Академический Документы
Профессиональный Документы
Культура Документы
F Usually R102
F
Hypotension Hypotension
Tachycardia Tachycardia
Respiratory alkalosis Respiratory alkalosis
a
May be negative if obtained late or if on antibiotic therapy.
Data fromCunha BA. Sepsis and its mimics in the CCU. In: Cunha BA, editor. Infectious dis-
eases in clinical practice. 2nd edition. New York: Informa Healthcare; 2007.
323 SEPSIS & SEPTIC SHOCK
Therapeutic approach
Eective empiric monotherapy should be started as soon as the medical
mimics of sepsis have been eectively ruled out and the presumptive diagno-
sis of sepsis has become the working diagnosis. The eects of antimicrobial
therapy are maximal when administered early in the infective process. The
most eective agent with an appropriate spectrum based on the site of the
infection and a high degree of activity against the presumed pathogen
should be selected for empiric monotherapy. The shotgun approach
with multiple drugs to be discontinued one by one subsequently indicates
that the prescriber does not understand the clinical pathologic concept
that site of infection clearly determines organisms. Although, local epidemi-
ologic resistance patterns need to be taken into account in selecting an ap-
propriate antimicrobial agent, because the spectrum of most agents remain
predictable over time. De-escalation therapy does not ensure that organisms
will not be missed. Rather, it duplicates coverage, which is often unneces-
sary, and may miss optimizing coverage against the most likely pathogens.
It is essential to get it right from the start and cover optimally the most likely
pathogens rather than all possible pathogens (Box 2) [4755].
Factors in empiric antibiotic therapy selection
Appropriate spectrum of activity
The selection of an empiric antibiotic for sepsis should take into account
spectrum, pharmacokinetics, resistance potential, safety prole, and cost.
Obviously, high degree of activity against the presumed pathogens (ie, spec-
trum) is the primary consideration, but side eect prole and resistance po-
tential are also important. If an antibiotic is used in high volume for the
empiric treatment of sepsis and is associated with frequent or severe side ef-
fects or high resistance potential, then the overall eect on patients in the
institution will ultimately be negative, although individual patients may
do well. Because of the primacy of spectrum, the antibiotic selected must
be based on the likely source of infection, which is the primary determinant
of the most likely pathogens to be encountered. Coverage should be directed
against the most common pathogens and does not need to be excessively
broad or contain unnecessary activity against uncommon pathogens. Anti-
biotics with the proper spectrum with similar side eects and resistant po-
tential will be equally eective in treating sepsis from various organs. If
these factors are equal, antibiotic selection may be based on dierences in
antibiotic costs [47,5355].
Prevention of antibiotic resistance
It is a popular misconception that overuse of antibiotics inevitably leads
to antibiotic resistance. The other common misconception is that over time
324 CUNHA
resistance to antibiotics is inevitable, leaving few eective antibiotics for
clinical use. Antibiotic resistance is associated with one or two antibiotics
in each antibiotic class. Antibiotic resistance is not only unrelated to class,
it is also unrelated to mechanism of antibiotic action or mechanism of
resistance. For example, except for ceftazidime, there is virtually no clini-
cally signicant antibiotic resistance among the other third-generation ceph-
alosporins, even after decades of high-volume use. Few other antibiotics
have been used as extensively as ceftriaxone and yet there is virtually no re-
sistance to this agent. Antibiotic resistance with a particular antibiotic is
Box 2. Clinical approach to the septic patient
Diagnosis
For both community and hospitalized patients presenting with
sepsis
Diagnose or rule out mimics of sepsis by history, physical
examination, and routine laboratory tests
Initiate medical therapy appropriate for disorders mimicking
sepsis
If mimics of sepsis are ruled out, determine site of septic focus in
critically ill patients presenting with sepsis, distinguish
colonization from infection in isolates from urine, respiratory
secretions, and noninfected wounds
Treat infection and avoid treating colonizing organisms
Interventions
Antibiotic interventions
Select empiric monotherapy based on coverage of predictable
pathogens determined by focus (organ) of infection
Select antibiotic with low resistance potential
Select antibiotic with a good safety prole
Non-antibiotic interventions
Administer aggressive and effective intravascular volume
replacement
If pressors are needed, give volume replacement before
pressors
Restore normothermia with heating blanket
Surgical intervention if sepsis is related to intra-abdominal
organ perforation or obstruction or abscess. For infected
devices, remove the device
Data from Cunha BA. Sepsis and its mimics in the CCU. In: Cunha BA, editor.
Infectious diseases in clinical practice. 2nd edition. New York: Informa Healthcare;
2007.
325 SEPSIS & SEPTIC SHOCK
usually related to one or two organisms. In the case of ceftazidime, resis-
tance is limited to P aeruginosa. Resistance to other aerobic GNBs is mini-
mal. Unfortunately, if ceftazidime is used to treat nonP aeruginosa aerobic
GNBs, resistance will develop to P aeruginosa [5660].
The other antibiotic resistance misconception that prolonged antibiotic
use inevitably leads to resistance, rendering the antibiotic ineectived has
been proven to be myth by the continued use of antibiotics (eg, doxycy-
cline) that have been used extensively for decades. Across all antibiotic
classes, similar analogies and examples substantiate the concept that anti-
biotic resistance is related to individual agents and not to classes, volume,
or duration of use. With the carbapenems, the same analogy applies. That
is, there is resistance to P aeruginosa with imipenem but not meropenem.
The resistance to imipenem, as with other high resistance potential an-
tibiotics appears early (ie, within 2 years postmarketing). Resistance either
occurs then or does not occur subsequently even after years of prolonged
use. Imipenem-resistant P aeruginosa was noted early and has continued.
When meropenem was introduced in 1996, there was some thought that
its lack of resistance was due to the newness of this carbapenem. There
was no resistance to P aeruginosa or other aerobic GNBs 2 years
postmeropenem release, which reliably predicted that there would be no
major resistance problems in the future with this antibiotic. Hence, mero-
penem is termed a low resistance potential antibiotic and its eectiveness
against P aeruginosa as well as against other aerobic GNBs continues to be
maintained.
Historical analysis, in the absence of a mechanistic explanation, pro-
vides the best way to describe the phenomenon of resistance involving dif-
ferent antibiotic classes. Neither structure activity relationships or
mechanism of resistance explains fully such dierences in resistance poten-
tial within each antibiotic class [5860]. Numerous examples may be given.
There are problems with tetracycline resistance to S pneumoniae and
S aureus, but doxycycline remains highly eective against S pneumoniae,
including penicillin-resistant strains, even after decades of use. Minocycline
is not only active MSSA, but is also a highly eective antibiotic against
MRSA, and its eectiveness has not diminished over time either. Among
the aminoglycosides, amikacin retains its eectiveness against aerobic
GNBs, including P aeruginosa, but resistance to gentamicin and tobramy-
cin remains a problem. For these reasons, amikacin may be termed a low
resistance potential antibiotic, whereas gentamicin and tobramycin can be
considered high resistance potential antibiotics. Excluding the clonal
spread of unusual or highly resistant GNBs, antibiotic-induced resistance
can be minimized by preferentially selecting low resistance potential an-
tibiotics in place of high resistance potential antibiotics for the treatment
of aerobic GNBs. Experience has validated this principle, which applies
to dierent antibiotic classes and to virtually all antibiotics in widespread
use [5658].
326 CUNHA
Control of antibiotic resistance
If an institution has a problem with a particular highly resistant
organism, infection control containment measures should prevent it from
spreading from patient to patient. In hospitals with a high prevalence of
multidrug-resistant GNBs, particular care should be taken with antibiotic
selection to not exacerbate an already dicult problem. Every attempt
should be made to avoid unnecessarily treating isolates that represent colo-
nization rather than infection. The most common errors made in this regard
relate to treating isolates from respiratory secretions in ventilated patients in
intensive care units. Treatment should be used when the clinical presentation
reects the pathologic expression (eg, clinical and chest x-ray features) of the
microbe isolated from respiratory secretions. Otherwise, isolates should be
considered colonizers until proven otherwise. The other common error in
mistaking and treating colonization for an infection occurs in patients
with indwelling Foley catheters. Catheter-associated bacteriuria nearly al-
ways represents colonization. While it is prudent to treat colonization of
the urinary tract in certain compromised hosts (eg, those with SLE, diabetes
mellitus, or multiple myeloma), there is no rationale for treating catheter-
associated bacteriuria in normal hosts. The reduction or elimination of
needless antimicrobial therapy directed against GNBs colonizing respiratory
secretions or urine would be an important step in reducing resistance in the
critical care setting. By avoiding treating of colonization and by using low
resistant potential antibiotics to treat bonied infections, antibiotic resis-
tance problems can be avoided, minimized, or eliminated [5659].
De-escalation therapy, intended to maximize initial coverage, is also in-
tended to decrease resistance by narrowing the spectrum of the eventual an-
tibiotic selected. However, there is no evidence that de-escalation therapy
actually decreases resistance. In treating CAP empirically with ceftriaxone,
there is no benet in changing therapy to penicillin if the organism is iden-
tied as S pneumoniae. The same analogy pertains to critical care medicine.
The key to optimal initial empiric therapy is in the careful selection of a sin-
gle agent that will cover the usually encountered pathogens [57,58].
For NPs and VAPs, optimal empiric monotherapy should be directed
against P aeruginosa. Antibiotics with a high degree of activity against P
aeruginosa will also be eective against other aerobic GNBs causing NP
and VAP. Adding anti-MRSA coverage is unnecessary because the inci-
dence of MRSA NP or VAP so low. In the rare event that an NP or
VAP patient should develop nosocomial MRSA pneumonia during hospi-
talization, then empiric anti-MRSA therapy may be added. If optimal anti-
pseudomonal monotherapy is selected using, for example, meropenem, then
an additional antipseudomonal agent (ie, cefepime, amikacin) need not be
added. An additional antipseudomonal drug is not needed since the antipseu-
domonal activity in meropenem is sucient for empiric antiP aeruginosa
coverage as well as monotherapy of P aeruginosa NP and VAP. If empiric
327 SEPSIS & SEPTIC SHOCK
therapy for NP or VAP consists of double antipseudomonal coverage plus
anti-MRSA coverage, the patient is subjected to two unnecessary antibiotics
[5760].
Monotherapy is always preferred to polypharmacy, which increases anti-
biotic costs, potential for antibiotic side eects, and potential for drugdrug
interactions. De-escalation therapy based on cultures from respiratory secre-
tions in ventilated patients is problematic, because of sampling error. Iso-
lates from respiratory secretions are not usually representative of lung
pathogens responsible for VAP. Because selective pressures in the respira-
tory ora brought about by antimicrobial therapy changes in the microbial
milieu of the intensive care unit, it is inaccurate to base antibiotic changes on
such isolates. The goal of empiric therapy should always be empiric mono-
therapy, thus avoiding the need to change or discontinue unnecessary anti-
biotics [58,60].
Antibiotic adverse eects
Patients who are septic already are critically ill and with varying degrees
of organ dysfunction. Antibiotic therapy is intended to halt and reverse the
septic process. Antibiotics used should not have serious side eects that
could add to the patients already precarious clinical state (eg, antibiotics as-
sociated with seizures [ie, imipenem, ciprooxacin, and metronidazole]). For
each of these drugs, there is an alternative not associated with seizures (eg,
meropenem, levooxacin, clindamycin) [60,61].
Critically ill patients being treated for sepsis are often complicated by an-
tibiotic-induced Clostridium dicile colitis. As with antibiotic resistance, the
antibiotic potential for causing C dicile diarrhea or colitis varies by anti-
biotic. Antibiotics that have little or no propensity or potential to cause
C dicile include carbapenems, linezolid, doxycycline, minocycline, tigecy-
cline, aminoglycosides, TMP-SMX, aztreonam, chloramphenicol, macro-
lides, vancomycin, colistin, and polymyxin B. The antibiotics most often
associated with C dicile are beta-lactam antibiotics, with the notable
exceptions of ceftriaxone, cefoperazone and piperacillin-tazobactam.
Quinolones vary in their potential for causing C dicile. There are also
good data to indicate that protein pump inhibitors predispose to C dicile
when combined with some antibiotics, particularly quinolones. Antibiotics
associated with severe hypersensitivity reactions and drug rashes, particu-
larly Steven-Johnson syndrome, should be avoided if possible and other
agents used instead (Table 3) [60,61].
Antibiotic therapy in the septic patient with penicillin allergy
Antimicrobial therapy in penicillin-allergic patients is problematic and is
particularly dicult in the critical care setting. Patients who are critically ill
are often unable to provide a history regarding allergic reactions to antimicro-
bials. Relatives and friends are often unfamiliar with or vague about details of
328 CUNHA
the patients hypersensitivity. Sometimes, but not always, medical records
help clarify the nature of the penicillin allergy. The physician should endeavor
to determine the nature of the penicillin allergy if at all possible. Particular
eort should be given to dierentiating anaphylactic from non-anaphylactic
reactions to penicillin. Nonanaphylactic reactions to penicillin include drug
fevers and drug rashes. Anaphlyactic reactions to penicillin include laryngo-
spasm, bronchospasm, hypotension, and generalized hives. Because hyper-
sensitivity reactions to antibiotics are stereotyped, ie, patients who have
laryngospasm upon penicillin rechallenge will manifest amaphylaxis again
as laryngospasm rather than as another hypersensitivity manifestation.
Patients who have a known history of nonanaphylactic penicillin reactions
may be given cephalosporins without concern. The cross-reactivity between
penicillins and cephalosporins is less than 5%. In the worst-case scenario, if
a patient with a nonanaphylactic penicillin allergy reacts to a cephalosporin,
the allergy would be manifested as either drug fever or drug rash and not as
an anaphylactoid reaction. Patients likely or are known to have had an ana-
phylactic reaction to penicillin should not be treated with penicillins or ceph-
alosporins. An antibiotic selected for such patients should have spectrum of
activity appropriate for the site of infection and should be from an antibiotic
class unrelated antigenically to penicillins or cephalosporins (eg, vancomycin,
linezolid, daptomycin, clindamycin, metronidazole, aminoglycosides, doxy-
cycline, quinolones, linezolid, azethreonam, tigecycline).
Table 3
Sepsis: antibiotic therapy based on infection source
Source or device Usual pathogens Usual nonpathogens
a
Emperic monotherapy
Lower gastrointestinal
tract, pelvis
b
B fragilis S aureus Meropenem
Aerobic GNBs E faecalis (VSE) Tigecycline
S aureus Ertapenem
Genitourinary tract,
kidney, prostate
b
Aerobic GNBs B fragilis Piperacillin-tazobactam
E faecalis (VSE) S aureus Meropenem
Central venous catheter
intravenous lines
S aureus B fragilis Meropenem
Aerobic GNBs Tigecycline
E faecalis Piperacillin/tazobactam
Pulmonary: NP, VAP P aeruginosa S aureus Meropenem
c
Aerobic GNBs Enterobacter sp Cefepime
B cepacia Cefoperazone
S maltophilia Levooxacin
E faecalis (VSE)
B fragilis
a
No need to include in empiric coverage.
b
Source unknown.
c
Vancomycin, daptomycin, or linezolid in most intravenous-line infections in institutions
where CVC infection due to MRSA more prevalent than CVC infection due to MSSA.
Data from Cunha BA, editor. Antibiotic essentials. 7th edition. Royal Oak (MI): Physicians
Press; 2008.
329 SEPSIS & SEPTIC SHOCK
Because of the structural similarities between beta-lactams and carbape-
nems, clinicians have been reluctant to use carbapenems in penicillin-allergic
patients. The cross-reactivity rates between carbapenems varies. Carbape-
nems are structurally related to beta-lactams. That is, they contain a beta-
lactam ring but are antigenically dissimilar. There is a very low but denite
cross-reactivity potential between imipenem-cilastatin in those allergic to
penicillins. However, there is little or no cross-reactivity potential with mer-
openem in treating penicillin-allergic patients. Hypersensitivity reactions
due to meropenem are extremely rare. Meropenem may be safely adminis-
tered, without penicillin skin testing. In the critical care setting, there is often
no time to perform penicillin allergy testing to patients giving a history of an
unknown penicillin allergy or with a denite history of anaphylaxis, and
without any allergic reactions. Because meropenem has become the corner-
stone of antibiotic monotherapy in critical care medicine in the treatment of
sepsis and septic shock, physicians should know that meropenem may be
given safely to such patients regardless of the type of previous penicillin-
hypersensitive reactions without the need of skin testing [6264].
Sepsis and septic shock: non-antibiotic therapies
Ventilatory and volume support are critical in patients with respiratory
insuciency or hypotension. Sepsis is an overly applied, imprecise diagnos-
tic term. It is all too frequently given to patients who become hypotensive
for any reason. Overzealous diuresis alone or dehydration can result in
hypotension with an increase in white blood cell count with a left shift ac-
companied by low-grade fevers. Thus diuresis, dehydration, and other non-
infectious disorders can result in pseudosepsis symptoms wrongly ascribed
to sepsis [37].
Septic shock is most frequently associated with lower abdominal pro-
cesses, such as a leak from or a rupture of an intra-abdominal abscess [35].
In such cases, the antibiotic treatment alone of septic shock will be ineec-
tive unless accompanied by early surgical intervention [44]. Patients with ur-
osepsis have the lowest mortality of patients with septic shock. Intravenous
linerelated sepsis has a high morbidity and mortality even if not compli-
cated by acute bacterial endocarditis [11,12,19].
Other adjunctive therapies have been used over the years in the treatment
of septic shock and include steroids and anticytokine agents. Antithrom-
botic drugs (eg, drotrecogin alpha) have serious side eects and no proven
benet. Since multiorgan dysfunction is, in part, endotoxin/cytokine medi-
ated, inhibition of endotoxin/cytokine release from GNB pathogens by
antibiotic therapy is important in septic shock. A few anti-GNB antibiotics
inhibit endotoxin/cytokine release, which is potentially benecial. Studies
vary in assessing the clinical eect of endotoxin inhibition or release depend
on the antibiotics used and how rapidly they were infused. Dierences in
330 CUNHA
endotoxin inhibition or release diers among studies. It appears that rapid
bolus antibiotic injection kills GNBs rapidly and minimizes the extent and
duration of endotoxin/cytokine eects, but slow and continuous infusion
prolongs endotoxin/cytokine release [6568]. Antibiotics that are often
used to treat sepsis and that are known to inhibit endotoxin/cytokine release
are meropenem, colistin, and polymyxin B. The cornerstone of septic shock
therapy remains early appropriate empiric therapy based on the site of infec-
tion as well as volume resuscitation, with or without pressors, and, if
needed, ventilatory support [43,55,60,6971].
Summary
Eective empiric antimicrobial therapy for sepsis depends upon selecting
an antibiotic which is highly active against a presumed pathogen which are
predictable and dependent upon the focus of the septic process. Unnecessarily
broad spectrum coverage for sepsis ignores basic infectious disease principles
based on location of infection and predictable pathogens determined by the
organ system involved. Unnecessarily broad or overlapping coverage with
multiple agents results in needless expense to the institution, the patient,
and the health care system. Polypharmacy increases potential drug side eects
as well as drugdrug interactions. It is almost always possible to empirically
treat sepsis with a single agent. Polypharmacy does not improve outcomes.
References
[1] Sibbald WJ, Marshall J, Christou N, et al. Sepsisdclarity of existing terminology or more
confusion? Crit Care Med 1991;19:9968.
[2] Lazaron V, Barke RA. Gram-negative bacterial sepsis and the sepsis syndrome. Urol Clin
North Am 1999;26:68799.
[3] Murray MJ, Kumar M. Sepsis and septic shock. Postgrad Med 1991;90:199202.
[4] Hardaway RM. A review of septic shock. Am Surg 2000;66:229.
[5] Annane D, Bellisant E, Cavaillon JR. Septic shock. Lancet 2005;365:6378.
[6] Opal SM, Cohen J. Clinical gram-positive sepsis: Does it fundamentally dier from gram
negative bacterial sepsis. Crit Care Med 1999;27:160816.
[7] Levy B, Bollaert PE. Clinical manifestations and complications of septic shock. In:
Dhainaut JG, Thijs LG, Park G, editors. Septic shock. Philadelphia: WB Saunders;
2000. p. 33952.
[8] Cruz K, Dellinger RP. Diagnosis and source of sepsis: the utility of clinical ndings. In:
Vincent CL, Carlet J, Opal SM, editors. The sepsis test. Boston: Kluwer Academic Pub-
lishers; 2002. p. 1128.
[9] Alberti C, Brun-Buisson C. The source of sepsis. In: Vincent JL, Carlet J, Opal SM, editors.
The sepsis text. Boston: Kluwer Academic Publishers; 2002. p. 491503.
[10] Marshall JC. Control of the source of sepsis. In: Vincent JL, Carlet J, Opal SM, editors. The
sepsis text. Boston: Kluwer Academic Publishers; 2002. p. 52538.
[11] Gill MV, Cunha BA. IV line sepsis. In: Cunha BA, editor. Infectious diseases in critical care
medicine. New York: Marcel Dekker; 1998. p. 5765.
[12] Cunha BA. Intravenous line infections. Crit Care Clin 1998;33946.
331 SEPSIS & SEPTIC SHOCK
[13] Sacks-Berg A, Strampfer MJ, Cunha BA. Intravenous line sepsis due to suppurative throm-
bophlebitis. Heart Lung 1987;16:31820.
[14] Bouza E, Burillo A, Munoz P. Catheter-related infections: diagnosis and intravascular treat-
ment. Clin Microbiol Infect 2002;8:26574.
[15] Cunha BA. Saureus bacteremia: clinical treatment guideline. Antibiotics for Clinicians 2006;
10:3657.
[16] Cunha BA. Central intraveous line infections in the critical care unit. In: Cunha BA, editor.
Infectious disease in critical care medicine. NewYork: Informa Healthcare; 2007. p. 28390.
[17] Cunha BA. Urosepsis. J Crit Illn 1997;12:61625.
[18] Cunha BA. Urosepsisddiagnostic and therapeutic approach. Intern Med 1996;17:8593.
[19] Cunha BA. Urosepsis in the CCU. In: Cunha BA, editor. Infectious diseases in critical care
medicine. 2nd edition. New York: Informa Healthcare; 2007.
[20] Sacks-Berg A, Calubiran OV, Cunha BA. Sepsis asociated with transhepatic cholangiogra-
phy. J Hosp Infect 1992;20:4350.
[21] Cunha BA, editor. Pneumonia essentials. 2nd edition. Royal Oak(MI): Physicians Press; 2008.
[22] Cunha BA. Severe community-acquired pneumonia in the critical care unit. In: Cunha BA,
editor. Infectious disease in critical care medicine. New York: Informa Healthcare; 2007.
p. 15768.
[23] Cunha BA. Ventilator associated pneumonia: Monotherapy is optimal if chosen wisely. Crit
Care Med 2006;10:e1412.
[24] Bouza E, Burilla A, Torres MV. Nosocomial pneumonia in the critical care unit. In: Cunha
BA, editor. Infectious disease in critical care medicine. NewYork: Informa Healthcare; 2007.
p. 169204.
[25] Cunha BA. Clinical manifestations and antimicrobial therapy of methicillin resistant Staph-
ylococcus aureus (MRSA). Clin Microbiol Infect 2005;11:3342.
[26] Magira EE, Zervakis D, Routsi C, et al. Community-acquired methicillin-resistant Staphy-
lococcus aureus carrying Panton-Valentine leukocidin genes: a lethal cause of pneumonia in
an adult immunocompetent patient. Scand J Infect Dis 2007;39:4669.
[27] Gopal V, Bisno AL. Fulminant pneumococcal infections in normal asplenic hosts. Arch
Intern Med 1977;137:152630.
[28] Waghorn DJ. Overwhelming infection in asplenic patients: Current best practice preventive
measures are not being followed. J Clin Pathol 2001;54:2148.
[29] Bridgen ML, Pattullo AL. Prevention and management of overwhelming postsplenectomy
infectiondan update. Crit Care Med 1999;27:83642.
[30] Fernbach DJ, Burdine JA Jr. Sepsis and functional asplenia. N Engl J Med 1970;282:
691.
[31] Bisno AL, Freeman JC. The syndrome of asplenia, pneumococcal sepsis, and disseminated
intravascular coagulation. Ann Intern Med 1970;72:38993.
[32] DiNubile MJ, Lipsky BA. Complicated infections of skin and skin structures: when the
infections is more than skin deep. J Antimicrob Chemother 2004;53:3750.
[33] Fontes RA Jr, Ogilvie CM, Miclau T. Necrotizing soft tissue infections. J Am Acad Orthop
Surg 2000;8:1518.
[34] Owa T, Hayashi S, Miyoshi M, et al. Successful treatment of necrotizing fasciitis due to
group A streptococcus with impending toxic shock syndrome. Intern Med 2003;42:9145.
[35] Stevens DL. Streptococcal toxic shock syndrome associated with necrotizing fasciitis. Annu
Rev Med 2000;51:27188.
[36] Kaiser ML, Wilson SE. Intra-abdominal surgical infections and their mimics in the critical
care unit. In: Cunha BA, editor. Infectious disease in critical care medicine. New York: In-
forma Healthcare; 2007. p. 291304.
[37] Cunha BA. Sepsis and its mimics. Intern Med 1992;13:4855.
[38] Wilson PG, Manji M, Neoptolemos JP. Acute pancreatitis as a model of sepsis. J Antimicrob
Chemother 1998;41:5163.
332 CUNHA
[39] Gabbay DS, Cunha BA. Pseudosepsis secondary to bilateral adrenal hemorrhage. Heart
Lung 1998;27:34851.
[40] Hamid N, Spadafora P, Khalife ME, et al. Pseudosepsis: rectus sheath hematoma mimicing
septic shock. Heart Lung 2006;35:4347.
[41] Melby MJ, Bergman K, Ramos T, et al. Acute adrenal insuciency mimicking septic shock:
a case report. Pharmacotherapy 1988;8:6971.
[42] McCriskin JW, Baisden CE, Spaccevento LJ, et al. Pseudosepsis after myocardial infarction.
Am J Med 1987;83:57780.
[43] Cunha BA. Sepsis and mimics in the CCU. In: Cunha BA, editor. Infectious diseases in crit-
ical care medicine. 2nd edition. New York: Informa Healthcare; 2007.
[44] Marshall JC. Intra-abdominal infections. Microbes Infect 2004;6:101525.
[45] Vincent JL. Management of sepsis in the critical ill patients: key aspects. Expert Opin Phar-
macother 2006;7:203745.
[46] Fry DE, editor. Surgical infections. Boston: Little, Brown and Company; 1995. p. 227302.
[47] Ambrose PG, Owens RC, Quintiliani R, et al. Antibiotic use in the critical care unit. Crit
Care Clin 1998;8:283308.
[48] Dellinger RP. Current therapy for sepsis. Infect Dis Clin North Am 1999;13:495509.
[49] Grossi P, Gasperina DD. Antimicrobial treatment of sepsis. Surg Infect 2006;7:8791.
[50] Finch RG. Empirical choice of antibiotic therapy in sepsis. J R Coll Physicians Lond 2004;
34:52832.
[51] Bochud PY, Glauser MP, Calandra T, et al. Antibiotics in sepsis. Intensive Care Med 2001;
27:3348.
[52] Carlet J. Antibiotic management of severe infections in critically ill patients. In: Dhainaut
JG, Thijs LG, Park G, editors. Septic shock. Philadelphia: WB Saunders; 2000. p. 44560.
[53] Cunha BA. Antibiotic treatment of sepsis. Med Clin North Am 1995;79:5518.
[54] Cunha BA. Factors in antibiotic selection for hospital formularies (Part I). Hosp Formul
1998;33:55872.
[55] Cunha BA. Antibiotic selection in the CCU. In: Cunha BA, editor. Infectious diseases in crit-
ical care medicine. 2nd edition. New York: Informa Healthcare; 2007.
[56] Cunha BA. Eective antibiotic resistance and control strategies. Lancet 2001;57:13078.
[57] Cunha BA. Antibiotic resistance: control strategies. Crit Care Clin 1998;8:30928.
[58] Cunha BA. Antibiotic selection and control of resistance in the critical care unit. In: Cunha
BA, editor. Infectious disease in critical care medicine. NewYork: Informa Healthcare; 2007.
p. 60924.
[59] Cunha BA. Newer uses for older antibiotics: nitrofurantoin, amikacin, colistin, polymyxin b,
doxycycline and minocycline revisited. Med Clin North Am 2006;90:1089107.
[60] Cunha BA, editor. Antibiotic essentials. 7thedition. Royal Oak (MI): Physicians Press; 2008.
[61] Granowitz EV, Brown RB. Adverse reactions to antibiotics. In: Cunha BA, editor. Infec-
tious disease in critical care medicine. New York: Informa Healthcare; 2007. p. 57594.
[62] Cunha BA. Clinical approach to antibiotic therapy in the penicillin allergic patient. Med Clin
North Am 2006;90:125764.
[63] Cunha BA. Antimicrobial therapy in the penicillin-allergic patient in the critical care unit. In:
Cunha BA, editor. Infectious disease in critical care medicine. New York: Informa Health-
care; 2007. p. 62530.
[64] Cunha BA: Meropenem: lack of cross reactivity in penicillin allergic patients. J Chemother
2008, in press.
[65] Cunha BA, Wu P, Qadri SMH. Meropenem inhibition of endotoxin release from E coli.
Advances of Therapy 1997;14:16871.
[66] Danner RL, Elin RJ, Hossein JM, et al. Endotoxemia in human septic shock. Chest 1991;99:
16975.
[67] Lepper PM, Tk Held, Schneider EM, et al. Clinical implications of antibiotic-induced endo-
toxin release in septic shock. Intensive Care Med 2002;28:82433.
333 SEPSIS & SEPTIC SHOCK
[68] Giamarellos-Bourboulis EJ, Mega A, Pavleas I, et al. Impact of carbapenem on systemic
endotoxemia in patients with severe sepsis and gram-negative bacteremia. J Chemother
2006;18:5026.
[69] Court O, Kumar A, Parrillo JE, et al. Clinical review: myocardial depression in sepsis and
septic shock. Crit Care 2002;6:5008.
[70] Vincent JL. International sepsis forumhemodynamic support in septic shock. Intensive Care
Med 2001;27:8092.
[71] Callister ME, Evans TW. Haemodynamic and ventilatory support in severe sepsis. J R Coll
Physicians Lond 2000;34:5228.
334 CUNHA