Wound Infection

Jian Huang , MD, Ph. D

Prof. in Surgical Oncology

Dept. of Surgical Oncology

2nd Affiliated Hospital
Zhejiang University School of Medicine

hjys@zju.edu.cn
A Major Surgical Site Infection (SSI)
is a Catastrophe!

From Lewis Kaplan, MD. Reprinted with permission of author.

 Abscess Cellulitis Ulcer

Skin/skin structure infections that:

 Involve deep soft tissue
 Require surgical intervention
 Are associated with significant underlying disease that
complicate the response to treatment (eg, diabetes
mellitus, peripheral vascular disease, peripheral
neuropathy, or lower venous insufficiency).
 Background
 美国年外科手术超3000万例，260万例次发生SSI；
 发病率：腹腔外2-5%，腹腔手术高达 20%
 医院感染中的14%为SSI
 导致住院时间延长（平均7天） Archives of Surgery 2005
 导致费用增加（ 3000 –50 000美元)
 若美国每年感染下降20％，可节约14亿美元 J. Hitt,
VHA study, 12/2004
 死亡率增加2倍，再入院增加5倍
 增加患者和家庭的痛苦
 如果采取循证预防措施，可大幅降低感染发生率
 Wound infection has probably always been a
major complication of surgery and trauma.
 Koch’s postulates proving the agency of an
infective organism :
 found in considerable numbers in the septic focus(脓毒
性病灶).
 be possible to culture it in a pure form that septic focus.
 be able to produce similar lesions when injected into
another host.
Large Gram-positive
cocci in pairs
Advances in control of infection in surgery

 Aseptic technique has replaced the toxic antiseptic

techniques.
 Antibiotics have transformed infection rates.
 Delayed closure remains useful in contaminated
wounds .
 Causes of reduced resistance to infection
抗感染下降的原因

 Metabolic: malnutrition, diabetes, uraemia,

jaundice
 Disseminated disease: cancer and AIDS
 Iatrogenic（医源性）: radiotherapy,
chemotherapy, steroids
Risk factors for increased risk of wound infection

 Malnutrition (obesity, weight loss)

 Metabolic disease (malnutrition, diabetes, uraemia,
jaundice)
 Immunosuppression (cancer, AIDS, steroids,
chemotherapy and radiotherapy)
 Colonisation and translocation in the gastrointestinal
tract
 Poor perfusion (systemic shock or local ischaemia)
 Foreign body material
 Poor surgical technique (deed space, haematoma)
Patients with Surgical-Site Infections:
Risk Factors and Infection Types
Factors Impairing Wound Healing

Local Systemic
Infection Inflammatory Mediators
Foreign Body Malnutrition
Ischemia/Hypoxia Cancer
Venous Insufficiency Diabetes
Toxins Uremia
Previous Trauma Jaundice
Radiation Old Age
Smoking Steroids
Chemotherapy
Alcoholism
Opportunistic Infection

Under certain circumstances, bacteria that are not

normally pathogenic may start to behave as
pathogens.
eg. When enteral feeding is suspended during the
perioperative period, bacteria translocate to
mesenteric （肠系膜） nodes. the endotoxins
that they release may further increase
susceptibility to infection.
 医院感染常见部位构成
Others Urinary
21% Tract
Infection
30%
Pneumonia
15%

Bloodstream
Surgical Site Infection
Infection (SSI) 18%
16%
N=1.9 million infections
 不同外科手术的SSI发生率研究
35
32.14
Yalcin报道的4146例手术表明了
30
不同手术SSI发生率的极大差异
25
21.13
SSI发生率

20
17.27
(%)

15
10.26
10
7.63

5
2.93 2.56
1.52
0.35 0 0
0
结肠切除术 胆囊切除术 阑尾切除术 疝修补术 剖腹产术 乳腺切除术
胃/食管手术 脾切除术 矫形手术 经腹子宫切除术甲状腺切除术
Factors that determine whether a wound will
became infected

 Virulence and dose of infective agent

 Vascularity and health of tissue being invaded
 Presence of dead or foreign tissue
 Presence of antibiotics during the decisive
period
 Decisive period

 The acute inflammatory , humoral（体液） and

cellular processes take up to 4 hours to mobilise
the body’s response to a breach in its defences.

 Prophylactic antibiotics should be given to cover

the period in preventing the infection
 Local and systemic manifestation

 Superficial surgical site infection (SSSI)-----

infection of surgical wounds
Infection of a wound can be de defined as the
invasion of organisms through tissues following
a breakdown of local and systemic host defences.
 Systemic inflammatory response syndrome
(SIRS)
Sepsis is the systemic manifestation of a
documented infection, the signs and symptoms
of which may also be caused by multiple trauma.
burns or pancreatitis.
 Multiple organ dysfunction syndrome ( MODS)

 Multiple system organ failure (MSOF)

 Definitions in sepsis

 Systemic inflammation response syndrome

(SIRS):
Two of :
 hyperthermia (>38℃)or hypothermia (<36 ℃)
 Tachycardia (>90min-1 no  blockers) or
tachypnoea (>20min-1)
 White cell count>12×109l-1 or <4×109l-1

 Sepsis is SIRS with a documented infection

 Severe sepsis or sepsis syndrome is sepsis with
evidence of one or more organ failure
[respiratory (acute respiratory distress syndrome),
cardiovascular, renal (usually acute tubular
necrosis) or central nervous system]
 Systemic Inflammatory Response Syndrome

 Breaking beyond the borders of the soft tissue

 Caused by an exaggerated response to inflammatory mediators
 Inflammatory mediators
 Cytokines
 Interleukins especially with Interleukin 1
 TNF
 Stimulated by gram negative bacteria especially with Lipoprotein A endotoxin
 Nitric Oxide
 Arachadonic acid
 Prostaglandin 3
 Leukotrienes and thromboxanes
 Activation of procoagulant pathways
 Complement activation – dysfunction of antithrombin, release of tissue
factors
 Treatment with activated protein C
 Definitions of infected states

 SSSI is an infected wound

 SIRS is the body’s systemic response to an
infected wound
 MODS is the effect that the infection has on the
whole body
 MSOF is the end stage of uncontrolled MODS
Bacteraemia(菌血症) and Septicaemia(败血症)

 Septicaemia is common after anastomotic breakdown

 Septicaemia may be associated with MSOF

 Bacteraemia is dangerous if the patient has a prosthesis(假

肢、假体)
Classification of sources of infection

 Primary: acquired from community or endo-

genous
 Secondary：acquired from operating theatre or
ward (nosocomial 医院的 ) or from
contamination at surgery
 A common cause is poor hand-washing, it may
also result from inadequately filtered air in the
operating theatre or contamination at surgery.
 Classification of Wounds
Classification Infection Rate Wound Characteristics

Clean 1.5 – 5.1 Atraumatic, Uninfected,; no

Class I entry of GU
（genitourinary ）, GI, or
Resp. Tract
Clean-Contaminated 7.7 - 10.8 Minor breaks in sterile tech; entry
of GU, GI, or resp tract w/o
Class II
significant spillage

Contaminated 15.2 - 16.3 Traumatic wounds; gross spillage from

GI; entry into infected tissue, bone,
Class III urine or bile

Dirty 28.0 - 40.0 Drainage of abscess; debridement of

soft tissue infection
Class IV
Wound infection rates currently seen after general surgery

Type of surgery Infection rate(%) Rate before prophylaxis

Clean 1-2 The same

Clean-contaminated <10 Gastric surgery uo to 30%

Biliary surgery up to 20%

contaminated 15-20 Variable but up to 60%

dirty <40 Up to 60% or more

 Surgical Site Infection SSI

 浅表切开 表皮

Superficial incisional 皮下组织

浅表感染
 深部切口 深部软组
Deep incisional 织
深部感
 器官和腔隙 染
Organ/Space 器官间
隙 器官
间隙
感染
Major wound infections

 Significant quantity of pus(脓).

 Delayed return home.
 Patients are systemically ill.
 Type of infection
furuncle

胸前壁疖

A furuncle is a skin infection involving

an entire hair follicle and the adjacent
subcutaneous tissue
furuncle
无头疖
furuncle

furuncle
Furunculosis
疖病
下腰及臀部多个散在疖肿，中央
有白色脓头。
Carbuncle
痈
Cellulitis and lymphangitis淋巴管炎

 Cellulitis: Non-suppurative invasive of tissue

spread of infection
localised at the point of injury and subsequent tissue:
 Lymphangitis: painful red streaks in affected lymphatics
 painful lymph node groups in the drainage area

 Systemic signs (toxaemia) is common: SIRS ,fever, chills

 Blood cultures : negative

 Commonly caused by streptococci, staphylococci or clostridia

lymphangitis
lymphangitis
Wound abscess

 Most abscesses take 7-9 days to form after

surgery. As many as 75% of infections may
present after the patient has left hospital
 Persistent chronic abscesses may lead to sinus or
fistula formation, eg. mycobacteria and
actinomyces
 The role of antibiotics in the treatment of
wound abscess is controversial unless there are
signs of spreading infection such as cellulitis,
lymphangitis or related sepsis
 Treatment of Abscesses

 Modern imaging techniques may allow guided

aspiration

 Abscesses should be cleaned and drained

 Antibiotics are indicated if the abscess is not localised

 Delayed primary closure is best

 Specific Wound Infection
 Gas gangrene
 Caused by Clostridium perfringens (spore-baring bacilli)
 Crepitus (gas in tissue) and smell (sweet-smelling) are
characteristic
 Immunocompromised(免疫功能低下)patients are most at
risk
 Antibiotic prophylaxis is essential when performing
amputations to remove dead tissue
 Large dose of intravenous penicillin
 Aggressive debridement : wider excision of necrosis tissue
and laying open
 Hyperbaric oxygen is controversial
Tetanus

Tetanus Prone Wounds

 >6hours
 >1 cm depth
 Missile, crush, burn, frostbite
 Infection, devitalized, contaminate

History of Tetanus-Prone Wounds Non-Tetanus-Prone

Tetanus Wounds
Immunization Td TIG Td TIG
(Doses)
Unknown or <3 Yes Yes Yes No

3 or more No No No No
(< 5years) (<10 years)
 Treatment
 Major wound infection with systemic signs or evidence of
cellulitis need treatment with appropriate antibiotics.

 the choice of antibiotics may need to be empirical initially but is

best based on culture and sensitivities of isolates harvested at
surgery.

 Evidence of suppuration, allow the pus escape or leave the

wound open ( delayed primary closure)

 Specimens sent fresh for microbiological culture or for

immediate Gram stain
 Prophylaxis
 Prophylactic antibiotics

 Preoperative preparation

 Scrubbing and preparation

 Postoperative care of wounds

Prevent SSI by implementing four components of care
1. Appropriate use of antibiotics
 Administered within 60 minutes before incision
 Prophylactic antibiotic consistent with guidelines
 Antibiotic D/C’d within 24 hours of surgical end time

2. Appropriate hair removal

(clipping if needed; never shaving)

3. Maintenance of postoperative glucose control* for major

cardiac surgery patients

4. Establishment of postoperative normothermia体温正常

* for colorectal surgery patients

 * These components of care are supported by clinical trials and experimental

evidence in the specified populations; they may prove valuable for other
surgical patients as well.
3. Maintenance of postoperative glucose
control* for major cardiac surgery patients

4. Establishment of postoperative
normothermia（体温正常） * for colorectal
surgery patients

 * These components of care are supported by clinical trials

and experimental evidence in the specified populations;
they may prove valuable for other surgical patients as well.
 手术区域备皮问题
关于手术部位备皮方法与切开感染率的关系

 备皮方法 剃毛备皮 5.6%

脱毛或不去毛 0.6%
 备皮时间 术前24小时前 >20%
 术前24小时内 7.1%
 术前即刻 3.1%
 方法/时间 术前即刻剪毛 1.8%
 前1晚剪/剃毛 4.0%
 温度控制
 200 pts with colorectal cancer
control - 常规术中加温护理
(average body temerature 34.70C)
 treatment- 积极加温 (average body temerature
36.60C)
 结果
 control- SSI： 19% (18/96)
 treatment – SSI： 6% (6/104)

P=0.009 Kurz A, et al. N. Engl J Med. 1996

electric carpet
 Prophylactic antibiotics

 Time : at induction of anaesthesia

repeated 8 and 16 hours later if long
operation, esp. insertion of prosthesis
Cost
Local resistance trend
NOT using newer, wider –spectrum antibiotics
 Benzylpenicillin should be used if Clostridium infection
is a possibility.

 Patients with heart valve disease or a prosthesis should

be protected from bacteraemia caused by dental work,
urethral instrumentation（尿道仪器） or viscus
surgery.

 Lower limb amputation : at induction of anaesthesia

and 6-hourly thereafter for 48 hours
Preoperative preparation--- Avoiding
nosocomial infections
Staff should always wash their hands between patients
Staff not allowed to enter the theatre with open, infected
skin lesions
Patient length of stay should be kept to a minimum
Preoperative shaving should be avoided if possible.
 Scrubbing and preparation

 Aqueous antiseptics and scrubbing (surgeon)

 Alcoholic antiseptics for skin preparation( patient)

 Numbers of staff and movement in the theatre

 Postoperative care of wounds
 Related to Secondary (exogenous) nosocomial
infection
 Presence of MRSA (methicillin-resistant
staphylococus aureus) is a marker of
inadequate postoperative wound care

 Surgeons manage their own audit and follow-up

Relative Distribution of Bacteria
From Superficial to Deep Infections

Superficial Staphylococcus
infection Streptococcus

Gram-
negative
Deep Bacilli
infection
Anaerobes

Nichols RL, et al. Clin Infect Dis. 2001;33(suppl 2):S84-S93.

 Bacteria involved in wound infection

 Streptococci

 Only some are normally pathogenic like Strep.

Pyogenes and faecalis.
 All remain sensitive to penicillin,
Cephalosporins is an alternative if patient
is allergic to it.
Staphylococci

 An important pathogen.

 Staphylococcus epidermidis is not normally pathogenic and

is found everywhere.

 Some stains are now

resistant to many antibiotics (MRSA)
resistant to vancomycin appearing.
highly resistant strains (multiply resistant, coagulase-
negative staphylococci, MRCNS) appearing.

 A major threat to prosthesis surgery.

 Pseudomonas

 Rates may be an indicator of wound care in a unit.

 Wound infections only need antibiotic therapy if spread
of infection.
 Principles of antimicrbial treatment
 Principles in the use of antibiotics
Known sensitive infection
narrow-spectrum antibiotics
Unknown or mixed infection
combination of broad-spectrum antibiotics
bacteriostatic and bactericidal(抑菌和杀菌)
 Given in the decisive period useful for prophylaxis
 Only spreading infection or signs of systemic infection
justify the use of antibiotics
 Whenever possible, the organism and sensitivity should
be determined
 Treatment of commensals(共生)that have
became opportunist pathogens.

 They are likely to have multiple antibiotic resistance.

 It may be necessary to rotate antibiotics.
 Wound Closure
Type of Closure Type of Wound Examples

Primary Small Wounds, No flap Post non-ruptured

or skin graft appendix or mass
requirements excision

Secondary Small or superficial that Puncture or abrasions

will heal within 2 weeks.
Contaminated or Dirty

Tertiary Dirty, bleeding, Debridement then

contaminated wounds closure.
Bacterial count < 105
Incidence of SSIs following closure/delayed
closure of an infected wound

Opening and re-closure Reinfection

times rate
Opening and re-closure at
50%
once
Opening and re-closure
20%
after two days
Opening and re-closure
5%
after four days
Opening and re-closure
10%
after nine days
What is the hemodynamic
significance of
SIRS/SEPSIS/SHOCK
 Antibiotic and
Antifungal Appropriate
use and reduction of
resistance
Adopted from David Wong, MD, FACS, FCCP
Department of Surgery
Arrowhead Regional Medical Center
Loma Linda University Medical Center
California, USA
 Improving Treatment Outcomes
•Immunocompromised
•Pregnancy
•Protected Sites
Host

Timing

•Sensitivities
•Resistance Pattern
•Spectrum
•Synergism
•Cost

Nicolau DP Am J Man Care 1998:4(suppl)s525-30

 The ICU Bugs
Emerging antimicrobial resistance in 40 USA medical centers

35
30
Incidence

25
20
15
10
5
0
VRE MRSA PRPP CRP ESBL
 Choosing an
Antibiotic/Antifungal
 Sensitivities
 In Vitro Minimum inhibitory concentration
(MIC). May not reflect in vivo activity
 Past antibiotic use

 Protected Sites – ie CSF

 Immunocompromised states
 Deciding on bactericidal vs bacteriostatic
 Double gram neg. coverage
 Choosing an Antibiotic/Antifungal
 Pregnancy
 Avoid tetracyclines, flouroquinolones, flagyl
 Narrow spectrum – base on culture and sensitivities
 Cost
 Resistance pattern
 SPACE
 Serratia
 Pseudomonas
 Acinetobacter
 Citrobacter
 Enterobacter
 Extended Spectrum Beta-Lactam producers
 E. Coli
 Klebsiella
 Timing of Antibiotic Therapy

90
80
70
Mortality

60 Before BAL
50
After BAL
40
30 After BAL
20 Results
10
0
adequate Inadequate

Luna CM, et al Chest 1997; 111:676-685

Timing of Antibiotic Therapy
14,069 patients/3555 hospitals

1.4
Adjusted Odds 30 day Mortality

1.2
1
0.8
0.6
0.4
0.2
0
1 2 3 4 5 6 7 8 9 10
Hours from administration

Meehan et al, JAMA 1997; 278:2080

 2847例选择性清洁或清洁污染切口

antibiotcs should be given half an hour before incision

or anesthisia
 Resistance and Inadequate coverage
Inadequate therapy more likely if antibiotic resistance is present, and certain
organisms (antibiotic resistant ones) more commonly associated with
inadequate therapy.
40
35
30
25
20 % inadequate
15 treatment

10
5
0
Pseu Serr Acin other Kleb

Kollef, et al. CID 2000;31:S 131-138

 Giving the Drug at the Right Time

 This measure reflects the percentage of patients

receiving antibiotics at the right time before the
surgical incision.

 Research has shown that antibiotics are most

effective in reducing risk of infection when given
as close to the beginning of the surgery as possible,
no earlier than 1 hour before the surgical incision.
 Stopping the Drug at the Right Time

 This measure reflects the percentage of patients

where the drug was discontinued at the right time.

 Research has shown that antibiotics are only

needed for a short time after surgery to reduce the
risk of infection. Continuing “preventive”
antibiotics for longer than necessary could increase
costs and risk of complications.
 Mechanisms of resistance
 Alteration in the target protein
 Alteration in the DNA gyrase in flouroquinolones
 Reduced access to the target
 Reduction in cell-wall permeability (imipenem resistance)
 Alteration in penicillin binding protein (methicillin-resistance)
 Actively pumping the antibiotic out of the cell (tetracycline
resistance)
 Enzymatic inactivation of the antibiotic
 B-lactams and aminoglycosides
 Other considerations to
Antibiotic Choice
 Inoculum effect
 Declining antimicrobial efficacy with increasing number
of organism
 Imepenem highly resistant to this effect
 Postantibiotic effect
 Delay in bacterial growth after the concentration fall
below MIC
 Allows intermittent dosing ie 24 hr dosing of gentamycin
 Flouroquinolones and aminoglycosides
 Imepenem in all gram + and some gram –
 Beta-lactams only with gram +
 Other considerations to
Antibiotic Choice
 Concentration-dependent killing
 Where the rate of bactericidal activity and the duration of
postantibiotic effect are proportional to the concentration of
the drug
 Flouroquinolones and aminoglycosides
 Time-dependent killing
 Bactericidal activity is proportional to the duration of the
time that the concentration of the antibiotic exceeds the MIC
 Not increased by higher concentrations
 Cell wall antibiotics (Vanco and B-lactams)
 Other considerations to
Antibiotic Choice
 Antibiotic Combinations
 Benefits (synergism, broader spectrum, reduction in dosing to
decrease toxicity, decrease resistance)
 Cell wall active drug with aminoglycoside
 B-lactam plus B-lactamase inhibitor
 Sequential metabolic targets (trimethoprim/sulfamethoxazole)
 Disadvantages (Antagonsim, select resistance, increase
toxicity and cost)
 Bacteriostatic agent with bactericidal drug
 Drug that induces B-lactam with B-lactam susceptible drug (ie
imipenem and cephalosporins)
 Is One Drug As Good As Two?
 Monotherapy: Studies prior to 1985, Overall response
rates were similar
 Less toxicity
 Combination Therapy:
 Broader antibacterial coverage
 Synergy may be helpful in life threatening infections in
patients with severe underlying disease
 May limit the emergence of superinfection(二重感染)and
reduce development of resistance
 Multinational, Prospective Study of
Combination vs Single Drug Rx of Bacteremic
Pneumococcal Pneumonia
 21 hospital/10 countries 12/98-12/00

 844 patients, observational study

 Overall mortality 139/844 (16.5%)

 In Severely ill categories:

 Mono: 55% mortality vs 23% Combo
 Class of drug did no appear to be a factor

Baddour et al, Abstract L-466, ICAAC, Sept 2003

 Consider Combination Therapy
 Documented infection with Pseudomonas Aeruginosa
or Enterobacter species outside of the urinary tract
 In febrile neutropenia, particularly with a documented
infection
 Empiric therapy for sepsis with hypotension
 Mono therapy with hypotension is equivalent
 Empiric therapy of nosocomial respiratory tract
infection
 Mono therapy if not considering pseudomonas or
enterobacter
 Antifungal
 Indications
 Most common fungal
 C Albicans, Tropicalis, Glabrata, Parapsilosis, Krusei
 Resistance
 Ampho B
 Polyene macrolide effecting membrane permeability by binding
ergosterol found preferentially in fungus
 Dosing, 6 mg/kg or at least 200 mg
 Flucanazole (triazole); Cancidas
 C krusei and C. Glabrata resistant
 Itracanazole (imidazoles)
 Aspergilosis
 Key Concepts in
Antibiotic/Antifungal Resistance
 Use antibiotics/antifungal only when necessary
 Clinical/laboratory/radiological support for infection
 Early adequate treatment improves outcome
 Selection of antibiotic without optimal clinical and
bacterial responses may promote resistance
 Clinical study results alone may not demonstrate
differences in potential to develop resistance
 A less potent and less pharmacodynamically active drug
could promulgate cross resistance
 De-escalate and narrow spectrum when cultures are
available
% of Patients Receiving Recommended Drug*
Statewide
Avg-62%

Medical Center 50%

University 77%

Memorial 65%

Community
98%
Memorial

Hospital 70%

0% 20% 40% 60% 80% 100%

•These data are taken from a sampling consistent with national standards based on information contained in patient medical
records as reflected by the surgeon’s choice of a preventive antibiotic for the surgical procedure performed”.
 Case Study
 44 yo in previously good health is s/p MVA
complicated by flail chest and requires
mechanical ventilation
 On PTD#4, develops fever 101 F, purulent
sputum, and WBC 18. CXR shows a new right
lower lob infiltrate, and the ET tube is in the
correct position
 Does the patient need combination therapy?
 Case Study: Pathogens
1. Pneumococcus
2. Haemophilus Influenzae
3. Pseudomonas Aeruginosa
4. E. Coli
5. Methicillin-susceptible Staphlococcus Aureus
SUPPLEMENT
 Classification by Mechanism
 Cell wall damage
 Beta-lactams and vancomycin
 Injury to cytoplasmic membrane
 Polymyxins
 Interference with nucleic acid synthesis or
metabolism
 Flouroquinolones and rifampin
 Inhibition of protein synthesis
 Aminogycosides, macrolides, tetracyclines
 Modification of energy metabolism
 Sulfonaides, trimethoprim
 Beta Lactams
 Bactericidal by acting as substrate for bacterial wall
transpeptidase enzyme
 Penicillins
 20% resistance to S. Aureus
 50% resistance to S. Epidermidis
 Carboxy and ureido-penicillins and gram neg coverage
esp with pseudomonas coverage by ureidopenicilins
 Cephalosporins (1st , 2nd, 3rd, 4th generation)
 Monobactams (ie aztreonam)
 Gram neg coverage mainly
 Does not induce B-lactams
 Beta Lactams (cont)
 Thienamycin or Carbapenems (ie imipenem)
 5 member carbon ring in trans configuration prevents
hydrolysis by betat-lactamases
 Combined with cilastatin, the renal excretion is decreased
 Big inducer of B-lactams (don’t mix with other beta-lactam
susceptible drug)
 Lowers seizure threshold
 Beta-lactam Inhibitor
 Sulbactam and Clavulanic acid
 Helps at broader gram neg coverage
 Vancomycin
 Bactericidal by wall synthesis inhibition
 Mainly gram pos.
 MRSA, Coag-neg Staph, pen ristant pneumococci,
and corynbacterium jeikeium
 Poor oral absorption but IV form shows good
tissue penetration including CSF
 Perfect for oral use in C. Difficile Colitis
 Not removed by dialysis
 Linezolid (Zyvox)

 Resist multidrug resistant organisms

 Bactericidal via 30s ribosomal binding
 New class oxazolidinone
 FDA approved for VRE, staph and strept
pneumonia and skin infections
 Aminoglycosides
 Bactericidal via 30s ribosomal subunit binding
 Gram pos and gram neg spectrum
 Synergistic with cell wall antibiotics
 Macrolides
 Bacteristatic by binding 60s ribosomes and
inhibition of protein synthesis
 Erythromycin, clarithromicin and azithromycin
 Gram + coverage including legionella,
mycoplasma and chlamydia,diptheria,
bartonelosis
 Clindamycin and lincomycin
 Bacteristatic agent that binds 50s ribosomal
subunit like chloramphenicol
 Excellent gram pos. coverage with anaerobic
coverage also
 Rapid reduction of the production of LPS in
sepsis may reduce inflammatory mediators
 Metronidazole
 Bactericidal by indirect damage to DNA by toxic
mediators
 Excellent anaerobic coverage and some
protozoan
 Poor aerobic coverage including gram pos.
coverage
 Trimethoprim and
Trimethoprim-Sulfamethoxazole

 Bactericidal by inhibition of dihydrofolate

reductase which results reduction in synthesis
of purines, and pyrimidines
 Synergism with sulfamethoxazole inhibits the
production of folic acid
 CI in pregnancy and G6PD deficiency
 UTI and pneumocystis infections
 Quinolones
 Bactericidal effect by inhibiting DNA gyrase
(halts transcription)
 Intracellular effect so it has postantibiotic effect
on both gram pos and neg
 Not all flouroquinolones are the same
 Levo is excreted by kidney so can treat UTI
 Do not use in kids (growth plate inhibition)
 Radiation Effects
 Initially
 Inflammation and Desquamation
 Improve chemotherapy
 Histological Changes
 Multiple vacoules, irregular rough ER
 Degenerating mitochndria, cytoplasmic inclusion bodies
 Chronic Changes
 Increased Collagen
 Fibrosis
 Hypertrophy of media of vessels
 Occlusion and decreased blood vessel
 Vitamin A may reverse some of these effects
 Wound Healing Physiology
Phases of wound healing (Histologic Changes)
Exposed endothelium Phospholipase A
Prostaglandins, NO
Coagulation (Platelets) IL 1, PDGF, TGF-B
Inflammatory (Neutrophils) IL
chemoattractants
Migratory (Macrophages) Fibroblast GF, TGF-B
Angiogenesis(Macs, Lymphocyte)
Proliferative (Fibroblasts –
fibrin and fibronectin)
Epithelization Epidermal GF
 Wound Healing Physiology
 Clinical presentation of phases of wound healing

6 weeks 2 weeks – 2 6 months to

years 2 years
Healing Remodeling Maturation
Exudate Red Pale
Scab Raised Flat
Fine Line Itchy Quiet
Tender Contracture
Contraction
Normal Physiology to Pathology
 Factors impairing wound healing overwhelms
normal course of wound healing
 Koch’s postulate
 Organism is found in considerable numbers
 Can be cultured

 Similar lesions can be produced in another host

 Clinical Presentations
 Severe wound scars
 Keloid, host factor
 Contractures
 Granulation tissue
 What is the histologic requirement?
 Soft tissue pathology
 Necrotizing fasciitis
 Cellulitis
 Non-suppurative, poorly localized
 Commonly due to stretocci, staphylococci
 SIRS
 Blood cultures are often negative
 Lymphangitis
 More confined than cellulitis
 Abscess
 Phlegmon as a precursor
 Incision and drainage
 Management
 Antibiotic/antifungal in systemic cases
 Open wounds and leave open
 Delayed primary closure