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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5524_Библиотеки_им_академика_М_И_Перельмана.pdf
448 R. T. Stovall
Ö We use the UA as a screen for infection in the catheterized trauma
patient in our ICU as a negative UA in this population greatly reduces
the chance of a positive urine culture in the workup of a fever. If
additional suspicion exists however, a culture needs to be sent.
Ö Urine cultures should be sent when the suspicion of a urinary tract
source of infectious fever is present.
Blood Cultures
Ö Incidence of bacteremia in the ICU varies based on population.
Ö CCM/IDSA guidelines recommend blood cultures for every fever,
but the evidence for this is lacking.
Ö Factors that suggest need for blood cultures include: long term
indwelling intravascular devices, immunosuppression, possibly
rigors.
Additional Cultures
Ö If the history and physical exam suggest alternative sources of
fever, especially surgical sites or other instrumented sites, effort
should be made to assess these sites and cultures should be sent.
Imaging
Ö Chest X-ray (CXR): Commonly ordered as respiratory infections
are common. Evidence suggests this is not necessary in every postoperative patient without other risk factors. However, most would
agree that a newly febrile intubated patient should have a CXR.
Ö Computed Tomography: Very useful when dictated by history and
physical but not a routine part of every fever workup.
Septic Patient Caveat: When a patient is febrile and septic, the risk-
benefit profile of additional testing shifts as finding the source of
infection and assuring appropriate antibiotics have survival benefit.
• Treatment
{ The treatment of fever is usually to treat the underlying cause. Treatment
of the fever itself is of unclear benefit and may have some detrimental
effects (e.g. in sepsis).
However, in certain situations, such as increased intracranial pres-
sures, a fever can have deleterious effects and the risk benefit likely
favors attempts to bring the temperature down.
Also, at very high levels, arguments are made to bring down the
temperature as life-threatening complications can ensue (e.g., rhabdomyolysis). This usually represents a different clinical scenario.
Evaluation of Fever 449
The need to treat a fever for the fever’s sake is variable and situation
dependent.
• Summary
A systematic and measured approach to the workup of a fever in the ICU
is the optimal management strategy. Routine batteries of test should not
be instituted. A thorough history and physical is warranted with each fever
and adjunctive studies should be ordered based on this assessment.
Fever plus risk factors should prompt adjunctive studies.
Treatment of a fever should be directed at treating the underlying cause.
In certain clinical situations, attempts to lower patient temperature
directly may be warranted.
Practical Algorithm(s)/Diagrams
Temperature >/= 38.5
Thorough History & Physical Exam
No signs of
sepsis/hemodynamic
compromise
Likely source of infection identified
No
Consider non-infectious sources of ICU
Fever or Ongoing Infections
Unlikely
If concern for infection persists but no
clear source identified on H&P then
send cultures based on existing risk
factors, local ICU patterns of infection
and repeated nature of fevers.
Remove or replace indwelling catheters
and devices.
Signs of
sepsis/hemodynamic
compromise
Ye s
Likely
Send Blood cultures,
UA/Urine cultures,
CXR, +/- Respiratory
culture and any
further indicated
cultures
Start broad spectrum
antibiotics
Send cultures or
obtain imaging to
confirm findings of
History and Physical
Exam
Consider starting
antibiotics
Diagnose and treat
non infectious source
while continuing to
assess possible
coincident infection
Fig. 1. Approach to fever.
450 R. T. Stovall
Review of Current Literature with References
• O’Grady N, Barie PS, Bartlett JG et al. Guidelines for evaluation of new fever
in critically ill adult patients: 2008 update from the American College of
Critical Care Medicine and the Infectious Diseases Society of America. Crit
Care Med 2008; 36: 1330–1349.
{ Consensus guideline from large society. Defines fever as >38.3°C.
Recommends blood culture and CXR on all febrile ICU patients. Reviews
components of other potential ICU causes of fever
• Dimopoulos G, Falagas ME. Approach to the febrile patient in the ICU Infect
Dis Clin North Am 2009; 23: 471–484.
{ Review of fever assessment in ICU. Similar to CCM/IDSA guideline.
• Perlino, Carl A. Postoperative Fever. Med Clin North Am 85: 1141.
{ Reviews general post-operative fever workup. Not specific to the ICU
patient, but may apply to situations in the ICU.
Chapter 10-(ii)
Antimicrobial Stewardship
Michelle K. Haas, MD* and Timothy Jenkins, MD*
*Assistant Professor of Medicine, University of Colorado School of Medicine
Take Home Points
• Antimicrobial stewardship is defined as a systematic approach for optimizing
antibiotic use in order to improve individual patient outcomes while minimizing
adverse events associated with antibiotic use.
• Antibiotic use has dramatically increased over the past 10 years reaching a
peak in 2010. This increase has been associated with: development of resistant organisms, C. difficile infection, adverse drug events, catheter-associated
complications, and excess medical costs. Prevention of unnecessary antibiotic
use can minimize all of these unintended consequences.
• Emergence of antibiotic resistance has been associated with: increased mor-
bidity and mortality, increased length of hospitalization and increased hospital
costs when compared with infections due to susceptible organisms.
Contact information: Denver Health Medical Center, University of Colorado Health
Sciences Center, 777 Bannock Street, MC 0206, Denver, CO 80204; Tel.: 303-602-5052,
email: Michelle.Haas@dhha.org; Timothy.Jenkins@dhha.org
451
452 M. K. Haas and T. Jenkins
• Unnecessary antibiotic use can be prevented by ensuring an appropriate indi-
cation for antibiotic therapy exists, selection of the appropriate antibiotic and
dose, and use of the shortest effective duration of therapy.
• Providers can improve antibiotic use further by ensuring judicious use of
broad-spectrum agents such as carbapenems as well as participating in the
development and implementation of institutional guidelines to further streamline care.
• For critically ill patients who have an unknown source of infection, use of
broad-spectrum empiric antimicrobial therapy is appropriate initially but
should consider local resistance patterns.
• In critically ill patients who receive broad spectrum antibiotic therapy,
de-escalate to the narrowest spectrum of activity as soon as possible as
microbiological cultures and clinical status allow.
• Treat for the shortest appropriate duration, referring to local and national
guidelines where appropriate.
• Maximize the ability to use diagnostic tests for decisions about antibiotic
therapy by making all attempts to obtain appropriate microbiologic specimens
for culture prior to starting empiric treatment.
• Take an “antibiotic time-out” on rounds each day to ask three key questions:
Is this an appropriate indication for an antibiotic? Is this the optimal antibiotic
choice/dose? What is the shortest effective duration of therapy?
Background
• While a lack of appropriate empiric antibiotics can be associated with
increased mortality,1 up to 50% of antibiotic use in healthcare settings may
be inappropriate, which can be associated with substantial negative effects
including the emergence of resistance, increased risk of C.difficile infection
and adverse drug events.
• Antibiotic use creates a selective pressure leading to emergence of resistance
in individual patients, intensive care units, hospitals and within communities.
The proportion of pathogens causing hospital-onset infections that are resistant
to target antimicrobial drugs continues to increase at an alarming rate.
Cabapenem resistant gram negatives were uncommon in 2001 and now have
been described in most states. Pseudomonas resistance has been associated
with all-carbapenem use, including use of “Pseudomonas-sparing” carbapenems such as ertapenem. Over the 10-year period from 1995–2004, the
proportion of enterococcal infections among ICU patients that were resistant
to vancomycin doubled from less than 15% to 30%. Within the Denver Health
Antimicrobial Stewardship 453
system, use of fluoroquinolones for urinary tract infections has been associated with emergence of fluoroquinolone resistance in E.coli. Infections with
drug resistant organisms are associated with increased morbidity and mortality, increased length of hospitalization and increased costs compared to
infections due to susceptible organisms.
• Clostridium difficile infection (CDI) has shown a 4-fold increase in incidence
in elderly since mid-1990s with an associated increase in severe cases necessitating colectomy (1.2 to 3.4 per 1,000 cases). Mortality has increased due to
CDI, at a rate of 35% between 1999–2004. The risk of CDI increases with
increasing cumulative doses of antibiotics, days of antibiotic exposure and the
number of antibiotics used. Not all antibiotics confer equal risk, with the
highest risk seen with 2
nd/3rd
generation cephalosporins and beta-lactam+
inhibitor combinations.
• Antibiotics are a leading cause of adverse events such as renal failure, neutro-
penia, severe drug eruptions, fevers and in rare cases, death. Vancomycin use
can be associated with the development of acute renal failure and neutropenia.
B-lactam antibiotics can be associated with drug-induced cholestasis and
hepatitis. Fluoroquinolones can cause QT prolongation and use has been
associated with serious arrhythmia. Azithromycin use has been associated
with an increased risk of sudden cardiac death.
• In 2007, the Infectious Disease Society of America (IDSA) recognized the
importance of promoting the rational use of antibiotics through developing
guidelines for implementing antimicrobial stewardship programs in the inpatient setting. Denver Health instituted an antimicrobial stewardship program
in 2008.
• The primary goal of hospital antimicrobial stewardship programs is to facili-
tate optimizing antibiotic use to improve patient outcomes. Stewardship
programs also aim to limit the emergence of resistant organisms associated
with excessive use of antibiotics and to control healthcare costs. This is
accomplished through strategies such as promoting judicious use of broad
spectrum antimicrobials, reviewing provider antibiotic prescriptions and giving feedback to providers, education and the implementation of guidelines.
• Data regarding the impact of implementing the aforementioned strategies has
met with success, decreasing broad spectrum antibiotic use while limiting the
emergence of resistance. There are limited data regarding the impact on mortality. However, studies evaluating the impact of antimicrobial stewardship in
the intensive care unit have been associated with improved prescribing practices and one study has shown reductions in length of stay, mechanical
2,3
ventilation days and mortality.
454 M. K. Haas and T. Jenkins
• Within the Denver Health system, our surgical intensive care unit has worked
closely with the antimicrobial stewardship program to implement strategies
promoting the judicious use of antibiotics. This effort has been associated
with success in reducing total antibiotic use, use of antibiotics with broad
spectrum activity and decreased costs (see Fig. 1).
• Providers can optimize antibiotic use in critically ill patients through daily
review of the appropriateness of antibiotic therapy including indication for
therapy, antibiotic choice, dose, and duration of therapy.
Main Body
• Choosing an empiric antimicrobial regimen
{ The importance of early goal directed therapy and adequacy of resuscita-
tion cannot be over-emphasized for critically ill patients with severe sepsis/
shock. For an in-depth discussion, refer to Chapter 5-(iv). Initial empiric
antibiotic therapy should be broad-spectrum to avoid failure to cover the
infecting pathogen and resultant increased mortality.
mon reasons for inadequate coverage are failure to cover MRSA and
failure to cover resistant gram negatives, therefore knowing local resistance
patterns is essential. However, while broad coverage is appropriate, use of
two gram negative agents did not offer any additional benefit over one
broad spectrum agent in one randomized controlled trial.7 Narrowerspectrum therapy, which decreases selective pressure for the development
of resistant organisms, decreases risk of C. difficile, and decreases costs,
must be weighed against the risk of creating a gap in coverage in critically
ill patients with severe sepsis/shock and an unknown source of infection.
{ Optimizing dosing of empiric antibiotic regimens will avoid undertreat-
ment of infections and excessive antibiotic use. For example, central
nervous system infections may require higher dosing of certain agents.
Many antibiotics need dose adjustments in the context of renal failure to
avoid toxic adverse effects. Dose adjustments are rarely needed for
patients with end stage liver disease.
{ Institutional guidelines or clinical pathways should be followed when
applicable, to standardize and streamline care, improve antimicrobial
prescribing, and decrease medical costs.
• Maximizing the ability to safely de-escalate therapy
{ In order to allow informed de-escalation of antibiotic therapy, it remains
important to maximize the yield and accuracy of diagnostic tests. Cultures
1,4–6
The most com-
Antimicrobial Stewardship 455
should be obtained from blood for culture prior to antibiotic administration when possible and should avoid cultures from central lines given the
increased risk of false positive cultures. Depending on the suspected
source of infection, additional cultures such as bronchoalveolar lavage
(BAL) may be appropriate and should ideally be obtained prior to administration of antibiotic therapy. Use of urinalysis alone may be sufficient in
SICU patients to exclude the presence of infection.
{ Isolation of an organism from culture does not necessarily indicate that it
8
is contributing to the patient’s infectious process. Cultures from nonsterile sites such as wound swabs must be interpreted with great caution
with consideration for the clinical context of the patient for they often do
not reflect the causative organism. Similarly, bronchoalveolar lavage
(BAL) specimens in patients who have been intubated for prolonged periods of time may reflect organisms colonizing the airway.
{ Procalcitonin (PCT) is a biomarker that is significantly increased in the
setting of a bacterial infection compared to viral or non-infectious inflammatory processes where the level of elevation correlates with disease
severity. Use of PCT is a promising aid for clinical decision-making,
particularly in the setting of acute lower respiratory tract infections and
sepsis. Data on the utility of procalcitonin to guide antibiotic therapy
are limited in immunocompromised individuals, pregnancy, parasitic
infections and in gram negative infections such as Pseudomonas and
Acinetobacter. Use in septic patients in surgical ICUs has been limited;
however one randomized trial demonstrated a reduction in duration of
therapy without a negative effect on clinical outcomes.9 While more data
are needed, there may still be a role in cautious use of PCT to guide
discontinuation of antimicrobial therapy in SICU patients.
• Narrowing therapy when an organism is isolated
{ Once susceptibilities are determined, antibiotic therapy should be nar-
rowed to the most effective, narrow spectrum agent. Interpreting
susceptibility reports should also consider the clinical context. Not all
antibiotics have equal penetration into certain preserved sites, such as the
central nervous system (CNS). Cefazolin, while appropriate for many
cases of methicillin susceptible S. aureus (MSSA) bacteremia, does not
penetrate well into the CNS and thus is not appropriate treatment for
meningitis or a brain abscess.
{ Other organism-specific examples of the importance of narrowing therapy
include rapid de-escalation from vancomycin to a B-lactam when MSSA
456 M. K. Haas and T. Jenkins
is isolated. Vancomycin is clearly inferior for MSSA and use is associated
with relapse rates of 20% as well as excess mortality compared to
B-lactam therapy. Therefore even in penicillin-allergic patients, every
attempt should be taken to administer B-lactam therapy for serious
S. aureus infections, including desensitization if needed.
{ Conversely, some organisms may be associated with emergence of resist-
ance to overly narrow spectrum therapy. Enterobacter has a propensity for
developing resistance while on therapy with 3rd generation cephalosporins. Therefore, treatment with these agents should be avoided even if
reported as susceptible. A broader spectrum agent such as a carbapenem
may be indicated depending on the clinical context.
{ Use of infectious diseases consultation has been associated with improved
outcomes for S. aureus bacteremia, including reductions in mortality.
Therefore where questions remain for de-escalating therapy, consultation
with your antimicrobial stewardship team or infectious disease specialists
is recommended.
{ While considering narrowing therapy, certain antibiotics have excellent
oral-bioavailability such as fluoroquinolones, azoles, macrolides and
clindamycin. Whenever appropriate, IV therapy should be changed to oral
therapy to limit adverse events associated with intravenous administration
as well as to reduce costs.
• De-escalating therapy if cultures are negative
{ At 48–72 hours, discontinue vancomycin in clinically stable patients
when no resistant gram-positive pathogens have been identified. Despite
recent trends in decreasing isolation of MRSA nationally, vancomycin is
often unnecessarily continued in antibiotic regimens despite absence of
cultured or suspected resistant gram-positive pathogens.
{ Absence of growth of gram-negative organisms from all microbiological
cultures should prompt consideration of de-escalation from dual gramnegative therapy to a single agent.
{ Negative cultures and studies may be useful in patients with selected sus-
pected infections. In patients in whom ventilator-associated pneumonia
was suspected, negative cultures at 72 hours obtained off antibiotics suggests an alternative cause of the clinical syndrome. Current Infectious
Diseases Society of America/American Thoracic Society guidelines for
healthcare-associated pneumonia advocate for cessation of antibiotic
therapy in stable patients with no other source of infection. Within our
SICU, a clinical pulmonary infection score (CPIS) of 6 or greater would
Antimicrobial Stewardship 457
be an indication to initiate antibiotic therapy. Antibiotics are discontinued
in patients with CPIS scores of less than 6 for three days with negative
cultures and no other source of infection. SICU patients with suspected
urinary tract infections, a negative urinalysis has a very high negative
predictive value, essentially excluding the presence of infection.
• Be patient. Allow sufficient time for a clinical response prior to changing
antibiotic regimens in clinically stable patients
{ Clinical improvement is not always immediately apparent, even with
appropriate therapy. Patients with S. aureus bacteremia may take up to 7
days to clear despite appropriate therapy and source control. Patients with
pyelonephritis may continue to have fevers for up to 72 hours after initiating appropriate therapy. Multiple changes to antibiotic regimens without
adequate time to determine the effect of a regimen can confuse the clinical
picture.
{ Conversely, slow clinical improvement could indicate an undrained focus
of infection such as an intra-abdominal abscess and need for surgical
intervention. Clinically stable patients who are thought to be responding
slower than expected to therapy should have a careful evaluation for
undrained focus of infection and non-infectious causes of fever prior to
changing antibiotic therapy. Escalating antibiotic therapy should be
reserved for patients with precipitous development of septic shock
without obvious source.
• Treat for the shortest effective duration for a given infection
{ Shorter course of therapy are less likely to select for antibiotic resistant
organisms, reduce the risk of C.difficile infection and limit the emergence
of adverse drug events associated with cumulative doses.
{ Duration of therapy may vary depending on the organism involved and the
site of infection as well as host factors. Current guidelines for the management of sepsis recommend 7–10 days with the caveat that longer courses
may be needed in selected clinical scenarios such as S. aureus bacteremia,
fungal infections and those with immunodeficiences. While exceptions
remain for certain non-lactose fermenting gram negative infections and
S. aureus, ventilator-associated pneumonia can be treated for 7–8 days in
the majority of cases. Catheter-associated blood stream infections have
established durations of therapy summarized in the Infectious Diseases
Society of America guidelines which depend on several factors including
the organism isolated. For infections requiring prolonged intravenous