Antibiotic Smart Use: Interactive Showcase

..

MODERATOR

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 1. 4

1 .
.

4
Physical
Ph i l examination:
i ti Abrasion
Ab i wounds
d
at rt hand, no sign of inflammation

 1. 4

1 .
.

4
Physical
Ph i l examination:
i ti Abrasion
Ab i wounds
d
at rt hand, no sign of inflammation

 1
rabies vaccine

 1
rabies vaccine

. Amoxicillin/clavulanate
. cloxacillin
. antibiotic

 1
rabies vaccine

. Amoxicillin/clavulanate
. cloxacillin
. antibiotic

Traumatic Wounds
Virtually all wounds are contaminated with bacteria, only a
small fraction (4.5-6.3%) developed traumatic wound
Best way to prevent wound infection
Thorough wound cleansing
Appropriate closure (consider delayed primary closure
in high-risk wound)
Radiographic imaging to evaluate foreign body
Appropriate antibiotic prophylaxis

Moran GJ, et al. Infect Dis Clin N Am 2008;22:117-43.

When to Give Prophylactic Antibiotics for Traumatic Wound

Available data do not support prophylactic antibiotics in simple
wounds, but recommended in high-risk situations:
Immunocompromised
p
patients (eg,
p
( g, p
poorlyy controlled
diabetes, steroid use, AIDS)
Open fractures or wounds into joints
Wounds involving tendons or cartilage
Grosslyy contaminated wounds that cannot be adequately
q
y
cleaned, esp. retained foreign body
Puncture wounds and crush injuries
Bite wounds
Oral wounds
Wounds with a significant delay (> 18 hours)
Moran GJ, et al. Infect Dis Clin N Am 2008;22:117-43.

Prophylactic Antibiotics for Traumatic Wound

Most settings for traumatic wound
Cloxacillin, dicloxacillin
1st cephalosporin: cephalexin
Grossly contaminated wounds, devitalized wound in
immunocompromised patients:
Amox/clav
Intraoral wounds
3-5 days for prophylaxis
Penicillin
7-10
7 10 days for treatment
Bite wound
of established infection
Amox/clav
Moran GJ, et al. Infect Dis Clin N Am 2008;22:117-43.

Antimicrobial Agents for Animal Bite Wounds

Source of
Bite

Dog, cat,
D
or
mammald

Organism(s)
Likely to Cause
Infection

Pasteurella
P
ll sp ,
S. aureus,
Streptococci,
anaerobes
anaerobes,

Capnocytophaga
sp, Moraxella sp,
Corynebacterium
sp, Neisseria sp

Antimicrobial Agent
Oral Route

AmoxicillinA
i illi
clavulanate
(Pasteurella
are resistant
to cephalexin,
cloxacillin,
erythromycin
erythromycin,
clindamycin)

Oral
Intravenous IV Alternatives
Alternatives
Routeb,c
for Penicillin
Penicillinfor PenicillinAllergy
Allergy
ExtendedE
d d
A i illi
Ampicillinspectrum
sulbactamf
cephalosporin
or
TMX-SMZ
PLUS
Clindamycin

ExtendedE
d d
spectrum
cephalosporin
or
TMX-SMZ
PLUS
Clindamycin
OR
Meropenem

IInfection
f i after
f cat bi
bites iis as hi
high
h as 50-80%;
50 80% infection
i f i after
f dog
d or human
h
bites
bi are
10-15%
AAP. Redbook 2012

Antimicrobial Agents for Animal Bite Wounds

Source
of Bite

Reptile

Organism(s)
Likely to
Cause
Infection

Enteric gramnegative
i
bacteria,
anaerobes

Antimicrobial Agent
Oral Route

Oral Alternatives
for PenicillinAllergic Patientsa

Intravenou
b
s Routeb,c

Intravenous
Alternatives for
PenicillinAllergic Patients

Amoxicillin
-clavulanate
l l

Extended-spectrum
cephalosporin
h l
i or
TMP-SMZ
PLUS
Cli d
Clindamycin
i

Ampicillinf
sulbactam
lb
PLUS
Gentamici
n

Clindamycin
PLUS
S
Gentamicin
OR
M
Meropenem

AAP. Redbook 2012

Antimicrobial Agents for Human Bite Wounds

Source off
S
Bite

H
Human

Organism(s)
O
i ()
Likely to
Cause
Infection

S
Streptococci
i
sp. Esp.

Streptococcus
anginosus
i
,
S. aureus,
Eikenella
corrodens
corrodens,
Haemophilus

A ti i bi l A
Antimicrobial
Agentt
Oral Route

AmoxicillinA
i illi
clavulanate

Oral
Intravenous
Alternatives for
Routeb,c
PenicillinAllergic Patientsa

Intravenous
Alternatives for
Penicillin-Allergic
Patients

ExtendedE
d d
spectrum
cephalosporin
or
TMP-SMZ
PLUS
Clindamycin

Extended
E
d d
spectrum
cephalosporin or
TMP SMZ
TMP-SMZ
PLUS
Clindamycin
OR
Meropenem

AmpicillinA
i illi
sulbactamf

sp, anaerobes

AAP. Redbook 2012

* ( 6 . )
* ////

(
(
)
)
9
9
9
9

9
9 /

()
()
9 6 .
9 5 .
9
9
9

9
9
9

steroid

()
()
9/
9
9
9
9

9 Amoxicillin-clavulanate (500:125) 3050 mg/kg/day 2

9 Ciprofloxacin
+ Clindamycin ( metronidazole)

Dicloxacillin 25 mg/kg/day 4
Cephalexin 25-50 mg/kg/day 3
Roxithromycin Clindamycin
3

Amoxicillin/Clavulanate
Amoxicillin/
Clavulanate Preparations
Syrup
4:1 Amox/Clav 156 (125/31)
7:1
7 1 Amox/Clav
A
/Cl 228 (200/28)
Amox/Clav 457 (400/57)
14:1 Amox/Clav ES (600/42.9)
Tablet
2:1
4:1
7:1
71
14:1

Amox/Clav 375 (250/125)

Amox/Clav 625 (500/125)
A
Amox/Clav
/Cl 1 G (875/125)
Amox/Clav SR (1000/62.5)

 2. 13 - year- old boy, underlying

Ewing sarcoma left femur post incision biopsy

Last ChemoRx 7 days before
1 day PTA, He developed high grade of fever and decreased appetite
At ER he was found to be hypotensive and tachycardia
Physical Examination
V/S: T 39.3o C, P 150/min (not full), BP 70/40 mmHg, RR 25/min
G/A: drowsiness, mild pale, capillary refill 4 sec
Left femur: mild swelling, no redness
Other : WNL

He received NSS load 20cc/kg/dose x 2

dose,
dopamine 20 mcg/kg/min and then
transfer to ICU
Investigation
CBC :Hb 7.7 g/dl, Hct 22.8% WBC
100 cell/mm3 ((N 26.9 %,, L
10.2%, Mo 62%, Eo 0.9%), ANC
0 plt.
0,
plt 12,000
12 000 cell/mm3
U/A : PH 6.5, sp.gr. 1.010, protein
neg, sugar neg, WBCC 0-1
0 1 /HPF
/
, RBC 0 /HPF
Lactate 9.7 mmol/L

CXR: no definite pulmonary infiltration

 2
Which is the appropriate empirical
antibiotic treatment in this patient ?

 2
Which is the appropriate empirical
antibiotic treatment in this patient ?
. Ceftazidime + amikacin
Meropenem
.
Piperacillin-tazobactam
.
Piperacillin tazobactam + vancomycin

 2
Which is the appropriate empirical
antibiotic treatment in this patient ?
. Ceftazidime + amikacin
Meropenem
.
Piperacillin-tazobactam
.
Piperacillin tazobactam + vancomycin

Initial assessment and investigations

11. PPresence off indwelling
i d lli IV catheters
th t
2. Symptoms or signs suggesting an infection focus

Respiratory system,
system GI,
GI Skin,
Skin Perineal region/GU,
region/GU Oropharynx,
Oropharynx CNS

3. Previous positive microbiology results

4 Routine investigations
4.
Blood testing to assess bone marrow, renal and liver function, Coagulation screen, CRP,
Blood cultures includingg cultures from indwellingg IV catheter, Urinalysis
y and culture,
Sputum microscopy and culture, Stool microscopy and culture, Skin lesion
(aspirate/biopsy/swab), CXR

5. Further investigations
(profound/prolonged neutropenia/following allografts)
High-resolution chest CT (despite
(
72 h of appropriate antibiotics))
Broncho-alveolar lavage

Surviving Sepsis Campaign: International Guidelines for

Management of Severe Sepsis and Septic Shock: 2012
Intravenous ATB administration within 1 hour of
recognition of septic shock (grade 1B) and severe sepsis
without septic shock (grade 1C)
The choice of empiric antibiotics for febrile neutropenia
should be based on local antibiotic susceptibility data.
data
Clinical Guideline for NICE by the National Collaborating Centre for Cancer (2012)
Critical Care Medicine 2013 ; 41( 2) :580-637

Empirical Antibiotic For Serious Systemic Infections

In nosocomial acquired or suspect resistant GNR
and life threatening, immunocompromised host
Carbapenem
C
In nosocomial acquired but not life threatening or
community
i acquired
i d with
i h suspectedd resistance
i
BL inhibitor (Cefoperz/sulbact, Pip/taz)
4th Gen.
Gen Cephalosporin
In community acquired and normal host
3rd Gen.
Gen Cephalosporin
Cephalosporin*

May add aminoglycoside in more serious

Add Vanco.
V
if suspectt MRSA
Add Metronidazole if suspect anaerobes

http://www.ped.si.mahidol.ac.th/

Evaluation of guideline for treatment of febrile neutropenia in

ppediatric cancer at Sirirajj Hospital.
p
A total of 148 FN episodes in 90
patients
The predominant underlying
g y was acute leukemia. About
malignancy
50% had ANC less than 100
cells/mm3 at the beginning and at
reassesment on day 3 of treatment.
The causes of infection with
microbiological confirmation was 25%.
Urinary tract infection was the
predominant
d i t source off infection
i f ti

62% responded to initial treatment

without changing of antibiotics.
antibiotics
Of all episodes, 91.2% were able to
complete
p treatment accordingg to the
CPG.
The mortality rate was 1.4%.
ANC <100 cell/mm3 on day 3 of
treatment was the significant risk
factor for prolonged duration of fever
and unresponsiveness to low risk
regimen
i off antibiotics.
tibi ti
J Med Assoc Thai 2005;88 Suppl 8:S124-34.

Progression
H/C (16/6/56)
P. aeruginosa
H/C (17/6/56): NG
U/C (17/6/56): NG
Treatment
Meropenem x 7 days + Amikacin x 5 days
Ceftazidime x 7 days

Pseudomonas aeruginosa Bloodstream Infection:

Importance of Appropriate Initial Antimicrobial Treatment
IInappropriate
i initial
i i i l antimicrobial
i i bi l treatment as an
independent predictor for hospital mortality (30.7%
versus 17.8%; P = 0.018).
Initial treatment with combination antimicrobial agents
directed against
g
P. aeruginosa
g
was statisticallyy more
likely to provide appropriate treatment than was
monotherapy.
th

Antimicrob Agents Chemother 2005; 49:1306-1311

 3. 2

3
trauma
Physical Examination
T 38o C,, AF 2x2 cm no bulging
g g
Right hip : warm and swelling, decrease movement of right leg

screaming when passive movement of right hip

Others: unremarkable

Investigation
g

CBC (30/8/56): Hb 12 g/dl, Hct 36% WBC 18,900

cell/mm3
(N 73.1%, L 20.6%, Mo 5.1%, Eo 0.9%,Ba
0.3%), plt. 420,000 cell/mm3
ESR 84 mm/hr,
mm/hr CRP 26.06
26 06 mg/L
H/C : pending

Film both hip

U/S Hip : joint effusion in right hip

 3
antibiotics

 3
antibiotics
. Cloxacillin
. Cefazolin
. Cefotaxime

 3

antibiotics

. Cloxacillin
. Cefazolin
. Cefotaxime

Septic arthritis

Clinical
Cli
i l manifestations:
if t ti
Neonates
eo ates and
a d young
you g infants
a ts
Septicemia or fever without a focus
Joint or extremity: swelling, red, warm
Pain: limitation of use of the involved extremity
(pseudoparalysis),
p
p y ppain on manipulation
p
Postural changes: positional preferences
Hip: flex and externally rotate

 M
More commonlyl in
i children
hild < 3 years.
Boy: girl 2:1
Mode of infection:

Septic arthritis:

Hematogenous spread: most common

Contiguous spread: complication of osteomyelitis.

Infection from the metaphysis to the joint by transphyseal

vessels. (obliterate by 18 mo of age)
z Some joint capsules cover the metaphysis:
hip, shoulder, elbow and ankle
Direct inoculation
z

Bone and joint infections in children. Pediatr Clin N Am 2005

 Site of infection:

Septic arthritis:

Monoarticular joint involvement: > 90%

CCommon sites:
it hip,
hi knee,
k
andd ankle
kl
Polyarticular involvement:
Neonates
N. gonorrhea, N. meningitidis, Salmonella spp.
And occasionally S. aureus

Investigations

Leukocytosis: 20-35% of cases

ESR and CRP: elevated in most patients
CRP: peaks within 36 -50 hr of onset of infection
normal within 7-10 days of successful treatment
ESR: peaks within 3-5 days of onset of infection
normal within up to 30 days of successful treatment
Blood culture: positive in approximately 40 %
Synovial fluid:
WBC count >50,000 cells/microL, with a predominance (>90%) of polymorphonuclear cells
Culture:
Cl
positive
i i in
i approximately
i l 500 to 60%
Confirmed bacterial etiology in 50-70% of cases
P

kk nen M, Peltola H. Pediatr Clin North Am. 2013 ;60(2):425-36

unkila-kallio L, et al. Pediatrics 1993;92(6):800-4

Investigations

Imaging
Plain radiographs:
widening of joint space
space, capsular swelling evidence of
osteomyelitis
Ultrasonography:
Useful and more available to detect joint effusion
Magnetic resonance imaging (MRI):
Highly accurate for detecting of joint effusion, but not
practical.

Septic arthritis
Age

Common pathogen

Empirical Antibiotics

0-3 mo

Staphylococcus aureus
Streptococcus
p
agalactiae
g
Gram-negative enteric bacteria
Neisseria gonorrhea
C did
Candida

antistaphylococcal agent (vancomycin or

nafcillin/oxacillin) +
3rdgen.cephalosporin eg: cefotaxime or
gentamicin

<5y

Staphylococcus aureus
Streptococcus pyogenes
Salmonella spp
Streptococcus pneumonia
Kingella kingae
Haemophilus influenza type b

Age < 2 y
3rdgen.cephalosporin:
gen cephalosporin: cefotaxime +/-/
gentamicin
Age 3-5 y
Cloxacillin or Cefazolin +/- gentamicin

>5 y

Staphylococcus aureus
Streptococcus pyogenes

Cloxacillin or cefazolin +/+/ gentamicin (severe

case)

Neisseria gonorrhea
(sexually active adolescents)

Cefotaxime or ceftriaxone

Surgical Treatment
Indication for arthrotomy :
Prompt drainage for
f hip and shoulder
Large amount of fibrin debris or loculations
Concomitant with osteomyelitis
Lack of clinical improvement after 48 hours of

antibiotic
tibi ti therapy
th
or persistent
i t t positive
iti cultures
lt
despite appropriate antimicrobial therapy and multiple
needle aspirations

Sequential Oral Antibiotic Therapy

Good clinical response to parenteral antibiotics:
Afebrile for 48 to 72 hours
Local signs
g and symptoms
y p
of infection are reduced considerably.
y
Normal peripheral leukocyte count
Decrease
D
ESR andd CRP llevel.l

Usually after 7 -10 days of intravenous therapy.

Ability to swallow, retain, and absorb an appropriate oral medication.
In
I neonates:
t parenteral
t l antibiotics
tibi ti ffor entire
ti course

Duration of Therapy
Generally 2 - 6 weeks depending on
Organism:

SS. aureus 3 wks

S. pneumoniae, K. kingae, or N. meningitidis 2-3 wks
Enterobacteriaceae or other unusual organisms: longer course
Clinical resolution of signs and symptoms:
Longer duration in hip
Resolution of inflammatory markers.

 Treatment
OR: Arthrotomy Rt. hip
Finding:
g

Pus in right hip 2 ml

Medial femoral head cartilage have
some destruction
Anterolateral cartilage
g smooth and
whitish surface

Pus from Rt.hipp

E.coli, ESBL neg

H/C : no growth
Stool c/s : no growth

Historyy

Progression
Treatment
Cefotaxime (300 MKD) x 4 wk.
wk

+Amikacin (15 mkd) x 5 days

30/8 6/9 13/9 20/9 27/9
ESR 84
95 61 54 20
CRP 26.06 32.47 7.92 4.1 0.18

f/u film hip : normal alignment , no bony destruction

Septic Arthritis

Long-term complications
Avascular necrosis
Limb length disparities
Pseudarthrosis (false joint)
Joint dislocations and joint
deformity

Risk factors for long-term complications

Age < 6 months
Concomitant osteomyelitis
Involvement of high risk joints: hip or
shoulder
Delay in appropriate initial management
(decompression and initiation of
antibiotics) by 4 days or longer.
longer
Enterobacteriaceae and S. aureus

Gutierrez KM. In:Long SS, Pickering LK, Prober CG, eds.

Principles and Practiceof Pediatric InfectiousDiseases,3rd ed . 2009:484492

 4
4. 2 6
2

BT 39.5 oC, others : unremarkable
CBC : Hb 12 g/dl, Hct 36%, wbc 10,300 cells/mm3(N 70, L 28, M
2), platelet 276,000
UA : WNL
Hemoculture

24

Hemoculture Streptococcus pneumoniae

.
hemoculture ,

oral amoxicillin
80-90 mg/kg/d
g g 24 .
. hemoculture ,
24
. , hemoculture ,
Ceftriaxone 50 mg/kg IV

.
hemoculture ,

oral amoxicillin
80-90 mg/kg/d
g g 24 .
. hemoculture ,
24
. , hemoculture ,
Ceftriaxone 50 mg/kg IV

Management of a Previously
Healthy Infant (28
(28
28--90 Days) with
FWS (T > 38
38..0c)

Baraff LJ. Ann Emerg Med 2000;36:602-614.

Low--risk Criteria for Febrile Infants

Low
Clinical criteria

Previously healthy,
healthy term infant
with uncomplicated nursery stay
Nontoxic clinical appearance
No focal bacterial infection on
examination (except otitis media)

Laboratory criteria

WBC count 5,000

5 000
15,000/mm3, <1,500
bands/mm3, or band/neutrophil
ratio <0.2
<0 2
Negative Gram stain of unspun
urine (preferred), or negative urine
leukocyte esterase and nitrite, or
<5 WBCs/hpf
When diarrhea present: <5
WBCs/hpf in stool
CSF: <5 WBCs/mm3 and negative
G
Gram
stain
t i ((option
ti 1 only)
l )
Baraff LJ. Ann Emerg Med 2000;36:602-614.

Management of a Previously
Healthy Child (3-36
(3 36 months)
with FWS

Baraff LJ. Ann Emerg Med 2000;36:602-614.

The Child not Appear Toxic, T > 39oC

Baraff LJ. Ann Emerg Med 2000;36:602-614.

Active p
prospective,
p
, hospital-based
p b d surveillance study
dy ((2008-2009))
Fever without a Source in Thai Infants and Children 28 days to <60 months from
PneumoNet study (n = 1263): overall bacteremia 2.3%*

Salmonella 19, 63.3% (Overall

(
1.5%))
S. pneumoniae 6, 20% (Overall 0.5%)
Moraxella spp.
spp 3,
3 10% (Overall 0.2%)
0 2%)
Hib 1, 3.3% (Overall 0.1%)

* Include some children with pneumonia (exclude contamination by coagulase

negative Staphylocci and Micrococcus )

5th Asian Congress of Pediatric Infectious Diseases, September 2326, 2010, Taipei, Taiwan.

Occult Pneumococcal Bacteremia

M
Majority
j i off children
hild
with
i h occult
l pneumococcall bacteremia
b
i
resolves without therapy
A retrospective
t
ti review
i ffrom th
the Child
Childrens
H
Hospital
it l iin
Boston, children with occult pneumococcal bacteremia
No ATB

Received ATB

Persistent fever

76.1%

23.9%

Persistent bacteremia

17.0%

1.6%

Hospitalization

50.0%

11.7%

Lee GM, et al. Arch Pediatr Adolesc Med. 1998;152:624-628.

Risk of Bacterial Meningitis in Occult Bacteremia

Baraff LJ. Ann Emerg Med 2000;36:602-614.

Revisit for Occult Pneumococcal Bacteremia

Febrile : Children who were well
well, but persistently febrile at the

revisit and did not receive antibiotics at the initial visit

33-42 % chance of persistent bacteremia
4.4 % chance of meningitis
4% chance of meningitis despite initial oral antibiotic therapy

High risk of SBI in patients with + H/C for S. pneumoniae who

are febrile on revisit

z
z
z

Should
Sh
ld undergo
d
a full
f ll sepsis
i evaluation
l ti ((consider
id LP iin iinfants)
f t)
Should receive parenteral antibiotics tailored to susceptibility
Oral antibiotic mayy be an alternative
Total duration 7-10 days

Bachur R, et al. Pediatrics 2000;105:502-9.

Revisit for Occult Pneumococcal Bacteremia

Afebrile : Well-appearing, afebrile children who did not receive
antibiotics at the initial visit with + H/C for S. pneumoniae
~ 9 % risk of persistent bacteremia
Another H/C before antibiotic therapy
p
Can be managed with antibiotics as an outpatient with close F/U
Antibiotic regimens
g
should provide
p
coverage
g for resistant

S. pneumoniae

Bachur R, et al. Pediatrics 2000;105:502-9.

Antimicrobial Susceptibility of S. pneumoniae Isolates Causing IPD,

Central Thailand, 20092009-2012
Antimicrobial agents

Susceptibility (%)
Susceptible

Intermediate

Resistant

Penicillin

234

89 7
89.7

60
6.0

43
4.3

Cefotaxime

234

95.7

2.6

1.7

Cefditoren*,#

82

90.2

6.1

3.7

Cefdinir#

80

50.0

7.5

42.5

Erythromycin

193

45.6

3.1

51.3

Azithromycin#

82

26 8
26.8

12
1.2

72 0
72.0

Clarithromycin#

82

26.8

6.1

67.1

Clindamycin

34

67.7

0.0

32.3

Tetracycline

99

41.4

0.0

58.6

TMP-SMZ

145

32.4

9.0

58.6

Ofl
Ofloxacin
i

95

97 9
97.9

10
1.0

11
1.1

Levofloxacin

14

100.0

0.0

0.0

Linezolid

95

97.9

0.0

2.1

Vancomycin

131

100

0.0

0.0

Phongsamart W, et al. The 31st ESPID Meeting, Milan, Italy, May 28 - June 1, 2013

 5
5. A 4-year-old girl who has a chronic
tracheostomy due to subglottic stenosis
3 days PTA she developed high grade fever with increased respiratory
distress, purulent tracheal secretions.
History of recurrent hospitalization
Physical examination
T39.5 o c, P 120/min (full), BP 100/60 mmHg, RR 40/min
G/A: looked sick, dyspnea, tachypnea, subcostal retraction
HEENT: pharynx mild injection,
Lungs: coarse crepitation at right lung

Investigation
CBC : Hb 12.3 g/dl,
Hct
H t 35.1%,
35 1% WBC 16,000
16 000 /mm
/ 3
(N 71%, L22%, Mo7%), plt.
339,000/ mm3
Sputum from treachal
secretions: Gram stain reveals
numerous WBC and gramgram
negative rods
Chest X-ray: as shown

 5
What is the BEST choice for empiric
antibiotic
tibi ti therapy
th
for
f this
thi patient?
ti t?

 5
What is the BEST choice for empiric
antibiotic
tibi ti therapy
th
for
f this
thi patient?
ti t?
. Ampicillin-sulbactam
. Piperacillin-tazobactam
. Clindamycin+Ceftriaxone

 5
What is the BEST choice for empiric
antibiotic
tibi ti therapy
th
for
f this
thi patient?
ti t?
. Ampicillin-sulbactam
. Piperacillin-tazobactam
. Clindamycin+Ceftriaxone

Comparison of antibacterial spectra

Serratia sp.
Proteus mirabilis
Citrobacter sp.
sp
Aeromonas sp.
Ps. aeruginosa
E. coli/Klebs sp. ESBL+
Enterobacter sp.
Acinetobacter sp.
sp

Amp/Sulb
0
+
0
+
0
0
0
+

Pip/Tazo
+
+
+
+
+
+
+
+

Ceftriaxone
+
+
+
+
+
0
+
0

The Sanford Guide to Antimicrobial Therapy 2012

Treatment outcome of TAZ/PIPC and SBT/ABPC as initial

empirical
i i l therapy
th
off aspiration
i ti pneumonia
i causedd
by Klebsiella pneumoniae (NI)
Effective rate
Survival rate
After 30 days
Early treatment
success rate

TAZ/PIP group
91.7% (11/12)
91 7% (11/12)
91.7%

SBT/ABP group
25.0% (3/12)
58 3% (7/12)
58.3%

p
0.003
0 155
0.155

91.7% (11/12)

41.7% (5/12)

0.027

J Infect Chemother (2012) 18:715721.

 6
6.
3
5
2

Physical examination
V/S : T 38o c, P 110/min, BP 100/60 mmHg, RR 30 /min
G/A : Alert, mild dyspnea
HEENT : pharynx mild injection, no oral ulcer, no conjunctivitis
RS : fine crepitation on both lungs
lungs, decreased breath sounds
on RLL,

CXR

Investigation
CBC:
CBC Hb 10.9g/dl,
10 9 /dl Hct
H t 32.6%,
32 6% WBC
6 530/mm3 (N 53.2%,
6,530/mm
53 2% L 42.9%,
42 9% Mo
33.5%,
5%, Eoo 00.2%,
%, Baa 00.2%),
%), Plt.
3
199,000/mm

. Levofloxacin
. Cefotaxime + azithromycin + oseltamivir
. Cefotaxime + azithromycin

. Levofloxacin
. Cefotaxime + azithromycin + oseltamivir
. Cefotaxime + azithromycin

Community-Acquired Pneumonia (CAP) in Childhood

Etiologic agents:
Viruses: most common pathogens30% - 67% of cases esp. in
children < 1 yr (77%)
Bacteria:
Streptococcus pneumoniae and Haemophilus influenzae type b
(Hib) mostt common
(Hib):
Mycoplasma pneumoniae and Chlamydia pneumoniae: up to 1/3
of cases.
23%- 33% of cases of pneumonia
mixed bacterial and viral infections.
Bacteremia: < 10%
Cilla G, et al. J Med Virol 2008;80(10):18439.
Michelow IC, et al. Pediatrics 2004;113(4):7017.

Microbial causes of CAP in childhood

Age
Birth-3 weeks

3 wk3 mo

Etiologic agents
Groupp B streptococci
p
Gram-negative enteric bacteria
y g
Listeria monocytogenes
Chlamydia trachomatis
RSV
Parainfluenza viruses esp.type 3
Streptococcus pneumoniae
Staphylococcus aureus
Bordetella pertussis
Pediatr Clin N Am 60 (2013) 437453.

Age

Etiologic agents

4 mo- 4 y

RSV, parainfluenza viruses, influenza virus,

adenovirus, rhinovirus
Haemophilus influenzae
Streptococcus pneumoniae
Mycoplasma pneumoniae
Mycobacterium tuberculosis

5-15 y

Mycoplasma pneumoniae
Chlamydia pneumoniae
Streptococcus pneumoniae Influenza A or B,
adenovirus
Nontypeable Haemophilus influenzae
Mycobacterium tuberculosis
Pediatr Clin N Am 60 (2013) 437453.

Incidence and Etiology of ALRI in Hospitalized Children < 5 yr

in Sa Kaeo and Nakhon Phanom,, Thailand.

N = 28,543 hospitalizations from 2005-2010

Blood cultures were collected from 28% of cases (n= 7,975)
1.8% (n=145)
(
) were positive blood cultures.
Most common pathogens:
Salmonella, non-typhoid 15%
Streptococcus pneumoniae 13%
Haemophilus influenzae 10%
E.coli 9%
Hasan R, et al. PIDJ 2013 Sep 11 [Epub ahead of print]

Incidence and Etiology of ALRI in

Hospitalized Children < 5 yr
in Sa Kaeo and Nakhon Phanom, Thailand.

25

20

20

17.9

n=145

16.7

1616
1616

St
Streptococcus
t
pneumoniae
i
Escherechia coli

15

Haemophilus influenzae

1212
12
12

11 9
11.9

11 9
11.9

11 9
11.9

Salmonella, non-typhoid

10.3

Staphylococcus aureus

10
8

77
7.7

Acinetobacter baumanii

77
7.7

Klebsiella spp

7.1 7.17.1

Moraxella cattarrhalis
Burkholderia pseudomallei

4.8

4.84.8

3.8 3.8
2.6
1.3
0 0

0
<6 m

6-23 m

24-59 m

Mycoplasma pneumoniae and Chlamydophila pneumoniae in children

with community
community-acquired
acquired pneumonia in Thailand
A prospective surveillance study: Dec 2001- Nov 2002
N = 245,
245 age: 2-15
2 15 yr.
17.5% of CAP (n=43) were caused by atypical pathogens.
46.5%
46 5% (20/43) were children aged 2-5
2 5 yr.
yr
Rates of current infection:
z M.
M pneumoniae 14.3%
14 3%
z C. pneumoniae
2.8%
z Coinfection
0 4%
0.4%
Among children with CAP: prevalence of atypical pneumonia
Age 22-55 yr.
yr 11%
Age > 5 yr.
36%
S. Lochindarat, et al. INT J TUBERC LUNG DIS 2007;11(7):814819

Parapneumonic effusion
2%12% children with pneumonia developed
parapneumonic effusions.
most frequently (50%) related to bacterial pneumonia
S. pneumoniae, S. pyogenes, S. aureus and
H. influenzae type b
Up to 20% of mycoplasma pneumonias.
10% of viral pneumonias.
pneumonias
IDSA Guidelines CID 2011;53(7):e25.

Mycoplasma pneumonia:
extrapulmonary involvement
skin: erythematous maculopapular rash, erythema
nodosum or urticaria to the Stevens-Johnson
Stevens Johnson
syndrome.
Other extrapulmonary manifestations:
Hemolytic

anemia, polyarthritis,
anemia
polyarthritis pancreatitis,
pancreatitis hepatitis
hepatitis, pericarditi
s, myocarditis, and neurologic complications

Empiric Therapy for Pediatric Community-Acquired Pneumonia (CAP)

All age

Bacterial pneumonia

Fully immunized : Hib,

PCV
Penicillin resistance in
invasive strains of
pneumococcus is
minimal

Ampicillin or penicillin G;
alternatives:
ceftriaxone or
cefotaxime

Not fully immunized Ceftriaxone or

Penicillin resistance in cefotaxime
invasive strains of
pneumococcus is
significant

Atypical pneumonia

Influenza
pneumonia

If atypical pneumonia in
Oseltamivir or
doubt Add Azithromycin
zanamivir
OR
Clarithromycin
Erythromycin,
Doxycycline for children.> 7
y Levofloxacin
As above

As above

IDSA Guidelines CID 2011;53(7):e25.

Antimicrobial Susceptibility of S. pneumoniae, Siriraj Hospital, 2008

%Suscep
%
ptible

N 170 (32 4% f
N=170(32.4%fromchildren<5years)
hild
5
)

Srifuengfung S, et al. J Med Assoc Thai 2010;93 Suppl 5:S27-34.

Progression
Cefotaxime
Azithromycin

Ciprofloxacin

Follow up

Treatment
Cefotaxime+ Azithromycin x 5 days
Ciprofloxacin x 7 days
Mycoplasma titers 1: 1280 1wk later Mycoplasma titer > 1: 20,480

Macrolide-Resistant Mycoplasma pneumoniae (MRMP)

First isolated from pediatric patients in 2000.
Mutation at A2063G
A2063G, A2063T,
A2063T or A2064G of the 23S ribosomal RNA
gene confers high resistance to macrolides (MIC90 > 64)
Prevalence of MRMP:
In Japan (children): 5.0% in 2003 to 87% in 2011
In Korea: 2.9% in 2003 to 63% in 2011
In China (children & adult): > 80%
In U.S.: 8.2%
In Europe: 3% in Germany, 10% in France, 26% in Italy and 32% in Israel

Macrolide-Resistant Mycoplasma pneumoniae(MRMP) Infection

in a 2011Outbreak Among Japanese Children
Among 202 M. pneumoniae isolates from
M pneumoniaeassociated
M.
pneumoniae associated pneumonia patients,
patients
176(87.1%) were MRMP.

Takafumi Okada, et al. CID 2012:55:1642-9

 7. 3
1 .
3
PE: T 38.5oC, Lt. ear: tympanic membrane:
injected and mild bulging,
bulging
no perforation
p
Others : WNL

. Cefdinir
. Amoxicillin/clavulanate, 90 mg/kg/day of
amoxicillin
. Amoxicillin 50 mg/kg/day

. Cefdinir
. Amoxicillin/clavulanate, 90 mg/kg/day of
amoxicillin
. Amoxicillin 50 mg/kg/day

Diagnosis of AOM
Clinicians should diagnose AOM in children who present with (B)
Moderate to severe bulging of the TM
New onset of otorrhea not due to acute otitis externa
Clinicians should diagnose AOM in children who present with (C)
Mild bulging of the TM and recent (<48 hours) onset of ear pain
(holding tugging,
(holding,
tugging rubbing of the ear in a nonverbal child)
Intense erythema of the TM
AAP. Pediatrics 2013;131:e964e999.

Normal TM
Translucent/transparent
Gray or pink color
Neutral position
Fully mobile with pneumatic otoscopy
No
N effusion
ff i

TM Characteristics in AOM
Opaque
Red, yellow or cloudy
Bulging or full position
Reduced mobility but may respond to positive

pressure on pneumatic otoscopy

Effusion present

Bacterial Etiology of Acute Otitis Media in Young Children (3 mo-<5 y) in

Thailand, 2008
[N = 118 AOM samples, 57 (48%) were C/S+]
47%
37%

12%

P. Intakorn, et al. 5th Asian Congress of Pediatric Infectious Diseases - Taipei, Taiwan; Sep 2226, 2010

Antimicrobial Susceptibility of S. pneumoniae, Siriraj Hospital, 2008

%Suscep
ptible

N=170(32.4%fromchildren<5years)
(
f
h ld
)

Srifuengfung S, et al. J Med Assoc Thai 2010;93 Suppl 5:S27-34.

Acute otitis media

Risk for DRSP:
>> Recent antimicrobial exposure
(within 3 mo)
>> Young age (<2 yo.)
>> Day-care attendance
Dowell. PIDJ 1999;18:1-9.

Betalactamase producing organisms in Thailand

100% of M. catarrhalis BUT high
g rate of
spontaneous clinical resolution
48.8% of H. influenzae
Overall, H. influenzae isolates are susceptible to
regular and high-dose
high dose amoxicillin 58-82%*
58 82%*
*AAP.
AAP. Pediatrics 2013;131:e964
2013;131:e964e999.
e999.
Critchley et al. J Chemother. 2002. 14: 147-154
Srifuengfung S, et al. Southeast Asian J Trop Med Public Health 2007;38(4):732-6

Bacteria causing AOM in

North America, 2012

Recommendations for Initial Management for Uncomplicated AOM

Age

Otorrhea Unilateral or
With
Bilateral AOM
AOM
With Severe
Symptoms *
6 mo - 2 y Antibiotic
A tibi ti Antibiotic
A tibi ti
therapy therapy
Antibiotic Antibiotic
2 y
therapy therapy

Bilateral AOM
Without Otorrhea

Unilateral AOM
Without Otorrhea

AAntibiotic
tibi ti
therapy
Antibiotic therapy or
Observation with
close F/U**

AAntibiotic
tibi ti therapy
th
or
Observation with close F/U**
Antibiotic therapy or
Observation with close F/U**

* Toxic-appearing , persistent otalgia > 48 h, T 39C in the past 48 h, or uncertain access to F/U
** Joint decision
decision-making
making with parents/caregiver,
parents/caregiver If observation is offered,
offered ensure F/U and begin
antibiotics if worsens or fails to improve within 48 - 72 h of onset

AAP. Pediatrics 2013;131:e964e999.

Recommended Antibiotics for

First line:
Amoxicillin
A i illi
z If the child has not received amoxicillin in the past 30 days
z No concurrent purulent conjunctivitis
((narrow spectrum,
p
effective, safe, low cost, acceptable
p
taste))
Amox/Clav
z If the
th child
hild has
h received
i d amoxicillin
i illi in
i the
th pastt 30 days
d
z With concurrent purulent conjunctivitis (more likely NTHi )
z History of recurrent AOM unresponsive to amoxicillin
Reassess the patient within 48 - 72 hours to determine whether a
change in therapy is needed

AOM

AAP. Pediatrics 2013;131:e964e999.

Recommended Antibiotics for AOM

Levofloxacin or linezolid,
linezolid may be indicated in refractory cases
AAP. Pediatrics 2013;131:e964e999.

Pichichero ME. Am Fam Physician 2000;61(8):2410-6

Duration of Therapy
py for AOM and F/U
Optimal
O ti l duration
d ti isi uncertain,
t i usually
ll recommendd
10 days
< 2 y and children with severe AOM : 10 days
y
2-5 y with mild to mod AOM: 7 days
> 6 y with mild to mod AOM: 5-7 days

AAP. Pediatrics 2013;131:e964e999.

- ( 80%) ( )
-

- Common cold
- Acute viral rhinosinusitis
- pharyngitis
- acute bronchitis
:

group A
beta hemolytic streptococcus
- 39 C
-
-
-
>3 3
1
- Amoxicillin 50 mg/kg/day 1-2 10

- penicillin Type I cephalexin 20
mg/kg/dose ( 500 mg/dose) 2 10
- Penicillin type I Roxithromycin 5-8
mg/kg/day ( 300 mg/day) 2 10
azithromycin 12 mg/kg/day ( 500
mg/dose)
/d )
5

clarithromycin
l ith
i 15
mg/kg/day ( 250 mg/dose) 2

(Acute Otitis Media,

Media AOM)
otoscope

-
- 2 AOM 2
-
-

(Acute rhinosinusitis)

- URI sinusitis facial pain,

postnasal drip, purulent discharge
- URI 10
- 5-6
X-Ray

2
(1) Amoxicillin 50-90 mg/kg/day 2-3 10
3
90 mg/kg/day
mg/kg/da
(2) penicillin Type I hypersensitivity
Cefdinir 14 mg/kg/day 1-2
Cefditoren 10 mg/kg/day 2-3
(3) penicillin Type I azithromycin 10
mg/kg/day 5 mg/kg/day
4 clarithromycin 15 mg/kg/day 10
72

amoxicillin/clavulanate (Amoxillin 80-90 mg/kg/day)
2 cefdinir, cefditoren (18 mg/kg/day)
levofloxacin (10

(10-20
20 mg/kg/day)

3
(1) Amoxicillin 50-90 mg/kg/day 2 10-14
5-7 3 high
dose (90 mg/kg/day)
mg/kg/da )

(2) penicillin Type I hypersensitivity

Cefdinir 14 mg.kg/day 2 cefditoren
18 mg/kg/day 2
(3) ) penicillin Type I Azithromycin clarithromycin
levofloxacin 10 mg/kg/day
3-5
amoxicillin/clavulanate (Amoxillin 90
mg/kg/day) 2 cefdinir, cefditoren + clindamycin
levofloxacin)

1.IDSA Guideline for GAS Pharyngitis 2012.CID

2. AAP Guideline for AOM 2013. Pediatrics
3. IDSA Guideline for ABRS 2012. CID

Indications for antibiotics

(Acute Otitis Media, AOM)
otoscope


-

- 2 AOM 2
-
-

Siriraj Guidelines: Antibiotics

z Amoxicillin 50-90 mg/kg/day 2-3 10 3
90 mg/kg/day
z non-type
t I penicillin
i illi hypersensitivity:
h
iti it
- Cefdinir 14 mg/kg/day 1-2 Cefditoren 10 mg/kg/day 2-3
z
Type
T I penicillin
i illi hypersensitivity
h
iti it
- Azithromycin 10 mg/kg/day 5 mg/kg/day 4
- clarithromycin 15 mg/kg/day 10

z 72

- Amoxicillin/clavulanate (Amoxillin 80-90 mg/kg/day) 2

g g y) levofloxacin ((10-20 mg/kg/day)
g g y)
cefdinir,, cefditoren ((18 mg/kg/day)

 8
8.

8 A previously healthy 9-months

9 months old infant
2 days PTA,
PTA She developed vomiting twice times/day,
times/day and three
episodes of non bloody diarrhea. She has been afebrile. She refuses
fluids but still alert.
alert
Physical examination
T 36.5 o c, P 120/min (full), BP 80/60 mmHg, RR 30/min
G/A: Alert, dry lip, no sunken eye ball, capillary refill < 2 sec, no rash
Res/CVS : WNL
soft no distension,
distension no hepato
hepato-splenomegaly
splenomegaly, active bowel sounds
Abd : soft,

 8
Treatment: She received ORS and motilium syrup
And F/U stool c/s report
p at OPD 3 days
y later
Investigation
CBC: Hb11.7g/dl, Hct 35.3%,
Wbc 8,560
8 560 cell/mm3 (N 60 %,
% L
38%, Eo 0.8%,Mo 0.9%,
Ba 0.3%), Plt. 388,000 cell/mm3
Stool exam : WBC 33-5,
5, no RBC

Stool c/s : Salmonella gr.c

 8
Which of the following is the most
appropriate
i t treatment
t t t off this
thi iinfant?
f t?

 8
Which of the following is the most
appropriate
i t treatment
t t t off this
thi iinfant?
f t?
. Ceftibuten 9 mg/kg/d x 3 days
. No antibiotics
. Ciprofloxacin 40 mg/kg/d x 3 days

 8
Which of the following is the most
appropriate
i t treatment
t t t off this
thi iinfant?
f t?
. Ceftibuten 9 mg/kg/d x 3 days
. No antibiotics
. Ciprofloxacin 40 mg/kg/d x 3 days

Antibiotics for treating salmonella gut infections

12 trials involving 778 participants (with at least 258
infants and children)
There were no significant differences in length of illness,
illness
diarrhoea or fever between any antibiotic regimen and
placebo.
Antibiotic regimens resulted in more negative cultures
during the first week of treatment.
Sirinavin S, Garner P. The Cochrane Collaboration 2009

Antibiotics for treating salmonella gut infections

Relapses were more frequent in those receiving
antibiotics, and there were more cases with
positive cultures in the antibiotic groups after 3
weeks.
Adverse drug reactions were more common in the
antibiotic groups (Peto odds ratio 1.67, 95% CI
1.05 to 2.67).
Sirinavin S, Garner P. The Cochrane Collaboration 2009

Empirical ATB Therapy in Acute Diarrhea

Consider in those without clue of viral infection
Severe or Persistent
Dysentery
Age < 6 months
Immunocompromised/ Underlying disease
(Otherwise treat only Cholera and Shigella)
Choices
Norfloxacin (or ciprofloxacin)
TMP/SMX (Neomycin
y not proven
p
effective)
Third gen cephalosporin

Comparison of the efficacy of ceftibuten and norfloxacin in

the treatment of acute gastrointestinal infection in children
A prospective randomized study at an ID hospital in Thailand.
Ceftibuten was compared with norfloxacin, both given orally for 5
days for treatment of acute gastroenteritis in children.
170 cases were included: 88 cases were treated with ceftibuten and
82 cases with norfloxacin.
No statistically significant differences in either comparison (p > 0.05).
Neither complications nor clinical relapses were observed.
Southeast Asian J Trop Med Public Health 1999 ;30(4):764-9.

Inappropriate Use of ATB in Diarrhea

Not shorten illness

Unnecessary cost
Risk for A/E
Prolong shedding (Salmonella)
Increase Risk of HUS (STEC)
Create drug resistance problem
More than 80% of acute diarrhea are from viral/ or self-limited

 9
9. 8
5 5 /
clinic

ORS, paracetamol, motilium

. 1

Physical examination: T 39.5o C, P 140/min, BP 90/60 mmHg
Alert, dry lips, AF 1x1 cm no bulging, no hepatosplenomegaly, Skin - no rash
CNS: Alert, pupil 2 mm BRTL, no facial palsy
Motor : equally
q y movement both, grade
g
V/V all
Stiffness of neck and brudzinskis sign : negative

Investigations

CBC :Hb 11
Stool
g/dl
g/dl,
Hct
Exam : WBC 0-1,
0 1 no RBC
32% WBC 12,060
C/S : pending
cell/mm3 ( N 41.6
H/C: pending
%,
L
CSF
51.8%, Mo 6.3%, Ba
WBC 6 /mm3, RBC 840/ mm3
0.3%), pplt. 175,000 /mm3
Protein 19 mg/dl,
mg/dl sugar 87/91 mg/dl
U/A : PH 6.5, sp.gr.
Gram stain: no organism found
1 020 protein
1.020,
ti
C/S : pending
neg,
sugar

. Cefotaxime
. Cefotaxime + Ciprofloxacin
. stool Rotavirus Ag, antibiotic

. Cefotaxime
. Cefotaxime + Ciprofloxacin
. stool Rotavirus Ag, antibiotic

Progression
Aft
After empirical
i i l antibiotic
tibi ti
cefotaxime
200 mg/kg/day
/k /d x 48 hr.
h
Patient still had high grade
f
fever,
but
b diarrhea
di h and
d
vomiting decreased
H/C report : gram
negative rod

Treatment
Cefotaxime (31/8-6/9/56)
(31/8 6/9/56)
x 7 days
Ciprofloxacin iv was

added

Progression

Stool c/s : no growth

CSF c/s : no growth
H/C (1,2/9/56)
(1 2/9/56) : Salmonella
S l
ll gr.C
C

Treatment
Cefotaxime
C f t i (31/8-6/9/56)
(31/8 6/9/56) x 7
days
Ciprofloxacin iv

(1-6/9/56) x 6 days
Bactrim (6-21/9/56) x 15 days
H/C
/ ( 4/9/56)
/ / ) : no ggrowth

Children with Invasive NonNon-Typhoidal Salmonella infection, Siriraj

Hospital, 20062006-2011 (n = 80)
80)
Data
Median age (range)
Underlying conditions
Previously healthy
Immnunodeficiency
Hematologic malignancies
SLE
HIV
Interleukin-12 deficiencyy
Others
Biliary atresia
Congenital heart diseases
Thalassemia
G-6-PD deficiency
Others
Clinical manifestations
Fever
Diarrhea
Hepatomegaly
Splenomegaly

N (%)
12 months (11 days 13.9 years)
42 (52.5)
10 (12.5)
(12 5)
6 (7.5)
4 (5.0)
1 ((1.2))
5 (6.3)
5 (6.3)
1 (1.2)
2 (2.5)
4 (5.0)
79 (98.7)
43 ((53.8))
7 (8.7)
4 (5.0)

Saihongthong S, Phongsamart W, et al. 15th International Congress on Infectious Diseases ,Bangkok , Thai land, June 13-1 6 , 2012

Children with Invasive Non

Non--Typhoidal Salmonella
infection, Siriraj Hospital, 20062006-2011 (n = 80)
80)
Data
Laboratory results
WBC (cells/mm3)
< 5,000
5 000 15 000
5,000-15,000
> 15,000
Thrombocytopenia
Outcome
Recurrence (NTS bacteremia)
Complications (1 meningitis with subdural empyema,
empyema 1 septic
shock)
Death

N (%)

15 (18.7)
43 (53.8)
(53 8)
22 (27.5)
22 (27.5)
2 (2.5)
2 (2.5)
(2 5)
2 (2.5)

Saihongthong S, Phongsamart W, et al. 15th International Congress on Infectious Diseases ,Bangkok , Thai land, June 13-1 6 , 2012,
# Abstract No. 45.065

 229 children 018 years in 2001-2010 with culture-proven invasive

Salmonella infections, 98.6% were non-typhoidal Salmonella
Median
di age ((IQR)
Q ) was 100 (19.5)
( 9 ) months,
h 63%
63 were previously
i l
healthy
Diarrhea
Di h were ffound
d in
i 40% off cases
23% presented with fever without source
53% off the
h cases h
had
d WBC within
i hi normall limits
li i (500015,000
(5000 15 000
cell/mm3)
The overall case fatality rate 4.8%
4 8%
Punpanich W, et al. Pediatr Infect Dis J 2012;31(8):e105-10.

Antimicrobial Resistance among Invasive Salmonellosis,

Salmonellosis,
Siriraj Hospital 20062006-2011 and QSNICH 2001
2001--2010
(n = 80 NTS1 and 2292)

% Resistance

Si i j H
SirirajHospital
it l
76.368.3
25 33.9

50
15.2

QSNICH

34

17.4

12.5

1. Saihongthong S, Phongsamart W, et al. 15th International Congress on Infectious Diseases Bangkok , Thai land, June 13-1 6 , 2012.
2. Punpanich W, et al. Pediatr Infect Dis J 2012;31(8):e105-10.

Susceptibility Testing for Salmonella

Decreased ciprofloxacin susceptibility/Nalidixic acid resistant is
correlated with delayed responses, clinical failures, and
i
increased
d mortality
li among patients
i
receiving
i i CIP ffor S.
S typhi
hi
and NTS
CLSI/NCCLS:
CLSI 2004 screen extra-intestinal Salmonella with CIP MICs 1 g/mL

for NAL resistance. If NAL resistance, lab was instructed to indicate to

clinicians that FQ treatment might not be efficacious
CLSI 2012: NAL screening does not detect all mechanisms of FQ
resistance CIP should also be tested and interpreted using the new
resistance,
susceptible MIC break point of 0.06 g/mL or zone size 31 mm with
disk diffusion

Humphries RM, et al. CID 2012;55(8):110713.

Treatment of Invasive Salmonellosis

Salmonella meningitis: high rates of mortality, complications and
relapse
UK1: imaging, document sterilization, Cefotaxime/ceftriaxone +

ciprofloxacin > 4 wks or > 3 wks after 1st sterile (repeat after Rx D4)
PIDST 2013-20142: combination of Cefotaxime/ceftriaxone
/
+
ciprofloxacin 4-6 wks

High rates of Ceftotaxime/ceftriaxone resistance

Consider adding ciprofloxacin in suspected/proven
invasive Salmonellosis pending for susceptibility results

Options
O i
ffor cefotaxime/ceftriaxone
f
i / f i
+ FQN resistance:
i
Co-trimoxazole if susceptible, Imipenem, or Azithromycin

1. Price EH, et al. J Antimicrob Chemother 2000;46:653-5.

2. Meningoencephalitis Guideline 2013-2014.