Transcript Combination therapy with colistin

MGR
case1
ERCP후 발생한 fever
Division of Infectious disease
R2 황연희
11471814
김0용 (M/73)
adm 2007-10-07
• Chief complaint
generalized weakness
o/s ) 약 10여일전
• Present illness
73세 남자 환자, 10여일전 부터 RUQ pain, diarrhea, vomiting 발생,
이후 pain은 감소하였으나 diarrhea, nausea 지속적으로 보이고
poor oral intake와 generalized weakness보여 응급실 통해
소화기 내과에 입원
• Past medical history
DM (-) HTN (+) Tb (-) Hepatitis (-)
Old CVA (+) 본원 신경과 f/u 중
• Family history
None
• Personal history
Alcohol (-)
Smoking (+) : 30 PY
Review of Systems
•
General
: fatigue(+) edema(-) weight loss(-)
•
Skin
: rash(-)
•
Head & Neck : headache(-) stiffness(-)
•
Eye & ENT
: sore throat(-) periorbital edema(-)
•
Respiratory
: cough(-) sputum(-) dyspnea(+)
•
Cardiac
: palpitation(-) chest discomfort(-) orthopnea(-)
•
Gastrointestinal : A/N/V/D/C (+/+/+/+/-) abdominal discomfort(+)
jaundice (+) melena (-)
•
Urinary
•
Musculoskeletal: myalgia(-) weakness(-) numbness(-)
•
Endocrine
: polydipsia (-) polyuria(-) cold intolerance(-)
•
Nervous
: Syncope(-) seizures(-) dizziness(-) tremor(-)
pigmentation(-)
Itching(-)
: dysuria(-) frequency(-) urgency(-)
Physical examination
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Vital sign
140/80 mmHg – 78/min – 20/min – 36.5 °C
Height : 171cm
Weight : 76kg
BMI : 25.9
General appearance Alert mentality
Skin
No rash or pigmentation
Head & Neck
No lymph node enlargement
No neck vein engorgement
Eyes and ENT
Isocoric pupils with PLR (++/++)
Yellowish sclera & pinkish conjunctivae
Chest
Clear breath sounds without crackle
Regular heart beats without murmur
Abdomen
Soft and flat abdomen
No tenderness or rebound tenderness
No palpable abdominal mass
Back and Extremities CVA tenderness ( - / - )
Pretibial pitting edema ( - / - )
Initial Lab Results
• CBC/DC
7900/mm3 – 15.5 g/dL– 44.6 % - 28K/mm3 (Seg 85.1%)
aPTT 44.5/34 INR 1.01
• Chemisrty
TB/ DB 7.17/ 4.88 mg/dL
ALP/ GGT 160 / 218 U/L
Prot/ Alb 5.6/ 2.8 g/dL
AST/ ALT 162/196 U/L
Bun/ Cr 81/ 5.2 mg/dL
Na/ K/ Cl 138/ 4.6/ 100 mmol/L
CRP 32.1 mg/dl
• Urinalysis
RBC 0-1/ HPF WBC 0-1/ HPF
Initial Assessment and Plan
#1. Acute cholangitis
항생제 투여와 수분공급
imaging study
필요시 ERCP 고려
#2. Renal insufficiency
FeNa, Feurea
hydration. medication 조절 (항생제 용량 조절)
#3. HTN
#4. Old CVA
Abdomen CT & MRCP
ERCP
Clinical course
ERCP
2007-10-24일 fever시 나간 blood culture
2007-10-24일 fever시 나간 bile fluid culture
2007-10-27 blood culture
case2
Spinal stenosis 수술후
수술부위 감염
Division of Infectious disease
11913833
김0자 (F/70)
adm 2007-07-05
• Chief complaint
수술부위 bleeding
o/s ) 2일전
• Present illness
70세 여자 환자, 2년전 low back pain으로 spinal stenosis로 진단,
내원 2일전 외부병원에서 수술 후 수술부위에서 출혈 지속적으로
보여 1일전, 내원 당일 재수술 하였으나 호전 없어 응급실 통해
신경외과에 입원
• Past medical history
DM (+) HTN (+) Tb (-) Hepatitis (-)
• Family history
None
• Personal history
Alcohol (-)
Smoking (-)
Review of Systems
•
General
: fatigue(-) edema(-) weight loss(-)
•
Skin
: rash(-)
•
Head & Neck
: headache(-) stiffness(-)
•
Eye & ENT
: sore throat(-) periorbital edema(-)
•
Respiratory
: cough(-) sputum(-) dyspnea(+)
•
Cardiac
: palpitation(+) chest discomfort(-) orthopnea(-)
•
Gastrointestinal: A/N/V/D/C(-/-/-/-/-) abdominal discomfort(-)
jaundice (-) melena (-)
•
Urinary
•
Musculoskeletal : myalgia(-) weakness(-) numbness(-)
•
Endocrine
: polydipsia (-) polyuria(-) cold intolerance(-)
•
Nervous
: Syncope(-) seizures(-) dizziness(-) tremor(-)
pigmentation(-)
Itching(-)
: dysuria(-) frequency(-) urgency(-)
Physical examination
•
•
•
•
•
•
•
•
Vital sign
90/60 mmHg – 131/min – 34/min – 37.5 °C
Height : 157cm
Weight : 58kg
BMI : 23.5
General appearance Alert mentality
Skin
No rash or pigmentation
Head & Neck
No lymph node enlargement
No neck vein engorgement
Eyes and ENT
Isocoric pupils with PLR (++/++)
clear sclera & pale conjunctivae
Chest
Coarse breath sounds without crackle
Regular & rapid heart beats without murmur
Abdomen
Soft and flat abdomen
No tenderness or rebound tenderness
No palpable abdominal mass
Back and Extremities CVA tenderness ( - / - )
Pretibial pitting edema ( - / - )
Initial Lab Results
• CBC/DC
34300/mm3 – 10.5 g/dL– 31.4 % - 100K/mm3 (Seg 85.1%)
aPTT 40.2 INR 2.38
• Chemisrty
TB/DB 1.56/0.53 mg/dL
ALP 32 U/L
GGT 11 U/L
Prot/Alb 3.3/1.7 g/dL
AST/ALT 130/97 U/L
Bun/Cr 21/1.0 mg/dL
Na/K/Cl 139/3.0/113 mmol/L
CRP 1.7 mg/dl
• Urinalysis
RBC 0-1/ HPF WBC 2-4/ HPF
Initial Assessment and Plan
#1. Op site bleeding
수분공급, 수혈
출혈 지속시 wound revision op고려
#2. Spinal stenosis
수술한 상태로 관찰
#3. DM
2007-08-13 MRSA , Acinetobacter baumannii
2007-09-05 Pseudomonas aeruginosa
2007-09-29 Pseudomonas aeruginosa
review
Reappraisement of Colistin
for MDR Gram (-) bacteria
그람 음성 구•간균
• Gram(-) facultative anaerobic bacilli
– Family Enterobacteriaceae
• Genus Escherichia
• Genus Edwardsiella
• Genus Citrobacter
• Genus Salmonella
• Genus Shigella
• Genus Klebsiella
• Genus Enterobacter
• Genus Hafnia
• Genus Serratia
• Genus Proteus
• Genus Yersinia
– Family Vibrionaceae
• Genus Vibrio
• Genus Aeromonas
• Genus Plesiomonas
– Family Pasteurellaceae
• Genus Pasteurella
• Genus Haemophilus
• Gram(-) aerobic bacilli or cocci
– Family Pseudomonacoaceae
• Genus Pseudomonas
• Genus Xanthomonas
– Family Legionellaceae
• Genus Legionella
– Family Neisseriaceae
• Genus Neisseria
• Genus Moraxella
• Genus Acinetobacter
– 과가 불분명한 속
• Genus Flavobacterium
• Genus Alcaligenes
• Genus Brucella
• Genus Bordetella
• Genus Francisella
Nosocomial GNB
• Enterobacter, Pseudomonas aeruginosa, Acinetobacter
– source
• water : contaminated nebulizer or respiratory device, etc
• hands of medical personnel
• GI tract : minor role than community-acquired GNB
• environment : air-borne?
– low virulence but highly resistant to antibiotics or antiseptics
• Multidrug-resistant Gram-negative bacteria
– Pseudomonas aeruginosa, Acinetobacter baumannii, and
Klebsiella pneumoniae
Alternative or salvage treatment
Colistin
Antibiotic Resistance
Community vs. Hospital Acquisition
• Comparison of A. baumanii isolates obtained from the hands of
homemakers to isolates obtained from 2 US hospitals
– 23/222 (10.4%) homemakers had A.baumanii isolated from
hands
Hospital
(n=101)
Community
(n=23)
Odds Ratio (CI95)
3rd generation
cephalosporins
88%
9%
78 (15-553)
Carbapenems
64%
4%
39 (5-811)
Aminoglycosides
43%
4%
16 (2-337)
Multidrug resistant*
37%
0%
Not calculable
Antimicrobial resistance
*3rd gen. cephalosporins + carbapenem + aminoglycoside
Zeana C. Infect Control Hosp Epidemiol 2003;24:275-279.
Polymyxin antibiotics
• A group of polypeptide antibiotics that consists of 5 chemically
different compounds (polymyxins A ~E)
• Only polymyxin B and polymyxin E (colistin) have been used in
clinically
• History
– The intravenous formulations of colistin and polymyxin B were
gradually abandoned in most parts of the world in the early
1980s because of the reported high incidence of nephrotoxicity
– Colistin was mainly restricted during the past 2 decades for the
treatment of lung infections due to multidrug-resistant (MDR),
gram-negative bacteria in patients with cystic fibrosis
Polymyxin antibiotics
colistin sulfate: oral, used for bowel decontamination
colistimethate sodium: (also called colistin methanesulfate, pentasodium
colistimethanesulfate, and colistin sulfonyl methate)- Intravenous formulation
Clinical Infectious Diseases 2005;40:1333-1341
Polymyxin antibiotics
•
Mechanism of action:
Target
• Bacterial cell membrane
• Colistin binding with the bacterial membrane occurs through
electrostatic interactions between the cationic polypeptide (colistin)
and anionic lipopolysaccharide (LPS) molecules in the outer membrane
– derangement of the cell membrane
– increase in the permeability of the cell envelope, leakage of cell
contents, and, subsequently, cell death.
Polymyxin antibiotics
Sections of a Pseudomonas aeruginosa
strain showing the alterations in the cell
following the administration of polymyxin B
(25 g/mL for 30 min) and colistin
methanesulfate (250 g/mL for 30 min).
A: untreated cell
B: cell treated with polymyxin B
C: cell treated with colistin methanesulfate;
D: cell treated with polymyxin B at higher
magnification.= 0.1 m
Clinical Infectious Diseases 2005;40:1333-1341
Polymyxin antibiotics
• Spectrum of activity
– Most gram-negative aerobic bacilli
• Acinetobacter species, P. aeruginosa, Klebsiella species,
Enterobacter species, Escherichia coli, Salmonella species,
Shigella species, Citrobacter species, Yersinia
pseudotuberculosis, Morganella morganii, and Haemophilus
influenzae
– No activity against
• Pseudomonas mallei, Burkholderia cepacia, Proteus species,
Providencia species, Serratia species, Edwardsiella species,
and Brucella
Polymyxin antibiotics
Route
Dosage
Intravenous
• 2.5-5 mg/kg (31,250-62,500 IU/kg) per day, divided into 2-4 equal
doses (1 mg of colistin equals 12,500 IU).
Modification of the total daily dose is required in the presence of renal
impairment
Intramuscular
•Same as IV
Inhalation
• 40 mg (500,000 IU) every 12 h for patients <40 kg and
• 80 mg (1 million IU) every 12 h for patients >40 kg
• For recurrent pulmonary infections, the dose can be increased to
160 mg (2 million IU) every 8 h
Intraventricular/
intrathecal
(not FDA approved)
• Intrathecal dosage ranged from 3.2 mg (40,000 IU) to 10 mg
(125,000 IU) given once per day
• Intraventricular dosage ranged from 10 mg (125,000 IU) to 20 mg
(250,000 IU) per day (divided into 2 doses)
Polymixin adverse effects
Neurotoxicity
Comments
Dizziness
Weakness
Paresthesias-most common
Vertigo
Visual disturbances
Confusion
Ataxia
Neuromuscular blockade-respiratory
failure
•7 % incidence of Colistin associated
neurotoxicity
•29% incidence in patients with Cystic
Fibrosis
•Toxicity is dose dependent
•Toxicity is reversible upon
discontinuation of medication
Polymixin adverse effects
Nephrotoxicity
•The majority of nephrotoxic events are reversible
•1970’s- incidence of nephrotoxicity was 20.2%
•More recent studies- incidence of nephrotoxicity ranged from 8%-18%
•Lower incidence of Nephrotoxicity at present:
•Greater supportive treatment to critically ill patients
•Close monitoring of renal function
•Avoidance of co-administered nephrotoxic agents
•Older formulations of colistin contained a greater proportion of
colistin sulfate (greater nephrotoxicity)
Characteristics and outcomes of treatment with intravenous colistimethate sodium for infections caused by
multidrug-resistant Gram-negative bacteria in some recent clinical reports
Lancet Infect Dis 2006; 6: 589–601
Characteristics and outcomes of treatment with intravenous colistimethate sodium for infections caused by
multidrug-resistant Gram-negative bacteria in some recent clinical reports
Lancet Infect Dis 2006; 6: 589–601
Combination therapy
with colistin
Combination therapy with colistin
Eradication of early Pseudomonas aeruginosa infection.
• Danish cystic fibrosis center
• For aggressive eradication therapy of lower respiratory tract
infections by multidrugresistant P aeruginosa
• A combination of nebulised colistimethate sodium and oral
ciprofloxacin
• chronic P aeruginosa infection was prevented in 85% of patients
treated with the combination compared with only 42% in the nontreated group (p<0.05)
• Furthermore, in spite of its use against intermittent P aeruginosa
colonisation for 15 years by this group, there has been no
development of antibiotic resistance
J Cyst Fibros 2005; 4: 49–54.
Combination therapy with colistin
Combination therapy with colistin
Combined colistin and rifampicin therapy for carbapenem-resistant Acinetobacter
baumannii infections: clinical outcome and adverse events.
Clin Microbiol Infect 2005; 11: 682–83
Combination therapy with colistin
Combination therapy with colistin
Journal of infection (2005) 51
The End