meropenem,
ertapenem, pip/tazo,
Normal indigenous flora in some sites:
This list shows normal colonizers. Normal urine, CSF, peritoneum and joints are considered
sterile, though transient colonization occurs in peritoneal fluid and urine.
SKIN (in brackets: prevalence in population)
S. epidermidis (85-100%)
lactobacillus (55%)
S. aureus (5-25%) – nose, axilla, perineum
Proprionibacterium acnes (45-100%)
C. perfringens esp. lower limb (2-60%)
"diptheroids" (55%) many others
MOUTH
Aerobic, anaerobic strep (100%)
Bacteroides, Prevotella, Porphyromonas
Fusobacterium spp, many (common)
ALIMENTARY TRACT
Stomach: has a few bugs which don’t mind acid; Helicobacter pylori
Jejunum: Gm pos facultatives (enterococci, lactobacilli,); anaerobes; total < 105/ml
Ileum: "enteric bacteria" (E. coli, etc.) ↑ anaerobes as go distally
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Colon: Anaerobic Gm neg rods esp Bacteroides, Fusobaceria 1000 times more numerous
than all others; facultative/aerobes: E. coli, and Enterococcus always; other Gm neg rods
(Proteus, Klebsiella etc) variable; Gm pos rods (eg clostridia) common; Gm pos cocci
(peptostreptococcus) usually; Pseudomonas 3-10%; Candida albicans 15-30%
ILEUS or OBSTRUCTION: UGI stasis: ↑anaerobes, bacteria resemble colon
Bacteria found in some important surgical infections (Note S. aureus in all):
SKIN
S. aureus, S. Pyogenes
BURNS
S. pyogenes (early), Pseudomonas
S. aureus, Gm neg enteric
BRAIN ABSCESS
Aerobic & anaerobic strep
Bacteroides
S. aureus
LUNG ABSCESS
Bacteroides, Fusobacteria, anaerobic strep,
S. aureus enteric bacteria (esp Klebsiella)
PERITONITIS & ABDOM ABSCESS
E. coli + other enteric rods
B. fragilis + other anaerobes
anaerobic strep, enterococcus
BILIARY TRACT
E. coli, other enterics;
Enterococcus; anaerobes in elderly, diab,
very ill
PYELONEPHRITIS + CYSTITIS
same as biliary; not anaerobes
OSTEOMYELITIS
S. aureus, Salmonella (+ other Gm neg
rods)
SEPTIC ARTHRITIS – S. aureus, N. gonorrhoeae
-----------------------------------------------------------------------------------------------------------Microbe pathogenicity + concentration influence the development & outcome of infection
Pathogenic microbes (pathogens) infect hosts and cause harm using mechanisms such as
adherence, invasion, + toxins. Some microbes are less pathogenic to healthy people, but
cause opportunistic infections when host defenses are impaired eg S. aureus invades
healthy hosts, contrasted with S. epidermidis which infects biomaterials by sticking
opportunistically to foreign surfaces, and Candida spp which infect patients on steroids
Bacterial concentration is a determinant of infection, eg burn wounds (# of bacteria/gm of
tissue); and incisional surgical site infections - the NRC-ACS (1964) classified surgical
wounds by degree of contamination, as follows:
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CATEGORY
CLEAN: elective; no GI, RESP,
GU, GYN entry; no inflam, no
break in sterility
CLEAN-CONTAM: GI, (inc
prep’d bowel), RESP, GU or
GYN opening but no gross spill;
minor sterility break
CONTAM: major break in
technique; acute inflam without
pus; open, recent traumatic
wound
DIRTY: trauma > 4hr; overt
infection; perf viscus; infected
foreign body or dead tissue
REPORTED INFECTION
RATE
IDEAL RATE
1-5%
1%
5-12%
5%
10-20%
7%
25-40%
10%
ENVIRONMENT OF INFECTION
Across a spectrum of factors from populations to patients, processes of health care delivery
influence the acquisition, spread and outcome of infections. Many initiatives promote
appropriate antibiotic use and infection control (do you know any?) to improve patient
outcomes and forestall a looming crisis of antimicrobial resistance. “Antibiotic stewardship”
seeks to restore and preserve microbial ecology by promoting appropriate use through
education, restrictions, computer decision support etc.
The local tissue environment is affected by contaminants, host factors and treatment:
Bacterial contaminants affect the local environment via toxins, enzymes, (digest,
necrose); chemistry (lo pH, redox), and physical barriers eg biofilms. Contaminating
adjuvants (blood, feces) provide substrates for bacteria and frustrate local host defenses
Local host factors include 1) pre-existing mechanical barriers (eg skin); special anatomy
(subdiaphragmatic lymphatics); sweepers and flushers (cilia, peristalsis, voiding);
colonization by nonpathogens; chemistry (acid skin, acid vagina); lysozyme (tears, saliva);
and humoral (mucosal IgA) and cellular immune/inflam effectors (eg macrophages, kinins);
and 2) immune/inflam responses: ↑ perfusion, Ig, complement, pmns, macrophages
If possible, fix factors that impair local defenses and increase infection risk: smoking
Ann Surg 2003;238:1; obesity Heart Lung 2005;34:108; hypothermia NEJM 1996; 334:
1209; hypoxia CID 2013;57:1465; hi blood sugar Circulation 2004;109:1497;
malnutrition; and minimize blood; necrosis; foreign bodies. Resuscitation and physiologic
support ensure adequate local blood flow and oxygen delivery NEJM 2013;369:1243;
perioperative normothermia and normoglycemia have become standards. Operation itself
may remove bacteria and foreign/dead material but exposes tissues to microbes, blood,
sutures, drains and dead tissue. Percutaneous and minimal access techniques lessen these
effects.
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SYSTEMIC HOST DEFENSES
A. Immunologically nonspecific
B. Immunologically specific
1) Phagocytes
2) nonspecific humoral
1) cell-mediated immunity
2) humoral immunity
Specificity implies antigen memory. These categories overlap more than appears below eg
macros are phagocytes and involved in specific immunity
A) Immunologically nonspecific
1) Nonspecific cellular defenses: phagocytes
a) Neutrophils: In response to microbial and host molecule chemical gradients (chemotaxis)
they adhere to and exit vessel walls (diapedesis); eat and kill opsonized bugs (phagocytosis
and killing) within 1h, peaking at 4-12h then macrophages predominate. Neutrophils are
crucial defenses vs bacteria (except intracellular bugs eg TB, Listeria).
b) Mononuclear phagocytes: are monocyte (in circulation) = macrophages (in tissues).
Reticulo-endothelial (RE) system = fixed mononuclear phagocytes, which start life as
blood monocytes; liver (Kupffer cells) comprise largest most important RE organ; lung
(alveolar macros); spleen, nodes, marrow (sinusoidal lining cells); brain (glial cells).
Macrophages are larger slower phagocytes; their many functions include antigen processing;
wound healing; debridement; cytokine emission.
2) Nonspecific humoral defenses include complement, cytokines, others: amplify and
modulate inflammatory and immune responses
("classical" pathway)
142
3, 5 → 9
Complement sequence:
properdin
("alternative" pathway)
Complement functions – chemotaxis (C5a); opsonization (C3b); ↑ vascular permeability;
interacts with other cascades eg clotting
Cytokines eg IL-1 (Interleukin-1), IL-2, IL-6, gamma interferon, Tumour Necrosis Factor
(TNF), High Mobility Group B1 (HMGB1) mediate nonspecific and specific immunity as
messengers between defense cells; TNF is a mediator of septic shock and multiple organ
failure. Other immunologically nonspecific humoral mechanisms include coagulation,
protein C, fibronectin, counter-regulatory hormones, apoptosis, integrins, defensins,
cathelicidns, antimicrobial peptides, TLRs, G-CSF and serum cholesterol
.
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B) Immunologically specific
1) Cell-Mediated Immunity: T-lymphocytes have antigen memory and regulate immune
responses. In AIDS, helper T-cells are diminished.
2) Humoral immunity: Plasma cells (derived from B-lymphocytes) synthesize
immunoglobulins (Ig) which have antigen memory. IgM is early responder; IgG is late +
secondary responder. Secretory IgA resides in mucous membranes. Only IgG is opsonic
but IgM fixes complement best. IgG has highest concentration (in serum). Ig neutralizes
toxins (eg tetanus) + viruses (vaccines), opsonizes bugs; kills Gm negs (with complement);
IgA prevents bacterial attachment to epithelial surfaces.
Defects in systemic host defenses
Congenital: specific, often single defects
Acquired: steroids, malnutrition, cancer, sepsis etc cause multiple defects in host
defenses. These are important therapeutic targets, including d/c steroids if possible, and
supplementary nutrition for major malnutrition before major surgery NEJM 2011; 365:506.
DURATION OF INFECTION
Duration of contamination before treatment is a key determinant of the development
and outcome of many infections that surgeons prevent and treat. This explains why nonlocalized (eg abdominal) infections are emergencies, and why antibiotic surgical site
prophylaxis is most effective when given before operation, and ineffective if given too late.
Seminal, classic studies established the " decisive period" of bacterial lodgment (Miles Br J
Exp Pathol 1957;38:79), and the "effective period" of antibiotics in preventing infection
(Burke Surgery 1961;50:161). Antibiotics given up to 3-4 hours after wounding and
contamination prevent infection in animals; but not after 4 hours. Polk (Surgery
1969;66:97) first transferred this knowledge to human patients in a RCT showing that preincisional antibiotics decreased surgical site infection frequency in contaminated
operations.
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