NOSOCOMIAL INFECTION

Nosocomial infections (NCI)

"nosus" = disease

"komeion" = to take care of

Infections that occur during hospitalization but are not present nor incubating upon hospital admission

History of Nosocomial Infection

• Ignaz Semmelweis, (1840s) demonstrated importance of hand hygiene

• No progress for next century• 1976, the Joint Commission on

Accreditation of Healthcare Organizations - standards for infection control

• Nosocomial infection still on the increase - emerging infection

Nosocomial Infections

• 5-10% of patients admitted to acute care hospitals acquire infections– 2 million patients/year– ¼ of nosocomial infections occur in ICUs– 90,000 deaths/year– Attributable annual cost: $4.5 – $5.7 billion

• Cost is largely borne by the healthcare facility not 3rd party payors

Weinstein RA. Emerg Infect Dis 1998;4:416-420.Jarvis WR. Emerg Infect Dis 2001;7:170-173.Weinstein RA. Emerg Infect Dis 1998;4:416-420.

Jarvis WR. Emerg Infect Dis 2001;7:170-173.

Nosocomial Infections

• 70% are due to antibiotic-resistant organisms

• Invasive devices are more important than underlying diseases in determining susceptibility to nosocomial infection

Burke JP. New Engl J Med 2003;348:651-656.Safdar N et al. Current Infect Dis Reports 2001;3:487-495.

Major Sites of Nosocomial Infections

• Urinary tract infection

• Bloodstream infection

• Pneumonia (ventilator-associated)

• Surgical site infection

• Virtually all microorganisms can cause nosocomial infections

• Viruses

• Bacteria

• Fungi

• Parasites

CAUSES OF HCAI

• BacteriaBacteria

• Gram +Gram +– Staphylococcus aureus– Staphylococcus epidermidis

• Gram -Gram -– Enterobacteriaceae – Pseudomonas aeruginosa– Acinetobacter baumanni

• Mycobacterium tuberculosisMycobacterium tuberculosis

BACTERIABACTERIA

• VirusesViruses– Blood borne

infections : HBV, HCV, HIV

– Others: CMV, rubella,

varicella, SARS

• FungiFungi– Candida – Aspergillus

NOSOCOMIAL PATHOGENSNOSOCOMIAL PATHOGENS

SOURCES OF INFECTIONSOURCES OF INFECTION

EndogenousEndogenoussource is the normal flora or source is the normal flora or

colonisers of skin and other colonisers of skin and other epithelial surfacesepithelial surfaces

ExogenousExogenousother persons (cross-infection)other persons (cross-infection)

inanimate objects (fomites)inanimate objects (fomites)

TYPES BY ORIGIN

1.Endogenous: Caused by the organisms that are present as

part of normal flora of the patient

2. Exogenous: caused by organisms acquiring by exposure to hospital personnel, medical devices or hospital environment

Downloaded from: Principles and Practice of Infectious Diseases

© 2004 Elsevier

Up to 20% of skin-associated bacteria in skin appendages (hair follicles, sebaceous glands) & are not eliminated by topical antisepsis. Transection of these skin structures by surgical incision may carry the patient's resident bacteria deep into the wound and set the stage for subsequent infection.

The inanimate environment is a reservoir of pathogens

~ Contaminated surfaces increase cross-transmission ~

Abstract: The Risk of Hand and Glove Contamination after Contact with a VRE (+) Patient Environment. Hayden M, ICAAC, 2001, Chicago, IL.

X represents a positive Enterococcus culture

The pathogens are ubiquitous

The inanimate environment is a reservoir of pathogens

Recovery of MRSA, VRE, C.diff CNS and GNR

Devine et al. Journal of Hospital Infection. 2001;43;72-75

Lemmen et al Journal of Hospital Infection. 2004; 56:191-197

Trick et al. Arch Phy Med Rehabil Vol 83, July 2002

Walther et al. Biol Review, 2004:849-869

The inanimate environment is a reservoir of pathogens

Recovery of MRSA, VRE, CNS. C.diff and GNR

Devine et al. Journal of Hospital Infection. 2001;43;72-75

Lemmen et al Journal of Hospital Infection. 2004; 56:191-197

Trick et al. Arch Phy Med Rehabil Vol 83, July 2002

Walther et al. Biol Review, 2004:849-869

The inanimate environment is a reservoir of pathogens

Recovery of MRSA, VRE, CNS. C.diff and GNR

Devine et al. Journal of Hospital Infection. 2001;43;72-75

Lemmen et al Journal of Hospital Infection. 2004; 56:191-197

Trick et al. Arch Phy Med Rehabil Vol 83, July 2002

Walther et al. Biol Review, 2004:849-869

SPREAD OF INFECTONSSPREAD OF INFECTONS

Air-borneAir-borneSkin scales, droplet nuclei

ContactContactDirect

HandsHands & clothing

Droplet contact followed by autoinoculation

Clinical equipment

Indirect

Bedpans, bowls, jugs, etc

SPREAD OF INFECTONSSPREAD OF INFECTONS

The hands are the most importantvehicle of transmission of HCAI

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Exogenous Infections

Exogenous Infections

Endogenous Infections

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Chain of Transmission

Universal Precautions

Universal Precautions

PRACTISE STANDARD PRECAUTIONS

CONTROL OF HCAI

Hand hygiene is thesingle most importantmeasure for controlof nosocomial infections

TYPES OF HAND HYGIENE PROCEDURES

• Hand washing– Hand washing is usually limited to hands and wrists– Hands are washed for a minimum of 10 – 15 seconds with soap

(plain or antimicrobial) and water– Transient micro-organisms are mechanically removed by rinsing.

• Hand antisepsis/decontamination– Hand antisepsis removes or destroys transient micro-organisms and

confers a prolonged effect. – Two ways:

• Wash hands and forearms with antimicrobial soap and water, for 15-30 seconds

• Decontaminate hands with a waterless, alcohol-based hand gel or hand rub for 15-30 seconds. Appropriate for hands that are not soiled with protein matter or fat.

TYPES OF HAND HYGIENE PROCEDURES

• Surgical hand antisepsis– Removes or destroys transient micro-organisms and

confers a prolonged effect. – Hands and forearms are washed thoroughly with an

antiseptic soap for a minimum of 2-3 minutes. – Hands are dried using a sterile towel.– Required before performing invasive procedures.

Alcohol based hand hygiene solutionsQuick Easy to use

Very effective antisepsis due to bactericidal properties of alcohol

Hand Hygiene

• Single most important method to limit cross transmission of nosocomial pathogens

• Multiple opportunities exist for HCW hand contamination– Direct patient care– Inanimate environment

• Alcohol based hand sanitizers are ubiquitous– USE THEM BEFORE AND AFTER PATIENT

CARE ACTIVITIES

HAND WASHING TECHNIQUE

Source: World Health Organization. Regional Office for Western Pacific.

PROTECT YOURSELF PROTECT YOURSELF THROUGH IMMUNISATIONTHROUGH IMMUNISATION

ImmunisationImmunisationBCGBCG

Hepatitis BHepatitis B

TetanusTetanus

RubellaRubella

VaricellaVaricella

InfluenzaInfluenza

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Agent Mechanisms of Action Comments

Surfactants Membrane Disruption; increased penetration

Soaps; detergents

Quats (cationic detergent)

Denature proteins; Disrupts lipids

Antiseptic - benzalconium chloride, Cepacol; Disinfectant

Organic acids and bases

High/low pH Mold and Fungi inhibitors; e.g., benzoate of soda

Heavy Metals Denature protein Antiseptic & Disinfectant; Silver Nitrate

Halogens Oxidizing agent Disrupts cell membrane

Antiseptic - Iodine (Betadine) Disinfectant - Chlorine (Chlorox)

Alcohols Denatures proteins; Disrupts lipids

Antiseptic & Disinfectant Ethanol and isopropyl

Phenolics Disrupts cell membrane

Disinfectant Irritating odor

Aldehydes Denature proteins  Gluteraldehyde - disinfectant (Cidex); Formaldehyde - disinfectant

Ethylene Oxide Denaturing proteins Used in a closed chamber to sterilize

Oxidizing agents Denature proteins Hydrogen peroxide – antiseptic; Hydrogen peroxide – disinfectan; Benzoyl peroxide – antiseptic

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Agent Mechanisms of Action Comments

Moist Heat, boiling Denatures proteins Kills vegetative bacterial cells and viruses Endospores survive

Moist Heat, Autoclaving

Denatures proteins 121°C at 15 p.s.i. for 30 min kills everything

Moist Heat, Pasteurization

Denatures proteins Kills pathogens in food products

Dry Heat, Flaming Incineration of contaminants

Used for inoculating loop

Dry Heat, Hot air oven

Oxidation & Denatures proteins

170°C for 2 hours; Used for glassware & instrument sterilization

Filtration Separation of bacteria from liquid (HEPA: from air)

Used for heat sensitive liquids

Cold, Lyophilization (also desiccation)

Desiccation and low temperature

Used for food & drug preservation; Does not necessarily kill so used for Long-term storage of bacterial cultures

Cold, Refrigeration Decreased chemical reaction rate

Bacteriostatic

Osmotic Pressure, Addition of salt or sugar

Plasmolysis of contaminants

Used in food preservation (less effective against fungi)

Radiation, UV DNA damage (thymine dimers)

Limited penetration

Radiation, X-rays DNA damage Used for sterilizing medical supplies

Strong vis. Light Line-drying laundry

Conclusion

Hospital Pathogen Unhappypatients

Unhappydirector

Hospital Surveillance HappyPatients

Happydirector

Hands Spread Disease

Why disinfection and sterilization?

• Contagious diseases• Hospital infection (e.g., OR, ID ward)

or other opportunistic infection • Lab contamination, etc. • Microbes:

- usually easy to grow in environment; - but also can be inhibited or killed by certain

environmental (physical or chemical) factors/conditions.

Terminology

• Disinfection

• Sterilization

• Bacteriostasis

• Antisepsis

• Asepsis

Disinfection

• Process of reducing or eliminating living pathogenic microorganisms in or on materials, so they are no longer a health hazard.

For example: use of alcohol before drug injection.

Sterilization

• Process of destroying all microbial forms. A sterile object is one free of all microbial forms, including bacterial spores.

• More thorough than disinfection

Bacteriostasis

• Process of inhibiting the growth of microorganisms, in vivo (mostly) or in vitro

For example: bacteriostatic antibiotics

Antisepsis

• Process of inhibiting or preventing growth of microbes, mostly in vitro and not bactericidal or sporicidal

For example: use of chemical agents on skin, other living tissues or food/beverage.

Asepsis

• A state where no living microorganism exists.

For example: OR (Operating Room)

Controlling Microorganisms with Physical Conditions

• High Temperature (heat)

• Radiation

• Ultrasound

• Filtration

• Low Temperature

• Desiccation

High Temperature ——Dry heat and Moist heat protein denaturation

and clotting; DNA strand breakdown

static action cidal action .

Dry heat ： protein oxidation

• Incineration– most thorough (>500 )℃– disposals and corpes

• Flaming (burner) – test tube opening, transferring loop

• Hot air sterilization/Baking– 160-170 , 2h℃– Glassware, syringes, needles, etc

• Infrared heat: similar to baking

Moist heat ： denaturing proteins and melt lipids• Autoclaving

– Most commonly used and effective– 121 (103℃ .4kPa), 15-20min– killing both vegetative organisms and

endospores

• Boiling– 100 (105 with 2% Na℃ ℃ 2CO2) , 15-20min– cidal for vegetative cells but not necessarily spores

• Regular Steam (Arnold Sterilizer)– 100 , 15-20min℃– cidal for vegetative cells but not necessarily spores

• Pasteurization– to kill pathogens in readily perishable objects (milk,

wine)– flash method : 71.6 , 15s ℃– holding method : 62.9 , 30 min℃

• Fractional sterilization– alternating exposure and cooling time for a

consecutive period:Steam heating (100 , 30 min) ℃ 30 for ℃

endospores to germinate 100 , 30 min to kill ℃germinated endospores 30-37 overnight for ℃remaining endospores to germinate 100 , 60 min to ℃kill last remaining germinated endospores

– for sugar- or milk-containing culture media

Moist Heat vs Dry Heat

Moist heat Dry heat

Penetrating potency higher lower

Temp for protein clotting lower higher

Extra heat released yes no

from condensation

Sterilizing potency: Moist heat >> Dry heatSterilizing potency: Moist heat >> Dry heat

Radiation • Ultraviolet (UV) radiation

– mechanism: blockage of DNA replication by forming thymidine dimmers

– microbicidal activity of UV depends on:• length of exposure • wavelength: 200-300 nm, with the best effect of 265-266nm• bulb life (4000hr)

– very poor penetrating power– for air or surface disinfection

(OR, ID ward, labs) – causing eye damage, burns

and mutation in skin cells

• Ionizing Radiation– X-rays, gamma rays and high-speed electrons – generating more energy and penetrating power

than UV– to sterilize pharmaceuticals, disposable medical

supplies (e.g., syringes, gloves, catheters, sutures) and foods

• Microwave – penetrating non-metal materials (glass, plastics)

• Ultrasound– more effective for gram-negative bacteria– Lack of thoroughness —— survivors remain

• Filtration – sterilize heat- or chemical-sensitive solutions– not effective for virus, ricketia, mycoplasma

Seitz filter

• Desiccation– static effect by inhibiting microbial enzymes– not effective against endospores– mainly for food reservation

• Low Temperature (-20 ℃ ～ -70 )℃– inhibits microbial growth by slowing down

microbial metabolism– a special form: lyophalization (freeze-drying),

used for long-term (years) reservation of bacteria stocks

• fast freezing + drying• protecting agents (glycerol, serum)

Control Microorganisms with Chemical Agents

(Disinfectants and Antiseptics)

Antimicrobial modes of action of disinfectants and antiseptics

• Denaturation of bacterial proteins by disrupting hydrogen and disulfide bonds—— phenol (high conc.), alcohol, heavy-metal (high conc.),

acids, alkalies, aldehydes)

• Damage to bacterial membrane (lipids and/or proteins), causing leakage of intracellular molecules—— phenol (low conc.), surfactants, dyes

• Interference of bacterial enzyme and metabolism—— oxidants, heavy-metals (low conc.), alkylating agents

• Phenol and phenol derivatives —— altering membrane permeability and

denaturing proteins

• 0.01% - 0.05% Chlorhexidine —— vaginal wash, OR hand-wash

• 3% - 5% carbonic acid or 2% Lysol —— floor or surface disinfection

• Alcohols —— denaturing bacterial proteins and

membranes

• 70% - 75% ethyl or isopropyl alcohol —— skin and thermometer disinfection

– ineffective against endospores and non-enveloped viruses

• Heavy metals (Hg2+ 、 Ag+)

—— denaturing proteins and inactivating enzymes

• 2% mercurochrome or 0.1% merthiolate —— skin, mucosa and wound

– bacteriostatic, ineffective against endospores

• 1% silver nitrate —— eye drops for newborns to prevent gonococcal ophthalmia

• Oxidants

—— oxidation, protein precipitation

• 0.1% potassium permanganate —— skin, fruits/vegetables

• 3% peroxiden —— small trauma wound, skin, mucosa

• 0.2% - 1% peroxyacetic acid —— plastics, glassware

• 0.2 – 0.5 ppm cholorines —— water and swimming pool

• Surfactants

—— damaging bacterial membranes, inactivating enzymes, protein precipitation

• 0.05-0.1% bromogeramine —— OR hand-wash, skin, surgical instruments

• Alkylating agent

—— alkylating proteins and nucleic acids

• formalin (formaldehyde) —— surface disinfection, air, surgical instruments

• glutaric dialdehyde —— high-precision instruments, endoscopes

• 50mg/L epoxy ethane —— surgical instruments and dressing

• Dyes

—— inhibiting bacterial growth by interfering with oxidation

• 2% - 4% methyl violet —— wound disinfection

• Acids and alkalies

—— destroying cell membrane and cell wall, denaturing proteins

• 5-10ml/m3 acetic acid evaporation —— air disinfection

• quicklime [Ca(OH)2] —— floor and excretion (feces, urine, sputum, pus) disinfection

Effectiveness of antimicrobial agents are affected by :

• The concentration/intensity and nature of the disinfectant;

• Length of exposure;• Species and number of the microbe(s); • Temperature and humidity;• Acidity (pH);• Presence of organic substances;• Presence of chemical antagonists• The nature of the material bearing the microbes

Summary 1. Application of chemical disinfectants

Patient excretion Chlorines, 5% carbonic acid, 2% Lysol

Skin (hands) 2% Lysol, 0.2-0.4% peroxyacetic acid for HBV, 70% ethyl alcohol, 2% mercurochrome

Mucosa oral - 3% peroxide; uri-reproductive - 0.01-

0.05%Chlorhexidine, 0.1% potassium permanganate ;

newborn eyes - 1% silver nitrate

Drinking water Chlorines

Toilets, sewage quicklime [Ca(OH)2]

Air (OR, ID ward) formalin steam (12.5-25ml/m3,12-24h),formalin 40ml + potassium permanganate

30g/m3;HBV ward- peroxyacetic acid 3g/m3 90min

Glassware, china, 0.5% iodophores, 0.2-0.4% peroxyacetic Rubber, metal aciddevices

Potency Definition Examples

High Killing all microbes including glutaric dialdehyde， endospores and TB formaldehyde peroxyacetic acid，

epoxy ethane

Medium Killing all non-spore microbes alcohol, chlorines, including TB iodophores

Low Killing vegetative bacteria chlorhexidine， and lipophilic (enveloped) bromogeramine

viruses, but resisted by endospores, TB and hydrophilic (non-enveloped) viruses

Summary 2. Potency levels of chemical disinfectants

Spore-killing disinfectants

– glutaric dialdehyde, formaldehyde, Iodines,

H2O2, epoxy ethane

Non spore-killing disinfectants

– alcohols, phenols, chlorhexidine,

bromogeramine

Summary 3. Spore-killing effects of chemical disinfectants

Disinfection and Disinfection and SterilizationSterilization

——For the course of Medical Microbiology for MBBS foreign students, Class 2006/2011, SYSU

September 18, 2007

Mengfeng Li （黎孟枫） , M.D. Department of Microbiology, Zhongshan School of

Medicine, SYSU, Guangzhou, China

limf@mail.sysu.edu.cn

Medical Microbiology Medical Microbiology