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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_885_Библиотеки_им_академика_М_И_Перельмана.pdf
458 M. K. Haas and T. Jenkins
antibiotic therapy such as S. aureus bacteremia or intracranial abscess
infectious disease consultation is recommended.
{ Counting the days of therapy, while a simple task can be challenging in
the reality of frequent hand-offs and multiple changes in antibiotic regimens. The first day of effective therapy should be counted as day one, and
the duration should include all current and prior effective therapy. Therapy
prescribed at discharge or recommended upon transfer from the ICU
should count these days of therapy, avoiding the tendency to reset the
clock when patients change locations or providers. Every effort should be
made to communicate both days of therapy and anticipated total duration
of therapy, including involving the patient, ancillary care teams as well as
documenting in the medical record. Failure to keep an accurate record of
days of appropriate antibiotic therapy commonly leads to unnecessary
prolongation of therapy. Prolongation of antibiotic therapy has been associated with the emergence of resistance and increases the risk of adverse
events such as C. difficile colitis and drug toxicities.
{ Many experts advocate for an antibiotic time-out each day on rounds to
ask three fundamental questions to ensure optimization of antibiotic
therapy: (1) Is this an appropriate indication for an antibiotic? (2) Is this
the optimal antibiotic choice/dose? (3) What is the shortest appropriate
duration of therapy?
• Prevent infections
{ Patients who do not develop infectious-related complications in the inten-
sive care unit are less likely to be exposed to antibiotic therapy. Therefore
every attempt should be made to reduce risk of infections in the following
ways:
Hand hygiene before and after every patient contact will limit spread
of resistant organisms between patients.
Remove vascular and urinary catheters as soon as possible as both are
associated with increased infections over time.
Prevent hospital-acquired pneumonia through the use of incentive
spirometry, ambulation if able, elevation of the head-of-bed and avoidance of unnecessary use of proton pump inhibitors.
Antimicrobial Stewardship 459
Practical Algorithm(s)/ Diagrams
Fig. 1. Antibiotic use over time after implementation of an antibiotic stewardship
program at a public safety net hospital. Monitoring antibiotic use in healthcare facilities
coupled with antibiogram data can inform future interventions.
460 M. K. Haas and T. Jenkins
Fig. 2. This represents one approach to applying antibiotic stewardship strategies in the
critically ill surgical patient. As with all guidelines, this approach may not be appropriate
for all patients and clinical judgment should determine its applicability.
Antimicrobial Stewardship 461
Review of Current Literature with References
1. Kollef MH, Sherman G, Ward S, Fraser VJ. Inadequate antimicrobial treat-
ment of infections: a risk factor for hospital mortality among critically ill
patients. Chest 1999; 115: 462–474.
• This prospective study of 2,000 patients admitted to intensive care units
evaluated the association between inadequate antimicrobial treatment of
their infections and mortality. Hospital mortality rate of patients receiving
inadequate treatment was 52.1% compared to 12.2% for those who
received adequate treatment for their infection. Inadequate antimicrobial treatment was determined to be an independent factor associated
with mortality after multivariate logistic regression analysis (OR 4.27,
95% CI 3.35–5.44, p < 0.001).
2. Katsios CM, Burry L, Nelson S et al. An antimicrobial stewardship program
improves antimicrobial treatment by culture site and the quality of antimicrobial prescribing in critically ill patients. Crit Care (London, England) 2012;
16: R216.
• This retrospective study reviewed consecutive patients admitted to an
intensive care unit over a two month period before and after the introduction of an antimicrobial stewardship program. The overall aim was to
determine the impact of the stewardship program on documentation of
antimicrobial use and decision to treat cultures from sterile sites compared
to non-sterile sites. They found an increase in the treatment of sterile site
cultures (64 vs. 83%, p = 0.01) and a reduction in the treatment of nonsterile site cultures (71 vs. 46%, p = 0.002.) There was no difference in
the percentage of cultures form sterile vs. non-sterile sites in either period.
There was an increase in the number of formally documented stop dates
(53% compared to 71%, p < 0.0001) and regimen de-escalation (15%
compared to 23%, p = 0.026).
3. Rimawi RH, Mazer MA, Siraj DS, Gooch M, Cook PP. Impact of regular
collaboration between infectious diseases and critical care practitioners on
antimicrobial utilization and patient outcome. Crit Care Med 2013; 41:
2099–2107.
• This retrospective study reviewed 246 patients admittted to a medical
ICU who received antibiotics for suspected infection to evaluate the
impact of of infectious disease fellow review of antibiotic prescribing.
Patients were selected over a 3 month period before the intervention
and then over the same 3 month period one year later. They evaluated
462 M. K. Haas and T. Jenkins
antibiotic use, treatment duration and severity of illness, including
mortality. While there were no differences in severity of illness between
the two groups, significant differences were seen in broad spectrum
antibiotic use including carbapenems and extended spectrum B-lactams.
Additionally they demonstrated a significant reduction in mechanical
ventilation days, length of stay and hospital mortality (p = 0.0367).
4. Kumar A, Ellis P, Arabi Y et al. Initiation of inappropriate antimicrobial
therapy results in a fivefold reduction of survival in human septic shock.
Chest 2009; 136: 1237–1248.
• In this retrospective study of 5,715 patients with septic shock in three
countries, the aim was to determine the appropriateness of initial antimicrobial therapy. The site of infection and infecting pathogens were also
reviewed and the major clinical endpoint reviewed was survival. The
survival rate after appropriate therapy was 52% which fell to 10.3% in
patients who received inappropriate therapy (OR, 9.45, 95% CI 7.74–
11.54, p < 0.0001). After adjustment for severity of illness, comorbid
conditions and other risk factors, inappropriate therapy remained
associated with the risk of death (OR 8.99, 95% CI 6.6–12.23)
5. Kumar A, Roberts D, Wood KE et al. Duration of hypotension before
initiation of effective antimicrobial therapy is the critical determinant of
survival in human septic shock. Crit Care Med 2006; 34: 1589–1596.
6. Gaieski DF, Mikkelsen ME, Band RA et al. Impact of time to antibiotics on
survival in patients with severe sepsis or septic shock in whom early goaldirected therapy was initiated in the emergency department. Crit Care Med
2010; 38: 1045–1053.
7. Brunkhorst FM, Oppert M, Marx G et al. Effect of empirical treatment
with moxifloxacin and meropenem vs meropenem on sepsis-related organ
dysfunction in patients with severe sepsis: a randomized trial. JAMA 2012;
307: 2390–2399.
• In this randomized open label trial of 600 patients with severe sepsis
or septic shock, the impact of use of meropenem alone compared to meropenem + moxifloxacin was evaluated on degree of organ failure.
Secondary outcomes included 28 day and 90 day all cause mortality.
There were 551 patients who were able to be evaluated at study closure
and of these individuals there was no statistically significant differences
in degree of organ failure, 28 day or 90 day mortality.
Antimicrobial Stewardship 463
8. Stovall RT, Haenal JB, Jenkins TC et al. A negative urinalysis rules out
catheter-associated urinary tract infection in trauma patients in the intensive
care unit. J Am College Surgeons 2013; 217: 162–166.
9. Schro eder S, Hochreiter M, Koehler T et al. Procalcitonin (PCT)-guided
algorithm reduces length of antibiotic treatment in surgical intensive care
patients with severe sepsis: results of a prospective randomized study.
Langenbeck’s Archives of Surgery /Deutsche Gesellschaft fur Chirurgie 2009;
394: 221–226.
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Sepsis
Chapter 10-(iii)
Heather Young, MD* and Connie Savor Price, MD
* Assistant Professor of Medicine, University of Colorado School of Medicine
†
Associate Professor of Medicine, University of Colorado School of Medicine
Take Home Points
• Surgical patients account for nearly one-third of sepsis cases in the United
States and sepsis is the leading cause of death in non-cardiac intensive care
units.
• Sepsis-related mortality remains prohibitively high (>40%).
• Early treatment is essential in the management of sepsis, and therapy should
be started as soon as the syndrome is recognized.
• Adequate fluid resuscitation, antibiotic therapy, intubation and mechanical
ventilation, and source control are key components of early sepsis therapy.
• Intravenous (IV) antibiotic therapy should be administered within 1 hour of
identifying sepsis.
• The delivery of evidence-based care and rapid source control can improve
patient outcomes.
†
Contact information: Denver Health Medical Center, University of Colorado School of
Medicine, 777 Bannock Street, MC 4000, Denver, CO 80204; Tel.: (Connie Savor Price):
303-602-5016, email: Connie.Price@dhha.org; Heather.Young2@dhha.org
465
466 H. Young and C. S. Price
Background
• Surgical patients account for nearly one-third of sepsis cases in the United
States. The mortality rate for septic shock in the perioperative period exceeds
that of both myocardial infarction and pulmonary embolism.
• Risk factors for both the development of sepsis and death from sepsis
included age older than 60 years, the need for emergency surgery, and the
presence of comorbid conditions.
• Intraabdominal infection is the most common source of sepsis among surgical
patients, accounting for approximately two-thirds of all cases.
• When septic shock follows sepsis, there is a 39% mortality rate among
emergent surgical patients and a 30% mortality rate among elective surgical
patients.
• The early identification of sepsis and implementation of early evidence-based
therapies have been documented to improve outcomes and decrease sepsisrelated mortality.
• The definition of sepsis is adapted from Levy MM, Fink MP, Marshall JC
et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions
Conference. Crit Care Med 2003; 31: 1250–1256. Sepsis is defined as the
presence (probable or documented) of infection together with systemic
manifestations of infection, including:
{ General variables
Fever (>38.3°C)
Hypothermia (core temperature <36°C)
Heart rate >90/min–1 or more than two sd above the normal value
for age
Tachypnea
Altered mental status
Significant edema or positive fluid balance (>20 mL/kg over 24 hr)
Hyperglycemia (Plasma glucose >140 mg/dL or 7.7 mmol/L) in the
absence of diabetes
{ Inflammatory variables
Leukocytosis (WBC count >12,000 μL–1)
Leukopenia (WBC count <4000 μL–1)
Normal WBC count with greater than 10% immature forms
Plasma C-reactive protein more than two sd above the normal value
Plasma procalcitonin more than two sd above the normal value
Hemodynamic variables
Sepsis 467
Arterial hypotension (SBP <90 mm Hg, MAP <70 mm Hg, or an
SBP decrease >40 mm Hg in adults or less than two sd below normal
for age)
{ Organ dysfunction variables
Arterial hypoxemia (PaO2/FiO2 <300)
Acute oliguria (urine output <0.5 mL/kg/hr for at least 2 hrs despite
adequate fluid resuscitation)
Creatinine increase >0.5 mg/dL or 44.2 μmol/L
Coagulation abnormalities (INR >1.5 or aPTT >60 s)
Ileus (absent bowel sounds)
Thrombocytopenia (platelet count <100,000 μL–1)
Hyperbilirubinemia (plasma total bilirubin >4 mg/dL or 70 μmol/L)
{ Tissue perfusion variables
Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling
• Diagnostic criteria for sepsis in the pediatric population are signs and
symptoms of inflammation plus infection with hyper- or hypothermia
(rectal temperature >38.5°C or <35°C), tachycardia (may be absent in
hypothermic patients), and at least one of the following indications of altered
organ function:
{ Altered mental status
{ Hypoxemia
{ Increased serum lactate level
{ Bounding pulses
• Severe sepsis definition is defined from the same as sepsis-induced tissue
hypoperfusion or organ dysfunction (any of the following thought to be due
to the infection):
{ Sepsis-induced hypotension
{ Lactate above upper limits laboratory normal
{ Urine output <0.5 mL/kg/hr for more than 2 hrs despite adequate fluid
resuscitation
{ Acute lung injury with PaO
/FiO2 <250 in the absence of pneumonia as
2
infection source
{ Acute lung injury with PaO
/FiO2 <200 in the presence of pneumonia as
2
infection source
{ Creatinine >2.0 mg/dL (176.8 μmol/L)