Evaluation of in-patients with fever

# Nosocomial Fever
#1 #2 #3 #4
Shock? Sepsis?
Hx

PE

Lab
Shock ?

Shock = inadequate tissue perfusion

- inadequate tissue perfusion to the brain = stupor
- inadequate tissue perfusion to the skin = cold skin
- inadequate tissue perfusion to the lung = dyspnea
- inadequate tissue perfusion to the kidney = oliguria
# Nosocomial Fevers
#3 #4
Shock? Sepsis ?

Hx ซึม?
ปํ สสาวะ
PE BP, ?HR,
RR
Cold
skin?
Lab CO2 content
Sepsis ???
Sepsis syndrome
(Bone RC : Crit Care Med 1989;17:389)

- No of patients = 191
- 41% were bacteremic
- 36% were in septic shock on study entry
- An additional 23% later developed shock;
70% within 24 hr of study entry
- 13% mortality in patients without shock
- 27.5% mortality in patients with shock on admission
- 43.2% mortality in patients with shock post admission
- 25% developed ARDS
Sepsis?
= Infection PLUS Systemic Inflammatory Response Syndrome
(SIRS)
= > 2 of -oral temp > 38oC or < 36oC
- HR > 90/min.
- RR > 24/min. (or pCO2 < 32 mmHg)
- WBC > 12,000 or < 4,000 (or band > 10%)
Ref : Bone RC, Chest 1992:101:1644.
# Nosocomial Fevers
#3 #4
Shock? Sepsis?

Hx ซึม?
ปํ สสาวะ
PE BP, ?HR, Fever or Subtemp
RR Tachycardia?
Cold Tachypnea?
skin?
CO2 content Leucocytosis?
Lab
Leucopenia?
Blood pH
 Take home message 1

In a febrile patient, check “ whether

the patient had shock or sepsis”first.
 If, no shock or sepsis.

What to do next???

Let us focus first on “fever”

 How high is the body
temperature to be called
“ having fever ”?
 Crit Care Med 2008; 36:1330–1349

“
“Normal body temperature is generally
considered to be 37.0°C (98.6°F). In
healthy individuals, this temperature
varies by 0.5 to 1.0°C, according to
circadian rhythm and menstrual cycle.”
“As a broad generalization, it is
reasonable in many ICUs to
consider everyone with a temp.
of >38.3°C (>101°F) to be febrile
and to warrant special attention
to determine whether infection is
present.”
 Take home message 2

Don’t initiate “fever work-up” if

temp.< 38.30C unless there is
obvious sign(s) of focal infection,
sepsis or shock.
Source of fever:

Where ???
 Source of infection
Source Episodes Percent(%)

Urinary tract 40 21.2

Gastrointestinal tract 31 16.4

Lower respiratory tract 28 14.8

Skin and soft tissue 26 13.8

Central Line catheter-
19 10.1
related
Unknown source 32 16.9
UTI?
The absence of pyuria in a symptomatic
patient suggests a diagnosis other than
CA-UTI (A-III).
Hooton TM et al.Diagnosis, Prevention, and Treatment of Catheter-
Associated Urinary Tract Infection in Adults:2009 International Clinical
Practice Guidelines from the Infectious Diseases Society of America.
Clinical Infectious Diseases 2010; 50:625–663
Pyuria: How many WBC is “pyuria?”
 “ More than 10 white blood
cells per high-power field via
automated microscopy of the
urine defined pyuria.”
Lin E et al. Overtreatment of enterococcal bacteriuria. Arch
Intern Med 2012;172:33e38.
 Take home message 3:
If there is no pyuria in the urinalysis,
we should not send for the urine
culture.

The lab should reject a request for

urine culture if the urinalysis
indicated that there was no pyuria.
If the transport of urine will be
delayed longer than approximately 1
hr, the specimen should be
refrigerated.
Guidelines for evaluation of new fever in critically ill adult patients: 2008 update
from the American College of Critical CareMedicine and the Infectious Diseases
Society of America Crit Care Med 2008; 36:1330–1349
In the catheterized patient, pyuria is
not diagnostic of CA-bacteriuria or
CA-UTI (AII).
Positive urine culture with pyuria but
without sign or symptom : Rx ?????
Arch Intern Med. 2012;172(1):33-38
 Positive urine
culture?

Signs or symptoms of UTI?

- Suprapubic tenderness
- Flank pain
- Rigors
- Gross hematuria
-- Fever
Arch Intern Med 2000;160:678-682
There were 235 (14.9%) new cases of
nosocomial CAUTI during the study
period. More than 90% of the infected
patients were asymptomatic.
Only 1 of the 235 episodes of CAUTI that
were prospectively studied was
unequivocally associated with
secondary bloodstream infection.
 PSU CA-UTI: Bacteremic ???

Only 6 of 92 episodes (6.5%) were

bacteremic, 3 with the same bacteria
as in urine ( 2 A baum & 1
Klebsiella)and three with different
bacteria.
 PSU CA-UTI: mortality ???

Only 7 patients ( 7.6%) died within 7

days of UTIs. (Two with MDR- A
baum UTI and bacteremia and one
with disseminated candidiasis).
Other four died from UTI plus
peritonitis (2) ,VAP (2) or pulmonary
embolism (1).
 Take home message 4:

In Foley catheter- related UTIs,

bacteremia is uncommon.ด ังนัน,้ ใจ
เย็นเย็น
 Take home message 5:

ต่อให้ม ี pyuria,ถ้าผู ป
้ ่ วยไม่มอ
ี าการ จง
อย่า treat
Antibiotics prescribed for PSU-UTIs
Appropriate Empirical Antibiotics afebrile in 7 days
Yes = 42/92 (45.7%) episodes 30/42(71%)
No = 50/92 (54.3%) episodes 27/50(54%)*

P=0.040
 Why were the empirical Rx for
nosocomial UTIs in PSU Hospital
so inaccurate?
 Organisms
1. E coli = 30/92 ( 32.6%)

2. Candida = 25/92 (27.2%)

3. Klebsiella = 16/92 (17.3%)

4. Enterococci = 13/92 (14%)

( none = VRE)
 Take home message 6:

Candiduria was overlooked and was

second only to E coli as the agent of
PSU CA-UTI.

It was the major cause of inappropriate

antibiotic prescription in 27% of patients
with CA-UTI.
How to improve the empirical antibiotic
accuracy in PSU Hospital ?

We should first rule out candiduria.

How ???
Only one out of 67 patients with various
bacteriuria had “ yeast” in urine
reported in routine urinalysis done by
PSU technicians.

( specificity=66/67= 98%)
Only one of 21 patients,who had “yeast”
reported as seen in the urinalysis did not
grew Candida in his urine. ( positive
predictive value = 20/21=95%)

This patient, who had E. coli cultured from his

urine, was on fluconazole Rx during this
febrile episode.
 Take home message :
Preliminary Dx of candiduria is easy.
Always look at the urinalysis result. If
the PSU Medtech said that he saw
“yeast” in the UA, the prob. is 95 in 100
that he is right. And if he reported that
there was no yeast, he was also 97%
right.

After we have R/O candiduria, we can

concentrate on the possibility of GNR
 Source of infection

Source Episodes Percent(%)

Urinary tract 40 21.2
Gastrointestinal tract 31 16.4
Lower respiratory
28 14.8
tract
Skin and soft tissue 26 13.8
Central Line catheter-
19 10.1
related
Unknown source 32 16.9
Surgical Wound Infections
How to Dx wound infections
 Dalor = pain
Tumor = swelling
Rubro = redness
Calor = heat
 Case
a 58-year-old man underwent surgery for
a carcinoma of the rectum. The surgeon
resects the rectal tumour with difficulty
and performs a stapled end-to-end
anastomosis 8 cm above the dentate
line.
Five days post procedure, the patient
begins to complain of pain in the wound.
He has a low-grade fever, but his pulse
and pressure are normal. He is mobile
and is tolerating a light diet.

On physical examination his chest is

clear, and the abdominal wound is tense,
fluctuant, erythematous and tender at
the superior aspect.
The wound is incised and a small
amount of pus drained. The patient
improves, but on the morning of
discharge, the patient reports ‘just
not feeling well’. His abdomen is soft
and the wound infection has resolved.
The nursing observation chart for the
last few days showed...
Basic investigations are unremarkable
apart from an elevated white cell count
of 18,000 per mm3.
What is your diagnosis and what should
you do?
 Postoperative Fever- Acute
• Fever > 38° is common in 1st few days
after major surgery
• Most early post-op fever caused by
inflammatory stimulus of surgery and
resolves spontaneously.
Fever due to trauma of surgery resolves within
2-3 days (fever due to severe head trauma
may be persistent and not resolve for days to
weeks)

Jennifer Caffey, D.O

Only one of 271 patients had
clinically evident signs of infection
in the initial 24 h postoperatively
(with positive urine and blood
cultures).

Ref.: Frank SM et al. Anesthesiology 2000; 93:1426–31

A urinalysis and culture are not
mandatory during the initial 72 hrs
postoperatively if fever is the only
indication.Urinalysis and culture
should be performed for those
febrile patients having indwelling
bladder catheters for >72 hrs
Level 3 recommendation. Guidelines for evaluation of new fever in critically ill
adult patients: 2008 update from the American College of Critical CareMedicine
and the Infectious Diseases Society of America Crit Care Med 2008; 36:1330–1349
 Postoperative Fever

•- after 96 hours
likely to represent
infection
– Wind,
– Water,
– Wound,
– Walk,
– Wonder drugs
 Acute Postoperative Fever
• Fever in days 5-7
• Wound. Most wound infections occur here.
Surgical wound infections relating to specific
operations generally present 3–7 days
postoperatively for example the failure of a bowel
anastomosis, with fistula formation and leakage
• Intra-abdominal sepsis from abscess is
considered after the 5th–7th postoperative day.
A rectal examination is performed.
Some fullness posteriorly and the
anastomosis cannot be felt.
What is your diagnosis and what should
you do?
The patient is returned to the operating room
and the abscess drained per rectum.
 Source of PSU
Nosocomial Bacteremia
Source Episodes Percent(%)
Urinary tract 40 21.2
Gastrointestinal tract 31 16.4
Lower respiratory
28 14.8
tract
Skin and soft tissue 26 13.8
Catheter-related 19 10.1
Unknown source 32 16.9
?Pneumonia
Why important?
“Respiratory tract infections
accounted for 49% of all antibiotics
prescribed in the ICU; 63% of the
antibiotics used, however, were for
clinically suspected and not proven
respiratory tract infections.”
Bergmans DC et al. JAC 1997;39:227
How to Dx VAP?
 NNIS Criteria for Defining Nosocomial Pneumonia
At least one of:
Fever or WBC<4000 or >=12,000
And >= 2 of:
Purulent sputum (>=25 PMNs and <=10 epithelials
Per low power field )
New cough or dyspnea or RR>25/min
Rales or bronchial breath sound
Worsening gas exchange
 Take home message 7:

In evaluating febrile patients with fever

and abnormal CXR, always look for
signs of acute respiratory dysfunction. If
there is no resp. dysfunction , they
probably don’t have acute pyogenic
pneumonia.
NNIS Criteria for Defining Nosocomial Pneumonia

One or more of the following CXR

findings:
-New and persistent infiltrate.
-Consolidation
-Cavitation
Fever with lung infiltrate:

Always pneumonia ?
Any other D/Dx s ?
 ?Pneumonia vs. Atelectasis
– Postoperative atelectasis generally occurs
within 48 hours.

•
 Daily incidence of lobar atelectasis after open
heart surgery
Day 0 Day 1 Day2
Left lung 2% 4% 20%
Right lung 0% 0% 3%
Both lungs 0% 0% 1%

Ref.: Engoren M. Chest 1995;107:81-84

Lansing and Jamieson placed sterile cotton
plugs in the left main bronchus of 30 dogs.
The animals became febrile (104-105o F) within
12 hr. Fourteen of the animals had positive
bacterial cultures of the exudates distal to the
plugs. Three of four dogs that were cultured
were bacteremic. Fever but not atelectasis
were prevented in 6 dogs that had received
penicillin and streptomycin at the time of
bronchial plugging.

Ref.: Lansing AM, Jamieson WG. Mechanisms of fever in pulmonary

atelectasis Arch Surg 1963;87:184-190
“Removal of the plug 24 to 72 hours
later was always followed by a return to
normal conditions within 12 hours.”
Ref.: Lansing AM, Jamieson WG. Mechanisms of fever in pulmonary
atelectasis Arch Surg 1963;87:184-190
 How to differentiate
atelectasis from VAP ?
 Take home message 8:

In evaluating febrile patients with

dyspnea, always look at their previous
and follow-up CXR films to see whether
the infiltrates evolve or resolve too
rapidly or not. If they do, they probably
have lung atelectasis or pulmonary
edema rather than having pneumonia.
 Source of infection

Source Episodes Percent(%)

Urinary tract 40 21.2
Gastrointestinal tract 31 16.4
Lower respiratory
28 14.8
tract
Skin and soft tissue 26 13.8
Central Line catheter-
19 10.1
related
Unknown source 32 16.9
Am J Med 1976; 61:346-350
16(76%) of 21 patients were bacteremic.
8= pure anaerobes,
8= anaerobes + Proteus (5)
+ Staph. (3)
+ E. coli (1)
12 of 17 who received appropriate
antibiotics had persistent
bacteremia. In 5 patients, bacteremia
was terminated only after surgical
debridement.

Ten of these 21 patients died, eight

despite appropriate antibiotics. Among
14 patients who underwent surgical
debridement,only four patients died.
 Source of infection

Source Episodes Percent(%)

Urinary tract 40 21.2
Gastrointestinal tract 31 16.4
Lower respiratory
28 14.8
tract
Skin and soft tissue 26 13.8
Central Line catheter-
19 10.1
related
Unknown source 32 16.9
Central-line associated bloodstream
infections (CLA-BSI)
?Any Clues?
1 The presence of an intravascular device.
2 Inflammation or purulence at the catheter
insertion site or along the tunnel.
3. Abrupt onset of infection that is associated with
fulminating shock.
4 Multiple blood cultures positive for coagulase-
negative, staphylococci), Corynebacterium jeikeium,
Bacillus species, Candida species, or Malassezia
species.
2013-2017 CLA-BSI Report:
Department of Surgery
 2013-2017 Dept of Surgery CLA BSI
Central line- Number of
Ward day คน Infection Rate
Total 35,480 7943 93 2.62
 Take home message:
There were ~5 central venous
catheter placements each day in
PSU. Patients had more than 30
thousand days ( 100 years) at risk of
developing infections. These
consumed a lot of our nursing care
and attention.
 2013-2017 Dept of Surgery CLA BSI
Central line- Number of
Ward day คน Infection Rate
SICU 16,756 4083 41 2.45
SRCU 4709 904 13 2.76
 2013-2017 Dept of Surgery CLA BSI
Central line- Number of
Ward day คน Infection Rate
Neurosurgery 979 283 4 4.09
ศ ัลย ์หญิง 3831 859 10 2.61
ศ ัลย ์ชาย1 3592 863 13 3.62
ศ ัลย ์ชาย2 4063 644 10 2.46
Trauma 1550 307 2 1.09
 CLA BSI -PSU
ปี พ.ศ. 2558––กย. 2559
Total = 46คน Dead=15/46 (32.6%)
Surgery = 30 (65.2%) Dead = 9/30 (30%)
Medicine = 8 (17.4%) Dead = 2/8 ( 25%)
PICU = 8 (17.4%) Dead = 3/8 (37.5%)
 Duration of central line placement:
กลุม ่ ดเชือเหล่
่ ทีติ ้ ้ ย่
านี คาสายเฉลี =16.3 วัน
(4-49วัน)

Onset of bacteremia:
Median = 10 d. after central lines were inserted.
(range = 3-47)
95% occurred after Day 3
78% occurred after Day 5
 Take home message 9:

Daily review the necessity to continue

retaining the central line catheter.
Remember that if it got infected, the
probability of death is at least one in
three.

Remember: 95% of CR- BSI in PSU

Hospital occurred after Day 3.
 Mx of central line vs. outcome
Lines off = 22/38 Pts. survived = 22/22 (100%)
(including 10/22 pts. with inappropriate empiric
Abics)

Lines still retained= 16/38 Pts.survived= 4/16

(25%)* P<.05
Catheter-related Bloodstream
Infections: ?Removal of Catheter?
If a patient is in shock or manifests
ominous new signs such as peripheral
embolization, disseminated intravascular
coagulation, or acute respiratory
distress syndrome,removal of all
intravascular catheters, with reinsertion
at new sites, is indicated even if the
catheters are cuffed or tunneled devices.

Ref.:Mayhall CG. Diagnosis and management of infections of

implantable devices used for prolonged venous access. Curr
Clin Top Infect Dis 1992;12:83-110
If there is evidence of a tunnel infection,
embolic phenomenon, vascular
compromise, or sepsis, the catheter
should be removed and cultured, and a
new catheter should be inserted at a
different site (B, II).
O’ Grady N. et al .Practice Guidelines for Evaluating
New Fever in Critically Ill Adult Patients. CID
1998;26:1042-59
Nosocomial Sinusitis
Nosocomial fever without
apparent source
– Wind,
– Water,
– Wound,
– Walk,
– Wonder drugs
 ?Drug Fever?
In one series, the lag time between initiating
treatment with certain drugs and the onset of
fever was 8 days (median).
 ่
การสังยา: จํานวนชนิ ด
ของยา & Drug Interactions
Possible numbers of
combinations = n!/ 2 (n-2)!
eg. n=5, combinations =
5*4*3*2*1/ 2 ( 3*2*1)
 ่
การสังยา
“จํานวนชนิ ดของยาที่
หมอให้คนไขั
เป็ นปฏิภาคผกพันกับ
สติปัญญา
ของหมอคนนัน” ้
 Treatment

• Remove unnecessary treatments including

medications and catheters
Multicenter retrospective study of 110
patients in three ICUs in Milan.

23 epidural hematomas, 38 subdural

hematomas, 32 contusions, and 17 cases of
diffuse damage.
80 (73%) had fevers.
In our study, 14.8% of all patients had
fever without a documented infection
(39.5% of febrile patients). Most of these
patients received antibiotics, which did
not affect the outcome of their illness as
compared with febrile patients with a
documented infection.
Of the 15 cats, 7 developed an obvious hyperpyrexic
response after infusion of blood. The mean latency
to the onset was 31.5 +/-6.4 min. The maximum
increase in core temp. was 0.6 to 1.4’C..
Vasoconstriction of the ear and paw skin and
shivering were noted.