INFECTION AND ANTIMICROBIAL RESISTANCE
| INFECTION AND THE ANESTHESIOLOGISTS AND INTENSIVISTS —Jeanine P. Wiener-Kronish, MD, Professor of
Anesthesia and Medicine, Vice-Chair, Department of Anesthesia and Perioperative Care, and Investigator, Cardiovascular
Research Institute, University of California, San Francisco, School of Medicine
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Health Care Worker
| Avian influenza: since 1889, human influenza pandemics have been caused by H1, H2, and H3 subtypes; newer H5 subtype
known as human avian influenza; influenza typically transmitted by sneezing and coughing; diarrhea most common
clinical sign seen with avian influenza (occurs in ≤70% of patients); 27 subtypes of influenza A virus; H5N1 subtype has
incubation time of 3 to 4 days and duration of 24 days; signs include fever, sore throat, nonproductive cough, conjunctivitis,
and diarrhea; systemic disease associated with lymphopenia, thrombocytopenia, acute respiratory distress syndrome
(ARDS), and death; does not link up in upper airway; instead, prefers α2-3 galactose linkage (GAL) deep in lung at bronchiolar-alveolar
junction and in type 2 cells; cats carry and transmit disease (eat birds; excrete virus in feces); universal
precautions necessary, not solely respiratory precautions; fatality rate 50% in humans and 90% in birds; unclear whether
characteristics similar to typical human influenza; resistance documented with, eg, amantadine, rimantadine, but high
doses of oseltamivir (Tamiflu) successful; infected birds found in all of Europe and Africa, and likely coming to United
States; genetic changes now seen; avian influenza being precisely monitored; viral genome already sequenced; infected
animals show virus going to brain; additional signs include disseminated intravascular coagulation (DIC) and intestinal
disease (reminiscent of sudden acute respiratory syndrome [SARS]); differential diagnosis includes SARS, community-
acquired pneumonia, and ARDS; obtain viral cultures and real-time polymerase chain reaction (PCR) values
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| Sudden acute respiratory syndrome: animals in close contact with humans enabled viral spread; began in China, but
spread to many countries; 8400 confirmed cases; 809 deaths; 35% mortality rate associated with respiratory failure (mortality
7% if <60 yr of age, 55% if >60 yr of age); presented with fever, cough and dyspnea, lymphopenia, elevated lactate
dehydrogenase (LDH) muscle enzymes and liver enzymes, and diarrhea; health care workers at particular risk during epidemics
of this type of virus (30% to 54% of SARS infections in Hong Kong in health care workers); duration of contact
with infected patient increased risk for infection; in Toronto, 51% of health care workers infected; 13% relative risk for infection
in personnel involved with intubation vs other activities
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| High-risk patients: include intensive care unit (ICU), requiring intubation, and undergoing bronchoscopy; not as dangerous
to draw blood; difficult intubation “good place” to contract virus; health care workers also risk infection when not
using eye protection; protective suits, gloves, and eye protection necessary; should be disposable; N-95 masks; air-powered
respirators also necessary for laryngoscopy and bronchoscopy; operating room (OR) should have separate air conditioning
and humidification systems; double equipment necessary (equipment touching patient can be disposed of or
placed into sterilizer); other recommendations—use of muscle relaxants (to avoid coughing); senior anesthesiologists
for intubation; consider not manipulating airway (use regional anesthesia); protect circuits; leave rings and wristwatch
outside OR
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Patient
| Endotracheal tube (ETT)–related infections: upon placement, ETT becomes coated with bacteria and biofilm; occurs
on outside and inside of ETT; after days of intubation, even normal patients with no comorbid diseases develop pneumonia;
may occur through suctioning or by oral secretions dripping into lungs; new ETT design attempting to limit
aspiration of oral secretions (low-volume, low-pressure cuff); currently use water-soluble lubricant to assist cuff in sticking
to trachea (effective for only 48 hr); new design continually monitors cuff pressure and maintains pressure at 30 cm
H2 O; high bacterial numbers seen in asymptomatic patient; disease indicated by decrement in host fitness; presence of
bacteria necessary but not sufficient to diagnose infection in patient with chronic airway manipulation
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 | Antibiotic resistance: common with most types of bacteria; many patients with fever and elevated white blood cell
(WBC) count do not have lung infection; treat patient with positive culture for 8 days; infectious diseases third leading
cause of death in United States; no new antibiotics foreseen in near future; speaker’s ICU does not allow antibiotics to
be prescribed for more than certain length of time without pharmacist and infectious disease personnel oversight due to
dramatic increasing resistance; strict isolation and restricted antibiotic administration helpful
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| Diagnostic requirements for ventilator-associated pneumonia: although important, decreased oxygenation not required;
requirements include hospitalization for 48 hr and 2 of following, fever or hypothermia, elevated WBC count, purulent
secretions, and recent or persistent infiltrate; obtain quantitative culture; able to identify only one third of patients who
appear infected; fever, WBC count, and chest x-ray findings do not identify lung infection in ICU (not specific or sensitive);
routine surveillance cultures important; at least 15% of patients at speaker’s institution do not have fever or elevated
WBC count but do have infection
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| Limiting ventilator-associated pneumonia: limit sedation; remove ETT as soon as possible; withhold antibiotics in one third
or more of patients by finding negative cultures; molecular biology vs culture; limit antibiotics (8 days adequate, except
in Pseudomonas or resistant gram-negative organism); speaker uses blind catheters; assume patient has resistant bacteria;
protect self and patients by using barrier techniques and alcohol-based soap before and after patient contact
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| Regional procedures and infections: one fourth of 5 million vascular catheters placed annually result in infection;
200,000 nosocomial bloodstream infections yearly in United States from vascular catheters; if in place <2 wk, infection
occurs from skin and area around hub; if in place >2 wk, infection occurs from inside catheter; controversial literature
suggests subclavian artery may be safest location to avoid infection; antibiotic-coated catheters cost-effective if rate of
infection >2%; speaker places antibiotic-coated catheter if likely to be in place >1 wk; unnecessary to change central
lines routinely to decrease infection; use total sterile technique in OR and ICU; always use eye protection, cap, gown, and
mask, and large sterile drape; diagnosis of catheter-related infection—data suggest 2 sets of blood cultures (one from
central line, other from periphery); if central line grows bacteria in ≥2 hr, that suggests central line infection; automated
system uses fluorescent probes to identify blood cultures; if patient hypotensive and in extremis, speaker removes central
line; dictums—positive blood culture for Staphylococcus aureus and Candida requires catheter removal (particularly
if positive after start of antibiotics; associated with metastatic disease); treat for 2 wk; check heart valves; transesophageal
echocardiography (TEE) limits antibiotic coverage for 1 wk; other organisms requiring catheter removal include
gram-negatives (eg, Pseudomonas), other types of fungus, and persistent bacteremia; no data showing guide wire
changes improve clinical situation; study comparing antibiotic-coated catheters indicates vigilance necessary (switch
when infection occurs)
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| Antibiotic prophylaxis for surgeries: 2% to 5% of patients undergoing extra-abdominal procedure have surgical-
site infection; increases to 20% when abdomen entered; development of infection results in admission to ICU; performance
measurements include number of patients receiving antibiotics 1 hr prior to incision, number receiving antibiotics
consistent with guidelines, and number who stopped receiving antibiotics after 24 hr; procedures with no controversy
about antibiotic coverage include coronary artery bypass grafting, vascular surgery, thromboendarterectomy and vein bypass,
general abdominal colorectal surgery, hip and knee arthroplasty, and abdominal and vaginal hysterectomy; achieve
drug levels before abdominal incision (give vancomycin 2 hr before); continued use of antibiotics after closure of surgical
incision “has a real downside” (pharmacists prefer 72 hr, panel suggests ≤48 hr for cardiac surgery); β-lactam antibiotics
most common; true signs of allergic reaction include urticaria, pruritus, and angioedema; do not change coverage
for penicillin allergy; alternatives include vancomycin or clindamycin; use vancomycin if colonized with methicillin-resistant
S aureus (MRSA); treatment for infection does not preclude prophylaxis; obese patients require increased dosages;
with cesarean delivery or ruptured membranes, give prophylactic antibiotic after clamping umbilical cord; cefazolin
also can be used for 24 hr for orthopedic arthroplasty; colorectal surgery involves giving oral antimicrobial preparation
(eg, neomycin, erythromycin) followed by cefoxitin, cefotetan, or cefazolin and metronidazole
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| ANTIMICROBIAL RESISTANCE: WHY SHOULD WE CARE? —Douglas B. Coursin, MD, Professor of Anesthesiology
and Medicine, University of Wisconsin School of Medicine and Public Health, Madison
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| Infectious disease: third overall cause of death in United States, second overall worldwide; hospital-acquired infections
major cause of morbidity and mortality in OR and ICU patients
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| Key points: wash hands before entering room, before starting case, before performing invasive procedure, and frequently
thereafter and between all patients; use standard, well-outlined techniques for central venous catheter placement (if possible,
avoid placement); avoid internal jugular vein for prolonged catheter placement; if possible, place single-lumen catheter
instead of triple-lumen catheter; timely and appropriate use of antibiotic prophylaxis
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| Antimicrobial resistance: not only big problem for patients, but also potentially big problem for clinician; 25% to
40% of pneumococcus in community now resistant to penicillin; increasing resistance in S aureus, Enterococcus, and
organisms that do not normally occur in community; sepsis leading cause of death in medical/surgical critically ill patients
and leading cause of death in surgical patients; infection control report cards likely coming in future for clinicians
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| Steps to prevent spread of resistant infections: Centers for Disease Control and Prevention plan available at
www.cdc.gov/drugresistance/healthcare/overview.htm
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| Infection prevention: enhanced vaccinations (health care worker should be vaccinated against hepatitis B [and maintain
antibodies]; hepatitis C vaccination may be in future); use good hand washing technique; administer antibiotics at appropriate
time; avoid unnecessary catheters; remove catheters as quickly as possible
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| Timely diagnosis and initiation of definitive treatment of infections: target pathogen
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| Judicious anti-infective use: treat infection, not contamination or colonization; treat patient, not clinician; stop treatment
when inappropriate, if ineffective, or when patient cured
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| Implementation of effective infection control principles to limit or avoid primary infection (ie, source control)
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| Sepsis and septic shock: affects 750,000 patients yearly (rivals acute myocardial infarction); leading cause of acute
lung injury and ARDS in United States; >50% require ICU admission; ≈20% require ventilation; mortality in many institutions
≈50% (lowered in cutting-edge institutions to 25% to 30%); results in ≈250,000 deaths yearly; projected cost
≈$17 billion
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| Incidence of resistance: ≈60% of S aureus resistant to methicillin; some strains of Enterococcus faecalis 100% resistant
to vancomycin; in speaker’s institution, >50% of Pseudomonas resistant to ciprofloxacin and quinolones; large number
of Klebsiella resistant; in Iraq war, Acinetobacter highly prevalent, and effective antibiotic therapy unavailable
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| Selection for antimicrobial resistance: resistant strains relatively rare; however, antimicrobial exposure results in domination
by resistant strains; sharing of genetic data (eg, gram-positive to gram-negative) results in cross-resistance
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| Guidelines for surviving sepsis: early (within 6 hr) goal-directed therapy (eg, hemodynamic monitoring and resuscitation
to reasonable end point); early broad-spectrum antibiotics; source control of infection; appropriate vasopressor and
inotropic support (avoid renal-dose dopamine; use norepinephrine); glycemic control; consider use of activated protein
C; target hemoglobin of 7 to 9 g/dL unless coronary artery disease (CAD) or bleeding present; protective low-stretch ventilatory
techniques (6 to 8 mL/kg) shown to lower development of ventilator-induced lung injury; judicious use of sedative
analgesics; prophylaxis for deep venous thrombosis (DVT)
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| Increasing antimicrobial resistance: more common in patients who have already had prolonged ICU stay within 1
yr, prior therapy with antibiotics, increasingly sick patients, and older, eg, nursing home, patient; clinicians “are
sometimes dummies when it comes to infection control” (eg, poor antibiotic selection; improper dosing; failure to adjust
antibiotic regime when infecting agent known); “the bugs are smarter than we give them credit”; fewer new drugs
and fewer effective drugs available; antimicrobial resistance to bacteria, fungi, and viruses; resistance more frequent
in immunosuppressed patients (eg, liver, lung, and bone marrow transplant population)
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| Intrinsic resistance: attribute of particular antibiotic and organism (ampicillin and vancomycin effective against most Enterococcus
, but cephalosporins ineffective)
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| Acquired resistance: reflects true change in genetic make-up of bacteria; once-effective drug becomes ineffective; ranges
from relative tolerance to absolute resistance
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Educational Objectives
| The goal of this program is to educate the listener about infection and antimicrobial resistance. After hearing and assimilating
this program, the participant will be better able to:
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| 1. Describe the risks related to anesthesia practice from avian influenza and the sudden acute respiratory syndrome.
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| 2. Review anesthesia practices that contribute to nosocomial infection, including endotracheal tube and vascular catheter
placement.
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| 3. Summarize antibiotic prophylaxis for surgeries.
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| 4. Outline the important steps to prevent the spread of resistant infections.
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| 5. Explain the guidelines for surviving sepsis.
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Discussed on This Program
Amantadine HCl [Symmetrel]
Ampicillin [Principen]
Azithromycin [Zithromax, Zmax]
Cefazolin sodium [Ancef, Zolicef]
Cefotetan disodium [Cefotan]
Cefoxitin sodium [Mefoxin]
Ceftazidime (several trade names)
Ceftriaxone sodium [Rocephin]
Cefuroxime [Ceftin, Kefurox, Zinacef]
Ciprofloxacin (several trade names)
Clarithromycin [Biaxin, Biaxin XL]
Clindamycin (several trade names)
Dobutamine [Dobutrex]
Dopamine HCl [Intropin, Dopamine HCl in 5% Dextrose]
Drotrecogin alfa (activated protein C) [Xigris]
Erythromycin base (several trade names)
Methicillin sodium [Celbenin, Staphcillin]
Metronidazole (several trade names)
Minocycline HCl (minomycin) [several trade names]
Moxifloxacin HCl [Avelox, Avelox I.V., Vigamox]
Norepinephrine bitartrate (levarterenol) [Levophed]
Oseltamivir phosphate [Tamiflu]
Penicillin G (several trade names)
Rifampin (rifampicin) [Rifadin, Rimactane]
Rimantadine HCl [Flumadine]
Vancomycin [Vancocin, Vancoled]
Vasopressin (8-arginine-vasopressin) [Pitressin]
Program of Related Interest
Karras, David J: Emerging infectious diseases and the upcoming pandemic. Audio-Digest Emergency Medicine
23:22 (Nov 21) 2006; Howton, Joseph C: What we need to know about the avian flu. Audio-Digest Emergency Medicine
23:22 (Nov 21) 2006.
Suggested Reading
Angus DC et al: Epidemiology of sepsis: an update. Crit Care Med 29:S109, 2001; Angus DC et al: Epidemiology
of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 29:1303,
2001; Berenholtz SM et al: Eliminating catheter-related bloodstream infections in the intensive care unit. Crit Care
Med 32:2014, 2004; Bratzler DW et al: Antimicrobial prophylaxis for surgery: an advisory statement from the National
Surgical Infection Prevention Project. Am J Surg 189:395, 2005; DeRiso AJ 2nd et al: Chlorhexidine gluconate
0.12% oral rinse reduces the incidence of total nosocomial respiratory infection and nonprophylactic systemic antibiotic use
in patients undergoing heart surgery. Chest 109:1556, 1996; Finkelstein R et al: Surgical site infection rates following
cardiac surgery: the impact of a 6-year infection control program. Am J Infect Control 33:450, 2005; Finkelstein R et
al: Vancomycin versus cefazolin prophylaxis for cardiac surgery in the setting of a high prevalence of methicillin-resistant
staphylococcal infections. J Thorac Cardiovasc Surg 123:326, 2002; Fourrier F et al: Effect of gingival and dental
plaque antiseptic decontamination on nosocomial infections acquired in the intensive care unit: a double-blind placebo-controlled
multicenter study. Crit Care Med 33:1728, 2005; Garcia-Lara J et al: Staphylococcus aureus: the search for
novel targets. Drug Discov Today 10:643, 2005; Kaye KS et al: Pathogens resistant to antimicrobial agents. Epidemiology,
molecular mechanisms, and clinical management. Infect Dis Clin North Am 14:293, 2000; Kollef MH et al: Methicillin-resistant
Staphylococcus aureus: a new community-acquired pathogen? Curr Opin Infect Dis 19:161, 2006;
Kollef MH: Bench-to-bedside review: antimicrobial utilization strategies aimed at preventing the emergence of bacterial
resistance in the intensive care unit. Crit Care 9:459, 2005; Kollef MH: Is antibiotic cycling the answer to preventing the
emergence of bacterial resistance in the intensive care unit? Clin Infect Dis 43 Suppl 2:S82, 2006; Kurz A et al: Perioperative
normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization. Study of Wound Infection
and Temperature Group. N Engl J Med 334:1209, 1996; Pittet D et al: Nosocomial bloodstream infections.
Secular trends in rates, mortality, and contribution to total hospital deaths. Arch Intern Med 155:1177, 1995; Polk HC Jr
et al: Prophylactic antibiotics in surgery and surgical wound infections. Am Surg 66:105, 2000; Raymond DP et al:
Preventing antimicrobial-resistant bacterial infections in surgical patients. Surg Infect (Larchmt) 3:375, 2002; Saint S et
al: Enhancing the safety of critically ill patients by reducing urinary and central venous catheter-related infections. Am J
Respir Crit Care Med 165:1475, 2002; Walsh FM et al: Microbiology and drug resistance mechanisms of fully resistant
pathogens. Curr Opin Microbiol 7:439, 2004; Willems L et al: Follow-up of antibiotic prophylaxis: impact on
compliance with guidelines and financial outcomes. J Hosp Infect 60:333, 2005.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial relationship
with the manufacturer or provider of any commercial product or service discussed. For this issue, the faculty reported
nothing to disclose.
Dr. Wiener-Kronish was recorded at the 80th Clinical and Scientific Congress, presented March 24-28, 2006, by the International
Anesthesia Research Society, and held in San Francisco, CA; Dr. Coursin, at the 56th Annual Postgraduate
Symposium on Anesthesiology, presented March 31, April 1-2, 2006, by the University of Kansas Medical Center Department
of Anesthesiology and University of Kansas Continuing Education, and held in Kansas City, MO. The Audio-Digest
Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.
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